TRIM32 Deficiency Impairs Synaptic Plasticity by Excitatory-Inhibitory Imbalance via Notch Pathway.

Synaptic plasticity is the neural basis of physiological processes involved in learning and memory. Tripartite motif-containing 32 (TRIM32) has been found to play many important roles in the brain such as neural stem cell proliferation, neurogenesis, inhibition of nerve proliferation, and apoptosis. TRIM32 has been linked to several nervous system diseases including autism spectrum disorder, depression, anxiety, and Alzheimer's disease. However, the role of TRIM32 in regulating the mechanism of synaptic plasticity is still unknown. Our electrophysiological studies using hippocampal slices revealed that long-term potentiation of CA1 synapses was impaired in TRIM32 deficient (KO) mice. Further research found that dendritic spines density, AMPA receptors, and synaptic plasticity-related proteins were also reduced. NMDA receptors were upregulated whereas GABA receptors were downregulated in TRIM32 deficient mice, explaining the imbalance in excitatory and inhibitory neurotransmission. This caused overexcitation leading to decreased neuronal numbers in the hippocampus and cortex. In summary, this study provides this maiden evidence on the synaptic plasticity changes of TRIM32 deficiency in the brain and proposes that TRIM32 relates the notch signaling pathway and its related mechanisms contribute to this deficit.

Financial cost to institutions on patients waiting for gall bladder disease surgery.

BACKGROUND: The aim of this study was to determine the financial costs to institution on patients waiting for gall bladder disease surgery and suggest measures to reduce them. METHODS: This multi-centre prospective descriptive survey was performed on all patients who underwent an elective cholecystectomy by three consultants at secondary care hospitals in Pakistan between Jan 2010 to Jan 2012. Data was collected on demographics, the duration of mean waiting time, specific indications and nature of disease for including the patients in the waiting list, details of emergency re-admissions while awaiting surgery, investigations done, treatment given and expenditures incurred on them during these episodes. RESULTS: A total of 185 patients underwent elective open cholecystectomy. The indications for listing the patients for surgery were biliary colic in 128 patients (69%), acute cholecystitis in 43 patients (23%), obstructive jaundice in 8 patients (4.5%) and acute pancreatitis in 6 patients (3.2%). 146 (78.9%) and 39 (21.1%) of patients were listed as outdoor electives and indoor emergencies respectively. Of the 185 patients, 54 patients (29.2%) were re-admitted. Financial costs in Pakistani rupees per episode of readmission were 23050 per episode in total and total money spent on all readmissions was Rs. 17,05,700/-. CONCLUSION: Financial costs on health care institutions due to readmissions in patients waiting for gall bladder disease surgery are high. Identifying patients at risk for these readmissions and offering them early laparoscopic cholecystectomy is very important.

A Case Report of Surgical Approach in Managing De Quervain's Tenosynovitis.

De Quervain's tenosynovitis is characterized by swelling of muscles (abductor pollicis longus (APL) and extensor pollicis (EPB) brevis), and they are located at the base of the thumb. This is a very irritating and painful condition. In many cases, late detection causes an increase in inflammation, and due to prolonged ignorance and neglect, the patient suffers from pain and discomfort that affects and restricts their daily routine work. The disorder tenosynovitis is triggered by preexisting tendon degeneration induced by excessive twisting actions. Inflammatory arthritis is primarily associated with the disorder. The tendon sheath thickens and becomes constricted if the inflammation and swelling persist. Patients who undergo high-torque wrist turning or other repetitive everyday movements, such as handshaking, have a higher risk of developing tenosynovitis. This disease can also occur without any sort of visible prior trauma or injury. Clinical evaluation is usually required for diagnosis; however, imaging studies might be used to confirm the diagnosis or check out alternate diseases. Nonsteroidal anti-inflammatory medication (NSAIDs), physical therapy, immobilization with splints, and rest are among the treatment options. Applying ice to the affected area and applying a splint are a few ways to ease the pain. Corticosteroid injections or surgery may be considered in situations that do not respond to preventive treatment; thus, patients are advised to go for minor surgery to get relief from prolonged pain.

Successful Knee Replacement in a Patient With a History of Multiple Knee Surgeries: A Case Report.

