Exploring medical students' perceptions of the challenges and benefits of volunteering in the intensive care unit during the COVID-19 pandemic: a qualitative study.

OBJECTIVES: In March 2020, the WHO declared SARS-CoV-2 a pandemic. Hospitals across the world faced staff, bed and supply shortages, with some European hospitals calling on medical students to fill the staffing gaps. This study aimed to document the impact of volunteering during the COVID-19 pandemic on students' professional development, resilience and future perceived career choices. DESIGN: This is a retrospective, qualitative study of student reflections, using purposive sampling.The Royal College of Surgeons in Ireland (RCSI) University of Medicine and Health Sciences recruited 26 medical student volunteers to assist in pronation and supination of ventilated patients affected by SARS-CoV-2. These students were invited to complete an anonymous survey based on their experiences as volunteers. Thematic analysis was performed on these written reflections. RESULTS: The results showed that volunteering during the COVID-19 pandemic developed key skills from RCSI's medical curriculum, significantly fostered medical students' resilience and guided their career choices. Major areas of development included communication, teamwork, compassion and altruism, which are not easily developed through the formal curriculum. A further area that was highlighted was the importance of evidence-based health in a pandemic. Finally, our respondents were early stage medical students with limited clinical exposure. Some found the experience difficult to cope with and therefore supports should be established for students volunteering in such a crisis. CONCLUSION: These results suggest that clinical exposure is an important driver in developing students' resilience and that volunteering during a pandemic has multiple benefits to students' professional development and professional identity formation.

ß-Methylamino-L-alanine-induced protein aggregation in vitro and protection by L-serine.

The cyanobacterial non-protein amino acid α-amino-ß-methylaminopropionic acid, more commonly known as BMAA, was first discovered in the seeds of the ancient gymnosperm Cycad circinalis (now Cycas micronesica Hill). BMAA was linked to the high incidence of neurological disorders on the island of Guam first reported in the 1950s. BMAA still attracts interest as a possible causative factor in amyotrophic lateral sclerosis (ALS) following the identification of ALS disease clusters associated with living in proximity to lakes with regular cyanobacterial blooms. Since its discovery, BMAA toxicity has been the subject of many in vivo and in vitro studies. A number of mechanisms of toxicity have been proposed including an agonist effect at glutamate receptors, competition with cysteine for transport system xc_ and other mechanisms capable of generating cellular oxidative stress. In addition, a wide range of studies have reported effects related to disturbances in proteostasis including endoplasmic reticulum stress and activation of the unfolded protein response. In the present studies we examine the effects of BMAA on the ubiquitin-proteasome system (UPS) and on chaperone-mediated autophagy (CMA) by measuring levels of ubiquitinated proteins and lamp2a protein levels in a differentiated neuronal cell line exposed to BMAA. The BMAA induced increases in oxidised proteins and the increase in CMA activity reported could be prevented by co-administration of L-serine but not by the two antioxidants examined. These data provide further evidence of a protective role for L-serine against the deleterious effects of BMAA.

Denial of Alcohol Treatment Need among Baby Boomers across Time: Implications for Social Work.

As baby boomers continue to enter older adulthood in the coming decades, research suggests that this cohort is expected to exhibit changes in alcohol usage and treatment need patterns compared to previous older-adult cohorts. The literature suggests that unmet alcohol treatment need may be related to denial of treatment need among baby boomers who possess a diagnosable alcohol-use disorder (AUD). Therefore, this study explores potential risk and protective factors predicting alcohol-use among baby boomers who d\eny treatment need at two time periods. Data was obtained from the National Survey of Drug and Health (NSDUH). Variable selection procedures were performed at each time period, resulting in two predictive models for baby boomers who denied alcohol treatment need when treatment was indicated by a concurrent diagnosable alcohol-use disorder. The primary findings suggest that generalized, nonspecific alcohol treatment may be ineffective for treating AUD baby boomers who deny alcohol treatment need. Rather, as baby boomers continue to enter older adulthood, individualized specialty treatments may be needed in order to provide effective alcohol treatment for this unprecedentedly large birth cohort.

Predictors of Alcohol Use Disorders Among Baby Boomers Across the Life Course.

Research suggests that baby boomers entering older adulthood may possess unique alcohol use patterns over time. Using the life course perspective as a guiding framework, this empirical study sought to examine correlates of alcohol use disorders among baby boomers by examining representative data from the National Survey on Drug Use and Health at two points in time, 1998 (N = 6,213) and 2010 (N = 5,880). Results from logistic regression analyses suggest that predictors of alcohol use disorders evolve over time as baby boomers continue to age. Risk factors for alcohol use disorders among baby boomers may include concurrent unprescribed pain reliever use, p < .01, while protective factors such as income, p < .01, and social supports, p = .01, may be of increased importance. Based on the findings of this study, practice implications and future research are discussed.

