A negative feedback loop underlies the Warburg effect.

Aerobic glycolysis, or the Warburg effect, is used by cancer cells for proliferation while producing lactate. Although lactate production has wide implications for cancer progression, it is not known how this effect increases cell proliferation and relates to oxidative phosphorylation. Here, we elucidate that a negative feedback loop (NFL) is responsible for the Warburg effect. Further, we show that aerobic glycolysis works as an amplifier of oxidative phosphorylation. On the other hand, quiescence is an important property of cancer stem cells. Based on the NFL, we show that both aerobic glycolysis and oxidative phosphorylation, playing a synergistic role, are required to achieve cell quiescence. Further, our results suggest that the cells in their hypoxic niche are highly proliferative yet close to attaining quiescence by increasing their NADH/NAD+ ratio through the severity of hypoxia. The findings of this study can help in a better understanding of the link among metabolism, cell cycle, carcinogenesis, and stemness.

An Analysis of the Anomalous Fissure of the Ligamentum Teres Hepatis: A Morphological Perspective in the North Indian Population.

Background The liver, being the largest internal organ of the body shows a variety of gross morphological variations about lobes, fissures and processes which may be clinically significant. Among various anatomical variations, the most found is the variant fissure for ligamentum teres hepatis. The present study was done to classify, review, compare and discuss the literature for anomalies in fissures for ligamentum teres hepatis. Methods A total of 100 formalin-preserved human livers were obtained from the Department of Anatomy of King George's Medical University, Lucknow, and studied for one year. Result In our study, 15% of the liver showed morphological variations in fissures for ligamentum teres hepatis. These were classified into four types. In type I (2%), the fissure was converted into a tunnel by pons hepatis. In type II (3%), there was an incomplete fissure for ligamentum teres hepatis extending into the diaphragmatic surface. In type III (4%), there was an incomplete fissure for ligamentum teres hepatis present only on the visceral surface. In type IV (6%), the fissure was covered by a thin membrane. Conclusion In this study of the North Indian population, 15% of liver have gross morphological variations. So thorough anatomical knowledge of the existence of variant or abnormal surface features on the liver is imperative to understanding the underlying pathology for radiologists and surgeons so that a favorable outcome can be achieved.

Chickpea: Its Origin, Distribution, Nutrition, Benefits, Breeding, and Symbiotic Relationship with Mesorhizobium Species.

Chickpea (Cicer arietinum L.), encompassing the desi and kabuli varieties, is a beloved pulse crop globally. Its cultivation spans over fifty countries, from the Indian subcontinent and southern Europe to the Middle East, North Africa, the Americas, Australia, and China. With a rich composition of carbohydrates and protein, constituting 80% of its dry seed mass, chickpea is also touted for its numerous health benefits, earning it the title of a 'functional food'. In the past two decades, research has extensively explored the rhizobial diversity associated with chickpea and its breeding in various countries across Europe, Asia, and Oceania, aiming to understand its impact on the sustainable yield and quality of chickpea crops. To date, four notable species of Mesorhizobium-M. ciceri, M. mediterraneum, M. muleiense, and M. wenxiniae-have been reported, originally isolated from chickpea root nodules. Other species, such as M. amorphae, M. loti, M. tianshanense, M. oportunistum, M. abyssinicae, and M. shonense, have been identified as potential symbionts of chickpea, possibly acquiring symbiotic genes through lateral gene transfer. While M. ciceri and M. mediterraneum are widely distributed and studied across chickpea-growing regions, they remain absent in China, where M. muleiense and M. wenxiniae are the sole rhizobial species associated with chickpea. The geographic distribution of chickpea rhizobia is believed to be influenced by factors such as genetic characteristics, competitiveness, evolutionary adaptation to local soil conditions, and compatibility with native soil microbes. Inoculating chickpea with suitable rhizobial strains is crucial when introducing the crop to new regions lacking indigenous chickpea rhizobia. The introduction of a novel chickpea variety, coupled with the effective use of rhizobia for inoculation, offers the potential not only to boost the yield and seed quality of chickpeas, but also to enhance crop productivity within rotation and intercropped systems involving chickpea and other crops. Consequently, this advancement holds the promise to drive forward the cause of sustainable agriculture on a global scale.

