Molecular phylogenetic analysis and seasonal dynamics of Eimeria species infecting broilers of Kashmir, India.

Globally, the poultry industry is seriously threatened by coccidiosis caused by various species of Eimeria. This protozoan parasite inhabits the epithelial lining of the gastrointestinal tract of poultry globally and can cause serious clinical disease. The present study was carried out on poultry farms located in various regions of Kashmir, India, to investigate the prevalence and phylogenetic relationships of Eimeria species affecting broiler chickens. Over a period of one year, fecal samples were collected from 60 poultry farms in Kashmir and morphological and molecular techniques were employed for Eimeria species identification. Results revealed a high prevalence of coccidiosis, with 58.3% (35/60) of farms positive for Eimeria. The most prevalent species were E. tenella (31/35, 88.6%) followed by E. acervulina (25/35, 71.4%), E. maxima (19/35, 54.3%), E. mitis (18/35, 51.4%), and E. necatrix (9/35, 25.7%). Seasonal variation in prevalence was also observed, with the highest rates in autumn (86.7%) and summer (66.7%). Additionally, younger birds (3-4 weeks) exhibited higher infection rates (85.7%) compared to older birds (57.9%) (5-6 weeks). Mixed infection was found in 94.2% (33/35) of positive farms. Phylogenetic analysis using ITS1 sequences confirmed species clustering and revealed evolutionary relationships among Eimeria species. E. tenella and E. necatrix formed a distinct clade, while E. acervulina formed another. The study underscores the importance of molecular techniques in accurate species identification and provides valuable insights into the epidemiology of coccidiosis in poultry in Kashmir. Effective control strategies, including vaccination and improved management practices, are necessary to mitigate the economic losses associated with this widespread poultry disease.

Home Sleep Apnea Testing for Obstructive Sleep Apnea.

Obstructive Sleep Apnea (OSA) is a major public health problem affecting almost one billion individuals worldwide. Ninety percent of patients with OSA are still undiagnosed. Although an attended polysomnography (PSG) testing is the gold standard to diagnose OSA, it is time-consuming and is associated with higher costs. The Home Sleep Apnea Testing (HSAT) is now available to diagnose OSA. Understanding the indications and limitations of HSAT is important to avoid misdiagnosis and improve patient outcomes.

Neuroinflammation with increased glymphatic flow in a murine model of decompression sickness.

This project investigated glial-based lymphatic (glymphatic) function and its role in a murine model of decompression sickness (DCS). DCS pathophysiology is traditionally viewed as being related to gas bubble formation from insoluble gas on decompression. However, a body of work implicates a role for a subset of inflammatory extracellular vesicles, 0.1 to 1 µm microparticles (MPs) that are elevated in human and rodent models in response to high gas pressure and rise further after decompression. Herein, we describe immunohistochemical and Western blot evidence showing that following high air pressure exposure, there are elevations of astrocyte NF-κB and microglial-ionized calcium-binding adaptor protein-1 (IBA-1) along with fluorescence contrast and MRI findings of an increase in glymphatic flow. Concomitant elevations of central nervous system-derived MPs coexpressing thrombospondin-1 (TSP) drain to deep cervical nodes and then to blood where they cause neutrophil activation. A new set of blood-borne MPs are generated that express filamentous actin at the surface that exacerbate neutrophil activation. Blood-brain barrier integrity is disrupted due to activated neutrophil sequestration that causes further astrocyte and microglial perturbation. When postdecompression node or blood MPs are injected into naïve mice, the same spectrum of abnormalities occur and they are blocked with coadministration of antibody to TSP. We conclude that high pressure/decompression causes neuroinflammation with an increased glymphatic flow. The resulting systemic liberation of TSP-expressing MPs sustains the neuroinflammatory cycle lasting for days.NEW & NOTEWORTHY A murine model of central nervous system (CNS) decompression sickness demonstrates that high gas pressure activates astrocytes and microglia triggering inflammatory microparticle (MP) production. Thrombospondin-expressing MPs are released from the CNS via enhanced glymphatic flow to the systemic circulation where they activate neutrophils. Secondary production of neutrophil-derived MPs causes further cell activation and neutrophil adherence to the brain microvasculature establishing a feed-forward neuroinflammatory cycle.

