Zinc(II) Complexes of SIRTi1/2 Analogues Transmetallating with Copper Ions and Inducing ROS Mediated Paraptosis.

As the SIRTi analogue series (HL1-HL6) show potent antitumor activity in vitro, we synthesized their corresponding zinc(II) complexes (ZnL1-ZnL6) and investigated their potential as anticancer agents. The Zn(II) complexes showed substantially greater cytotoxicity than HL1-HL6 alone in several cancer cell-types. Notably, distinct structure-activity relationships confirmed the significance of tert-butyl (ZnL2) pharmacophore inclusion in their activity. ZnL2 complexes were found to transmetalate with copper ions inside cells, causing the formation of redox-active copper complexes that induced reactive oxygen species (ROS) production, mitochondrial membrane depolarization, ATP decay, and cell death. This is the first study to exhibit Zn(II) complexes that mediate their activity via transmetalation with copper ions to undergo paraptosis cell death pathway. To further confirm if the SIRT1/2 inhibitory property of SIRTi analogues is conserved, a docking simulation study is performed. The binding affinity and specific interactions of the Cu(II) complex obtained after transmetalation with ZnL2 were found to be higher for SIRT2 (K i = 0.06 µM) compared to SIRT1 (K i = 0.25 µM). Thus, the concurrent regulation of several biological targets using a single drug has been shown to have synergistic therapeutic effects, which are crucial for the effective treatment of cancer.

In vitro and in vivo assessment of curcumin-quercetin loaded multi-layered 3D-nanofibroporous matrix prepared by solution blow-spinning for full-thickness burn wound healing.

Burn wounds (BWs) cause impairment of native skin tissue and may cause significant microbial infections that demand immediate care. Curcumin (Cur) and quercetin (Que) exhibit antimicrobial, hemocompatibility, ROS-scavenging, and anti-inflammatory properties. However, its instability, water insolubility, and low biological fluid absorption render it challenging to sustain local Cur and Que doses at the wound site. Therefore, to combat these limitations, we employed blow-spinning and freeze-drying to develop a multi-layered, Cur/Que-loaded gelatin/chitosan/PCL (GCP-Q/C) nanofibroporous (NFP) matrix. Morphological analysis of the NFP-matrix using SEM revealed a well-formed multi-layered structure. The FTIR and XRD plots demonstrated dual-bioactive incorporation and scaffold polymer interaction. Additionally, the GCP-Q/C matrix displayed high porosity (82.7 ± 2.07 %), adequate pore size (∼121 µm), enhanced water-uptake ability (∼675 % within 24 h), and satisfactory biodegradation. The scaffolds with bioactives had a long-term release, increased antioxidant activity, and were more effective against gram-positive (S. aureus) and gram-negative (E. coli) bacteria than the unloaded scaffolds. The in vitro findings of GCP-Q/C scaffolds showed promoted L929 cell growth and hemocompatibility. Additionally, an in vivo full-thickness BW investigation found that an implanted GCP-Q/C matrix stimulates rapid recuperation and tissue regeneration. In accordance with the findings, the Gel/Ch/PCL-Que/Cur NFP-matrix could represent an effective wound-healing dressing for BWs.

Graphene-silymarin-loaded chitosan/gelatin/hyaluronic acid hybrid constructs for advanced full-thickness burn wound management.

Burn wounds (BWs) with extensive blood loss, along with bacterial infections and poor healing, may become detrimental and pose significant rehabilitation obstacles in medical facilities. Therefore, the freeze-drying method synthesized novel hemocompatible chitosan, gelatin, and hyaluronic acid infused with graphene oxide-silymarin (CGH-SGO) hybrid constructs for application as a BW patch. Most significantly, synthesized hybrid constructs exhibited an interconnected-porous framework with precise pore sizes (≈118.52 µm) conducive to biological functions. Furthermore, the FTIR and XRD analyses document the constructs' physiochemical interactions. Similarly, enhanced swelling ratios, adequate WVTR (736 ± 78 g m-2 hr-1), and bio-degradation rates were seen during the physiological examination of constructs. Following the in vitro investigations, SMN-GO added to constructs improved their anti-bacterial (against E.coli and S. aureus), anti-oxidant, hemocompatible, and bio-compatible characteristics in conjunction with prolonged drug release. Furthermore, in vivo, implanting constructs on wounds exhibited significant acceleration in full-thickness burn wound (FT-BW) healing on the 14th day (CGH-SGO: 95 ± 2.1 %) in contrast with the control (Gauze: 71 ± 4.2 %). Additionally, contrary to gauze, the in vivo rat tail excision model administered with constructs assured immediate blood clotting. Therefore, CGH-SGO constructs with an improved porous framework, anti-bacterial activity, hemocompatibility, and biocompatibility could represent an attractive option for healing FT-BWs.

