A systematic review and meta-analysis of morbidity and pancreatic fistula after distal pancreatectomy with versus without prophylactic intra-abdominal drainage.

BACKGROUND: The omission of a prophylactic intra-abdominal drainage has been under debate in pancreatic surgery due to the high risk of complications and especially of postoperative pancreatic fistula (POPF). Recently, the second randomized controlled trial (RCT) and two propensity score-matched comparative studies assessing risks and benefits of a no-drainage policy versus prophylactic drainage after distal pancreatectomy (DP) have been published. This systematic review with meta-analysis provides an updated summary of the available evidence on this topic. METHODS: RCTs and non-randomized comparative studies (NCS) investigating outcomes of no drainage versus drainage after DP were searched systematically in MEDLINE, Embase and CENTRAL. Random effects meta-analyses were performed, and the results presented as weighted odds ratios (OR) or mean differences (MD) with their corresponding 95% confidence intervals (c.i.). Subgroup analyses were performed to account for inter-study heterogeneity between RCTs and NCS. RESULTS: Two RCTs and six NCS with a total of 3,610 patients undergoing DP were included of whom 1,038 (28.8%) patients did not receive prophylactic drainage. A no-drainage policy was associated with significantly lower risks of POPF (OR 0.38, 95% c.i. 0.25-0.56; P<0.00001), reduced major morbidity (OR 0.64, 95% c.i. 0.47-0.89; P=0.008), less reinterventions (OR 0.70, 95% c.i. 0.52-0.95; P=0.02) and fewer readmissions (OR 0.69, 95% c.i. 0.54-0.88; P=0.003) as well as shorter length of hospital stay (MD -1.74, 95% c.i. -2.70- -0.78; P=0.0004). Subgroup analyses including only RCTs confirmed benefits of the no-drainage policy. CONCLUSION: A no-drainage policy is associated with reduced POPF and morbidity and can therefore be recommended as standard procedure in patients undergoing DP.

Expansion of osteopathic medicine practitioner education on substance use disorders.

CONTEXT: Medical school graduates are generally not well prepared to treat patients with substance use disorders (SUDs), even though opioid overdose deaths in the United States have increased in recent years. When it comes to training in SUDs, osteopathic medicine lags far behind allopathic medicine. It was only in 2019 that the American Osteopathic Association approved Board Certification in Addiction Medicine to help combat the opioid epidemic. Few articles have been published in the literature pertaining to substance use education for osteopathic students and trainees. OBJECTIVES: The goal of this study was to expand the education of osteopathic medical students and primary care residents in SUDs and measure the effect that education had on the attitudes and knowledge of student and residents about SUDs. METHODS: This study collected anonymous data in the form of a voluntary online survey from third- and fourth-year students at an osteopathic medical school and family medicine residents. The survey was completed by 115 students and 29 family medicine residents. Participants completed a pretest survey and then participated in the Physician Undergraduate and Resident Substance Use Education (PURSUE) curriculum developed by the researchers. This consisted of three online modules covering Screening, Brief Intervention, and Referral to Treatment (SBIRT), substance use assessments, and treatment of SUDs. Upon conclusion of the training modules, medical student participants then completed a posttest survey to assess for any changes in knowledge and attitude. Participants also answered questions related to clinical case scenarios involving patients at varying risk levels who were assessed utilizing SBIRT. RESULTS: Students and residents who participated in the training demonstrated an increase in their average scores between the pretest and posttest, indicating effectiveness in learning from the modules. The overall increase in average scores on the pretest and posttest was 6.5 %, which was determined to be statistically significant (p<0.01). Interestingly, participants who reported growing up in underprivileged circumstances performed worse than those participants who reported not growing up in underprivileged circumstances. CONCLUSIONS: The results of our project support the need and benefit of incorporating educational modules on this topic area within medical school curriculums and residency training. Expanding the number of healthcare workers proficient in providing this type of care in these types of settings will improve the quality of and access to medical care in some of our highest-need populations.

Empathy and the Medical Student House Call: The Effect of Clinical Settings on Empathy in Third Year Medical Students.

