Racial and ethnic differences in health insurance coverage for adults with diabetes.
To evaluate the extent and types of health insurance coverage in a representative sample of adults with diabetes in the U.S. The Third National Health and Nutrition Examination Survey included national samples of non-Hispanic whites, non-Hispanic blacks, and Mexican-Americans aged > or = 20 years. Information on medical history and treatment of diabetes was obtained to determine subjects who had been diagnosed with diabetes by a physician before the survey (n = 1,503) and subjects without diagnosed diabetes (n = 17,319). Information on health insurance coverage was obtained via a structured questionnaire for 96% of participants. A total of 93% of all adults with diabetes had some form of health insurance. Of these subjects, 73% had private insurance, 48% had Medicare coverage, 15% had Medicaid coverage, and 5% had Champus/Veterans Affairs coverage. Approximately 52% of adults with diabetes had multiple types of health insurance, and 54% had health care coverage through one or more government-sponsored programs. A greater proportion of non-Hispanic whites (91%) and non-Hispanic blacks (89%) than Mexican-Americans (66%) had health insurance among subjects aged 20-64 years. For those aged > or = 65 years, coverage was virtually 100% for all racial and ethnic groups. Non-Hispanic whites had the highest rate of coverage through private insurance (81%), with non-Hispanic blacks having an intermediate rate (56%) and Mexican-Americans having the lowest rate (45%). Rates of coverage were similar for adults with and without diabetes in each racial and ethnic group for any type of insurance and for private insurance. There are marked racial and ethnic differences in health insurance coverage for adults with diabetes, although these differences are similar to those for adults without diabetes. Whether these racial and ethnic disparities influence access to care, quality of care, or health outcomes for people with diabetes remains to be determined.


Including Nonlinguistic Processing Tasks in the Identification of Developmental Language Disorder.
Purpose Accurate identification of developmental language disorder (DLD) remains challenging, particularly for children who speak different dialects, languages, or more than 1 language. Children with DLD, on average, have shown subtle deficits on nonlinguistic cognitive processing tasks, and performance on such tasks may be minimally influenced by language experience. This study explores whether nonlinguistic cognitive processing tasks can contribute to the identification of DLD in children from diverse linguistic backgrounds. Method Study 1 combined data from 4 U.S.-based investigations to yield a sample of 395 children, ages 6-10 years, who spoke only English or both Spanish and English. Study 2 consisted of an international sample of 55 kindergarten children living in Vietnam. Each study included children with DLD and children with typical development. Participants completed nonlinguistic cognitive tasks of processing speed, auditory working memory, and attentional control. Data analysis compared typically developing to DLD groups by age and language background. Then, we empirically derived cut-points to report diagnostic accuracy (sensitivity, specificity, and positive and negative likelihood ratios). Results For all 3 tasks, adequate sensitivity or specificity (but not both in most cases) was achieved in nearly all age groups. Likelihood ratios reached moderately to very informative levels in several instances. Diagnostic results were maintained when monolingual and bilingual samples were combined into a single group. Conclusions Nonlinguistic cognitive processing tasks may contribute to accurate identification of DLD in combination with other measures. Further research is needed to refine tasks, confirm cut-points established here, and extend findings to children from additional language backgrounds.


Evolution of in vitro fertilization at the University of the West Indies, Jamaica.
In vitro fertilization (IVF) provides hope for many couples who believed that they could not have children. This paper tracks the development of IVF treatment at The University of the West Indies (UWI), Mona, from its genesis in 2000. It highlights changes over the years in the population seeking IVF at UWI, Mona, and describes clinical services offered to clients, comparing success rates of services internationally. It also reports on seminal research emerging out of UWI, Mona, in the field of assisted reproductive health. The Hugh Wynter Fertility Management Unit (HWFMU), UWI, Mona, leads the way in shaping how society views those challenged with infertility and in its use of assisted reproductive technologies that improve the quality of life for many locally, within the Caribbean and the Diaspora.


Medical student perceptions of medical school education about suffering: a multicenter pilot study.
Little is known about what students perceive they are taught about suffering in medical school. We sought to explore medical student perceptions of their medical school education about suffering. We used an online survey of medical students enrolled in four US medical schools with chi-square analysis of responses by gender and preclinical/clinical status. A total of 1,043 students (38%) responded and indicated that teaching about suffering is occurring in the schools surveyed. Respondents most strongly endorsed statements that their medical school education explicitly teaches that the relief of suffering is an inherent function of being a physician (46.5%) and that most of what they learned about dealing with suffering patients is taught by modeling (46.6%). They reported that their education explicitly teaches about suffering (32.8%), provides a good understanding of suffering (31.7%), and teaches how to interact with suffering patients (31.7%). Students gave the least support to statements that their education prepares them to personally deal with their reactions to the suffering of patients (25.1%) and teaches how to diagnose suffering (15.3%). Responses varied markedly according to gender and clinical status at two of the four schools surveyed. Teaching about suffering is occurring in the schools surveyed and can be variably experienced according to gender and clinical status. Implied curricular gaps include teaching about how to diagnose suffering and how to personally deal with the feelings that arise when caring for suffering patients. Further research on how students are learning about suffering is warranted to guide curriculum development and implementation.


Baseline characteristics of the HAARLEM study: 100 male amateur athletes using anabolic androgenic steroids.
The use of anabolic androgenic steroids (AAS) is common among visitors of fitness centers. Knowledge about health risks of AAS use is limited due to lack of clinical studies. One hundred men, at least 18 years old, intending to start a cycle of AAS were recruited. Baseline demographical data and reasons for AAS use were recorded. Subjects provided samples of AAS for analysis with UPLC-QTOF-MS/MS. One hundred and eleven men were seen for a baseline visit. Nineteen percent had competed in bodybuilding competitions. Recent illicit drug use was reported by 56%. Seventy-seven percent of participants had used AAS in the past, and 97% of them had experienced side effects. After exclusion, 100 men comprised the cohort for follow-up. The AAS cycle performed had a median duration of 13 weeks (range 2-52), and the average dose of AAS equivalents was 901 mg per week (range 250-3.382). Subjects used other performance and image-enhancing drugs (PIEDs) such as growth hormone (21%). In total, 272 AAS samples were analyzed and 47% contained the AAS indicated on the label. The principal reason for AAS use was gain of muscle mass (44%). Forty-eight percent self-reported to being addicted to AAS. The HAARLEM study cohort shows that strength athletes use AAS in a wide variety of cycles and often also use illicit drugs and other potentially harmful PIEDs. The quality of the AAS used is strikingly low. Follow-up of the cohort will provide novel data regarding health risks of AAS use.


New nitric oxide donors based on ruthenium complexes.
Nitric oxide (NO) donors produce NO-related activity when applied to biological systems. Among its diverse functions, NO has been implicated in vascular smooth muscle relaxation. Despite the great importance of NO in biological systems, its pharmacological and physiological studies have been limited due to its high reactivity and short half-life. In this review we will focus on our recent investigations of nitrosyl ruthenium complexes as NO-delivery agents and their effects on vascular smooth muscle cell relaxation. The high affinity of ruthenium for NO is a marked feature of its chemistry. The main signaling pathway responsible for the vascular relaxation induced by NO involves the activation of soluble guanylyl-cyclase, with subsequent accumulation of cGMP and activation of cGMP-dependent protein kinase. This in turn can activate several proteins such as K+ channels as well as induce vasodilatation by a decrease in cytosolic Ca2+. Oxidative stress and associated oxidative damage are mediators of vascular damage in several cardiovascular diseases, including hypertension. The increased production of the superoxide anion (O2-) by the vascular wall has been observed in different animal models of hypertension. Vascular relaxation to the endogenous NO-related response or to NO released from NO deliverers is impaired in vessels from renal hypertensive (2K-1C) rats. A growing amount of evidence supports the possibility that increased NO inactivation by excess O2- may account for the decreased NO bioavailability and vascular dysfunction in hypertension.


The transtheoretical model of smoking: comparison of pregnant and nonpregnant smokers.
Pregnant smokers represent a special population of women smokers. Since smoking affects both the mother and the unborn child, it might be hypothesized that pregnant women should be highly motivated to quit smoking during pregnancy. Results from both naturalistic studies and intervention studies have generally shown only modest changes in smoking during pregnancy. To help design more effective interventions tailored for this special population of smokers, more information is needed on how they differ from other smokers. The current study was designed to examine patterns and differences on constructs of the Transtheoretical Model between low-income culturally diverse pregnant and nonpregnant female smokers. Groups were compared on the distribution of the stages of change. In addition, stage and group comparisons were conducted for the pros and cons of smoking, situational temptations to smoke, and the processes of change. The sample included 103 economically disadvantaged, culturally diverse pregnant women and a matched group of 103 nonpregnant women smokers. Pregnant smokers as a group were similar to their nonpregnant peers on their readiness for quitting. In general, the patterns observed across the stages of change were consistent with those seen in other populations of smokers. The primary difference found between the groups were on the cons of smoking, habit-related temptations to smoke, and experiential processes of change. Specifically, pregnant women perceived a less negative attitude toward their smoking, were more tempted in habit-related situations, and made less use of important experiential processes of change. The implications of these findings for designing interventions tailored for this special group of smokers are discussed.


Gastrointestinal manifestations of multiple endocrine neoplasia type 2.
To determine the clinical features, natural history, and role of surgery for gastrointestinal manifestations of the multiple endocrine neoplasia type 2 (MEN 2) syndromes. The MEN 2 syndromes are characterized by medullary thyroid carcinoma and other endocrinopathies. In addition, some patients with MEN 2A develop Hirschsprung's disease (HD), and all patients with MEN 2B have intestinal neuromas and megacolon that can cause significant gastrointestinal problems. From 83 families with MEN 2A, eight patients with HD were identified (MEN 2A-HD). These and all patients with MEN 2B followed at the authors' institution (n = 53) were sent questionnaires to describe the onset and type of gastrointestinal symptoms and treatment they had before the diagnosis of MEN 2. Records of all patients responding were reviewed, including radiographic imaging, histology, surgical records, and genetic testing. Thirty-six of the 61 patients (59%) responded (MEN 2A = 8, MEN 2B = 28) to the questionnaires. All patients with MEN 2A-HD were operated on for HD 2 to 63 years before being diagnosed with MEN 2. All patients responding were underweight as infants and had symptoms of abdominal pain, distention, and constipation. Eighty-eight percent had hematochezia, 63% had emesis, and 33% had intermittent diarrhea before surgery. All patients with MEN 2A-HD had rectal biopsies with a diverting colostomy as the initial surgical procedure. This was followed by a colostomy takedown and pull-through procedure at a later interval. Ninety-three percent of patients with MEN 2B had gastrointestinal symptoms 1 to 24 years before the diagnosis of MEN 2. Symptoms included flatulence (86%), abdominal distention or being underweight as a child (64%), abdominal pain (54%), constipation or diarrhea (43%), difficulty swallowing (39%), and vomiting (14%). Seventy-one percent of patients with MEN-2B with gastrointestinal symptoms had radiographic imaging, 32% were admitted to the hospital, and 29% underwent surgery. Patients with MEN 2A-HD had a typical HD presentation and always required surgery. Patients with MEN 2B have significant gastrointestinal symptoms, but less than a third had surgical intervention. Understanding the clinical course and differences in these patients will improve clinical management.