Pyridine-2,6-Dicarboxamide Proligands and their Cu(II)/Zn(II) Complexes Targeting Staphylococcus Aureus for the Attenuation of In Vivo Dental Biofilm.

In the pursuit to combat stubborn bacterial infections, particularly those stemming from gram-positive bacteria, this study is an attempt to craft a precision-driven platform characterized by unparalleled selectivity, specificity, and synergistic antimicrobial mechanisms. Leveraging remarkable potential of metalloantibiotics in antimicrobial applications, herein, this work rationally designs, synthesizes, and characterizes a new library of Pyridine-2,6-dicarboxamide ligands and their corresponding transition metal Cu(II)/Zn(II) complexes. The lead compound L11 demonstrates robust antibacterial properties against Staphylococcus aureus (Minimum Inhibitory Concentration (MIC) = 2-16 µg mL-1), methicillin and vancomycin-resistant S. aureus (MIC = 2-4 µg mL-1) and exhibit superior antibacterial activity when compared to FDA-approved vancomycin, the drug of last resort. Additionally, the compound exhibits notable antimicrobial efficacy against resistant enterococcus strains (MIC = 2-8 µg mL-1). To unravel mechanistic profile, advanced imaging techniques including SEM and AFM are harnessed, collectively suggesting a mechanistic pathway involving cell wall disruption. Live/dead fluorescence studies further confirm efficacy of L11 and its complexes against S. aureus membranes. This translational exploration extends to a rat model, indicating promising in vivo therapeutic potential. Thus, this comprehensive research initiative has capabilities to transcends the confines of this laboratory, heralding a pivotal step toward combatting antibiotic-resistant pathogens and advancing the frontiers of metalloantibiotics-based therapy with a profound clinical implication.

Ab initio modeling of human IRS1 protein to find novel target to dock with drug MH to mitigate T2DM diabetes by insulin signaling.

IRS1 is a cytoplasmic adaptor protein that helps in cellular growth, glucose metabolism, proliferation, and differentiation. Highly disordered (insulin receptor substrate 1) IRS1 protein sequence (mol.wt- 131,590.97 da) has been used to develop model using ab initio modeling technique by I-Tassar tool and Discovery Studio/ DogSite Server to decipher a novel active site. The constructed protein model has been submitted with PMDB Id- PM0082210. GRAVY index of IRS1 model ( - 0.675) indicated surface protein-water interaction. Protparam tool instability index (75.22) demonstrated disorderedness combined with loops owing to prolines/glycines. After refinement, the Ramachandran plot showed that 88 percent of AAs were present in the allowed region and only 0.5% in the disallowed region. Novel IRS1 model protein has 10 α-helices, 22 ß-sheets, 20 ß-hairpins, 5 ß-bulges, 47 strands, 105 ß-turns, and 8 γ-turns. Docking of IRS1 with drug MH demonstrated interaction of Ser-70, Thr-18, and Pro-69 with C-H bonds; Gln-71, and Glu-113 with hydrogen bonds; while both Glu-114 and Glu-113 with salt-bridge connection. Permissible 1.0-1.5 Å range of RMSD fluctuation between 20 and 45 ns was obtained in simulation of IRS1 and IRS1-met complex confirmed that both complexes were stable during whole simulation process. RMSF result showed that except positions 57AA and 114AA, the binding of drug had no severe effects on the flexibility of the IRS1 and IRS1-met complex. The RoG value of compactness and rigidity showed little change in IRS1 protein. SASA value of IRS1 indicated non-significant fluctuation between IRS1 and drug MH means ligand (drug) and IRS1 receptor form stable structure. Hydrogen bond strength of IRS1 and IRS1-met was 81.2 and 76.4, respectively, which suggested stable interaction.

A Case Study of the Development of a Valid and Pragmatic Implementation Science Measure: The Barriers and Facilitators in Implementation of Task-Sharing Mental Health Interventions (BeFITS-MH) Measure.

