Carbamazepine versus levetiracetam in epilepsy due to neurocysticercosis.

BACKGROUND: The choice of antiepileptic drug (AED) in newly diagnosed neurocysticercosis (NCC) patients with epilepsy continues to be arbitrary. We compared efficacy and side effect profile of levetiracetam (LEV) and carbamazepine (CBZ) for the treatment of seizures in newly diagnosed patients with NCC. PATIENTS AND METHODS: This was an open-labeled randomized comparative monotherapy study including newly diagnosed drug naïve patients of NCC (n = 99) presenting with seizures who were randomized in 1:1 ratio using computed generated numbers. All patients were followed up for at least six months after start of treatment. The primary outcome measure was seizure control over six months following start of AEDs. RESULTS: Fifteen (15.2%) patients [CBZ- 4(8.2%); LEV- 11(22%)] developed recurrence of seizures. A trend (p = 0.09) was found toward better control of seizures in CBZ compared to LEV. Two (4%) patients in LEV group and 17 (34.6%) patients in CBZ group developed drug-related minor side effects (p < 0.0001). Three patients in CBZ group needed discontinuation of therapy due to skin rash. Eleven patients who relapsed while on LEV did not have any recurrence of seizures after switching over to CBZ. Out of 3 patients who relapsed while receiving CBZ and were changed to LEV, two developed seizures during follow-up. CONCLUSION: CBZ and LEV could be used as alternatives in newly diagnosed patients of NCC at the behest of minor side effects in the CBZ group.

Behind Closed Doors: The Hidden Realities of Indian Children Living With Alcohol-Dependent Parents.

BACKGROUND: The negative impact of Paternal Alcohol Use Disorder (PAUD) on children's psychosocial well-being is an overlooked issue that warrants more global research attention. Alcohol dependence is often seen as a hidden problem with subtle yet harmful effects, especially on the children of those with alcohol dependence. These children often remain invisible due to their loyalty and unwillingness to disclose their dysfunctional family situation. However, in the Indian context, these invisible children receive limited and insufficient support. AIM: This study aims to narrate the profound experiences of children growing up with fathers with Alcohol Use Disorder (AUD), highlighting the challenges of invisibility and the support they receive within the Indian cultural context. METHODS: The study used a qualitative narrative research design, with a panel of child psychology experts selecting 12 participants aged 11-13 years. Data were collected through in-depth interviews and a semi-structured interview guide. The data collected were transcribed from the local language into English and analyzed using narrative thematic analysis. RESULTS: The study revealed how PAUD negatively influences children's experiences and societal norms surrounding family honour and reputation. It also sheds light on the children's reluctance to seek help due to stigmatization, the circumstances that compel them to disclose their problems, and the support they receive to cope with these challenges. IMPLICATIONS:  This study highlights the critical need for culturally specific interventions and support mechanisms in India to address the psychosocial challenges faced by children, emphasizing the importance of societal acknowledgment and strategic interventions to alleviate the detrimental impact of parental AUD on child well-being.

Parenting Amid Shadows: Exploring the Child-Rearing Experiences of Wives of Individuals With Alcohol Use Disorder.

INTRODUCTION: The pervasive impact of alcohol use disorder (AUD) within families, particularly on parenting roles in Kerala, India, necessitates an in-depth exploration. This study aims to uncover the unique challenges and coping strategies employed by wives of individuals with AUD against a backdrop of societal stigma and economic hardship. METHODOLOGY: This study, employing a qualitative narrative research design, delves into the experiences of 30 wives of men with AUD in Kerala. The study delves into the complexities of navigating parenting responsibilities amid challenges related to AUD, employing in-depth interviews with the aid of a semi-structured interview guide conducted in Malayalam.​​​​​ The researchers used narrative analysis to extract the themes related to coping mechanisms, resilience, and the impact on children's psychological health. RESULTS: The study highlights significant emotional and social burdens on wives, including solo parenting, financial strain, and social stigma. Despite these challenges, the resilience and adaptive strategies of these women stand out, with extended family support, community resources, and personal beliefs playing crucial roles in their coping mechanisms. The study points out variations in coping strategies across different socio-economic and educational backgrounds. IMPLICATIONS: The findings underscore the necessity for comprehensive support systems sensitive to the socio-demographic differences among families affected by AUD. Tailored interventions that enhance access to professional support, foster community solidarity, and provide economic assistance are critical. Moreover, efforts to reduce stigma and promote understanding are essential for improving the psychological health and overall quality of life of these families.