This case report describes the successful total knee arthroplasty (TKA) in a 58-year-old female with a prior history of multiple knee surgeries. The patient had three prior surgical procedures. The first surgery of the patient was a partial knee replacement, the second surgery the patient underwent was an arthroscopic meniscectomy, and the third surgery was a high tibial osteotomy (HTO) that left her with an extensive amount of scar tissue and a change in physical structure. When scar tissue develops over or close to a joint, the surrounding tissues are pulled inward by this shrinking or contraction. A joint may experience restricted movement as a result of this tightness. Stretchy and excessively flexible joints are common in people with Ehlers-Danlos syndrome. This may become an issue if you need sutures for a wound because the skin is frequently not strong enough to support them. The patient already undergone three surgeries prior but still showed signs of severe pain, swelling, and stiffness in the knee which made the patient suffer more during rest position and also made it sometimes so difficult that it affected everyday tasks. In this situation when the patient consulted the doctors, the patient was suggested to undergo TKA. TKA is the method of orthopedic surgical technique that is most consistently successful and highly effective. Patients with end-stage degenerative knee osteoarthritis might expect reliable results from this surgery. The case demonstrates the preoperative planning, surgical methods, and postoperative care needed to successfully treat a complicated patient profile. Hospital protocols were followed, and the patient's surgery was done with proper care and hygiene.

Total Hip Arthroplasty in Ankylosing Spondylitis: A Case Report of Ankylosed Hip.

Ankylosing spondylitis (AS) is a chronic inflammatory arthritic disease that primarily affects the axial skeleton, and its association with the secondary development of osteoarthritis (OA) in peripheral joints, particularly the hips, is increasingly recognized. This case report elucidates the diagnostic and therapeutic challenges encountered in a patient with bilateral hip osteoarthritis secondary to AS. The patient's medical history included AS and a failed attempt at core decompression of the left hip joint. The patient was managed with total hip arthroplasty (THA) on the left side due to persistent symptoms. Total hip arthroplasty on the left side involved a meticulous surgical approach, addressing the unique challenges posed by underlying ankylosis. The procedure was conducted uneventfully, with the implantation of a modular femoral head, uncemented femoral stem, and modular shell. Postoperatively, the patient experienced significant pain relief and improved functionality. Successful rehabilitation and management were integral to the overall positive outcome. This case report highlights the complex interplay between AS and hip osteoarthritis, emphasizing the importance of tailored diagnostic and therapeutic strategies. Successful total hip arthroplasty in the setting of AS-related hip osteoarthritis suggests that joint replacement can be effective, but ongoing research is necessary to optimize surgical planning and long-term outcomes in this patient population.

Cell-specific Nav1.6 knockdown reduced astrocyte-derived Aß by reverse Na+-Ca2+ transporter-mediated autophagy in alzheimer-like mice.

INTRODUCTION: Nav1.6 is closely related to the pathology of Alzheimer's Disease (AD), and astrocytes have recently been identified as a significant source of ß-amyloid (Aß). However, little is known about the connection between Nav1.6 and astrocyte-derived Aß. OBJECTIVE: This study explored the crucial role of Nav1.6 in mediated astrocyte-derived Aß in AD and knockdown astrocytic Nav1.6 alleviates AD progression by promoting autophagy and lysosome-APP fusion. METHODS: A mouse model for astrocytic Nav1.6 knockdown was constructed to study the effects of astrocytic Nav1.6 on amyloidosis. The role of astrocytic Nav1.6 on autophagy and lysosome-APP(amyloid precursor protein) fusion was used by transmission electron microscope, immunostaining, western blot and patch clamp. Glial cell activation was detected using immunostaining. Neuroplasticity and neural network were assessed using patch-clamp, Golgi stain and EEG recording. Behavioral experiments were performed to evaluate cognitive defects. RESULTS: Astrocytic Nav1.6 knockdown reduces amyloidosis, alleviates glial cell activation and morphological complexity, improves neuroplasticity and abnormal neural networks, as well as promotes learning and memory abilities in APP/PS1 mice. Astrocytic Nav1.6 knockdown reduces itself-derived Aß by promoting lysosome- APP fusion, which is related to attenuating reverse Na+-Ca2+ exchange current thus reducing intracellular Ca2+ to facilitate autophagic through AKT/mTOR/ULK pathway. CONCLUSION: Our findings unveil the crucial role of astrocyte-specific Nav1.6 in reducing astrocyte-derived Aß, highlighting its potential as a cell-specific target for modulating AD progression.

Graphene Oxide-Grafted Hybrid Diblock Copolymer Brush (GO-graft-PEG6k-block-P(MA-POSS)) as Nanofillers for Enhanced Lithium Ion Conductivity of PEO-Based Nanocomposite Solid Polymer Electrolytes.

