The amyotrophic lateral sclerosis 8 protein VAPB is cleaved, secreted, and acts as a ligand for Eph receptors.

VAP proteins (human VAPB/ALS8, Drosophila VAP33, and C. elegans VPR-1) are homologous proteins with an amino-terminal major sperm protein (MSP) domain and a transmembrane domain. The MSP domain is named for its similarity to the C. elegans MSP protein, a sperm-derived hormone that binds to the Eph receptor and induces oocyte maturation. A point mutation (P56S) in the MSP domain of human VAPB is associated with Amyotrophic lateral sclerosis (ALS), but the mechanisms underlying the pathogenesis are poorly understood. Here we show that the MSP domains of VAP proteins are cleaved and secreted ligands for Eph receptors. The P58S mutation in VAP33 leads to a failure to secrete the MSP domain as well as ubiquitination, accumulation of inclusions in the endoplasmic reticulum, and an unfolded protein response. We propose that VAP MSP domains are secreted and act as diffusible hormones for Eph receptors. This work provides insight into mechanisms that may impact the pathogenesis of ALS.

Postmastectomy radiation therapy and immediate autologous breast reconstruction: integrating perspectives from surgical oncology, radiation oncology, and plastic and reconstructive surgery.

BACKGROUND AND OBJECTIVES: The effect of postmastectomy radiation therapy (PMRT) on immediately reconstructed abdominal wall-based tissue remains imprecisely defined. We evaluated evidence from all fields involved in care of the breast cancer patient in order to advance a unified recommendation regarding this therapeutic sequence. METHODS: We performed a MEDLINE and manual reference search to identify studies of PMRT with immediate autologous breast reconstruction. Inclusion criteria required studies to describe patients, flaps, and complication rates. Analyses were based on a random effects model. Surgical and radiation oncology literature was reviewed. RESULTS: Eleven retrospective studies of 337 patients with an average follow-up of 18-60 months (out of 268 patients) were selected for inclusion. Overall rates of fat necrosis, revisional surgery, volume loss, and fibrosis/contracture ranged from 16.9% to 35.4%. One out of 260 patients experienced total flap loss. There was an increased probability of fat necrosis in the irradiated breast (OR = 3.13, 95% CI = 1.42-6.89, P = 0.005) among three studies with non-irradiated controls. Five studies evaluated aesthetics with variable outcomes. CONCLUSIONS: There is mixed evidence for the utility of PMRT with immediate autologous abdominal wall breast reconstruction. Further investigation requires prospective studies with collaboration among surgical oncologists, radiation oncologists, and plastic surgeons.

Distinctive Clinico-electrographic and Radiological Profile of Childhood and Adolescent Seizures.

AIM: Electroencephalogram (EEG) is specific, but not sensitive, for the diagnosis of epilepsy. This study aimed to correlate the clinico-electrographic and radiological features of seizure disorders in children attending a tertiary care centre in northern India. METHODS: Children aged between one to 18 years with seizure episodes were included. Clinical details, including historical as well as physical findings, were evaluated along with EEG and neuroimaging (Magnetic resonance imaging). Details were noted on pre-designed proforma. Variables were analysed by using appropriate statistical methods. RESULTS: A total of 110 children with seizures were enrolled in the study. Male to female ratio was 1.6: 1, and the mean age of the study children was 8 years. The majority of the children were symptomatic for more than one year. The most common seizure type was Generalised Tonic Clonic Seizure (GTCS), and Hypoxic-ischemic Encephalopathy (HIE) sequelae was the most commonly attributed etiology, followed by neurocysticercosis. EEG and neuroimaging findings were found to correlate well with seizure semiology from history. The incidence of febrile seizures was 10% in this study, with nearly three-fourths of them being simple febrile seizures. CONCLUSION: Microcephaly and developmental delay were the most distinctive clinical correlates in children with seizures. There was a fair agreement between the types of seizures described in history and depicted on EEG with Cohen's kappa of 0.4. Also, there was a significant association between the type of seizures on EEG and the duration of symptoms.

Long Term Surgical and Radiological Outcome of Discoid Lateral Meniscus: An Updated Systematic Review.

