Erratum to 'Exploring the cost-effectiveness of high versus low perioperative fraction of inspired oxygen in the prevention of surgical site infections among abdominal surgery patients in three low- and middle-income countries' [BJA Open 7 (2023) 100207].

[This corrects the article DOI: 10.1016/j.bjao.2023.100207.].

Erratum to "Exploring the cost-effectiveness of high versus low perioperative fraction of inspired oxygen in the prevention of surgical site infections among abdominal surgery patients in three low- and middle-income countries" [BJA Open 7 (2023) 100207].

[This corrects the article DOI: 10.1016/j.bjao.2023.100207.].

Undergraduate dermatology education: The importance of curriculum review.

In this letter, we highlight the considerable diversity in undergraduate dermatology training in the United Kingdom and acknowledge the barriers faced in implementing the revised national undergraduate curriculum provided by the British Association of Dermatologists (BAD). We provide a pragmatic approach of ensuring that our dermatology placement aligns with the BAD national undergraduate curriculum and Medical Licensing Assessment (MLA) content map, in the face of limited clinician time and placement length. We urge other medical schools to adopt our approach of curriculum mapping, particularly in light of the upcoming MLA, and sustainable educational resource development.

Complications following dental treatment in a child with haemophilia A: lessons to be learnt.

A boy in his middle childhood with severe haemophilia reported with facial swelling following dental treatment for a carious upper primary molar done at a private dental clinic elsewhere. On presentation, he had a large, tense and tender swelling of the left cheek and a haematoma on the buccal mucosa adjacent to the treated tooth. The child was found to have a low haemoglobin level. He was taken for an emergency procedure under general anaesthesia for dental extraction with incision and drainage, and simultaneously underwent packed cells and factor replacement. He recovered in the ward postoperatively with no complications and with a gradual reduction of the swelling. This report highlights the importance of caries prevention in children, especially those with haemophilia. They need to be educated about restricting cariogenic foods in their diet and maintaining good oral hygiene. Management of such patients should be carefully coordinated to minimise undesirable outcomes.

Tyrosine-Derived Polymers as Potential Biomaterials: Synthesis Strategies, Properties, and Applications.

Peptide-based polymers are evolving as promising materials for various biomedical applications. Among peptide-based polymers, polytyrosine (PTyr)-based and l-tyrosine (Tyr)-derived polymers are unique, due to their excellent biocompatibility, degradability, and functional as well as engineering properties. To date, different polymerization techniques (ring-opening polymerization, enzymatic polymerization, condensation polymerization, solution-interfacial polymerization, and electropolymerization) have been used to synthesize various PTyr-based and Tyr-derived polymers. Even though the synthesis starts from Tyr, different synthesis routes yield different polymers (polypeptides, polyarylates, polyurethanes, polycarbonates, polyiminocarbonate, and polyphosphates) with unique functional characteristics, and these polymers have been successfully used for various biomedical applications in the past decades. This Review comprehensively describes the synthesis approaches, classification, and properties of various PTyr-based and Tyr-derived polymers employed in drug delivery, tissue engineering, and biosensing applications.

Melanoma in pregnancy: Diagnosis and management in early-stage and advanced disease.

Approximately one-third of women diagnosed with melanoma are of child-bearing age. The annual incidence of melanoma has risen steadily over the last 40 years, resulting in increasing numbers of women diagnosed with melanoma both during pregnancy, and post-partum. To date, there are no formal guidelines on the management of pregnancy associated melanoma (PAM), both early stage and metastatic. This article reviews the existing literature and provides a framework for the investigation and multidisciplinary management of PAM.

Intensive Care Unit-acquired Neuromuscular Weakness: A Prospective Study on Incidence, Clinical Course, and Outcomes.

