Ribosome-Associated Vesicles promote activity-dependent local translation.

Local protein synthesis in axons and dendrites underpins synaptic plasticity. However, the composition of the protein synthesis machinery in distal neuronal processes and the mechanisms for its activity-driven deployment to local translation sites remain unclear. Here, we employed cryo-electron tomography, volume electron microscopy, and live-cell imaging to identify Ribosome-Associated Vesicles (RAVs) as a dynamic platform for moving ribosomes to distal processes. Stimulation via chemically-induced long-term potentiation causes RAV accumulation in distal sites to drive local translation. We also demonstrate activity-driven changes in RAV generation and dynamics in vivo, identifying tubular ER shaping proteins in RAV biogenesis. Together, our work identifies a mechanism for ribosomal delivery to distal sites in neurons to promote activity-dependent local translation.

Prevalence and correlates of depression, anxiety, and stress among high school students in a block of Hooghly district, West Bengal: Across-sectional study.

BACKGROUND: Adolescent mental health is a concern. A high magnitude of deranged mental health conditions among adolescents is prevailing, which often gets extended into adulthood too. Hence, assessment of mental health morbidities like depression, anxiety, and stress is crucial to address them. This study aimed to estimate the prevalence of depression, anxiety, and stress among school-going adolescents studying in classes IX-XII and find out its correlates among the subjects. MATERIALS AND METHODS: This cross-sectional study was conducted among 812 adolescents studying in classes IX-XII in four randomly selected schools of Haripal block of Hooghly district, West Bengal, in 2022. A complete enumeration of students in each class of the selected schools was done. Data were collected by using a pretested schedule that included standardized depression, anxiety, and stress scale (DASS-21). Descriptive statistics and a Chi-square test were applied. Regression analysis was doneto determine associations and compute the adjusted odds ratio. Data were analyzed using SPSS version 23. RESULTS: Overall prevalence of depression, anxiety, and stress were found to be 52.3%, 47.4%, and 33.7% respectively. Subscale scores shows 16.1% and 10.8% suffered from extremely severe depression and anxiety, respectively. It was noted that these were more common among female students, the late adolescent age group (16-19 years), students having social problems in the family, and those reporting using substances. CONCLUSION: The prevalence of depression, anxiety, and stress being high among school students indicates a significant burden of mental health disease. Effective strategies to alleviate the adverse mental health, along with early identification of disease, can help in along way.

Access to chronic kidney disease (CKD) care: Its barriers and facilitators in a community development block in Purba Bardhaman, West Bengal: A qualitative study.

Background: Chronic kidney disease (CKD), a leading public health problem, has potential risks and serious implications on the health of individuals and society at large. Few studies explored the factors that influence access to CKD care at the community level in rural areas of West Bengal. A qualitative study was planned among key stakeholders to explore their views and experiences and to identify the barriers and potential facilitators that influence access to CKD care at the primary care level. Methods: Total 23 stakeholders participated in the study. Seventeen in-depth interviews (IDIs) were conducted on a purposive sample of stakeholders (CKD patients, healthcare providers (HCPs) and health planners) and one focus group discussion (FGD) among six community health workers. The audio-recorded interviews were transcribed verbatim. The Lévesque's framework for access to care as modified by Jodie Bailie et al. was employed to construct interview guides and structure the initial codes. Thematic analysis was undertaken using QSR NVivo version 11 using both inductive and deductive approaches. Results: The major barriers to CKD care at patient level were poor knowledge and awareness of CKD and at the health system level was shortage of skilled staffs, diagnostics and medicines and fragmented referrals. The potential facilitators identified were educational activities to increase the awareness of CKD among HCPs and patients; provision of CKD-related supplies and a system-level approach to care coordination along with m-health-based care. Conclusions: Targeted CKD screening programs and CKD specific trainings may improve awareness of CKD. Additionally, stronger primary care infrastructure, availability of essential drugs and diagnostics and creating an efficient referral process for the quality CKD care are the need of the hour.

