Challenges and strategies regarding anaesthetic management of twin pregnancy undergoing redo aortic valve replacement.

INTRODUCTION AND IMPORTANCE: Redo aortic valve replacement in twin pregnancy presents significant challenges because of the elevated risks for both maternal and fetal health. Mortality rates range from 12 % to 21 % in specialised centres, with previous cardiac surgeries further elevating the risk. Pregnancy complicates cardiac surgery, with fetal mortality rates as high as 16-33 %. PRESENTATION OF CASE: A 31-year-old woman, 15 weeks pregnant with twins and with a history of mechanical aortic valve replacement, presented with worsening breathlessness and grade III dyspnoea. Echocardiography revealed severe valve obstruction, necessitating redo-aortic valve replacement and posterior aortic root enlargement. Despite intraoperative challenges, including ventricular fibrillation and postoperative heart block, she underwent successful surgery and pacemaker implantation, with both mother and fetuses remaining stable. DISCUSSION: Optimal timing of surgery is crucial, considering fetal developmental vulnerability in the first trimester and maternal cardiac workload in the third trimester. Second-trimester risks are comparable to non-pregnant patients. A limited understanding of fetal-placental perfusion during bypass necessitates cautious management strategies, with emerging techniques like pulsatile perfusion showing promise. Anaesthesia selection prioritises fetal safety while monitoring fetal distress during surgery remains challenging. To achieve successful outcomes for both mother and babies in a twin pregnancy undergoing a redo aortic valve replacement, careful timing, appropriate surgical techniques, and meticulous perioperative care are essential. CONCLUSION: A multidisciplinary approach is crucial for managing twin pregnancy following redo aortic valve surgery. Careful planning, close monitoring, and specialised surgical and anaesthetic techniques are key to minimising risks to both mother and fetus.

Effectiveness and safety of preoperative distraction using modified halo-pelvic Ilizarov distraction assembly in patients with severe kyphoscoliosis.

Study Design: A 2-year follow-up study. Purpose: To evaluate the effectiveness of modified halo-pelvic Ilizarov distraction assembly in the management of patients with severe kyphoscoliosis. Overview of Literature: Severe and rigid scoliosis curves are always a challenge for operating surgeons. Preoperative correction through halo-pelvic devices successfully minimizes the severity of the curve; however, cumbersome complications are also reported with its use. Modified assembly could be safe for these cases. Methods: Patients with severe kyphoscoliosis having coronal Cobb angle >90° were applied with modified halo-pelvic Ilizarov distraction assembly preoperatively. The modified assembly consisted of a pelvic component and halo ring, and distraction was given at the rate of 2-3 mm/day for 6-12 weeks. Complete clinical assessments along with pulmonary function tests were performed, and scoliosis series X-ray images were assessed for coronal and sagittal Cobb angle and other spinopelvic parameters before applying the assembly and during 2 years of follow-up. Results: Thirty-four patients (age, 9-27 years; male/female ratio of 18:16) were included. The coronal and sagittal Cobb angles were 116°±16.2° and 84°±28.3°, respectively. Correction rates obtained through modified halo-pelvic assembly were nearly 52% (p=0.001) in coronal and 40% (p=0.001) in sagittal Cobb angles, with improvement in height (p=0.001). Apical vertebral translation and coronal balance were also improved significantly (p=0.001). Further improvements in all the parameters were obtained after definitive surgery, with improvements in the forced expiratory volume in 1 second (p =0.002) and forced vital capacity (p=0.001). Conclusions: Our modified halo-pelvic Ilizarov distraction assembly can achieve good correction in severe spinal deformities without significant risk to neurology, has fewer complications, and promotes good patient compliance.

Clinical phenotype and management of sound-induced pain: Insights from adults with pain hyperacusis.

