American family insurance cedar rapids iowa

Emergencies and cruises really don't mix.

2023.06.10 08:27 SilenceHeathen Emergencies and cruises really don't mix.

First and foremost, make sure you have travel insurance when you want to take a cruise just for the medical costs. They'll make you pay them upfront but you should be able to get some reimbursement afterwards.
What brought about this lovely statement was a defibrillator fire in my grand uncle that frightened him. Granted, after it freaked him out, it fired twice in rapid succession. He went down to medical where we learned his electrolytes were out of balance which was already my and my grandmother's guest (pharmacist and rn respectively) and they wanted to fly him out that evening and make my grand aunt find her own way back to him.
After talking it over, it was decided to wait until our port today to take him to the hospital and have his defib double checked and whatnot. Medical watched him for 36 hours roughly despite paperwork to check him AMA so they wouldn't put him on a plane by himself, and they charged 25,000 to play babysitter.
Grandmother signed papers to take care of an agreed 2,000 in additional early disembark fees, but the service desk shoved all of their charges onto our room number because my aunt had prepaid cash to dip into with no credit card. When my grandmother protested that she never agreed to pay medical, we were subtley threatened about having difficulty when it came time to disembark. (This is a whole other matter that my stateside family intends to tackle tomorrow... anyways)
I'm definitely never stepping foot on one of these hellships again. I wasn't really enthused with my experience overall, but I'm more than soured now.
Gotta love emergency healthcare!
submitted by SilenceHeathen to healthcare [link] [comments]

2023.06.10 06:34 flippenphil (OFFER) Trauma Center, the little mermaid, super troopers 2, yesterday, marauders, mr. holmes, scary stories, a thousand words, the dark tower, big hero 6, jungle cruise, strange world (REQUEST) Ambulance, the Menu, ISO on bottom / offers

MA = Movies Anywhere
GP = Googleplay
[?] = unknown definition
title = pending trade
If a title is no longer listed = It has been traded
COMBO Films
MOVIES
TV Series Marked
Vudu Only
ITUNES Only
ITUNES Only MOVIES - No Port - Marked
CANADIAN CODES: GOOGLE PLAY / ITUNES MARKED I do not know any of these port
WANT LIST
Titles I am looking for
submitted by flippenphil to uvtrade [link] [comments]

2023.06.10 05:57 Dry-Organization236 23 Bowman - Auto nonauto

23 Bowman - Auto nonauto
As the title states.
This came out of a 2023 bowman mega box. Is this a regular occurrence this year, or am I just that fortunate soul? Any info is appreciated.
submitted by Dry-Organization236 to baseballcards [link] [comments]

2023.06.10 05:32 ChaosReignUnderUs Matchday Thread: All Games 6/10 (June 10)

NISA

Time (Eastern Time) Home Away Link
6:00 PM Flower City Union Gold Star FC Detroit Link
7:00 PM Maryland Bobcats FC Savannah Clovers FC Link
7:30 PM Club De Lyon FC Michigan Stars FC Link

NISA Nation

Time (Eastern Time) Home Away Link
6:00 PM Lobos FC AS Los Angeles FC -
10:00 PM JASA RWC Modesto City FC -

Eastern Premier Soccer League

Time (Eastern Time) Home Away Link
7:30 PM Nova FC Estudiantes FC -
7:30 PM NY Pancyprian Freedoms NY Greek Americans Game In Frame

Midwest Premier League

Time (Eastern Time) Home Away Link
2:00 PM Troy United FC 1927 SC Michigan Soccer Network
2:00 PM Cedar Rapids Inferno SC Club Atletico St. Louis -
5:00 PM Indy Boyz FC Steel City FC -
6:00 PM AIM SC West Michigan Bearings SC -
6:00 PM AFC Columbia Southeast Soccer Academy -
6:45 PM Liquid Football Futsal Factory Academy -
7:00 PM Livonia City FC United West FC -
7:30 PM Bavarian United SC Edgewater Castle FC -
7:30 PM Chicago House AC Czarni Jaslo Sports Broadcast Solutions
8:00 PM Thundercats SC Cedars FC -
8:30 PM RWB Adria Berber City FC -

Gulf Coast Premier League

Time (Eastern Time) Home Away Link
4:00 PM Gulf Coast United Florida Roots -
6:30 PM Hattiesburg FC Union 10 FC -
7:00 PM Crescent City FC BRSC Capitals -
7:15 PM Gaffa FC Central Louisiana FC -
7:15 PM FC Sharp Keys Daggers CTX -
7:15 PM StrikerZ DFW Shreveport United -
7:15 PM Pensacola Bay United SOWEGANS SC -

Southwest Premier League

Time (Eastern Time) Home Away Link
7:00 PM ARIZONA SAHUAROS SPORTING ARIZONA -
8:00 PM SANTA CLARA SPORTING CLUB HAYWARD FC -

Cascadia Premier League

Time (Eastern Time) Home Away Link
5:30 PM Nido Aguila 2 Mt. Rainier F.C. -
9:00 PM Snohomish County Seattle Celtic Youtube
submitted by ChaosReignUnderUs to NISA [link] [comments]

2023.06.10 04:12 chameleonflower Advice on parking downtown (for a concert)?

Hi, I live in Iowa City but I’m not super familiar with Cedar Rapids. There’s a concert I’m going to in July at the Alliant Energy powerhouse. I was just wondering if anyone had any tips for parking? I see on the venue website that you can reserve parking through parkmobile (I don’t think I can do it for my event yet because it’s too far out still). Would this be the best way? Or should I just try to find a parking ramp on the day of? I’d like to be in walking distance if I can 😅 Thank you for any advice!
submitted by chameleonflower to cedarrapids [link] [comments]

2023.06.10 03:43 Cadoc7 UW and Premera signed their new agreement

Premera Blue Cross and UW Medicine announced June 9, a new multi-year agreement, effective July 1, 2023. The agreement allows UW Medicine to continue as an in-network provider for Premera members.
The two organizations began negotiations several months ago with a mutual goal of reaching an agreement that balances fair compensation for the healthcare system and continued access to high-quality, affordable care for UW Medicine patients and Premera members.
"This agreement represents our shared commitment to making healthcare work better," said Lee McGrath, executive vice president of healthcare services, Premera Blue Cross. "We appreciate our customers' patience as we worked tirelessly to ensure continued access to the innovative, high-quality care UW Medicine provides."
"The new contract represents a collaboration between two organizations that provides stability in today’s rapidly changing healthcare environment," said Dr. Tim Dellit, interim chief executive officer, UW Medicine, and interim dean, University of Washington School of Medicine in Seattle. "I am delighted that we can continue to provide in-network access to the high-quality care at UW Medicine for all of our Premera patients and families."
The agreement announced today will ensure that there is no disruption for Premera members who receive care at UW Medicine. It applies to all Premera lines of business, including commercial, Premera Blue Cross individual, LifeWise Assurance Company (student insurance) and Medicare Advantage.
I noticed the new statement on the UW website when I went to schedule my annual checkup. https://www.uwmedicine.org/premera
submitted by Cadoc7 to Seattle [link] [comments]

2023.06.10 01:58 the_divine_counsel Others experiencing American family insurance intentional claim payment delays?

