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Biomedical subjects

Anand Kumar

Publications and source records attributed to Anand Kumar.

At least 19 recordsLinked to original sources

Mechanistic Perspectives From Genomics and Pangenomics of Medicinal and Aromatic Plants: Linking Genome Architecture to Phytochemical Diversity.

Medicinal and aromatic plants (MAPs) produce a remarkable diversity of specialized metabolites with significant pharmaceutical, nutraceutical, and industrial value. Although advances in long-read sequencing, chromosome-scale genome assembly, and pangenomics have greatly expanded genomic resources, the mechanistic links between genome architecture and phytochemical diversity remain incompletely understood. The present review synthesizes current evidence describing how structural genomic variation may contribute to phytochemical diversity, while acknowledging that many proposed genome-to-metabolite relationships require further experimental validation. Examples illustrate how genome architecture is associated with specialized-metabolite biosynthesis through multiple regulatory processes. However, the strength of supporting evidence varies considerably among MAP species. Moreover, relatively few genome-to-metabolite relationships have been confirmed through direct functional validation. We further discuss how pangenomics, multiomics integration, genome editing, synthetic biology, and artificial intelligence support the discovery, validation, and engineering of specialized metabolic pathways. Casual conclusions are evaluated according to the strength of available evidence, highlighting where causal relationships have been experimentally established and where conclusions remain primarily association-based. Overall, this review provides an integrated conceptual and evidence-based perspective summarizing proposed relationships between genome architecture and phytochemical diversity and outlines future priorities for functional genomics, precision breeding, metabolic engineering, and sustainable utilization of MAPs.

artificial intelligence↗

Genome Editing in Solanaceae: Harnessing CRISPR-Cas Technology for Precision Crop Improvement.

Malnutrition and climate-induced stress remain major constraints to global food and nutritional security despite the yield gains of the Green Revolution. Solanaceae crops such as tomato, potato, brinjal, and pepper are key sources of vitamins, minerals, and bioactive compounds. Yet, their genetic improvement has been limited by narrow diversity and complex polygenic traits. The advent of CRISPR/Cas-mediated genome editing provides a transformative platform for precision crop improvement by enabling targeted modification of genes controlling stress tolerance, yield, and nutritional quality. In Solanaceae, CRISPR/Cas applications have successfully enhanced resistance against major pathogens (SlMlo1, SlPelo, SlDCL2), improved abiotic stress tolerance through editing of SlMAPK3, SlCBF1, and SlBZR1, and optimized fruit quality traits via modulation of Psy1, CrtR-b2, and fiAD2/3. Emerging innovations, such as base and prime editing, and RNP-mediated transgene-free delivery, are expanding the precision and scope of editing. However, challenges persist, including genotype-dependent transformation, low HDR efficiency, and incomplete understanding of off-target and epigenetic effects. Integrating CRISPR with omics-guided gene discovery, efficient transformation systems, and regulatory harmonization can accelerate the development of nutritionally enriched, stress-resilient, and sustainable Solanaceae varieties. This review synthesizes recent advances, identifies critical limitations, and outlines future opportunities for deploying CRISPR/Cas technology to achieve next-generation breeding and food system resilience.

CRISPR/Cas↗

Risk factors for bleeding after endoscopic retrograde cholangiopancreatography: a systematic review and meta-analysis.

