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Byline: Shalesh. Rohatgi, Prajwal. Rao, Satish. Nirhale, Pravin. Naphade, Sravya. Kotharu, Sahil. Gupta Neuromyelitis Optica (NMO) is a demyelinating disease predominantly involving optic nerves, spinal cord and peri-ventricular regions which [...]

Macrophages in the tumor microenvironment respond to complex cytokine signals. How these responses shape the phenotype of tumor-associated macrophages (TAMs) is incompletely understood. Here we explored how cytokines of the tumor milieu, interleukin (IL)-6 and IL-4, interact to influence target gene expression in primary human monocyte-derived macrophages (hMDMs). We show that dual stimulation with IL-4 and IL-6 synergistically modified gene expression. Among the synergistically induced genes are several targets with known pro-tumorigenic properties, such as CC-chemokine ligand 18 (CCL18), transforming growth factor alpha (TGFA) or CD274 (programmed cell death 1 ligand 1 (PD-L1)). We found that transcription factors of the signal transducer and activator of transcription (STAT) family, STAT3 and STAT6 bind regulatory regions of synergistically induced genes in close vicinity. STAT3 and STAT6 co-binding further induces the basic leucine zipper ATF-like transcription factor (BATF), which participates in synergistic induction of target gene expression. Functional analyses revealed increased MCF-7 and MDA-MB 231 tumor cell motility in response to conditioned media from co-treated hMDMs compared to cells incubated with media from single cytokine-treated hMDMs. Flow cytometric analysis of T cell populations upon co-culture with hMDMs polarized by different cytokines indicated that dual stimulation promoted immunosuppressive properties of hMDMs in a PD-L1-dependent manner. Analysis of clinical data revealed increased expression of BATF together with TAM markers in tumor stroma of breast cancer patients as compared to normal breast tissue stroma. Collectively, our findings suggest that IL-4 and IL-6 cooperate to alter the human macrophage transcriptome, endowing hMDMs with pro-tumorigenic properties.

Arachidonate 15-lipoxygenase (ALOX15) and arachidonate 15-lipoxygenase, type B (ALOX15B) catalyze the dioxygenation of polyunsaturated fatty acids and are upregulated in human alternatively activated macrophages (AAMs) induced by Th2 cytokine interleukin-4 (IL-4) and/or interleukin-13. Known primarily for roles in bioactive lipid mediator synthesis, 15-lipoxygenases (15-LOXs) have been implicated in various macrophage functions including efferocytosis and ferroptosis. Using a combination of inhibitors and siRNAs to suppress 15-LOX isoforms, we studied the role of 15-LOXs in cellular cholesterol homeostasis and immune function in naïve and AAMs. Silencing or inhibiting the 15-LOX isoforms impaired sterol regulatory element binding protein (SREBP)-2 signaling by inhibiting SREBP-2 processing into mature transcription factor and reduced SREBP-2 binding to sterol regulatory elements and subsequent target gene expression. Silencing ALOX15B reduced cellular cholesterol and the cholesterol intermediates desmosterol, lanosterol, 24,25-dihydrolanosterol, and lathosterol as well as oxysterols in IL-4-stimulated macrophages. In addition, attenuating both 15-LOX isoforms did not generally affect IL-4 gene expression but rather uniquely impacted IL-4-induced CCL17 production in an SREBP-2-dependent manner resulting in reduced T cell migration to macrophage conditioned media. In conclusion, we identified a novel role for ALOX15B, and to a lesser extent ALOX15, in cholesterol homeostasis and CCL17 production in human macrophages.