Anybody else having intentional claim payout delays regarding the most recent April storms that hit Illinois in April? Apparently from my chats around the various obviously happy employees there, there is actually a known regional office of American family that causes delays, doesn’t respond to customers, etc. well, apparently I have happened upon them. I have a basic cut and dry claim for storm damage but 3 inspections, a lost inspection report and many many unreturned calls later I’m looking into taking legal action and have filed a case with the Illinois dept of insurance.
submitted by the_divine_counsel to Insurance [link] [comments]

2023.06.10 01:40 fitznerd Nanny jobs in Iowa

I’ve noticed there aren’t too many agencies out here. I’ve found only one so far. How else do you find out about nanny jobs in Iowa? Specifically around Iowa city or the Cedar Rapids area. Any tips/advice would be great!
submitted by fitznerd to Nanny [link] [comments]

2023.06.09 21:57 JC3FL [WTS] American Eagles, Philharmonics, Libertads, Upper Deck Hockey, Maples, Bars, Rounds, Skull Coins, Terracotta Army, Stackers, and a Kilo

Proof and Album
** Silver **
8 7 - 1985 Engelhard Prospector 1 oz .999 Silver Rounds Eagle Back - $34 ea
7 - 2015 Republic of Ghana Year of the Goat Skull 999 Silver Coin with COA (serialized on edge) - $35 ea
Lot of 4 - 2014 Canada Maple 1 oz .999 silver coins (milk spotty) - $111
2000 Sacagawea 4 oz .999 Silver with 24k Gold layered Commemorative Round in Capsule - $114
2001 Liberty 4 oz .999 Silver with Gold Highlighting Commemorative Round in Capsule (toning) - $114
2018 Fiji * Terracotta Army * 5 oz .999 Silver with Bag and COA - $158
4 3 - Scottsdale 10 oz .999 Stacker bars - $273 Shipped Ea, All: $1075 Shipped
2 - Scottsdale 20 oz .999 Silver Poured Bar - $530 ea shipped
Tube of 20 - 2014 Austria Philharmonic 1 oz .999 Silver Coins (milk spots) - $540 Shipped
2017 Upper Deck Grandeur Hockey Complete 20 - 1 oz .999 Coin Colorized Set with all packaging (NOTE: I ONLY pulled one out of the packaging. I noticed they are stamped with serial numbers. I DO NOT KNOW IF ALL THE COINS HAVE THE SAME SERIAL NUMBER. TALK TO ME IF THIS IS IMPORTANT - $590 Shipped
IGR 1000 Gram (1 Kilo) .999 Silver Bar Sealed with COA - $830 shipped
Tube of 25 - 2016 Libertad 1 oz .999 Silver Coins - $930 Shipped
** Gold **
1/10 oz .999 Apmex Round - $220 shipped
​
PENDING 5 - 2008 American Silver Eagle 1 oz .999 Coins (some light scratches) - $33 ea PENDING 4 - American Silver Eagle 1 oz .999 Coins (2001, 3-2009) (spots and marks) - $33 ea; All:130 4 - Engelhard 1 oz .999 Silver Bars Landscape - $34ea Engelhard 1 oz .999 Silver Bars Portrait - $34 2016 Canada Maple 1/10 oz .999 Gold Coin (a few small marks) - $220 shipped PENDING 2 - 1986 American Silver Eagle 1 oz .999 Coins - $43 ea; Both: $85 PENDING Lot of 6 - 1990's American Silver Eagle 1 oz .999 Coins(1990, 91, 92, 94, 95, 97) (toning and light scratches) - $200 Shipped
​
Payment:
PREFERED Zelle, Cashapp, Paypal Friends & Family (Please leave Comment box empty), PayPal Goods & Services (please add 3%), Personal Check, Money Order
Insurance available at Buyer Expense
Shipping:
Less than $199 -> $5
$200 + -> Free
submitted by JC3FL to Pmsforsale [link] [comments]

2023.06.09 20:42 PritchettRobert506 [HIRING] 25 Jobs in OH Hiring Now!

Company Name Title City
Best Service Heating & Cooling Part-time Customer Service Rep Whitehall
Best Service Heating & Cooling HVAC Technician Whitehall
American Family Insurance Senior Security Consultant Akron
Ohio University Assistant Director, Access and Inclusion and Senior Assistant Director, Access and Inclusion Athens
Ohio University Director of Diversity Affairs Athens
Ohio University Director of Diversity Equity & Inclusion Athens
Beckett Springs Outpatient Registered Nurse Camp Dennison
VineBrook Homes, LLC Director, Accounts Payable & Utilities Catawba
Clean Harbors Cleanpack Chemist Cleveland
Beckett Springs Registered Nurse (RN) Cleves
Zipline Logistics LLC Operations Associate Columbus
Green Bay Packaging, Inc. Maintenance Technician - Electrical Cuba
VineBrook Homes, LLC Director, Accounts Payable & Utilities Dayton
Kettering Health Network CMA Dayton
ProMedica LPN Defiance
ProMedica Licensed Practical Nurse (LPN) Defiance
Quantum Health Digital Accessibility Lead Dublin
VineBrook Homes, LLC Director, Accounts Payable & Utilities Englewood
ProMedica Registered Nurse (RN) Fostoria
ProMedica RN Fostoria
Valley View Healthcare Center Scheduling Coordinator - RN/LPN/STNA Fremont
L3Harris Technologies Specialist, Quality Engineering Goshen
Beckett Springs Registered Nurse (RN) Harrison
L3Harris Technologies Specialist, Quality Engineering Harrison
Beckett Springs Outpatient Registered Nurse Harrison
Hey guys, here are some recent job openings in oh. Feel free to comment here or send me a private message if you have any questions, I'm at the community's disposal! If you encounter any problems with any of these job openings please let me know that I will modify the table accordingly. Thanks!
submitted by PritchettRobert506 to OhioJobsForAll [link] [comments]

2023.06.09 17:07 ToastTurtle Reliq Health signs six contracts in Calif., Fla., Nev.

Reliq Health signs six contracts in Calif., Fla., Nev.

2023-06-09 09:06 ET - News Release
Dr. Lisa Crossley reports
RELIQ HEALTH TECHNOLOGIES, INC. ANNOUNCES SIX NEW CONTRACTS IN CA, FL AND NV
Reliq Health Technologies Inc. has signed six new contracts with physician practices in California, Florida and Nevada. These new contracts are expected to add over 3,000 new patients to Reliq's iUGO Care platform by the end of Q1 calendar year 2024, at an average revenue of $65 per patient per month.
"We are very pleased with our continued traction in California, Florida and Nevada," said Dr. Lisa Crossley, chief executive officer at Reliq Health Technologies. "The southern U.S. states are a particularly attractive market segment for Reliq due to demographics. With many older Americans choosing to move south in retirement, there is a very large population of Medicare-covered patients in these states who are eligible for Reliq's services. The three states where we have the largest number of patients -- California, Florida and Texas -- make up over 25 per cent of the total U.S. population, with over 90 million residents. The new clients will be using the iUGO Care remote patient monitoring (RPM), chronic care management (CCM) and behavioural health integration (BHI) modules to improve health outcomes and reduce the cost of care for their chronic disease patients. We expect to add over 3,000 patients to the iUGO Care platform by the end of March, 2024, through these contracts, at an average of $65 per patient per month with an expected 75-per-cent gross margin. All six practices will go live next month."
About Reliq Health Technologies Inc.
Reliq Health Technologies is a rapidly growing global health care technology company that specializes in developing innovative virtual care solutions for the multibillion-dollar health care market. Reliq's powerful iUGO Care platform supports care co-ordination and community-based virtual health care. iUGO Care allows complex patients to receive high-quality care at home, improving health outcomes, enhancing quality of life for patients and families, and reducing the cost of care delivery. iUGO Care provides real-time access to remote patient monitoring data, allowing for timely interventions by the care team to prevent costly hospital readmissions and emergency room visits.
We seek Safe Harbor.
Link: https://www.stockwatch.com/News/Item/Z-C!RHT-3420266/C/RHT
submitted by ToastTurtle to ReliqhealthStock [link] [comments]