BACKGROUND AND AIMS: ERCP is associated with adverse events, including bleeding, which occurs in up to 1.3% of cases. This meta-analysis aims to identify and quantify risk factors associated with post-ERCP bleeding. METHODS: A comprehensive literature search of electronic databases was conducted from inception to January 10, 2025. Studies were eligible if they used multivariate analysis to identify predictors of post-ERCP bleeding. Risk factors reported in at least 2 studies were pooled using a random-effects model to calculate odds ratios (ORs) with 95% CIs. A further subgroup analysis was performed, including risk factors for postsphincterotomy bleeding and postendoscopic papillectomy bleeding. RESULTS: Twenty-seven studies (4 prospective and 23 retrospective studies) comprising 149,870 patients were included, of whom 1865 experienced post-ERCP bleeding. Twenty potential risk factors were analyzed. The meta-analysis identified several factors significantly associated with increased odds of post-ERCP bleeding in the pooled adjusted analysis, including male gender (OR, 1.24; 95% CI, 1.05-1.46), anticoagulation therapy (OR, 2.75; 95% CI, 1.66-4.56), cirrhosis (OR, 2.54; 95% CI, 1.76-3.65), hemodialysis (OR, 5.82; 95% CI, 3.32-10.18), coagulopathy (OR, 11.01; 95% CI, 2.50-48.40), endoscopic sphincterotomy (EST) (OR, 3.19; 95% CI, 1.69-6.01), precut sphincterotomy (OR, 2.24; 95% CI, 1.52-3.30), and intraoperative bleeding (OR, 2.57; 95% CI, 1.80-3.66). Several factors in the pooled adjusted analysis were not found to be significantly associated with higher odds of post-ERCP bleeding, including high body mass index (BMI), nonsteroidal anti-inflammatory drug (NSAID) use, antiplatelet therapy, thrombocytopenia, common bile duct stones, cholangitis, endoscopic papillary balloon dilatation, and covered self-expandable metal stent insertion. CONCLUSIONS: This meta-analysis identified that the anticoagulation therapy, cirrhosis, hemodialysis, coagulation disorder, EST, precut sphincterotomy, and male gender are associated with increased odds of post-ERCP bleeding in the pooled adjusted analysis. Conversely, age, high BMI, cholangitis, choledocholithiasis, pancreatic duct stones, needle-knife sphincterotomy, NSAID use, and antiplatelet therapy were not significantly associated with higher odds of post-ERCP bleeding in the pooled adjusted analysis. Incorporating our results into a prediction model may assist in identifying patients at increased risk, optimizing informed consent, and guiding prevention and management strategies for post-ERCP bleeding.

Humans↗

Nonfamilial juvenile polyposis coli manifesting as massive lower gastrointestinal hemorrhage: report of two cases.

Juvenile polyposis syndrome is an uncommon hamartomatous disorder with gastrointestinal (GI) manifestations of varying degree and malignant potential. We report the cases of an 8-year-old girl and a 5-year-old girl who suffered massive lower GI hemorrhage. Neither patient had a family history of polyposis. After the patients were stabilized, radiological evaluation, laparotomy, and intraoperative colonoscopy revealed multiple polyps in the colon. Both patients underwent total colectomy, mucosal proctectomy, and ileoanal anastomosis. The diagnosis of nonfamilial juvenile polyposis was based on the histological findings and the absence of a family history. To our knowledge, this presentation of juvenile polyposis has been reported only twice before. We discuss the clinical features and diagnosis of juvenile polyposis and the treatment options. Although juvenile polyposis is a rare condition in children, it should be considered in the differential diagnosis of life-threatening GI hemorrhage.

Child↗

Transforming growth factor-beta1 blocks in vitro cardiac myocyte depression induced by tumor necrosis factor-alpha, interleukin-1beta, and human septic shock serum.

OBJECTIVE: Serum from patients with septic shock induces depression of myocyte contractility in vitro that is proportional the reduction of ejection fraction in vivo. This effect is mediated, in part, by tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta. Transforming growth factor (TGF)-beta is an immunomodulatory cytokine with a broad range of anti-inflammatory effects. Using an in vitro assay, this study sought to determine the effect of TGF-beta1 on myocyte depression induced by TNF-alpha, IL-1beta, and serum with known depressant activity from patients with septic shock. DESIGN: The maximum extent of shortening of electrically paced rat cardiac myocytes in tissue culture was quantified by a closed-loop video tracking system. Myocytes were exposed to different combinations of TNF-alpha, IL-1beta, septic serum, and TGF-beta1. SETTING: Basic research laboratory. MEASUREMENTS AND MAIN RESULTS: Increasing concentrations of TNF-alpha and IL-1beta each caused significant depression of maximum extent of myocyte shortening in vitro over 30 mins (p<.0001). Similarly, a synergistic combination of TNF-alpha and IL-1beta as well as serum with known depressant activity from five patients with acute septic shock induced significant depression of cardiac myocyte contraction (p<.01). Increasing concentrations of TGF-beta1 alone had no effect on maximum extent of cardiac myocyte contraction. However, myocytes that were co-incubated with increasing concentrations of TGF-beta1 demonstrated dose-dependent reversal of depression induced by TNF-alpha or IL-1beta (p<.0001). Similarly, depressant effects caused by synergistic concentrations of TNF-alpha and IL-1beta and serum from all five patients with septic shock were prevented by co-incubation with TGF-beta1. CONCLUSIONS: These data demonstrate that depression of in vitro cardiac myocyte contraction induced by proinflammatory cytokines and septic serum can be blocked by TGF-beta1. TGF-beta1 may have potential as therapy for sepsis-associated myocardial depression in humans.

Animals↗

Measurement of brain metabolites in patients with type 2 diabetes and major depression using proton magnetic resonance spectroscopy.