BACKGROUND: Neuromuscular weakness may manifest subsequent to critical illness in intensive care unit (ICU) patients. This weakness termed as "ICU-acquired weakness" (ICUAW) has a significant bearing on the length of mechanical ventilation, duration of ICU stays, long-term disability, and survival rate. Early identification of ICUAW helps in planning appropriate strategies, as well as in predicting the prognosis and long-term outcomes of these patients. AIMS AND OBJECTIVES: To identify the incidence of new-onset neuromuscular weakness developing among patients admitted in the ICU (ICUAW) and study its clinical course and impact on the duration of ICU stay. METHODS: This prospective observational study evaluated patients admitted to the ICU over a period of 1 year and 3 months (November 1, 2015, to January 31, 2017). All patients fulfilling the inclusion and exclusion criteria were evaluated with the Medical Research Council (MRC) score for muscle strength. Patients with an average score <4 were diagnosed with ICUAW. Included patients were examined on alternate days to study the clinical progression of the weakness till ICU discharge or death of the patient. The duration of ICU stay was noted. RESULTS AND CONCLUSION: The study revealed a significant association of ICUAW with age, Acute Physiology And Chronic Health Evaluation (APACHE II) Score, duration of mechanical ventilation, and ICU mortality. The incidence of the weakness was found to be 7.83% among the patients who survived and 50% among those patients who did not survive critical illness. HOW TO CITE THIS ARTICLE: Baby S, George C, Osahan NM. Intensive Care Unit-acquired Neuromuscular Weakness: A Prospective Study on Incidence, Clinical Course, and Outcomes. Indian J Crit Care Med 2021;25(9):1006-1012.

Comparing paediatric- and adult-onset linear morphoea in a large tertiary-referral scleroderma centre.

Background: Linear morphoea is a severe morphoea subtype associated with extracutaneous manifestations, potentially permanent disfigurement and functional impairment. Linear morphoea is more prevalent in paediatric patients, and knowledge of disease in adults is limited. The objective of this study was to compare paediatric- and adult-onset linear morphoea, in an exclusively adult population. Methodology: This was a retrospective cohort study of adult patients with linear morphoea seen over a 3-year period at a single-site adult tertiary-referral Connective Tissue Disease centre. Clinical markers of disease severity and course, including anatomical distribution, extracutaneous manifestations, cutaneous symptoms, associated autoimmunity, inflammatory blood parameters, Dermatology Life Quality Index scores, treatment requirements and modified Localised Scleroderma Activity Tool were assessed and compared in paediatric- and adult-onset linear morphoea. Results: Of 298 patients with morphoea seen during the study period, 135 had linear morphoea and 133 were included in the study. Most were female (78.9%), the mean age was 36.5 years and almost half (43.6%) had adult-onset disease. Disease was similarly severe between groups with regard to anatomical distribution, cutaneous symptoms (n = 89, 66.9%), extracutaneous manifestations (n = 76, 57.1%), antinuclear antibody-positivity (n = 40, 40.4%), raised erythrocyte sedimentation rate (n = 27, 25.0%) and associated autoimmune diagnoses (n = 15, 11.3%). Prescribed treatments were similar between groups; 73.7% receiving methotrexate and almost one-third (32.3%) requiring more than one steroid-sparing agent. Those with paediatric-onset had more disease-related damage, with a mean modified Localised Scleroderma Skin Damage Index score of 19.5 (95% confidence interval: 17.0-22.0) versus 8.1 (95% confidence interval: 4.4-11.8; p < 0.001). Significantly more patients with adult-onset linear morphoea had quiescent disease (p = 0.0332), and even after correcting for disease duration, paediatric-onset patients still had 2.6 times greater odds of active disease (odds ratio = 2.59, 95% confidence interval: 0.9-7.6; p = 0.083). Conclusion: Linear morphoea in adults can be a severe disease with extracutaneous, autoimmune and systemic features. Adults with paediatric-onset disease appear to have more severe cumulative damage, greater functional impairment and ongoing disease activity. This patient subgroup may require particularly close monitoring and more aggressive therapy.