[The isolation of a pure culture of Proteus hauseri from associated bacteria].
A simple method for isolation of P. vulgaris and P. mirabilis pure culture from associations with other microorganisms has been developed. Medium for inoculation of a bacterial culture suspected of an association contains glycerin and asparaginic acid. The suggested method is simple and highly effective, reproducible at any bacteriologic laboratory, and is particularly valuable for improving the quality of etiologic diagnosis of pyoseptic diseases.


[The onset of the ovarian cycle following calving].
The onset of ovarian activity post partum was investigated by measuring progesterone concentrations in milk samples, in two dairy herds consisting of 118 cows with an average milk yield of 8340 kg FCM. Samples were taken three times a week till 50 days post partum. In 17 cows (14.4%) anoestrus occurred. The daily milk yield in this group was 2.65 kg FCM higher than the average yield in the group returning to oestrus before day 50 post partum. In cows returning to oestrus within 50 days post partum the first rise in progesterone was detected on average 27.6 days after calving. In first calvers (31.4 +/- 10.2) and in multiparous cows in the winter period (26.9 +/- 9.4) the onset of ovarian activity was delayed compared to start of ovarian activity in the summer period. In the first cycle only 28% of the cows had a normal luteal phase (12-17 days), 36% of the cows had a shortened luteal phase (less than 6 days), and 24% of the cows had a short luteal phase (6-11 days). In 12% of the cows the luteal phase was longer than 17 days. In the second cycle 56% of the cows had a normal luteal phase while 17% had a shortened luteal phase, and 17% had a short luteal phase. Pregnancy rates after first insemination in cows with a short dioestrus (10-25 days) were higher than in cows with a prolonged dioestrus (26-50 days). On the basis of these result it might be expected that postponing the first insemination until the second or even the third cycle in high-yielding cows will have only a marginal effect on the number of open days and a large effect on the number of inseminations per pregnancy.


Mortality with musculoskeletal disorders as underlying cause in Sweden 1997-2013: a time trend aggregate level study.
The aim was to assess time trend of mortality with musculoskeletal disorders (MSD) as underlying cause of death in Sweden from 1997 to 2013. We obtained data on MSD as underlying cause of death across age and sex groups from the National Board of Health and Welfare's Cause of Death Register. Age-standardized mortality rates per million population for all MSD, its six major subgroups, and all other ICD-10 (International Classification of Disease) chapters were calculated. We computed the average annual percent change (AAPC) in the mortality rates across age/sex groups using joinpoint regression analysis by fitting a regression line to the natural logarithm of the age-standardized mortality rates and calendar year as a predictor. There were a total of 7 976 deaths (0.5% of all causes deaths) with MSD as the underlying cause of death (32.5% of these deaths caused by rheumatoid arthritis [RA]). The overall age-standardized mortality rates (95% CI) were 16.0 (15.4 to 16.7) and 24.9 (24.1 to 25.7) per million among men and women, respectively (women/men rate ratio 1.55; 95%CI 1.47 to 1.63). On average, mortality rate declined by 2.3% per year and only circulatory system mortality had a more favourable decline than mortality with MSD as underlying cause. Among MSD the highest decline was observed in RA (3.7% per year) during study period. Across age groups, while there were generally stable or declining trends, spondylopathies and osteoporosis mortality among people ≥ 75 years increased by 2 and 1.5% per year, respectively. In overall, mortality with MSD as underlying cause has declined in Sweden over last two decades, with the highest decline for RA. However, there are variations across MSD subgroups which warrants further investigations.


A massive, quiescent galaxy at a redshift of 3.717.
Finding massive galaxies that stopped forming stars in the early Universe presents an observational challenge because their rest-frame ultraviolet emission is negligible and they can only be reliably identified by extremely deep near-infrared surveys. These surveys have revealed the presence of massive, quiescent early-type galaxies appearing as early as redshift z ≈ 2, an epoch three billion years after the Big Bang. Their age and formation processes have now been explained by an improved generation of galaxy-formation models, in which they form rapidly at z ≈ 3-4, consistent with the typical masses and ages derived from their observations. Deeper surveys have reported evidence for populations of massive, quiescent galaxies at even higher redshifts and earlier times, using coarsely sampled photometry. However, these early, massive, quiescent galaxies are not predicted by the latest generation of theoretical models. Here we report the spectroscopic confirmation of one such galaxy at redshift z = 3.717, with a stellar mass of 1.7 × 1011 solar masses. We derive its age to be nearly half the age of the Universe at this redshift and the absorption line spectrum shows no current star formation. These observations demonstrate that the galaxy must have formed the majority of its stars quickly, within the first billion years of cosmic history in a short, extreme starburst. This ancestral starburst appears similar to those being found by submillimetre-wavelength surveys. The early formation of such massive systems implies that our picture of early galaxy assembly requires substantial revision.


Home food environment of older adults transitioning from hospital to home.
Only anecdotal information is known about foods available in the home of hospital-discharged older adults. This study describes the home food environment of this population and examines associations between health/nutrition risk factors and ability to shop and prepare meals. Data were collected from 512 hospital-discharged older adults residing in 6 U.S. states; food available within the home was assessed. Most households had a variety of food present; however, 20% of households lacked fresh fruit, 15% lacked fresh vegetables, and 35% had no fresh meat. About 35% of participants reported an inability to both prepare meals and shop for food. Among those unable to do both activities, the prevalence of depressive symptoms, food-related anxiety, and poor self-rated health was significantly (p < 0.01) higher than those able to do both activities. Homebound older adults may face additional challenges to recuperation from illness based on inability to prepare meals, regardless of availability of food following hospital discharge.


Biochemical characterization of the Drosophila insulin receptor kinase and longevity-associated mutants.
Drosophila melanogaster (fruit fly) insulin receptor (D-IR) is highly homologous to the human counterpart. Like the human pathway, D-IR responds to numerous insulin-like peptides to activate cellular signals that regulate growth, development, and lipid metabolism in fruit flies. Allelic mutations in the D-IR kinase domain elevate life expectancy in fruit flies. We developed a robust heterologous expression system to express and purify wild-type and longevity-associated mutant D-IR kinase domains to investigate enzyme kinetics and substrate specificities. D-IR exhibits remarkable similarities to the human insulin receptor kinase domain but diverges in substrate preferences. We show that longevity-associated mutations reduce D-IR catalytic activity. Deletion of the unique kinase insert domain portion or mutations proximal to activating tyrosines do not influence kinase activity, suggesting their potential role in substrate recruitment and downstream signaling. Through biochemical investigations, this study enhances our comprehension of D-IR's role in Drosophila physiology, complementing genetic studies and expanding our knowledge on the catalytic functions of this conserved signaling pathway.


Determinants of the renal handling of 2, 4-dichlorophenoxyacetic acid by winter flounder.
The factors determining the renal handling of 2,4-dichlorophenoxyacetic acid (2,4-D) were examined in winter flounder, Pseudopleuronectes americanus, using isolated tubules and clearance techniques. In vitro, extensive energy-dependent uptake was seen with tissue/medium ratios of 30-fold at 1 micronM 2,4-D. The velocity of uptake was concentration-dependent with apparent Km and Vmax v,lues of 70 micronM and 3.6 micronmol/g of tubules per hr, respectively. Uptake was inhibited by other organic acids and 2,4-D competitively inhibited p-aminohippurate uptake. 2,4-D did not inhibit organic cation transport by the tubules. In vivo, 2,4-D was actively secreted with clearances of nearly 500 times the glomerular filtration rate at 1 micronM 2,4-D in plasma. At higher plasma concentrations (10-60 micronM) a transport maximum of 0.85 micronmol/g of kidney per hr was observed. Secretion was inhibited by other organic acids. 2,4-D also inhibited p-aminohippurate secretion in vivo. Little metabolism was noted; approximately 10% was excreted as the taurine conjugate. Plasma binding was 70%. Examination of the effects of added proteins on in vitro uptake showed that protein binding could limit 2,4-D transport but that flounder plasma (low in albumin) was far less effective than bovine serum albumin in binding and inhibition of transport. The roles of plasma binding, intracellular binding and metabolism in determining the rate of 2,4-D elimination by the kidney are discussed.


Time-varying respiratory pattern characterization in chronic heart failure patients and healthy subjects.
Patients with chronic heart failure (CHF) with periodic breathing (PB) and Cheyne-Stokes respiration (CSR) tend to exhibit higher mortality and poor prognosis. This study proposes the characterization of respiratory patterns in CHF patients and healthy subjects using the envelope of the respiratory flow signal, and autoregressive (AR) time-frequency analysis. In time-varying respiratory patterns, the statistical distribution of the AR coefficients, pole locations, and the spectral parameters that characterize the discriminant band are evaluated to identify typical breathing patterns. In order to evaluate the accuracy of this characterization, a feature selection process followed by linear discriminant analysis is applied. 26 CHF patients (8 patients with PB pattern and 18 with non-periodic breathing pattern (nPB)) are studied. The results show an accuracy of 83.9% with the mean of the main pole magnitude and the mean of the total power, when classifying CHF patients versus healthy subjects, and 83.3% for nPB versus healthy subjects. The best result when classifying CHF patients into PB and nPB was an accuracy of 88.9%, using the coefficient of variation of the first AR coefficient and the mean of the total power.