Background: Few implementation science (IS) measures have been evaluated for validity, reliability and utility - the latter referring to whether a measure captures meaningful aspects of implementation contexts. In this case study, we describe the process of developing an IS measure that aims to assess Barriers and Facilitators in Implementation of Task-Sharing in Mental Health services (BeFITS-MH), and the procedures we implemented to enhance its utility. Methods: We summarize conceptual and empirical work that informed the development of the BeFITS-MH measure, including a description of the Delphi process, detailed translation and local adaptation procedures, and concurrent pilot testing. As validity and reliability are key aspects of measure development, we also report on our process of assessing the measure's construct validity and utility for the implementation outcomes of acceptability, appropriateness, and feasibility. Results: Continuous stakeholder involvement and concurrent pilot testing resulted in several adaptations of the BeFITS-MH measure's structure, scaling, and format to enhance contextual relevance and utility. Adaptations of broad terms such as "program," "provider type," and "type of service" were necessary due to the heterogeneous nature of interventions, type of task-sharing providers employed, and clients served across the three global sites. Item selection benefited from the iterative process, enabling identification of relevance of key aspects of identified barriers and facilitators, and what aspects were common across sites. Program implementers' conceptions of utility regarding the measure's acceptability, appropriateness, and feasibility were seen to cluster across several common categories. Conclusions: This case study provides a rigorous, multi-step process for developing a pragmatic IS measure. The process and lessons learned will aid in the teaching, practice and research of IS measurement development. The importance of including experiences and knowledge from different types of stakeholders in different global settings was reinforced and resulted in a more globally useful measure while allowing for locally-relevant adaptation. To increase the relevance of the measure it is important to target actionable domains that predict markers of utility (e.g., successful uptake) per program implementers' preferences. With this case study, we provide a detailed roadmap for others seeking to develop and validate IS measures that maximize local utility and impact.

A Review on Osteoarthritis and its Eradication Approaches: An Update.

Osteoarthritis (OA) is a disease characterized by degeneration of cartilage or wear and tear. OA is a cause of disability and health issues. It is a disease that affects more than 500 million adults annually worldwide, of which India accounts for about 22 to 39% of OA patients. The most common type of osteoarthritis is knee OA. Pathogenesis of OA requires evolution in basic science and clinical research to enhance our understanding of the pathogenesis and as well as different treatment options. It is mainly classified as primary and secondary OA. The treatment for OA can only reduce the symptoms and cannot cure the disease itself, including pharmacological treatment, like non-steroidal anti-inflammatory drugs (NSAIDs), acting on COX1 (cyclooxygenase 1) and COX2 (cyclooxygenase 2) enzymes. Non-pharmacological treatments for OA include exercise like walking, and aerobic exercise, diet, weight loss, hot and cold therapy, as well as electrotherapy, which improves muscle strength and decreases joint pain. Surgical treatment is the last treatment option for OA patients, which includes arthroscopy and joint replacement therapy. Thus, necessary precautions should be taken for joints to be healthy and disease-free.

Concurrent Cu(II)-initiated Fenton-like reaction and glutathione depletion to escalate chemodynamic therapy.

Chemodynamic therapy is an evolving therapeutic strategy but there are certain limitations associated with its treatment. Herein, we present de novo synthesis and mechanistic evaluation of HL1-HL8 ligands and their corresponding CuII(L1)2-CuII(L8)2. The most active Cu(L2)2 (IC50 = 5.3 µM, MCF-7) complex exclusively depletes glutathione while simultaneously promoting ROS production. Cu(L2)2 also affects other macromolecules like the mitochondrial membrane and DNA while activating the unfolded protein response cascade.

Primary Dural Non-Hodgkin's Lymphoma as a Diagnostic Pitfall: Report of a Rare Presentation with Review of Literature.

