Men who have undergone bariatric surgery as a long-term way of losing weight might also benefit from increased testosterone levels post-surgery. However, there is no evidence that the sperm quality of a patient improves. These are the findings of a comprehensive review in the Springer journal Obesity Surgery, which is the official publication of the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO). The research was led by Shahzeer Karmali and was a collaborative effort between Yung Lee of McMaster University and Jerry Dang of the University of Alberta in Canada.
Hormonal changes, a drop in sexual functioning, and less satisfaction in bed are among the many downsides of obesity. Obese men in particular are known to experience lower testosterone levels, lower sexual satisfaction, and reduced fertility compared to men of normal weight. On average the odds of male infertility are said to increase by 10 per cent for every nine kilograms a man is overweight.
Up until now most studies on the relationship between fertility and bariatric surgery have been focused on women. So Lee and his colleagues set out to review the available research on the influence of this procedure on male sex hormones and sperm quality.
“As the prevalence of both male infertility and bariatric surgery increases, knowledge of how surgical intervention affects fertility outcomes may better inform patient and surgeon decisions on pursuing this procedure,” says Lee.
In all, 28 studies carried out between 1998 and 2018 drawing on data from more than 1000 patients were included in the review. The studies all examined the effect of bariatric surgery on male sex hormones or sperm characteristics in patients with obesity.
Lee and his colleagues found that patients’ testosterone levels significantly increased after they had undergone bariatric surgery. Consistent with an increase in testosterone, levels of the hormones LH, FSH, and SHBG were also boosted. The amount of the female sex hormones estradiol and prolactin also notably dropped. These hormonal changes meant that erectile function also significantly increased after bariatric surgery. However, sperm characteristics such as volume, concentration, ability to move and build did not change much after bariatric surgery. In fact, several cases reported the worsening of such sperm parameters.
“This may be because any positive hormonal changes after bariatric surgery are counterbalanced by nutritional malabsorption and insufficiencies,” explains Lee.
“Bariatric surgery appears to be effective in increasing male sex hormones and decreasing female sex hormones in obese male patients. However, our review also suggests that bariatric surgery has no benefits on sperm parameters,” explains Lee. “Long-term comparative studies or adequately powered randomized controlled trials are warranted to further examine the impact of bariatric surgery on male sex hormones and sperm quality.”
The development of immunotherapy, which mobilizes the body’s own immune system to destroy cancer cells, is one of the greatest advances in cancer treatment, but immunotherapy can cause harm to healthy tissue in some patients. Researchers at UT Southwestern have identified blood-based biomarkers that may help identify those patients at greatest risk of developing autoimmune side effects from the treatment.
The researchers found that levels of certain cytokines — molecules that signal parts of the immune system to ramp up — were particularly low before treatment in patients who developed immune-related adverse events. Further, these patients also showed greater increases in cytokine levels immediately after treatment was started than patients who did not develop problems.
The findings, published in the British Journal of Cancer, suggest that patients at high risk for complications from immunotherapy may have pre-existing immune-regulation problems.
What is immunotherapy?
Immunotherapy is a type of cancer treatment that uses the patient’s own immune system to fight the cancer. Over the past decade, it has become widely used to treat certain types of cancer.
Immunotherapy is approved to treat melanoma, lung cancer, kidney cancer, certain gastrointestinal cancers, liver cancer, lymphoma, and childhood leukemia.
Checkpoint inhibitors, the most commonly used type of immunotherapy, work by taking the “brakes” off the immune system. Checkpoint inhibitors are administered intravenously every two to six weeks.
“Almost a decade into the remarkable era of cancer immunotherapy, immune-related adverse events continue to plague patients and puzzle clinicians,” said senior author Dr. David Gerber, Professor of Internal Medicine and Clinical Sciences and Associate Director for Clinical Research in the Harold C. Simmons Comprehensive Cancer Center. “While some of these toxicities, such as rash and thyroid dysfunction, can be easily managed, others such as pulmonary toxicity may result in hospitalization and even ICU-level care. Identifying these cytokines and other biomarkers for the prediction and tracking of autoimmune toxicity could help us customize immunotherapy, tailor monitoring and increase patient safety, and possibly even expand the use of immunotherapy to populations that are currently excluded.”
