Frequency and Characteristics of Social Media Use among General Surgery Trainees.

INTRODUCTION: With increased social isolation due to COVID-19, social media has been increasingly adopted for communication, education, and entertainment. We sought to understand the frequency and characteristics of social media usage among general surgery trainees. MATERIALS AND METHODS: General surgery trainees in 15 American training programs were invited to participate in an anonymous electronic survey. The survey included questions about demographics, frequency of social media usage, and perceptions of risks and benefits of social media. Univariate analysis was performed to identify differences between high users of social media (4-7 h per week on at least one platform) and low users (0-3 h or less on all platforms). RESULTS: One hundred fifty-seven of 591 (26.6%) trainees completed the survey. Most respondents were PGY3 or lower (75%) and high users of social media (74.5%). Among high users, the most popular platforms were Instagram (85.7%), YouTube (85.1%), and Facebook (83.6%). YouTube and Twitter were popular for surgical education (77.3% and 68.2%, respectively). The most reported benefits of social media were improving patient education and professional networking (85.0%), where high users agreed more strongly about these benefits (P = 0.002). The most reported risks were seeing other residents (42%) or attendings (17%) with unprofessional behavior. High users disagreed more strongly about risks, including observing attendings with unprofessional behavior (P = 0.028). CONCLUSIONS: Most respondents were high users of social media, particularly Instagram, YouTube, and Facebook. High users incorporated social media into their surgical education while perceiving more benefits and fewer risks of social media.

Integration of the Cortical Haemodynamic Response Measured by Functional Near-Infrared Spectroscopy and Amino Acid Analysis to Aid in the Diagnosis of Major Depressive Disorder.

BACKGROUND: Major depressive disorder (MDD) is a debilitating condition with a high disease burden and medical comorbidities. There are currently few to no validated biomarkers to guide the diagnosis and treatment of MDD. In the present study, we evaluated the differences between MDD patients and healthy controls (HCs) in terms of cortical haemodynamic responses during a verbal fluency test (VFT) using functional near-infrared spectroscopy (fNIRS) and serum amino acid profiles, and ascertained if these parameters were correlated with clinical characteristics. METHODS: Twenty-five (25) patients with MDD and 25 age-, gender-, and ethnicity-matched HCs were recruited for the study. Real-time monitoring of the haemodynamic response during completion of a VFT was quantified using a 52-channel NIRS system. Serum samples were analysed and quantified by liquid chromatography-mass spectrometry for amino acid profiling. Receiver-operating characteristic (ROC) curves were used to classify potential candidate biomarkers. RESULTS: The MDD patients had lower prefrontal and temporal activation during completion of the VFT than HCs. The MDD patients had lower mean concentrations of oxy-Hb in the left orbitofrontal cortex (OFC), and lower serum histidine levels. When the oxy-haemoglobin response was combined with the histidine concentration, the sensitivity and specificity of results improved significantly from 66.7% to 73.3% and from 65.0% to 90.0% respectively, as compared to results based only on the NIRS response. CONCLUSIONS: These findings demonstrate the use of combination biomarkers to aid in the diagnosis of MDD. This technique could be a useful approach to detect MDD with greater precision, but additional studies are required to validate the methodology.

Analysis of over-the-counter products marketed to treat molluscum contagiosum.

Many over-the-counter (OTC) products are marketed to treat molluscum contagiosum, a common childhood viral infection with an estimated point prevalence of 5%-11%. As optimal treatment has not been defined, a comprehensive internet search was performed to identify OTC products marketed for treating molluscum and to collect information on packaging, ingredients, application instructions, and dosing. Nine OTC products were identified and varied widely in cost, packaging size, and ingredients; six of the nine products contained Thuja occidentalis. Overall, the majority of OTC package labels do not include sufficient information about their plant-based ingredients or appropriate dosing.

Pulse pressure as a predictor of response to treatment for severe hypertension in pregnancy.