Objective: This study measured the effect the experience of house calls might have on third-year medical students. Methods: Students were surveyed via an anonymous online survey at the start of their geriatrics clerkship, again at the end of their clerkship, and once more three months later. Empathy was measured using the Jefferson Scale of Empathy - Student version (JSE) and student attitudes towards the geriatrics population was measured using the UCLA Geriatrics Attitudes Scale (GAS). Data were analyzed using SPSS version 27.0. Results: No changes in empathy were found when comparing students who completed house calls versus those who did not. However, students who trained in office settings were noted to have higher JSE scores at the three-month follow-up survey, students who worked in hospital settings had higher JSE scores at the completion of the clerkship, and student who worked in assisted living facilities had higher GAS scores at the completion of the clerkship. Conclusions: Teaching students ways to improve empathy can be challenging. The setting in which a student trains may be an area of focus for improving empathy among trainees and should be researched further.

Single-molecule Taq DNA polymerase dynamics.

Taq DNA polymerase functions at elevated temperatures with fast conformational dynamics-regimes previously inaccessible to mechanistic, single-molecule studies. Here, single-walled carbon nanotube transistors recorded the motions of Taq molecules processing matched or mismatched template-deoxynucleotide triphosphate pairs from 22° to 85°C. By using four enzyme orientations, the whole-enzyme closures of nucleotide incorporations were distinguished from more rapid, 20-µs closures of Taq's fingers domain testing complementarity and orientation. On average, one transient closure was observed for every nucleotide binding event; even complementary substrate pairs averaged five transient closures between each catalytic incorporation at 72°C. The rate and duration of the transient closures and the catalytic events had almost no temperature dependence, leaving all of Taq's temperature sensitivity to its rate-determining open state.

Different Single-Enzyme Conformational Dynamics upon Binding Hydrolyzable or Nonhydrolyzable Ligands.

Single-molecule measurements of protein dynamics help unveil the complex conformational changes and transitions that occur during ligand binding and catalytic processes. Using high-resolution single-molecule nanocircuit techniques, we have investigated differences in the conformational dynamics and transitions of lysozyme interacting with three ligands: peptidoglycan substrate, substrate-based chitin analogue, and indole derivative inhibitors. While processing peptidoglycan, lysozyme followed one of the two mechanistic pathways for the hydrolysis of the glycosidic bonds: a concerted mechanism inducing direct conformational changes from open to fully closed conformations or a nonconcerted mechanism involving transient pauses in intermediate conformations between the open and closed conformations. In the presence of either chitin or an indole inhibitor, lysozyme was unable to access the fully closed conformation where catalysis occurs. Instead, lysozymes' conformational closures terminated at slightly closed, "excited" conformations that were approximately one-quarter of the full hinge-bending range. With the indole inhibitor, lysozyme reached this excited conformation in a single step without any evidence of rate-liming intermediates, but the same conformational motions with chitin involved three hidden, intermediate processes and features similar to the nonconcerted peptidoglycan mechanism. The similarities suggest that these hidden processes involve attempts to accommodate imperfectly aligned polysaccharides in the active site. The results provide a detailed glimpse of the enzyme-ligand interplay at the crux of molecular recognition, enzyme specificity, and catalysis.

Discrimination of single-point mutations in unamplified genomic DNA via Cas9 immobilized on a graphene field-effect transistor.

Simple and fast methods for the detection of target genes with single-nucleotide specificity could open up genetic research and diagnostics beyond laboratory settings. We recently reported a biosensor for the electronic detection of unamplified target genes using liquid-gated graphene field-effect transistors employing an RNA-guided catalytically deactivated CRISPR-associated protein 9 (Cas9) anchored to a graphene monolayer. Here, using unamplified genomic samples from patients and by measuring multiple types of electrical response, we show that the biosensors can discriminate within one hour between wild-type and homozygous mutant alleles differing by a single nucleotide. We also show that biosensors using a guide RNA-Cas9 orthologue complex targeting genes within the protospacer-adjacent motif discriminated between homozygous and heterozygous DNA samples from patients with sickle cell disease, and that the biosensors can also be used to rapidly screen for guide RNA-Cas9 complexes that maximize gene-targeting efficiency.

The role of extracurricular activities and lectures in mitigating medical student burnout.