An Unexpected Cause of Syncope.

Syncope is a common chief complaint among patients presenting to the emergency department, the etiology of which can often be discerned with a thorough history and physical examination. Inversely, liposarcomas are rare tumors that frequently pose a diagnostic challenge as the clinical presentation is highly nonspecific and varies greatly depending on the anatomic location and size of the tumor. Here we present a case of retroperitoneal liposarcomas (RLS) presenting to the emergency department (ED) with a sole complaint of syncope, resulting in a diagnostic dilemma. This clinical scenario highlights the significance of thorough physical examination regardless of the presenting chief complaint, as unexpected physical examination findings prompted an extended work-up and thus facilitated the diagnosis, providing the opportunity for early intervention and resection of the tumor.

Maintenance of a short-lived protein required for long-term memory involves cycles of transcription and local translation.

Activity-dependent expression of immediate early genes (IEGs) is critical for long-term synaptic remodeling and memory. It remains unknown how IEGs are maintained for memory despite rapid transcript and protein turnover. To address this conundrum, we monitored Arc, an IEG essential for memory consolidation. Using a knockin mouse where endogenous Arc alleles were fluorescently tagged, we performed real-time imaging of Arc mRNA dynamics in individual neurons in cultures and brain tissue. Unexpectedly, a single burst stimulation was sufficient to induce cycles of transcriptional reactivation in the same neuron. Subsequent transcription cycles required translation, whereby new Arc proteins engaged in autoregulatory positive feedback to reinduce transcription. The ensuing Arc mRNAs preferentially localized at sites marked by previous Arc protein, assembling a "hotspot" of translation, and consolidating "hubs" of dendritic Arc. These cycles of transcription-translation coupling sustain protein expression and provide a mechanism by which a short-lived event may support long-term memory.

Real-time imaging of Arc/Arg3.1 transcription ex vivo reveals input-specific immediate early gene dynamics.

The ability of neurons to process and store salient environmental features underlies information processing in the brain. Long-term information storage requires synaptic plasticity and regulation of gene expression. While distinct patterns of activity have been linked to synaptic plasticity, their impact on immediate early gene (IEG) expression remains poorly understood. The activity regulated cytoskeleton associated (Arc) gene has received wide attention as an IEG critical for long-term synaptic plasticity and memory. Yet, to date, the transcriptional dynamics of Arc in response to compartment and input-specific activity is unclear. By developing a knock-in mouse to fluorescently tag Arc alleles, we studied real-time transcription dynamics after stimulation of dentate granule cells (GCs) in acute hippocampal slices. To our surprise, we found that Arc transcription displayed distinct temporal kinetics depending on the activation of excitatory inputs that convey functionally distinct information, i.e., medial and lateral perforant paths (MPP and LPP, respectively). Moreover, the transcriptional dynamics of Arc after synaptic stimulation was similar to direct activation of GCs, although the contribution of ionotropic glutamate receptors, L-type voltage-gated calcium channel, and the endoplasmic reticulum (ER) differed. Specifically, we observed an ER-mediated synapse-to-nucleus signal that supported elevations in nuclear calcium and, thereby, rapid induction of Arc transcription following MPP stimulation. By delving into the complex excitation-transcription coupling for Arc, our findings highlight how different synaptic inputs may encode information by modulating transcription dynamics of an IEG linked to learning and memory.

Severe Thrombocytopenia Associated with Dengue Fever: An Evidence-Based Approach to Management of Thrombocytopenia.

Dengue is a mosquito-borne viral illness common in tropical and subtropical countries but very rare in the United States. Patients infected with dengue often present with thrombocytopenia. In the setting of dengue, platelet transfusions as a treatment for thrombocytopenia have no clear benefits in reduction of severe bleeding or improvement of the platelet count. Here, we present a case of a traveler infected with dengue virus and discuss the approach to treat thrombocytopenia.

Sphingomonas paucimobilis bacteremia and tricuspid valve endocarditis in a patient with intravenous drug use.