Pattern and Correlates of Depression among Medical Students: An 18.Month Follow-Up Study.

BACKGROUND: Medical students are subjected to various challenges, which are possibly etiological in the onset and persistence of depression. There is inadequate research on the longitudinal pattern and correlates of the emotional health of medical students in India. We aim to delineate the longitudinal pattern of depression among medical students and the factors predictive of depression. METHODS: An 18-month follow-up design with 350 students (2012 intake) from two medical colleges in Kerala, India, was employed. A semistructured questionnaire and the Patient Health Questionnaire 9 were administered 2, 8, and 18 months into the course. RESULTS: Depression was present in 42.80%, 36.20%, and 42.50% of the students at the three assessments. Variables significantly associated with depression on univariate analysis were the course not being of the student's choice at the first assessment; having an unemployed parent (mother) at the second assessment; alcohol use and male gender at the third assessment. On multivariate analysis, male gender (OR = 1.95[1.11-3.41]) and the presence of depression at 2 months (OR = 2.30[1.31-4.05]) and 8 months (OR = 2.48[1.39-4.44]) were predictive of depression at 18 months. CONCLUSIONS: The high rates of depression and the pattern of high rates early in the course among the medical students contrasts with that reported from other countries. Early depression and male gender were predictive of depression later in the course. The implications of this are to be taken into consideration when undergraduate intervention programs are planned.

Effectiveness of a group intervention led by lay health workers in reducing the incidence of postpartum depression in South India.

BACKGROUND: Postnatal depression is a highly prevalent disorder with serious implications on maternal and child outcomes. There are few studies examining feasible interventions in low-middle-income community settings. AIMS: To assess the effectiveness of a low intensity group intervention led by lay workers during the antenatal period in reducing postnatal depression at 6-2 weeks postpartum. METHODS: A parallel group design with both positive and negative controls was employed. 1 community site was allocated to each of the 3 arms. The active intervention consisted of problem based sessions with cognitive behavioural components. The primary outcome was the presence of depression on CIS-R and secondary outcome measures where Global Assessment of Functioning (GAF) scores, EPNDS scores and participant perceptions. RESULTS: 69, 75 and 70 women received active, positive control and negative control interventions respectively. Post partum depression diagnosed with the CIS-R was present in 14.06% (C.I.- 5.55%-22.57%) and 22.62% (C.I.15.62%-29.63%) in the active arm and two control (combined) arms respectively. There was a 1/3 lower proportion of postpartum depression and impaired functioning in the intervention group, though statistical significance was not reached (p = 0.30). There were high levels of satisfaction reported for the active intervention. CONCLUSION: There were trends for the possible effectiveness for this low intensity intervention and conclusions regarding its effectiveness can't be made as the sample size was small. There is a need to explore and develop locally relevant, innovative and feasible strategies for prevention of postnatal depression in resource constrained enviroments.

Ciliary neurotrophic factor signaling in the rat orbitofrontal cortex ameliorates stress-induced deficits in reversal learning.

Deficits in cognitive flexibility, i.e. the ability to modify behavior in response to changes in the environment, are present in several psychiatric disorders and are often refractory to treatment. However, improving treatment response has been hindered by a lack of understanding of the neurobiology of cognitive flexibility. Using a rat model of chronic stress (chronic intermittent cold stress, CIC) that produces selective deficits in reversal learning, a form of cognitive flexibility dependent on orbitofrontal cortex (OFC) function, we have previously shown that JAK2 signaling is required for optimal reversal learning. In this study we explore the molecular basis of those effects. We show that, within the OFC, CIC stress reduces the levels of phosphorylated JAK2 and of ciliary neurotrophic factor (CNTF), a promoter of neuronal survival and an activator of JAK2 signaling, and that neutralizing endogenous CNTF with an intra-OFC microinjection of a specific antibody is sufficient to produce reversal-learning deficits similar to stress. Intra-OFC delivery of recombinant CNTF to CIC-stressed rats, at a dose that induces JAK2 and Akt but not STAT3 or ERK, ameliorates reversal-learning deficits, and Akt blockade prevents the positive effects of CNTF. Further analysis revealed that CNTF may exert its beneficial effects by inhibiting GSK3ß, a substrate of Akt and a regulator of protein degradation. We also revealed a novel mechanism of CNTF action through modulation of p38/Mnk1/eIF4E signaling. This cascade controls translation of select mRNAs, including those encoding several plasticity-related proteins. Thus, we suggest that CNTF-driven JAK2 signaling corrects stress-induced reversal learning deficits by modulating the steady-state levels of plasticity-related proteins in the OFC.