CONTEXT: Strong evidence throughout the literature highlights burnout as a significant and increasing problem among medical students, impacting students' ability to effectively care for and empathize with patients. OBJECTIVES: To examine how involvement in extracurricular activities and attendance at burnout lectures can impact burnout among medical students. METHODS: An anonymous digital survey including the Maslach Burnout Inventory (MBI) was sent to all students (n=765) at Rowan University School of Osteopathic Medicine. The survey included questions regarding the number of burnout/wellness lectures respondents had attended, the number of clubs in which the respondents participated, the number of hours spent in these clubs, and any leadership positions held by the respondents. RESULTS: Of the 765 students enrolled, 597 completed the survey. Results indicated that women participated in significantly more clubs than men (t[456]=-4.30; p<0.001). Men had higher scores on the depersonalization subscale of the MBI than women (t[463)=2.98; p<0.01]. There were no gender differences in emotional exhaustion or personal accomplishment. Linear regression analyses including gender and club participation as predictors of each of the burnout subscales indicated a significant interaction between gender and number of clubs (ß=0.34; p<0.05), in that more club participation was associated with higher depersonalization scores for women, but lower depersonalization scores for men. The number of wellness/burnout prevention lectures attended was not predictive of scores on any of the burnout subscales. CONCLUSIONS: Our results indicate the importance of understanding what drives burnout on the individual level and adapting interventions to suit the needs of individual students, rather than the student body as a whole.

Transforming a clerkship with telemedicine.

The coronavirus disease 2019 (COVID-19) pandemic had an overwhelming impact on both clinical practices and learning environments. On March 17th, 2020, the American Association of Colleges of Osteopathic Medicine and Commission on Osteopathic College Accreditation issued a statement recommending a "pause" in medical student participation in-person at clinical sites. In response, the Family Medicine Department at the Rowan University School of Osteopathic Medicine recognized the need to evolve the traditional curriculum and quickly transitioned to an online format, incorporating telemedicine into the clerkship. This new model enabled 44 third-year medical students to obtain high-quality, offsite, virtual education and learn new skills.

Undergraduate Knowledge of Osteopathic Medicine: What Premedical Students Know About Osteopathic Medicine and Its Effect on Burnout.

CONTEXT: Undergraduate student interest in becoming a physician continues to rise, but so too does the difficulty of earning acceptance to medical school. In this competitive environment, little is known about premedical students' knowledge of their medical school options. Moreover, as undergraduate students' emotional health continues to decline, little is known about whether premedical students experience or are at increased risk for the burnout symptoms reported by medical students and other physicians in training. OBJECTIVE: To examine premedical undergraduate students' knowledge of osteopathic medicine, assess how they learned of osteopathic medicine, and collect information about any reported feelings of burnout. METHODS: In this institutional review board-approved study, we electronically distributed an anonymous survey to 342 premedical undergraduate students at a midsize, public research undergraduate institution. The survey included 56 questions. Students were surveyed on their preference of medical schools, knowledge of osteopathic medicine, and experience with burnout via the Maslach Burnout Inventory which measures exhaustion, cynicism, and professional efficacy. Of those who completed the survey, only those who confirmed that they currently considered themselves to be premedical students were included in our analysis. A 2×2 factorial analysis of variance (ANOVA) test was applied to assess main and interaction effects amongst respondents who preferred osteopathic or allopathic programs, whether they learned of osteopathic medicine programs by their own research, and their scores on the 3 measures of the Maslach Burnout Inventory: exhaustion, cynicism, and professional efficacy. Bivariate and factorial analyses were completed using SPSS v26 software (IBM). All tests were 2-tailed and used a .05 standard P value. RESULTS: Of 342 students to whom the survey was sent, 160 (46.8%) responded, and only 92 (26.9%) considered themselves premedical students. Of the 160 students analyzed in our study, 80 (50%) reported first learning of osteopathic medicine through their own research. A 2×2 factorial ANOVA revealed a significant interaction effect for cynicism in respondents who reported learning of osteopathic medicine programs on their own. Conversely, when respondents reported learning of osteopathic medicine programs from another source, they also reported significantly lower cynicism (F[1,1]5.23, P=.03) and exhaustion (F[1,13] 5.79, P=.02) scores. Of the 92 respondents, only 2 students (2.2%) answered all questions regarding general osteopathic medical knowledge correctly. CONCLUSION: The results of this study suggest that among premedical students, knowledge of osteopathic medicine may be incomplete and may be impeding medical school applications. Furthermore, respondents who reported interest in osteopathic medical schools and learned of this option through their own research seemed to experience greater burnout. Based on these findings, increased outreach and education have the potential to not only better inform students of the osteopathic profession, but also to reduce burnout.

Pyrocinchonimides Conjugate to Amine Groups on Proteins via Imide Transfer.