Sphingomonas paucimobilis is an aerobic, yellow-pigmented, glucose non-fermenting, gram negative bacillus that is a rare cause of human infection found mostly in the immunocompromised and also in intravenous (IV) drug users. We report a case of a 31-year-old female with current IV drug use, who presented with chest pain and was diagnosed with tricuspid valve endocarditis with S. paucimobilis bacteremia and pulmonary infarction of the right middle lobe. The patient initially presented with sharp right sided chest pain. She was treated with meropenem and levofloxacin based on the susceptibility profile. Our purpose is to highlight the treatment options and raise awareness of this uncommon organism. Even though Sphingomonas is considered to be of low-pathogenicity, it can be fatal if not treated properly and not diagnosed early.

A Unique Presentation of Acute Kidney Injury With COVID-19.

Although the respiratory system is the primary target of COVID-19 pneumonia, it can also notably affect the other systemic organs such as renal and cardiac. The incidence and prevalence of SARS CoV-2 associated acute renal failure are emerging day by day. While the pathogenesis is not clearly understood, it is considered multifactorial. Initially, the COVID-19-associated renal dysfunction was limited to acute tubular injury. However, over time a wide spectrum of clinical manifestations has been reported. Therefore, prompt investigation and early initiation of supportive treatment can potentially reduce the mortality and morbidity associated with this systemic disease. In this case report, we present a unique presentation of a COVID-19 with acute kidney injury where the patient was admitted to the intensive care unit with clinical features of acute renal failure with concomitant diagnosis of COVID-19, unlike other reported cases where patients were admitted to the intensive unit with respiratory distress and subsequently developed renal failure.

Non-aromatic Anticonvulsant (Divalproex Sodium)-Induced Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) Syndrome.

A wide array of commonly prescribed antiepileptic medications, antibiotics, antivirals, anti-parasitic, and antihyperuricemic can cause Drug Reaction Eosinophilia and Systemic Syndrome (DRESS)- a drug induced hypersensitivity reaction characterized by cutaneous manifestation, fever, eosinophilia, thrombocytopenia and one or more visceral organ involvement. The rare occurrence in clinical settings and wide variety of clinical presentations make DRESS a diagnostically challenging case. A vast majority of DRESS cases are attributed to the most commonly prescribed anticonvulsant medications - phenytoin and carbamazepines. Even though non-aromatic divalproex sodium/valproic acid (VPA) can cause life-threatening fatal hypersensitivity reactions on rare occasions, a handful cases of valproate-induced DRESS have been reported. We hereby report a case of a 57-year-old cognitively impaired person with polypharmacy who presented with worsening diffuse skin rash, fever, dysphagia, eosinophilia, thrombocytopenia, and mixed type of hepatic injury. The patient was eventually diagnosed with DRESS due to divalproex sodium- an anticonvulsant medication. The objective of our report is to identify and recognize the rare yet proper causative agent that induces DRESS and potential mitigation of significant systemic consequences by its subsequent withdrawal.

Spatiotemporal Insights Into RNA-Organelle Interactions in Neurons.

Neurons exhibit spatial compartmentalization of gene expression where localization of messenger RNAs (mRNAs) to distal processes allows for site-specific distribution of proteins through local translation. Recently, there have been reports of coordination between mRNA transport with vesicular and organellar trafficking. In this review, we will highlight the latest literature on axonal and dendritic local protein synthesis with links to mRNA-organelle cotransport followed by emerging technologies necessary to study these phenomena. Recent high-resolution imaging studies have led to insights into the dynamics of RNA-organelle interactions, and we can now peer into these intricate interactions within subcellular compartments of neurons.

Intracellular mRNA transport and localized translation.