First-in-Class Phosphorylated-p68 Inhibitor RX-5902 Inhibits ß-Catenin Signaling and Demonstrates Antitumor Activity in Triple-Negative Breast Cancer.

RX-5902 is a first-in-class anticancer agent targeting phosphorylated-p68 and attenuating nuclear shuttling of ß-catenin. The purpose of this study was to evaluate the efficacy of RX-5902 in preclinical models of triple-negative breast cancer (TNBC) and to explore effects on ß-catenin expression. A panel of 18 TNBC cell lines was exposed to RX-5902, and changes in proliferation, apoptosis, cellular ploidy, and effector protein expression were assessed. Gene expression profiling was used in sensitive and resistant cell lines with pathway analysis to explore pathways associated with sensitivity to RX-5902. The activity of RX-5902 was confirmed in vivo in cell line and patient-derived tumor xenograft (PDX) models. RX-5902 demonstrated potent antiproliferative activity in vitro against TNBC cell lines with an average IC50 of 56 nmol/L in sensitive cell lines. RX-5902 treatment resulted in the induction of apoptosis, G2-M cell-cycle arrest, and aneuploidy in a subset of cell lines. RX-5902 was active in vivo against TNBC PDX models, and treatment resulted in a decrease in nuclear ß-catenin. RX-5902 exhibited dose-proportional pharmacokinetics and plasma and tumor tissue in nude mice. Pathway analysis demonstrated an increase in the epithelial-to-mesenchymal transformation (EMT), TGFß, and Wnt/ß-catenin pathways associated with sensitivity to RX-5902. RX-5902 is active against in vitro and in vivo preclinical models of TNBC. Target engagement was confirmed with decreases in nuclear ß-catenin and MCL-1 observed, confirming the proposed mechanism of action. This study supports the continued investigation of RX-5902 in TNBC and combinations with immunotherapy.

Age- and Sex-Specific Plasticity in Dopamine Transporter Function Revealed by Food Restriction and Exercise in a Rat Activity-Based Anorexia Paradigm.

Eating disorders such as anorexia typically emerge during adolescence, are characterized by engagement in compulsive and detrimental behaviors, and are often comorbid with neuropsychiatric disorders and drug abuse. No effective treatments exist. Moreover, anorexia lacks adolescent animal models, contributing to a poor understanding of underlying age-specific neurophysiological disruptions. To evaluate the contribution of dopaminergic signaling to the emergence of anorexia-related behaviors during the vulnerable adolescent period, we applied an established adult activity-based anorexia (ABA) paradigm (food restriction plus unlimited exercise access for 4 to 5 days) to adult and adolescent rats of both sexes. At the end of the paradigm, measures of plasma volume, blood hormone levels, dopamine transporter (DAT) expression and function, acute cocaine-induced locomotion, and brain water weight were taken. Adolescents were dramatically more affected by the ABA paradigm than adults in all measures. In vivo chronoamperometry and cocaine locomotor responses revealed sex-specific changes in adolescent DAT function after ABA that were independent of DAT expression differences. Hematocrit, insulin, ghrelin, and corticosterone levels did not resemble shifts typically observed in patients with anorexia, though decreases in leptin levels aligned with human reports. These findings are the first to suggest that food restriction in conjunction with excessive exercise sex-dependently and age-specifically modulate DAT functional plasticity during adolescence. The adolescent vulnerability to this relatively short manipulation, combined with blood measures, evidence need for an optimized age-appropriate ABA paradigm with greater face and predictive validity for the study of the pathophysiology and treatment of anorexia. SIGNIFICANCE STATEMENT: Adolescent rats exhibit a distinctive, sex-specific plasticity in dopamine transporter function and cocaine response after food restriction and exercise access; this plasticity is both absent in adults and not attributable to changes in dopamine transporter expression levels. These novel findings may help explain sex differences in vulnerability to eating disorders and drug abuse during adolescence.