2023.06.09 16:49 AdamLikesBeer Weekend Rundown June 9th - 11th

Around Town:

Friday

Saturday

Sunday

Sports

I have had suggestions for a patreon or something of the sort in the past. I do this because I like to provide whatever tiny help I can to the community. BUT I also like to raise money for Gillette's Children Hospital every year. So if you have some virtual loose change you can help me help dem kids here: https://www.extra-life.org/participant/482633

Links

Be da real MVP and add anything I missed below.
submitted by AdamLikesBeer to TwinCities [link] [comments]

2023.06.09 16:48 AdamLikesBeer Weekend Roundup 6/9-11

Around Town:

Friday

Saturday

Sunday

Sports

I have had suggestions for a patreon or something of the sort in the past. I do this because I like to provide whatever tiny help I can to the community. BUT I also like to raise money for Gillette's Children Hospital every year. So if you have some virtual loose change you can help me help dem kids here: https://www.extra-life.org/participant/482633

Links

Be da real MVP and add anything I missed below.
submitted by AdamLikesBeer to Minneapolis [link] [comments]

2023.06.09 16:41 chancebone1990 Hopefully this guy can change...

Hopefully this guy can change... submitted by chancebone1990 to IThinkYouShouldLeave [link] [comments]

2023.06.09 12:26 pediatricnephrology1 Nephrotic Syndrome: Understanding Symptoms, Causes, and Management

Introduction Nephrotic syndrome is a complex kidney disorder characterized by a specific set of symptoms, including edema (swelling), proteinuria (excessive protein in urine), hypoalbuminemia (low levels of albumin in the blood), and hyperlipidemia (elevated levels of lipids in the blood). It can affect both children and adults, with varying causes and treatment approaches. In this blog post, we will delve into the details of nephrotic syndrome, exploring its causes, symptoms, and management options. Our expert for this discussion is Dr. Sidharth Kumar Sethi, a renowned pediatric nephrologist specializing in the treatment of nephrotic syndrome. Understanding Nephrotic Syndrome Nephrotic syndrome occurs when the kidneys' filtering units, known as nephrons, become damaged, leading to a disruption in their normal function. This damage can result from various underlying conditions or diseases. The most common cause of nephrotic syndrome in children is minimal change disease, which typically responds well to corticosteroid treatment. However, some cases, such as those associated with focal segmental glomerulosclerosis, may be resistant to corticosteroids and may progress to kidney failure, potentially requiring renal transplantation. Symptoms and Diagnosis The hallmark symptoms of nephrotic syndrome include swelling in various parts of the body, particularly the legs and around the eyes, due to fluid retention. Proteinuria, which causes foamy urine, is another key indicator. Hypoalbuminemia and hyperlipidemia can be detected through blood tests. To diagnose nephrotic syndrome, a thorough evaluation is necessary, including a medical history assessment, physical examination, and laboratory tests. A kidney biopsy may also be performed to determine the underlying cause of the condition. Management and Treatment The management of nephrotic syndrome involves addressing the underlying cause, relieving symptoms, and preventing complications. Dr. Sidharth Kumar Sethi emphasizes the importance of individualized treatment plans based on the patient's age, medical history, and specific condition. For children with minimal change disease, corticosteroids are commonly prescribed and have shown significant success in achieving remission of proteinuria. However, some children may experience relapses and require further treatment. In cases of steroid-resistant nephrotic syndrome, alternative treatment options may be explored, including immunosuppressive medications and other targeted therapies. Dr. Sidharth Kumar Sethi's expertise in pediatric nephrology enables him to develop comprehensive treatment plans that prioritize the well-being and long-term outcomes of his patients.
Dr. Sidharth Kumar Sethi Kidney & Urology Institute He was trained as a Fellow (International Pediatric Nephrology Association Fellowship) and Senior Resident in Pediatric Nephrology at All India Institute of Medical Sciences and Division of Pediatric Nephrology and Transplant Immunology, Cedars Sinai Medical Centre, Los Angeles, California. He has been actively involved in the care of children with all kinds of complex renal disorders, including nephrotic syndrome, tubular disorders, urinary tract infections, hypertension, chronic kidney disease, and renal transplantation. He has been a part of an 8-member writing committee for the guidelines of Steroid Sensitive Nephrotic Syndrome and an Expert committee involved in the formulation of guidelines for Pediatric Renal Disorders including Steroid Resistant Nephrotic Syndrome and urinary tract infections. He has more than 30 indexed publications in Pediatric Nephrology and chapters in reputed textbooks including Essential Pediatrics (Editors O.P. Ghai) and “Pediatric Nephrology” (Editors A Bagga, RN Srivastava). He is a part of the Editorial Board of “The World Journal of Nephrology” and “eAJKD- Web version of the American Journal of Kidney Diseases”. He is a reviewer of Pediatric Nephrology related content for various Pediatric and Nephrology journals Conclusion Nephrotic syndrome is a complex kidney disorder characterized by specific symptoms and underlying causes. Early diagnosis and appropriate management are crucial for achieving remission, preventing complications, and ensuring the best possible outcomes for patients. Dr. Sidharth Kumar Sethi, an esteemed pediatric nephrologist, brings extensive knowledge and expertise to the field of nephrotic syndrome treatment. His individualized approach and focus on evidence-based practices make him a trusted resource for patients and their families. Name: Pediatric Nephrology India Address: Division of Pediatric Nephrology, Kidney Institute, Medanta, The Medicity, Gurgaon, Haryana, India, 122001 Phone: 0124-4141414 Website: www.pediatricnephrologyindia.com
submitted by pediatricnephrology1 to u/pediatricnephrology1 [link] [comments]