Nanocomposite solid polymer electrolytes (NSPEs) with PEO as the matrix and (i) GO or (ii) GO-graft-PEG6k or (iii) GO-graft-PEG6k-block-P(MA-POSS) as nanofillers have been fabricated to elucidate the impact of the filler morphology on the lithium ion conductivity. GO-graft-PEG6k was obtained by grafting PEG6k onto GO via esterification. GO-graft-PEG6k-block-P(MA-POSS) was prepared via surface-initiated atom transfer radical polymerization. Fourier-transform infrared spectroscopy revealed enhanced salt dissociation and complexation between the filler and PEO host that could be attributed to Lewis acid-base interactions. Electrochemical impedance spectroscopy revealed the improved ion conductivity of the fabricated NSPEs as compared with the pristine PEO-LiClO4. As an example, at 50 °C, the ion conductivity increased to 4.01 × 10-5 and 6.31 × 10-5 S cm-1 with 0.3% GO and 0.3% GO-graft-PEG6k, respectively, from 2.36 × 10-5 S cm-1 of PEO-LiClO4, suggesting that the filler with brush-like architecture (GO-graft-PEG6k) is more efficient in enhancing the ion conductivity. Further increase in filler content resulted in lowering of the ion conductivity that could be ascribed to aggregation of the filler. The most dramatic impact on conductivity was observed with the incorporation of brush-like GO-graft-PEG6k-block-P(MA-POSS) as a nanofiller (3.0 × 10-4 S cm-1 at 50 °C with 1.0 wt % filler content). The increase in ion conductivity in the current systems, as opposed to the conventional view, could not be correlated with the content of the amorphous phase of the matrix. The conduction mechanism is still unclear; nevertheless, it could be assumed that in addition to the ion conduction through the PEO matrix, the filler forms additional low-energy ion conducting channels at its interface with the matrix. The pendent POSS nanocages of GO-graft-PEG6k-block-P(MAPOSS) might probably increase the free volume at the interface with the matrix that is associated with higher chain and ion mobility, thus further enhancing the ion conductivity as compared with GO and GO-graft-PEG6k. The faster ion dynamics in 1.0 wt % GO-graft-PEG6k-block-P(MAPOSS) NSPEs has also been verified by the dielectric relaxation studies. Thus, integration of both the PEG and POSS nanocages into GO-grafted brush-like architecture offers a new tool for tuning the lithium ion conductivity for potential Li ion battery applications.

Management of Chronic Obstructive Pulmonary Disease (COPD) Exacerbations in Hospitalized Patients From Admission to Discharge: A Comprehensive Review of Therapeutic Interventions.

Chronic obstructive pulmonary disease (COPD) is a common and debilitating condition that often necessitates hospitalization for exacerbations. Since COPD exacerbations can cause significant morbidity and mortality, managing them is crucial for patient care. Effective management of COPD exacerbations is essential to prevent complications, as COPD exacerbations are associated with increased healthcare costs and decreased quality of life. This review aims to comprehensively discuss the management of COPD exacerbations, covering various pharmacologic and non-pharmacologic strategies. These include inhaled bronchodilators, systemic steroids, antibiotics, invasive and non-invasive ventilation, oxygen therapy, smoking cessation, immunization with pneumococcal vaccine, inhalers at discharge, pulmonary rehabilitation, long-term oxygen therapy (LTOT), ambulatory oxygen therapy, short-burst oxygen therapy, extracorporeal membrane oxygenation (ECMO), lung volume reduction surgery (LVRS), endobronchial procedures, and lung transplant. It is drawn upon various sources, including clinical studies, systemic reviews, and observational studies, to provide a comprehensive overview of current practices and identify areas for future research and innovation in managing COPD exacerbations. Addressing these areas of interest can improve patient outcomes and quality of life.

Comparison of rate of surgical wound infection, length of hospital stay and patient convenience in complicated appendicitis between primary closure and delayed primary closure.

OBJECTIVE: To compare the difference in the rate of surgical wound infection, patient's convenience and length of hospital stay between Primary Closure and Delayed Primary Closure in cases of complicated appendicitis in adults. METHODS: This randomised control trial was conducted at the Combined Military Hospital, Kharian and Malir from June 5, 2006, to September 10, 2009. Patients > or = 15 years of both gender who underwent appendectomy through grid iron or Lanz incision and having complicated appendicitis were included. The 100 patients who were included in the study out of the initial size of 393, were randomised into two equal groups of 50 each (Group A: Primary Closure; Group B: Delayed Primary Closure) using a computer-generated table. All the surgeries were done by the same surgeon and the operative steps and antibiotic coverage were standardised. The rate of surgical wound infection, patient's convenience (on visual analogue scale in mm) and the length of hospital stay were recorded. Data was analysed using SPSS version 11, and p value was calculated. RESULTS: Demographic data, comorbids and medication of both the groups was comparable. There was no significant difference in rate of surgical wound infection (p > 0.05). The difference in patient's convenience and length of hospital stay were significant (p < 0.05), showing superiority of Primary Closure over Delayed Primary Closure with no added morbidity/mortality. CONCLUSION: Primary Closure in complicated appendicitis not only reduces the cost of treatment, but is also more convenient and satisfying for the patients, with no added risk of surgical wound infection.