BACKGROUND: Pulse pressure is a proposed means of tailoring antihypertensive therapy for treatment of acute-onset, severe hypertension in pregnancy. OBJECTIVE: This study aimed to determine whether pulse pressure predicts response to the various first-line antihypertensive medications. STUDY DESIGN: This is a retrospective cohort study from a single academic tertiary care center between 2015 and 2018. Patients were screened for inclusion if they had severe hypertension (defined as systolic blood pressure of ≥160 mm Hg or diastolic blood pressure of ≥110 mm Hg) lasting at least 15 minutes and were initially treated with intravenous labetalol, intravenous hydralazine, or immediate-release oral nifedipine. If a patient had multiple episodes of acute treatment during the pregnancy, only one episode was included in the analysis. The primary outcome was time to resolution (in minutes) of severe hypertension. To adjust for factors that may have affected time to resolution, we first compared baseline characteristics on the basis of the antihypertensive agent received. We then assessed the association between baseline characteristics and resolution of severe hypertension within 60 minutes of treatment. Regression analysis incorporated pulse pressure and antihypertensive agents into a model to predict resolution within 60 minutes of onset of severe hypertension. RESULTS: A total of 479 women hospitalized with severe maternal hypertension met the inclusion criteria. Hydralazine was the initial antihypertensive agent administered to 113 women, whereas 233 received labetalol, and 133 received nifedipine. Those who initially received nifedipine had a shorter mean time to resolution of severe hypertension (32.6 minutes vs 46.3 for hydralazine and 50.3 for labetalol; P<.01) and were more likely to have resolution of severe hypertension within 60 minutes (91.0% vs 77.9% for hydralazine and 76.8% for labetalol; P<.01). Nifedipine also resulted in a lower mean posttreatment blood pressure. Regression analysis revealed that a lack of resolution of severe hypertension within 60 minutes was independently associated with 2 measures of hypertension severity (mean arterial pressure of ≥125 mm Hg and the need for ≥2 doses of medication) and pulse pressure of >75 mm Hg at the time of treatment, initial treatment with labetalol, and gestational age of <37 weeks at the time of the hypertensive event (or at delivery if treatment was after delivery). The model's bias-corrected bootstrapped area under the receiver operating characteristic curve was 0.85 (95% confidence interval, 0.79-0.88). Interaction terms between pulse pressure and each antihypertensive agent were not significant and therefore not incorporated into the final model. CONCLUSION: Pulse pressure did not predict response to the various first-line antihypertensive agents. Initial treatment with oral nifedipine was associated with a higher likelihood of resolution of severe hypertension within 60 minutes of treatment than with intravenous labetalol.

From bedside to bench: regulation of host factors in SARS-CoV-2 infection.

The zoonotic coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2), which causes COVID-19 (coronavirus disease-2019), has resulted in a pandemic. This has led to an urgent need to understand the molecular determinants of SARS-CoV-2 infection, factors associated with COVID-19 heterogeneity and severity, and therapeutic options for these patients. In this review, we discuss the role of host factors in SARS-CoV-2 infection and describe variations in host factor expression as mechanisms underlying the symptoms and severity of COVID-19. We focus on two host factors, angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), implicated in SARS-CoV-2 infection. We also discuss genetic variants associated with COVID-19 severity revealed in selected patients and based on genome-wide association studies (GWASs). Furthermore, we highlight important advances in cell and chromatin biology, such as single-cell RNA and chromatin sequencing and chromosomal conformation assays, as methods that may aid in the discovery of viral-host interactions in COVID-19. Understanding how regulation of host factor genes varies in physiological and pathological states might explain the heterogeneity observed in SARS-CoV-2 infection, help identify pathways for therapeutic development, and identify patients most likely to progress to severe COVID-19.

Functional near-infrared spectroscopy during a decision-making task in patients with major depressive disorder.