A Transformative Journey Through Support Group Participation: Narratives of the Wives of Individuals With Alcohol Use Disorder.

The issue of alcohol use disorder (AUD) has received significant attention, with a primary focus on individuals directly afflicted by the disorder. This extensive focus, while necessary, often overlooks the profound impact that AUD has on the family unit, particularly on spouses who play a crucial role in the dynamics of coping and recovery. However, the psychosocial and emotional challenges encountered by wives of those with AUD have been largely neglected in both research and therapeutic interventions. This oversight not only minimizes their suffering but also overlooks their potential contribution to the recovery process, underscoring the need for a more inclusive approach to understanding and addressing AUD. Building upon this foundation, the current study delves into the less explored terrain of the psychosocial and emotional ramifications borne by wives of individuals suffering from AUD. By highlighting the pivotal role that these women fulfil in family dynamics, it seeks to shed light on the transformative effects of their engagement in support groups, aiming to demonstrate how these networks promote resilience, empowerment, and healing for both the women and their families, thus offering a more comprehensive perspective on AUD's impact on society. Employing a qualitative narrative research design, the study utilized purposive sampling to select 36 participants from the northern, southern, and central regions of Kerala, India. Data collection was conducted through in-depth interviews using a semi-structured interview guide. The interviews, conducted initially in the local language, were transcribed into English and analyzed using the constant comparative method, ensuring that ethical considerations were upheld throughout the research process. The results of the study illuminate the multifaceted challenges faced by wives of individuals with AUD, including financial burdens, domestic violence, marital discord, and psychosocial issues. Notably, the participants reported a significant positive shift in their lives following their involvement in support groups, experiencing enhanced mental peace and tranquillity. This transformation enabled some participants to resume their education, engage with the community as role models and leaders, and reconstruct their lives. Most participants viewed their support group participation as a pivotal moment of hope restoration in their lives. The study reveals the necessity for integrating culturally sensitive support mechanisms into rehabilitation programs for families affected by AUD, advocating for broader adoption of support groups that cater to the specific sociocultural dynamics of affected communities.

A Post-marketing Surveillance, Single-Centric Study to Evaluate the Safety and Tolerability of VELNEZ as a Space-Occupying Dressing Pack After Ear Surgery.

PURPOSE: The purpose of this study was to evaluate the safety and tolerability of VELNEZ (Datt Mediproducts Pvt. Ltd., New Delhi, India) as a space-occupying dressing for controlling hemorrhage after ear surgery. METHOD: A total of 21 patients were included in an open-label, interventional, single-arm post-marketing surveillance study to investigate the safety and efficacy of the VELNEZ ear pack. The patients were questioned for collecting data related to the subject's safety and comfort, adverse events, site assessment, and otoscopic examination from discharge day to last follow-up (eight follow-up visits) at regular intervals. The standardized questionnaires for VELNEZ tolerability (pain/pressure effect, infection, and general satisfaction) were used after ear surgery. RESULTS:  The average hemorrhage control time was 1.08 ± 0.16 minutes. None of the subjects reported moderate pain at any of the study visits following surgery. This biodegradable ear pack had an average disintegration time of 25.4 days in the ear cavity. No postoperative adverse events or serious adverse events were observed. CONCLUSION: VELNEZ is safe and effective as a space-occupying dressing pack after ear surgery and is well-tolerated by patients.

The diagnostic accuracy of point-of-care ultrasound parameters for airway assessment in patients undergoing intubation in emergency department-an observational study.