Carpal tunnel syndrome secondary to a giant lipoma of the wrist and distal forearm.

In up to 2% of the population, benign tumours called lipomas can develop. When they are more than 5 cm, they are considered giant lipomas. Giant lipomas of the distal forearm and hand may cause compression to the underlying tissues, nerves and muscles, even though they are typically asymptomatic. An older woman with soft tissue swelling in her right wrist and forearm, and numbness and pain in her right hand presented to the general surgery outpatient clinic. Her numb fingers indicated that the median nerve was compressed, and an MRI scan of her wrist and forearm revealed median nerve compression due to a giant lipoma with a dimension of about 9.2×3.4×4 cm. A surgical excision was done with an intraoperative nerve stimulator, and the specimen sent for histopathology confirmed the diagnosis of lipoma. Pain, numbness and motor power improved within 1 week postoperatively, and the patient was discharged.

Unilateral Enlarged Right Accessory Axillary Breast Tissue in a Male: A Case Report.

Accessory breast tissue, associated with polymastia and polythelia, presents challenges and concerns, particularly when patients fear malignancy. While occurring in 1-6% of cases, accessory breasts, often located bilaterally in the axillae, necessitate careful examination. We report a 35-year-old male with painful axillary swelling who underwent high-resolution ultrasonography (HR-USG) and fine-needle aspiration cytology (FNAC), revealing proper axillary breast tissue. Subsequent excision biopsy confirmed accessory axillary breast without malignancy. In conclusion, surgical removal of accessory axillary breasts is advisable, addressing cosmetic concerns and minimizing cancer risks.

Evaluation of Pertussis Disease in Young Infants in India: A Hospital-Based Multicentric Observational Study.

OBJECTIVES: To evaluate the incidence of laboratory-confirmed pertussis (LCP) among infants hospitalized with acute respiratory infections (ARIs) and meeting the Centers for Disease Control and Prevention (CDC)-recommended clinical case definition. METHODS: An investigator-initiated active surveillance for clinically suspected cases (CSCs) of pertussis screened infants aged ≤6 mo hospitalized with ARIs during January 2020-April 2022 at seven centers across India. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect Bordetella pertussis in nasopharyngeal swabs. Infants were classified as having 'LCP' or 'probable pertussis' (PP). RESULTS: Among 1102 screened infants, 400 participants met the CDC-2020 clinical case definition for pertussis. Of these, 34/400 (8.5%) had LCP and 46/400 (11.5%) had PP. The proportion of participants with LCP and PP was similar among infants aged 0-3 and 4-6 mo [LCP: 0-3 mo, 21/248 (~9%); 4-6 mo, 13/152 (~9%); PP: 0-3 mo, 30/248 (~12%); 4-6 mo, 16/152 (~11%)]. Cough illness lasted ≥2 wk in 3/34 (~9%) and 34/46 (~74%) participants with LCP and PP, respectively. Notably, 80% CSCs had neither LCP nor PP, and a respiratory pathogen apart from B. pertussis was detected in ~32%. Ventilation was required in 12 participants with LCP/PP. CONCLUSIONS: In this first study from India based on revised CDC guidelines, the incidence of LCP was 8.5%; cough illness was not a predominant feature. Infants below the age appropriate for vaccination are prone to pertussis-related hospital admissions, ICU care, and ventilation. Maternal immunization may be evaluated for neonatal protection, in addition to other strategies, to decrease disease burden in this highly vulnerable group. CLINICAL TRIAL REGISTRATION NUMBER: CTRI/2019/12/022449.

Isolated adult ileocecal intussusception in sigmoid colon due to non-specific inflammation.

Adult ileocecal intussusception due to non-specific inflammation is a rare condition. Intussusception is the intestinal segment telescoping into the adjacent intestinal lumen. Typically, a pathological lesion is discovered with a high percentage of malignancy. Intussusception of the most common ileocolic kind includes the appendix, but it is uncommon for an appendix to serve as the lead point. The patient was admitted to the emergency department with a complaint of acute intestinal obstruction. After getting a diagnostic workup, an exploratory laparotomy was done, and the ileocecal and ascending colon segment was intussuscepted directly into the sigmoid colon. Transverse and descending colon were normal, and resection of necrosed intussuscepted bowel, primary repair of sigmoid colon with ileostomy with transverse colon as distal mucus fistula done, after the 3-month restoration of bowel continuity done, patient discharged and doing well. After the diagnosis of intussusception, the best surgical choice is in the hands of an experienced surgeon.