Purpose of the study: This study aimed to reach a consensus for ideal surgical treatment of discoid lateral meniscus (DLM) and to evaluate its long term surgical and radiological outcome. Methods: All authors independently searched for peer reviewed publications with keywords like discoid lateral meniscus, tibial menisci abnormalities, tibial menisci surgery and clinical outcome and their representative Medical Subjects Headings (MeSH) in databases of PubMed, EBSCO, Cochrane Central Register of Controlled Trials, from inception to December 2022. Original articles in English language on discoid lateral meniscus reporting clinical, surgical, or radiological outcomes with five or more years of follow-up were included in this systematic review. Study details and outcome data were analysed according to the age, follow-up period, kind of surgery, DLM type, and alignment. Results: Our search strategy yielded 654 articles in PubMed, 222 articles in EBSCO and 5 articles in CENTRAL i.e. a total of 881 articles. After detailed assessment and screening, 12 articles were included in the final analysis, which included 444 DLM cases. The mean patient age at surgery ranged from 9.9 to 35.9 years, and the mean follow-up period ranged from 5.2 to 16 years. Partial meniscectomy and meniscoplasty are the recommended treatment because of the concerns of degenerative arthritis development after the total and subtotal meniscectomies. Two studies have documented better results with meniscal allograft transplantation. Conclusion: Satisfactory clinico-radiological outcome can be obtained after surgical treatment of discoid lateral meniscus with meniscus reshaping and repair of peripheral unstable part. Meniscal allograft transplantation (MAT) is gaining popularity in patients with total meniscectomy with satisfactory long term functional outcome.

Maternal and Child Health Training of Traditional Birth Attendants and Pregnancy Outcomes: A Systematic Review and Meta-analysis.

INTRODUCTION: In remote communities, maternal and child health is often compromised due to limited access to healthcare. Simultaneously, these communities historically rely greatly on traditional birth attendants (TBAs). However, optimal integration of these traditional methods with modern healthcare practices remains a topic of debate. We assessed the effect of maternal and child health training of traditional birth attendants on adverse pregnancy outcomes. METHODS: We conducted a systematic review and meta-analysis to answer the above research question. We independently screened studies using databases like PubMed, Scopus, and CENTRAL, extracted data, and assessed the study quality. Due to fewer original studies in this field, we considered both pre-post and between-group differences to assess the effect of differences. These were synthesised separately, assessed against a p-value function, and subjected to sensitivity analyses. RESULTS: We included six interventional studies. Training TBAs reduced the risk of perinatal mortality [0.69, 0.61-0.78] and 7-day neonatal mortality [0.65, 0.53-0.80] but not stillbirth [0.70, 0.39-1.26]. In randomized controlled trials, there is a lower risk of perinatal mortality [0.73, 0.67-0.79] and neonatal mortality [0.70, 0.62-0.80] but not stillbirth [0.81, 0.56-1.18] with trained traditional birth attendants. There are methodological concerns with most existing studies, including domains like allocation concealment. DISCUSSION: There is some evidence of the benefit of training TBAs, though of a low to very low certainty. Due to fewer studies, inconsistent estimates for different critical outcomes, and concerns with the existing studies, further well-designed studies can give more insights. They can also help optimize the contents of TBA training interventions. PROTOCOL: CRD42023412935 (PROSPERO).

Going the extra mile: Developing an interactive mobile application for maternal and infant care for tribal birth attendants.