Fine-tuning cellular physiology in response to intracellular and environmental cues requires precise temporal and spatial control of gene expression. High-resolution imaging technologies to detect mRNAs and their translation state have revealed that all living organisms localize mRNAs in subcellular compartments and create translation hotspots, enabling cells to tune gene expression locally. Therefore, mRNA localization is a conserved and integral part of gene expression regulation from prokaryotic to eukaryotic cells. In this Review, we discuss the mechanisms of mRNA transport and local mRNA translation across the kingdoms of life and at organellar, subcellular and multicellular resolution. We also discuss the properties of messenger ribonucleoprotein and higher order RNA granules and how they may influence mRNA transport and local protein synthesis. Finally, we summarize the technological developments that allow us to study mRNA localization and local translation through the simultaneous detection of mRNAs and proteins in single cells, mRNA and nascent protein single-molecule imaging, and bulk RNA and protein detection methods.

Uncommon Coronary Abnormalities in a Patient with Discoid Lupus Erythematosus.

A 43-year-old male presented with shortness of breath and palpitations. Physical examination was significant for skin lichenification, an erythematous maculopapular rash with annular plaques, a fissured tongue, and digital clubbing. Electrocardiogram captured a supraventricular tachycardia and right bundle branch block. Left heart catheterization found several proximal left coronary artery branch aneurysms, a right coronary-pulmonary artery fistula, venous-luminal vessels between the right heart chambers and cardiac veins, and thebesian venous lakes. Functional cardiac capacity was reduced, with left ventricular ejection fraction of 35 to 40%, on ventriculogram. A diagnosis of discoid lupus erythematosus was established after skin biopsies revealed systemic lupus erythematosus-like features but negative anti-nuclear, anti-Smith, anti-ds-deoxyribonucleic acid, anti-Ro, and anti-La antibodies. The case reported is unique, in that while our patient had pathologic electrophysiologic changes typically seen with autoimmune disease, the patient had many anatomical cardiac anomalies without atherosclerotic coronary disease. It is uncertain whether these findings are purely incidental or are related to an underlying genetic disorder.

Imaging of DNA and RNA in Living Eukaryotic Cells to Reveal Spatiotemporal Dynamics of Gene Expression.

This review focuses on imaging DNA and single RNA molecules in living cells to define eukaryotic functional organization and dynamic processes. The latest advances in technologies to visualize individual DNA loci and RNAs in real time are discussed. Single-molecule fluorescence microscopy provides the spatial and temporal resolution to reveal mechanisms regulating fundamental cell functions. Novel insights into the regulation of nuclear architecture, transcription, posttranscriptional RNA processing, and RNA localization provided by multicolor fluorescence microscopy are reviewed. A perspective on the future use of live imaging technologies and overcoming their current limitations is provided.

Partial Fanconi Syndrome Induced by Ifosfamide.

Several commonly used chemotherapeutic agents, antibiotics, antivirals, and antiepileptic medications can cause partial or full Fanconi syndrome, disorders which can generally be described as transport defects in the proximal renal tubule, associated with non-anion gap metabolic acidosis. Fanconi syndrome is underreported and therefore often missed in the clinical setting. Herein, we present a case report that details the course of a 64-year-old female with a history of stage IV undifferentiated pleomorphic sarcoma who after her sixth chemotherapeutic cycle (adriamycin, ifosfamide, and mesna) developed severe hypokalemia, hypophosphatemia, and proteinuria without glycosuria, eventually diagnosed with partial Fanconi syndrome. The aim of this report is to highlight the importance of routine serum and urine monitoring in patients undergoing therapy with potentially nephrotoxic agents to avoid potentially fatal renal nephrotoxicity, including partial and full Fanconi syndrome.

The travels of mRNAs in neurons: do they know where they are going?

Neurons are highly polarized cells that can extend processes far from the cell body. As such, transport of messenger RNAs serves as a set of blueprints for the synthesis of specific proteins at distal sites. RNA localization to dendrites and axons confers the ability to regulate translation with extraordinary precision in space and time. Although the rationale for RNA localization is quite compelling, it is unclear how a neuron orchestrates such a complex task of distributing over a thousand different mRNAs to their respective subcellular compartments. Recent single-molecule imaging studies have led to insights into the kinetics of individual mRNAs. We can now peer into the transport dynamics of mRNAs in both dendrites and axons.

