Bisphenol A contamination in aquatic environments: a review of sources, environmental concerns, and microbial remediation.

The production of polycarbonate, a high-performance transparent plastic, employs bisphenol A, which is a prominent endocrine-disrupting compound. Polycarbonates are frequently used in the manufacturing of food, bottles, storage containers for newborns, and beverage packaging materials. Global production of BPA in 2022 was estimated to be in the region of 10 million tonnes. About 65-70% of all bisphenol A is used to make polycarbonate plastics. Bisphenol A leaches from improperly disposed plastic items and enters the environment through wastewater from plastic-producing industries, contaminating, sediments, surface water, and ground water. The concentration BPA in industrial and domestic wastewater ranges from 16 to 1465 ng/L while in surface water it has been detected 170-3113 ng/L. Wastewater treatment can be highly effective at removing BPA, giving reductions of 91-98%. Regardless, the remaining 2-9% of BPA will continue through to the environment, with low levels of BPA commonly observed in surface water and sediment in the USA and Europe. The health effects of BPA have been the subject of prolonged public and scientific debate, with PubMed listing more than 17,000 scientific papers as of 2023. Bisphenol A poses environmental and health hazards in aquatic systems, affecting ecosystems and human health. While several studies have revealed its presence in aqueous streams, environmentally sound technologies should be explored for its removal from the contaminated environment. Concern is mostly related to its estrogen-like activity, although it can interact with other receptor systems as an endocrine-disrupting chemical. Present review article encompasses the updated information on sources, environmental concerns, and sustainable remediation techniques for bisphenol A removal from aquatic ecosystems, discussing gaps, constraints, and future research requirements.

Crp/fnr family protein binds to promoters of atxA and sodmn genes that regulate the expression of exotoxins in Bacillus anthracis.

Bacillus anthracis produces a tripartite exotoxin, which is regulated by AtxA. Sodmn is constitutively expressed during invasion. Crp/Fnr family transcriptional regulators are known to bind promoters of toxin regulators as well as constitutively expressed genes during pathogenesis. B. anthracis fnr gene was cloned, over-expressed in E. coli and recombinant protein was purified. Oligomeric nature of recombinant rFnr protein was studied by diamide treatment and DTT reduction. DNA binding of rFnr protein was studied by EMSA. We observed that rFnr exists in both monomeric and oligomeric forms. It was found that rFnr was able to oligomerize after diamide treatment which was reversible through DTT reduction. Promoter regions of atxA and sodmn show binding to monomeric form of rFnr, however, dimeric form was unable to bind. Fnr might be playing a role in regulation of toxin gene expression via regulation of atxA gene. It can also be involved in regulation of pathogenesis by regulating the sodmn expression. Oligomerization can act as an ON/OFF switch for the Fnr mediated regulation.

Effect of Aerobic Exercise Training on Mood in People With Traumatic Brain Injury: A Pilot Study.

BACKGROUND: Exercise training is associated with elevations in mood in patients with various chronic illnesses and disabilities. However, little is known regarding the effect of exercise training on short and long-term mood changes in those with traumatic brain injury (TBI). OBJECTIVE: The purpose of this study was to examine the time course of mood alterations in response to a vigorous, 12-week aerobic exercise training regimen in ambulatory individuals with chronic TBI (>6 months postinjury). METHODS: Short and long-term mood changes were measured using the Profile of Mood States-Short Form, before and after specific aerobic exercise bouts performed during the 12-week training regimen. RESULTS: Ten subjects with nonpenetrating TBI (6.6 ± 6.8 years after injury) completed the training regimen. A significant improvement in overall mood was observed following 12 weeks of aerobic exercise training (P = .04), with moderate to large effect sizes observed for short-term mood improvements following individual bouts of exercise. CONCLUSIONS: Specific improvements in long-term mood state and short-term mood responses following individual exercise sessions were observed in these individuals with TBI. The largest improvement in overall mood was observed at 12 weeks of exercise training, with improvements emerging as early as 4 weeks into the training regimen.

Advancements in unravelling the fundamental function of the ATAD3 protein in multicellular organisms.