Association of preoperative magnetic resonance imaging findings with surgical features in Dachshunds with thoracolumbar intervertebral disk extrusion.
To evaluate the accuracy of specific magnetic resonance imaging (MRI) sequences in determining the site, lateralization, and extent of extruded intervertebral disk material (EIDM), compared with surgical findings, in Dachshunds with thoracolumbar intervertebral disk extrusion (TLIDE). Prospective clinical study. 16 Dachshunds with clinical signs of intervertebral disk disease. Preoperative T1-weighted, T2-weighted, and short tau inversion recovery (STIR) MRI measurements and description of the location of EIDM were compared with intraoperative measurements and determination of the EIDM position. The T12-13 intervertebral disk space was the most frequent site of EIDM (6/16 dogs). The EIDM lateralized with equal frequency to the left and right sides; no central extrusions were seen. There was moderate to substantial agreement (kappa, 0.59) between MRI and surgical findings for evaluation of the craniocaudal distribution of the EIDM. For measurement of the length of EIDM, the T1-weighted, T2-weighted, and STIR sequences had a mean error of -1.15, -0.38, and -1.93 mm, respectively; concordance correlation coefficients were 0.666, 0.904, and 0.458, respectively. Mean absolute errors were 2.54, 1.35, and 2.90 mm, respectively; these values did not differ significantly. In the thoracolumbar vertebral column of Dachshunds with clinical signs of intervertebral disk disease, MRI is a valuable technique for determining location and craniocaudal length of EIDM. Compared with T1-weighted and STIR images, T2-weighted images appeared to be more accurate and precise and are potentially more reliable for determination of the length of EIDM in those dogs.


Simvastatin and purine analogs have a synergic effect on apoptosis of chronic lymphocytic leukemia cells.
Despite many therapeutic regimens introduced recently, chronic lymphocytic leukemia (CLL) is still an incurable disorder. Thus, there is an urgent need to discover novel, less toxic and more effective drugs for CLL patients. In this study, we attempted to assess simvastatin, widely used as a cholesterol-lowering drug, both as a single agent and in combination with purine analogs-fludarabine and cladribine-in terms of its effect on apoptosis and DNA damage of CLL cells. The experiments were done in ex vivo short-term cell cultures of blood and bone marrow cells from newly diagnosed untreated patients. We analyzed expression of active caspase-3 and the BCL-2/BAX ratio as markers of apoptosis and the expression of phosphorylated histone H2AX (named γH2AX) and activated ATM kinase (ataxia telangiectasia mutated kinase), reporters of DNA damage. Results of our study revealed that simvastatin induced apoptosis of CLL cells concurrently with lowering of BCL-2/BAX ratio, and its pro-apoptotic effect is tumor-specific, not affecting normal lymphocytes. We observed that combinations of simvastatin+fludarabine and simvastatin+cladribine had a synergic effect in inducing apoptosis. Interestingly, the rate of apoptosis caused by simvastatin alone and in combination was independent of markers of disease progression like ZAP-70 and CD38 expression or clinical stage according to Rai classification. We have also seen an increase in γH2AX expression in parallel with activation of ATM in most of the analyzed samples. The results suggest that simvastatin can be used in the treatment of CLL patients as a single agent as well as in combination with purine analogs, being equally effective both in high-risk and good-prognosis patients. One of the mechanisms of simvastatin action is inducing DNA damage that ultimately leads to apoptosis.


Formoterol, a β2-adrenoreceptor agonist, induces mitochondrial biogenesis and promotes cognitive recovery after traumatic brain injury.
Traumatic brain injury (TBI) leads to acute necrosis at the site of injury followed by a sequence of secondary events lasting from hours to weeks and often years. Targeting mitochondrial impairment following TBI has shown improvements in brain mitochondrial bioenergetics and neuronal function. Recently formoterol, a highly selective β2-adrenoreceptor agonist, was found to induce mitochondrial biogenesis (MB) via Gβγ-Akt-eNOS-sGC pathway. Activation of MB is a novel approach that has been shown to restore mitochondrial function in several disease and injury models. We hypothesized that activation of MB as a target of formoterol after TBI would mitigate mitochondrial dysfunction, enhance neuronal function and improve behavioral outcomes. TBI-injured C57BL/6 male mice were injected (i.p.) with vehicle (normal saline) or formoterol (0.3 mg/kg) at 15 min, 8 h, 16 h, 24 h and then daily after controlled cortical impact (CCI) until euthanasia. After CCI, mitochondrial copy number and bioenergetic function were decreased in the ipsilateral cortex of the CCI-vehicle group. Compared to CCI-vehicle, cortical and hippocampal mitochondrial respiration rates as well as cortical mitochondrial DNA copy number were increased in the CCI-formoterol group. Mitochondrial Ca2+ buffering capacity in the hippocampus was higher in the CCI-formoterol group compared to CCI-vehicle group. Both assessments of cognitive performance, novel object recognition (NOR) and Morris water maze (MWM), decreased following CCI and were restored in the CCI-formoterol group. Although no changes were seen in the amount of cortical tissue spared between CCI-formoterol and CCI-vehicle groups, elevated levels of hippocampal neurons and improved white matter sparing in the corpus callosum were observed in CCI-formoterol group. Collectively, these results indicate that formoterol-mediated MB activation may be a potential therapeutic target to restore mitochondrial bioenergetics and promote functional recovery after TBI.


Fundamentals of clinical trial design.
Most errors in clinical trials are a result of poor planning. Fancy statistical methods cannot rescue design flaws. Thus careful planning with clear foresight is crucial. Issues in trial conduct and analyses should be anticipated during trial design and thoughtfully addressed. Fundamental clinical trial design issues are discussed.


The role of different sugars, amino acids and few other substances in chemotaxis directed motility of helicobacter pylori.
Motility plays a major role in pathogenicity of Helicobacter pylori, yet there is scarce data regarding its chemotactic behaviour. The present study was designed to investigate the chemotactic responses of local isolates of H. pylori towards various sugars, amino acids, as well as some other chemical substances. Chemotaxis was assayed by a modified Adler's method. We used solutions of sugars, amino acids as well as urea, sodium chloride, sodium and potassium bicarbonate, sodium deoxycholate and keratin at 10 mM concentrations. Despite some small differences, tested H. pylori isolates generally had a positive chemotaxis towards the tested sugars (P< 0.05). Among amino acids, phenylalanine, aspartic acid, glutamic acid, isoleucine and leucine showed a positive chemotaxis (P< 0.05) ; however, tyrosine showed negative chemotaxis (repellent) (P< 0.15). Urea, sodium chloride, sodium and potassium bicarbonate showed to be attractants (P< 0.05), but sodium deoxycholate was repellent (P< 0.05). It seems that, sugars and many amino acids by their attraction for H.pylori, many amino acids, may enhance the activity of this bacterium and probably aggravate the symptoms of its infection. However, those like L-tyrosine, may possibly be employed as deterrents for H. pylori and thus can control its infections. However, we suggest that further investigations on chemotactic behaviour of many more strains of H. pylori should be carried out before a final conclusion.


Electrophilic amination: the case of nitrenoids.
Among the numerous approaches and reagents employed for electrophilic amination, nitrenoids have long stayed out of the limelight. Here, we systematically review the discovery, structural features and chemical reactivity of these promising reagents. We highlight advances in applying the chemistry of nitrenoids as well as outline current limitations and future directions.


Effects of Vitamin K3 Combined with UVB on the Proliferation and Apoptosis of Cutaneous Squamous Cell Carcinoma A431 Cells.
Cutaneous squamous cell carcinoma (cSCC) is the second most common form of skin cancer and its incidence continues to rise yearly. Photodynamic therapy (PDT) is a non-invasive form of cancer therapy, which utilizes the combined action of a photosensitizer, light, and oxygen molecules to selectively cause cellular damage to tumor cells. Vitamin K3 (VitK3) has been shown to induce apoptosis and inhibit the growth of tumor cells in humans. The purpose of this study was to determine the effect of VitK3 and ultraviolet radiation B (UVB) on oxidative damage, proliferation and apoptosis of A431 cells. CCK-8 assay was used to detect cell proliferation; Hoechst staining, TUNEL assay and flow cytometry analysis were used to detect apoptosis. Western Blot was perfomed to measure the expression of apoptosis-related proteins. Flow cytometry analysis was employed to detect the reactive oxygen species (ROS) levels and mitochondrial membrane potential. Finally, the role of VitK3 in combination with UVB on the proliferation and apoptosis of A431 cells was investigated using mice xenograft models. We found that the co-treatment of VitK3 combined with UVB more significantly inhibited the growth and proliferation of A431 cells than either VitK3 or UVB alone. Hoechst 33258 staining and flow cytometry analysis revealed that apoptosis was more pronounced in the VitK3-UVB group compared to the VitK3 and UVB groups. Moreover, flow cytometry analysis showed that ROS and the depolarization of the mitochondrial membrane potential were higher in all the co-treatment groups compared to the control, VitK3, and UVB groups. The VitK3-UVB group exhibited a significantly lower tumor growth rate in mouse xenograft models. This study reveals that VitK3 combined with UVB inhibits the growth and induces apoptosis of A431 cells in vitro and suppresses tumor growth and promotes apoptosis of cSCC in vivo.


Comparison of enzyme-linked immunosorbent assay and radioimmunoassay for prostate-specific acid phosphatase in prostatic disease.
We compared results by an enzyme-linked immunosorbent assay (ELISA) with those by a standard radioimmunoassay (RIA) for detection and quantitation of prostate-specific acid phosphatase (EC 126.96.36.199) in serum. Control subjects, patients with benign prostatic hyperplasia, and patients in all four clinical stages of prostatic adenocarcinoma were tested. The upper limit of normal (95% of the population) by the ELISA was 2.0 micrograms/L, and by the RIA was 2.2 micrograms/L. In prostatic adenocarcinoma stage I (not detectable by digital rectal examination), ELISA was slightly more sensitive than RIA, but sensitivity was still relatively low (20%). As tumor mass increased (stages II through IV), the frequency of increased concentrations of prostatic acid phosphatase in serum also increased. We confirmed this increase in circulating enzyme in some cases of benign prostatic hyperplasia and suggest that this finding is related to either acinar cytolysis or an increase in acini size and number. Although prostate-specific acid phosphatase is not a cancer-specific enzyme, we conclude that its measurement may be of considerable value in monitoring prostatic disease.