Dr. Gerber said their study included patients with a variety of cancer types. “Earlier studies of immune-related adverse events focused almost exclusively on melanoma patients, who are often treated with types of immunotherapy not used in other cancers. Our study enrolled a variety of patients with different cancer types and who were treated with widely used immunotherapy drugs.”
With a grant from the American Cancer Society and the Melanoma Research Alliance, this research will be expanded to a large, multicenter clinical trial that will look at a variety of potential biomarkers that can predict the autoimmune effect.
The published pilot study included 65 patients and 13 healthy controls who were evaluated for levels of 40 cytokines before treatment and two times following treatment. The forthcoming multicenter clinical trial will enroll 600 patients and include evaluations of 130 auto-antibodies; genetic tests for genes associated with autoimmune and inflammatory diseases; and functional tests, including cytokines. Blood samples will be taken before treatment, about six weeks after immunotherapy is started, and at the time of an immune-related adverse event, if one occurs.
Dr. Edward Wakeland, Professor of Immunology and a co-author, said the results of the study are an initial step toward greater understanding of the adverse events that occur with immunotherapy.
“Regulating the immune system is extremely complex, and a variety of patient-specific factors, including genetic predisposition, humoral immunity, interactions with the microbiome, and functional activation all play important roles in determining whether a beneficial or detrimental immune response develops. Nevertheless, our initial findings bode well for ultimately developing patient-specific strategies for effective and safe cancer immunotherapy,” said Dr. Wakeland, who holds the Edwin L. Cox Distinguished Chair in Immunology and Genetics.
“The key finding is that there is some sort of underlying immune dysregulation in patients who develop autoimmune toxicities. Ongoing studies are focused on utilizing immune monitoring, immunogenomics, and single-cell genomics strategies in identifying biomarkers and understanding the mechanisms underlying immune-related adverse events in larger patient populations,” said Dr. Shaheen Khan, Instructor of Immunology and first author of the study.
Inflammation, which is the root cause of autoimmune disorders including arthritis, type 1 diabetes, irritable bowel syndrome and Crohn’s disease, has unexpected effects on body clock function and can lead to sleep and shiftwork-type disorders, a new study in mice found.
Do ideologically extreme politicians deemed ‘polarized’ misrepresent a more moderate populace? According to a new article, that’s not the case. In fact, researchers argue, enacting campaign finance or election reform to reduce polarization in government would likely degrade the quality of political representation.
A new study finds that neonatal birthweights increase in direct proportion with the number of births of the mother in at least 30 percent of all cases. Large for gestational weight (LGA) babies are at risk for several neonatal complications, including jaundice, low sugar levels after birth and more.
Researchers at the University of Georgia have found that a high-fat diet enriched with cottonseed oil drastically improved cholesterol profiles in young adult men.
The researchers conducted a five-day outpatient feeding trial of 15 healthy, normal weight men to test the effects of diets enriched with cottonseed oil and olive oil on lipid profiles.
Participants showed significant reductions in cholesterol and triglycerides in the cottonseed oil trial compared to minimal changes on the olive oil-enriched diet.
The results appear in the journal Nutrition Research.
“One of the reasons these results were so surprising is because of the magnitude of change observed with the cottonseed oil diet,” said Jamie Cooper, an associate professor in the UGA College of Family and Consumer Sciences’ department of foods and nutrition and the corresponding author of the journal article. “To see this amount of change in such a short period of time is exciting.”
The subjects, all healthy men between the ages of 18 and 45, were provided high-fat meals for five days in two separate, tightly controlled trials, the only difference being the use of either cottonseed oil or olive oil in the meals.
Participants showed an average decrease of 8 percent in total cholesterol on the cottonseed oil diet, along with a 15 percent decrease in low-density lipoprotein, or LDL (the “bad” cholesterol) and a 30 percent decrease in triglycerides.
This diet also increased high-density lipoproteins, or HDL (the “good” cholesterol) by 8 percent.
Researchers suggested a fatty acid unique to cottonseed oil, dihydrosterculic acid, may help prevent the accumulation of triglycerides, a type of fat, in the body.
“By doing that, it pushes the body to burn more of that fat because it can’t store it properly, so you have less lipid and cholesterol accumulation,” Cooper said.
That mechanism, in addition to the high polyunsatured fat and omega-6 content of cottonseed oil, seems to be a key component to the beneficial effects on lipid profiles, Cooper said.
Researchers plan to expand the study to include older adults with high cholesterol as well as a longer feeding intervention.