2023.06.09 09:07 DBCooper_OG There is no place like Nebraska

I grew up in rural Lincoln, I lived in Lincoln for college, and moved to LA almost 20 years ago. There's a whole network of Nebraskans out here, it's really one of a kind. And we get a lot of compliments for our midwest accents, enthusiastic naivete, and our straightforward demeanor. We know how to work hard, we're polite, humble, hospitable, family-oriented, we're well educated, and generally a lot of fun to be around. And Husker football is literally famous, there's no lack of opinions on how... I digress. To put it plainly, there's a lot to take pride in for Nebraskans.
Generally speaking, and perhaps our hugest source of pride, is that we've always taken care of ourselves, and have thrived doing so. We have innovated and provided general access to state-of-the-art agricultural, medical, and fintech opportunities, have some of the cleanest environments in the entire US, we're a formidable player in green energy, we have a unicameral and divide our electoral votes, Omaha Steaks sets a worldwide standard, we give back to the Fed (Nation) more than we borrow, etc; and there is a sense from living there that you can go anywhere in the entire State and find fellow Nebraskans who are polite, well-educated, and eager to find common ground - at the very least we'll have a beer with ya. Much like out here in LA, by simply being a Nebraskan (or first degree acquainted) you're entitled to our kinship worldwide; very few Americans can claim such an honor.
Nebraskans also recognize that there isn't, or at least hasn't, been a wide gap in classism. You can be Warren Buffett and visit a drive-thru every morning, and we could think nothing of it. The Nebraska community is relatively small, and so the contractor who built your house, your insurance agent, accountant, teacher, pastor, organist, nurse, babysitter, bartender, barista, the student who you see at the coffee house, these are all folks who literally live next door to you and call Nebraska home. True Nebraskans understand that they're all our neighbors and are all entitled to the same world-famous Nebraska-brand respect. Although there was some distinction between neighborhoods when I called Lincoln home, there was literally nowhere in the city my friends or I would avoid. We're all in it together, trying to make it The Good Life for ALL Nebraskans. I love Nebraska.
But this year is certainly different. I haven't been away for so long that Nebraska should be unrecognizable. How is it that I read news of our neighbors hating each other over trivial, personal matters? That shit used to NOT be important! Nebraska used to be a SAFE haven against the crazy outside world, a place where you felt comfortable around your neighbors because, like you, they're Nebraskans! All of 'em!
Get your shit together folks, we have literally a GLOBAL reputation to uphold of being good people. Let's take care of our fellow Nebrakans, we bleed Husker Red all the same. I know we are better than this b.s. I'm hearing about, go out and vote to correct these mistakes. Please, vote for yourselves and for all the rest of your fellow Nebraskans out in the world upholding REAL Nebraskan values.
Show 'em what ya got, good 'ol Nebraska, you.
submitted by DBCooper_OG to Nebraska [link] [comments]

2023.06.09 08:56 Snovasys25 4 Facts You Didn’t Know About the Remote Workforce

4 Facts You Didn’t Know About the Remote Workforce The remote workforce is on the rise, but there are still a lot of
misconceptions about remote work in different countries.
Here are four facts you didn't know about remote work in America.
  1. Remote work is in demand across all industries
According to the Bureau of Labour Statistics, in April 2018, 42% percent of employed Americans were "self-employed," which includes freelancers and independent contractors.
That's up from just 26% percent in 1997. With that being said, even though more jobs being done remotely now than ever before, many people have misconceptions that it's just for creative types or consultants—but freelance jobs span every industry and skill level possible.
There are several reasons for this trend. For one , remote work can offer a better work-life balance. Employees working from home or in coworking spaces can often avoid commute times and have more flexible hours. Additionally, remote work can be an excellent option for parents or caregivers who need to be available for their families.
Another reason for the growing popularity of remote work is that it's simply more efficient in many cases. Advancements in technology have made it simple to stay in touch and productive when working remotely.
  1. Remote work isn't just a millennial thing
According to a 2020 poll from Flex Jobs, millennials are more likely to work remotely than older generations.
61% of millennials surveyed said they were "enthusiastic" about the prospect of working from home, while only 42% of Generation X-errs and 32% of baby boomers felt the same way.
But the data shows that remote work is gaining popularity across age groups. Various factors are influencing this recent phenomenon; among them is the rapid increase in the availability and use of personal electronics and high-speed digital internet connections.
What's more, the study found that remote work is not just a millennial thing. Most remote workers are over the age of 35.
So, if you're considering switching to remote work, know that you're not alone. Plenty of us are doing it, and we love it!
  1. Remote workers aren't all freelancing full-time
According to a study by Global Workplace Analytics, 72% of people who telecommute do so at least 1 day per month for their primary employer.
So while we hear a lot about freelancing and remote jobs, there's a lot of people who work remotely and full-time for their primary job.
The demand for remote workers is high in the United States, especially among millennials. A recently published report shows that about half of US workers consider themselves better suited for work from home as an alternative. The presence of flexible schedules, no commuting, no required commute, and remote working are just some of the many reasons that working remotely is an excellent capability.
Of course, working remotely has its share of difficulties. For instance, it is impossible to maintain motivation when you are not working.
  1. Remote work isn't just technology-related
While remote work is most often associated with tech companies, according to The Balance, there are remote opportunities in pretty much every industry.
Whether in the arts, healthcare, retail, education, or science… there's a job out there for you! So why is remote work so popular? There are several reasons. First, it offers a great deal of flexibility and independence. Workers can often set their hours and work anywhere they want (including from home).
Second, remote work tends to be very technology driven. This means that workers need to be comfortable using various types of technology, including computers, tablets, and smartphones.
Finally, remote work is often more productive than traditional office work. To build a remote team and a company, you must equip with tools and techniques to get the insight and work to A
To get insight, Time, Champ is the perfect software to manage your remote team and project simultaneously.
Time Champ offers productivity features to ensure that teams stay focused and on task.
  1. Website and App Monitoring
  2. Detailed Reporting
  3. Optional Screenshots
  4. Customizable Productivity Settings
  5. And many more
Take the next step
See Time Champ in action! Watch our on-demand demo webinar
Want to know more? Book a Demo
Don’t have Time Champ? Sign up for a free account in minutes , no credit card required
submitted by Snovasys25 to u/Snovasys25 [link] [comments]

2023.06.09 07:05 NoPersonality4860 Cedar Rapids movie (2011)

I just watched this and it was pretty funny!! I haven’t heard anyone talk about it before,so I thought I’d post it on here incase anyone is interested. I definitely recommend it! :)
submitted by NoPersonality4860 to cedarrapids [link] [comments]