Cutting edge: biasing immune responses by directing antigen to macrophage Fc gamma receptors.
An immune response can deviate toward either a Th1- or Th2-like response. In this work we examine the contribution that activated macrophages and IgG Abs make toward this deviation. The use of activated macrophages as APCs resulted in a strong polarized T cell response that was predominated by IFN-gamma. However, when Ag was targeted to FcgammaRs on these macrophages, the T cell response was reversed and biased toward a Th2-like response. This Th2-like phenotype was stable and was retained when the T cells were subsequently restimulated under nonbiasing conditions. The T cell biasing and its reversal via FcgammaR was also observed in vivo. Mice vaccinated with IgG-opsonized OVA made high levels of IgG Ab of the IgG1 isotype. These studies demonstrate that the ligation of FcgammaR on activated macrophages can reverse the Th1 biasing that occurs as a result of innate immune responses to microbial products.


Effect of oxygen radical scavengers on K-cell cytolysis.
We have shown that the hydroxyl radical scavengers sodium benzoate, phenol, dimethyl sulfoxide, sodium formate, and mannitol protect chicken erythrocyte (Ec) target cells from lysis by K-cells in plaque assays. The protection afforded by benzoate, phenol, mannitol, and dimethyl sulfoxide was abrogated if the target cells were pretreated with sodium chromate. Neither superoxide dismutase nor catalase protected Ec target cells, indicating that superoxide and H2O2 are not involved in lysis. The lysis obtained on chromium-treated Ec target cells in the presence of benzoate, phenol, and mannitol is likely due to singlet oxygen, because 1,4-diazabicyclo[2.2.2]octane and bilirubin, singlet oxygen scavengers, protected chromium-treated Ec target cells in the presence of phenol. Ec target cells not treated with chromium were not protected by either of the singlet oxygen scavengers.


CD38 triggers cytotoxic responses in activated human natural killer cells.
Receptors used by natural killer (NK) cells to mediate natural cytotoxicity are poorly defined, although it is now clear that a number of adhesion molecules can serve this function. CD38 transduces signals on T- and B-cell lines, and we asked whether it could trigger lytic and secretory responses in human NK cells. By using an anti-CD38 monoclonal antibody in reverse antibody-dependent cellular cytotoxicity experiments, it is shown that CD38 engagement triggers cytotoxic responses by activated NK cells, but not by cytotoxic T lymphocytes or fresh NK cells. Cross-linking with anti-CD38 F(ab')(2) caused activated NK cells to release granzymes and cytokines, but did not trigger an increase in intracellular Ca(2+). Fresh NK cells acquired CD38-dependent lytic function during activation with interleukin-2 (IL-2), and inhibitor studies suggested that IL-2 stimulated the de novo expression of proteins that act between CD38 and the lytic machinery in NK cells. The induction of proteins that link commonly expressed adhesion molecules to effector mechanisms could provide a paradigm for pathogen recognition by the innate immune system.


Attributed concept maps: fuzzy integration and fuzzy matching.
A concept map, typically depicted as a connected graph, is composed of a collection of propositions. Each proposition forming a semantic unit consists of a small set of concept nodes interconnected to one another with relation links. Concept maps possess a number of appealing features which make them a promising tool for teaching, learning, evaluation, and curriculum planning. We extend concept maps by associating their concept nodes and relation links with attribute values which indicate the relative significance of concepts and relationships in knowledge representation. The resulting maps are called attributed concept maps (ACM). Assessing students will be conducted by matching their ACMs with those prebuilt by experts. The associated techniques are referred to as map matching techniques. The building of an expert ACM has in the past been done by only one specialist. We integrate a number of maps developed by separate experts into a single map, called the master map (MM), which will serve as a prototypical map in map matching. Both map integration and map matching are conceptualized in terms of fuzzy set discipline. Experimental results have shown that the proposed ideas of ACM, MM, fuzzy map integration, and fuzzy map matching are well suited for students with high performances and difficult subject materials.


[Nosema sp. in white rats].
In 14 days after the intraperitoneal infection of mice with 30% brain emulsion of white mice or of newly-born rats in the peritoneal liquid there were found spores of Nosema sp. 5.37 plus or minus 0.88 x 3.04 plus or minus 0.07 in size. The subsequent attempts to passage this organism on the mice by adminestering into them the suspension from the brain and internal organs of infected animals yielded ho results. The material for diagnosing on microsporidians of mammals is being discussed.


Host-Specific NS5 Ubiquitination Determines Yellow Fever Virus Tropism.
The recent yellow fever virus (YFV) epidemic in Brazil in 2017 and Zika virus (ZIKV) epidemic in 2015 serve to remind us of the importance of flaviviruses as emerging human pathogens. With the current global flavivirus threat, there is an urgent need for antivirals and vaccines to curb the spread of these viruses. However, the lack of suitable animal models limits the research questions that can be answered. A common trait of all flaviviruses studied thus far is their ability to antagonize interferon (IFN) signaling so as to enhance viral replication and dissemination. Previously, we reported that YFV NS5 requires the presence of type I IFN (IFN-α/β) for its engagement with human signal transducer and activator of transcription 2 (hSTAT2). In this manuscript, we report that like the NS5 proteins of ZIKV and dengue virus (DENV), YFV NS5 protein is able to bind hSTAT2 but not murine STAT2 (mSTAT2). Contrary to what has been demonstrated with ZIKV NS5 and DENV NS5, replacing mSTAT2 with hSTAT2 cannot rescue the YFV NS5-STAT2 interaction, as YFV NS5 is also unable to interact with hSTAT2 in murine cells. We show that the IFN-α/β-dependent ubiquitination of YFV NS5 that is required for STAT2 binding in human cells is absent in murine cells. In addition, we demonstrate that mSTAT2 restricts YFV replication in vivo These data serve as further impetus for the development of an immunocompetent mouse model that can serve as a disease model for multiple flaviviruses.IMPORTANCE Flaviviruses such as yellow fever virus (YFV), Zika virus (ZIKV), and dengue virus (DENV) are important human pathogens. A common flavivirus trait is the antagonism of interferon (IFN) signaling to enhance viral replication and spread. We report that like ZIKV NS5 and DENV NS5, YFV NS5 binds human STAT2 (hSTAT2) but not mouse STAT2 (mSTAT2), a type I IFN (IFN-α/β) pathway component. Additionally, we show that contrary to what has been demonstrated with ZIKV NS5 and DENV NS5, YFV NS5 is unable to interact with hSTAT2 in murine cells. We demonstrate that mSTAT2 restricts YFV replication in mice and that this correlates with a lack of IFN-α/β-induced YFV NS5 ubiquitination in murine cells. The lack of suitable animal models limits flavivirus pathogenesis, vaccine, and drug research. These data serve as further impetus for the development of an immunocompetent mouse model that can serve as a disease model for multiple flaviviruses.


Medication use practices and perceptions among patients in a U.S.-Mexico border community.
To identify themes surrounding medication use practices and perceptions among individuals from a U.S.-Mexico border community recruited to participate in focus groups. This study was conducted in El Paso, TX. Adult participants considered to be at risk for medication therapy problems (i.e., older adults, pregnant or breast-feeding women, parents of young children) were recruited for participation. Focus groups and a survey were used to evaluate perceptions, concerns, and patterns of use of U.S. medications, Mexican medications, and herbal products. A sample of 73 adults, most of whom were Hispanic women (n = 60 [82%]), were recruited for participation in seven focus groups. Across groups, the majority participated in the older adult cohort (n = 42 [58%]), reported having an annual household income of less than $15,000 (n = 57 [78%]), and identified that they had less than a high school education (n = 40 [55%]). Four dominant themes emerged from the participants who completed both the survey and focus groups: (1) a "comfort" level for using a combination of U.S. medications, Mexican medications, and herbal products; (2) customary use of different drug information sources including physicians, Mexican pharmacy staff, U.S. pharmacists, and family members; (3) inconsistent levels of confidence in interpreting, measuring, and using medications; and (4) a sense of frustration regarding medication costs, which led participants to seek alternative options. These qualitative results provide an increased understanding of medication use practices and perceptions in this population. Findings such as these can provide guidance and insight into the development of interventions to improve safe and effective medication use.


Efficacy of probiotics in the treatment of minimal hepatic encephalopathy: A systematic review and meta-analysis.
Patients with minimal hepatic encephalopathy (MHE) have no recognizable clinical symptoms of hepatic encephalopathy (HE), but the mild cognitive and psychomotor deficits have been shown to negatively affect their daily functioning and quality of life. Treatment with probiotics has shown benefit in some clinical trials. This review aimed to systematically analyze the efficacy of probiotics in the treatment of MHE. A systematic search of the electronic databases PubMed, Science Direct, and Cochrane Library was conducted for randomized controlled trials (RCTs) in adult patients with MHE who had been given probiotics intervention. The primary outcomes were reversal of MHE and improvement of neuropsychometric tests, while the secondary outcome was the reduction of serum ammonia. Nine RCTs involving 776 MHE patients were included, consisting of 311 patients receiving probiotics and 465 patients receiving comparator (placebo or no treatment, lactulose, L-ornithine L-aspartate [LOLA], or rifaximin). The meta-analysis showed that probiotics significantly reversed MHE (OR = 3.95, p < 0.0001, 95% CI: 2.05 to 7.60) compared with placebo or no treatment. Probiotics also significantly reduced serum ammonia compared with placebo (pooled mean difference -25.94, p = 0.04, 95% CI: -50.21 to -1.66). However when compared to lactulose and LOLA, probiotics did not show a significant difference in reversal of MHE or reduction of serum ammonia levels. Probiotics were more effective in reversal of MHE and reduced serum ammonia levels in patients with MHE compared to placebo or no treatment, but not more effective than lactulose or LOLA.


Escherichia coli LPS-induced LV dysfunction: role of toll-like receptor-4 in the adult heart.
The precise molecular mechanisms responsible for sepsis-induced myocardial dysfunction remain undefined. Toll-like receptor-4 (TLR-4) engages lipopolysaccharide (LPS) and activates signaling pathways leading to the expression of proinflammatory cytokines implicated in myocardial dysfunction. We determined whether TLR-4 was necessary for LPS-induced myocardial dysfunction in vivo. The effects of LPS on left ventricular (LV) function were studied in mice with defective TLR-4 signaling (C3H/HeJ, TLR-4 deficient) and wild-type mice (C3HeB/FeJ). Mice (n = 5/group) were injected with LPS or diluent, and LV function was examined by using two-dimensional echocardiography and conductance catheters. LPS significantly decreased all indexes of LV function in wild-type mice when compared with controls; LV function was not depressed in the LPS-treated TLR-4-deficient mice relative to controls. LPS increased myocardial nitric oxide synthase-2 expression and cGMP only in wild-type mice. This study suggests that TLR-4 mediates the LV dysfunction that occurs in LPS-induced shock. Therefore, TLR-4 might be a therapeutic target for attenuating the effects of LPS on the heart.


