PI3Kγ activity in leukocytes promotes adipose tissue inflammation and early-onset insulin resistance during obesity
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Dual modulator of macrophages
The kinase PI3Kγ is thought to inhibit classical macrophage activation, an effect that enables tumor progression. However, Breasson et al. found that PI3Kγ promoted the activation of macrophages in two different mouse models of obesity.
Analysis of mice with whole-body or tissue-specific deficiencies in PI3Kγ revealed that PI3Kγ in a nonhematopoietic cell type regulated adiposity but that PI3Kγ in leukocytes was required for the recruitment of neutrophils to adipose tissue, which was associated with macrophage activation and inflammation.
Thus, PI3Kγ can either inhibit or stimulate macrophages depending on the pathophysiological context.
Abstract
The phosphoinositide 3-kinase γ (PI3Kγ) plays a major role in leukocyte recruitment during acute inflammation and has been proposed to inhibit classical macrophage activation by driving immunosuppressive gene expression. PI3Kγ plays an important role in diet-induced obesity and insulin resistance.
In seeking to determine the underlying molecular mechanisms, we showed that PI3Kγ action in high-fat diet–induced inflammation and insulin resistance depended largely on its role in the control of adiposity, which was due to PI3Kγ activity in a nonhematopoietic cell type.
However, PI3Kγ activity in leukocytes was required for efficient neutrophil recruitment to adipose tissue. Neutrophil recruitment was correlated with proinflammatory gene expression in macrophages in adipose tissue, which triggered insulin resistance early during the development of obesity.
Our data challenge the concept that PI3Kγ is a general suppressor of classical macrophage activation and indicate that PI3Kγ controls macrophage gene expression by non–cell-autonomous mechanisms, the outcome of which is context-dependent.
Connie’s comments: To prevent adipose tissue inflammation, eat whole foods, avoid tobacco, too much caffeine, exercise, get sufficient sleep and detox (combo of fasting, juicing and other healing ways).
Tag team in home care with family members and pay out of pocket for senior care expense
Tag team in home care with family members and pay out of pocket for senior care expense
In patients with new-onset rheumatoid arthritis (RA), what is the risk for ischemic and nonischemic heart failure (HF)?
Clinical Impact Ratings
Question
In patients with new-onset rheumatoid arthritis (RA), what is the risk for ischemic and nonischemic heart failure (HF)?
Methods
Design
Inception cohort followed for a median of approximately 5 years.
Setting
Sweden.
Patients
12 943 patients ≥ 18 years of age (mean age 58 y, 69% women) with new-onset RA (< 12 mo of symptoms) were identified from the Swedish Rheumatology Quality Register. The control group comprised 113 884 people from the general population who were matched on birth year, sex, and area of residency. Exclusion criteria were heart failure before start of follow-up.
Prognostic factors
New-onset RA, sex, age, and area of residency.
Outcomes
First-ever diagnosis of HF during inpatient or specialized outpatient care, categorized as ischemic HF (previous history of ischemic heart disease or diagnostic code for ischemic HF) or nonischemic HF (data obtained by linkage with National Patient Registry).
Main results
The main results are in the Table. 332 (2.6%) patients with new-onset RA developed HF during follow-up.
Conclusion
Adults in Sweden with new-onset rheumatoid arthritis had increased risk for ischemic and nonischemic heart failure over 5 years of follow-up.
Risk for heart failure in Swedish adults with new-onset rheumatoid arthritis (RA)*
| Outcomes | Subgroup | Event rate/1000 person-y | At a median 5 y | |
|---|---|---|---|---|
| Rheumatoid arthritis | Control† | Hazard ratio (95% CI)‡ | ||
| HF | All | 4.1 | 3.2 | 1.2 (1.1 to 1.4) |
| Ischemic HF | All | 1.9 | 1.4 | 1.3 (1.1 to 1.5) |
| Nonischemic HF | All | 2.5 | 2.0 | 1.2 (1.0 to 1.4) |
| HF | RF positive | 4.0 | 3.2 | 1.4 (1.2 to 1.6)§ |
| Ischemic HF | RF positive | 1.9 | 1.4 | 1.5 (1.2 to 1.8)§ |
| Nonischemic HF | RF positive | 2.4 | 2.0 | 1.3 (1.1 to 1.6)§ |
| HF | RF negative | 4.2 | 3.2 | 1.0 (0.83 to 1.2)§ |
| Ischemic HF | RF negative | 1.8 | 1.4 | 0.97 (0.73 to 1.3)§ |
| Nonischemic HF | RF negative | 2.6 | 2.0 | 1.0 (0.79 to 1.3)§ |
*HF = heart failure; RF = rheumatoid factor; other abbreviations defined in Glossary.
†113 884 people from the general population were matched on birth year, sex, and area of residency.
‡Adjusted for sex, age, and area of residency.
§Compared with the entire control group.
Source of funding: No external funding.
For correspondence: Dr. A. Mantel, Karolinska Institutet, Stockholm, Sweden. E-mail angla.mantel@ki.se.
