The histone methyltransferase SETD2 regulates HIV expression and latency.

Understanding the mechanisms that drive HIV expression and latency is a key goal for achieving an HIV cure. Here we investigate the role of the SETD2 histone methyltransferase, which deposits H3K36 trimethylation (H3K36me3), in HIV infection. We show that prevention of H3K36me3 by a potent and selective inhibitor of SETD2 (EPZ-719) leads to reduced post-integration viral gene expression and accelerated emergence of latently infected cells. CRISPR/Cas9-mediated knockout of SETD2 in primary CD4 T cells confirmed the role of SETD2 in HIV expression. Transcriptomic profiling of EPZ-719-exposed HIV-infected cells identified numerous pathways impacted by EPZ-719. Notably, depletion of H3K36me3 prior to infection did not prevent HIV integration but resulted in a shift of integration sites from highly transcribed genes to quiescent chromatin regions and to polycomb repressed regions. We also observed that SETD2 inhibition did not apparently affect HIV RNA levels, indicating a post-transcriptional mechanism affecting HIV expression. Viral RNA splicing was modestly reduced in the presence of EPZ-719. Intriguingly, EPZ-719 exposure enhanced responsiveness of latent HIV to the HDAC inhibitor vorinostat, suggesting that H3K36me3 can contribute to a repressive chromatin state at the HIV locus. These results identify SETD2 and H3K36me3 as novel regulators of HIV integration, expression and latency.

A leaky human colon model reveals uncoupled apical/basal cytotoxicity in early Clostridioides difficile toxin exposure.

Clostridioides difficile (C. difficile) toxins A (TcdA) and B (TcdB) cause antibiotic-associated colitis in part by disrupting epithelial barrier function. Accurate in vitro models are necessary to detect early toxicity kinetics, investigate disease etiology, and develop preclinical models for new therapies. Properties of cancer cell lines and organoids inherently limit these efforts. We developed adult stem cell-derived monolayers of differentiated human colonic epithelium (hCE) with barrier function, investigated the impact of toxins on apical/basal aspects of monolayers, and evaluated whether a leaky epithelial barrier enhances toxicity. Single-cell RNA-sequencing (scRNAseq) mapped C. difficile-relevant genes to human lineages. Transcriptomics compared hCE to Caco-2, informed timing of in vitro stem cell differentiation, and revealed transcriptional responses to TcdA. Transepithelial electrical resistance (TEER) and fluorescent permeability assays measured cytotoxicity. Contribution of TcdB toxicity was evaluated in a diclofenac-induced leaky gut model. scRNAseq demonstrated broad and variable toxin receptor expression. Absorptive colonocytes in vivo displayed increased toxin receptor, Rho GTPase, and cell junction gene expression. Advanced TcdA toxicity generally decreased cytokine/chemokine and increased tight junction and death receptor genes. Differentiated Caco-2 cells remained immature whereas hCE monolayers were similar to mature colonocytes in vivo. Basal exposure of TcdA/B caused greater toxicity and apoptosis than apical exposure. Apical exposure to toxins was enhanced by diclofenac. Apical/basal toxicities are uncoupled with more rapid onset and increased magnitude postbasal toxin exposure. Leaky junctions enhance toxicity of apical TcdB exposure. hCE monolayers represent a physiologically relevant and sensitive system to evaluate the impact of microbial toxins on gut epithelium.NEW & NOTEWORTHY Novel human colonocyte monolayer cultures, benchmarked by transcriptomics for physiological relevance, detect early cytopathic impacts of Clostridioides difficile toxins TcdA and TcdB. A fluorescent ZO-1 reporter in primary human colonocytes is used to track epithelial barrier disruption in response to TcdA. Basal TcdA/B exposure generally caused more rapid onset and cytotoxicity than apical exposure. Transcriptomics demonstrate changes in tight junction, chemokine, and cytokine receptor gene expression post-TcdA exposure. Diclofenac-induced leaky epithelium enhanced apical exposure toxicity.

The influence of radiation dose on taste impairment in a prospective observational study cohort of oropharyngeal cancer patients.