Primary central nervous system lymphomas (PCNSLs) account for 2%-3% of all primary brain tumors. Lymphomas arising from the dura, without brain and other systemic involvement, constitute a tiny fraction of this rare group. Most dural lymphomas present as dural-based masses and an acute presentation as a subdural hematoma is exceptional, with only five such cases reported previously in the literature. We present the case of a 65-year-old female who was admitted with complaints of slurring of speech, visual disturbances, and reduced appetite for 2 days. Computerized tomography scan showed a crescentic hyperdense area in the left fronto-temporo-parietal region with no bony or extracranial involvement suggestive of acute subdural hematoma. There was a history of a similar episode 3 months back, wherein she was operated upon and followed up conservatively. Craniotomy for drainage was performed, and histopathology revealed a non-Hodgkin's Lymphoma. Primary lymphoma of the dura is a rare subtype of PCNSL. This case is being reported for its unusual presentation as a common entity-an acute subdural hematoma.

Adaptation of the Patient Reported Outcome Measurement Information System (PROMIS) tool for childhood cancer in India: A qualitative study.

BACKGROUND: To fill the gap in patient-reported outcome (PRO) assessment in children with cancer in India, we planned to adapt domains from the HealthMeasures Patient Reported Outcomes Measurement Information System (PROMIS) tool. This study attempted to identify and pool outcomes relevant to children with cancer and their caregivers in Northern India. METHODS: The study was qualitative and conducted through focussed group discussions (FGDs) and in-depth interviews of children with cancer and their caregivers. Content analysis of transcripts from the sessions was done. The collected themes were collated with existing item banks of the PROMIS tool and new concepts unique to our population were compiled. RESULTS: A set of three FGDs and 14 interviews each for children and their caregivers were conducted. Following content analysis, 121 themes were identified including 10 new concepts. Themes pertaining to the physical domain were cited most. The theme distribution across the three domains was similar among children and caregivers. In the survivor cohort, the relative frequency of mention of psychological and social themes was higher compared to the whole cohort. Themes pertaining to mobility, cognitive dysfunction and peer relationships were more common among survivors. CONCLUSIONS: This qualitative study in children with cancer and their caregivers in India has facilitated a better understanding of the issues pertaining to cancer care that are of most importance to its stake holders. The themes collected may be used to formulate a PRO tool uniquely tailored for use in this population.

Implementation strategy in collaboration with people with lived experience of mental illness to reduce stigma among primary care providers in Nepal (RESHAPE): protocol for a type 3 hybrid implementation effectiveness cluster randomized controlled trial.

BACKGROUND: There are increasing efforts for the integration of mental health services into primary care settings in low- and middle-income countries. However, commonly used approaches to train primary care providers (PCPs) may not achieve the expected outcomes for improved service delivery, as evidenced by low detection rates of mental illnesses after training. One contributor to this shortcoming is the stigma among PCPs. Implementation strategies for training PCPs that reduce stigma have the potential to improve the quality of services. DESIGN: In Nepal, a type 3 hybrid implementation-effectiveness cluster randomized controlled trial will evaluate the implementation-as-usual training for PCPs compared to an alternative implementation strategy to train PCPs, entitled Reducing Stigma among Healthcare Providers (RESHAPE). In implementation-as-usual, PCPs are trained on the World Health Organization Mental Health Gap Action Program Intervention Guide (mhGAP-IG) with trainings conducted by mental health specialists. In RESHAPE, mhGAP-IG training includes the added component of facilitation by people with lived experience of mental illness (PWLE) and their caregivers using PhotoVoice, as well as aspirational figures. The duration of PCP training is the same in both arms. Co-primary outcomes of the study are stigma among PCPs, as measured with the Social Distance Scale at 6 months post-training, and reach, a domain from the RE-AIM implementation science framework. Reach is operationalized as the accuracy of detection of mental illness in primary care facilities and will be determined by psychiatrists at 3 months after PCPs diagnose the patients. Stigma will be evaluated as a mediator of reach. Cost-effectiveness and other RE-AIM outcomes will be assessed. Twenty-four municipalities, the unit of clustering, will be randomized to either mhGAP-IG implementation-as-usual or RESHAPE arms, with approximately 76 health facilities and 216 PCPs divided equally between arms. An estimated 1100 patients will be enrolled for the evaluation of accurate diagnosis of depression, generalized anxiety disorder, psychosis, or alcohol use disorder. Masking will include PCPs, patients, and psychiatrists. DISCUSSION: This study will advance the knowledge of stigma reduction for training PCPs in partnership with PWLE. This collaborative approach to training has the potential to improve diagnostic competencies. If successful, this implementation strategy could be scaled up throughout low-resource settings to reduce the global treatment gap for mental illness. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04282915 . Date of registration: February 25, 2020.