Elevations of Extracellular Vesicles and Inflammatory Biomarkers in Closed Circuit SCUBA Divers.

Blood-borne extracellular vesicles and inflammatory mediators were evaluated in divers using a closed circuit rebreathing apparatus and custom-mixed gases to diminish some diving risks. "Deep" divers (n = 8) dove once to mean (±SD) 102.5 ± 1.2 m of sea water (msw) for 167.3 ± 11.5 min. "Shallow" divers (n = 6) dove 3 times on day 1, and then repetitively over 7 days to 16.4 ± 3.7 msw, for 49.9 ± 11.9 min. There were statistically significant elevations of microparticles (MPs) in deep divers (day 1) and shallow divers at day 7 that expressed proteins specific to microglia, neutrophils, platelets, and endothelial cells, as well as thrombospondin (TSP)-1 and filamentous (F-) actin. Intra-MP IL-1ß increased by 7.5-fold (p < 0.001) after day 1 and 41-fold (p = 0.003) at day 7. Intra-MP nitric oxide synthase-2 (NOS2) increased 17-fold (p < 0.001) after day 1 and 19-fold (p = 0.002) at day 7. Plasma gelsolin (pGSN) levels decreased by 73% (p < 0.001) in deep divers (day 1) and 37% in shallow divers by day 7. Plasma samples containing exosomes and other lipophilic particles increased from 186% to 490% among the divers but contained no IL-1ß or NOS2. We conclude that diving triggers inflammatory events, even when controlling for hyperoxia, and many are not proportional to the depth of diving.

Efficacy of serum anti-mullerian hormone (AMH) levels for prediction of polycystic ovary syndrome (PCOS) and its association with clinical, biochemical and hormonal parameters.

Anti-mullerian hormone (AMH) has been proposed to add significance to diagnosis of PCOS in case of ambiguity. However, variable cutoffs of AHM among PCOS women have been reported. Using case-control design, this study investigated the diagnostic threshold of serum AMH levels among age matched 113 PCOS and 75 normo-ovulatory women and its correlation with clinical, hormonal and ultrasonographic parameters.PCOS was defined as per Rotterdam criteria 2003. Results depicted the mean serum AMH level to be significantly higher in PCOS group (7.84 ± 3.67vs. 3.23 ± 1.56 ng/mL) than controls. The AMH levels were positively(p = 0.001) associated with ovarian volume (r = 0.521) as well as number of ovarian follicles(r = 0.461). Further, serum AMH levels showed a positive correlation with luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio (r = 0.206, p = 0.02), but no correlation significant with age, BMI,FG score and testosterone levels. As per receiver operating characteristic (ROC) curve, cut-off was worked out to be 3.76 ng/ml with 86.7% sensitivity and 62.7% specificity. The mean level of AMH were highest among PCOS women with phenotype A (12.67 ± 3.46 ng/ml) with least among PCOS women displaying phenotype B(7.28 ± 1.60 ng/ml) where there is absence of PCOM. In conclusion, serum AMH levels are highly predictive of PCOM and high LH/FSH ratio among PCOS women and may be a potent diagnostic marker of ovarian dysfunction either alone or in conjunction with other tools. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-022-01058-4.

Functional foods and their impact on health.

Functional foods play an important role in maintaining a healthy lifestyle and reducing the risk factors of various diseases. Most foods have a functional element which is responsible for improving the healthy state. All food substances such as fruits, vegetables, cereals, meat, fish, dairy contain functional ingredients. A wide range of naturally occurring substances from plant and animal sources having active components which play a role in physiological actions deserve attention for their optimal use in maintaining health. The market for functional food is keep on expanding, and the global market is projected to reach a value of at least 91 billion USD soon. Overwhelming evidence from preclinical (in vitro and in vivo) and clinical studies have shown that intake of functional foods could have an impact on the prevention of chronic diseases, especially cancer, cardiovascular diseases, gastrointestinal tract disorders and neurological diseases. Extensive research needs to be done to determine the potential health benefits for the proper application of these foods to improve health state and combat chronic disease progression. The aim of this review is to conduct a thorough literature survey, to understand the various classification of functional foods and their health benefits.