The Utility of Supracutaneous Plating in the Staged Management of Compound Distal Femur Fracture: A Case Report.

The aim of this report is to draw attention to the use of a vilipend technique 'supracutaneous plating' in the management of compound distal femur fractures. Treatment of compound fractures of the distal femur with bone defects and microbial infection remains a challenging task for orthopaedic trauma surgeons. In this case report, we share our experience with the use of the locking distal femoral plate as an external fixator for the staged management of a compound infected distal femur fracture in a 22-year-old male patient. Staged procedures with proper planning give excellent results for infected fractures. Supracutaneous plating can be a viable and patient-friendly alternative in the staged management of compound distal femur fractures instead of the conventional external fixators.

The Importance of Prompt Management of Morel-Lavallée Lesions.

The Morel-Lavallée lesion (MLL) is a closed soft-tissue injury that is frequently associated with high-intensity trauma. The thigh, hip, and pelvic regions are the most typically affected regions. It is critical to recognize and treat an MLL as soon as possible because it is often neglected or its identification is delayed because of other distracting injuries in a polytrauma patient. Bacterial colonization of these closed soft-tissue wounds can result in an increased risk of perioperative and postoperative infection. Magnetic resonance imaging has recently been used to define and grade these lesions. To reduce the dangers of these situations, clinical suspicion and on-the-spot identification of these lesions are essential. Here, we report an operated case of fracture shaft femur associated with MLLs and discuss the diagnostic and surgical approaches.

Outcome Analysis of Distal End Radius Fractures Managed With Antegrade Intramedullary K-wire Fixation.

Background The most frequent upper limb fractures are distal end radius fractures, accounting for around 17% of all fractures in clinical practice. Falling on an outstretched hand is the most common mechanism of injury, and it can also occur in high-energy trauma in young individuals. A minimally invasive technique of percutaneous pinning was introduced to sustain the fracture's reduction after manipulation and avoid the re-displacement of fractured fragments. Antegrade intramedullary K-wire fixation is a cost-efficient procedure that can be done in rural settings. Methodology A total of 30 patients with fractures of the distal end radius managed with antegrade intramedullary K-wire fixation were included in the study. Operated patients were followed up at one month, three months, and six months for functional assessment. An X-ray was taken on every follow-up to assess the union and implant positioning. Results In our study, the mean age was 45.6 years. Out of the 30 patients, 12 were males and 18 were females. All 30 patients at the final follow-up showed good functional improvement, with statistically significant improvements in palmar flexion, adduction and abduction, and pain scale scores. Conclusions Antegrade K-wire fixation is an effective technique for fractures of the distal end radius that can be performed in rural settings with effective results.

Traumatic First Rib Fracture: An Indication of Life-threatening Injuries.

Introduction: First rib fracture is a very uncommon injury due to protection provided to it by clavicle. In isolation, it may be associated with neurovascular injury rarely but as part of poly trauma the first rib fracture may be associated with vascular injury in significant number of cases. There is definite role of computed tomography scan thorax in diagnosis of this fracture which can be missed on X-ray chest. Management includes early diagnosis of associated life-threatening complications and its prompt treatment. Case Report: A case of poly trauma associated with right first rib fracture with subclavian artery thrombosis resulting in gross ischemia of the right upper limb and fractures in the right upper limb and right lower limb long bones is reported. The patient developed signs of ischemia and lung complications 24 h later. Subclavian artery damage was diagnosed on Doppler ultrasound and angiography. The case was managed by surgical repair of subclavian artery damage and stabilization of fractures. Conclusion: The case is reported to highlight association of first rib fracture with life-threatening complication of subclavian artery laceration causing extensive swelling around shoulder, ischemia to the right upper limb, lung damage, and problem of its detection and management.

Scorpion venom heat-resistant synthesized peptide ameliorates 6-OHDA-induced neurotoxicity and neuroinflammation: likely role of Nav 1.6 inhibition in microglia.