Early phase insulin secretion is increased in subjects with normal fasting glucose and metabolic syndrome: a premature feature of beta-cell dysfunction.
Metabolic syndrome (MS) has been mainly related to insulin resistance, but the role of changes in insulin secretion has not been thoroughly investigated. Using an oral glucose tolerance test (OGTT) we studied beta-cell function and insulin sensitivity in subjects with normal fasting glucose with and without MS, and their relationship to fatty liver which was evaluated by abdominal-ultrasonography. In MS early phase insulin secretion, as measured by insulinogenic index (IG(30)), was increased (p<0.05) independently from insulin sensitivity. Furthermore IG(30) was progressively higher as the number of factors needed for the diagnosis of MS increased (p<0.01). Insulin and C-peptide AUC were also increased (p<0.01 and p<0.05, respectively) but, in contrast to IG(30), these differences disappeared when ISI was used as a covariate. After OGTT, 51% of the subjects with MS had altered post-load glucose tolerance compared to 24.9% without MS (p<0.01). In both groups, the altered glucose tolerance was associated with a similar IG(30) reduction. In normo-tolerant subjects with MS the IG(30) was higher (+54.1%, p<0.01), and this elevation occurred irrespective of ISI; however, the beta-cell compensatory capacity for insulin resistance (disposition index) was impaired (p<0.001). Fatty liver was more frequent (p<0.001) and more severe (p<0.01) in MS, and it was significantly related to total AUC-insulin (p<0.001), independently from ISI. These findings indicate that the prevalence of altered tolerance is more frequent in subjects with normal fasting glucose and MS. The hyperinsulinemia might not only be an adaptive response to insulin resistance, but a primary defect of beta-cell function contributing to glucose intolerance.


Species distribution and antifungal susceptibilities of dermatophytes during a one year period at a university hospital in Turkey.
Dermatophyte infections have been considered to be a major public health problem in many parts of the world. The aim of this study was to determine the causative agents of dermatophytoses and their antifungal susceptibilities in a Turkish University Hospital, west of Turkey. A total of 926 patients suspected to have dermatophytic lesions were examined over a period of 1 year (2001-2002). Samples collected from skin, hair and nails were submitted to direct microscopical examination using KOH and Calcofluor white stain, cultured on Sabouraud dextrose agar and Mycosel agar. The prevalence of dermatophytoses was 7.34% (68/926). Trichophyton rubrum was the most frequent dermatophyte isolated (56%) followed by T. mentagrophytes (38%), T. violaceum (1.5%), T. verrucosum (1.5%), Microsporum canis (1.5%) and Epidermophyton floccosum (1.5%). Tinea pedis (47%) was the most common type of infection, followed by tinea unguium (29%), tinea inguinalis (15%), tinea corporis (7.4%) and tinea capitis (1.6%). Secondary, we have tested 68 strains of dermatophytes against four antifungal agents following mainly the National Committee for Clinical Laboratory Standards M38-P standard for filamentous fungi. In general, all antifungals were shown to be highly effective and itraconazole and naftifine appeared more active than ketoconazole and oxiconazole.


Validity and Reliability of the Turkish Version of the Pediatric Assessment Scale for Severe Feeding Problems.
The purpose of this study was to translate the Pediatric assessment scale for severe feeding Problems (PASSFP) into Turkish and investigate its validity and reliability. The study included Turkish translation of the PASSFP, and investigating its reliability and criterion validity in relation with Children's eating behavior questionnaire (CEBQ). Cronbach Alpha reliability of T-PASSFP was 0.79, and of its subscales, i.e. Form A and B, were 0.67, and 0.73, respectively. Test-retest correlation was 0.99 for the scale and Form A, and 0.94 for Form B. There were positive correlations between total scale and Enjoyment of food and Food fussiness subscales of CEBQ. Form A had positive relationships with Food responsiveness, Enjoyment of food, and Food fussiness subscales. Form B had positive correlations with Enjoyment of food and negative correlations with Slowness in eating subscales. The Turkish PASSFP is valid and reliable in evaluating feeding in children with neurodevelopmental disorders. Form A is applied for all children, and Form B is used for partially or totally oral-fed children.


Effects of kefir on coccidial oocysts excretion and performance of dairy goat kids following weaning.
The aim of this study was to investigate effects of kefir, a traditional source of probiotic, on coccidial oocysts excretion and on the performance of dairy goat kids following weaning. Twin kids were randomly allocated to one of two groups at weaning. Kids of the first group received 20 ml of kefir daily for 6 weeks (KEF), while kids in the control group were given a placebo (CON). Individual faecal samples were regularly (n = 18 per kid) taken to quantify the number of coccidial oocysts per gram of faeces (OpG). There were no differences between the groups in terms of body weight development (P > 0.05) and feed consumption. Kids of both groups were not able to consume enough feed to meet their nutrient requirements during the first 3 weeks following weaning. KEF had a lower frequency of OpG positive samples than CON (P = 0.043). Kefir did not affect the maximum oocyst excretion and age of the kids at the highest oocyst excretion (P > 0.05). KEF shed numerically 35% lower coccidial oocysts than the controls, which corresponded to a statistical tendency (P = 0.074) in lowering Log-OpG in comparison to CON. While KEF had a lower frequency of OpG positive samples and tended to shed lower OPG by around one-third, the frequency of diarrhea, level of highest oocyst excretion, and performance of the kids remained unaffected. Therefore, it is concluded that overall effects of kefir do not have a significant impact on sub-clinical infection and performance in weaned kids under relatively high-hygienic farming conditions.


Applications of a rat multiple tissue gene expression data set.
With the sequencing and assembly of the rat genome comes the difficult task of assigning functions to genes. Tissue localization of gene expression gives some information about the potential role of a gene in physiology. Various examples of the utility of multiple tissue gene expression data sets are illustrated here. First, we highlight their use in finding genes that might play an important role in a particular tissue on the basis of exclusive expression in that tissue or coexpression with a gene or genes with known function. Second, we show how this data might be used to explain known phenotypic differences between strains. Third, we show how expression patterns of genes in a genomic interval might identify candidate genes in quantitative trait loci (QTL) mapping studies. Lastly, we show how multiple tissue and species data can help researchers prioritize follow up studies to microarray experiments. All of these applications of multiple tissue gene expression data sets will play a role in functionally annotating the rat genome.


Implementation of formative assessment and its effectiveness in undergraduate medical education: an experience at a Caribbean Medical School.
This article was migrated. The article was marked as recommended. Two types of assessments used in the medical education are summative and formative assessments. Summative assessments evaluate a student's learning progress and typically provide concrete grades or pass/fail decisions. The main purpose of the formative assessments is to provide the feedback and improve the learning behavior of the students. However, it is less known about the impact of the formative assessments on overall student's performance in summative assessments. This study is intended to study the effects after the implementation of formal formative assessments on students overall performance in summative assessments or any changes in the total grade point average in a Caribbean Medical School which is a low resource context. A longitudinal cohort study was conducted among the basic sciences students at AUSOM in May 2017. The study was supported by quantitative data, quantitative and qualitative questionnaires to address the objectives of the study. Data collected and analyzed with Stata (Stata 15). 58, among 67 total students took part in the study. The mean grade point average (GPA) with and without formative assessment was 2.83 (SD±.624745) and 2.29 (SD±.76575) respectively. There was a significant improvement in the overall GPA after the introduction of the formative assessments t (58) = 0.000567, p < .001. There was a significant improvement in the student's academic performance after the implementation of formative assessments. Formative assessments consolidate the learning and reinforce the learning behavior. It is necessary that formative assessments should be incorporated into the regular assessment system for the optimal educational output.


Understanding the MIND phenotype: macrophage/microglia inflammation in neurocognitive disorders related to human immunodeficiency virus infection.
Tissue macrophages play important roles in maintaining homeostasis in most organs of the body including the brain where microglia represent the resident phagocytic cells of this compartment. The possibility of one day harnessing macrophage plasticity to treat or ameliorate disorders including obesity, cancer, organ damage, intestinal disorders, neurodegeneration, and cardiovascular disease in which these cells play a role, is a very exciting prospect. Inflammatory signaling is required for regenerative repair, healing, and pathogen clearance functions. However, when the inflammatory response persists in a chronic fashion over an extended period of time, damage to neurons is followed by neuronal injury and dysfunction. Macrophages in the brain are heterogeneous arising from tissues during embryogenesis, and in the adult, from bone marrow derived monocytes that enter through the blood-brain-barrier. While much of our insight regarding macrophage functional subtypes has been garnered through elegant studies in mice, which are amenable to genetic manipulation, far less is known about such cells in human tissues, and particularly in the brain under normal, disease, or injurious conditions. In this regard, non-human primate models for human immunodeficiency virus have been extremely useful for understanding the contribution of bone marrow-derived monocytes in neurological disease and their interaction and impact on the activation state of resident microglia in the brain. This review will focus on what has been learned from the rhesus macaque models about the types of macrophages present in the brains of animals with encephalitis. In vitro studies, which have used human blood monocytes differentiated into macrophages to address the question of macrophage subsets in HIV infection will be highlighted. Recent insights on macrophage phenotype and persistent inflammation in the brain in HIV-associated neurocognitive disorder from immunohistochemical studies on human autopsy tissue will be examined.