Advances in bioconjugation, the ability to link biomolecules to each other, small molecules, surfaces, and more, can spur the development of advanced materials and therapeutics. We have discovered that pyrocinchonimide, the dimethylated analogue of maleimide, undergoes a surprising transformation with biomolecules. The reaction targets amines and involves an imide transfer, which has not been previously reported for bioconjugation purposes. Despite their similarity to maleimides, pyrocinchonimides do not react with free thiols. Though both lysine residues and the N-termini of proteins can receive the transferred imide, the reaction also exhibits a marked preference for certain amines that cannot solely be ascribed to solvent accessibility. This property is peculiar among amine-targeting reactions and can reduce combinatorial diversity when many available reactive amines are available, such as in the formation of antibody-drug conjugates. Unlike amides, the modification undergoes very slow reversion under high pH conditions. The reaction offers a thermodynamically controlled route to single or multiple modifications of proteins for a wide range of applications.

Lifestyle Changes for Disease Prevention.

In primary care, physicians have the opportunity to address preventative causes of morbidity and mortality. Primary care physicians have a distinct opportunity to provide counseling regarding lifestyle changes and disease prevention in a variety of settings, both during the treatment of acute illnesses and with wellness examinations. Questions from patients regarding specific recommendations and interventions are common. In this article, we address barriers to and tools to encourage lifestyle changes in the areas of smoking cessation, weight loss, physical activity, mental health, and substance abuse/misuse.

Utility of time-lapse photography in studies of seabird ecology.

Marine ecosystems are heavily influenced by a wide range of human-related impacts, and thus monitoring is essential to preserve and manage these sensitive habitats. Seabirds are considered important bioindicators of the oceans, but accessing breeding populations can be difficult, expensive and time consuming. New technologies have been employed to facilitate data collection on seabirds that can reduce costs and minimize disturbance. Among these, the use of time-lapse photography is a potentially effective way to reduce researcher effort, while collecting valuable information on key ecological parameters. However, the feasibility of this approach remains uncertain. Here, we assessed the use of time-lapse photography as a tool for estimating foraging behaviour from breeding seabirds, and evaluate ways forward for this method. We deployed cameras in front of active nests at a colony of black-legged kittiwakes (Rissa tridactyla) during two breeding seasons, 5 nests in 2013 and 5 in 2014, taking pictures every 4 minutes. A subsample of monitored individuals were also equipped with accelerometers. Approximately 100,000 frames, covering incubation and chick-rearing periods, were analysed. Estimates of foraging trip duration from images were positively correlated with accelerometry estimates (R2 = 0.967). Equal partitioning of effort between pairs, predation events, nest attendance patterns and variation in trip metrics with breeding stage were also identified. Our results suggest that time-lapse photography is potentially a useful tool for assessing foraging trip duration and other fine-scale nesting ecology parameters as well as for assessing the effect of bio-logging devices on seabird foraging behaviour. Nevertheless, the time investment to manually extract data from images was high, and the process to set up cameras was not straightforward. To encourage wide use of time-lapse photography in seabird ecology, we thus provide guidelines for camera deployment and we suggest a need for further development of automated approaches to allow data extraction.

Thyroid Disorders in Athletes.

When athletic performance begins to deteriorate, it is important to identify possible underlying etiologies to explain such a phenomenon. Causes include inadequate nutrition, improper training habits, infection, and hematologic or endocrine diseases. In athletes, a thorough investigation of potentially reversible underlying medical conditions may be warranted when there are noted disruptions in training, competition, and recovery. Thyroid disorders should be considered in athletes in whom such a condition is suspected. The clinical picture may not be entirely clear, as athletes may have serum laboratory values that do not accurately correlate with the presenting signs and symptoms, as one might expect. That picture is even further muddled in individuals undergoing significant physiologic stress, and in whom anabolic agents or exogenous thyroid hormone are used. Because there are currently no consensus guidelines on the matter, return to play issues must be addressed when implementing treatment strategies and monitoring serial laboratory values on a case-by-case basis.

Single Molecule Bioelectronics and Their Application to Amplification-Free Measurement of DNA Lengths.