Influence of medical trainee sleep pattern (chronotype) on burn-out and satisfaction with work schedules: a multicentre observational study.

BACKGROUND: Medical trainees' work schedule is designed to cover duties without consideration of differences in circadian rhythms during a 24-hour period (chronotype). OBJECTIVE: To explore chronotype variation among medical trainees and understand its association with burn-out and schedule satisfaction. METHODS: In a multicentre observational study, we conducted two surveys between 1 October 2018 and 1 April 2019. Trainees from nine centres across the USA participated. We measured burn-out using Maslach Burnout Inventory (MBI), and trainee chronotype using the Morningness-Eveningness Questionnaire (MEQ). RESULTS: 324 (32%) out of 1012 responded to our survey. Participants were 51% female and had a mean age of 30.8 years. Most participants had an intermediate MEQ type (65%). A large proportion of participants had burn-out on at least one of three tested MBI scales (62%); 5% of participants had burn-out on all three MBI scales. More participants with evening MEQ type had burn-out (66%) compared with morning MEQ type (55%), however, the results were not statically significant (p=0.294). Overall satisfaction with work shifts was 6.5 (95% CI 6.3 to 6.7), with higher satisfaction with day shift 7.7 (95% CI 7.5 to 7.9) and lowest satisfaction with overnight 24-hour call 3.5 (95% CI 3.2 to 3.9). Satisfaction was lower in trainees with burn-out 6.0 (95% CI 5.7 to 6.4), (p<0.001). In the follow-up survey, burn-out was present in at least one scale in 64% compared with 60% of respondents in the initial survey. CONCLUSION: Burn-out is prevalent among medical trainees. Improving alignment between trainee preferences may improve performance, reduce human errors and burn-out.

Phosphodiesterase-4 enzyme as a therapeutic target in neurological disorders.

Phosphodiesterases (PDE) are a diverse family of enzymes (11 isoforms so far identified) responsible for the degradation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) which are involved in several cellular and biochemical functions. Phosphodiesterase 4 (PDE4) is the major isoform within this group and is highly expressed in the mammalian brain. An inverse association between PDE4 and cAMP levels is the key mechanism in various pathophysiological conditions like airway inflammatory diseases-chronic obstruction pulmonary disease (COPD), asthma, psoriasis, rheumatoid arthritis, and neurological disorders etc. In 2011, roflumilast, a PDE4 inhibitor (PDE4I) was approved for the treatment of COPD. Subsequently, other PDE4 inhibitors (PDE4Is) like apremilast and crisaborole were approved by the Food and Drug Administration (FDA) for psoriasis, atopic dermatitis etc. Due to the adverse effects like unbearable nausea and vomiting, dose intolerance and diarrhoea, PDE4 inhibitors have very less clinical compliance. Efforts are being made to develop allosteric modulation with high specificity to PDE4 isoforms having better efficacy and lesser adverse effects. Interestingly, repositioning PDE4Is towards neurological disorders including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), multiple sclerosis (MS) and sleep disorders, is gaining attention. This review is an attempt to summarize the data on the effects of PDE4 overexpression in neurological disorders and the use of PDE4Is and newer allosteric modulators as therapeutic options. We have also compiled a list of on-going clinical trials on PDE4 inhibitors in neurological disorders.

Cocoa beans improve mitochondrial biogenesis via PPARγ/PGC1α dependent signalling pathway in MPP+ intoxicated human neuroblastoma cells (SH-SY5Y).

