Mechanical forces across compartments coordinate cell shape and fate transitions to generate tissue architecture.

Morphogenesis and cell state transitions must be coordinated in time and space to produce a functional tissue. An excellent paradigm to understand the coupling of these processes is mammalian hair follicle development, which is initiated by the formation of an epithelial invagination-termed placode-that coincides with the emergence of a designated hair follicle stem cell population. The mechanisms directing the deformation of the epithelium, cell state transitions and physical compartmentalization of the placode are unknown. Here we identify a key role for coordinated mechanical forces stemming from contractile, proliferative and proteolytic activities across the epithelial and mesenchymal compartments in generating the placode structure. A ring of fibroblast cells gradually wraps around the placode cells to generate centripetal contractile forces, which, in collaboration with polarized epithelial myosin activity, promote elongation and local tissue thickening. These mechanical stresses further enhance compartmentalization of Sox9 expression to promote stem cell positioning. Subsequently, proteolytic remodelling locally softens the basement membrane to facilitate a release of pressure on the placode, enabling localized cell divisions, tissue fluidification and epithelial invagination into the underlying mesenchyme. Together, our experiments and modelling identify dynamic cell shape transformations and tissue-scale mechanical cooperation as key factors for orchestrating organ formation.

Cell-state transitions and collective cell movement generate an endoderm-like region in gastruloids.

Shaping the animal body plan is a complex process that involves the spatial organization and patterning of the different germ layers. Recent advances in live imaging have started to unravel the cellular choreography underlying this process in mammals, however, the sequence of events transforming an unpatterned cell ensemble into structured territories is largely unknown. Here, using gastruloids -3D aggregates of mouse embryonic stem cells- we study the formation of one of the three germ layers, the endoderm. We show that the endoderm is generated from an epiblast-like homogeneous state by a three-step mechanism: (i) a loss of E-cadherin mediated contacts in parts of the aggregate leading to the appearance of islands of E-cadherin expressing cells surrounded by cells devoid of E-cadherin, (ii) a separation of these two populations with islands of E-cadherin expressing cells flowing toward the aggregate tip, and (iii) their differentiation into an endoderm population. During the flow, the islands of E-cadherin expressing cells are surrounded by cells expressing T-Brachyury, reminiscent of the process occurring at the primitive streak. Consistent with recent in vivo observations, the endoderm formation in the gastruloids does not require an epithelial-to-mesenchymal transition, but rather a maintenance of an epithelial state for a subset of cells coupled with fragmentation of E-cadherin contacts in the vicinity, and a sorting process. Our data emphasize the role of signaling and tissue flows in the establishment of the body plan.

Psychiatric impact on COVID-19 patients isolated in a tertiary care hospital in Pakistan.

BACKGROUND: Adverse psychological effects have been associated with COVID-19-related disease containment measures, but little is known about the psychiatric symptoms and distress. AIMS: This study aimed to explore and understand the psychiatric symptoms and distress in suspected or confirmed COVID-19 patients isolated and quarantined in hospital. METHODS: A mixed methods study was conducted in the COVID-19 units of Mayo Hospital, Lahore, Pakistan; 114 out of 160 adult patients were assessed by telephone using validated scales (Stress Reactions and Adjustment Disorder Checklist, 9-item Patient Health Questionnaire, 7-item Generalized Anxiety Disorder Scale and Insomnia Severity Index) and a few open-ended questions about expectations and anticipated areas of need during hospitalization, including experiences with isolation. RESULTS: The prevalence of adjustment disorder, acute stress disorder, anxiety, depressive symptoms and insomnia was 67.5%, 3.5%, 16.7%, 18.4%, and 29.8% respectively. One male patient tried to commit suicide during the study period. Fear, anger, low mood, anxiety and sleep disturbances were the most notable psychological consequences in qualitative the responses. Inadequate communication, poor ward facilities, concerns about the health of family members and financial problems were the most commonly identified factors leading to distress. CONCLUSION: Our results show alarmingly high levels of stress-related symptoms - insomnia, depression and anxiety - among COVID-19 confirmed or suspected hospitalized patients. There is a need to incorporate psychological services in the acute phase of illness for prompt recognition and management of psychiatric problems.