Commentary
Cardiovascular disease is a major extraarticular comorbidity and a leading cause of premature mortality in RA (1). Traditional risk factors are prevalent and mediate ischemic events and HF, but nonischemic, RA-associated inflammatory mechanisms may have an independent role in the pathogenesis of HF (2).
Mantel and colleagues used an impressive large-scale contemporary cohort study to confirm an increased risk for both ischemic and nonischemic HF (hazard ratio 1.33 to 1.45, narrow CI) in RF-positive patients recently diagnosed with RA. This is a new observation, which suggests inflammation-induced myocardial damage, possibly mediated by cytokines, such as tumor necrosis factor-α (TNF) (2).
At RA onset, risk for HF was not increased, and notably, incident nonischemic HF peaked in the first year of RA (hazard ratio 2.06) in correlation with markers of disease severity. In contrast, ischemic HF risk took > 10 years to evolve. Although 2.6% of patients in the cohort had HF, incidence is probably higher in patients with more severe disease and when asymptomatic HF (detected by screening echocardiography or B-type natriuretic peptide) is included.
The findings of Mantel and colleagues highlight that HF prevention is an additional compelling reason to diagnose and treat RA as early as possible, monitoring markers to ensure optimal disease suppression. In addition, strict attention to identifying and aggressively treating traditional ischemic risk factors seems essential; this may include use of corticosteroids as adjunctive therapy while trying to avoid high cumulative doses that may worsen atherosclerosis (3).
Biologic treatments, primarily TNF inhibitors, should be avoided in patients with previous HF; however, together with methotrexate, they are effective for treatment of patients with more severe new-onset RA where TNF may contribute to the cause of HF (2). Future studies may confirm a reduction in HF with the use of TNF inhibitors, in addition to the reduced risk for cardiovascular events.
Tag team in home care with family members and pay out of pocket for senior care expense
California Elder Care Costs for 2016
California Assisted Living Costs:
The average cost of assisted living in California in 2016 is $4,000 / month. In the most expensive areas of the state; Marin County, which includes the San Francisco area, San Mateo, San Luis Obispo, and Santa Cruz, the monthly cost ranges from $4,800 – $5,900. The least expensive assisted living can be found inland, in the cities of Madera, Merced, Stockton and Modesto. In these areas, the monthly cost is closer to $3,000.
Alzheimer’s residential care, also called Memory Care, can add as much as $1,100 to the monthly cost of assisted living.
California Home Care Costs:
The average hourly rate for home care across California is $23. The least expensive areas of the state for home care are Chico, Stockton, Vallejo, and Riverside where the cost is closer to $17 / hour. In Napa, San Jose, and San Mateo, the cost is approximately $27 / hour.
California Adult Day Care Costs:
Adult day care is the most affordable care option for seniors. In 2016, the average daily cost is $77. In San Jose, Chico, and Santa Rosa, it is more expensive, ranging from $90 – $125 / day. The least expensive areas of the state for adult day care are Stockton, Vallejo, and Visalia. Los Angeles is also slightly below the state’s average daily cost at $73 / day.
CA Financial Assistance Programs
Medi-Cal Waivers for the Elderly
Medicaid in California is called Medi-Cal. It is a program for disabled and elderly individuals and persons with limited income and resources. Through Medi-Cal, some personal care and nursing home care is provided. In addition, 4 programs (or “waivers”), also referred to as Home and Community Based Services waivers, are available that provide assistance for home care, adult day care, home modifications, and assisted living, to help prevent nursing home placement.
1) In some areas of California, Medi-Cal offers the Assisted Living Waiver, which help individuals who are eligible for nursing home care, but would prefer to live in an assisted living community. Read about the Assisted Living Waiver eligibility, benefits and locations.
2) The Multipurpose Senior Services Program (MSSP) Waiver helps nursing home eligible individuals that prefer to stay in their homes. It covers care management and supportive services, but doesn’t pay for medical care. This program unfortunately is not available in every county of California. Read about Medi-Cal MSSP Waiver eligibility requirements and benefits.
3) The Medi-Cal Nursing Facility / Acute Hospital (NF/AH) Waiver is a combination of several former waivers that helps nursing home eligible individuals receive care services, including medical care in their homes. This program also offers assistance to individuals currently residing in a nursing facility who wish to move back to their home. Read about NF/AH Waiver eligibility and benefits.
4) Medi-Cal’s Adult Day Health Care program has transitioned into the newly created Community Based Adult Services (CBAS) program. This program provides daytime care, meals, social activities, therapies, and skilled nursing. Functional needs must be met.
In order to qualify for the state Medicaid plan or one of the waivers, Medi-Cal has both income and asset qualifications. These limits depend on one’s age and marital status. As of 2016, a single elderly individual’s monthly income cannot exceed approximately $1,220 or $1,645 as a couple. An individual can qualify for Medi-Cal if the total value of their assets does not exceed $2,000, and for a couple, $3,000. One’s home and vehicle are not included in the asset calculation.