Polyphenols are shown to protect from or delay the progression of chronic neurodegenerative diseases. Mitochondrial dysfunction plays a key role in the pathogenesis of Parkinson's disease (PD). This study was aims to gain insight into the role of ahydroalcoholic extract of cocoa (standardised for epicatechin content) on mitochondrial biogenesis in MPP+ intoxicated human neuroblastoma cells (SHSY5Y). The effects of cocoa on PPARγ, PGC1α, Nrf2 and TFAM protein expression and mitochondrial membrane potential were evaluated. A pre-exposure to cocoa extract decreased reactive oxygen species formation and restored mitochondrial membrane potential. The cocoa extract was found to up-regulate the expression of PPARγ and the downstream signalling proteins PGC1α, Nrf2 and TFAM. It increased the expression of the anti-apoptotic protein BCl2 and increased superoxide dismutase activity. Further, the cocoa extract down-regulated the expression of mitochondria fission 1 (Fis1) and up-regulated the expression of mitochondria fusion 2 (Mfn2) proteins, suggesting an improvement in mitochondrial functions in MPP+ intoxicated cells upon treatment with cocoa. Interestingly, cocoa up-regulates the expression of tyrosine hydroxylase, the rate limiting enzyme in dopamine synthesis. No change in the expression of PPARγ on treatment with cocoa extract was observed when the cells were pre-treated with PPARγ antagonist GW9662. This data suggests that cocoa mediates mitochondrial biogenesis via a PPARγ/PGC1α dependent signalling pathway and also has the ability to improve dopaminergic functions by increasing tyrosine hydroxylase expression. Based on our data, we propose that a cocoa bean extract and products thereof could be used as potential nutritional supplements for neuroprotection in PD.

Sleep in the Elderly.

Aging is associated with several changes in sleep patterns. Older adults have increased prevalence of primary sleep disorders including insomnia, sleep disordered breathing, restless legs syndrome, REM sleep behavior disorder, and circadian rhythm disturbances. These can be further compromised by sleep disturbances secondary to medical or psychiatric disorders, and medication side effects. This review discusses age-related changes in sleep architecture, etiology, clinical presentation, and treatment options of various sleep disorders in the elderly.

Unique Aspects of Sleep in Women.

Sleep in women differs in many respects from that of men. In general, women appear to report a greater need for sleep and more subjective complaints of non-refreshing sleep than men. Sleep in women is affected at least partially by hormonal factors, with women typically suffering from sleep disturbance in connection with the menstrual cycle, pregnancy, and menopause Menstrual cycles are associated with prominent changes in reproductive hormones that may influence sleep. Sleep apnea and restless legs syndrome may be aggravated by pregnancy. Women may also develop insomnia during pregnancy, childbirth and menopause.

Genetic diversity and occurrence of Eimeria species causing cattle coccidiosis in Kashmir, India.

This study focuses on the occurrence, identification, and molecular characterization of Eimeria species causing coccidiosis in cattle in the Kashmir Valley, India. Coccidiosis, caused by apicomplexan parasites of the genus Eimeria, poses a significant threat to global cattle farming. Conventional techniques for identification, which rely on the morphology of sporulated oocysts, have drawbacks, leading to the adoption of molecular techniques to accurately delimit species. A total of 190 cattle were sampled in nine farms and parasitological examination revealed an occurrence of 45.7% for Eimeria spp. Molecular analysis using PCR and sequencing identified three predominant species: E. zuernii, E. alabamensis, and E. bovis. The study highlights the widespread occurrence of these species globally, as supported by previous research conducted in Bangladesh, Austria, Egypt, and Brazil. The phylogenetic analysis based on internal transcribed spacer (ITS-1) gene sequences revealed distinct clusters for E. zuernii and E. bovis, while E. alabamensis formed a separate clade. The genetic diversity and phylogenetic connections provide insights into the evolutionary relationships among these Eimeria species. This study contributes valuable information for understanding the epidemiology and genetic diversity of cattle coccidiosis in the Kashmir Valley, emphasizing the importance of molecular characterization for accurate species identification.

Microparticles in Human Perspiration as an Inflammatory Response Index.