BACKGROUND: To analyze the influence of radiation dose on late radiation-associated taste impairment in oropharyngeal cancer (OPC) patients treated with intensity-modulated radiotherapy (IMRT) using the taste bud bearing tongue mucosa as organ at risk. MATERIAL AND METHODS: This study is part of an ongoing, prospective observational study. Cancer-free OPC survivors with at least 24 months from IMRT were included in this analysis. Scores for taste impairment and dry mouth were extracted from the MD Anderson Symptom Inventory Head and Neck module (MDASI-HN) with scores of ≥5 considered as moderate-to-severe symptoms. The mean dose, minimum and maximum dose to the taste bud bearing tongue mucosa, the ipsi- and contralateral parotid and submandibular glands were extracted and analyzed for correlation with moderate-to-severe taste impairment. RESULTS: One hundred sixteen T1-4 OPC patients were included (81% males, median age: 55). The primary tumor was in the tonsil in 92 cases (79%) and in the base of tongue in 21 cases (18%). Patients were treated with 64.2-72.0 Gy; 37 patients (32%) received concurrent chemotherapy and 22 (19%) concurrent targeted therapy. After a median of 58 months from RT (IQR: 43-68) 38 patients (33%) suffered from moderate-to-severe long-term radiation-associated taste impairment. No dose volume parameter of the taste bud bearing tongue mucosa and the salivary glands was significantly associated with moderate-to-severe taste impairment for the whole patient cohort. For patients without concurrent chemotherapy, the minimum and mean dose to the ipsilateral parotid gland, and the maximum dose to the submandibular gland was significantly associated with late taste impairment (all p < 0.05). A significant correlation was found between taste impairment and dry mouth (p < 0.001). CONCLUSION: The dose to the ipsilateral parotid gland seems to play an important role in the development of late taste impairment. The influence of dose to the taste bud bearing tongue mucosa remains unclear and needs further investigation.

Investigating the Dietary Impact on Trans-Vaccenic Acid (Trans-C18:1 n-7) and Other Beneficial Fatty Acids in Breast Milk and Infant Formulas.

Maternal diet plays a significant role in the fatty acid composition of breast milk. Dietary products such as milk and meat are the primary sources of natural TFAs for humans. These peculiar fatty acids hold nutritional significance as they not only lack the detrimental effects of industrially produced trans fats on the endothelium characteristic, but they also exhibit anti-inflammatory properties. The relationship between the presence of eight fatty acids in breast milk (including natural TFAs trans-vaccenic and conjugated linoleic acid) and the maternal diet has been explored, and their abundance has been compared to that of infant formulas. Two cohorts of lactating women, originating from a Spanish region, participated in this study; they adhered to the Southern European Atlantic diet or the Atlantic diet. While the consumption of conventional meat or dairy products does not seem to increase the abundance of TFAs in breast milk, trans-vaccenic and oleic acid are among the most distinctive features of breast milk fat in mothers consuming naturally improved dairy products with an improved fatty acid profile. The most significant differences between natural breastfeeding and formula feeding lie in natural TFAs, since formulas are notably deficient in natural TFAs while being overfortified in alpha-linolenic acid in comparison to breast milk. We suggest an improvement in the formulation of these products through using cow's milk with an optimal fatty acid profile that better mimics the fatty acid composition found in human milk.

Single-cell transcriptomics predict novel potential regulators of acute epithelial restitution in the ischemia-injured intestine.

Intestinal ischemic injury damages the epithelial barrier predisposes patients to life-threatening sepsis unless that barrier is rapidly restored. There is an age-dependency of intestinal recovery in that neonates are the most susceptible to succumb to disease of the intestinal barrier versus older patients. We have developed a pig model that demonstrates age-dependent failure of intestinal barrier restitution in neonatal pigs which can be rescued by the direct application of juvenile pig mucosal tissue, but the mechanisms of rescue remain undefined. We hypothesized that by identifying a subpopulation of restituting enterocytes by their expression of cell migration transcriptional pathways, we can then predict novel upstream regulators of age-dependent restitution response programs. Superficial mucosal epithelial cells from recovering ischemic jejunum of juvenile pigs were processed for single cell RNA sequencing analysis, and predicted upstream regulators were assessed in a porcine intestinal epithelial cell line (IPEC-J2) and banked tissues. A subcluster of absorptive enterocytes expressed several cell migration pathways key to restitution. Differentially expressed genes in this subcluster predicted their upstream regulation included colony stimulating factor-1 (CSF-1). We validated age-dependent induction of CSF-1 by ischemia and documented that CSF-1 and CSF1R co-localized in ischemic juvenile, but not neonatal, wound-adjacent epithelial cells and in the restituted epithelium of juveniles and rescued (but not control) neonates. Further, the CSF1R inhibitor BLZ945 reduced restitution in scratch wounded IPEC-J2 cells. These studies validate an approach to inform potential novel therapeutic targets, such as CSF-1, to improve outcomes in neonates with intestinal injury in a unique pig model. NEW & NOTEWORTHY: These studies validate an approach to identify and predict upstream regulation of restituting epithelium in a unique pig intestinal ischemic injury model. Identification of potential molecular mediators of restitution, such as CSF-1, will inform the development of targeted therapeutic interventions for medical management of patients with ischemia-mediated intestinal injury.