It’s called the MacBook Air, but it’s an Air in name only. This new version of the popular laptop might as well be called the MacBook Pro Lite, because that’s essentially what it is.
The long-standing tapered Air design, with its thick screen bezels, smallish touchpad, deep keys and multiple types of ports is gone, replaced by the familiar design cues of the post-2016 MacBook ($1,279 at Amazon Marketplace) and MacBook Pro. If anything, the new Air looks and feels like a half-step between the 12-inch MacBook and the 13-inch MacBook Pro, rather than an evolution of the classic Air.
In person, as seen during a hands-on demo session following Apple’s Oct. 30 event, it was hard to distinguish this new Air from Apple’s other laptops at first glance. (One Apple rep misidentified a nearby new Air as a Pro to us.) Picking up the new Air, it immediately felt lighter and smaller than the current Air, which — having had the same basic design since 2010 — many of us are intimately familiar with.
You get more screen and less body, thanks to a display that cuts the thick bezel border by half and adds edge-to-edge glass over it. Now the Air display looks much like the one on the MacBook Pro, with the same True Tone color shifting and wider color range.
At 2.7 pounds (1.25 kg) and about 15mm thick, its size and weight is actually very middle-of-the-road when it comes to 13-inch laptops. The slimmest systems get down under 10mm, but at the expense of battery, features and processing power. If you want super thin and light, step up to that aforementioned 12-inch MacBook for just $100 more — but know you’ll be losing considerable features and power.
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MacBook Air 2018 now has a Retina display
While size and weight aren’t particularly unusual versus other laptops in this price class, the new MacBook Air does feel substantially more solidly constructed than most of the competition. Like the current Pro and 12-inch MacBook, the new Air still feels as tough as a tank, with its one-piece aluminum construction (now 100-percent recycled aluminum, according to Apple). That’s one of the reasons MacBooks, both Air and Pro, have been able to command premium prices for so long — because you’re making an investment in a product that will hopefully last for several years, which has often been the case for the traditional MacBook Air.
It’s all about the keyboard
As the only MacBook with a traditional island-style keyboard, the MacBook Air was the one refuge for those who disliked the super-flat butterfly mechanism keyboards in newer MacBooks. Now the new Air is firmly in the same camp as the other models.
Some may lament the loss of the older style of keyboard. Personally, I’ve never found the butterfly keyboard as troublesome as others, and I’ve certainly dealt with more difficult keyboards in more expensive products. (I admit this may be a minority opinion.)
It takes a period of adjustment to get used to the subtle tactile feedback, but once you get used to it, it’s fine for even long-form typing. But yes, you may never grow to love it.
But the positive tradeoff is that the new Air also includes a much bigger touchpad. It’s the same Force Touch style as on all the other MacBooks, which means it doesn’t have a diving-board hinge on the back, and instead uses four corner sensors to register clicks. The larger surface area is frankly more important than the mechanics behind it.
Will diehards take this change hard? They might, but that old keyboard was never as great as you remember, and the bigger touchpad is a great addition.
Ports of call
If the keyboard change bothers you, the port situation isn’t going to be much better. Following not only other Apple laptops but also many of the premium Windows laptops from the past two years, the MacBook Air is now USB-C only. That means any of your USB-A peripherals are going to need a dreaded dongle.
That said, it’s got two USB-C ports, instead of the single one on the 12-inch MacBook, so you can do more than one thing at a time, like connect a peripheral and the power cable. And these are Thunderbolt 3-enabled USB-C ports, so they cover the full range of high-end duties: high-speed data transfer, for example, or output to 4K and 5K displays. External GPU boxes (eGPUs) are also supported, but I have yet to try one with the new Air. (Those tests will follow soon.)
But back to that power cable issue: The late, great MagSafe connector is gone, so one of those two USB-C ports will often be used for power. While it’s great to see Apple using industry-standard USB-C ports for that — you can invest in third-party USB-C power delivery (PD) battery packs, for instance — it still means that you may be back down to a single open port.
The entry-level 13-inch MacBook Pro has a similar pair of Thunderbolt 3 USB-C ports, but lacks the Touch ID fingerprint reader found here. The fingerprint reader is really the best part of the Touch Bar experience, and it’s a great addition to the MacBook Air. I didn’t have a chance to register my own fingerprint and try it in action, but based on my use of the fingerprint reader in MacBook Pro systems (powered by the same T2 security chip), it’s a system that works quickly and reliably.
