Further characterization of 19 cases of rea(21q21q) and delineation as isochromosomes or robertsonian translocations in down syndrome

We have used 9 conventional RFLPs and 6 dinucleotide repeat polymorphisms on chromosome 21q to demonstrate that 17 of 19 cases of rea(21q21q) were consistent with isochromosomes i(21q) with the remaining 2 being true Robertsonian translocations. Eight of the 17 isochromosomes were of maternal origin and 9 cases were paternally derived. The 2 Robertsonian translocations were both maternally derived. Of the 17 isochromosomes, 7 were dicentric Wc(21q)I and 10 were monocentric M21q)l. Both rob(21q21q) were monocentric. Our findings agree with those made in 17 previously published cases of rea(21q21q). The parental origins of the i(21q) were equally divided between maternal (n = 17) and paternal (n = 15) origins. All 4 true rob(21q21q) reported to date are of maternal origin. Collectively, it appears that most homologous rearrangements of chromosome 21 are isochromosomes and only a small proportion are consistent with true Robertsonian translocations. © 1993 Wiley-Liss, Inc.     

Predictors of HIV Risk Among College Students: A CHAID Analysis1

SUMMARY The purpose of this study was to identify predictors of risk behaviors among college students and to determine how students differed in HIV risk practices. Participants were from six colleges and universities in a large southeastern metropolitan area. The present analysis was limited to participants who were 18 to 25 years of age; single; White, African American, or Asian; and reported initiation of sexual intercourse. The results demonstratedsignificant associations of gender and race with having sex within the past3 months, number of partners, condom use, length of time one knew one's sexual partner, substance use, and asking one's partner about sexualhistory. Using Chi-Square Automatic Interaction Detection (CHAID), the strongest predictor of condom use was noted to be gender, and the strongest predictor of number of partners was race. The findings of this study indicate that HIV risk factors vary dependingon a college student's ethnicity, gender, academic status, and substanceuse. Most importantly, African American men, particularly men who use drugs, and White and Asian men who use alcohol tend to report higher numbers of sexual partners. Females, particularly upperclass White females, and White men who do not use alcohol report infrequent condom use. These findings areuseful for health educators who have begun to recognize the importance ofconsidering the HIV risk factors of students and incorporating informationrelated to these factors into HIV prevention programs. From the results ofthis study, we have several suggestions that health educators and researchersmay want to consider when developing programs for college students: 1. Although students may not need extensive information about basic HIVfacts, they may need reinforcement of the information. In particular, students need to be made aware that lambskin condoms do not offer protection against HIV transmission. 2. Females need to be encouraged and taught the skills to negotiate theuse of and to actually use condoms. These skills need to be reinforced throughout college, particularly as women adopt other methods of birth control (i.e., the pill). 3. The general acceptance of condom use among African Americans and Asians may be a useful tool for the health educator. Promoting and reinforcingthis norm and behavior, while addressing some of the other risk factors inthese groups, may be a particularly effective approach to HIV prevention. 4. For White students whose condom use rates are lower, messages can include the use of condoms for STD and pregnancy protection. Messages for male students could include control over preventing pregnancy or sharing control for pregnancy prevention. 5. Couples often abandon using condoms when they feel they know each other “well enough.” Some guidelines for when to give up condoms might also be given to provide couples with responsible and realistic directions for minimizing their risk when choosing to engage in unprotected sex. These guidelines would include HIV testing two times at least 6 months apart, no evidence of STDs in either partner, and a commitment of both partners to a monogamous relationship. 6. When addressing the number of sexual partners as a risk factor, African American men and women may hold the greatest potential for change, given the greater likelihood of multiple partners in these groups. 7. With respect to drug and alcohol use, health educators may want to include discussions about the influence of drugs (particularly for African American students) and alcohol (particularly for White and Asian students) on inhibiting logical decision-making as it relates to sexual intercourse.     