COVID-19 infection, and reinfection, and vaccine effectiveness against symptomatic infection among health care workers in the setting of omicron variant transmission in New Delhi, India.

Background: Surge of SARS CoV-2 infections ascribed to omicron variant began in December 2021 in New Delhi. We determined the infection and reinfection density in a cohort of health care workers (HCWs) along with vaccine effectiveness (VE) against symptomatic infection within omicron transmission period (considered from December 01, 2021 to February 25, 2022. Methods: This is an observational study from the All India Institute of Medical Sciences, New Delhi. Data were collected telephonically. Person-time at risk was counted from November 30, 2021 till date of infection/ reinfection, or date of interview. Comparison of clinical features and severity was done with previous pandemic periods. VE was estimated using test-negative case-control design [matched pairs (for age and sex)]. Vaccination status was compared and adjusted odds ratios (OR) were computed by conditional logistic regression. VE was estimated as (1-adjusted OR)X100-. Findings: 11474 HCWs participated in this study. The mean age was 36⋅2 (±10⋅7) years. Complete vaccination with two doses were reported by 9522 (83%) HCWs [8394 (88%) Covaxin and 1072 Covishield (11%)]. The incidence density of all infections and reinfection during the omicron transmission period was 34⋅8 [95% Confidence Interval (CI): 33⋅5-36⋅2] and 45⋅6 [95% CI: 42⋅9-48⋅5] per 10000 person days respectively. The infection was milder as compared to previous periods. VE was 52⋅5% (95% CI: 3⋅9-76⋅5, p = 0⋅036) for those who were tested within 14-60 days of receiving second dose and beyond this period (61-180 days), modest effect was observed. Interpretation: Almost one-fifth of HCWs were infected with SARS CoV-2 during omicron transmission period, with predominant mild spectrum of COVID-19 disease. Waning effects of vaccine protection were noted with increase in time intervals since vaccination. Funding: None.

Ultrastructural changes in cristae of lymphoblasts in acute lymphoblastic leukemia parallel alterations in biogenesis markers.

We explored the link between mitochondrial biogenesis and mitochondrial morphology using transmission electron microscopy (TEM) in lymphoblasts of pediatric acute lymphoblastic leukemia (ALL) patients and compared these characteristics between tumors and control samples. Gene expression of mitochondrial biogenesis markers was analysed in 23 ALL patients and 18 controls and TEM for morphology analysis was done in 15 ALL patients and 9 healthy controls. The area occupied by mitochondria per cell and the cristae cross-sectional area was observed to be significantly higher in patients than in controls (p-value = 0.0468 and p-value< 0.0001, respectively). The mtDNA copy numbers, TFAM, POLG, and c-myc gene expression were significantly higher in ALL patients than controls (all p-values< 0.01). Gene Expression of PGC-1α was higher in tumor samples. The analysis of the correlation between PGC-1α expression and morphology parameters i.e., both M/C ratio and cristae cross-sectional area revealed a positive trend (r = 0.3, p = 0.1). The increased area occupied by mitochondria and increased cristae area support the occurrence of cristae remodelling in ALL. These changes might reflect alterations in cristae dynamics to support the metabolic state of the cells by forming a more condensed network. Ultrastructural imaging can be useful for affirming changes occurring at a subcellular organellar level.

Acculturation, coping, and PTSD in Hispanic 9/11 rescue and recovery workers.

Objective: Research examining the responders of the World Trade Center terrorist attacks of 9/11 has found that Hispanic responders are at greater risk for posttraumatic stress disorder (PTSD) than non-Hispanic White responders. However, no studies have examined how acculturation may influence the relationship between coping and PTSD in Hispanic 9/11 responders. This novel study is the first to examine differences in coping and PTSD among Hispanic responders by level of acculturation. Methods: The sample is composed of 845 Hispanic 9/11 responders who were seen at the World Trade Center Health Program and participated in a web-based survey. Using logistic and multiple linear regression, we examined how acculturation is related to their coping strategies and risk for PTSD. We also tested for interaction to examine whether level of acculturation moderated the relationship between coping and PTSD symptom severity. Results: Key findings revealed that higher acculturation is associated with the use of substances, venting, and humor to cope, while lower acculturation is associated with the use of active coping and self-distraction in this sample. We also found that less acculturated responders were more likely to experience more severe PTSD. Lastly, our findings revealed that Hispanics who are more acculturated and used substances to cope had more severe PTSD than less acculturated responders. Conclusion: These findings highlight the need to consider the role of acculturation in Hispanic responders' coping and PTSD. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

The Burden of Subthreshold Posttraumatic Stress Disorder in World Trade Center Responders in the Second Decade After 9/11.