Background: Mobile health applications are an established tool for healthcare management, patient education, and even capacity building for healthcare providers. However, its use among traditional birth attendants (TBAs) is limited. The aim of this study is to explore the needs and bottlenecks of developing an interactive mobile application for maternal and infant care (MAI) of TBAs. Materials and Methods: It is a qualitative study having in-depth interviews (face-to-face approach) conducted among the seekers of MAI services. Setting: This study is conducted in tribal and rural locations in the district Sirohi, Rajasthan. Participants: TBAs and tribal females of reproductive age in tribal-dominated areas have participated. The development of an interactive mobile application MAI has three phases: (1) a need-based approach to identify the needs on the ground; (2) identifying intervention bottlenecks and possible solutions; (3) design and development of the mobile application. Results: Ninety-six tribal females of reproductive age participated in the needs assessment. Eighty percent of them were ≤ 30 years of age and 40% of them were uneducated. Most participants informed that lack of information (culturally/locally appropriate content), peer advocacy, affordability, lack of transportation, and the influence of TBAs are the significant factors for less uptake of maternity and child health services in the tribal and rural areas. Conclusion: The MAI app has culturally/locally appropriate content and is prepared by the local TBAs and Accredited Social Health Activists, with full local character and clothing. MAI app has videos and audio in the local language (Marwari) with pictorial quizzes. Using the MAI app, TBAs may self-educate and guide tribal pregnant women about maternal hygiene and infant healthcare as needed at various stages of pregnancy and childbirth.

Malaria in newborn: A missed entity for primary care physician.

Neonatal malaria and congenital malaria, though thought to be a rare entity in non-endemic areas but incidences from epidemic countries are eye openers. It is still thought by primary care physicians that its existence among neonates is not common even in endemic areas due to a low index of suspicion. In order to attain the objective set out in the global technical strategy against malaria 2016-2030, it is important to have a gravity of this disease in all age groups, especially in children and neonates in which misconception of low burden of infection results in underestimation of its morbidity and mortality in these age groups. This disease is only the tip of the iceberg due to unidentified, underreported and neglected illness and being a pointer towards higher circulation among society and pregnant women. So this review article highlights pathophysiology, epidemiology, clinical features, complications, prognosis, treatment and prevention of malaria in newborns and intends to bring awareness among the caregivers to understand the need for attention towards this neglected disease of neonates so that they should be able to identify and manage the disease in this vulnerable age group.

Perinatal Exposure to Trace Elements: The Dubious Culprit of Autistic Spectrum Disorder in Children.

There is evidence that few trace elements in the environment work as hazardous materials in terms of their exposure in the perinatal period, causing autistic spectrum disorder (ASD) in children, and avoiding these exposures in the environment can reduce the number of new cases. This perspective study provides preliminary evidence to consider a few trace elements as culprits for ASD. More studies with larger cohorts are needed, but meanwhile, as per available evidence, exposure to these hazardous materials must be warranted during pregnancy and early stages of life.

Knowlesi Malaria in Children.

The fifth malaria parasite causing malaria- Plasmodium knowlesi (Pk), is not a novel emergent species but was an undiagnosed species before the availability of molecular methods as a tool from diagnostics and sometimes confused with morphologically similar human malaria parasite P. malariae or P. falciparum. Now it is well-distributed species in Southeast Asia, especially in Malaysia. Since 2004, cases of Pk malaria are continuously being reported in adults. Though adult age, forest-related activities and a recent visit to forested areas are well-known factors, childhood did not remain untouched by this disease. Few pieces of research and reports in the literature indicate that Infection in children is uncomplicated, but this may be attributed to the scarcity of data and research in this field. Pk malaria in pregnant females and infants are being well reported, so this indicates that the problem is not only restricted to known factors related to the disease, but we should think out of the box and take action before the disease takes the form of significant health burden on the human population as P. vivax and P. falciparum species did in the past. With the reports in literature of Pk malaria in pregnancy and early infancy, the possibility of congenital and neonatal malaria also cannot be denied. So more and more research is needed to understand Pk malaria in the pediatric population clearly. So this running review covers the problem status, demographic profile, clinical and haematological features, diagnosis, management and outcome of Pk malaria in paediatric group worldwide. This review also discusses the gaps in our present knowledge of the real problem status, prevention, control, diagnosis and management of Pk malaria, particularly in this age group.

The 2022 outbreak and the pathobiology of the coxsackie virus [hand foot and mouth disease] in India.