Sleep deprivation as a probe in the elderly

Decreased slow-wave sleep (SWS) and sleep continuity are major effects of healthy aging and of associated psychopathological states. Using sleep deprivation, we studied the extent to which age- and psychopathology-related sleep "decay" is reversible in aged normal, depressed, and demented subjects. Depression or probable Alzheimer's dementia compromised the augmentation of sleep continuity and SWS seen in healthy elderly following sleep deprivation. Rapid eye movement (REM) latency decreased during recovery sleep in the controls but increased in both patient groups. Compared with demented patients, depressed elderly had greater severity of sleep continuity disturbance both before and after sleep deprivation, a more protracted course of recovery sleep, and increased slow-wave density in the second non-REM (NREM) sleep period (during recovery). The REM sleep time was diminished in dementia compared with depression both at baseline and during recovery sleep. These differential effects of age, health, and neuropsychiatric disease on recovery from sleep loss are relevant to recovery or reversal theories of sleep and have implications for daytime well-being in the elderly.     

Cocoa Flavanols Adjuvant to an Oral Nutritional Supplement Acutely Enhances Nutritive Flow in Skeletal Muscle without Altering Leg Glucose Uptake Kinetics in Older Adults

Ageing is associated with postprandial muscle vascular and metabolic dysfunction, suggesting vascular modifying interventions may be of benefit. Reflecting this, we investigated the impact of acute cocoa flavanol (450–500 mg) intake (versus placebo control) on vascular (via ultrasound) and glucose/insulin metabolic responses (via arterialised/venous blood samples and ELISA) to an oral nutritional supplement (ONS) in twelve healthy older adults (50% male, 72 ± 4 years), in a crossover design study. The cocoa condition displayed significant increases in m. vastus lateralis microvascular blood volume (MBV) in response to feeding at 180 and 240-min after ONS consumption (baseline: 1.00 vs. 180 min: 1.09 ± 0.03, p = 0.05; 240 min: 1.13 ± 0.04, p = 0.002), with MBV at these timepoints significantly higher than in the control condition (p < 0.05). In addition, there was a trend (p = 0.058) for MBV in m. tibialis anterior to increase in response to ONS in the cocoa condition only. Leg blood flow and vascular conductance increased, and vascular resistance decreased in response to ONS (p < 0.05), but these responses were not different between conditions (p > 0.05). Similarly, glucose uptake and insulin increased in response to ONS (p < 0.05) comparably between conditions (p > 0.05). Thus, acute cocoa flavanol supplementation can potentiate oral feeding-induced increases in MBV in older adults, but this improvement does not relay to muscle glucose uptake.     

A review of burn symptoms and potential novel neural targets for non-invasive brain stimulation for treatment of burn sequelae

Burn survivors experience myriad associated symptoms such as pain, pruritus, fatigue, impaired motor strength, post-traumatic stress, depression, anxiety, and sleep disturbance. Many of these symptoms are common and remain chronic, despite current standard of care. One potential novel intervention to target these post burn symptoms is transcranial direct current stimulation (tDCS). tDCS is a non-invasive brain stimulation (NIBS) technique that modulates neural excitability of a specific target or neural network. The aim of this work is to review the neural circuits of the aforementioned clinical sequelae associated with burn injuries and to provide a scientific rationale for specific NIBS targets that can potentially treat these conditions. We ran a systematic review, following the PRISMA statement, of tDCS effects on burn symptoms. Only three studies matched our criteria. One was a feasibility study assessing cortical plasticity in chronic neuropathic pain following burn injury, one looked at the effects of tDCS to reduce pain anxiety during burn wound care, and one assessed the effects of tDCS to manage pain and pruritus in burn survivors. Current literature on NIBS in burn remains limited, only a few trials have been conducted. Based on our review and results in other populations suffering from similar symptoms as patients with burn injuries, three main areas were selected: the prefrontal region, the parietal area and the motor cortex. Based on the importance of the prefrontal cortex in the emotional component of pain and its implication in various psychosocial symptoms, targeting this region may represent the most promising target. Our review of the neural circuitry involved in post burn symptoms and suggested targeted areas for stimulation provide a spring board for future study initiatives.     