OBJECTIVE: Patients with major depressive disorder tend to exhibit poorer decision-making capacity than the general population, but neurobiological evidence is lacking. Functional near-infrared spectroscopy monitors changes in oxy-haemoglobin concentration in the cerebral cortex. It may provide an objective assessment of neurophysiological responses during decision-making processes. Thus, this study investigated the effect of major depressive disorder diagnosis and severity on prefrontal cortex activity during the Iowa gambling task. METHODS: Right-handed healthy controls (n = 25) and patients with major depressive disorder (n = 25) were matched for age, gender, ethnicity and years of education in this cross-sectional study. Functional near-infrared spectroscopy signals and the responses made during a computerised Iowa gambling task were recorded. In addition, demographics, clinical history and symptom severity were noted. RESULTS: Compared to healthy controls, patients with major depressive disorder had reduced haemodynamic response in several cortical regions of the frontal lobe (Hedge's g range from 0.71 to 1.52; p values range from ⩽0.001 to 0.041). Among patients, mean oxy-haemoglobin declined with major depressive disorder severity in the right orbitofrontal cortex (Pearson's r = -0.423; p = 0.024). CONCLUSION: Haemodynamic dysfunction of the prefrontal cortex during decision-making processes is associated with major depressive disorder diagnosis and severity. These neurophysiological alterations may have a role in the decision-making capacity of patients with major depressive disorder.

Stakeholder perspective on barrier to the implementation of Advance Care Planning in a traditionally paternalistic healthcare system.

BACKGROUND: Advance psychiatric agreements could guide medical teams in providing care consistent with the incapacitated service user's wishes. However, these types of agreements are rarely completed in Asian settings. What challenges can a traditionally paternalistic healthcare system expect to encounter when attempting to implement psychiatric advance directives? METHODS: We answered this research question by exploring the cultural, administrative and logistical challenges that might impede the implementation of the system supporting the service. We interviewed key stakeholders, 28 service users and 22 service providers, to seek their views and interests in the implementation of directives. We structured our analyses along a literature-review-based framework designed to guide further implementation studies, proposed by Nicaise and colleagues (2013). Accordingly, we divided our inductively generated themes into four longitudinal categories: pre-development stage, development stage, implementation stage, post-implementation stage. RESULTS: Overall, the findings indicated that many service users and service providers are interested in advance care planning. They believed that foreseeable challenges could be overcome with appropriate measures. However, the multiple challenges of implementation led some service providers to be ambivalent about their implementation and led service users to dismiss them. Specifically, factors related to the local culture in Singapore necessitated adjustments to the content and structure of the directives. These include language barriers in a multicultural society, conflicting wishes in a collectivist society, taboos for speaking about undesirable outcomes in a traditionalist society, and time limitations in a fast-paced society. CONCLUSION: While culture-specific changes may be required to enable service users in a small Asian country to employ existing advance psychiatric agreement approaches, service providers and service users see their benefits. However, service providers must be mindful not to assume that service users are willing to defer every decision to their physician.

Contextual fear memory retrieval by correlated ensembles of ventral CA1 neurons.

Ventral hippocampal CA1 (vCA1) projections to the amygdala are necessary for contextual fear memory. Here we used in vivo Ca2+ imaging in mice to assess the temporal dynamics by which ensembles of vCA1 neurons mediate encoding and retrieval of contextual fear memories. We found that a subset of vCA1 neurons were responsive to the aversive shock during context conditioning, their activity was necessary for memory encoding, and these shock-responsive neurons were enriched in the vCA1 projection to the amygdala. During memory retrieval, a population of vCA1 neurons became correlated with shock-encoding neurons, and the magnitude of synchronized activity within this population was proportional to memory strength. The emergence of these correlated networks was disrupted by inhibiting vCA1 shock responses during memory encoding. Thus, our findings suggest that networks of cells that become correlated with shock-responsive neurons in vCA1 are essential components of contextual fear memory ensembles.

More Than Knee Pain: A Case of Hypertrophic Osteoarthropathy Secondary to Lung Cancer.