Almost 50 Years of Monomeric Extracellular Ubiquitin (eUb).

Monomeric ubiquitin (Ub) is a 76-amino-acid highly conserved protein found in eukaryotes. The biological activity of Ub first described in the 1970s was extracellular, but it quickly gained relevance due to its intracellular role, i.e., post-translational modification of intracellular proteins (ubiquitination) that regulate numerous eukaryotic cellular processes. In the following years, the extracellular role of Ub was relegated to the background, until a correlation between higher survival rate and increased serum Ub concentrations in patients with sepsis and burns was observed. Although the mechanism of action (MoA) of extracellular ubiquitin (eUb) is not yet well understood, further studies have shown that it may ameliorate the inflammatory response in tissue injury and multiple sclerosis diseases. These observations, compounded with the high stability and low immunogenicity of eUb due to its high conservation in eukaryotes, have made this small protein a relevant candidate for biotherapeutic development. Here, we review the in vitro and in vivo effects of eUb on immunologic, cardiovascular, and nervous systems, and discuss the potential MoAs of eUb as an anti-inflammatory, antimicrobial, and cardio- and brain-protective agent.

Faecal Microbiota Transplantation is a simple, effective and safe treatment in the management of C. difficile infection in daily clinical practice.

INTRODUCTION: Faecal microbiota transplantation (FMT) is a treatment supported by wide scientific evidence and proved to be very effective in the management of Clostridioides difficile infection (CDI). The objective of this study is to analyze its effectiveness and safety in a real clinical practice setting. METHODS: Retrospective, single-center and descriptive observational study in which all FMT performed between May 2016 and December 2020 were included. Technical success was defined as the successful administration of the faecal preparation in the patient's gastrointestinal tract and clinical success the disappearance of diarrhoea in the first 72 h after the procedure with no relapse within the following 8 weeks after the therapy was started. RESULTS: 15 FMT were performed in 13 patients. Median age was 79 years (range: 40-98 years); being 60% women and 33.3% depedent persons. The indication for FMT was recurrent CDI in 84.6%. All FMTs were performed by colonoscopy and from related donors. With a first procedure, the FMT was effective in 11 of 13 patients (84.61%; 95% CI; 54.55-98.07). Time until resolution of symptoms was less than 48 h in all cases. Post-transplant follow-up was 25.66 ±â€¯17.5 months. No significant short or long-term complications were recorded at follow-up. CONCLUSION: TMF is a simple, effective and safe procedure in CD infection, even in elderly patients or those with great comorbidities.

Treatment With Adalimumab 80 mg Every Other Week in Inflammatory Bowel Disease: Results of Treatment Intensification in Clinical Practice.

