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Jeffrey Man Hay Wong,1 Neha Kanga,1 Nupur Dogra,1 Mary Shilalukey Ngoma,2 Lena Serghides,3 Michael Silverman4 1Faculty of Medicine, University of Toronto, Toronto, ON, Canada; 2Department of Pediatrics, University of Zambia, Lusaka, Zambia; 3Toronto General Research Institute, University Health Network, Toronto, ON, Canada; 4Department of Infectious Diseases, Western University, London, ON, Canada Introduction: Intramuscular and vaginal progesterone are recommended for prevention of preterm labor (PTL) in women with risk factors. Studies are emerging to indicate that HIV-infected women on combination antiretroviral therapy (cART) are at risk of PTL and low birth weight (LBW), and may benefit from supplemental progesterone. This study aims to determine the perceived acceptability of various modes of progesterone supplementation to prevent PTL and LBW in HIV-infected and HIV-uninfected women.Methods: HIV-infected and HIV-uninfected women were recruited in Lusaka, Zambia. The participants completed a questionnaire to assess their willingness to take oral, vaginal, or intramuscular progesterone supplementation for preventing PTL and LBW, preferred modes of supplementation, and concern for PTL and LBW.Results: The study questionnaire was completed by 147 participants. Of the participants, 98.6% would consider using a medication to help prevent PTL and LBW, of whom 97.9% would consider using an oral form of progesterone. In addition, 83.3% and 84.0% of women would consider intramuscular and vaginal (gel or tablet) administration of progesterone respectively. Between intramuscular and vaginal modes of progesterone, 60.5% of participants (n=147) preferred intramuscular progesterone, while 39.5% preferred vaginal progesterone. There was no difference in preference between HIV-infected (n=70) and HIV-uninfected (n=77) women.Conclusions/implications: Pregnant Zambian women demonstrated a high degree of acceptance for all modes of progesterone supplementation for the prevention of PTL and LBW. Women preferred intramuscular over vaginal supplementation. Progesterone supplementation can be considered a feasible intervention for preventing PTL and LBW in both HIV-infected and HIV-uninfected pregnant Zambian women. Keywords: HIV/AIDS, progesterone, preterm labor, low birth weight, global health

Introduction To highlight intraoperative and postoperative challenges in patient with esophageal atresia or stricture undergoing esophageal replacement surgery. We report two such cases and important considerations in its management. Case report: First case. 4 year old child, weighing 16 kgs, with history of corrosive ingestion 1 year back, which lead to development of stricture. He was planned for jejunal transposition surgery. Second case. 18 months old infant, weighing 10 kgs. He had esophageal atresia and esophagostomy and gastrostomy was done on 2nd day of life. Gastric pullup surgery was planned for the patient. In preanesthetic examination no associated congenital anomaly was present. We planned for general anesthesia along with lumbar epidural for intraoperative and postoperative analgesia. Proper oropharyngeal suction was done. After premedication with midazolam and glycopyrrolate, fentanyl 2µg/kg was given. Thiopentone and succinylcholine were used for induction. After endotracheal intubation, lumbar epidural was given in L3-L4 intervertebral space and epidural catheter was inserted followed by 0.2% ropivacaine 0.5 ml/kg bolus. Intraoperatively hypotension occurred in first case but managed successfully with blood transfusion and vasopressors. Postoperatively both patients were shifted intubated to ICU for elective ventilation and kept sedated with midazolam 2µg/kg/min. Analgesia was maintained with epidural 0.2% ropivacaine combined with 0.5µg/kg dexmedetomidine 6 hourly. Both were extubated on 2nd and 3rd postoperative day. Conclusion Esophageal replacement surgery is challenging case for anesthesiologists in various perspects including risk for major blood loss, requirement for adequate intraoperative and postoperative analgesia, pediatric patient and need for postoperative elective ventilation and adequate sedation. Cautious management is required in all these aspects for a favourable patient outcome. [ABSTRACT FROM AUTHOR]