BACKGROUND AND PURPOSE: Microglia-related inflammation is associated with the pathology of Parkinson's disease. Functional voltage-gated sodium channels (VGSCs) are involved in regulating microglial function. Here, we aim to investigate the effects of scorpion venom heat-resistant synthesized peptide (SVHRSP) on 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease-like mouse model and reveal its underlying mechanism. EXPERIMENTAL APPROACH: Unilateral brain injection of 6-OHDA was performed to establish Parkinson's disease mouse model. After behaviour test, brain tissues were collected for morphological analysis and protein/gene expression examination. Primary microglia culture was used to investigate the role of sodium channel Nav 1.6 in the regulation of microglia inflammation by SVHRSP. KEY RESULTS: SVHRSP treatment attenuated motor deficits, dopamine neuron degeneration, activation of glial cells and expression of pro-inflammatory cytokines induced by 6-OHDA lesion. Primary microglia activation and the production of pro-inflammatory cytokines induced by lipopolysaccharide (LPS) were also suppressed by SVHRSP treatment. In addition, SVHRSP could inhibit mitogen-activated protein kinases (MAPKs) pathway, which plays pivotal roles in the pro-inflammatory response. Notably, SVHRSP treatment suppressed the overexpression of microglial Nav 1.6 induced by 6-OHDA and LPS. Finally, it was shown that the anti-inflammatory effect of SVHRSP in microglia was Nav 1.6 dependent and was related to suppression of sodium current and probably the consequent Na+ /Ca2+ exchange. CONCLUSIONS AND IMPLICATIONS: SVHRSP might inhibit neuroinflammation and protect dopamine neurons via down-regulating microglial Nav 1.6 and subsequently suppressing intracellular Ca2+ accumulation to attenuate the activation of MAPKs signalling pathway in microglia.

Efficacy of combination of 0.2% GTN and lignocaine ointments in wound healing and pain relief after Milligan Morgan hemorrhoidectomy--a comparison with lignocaine and 0.2% GTN ointments separately.

OBJECTIVE: To compare the analgesic efficacy and rate of wound healing of combination of 0.2% Glyceryl Trinitrate and 2% lignocaine ointments with 0.2% Glyceryl Trinitrate and 2% lignocaine ointment separately after Milligan Morgan hemorrhoidectomy. DESIGN: Randomized control trial. PLACE AND DURATION OF STUDY: Combined Military Hospital, Kharian, Malir and Bannu. November 2007 to August 2011. PATIENTS AND METHODS: Patients undergoing Milligan Morgan hemorrhoidectomy were randomized into 3 groups by using computer generated table. Group A received combination of 0.2% Glyceryl Trinitrate and 2% lignocaine ointment, Group B 2% lignocaine and Group C received 0.2% Glyceryl Trinitrate ointment. These ointments were given on twice daily basis. Pain scores were measured on a 100 mm Visual Analog Scale. Pain scores and quantity of oral analgesics used were compared daily until the 7th post-operative day. The time required for complete healing (in weeks) was also compared. RESULTS: Out of 210 patients, 192 (67 Group A, 64 Group B and 61 Group C) completed the study. Demographic data were comparable in all three groups. There were statistically significant reductions in pain scores and quantity of analgesics used from the first to the fourth post-operative days in Group A. The time required for complete healing was also significantly reduced in the combination group. There were no significant side effects in any group. CONCLUSION: The combination of 0.2% GTN and 2% lignocaine showed better pain relief resulting in less use of oral analgesics and faster healing of the wound after Milligan Morgan hemorrhoidectomy.

Role of prophylactic antibiotics in Milligan Morgan hemorrhoidectomy - a randomized control trial.

OBJECTIVE: Role of prophylactic antibiotics in Milligan Morgan hemorrhoidectomy - A prospective, randomized control trial. DESIGN: Randomized control trial. PLACE AND DURATION OF STUDY: Combined Military Hospital Malir, Bannu and HIT hospital Taxilla, September 2008 to February 2011. PATIENTS AND METHODS: Patients undergoing Milligan Morgan hemorrhoidectomy for grade III and IV hemorrhoids were randomized in 2 groups by using computer generated table. Group A did not receive any prophylactic antibiotic whereas group B received 500 mg I/V metronidazole and 1 g Ceftriaxone I/V before induction of anesthesia. All the patients had standardized post operative care. Pain scores on 100 mm Visual Analogue Scale and consumption of oral analgesics were noted from 1st to 7th post operative day. Time required for complete healing was also noted. Data was entered on SPSS 16.0 and p value was calculated. RESULTS: Out of 100 patients, 96 patients (47 in group A and 49 in group B) completed the study. Demographical data was comparable in both the groups. There was no difference in the pain scores, analgesic consumption and rate of healing between both the groups. CONCLUSION: Prophylactic antibiotics have got no role in cases of Milligan Morgan hemorrhoidectomy.