Background: Loss of response to anti-tumor necrosis factor drugs in patients with inflammatory bowel disease (IBD) is frequent and, in case of low drug levels, treatment intensification is recommended. In addition, in cases in which clinical response without attainment of remission (clinical, endoscopic, or radiological), intensification could be justified since higher drug levels are associated with better outcomes. For adalimumab (ADA), the standard intensification regimen is 40 mg every week (ew). Availability of ADA 80 mg prefilled pens has enabled every other week (eow) intensification. We assessed the clinical efficacy of intensification with ADA 80 mg eow. Methods: This retrospective study was conducted at a tertiary hospital in Spain. Patients with IBD receiving maintenance ADA 80 mg eow with clinical, biomarker, and drug-level assessments were included. Demographics and clinical, biological, and endoscopic evaluation of the disease before and after ADA intensification, and pharmacokinetic assessments, were collected. Results: Eighty-seven patients (72 Crohn's disease, 15 ulcerative colitis; average age 50 years) were included. Reasons for ADA intensification were: low ADA levels-<5 µg mL-1-(17%), low ADA levels-<5 µg mL-1-without clinical response (63%), clinical response without clinical remission (15%) and active disease on objective evaluation (including colonoscopy, magnetic resonance imaging, capsule endoscopy, and/or intestinal ultrasound; 5%). Following treatment intensification to ADA 80 mg eow, 75 patients (86%) were in clinical remission and 69 (79.3%) were in biologic remission (clinical remission and normalization of biomarkers). After a median follow-up of 19 months (interquartile range 13-25), 63 patients (72%) remained on treatment and in clinical remission. There were no serious infections, hospitalizations, or deaths. Drug costs did not increase with the 80 mg eow regimen versus a standard intensification regimen. Conclusions: ADA intensification to 80 mg eow was safe, effective, and did not increase drug costs versus standard intensification to 40 mg ew in our experience.

Quantifying current and future raw milk losses due to bovine mastitis on European dairy farms under climate change scenarios.

Bovine mastitis is an infectious disease that causes udder inflammation and is responsible for raw milk losses across European dairy farms. It is associated with reduced cow milk yield and contributes to elevated Somatic Cell Count (SCC) in raw milk. Staphylococcus aureus is one of the most prevalent mastitis pathogens that cause subclinical and clinical mastitis and can be present as a coloniser bacterium in cows. Climate change and geographical variability may influence the prevalence of this pathogen. Thus, this research aimed to predict the raw milk losses in three major dairy-producing regions across Europe (i.e. Mediterranean, Atlantic and Continental) under climate change scenarios. An exposure assessment model and a stepwise probabilistic model were developed to predict potential cow milk yield reduction, S. aureus and SCC concentrations in the bulk tank milk at dairy farms. Baseline (i.e. present) and future climate change scenarios were defined, and the resultant concentrations of SCC and S. aureus were compared to the actual European regulatory limits. Across the three regions, raw milk losses ranged from 1.06% to 2.15% in the baseline. However, they increased up to 3.21% in the climate change scenarios when no on-farm improvements were considered. Regarding geographical variation, the highest potential milk losses were reported for the Mediterranean and the lowest for the Continental region. Concerning the fulfilment of the regulatory limits, the mean of S. aureus and SCC levels in milk did not exceed them either in any region or scenario. Nevertheless, when looking at percentiles, the 10th percentile remained above the limits of S. aureus in Atlantic and Mediterranean, but not in the Continental region. The findings provide a snapshot of climate change impacts on raw milk losses due to mastitis. They will allow farmers to detect weaknesses and prepare them to develop adaptation plans to climate change.

Telemonitoring System Oriented towards High-Risk Pregnant Women.

A high-risk pregnancy is one in which pathological problems or abnormal conditions are latent during pregnancy and childbirth, increasing dangers to the mother's or the infant's health. Based on international standards and studies, most of the harms and risks to both the mother and the infant can be detected, treated, and prevented through proper pregnancy monitoring, as well as through appropriate and timely diagnosis. In this paper, we present the analysis, design, development, and usability assessment of a telemonitoring system focused on the remote monitoring and control of pregnancy in women suffering from hypertension, diabetes, or high-risk pregnancy. Our system is composed of two mobile web applications. One of these is designed for the medical area, allowing remote monitoring of the patient's pregnancy, and the other one is directed towards the patient, who enters the alarm symptom data, hypertension data, diabetes data, and clinical analyses, allowing the detection of a risk situation on time. Furthermore, we performed a usability assessment of our system based on a laboratory study with seven doctors and seven patients to evaluate the users' satisfaction. Our telemonitoring system shows a satisfactory/favorable opinion from the users' perspectives based on the obtained results.

Efficient transgenesis and homology-directed gene targeting in monolayers of primary human small intestinal and colonic epithelial stem cells.