The incidence and fate of endoleaks vary between ruptured and elective endovascular abdominal aortic aneurysm repair.

BACKGROUND: The number of ruptured abdominal aortic aneurysm (r-AAA) patients who are treated by endovascular means is increasing as ruptured endovascular aneurysm repair (r-EVAR) enters the mainstream. However, even today, data on the incidence and behavior of endoleaks after r-EVAR are scarce. This study analyzed whether endoleaks behave differently after EVAR for rupture vs elective AAA repair. METHODS: From 2002 to 2013, there were 2052 patients who underwent EVAR for treatment of rupture (n = 166 [8.1%]) and elective repair (n = 1886 [91.9%]) of infrarenal AAA. Follow-up included computed tomography angiography at 1 month, at 6 months, and yearly thereafter. All type I and type III endoleaks were treated at the time of or shortly after the diagnosis. Persistent type II endoleaks at >6 months after EVAR without a decrease in AAA sac underwent translumbar or transfemoral embolization procedures. Data were prospectively collected in a vascular database. RESULTS: During a mean follow-up of 30 months, patients had a significantly lower incidence of type II endoleaks after r-EVAR compared with elective endovascular aneurysm repair (e-EVAR; n = 15 [9.0%] vs n = 380 [20.2%]; P < .01). Although the incidence of type I endoleaks is similar after r-EVAR (n = 9 [5.4%] and e-EVAR (n = 83 [4.4%]; P = .68), the r-EVAR patients required stent graft explantation more frequently (n = 9 [5.4%] vs n = 20 [1.1%]; P < .01). Whereas the need for secondary intervention was comparable in both r-EVAR (n = 33 [19.9%]) and e-EVAR (n = 439 [23.3%]; P = .37) groups, patients undergoing percutaneous embolization procedures trended toward significance between the two groups (n = 11 [6.6%] vs n = 216 [11.5%]; P = .06) with endoleaks. CONCLUSIONS: Compared with e-EVAR, patients who undergo r-EVAR experience a similar incidence of type I endoleaks and a significantly lower incidence of type II endoleaks. The endoleaks in both e-EVAR and r-EVAR patients can frequently be managed by endovascular means. However, r-EVAR patients with type I and type II endoleaks are at a significantly higher risk for stent graft explantation.

Comparison of Bruch's Membrane Opening Minimum Rim Width Among Those With Normal Ocular Health by Race.

PURPOSE: To examine if racial differences in Bruch's membrane opening minimum rim width (BMO-MRW) in spectral-domain optical coherence tomography (SDOCT) exist, specifically between people of African descent (AD) and European descent (ED) in normal ocular health. DESIGN: Cross-sectional study. METHODS: Patients presenting for a comprehensive eye examination at retail-based primary eye clinics were enrolled based on ≥1 of the following at-risk criteria for glaucoma: AD aged ≥40 years, ED aged ≥50 years, diabetes, family history of glaucoma, and/or pre-existing diagnosis of glaucoma. Participants with normal optic nerves on examination received SDOCT of the optic nerve head (24 radial scans). Global and regional (temporal, superotemporal, inferotemporal, nasal, superonasal, and inferonasal) BMO-MRW were measured and compared by race using generalized estimating equations. Models were adjusted for age, sex, and BMO area. RESULTS: SDOCT scans from 269 eyes (148 participants) were included in the analysis. Mean global BMO-MRW declined as age increased. After adjusting for age, sex, and BMO area, there was not a statistically significant difference in mean global BMO-MRW by race (P = .60). Regionally, the mean BMO-MRW was lower in the crude model among AD eyes in the temporal, superotemporal, and nasal regions and higher in the inferotemporal, superonasal, and inferonasal regions. However, in the adjusted model, these differences were not statistically significant. CONCLUSIONS: BMO-MRW was not statistically different between those of AD and ED. Race-specific normative data may not be necessary for the deployment of BMO-MRW in AD patients.

Management and Outcomes of Bleeding Events in Patients in the Emergency Department Taking Warfarin or a Non-Vitamin K Antagonist Oral Anticoagulant.