Zipcode Binding Protein 1 (ZBP1; IGF2BP1): A Model for Sequence-Specific RNA Regulation.

The fate of an RNA, from its localization, translation, and ultimate decay, is dictated by interactions with RNA binding proteins (RBPs). ß-actin mRNA has functioned as the classic example of RNA localization in eukaryotic cells. Studies of ß-actin mRNA over the past three decades have allowed understanding of how RBPs, such as ZBP1 (IGF2BP1), can control both RNA localization and translational status. Here, we summarize studies of ß-actin mRNA and focus on how ZBP1 serves as a model for understanding interactions between RNA and their binding protein(s). Central to the study of RNA and RBPs were technological developments that occurred along the way. We conclude with a future outlook highlighting new technologies that may be used to address still unanswered questions about RBP-mediated regulation of mRNA during its life cycle, within the cell.

A transgenic mouse for imaging activity-dependent dynamics of endogenous Arc mRNA in live neurons.

Localized translation plays a crucial role in synaptic plasticity and memory consolidation. However, it has not been possible to follow the dynamics of memory-associated mRNAs in living neurons in response to neuronal activity in real time. We have generated a novel mouse model where the endogenous Arc/Arg3.1 gene is tagged in its 3' untranslated region with stem-loops that bind a bacteriophage PP7 coat protein (PCP), allowing visualization of individual mRNAs in real time. The physiological response of the tagged gene to neuronal activity is identical to endogenous Arc and reports the true dynamics of Arc mRNA from transcription to degradation. The transcription dynamics of Arc in cultured hippocampal neurons revealed two novel results: (i) A robust transcriptional burst with prolonged ON state occurs after stimulation, and (ii) transcription cycles continue even after initial stimulation is removed. The correlation of stimulation with Arc transcription and mRNA transport in individual neurons revealed that stimulus-induced Ca2+ activity was necessary but not sufficient for triggering Arc transcription and that blocking neuronal activity did not affect the dendritic transport of newly synthesized Arc mRNAs. This mouse will provide an important reagent to investigate how individual neurons transduce activity into spatiotemporal regulation of gene expression at the synapse.

Quality of life among menopausal women: A community-based study in a rural area of West Bengal.

INTRODUCTION: During menopausal transition, there is a lot of fluctuation in the hormone levels making the peri and postmenopausal women susceptible to various mental and physical disorders. There is considerably lack of awareness about the effects of the menopausal symptoms in women in India. Studies on issues relating to menopause, especially among rural women, are also lacking. With this background, the current study was carried out in a rural area of West Bengal with the objective to assess the quality of life (QOL) of peri-menopausal women. METHODOLOGY: The study was carried out among 100 peri and postmenopausal women (40-60 years) in Dearah village of West Bengal which is the rural field practice area of All India Institute of Hygiene and Public Health during February-March 2014. The questionnaire used as study tool had two parts - Part 1: Sociodemographic characteristics. Part 2: About QOL due to menopausal symptoms based on four domains (vasomotor, psychosocial, physical, and sexual) using the 29-item Menopause-Specific Quality of Life Questionnaire. RESULTS: Occurrence of vasomotor symptoms was average with 60% of them reporting hot flushes and 47% sweating. Most prevalent psychosocial symptoms reported were feeling of anxiety and nervousness (94%) and overall depression (88%). Physical symptoms were quite varying in occurrence with some symptoms such as feeling tired or worn out, decrease in physical strength and lack of energy occurring in 93% of the women to only 5% suffering from growth of facial hair. Overall sexual changes were reported among 49% who reported of avoiding intimacy with a partner and 26% complained of vaginal dryness. CONCLUSIONS: The results support that menopause causes both physical and psychiatric problems. Education, creating awareness and providing suitable intervention to improve their QOL are important which should be imparted to menopausal women at both individual and community level.