ATPase family AAA domain containing protein 3, commonly known as ATAD3 is a versatile mitochondrial protein that is involved in a large number of pathways. ATAD3 is a transmembrane protein that spans both the inner mitochondrial membrane and outer mitochondrial membrane. It, therefore, functions as a connecting link between the mitochondrial lumen and endoplasmic reticulum facilitating their cross-talk. ATAD3 contains an N-terminal domain which is amphipathic in nature and is inserted into the membranous space of the mitochondria, while the C-terminal domain is present towards the lumen of the mitochondria and contains the ATPase domain. ATAD3 is known to be involved in mitochondrial biogenesis, cholesterol transport, hormone synthesis, apoptosis and several other pathways. It has also been implicated to be involved in cancer and many neurological disorders making it an interesting target for extensive studies. This review aims to provide an updated comprehensive account of the role of ATAD3 in the mitochondria especially in lipid transport, mitochondrial-endoplasmic reticulum interactions, cancer and inhibition of mitophagy.

Molecular clues unveiling spinocerebellar ataxia type-12 pathogenesis.

Spinocerebellar Ataxia type-12 (SCA12) is a neurodegenerative disease caused by tandem CAG repeat expansion in the 5'-UTR/non-coding region of PPP2R2B. Molecular pathology of SCA12 has not been studied in the context of CAG repeats, and no appropriate models exist. We found in human SCA12-iPSC-derived neuronal lineage that expanded CAG in PPP2R2B transcript forms nuclear RNA foci and were found to sequester variety of proteins. Further, the ectopic expression of transcript containing varying length of CAG repeats exhibits non-canonical repeat-associated non-AUG (RAN) translation in multiple frames in HEK293T cells, which was further validated in patient-derived neural stem cells using specific antibodies. mRNA sequencing of the SCA12 and control neurons have shown a network of crucial transcription factors affecting neural fate, in addition to alteration of various signaling pathways involved in neurodevelopment. Altogether, this study identifies the molecular signatures of SCA12 disorder using patient-derived neuronal cell lines.

Functional annotation of uncharacterized proteins from Fusobacterium nucleatum: identification of virulence factors.

Fusobacterium nucleatum is a gram-negative bacteria associated with diverse infections like appendicitis and colorectal cancer. It mainly attacks the epithelial cells in the oral cavity and throat of the infected individual. It has a single circular genome of 2.7 Mb. Many proteins in F. nucleatum genome are listed as "Uncharacterized." Annotation of these proteins is crucial for obtaining new facts about the pathogen and deciphering the gene regulation, functions, and pathways along with discovery of novel target proteins. In the light of new genomic information, an armoury of bioinformatic tools were used for predicting the physicochemical parameters, domain and motif search, pattern search, and localization of the uncharacterized proteins. The programs such as receiver operating characteristics determine the efficacy of the databases that have been employed for prediction of different parameters at 83.6%. Functions were successfully assigned to 46 uncharacterized proteins which included enzymes, transporter proteins, membrane proteins, binding proteins, etc. Apart from the function prediction, the proteins were also subjected to string analysis to reveal the interacting partners. The annotated proteins were also put through homology-based structure prediction and modeling using Swiss PDB and Phyre2 servers. Two probable virulent factors were also identified which could be investigated further for potential drug-related studies. The assigning of functions to uncharacterized proteins has shown that some of these proteins are important for cell survival inside the host and can act as effective drug targets.

Melanotic neuroectodermal tumor of infancy (MNTI) - A rare entity.

Melanotic neuroectodermal tumor of infancy is a rare pigmented pediatric tumor seen at craniofacial sites with the most common site being maxilla. This tumor arises from neural crest origin with a polyphenotypic expression of epithelial, neuroblastic, and melanotic markers. It is a locally aggressive tumor with rapid, expansile, and destructive growth. The tumor has fairly high chances of recurrence and malignant transformation, if not diagnosed and treated with time. There is no standard protocol for management owing to its rarity. Hereby, we present one such case of a 2-month-old male child with rapidly enlarging upper jaw swelling. The patient was treated with wide local excision, followed by two cycles of chemotherapy. The patient is in follow-up and doing well with no evidence of any local recurrence or metastasis till date.

Clinical and Radiological Profile of 122 Cases of Idiopathic Intracranial Hypertension in a Tertiary Care Centre of India: An Observational Study.