BACKGROUND: Most comparisons of bleeding patients who are taking warfarin or a non-vitamin K oral anticoagulant (NOAC) have been limited to admitted patients and major bleeding events in well-controlled, clinical trial settings. OBJECTIVES: We describe the clinical characteristics, interventions, and outcomes in patients who are taking warfarin or a NOAC who presented to the emergency department (ED) with any bleeding event. METHODS: We conducted a structured, retrospective, observational study of nonvalvular atrial fibrillation, pulmonary embolism, or deep vein thrombosis warfarin- or NOAC-treated patients presenting with any bleeding event to a large, academic ED between January 2012 and March 2015. We used descriptive statistics to summarize baseline characteristics, treatments, and outcomes and performed subgroup analyses based on the type of anticoagulant and site of bleeding. RESULTS: The electronic search yielded 95 cases of patients taking a NOAC (i.e., dabigatran [33], rivaroxaban [32], or abixaban [30]) and 342 patients taking warfarin. Reversal agents were rarely used in all anticoagulant groups. Case fatality rates were similar among warfarin- and NOAC-treated patients for gastrointestinal bleeding (7% vs. 7%) and intracranial hemorrhage (18% vs. 4%), respectively. After adjustment for other factors, only intracranial hemorrhage (odds ratio 4.4; 95% confidence interval 1.4-13.3) was associated with mortality. CONCLUSIONS: Despite the rare use of reversal strategies, mortality was low and outcomes were comparable among patients with bleeding events presenting to the ED while taking a NOAC compared with warfarin.

Role of vacuolar membrane proton pumps in the acidification of protein storage vacuoles following germination.

During soybean (Glycine max (L.) Merrill) seed development, protease C1, the proteolytic enzyme that initiates breakdown of the storage globulins ß-conglycinin and glycinin at acidic pH, is present in the protein storage vacuoles (PSVs), the same subcellular compartments in seed cotyledons where its protein substrates accumulate. Actual proteolysis begins to be evident 24 h after seed imbibition, when the PSVs become acidic, as indicated by acridine orange accumulation visualized by confocal microscopy. Imidodiphosphate (IDP), a non-hydrolyzable substrate analog of proton-translocating pyrophosphatases, strongly inhibited acidification of the PSVs in the cotyledons. Consistent with this finding, IDP treatment inhibited mobilization of ß-conglycinin and glycinin, the inhibition being greater at 3 days compared to 6 days after seed imbibition. The embryonic axis does not appear to play a role in the initial PSV acidification in the cotyledon, as axis detachment did not prevent acridine orange accumulation three days after imbibition. SDS-PAGE and immunoblot analyses of cotyledon protein extracts were consistent with limited digestion of the 7S and 11S globulins by protease C1 starting at the same time and proceeding at the same rate in detached cotyledons compared to cotyledons of intact seedlings. Embryonic axis removal did slow down further breakdown of the storage globulins by reactions known to be catalyzed by protease C2, a cysteine protease that normally appears later in seedling growth to continue the storage protein breakdown initiated by protease C1.

Prescription pain reliever misuse prevalence, correlates, and origin of possession throughout the life course.

INTRODUCTION: While a considerable amount of information is available concerning who is most likely to engage in prescription pain reliever misuse, few studies have examined whether the correlates of pain reliever misuse and sources of pain reliever possession are consistent across the life span. METHODS: Data from the 2011-2012 National Survey in Drug Use and Health (NSDUH). Multivariate logistic regression examined clinical and social correlates of past-year pain reliever misuse, stratified by age. Additionally, bivariate analyses examined sources of pain reliever possession, and whether these origins differ by age. RESULTS: Among respondents, 4.7% reported past-year prescription pain reliever misuse. Prevalence for individuals aged 12 to 17 was 5.9%, 18 to 25 was 10.2%, 26-34 was 7.7%, 35 to 49 was 4.3%, and individuals aged 50 or older was 1.7%. While many social and clinical correlates of pain reliever misuse emerged among younger respondents, these correlates diminished in significance among older adults. Only past-year illicit drug use disorders (marijuana, cocaine, crack cocaine, heroin, and hallucinogen use) was a significant predictor of pain reliever misuse among all age groups. Also, older adults were more likely to report pain reliever possession from multiple medical doctors, whereas younger individuals were more likely to possess pain reliever from friends/relatives or through purchase from a drug dealer/stranger. CONCLUSIONS: Increased efforts to better screen for illicit drug use and greater efforts to coordinate patient prescription records among medical care providers may be high priorities in developing interventions to reduce rates of misuse of prescription pain relievers, especially among older adults.

Social networks and alcohol use disorders: findings from a nationally representative sample.