Two-dimensional (2D) cultures of intestinal and colonic epithelium can be generated using human intestinal stem cells (hISCs) derived from primary tissue sources. These 2D cultures are emerging as attractive and versatile alternatives to three-dimensional organoid cultures; however, transgenesis and gene-editing approaches have not been developed for hISCs grown as 2D monolayers. Using 2D cultured hISCs we show that electroporation achieves up to 80% transfection in hISCs from six anatomical regions with around 64% survival and produces 0.15% transgenesis by PiggyBac transposase and 35% gene edited indels by electroporation of Cas9-ribonucleoprotein complexes at the OLFM4 locus. We create OLFM4-emGFP knock-in hISCs, validate the reporter on engineered 2D crypt devices, and develop complete workflows for high-throughput cloning and expansion of transgenic lines in 3-4 weeks. New findings demonstrate small hISCs expressing the highest OLFM4 levels exhibit the most organoid forming potential and show utility of the 2D crypt device to evaluate hISC function.

A Planar Culture Model of Human Absorptive Enterocytes Reveals Metformin Increases Fatty Acid Oxidation and Export.

BACKGROUND & AIMS: Fatty acid oxidation by absorptive enterocytes has been linked to the pathophysiology of type 2 diabetes, obesity, and dyslipidemia. Caco-2 and organoids have been used to study dietary lipid-handling processes including fatty acid oxidation, but are limited in physiological relevance or preclude simultaneous apical and basal access. Here, we developed a high-throughput planar human absorptive enterocyte monolayer system for investigating lipid handling, and then evaluated the role of fatty acid oxidation in fatty acid export, using etomoxir, C75, and the antidiabetic drug metformin. METHODS: Single-cell RNA-sequencing, transcriptomics, and lineage trajectory was performed on primary human jejunum. In vivo absorptive enterocyte maturational states informed conditions used to differentiate human intestinal stem cells (ISCs) that mimic in vivo absorptive enterocyte maturation. The system was scaled for high-throughput drug screening. Fatty acid oxidation was modulated pharmacologically and BODIPY (Thermo Fisher Scientific, Waltham, MA) (B)-labeled fatty acids were used to evaluate fatty acid handling via fluorescence and thin-layer chromatography. RESULTS: Single-cell RNA-sequencing shows increasing expression of lipid-handling genes as absorptive enterocytes mature. Culture conditions promote ISC differentiation into confluent absorptive enterocyte monolayers. Fatty acid-handling gene expression mimics in vivo maturational states. The fatty acid oxidation inhibitor etomoxir decreased apical-to-basolateral export of medium-chain B-C12 and long-chain B-C16 fatty acids, whereas the CPT1 agonist C75 and the antidiabetic drug metformin increased apical-to-basolateral export. Short-chain B-C5 was unaffected by fatty acid oxidation inhibition and diffused through absorptive enterocytes. CONCLUSIONS: Primary human ISCs in culture undergo programmed maturation. Absorptive enterocyte monolayers show in vivo maturational states and lipid-handling gene expression profiles. Absorptive enterocytes create strong epithelial barriers in 96-Transwell format. Fatty acid export is proportional to fatty acid oxidation. Metformin enhances fatty acid oxidation and increases basolateral fatty acid export, supporting an intestine-specific role.

Altered neutrophil-to-lymphocyte ratio in sepsis secondary to canine parvoviral enteritis treated with and without an immunomodulator in puppies.

Neutrophil-to-lymphocyte ratio (NLR) is a cheap and easy-to-obtain biomarker that mirrors the balance between innate and adaptive immunity. Cortisol and catecholamines have been identified as major drivers of NLR. High cortisol levels increase neutrophils while simultaneously decreasing lymphocyte counts. Likewise, endogenous catecholamines may cause leukocytosis and lymphopenia. Thus, NLR allows us to monitor patient severity in conditions such as sepsis. Twenty-six puppies with sepsis secondary to canine parvoviral enteritis were treated with and without an immunomodulator. Our group determined the NLR and the plasmatic cortisol levels by chemiluminescence, and norepinephrine (NE) and epinephrine (E) by HPLC during the first 72 h of clinical follow-up. Our results showed that at admission puppies presented an NLR value of 1.8, cortisol of 314.9 nmol/L, NE 3.7, and E 3.3 pmol/mL. Both treatments decreased admission NLR values after 24 h of treatment. However, only the puppies treated with the immunomodulator (I) remained without significant changes in NLR (0.7-1.4) compared to the CT group, and that showed a significant difference (P < 0.01) in their NLR value (0.4-4.6). In addition, we found significant differences in the slope values between the admission and final values of NLR (P < 0.005), cortisol (P < 0.02), and E (P < 0.05) between treatments. Then, our data suggest that the immunomodulator positively affects the number of lymphocytes and neutrophils involved in NLR as well as major drivers like cortisol and epinephrine, which is reflected in clinical parameters and survival.