Outbreaks of HFMD in children aged <5 years have been reported worldwide and the major causative agents are Coxsackievirus (CV) A16, enterovirus (EV)-A71 and recently CVA6. In India, HFMD is a disease that is not commonly reported. The purpose of the study was to identify the enterovirus type(s) associated with large outbreak of Hand, foot, and mouth disease during COVID-19 pandemic in 2022. Four hundred and twenty five clinical samples from 196-suspected cases were collected from different parts of the country. This finding indicated the emergence of CVA6 in HFMD along with CVA16, soon after the gradual easing of non-pharmaceutical interventions during-pandemic COVID-19 and the relevance of continued surveillance of circulating enterovirus types in the post-COVID pandemic era.

An optimized dual-surgeon simultaneous orthotopic hind-limb allotransplantation model in rats.

Composite tissue allograft (CTA) transplantation is a promising treatment in reconstructive surgery for complex tissue injuries in humans. However, continued research is required to optimize the risk to benefit ratios. In this study, we describe, in detail, an optimized simultaneous dual-surgeon orthotopic hind-limb transplantation model in direct comparison to a single-surgeon model. In this study 75 hind-limb CTAs were performed, employing either a dual-surgeon model (n = 60) or a single-surgeon model (n = 15) for the transplantation of two hind-limbs. Operative times, complication rates, and costs were compared. The dual-surgeon approach showed a significant reduction of 45.4% in overall operative time (p < 0.05). Overall complication rate was 8%. The dual-surgeon model was ∼30.5% more cost-effective than the traditional single-surgeon approach. Benefits of the proposed simultaneous dual-surgeon orthotopic rat hind-limb CTA model include decreased operating times, decreased complication rates, and reduced financial costs when compared with the established single-surgeon model.

Urinary tract infection in children with Nephrotic syndrome: One of the hurdles for primary care physician and pediatrician towards timely diagnosis and optimum management of the disease.

Background: Urinary tract infection (UTI) is a common infection in children with nephrotic syndrome (NS). Clinical experience suggests that childhood nephrotic syndrome is frequently diagnosed incorrectly and managed inadequately on the top of this existing UTI in the episode becomes an additive obstacle for the primary care physicians or pediatricians towards optimum management, leading to poor outcome. So, we have conducted this clinico- microbiological study of UTI in NS in children to provide the exact picture of UTI with NS so that the primary care providers can be helped in having high index of suspicion of this infection and knowing prevalent organisms and their antimicrobial sensitivity pattern. Aim: The aim of the study was to study clinical features and identify the responsible organisms with its drug sensitivity pattern with response to treatment in various types and stages of NS with UTI in children. Methods: This cross-sectional hospital based study was conducted on 50 children of 2-18 years of age with NS attending nephrology clinic or admitted to the Paediatric ward of AIIMS, Rishikesh. Demographic, clinical, and microbiological data were recorded and details were entered in a predesigned proforma sheet. Results: Out of 50 cases, 8 (16%) had a positive urine culture. Six (75%) out of them had first episode and two (25%) were frequent relapsers of NS. Fever, decreased urine output, and generalized edema were the presenting features. The most common bacteria responsible for UTI was Pseudomonas aeruginosa (in around 25% isolates). Escherichia coli and Citrobacter koseri were the most resistant organisms. Patients were treated with antibiotics according to sensitivity pattern which resulted in resolution of symptoms and repeat urine culture became sterile subsequently. Conclusion: About one-sixth of children with Nephrotic Syndrome had UTI. UTI should be ruled out in every case of NS in active phase to prevent long-term morbidity and mortality.

Congenital Malaria in Newborns Delivered to Malaria-infected Mothers in the Hilly Region of Northern India: Is it Deadly?