BACKGROUND: While some argue that social network ties of individuals with alcohol use disorders (AUD) are robust, there is evidence to suggest that individuals with AUDs have few social network ties, which are a known risk factor for health and wellness. OBJECTIVES: Social network ties to friends, family, co-workers and communities of individuals are compared among individuals with a past-year diagnosis of alcohol dependence or alcohol abuse to individuals with no lifetime diagnosis of AUD. METHOD: Respondents from Wave 2 of the National Epidemiologic Survey on Alcohol Related Conditions (NESARC) were assessed for the presence of past-year alcohol dependence or past-year alcohol abuse, social network ties, sociodemographics and clinical characteristics. RESULTS: Bivariate analyses showed that both social network size and social network diversity was significantly smaller among individuals with alcohol dependence, compared to individuals with alcohol abuse or no AUD. When social and clinical factors related to AUD status were controlled, multinomial logistic models showed that social network diversity remained a significant predictor of AUD status, while social network size did not differ among AUD groups. CONCLUSION: Social networks of individuals with AUD may be different than individuals with no AUD, but this claim is dependent on specific AUD diagnosis and how social networks are measured.

Determination of ultrafilterable prolactin: elimination of macroprolactin interference with a monomeric prolactin-selective sample pretreatment.

CONTEXT: Macroprolactin (macroPRL), present in as many as 25% of serum specimens with elevated serum prolactin concentrations, can cause apparent hyperprolactinemia in the absence of clinical features and lead to unnecessary clinical, laboratory, and neuroradiological workups. OBJECTIVE: To develop an ultrafiltration method that eliminates macroPRL interference from PRL immunoassays. DESIGN: The method involves centrifugation of undiluted serum in a Centricon-100 filter device followed by a PRL assay of the serum ultrafiltrate. RESULTS: Ultrafiltrates prepared by this technique are devoid of gamma globulins and contain (mean +/- SE) 19% +/- 7% of the albumin concentration of the original serum. These ultrafiltrates contain 85% +/- 7% of the total PRL immunoreactivity of serum spiked with 23 kd recombinant human prolactin (rHuPRL) and less than 2% of the 50 kd big PRL (bPRL) of whole serum. The fractional recovery of ultrafilterable PRL (uPRL) from serum samples of 54 female patients was 0.78 (confidence interval 0.73-0.83) of the total. The run-to-run coefficient of variation of the uPRL assay was 4.3%. The uPRL concentration (mean +/- SD) in a group of healthy female controls was 8.0 +/- 3.1 ng/mL. CONCLUSIONS: Ultrafiltration is a rapid and simple method for eliminating analytical interference by macroPRL. Ultrafiltrates can be analyzed by most, if not all, currently available PRL immunoassays and represent a practical and precise alternative to gel filtration chromatography for the estimation of the monomeric prolactin concentration of serum.

Clear cell sarcoma of the small bowel: a potential pitfall. Case report.

Clear cell sarcoma (soft-part melanoma) is a very rare entity with a distinctive histopathologic and molecular profile. Herein, we present the sixth reported case of a primary gastrointestinal clear cell sarcoma discovered in a 21-year-old woman. The patient underwent numerous tests prior to the diagnosis of her small bowel pathology, including the use of capsule endoscopy, which allowed for visualization and final localization of the tumour. Additionally, we discuss this rare type of sarcoma that affects young adults and has a poor prognosis characterized by the balanced chromosomal translocation t(12;22)(q13;q12) with special emphasis on the necessity for pathologists to be able to distinguish it from melanoma -- potentially a major pitfall in diagnosis.

Uncovering histologic criteria with prognostic significance in toxic epidermal necrolysis.