Pain hyperacusis, also known as noxacusis, causes physical pain in response to everyday sounds that do not bother most people. How sound causes excruciating pain that can last for weeks or months in otherwise healthy individuals is not well understood, resulting in a lack of effective treatments. To address this gap, we identified the most salient physical and psychosocial consequences of debilitating sound-induced pain and reviewed the interventions that sufferers have sought for pain relief to gain insights into the underlying mechanisms of the condition. Adults (n = 32) with pain hyperacusis attended a virtual focus group to describe their sound-induced pain. They completed three surveys to identify common symptoms and themes that defined their condition and to describe their use of pharmaceutical and non-pharmaceutical therapies for pain relief. All participants endorsed negative effects of pain hyperacusis on psychosocial and physical function. Most reported sound-induced burning (80.77%), stabbing (76.92%), throbbing (73.08%), and pinching (53.85%) that occurs either in the ear or elsewhere in the body (i.e., referred pain). Participants reported using numerous pharmaceutical and non-pharmaceutical interventions to alleviate their pain with varying degrees of pain relief. Benzodiazepines and nerve blockers emerged as the most effective analgesic options while non-pharmaceutical therapies were largely ineffective. Symptoms of pain hyperacusis and therapeutic approaches are largely consistent with peripheral mechanistic theories of pain hyperacusis (e.g., trigeminal nerve involvement). An interdisciplinary approach to clinical studies and the development of animal models is needed to identify, validate, and treat the pathological mechanisms of pain hyperacusis.

Copper stress in rice: Perception, signaling, bioremediation and future prospects.

Copper (Cu) is an indispensable micronutrient for plants, animals, and microorganisms and plays a vital role in different physiological processes. However, excessive Cu accumulation in agricultural soil, often through anthropogenic action, poses a potential risk to plant health and crop productivity. This review article provided a comprehensive overview of the available information regarding Cu dynamics in agricultural soils, major sources of Cu contamination, factors influencing its mobility and bioavailability, and mechanisms of Cu uptake and translocation in rice plants. This review examined the impact of Cu toxicity on the germination, growth, and photosynthesis of rice plants. It also highlighted molecular mechanisms underlying Cu stress signaling and the plant defense strategy, involving chelation, compartmentalization, and antioxidant responses. This review also identified significant areas that need further research, such as Cu uptake mechanism in rice, Cu signaling process, and the assessment of Cu-polluted paddy soil and rice toxicity under diverse environmental conditions. The development of rice varieties with reduced Cu accumulation through comprehensive breeding programs is also necessary. Regulatory measures, fungicide management, plant selection, soil and environmental investigation are recommended to prevent Cu buildup in agricultural lands to achieve sustainable agricultural goals.

Cohesin-mediated 3D contacts tune enhancer-promoter regulation.

Enhancers are key drivers of gene regulation thought to act via 3D physical interactions with the promoters of their target genes. However, genome-wide depletions of architectural proteins such as cohesin result in only limited changes in gene expression, despite a loss of contact domains and loops. Consequently, the role of cohesin and 3D contacts in enhancer function remains debated. Here, we developed CRISPRi of regulatory elements upon degron operation (CRUDO), a novel approach to measure how changes in contact frequency impact enhancer effects on target genes by perturbing enhancers with CRISPRi and measuring gene expression in the presence or absence of cohesin. We systematically perturbed all 1,039 candidate enhancers near five cohesin-dependent genes and identified 34 enhancer-gene regulatory interactions. Of 26 regulatory interactions with sufficient statistical power to evaluate cohesin dependence, 18 show cohesin-dependent effects. A decrease in enhancer-promoter contact frequency upon removal of cohesin is frequently accompanied by a decrease in the regulatory effect of the enhancer on gene expression, consistent with a contact-based model for enhancer function. However, changes in contact frequency and regulatory effects on gene expression vary as a function of distance, with distal enhancers (e.g., >50Kb) experiencing much larger changes than proximal ones (e.g., <50Kb). Because most enhancers are located close to their target genes, these observations can explain how only a small subset of genes - those with strong distal enhancers - are sensitive to cohesin. Together, our results illuminate how 3D contacts, influenced by both cohesin and genomic distance, tune enhancer effects on gene expression.

Designing an mRNA Vaccine against P. jirovecii Involved in Fatal Pneumonia Infections via Comparative Proteomics and Reverse Vaccinology Approaches.