A blood component analysis is an early step for evaluating inflammatory disorders, but it can be unfeasible in some settings. This pilot study assessed whether extracellular vesicle (EV) changes in perspiration are parallel to those occurring in blood as an alternative or complementary option to diagnose an inflammatory response. In parallel studies, EVs were analyzed in perspiration and blood obtained before and after five self-contained underwater breathing apparatus (SCUBA) divers at the National Aquarium in Baltimore performed a dive to 3.98 m of sea water for 40 min, and five non-divers performed an exercise routine at ambient atmospheric pressure. The results demonstrated that microparticles (MPs) are present in perspiration, their numbers increase in the blood in response to SCUBA diving, and the interleukin (IL)-1ß content increases. In contrast, while blood-borne MPs became elevated in response to terrestrial exercise, no statistically significant increases occurred in perspiration, and there were no changes in IL-1ß. There were no statistically significant elevations in the exosomes in perspiration or blood in response to SCUBA diving and few changes following terrestrial exercise. These findings suggest that an MP perspiration analysis could be a non-invasive method for detecting inflammatory responses that can occur due to the oxidative stress associated with SCUBA diving.

Beyond parasitism: Exploring the microbial profile of Haemonchus contortus and its predilection site (abomasum) in Kashmir Merino sheep.

Gastrointestinal helminth infection, particularly by Haemonchus contortus, poses significant challenges to sheep farming worldwide. While anthelmintic drugs have been traditional control measures, the emergence of resistance calls for alternative strategies. Understanding the interaction between parasites, host, and their microbiome is crucial for management of helminth infection. This study intricately explores the interactions between microbial communities in Kashmir Merino sheep infected with H. contortus, to understand the complex interplay between host, parasite, and their microbiome. Sheep abomasal contents and H. contortus were collected from infected and control groups, processed for DNA extraction, and subjected to metagenomic sequencing of the 16 S rRNA gene. Downstream analysis unveils distinct microbial patterns, where Proteobacteria were dominant in H. contortus, while Bacteroidota and Firmicutes prevailed in the sheep abomasum. The revelation of unique genera and shifts in diversity indices underscored helminth-induced disruptions in the host. Beta diversity analysis further showed significant variations in bacterial profiles, providing insights into the intricate host, parasite, and microbiome dynamics. Additionally, this study elucidated the presence of pathogenic bacteria within H. contortus, accentuating their potential role in exacerbating sheep health issues. This finding underscores the complexity of the host-parasite-microbiome interaction showing helminth-induced microbiome alterations of the host.

Persistent neuroinflammation and functional deficits in a murine model of decompression sickness.

We hypothesized that early intra-central nervous system (CNS) responses in a murine model of decompression sickness (DCS) would be reflected by changes in the microparticles (MPs) that exit the brain via the glymphatic system, and due to systemic responses the MPs would cause inflammatory changes lasting for many days leading to functional neurological deficits. Elevations on the order of threefold of blood-borne inflammatory MPs, neutrophil activation, glymphatic flow, and neuroinflammation in cerebral cortex and hippocampus were found in mice at 12 days after exposure to 760 kPa of air for 2 h. Mice also exhibited a significant decline in memory and locomotor activity, as assessed by novel object recognition and rotarod testing. Similar inflammatory changes in blood, neuroinflammation, and functional impairments were initiated in naïve mice by injection of filamentous (F-) actin-positive MPs, but not F-actin-negative MPs, obtained from decompressed mice. We conclude that high pressure/decompression stress establishes a systemic inflammatory process that results in prolonged neuroinflammation and functional impairments in the mouse decompression model.NEW & NOTEWORTHY Elevated glymphatic flow due to astrocyte and microglial activation from high-pressure exposure triggers release of microparticles (MPs) to the circulation where neutrophil activation and production of filamentous (F)-actin expressing MPs result in a persistent feed-forward neuroinflammatory cycle and functional deficits lasting for at least 12 days.

Gender Differences in the Clinical Profile of Sodium-Glucose Cotransporter-2 Inhibitor-Related Urinary Tract Infections.