A Proximal-to-Distal Survey of Healthy Adult Human Small Intestine and Colon Epithelium by Single-Cell Transcriptomics.

BACKGROUND & AIMS: Single-cell transcriptomics offer unprecedented resolution of tissue function at the cellular level, yet studies analyzing healthy adult human small intestine and colon are sparse. Here, we present single-cell transcriptomics covering the duodenum, jejunum, ileum, and ascending, transverse, and descending colon from 3 human beings. METHODS: A total of 12,590 single epithelial cells from 3 independently processed organ donors were evaluated for organ-specific lineage biomarkers, differentially regulated genes, receptors, and drug targets. Analyses focused on intrinsic cell properties and their capacity for response to extrinsic signals along the gut axis across different human beings. RESULTS: Cells were assigned to 25 epithelial lineage clusters. Multiple accepted intestinal stem cell markers do not specifically mark all human intestinal stem cells. Lysozyme expression is not unique to human Paneth cells, and Paneth cells lack expression of expected niche factors. Bestrophin 4 (BEST4)+ cells express Neuropeptide Y (NPY) and show maturational differences between the small intestine and colon. Tuft cells possess a broad ability to interact with the innate and adaptive immune systems through previously unreported receptors. Some classes of mucins, hormones, cell junctions, and nutrient absorption genes show unappreciated regional expression differences across lineages. The differential expression of receptors and drug targets across lineages show biological variation and the potential for variegated responses. CONCLUSIONS: Our study identifies novel lineage marker genes, covers regional differences, shows important differences between mouse and human gut epithelium, and reveals insight into how the epithelium responds to the environment and drugs. This comprehensive cell atlas of the healthy adult human intestinal epithelium resolves likely functional differences across anatomic regions along the gastrointestinal tract and advances our understanding of human intestinal physiology.

Children in Monetary Poor Households: Baseline and COVID-19 Impact for 2020 and 2021.

The impact of the global economic crisis caused by the COVID-19 pandemic will not affect all children equally: those in poorer households and children who are disadvantaged face the most serious consequences. As parents lose their jobs and incomes, the impact on children living in impoverished households must be measured. In this article, we assess the economic consequences of the pandemic on these children. Given that poorer families have a larger number of children than other families, the analysis first establishes the proportion of children living in monetary poor households, as defined by national standards, across developing countries. Then, using historical changes and trends of income distribution per country, the latest projections about economic decline due to the pandemic, and demographic information about the distribution of children by deciles, we estimate the expected increase in the number of children in monetary poor households in developing countries as of end of 2020 to be an additional 122-144 million and, at best, a moderate decline in these numbers by end of 2021.

Inverted Meckel's diverticulum diagnosed using capsule endoscopy: A case report.

BACKGROUND: Meckel's diverticulum is a common asymptomatic congenital gastrointestinal anomaly. However, its presentation as an inverted Meckel's diverticulum is a rare complication, of which few cases have been reported in the literature. CASE SUMMARY: Here, we report the case of a 33-year-old man with iron deficiency anemia without manifestation of gastrointestinal bleeding. An upper gastrointestinal endoscopy and total colonoscopy were performed, but no abnormalities were found within the observed area. Finally, a capsule endoscopy was performed and offered us a clue to subsequently confirm the diagnosis of inverted Meckel's diverticulum via computed tomography scan. Laparoscopic intestinal resection surgery was performed. The final pathology report described a Meckel's diverticulum. CONCLUSION: Since inverted Meckel's diverticulum is an uncommon disease and its clinical presentation is not specific, it may go undetected by capsule endoscopy. Successful diagnosis and treatment of this disease requires a high index of clinical suspicion.

