Case report: A novel de novo loss of function variant in the DNA-binding domain of TBX2 causes severe osteochondrodysplasia

Background: T-box family members are transcription factors characterized by highly conserved residues corresponding to the DNA-binding domain known as the T-box. TBX2 has been implicated in several developmental processes, such as coordinating cell fate, patterning, and morphogenesis of a wide range of tissues and organs, including lungs, limbs, heart, kidneys, craniofacial structures, and mammary glands.Methods: In the present study, we have clinically and genetically characterized a proband showing a severe form of chondrodysplasia with developmental delay. Whole-exome sequencing (WES), Sanger sequencing, and 3D protein modeling were performed in the present investigation.Results: Whole-exome sequencing revealed a novel nonsense variant (c.529A>T; p.Lys177*; NM_005994.4) in TBX2. 3D-TBX2 protein modeling revealed a substantial reduction of the mutated protein, which might lead to a loss of function (LOF) or nonsense-mediated decay (NMD).Conclusion: This study has not only expanded the mutation spectrum in the gene TBX2 but also facilitated the diagnosis and genetic counseling of related features in affected families

Early Cholecystectomy versus Conservative Management in Mucocele Gall Bladder

Aim: To compare the early cholecystectomy versus conservative management in mucocele gall bladder. Study design: Retrospective study Place and duration of study: Department of General Surgery, Ward-2, JPMC/Jinnah Sindh Medical University, Karachi from 1st October 2020 to 30th September 2022. Methodology: One hundred patients suffering from cholelithiasis with mucocele gall bladder were included. The patients were divided into two groups on the basis of stone location. Group 1 was those where the stone was found on the base of common bile duct (CBD) and elective/early surgery was conducted for the cases of cholelithiasis. Group 2 was those where conservative/delayed surgical technique was applied due to stone location not in the CBD for treatment. While in each group there were 50 cases which were age and gender matched. The first priority for surgical option was through laparoscopic surgery. Results: The mean age of the patients was 45.2±3.3 years. Out of the total cases in group 1 the process of ERCP was conducted in 64% of the cases before laparoscopy. There were 1% and 10% cases which were shifted to open surgery from laparoscopic in group1 and 2 respectively. Consequently, the mean operative time and hospital duration was increased in group 2. Within the Group 2 cases the risk of sepsis, wound contamination and perforation of gall bladder was much higher than in the Group 1 by a value of 10%, 12% and 6% respectively. There was 1 case of mortality and 2 cases of pancreatitis in group 2. Conclusion: The early cholecystectomy is a much safer and efficient procedure on treatment of mucocele gall bladder cases verses conservative management. Keywords: Early cholecystectomy, Conservative management, Mucocele gall bladder</jats:p

Vein Stripping Versus No Stripping in Varicose Vein Disease

Aim: To comparative analysis of vein stripping versus no stripping in varicose vein disease. Study design: Comparative study Place and duration of study: Department of Surgery, CMH Kharian Medical College, Kharian from 01-01-2019 to 31-12-2021. Methodology: Eighty cases of varicose vein which were having sapheno-femoral valve incompetence as well as perforators-incompetence were enrolled. The age of the cases was between 16 and 70 year. Electrocardiography (ECG), as well as venous Doppler of the affected limb was accomplished. Each group comprised 40 cases. Group A and Group B were constituted in accordance to difference in the operating procedure where vein stripping was done in Group A and without vein stripping was conducted in Group B. Results: The mean age of the patients was 42.3±4.5 years. There was higher number of females than males in this study. In the present study there were higher cases of hematoma observed in group A than in Group B with a percentage difference of 27.7% to 4.4% which was statistically significant. Ambulation comfort was observed higher in cases with ligation then having venous stripping. Pain relief of the patients post 2 months of the surgery was analyzed as higher in the Group A such as venous stripping group in comparison with the without venous stripping group (Group B). Conclusion: The technology of ligation where no vein stripping is conducted is more efficient and reliable then vein stripping methods in terms of pain, hematoma reduction, and trauma reduction with augmenting ambulation comfort. Keywords: Varicose, Mortality, Peroneal vein, Tibia, Femor</jats:p

Comparison of Open vs Laparoscopic Cholecystectomy in patients of Cholelithiasis having Previous Abdominal Surgeries