BACKGROUND: Malaria is endemic in many states of India. Though there are reports of maternal and congenital malaria from endemic areas, however, there remains a paucity of data from hilly terrains. The present study evaluated the prevalence, clinical and microbiological spectrum of maternal and congenital malaria at a tertiary health care facility in Northern India over a period of 18 months. METHODS: In this observational study, mothers along with their newborns were evaluated for malaria by maternal, placental, and cord blood smear examination and rapid point-of-care diagnostic serological tests. Positive cases were confirmed by polymerase chain reaction. Mother-newborn duos were followed up till discharge from the hospital. RESULTS: A total of 843 mothers delivered during the study period and were screened along with their newborns and placentae. A total of Ten (1.18%) mothers had evidence of malarial parasitemia (Plasmodium vivax, n=7 and Pl. falciparum, n=3), however, none of the placental and cord blood samples were positive for malaria. Overall, 127 (15.1%) neonates required admission in neonatal intensive care unit for various morbidities. Incidence of small for gestational age (SGA) was high (n=210; 24.9%). Multivariate logistic regression analysis demonstrated maternal malaria to be an independent contributor for SGA [Odds Ratio (95% Confidence Interval), 10.7 (2.06 - 49.72)]. However, only 2% variance of SGA could be explained by maternal malaria alone. CONCLUSION: We report an encouragingly lower incidence of maternal malaria in mothers attending for delivery and a 'Zero' incidence for placental and congenital malaria during the study period as compared to national data (upto 7.4% in non-immune mothers), although maternal malaria could be a causative factor for SGA.

Congenital malaria due to chloroquine-resistant Plasmodium vivax: a case report.

The clinical manifestation of malaria in neonates and young infants is non-specific and differs from that of adults and older children. So a high index of suspicion is needed to diagnose malaria in early infancy. Chloroquine is the first-line treatment for Plasmodium vivax malaria in most parts of the world. This case report details a case of chloroquine-resistant malaria due to P. vivax by transplacental transmission from mother with mixed infection of P. falciparum and P. vivax in a 26-day-old young infant who presented with moderate grade fever and reviews the literature of malaria in infantile and neonatal age groups. And we concluded that high suspicion of malaria is needed to diagnose congenital malaria. Primigravida women with placental malaria pose high risk for congenital infection in baby and emerging chloroquine-resistant P. vivax in congenital malaria.

Otologic and Audiology Concerns of Microtia Repair.

Microtia is a congenital auricular deformity that commonly presents with associated congenital aural atresia. The most acute concern in these patients is concomitant hearing loss at birth. A team-based approach by plastic surgeons and otologists is necessary to address both the otologic and audiologic concerns of microtia and atresia. Hearing rehabilitation is imperative; yet it should not compromise the aesthetic components of reconstruction and vice versa. Here, the authors propose a framework to evaluate and manage patients with microtia and atresia with the goal of optimizing functional and cosmetic outcomes.

Noninvasive Facial Rejuvenation. Part 2: Physician-Directed-Neuromodulators and Fillers.

A proper knowledge of noninvasive facial rejuvenation is integral to the practice of a cosmetic surgeon. Noninvasive facial rejuvenation can be divided into patient- versus physician-directed modalities. Patient-directed facial rejuvenation combines the use of facial products such as sunscreen, moisturizers, retinoids, α-hydroxy acids, and various antioxidants to both maintain youthful skin as well as rejuvenate damaged skin. Physicians may recommend and often prescribe certain products, but patients are in control with this type of facial rejuvenation. On the other hand, physician-directed facial rejuvenation entails modalities that require direct physician involvement, such as neuromodulators, filler injections, laser resurfacing, microdermabrasion, and chemical peels. With the successful integration of each of these modalities, a complete facial regimen can be established and patient satisfaction can be maximized. This article is the second in a three-part series describing noninvasive facial rejuvenation. Here the authors discuss neuromodulators and fillers in detail, focusing on indications for use, techniques, and common side effects.

Clinico-Hematological Features and Management Outcome in Neonatal Malaria: A Nine Years Analysis from North India.