Background: Idiopathic intracranial hypertension (IIH) is well-described entity in literature. However, large studies on clinical and radiological profile are still very few from the Indian subcontinent. Aims: To analyze the clinical and radiological profile of IIH and correlation of various clinical and radiological parameters with papilledema and CSF opening pressure. Setting and Design: Hospital-based observational, descriptive study. Materials and Methods: This study analyzed 122 patients admitted in the department of Neurology (from January 2014 to December 2018) for detailed history, clinical examination, and neuroimaging. CSF manometry and routine CSF analysis were done. All participants met the modified Dandy criteria. Patients with secondary causes of raised ICP and primary ocular pathology were excluded. Statistical Analysis Used: Descriptive statistics and Chi-square test. Results: Among 122 cases 86 (70.49%) were females. The mean age was 33 years. 62 (50.82%) cases were obese. Headache was the most common symptom (114/122; 93.44%). Bilateral papilledema was noted in 114 (93.44%) cases. Higher grades of papilledema had a correlation with higher CSF opening pressure. Empty sella was the most common radiological finding (100/122; 81.97%). All radiological findings except empty sella had a correlation with higher CSF opening pressure. Conclusion: IIH typically affects obese females of childbearing age group. However, it is not uncommon in the nonobese and male sex. Obesity may not be a dominant risk factor for the development of IIH in the Indian subcontinent. Cases with normal BMI and male sex with clinical features of raised intracranial pressure and normal neuroimaging should also be evaluated for IIH. Cases with refractory headache and empty sella on MRI should be evaluated for IIH.

Pharmacotherapy for SARS-CoV-2 and Seizures for Drug Repurposing Presumed on Mechanistic Targets.

The currently circulating novel SARS-CoV-2 coronavirus disease (COVID-19) has brought the whole world to a standstill. Recent studies have deciphered the viral genome structure, epidemiology and are in the process of unveiling multiple mechanisms of pathogenesis. Apart from atypical pneumonia and lung disease manifestations, this disease has also been found to be associated with neurological symptoms, which include dizziness, headache, stroke, or seizures, among others. However, a possible direct or indirect association between SARS-CoV-2 and seizures is still not clear. In any manner, it may be of interest to analyze the drugs being used for viral infection in the background of epilepsy or vice versa. To identify the most credible drug candidate for COVID-19 in persons with epilepsy or COVID-19 patients experiencing seizures. A literature search for original and review articles was performed, and further, the Comparative Toxicogenomics Database was used to unearth the most credible drug candidate. Our search based on common mechanistic targets affecting SARS-CoV-2 and seizures revealed ivermectin, dexamethasone, anakinra, and tocilizumab for protection against both COVID-19 and seizures. Amongst the antiseizure medications, we found valproic acid as the most probable pharmacotherapy for COVID-19 patients experiencing seizures. These findings would hopefully provide the basis for initiating further studies on the pathogenesis and drug targeting strategies for this emerging infection accompanied with seizures or in people with epilepsy.

Lab resource: Single cell line generation and characterization of a human-derived induced pluripotent stem cell line (IGIBi005-A) from a patient with spastic paraplegia/ataxia/ALS phenotype due to the mutation of the gene Kinesin Family Member 5A (KIF5A).

Human Kinesin Family Member 5A (KIF5A) gene mutations have been identified as a putative genetic cause of amyotrophic lateral sclerosis (ALS). Disease modelling using human-induced pluripotent stem cells (HiPSCs) is the next-generation approach to studying numerous human diseases. For the current investigation, we report the generation of patient-specific KIF5A iPSC lines with a mutation at the splice site mutation (c.3020 + 3 A > T) in the intronic region. The resulting line displayed markers for pluripotency, a healthy karyotype, the ability to differentiate into three germ layers in vitro, vector clearance, the KIF5A mutation, STR-based genomic identity, and contamination-free culture.

Generation of two induced pluripotent stem cell (iPSC) lines from patients with Duchenne muscular dystrophy (IGIBi006-A and IGIBi008-A) carrying exonic deletions in the dystrophin gene.

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder with defect in dystrophin gene that shows features of degeneration of muscle tissue at an early age. Here, we describe iPSC lines generated from LCL of two patients of Indian origin carrying 46-48 and 49-50 exons deletions in DMD. The resulting iPSC lines IGIBi006-A and IGIBi008-A showed all the characteristic features of pluripotency, differentiated into cells of three germ layers in vitro and have no major genetic alterations due to reprogramming process. These lines can serve as a useful cell model for studying disease pathogenesis and will aid in precision therapy.

Genetics of Ataxias in Indian Population: A Collative Insight from a Common Genetic Screening Tool.