Genetic variations in the CYP17A1 and NT5C2 genes are associated with a reduction in visceral and subcutaneous fat areas in Japanese women.
Visceral fat accumulation has an important role in increasing the morbidity and mortality rates, by increasing the risk of developing several metabolic disorders, such as type 2 diabetes, dyslipidemia and hypertension. New genetic loci that are associated with increased systolic and diastolic blood pressures have been identified by genome-wide association studies in Caucasian populations. This study investigates whether single nucleotide polymorphisms (SNPs) that confer susceptibility to high blood pressure are also associated with visceral fat obesity. We genotyped 1279 Japanese subjects (556 men and 723 women) who underwent computed tomography for measuring the visceral fat area (VFA) and subcutaneous fat area (SFA) at the following SNPs: FGF5 rs16998073, CACNB2 rs11014166, C10orf107 rs1530440, CYP17A1 rs1004467, NT5C2 rs11191548, PLEKHA7 rs381815, ATP2B1 rs2681472 and rs2681492, ARID3B rs6495112, CSK rs1378942, PLCD3 rs12946454, and ZNF652 rs16948048. In an additive model, risk alleles of the CYP17A1 rs1004467 and NT5C2 rs11191548 were found to be significantly associated with reduced SFA (P=0.00011 and 0.0016, respectively). When the analysis was performed separately in men and women, significant associations of rs1004467 (additive model) and rs11191548 (recessive model) with reduced VFA (P=0.0018 and 0.0022, respectively) and SFA (P=0.00039 and 0.00059, respectively) were observed in women, but not in men. Our results suggest that polymorphisms in the CYP17A1 and NT5C2 genes influence a reduction in both visceral and subcutaneous fat mass in Japanese women.


Representational Organization of Novel Task Sets during Proactive Encoding.
Recent multivariate analyses of brain data have boosted our understanding of the organizational principles that shape neural coding. However, most of this progress has focused on perceptual visual regions (Connolly et al., 2012), whereas far less is known about the organization of more abstract, action-oriented representations. In this study, we focused on humans' remarkable ability to turn novel instructions into actions. While previous research shows that instruction encoding is tightly linked to proactive activations in frontoparietal brain regions, little is known about the structure that orchestrates such anticipatory representation. We collected fMRI data while participants (both males and females) followed novel complex verbal rules that varied across control-related variables (integrating within/across stimuli dimensions, response complexity, target category) and reward expectations. Using representational similarity analysis (Kriegeskorte et al., 2008), we explored where in the brain these variables explained the organization of novel task encoding, and whether motivation modulated these representational spaces. Instruction representations in the lateral PFC were structured by the three control-related variables, whereas intraparietal sulcus encoded response complexity and the fusiform gyrus and precuneus organized its activity according to the relevant stimulus category. Reward exerted a general effect, increasing the representational similarity among different instructions, which was robustly correlated with behavioral improvements. Overall, our results highlight the flexibility of proactive task encoding, governed by distinct representational organizations in specific brain regions. They also stress the variability of motivation-control interactions, which appear to be highly dependent on task attributes, such as complexity or novelty.SIGNIFICANCE STATEMENT In comparison with other primates, humans display a remarkable success in novel task contexts thanks to our ability to transform instructions into effective actions. This skill is associated with proactive task-set reconfigurations in frontoparietal cortices. It remains yet unknown, however, how the brain encodes in anticipation the flexible, rich repertoire of novel tasks that we can achieve. Here we explored cognitive control and motivation-related variables that might orchestrate the representational space for novel instructions. Our results showed that different dimensions become relevant for task prospective encoding, depending on the brain region, and that the lateral PFC simultaneously organized task representations following different control-related variables. Motivation exerted a general modulation upon this process, diminishing rather than increasing distances among instruction representations.


In vitro antifungal susceptibility of Malassezia furfur from bloodstream infections.
Fungaemia caused by Malassezia spp. in hospitalized patients requires prompt and appropriate therapy, but standard methods for the definition of the in vitro antifungal susceptibility have not been established yet. In this study, the in vitro susceptibility of Malassezia furfur from bloodstream infections (BSIs) to amphotericin B (AMB), fluconazole (FLC), itraconazole (ITC), posaconazole (POS) and voriconazole (VRC) was assessed using the broth microdilution (BMD) method of the Clinical and Laboratory Standards Institute (CLSI) with different media such as modified Sabouraud dextrose broth (SDB), RPMI and Christensen's urea broth (CUB). Optimal broth media that allow sufficient growth of M. furfur, and produce reliable and reproducible MICs using the CLSI BMD protocol were assessed. Thirty-six M. furfur isolates collected from BSIs of patients before and during AMB therapy, and receiving FLC prophylaxis, were tested. A good growth of M. furfur was observed in RPMI, CUB and SDB at 32 °C for 48 and 72 h. No statistically significant differences were detected between the MIC values registered after 48 and 72 h incubation. ITC, POS and VRC displayed lower MICs than FLC and AMB. These last two antifungal drugs showed higher and lower MICs, respectively, when the isolates were tested in SDB. SDB is the only medium in which it is possible to detect isolates with high FLC MICs in patients receiving FLC prophylaxis. A large number of isolates showed high AMB MIC values regardless of the media used. In conclusion, SDB might be suitable to determine triazole susceptibility. However, the media, the drug formulation or the breakpoints herein applied might not be useful for assessing the AMB susceptibility of M. furfur from BSIs.


Gastric Carcinoid in a Young Woman with Systemic Lupus Erythematosus and Atrophic Autoimmune Gastritis.
Gastric carcinoid is a rare tumour that is associated with chronic atrophic gastritis in the majority of cases. It usually occurs in the 6th or 7th decade of life and is rarely diagnosed in patients under 30 years of age. We describe a case of multiple gastric carcinoids in a 23-year-old woman with systemic lupus erythematosus and atrophic autoimmune gastritis--an association that has not been reported previously. The combination of atrophic autoimmune gastritis and gastric carcinoid with other autoimmune disorders has rarely been reported in the English medical literature. The fact that it mostly concerns (relatively) young patients may suggest a potential causative relation between those autoimmune disorders and the early development of atrophic gastritis with hypergastrinaemia, which subsequently leads to the occurrence of gastric carcinoid tumours at a young age.


[Results of the Program for the Rational Use of Antimicrobials in a Mexican hospital, 2013-2018Resultados de um programa para o uso racional de antimicrobianos num hospital no México, 2013-2018].
Describe the results of the Program for the Rational Use of Antimicrobials at Mexico's Juárez Hospital. An observational, cross-sectional, retrospective, descriptive study was designed. For the consumption of antimicrobial agents, data from January 2013 to December 2018 were analyzed by calculating the defined daily dose (DDD). For the cost analysis, a traditional costing calculation was used. For the group of carbapenem agents, there was a sizeable reduction in the consumption of imipenem / cilastatin: the DDD declined from 2.3 in 2013 to 0.7 in 2018, a decrease of 70%. By contrast, for the other two agents, increases were observed. The consumption of meropenem increased by 2% (from 2.4 in 2013 to 2.5 in 2018); the consumption of ertapenem increased by 75% (from 1 in 2013 to 1.8 in 2018). The total expenditure on antimicrobial agents was USD 930 556.46 during 2013, compared to USD 856 079.10 during 2018, representing a difference of 8% or USD 74 905.61 of the total expenditure. Programs for the rational use of antimicrobials need to be evaluated continuously, by monitoring both consumption of agents by patients and related institutional expenditures.


Genetic correction of PSA values using sequence variants associated with PSA levels.
Measuring serum levels of the prostate-specific antigen (PSA) is the most common screening method for prostate cancer. However, PSA levels are affected by a number of factors apart from neoplasia. Notably, around 40% of the variability of PSA levels in the general population is accounted for by inherited factors, suggesting that it may be possible to improve both sensitivity and specificity by adjusting test results for genetic effects. To search for sequence variants that associate with PSA levels, we performed a genome-wide association study and follow-up analysis using PSA information from 15,757 Icelandic and 454 British men not diagnosed with prostate cancer. Overall, we detected a genome-wide significant association between PSA levels and single-nucleotide polymorphisms (SNPs) at six loci: 5p15.33 (rs2736098), 10q11 (rs10993994), 10q26 (rs10788160), 12q24 (rs11067228), 17q12 (rs4430796), and 19q13.33 [rs17632542 (KLK3: I179T)], each with P(combined) <3 × 10(-10). Among 3834 men who underwent a biopsy of the prostate, the 10q26, 12q24, and 19q13.33 alleles that associate with high PSA levels are associated with higher probability of a negative biopsy (odds ratio between 1.15 and 1.27). Assessment of association between the six loci and prostate cancer risk in 5325 cases and 41,417 controls from Iceland, the Netherlands, Spain, Romania, and the United States showed that the SNPs at 10q26 and 12q24 were exclusively associated with PSA levels, whereas the other four loci also were associated with prostate cancer risk. We propose that a personalized PSA cutoff value, based on genotype, should be used when deciding to perform a prostate biopsy.


Erythropoietin as a neuroprotective agent in traumatic brain injury Review.
In the United States, TBI remains a major cause of morbidity and mortality in children and young adults. A total of 1.5 million Americans experience head trauma every year, and the yearly economic cost of this exceeds $56 billion. The magnitude of this problem has generated a great deal of interest in elucidating the complex molecular mechanism underlying cell death and dysfunction after TBI and in the development of neuroprotective agents that will reduce morbidity and mortality. A review of recent literature on EPO, TBI, and apoptosis is conducted with analysis of pathophysiologic mechanisms of TBI. In addition, animal experiments and clinical trials pertaining to mechanisms of cell death in TBI and EPO as a neuroprotective agent are reviewed. The literature and evidence for EPO as a potent inhibitor of apoptosis and promising therapeutic agent in a variety of neurological insults, including trauma, are mounting. With the recent interest in clinical trials of EPO in human stroke, it is both timely and prudent to consider the use of this pharmaceutical avenue in TBI in man.


Tests of muscle power output: the role of body size.
The effect of body size on the output of the tests of directly assessed muscle power has been mainly ignored in the applied research. We hypothesized that the muscle power output would reveal a positive relationship with body size closely in line with the theoretical predictions, as well as that the strength of the studied relationship could justify standardized normalization procedures applied in routine testing. Male physical education students (n = 111) were evaluated in 10 standard tests of direct assessment of muscle power output. A standard allometric relationship P = A SB was applied to assess the relationship between the tested power output P and selected indices of body size S ( B = allometric exponent; A = parameter). The correlation coefficients obtained between the tested power output and body size ranged within 0.21 - 0.56 for body mass and 0.10 - 0.49 for body height. The mean (SD) values of the allometric exponents B obtained with respect to body mass and body height were 0.55 (0.15) and 1.15 (0.62), respectively. This relationship proved to be strong enough to merit applying a standard normalization. The normalization method should be based on body mass as a preferred index of body size, while the allometric exponent could correspond to the theoretically predicted one (i.e., B = 0.67).