Background Sodium-glucose cotransporter-2 inhibitors (SGLT2Is) are a novel class of oral antidiabetic agents with proven cardiovascular and mortality benefits. By promoting glucosuria, SGLT2Is increase the risk of genital and urinary tract infections (UTIs), which remain uncomplicated in most cases. Comparative studies detailing the gender differences in the clinical profile of SGLT2I-related UTIs (SUTIs) are lacking. Hence, this study was designed to investigate the gender-related differences in the clinical profile of SUTIs. Methodology This prospective study enrolled 100 consecutive diabetes mellitus patients with UTI symptoms who were on SGLT2Is. In addition to collecting clinical details, patients were subjected to the following investigations: complete blood counts, urea, creatine, liver function, lipid components, urine analysis, urine culture, and ultrasonography. Results Females (n = 80) outnumbered males (n = 20). Although females were younger than males (53.68 ± 10.26 vs. 63.30 ± 10.75 years, p = 0.003), body mass index (29.84 ± 7.22 vs. 24.62 ± 3.10 kg/m2, p = 0.008) and waist circumference (103.01 ± 14.49 vs. 93.75 ± 4.50 cm, p = 0.109) were higher in females. About 22.5% of females had undergone hysterectomy. The mean duration of diabetes mellitus was longer in males (10.64 ± 6.74 vs. 7.78 ± 4.75 years), whereas the median duration of SGLT2I use (4 (interquartile range (IQR) = 1-12) vs. 3 (IQR = 2-4) months) and mean HbA1c levels were not different between the two groups. A greater proportion of males were complicated by retinopathy (55% vs. 15%) and proteinuria (65% vs. 17.5%), while neuropathy (85% vs. 71.25%) rates were similar. Overall, 35% of males had complicated UTIs (renal abscess, pyelonephritis, prostatic abscess) compared to only 3.75% of females (p = 0.001). Conclusions The majority of SUTIs are uncomplicated in females whereas in males one-third are complicated infections. Although females with SUTI had a higher prevalence of obesity and dyslipidemia, males had a longer duration of diabetes mellitus and higher retinopathy prevalence. Extreme caution should be exercised in patients at risk for SUTI before prescribing SGLT2I.

DOE-Assisted Formulation, Optimization, and Characterization of Tioconazole-Loaded Transferosomal Hydrogel for the Effective Treatment of Atopic Dermatitis: In Vitro and In Vivo Evaluation.

The present study was performed to determine the therapeutic effects of tioconazole (Tz)-loaded novel transferosome carriers (TFs) for the treatment of atopic dermatitis (AD). METHOD: Tioconazole transferosomes suspension (TTFs) was formulated and optimized using a 32 factorial design. After that, the optimized batch of TTFs loaded into Carbopol 934 and sodium CMC was prepared with hydrogel and noted as TTFsH. Subsequently, it was evaluated for pH, spread ability, drug content, in vitro drug release, viscosity, in vivo scratching and erythema score, skin irritation, and histopathology study. RESULT: The optimized batch of TTFs (B4) showed the values of vesicle size, flux, and entrapment efficiency to be 171.40 ± 9.03 nm, 48.23 ± 0.42, and 93.89 ± 2.41, respectively. All batches of TTFsH showed sustained drug release for up to 24 h. The F2 optimized batch released Tz in an amount of 94.23 ± 0.98% with a flux of 47.23 ± 0.823 and followed the Higuchi kinetic model. The in vivo studies provided evidence that the F2 batch of TTFsH was able to treat atopic dermatitis (AD) by reducing the erythema and the scratching score compared to that of the marketed formulation (Candiderm cream, Glenmark). The histopathology study supported the result of the erythema and scratching score study with intact skin structure. It showed that a formulated low dose of TTFsH was safe and biocompatible to both the dermis and the epidermis layer of skin. CONCLUSION: Thus, a low dose of F2-TTFsH is a promising tool that effectively targeted the skin for the topical delivery of Tz to treat atopic dermatitis symptoms.

Innovative Wound Healing Hydrogel Containing Chicken Feather Keratin and Soy Isoflavone Genistein: In Vivo Studies.