BACKGROUND: Malaria is an important cause of death and illness in children worldwide. Most cases of neonatal malaria are misdiagnosed because of lack of specific symptoms and general lack of awareness. Nothing much is known in literature about the hematological changes during malaria infection and outcome of disease in neonates. Neonatal malaria is an underdiagnosed entity. So this hospital based observational study aims to assess diagnostic features of neonatal malaria. METHODS: From August 2004 to August 2013, information of all slide positive for malaria cases aged 0 to 28 days admitted to our pediatric hospital was collected and analysed. RESULTS: 28 slide positive cases of neonatal malaria were studied, four out of them were congenital malaria. Fever (93%) was the most common symptom followed by pallor (72%) and diarrhoea (50%). We also found respiratory distress in four (14%) cases. Apart from anemia and atypical lymphocytosis, We also found thrombocytopenia and low hematocrit, MCV and RBC count. Two cases with bleeding manifestations expired during course of treatment. DISCUSSION: Malaria in the first few months of life can simulate transplacentally or postnatally acquired infection such as TORCH, syphilis, neonatal hepatitis and septicemia all having an important symptom complex of fever jaundice, hepatosplenomegaly and anemia. Although in our cases clinical presentation has been similar to septicemia but culture of blood, CSF and urine were sterile. The dilemma of distinguishing neonatal malaria alone versus neonatal sepsis or both existing does not seem to be easily resolved by the use of clinical features alone. The laboratory diagnosis of parasitemia in neonates require special attention in Giemsa staining as well as the technical skill involved in malaria microscopy because parasite densities are low. So high degree of suspicion is needed to diagnose malaria in newborns presenting with fever and anemia.

Improving Antimicrobial Regimens for the Treatment of Breast Tissue Expander-Related Infections.

BACKGROUND: Infectious complications in tissue expander (TE) breast reconstruction can be devastating and costly. Therefore, to optimize care, we examined patient's demographics, microbiology of TE infections, and the efficacy of empiric antimicrobial regimens and thereafter generated an algorithm for the treatment of these complex infections. METHODS: We retrospectively reviewed all patients who underwent TE breast reconstruction between 2003 and 2012 and analyzed those patients who developed a "definite" device-related infection leading to TE explantation and had a positive intraoperative culture. RESULTS: A total of 3,082 patients underwent immediate breast reconstruction with TE. Of these, 378 patients (12.3%) developed an infection, 189 (6.1%) eventually proceed with explantation, and 118 (3.8%) had a positive intraoperative culture. Gram-positive organisms caused 73% of infections, and Gram-negative organisms caused 27% of infections. Narrow-spectrum empiric antimicrobials with predominantly Gram-positive coverage were deemed appropriate in only 62% of cases, and those with Gram-negative coverage were appropriate in 46%. Broad-spectrum antimicrobials were used in 47% of cases, mainly recommended by infectious disease specialists, and were considered appropriate in >90% of the occasions. CONCLUSIONS: Current empiric antibiotic regimens do not cover the vast spectrum of organisms causing TE infections. To increase the salvage rate of an infected TE, at the first sign of infection, in addition to benefiting with an infectious diseases consultation, empiric coverage with broad-spectrum antibiotics active against biofilm-embedded organisms should be administered.

Treatment of Infected Facial Implants.

Alloplastic facial implants have a wide range of uses to achieve the appropriate facial contour. A variety of materials such as metals, polymers, ceramics and synthetic injectable fillers are available to the reconstructive and aesthetic surgeon. Besides choosing the right surgical technique and the adequate material, the surgeon must be prepared to treat complications. Infection is an uncommon but serious complication that can cause displeasing consequences for the patient. There are few references in literature regarding treatment and management of facial implant-related infections. This study aims to discuss the role of biofilm in predisposing alloplastic materials to infection, to provide a review of literature, to describe our own institutional experience, and to define a patient care pathway for facial implant-associated infection.

Plant thorn synovitis of elbow in children.

Four rare cases of plant thorn synovitis of left elbow were admitted at our institution, which were initially misdiagnosed as partially treated septic arthritis of elbow or Juvenile inflammatory arthritis. All of them were of paediatric age group. Symptoms included pain, swelling, and decreased range of motion of affected joint. On examination synovitis was present in all patients. Roentgenograms & Ultrasonography were inconclusive in all patients, Definitive diagnosis was made only after arthrotomy, Thorn fragments (Acacia arabica) were recovered from the hypertrophied synovium & subtotal synovectomy was done and sent for histopathological examination. All patients improved after surgery with mean residual flexion deformity of 12.5 ± 2.86°. Plant thorn induced synovitis of elbow is rare, it must be included in the differential diagnosis of monoarthritis of elbow and a high index of suspicion is needed for retained thorn fragments in elbow joint causing synovitis. Its optimal treatment is arthrotomy, foreign body removal and total/subtotal synovectomy.