BACKGROUND: Pneumocystis jirovecii is the most emerging life-threating health problem that causes acute and fatal pneumonia infection. It is rare and more contagious for patients with leukemia and immune-deficiency disorders. Until now there is no treatment available for this infection therefore, it is needed to develop any treatment against this pathogen. METHODS: In this work, we used comparative proteomics, robust immune-informatics, and reverse vaccinology to create an mRNA vaccine against Pneumocystis jirovecii by targeting outer and transmembrane proteins. Using a comparative subtractive proteomic analysis of two Pneumocystis jirovecii proteomes, a distinct non-redundant Pneumocystis jirovecii (strain SE8) proteome was chosen. Seven Pneumocystis jirovecii transmembrane proteins were chosen from this proteome based on hydrophilicity, essentiality, virulence, antigenicity, pathway interaction, protein-protein network analysis, and allergenicity. OBJECTIVE: The reverse vaccinology approach was used to predict the immunogenic and antigenic epitopes of major histocompatibility complex (MHC) I, II and B-cells from the selected proteins on the basis of their antigenicity, toxicity and allergenicity. These immunogenic epitopes were linked together to construct the mRNA-based vaccine. To enhance the immunogenicity, suitable adjuvant, linkers (GPGPG, KK, and CYY), and PRDRE sequences were used. RESULTS: Through predictive modeling and confirmation via the Ramachandran plot, we assessed secondary and 3D structures. The adjuvant RpfE was incorporated to enhance the vaccine construct's immunogenicity (GRAVY index: -0.271, instability index: 39.53, antigenicity: 1.0428). The physiochemical profiling of vaccine construct was predicted it an antigenic, efficient, and potential vaccine. Notably, strong interactions were observed between the vaccine construct and TLR-3/TLR-4 (-1301.7 kcal/mol-1 and -1374.7 kcal/mol-1). CONCLUSIONS: The results predicted that mRNA-based vaccines trigger a cellular and humoral immune response, making the vaccine potential candidate against Pneumocystis jirovecii and it is more suitable for in-vitro analysis and validation to prove its effectiveness.

Hamman Syndrome with a Rare Feature of Pneumorrhachis - An Unusual Complication of Polysubstance abuse and e-vaping.

Hamman syndrome is defined as dissection of air in mediastinum and skin fascia usually due to increased intrathoracic pressure. The air leak tends to make its way into pleural and pericardial layers; however, in rare instances air can also dissect into epidural spaces, regarded as pneumorrhachis. We present a case of a young male with a history of polysubstance abuse and e-vaping, who presented with symptoms of altered mental status. Given the concerning physical examination, a computed tomography of the chest was undertaken, which showed pneumothorax, pneumomediastinum and pneumorrhachis. The patient was closely monitored in the intensive care unit and improved after symptomatic management. The symptoms of pneumorrhachis depend on the volume and location of air in intracranial and intraspinal space. Although asymptomatic in our case, it is crucial for clinicians to be aware that pneumorrhachis with Hamman syndrome can potentially cause neurological deficits and cardiopulmonary arrest in severe cases due to increased intraspinal and intracranial hypertension, emphasising the need for close monitoring. LEARNING POINTS: Elevated intrathoracic pressure generated by deep inhalation of an aerosolised product is one of the triggers of air dissection in pleural, pericardial, and mediastinal regions. In rare instances, air can also translocate into intracranial and intraspinal spaces, which is referred to as pneumorrhachis.Mostly asymptomatic, pneumorrhachis has the potential to develop acute neurological deficits due to increased intracranial and intraspinal pressure, validating the need for acute monitoring.Most cases of pneumorrhachis are managed conservatively. However, severe cases warrant decompression or high concentrations of oxygen administration to facilitate air absorption.

Drug repurposing for bacterial infections.