Mycobacterium microti-infected mouse peritoneal microphages produced high amounts of prostaglandin E2 (PGE2) and nitric oxide (NO) when activated with interferon-γ (IFN-γ). In order to understand the relation between PGE2 and NO production and the expression of interleukin-12 (IL-12), interleukin-10 (IL-10) and MHC class-II (Ia) molecules by M. microti-infected and IFN-γ-stimulated macrophages, we analyzed the level of these molecules in the presence or absence of PGE2 and NO inhibitors. Addition of N G-methyl- l-arginine ( l-NMA) and indomethacin (IM) caused a significant increase in IL-12 level (2.6- and 1.9-fold, respectively) whereas IL-10 level decreased by 88 and 56%, respectively, relative to M. microti-infected and IFN-γ-treated control macrophages. Enhanced PGE2 and NO upregulated IL-10 expression and down-regulated IL-12 and MHC class-II (Ia) expression in M. microti-infected and IFN-γ-treated mouse peritoneal macrophages. [ABSTRACT FROM AUTHOR]

A strain of Micrococcus sp. was isolated for its capability of side chain degradation of cholesterol. This strain was characterized and identified as Micrococcus roseus. It was found to be the best strain for the production of androsta-1,4-diene-3, 17-dione and androst-4-ene-3, 17-dione compared with other Micrococcus strains. [ABSTRACT FROM AUTHOR]

A comparative study was done using J774A.1 and J774A. 1-derived transfected cells (J774A.1 C.1) containing antisense tumor necrosis factor α (TNF-α) plasmid to determine the role of endogenous TNF-α on nitric oxide production as well as on the growth of Mycobacterium microti in interferon γ (IFN-γ)- and lipopolysaccharide (LPS)-treated cells. On stimulation with IFN-γ and LPS a higher level of NO was observed in J774A.1 cells compared to J774A.1 C.1 which indicated that endogenous TNF-α is required for the production of NO. Comparing the effect of IFN-γ and LPS on the intracellular growth of M. microti, the growth-reducing activity was higher in J774A.1 cells than in J774A.1 C.1 cells and was not completely abrogated in the presence of the nitric oxide inhibitor N G-methyl- l-arginine ( l-NMA). J774A.1 C.1 cells infected with M. microti produced a significant amount of NO when exogenous TNF-α was added along with IFN-γ and LPS and the concentration of intracellular bacteria decreased almost to that in IFN-γ and LPS treated parental J774A.1 cells. Addition of exogenous TNF-α even in the presence of l-NMA in J774.1 C.1 cells could also partially restore intracellular growth inhibition of M. microti caused by IFN-γ and LPS. TNF-α is probably required for the production of NO in J774A.1 cells by IFN-γ and LPS but TNF-α and NO are independently involved in the killing of intracellular M. microti with IFN-γ and LPS. [ABSTRACT FROM AUTHOR]

The study reports a record of palynological and palynofacies assemblage comprising 29 genera and 34 species of acritarchs, pteridophytes, gymnosperms, fungal and dinoflagellates from the Kothar Section of Nilkanth, Uttarakhand. The lower part of the succession indicates terrestrial warm and humid conditions with intermittent marine influences. Presence of dinoflagellate cysts in the middle part shows slight deepening of the shallow basin, while nummulites in the upper part indicate marine conditions. The overall assemblage of the Subathu Kothar area succession dates this formation to Early-Middle Eocene. [ABSTRACT FROM AUTHOR]

We observe cavity mediated spin-dependent interactions in an off-resonantly driven multilevel atomic Bose-Einstein condensate that is strongly coupled to an optical cavity. Applying a driving field with adjustable polarization, we identify the roles of the scalar and the vectorial components of the atomic polarizability tensor for single and multicomponent condensates. Beyond a critical strength of the vectorial coupling, we infer the formation of a spin texture in a condensate of two internal states from the analysis of the cavity output field. Our work provides perspectives for global dynamical gauge fields and self-consistently spin-orbit coupled gases. [ABSTRACT FROM AUTHOR]

Lichen scrofulosorum is a tuberculid that is usually seen in children or young adults. Although a rare occurrence, this tuberculid is an important marker of occult tuberculosis, which may not be detected otherwise. We report here a case of lichen scrofulosorum in a ten year-old boy with typical grouped lichenoid papules on the trunk associated with axillary tuberculous lymphadenitis.