2023.06.09 06:53 SectorComplex8079 "All over but the Shouting" achievement guide

TLDR: Be anti-communist and attack Truman often.
Visits: All in NY
VP: Earl Warren
Difficulty: Normal
Q1: 1 option
Q2: Absolutely not. This is a perfectly reasonable measure, designed to prevent a strike in one industry from crippling the American economy.
Q3: I've supported the Israeli state from the beginning. I'm glad that Truman came around, but he absolutely sent the wrong message by vacillating on this issue until the very last moment.
Q4: Not only will I speak about this issue, but I will use it to attack Truman. I've supported civil rights all along, while Truman seems to have come around at the 11th hour, and for transparent political gain.
Q5: Not only is this a serious issue, but Harry Truman is complicit in it. It is no secret that he is, along with most Democrats, complacent on the issue of Communist infiltration.
Q6: I support our current airlift and hope that it leads to an agreeable conclusion.
Q7: I will talk about what I have accomplished in New York -- public works, a balanced budget, anti-discrimination laws, business creation, and funding for teachers and universities. This is the future of our party.
Q8: Eastern Seaboard
Q9: I think there are definitely programs that the federal government can get involved in to improve public health, but I also support our current system of private care and insurance.
Q10: This is something that we will research and consider seriously over the next four years. I'd have to see the details of any proposal before I could give my opinion.
Q11: We are the only thing standing between the world and global domination by the Soviets. I'm prepared to take any measure to prevent the advance of Communism.
Q12: What Truman really means when he calls this the "Do-Nothing" Congress is that they won't pass a program for national health insurance or the drastic expansion of Social Security. I will attack Truman for calling a pointless session for his own political purposes.
Q13: I support Social Security, but I think the program is most solvent in its current form.
Q14: I can't make a conclusive statement on this issue. I'm sure that between myself and Congress we can work out a good solution once I'm elected.
Q15: Eastern Seaboard
Q16: I support the Marshall Plan and believe that it is a force for the future peace and prosperity of our world.
Q17: We have already passed the Taft-Hartley Act and a modernized system of price supports for food, and their effect can clearly be seen in the drop in inflation since 1947. I'm confident this trend will continue.
Q18: I support the HUAC, although I do wish it could be a little more aggressive in its rooting out of Communist influence.
Q19: I support this Amendment as a necessary step towards the political health of this nation. We need to, periodically, have a fresh point of view in government. Ours is not an imperial nation.
Q20: We are clearly overcrowding our urban areas at the moment. At the very least, we can expand the federal highway system to make more areas accessible to families and developers.
Q21: Seaboard!
Q22: Only if we had clear assurances that other nations would not develop a nuclear bomb, and a means of enforcing those assurances.
Q23: Anyone can see that I've supported road development throughout my career, and I think this would be a positive step for the country.
Q24: Guess.
Q25: New York itself
​
Conclusion: With this guide, and honestly these aren't the best answers probably, you should win comfortably from 0.4 to 1 percent more than Truman. It's a pretty easy achievement if you know the winning points for the 1948 GOP.
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2023.06.09 04:56 Money-Camera1326 Bleeding post cold knife cone biopsy

Female- 32 years of age. PMH: 2 miscarriages, one live birth. Small non cancerous tumor in thyroid with normal thyroid function. Les than 1 cm. High risk HPV positive. No idea what kind. Normal height and weight. BMI 25. No other medical history. Back on May 24 I had a cold knife cone biopsy to remove and diagnose some high-grade cell changes on my cervix that had glandular involvement. Fast forward to June 1 and I was informed that I had negative margins, and that my next Pap smear should be in a year. They also did a D & C to make sure that I didn’t have cell changes up inside my uterus. The sales weren’t cancer yet but they were very high grade. That D&Ccame back negative for any type of abnormal cells. So on June 3 I went back to work where I have to stand and walk around for 12 hours. If you guessed it, I’m a nurse. The first day went well. I had some mild spotting which I had had since the procedure, but on the second day I went back to work, which was the fourth of June I hemorrhaged at the end of my shift. I was promptly wheeled straight down to the ER where I showed the ER doctor, my pad that I soaked in one second and a handful of paper towels that I bunched up and shoved into my pants because I was bleeding out of my pants, and into my scrubs, and all over everything. I stopped moving immediately and I laid down, and the bleeding slowly came to a halt, and all I had was clots coming out of me that were about the size of a tennis ball to a baseball. By the time the doc took a look, he did not see any active bleeding and my hemoglobin was very good so they sent me home. The next morning I hemorrhaged again before I even got out of bed. That time I bled out the side of an adult diaper and all over my floor. I called my dad who took me to the ER and I bled a bunch more and had clots come out but because I stopped moving and I laid there for hours upon hours I ended up stopping bleeding by the time the ER doctor looked. He said that he believed that the bleeding was somewhere behind my incision site so he called the OB/GYN who was caring for me and she was out of state, but she advised him to paint monsels solution onto my cervix. So he put two coats of that and I actually stopped bleeding for the rest of the day. The following day I had light pink spotting that has gotten progressively darker so I saw the OB/GYN on Tuesday and she just painted some silver nitrate over the incision site. After that my spotting stopped again, however, today I stopped back into her office because I saw all of the silver nitrate fall out and I was back with bright, red ketchup, stain looking spotting. She painted silver nitrate again just to make us both feel better. She told me to go back to the ER and call her if I soak through a Pad again rapidly, but other than that to expect some bleeding.. I just don’t feel comfortable even standing up. I feel pressure down there and it just doesn’t seem right.. it feels kind of like a pinch and I never had pain before this. And of course, now what I’m having is actual red blood bleeding, but I am just trying to lay down and do nothing…I haven’t had fevers and I haven’t felt crummy, but all I do is sit down. I do still have to go to the store and buy groceries because I have a four-year-old so I literally use one of those electric carts and anywhere else I go someone from my family just pushes me in a wheelchair. I still have to wash dishes, but I do that sitting down in a chair. It’s so weird, but I have had this hemorrhage issue before after a miscarriage. I ended up having retained tissue but that was really painful and this hasn’t hurt until tonight. Tonight I’m just feeling some pressure down there that I haven’t felt before Sidenote, there is no way that I’m pregnant because I haven’t had sex in almost a year. But they did check my hCG, which was like zero so that’s not even a possibility. I just don’t know where to go from here because I’m supposed to return to work in a week and I’m not sure if I just have to lay down for an entire week straight. And I don’t even know how I’m gonna do that, because I have a small child to take care of. I’m gettin so upset because I literally have to work and I’m just waiting for it to hemorrhage again only to go to ER and get sent home 90 more times. This isn’t getting better. Every doc who looks says sutures look good. I’ve been examined a total of 6 times. I can only go to my hospital due to insurance.
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2023.06.09 04:29 Bubzoluck [30 min read] The Opioid Epidemic before the Opioid Epidemic - Exploring Morphine Derivatives and the First Opium War (Part 1)

[30 min read] The Opioid Epidemic before the Opioid Epidemic - Exploring Morphine Derivatives and the First Opium War (Part 1)
Hello and welcome back to SAR! I have written and rewritten this post a few times now and I think I have landed on a format I am happy with. When we talk about the impact of medicine on history its important to get the context right, and I think I have found a way to talk about our topic. So what is it? No chemical is more important to the world of medicine than Opium, okay maybe Penicillin, but today we will say its Opium. Principally an analgesic (anti-pain), the Opium Poppy allowed for humans to take away pain in great degrees and further development on the natural chemicals has opened up surgery and post-op recovery. While we tend to look at the recent Opioid Epidemic as the only issue regarding Opiates, history reveals to us a very similar precursor. Also please head over to u/jtjdp post about morphine derivatives here! She does an amazing job explaining the higher level concepts of medicinal chemistry that I just wouldn’t do justice. Alright, enough quibbling, let’s get to the good stuff.
Disclaimer: this post is not designed to be medical advice. It is merely a look at the chemistry of medications and their general effect on the body. Each person responds differently to therapy. Please talk to your doctor about starting, stopping, or changing medical treatment.

How Much do you Know About Pain?