Repurposing pharmaceuticals is a technique used to find new, alternate clinical applications for approved drug molecules. It may include altering the drug formulation, route of administration, dose or the dosage regimen. The process of repurposing medicines starts with screening libraries of previously approved drugs for the targeted disease condition. If after an the initial in silico, in vitro or in vivo experimentation, the molecule has been found to be active against a particular target, the molecule is considered as a good candidate for clinical trials. As the safety profile of such molecules is available from the previous data, significant time and resources are saved. These advantages of drug repurposing approach make it especially helpful for finding treatments for rapidly evolving conditions including bacterial infections. An ever-increasing incidence of antimicrobial resistance, owing to the mutations in bacterial genome, leads to therapeutic failure of many approved antibiotics. Repurposing the approved drug molecules for use as antibiotics can provide an effective means for the combating life-threatening bacterial diseases. A number of drugs have been considered for drug repurposing against bacterial infections. These include, but are not limited to, Auranofin, Closantel, and Toremifene that have been repurposed for various infections. In addition, the reallocation of route of administration, redefining dosage regimen and reformulation of dosage forms have also been carried out for repurposing purpose. The current chapter addresses the drug discovery and development process with relevance to repurposing against bacterial infections.

Sex disparity of DAPT noncompliance in patients with left main stem PCI with DES.

This retrospective study aims to explore the sex disparity in dual antiplatelet therapy (DAPT) noncompliance among left main stem percutaneous coronary intervention (PCI) patients with drug-eluting stent (DES) and identify predictors associated with non-adherence. Data were collected from the medical records of 1585 patients, including 1104 males and 481 females, who underwent left main stem PCI with DES. Baseline characteristics, angiographic features, and DAPT compliance rates at 1 month and 12 months were analyzed. Univariate logistic regression was used to identify predictors of DAPT noncompliance. The overall DAPT noncompliance rate at 1 month was 8.5%, increasing to 15.5% at 12 months. Females exhibited slightly higher noncompliance rates than males at both 1 month (15.6% vs 14.5%) and 12 months (28.1% vs 19.0%), although the difference was not statistically significant. Smoking status showed a modest impact on non-adherence, with current smokers exhibiting a lower noncompliance rate (14.9% at 1 month). Prior coronary artery disease history was associated with increased noncompliance at 12 months (18.9%). Angiographic characteristics, including lesion location and Syntax score, had no consistent association with DAPT noncompliance. This study highlights sex disparity in DAPT noncompliance among patients undergoing left main stem PCI with DES. Comorbidities, socioeconomic status, smoking status, and prior coronary artery disease history were identified as predictors of non-adherence.

A fully automated and explainable algorithm for predicting malignant transformation in oral epithelial dysplasia.

Oral epithelial dysplasia (OED) is a premalignant histopathological diagnosis given to lesions of the oral cavity. Its grading suffers from significant inter-/intra-observer variability, and does not reliably predict malignancy progression, potentially leading to suboptimal treatment decisions. To address this, we developed an artificial intelligence (AI) algorithm, that assigns an Oral Malignant Transformation (OMT) risk score based on the Haematoxylin and Eosin (H&E) stained whole slide images (WSIs). Our AI pipeline leverages an in-house segmentation model to detect and segment both nuclei and epithelium. Subsequently, a shallow neural network utilises interpretable morphological and spatial features, emulating histological markers, to predict progression. We conducted internal cross-validation on our development cohort (Sheffield; n = 193 cases) and independent validation on two external cohorts (Birmingham and Belfast; n = 89 cases). On external validation, the proposed OMTscore achieved an AUROC = 0.75 (Recall = 0.92) in predicting OED progression, outperforming other grading systems (Binary: AUROC = 0.72, Recall = 0.85). Survival analyses showed the prognostic value of our OMTscore (C-index = 0.60, p = 0.02), compared to WHO (C-index = 0.64, p = 0.003) and binary grades (C-index = 0.65, p < 0.001). Nuclear analyses elucidated the presence of peri-epithelial and intra-epithelial lymphocytes in highly predictive patches of transforming cases (p < 0.001). This is the first study to propose a completely automated, explainable, and externally validated algorithm for predicting OED transformation. Our algorithm shows comparable-to-human-level performance, offering a promising solution to the challenges of grading OED in routine clinical practice.

Multilayered regulation and implication of flowering time in plants.