Antibody Persistence Following Administration of a Hexavalent DTwP-IPV-HB-PRP~T Vaccine Versus Separate DTwP-HB-PRP~T and IPV Vaccines and Safety and Immunogenicity of a Booster Dose of DTwP-IPV-HB-PRP~T Administered With an MMR Vaccine in Healthy Infants in India.

BACKGROUND: Antibody persistence of a whole-cell pertussis-containing hexavalent vaccine (DTwP-IPV-HB-PRP~T) and its co- or sequential administration with measles, mumps, rubella (MMR) vaccine were evaluated. METHODS: Phase III, open-label, randomized, multicenter study in India. Healthy toddlers 12-24 months of age who had received DTwP-IPV-HB-PRP~T or separate DTwP-HB-PRP~T+IPV primary vaccination at 6-8, 10-12 and 14-16 weeks of age received a DTwP-IPV-HB-PRP~T booster concomitantly with MMR (N = 336) or 28 days before MMR (N = 340). Participants had received a first dose of measles vaccine. Immunogenicity assessment used validated assays and safety was by parental reports. All analyses were descriptive. RESULTS: All participants had prebooster anti-T ≥0.01 IU/mL and anti-polio 1 and 3 ≥8 1/dil, and ≥96.5% had anti-D ≥0.01 IU/mL, anti-HBs ≥10 mIU/mL, anti-polio 2 ≥8 1/dil and anti-PRP ≥0.15 µg/mL; for pertussis, antibody persistence was similar in each group. Postbooster immunogenicity for DTwP-IPV-HB-PRP~T was similar for each antigen in each group: ≥99.5% of participants had anti-D ≥0.01 IU/mL, anti-T ≥0.01 IU/mL, anti-polio 1, 2 and 3 >8 1/dil, anti-HBs ≥10 mIU/mL and anti-PRP ≥1 µg/mL; for pertussis, vaccine response was similar in each group [72.0%-75.9% (anti-PT), 80.8%-81.4% (anti-FIM), 77.6%-79.5% (anti-PRN), 78.2%-80.8% (anti-FHA)]. There was no difference in MMR immunogenicity between groups, and no difference in DTwP-IPV-HB-PRP~T booster immunogenicity based on the primary series. There were no safety concerns. CONCLUSIONS: DTwP-IPV-HB-PRP~T antibody persistence was similar to licensed comparators. Booster immunogenicity was robust after DTwP-IPV-HB-PRP~T with or without MMR, and MMR immunogenicity was not affected by coadministration with DTwP-IPV-HB-PRP~T. CLINICAL TRIALS REGISTRY INDIA NUMBER: CTRI/2020/04/024843.

Biomedical,clinical and environmental applications of platinum-based nanohybrids: An updated review.

Platinum nanoparticles (Pt NPs) have numerous applications in various sectors, including pharmacology, nanomedicine, cancer therapy, radiotherapy, biotechnology and environment mitigation like removal of toxic metals from wastewater, photocatalytic degradation of toxic compounds, adsorption, and water splitting. The multifaceted applications of Pt NPs because of their ultra-fine structures, large surface area, tuned porosity, coordination-binding, and excellent physiochemical properties. The various types of nanohybrids (NHs) of Pt NPs can be fabricated by doping with different metal/metal oxide/polymer-based materials. There are several methods to synthesize platinum-based NHs, but biological processes are admirable because of green, economical, sustainable, and non-toxic. Due to the robust physicochemical and biological characteristics of platinum NPs, they are widely employed as nanocatalyst, antioxidant, antipathogenic, and anticancer agents. Indeed, Pt-based NHs are the subject of keen interest and substantial research area for biomedical and clinical applications. Hence, this review systematically studies antimicrobial, biological, and environmental applications of platinum and platinum-based NHs, predominantly for treating cancer and photo-thermal therapy. Applications of Pt NPs in nanomedicine and nano-diagnosis are also highlighted. Pt NPs-related nanotoxicity and the potential and opportunity for future nano-therapeutics based on Pt NPs are also discussed.