Pyoderma gangrenosum - a guide to diagnosis and management .

Pyoderma gangrenosum (PG) is a reactive non-infectious inflammatory dermatosis falling under the spectrum of the neutrophilic dermatoses. There are several subtypes, with 'classical PG' as the most common form in approximately 85% cases. This presents as an extremely painful erythematous lesion which rapidly progresses to a blistered or necrotic ulcer. There is often a ragged undermined edge with a violaceous/erythematous border. The lower legs are most frequently affected although PG can present at any body site. Other subtypes include bullous, vegetative, pustular, peristomal and superficial granulomatous variants. The differential diagnosis includes all other causes of cutaneous ulceration as there are no definitive laboratory or histopathological criteria for PG. Underlying systemic conditions are found in up to 50% of cases and thus clinicians should investigate thoroughly for such conditions once a diagnosis of PG has been made. Treatment of PG remains largely anecdotal, with no national or international guidelines, and is selected according to severity and rate of progression. Despite being a well-recognised condition, there is often a failure to make an early diagnosis of PG. This diagnosis should be actively considered when assessing ulcers, as prompt treatment may avoid the complications of prolonged systemic therapy, delayed wound healing and scarring.

Prevalence, correlates of depression, and its impact on quality of life of cancer patients attending a palliative care setting in South India.

OBJECTIVE: Depression is an easily treatable yet frequently underdiagnosed affliction in palliative population with deleterious implications on their quality of life. It has been studied poorly in developing countries like India. METHODS: A cross-sectional study was done with 234 consenting subjects attending a palliative care unit. Patient Health Questionnaire-9 (PHQ-9), World Health Organization Quality of Life (WHOQOL-BREF), and semi-structured proforma were used by trained nonmental health professional to collect data. RESULTS: The prevalence of major depression was 70%. Being a resident of nuclear family (p = .004), absence of insurance coverage (p = .01), presence of financial difficulties (p = .002), and absence of cancer recurrence (p = .001) were significantly associated with major depression in univariate analysis. In multivariate analysis, presence of financial difficulties (OR = 3.9; 95% CI, 2.00-7.61) and absence of health insurance (OR = 1.92; 95% CI, 1.02-3.7) were independently associated with major depression. The presence of depression showed significant negative correlation with physical health (p = .03), psychological health (p = .002), and environmental (p = .002) domains of the WHOQOL-BREF. CONCLUSION: This study brings to the fore the high rates of depression and its negative impact on the quality of life of terminally ill cancer patients. An improvement in their quality of life requires measures to reduce the rate of underdiagnosed psychiatric morbidities, especially in those who are financially burdened and lack insurance coverage.

Hysterectomy Uniquely Impacts Spatial Memory in a Rat Model: A Role for the Nonpregnant Uterus in Cognitive Processes.