Still the ultimate student laptop?
One area where the new MacBook Air may lose some ground is as the default student laptop on many college campuses (and the default work laptop at many companies). Even though this is a much better laptop in nearly every regard, it loses one big advantage the previous MacBook Air had — its price.
At $999 in the US, the MacBook Air was an affordable luxury for many students, artists, writers and anyone who wanted a premium experience at a less-than-premium price. The new Air starts at $1,199 (£1,199, AU$1,849), which is a 20 percent jump, even though both the old and new entry-level models have 8GB of RAM and 128GB of solid state storage. That puts it just below premium laptops such as the $1,299 MacBook, which lacks a second USB-C port and fingerprint reader, and the $1,299 13-inch MacBook Pro, which lacks the fingerprint reader.
The overall design and usability, and the jump from fifth-gen Intel processors to eighth-gen ones, certainly makes this well more than $200 better than the old MacBook Air. But it also moves to being that much more of a stretch for many would-be owners.
Fortunately, that old-school Air is still available, at least for now, just as the old 13-inch MacBook Pro was for more than a year after the newest design debuted in 2016. If you’re firm in your need for USB-A or HDMI ports, or an island-style keyboard, pick one up now, because no one knows how long it’s going to last. But note that based on the past several years of concerns we’ve had about the low-res screen, thick bezel and outdated CPU, it’s hard to recommend that classic model right now.
We hope to test and fully review the new MacBook Air soon, so stay tuned for our benchmark results and full review.
Group A Streptococcus (GAS), sometimes known as “flesh-eating bacteria,” causes invasive infections that result in high mortality. GAS is susceptible to many antibiotics, but continues to cause devastating infections. Many studies have attempted to understand the mechanism for immune recognition of GAS; none has provided a clear explanation, until now.
In a new study published in the Proceedings of the National Academy of Sciences (PNAS) , an international research team led by experts from Osaka University investigated a variety of genes activated by the inflammatory components of GAS cells. They found that macrophage inducible C-type lectin (Mincle), an innate immune receptor, was strongly activated by exposure to these components.
GAS is a Gram-positive bacterial pathogen that can cause severe invasive infections, such as streptococcal toxic shock syndrome, necrotizing fasciitis, and bacteremia. Although GAS is sensitive to antibiotics, these infections continue to be associated with high mortality. In the study, the research team clarified the mechanism by which invasive GAS evades the host immune response. This understanding is essential for improving treatment of infections caused by this pathogen.
“We found that GAS produces a glycolipid, ‘DGDG’, which inhibits the immune receptor activity of Mincle,” says Sho Yamasaki, corresponding author on the study. “We suspect that this inhibition contributes to immune evasion by GAS.”
In the study, DGDG inhibited activation of Mincle by other GAS proteins in an in vitro assay. In a mouse model of GAS infection, mice without the Mincle receptor showed higher rates of mortality, suggesting that this receptor plays a critical role in the immune response to GAS.
“Our results suggest that blockade of DGDG production by GAS may provide a therapeutic option by increasing the ability of Mincle to initiate antibacterial immunity against invasive GAS,” says Takashi Imai, lead author on the study. “We expect that antibacterial drugs can be made to target the enzymes responsible for producing DGDG.”
In addition to providing a potential drug target, this increased understanding of the immune evasion mechanism is likely to guide new and improved treatment methods and strategies for combating GAS infection, including potential ligands for inclusion in vaccines against the bacteria.
GAS is a bacterial pathogen that can cause severe invasive infections associated with high mortality. This study clarified the mechanism by which invasive GAS evades the host immune response, and provided critical guidance for new curative and preventive therapies for GAS infections.
People who regularly take cocaine cut with the animal anti-worming agent levamisole demonstrate impaired cognitive performance and a thinned prefrontal cortex. These findings from two recent studies at the University of Zurich indicate that levamisole could have a toxic effect on the brain. Drug-checking programs should therefore be expanded, argue the researchers.
Cocaine is the second-most commonly consumed illegal substance worldwide after cannabis. The cocaine sold on the streets is usually cut with other substances such as local anesthetic agents, painkillers and caffeine. Around 10 years ago, however, a new adulterant made an appearance which is now widely spread in street cocaine in Europe and North America: The animal anti-worming agent levamisole. It’s not fully understood why levamisole is added to cocaine, but it is assumed that it may increase or prolong the effects of cocaine.