The impact of tongue-deviating and tongue-depressing oral stents on long-term radiation-associated symptoms in oropharyngeal cancer survivors.

OBJECTIVES: To evaluate whether the use of oral stents during intensity modulated radiation therapy (IMRT) for oropharyngeal cancer (OPC) is associated with long-term patient reported symptoms. MATERIALS AND METHODS: Data was obtained from a prospective observational study of disease-free head and neck cancer survivors. Radiation-associated patient reported symptoms were assessed using the MD Anderson Symptom Inventory Head and Neck module (MDASI-HN). Scores of ≥5 (11-point Likert scale, 0-10) were considered moderate/severe. Stratification was performed regarding IMRT volume (uni- versus bilateral neck) and stent utilization, with non-parametric analyses between groups. RESULTS: 462 OPC survivors formed the cohort (54% tonsil, 46% base of tongue primaries). A tongue-deviating stent was used in 17%, tongue-depressing stent in 46%, and no stent in 37%. Median prescribed dose to the high dose clinical target volume was 66.0 Gy. Median follow-up from RT to MDASI-HN assessment was 68 months. Twenty percent had received unilateral neck RT (all had tonsil primaries), in whom a significant improvement in the proportion of patients with moderate/severe taste impairment (2% vs. 15%, p = 0.047) and lack of appetite (0% vs. 9%, p = 0.019) was associated with the use of tongue-deviating stents compared to no oral stent. In those who had received bilateral neck RT, a significant improvement in the proportion of patients with moderate/severe difficulty swallowing/chewing was associated with use of a tongue-depressing stent (21% vs. 31% without oral stent, p = 0.013). CONCLUSION: Disease-site specific select use of oral stents during IMRT was associated with reduced long-term patient reported symptoms in OPC survivors.

Efficacy of a social cognition training program for schizophrenic patients: a pilot study.

Psychosocial functioning impairment is recognized as a core feature of schizophrenia. Numerous studies have assessed the process that may underlie this impairment. In the last years, one of these processes that has been studied more is social cognition, which has been proposed as a mediator variable between neurocognition and functional outcome. Social cognition includes the subdomains of emotion recognition and social perception, and in recent years several authors have developed diverse training programs in these areas. The purpose of the present article is to assess the efficacy of the Social Cognition Training Program, a program that includes emotion recognition training and social perception training. The sample was made up of 14 outpatients with a diagnosis of schizophrenia according to CIE-10 criteria, randomly divided into two groups: experimental and control. All patients were assessed before and after the training program. Cognitive and psychopathological variables, social functioning, emotion recognition and social perception performance were assessed. Results suggest improvement in social perception and interpretation in the experimental group, in comparison with the control group, but not in emotion recognition. No significant correlations were obtained between social cognition training and other variables tested.

Effect of cluster set warm-up configurations on sprint performance in collegiate male soccer players.

The purpose of this study was to determine if back squat cluster sets (CS) with varying inter-repetition rest periods would potentiate greater sprint performance compared with a traditional set parallel back squat in collegiate soccer players. Twelve collegiate male soccer players (age, 21.0 ± 2.0 years; height, 180.0 ± 9.0 cm; body mass, 79.0 ± 9.5 kg) performed a 20-m sprint prior to a potentiation complex and at 1, 4, 7, and 10 min postexercise on 3 separate, randomized occasions. On each occasion, the potentiation complex consisted of 1 set of 3 repetitions at 85% 1-repetition maximum (1RM) for the traditional parallel back squat. However, on 1 occasion the 3-repetition set was performed in a traditional manner (i.e., continuously), whereas on the other 2 occasions, 30s (CS30) and 60 s (CS60) of rest were allotted between each repetition. Repeated-measures ANOVA revealed greater (p = 0.022) mean barbell velocity on CS60 compared with the traditional set. However, faster (p < 0.040) 20-m sprint times were observed for CS30 (3.15 ± 0.16 s) compared with traditional (3.20 ± 0.17 s) only at 10 min postexercise. No other differences were observed. These data suggest that a single cluster set of 3 repetitions with 30-s inter-repetition rest periods at 85% 1RM acutely improves 20-m sprinting performance. Strength and conditioning professionals and their athletes might consider its inclusion during the specific warm-up to acutely improve athletic performance during the onset (≤10 min) of training or competition.