Drug use and road traffic injuries (RTIs) are significant public health concerns globally, with the majority of RTIs occurring in low- and middle-income countries. Driving under the influence of alcohol and drugs is a major factor in RTIs, as psychoactive drugs can impair mental functioning and vehicular control. While alcohol-related traffic deaths have declined, drug-impaired driving is increasing. In India, RTIs are on the rise, and there is a need for more research on drug use and driving under the influence. The lack of research evidence in India contributes to a lack of comprehensive laws and policies for prevention and treatment of drug-related RTIs. It is recommended that research focus on various aspects of drug-impaired driving, and trauma centers should be equipped with testing and treatment services. [Extracted from the article]

Introduction: Cavernous sinus syndrome (CSS) is a condition with varied etiology. It is characterized by ophthalmoplegia, facial sensory loss, and Horner’s syndrome. The objective of this study was to determine the clinical and radiological presentations and to identify the factors that could help in the identification of etiology. Methods: We prospectively observed all the patients presenting with CSS from October 2019 to September 2021 at a tertiary care hospital. Patients with coronavirus disease 2019 (COVID‑19)‑associated mucormycosis were excluded. All of these patients underwent detailed clinical examination, hematological, radiological, and specialized investigations based on clinical suspicion. Clinical presentations, imaging characteristics, etiology, and clinical outcomes were analyzed. 45 patients were included in our study. Results: The mean age was 44.6 ± 10.8 years with a female preponderance. The most common presentation was diplopia which was seen in all patients. The commonest cranial nerve involved was the abducens (75.9%). Infections (12 (26.6%)) constituted the commonest cause of CSS, followed by neoplastic involvement in 11 (24.4%), Tolosa–Hunt syndrome in 9 (20%) and vascular involvement in 8 (17.7%) patients. Other inflammatory causes were seen in 5 (11%) patients. Diabetes was positively associated with fungal infections. The presence of bruit was strongly associated with vascular etiology. The presence of sinusitis with bony erosions was strongly associated with fungal infections. Evidence of dilated superior ophthalmic vein with early filling in the angiographic phase was associated with carotid‑cavernous fistulas. Conclusions: CSS has variable etiology and radiological presentation. The presence of rapid progressive ophthalmoplegia with underlying diabetes with imaging evidence of sinusitis and bony erosions mandates a high degree of suspicion of fungal infections and empirical antifungal therapy needs to be considered for better outcomes. [ABSTRACT FROM AUTHOR]

Red-wattled Lapwings Vanellus indicus are resident waders in Asia. They usually inhabit areas close to water and are mainly insectivorous. Their principal habitats are grasslands, wetlands, arable lands, gardens and open forests. These highly active and vocal birds are known for their wide range of distraction displays. A field investigation of distribution across different seasons and diverse habitats in Udaipur, Rajasthan was conducted from 2019 to 2021. Populations of lapwings varied significantly among locations, with the largest documented at Fateh Sagar Lake and the lowest at Rang Sagar Lake. Both habitat types and seasons (summer, monsoon and winter) had significant effects on lapwing distribution. Wetlands were the most preferred habitat at ten major study locations, and the monsoon was found to be the most favored season. Bird activity patterns did not exhibit significant variation with seasons, with locomotion, vigilance, feeding and maintenance being the most performed activities. [ABSTRACT FROM AUTHOR]

Background: Healthcare providers working with victims of physical trauma are exposed to significant human suffering at work. This may place them at risk of burnout, secondary traumatic stress (STS), and other psychological disturbances. This study aimed to evaluate the professional quality of life and psychological well-being among trauma professionals. Methodology: This was a cross-sectional study conducted among 153 staff members (nursing officers, resident doctors, and faculty) of a Level 1 trauma center in North India. The Professional Quality of Life (ProQoL-5) and Depression, Anxiety, and Stress (DASS-21) Scales were used. Results: More than 50% of the participants had a moderate risk of burnout and STS. In addition, 54% of participants reported having anxiety, 40% stress, and 36% depressive symptoms. Depression, anxiety, and stress were all strongly predicted by burnout and STS. Conclusion: Psychological distress symptoms were seen in a significant portion of professionals working in the trauma center. Workplace interventions for the promotion of psychological well-being among trauma professionals are recommended. [ABSTRACT FROM AUTHOR]