BACKGROUND: Hypertrophic osteoarthropathy (HOA) is a musculoskeletal pathology that often occurs as a paraneoplastic syndrome. 90% of HOA cases occur secondary to malignancy. 60 to 80% of which are lung cancers. CASE REPORT: We present a case of a 61-year-old man who had worsening knee pain. HOA was incidentally noted on extremity X-ray. The patient was found to have a soft-tissue attenuating mass on chest X-ray. The diagnosis of non-small cell lung cancer was made after bronchoscopy. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: HOA can be an indication of malignancy, most commonly lung cancer, so it is important to recognize the key radiographic findings associated with HOA. When treating patients with bone pain and clubbed digits, emergency physicians should strongly consider screening for more severe primary pathology.

Psychiatric Advance Directives and their relevance to improving psychiatric care in Asian countries.

People with mental illness may be unable to provide critical input about the care they wish to receive during a psychiatric crisis because of altered mental states. It is therefore imperative that clinicians seek to understand service users' wishes for care while they are well and able to provide meaningful input into the discussion. Achieving such an end may be done by discussing and completing a psychiatric advance directive. However, very few Asian countries have legislation that supports such advance directives. The present article seeks to give physicians more information about advance psychiatric directives and the potential role they could play to improve the healthcare provided in Asia to people at risk of losing capacity due to a mental illness. The degree to which mental health legislation supports psychiatric advance directives is documented for each country of South East Asia and Eastern Asia.

Salmonella Effector SteE Converts the Mammalian Serine/Threonine Kinase GSK3 into a Tyrosine Kinase to Direct Macrophage Polarization.

Many Gram-negative bacterial pathogens antagonize anti-bacterial immunity through translocated effector proteins that inhibit pro-inflammatory signaling. In addition, the intracellular pathogen Salmonella enterica serovar Typhimurium initiates an anti-inflammatory transcriptional response in macrophages through its effector protein SteE. However, the target(s) and molecular mechanism of SteE remain unknown. Here, we demonstrate that SteE converts both the amino acid and substrate specificity of the host pleiotropic serine/threonine kinase GSK3. SteE itself is a substrate of GSK3, and phosphorylation of SteE is required for its activity. Remarkably, phosphorylated SteE then forces GSK3 to phosphorylate the non-canonical substrate signal transducer and activator of transcription 3 (STAT3) on tyrosine-705. This results in STAT3 activation, which along with GSK3 is required for SteE-mediated upregulation of the anti-inflammatory M2 macrophage marker interleukin-4Rα (IL-4Rα). Overall, the conversion of GSK3 to a tyrosine-directed kinase represents a tightly regulated event that enables a bacterial virulence protein to reprogram innate immune signaling and establish an anti-inflammatory environment.

Associative stigma among mental health professionals in Singapore: a cross-sectional study.

OBJECTIVES: (1) Investigate and explore whether different classes of associative stigma (the process by which a person experiences stigmatisation as a result of an association with another stigmatised person) could be identified using latent class analysis; (2) determine the sociodemographic and employment-related correlates of associative stigma and (3) examine the relationship between associative stigma and job satisfaction, among mental health professionals. DESIGN: Cross-sectional online survey. PARTICIPANTS: Doctors, nurses and allied health staff, working in Singapore. METHODS: Staff (n=462) completed an online survey, which comprised 11 associative stigma items and also captured sociodemographic and job satisfaction-related information. Latent class analysis was used to classify associative stigma on patterns of observed categorical variables. Multinomial logistic regression was used to examine associations between sociodemographic and employment-related factors and the different classes, while multiple linear regression analyses were used to examine the relationship between associative stigma and job satisfaction. RESULTS: The latent class analysis revealed that items formed a three-class model where the classes were classified as 'no/low associative stigma', 'moderate associative stigma' and 'high associative stigma'. 48.7%, 40.5% and 10.8% of the population comprised no/low, moderate and high associative stigma classes, respectively. Multinomial logistic regression showed that years of service and occupation were significantly associated with moderate associative stigma, while factors associated with high associative stigma were education, ethnicity and occupation. Multiple linear regression analyses revealed that high associative stigma was significantly associated with lower job satisfaction scores. CONCLUSION: Associative stigma was not uncommon among mental health professionals and was associated with sociodemographic factors and poorer job satisfaction. Associative stigma has received comparatively little attention from empirical researchers and continued efforts to address this understudied yet important construct in conjunction with future efforts to dispel misconceptions related to mental illnesses are needed.