Severity and mortality associated with COVID-19 among children hospitalised in tertiary care centres in India: a cohort study.

Background: It is critical to identify high-risk groups among children with COVID-19 from low-income and middle-income countries (LMICs) to facilitate the optimum use of health system resources. The study aims to describe the severity and mortality of different clinical phenotypes of COVID-19 in a large cohort of children admitted to tertiary care hospitals in India. Methods: Children aged 0-19 years with evidence of SARS-CoV-2 infection (real time polymerase chain reaction or rapid antigen test positive) or exposure (anti-SARS-CoV-2 antibody, or history of contact with SARS-CoV-2) were enrolled in the study, between January 2021 and March 2022 across five tertiary hospitals in India. All study participants enrolled prospectively and retrospectively were followed up for three months after discharge. COVID-19 was classified into severe (Multisystem Inflammatory Syndrome in Children (MIS-C), severe acute COVID-19, 'unclassified') or non-severe disease. The mortality rates were estimated in different phenotypes. Findings: Among 2468 eligible children enrolled, 2148 were hospitalised. Signs of illness were present in 1688 (79%) children with 1090 (65%) having severe disease. High mortality was reported in MIS-C (18.6%), severe acute COVID-19 (13.3%) and the unclassified severe COVID-19 disease (12.3%). Mortality remained high (17.5%) when modified MIS-C criteria was used. Non-severe COVID-19 disease had 14.1% mortality when associated with comorbidity. Interpretation: Our findings have important public health implications for low resource settings. The high mortality underscores the need for better preparedness for timely diagnosis and management of COVID-19. Children with associated comorbidity or coinfections are a vulnerable group and need special attention. MIS-C requires context specific diagnostic criteria for low resource settings. It is important to evaluate the clinical, epidemiological and health system-related risk factors associated with severe COVID-19 and mortality in children from LMICs. Funding: Department of Biotechnology, Govt of India and Department of Maternal, Child and Adolescent Health and Aging, WHO, Geneva, Switzerland.

Morphological and molecular characterization of Lasiodiplodia theobromae associated with leaf spot and blight disease of Coscinium fenestratum (Gaertn.) Colebr.-a new host record from India.

Coscinium fenestratum is a medicinally significant critically endangered plant found in Western Ghats of India. The leaf spot and blight was observed in Kerala during 2021 with disease incidence of 40% in 20 assessed plants in 0.6 hectare. The associated fungus was isolated on potato dextrose agar medium. A total of six morpho-culturally identical isolates were isolated and morphologically identified. Based on morpho-cultural features, the fungus was identified at genus level as Lasiodiplodia sp., which was further authentically confirmed as Lasiodiplodia theobromae by molecular identification with a representative isolate (KFRIMCC 089) using multigene (ITS, LSU, SSU, TEF1-α, and TUB2) sequence analysis and concatenated phylogenetic analysis (ITS-TEF1-α-TUB2). Pathogenicity tests were also assessed in vitro and in vivo using mycelial disc and spore suspension of L. theobromae, and the isolated fungus's pathogenic behaviour was confirmed after re-isolation and morpho-cultural features. Literature survey reveals that there are no reports of L. theobromae on C. fenestratum from all over the world. Hence, C. fenestratum is being firstly reported as a new host record for L. theobromae from India.

CtBP: A global regulator of balancing acts and homeostases.

The classical role of C-terminal binding protein (CtBP) is that of a global corepressor. However, its exact mechanism of repression is not known. In this review, we elucidate the repression motif used by CtBP. Further, we provide other unifying features of its mechanism of action. For example, in the presence of a high NADH/NAD+ ratio in the cell, causing a low glycolytic condition, the NADH-bound dimeric form of CtBP causes global repression, maintaining balances and homeostases of many cellular processes, under the cell surveillance of p53 and NFkB. In contrast, in the presence of a low NADH/NAD+ ratio, causing a high glycolytic condition, the NADH-free monomeric form of CtBP blocks p53 function and NFkB-mediated transcription. Further, a low NADH/NAD+ ratio upsets the homeostases and balances in the absence of the cell surveillances of p53 and NFkB, causing global instability, the dominant outcome of CtBP's action in carcinogenesis, in cells in a high glycolytic state.