Sequential non-invasive mechanical ventilation following short-term invasive mechanical ventilation in COPD induced hypercapnic respiratory failure.
To estimate the feasibility and the efficacy of early extubation and sequential non-invasive mechanical ventilation (MV) in chronic obstructive pulmonary disease (COPD) with exacerbated hypercapnic respiratory failure. Twenty-two intubated COPD patients with severe hypercapnic respiratory failure due to pulmonary infection (pneumonia or purulent bronchitis) were involved in the study. At the time of pulmonary infection control window (PIC window) appeared, when pulmonary infection had been significantly controlled (resolution of fever and decrease in purulent sputum, radiographic infiltrations, and leukocytosis) after the antibiotic and the comprehensive therapy, the early extubation was conducted and followed by non-invasive MV via facial mask immediately in 11 cases (study group). Other 11 COPD cases with similar clinical characteristics who continuously received invasive MV after PIC window were recruited as control group. All patients had similar clinical characteristics and gas exchange before treatment, as well as the initiating time and all indices at the time of the PIC window. For study group and control group, the duration of invasive MV was (7.1 +/- 2.9) vs (23.0 +/- 14.0) days, respectively, P < 0.01. The total duration of ventilatory support was (13 +/- 7) vs (23 +/- 14) days, respectively, P < 0.05. The incidence of ventilator associated pneumonia (VAP) were 0/11 vs 6/11, respectively, P < 0.01. The duration of intensive care unit (ICU) stay was (13 +/- 7) vs (26 +/- 14) days, respectively, P < 0.05. In COPD patients requiring intubation and MV for pulmonary infection and hypercapnic respiratory failure, early extubation followed by non-invasive MV initiated at the point of PIC window significantly decreases the invasive and total durations of ventilatory support, the risk of VAP, and the duration of ICU stay.


Joint contact force and movement deceleration among badminton forward lunges: a musculoskeletal modelling study.
Joint contact force is the actual force applied on the articular surface that could predict performance and injuries, but rarely reported for badminton sport. The study sought to calculate lower limb joint contact force and decelerative kinematics for badminton forward lunges. Fifteen badminton players performed backhand and forehand forward lunges in random order. The kinematic and kinetic data were input to scale a musculoskeletal model and solve inverse dynamics in the simulations. Outcome variables were compared between lunge conditions using repeated measures MANOVA. Forehand lunge produced higher compressional ankle contact force (p = 0.040, partial η2 = 0.14), faster touchdown hip abduction (p = 0.031, partial η2 = 0.16), and larger horizontal deceleration of the mass centre (p = 0.016, partial η2 = 0.19) and torso (p = 0.031, partial η2 = 0.16) compared to backhand lunge. Despite the statistical significance, we found that the increments of joint loading in forehand lunge were small (<5%) with limited effect size and could be attributed to the larger movement deceleration during braking. These force changes could possess performance merits. However, its linkage to injury risk is unclear and warrants further investigation.


[Pathogenic role of free-radical damage in radiation-induced atherosclerosis].
According clinico-epidemiological and experimental data there are positive correlation between irradiation and risk of atherosclerosis development. Taking into account that primary physico-chemical effects of ionising radiation influences on organism were connected with biologically active free-radical and their products formation, its pathogenic role under radiation-induced atherosclerotic injures of cardiovascular system is postulate. The development of atherosclerosis includes some consecutive stages beginning with free-radical activation in arterial tissues and blood. The free radical and their reactive species involves physico-chemical changes in plasmatic membranes and lipoproteins, damages of genome, cytotoxicity (apoptosis or reproductive death) and opposite effect of cytoprotection. The activation of intrinsic recovery/repair mechanisms after above types of injury has been associated with the induction of changes in amount of B,E- receptors and lipoproteins modification, the increase of the complexes lipoprotein-antibody. The subsequent events demonstrate the development of dyslipoproteinemias, the functional and morphological injures, appearance of "foam cells" and atherosclerotic damages of arterial wall.


Importance of Surveillance of New Delhi Metallo-Beta-Lactamase Klebsiella pneumoniae: Molecular Characterization and Clonality of Strains Isolated in the Lazio Region, Italy.
New Delhi metallo-β-lactamase producing Klebsiella pneumoniae (NDM-Kpn) strains have been causing healthcare-associated infections worldwide. The aim of this study was to describe the molecular mechanisms of antimicrobial resistance and to analyze the clonality of NDM-Kpn isolates collected between January 2019 and June 2020 from patients admitted to hospitals from the Lazio region, Italy. We performed a retrospective cohort study. Whole-genome sequencing (WGS) was performed on all NDM-Kpn strains; clonality and genetic relationships were further investigated. During the surveillance period, 17 NDM-Kpn isolates were obtained from 17 patients admitted to seven different hospitals. Eight different sequence types (STs) were detected: ST147 (n = 4), ST383 (n = 4), ST15 (n = 3), ST11 (n = 2), ST17 (n = 1), ST29 (n = 1), ST307 (n = 1) and the newly identified ST4853 (n = 1). Genetic relationships were further investigated by the WGS-based core genome MLST (cgMLST) scheme, and 5 cluster types (CTs) were identified. Whereas a substantial overall heterogeneity among isolates was detected (8 different STs were identified out of 17 isolates), the strains within each cluster showed a very high level of genome similarity. Our study highlights the key role of surveillance, which allowed taking a picture of a part of the NDM-Kpn strains circulating in Italy, adding further insight into their molecular features.


Non-invasive measurement of limb and digit blood flow.
There are many clinical applications for non-invasive measurements of limb and digit blood flow, but often plethysmographs are inconvenient to use. Most experimental work has been carried out on patients with vascular disease. The variation of blood flow with various environmental and physiological factors has been investigated. Little information is available on the effects of injury or surgical trauma on blood flow in limbs. Plethysmographic methods measure arterial flow or pulse volume by several techniques including volumetric displacement, electrical impedance, gravimetry and the mercury in rubber strain gauge. Calorimetric, Doppler and isotope clearance techniques have also been applied to the measurement of blood flow in digits. None of these methods fulfils all the criteria for the requirements of an ideal device and some are too complicated, uncomfortable or cumbersome for widespread use. The results from different techniques are compared and the reasons for variability are discussed. Possible mechanisms for the effects of trauma on limb blood flow are suggested. Experimental comparisons of different plethysmographs are described and the requirements for future development of these devices are defined.


Studies on the phospholipases of rat intestinal mucosa.
1. Subcellular distribution and characteristics of different phospholipases of rat intestinal mucosa were studied. 2. The presence of free fatty acid was necessary for the maximal hydrolysis of lecithin (phosphatidylcholine), but there was no accumulation of lysolecithin (1 or 2-acylglycerophosphorylcholine);lysolecithin accumulated when the reaction was carried out in the presence of sodium deoxycholate and at or above pH8.0. 3. The fatty acid-activated phospholipase B as well as lysolecithinase showed optimum activity at pH6.5, whereas for the phospholipase A it was about pH8.6. 4. The bulk of the phospholipase A was present in the microsomal fraction, whereas the phospholipase B and lysolecithinase activities were distributed between the microsomal and soluble fractions of the mucosal homogenate. 5. Phospholipase A was equally distributed between the brush border and brush-border-free particulate fraction, with the brush border having highest specific activity, whereas the other two activities were distributed between the brush-border-free particulate and soluble fractions. 6. Various treatments showed marked differences between the phospholipase A and phospholipase B activities, but not between phospholipase B and lysolecithinase activities. 7. By using (beta[1-(14)C]-oleoyl) lecithin it was shown that the mucosal phospholipase A was specific for the beta-ester linkage of the lecithin molecule.


Bio-NCs--the marriage of ultrasmall metal nanoclusters with biomolecules.
Ultrasmall metal nanoclusters (NCs) have attracted increasing attention due to their fascinating physicochemical properties. Today, functional metal NCs are finding growing acceptance in biomedical applications. To achieve a better performance in biomedical applications, metal NCs can be interfaced with biomolecules, such as proteins, peptides, and DNA, to form a new class of biomolecule-NC composites (or bio-NCs in short), which typically show synergistic or novel physicochemical and physiological properties. This feature article focuses on the recent studies emerging at the interface of metal NCs and biomolecules, where the interactions could impart unique physicochemical properties to the metal NCs, as well as mutually regulate biological functions of the bio-NCs. In this article, we first provide a broad overview of key concepts and developments in the novel biomolecule-directed synthesis of metal NCs. A special focus is placed on the key roles of biomolecules in metal NC synthesis. In the second part, we describe how the encapsulated metal NCs affect the structure and function of biomolecules. Followed by that, we discuss several unique synergistic effects observed in the bio-NCs, and illustrate them with examples highlighting their potential biomedical applications. Continued interdisciplinary efforts are required to build up in-depth knowledge about the interfacial chemistry and biology of bio-NCs, which could further pave their ways toward biomedical applications.


Genetic changes induced by the pesticide Ridomol in the soybeans sprouted from the seeds of different ages.
An objective of presented study was to investigate the effect of the genetically active xenobiotics Ridomili on the genetic apparatus of the plants sprouted from the soybean seeds of different ages. The experiments were conducted on the soybean (Glycine max) genetic line L65-1237. The studies were performed on the 1-, 2- or 3- year old seeds of the heterozygous Y(11)y(11) plants. The seeds of different ages were exposed to the pesticide Ridomili diluted in distilled water in different concentrations--0.02%, 0.04%, 0.06%, 0.08% and 0.1%. Three phenotype classes--green (Y(11)Y(11)), light-green (Y(11)y(11)) and yellow (y(11)y(11)) in proportion 1:2:1. All the concentrations of the substance caused mitotic crossingovers in the plants sprouted from the 3-year-old seeds. The higher doses of Ridomil (0.06-0.1%) caused induction of reversions much more frequently than in the case of 1- and 2-year-old seeds. The tendency to the dose-dependant effect was also observed. Embryonic cells of 3-year-old seeds were found to be highly sensitive. The levels of direct mutations were rather common there.