Background: Most of the surgeons in our setups perform open cholecystectomy (OC) in patients of cholelithiasis having previous abdominal surgery. This is the era of laparoscopic and robotic surgery and laparoscopic cholecystectomy (LC) should be the preferred treatment for these patients as well. Aim: To observe the effect of previous abdominal surgeries on laparoscopic cholecystectomy. Study design: Randomized, controlled and multicenter experimental study. Place and duration of study: Department of Surgery, Central Park Teaching Hospital, Lahore, Noor Hospital, Kot Radha Kishan and Bilquees Hospital, Kasur from 1st January 2020 to 31st December 2021. Methodology: Fifty eight patients were allocated into 2 groups (29 in each group) not considering age and sex. Both types of surgeries were analyzed on the basis of operating time, post-operative pain (VAS) and complications. Complications were noted i.e. wound infection, bile leakage from cystic duct/CBD injury, gut injury and per operative bleeding). Type of previous surgery was also noted. Data of conversion to open cholecystectomy from laparoscopic cholecystectomy was also recorded. Results: Mean age of patients in group A was 45.99±13.42 years while mean age of patients in group B was 41.87±14.65 years and p-value 0.105. 75.2% patients in group A were female while 82.1% patients in group B were female (p-value 0.185). Operative time in group A was 45.51±8.32 minutes while operative time in group B was 70.33±13.40 minutes (p-value 0.001). VAS score was 7.34±1.80 in group A while it was 5.24±1.93 in group B (p-value 0.001). 4 patients (13.79%) in group A developed wound infection while 1 patient (3.45%) from group B developed wound infection (p-value 0.005). Bile leakage and gut injury were not seen in any of the patient from both groups. Peroperative bleeding (more than 50ml) was seen in 2 patients of group A (6.90%) while it was seen in 8 patients of group B (27.59%) p-value 0.001. Type of previous surgeries were 24 cases were of mesh hernioplasty (41.38%), 16 cases of herniorrhaphy (27.59%), 10 laparotomies for peritonitis/intestinal obstruction (17.24%) and 8 cases of laparotomies for gynecological problems (13.79%). No case of laparoscopic cholecystectomy was converted to open cholecystectomy. Conclusion: Laparoscopic cholecystectomy is a safe and excellent option in patients of cholelithiasis having previous abdominal surgery. Even though LC takes more time due to adhesions but this issue does not out weights the benefits of laparoscopic cholecystectomy over open cholecystectomy. Keywords: Laparoscopic cholecystectomy, Cholelithiasis</jats:p

Role of Metronidazole after Appendicectomy in Simple Cases of Acute Appendicitis

Background: Simple cases of acute appendicitis are usually dealt with appendicectomy and post-operative antibiotics. Causative organisms include both aerobes as well as anaerobes. The antibiotic spectrum to cover aerobes varies from hospital to hospital but the drug Metronidazole is used to cover anaerobes which is fairly common Aim: To determine the role of metronidazole after appendicectomy in simple cases of acute appendicitis Study design: Randomized, controlled, multicenter trial. Place and duration of study: Department of Surgery, Central Park Teaching Hospital Lahore, Noor Hospital, Kot Radha Kishan and Bilquees Hospital, Kasur from 1st January 2020 to 31st December 2021 Methodology: One hundred and thirty patients were included in the study divided into 2 groups (65 in each group). Inclusion criteria included all patients of simple acute appendicitis from age 13 to 70 years. Exclusion criteria were patients with complications of acute appendicitis. Patients receiving Metronidazole were allocated group A, while those not receiving this drug were allocated group B. Open appendicectomy was done in all cases. Variables of interest were post-operative wound infection, hospital stay and nausea/vomiting. Results: Mean age of patients of group A was 29.39±16.32 years while mean age of patients in group B was 34.18±18.05 years. 44.6% patients of group A were male and 55.4% were females. On the other hand 50.8% patients of group B were male and 49.2% were females. In group A, 6 patients got wound infection (9.2%) while 59 patients had uneventful recovery (90.8%). In group B, 4 patients got wound infection making it 6.2% while rest of the 61 patients had uneventful recovery (93.8%). The difference between the 2 groups was not statistically significant (p-value 0.11). Mean hospital stay in group A patients was 2.28±0.89 days while in group B it was 2.12±0.73 days. Conclusion: Metronidazole is an effective drug against anaerobes but in simple cases of non-perforated appendicitis this drug does not decreases the wound infection rate after appendicectomy. Keywords: Metronidazole, Appendicitis, Appendicectomy</jats:p

Safeguarding Online Spaces: A Powerful Fusion of Federated Learning, Word Embeddings, and Emotional Features for Cyberbullying Detection

Cyberbullying has emerged as a pervasive issue in the digital age, necessitating advanced techniques for effective detection and mitigation. This research explores the integration of word embeddings, emotional features, and federated learning to address the challenges of centralized data processing and user privacy concerns prevalent in previous methods. Word embeddings capture semantic relationships and contextual information, enabling a more nuanced understanding of text data, while emotional features derived from text extend the analysis to encompass the affective dimension, enhancing cyberbullying identification. Federated learning, a decentralized learning paradigm, offers a compelling solution to centralizing sensitive user data by enabling collaborative model training across distributed devices, preserving privacy while harnessing collective intelligence. In this study, we conduct an in-depth investigation into the fusion of word embeddings, emotional features, and federated learning, complemented by the utilization of BERT, Convolutional Neural Networks (CNN), Deep Neural Networks (DNN), and Long Short-Term Memory (LSTM) models. Hyperparameters and neural architecture are explored to find optimal configurations, leading to the generation of superior results. These techniques are applied in the context of cyberbullying detection, using publicly available multi-platform (social media) cyberbullying datasets. Through extensive experiments and evaluations, our proposed framework demonstrates superior performance and robustness compared to traditional methods. The results illustrate the enhanced ability to identify and combat cyberbullying incidents effectively, contributing to the creation of safer online environments. Particularly, the BERT model consistently outperforms other deep learning models (CNN, DNN, LSTM) in cyberbullying detection while preserving the privacy of local datasets for each social platform through our improved federated learning setup. We have provided Differential Privacy based security analysis for the proposed method to further strengthen the privacy and robustness of the system. By leveraging word embeddings, emotional features, and federated learning, this research opens new avenues in cyberbullying research, paving the way for proactive intervention and support mechanisms. The comprehensive approach presented herein highlights the substantial strengths and advantages of this integrated methodology, setting a foundation for future advancements in cyberbullying detection and mitigation