To be alive is to feel pain, and emo sentiments aside, this is one of the biggest biological properties of the central nervous system. When you think about it, how does the body take external stimuli and allow you to recognize it? The answer is the sensory nervous system which is responsible for sensing many different types of stimuli: temperature, pressure, pain, and chemicals. These sensory neurons carry the information from the extremities and transmit it up the spinal cord into the brain for processing. From there the brain alerts you to the issue allowing you to correct whatever problem is causing the pain. Let’s take a look:
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  • We call these receptors Nociceptors and activation of these neurons in the periphery leads to a signal being sent towards the spinal cord. Those peripheral nerves eventually complex with the Dorsal Horn of the spinal cord and interface with the central nervous system to transfer the pain signal. This signal is then sent Ascending to the Thalamus where the pain signal is recognized and initiates a response (such as pulling your hand away from the hot stove). But that’s not the full story, the brain also sends signals back down Descending to modify the incoming signal and dampen it. Its this modifying that makes pain fade over time when you aren’t focusing on it—otherwise the brain would be overwhelmed by the repetitive signal and continuously think injury is still happening. Now let’s divide this process into its two parts, first up the Ascending pathway.
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  • As the Action Potential travels from the periphery towards the Spine it causes the influx of Calcium into the Presynaptic Neuron. This neuron is what carries the original signal to then transfer into the Spine for further traveling. Eventually we reach the Synapse where the finger-nerve and spine meet and we get the transfer of information via Neurotransmitters. In this case, two chemicals are released: Glutamate and Substance P (which literally stands for Substance Pain). Glutamate will activate two receptors (AMPA and NMDA) which are Excitatory and stimulate the continuation of the pain signal up to the brain. Substance P activates the NK1 receptor which enhances the frequency of the pain signal (the throbbing) and the intensity of the pain burst. So to simplify, Glutamate allows the signal to be passed up to the brain but depending on the strength of the original pain signal more or less Substance P is released which modulates the strength and attention-grabbing nature of it. Okay great, we sent the pain pathway up and it will get processed in multiple different parts of the brain. But the brain can’t have that signal stinging it so it must send information back down to dampen that pain signal. This is where that aforementioned Descending pathway comes in. Above you can see how the blue line reaches down out of the brain and back into the spine to turn ‘off’ the signal. This is the basis of Analgesia or pain relief.
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  • Okay so now we have to divide the action of the Descending pathway which acts to dampen and modulate the original signal coming into the brain. Now, normally at rest this Descending neuron is inhibited so any fresh incoming signal is not inhibited from the get go but once that pain signal does come in, we get the good stuff! In response to pain the brain releases substances called Endorphins which activate the mu Opioid Receptor (MOR) located on the Descending pathway. Now MOR are inhibitory in nature so they are inhibiting the inhibitory resting state of neurons, or in other words, are allowing the Descending neuron to activate. And this is an important fact to recognize, Opiates do not inhibit pain, they inhibit the physiology of the nervous system that prevents modulation of the pain signal.
    • Once the inhibition is inhibited, the Descending neuron is free to release two neurotransmitters onto the nerve that was carrying the original pain signal. Both Norepinephrine and Serotonin are released to activate their respective receptors which inhibit the release of Substance P and Glutamate thus decreasing the incoming pain signal. Likewise MOR receptors are found directly on the incoming nerve and further prevent the release of Glutamate and Substance P as well as being found on the Ascending neuron preventing the activation of the NMDA/AMPA and NK1 receptors. The result: dampened incoming signal and decreased pain sense being sent to the brain.

The Stars Align in the Shape of a Poppy

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To start our story about Opiates we need to turn to the great precursor—Opium. Opium itself is not a chemical but rather a really thick liquor (called latex) that contains a high concentration of Morphine (and some Codeine). There are 38 species of Poppy plants but only two produce Opium is great enough supply that it is worth farming them and humans have been cultivating these varieties for as long as we have known about the plants. When humans settled into Mesopotamia (near modern day Iraq), Poppies were one of the few plants grown in plots as large grain or vegetable fields (meaning that they were thought of as valuable as food). Throughout the Greek age of medicine (pre-500 BCE) through the Islamic medicinal revolution (500 BC-1500 AD), Opium was a major component of treatment, assisted suicide, and poison. In fact its through the rise of the Muslim Caliphates that we see the export of Opium to other parts of the world, especially through the Mediterranean Sea once the Crusaders return. Opium trading to the East via the silk roads was an almost continuous affair since time immemorial and Pakistan was a major growing area for the Eastern Poppy trade.
  • By the time after the Crusades (11-13th centuries), we start to see the West’s fixation on Opium. For many reasons Europe didn’t develop many psychoactive plants to the same degree as more humid/hot climates like Africa, the Middle East, and India. This is why the importation of Opium (and also Marijuana) was such a trade commodity and staple in the development of Western medicine. During the Renaissance and the revival of Greek philosophy we start to see the re-fascination with Opium and by the 1600s we see merchants importing Laudanum into Europe for recreational and medicinal use. The standard use of Tincture of Opium (which is Opium dissolved in ethanol, a DEADLY combination) was a particularly favorite preparation which was prescribed to the lowest day-worker all the way up to kings.
    • The importation and use of Opium exploded in the late 1700s once the British conquered a major Poppy growing region of India. This region (western India and most of Pakistan) was originally slated to grow cotton like the American colonies but the region wasn’t wet enough to sustain the plant—it could however grow copious fields of Poppy plants to create Opium. Throughout the 18th century the British Raj became the largest exporter of Opium to Europe and after the discovery that Mercury and Arsenic may not be safe, Opium took over their duties. By 1780 almost all major remedies incorporated the use of Opium in some capacity and with the huge supply, it was incredibly cheap.
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  • Poppy wasn’t only important to the British for its medicinal properties but also to bolster the huge amount of loss they were incurring in global trade to one trade partner—China. After she made contact with China in the mid-1500s, Britain starting to import HUGE amounts of tea as the Brits became literally addicted to the substance. By 1800 a full 15% of the ENTIRE British Empire’s revenue was being spent on importing tea, that’s 30 million pounds per YEAR, leading to a massive trade deficit. This means that more money was being sent to China literally enriching a foreign country while the British public was getting their fix on the black stuff. Oh and just in case you think things haven’t changed, Britain still accounts for 42.6% of the world’s tea consumption—seriously Brits, ever heard of coffee? Anyways, all this money leaving the British economy to be spent on non-Empire sustaining commodities was a major national security risk for the British. It would be different if they were importing gunpowder like the Dutch were or Silver as the Spanish had but literally they were consuming the riches they were spending the money on.
    • Remember too that the British were not in the best position by the turn of the 19th century—they had just lost their colonies in the Americas, involvement in the Napoleonic Wars killed a generation of men, and the push to develop industries over public health led to a focus on fast growth rather than smart growth. One of the results of the Napoleonic Wars was the British occupation of the Island of Java which developed a very potent Opium which was traded with Chinese merchants regularly. Soon British merchants realized they could rebalance the trade deficit by selling Javanese Opium into China but the small island was unable to produce enough Poppies to meet the demand. So Britain turned to another one of its colonies, India.
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  • India by the end of the 1700s was a bit of a challenge. The British hold on the subcontinent was firm but they couldn’t grow the cash crops they wanted. Indian cotton was nothing compared to Egyptian or Southern American (i.e. Virginia/North Carolina/Georgia) cotton and the Indian tobacco was known for being bitter. But by the 1770s the British government realized that Poppy was an easy crop to grow and the demand across the border with China was an easy market; British traders brought their cargo to small islands off the coast of China where it was sold for silver. Initially the Chinese didn’t mind the sale of Opium in their territory—when the British traders collected the silver from the sale they would almost immediately use it to buy Chinese goods, thus driving tax revenue for the Chinese government.
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  • But if you buy Opium, people are going to use that Opium. By the 1810s all trade with foreigners was restricted to just one port, Canton, and slowly the city started to develop a habit for the drug. The use of mind altering substances was curtailed pretty quickly for hundreds of years in China—the Ming Dynasty banned tobacco in 1640 and the Qing banned Madak (a powdered Opium containing tobacco) was similarly banned in 1729. But by 1790 more and more Chinese citizens were becoming addicted to the substance; what started as a recreational drug slowly became a crippling addiction that took hold over Canton. For a rigid society, the crippling Opiate addiction was a moral corruption for the Qing government and forced them to curtail Opium importation in 1780 and then an outright ban in 1796.
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  • Knowing just how devastating the Opium was having on the inhabitants of Canton, as well as how it spread further inland, British merchants kept peddling their drug. Older ships with larger hulls were converted into floating warehouses and parked just outside of navigable waters. Once set up, Opium smugglers would pull up, purchase the Opium and avoid any oversight by the Chinese government to prevent the sale of the drug. Following their mother country, American merchants started to sell Turkish Opium, an inferior variety, at a much cheaper rate leading to drug peddling competition with more and more tons of Opium being sent into China. This drove down the price of Opium considerably which ultimately increased the demand.
    • This demand eventually led to reversal of trade, meaning that more silver was leaving China to pay for Opium than the British were using to pay for Chinese goods. American and European traders could show up in Canton with holds full of Opium, sell it off for a profit, and then make a tidy silver profit to bring back to Europe. Likewise the importation of cheap machine-made cotton, furs, clocks, and steel into China driving down domestic profits.