Mortality prognostication scores do not predict long-term,health-related quality of life after burn: A burn model system national database study

ObjectiveDespite improved mortality rates after burn injury, many patients face significant long-term physical and psychosocial disabilities. We aimed to determine whether commonly used mortality prognostication scores predict long-term, health-related quality of life after burn injury. By doing so, we might add evidence to support goals of care discussions and facilitate shared decision-making efforts in the hours and days after a life-changing injury.MethodsWe used the multicenter National Institute of Disability, Independent Living and Rehabilitation Research Burn Model System database (1994–2019) to analyze SF-12 physical (PCS) and mental component (MCS) scores among survivors one year after major burn injury. Ninety percent of the observations were randomly assigned to a model development dataset. Multilevel, mixed-effects, linear regression models determined the relationship between revised Baux and Ryan Scores and SF-12 measures. Additionally, we tested a model with disaggregated independent and other covariates easily obtained around the time of index admission: age, sex, race, burn size, inhalation injury. Residuals from the remaining 10% of observations in the validation dataset were examined.ResultsThe analysis included 1606 respondents (median age 42 years, IQR 28–53 years; 70% male). Median burn size was 16% TBSA (IQR 6–30) and 13% of respondents sustained inhalation injury. Higher revised Baux and Ryan Scores and age, burn size, and inhalation injury were significantly correlated with lower PCS, but were not correlated with MCS. Female sex, black race, burn size, and inhalation injury correlated with lower MCS. All models poorly explained the variance in SF-12 scores (adjusted r² 0.01–0.12).ConclusionHigher revised Baux and Ryan Scores negatively correlated with long-term physical health, but not mental health, after burn injury. Regardless, the models poorly explained the variance in SF-12 scores one year after injury. More accurate models are needed to predict long-term, health-related quality of life and support shared decision-making during acute burn care.     

Guidelines for gastrostomy tube placement and enteral nutrition in patients with severe,refractory hypoglycemia after gastric bypass

BackgroundPostbariatric hypoglycemia (PBH) affects up to 38% of Roux-en-Y gastric bypass (RYGB) patients. Severe cases are refractory to diet and medications. Surgical treatments including bypass reversal and pancreatectomy are highly morbid and hypoglycemia often recurs. We have developed a highly effective method of treatment by which enteral nutrition administered through a gastrostomy (G) tube placed in the remnant stomach replaces oral diet: if done correctly this reverses hyperinsulinemia and hypoglycemia, yielding substantial health and quality of life benefits for severely affected patients.ObjectivesTo provide clinical guidelines for placement of a G-tube to treat postRYGB hypoglycemia, including candidate selection, preoperative evaluation, surgical considerations, and post-RYGB management.SettingStanford University Hospital and Clinics.MethodsBased on our relatively large experience with placing and managing G-tubes for PBH treatment, an interdisciplinary task force developed guidelines for practitioners.ResultsA team approach (endocrinologist, dietitian, surgeon, psychologist) is recommended. Appropriate candidates have a history of RYGB, severe hypoglycemia refractory to medical-nutrition therapy, and significantly affected quality of life. Preoperative requirements include education and expectation setting, determination of initial enteral feeding program, and establishing service with a home enteral provider. Close postoperative follow-up is needed to ensure success and may require adjustments in formula and mode/rate of delivery to optimize tolerance and meet nutritional goals. G-tube nutrition must fully replace oral nutrition to prevent hypoglycemia.ConclusionsG-tube placement in the remnant stomach represents a relatively well-tolerated and effective treatment for severe, refractory hypoglycemia after RYGB.     

Factors associated with completion of patient surveys 1 year after bariatric surgery