Abstract Background There is considerable ambiguity in the subjective dimensions that comprise much of the relational dynamic of the clinical encounter. Comfort with this ambiguity, and recognition of the potential uncertainty of particular domains of medicine (e.g. – cultural factors of illness expression, value bias in diagnoses, etc) is an important facet of medical education. This paper begins by defining ambiguity and uncertainty as relevant to clinical practice. Studies have shown differing patterns of students' tolerance for ambiguity and uncertainty that appear to reflect extant attitudinal predispositions toward technology, objectivity, culture, value- and theory-ladeness, and the need for self-examination. This paper reports on those findings specifically related to the theme of uncertainty as relevant to teaching about cultural diversity. Its focus is to identify how and where the theme of certainty arose in the teaching and learning of cultural diversity, what were the attitudes toward this theme and topic, and how these attitudes and responses reflect and inform this area of medical pedagogy. Methods A semi-structured interview was undertaken with 61 stakeholders (including policymakers, diversity teachers, students and users). The data were analysed and themes identified. Results There were diverse views about what the term cultural diversity means and what should constitute the cultural diversity curriculum. There was a need to provide certainty in teaching cultural diversity with diversity teachers feeling under considerable pressure to provide information. Students discomfort with uncertainty was felt to drive cultural diversity teaching towards factual emphasis rather than reflection or taking a patient centred approach. Conclusion Students and faculty may feel that cultural diversity teaching is more about how to avoid professional, medico-legal pitfalls, rather than improving the patient experience or the patient-physician relationship. There may be pressure to imbue cultural diversity issues with levels of objectivity and certainty representative of other aspects of the medical curriculum (e.g. – biochemistry). This may reflect a particular selection bias for students with a technocentric orientation. Inadvertently, medical education may enhance this bias through training effects, and accommodate disregard for subjectivity, over-reliance upon technology and thereby foster incorrect assumptions of objective certainty. We opine that it is important to teach students that technology cannot guarantee certainty, and that dealing with subjectivity, diversity, ambiguity and uncertainty is inseparable from the personal dimension of medicine as moral enterprise. Uncertainty is inherent in cultural diversity so this part of the curriculum provides an opportunity to address the issue as it relates to pateint care.

Abstract Background Cultural diversity teaching is increasingly present in both undergraduate and postgraduate training programmes. This study explored the views of stakeholders in medical education about the potential outcomes of cultural diversity teaching and how they thought cultural diversity programmes might be effectively evaluated. Methods A semi-structured interview was undertaken with 61 stakeholders (including policymakers, diversity teachers, students and users). The data were analysed and themes identified. Results Many participants felt that clinical practice was improved through 'cultural diversity teaching' and this was mostly as a result of improved doctor-patient communication. There was a strong view that service users need to participate in the evaluation of outcomes of cultural diversity teaching. Conclusion There is a general perception, rather than clear evidence, that cultural diversity teaching can have a positive effect on clinical practice. Cultural diversity teaching needs to be reviewed in undergraduate and postgraduate medicine and better evaluation tools need to be established.

Use of online sources to track disease outbreaks and deliver real-time surveillance in emerging public health threats is becoming the need of the hour as resurgence of diseases challenge global health systems. Recent advances in Geographical Information System (GIS) and mapping technologies have enhanced diseases surveillance programs. The current paradigm shifts are moving towards greater adoption of the ubiquitous internet for GIS deployment. This paper attempts to highlight the applicability of three online disease mapping tools - Google trends (GT), HealthMap and Kazemill as newer paradigms of disease surveillance in India. The study has been limited to comparing the trends obtained from the online tools with freely available public health data for few diseases such as malaria, typhoid and cholera that commonly occur in India. We conclude that G T could possibly be used for providing first hand information of impending disease outbreaks subject to further validation against past trends of the disease to have more relevance. [ABSTRACT FROM AUTHOR]

Stress shielding in dental and orthopedic implants is a long-standing hurdle, and trabecular porous architecture to improve bone ingrowth is deemed to be a potential solution. Fabricating Ti 6 Al 4 V components with dense-porous bilayer structures is complicated with limited lab-scale and commercial success. Here, a green dough-forming technique with metal powders is successfully explored to develop heterogeneous structures with a monolith-like dense-porous interface. The porous region achieved 70% porosity with a 25 MPa compressive strength comparable to human cancellous bone. Due to its simplicity and versatility, this process is a promising solution for developing and mass-manufacturing customized designs for bone-related implants with improved bone ingrowth and osseointegration.