Initiation of flowering is a key switch for plants to shift from the vegetative growth to the phase of reproductive growth. This critical phase is essential not only for achieving successful reproduction, but also for facilitating environmental adaptation and maximizing yield potential. In the past decades, the environmental factors and genetic pathways that control flowering time have undergone extensive investigation in both model plant Arabidopsis and various crop species. The impact of environmental factors on plant flowering time is well documented. This paper focuses on the multilayered modulation of flowering time. Recent multi-omics approaches, and genetic screens have revealed additional components that modulate flowering time across various levels, encompassing chromatin modification, transcriptional and post-transcriptional control, as well as translational and post-translational regulation. The interplay between these various layers of regulation creates a finely-tuned system that can respond to a wide variety of inputs and allows plants to adjust flowering time in response to changing environmental conditions. In this review, we present a comprehensive overview of the recent progress made in understanding the intricate regulation of flowering time in plants, emphasizing the pivotal molecular components and their intricate interactions. Additionally, we provide an exhaustive list of key genes implicated in the intricate modulation of flowering time and offer a detailed summary of regulators of FLOWERING LOCUS T (FT) and FLOWERING LOCUS (FLC). We also discuss the implications of this knowledge for crop improvement and adaptation to changing environments.

Atypical haemolytic uremic syndrome in a patient with severe Babesiosis.

Babesiosis is a tick-borne parasitic infection that can result in various haematological complications. This case report discusses a patient with severe Babesiosis complicated by an unorthodox presentation of Babesiosis-associated haemolytic uremic syndrome. Discussed here is the patient's clinical course and the management strategies employed, with an emphasis on early recognition and treatment of renal failure in the context of severe Babesiosis. Haematologic manifestations of Babesia are common and the severity of disease is dependent on parasite load. While treatment options such as red blood cell exchange have been proposed for severe cases, their impact on clinical outcomes is limited and they may not be readily available in resource-limited settings. Traditional management using antimicrobials has been proposed but there is limited discussion about managing unique presentations such as renal failure in Babesiosis. Hence, understanding the pathophysiology, early recognition and aggressive treatment strategies can optimise clinical outcomes and reduce mortality.

Single stage cricoid split laryngoplasty with costochondral rib grafting is a novel approach to treat subglottic stenosis in a paediatric patient: A case report.

INTRODUCTION AND IMPORTANCE: Subglottic stenosis (SGS) appears to be a commonly encountered condition in the paediatric age group. Single stage cricoid split laryngoplasty with costochondral rib grafting in paediatric patients is a unique, innovative, and advanced operation in nature. Morbidity and mortality rates can be minimized with early diagnosis and prompt treatment. PRESENTATION OF CASE: Presenting the case of a 13-month-old child diagnosed with Grade II SGS who was managed for cricoid split laryngoplasty with a costochondral rib graft. It was a unique strategy for providing infants and neonates with symptomatic SGS with a safe and efficient substitute for long-term tracheostomy. When healing was completed, the patient regained the function of their airway. The approach was successful, and preventable to long-term tracheostomy. DISCUSSION: Performing this procedure early in children has shown higher rates of success and it is safe and effective. Further extensive research and studies need to be conducted in this domain, and every patient's status should be reviewed time and again to tend to their specific needs, and the choice of procedure should be made optimally based on clinical evaluations. CONCLUSION: Successful management of a 13-month-old child with Grade II subglottic stenosis through cricoid split laryngoplasty with costochondral rib grafting is a challenging and novel approach to treating single-stage SGS.

ephrin-B2 promotes nociceptive plasticity and hyperalgesic priming through EphB2-MNK-eIF4E signaling in both mice and humans.