OBJECTIVE: To characterize the prevalence, risk and protective correlates, and clinical characteristics associated with probable subthreshold posttraumatic stress disorder (PTSD) in police and nontraditional (eg, construction workers) World Trade Center (WTC) responders a median of 12.2 years after September 11, 2001. METHODS: A total of 4,196 WTC responders, monitored via the WTC Health Program, completed a web-based survey between 2012 and 2014 assessing a range of variables, including demographics, WTC exposures, medical and psychiatric comorbidities, and mental health services use. The sample included 2,029 police responders and 2,167 nontraditional responders. Current (past-month) probable WTC-related PTSD level (none, subthreshold, or full PTSD) was assessed based on DSM-IV criteria using the PTSD Checklist-Specific Stressor version (PCL-S). RESULTS: The prevalence of current probable full and subthreshold WTC-related PTSD in police responders was 9.3% and 17.5%, respectively, and in nontraditional responders was 21.9% and 24.1%, respectively. Risk and protective correlates for subthreshold PTSD included post-9/11 medical comorbidities and traumatic events (odds ratios [ORs] = 1.1-1.2). Clinical characteristics included elevated rates of comorbid depression (OR = 3.2 and 3.9 for subthreshold PTSD and 17.2 and 30.3 for full PTSD for nontraditional and police responders, respectively). Among responders with subthreshold PTSD, police were more likely to have accessed mental health services and utilized a greater variety of treatments than nontraditional responders. CONCLUSIONS: Overall, 26.8% of police and 46.0% of nontraditional responders met criteria for probable WTC-related full or subthreshold PTSD an average of 12 years after 9/11. Probable subthreshold PTSD, which is not typically assessed in clinical settings, was more prevalent than probable full PTSD and was associated with significantly elevated rates of psychiatric comorbidities, functional impairment, and reduced quality of life. These findings underscore the importance of assessing, monitoring, and possibly treating subthreshold PTSD in WTC and other disaster responders.

Hansenula polymorpha Pex37 is a peroxisomal membrane protein required for organelle fission and segregation.

Here, we describe a novel peroxin, Pex37, in the yeast Hansenula polymorpha. H. polymorpha Pex37 is a peroxisomal membrane protein, which belongs to a protein family that includes, among others, the Neurospora crassa Woronin body protein Wsc, the human peroxisomal membrane protein PXMP2, the Saccharomyces cerevisiae mitochondrial inner membrane protein Sym1, and its mammalian homologue MPV17. We show that deletion of H. polymorpha PEX37 does not appear to have a significant effect on peroxisome biogenesis or proliferation in cells grown at peroxisome-inducing growth conditions (methanol). However, the absence of Pex37 results in a reduction in peroxisome numbers and a defect in peroxisome segregation in cells grown at peroxisome-repressing conditions (glucose). Conversely, overproduction of Pex37 in glucose-grown cells results in an increase in peroxisome numbers in conjunction with a decrease in their size. The increase in numbers in PEX37-overexpressing cells depends on the dynamin-related protein Dnm1. Together our data suggest that Pex37 is involved in peroxisome fission in glucose-grown cells. Introduction of human PXMP2 in H. polymorpha pex37 cells partially restored the peroxisomal phenotype, indicating that PXMP2 represents a functional homologue of Pex37. H.polymorpha pex37 cells did not show aberrant growth on any of the tested carbon and nitrogen sources that are metabolized by peroxisomal enzymes, suggesting that Pex37 may not fulfill an essential function in transport of these substrates or compounds required for their metabolism across the peroxisomal membrane.

Intramedullary schwannoma of conus medullaris: rare site for a common tumor with review of literature.