BACKGROUND: Endotracheal intubation is an essential resuscitative procedure in the emergency setting. Airway assessment parameters such as the Mallampati classification are difficult to perform in an emergency setting. As point-of-care ultrasound (POCUS) assessment of airway parameters does not require patients to perform any mandatory action, ultrasound may become the potential first-line noninvasive airway assessment tool in the emergency department (ED). The use of POCUS in the ED has not been sufficiently studied. Using POCUS in airway assessment for predicting difficult intubation may be the next step in successful airway management. METHODOLOGY: The study was an observational study conducted at the ED of the All India Institute of Medical Sciences (Rishikesh). The treating emergency physician recorded the patient history and systemic examination along with an indication for intubation. The POCUS assessment of airway parameters pre-epiglottis to epiglottic vocal cord ratio (Pre-E/E-VC), tongue thickness, hyomental distance, and distance from skin to the hyoid bone was performed by the study investigator. During laryngoscopy, Cormack-Lehane (CL) grading was assessed. The data was entered and analyzed. RESULTS: Seventy patients who required intubation in the ED were enrolled in the study. Among the study population, 48.6%, 28.6%, 14.3%, 1.4%, and 7.1% were classified with the following CL grading: 1, 2a, 2b, 3a, and 3b, respectively. At a cutoff of ≥ 1.86, Pre-E/E-VC predicts difficult laryngoscopy (AUC 0.835) with a sensitivity of 83% and a specificity of 94%. At a cutoff of ≥ 5.98 cm, tongue thickness predicts difficult laryngoscopy (AUC 0.78) with a sensitivity of 83% and a specificity of 88%. At a cutoff of hyomental distance ≤ 6 cm, it predicts difficult laryngoscopy with a sensitivity of 83% and a specificity of 88%. All parameters can act as a promising tool for predicting difficult laryngoscopy, with the single best parameter being Pre-E/E-VC. CONCLUSION: Assessment of the airway with POCUS may be helpful to the emergency physician when the clinical airway assessment parameters fail to predict difficult laryngoscopy as most patients requiring intubation are uncooperative. Assessment of the parameters in our study Pre-E/E-VC, tongue thickness, and hyomental distance can act as a promising tool for predicting difficult laryngoscopy in the emergency scenario.

Integrated multi-omic data analysis and validation with yeast model show oxidative phosphorylation modulates protein aggregation in amyotrophic lateral sclerosis.

Amyotrophic Lateral Sclerosis is a progressive, incurable amyloid aggregating neurodegenerative disease involving the motor neurons. Identifying potential biomarkers and therapeutic targets can assist in the better management of the disease. We used an integrative approach encompassing analysis of transcriptomic datasets of human and mice from the GEO database. Our analysis of ALS patient datasets showed deregulation in Non-alcoholic fatty acid liver disease and oxidative phosphorylation. Transgenic mice datasets of SOD1, FUS and TDP-43 showed deregulation in oxidative phosphorylation and ribosome-associated pathways. Commonality analysis between the human and mice datasets showed oxidative phosphorylation as a major deregulated pathway. Further, protein-protein and protein-drug interaction network analysis of mitochondrial electron transport chain showed enrichment of proteins and inhibitors of mitochondrial Complex III and IV. The results were further validated using the yeast model system. Inhibitor studies using metformin (Complex-I inhibitor) and malonate (Complex-II inhibitor) did not show any effect in mitigating the amyloids, while antimycin (Complex-III inhibitor) and azide (Complex-IV inhibitor) reduced amyloidogenesis. Knock-out of QCR8 (Complex-III) or COX8 (Complex-IV) cleared the amyloids. Taken together, our results show a critical role for mitochondrial oxidative phosphorylation in amyloidogenesis and as a potential therapeutic target in ALS.Communicated by Ramaswamy H. Sarma.

Regional Disparities of Cardiovascular Risk Factors and Major Cardiovascular Events in Non-electively Hospitalized Young Adults.

Background: Cardiovascular diseases contribute to considerable morbidity and mortality in the USA. We sought to establish regional disparities across the nation contributing to cardiovascular disease (CVD) among non-elective young adult hospitalizations. Methods: The National Inpatient Sample (2019) was utilized to identify the incidence of non-elective hospitalizations among young adults (18-44 yrs) and analyze the burden of CVD risk factors and outcomes (MACCE; all-cause mortality, AMI, cardiac arrest and stroke) in different US regions. Results: A total of 5,833,930 (median age 32 [26-37] years) non-elective admissions were recorded; plurality from the south (39.6%). Most admissions were white (51.4%) and female (65.5%) amid all regions. The burden of CVD risk factors was significantly higher in the South followed by the Mid-west regions. The South had the highest and the Northeast had the lowest rates of MACE (2.9% vs 2.3%) and stroke (1.0% vs 0.8%). The risk of AMI was high for the south and Midwest regions (1.1%). All-cause mortality was highest in South and West regions (0.7%). Multivariate adjusted odds for these cardiovascular events were higher in the West (aOR 1.22; 95%CI 1.12-1.33) followed by South (aOR 1.16; 95%CI 1.07-1.26) regions. Conclusions: This population-based study assessing non-elective admissions in the young revealed a higher burden of CVD risk factors and rate of MACCE in the South compared to other areas of the USA. Regional policies should be tailored to the local CVD risk burden.