Ephrin-B-EphB signaling can promote pain through ligand-receptor interactions between peripheral cells, like immune cells expressing ephrin-Bs, and EphB receptors expressed by DRG neurons. Previous studies have shown increased ephrin-B2 expression in peripheral tissues like synovium of rheumatoid and osteoarthritis patients, indicating the clinical significance of this signaling. The primary goal of this study was to understand how ephrin-B2 acts on mouse and human DRG neurons, which express EphB receptors, to promote pain and nociceptor plasticity. We hypothesized that ephrin-B2 would promote nociceptor plasticity and hyperalgesic priming through MNK-eIF4E signaling, a critical mechanism for nociceptive plasticity induced by growth factors, cytokines and nerve injury. Both male and female mice developed dose-dependent mechanical hypersensitivity in response to ephrin-B2, and both sexes showed hyperalgesic priming when challenged with PGE2 injection either to the paw or the cranial dura. Acute nociceptive behaviors and hyperalgesic priming were blocked in mice lacking MNK1 (Mknk1 knockout mice) and by eFT508, a specific MNK inhibitor. Sensory neuron-specific knockout of EphB2 using Pirt-Cre demonstrated that ephrin-B2 actions require this receptor. In Ca2+-imaging experiments on cultured DRG neurons, ephrin-B2 treatment enhanced Ca2+ transients in response to PGE2 and these effects were absent in DRG neurons from MNK1-/- and EphB2-PirtCre mice. In experiments on human DRG neurons, ephrin-B2 increased eIF4E phosphorylation and enhanced Ca2+ responses to PGE2 treatment, both blocked by eFT508. We conclude that ephrin-B2 acts directly on mouse and human sensory neurons to induce nociceptor plasticity via MNK-eIF4E signaling, offering new insight into how ephrin-B signaling promotes pain.

Community-Acquired Meningitis Complicated With Pyogenic Ventriculitis and Hydrocephalus in a Patient With Haematological Malignancy: A Case Report and Literature Review.

Meningitis, an infection of the meninges of the central nervous system (CNS), can advance quickly and carries a mortality rate reaching 30% among affected patients. It may become complicated by conditions such as hydrocephalus, ventriculitis, and cerebral abscess. Here, we describe a case of meningitis that was complicated by pyogenic ventriculitis and hydrocephalus in a patient with diffuse large B-cell lymphoma (DLBCL) who underwent chemotherapy and radiotherapy. The patient presented with acute change in mental status and high-grade fever, with few episodes of non-bloody vomiting. Blood culture and cerebrospinal fluid (CSF) culture grew Streptococcus pneumoniae, which was sensitive to ceftriaxone. CT scan of the head showed ventriculomegaly, pansinusitis, and a large left mastoid effusion. MRI of the brain showed layering in ventricles, hydrocephalus, and dural enhancement consistent with pachymeningitis. She was treated with ceftriaxone for 21 days with a meaningful outcome. She was discharged home with near-baseline mental capacity for further physical therapy.

Mitigating potential of polystyrene microplastics on bioavailability, uptake, and toxicity of copper in maize (Zea mays L.).

The coexistence of polystyrene microplastics (PSMPs) and copper (Cu) has become a pressing issue for croplands. However, limited literature is available regarding the interaction of PSMPs with essential micronutrients in Cu-contaminated soils. Therefore, the present study aimed to analyze the immobilization potential of PSMPs for micronutrient bioavailability in soil and Cu toxicity in maize (Zea mays L.). A pot experiment was conducted with maize variety "Islamabad gold" exposed to varying Cu concentrations (0, 50, 100, 200, and 400 mg/kg) and PSMPs (150-250 µm size, 0, 1, and 3% w/w) via soil spiking for 60 days. The concentrations of essential micronutrients (Zn, Cu, Mn, Fe) in soil and plant tissues were measured using an atomic absorption spectrophotometer. Moreover, malondialdehyde (MDA) and antioxidant activities (superoxide dismutase, ascorbate peroxidase, catalase, and peroxidase) were recorded. The concentration of Cu showed significant reduction in post-harvesting soil by 21, 24.8, 27.6, 29.2, and 30.2% from Cu0 to Cu400 mg/kg respectively from pre-sowing soil. On the other hand, the addition of 1%PSMPs and 3%PSMPs declined Cu by 16, 21.6, 24.4, 25.9, 27.8, and 12.6, 16.5, 19.9, 23.2, 25% from Cu0 to Cu400 mg/kg respectively. Maize showed significant improvement in growth under combined exposure of Cu and 3% PSMPs compared to individual exposure. The MDA level was decreased under the combined presence of Cu and PSMPs compared to individual Cu exposure. The percentage difference with 1%PSMPs was 98.1, 95.0, 92.0, 90.0, and 89.6%, while with 3%PSMPs was 93.2, 93.2, 87.7, 81.4, and 79.2% from Cu0 to Cu400 mg/kg respectively. Moreover, the impact of PSMPs was more prominent at a 3% dose compared to a 1% dose. The findings provided significant knowledge about the potential of PSMPs to mitigate Cu toxicity in maize. Future research should incorporate a variety of particle size distributions at natural conditions for variety-specific differences.