As biosensing devices shrink smaller and smaller, they approach a scale in which single molecule electronic sensing becomes possible. Here, we review the operation of single-enzyme transistors made using single-walled carbon nanotubes. These novel hybrid devices transduce the motions and catalytic activity of a single protein into an electronic signal for real-time monitoring of the protein's activity. Analysis of these electronic signals reveals new insights into enzyme function and proves the electronic technique to be complementary to other single-molecule methods based on fluorescence. As one example of the nanocircuit technique, we have studied the Klenow Fragment (KF) of DNA polymerase I as it catalytically processes single-stranded DNA templates. The fidelity of DNA polymerases makes them a key component in many DNA sequencing techniques, and here we demonstrate that KF nanocircuits readily resolve DNA polymerization with single-base sensitivity. Consequently, template lengths can be directly counted from electronic recordings of KF's base-by-base activity. After measuring as few as 20 copies, the template length can be determined with <1 base pair resolution, and different template lengths can be identified and enumerated in solutions containing template mixtures.

Interpreting behaviors from accelerometry: a method combining simplicity and objectivity.

Quantifying the behavior of motile, free-ranging animals is difficult. The accelerometry technique offers a method for recording behaviors but interpretation of the data is not straightforward. To date, analysis of such data has either involved subjective, study-specific assignments of behavior to acceleration data or the use of complex analyses based on machine learning. Here, we present a method for automatically classifying acceleration data to represent discrete, coarse-scale behaviors. The method centers on examining the shape of histograms of basic metrics readily derived from acceleration data to objectively determine threshold values by which to separate behaviors. Through application of this method to data collected on two distinct species with greatly differing behavioral repertoires, kittiwakes, and humans, the accuracy of this approach is demonstrated to be very high, comparable to that reported for other automated approaches already published. The method presented offers an alternative to existing methods as it uses biologically grounded arguments to distinguish behaviors, it is objective in determining values by which to separate these behaviors, and it is simple to implement, thus making it potentially widely applicable. The R script coding the method is provided.

Processive Incorporation of Deoxynucleoside Triphosphate Analogs by Single-Molecule DNA Polymerase I (Klenow Fragment) Nanocircuits.

DNA polymerases exhibit a surprising tolerance for analogs of deoxyribonucleoside triphosphates (dNTPs), despite the enzymes' highly evolved mechanisms for the specific recognition and discrimination of native dNTPs. Here, individual DNA polymerase I Klenow fragment (KF) molecules were tethered to a single-walled carbon nanotube field-effect transistor (SWCNT-FET) to investigate accommodation of dNTP analogs with single-molecule resolution. Each base incorporation accompanied a change in current with its duration defined by τclosed. Under Vmax conditions, the average time of τclosed was similar for all analog and native dNTPs (0.2 to 0.4 ms), indicating no kinetic impact on this step due to analog structure. Accordingly, the average rates of dNTP analog incorporation were largely determined by durations with no change in current defined by τopen, which includes molecular recognition of the incoming dNTP. All α-thio-dNTPs were incorporated more slowly, at 40 to 65% of the rate for the corresponding native dNTPs. During polymerization with 6-Cl-2APTP, 2-thio-dTTP, or 2-thio-dCTP, the nanocircuit uncovered an alternative conformation represented by positive current excursions that does not occur with native dNTPs. A model consistent with these results invokes rotations by the enzyme's O-helix; this motion can test the stability of nascent base pairs using nonhydrophilic interactions and is allosterically coupled to charged residues near the site of SWCNT attachment. This model with two opposing O-helix motions differs from the previous report in which all current excursions were solely attributed to global enzyme closure and covalent-bond formation. The results suggest the enzyme applies a dynamic stability-checking mechanism for each nascent base pair.

One-Dimensional Poole-Frenkel Conduction in the Single Defect Limit.

A single point defect surrounded on either side by quasi-ballistic, semimetallic carbon nanotube is a nearly ideal system for investigating disorder in one-dimensional (1D) conductors and comparing experiment to theory. Here, individual single-walled nanotubes (SWNTs) are investigated before and after the incorporation of single point defects. Transport and local Kelvin Probe force microscopy independently demonstrate high-resistance depletion regions over 1.0 µm wide surrounding one point defect in semimetallic SWNTs. Transport measurements show that conductance through such wide depletion regions occurs via a modified, 1D version of Poole-Frenkel field-assisted emission. Given the breadth of theory dedicated to the possible effects of disorder in 1D systems, it is surprising that a Poole-Frenkel mechanism appears to describe defect scattering and resistance in this semimetallic system.