Quality of life assessment in testicular non-seminomatous germ cell tumour survivors.

PURPOSE: Patients with Germ cell tumours (GCT) are at risk of long-term toxicities due to multimodality therapy. It is debatable whether there is an impact on the quality of life(QoL) of GCT survivors. METHODS: A case-control study was conducted at a tertiary care centre in India, using the EORTC QLQ C30 questionnaire, to compare the QoL between GCT survivors(disease free > 2 years) and healthy matched controls. A multivariate regression model was used to identify factors affecting QoL. RESULTS: A total of 55 cases and 100 controls were recruited. Cases had a median age of 32 years (interquartile range, IQR 28-40 years), ECOG PS of 0-1(75%), advanced stage III (58%), chemotherapy (94%) and 66% were > 5 years from diagnosis. The median age of controls: 35 years (IQR 28-43 years). A statistically significant difference was seen for emotional (85.8 ± 14.2 vs 91.7 ± 10.4, p 0.005), social(83.0 ± 22.0 vs 95.2 ± 9.6, p < 0.001) and global scales (80.4 ± 21.1 vs 91.3 ± 9.7, p < 0.001). Cases had more nausea and vomiting(3.3 ± 7.4 vs 1.0 ± 3.9, p 0.015), pain(13.9 ± 13.9 vs 4.8 ± 9.8, p < 0.001), dyspnea(7.9 + 14.3 vs 2.7 ± 9.1, p 0.007), and appetite loss(6.7 ± 14.9 vs 1.9 ± 7.9, p 0.016) and greater financial toxicity(31.5 ± 32.3 vs 9.0 ± 16.3, p < 0.001). Adjusting for age, performance status, BMI, stage, chemotherapy, RPLND, recurrent disease, and time since diagnosis, no predictive variables were significant. CONCLUSION: There is a detrimental impact of history of GCT in long term survivors of GCT.

Pragmatic Coarse-Graining of Proteins: Models and Applications.

The molecular details involved in the folding, dynamics, organization, and interaction of proteins with other molecules are often difficult to assess by experimental techniques. Consequently, computational models play an ever-increasing role in the field. However, biological processes involving large-scale protein assemblies or long time scale dynamics are still computationally expensive to study in atomistic detail. For these applications, employing coarse-grained (CG) modeling approaches has become a key strategy. In this Review, we provide an overview of what we call pragmatic CG protein models, which are strategies combining, at least in part, a physics-based implementation and a top-down experimental approach to their parametrization. In particular, we focus on CG models in which most protein residues are represented by at least two beads, allowing these models to retain some degree of chemical specificity. A description of the main modern pragmatic protein CG models is provided, including a review of the most recent applications and an outlook on future perspectives in the field.

Integrated Omic Analysis Delineates Pathways Modulating Toxic TDP-43 Protein Aggregates in Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a multi-systemic, incurable, amyloid disease affecting the motor neurons, resulting in the death of patients. The disease is either sporadic or familial with SOD1, C9orf72, FUS, and TDP-43 constituting the majority of familial ALS. Multi-omics studies on patients and model systems like mice and yeast have helped in understanding the association of various signaling and metabolic pathways with the disease. The yeast model system has played a pivotal role in elucidating the gene amyloid interactions. We carried out an integrated transcriptomic and metabolomic analysis of the TDP-43 expressing yeast model to elucidate deregulated pathways associated with the disease. The analysis shows the deregulation of the TCA cycle, single carbon metabolism, glutathione metabolism, and fatty acid metabolism. Transcriptomic analysis of GEO datasets of TDP-43 expressing motor neurons from mice models of ALS and ALS patients shows considerable overlap with experimental results. Furthermore, a yeast model was used to validate the obtained results using metabolite addition and gene knock-out experiments. Taken together, our result shows a potential role for the TCA cycle, cellular redox pathway, NAD metabolism, and fatty acid metabolism in disease. Supplementation of reduced glutathione, nicotinate, and the keto diet might help to manage the disease.

Recommendations for Diagnosis and Treatment of Odontoid Fractures in Geriatric Patients. / Empfehlungen zu Diagnostik und Behandlung von Frakturen des Dens axis bei geriatrischen Patienten.