Persons with income and assets over these limits can still become eligible for Medi-Cal assistance. Individuals whose income exceeds the limit, but have high medical expenses may qualify through a Medi-Cal spenddown program called Share of Cost. Persons with assets valued over the limit might become eligible by working with a Medi-Cal planner to structure their resources appropriately. If there is some question regarding qualification, it is strongly recommended individuals contact a Medi-Cal Planner prior to application.
State (Non-Medicaid) Assistance Programs
California also offers assistance programs for the elderly that do not require an individual to qualify for Medicaid (Medi-Cal). Unfortunately, as of 2012, the budget for Alzheimer’s Day Care Resource Centers (ADCRC) was cut by the state. However, some Area Agency on Aging officesmay have funding to assist with the cost of adult day care.
The In-Home Supportive Services (IHSS) program is open to both Medicaid eligible and non-eligible persons and provides a variety of personal care supports to participants in their homes. This includes assistance with bathing, eating, dressing, meal preparation, housekeeping, and transportation assistance. This program allows individuals to choose the provider of their choosing, including family members. Read more about California IHSS eligibility and benefits
Another option for working families caring for a loved one is California Paid Family Leave. This program provides paid time off for working professionals, specifically to care for a family member.
Other Financial Options for Care
In addition to these state specific options that help pay for care, there are many non-profit and federal options. Use our Resource Locator Toolto find other programs that help pay for or reduce the cost of care. There are also programs that help veterans with assisted living and there are eldercare loans available in California.
While reverse mortgages are available nationwide, California’s real estate values have resulted in two unique financial products which are alternatives to reverse mortgages and can be used to pay for elder care. These are Rex Agreements and Equity Key. Unfortunately, as of March 2016, Equity Key was no longer taking applications. It currently is undetermined when they will begin accepting applications again.
Connie’s comments: Call 408-854-1883 for the most affordable senior care with live in caregivers for homebound bay area seniors.
Artificial Sweeteners May Cause Weight Gain
Artificial Sweeteners May Cause Weight Gain
Artificial Sweeteners May Cause Weight Gain
Though one expert warns there’s not enough info to place all blame on artificial sweeteners
(NEWSER) – If you think you’re avoiding artificial sweeteners because you don’t put them in your coffee or tea, think again. These additives are found in everything from yogurt and baked goods to sauces and diet colas, per the CBC, with “a lot of people … consuming them in foods and not realizing it,” says University of Manitoba researcher Meghan Azad. Azad, the co-author of a new study published Monday in the Canadian Medical Association Journal, also notes that 40% of adults report using artificial sweeteners on a regular basis—which may prove pointless when it comes to dropping pounds, as her team has found no evidence that the sweeteners help with weight loss and may even cause other health issues. Azad’s team conducted a meta analysis of 37 previously published studies of the diets of nearly 407,000 people, only seven of which were randomized control trials.
“A lot of the studies we found were observational, meaning they could show a link, but they can’t prove a cause-and-effect relationship,” she tells CTV News. Among the seven more-rigorous trials, regular consumption of artificial sweeteners had no significant effect on weight loss, while among the 30 observational studies, regular consumption was tied to a higher risk of Type 2 diabetes and high blood pressure, as well as “modest” weight gain.
Possible reasons for the weight gain, per Azad: Our bodies may metabolize based on sweetness perception (not sugar content), gut bacteria affected by sweeteners may affect obesity, or we may give ourselves permission to eat more sweets after eating diet products. An internal medicine expert says the studies aren’t clear enough to cast all blame on artificial sweeteners; Azad says there isn’t enough evidence the sweeteners are “truly harmless.” (When it comes to higher blood sugar, gut bacteria may play a role.)
Connie’s comments: Artificial food products are like toxins to our cells, destroying them. So that the first attack is hormonal imbalance, the brain and the nervous system and our immune system. In the case of the insulin hormone, our pancreatic cells are invaded by these toxins. Avoid them. I have seniors with Parkinsons who love artificial sweeteners. I check the food supply in the kitchen to learn about food and eating habits of seniors to understand the possible root causes of their health issues. The so many medications including Tramadol of my client with Parkinson’s and stress in living alone exacerbated her health issues.
Could Donald Trump Jr., Jared Kushner, or Paul Manafort be charged under the Espionage Act?
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Get faster response when looking for a live-in caregiver for seniors in the bay area
Get faster response when looking for a live-in caregiver for seniors in the bay area
You will be asked your city, how much you can afford and the day you need the caregiver. At Motherhealth, 408-854-1883, we can provide you with caregivers the next day as long as it is live-in even 2 hours away from the bay area.
We need to know if the client is bed-ridden and needs heavy lifting. And if you have long term care insurance. If you do not have long term care insurance, we try to fit the fee based on your budget. For 24/7 care, we try to assign 2 caregivers, 3 and 4 days to prevent burn out. We ensure that our caregivers believe in our mission of caring for seniors like their own family.
We asked for weekly payments and that we will do the monitoring, training and hiring of caregivers. To hire our caregivers directly without us in the coordination efforts will cost extra.
It is recommended to hire a team like us to coordinate care together with you.
Email motherhealth@gmail.com for this house to be installed in your location that ships from NC and cost is $25k for a 500 sq ft.