Human Müller cells express VEGF183, a novel spliced variant of vascular endothelial growth factor.
Vascular endothelial growth factor (VEGF) is a potent angiogenic factor expressed as multiple RNA transcripts due to alternative splicing. During an investigation of the expression of VEGF mRNA in human Müller cells cultured under hypoxic conditions, a cDNA species was isolated whose size was incompatible with known VEGF transcripts. This study was performed to determine the nucleotide sequence of the candidate VEGF species and examine the effects of hypoxia on its expression. Cultured human Müller cells were exposed to normoxic (20% O2, 5% CO2, 75% N2) or hypoxic (2% O2, 5% CO2, 93% N2) conditions at 37 degrees C for 4 hours and processed for reverse transcription-polymerase chain reaction (RT-PCR), molecular cloning, Southern hybridization, nucleotide sequencing, semiquantitative RT-PCR, and ribonuclease protection assay. The nucleotide sequence of the novel VEGF species isolated from human Müller cells had a short exon 6-encoded sequence without 18-bp nucleotides immediately upstream of the exon 7-encoded sequence in VEGF189. The 18-bp deletion (corresponding to the six amino acids Tyr-Lys-Ser-Trp-Ser-Val) was compatible with a polypeptide containing 183 amino acids (VEGF183). Although VEGF183 mRNA was found in all tissues studied, its expression seemed to be higher than that of VEGF 189 in the brain and spleen; lower in the kidney, retina, skeletal muscle, and liver; and at similar level in the heart. Exposure to hypoxic conditions for 4 hours promoted increased levels of VEGF mRNA including that of VEGF183. The expression of the novel isoform VEGF 183 in human Müller cells, its variable tissue expression, and its modulation by hypoxia may provide another pathway for VEGF induction of angiogenesis in the retina.


Patterns of astragalar fibular facet orientation in extant and fossil primates and their evolutionary implications.
A laterally sloping fibular facet of the astragalus (=talus) has been proposed as one of few osteological synapomorphies of strepsirrhine primates, but the feature has never been comprehensively quantified. We describe a method for calculating fibular facet orientation on digital models of astragali as the angle between the planes of the fibular facet and the lateral tibial facet. We calculated this value in a sample that includes all major extant primate clades, a diversity of Paleogene primates, and nonprimate euarchontans (n = 304). Results show that previous characterization of a divide between extant haplorhines and strepsirrhines is accurate, with little overlap even when individual data points are considered. Fibular facet orientation is conserved in extant strepsirrhines despite major differences in locomotion and body size, while extant anthropoids are more variable (e.g., low values for catarrhines relative to non-callitrichine platyrrhines). Euprimate outgroups exhibit a mosaic of character states with Cynocephalus having a more obtuse strepsirrhine-like facet and sampled treeshrews and plesiadapiforms having more acute haplorhine-like facets. Surprisingly, the earliest species of the adapiform Cantius have steep haplorhine-like facets as well. We used a Bayesian approach to reconstruct the evolution of fibular facet orientation as a continuous character across a supertree of living and extinct primates. Mean estimates for crown Primatomorpha (97.9°), Primates (99.5°), Haplorhini (98.7°), and Strepsirrhini (108.2°) support the hypothesis that the strepsirrhine condition is derived, while lower values for crown Anthropoidea (92.8°) and Catarrhini (88.9°) are derived in the opposite direction.


From In Situ to satellite observations of pelagic Sargassum distribution and aggregation in the Tropical North Atlantic Ocean.
The present study reports on observations carried out in the Tropical North Atlantic in summer and autumn 2017, documenting Sargassum aggregations using both ship-deck observations and satellite sensor observations at three resolutions (MSI-10 m, OLCI-300 m, VIIRS-750 m and MODIS-1 km). Both datasets reported that in summer, Sargassum aggregations were mainly observed off Brazil and near the Caribbean Islands, while they accumulated near the African coast in autumn. Based on in situ observations, we propose a five-class typology allowing standardisation of the description of in situ Sargassum raft shapes and sizes. The most commonly observed Sargassum raft type was windrows, but large rafts composed of a quasi-circular patch hundreds of meters wide were also observed. Satellite imagery showed that these rafts formed larger Sargassum aggregations over a wide range of scales, with smaller aggregations (of tens of m2 area) nested within larger ones (of hundreds of km2). Match-ups between different satellite sensors and in situ observations were limited for this dataset, mainly because of high cloud cover during the periods of observation. Nevertheless, comparisons between the two datasets showed that satellite sensors successfully detected Sargassum abundance and aggregation patterns consistent with in situ observations. MODIS and VIIRS sensors were better suited to describing the Sargassum aggregation distribution and dynamics at Atlantic scale, while the new sensors, OLCI and MSI, proved their ability to detect Sargassum aggregations and to describe their (sub-) mesoscale nested structure. The high variability in raft shape, size, thickness, depth and biomass density observed in situ means that caution is called for when using satellite maps of Sargassum distribution and biomass estimation. Improvements would require additional in situ and airborne observations or very high-resolution satellite imagery.


Background luminance effects on pupil size associated with emotion and saccade preparation.
Pupil dilation is consistently evoked by affective and cognitive processing, and this dilation can result from sympathetic activation or parasympathetic inhibition. The relative contributions of the sympathetic and parasympathetic systems on the pupillary response induced by emotion and cognition may be different. Sympathetic and parasympathetic activity is regulated by global luminance level. Higher luminance levels lead to greater activation of the parasympathetic system while lower luminance levels lead to greater activation of the sympathetic system. To understand the contributions of the sympathetic and parasympathetic nervous systems to pupillary responses associated with emotion and saccade preparation, emotional auditory stimuli were presented following the fixation cue whose color indicated instruction to perform a pro- or anti-saccade while varying the background luminance level. Pupil dilation was evoked by emotional auditory stimuli and modulated by arousal level. More importantly, greater pupil dilation was observed with a dark background, compared to a bright background. In contrast, pupil dilation responses associated with saccade preparation were larger with the bright background than the dark background. Together, these results suggest that arousal-induced pupil dilation was mainly mediated by sympathetic activation, but pupil dilation related to saccade preparation was primarily mediated by parasympathetic inhibition.


UV crosslinked poly(acrylic acid): a simple method to bio-functionalize electrolyte-gated OFET biosensors.
A simple and time-saving wet method to endow the surface of organic semiconductor films with carboxyl functional groups is presented. A thin layer of poly(acrylic acid) (pAA) is spin-coated directly on the electronic channel of an electrolyte-gated organic FET (EGOFET) device and cross-linked by UV exposure without the need for any photo-initiator. The carboxyl functionalities are used to anchor phospholipid bilayers through the reaction with the amino-groups of phosphatidyl-ethanolamine (PE). By loading the membranes with phospholipids carrying specific functionalities, such a platform can be easily implemented with recognition elements. Here the case of biotinylated phospholipids that allow selective streptavidin electronic detection is described. The surface morphology and chemical composition are monitored using SEM and XPS, respectively, during the whole process of bio-functionalization. The electronic and sensing performance level of the EGOFET biosensing platform is also evaluated. Selective analyte (streptavidin) detection in the low pM range is achieved, this being orders of magnitude lower than the performance level obtained by the well assessed surface plasmon resonance assay reaching the nM level, at most.


Assigning protein function from domain-function associations using DomFun.
Protein function prediction remains a key challenge. Domain composition affects protein function. Here we present DomFun, a Ruby gem that uses associations between protein domains and functions, calculated using multiple indices based on tripartite network analysis. These domain-function associations are combined at the protein level, to generate protein-function predictions. We analysed 16 tripartite networks connecting homologous superfamily and FunFam domains from CATH-Gene3D with functional annotations from the three Gene Ontology (GO) sub-ontologies, KEGG, and Reactome. We validated the results using the CAFA 3 benchmark platform for GO annotation, finding that out of the multiple association metrics and domain datasets tested, Simpson index for FunFam domain-function associations combined with Stouffer's method leads to the best performance in almost all scenarios. We also found that using FunFams led to better performance than superfamilies, and better results were found for GO molecular function compared to GO biological process terms. DomFun performed as well as the highest-performing method in certain CAFA 3 evaluation procedures in terms of [Formula: see text] and [Formula: see text] We also implemented our own benchmark procedure, Pathway Prediction Performance (PPP), which can be used to validate function prediction for additional annotations sources, such as KEGG and Reactome. Using PPP, we found similar results to those found with CAFA 3 for GO, moreover we found good performance for the other annotation sources. As with CAFA 3, Simpson index with Stouffer's method led to the top performance in almost all scenarios. DomFun shows competitive performance with other methods evaluated in CAFA 3 when predicting proteins function with GO, although results vary depending on the evaluation procedure. Through our own benchmark procedure, PPP, we have shown it can also make accurate predictions for KEGG and Reactome. It performs best when using FunFams, combining Simpson index derived domain-function associations using Stouffer's method. The tool has been implemented so that it can be easily adapted to incorporate other protein features, such as domain data from other sources, amino acid k-mers and motifs. The DomFun Ruby gem is available from https://rubygems.org/gems/DomFun . Code maintained at https://github.com/ElenaRojano/DomFun . Validation procedure scripts can be found at https://github.com/ElenaRojano/DomFun_project .


RV144 HIV-1 vaccination impacts post-infection antibody responses.
The RV144 vaccine efficacy clinical trial showed a reduction in HIV-1 infections by 31%. Vaccine efficacy was associated with stronger binding antibody responses to the HIV Envelope (Env) V1V2 region, with decreased efficacy as responses wane. High levels of Ab-dependent cellular cytotoxicity (ADCC) together with low plasma levels of Env-specific IgA also correlated with decreased infection risk. We investigated whether B cell priming from RV144 vaccination impacted functional antibody responses to HIV-1 following infection. Antibody responses were assessed in 37 vaccine and 63 placebo recipients at 6, 12, and 36 months following HIV diagnosis. The magnitude, specificity, dynamics, subclass recognition and distribution of the binding antibody response following infection were different in RV144 vaccine recipients compared to placebo recipients. Vaccine recipients demonstrated increased IgG1 binding specifically to V1V2, as well as increased IgG2 and IgG4 but decreased IgG3 to HIV-1 Env. No difference in IgA binding to HIV-1 Env was detected between the vaccine and placebo recipients following infection. RV144 vaccination limited the development of broadly neutralizing antibodies post-infection, but enhanced Fc-mediated effector functions indicating B cell priming by RV144 vaccination impacted downstream antibody function. However, these functional responses were not associated with clinical markers of disease progression. These data reveal that RV144 vaccination primed B cells towards specific binding and functional antibody responses following HIV-1 infection.