Loss of Sigma-2 Receptor/TMEM97 Is Associated with Neuropathic Injury-Induced Depression-Like Behaviors in Female Mice.

Previous studies have shown that ligands that bind to sigma-2 receptor/TMEM97 (s2R/TMEM97), a transmembrane protein, have anxiolytic/antidepressant-like properties and relieve neuropathic pain-like effects in rodents. Despite medical interest in s2R/TMEM97, little affective and pain behavioral characterization has been done using transgenic mice, which limits the development of s2R/TMEM97 as a viable therapeutic target. Using wild-type (WT) and global Tmem97 knock-out (KO) mice, we sought to identify the contribution of Tmem97 in modulating affective and pain-like behaviors using a battery of affective and pain assays, including open field, light/dark preference, elevated plus maze, forced swim test, tail suspension test, and the mechanical sensitivity tests. Our results demonstrate that female Tmem97 KO mice show less anxiety-like and depressive-like behaviors in light/dark preference and tail suspension tests but not in an open field, elevated plus maze, and forced swim tests at baseline. We next performed spared nerve injury in WT and Tmem97 KO mice to assess the role of Tmem97 in neuropathic pain-induced anxiety and depression. WT mice, but not Tmem97 KO mice, developed a prolonged neuropathic pain-induced depressive-like phenotype when tested 10 weeks after nerve injury in females. Our results show that Tmem97 plays a role in modulating anxiety-like and depressive-like behaviors in naive animals with a significant change in the presence of nerve injury in female mice. Overall, these data demonstrate that Tmem97 could be a target to alleviate affective comorbidities of pain disorders.

Vertebral Endplate Defects Induced Mechanical Alterations and Disc Calcification.

STUDY DESIGN: Cross sectional comparative study. OBJECTIVES: The current study aims to explore the calcification potential (BMP2 expression) of intervertebral discs and its association with the presence of vertebral endplate defects visible on MRI. METHODS: Forty-seven herniated lumbar disc samples obtained from patients aged 20-76 (31 M/16F) undergoing surgery. Five-µm thin sections were stained with H&E in order to assign a histological degeneration score (HDS) from 0-15 on the basis of cell density (0-5), structural alterations (0-4), granular changes (0-3) and mucus degeneration (0-3). Sections were immuno-stained with anti BMP-2 antibodies to observe the calcification potential in these discs. In addition, pre-operativeT2-T1 W MRI images of the lumbar spine were analyzed for the presence and type (typical or atypical) of vertebral endplate defects, grade of disc degeneration (Pfirrmann grade I-V), presence of high intensity zones (HIZ), and Modic changes at the operated level. RESULTS: Vertebral endplate defects, Modic changes & HIZ were observed in 81%, 29% and 21% of patients respectively. Mean HDS & BMP-2 expression was 9 ± 2 and mean 71 ± 36 spots/mm2 respectively. Discs with adjacent vertebral endplate defects showed increased cell density (P = .004), mucus degeneration (P = .002), HDS (P = .01) and BMP-2 expression (P = .01). Discs with HIZ also had increased HDS, but significance was seen with increased BMP2 expression (P = .006). HDS showed a positive correlation with BMP 2 expression (r = .30, P = .04). CONCLUSION: These findings suggest that the altered mechanical environment of discs is strongly associated with BMP-2 expression which is an important marker of intervertebral disc calcification.