BackgroundPatient-reported outcomes (PRO) obtained from follow-up survey data are essential to understanding the longitudinal effects of bariatric surgery. However, capturing data among patients who are well beyond the recovery period of surgery remains a challenge, and little is known about what factors may influence follow-up rates for PRO.ObjectivesTo assess the effect of hospital practices and surgical outcomes on patient survey completion rates at 1 year after bariatric surgery.SettingProspective, statewide, bariatric-specific clinical registry.MethodsPatients at hospitals participating in the Michigan Bariatric Surgery Collaborative are surveyed annually to obtain information on weight loss, medication use, satisfaction, body image, and quality of life following bariatric surgery. Hospital program coordinators were surveyed in June 2017 about their practices for ensuring survey completion among their patients. Hospitals were ranked based on 1-year patient survey completion rates between 2011 and 2015. Multivariable regression analyses were used to identify associations between hospital practices, as well as 30-day outcomes, on hospital survey completion rankings.ResultsOverall, patient survey completion rates at 1 year improved from 2011 (33.9% ± 14.5%) to 2015 (51.0% ± 13.0%), although there was wide variability between hospitals (21.1% versus 77.3% in 2015). Hospitals in the bottom quartile for survey completion rates had higher adjusted rates of 30-day severe complications (2.6% versus 1.7%, respectively; P = .0481), readmissions (5.0% versus 3.9%, respectively; P = .0157), and reoperations (1.5% versus .7%, respectively; P = .0216) than those in the top quartile. While most hospital practices did not significantly impact survey completion at 1 year, physically handing out surveys during clinic visits was independently associated with higher completion rates (odds ratio, 13.60; 95% confidence interval, 1.99?93.03; P =.0078).ConclusionsHospitals vary considerably in completion rates of patient surveys at 1 year after bariatric surgery, and lower rates were associated with hospitals that had higher complication rates. Hospitals with the highest completion rates were more likely to physically hand surveys to patients during clinic visits. Given the value of PRO on longitudinal outcomes of bariatric surgery, improving data collection across multiple hospital systems is imperative.     

T cell antigenicity and immunogenicity of allogeneic exosomes

Extracellular vesicles, including exosomes, are regularly released by allogeneic cells after transplantation. Recipient antigen-presenting cells (APCs) capture these vesicles and subsequently display donor MHC molecules on their surface. Recent evidence suggests that activation of alloreactive T cells by the so-called cross-dressed APCs plays an important role in initiating the alloresponse associated with allograft rejection. On the other hand, whether allogeneic exosomes can bind to T cells on their own and activate them remains unclear. In this study, we showed that allogeneic exosomes can bind to T cells but do not stimulate them in vitro unless they are cultured with APCs. On the other hand, allogeneic exosomes activate T cells in vivo and sensitize mice to alloantigens but only when delivered in an inflammatory environment.     

Transcriptomic and Immunophenotypic Characterization of Tumor Immune Microenvironment in Squamous Cell Carcinoma of the Oral Tongue

The tumor immune microenvironment of oral tongue squamous cell carcinoma may be accountable for differences in clinical behavior, particularly between different age groups. We performed RNA expression profiling and evaluated tumor infiltrating lymphocytes (TILs) and their T-cell subsets in order to assess the functional status of oral tongue squamous cell carcinoma tumor microenvironment and detect potentially clinically useful associations. Archival surgical pathology material from sixteen oral tongue squamous cell carcinoma patients was microscopically evaluated for TIL densities. RNA was extracted from macrodissected whole tumor sections and normal controls and RNA expression profiling was performed by the NanoString PanCancer IO 360 Gene Expression Panel. Immunostains for CD4, CD8 and FOXP3 were evaluated manually and by digital image analysis. Oral tongue squamous cell carcinomas had increased TIL densities, numerically dominated by CD4 + T cells, followed by CD8 + and FOXP3 + T cells. RNA expression profiling of tumors versus normal controls showed tumor signature upregulation in inhibitory immune signaling (CTLA4, TIGIT and PD-L2), followed by inhibitory tumor mechanisms (IDO1, TGF-β, B7-H3 and PD-L1). Patients older than 44 years showed a tumor microenvironment with increased Tregs and CTLA4 expression. Immunohistochemically assessed CD8% correlated well with molecular signatures related to CD8 + cytotoxic T-cell functions. FOXP3% correlated significantly with CTLA4 upregulation. CTLA4 molecular signature could be predicted by FOXP3% assessed by immunohistochemistry (R² = 0.619, p = 0.026). Oral tongue squamous cell carcinoma hosts a complex inhibitory immune microenvironment, partially reflected in immunohistochemically quantified CD8 + and FOXP3 + T-cell subsets. Immunohistochemistry can be a useful screening tool for detecting tumors with upregulated expression of the targetable molecule CTLA4.Electronic supplementary materialThe online version of this article (10.1007/s12105-020-01229-w) contains supplementary material, which is available to authorized users.