The challenge of Burnout in Public Medical Teachers in Pakistan: A mixed methods study.

BACKGROUND AND OBJECTIVES: Burnout is common in healthcare workers and affects multiple domains of functioning. The objective of this study was to assess burnout in medical teachers in a large public medical university in Lahore, Pakistan and explore the factors behind it. METHODS: Using an explanatory sequential mixed methods design, we first sent out the abbreviated Maslach Burnout Inventory (aMBI) to all teaching faculty of basic and clinical science at King Edward Medical University (KEMU) Lahore. Descriptive analysis was performed on the 203 respondents who returned the survey. Of those who scored higher on the aMBI, 10 respondents (8 clinical science faculty and two basic science faculty) were selected for detailed semi-structured interviews exploring possible reasons for burnout. Thematic analysis of interview transcripts was performed using Interpretive Phenomenological Analysis. Triangulation and member checking was used for validation. RESULTS: About 38.9% of respondents scored high on the Emotional Exhaustion subscale and 31.5% scored high on the Depersonalization subscale. There were statistically significant differences on the mean Emotional Exhaustion scores (p <0.001) between Basic and Clinical Sciences Departments with respondents from the Clinical Departments having higher scores (7.84 ± 4.32). Four main themes and multiple sub-themes emerged around burnout after qualitative analysis of the data. These included 1. Work-related factors 2. Family and social factors including challenges related specifically to women 3. Feelings and emotions and 4. Personal Qualities. CONCLUSION: A significant proportion of medical faculty experiences burnout related to their professional and personal responsibilities. The reasons are varied. Policy planners and University/College administrators must acknowledge the negative effects of burnout on medical teachers and take steps to ameliorate it in the interests of improving medical education and training.

Role of Oxytocin in the Pathogenesis and Modulation of Borderline Personality Disorder: A Review.

Borderline personality disorder (BPD) is a serious psychiatric condition characterized by dysfunctional relations, abnormal social behavior, and high morbidity. Many studies have implicated abnormal oxytocinergic system as a causative factor of behavioral dysregulation in BPD patients. The objective of this review is to provide a comprehensive analysis of the association of oxytocin with the pathogenesis of BPD and its possible role as a therapeutic agent. Our review indicates that a combination of genetic and environmental factors causes BPD patients to have lower baseline levels of oxytocin, leading to increased activation of the amygdala. This results in defective cognition of social stimuli, leading to abnormal behaviors like affective instability, unresolved attachment, and emotional dysregulation. Clinical trials conducted on BPD patients using intranasal oxytocin have shown both prosocial and trust-lowering effects. The effects of oxytocin depend upon various patient characteristics like the history of childhood trauma and the nature of attachment. Even though evidence of oxytocin's role in modulating behavior in BPD patients already exists, further studies are required to more clearly elaborate on this role to fully explore oxytocin's potential as a therapeutic agent.

Scarlett Letter: A study based on experience of stigma by COVID-19 patients in quarantine.

BACKGROUND AND OBJECTIVES: Stigma around COVID-19 is a major barrier in global efforts to control the COVID 19 pandemic. Limited data is available regarding stigma faced by COVID-19 patients in low- and middle-income countries (LMIC). The aim of the current study was to explore the stigma experienced by hospitalized patients with COVID-19 illness in Lahore, Pakistan. METHODS: Following Institutional Review Board approval and informed consent, patients were assessed using modified HIV short form stigma scale and open-ended questions. Questions focused on experiences, feelings, and opinions as to how patients feel and how they were treated prior to and during the hospitalization. Data analysis for quantitative data was performed using SPSS-20, while qualitative responses were interpreted by content analysis method. RESULTS: One hundred and fourteen patients were interviewed (Mean age 38.8 years + 15.3) with 53.5% being males. Widespread experience of stigma was reported by patients particularly for concerns about public attitudes (7.43 + 1.43) & disclosure (6.89 + 1.45). Main themes which emerged from the qualitative responses were social stigma and rejection, humiliating behaviour of others, breach of confidentiality, loss of trust/ respect, and impact of COVID-19 diagnosis on their business. CONCLUSIONS: Existence of significant stigma among COVID-19 patients isolated in a tertiary care hospital in a LMIC highlights the need for culturally sensitive strategies to address it.