Effectiveness of Local Anesthetic Nerve Block compared with Spinal Anesthesia in cases of Rhomboid excision and Limberg flap closure for Pilonidal Disease

Background: Modified Limberg Flap (MLF) is regarded as the mainstay of treatment for Sacrococcygeal Pilonidal disease due to less postoperative complications as compared to other available surgical procedures. This Operative procedure can be performed under Spinal anesthesia as well as Local Anesthesia. Aim: To compare outcome of patients undergoing Modified Limberg Flap for Sacrococcygeal pilonidal sinus under Local anesthesia with adrenaline versus Spinal anesthesia in terms of post-operative pain, Seroma formation &amp; Hospital stay. Methods: This was a randomized controlled clinical trial conducted at Department of Surgery, Sughra Shafi Medical Complex, Narowal. Study was conducted for a period of 06 months and 80 patients were included through non-probability consecutive sampling technique. Patients were randomly divided into 2 equal groups by computer generated method. Patients in group LA underwent MLF under Local anesthesia with adrenaline while patients in group SA underwent MLF under Spinal anesthesia. Informed written consent was obtained from all the participating patients. Results: Mean age of all patients was 24.78±5.12 years. Minimum and maximum age of patients was 16 and 37 years respectively. Gender distribution shows that 96.25% were male while 3.75% were female. Seroma formation in Group-LA was 0% while in Group-SA, it was 7.5%. Hospital stay of patients in Group-LA and in Group-SA was 9.60±9.39 and 29.10±9.37 hours respectively. Mean operation time in Group-LA was 42±5.64 minutes whereas in Group-SA mean operation time was 46±7.53 minutes. Mean pain score in Group-LA was 2±1.04 at 12th hour of surgery and in Group-SA it was 3.83±1.06 at 12th hour of surgery. Conclusion: It is concluded that Modified Limberg Flap can be performed under local anesthesia as a day case procedure to save time, reduce work burden and cost of surgery. Keywords: Modified Limberg Flap, Sacrococcygeal Pilonidal Sinus Disease, Local Anesthesia, Adrenaline, Spinal Anesthesia.</jats:p

Amyloid solutions: lecanemab, gantenerumab, and donanemab in the treatment of Alzheimer's disease

Abstract Alzheimer’s disease (AD), the leading cause of dementia, is a multifaceted neurodegenerative disorder characterized by amyloid-beta (Aβ) aggregation, tau pathology, and neuroinflammation. Recent advances in immunotherapy have yielded monoclonal antibodies (mAbs) with unprecedented precision in targeting Aβ species, offering hope for altering the disease trajectory. Lecanemab’s selective affinity for protofibrillar Aβ disrupts early neurotoxic aggregates, providing a proactive approach for mitigating synaptic dysfunction. Donanemab, by targeting pyroglutamate-modified plaques, combines high specificity with microglial-mediated clearance, while gantenerumab enhances Fc receptor-mediated phagocytosis of both soluble and fibrillar Aβ. These therapies represent a shift from symptomatic treatment to disease modification, reducing the Aβ burden and slowing cognitive decline. However, challenges, such as amyloid-related imaging abnormalities (ARIA), underscore the complexity of balancing efficacy and safety. This review explores the transformative potential of these therapies and contextualizes their mechanisms within the evolving understanding of AD pathophysiology. This highlights the interplay between immune modulation, neuroprotection, and personalized medicine, highlighting the need for future innovations in tackling one of the most formidable challenges in neurology

Case report: A novel de novo loss of function variant in the DNA-binding domain of TBX2 causes severe osteochondrodysplasia

Background: T-box family members are transcription factors characterized by highly conserved residues corresponding to the DNA-binding domain known as the T-box. TBX2 has been implicated in several developmental processes, such as coordinating cell fate, patterning, and morphogenesis of a wide range of tissues and organs, including lungs, limbs, heart, kidneys, craniofacial structures, and mammary glands.Methods: In the present study, we have clinically and genetically characterized a proband showing a severe form of chondrodysplasia with developmental delay. Whole-exome sequencing (WES), Sanger sequencing, and 3D protein modeling were performed in the present investigation.Results: Whole-exome sequencing revealed a novel nonsense variant (c.529A&amp;gt;T; p.Lys177*; NM_005994.4) in TBX2. 3D-TBX2 protein modeling revealed a substantial reduction of the mutated protein, which might lead to a loss of function (LOF) or nonsense-mediated decay (NMD).Conclusion: This study has not only expanded the mutation spectrum in the gene TBX2 but also facilitated the diagnosis and genetic counseling of related features in affected families.</jats:p