Let’s Look at the Drugs a Bit

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Stepping away from the history a bit, let’s introduce the Family. Okay so we understand how pain is sent to the brain and how it modulates but there is so much more to the mu Opioid Receptor and that’s not the only kind of Opioid receptor that we have. The two most clinically useful receptors are the Mu and Kappa Opioid Receptors (KOR) because they result in analgesia but there is a Delta Opioid Receptor (DOR) that is worth mentioning. The majority of the Opiates that we know and love are Mu agonists but there are some very interesting Kappa agonists that are worth mentioning as well.
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  • Above is a chart that shows the binding affinities of select Opiates to the Mu receptor. The smaller the number is, the more tightly they bond. Now affinity is different than potency—potency is a measure of how much drug (in g) is required to produce the same effect. So even though morphine has a higher affinity than fentanyl, fentanyl has a MUCH more potent effect (which is why it can be so dangerous, you only need a little). Now many of the opiates cause the same effect so I want to spend more time on what makes them all so different:
  • First up we have the 5-Ring Morphinians which are derived from the natural product Morphine. These structures have 5 component parts: an aromatic benzene ring (A), a completely saturated bridge ring (B), a partially unsaturated ring with an alcohol attachment (C), a piperidine heterocycle above the rest of the structure (D) and finally a ether linkage between the top and bottom of the structure to keep it fairly rigid (E). Truthfully we are only going to focus on two locations—firstly the top alcohol (red circle) can be methylated to form Codeine, a natural Prodrug of Morphine. A Prodrug is one that is biologically inactive but goes through an initial metabolism once ingested that makes it active.
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  • In fact it’s this initial metabolism of Codeine that makes it very interesting. In order for Codeine to exert any pain relief it needs to be converted to Morphine which actually exerts the desirable properties. This is done by the liver enzyme CYP2D6 which is a pretty minor pathway for Codeine—only about 10% of the Codeine is actually converted to Morphine to have some action. Because of this 2D6 dependent pathway we have to be careful about administering drugs that might inhibit the 2D6 pathway because that would mean we are preventing codeine from being active. Drugs like Fluoxetine (Prozac) and Paroxetine (Paxil) are strong 2D6 inhibitors and so if we administered Codeine to someone taking this drug they’d never get any benefit from the Codeine. In addition there are genetic/ethnic differences that pharmacists can account for such as 2D6 activity. If you are someone with very little 2D6 activity then you would also not convert Codeine to Morphine and thus get no action from the drug—this may be a reason why some people say Codeine doesn’t work for them. Another reason could be that they are Rapid Metabolizers and quickly convert the Codeine to Morphine and thus get a massive hit quickly after ingestion—in that cause you’d need a much smaller dose than another person for the same effect.
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  • A different drug that is the opposite of Codeine is Hydromorphone (Dilaudid) which has a Ketone on ring C. This ketone and the lack of the double bond on this ring increases the lipophilicity of the drug and increases its ability to penetrate into the brain and thus have a greater effect. In fact Hydromorphone is 5-10x more potent than Morphine due to its greater ability to penetrate into the brain and increased receptor affinity for the mu receptor. Because the A ring OH is not capped with a methyl group, we don’t need to rely on 2D6 to metabolize Hydromorphone into an active drug form which again increases the activity of this drug compared to Codeine.
  • So combine these two structural changes—the capped OH on ring A as seen in Codeine and the increased affinity found with the ketone in Hydromorphone and we get Hydrocodone (Norco, Lorcet). Well in this case you’d get a drug that has very good affinity for the mu receptor (better than codeine) BUT is still reliant on the small 2D6 pathway for activation (worse than morphine). In this regard only about 10% of Hydrocodone is active at a time. We can see this effect in the relative doses for equivalent effect: to match the effect of 30mg of Morphine, we’d need only 7.5mg of Hydromorphone (more active) but need 200mg of Codeine (less active).
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  • This brings us to our last drug of this class, Oxycodone which has a special OH group found on Ring B. What you’ll notice is that Oxycodone has that capped OH on ring A so it requires metabolism through 2D6 just like Codeine and Hydrocodone. When it is uncapped it becomes Oxymorphone which has 3 times as much effect as Morphine BUT that extra OH makes Oxycodone an exclusive Mu receptor agonist. Unlike the other drugs which may go to other receptors causing side effects (more on this later).
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  • Next up I want to look at some Mu opioid receptor Antagonists or those than inhibit the function of the opioid receptor. Looking at the first two drugs, Naloxone and Naltrexone, we can see that they have the structure similar to Hydromorphone so they would have incredible brain penetration and affinity for opioid receptors BUT they contain that funky Nitrogen tail. Now normally there is a short methyl tail that is required for the function of Morphine but by adding a bulkier tail the drug is able to fit inside the receptor but prevent activation. What’s most important about these two drugs is that they have much more affinity for the receptor than other opiates. We can see this effect in the graph above: when no Naloxone is present, Fentanyl occupies the opiate receptor about 75% of the time. But as soon as Naloxone is administered that number drops swiftly (within minutes)--this is because Naloxone has a higher affinity for sitting in the receptor than Fentanyl. Think of it like the bully Naloxone coming up and pushing the poor defenseless Fentanyl off the swings so the bully can play on it (except in this instance Fentanyl is causing an overdose and we need to save someone’s life).
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  • Buprenorphine is similar but it is a Partial Agonist instead of being a full antagonist. Buprenorphine is not a 5-ring Morphinian byt a 6-ring Oripavine that has a few different modifications. The biggest additions is that it has the bulky Nitrogen tail found in full Antagonists but it has this funky C ring tail which fights the antagonism. The result is a tug of war between the antagonism of the Nitrogen tail and the agonism of this new C-ring tail resulting in Partial agonism—so if you took Buprenorphine you’d notice a markedly decreased pain relieving ability but importantly there is a ceiling effect, its much harder to overdose on Buprenorphine than other full agonists. In addition in the second graph we can see that Buprenorphine has the greatest affinity for the receptor than our other agonists which prevents someone from taking a more potent opiate while taking Buprenorphine. In this case the bully is already sitting on the swing and scaring away the other kids thus preventing them from having a turn (and potentially causing an overdose). This does mean that if someone was taking a more potent drug (like Fentanyl) and then took Buprenorphine, it would cause withdrawal just like Naloxone or Naltrexone.
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  • Speaking of withdrawal, let’s take a look at how that happens. Remember that the pain signal is caused by the activation of AMPA and NMDA receptors from the peripheral nerve. AMPA is a type of receptor called a G-Protein Coupled Receptor or GPCR which in this case is linked to an Excitatory G-protein which leads to the activation of the nerve. When AMPA is activated, the G-protein (Ga) activates an enzyme called Adenylate Cyclase (AC) which increases the production of pro-activity cAMP—or in simpler terms—when AMPA is activated, it leads to an increase in levels of pro-pain molecule cAMP. The Opioid receptor is also a GPCR but it is linked to an inhibitory G-protein which prevents the action of Adenylate Cyclase and thus leads to a decrease in cAMP levels. So Opiates prevent pro-pain cAMP signaling from continuing.
    • In the second graph we can see how tolerance forms. Initially (A), Adenylate Cyclase and cAMP levels are not affected by having opiates even though their ability to push along the pain signal is blocked. After a few hours, the leftover cAMP is degraded and cAMP levels start to drop significantly (B). In response to these levels going down, the activity of Adenylate Cyclase starts to increase and increase (C) which raises the level of cAMP. This rise in Adenylate Cyclase activity opposes the action of the opiate which necessitates the need for increased doses of Opiates and is why tolerance forms. As sustained inhibition of Adenylate Cyclase continues, the body upregulates Adenylate Cyclase activity to create more cAMP and to combat this we increase the dose.
    • Now what if after years of taking an Opiate we suddenly administer Naloxone, an Opiate antagonist. Well after weeks to months of taking an Opiate, the level of Adenylate Cyclase activity is WAY above baseline. When you administer the antagonist, suddenly Adenylate Cyclase is able to produce a TON of cAMP that normally is blocked which leads to a MASSIVE amount of downstream signaling. The result is intense nausea and vomiting, stomach cramps, fever, anxiety, insomnia, and cravings. Thankfully the withdrawal process ends after about 72 hours but is one of the worst experiences someone can go through which is why proper down-tapering of Opiates is extremely important.