The current study was performed to isolate keratin from chicken feathers with an intention to develop a keratin-genistein wound-healing hydrogel, along with its in vivo analysis. Pre-formulation aspects were analysed by using FTIR; SEM; HPTLC, while gel was characterized for gel strength, viscosity, spreadability, drug content, etc. Additionally, an in vivo study along with biochemical factors against pro-inflammatory factors and histopathological studies were conducted to determine possible wound-healing and anti-inflammatory effects. Pre-formulation studies revealed the presence of amide bonds with region of dense fibrous keratin and an internal porous network in extracted keratin, which corresponds with standard keratin. Evaluation of optimised keratin-genistein hydrogel indicated the development of neutral, non-sticky hydrogel which spread evenly on the skin. In vivo studies in rats indicate higher degrees of wound-healing in combined hydrogel (94.65%) for a duration of 14 days as compared to an individual hydrogel formulation with the development of the epidermis and excessive proliferation of fibrous connective tissue indicating wound repair. Furthermore, the hydrogel inhibited the overexpression of IL-6 gene along with other pro-inflammatory factors, indicating its anti-inflammatory effects. In order to find out the possibility of closure of wounds and anti-inflammatory properties of the novel product, an in vivo investigation into the healing of wounds in laboratory animals was carried out through biochemical (ELISA and qRT-PCR) analyses against inflammatory markers (IL-2, IL-6, IL-1, IL-10, and COX-2) and histopathological (liver, skin, and the kidneys) investigations. Based on the results, we conclude that keratin-genistein hydrogel is a promising therapeutic molecule for the management of wound repair.

A novel mutation in the KCNJ11 gene (p.Val36Glu), predisposes to congenital hyperinsulinemia.

The hypoglycemia induced by insulin hypersecretion in congenital hyperinsulinemia (CHI), a rare life-threatening condition can lead to irreversible brain damage in neonates. Inactivating mutations in the genes encoding KATP channel (ABCC8 and KCNJ11) as well as HNF4A, HNF1A, HADH, UCP2, and activating mutations in GLUD1, GCK, and SLC16A1 have been identified as causal. A 3-month-old male infant presenting tonic-clonic seizures and hyperinsulinemia was clinically assessed and subjected to genetic analysis. Besides the index patient, his parents were clinically investigated, and a detailed family history was also recorded. The laboratory investigations and the genetic test results of the parents were compared with the index patient. The biochemical and hormonal profile of the patient confirmed his suffering from CHI and did not respond to diazoxide treatment. The genetic testing revealed that the subject harbored a novel homozygous missense mutation in the KCNJ11 gene, (c.107T>A, p.Val36Glu.). The bioinformatic analysis revealed that valine is highly conserved and predicted that the variant allele (p.Val36Glu) is likely pathogenic and causal for CHI. Parents were heterozygous carriers and did not report any abnormal metabolic profile. Identification of such mutations is critical and likely to change the therapeutic interventions for such patients in the future.

Blood-Borne Microparticles Are an Inflammatory Stimulus in Type 2 Diabetes Mellitus.

The proinflammatory state associated with diabetes mellitus (DM) remains poorly understood. We found patients with DM have 3- to 14-fold elevations of blood-borne microparticles (MPs) that bind phalloidin (Ph; Ph positive [+] MPs), indicating the presence of F-actin on their surface. We hypothesized that F-actin-coated MPs were an unrecognized cause for DM-associated proinflammatory status. Ph+MPs, but not Ph-negative MPs, activate human and murine (Mus musculus) neutrophils through biophysical attributes of F-actin and membrane expression of phosphatidylserine (PS). Neutrophils respond to Ph+MPs via a linked membrane array, including the receptor for advanced glycation end products and CD36, PS-binding membrane receptors. These proteins in conjunction with TLR4 are coupled to NO synthase 1 adaptor protein (NOS1AP). Neutrophil activation occurs because of Ph+MPs causing elevations of NF-κB and Src kinase (SrcK) via a concurrent increased association of NO synthase 2 and SrcK with NOS1AP, resulting in SrcK S-nitrosylation. We conclude that NOS1AP links PS-binding receptors with intracellular regulatory proteins. Ph+MPs are alarmins present in normal human plasma and are increased in those with DM and especially those with DM and a lower-extremity ulcer.