Pregnancy Zone Protein Is Associated with Airway Infection, Neutrophil Extracellular Trap Formation, and Disease Severity in Bronchiectasis.

Rationale: PZP (pregnancy zone protein) is a broad-spectrum immunosuppressive protein believed to suppress T-cell function during pregnancy to prevent fetal rejection. It has not previously been reported in the airway.Objectives: To characterize PZP in the bronchiectasis airway, including its relationship with disease severity.Methods: Label-free liquid chromatography/mass spectrometry was performed for sputum protein profiling of patients with bronchiectasis confirmed by high-resolution computed tomography. Results for patients with and without Pseudomonas aeruginosa infection were compared. Sputum and serum PZP was measured by validated ELISA. Airway infection status was established by culture and 16S ribosomal RNA sequencing. Immunofluorescence, ELISA, and electron microscopy were used to identify the cellular source of PZP in neutrophils treated with multiple stimuli.Measurements and Main Results: Elevated PZP was identified by label-free liquid chromatography/mass spectrometry as being associated with P. aeruginosa infection. In a validation study of 124 patients, sputum but not serum concentrations of PZP were significantly associated with the Bronchiectasis Severity Index, the frequency of exacerbations, and symptoms. Airway infection with Proteobacteria such as P. aeruginosa was associated with higher concentrations of PZP. PZP in sputum was directly related to airway bacterial load. Neutrophils induced to form neutrophil extracellular traps (NETs) with phorbol myristate acetate released high concentrations of PZP in vitro, and fluorescence microscopy confirmed the presence of PZP in NETs, whereas fluorescence and electron microscopy localized PZP to the cytoplasm and nuclei of neutrophils. Effective antibiotic therapy reduced sputum PZP.Conclusions: PZP is released into NETs. We report a novel link between airway infection, NET formation, and disease severity in bronchiectasis during chronic airway inflammation.

Antimicrobial peptides, disease severity and exacerbations in bronchiectasis.

RATIONALE: Recently a frequent exacerbator phenotype has been described in bronchiectasis, but the underlying biological mechanisms are unknown. Antimicrobial peptides (AMPs) are important in host defence against microbes but can be proinflammatory in chronic lung disease. OBJECTIVES: To determine pulmonary and systemic levels of AMP and their relationship with disease severity and future risk of exacerbations in bronchiectasis. METHODS: A total of 135 adults with bronchiectasis were prospectively enrolled at three European centres. Levels of cathelicidin LL-37, lactoferrin, lysozyme and secretory leucocyte protease inhibitor (SLPI) in serum and sputum were determined at baseline by ELISA. Patients were followed up for 12 months. We examined the ability of sputum AMP to predict future exacerbation risk. MEASUREMENTS AND MAIN RESULTS: AMP levels were higher in sputum than in serum, suggesting local AMP release. Patients with more severe disease at baseline had dysregulation of airway AMP. Higher LL-37 and lower SLPI levels were associated with Bronchiectasis Severity Index, lower FEV1 (forced expiratory volume in 1 s) and Pseudomonas aeruginosa infection. Low SLPI levels were also associated with the exacerbation frequency at baseline. During follow-up, higher LL-37 and lower SLPI levels were associated with a shorter time to the next exacerbation, whereas LL-37 alone predicted exacerbation frequency over the next 12 months. CONCLUSIONS: Patients with bronchiectasis showed dysregulated sputum AMP levels, characterised by elevated LL-37 and reduced SLPI levels in the frequent exacerbator phenotype. Elevated LL-37 and reduced SLPI levels are associated with Pseudomonas aeruginosa infection and can predict future risk of exacerbations in bronchiectasis.