OBJECTIVE: To identify histologic criteria and prognostic significance in patients with toxic epidermal necrolysis (TEN), a frequently lethal disease that usually represents an adverse drug reaction. DESIGN: Retrospective analysis of clinical records and histologic material from a 10-year period (1994-2004). Two investigators blinded to clinical data reviewed hematoxylin-eosin-stained sections. SETTING: North American tertiary care, university-based burn unit. Patients Thirty-seven patients treated for TEN between 1994 and 2004 who had sloughing of 30% or more of their total body surface area and who underwent skin punch biopsies immediately following admission. Main Outcome Measure The degree of dermal mononuclear (DM) inflammation was graded (sparse, moderate, or extensive) at least 2 high-power fields (HPF) away from the perimeter of epidermal detachment, and the mean number of DM cells/5 HPF was quantified for each patient. Clinical records were reviewed and the following data extracted: age, history of cancer, percentage of total body surface area slough, heart rate, and serum glucose, bicarbonate, and serum urea nitrogen values on admission. Severity scores for TEN (SCORTEN) were calculated, and clinical outcome was recorded as survived or died during hospitalization. RESULTS: Extent of inflammation was assessed by categorizing the mean +/- SD DM cell counts as follows: sparse, 161 +/- 36 cells/HPF (n = 15); moderate, 273 +/- 76 cells/HPF (n = 15); and extensive, 392 +/- 124 cells/HPF (n = 7). There was good concordance between observer ratings (P<.001). While 73% of patients (n = 11) with sparse inflammation survived, only 47% (n = 7) with moderate and 29% (n = 2) with extensive inflammation survived. The accuracy in predicting patient outcome was 65% using grade of inflammation, 68% with mean cell count, and 71% with SCORTEN. CONCLUSIONS: There is a histologic spectrum with TEN that ranges from sparse to extensive DM inflammation, and degree of inflammation predicts clinical outcome approximately as well as SCORTEN. Future clinical trials should consider the possibility that various patient subsets exist within the TEN population, and a role for immunocytes needs to be critically reevaluated in this devastating disease.

Cytologic features of recurrent lymphoma involving the urinary bladder.

Recurrent lymphoma of the bladder only occasionally presents with genitourinary symptoms, and there are very few cases in the literature reporting the cytologic findings of involvement of the urinary bladder by lymphoma. We report the findings from a case of diffuse large B-cell lymphoma with immunoblastic morphology that was identified in a bladder barbotage specimen of a 77-year-old man who presented with recurrent urinary tract infection and hematuria. We describe the cytomorphological features of lymphoma cells in the urine and discuss the differential diagnoses. Correlation of cytologic findings with immunohistochemical results is crucial in the diagnosis of lymphoma involving the urinary bladder.

Graft-versus-host disease of the skin: life and death on the epidermal edge.

Despite impressive advances in the field of allogeneic hematopoietic transplantation, graft versus host disease (GVHD) remains a significant obstacle to be overcome; it would enhance the safety and efficacy of this life-saving therapy. This review provides a framework for understanding the molecular and cellular basis underlying GVHD. We propose a 3-phase model of GVHD that highlights the importance of the conditioning regimen on the recipient tissues administered prior to infusion of donor bone marrow inoculum. A novel skin explant model, designed to take into consideration the immunobiological consequences of conditioning regimens on resident host cells, is proposed to advance our understanding of GVHD and serve as a potential prognostic tool when allogeneic recipient/donor combinations are being contemplated in the clinic. Within this review, specific emphasis is placed on the importance of defining the apoptotic machinery engaged in epidermal keratinocytes triggered by both conditioning regimens, and by host resident and recruited immunocytes and soluble mediators produced at sites of injury. The review is completed with a working model for cutaneous GVHD. Although the skin is highlighted because of its accessibility for clinical observations and serial sampling opportunities, lessons learned from studies of cutaneous GVHD are likely to provide valuable insights into GVHD occurring in the gastrointestinal tract, lung, and liver. With new insights designed to better predict and prevent GVHD and novel agents designed to treat GVHD, overcoming this current impediment to successful bone marrow transplantation should become increasingly feasible.

Extramammary Paget disease of the scrotum with features of Bowen disease.

The scrotum is an uncommon site for the presentation of extramammary Paget disease (EMPD). We describe a case of EMPD that was discovered in a patient who had been previously diagnosed and treated for squamous cell carcinoma in situ of the scrotum 3 years earlier. Pathologic examination of the current scrotectomy specimen revealed an erythematous patch with areas of pale induration. Microscopic examination revealed areas with the characteristic histology of Paget disease adjacent to areas characteristic of Bowen disease. Immunohistochemical findings demonstrated a strong expression of carcinoembryonic antigen, cytokeratin 7, and low-molecular-weight cytokeratins (CAM 5.2) in both of these areas, giving support to the overall diagnosis of EMPD. High-molecular-weight cytokeratins (34betaE12) were uncharacteristically expressed in the cytoplasm of the Paget cells with equal or greater strength than in the surrounding keratinocytes, suggesting some degree of squamous differentiation. Very few publications have reported the coexistence of EMPD with squamous cell carcinoma in situ, occurring mostly in the vulva. To our knowledge, our case is the first report of scrotal EMPD with features of Bowen disease. Our findings support the theory that primary EMPD arises multifocally from multipotential epidermal cells.