What is known is that levamisole can lead to severe side effects such as changes to blood counts and blood vessels. Initial animal testing also revealed that the substance can attack the nervous system. A team of researchers from the Psychiatric Hospital and the Institute of Forensic Medicine of the University of Zurich have now researched the extent to which the common cutting agent impairs the cognitive performance and alters the brain structure of people who consume it, thereby increasing the well-described negative effects of cocaine on the brain.
Higher levamisole content, lower brain power
In order to estimate the consumption of cocaine and the amount of levamisole content, the scientists analyzed hair samples of their study participants. Based on this, they examined the cognitive performance of those who had taken cocaine with a high levamisole content (more than 25% proportional to the cocaine) and those who had taken cocaine with a low levamisole content (less than 25%), and compared the results with a control group who had not taken cocaine.
As expected, the cocaine users showed lower performance than non-users in all areas — attention, working memory, long-term memory, and executive functions. However, those who had consumed cocaine that also contained a high level of levamisole showed even greater impairment in their executive functions than those who consumed cocaine with lower levels of levamisole, even though the amount of cocaine they had taken was the same.
Changes in the brain’s structure
In a second, independent study, the researchers used magnetic resonance imaging (MRI) to find out whether there was also a difference in the brain anatomy of people who consumed cocaine containing a higher or lower proportion of levamisole. The same effect was seen in this study: People who consumed cocaine with a high levamisole content clearly displayed a thinner prefrontal cortex — the area of the brain associated with executive functions.
Better protection through drug checking
For research leader Boris Quednow, the functional and structural changes observed in the brain clearly indicate that levamisole could have a toxic effect on the brain for cocaine users. “We can assume from our findings that it is not just cocaine that changes the brain, but that the adulterant levamisole has an additional harmful effect. The sorts of cognitive impairment often exhibited by cocaine users may therefore be exacerbated by levamisole.” The UZH professor and his research colleagues are therefore calling for public health protection authorities to expand their drug-checking programs. “Such programs mean users can have their drugs tested for purity and therefore avoid taking cocaine that has very high levels of levamisole,” says Quednow.
Breakthrough research to culture human skin cells called keratinocytes to produce skin grafts has been published by a team of researchers from Duke-NUS Medical School and the Singapore General Hospital (SGH). This method is the first to use a specific type of tissue-proteins known as laminins, found in the human body, to create a safer treatment for severe burns or other skin-related defects.
For over four decades, skin keratinocytes have been cultivated using a combined human-animal culture system. From a clinical application standpoint, this approach exposes patients to the potential risk of infections and adverse immune reactions. The animal derived products and biological agents used in the culture system are considered high-risk under a pharmaceutical standard called the Good Manufacturing Practice (GMP) system. Regulatory agencies, such as the U.S. Food and Drug Administration (FDA), have classified such cultured products as xenografts, which are approved only for treatment of severe burns (above 30% of total body surface area) or for compassionate use.
In this Singapore study, specific laminin proteins LN-511 or LN-421 are used as a supportive cell culture matrix and have been found to support the growth of human keratinocytes in a similar way. Lead author, Professor Karl Tryggvason, from the Cardiovascular and Metabolic Disorders Programme, Duke-NUS Medical School, who is also the Tanoto Foundation Professor in Diabetes Research, said, “Laminins have been transforming cell biology and are known to maintain stem cells and tissues architecture and function in a way that mimics the situation in the human body. The laminins play an important role in several human diseases, such as those of skin. Our method of using biologically relevant laminins in their pure forms to develop a fully human cell culture system for growing skin keratinocytes in the laboratory is a first and is likely to translate into novel treatments for many different skin disorders and wounds.”
“This new method provides a robust yet safer system for our burn patients. More importantly, it sets the stage for a cell culture platform for other regenerative medicine applications — these include the cultivation of cells from other surface tissues of the body, such as the cornea or oral mucosa ,” said the co-lead author of the study, Dr Alvin Chua, Medical Laboratory Scientist & Deputy Head of the Skin Bank Unit at the Singapore General Hospital’s (SGH), Department of Plastic, Reconstructive & Aesthetic Surgery and Adjunct Assistant Professor of Duke-NUS Medical School, Musculoskeletal Sciences Academic Clinical Programme.
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