Severe Acute Hepatitis: An Emerging Grave Illness in Children.

Acute hepatitis of unknown origin in children has been recently described in the literature, and a case definition has also been proposed for this condition. The exact etiology is unknown and exclusion of infectious, metabolic, autoimmune and toxin mediated injuries is essential. Management for this condition is supportive, but some may require liver transplantation. Infection prevention and control practices are important as the etiology remains unidentified.

Nucleic Acid Nanotechnology: Trends, Opportunities and Challenges.

Nucleic acids (DNA and RNA) hold great potential for the advancement of future medicine but suffer from unsatisfactory clinical success due to the challenges accompanied with their delivery. Nucleic acid-mediated nanomaterials have riveted the researchers from the past two decades and exhilarating tasks have prevailed. Nucleic acid nanotechnology offers unique control over the shape, size, time, mechanics and anisotropy. It can transfect numerous types of tissues and cells without any toxic effect, minimize the induced immune response, and penetrate most of the biological barriers and hence it reveals itself as a versatile tool for multidisciplinary research field and for various therapeutic purposes. Nucleic acid combines with other nanoscale objects also by altering the chemical functional groups and reproducing the varied array of nanomaterials. Interestingly, nucleic acidderived nanomaterials are characterized easily at atomic level accuracy. However, this advent of nanoscience has vital issues which must be addressed, such as the high cost of nucleic acids, their self-assembly nature, etc. Hence, the aim of this review is to highlight the systematic advances and methodology of nucleic acid-mediated synthesis of nanomaterials and their therapeutic applications.

Loss of Epidermal Homeostasis Underlies the Development of Squamous Cell Carcinoma.

Squamous cell carcinoma (SCC) is one of the most common skin cancers. To develop targeted therapies for SCC, a comprehensive understanding of the disease through a systems approach is required. Here, we have collated and analyzed the literature on SCC and pathways that maintain skin homeostasis. Since, the loss of the Notch and the overactivation of the Wnt pathways in the epidermis cause SCC, we focused on these two pathways. We found that the two pathways are critical in maintaining epidermal homeostasis. Further, we found that the cancer stem cell (CSC) marker CD44 causes the transcription of SOX2, another CSC marker of SCC, activates the Wnt pathway, and blocks the Notch pathway. Similarly, the Wnt pathway causes the transcription of CD44 and SOX2 and blocks the Notch pathway. In this paper, we have discussed how the notch and the Wnt pathways affect epidermal homeostasis and the three CSCs (CD44, SOX2, and LGR6) affect the two pathways, linking the CSCs with epidermal homeostasis.

Giant Plexiform Schwannoma on the Medial Aspect of the Left Thigh.

Plexiform schwannoma (PS), or neurilemmoma, is an uncommon benign tumor originating from a peripheral nerve sheath. It consists of Schwann cells organized in an intricate, web-like pattern. A male farmer in his 50s from rural India sought medical attention for a painless mass on his left thigh, present for 30 years. Physical examination revealed a firm, non-tender mass with restricted mobility. Imaging, including X-ray and ultrasound, indicated a neoplastic lesion. Fine needle aspiration (FNA) cytology revealed spindle-shaped cells, prompting a provisional diagnosis of a spindle cell lesion. Surgical excision was performed successfully, with histopathological examination confirming PS. He experienced no postoperative complications, and at the one-year follow-up, the complete resolution of symptoms and normal daily activities were observed.

Homeostases of epidermis and hair follicle, and development of basal cell carcinoma.

Hedgehog signaling (Hh) plays a critical role in embryogenesis. On the other hand, its overactivity may cause basal cell carcinoma (BCC), the most common human cancer. Further, epidermal and hair follicle homeostases may have a key role in the development of BCC. This article describes the importance of different signaling pathways in the different stages of the two processes. The description of the homeostases brought up the importance of the Notch signaling along with the sonic hedgehog (Shh) and the Wnt pathways. Loss of the Notch signaling adversely affects the late stages of hair follicle formation and allows the bulge cells in the hair follicles to take the fate of the keratinocytes in the interfollicular epidermis. Further, the loss of Notch activity upregulates the Shh and Wnt activities, adversely affecting the homeostases. Notably, the Notch signaling is suppressed in BCC, and the peripheral BCC cells, which have low Notch activity, show drug resistance in comparison to the interior suprabasal BCC cells, which have high Notch activity.