Between a Rock and a Hard Place - Gender Dysphoria and Comorbid Depression in a Young, Low-Income, Pakistani Transgender Man.

Gender dysphoria (GD) describes an incongruence between a person's assigned and expressed gender and the distress associated with it. The management of GD ideally involves a team of healthcare professionals, including psychiatrists, endocrinologists, and surgeons, and may include one or more of the following - psychotherapy, hormone therapy, and gender reassignment surgeries. While Pakistan still has a sizeable population of the traditional 'khwaja siras' or 'hijras,' many young transgender Pakistanis are now adopting global transgender identities and seeking sex-reassignment procedures from a state-run healthcare system, which still heavily discriminates against them. In spite of the passage of a new law protecting the fundamental human rights of transgendered Pakistanis, they continue to be oppressed and deprived of education, employment, and healthcare. This case report describes one such young transman from a low-income Pakistani household, who, owing to the legal red tape, family pressure, religious disapproval, and hefty hospital expenses, is left with only two options - to undergo unsafe, unstandardized procedures at the hands of quacks or live the rest of his life trapped in the wrong body. There is a dire need for a wide-scale awareness campaign to educate and sensitize the general public about transgender rights. Medical students must also be exposed to transgender patients during their medical school training in order to familiarize them with the special medical needs of transgender individuals.

New Horizons: COVID-19 and the Burden of Neuropsychiatric Illness in Pakistan.

This manuscript reviews the current state of knowledge about the burden of mental illness and assesses the impact of COVID-19 illness on mental health in Pakistan. For this we analyzed secondary data obtained from the Institute of Health Metrics and Evaluation. The Global Burden of Disease (GBD) study draws from a wide range of data sources to quantify global and regional effects of a disease. We also did a literature search on the effects of COVID-19 illness on mental health and the psychosocial effects of COVID-19 and other Corona virus related illnesses such as SARS-CoV and MERS-CoV. Data from the studies obtained was utilized to extrapolate the anticipated effects of COVID-19 illness on healthcare workers, COVID-19 patients and the general public in Pakistan. Mental illness poses a significant challenge to Pakistan's under resourced health care system. COVID-19 has the potential to strain Pakistan's healthcare system to the breaking point. So far, the general morbidity from COVID-19 illness in Pakistan has been low compared to other countries but this could change in the coming weeks and months. Hidden within this crisis are also some opportunities for both healthcare and education.

Smart phones and medical students: Pleasant distraction or dangerous addiction?

Smart phones are central to communication in the current century. We administered a survey to determine the impact of excessive smart phone use on academic performance, interpersonal relationships and mental health in medical students. During the study, 700 medical students from King Edward Medical University, Lahore, Pakistan, were administered a questionnaire which recorded information about demographics, academic performance, interpersonal relationships and psychological problems. Out of 630 respondents, 255(40.5%) were males and 375(59.5%) were females with a mean age of 21.1}1.8 years. Results showed smart phone use during class lectures was associated with significant reduction in academic performance and problems with interpersonal relationships. Medical students bullied via smart phones were likely to bully others. Excessive use of smart phones was associated with students preferring to communicate emotions through texting rather than verbal communication. Various psychological problems were found prevalent in excessive users of smart phones.

The importance of identification when measuring performance in addiction treatment.