Glioblastoma (GBM) is the highest grade of glioma for which no effective therapy is currently available. Despite extensive research in diagnosis and therapy, there has been no significant improvement in GBM outcomes, with a median overall survival continuing at a dismal 15-18 months. In recent times, glioblastoma stem cells (GSCs) have been identified as crucial drivers of treatment resistance and tumor recurrence, and GBM therapies targeting GSCs are expected to improve patient outcomes. We used a multistep in silico screening strategy to identify repurposed candidate drugs against selected therapeutic molecular targets in GBM with potential to concomitantly target GSCs. Common differentially expressed genes (DEGs) were identified through analysis of multiple GBM and GSC datasets from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). For identification of target genes, we selected the genes with most significant effect on overall patient survival. The relative mRNA and protein expression of the selected genes in TCGA control versus GBM samples was also validated and their cancer dependency scores were assessed. Drugs targeting these genes and their corresponding proteins were identified from LINCS database using Connectivity Map (CMap) portal and by in silico molecular docking against each individual target using FDA-approved drug library from the DrugBank database, respectively. The molecules thus obtained were further evaluated for their ability to cross blood brain barrier (BBB) and their likelihood of resulting in drug resistance by acting as p-glycoprotein (p-Gp) substrates. The growth inhibitory effect of these final shortlisted compounds was examined on a panel of GBM cell lines and compared with temozolomide through the drug sensitivity EC50 values and AUC from the PRISM Repurposing Secondary Screen, and the IC50 values were obtained from GDSC portal. We identified RPA3, PSMA2, PSMC2, BLVRA, and HUS1 as molecular targets in GBM including GSCs with significant impact on patient survival. Our results show GSK-2126458/omipalisib, linifanib, drospirenone, eltrombopag, nilotinib, and PD198306 as candidate drugs which can be further evaluated for their anti-tumor potential against GBM. Through this work, we identified repurposed candidate therapeutics against GBM utilizing a GSC inclusive targeting approach, which demonstrated high in vitro efficacy and can prospectively evade drug resistance. These drugs have the potential to be developed as individual or combination therapy to improve GBM outcomes., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Understanding the mechanisms underlying resistance is critical to improving therapeutic outcomes in patients with metastatic castration-resistant prostate cancer. Previous work showed that dynamic interconversions between epithelial-mesenchymal transition to mesenchymal-epithelial transition defines the phenotypic landscape of prostate tumors, as a potential driver of the emergence of therapeutic resistance. In this study, we use in vitro and in vivo preclinical MDA PCa patient-derived xenograft models of resistant human prostate cancer to determine molecular mechanisms of cross-resistance between antiandrogen therapy and taxane chemotherapy, underlying the therapeutically resistant phenotype. Transcriptomic profiling revealed that resistant and sensitive prostate cancer C4-2B cells have a unique differential gene signature response to cabazitaxel. Gene pathway analysis showed that sensitive cells exhibit an increase in DNA damage, while resistant cells express genes associated with protein regulation in response to cabazitaxel. The patient-derived xenograft model specimens are from patients who have metastatic lethal castration-resistant prostate cancer, treated with androgen deprivation therapy, antiandrogens, and chemotherapy including second-line taxane chemotherapy, cabazitaxel. Immunohistochemistry revealed high expression of E-cadherin and low expression of vimentin resulting in redifferentiation toward an epithelial phenotype. Furthermore, the mitotic kinesin-related protein involved in microtubule binding and the SLCO1B3 transporter (implicated in cabazitaxel intracellular transport) are associated with resistance in these prostate tumors. Combinational targeting of kinesins (ispinesib) with cabazitaxel was more effective than single monotherapies in inducing cell death in resistant prostate tumors. Implications: Our findings are of translational significance in identifying kinesin as a novel target of cross-resistance toward enhancing therapeutic vulnerability and improved clinical outcomes in patients with advanced prostate cancer., (©2024 American Association for Cancer Research.)