Efficacy and safety of Bacillus clausii (O/C, N/R, SIN, T) probiotic combined with oral rehydration therapy (ORT) and zinc in acute diarrhea in children: a randomized, double-blind, placebo-controlled study in India.

BACKGROUND: Childhood diarrhea remains a major disease burden, particularly in developing countries, and is a leading cause of death in children aged < 5 years, worldwide. Treatment of acute diarrhea now includes probiotics to potentially reduce the duration and severity of the illness. This phase 3, randomized, placebo-controlled, double-blind study assessed the efficacy and safety of four strains (O/C, N/R, SIN, T) of Bacillus clausii probiotic (Enterogermina®) plus oral rehydration therapy (ORT) and zinc, versus placebo plus ORT and zinc, in infants and children in India with acute moderate diarrhea. METHODS: Patients aged 6 months to 5 years with acute moderate diarrhea (WHO 2005 definition) of < 48 h' duration were randomly assigned to receive one mini bottle of either polyantibiotic-resistant B. clausii (oral suspension of 2 billion spores per 5 mL bottle) or matching placebo twice daily (morning and evening) for 5 days. Exclusion criteria included known hypersensitivity to B. clausii or excipients in the study treatment, or to other probiotics. Patients were admitted to hospital from Day 1 and discharged ≥6 h after diarrhea resolution, or a maximum of 5 days. The primary endpoint was duration of acute diarrhea from randomization to recovery. Secondary endpoints included frequency of stools, diapers with stools, or dehydration status. RESULTS: In total, 457 patients were randomized; 454 were treated. Similar proportions of patients showed recovery from diarrhea over the 120 h after randomization (97.0% in the B. clausii group [n = 227]; 98.0% on placebo [n = 227]). Median time to recovery was also similar: 42.83 (95% CI: 40.90-44.90) hours for B. clausii and 42.13 (95% CI: 39.80-43.87) hours for placebo. However, no statistically significant difference was observed between groups (hazard ratio = 0.93 [95% CI: 0.77-1.13]; p = 0.6968); nor were there statistically significant differences between groups for the secondary endpoints. Treatment with B. clausii was well tolerated with incidence of adverse events (9.7%) similar to that for placebo (12.3%). CONCLUSIONS: No significant difference in efficacy between B. clausii and placebo was demonstrated. Sample size may have been inadequate to allow detection of a between-group difference in efficacy, given the mild/moderate severity (only ~ 20% of patients had nausea/vomiting or abdominal pains) and short duration of disease among subjects, the relatively late start of treatment (most were already on Day 2 of their disease episode when study treatment started) and the effectiveness of the standard of care with ORT and zinc in both treatment groups. TRIAL REGISTRATION: CTRI number CTRI/2018/10/016053 . Registered on 17 October 2018. EudraCT number 2016-005165-31 . Registered 14 May 2020 (retrospectively registered).

Switching a conflicted bacterial DTD-tRNA code is essential for the emergence of mitochondria.

Mitochondria emerged through an endosymbiotic event involving a proteobacterium and an archaeal host. However, the process of optimization of cellular processes required for the successful evolution and survival of mitochondria, which integrates components from two evolutionarily distinct ancestors as well as novel eukaryotic elements, is not well understood. We identify two key switches in the translational machinery­one in the discriminator recognition code of a chiral proofreader DTD [d-aminoacyl­transfer RNA (tRNA) deacylase] and the other in mitochondrial tRNAGly­that enable the compatibility between disparate elements essential for survival. Notably, the mito-tRNAGly discriminator element is the only one to switch from pyrimidine to purine during the bacteria-to-mitochondria transition. We capture this code transition in the Jakobida, an early diverging eukaryotic clade bearing the most bacterial-like mito-genome, wherein both discriminator elements are present. This study underscores the need to explore the fundamental integration strategies critical for mitochondrial and eukaryotic evolution.