Cerebellar ataxias (CAs) represent a group of autosomal dominant and recessive neurodegenerative disorders affecting cerebellum with or without spinal cord. Overall, CAs have preponderance for tandem nucleotide repeat expansions as an etiological factor (10 TREs explain nearly 30-40% of ataxia cohort globally). The experience of 10 years of common genetic ataxia subtypes for ≈5600 patients' referrals (Pan-India) received at a single center is shared herein. Frequencies (in %, n) of SCA types and FRDA in the sample cohort are observed as follows: SCA12 (8.6%, 490); SCA2 (8.5%, 482); SCA1 (4.8%, 272); SCA3 (2%, 113); SCA7 (0.5%, 28); SCA6 (0.1%, 05); SCA17 (0.1%, 05), and FRDA (2.2%, 127). A significant amount of variability in TRE lengths at each locus is observed, we noted presence of biallelic expansion, co-occurrence of SCA-subtypes, and the presence of premutable normal alleles. The frequency of mutated GAA-FRDA allele in healthy controls is 1/158 (0.63%), thus an expected FRDA prevalence of 1:100 000 persons. The data of this study are relevant not only for clinical decision making but also for guidance in direction of genetic investigations, transancestral comparison of genotypes, and lastly provide insight for policy decision for the consideration of SCAs under rare disease category.

Liver X receptors and skeleton: Current state-of-knowledge.

The liver X receptors (LXR) is a nuclear receptor that acts as a prominent regulator of lipid homeostasis and inflammatory response. Its therapeutic effectiveness against various diseases like Alzheimer's disease and atherosclerosis has been investigated in detail. Emerging pieces of evidence now reveal that LXR is also a crucial modulator of bone remodeling. However, the molecular mechanisms underlying the pharmacological actions of LXR on the skeleton and its role in osteoporosis are poorly understood. Therefore, in the current review, we highlight LXR and its actions through different molecular pathways modulating skeletal homeostasis. The studies described in this review propound that LXR in association with estrogen, PTH, PPARγ, RXR hedgehog, and canonical Wnt signaling regulates osteoclastogenesis and bone resorption. It regulates RANKL-induced expression of c-Fos, NFATc1, and NF-κB involved in osteoclast differentiation. Additionally, several studies suggest suppression of RANKL-induced osteoclast differentiation by synthetic LXR ligands. Given the significance of modulation of LXR in various physiological and pathological settings, our findings indicate that therapeutic targeting of LXR might potentially prevent or treat osteoporosis and improve bone quality.

Primary squamous cell carcinoma, breast: A challenging diagnosis.

BACKGROUND: Primary squamous cell carcinoma of the breast is an extremely rare malignancy constituting less than 0.1% of all breast cancers with very few cases reported in literature. It is an aggressive, triple-hormone negative tumor, and its appropriate management is still debated. It is diagnostically challenging on both histopathology as well as radiology. Different diagnostic criteria are established for its definite diagnosis. As squamous cells are not found normally in the breast, various theories have been proposed regarding its origin. But the exact pathogenesis is still unclear. We report one such case encountered. CASE: A 54-year-old female presented with gradually progressive painless lump in the right breast for 3 months with no other clinical features. There was neither any history of chronic or malignant disease in the patient nor in her family. On clinical examination, there was well-defined, firm and nontender swelling in upper inner quadrant measuring 3 × 2 cm with overlying skin being normal. There was no swelling in the contralateral breast as well as in the bilateral axillary region. A suspicion of malignancy was raised on initial core needle biopsy and, on repeat biopsy, was diagnosed as metaplastic carcinoma with squamous differentiation. Later, on final resection, specimen was reported as primary squamous cell carcinoma of the breast without any nodal metastasis. All the metastatic causes were ruled out through proper clinical, radiological, and histopathological correlation. CONCLUSION: Primary squamous cell carcinoma of the breast is an aggressive tumor with its treatment protocol being still unclear, owing to its rarity. It is important to rule out the metastatic causes. It is relatively resistant to conventional chemotherapy, and its prognosis is also unpredictable. Hence, this requires further studies in terms of management and prognosis.

A rare case report of transitional urothelial carcinoma metastasizing to isolated upper cervical lymph node diagnosed on cytology.

Transitional urothelial carcinoma frequently metastasizes to pelvic and retroperitoneal lymph nodes usually within 2 years of primary diagnosis but isolated metastasis to upper cervical lymph node after 5 years of primary diagnosis is extremely rare. We report here a case of a 53-year-old male who presented with Level II cervical node enlargement after 5 years of being diagnosed and treated for urothelial carcinoma. The diagnosis of cervical metastasis from urothelial carcinoma was suggested by fine-needle aspiration cytology and confirmed by immunocytochemistry.

Effect of the Noninvasive Follicular Thyroid Neoplasm With Papillary-Like Nuclear Features (NIFTP) Nomenclature Revision on Indian Thyroid Fine-Needle Aspiration Practice.