INTRODUCTION: Schwannomas at an intramedullary location constitute only 0.3% of primary spinal tumors. Those in the conus are extremely rare, especially in the absence of neurofibromatosis, with only 12 cases reported in the literature so far, excluding the present case. CASE PRESENTATION: We report the case of a 27-year-old female who presented with complaints of backache since 1 year, weakness in both lower limbs with tingling and numbness since 6 months, and urinary incontinence since 1 month. There was no history of trauma or any skin lesions. Magnetic resonance imaging (MRI) of the spine provided a provisional diagnosis of ependymoma. The patient was operated upon, histopathology revealed it to be a schwannoma. DISCUSSION: Intramedullary schwannomas without neurofibromatosis are extremely rare at the conus and can be completely resected unless there is infiltration. Gliomas and ependymomas are commoner entities at this site, which are usually subtotally resected. This case highlights that although extremely rare, the possibility of a schwannoma may be considered in the differentials of an intramedullary spinal lesion.

Peripheral neuropathy and the role of nerve biopsy: A revisit.

BACKGROUND: Nerve biopsy has been widely used to investigate patients with peripheral neuropathy and in many centers, it is still a part of the diagnostic armamentarium. In this study, the histopathological spectrum of the nerve biopsies received is being revisited to analyze the various clinical and pathologic features and also to assess their relevance. MATERIALS AND METHODS: Retrospective analysis of the data retrieved was done for 74 cases of nerve biopsies. RESULTS: On the basis of the data and histopathological features, broad diagnoses were obtained in 52 cases and further categorized into biopsies being supportive for patient management (including acute and chronic axonopathies and demyelinating neuropathies) and biopsies considered essential for patient management (including vasculitic neuropathies, leprous neuropathies, hereditary neuropathies, and chronic inflammatory demyelinating neuropathies). Nine nerve biopsies did not show any abnormal histopathological features, while 13 nerve biopsies were found to be inadequate for diagnosis, both these groups were categorized as noncontributory. CONCLUSION: With advanced nerve conduction studies available, nerve biopsy is losing its relevance. However, in our experience, nerve biopsy did complement the clinical findings and nerve conduction studies, with which a close correlation is required to make the histopathology of nerve biopsy more relevant in terms of guiding further specific workup and management.

Primary osteoclast-like giant cell tumor of parotid gland: A rare extraskeletal presentation with diagnostic challenges.

Primary osteoclast-like giant cell tumor (OC-GCT) has been rarely described in extraskeletal sites. The diagnosis primarily hinges on the detection of giant cells. However, these giant cells are also seen in many giant cell lesions, thus creating diagnostic confusion and dilemma. Here, we describe a rare case of a 24-year-old male with primary extraskeletal, OC-GCT presenting as a swelling in the right parotid region and highlight its cytological, histological and immunohistochemical characteristics with diagnostic challenges.

Risk, coping and PTSD symptom trajectories in World Trade Center responders.

Trajectories of disaster-related posttraumatic stress disorder (PTSD) symptoms are often heterogeneous, and associated with common and unique risk factors, yet little is known about potentially modifiable psychosocial characteristics associated with low-symptom and recovering trajectories in disaster responders. A total of 4487 rescue and recovery workers (1874 police and 2613 non-traditional responders) involved during and in the aftermath of the unprecedented World Trade Center (WTC) attacks, were assessed an average of 3, 6, 8, and 12 years post-9/11/2001. Among police responders, WTC-related PTSD symptoms were characterized by four trajectories, including no/low-symptom (76.1%), worsening (12.1%), improving (7.5%), and chronic (4.4%) trajectories. In non-traditional responders, a five-trajectory solution was optimal, with fewer responders in a no/low-symptom trajectory (55.5%), and the remainder in subtly worsening (19.3%), chronic (10.8%), improving (8.5%), and steeply worsening (5.9%) trajectories. Consistent factors associated with symptomatic PTSD trajectories across responder groups included Hispanic ethnicity, pre-9/11 psychiatric history, greater WTC exposure, greater medical illness burden, life stressors and post-9/11 traumas, and maladaptive coping (e.g., substance use, avoidance coping). Higher perceived preparedness, greater sense of purpose in life, and positive emotion-focused coping (e.g., positive reframing, acceptance) were negatively associated with symptomatic trajectories. Findings in this unique cohort indicate considerable heterogeneity in WTC-related PTSD symptom trajectories over 12 years post-9/11/2001, with lower rates of elevated PTSD symptoms in police than in non-traditional responders. They further provide a comprehensive risk prediction model of PTSD symptom trajectories, which can inform prevention, monitoring, and treatment efforts in WTC and other disaster responders.