Background: Identifying and effectively treating individuals with substance use disorders (SUDs) is an important priority for state Medicaid programs, given the enormous toll that SUDs take on individuals, their families, and their communities. In this paper, we describe how the Healthcare Effectiveness Data and Information Set (HEDIS) measure "Identification of Alcohol and Other Drug Services" can be used, along with eligible population prevalence rates, to expand states' ability to track how well their Medicaid programs identify enrollees with SUDs and link them with treatment (measured by initiation and engagement performance measures). Methods: We use the 2009 Medicaid MAX data on utilization and enrollment along with information from the National Survey of Drug Use and Health (NSDUH) to obtain state-level estimates of alcohol and drug abuse and dependence among Medicaid beneficiaries for 7 illustrative states. We calculate identification, initiation, and engagement measures using specifications from the National Committee on Quality Assurance (NCQA). Results: NSDUH data showed that the eligible population prevalence rate (the average rate of alcohol or drug abuse or dependence) among the 7 states was 10.0%, whereas the average identification rate was 2.9%. The gap between the prevalence and identification rates ranged from 5.1% to 11.0% among the 7 states. The initiation rates ranged from 36.9% to 57.1%. The states' engagement rates ranged from 11.8% to 31.1%, although rates differ by age, gender, and race/ethnicity in some states. Conclusion: Including identification along with initiation and engagement measures allows states to determine how well they are performing in a more complete spectrum from need, to recognition and documentation of enrollees with SUDs, to initiation of treatment, to continuation of early treatment.

Microparticle self-assembly induced by travelling surface acoustic waves.

We present an acoustofluidic method based on travelling surface acoustic waves (TSAWs) to induce self-assembly of microparticles inside a microfluidic channel. The particles are trapped above an interdigitated transducer, placed directly beneath the microchannel, by the TSAW-based direct acoustic radiation force (ARF). This approach was applied to trap 10 µm polystyrene particles, which were pushed towards the ceiling of the microchannel by 72 MHz TSAWs to form single- and multiple-layer colloidal structures. The repair of cracks and defects within the crystal lattice occurs as part of the self-assembly process. The sample flow through the first inlet can be switched with a buffer flow through the second inlet to control the number of particles assembled in the crystalline structure. The constant flow-induced Stokes drag force on the particles is balanced by the opposing TSAW-based ARF. This force balance is essential for the acoustics-based self-assembly of microparticles inside the microchannel. Moreover, we studied the effects of varying input voltage and fluid flow rate on the position and shape of the colloidal structure. The active self-assembly of microparticles into crystals with multiple layers can be used in the bottom-up fabrication of colloidal structures with dimensions greater than 500 µm × 500 µm, which is expected to have important applications in various fields.

Restless Legs Syndrome Among Veterans With Spinal Cord Lesions.

Researchers developed a restless legs syndrome questionnaire using diagnostic criteria to assess its prevalence among veterans with spinal cord injuries and disorders.

Intensive Care and its Discontents: Psychiatric Illness in the Critically Ill.

Critically ill patients can develop a host of cognitive and psychiatric complaints during their intensive care unit (ICU) stay, many of which persist for weeks or months following discharge from the ICU and can seriously affect their quality of life, including their ability to return to work. This article describes some common psychiatric problems encountered by clinicians in the ICU, including their assessment and management. A comprehensive approach is needed to decrease patient suffering, improve morbidity and mortality, and ensure that critically ill patients can return to the highest quality of life after an ICU stay.

Insomnia during pregnancy: Diagnosis and Rational Interventions.

UNLABELLED: Sleep disturbances are common in pregnancy. Insomnia is a frequent sleep disturbance experienced by pregnant women which can be primary or due to co-morbid conditions. The differential diagnosis of insomnia in pregnancy includes anxiety disorders, mood disorders, breathing related sleep disorders and restless legs syndrome. Early interventions to treat the sleep disturbance are recommended to avoid adverse pregnancy outcomes. Management strategies include improving sleep hygiene, behavioral therapies, and pharmacotherapy. The risks of pharmacotherapy must be weighed against their benefits due to the possible risk of teratogenicity associated with some medications. METHODS: We searched PubMed and Google Scholar employing a combination of key words: pregnancy, sleep disturbances, Obstructive Sleep Apnea, Sleep disorders and insomnia. We included original studies, review articles, meta-analysis and systematic reviews in our search prioritizing articles from the last 10-15 years. Articles older than 15 years were only included if their findings had not been superseded by more recent data. Further selection of articles was done from bibliographies and references of selected articles. CONCLUSION: Sleep disturbances in pregnancy are common and cause considerable morbidity. Management includes a combination of non-pharmacological and pharmacological treatments carefully weighing the risks and benefits of each for the expectant mother and fetus.