OBJECTIVES: To analyze risk of malignancy (ROM) in Bethesda categories (BCs) and the impact of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) reclassification on malignancy risk and surgical outcome. METHODS: In this retrospective study based on fine-needle aspiration samples with histologic follow-up, ROM was analyzed in BCs. Possible cases of NIFTP were reviewed, followed by the analysis of impact of this reclassification on ROM in BCs. RESULTS: The incidence of NIFTP was 6.9% among excised thyroid nodules and 16.8% among all resected neoplastic lesions. ROM for BCs I to VI was 37.5%, 9.6%, 40.0%, 46.5%, 88.8%, and 96.8%, respectively. Risk of neoplasia was 50.0%, 13.8%, 55.0%, 71.2%, 88.8%, and 96.8% respectively. When NIFTPs were considered nonmalignant lesions, ROM decreased by 6.3%, 4.3%, 20%, 19.1%, 22.5%, and 1.5% in each Bethesda category (I-VI), respectively. Inability to diagnose NIFTP preoperatively led to overtreatment in 16.2%. CONCLUSIONS: Prevalence of NIFTP in Asian countries may be higher than expected. Substantial cases of NIFTP have a benign preoperative cytology; hence, cases of follicular adenoma and adenomatous colloid nodule should be included in the review. NIFTP reclassification has significantly reduced the ROM in indeterminate BCs, suggesting diagnostic lobectomy rather than total thyroidectomy. Countries should establish their own malignancy risk range and parameters.

Cystic adrenal lesions: A report of five cases.

BACKGROUND: Cystic adrenal lesions are rare and uncommon manifestation with few cases reported so far. Different types of adrenal cysts have been described with heterogeneous etiology and overlapping clinical findings, ranging from benign to malignant cystic neoplasm. They are usually asymptomatic or may rarely present with abdominal pain or fullness. Optimum management of adrenal cysts still remain controversial, owing to its low incidence. In this study, we report our institutional experience on diagnosis and management of different histological types of cystic adrenal lesions. CASES: During 4 years period, 55 patients underwent adrenalectomy with five cases presenting as adrenal cysts. All the five patients were biochemically nonfunctional and underwent adrenalectomy (laparoscopic anterior n = 2, retroperitoneoscopic approach n = 1, and open anterior transperitoneal approach n = 2). The primary indications for surgery were larger size and/or suspicion of malignancy. Histological evaluation revealed two epithelial cysts, one endothelial cyst, one pseudocyst, and a very rare case of adrenocortical carcinoma arising in a pseudocyst. CONCLUSION: Cystic adrenal lesions are rare with varied etiologic and clinical presentation that may sometimes lead to diagnostic and management dilemma. These cases must undergo biochemical and radiological evaluation to rule out underlying malignancy followed by referral for surgical intervention.

Clinical and functional outcome of modified Quad surgery in adult obstetric brachial plexus injury patients: Case reports.

Untreated adult obstetric brachial plexus injury (OBPI) patients, in general, use compensatory strategies to achieve their lost upper extremity functions; they cause some adverse effects. Our present study is a case series of 3 female adult OBPI patients, aged 46, 23 and 21 years old. They all had a modified Quad surgical procedure. All patients were assessed preoperatively and postoperatively by evaluating video recordings of standardized upper extremity movements using the modified Mallet scale. The average postoperative follow-up was 4.3 months (1 to 9 months). Total Mallet score significantly improved from 15 and 18 to 21 in two patients. Supination angle measured from active movement of these 3 patients improved from 40°, 0° and -60° to 80°, 40° and -40°, respectively. The modified Quad surgical procedure significantly improves active abduction and other shoulder functions not only in young pediatric and adolescent patients, as we have previously reported, but also in adult patients with muscle imbalance secondary to brachial plexus injury sustained at birth.

Annotation of a hypothetical protein (WP_002969292.1) from Brucella abortus.

Brucellosis is a zoonotic disease caused mainly by the bacteria belonging to the genus Brucella, most common of them is Brucella abortus. Genome sequencing of Brucella was completed in 2005. While majority of the proteins were assigned function, a large number of the peptides remained un-annotated and were referred as 'hypothetical'. These hypothetical proteins may contain crucial information about the biology and pathogenesis of the B. abortus. Therefore, it is of interest to annotate one such hypothetical protein as a multiple antibiotic resistance regulator protein, MarR. The physiological parameters, localization and the structural features were predicted for this protein which corroborated as the winged-helix type DNA-binding domain superfamily of transcription factors.