Approximately one-third of women experience hysterectomy, or the surgical removal of the uterus, by 60 years of age, with most surgeries occurring prior to the onset of natural menopause. The ovaries are retained in about half of these surgeries, whereas for the other half hysterectomy occurs concurrently with oophorectomy. The dogma is that the nonpregnant uterus is dormant. There have been no preclinical assessments of surgical variations in menopause, including hysterectomy, with and without ovarian conservation, on potential endocrine and cognitive changes. We present a novel rat model of hysterectomy alongside sham, ovariectomy (Ovx), and Ovx-hysterectomy groups to assess effects of surgical menopause variations. Rats without ovaries learned the working memory domain of a complex cognitive task faster than did those with ovaries. Moreover, uterus removal alone had a unique detrimental impact on the ability to handle a high-demand working memory load. The addition of Ovx, that is, Ovx-hysterectomy, prevented this hysterectomy-induced memory deficit. Performance did not differ amongst groups in reference memory-only tasks, suggesting that the working memory domain is particularly sensitive to variations in surgical menopause. Following uterus removal, ovarian histology and estrous cycle monitoring demonstrated that ovaries continued to function, and serum assays indicated altered ovarian hormone and gonadotropin profiles by 2 months after surgery. These results underscore the critical need to further study the contribution of the uterus to the female phenotype, including effects of hysterectomy with and without ovarian conservation, on the trajectory of brain and endocrine aging to decipher the impact of common variations in gynecological surgery in women. Moreover, findings demonstrate that the nonpregnant uterus is not dormant, and indicate that there is an ovarian-uterus-brain system that becomes interrupted when the reproductive tract has been disrupted, leading to alterations in brain functioning.

High Salt Intake Lowers Behavioral Inhibition.

Stress-related neuropsychiatric (e.g., anxiety, depression) and cardiovascular diseases are frequently comorbid, though discerning the directionality of their association has been challenging. One of the most controllable risk factors for cardiovascular disease is salt intake. Though high salt intake is implicated in neuropsychiatric diseases, its direct neurobehavioral effects have seldom been explored. We reported that elevated salt intake in mice augments neuroinflammation, particularly after an acute stressor. Here, we explored how high salt consumption affected behavioral responses of mice to mildly arousing environmental and social tests, then assessed levels of the stress-related hormone corticosterone. Unexpectedly, anxiety-related behaviors in the elevated plus maze, open field, and marble burying test were unaffected by increased salt intake. However, nest building was diminished in mice consuming high salt, and voluntary social interaction was elevated, suggesting reduced engagement in ethologically-relevant behaviors that promote survival by attenuating threat exposure. Moreover, we observed significant positive correlations between social preference and subsequent corticosterone only in mice consuming increased salt, as well as negative correlations between open arm exploration in the elevated plus maze and corticosterone selectively in mice in the highest salt condition. Thus, heightened salt consumption reduces behavioral inhibition under relatively low-threat conditions, and enhances circulating corticosterone proportional to specific behavioral shifts. Considering the adverse health consequences of high salt intake, combined with evidence that increased salt consumption impairs inhibition of context-inappropriate behaviors, we suggest that prolonged high salt intake likely promulgates maladaptive behavioral and cardiovascular responses to perceived stressors that may explain some of the prevalent comorbidity between cardiovascular and neuropsychiatric diseases.

Anesthetic and Surgical Management of Mucoid Retention Cyst in the Vallecular Region: An Airway Challenge.

Growth of any kind in the oropharynx poses a threat to the airway especially during anaesthesia. Being aware of the challenges and adequately equipped to handle the situation is the duty of the anesthesiologist. METHODS AND MATERIAL: An eight year old girl diagnosed case of multiple mucous cysts presented to the outpatient department for excision of a lower lip mucous cyst. So an ultrasound was done which revealed a large intramural mucous cyst. After a preanaesthetic checkup she was posted for the excision of the cyst. RESULTS: The girl was posted for Elective surgery and was induced without prior premedication as she had revealed a history of snoring in supine position. After preoxygenating with 100% oxygen, she was induced with Injection Ketamine and Sevoflurane. She started desaturated abruptly so nasal airway and finally # 2.5 LMA was inserted but SpO2 didn't improve. With backup of Ent and paediatric surgeons direct larngoscopy was attempted and #5 ETT was inserted successfully. Following which the huge vallecular cyst was removed.