Burnout and quality of life in nurses of a tertiary care hospital in Pakistan.

OBJECTIVE: To determine the relationship of burnout and quality of life among nurses of different departments at a tertiary care hospital. METHODS: The observational, cross-sectional study was conducted at Mayo Hospital, Lahore, from November 2013 to May2014, and comprised nurses recruited by convenience sampling. Maslach Burnout Inventory was used to assess burnout and World Health Organisation Quality of life instrument's BREF version was used to assess quality of life of the subjects. Data was analysed using SPSS 16. RESULTS: Of the 106 nurses with a mean age of 35.5±7 years, 83(79%) were experiencing severe burnout and a low quality of life. Nurses of Surgery and Obstetrics/Gynaecology departments who worked longer hours on the night shift scored higher on burnout and lower on quality of life. CONCLUSIONS: Burnout in nurses was very common because of increasing workload and can negatively affect their quality of life leading to compromised patient care.

Hepatic Dysfunction in Patients Receiving Intravenous Amiodarone.

OBJECTIVES: Amiodarone is a commonly used antiarrhythmic drug. Hepatotoxicity following chronic oral administration occurs in 1% to 3% of patients. Hepatotoxicity following intravenous (IV) administration is infrequent but may be associated with dramatic increases in serum transaminases. We describe the incidence of liver toxicity among patients receiving IV amiodarone during a 5-year period. METHODS: This was a single-center retrospective review of patients receiving IV amiodarone for any cause. The outcome measures were development of elevated serum transaminases and the relation of transaminitis to all-cause 30-day mortality. RESULTS: A total of 1510 patients received amiodarone intravenously between 2005 and 2011; 77 (5%) developed elevated liver enzymes. Enzyme elevation was divided into mild (100-300 IU/L), moderate (300-1000 IU/L), and severe (>1000 IU/L). The median alanine aminotransferase was 189 (37-10,006) IU/L and aspartate aminotransferase was 253 (84-12,005) IU/L. The 30-day mortality among those with transaminitis was 22%; however, no patient died of amiodarone-related liver disease. CONCLUSIONS: Amiodarone can cause severe elevation in liver enzymes. The incidence of severe transaminitis is low; deaths following IV amiodarone are rarely caused by drug-induced liver failure.

Urdu translation of the Hamilton Rating Scale for Depression: Results of a validation study.

OBJECTIVE: To develop a standardized validated version of the Hamilton Rating Scale for Depression (HAM-D) in Urdu. METHODS: After translation of the HAM-D into the Urdu language following standard guidelines, the final Urdu version (HAM-D-U) was administered to 160 depressed outpatients. Inter-item correlation was assessed by calculating Cronbach alpha. Correlation between HAM-D-U scores at baseline and after a 2-week interval was evaluated for test-retest reliability. Moreover, scores of two clinicians on HAM-D-U were compared for inter-rater reliability. For establishing concurrent validity, scores of HAM-D-U and BDI-U were compared by using Spearman correlation coefficient. The study was conducted at Mayo Hospital, Lahore, from May to December 2014. RESULTS: The Cronbach alpha for HAM-D-U was 0.71. Composite scores for HAM-D-U at baseline and after a 2-week interval were also highly correlated with each other (Spearman correlation coefficient 0.83, p-value < 0.01) indicating good test-retest reliability. Composite scores for HAM-D-U and BDI-U were positively correlated with each other (Spearman correlation coefficient 0.85, p < 0.01) indicating good concurrent validity. Scores of two clinicians for HAM-D-U were also positively correlated (Spearman correlation coefficient 0.82, p-value < 0.01) indicated good inter-rater reliability. CONCLUSION: The HAM-D-U is a valid and reliable instrument for the assessment of Depression. It shows good inter-rater and test-retest reliability. The HAM-D-U can be a tool either for clinical management or research.