Focus on Formononetin: Anticancer Potential and Molecular Targets.

Formononetin, an isoflavone, is extracted from various medicinal plants and herbs, including the red clover (Trifolium pratense) and Chinese medicinal plant Astragalus membranaceus. Formononetin's antioxidant and neuroprotective effects underscore its therapeutic use against Alzheimer's disease. Formononetin has been under intense investigation for the past decade as strong evidence on promoting apoptosis and against proliferation suggests for its use as an anticancer agent against diverse cancers. These anticancer properties are observed in multiple cancer cell models, including breast, colorectal, and prostate cancer. Formononetin also attenuates metastasis and tumor growth in various in vivo studies. The beneficial effects exuded by formononetin can be attributed to its antiproliferative and cell cycle arrest inducing properties. Formononetin regulates various transcription factors and growth-factor-mediated oncogenic pathways, consequently alleviating the possible causes of chronic inflammation that are linked to cancer survival of neoplastic cells and their resistance against chemotherapy. As such, this review summarizes and critically analyzes current evidence on the potential of formononetin for therapy of various malignancies with special emphasis on molecular targets.

Prevalence and correlates of diabetes mellitus and dyslipidaemia in a long-stay inpatient schizophrenia population in Singapore.

INTRODUCTION: Patients with schizophrenia have shorter life expectancy and one of the main causes of death is cardiovascular disease (CVD). Modifiable risk factors for CVD include diabetes mellitus (DM) and dyslipidaemia. This study aimed to establish: (a) the prevalence and correlates of DM and dyslipidaemia; (b) the proportion of those whose condition was well controlled; and (c) the incidence of undiagnosed DM and dyslipidaemia in a long-stay inpatient schizophrenia population. METHODS: Data was collected to assess the physical health status of 110 inpatients with schizophrenia who had been in hospital for over one year. Information on sociodemographic characteristics, diagnosis of physical and mental illnesses, and current medications was obtained from their medical records. The overall prevalence of DM and dyslipidaemia was based on diagnosis in the medical records, current medications and fasting blood test results. RESULTS: The patient group was predominantly male (85.5%), with a mean age of 55.9 ± 9.9 (range 25-90) years. Overall prevalence of DM and dyslipidaemia was 19.1% and 62.7%, respectively. Multivariate logistic regression analysis showed that Malay (odds ratio [OR] 14.97) and Indian (OR 25.71) patients were significantly more likely to have DM when compared to Chinese patients. CONCLUSION: In comparison to the general population, the prevalence of DM and dyslipidaemia was found to be higher in inpatients with schizophrenia. However, the two chronic illnesses were well controlled in inpatients and few were undiagnosed, perhaps due to the regular monitoring, supervised diet and regular physical activities arranged for inpatients in the long-stay inpatient wards.

Anxiety Cells in a Hippocampal-Hypothalamic Circuit.

The hippocampus is traditionally thought to transmit contextual information to limbic structures where it acquires valence. Using freely moving calcium imaging and optogenetics, we show that while the dorsal CA1 subregion of the hippocampus is enriched in place cells, ventral CA1 (vCA1) is enriched in anxiety cells that are activated by anxiogenic environments and required for avoidance behavior. Imaging cells defined by their projection target revealed that anxiety cells were enriched in the vCA1 population projecting to the lateral hypothalamic area (LHA) but not to the basal amygdala (BA). Consistent with this selectivity, optogenetic activation of vCA1 terminals in LHA but not BA increased anxiety and avoidance, while activation of terminals in BA but not LHA impaired contextual fear memory. Thus, the hippocampus encodes not only neutral but also valence-related contextual information, and the vCA1-LHA pathway is a direct route by which the hippocampus can rapidly influence innate anxiety behavior.