BACKGROUND: Odontoid fractures in geriatric patients represent an entity of increasing incidence with a high rate of morbidity and mortality. The optimal diagnostic and therapeutic management is being controversially discussed in the literature. METHODS: In a consensus process and based on the current literature, the members of the working groups "Osteoporotic Fractures" and "Upper Cervical Spine" of the German Society for Orthopaedics and Trauma Surgery (DGOU) defined recommendations for the diagnostics and treatment of odontoid fractures in geriatric patients. RESULTS: For the diagnosis of odontoid fractures in symptomatic patients, computed tomography represents the gold standard, along with conventional radiographs. Magnetic resonance and dynamic imaging can be used as ancillary imaging modalities. With regard to fracture classification, the systems described by Anderson/D'Alonzo and by Eysel/Roosen have proved to be of value. A treatment algorithm was developed based on these classifications. Anderson/D'Alonzo type 1, type 3, and non-displaced type 2 fractures usually can be treated non-operatively. However, a close clinical and radiological follow-up is essential. In Anderson/D'Alonzo type 2 fractures, operative treatment is associated with better fracture healing. Displaced type 2 and type 3 fractures should be stabilized operatively. Type 2 fractures with suitable fracture patterns (Eysel/Roosen 2A/B) can be stabilized anteriorly. Posterior C I/II-stabilization procedures are well established and suitable for all fracture patterns.

Treatment of Fractures of the Thoracolumbar Spine: Recommendations of the Spine Section of the German Society for Orthopaedics and Trauma (DGOU).

STUDY DESIGN: consensus paper with systematic literature review. OBJECTIVE: The aim of this study was to establish recommendations for treatment of thoracolumbar spine fractures based on systematic review of current literature and consensus of several spine surgery experts. METHODS: The project was initiated in September 2008 and published in Germany in 2011. It was redone in 2017 based on systematic literature review, including new AOSpine classification. Members of the expert group were recruited from all over Germany working in hospitals of all levels of care. In total, the consensus process included 9 meetings and 20 hours of video conferences. RESULTS: As regards existing studies with highest level of evidence, a clear recommendation regarding treatment (operative vs conservative) or regarding type of surgery (posterior vs anterior vs combined anterior-posterior) cannot be given. Treatment has to be indicated individually based on clinical presentation, general condition of the patient, and radiological parameters. The following specific parameters have to be regarded and are proposed as morphological modifiers in addition to AOSpine classification: sagittal and coronal alignment of spine, degree of vertebral body destruction, stenosis of spinal canal, and intervertebral disc lesion. Meanwhile, the recommendations are used as standard algorithm in many German spine clinics and trauma centers. CONCLUSION: Clinical presentation and general condition of the patient are basic requirements for decision making. Additionally, treatment recommendations offer the physician a standardized, reproducible, and in Germany commonly accepted algorithm based on AOSpine classification and 4 morphological modifiers.

Contact patterns between helices and strands of sheet define protein folding patterns.

Comparing and classifying protein folding patterns allows organizing the known structures and enumerating possible protein structural patterns including those not yet observed. We capture the essence of protein folding patterns in a concise tableau representation based on the order and contact patterns of secondary structures: helices and strands of sheet. The tableaux are intelligible to both humans and computers. They provide a database, derived from the Protein Data Bank, mineable in studies of protein architecture. Using this database, we have: (i) determined statistical properties of secondary structure contacts in an unbiased set of protein domains from ASTRAL, (ii) observed that in 98% of cases, the tableau is a faithful representation of the folding pattern as classified in SCOP, (iii) demonstrated that to a large extent the local structure of proteins indicates their complete folding topology, and (iv) studied the use of the representation for fold identification.

Multivessel transradial percutaneous coronary angioplasty in a single coronary artery originating from the right sinus of Valsalva.

Percutaneous coronary intervention in patients with an anomalous coronary artery is technically challenging. Selective cannulation and coaxial positioning in the anomalous artery and optimum stability during the procedure are pivotal for successful completion of the procedure. Selection of the appropriate guide catheter is of paramount importance in these situations. In patients with congenital coronary artery anomalies, increasing use of multidetector computed tomography for cardiac imaging may yield diagnostic information not obtained with coronary angiography. Axial, multiplanar, and three-dimensional volume-rendered reconstructions aid in detecting and interpreting such anomalies and in selecting appropriate hardware during percutaneous coronary intervention in these patients. We report a case of successful stent implantation in the right coronary artery and proximal circumflex coronary artery in a patient with a single coronary artery arising from the right sinus of Valsalva.