A Change in Trade Policy

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Oh, you’re still here. Neat! So by the 1820s the Qing dynasty was running into many problems regarding Opium. Firstly they needed the Opium taxes to fund their efforts to put down the White Lotus Rebellion and retain power. But after almost 30 years of trade the effects on Chinese communities could not be ignored along with local officials operating under the imperial trade department, the Hong, profiting from bribes to allow Opium. Regardless of initial efforts things were getting out of hand for the Qing government. In 1800, about 4000 chests of Opium or 560,000 pounds entered the country but by 1830 that number exploded to 20,000 chests or about 3 million pounds. But more than the amount of Opium actually entering the country was the incessant rudeness of the British government to open trade.
  • One of the “problems” for the British traders was how clamped down trade was with China. By 1800 all trade was limited to just Canton and the Hong was a strict master of trade. Foreigners were not allowed to appeal decisions made by the Hong and only Chinese traders could sell goods further inland than Canton. Traders chafed against this extreme oversight and sent hundreds of letters to the Hong requesting special dispensations which were summarily denied. Things changed significantly in 1834 when the Chinese trade was de-monopolized away from the East India Company allowing any private trader to get involved in the Eastern trade.
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  • In August of 1834, the British sent Lord William John Napier to Macau as superintendent of Chinese trade with the explicit order to follow all Chinese regulations. Thinking he knows best, Napier decided that the restrictive Chinese trade system was too restrictive and sent a letter to the Viceroy of Canton. This was unheard of—NO foreign traders were allowed to speak directly with Chinese officials and the Viceroy refused to accept it. So why not double down by ordering two British ships to BOMBARD two Pearl River forts as a show of force? Luckily Napier died of Typhus almost directly after else it would have resulted in a full blown war.
  • In 1839 the Qing government appointed Lin Zexu as the Opium czar to completely eradicate the Opium trade from China. Lin banned the sale of Opium in China completely, set up rehabilitation centers for those affected by the drug, and put addicts to work to distract them while detoxing. Lin demanded that all Opium supplies must be surrendered to Qing authorities and any Chinese citizen disobeying the order would be punishable by death. He even went as far as closing the Pearl River Channel, trapping British traders in Canton and seizing their Opium warehouse stockpiles.
  • The replacement for Napier was Admiral Sir Charles Elliot who protested the seizure of the Opium stockpile but knew that they could do nothing. He ordered all Opium ships to flee and prepare for battle which caused Lin Zexu to beseige a group of traders inside a Canton warehouse. Elliot convinced the traders to cooperate with the Chinese government and surrender their stock, saying that the British government would compensate for the lost Opium (which he had no authority to do). During April and May 1839 the British (and American) traders to surrender 20,000 chests of Opium which was burned for three days outside Canton. Following the burning, trade resumed to normal except no more Opium was allowed. Like many other instances of the government removing legitimate sale of a drug, the black market increased markedly.
  • In July 1839 a new scandal rocked the British-Chinese trade system; two British sailors became drunk and beat a man death outside of his village. In response, Superintendent Elliot arrested the two men and paid compensation to the villager’s family for the loss of the man but Elliot refused to hand over the sailors to the Qing government. Lin Zexu saw this as a blatant disregard for Chinese law—afterall traders needed to understand that they can’t just come to China and violate Chinese law as they saw fit. Elliot offered to hold a trial on a British ship in front of Chinese officials to show that the men would not get off free. This incident would start the smoldering.
    • On September 4th, Elliot sent two ships to Kowloon to buy food and provisions from Chinese peasants. While approaching the harbor, three Chinese war junks gave permission to the two British ships to trade but that permission was rescinded by the commander of Kowloon fort. Elliot fumed against the slight and said that if the British were not allowed to trade by 3pm, he would fire on the fort. 3pm passed and the British opened fire on the fort causing the Chinese junks to return fire. The fighting continued for 7 hours until nightfall and Elliot had to prevent the British officers from pressing the attack, thus ending the Battle of Kowloon. Having driven off the Chinese ships, the British purchased the supplies they needed while the Kowloon commander claimed that both ships were sunk and 50 British sailors killed.
    • The reaction in Britain was about as much as you expect. Prime Minister Palmerston sent out letters to the Governor General of India to prepare marines to invade China and another letter to the Chinese Emperor telling him that Britain would send a military force. He sent a letter to Superintendent Elliot to set up a blockade on the Pearl River and capture Chusan Island. He also instructed Elliot to accomplish the following objectives:
      • Demand the respect as a British envoy from the Qing Government.
      • Secure the right for British law to be doled out on British subjects
      • Get recompense for destroyed British property, especially the illegal drugs that they destroyed
      • And most important, End the Canton System thus opening up China to free trade for the first time, ever.
Alright this is where we will leave things off for now, on the brink of war with China. Stay tuned!
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