Type 2 diabetes and major depression are disorders that are mutual risk factors and may share similar pathophysiological mechanisms. To further understand these shared mechanisms, the purpose of our study was to examine the biochemical basis of depression in patients with type 2 diabetes using proton MRS. Patients with type 2 diabetes and major depression (n=20) were scanned along with patients with diabetes alone (n=24) and healthy controls (n=21) on a 1.5 T MRI/MRS scanner. Voxels were placed bilaterally in dorsolateral white matter and the subcortical nuclei region, both areas important in the circuitry of late-life depression. Absolute values of myo-inositol, creatine, N-acetyl aspartate, glutamate, glutamine, and choline corrected for CSF were measured using the LC-Model algorithm. Glutamine and glutamate concentrations in depressed diabetic patients were significantly lower (p<0.001) in the subcortical regions as compared to healthy and diabetic control subjects. Myo-inositol concentrations were significantly increased (p<0.05) in diabetic control subjects and depressed diabetic patients in frontal white matter as compared to healthy controls. These findings have broad implications and suggest that alterations in glutamate and glutamine levels in subcortical regions along with white matter changes in myo-inositol provide important neurobiological substrates of mood disorders.

Adult↗

Cognitive function in adults with type 2 diabetes and major depression.

The aim of this study was to identify characteristics of neuropsychological functioning among type 2 diabetic adults with and without major depression. Twenty type 2 diabetics with major depression, 20 non-depressed type 2 diabetics and 34 controls without diabetes or depression were compared. A mixed effects repeated measures analysis of covariance indicated significant differences in overall cognitive functioning between diagnostic groups, specifically depressed diabetics demonstrated greater cognitive dysfunction than controls. Further comparisons indicated that depressed diabetics performed significantly worse than non-depressed diabetics in attention/information processing speed. Relative to controls, depressed diabetics performed significantly worse in attention/information processing speed and executive functioning, while there was a trend for non-depressed diabetics to perform worse in executive functioning. These findings suggest that depression negatively impacts cognitive performance among adults with type 2 diabetes, which may have implications for neural circuitry underlying cognitive and mood changes in diabetic patients.

Adult↗

Executive dysfunction and memory in older patients with major and minor depression.

Executive function, known to be impaired during late-life depression, is dependent on frontostriatal pathways. Memory is also frequently observed to be impaired among late-life depressed patients, so we assessed the possibility that executive function mediates the learning and recall deficit as a "downstream" effect of the frontostriatal compromise in executive function. A cross-sectional sample of minor and major depressed patients (N=95) and nondepressed volunteers (N=71), screened for other Axis I disorders, dementia, medical comorbidity, and severity of depression, completed a neuropsychological battery that included the California Verbal Learning Test and other tests selected for convergent and divergent validity testing. Depressed patients differed from controls on learning the word list and on verbal and nonverbal executive tasks. Executive function was a mediator for depressed patients verbal learning scores (z=-2.67, p=.01). A nonverbal executive score also mediated verbal learning (z=-2.18, p=.03) indicating convergent validity of executive dysfunction during verbal learning exercises. In conclusion, the verbal memory deficits typically attributed to late-life depression may result from impaired executive functioning during the learning phase of the recall task.

Age of Onset↗

Hypoandrogenaemia is associated with subclinical hypothyroidism in men.

Hypothyroidism has been shown to be associated with a reduction in serum testosterone level in males. This reduction in testosterone is reversible by thyroxine replacement therapy. However, to the best of our knowledge, it is not yet known, whether a similar reduction in serum testosterone level is observed in subclinically hypothyroid males [thyroid-stimulating hormone (TSH) < 10 mIU/L] in whom the benefits of thyroxine replacement therapy are still controversial. Our goal was to investigate the putative connections between subclinical hypothyroidism and the circulating levels of gonadotrophins and gonadal steroids in males (mean age +/- SEM, 34.67 +/- 1.52 years; ranging from 20 to 54 years). The serum samples from patients showing normal euthyroid and subclinical hypothyroid profiles (TSH < 10 mIU/L) were further analysed for the levels of luteinizing hormone, follicle-stimulating hormone, prolactin, testosterone, sex hormone-binding globulin, progesterone and oestradiol. Subclinical hypothyroidism was associated with a decrease in the levels of serum testosterone and its precursor progesterone. The data suggest that serum testosterone declines because of the non-availability of its precursor progesterone. The level of oestradiol was similar in both the groups, suggesting a greater conversion rate of testosterone to oestradiol in subclinically hypothyroid males, in order to maintain the oestradiol levels. Prolactin levels were slightly but significantly increased in subclinical hypothyroidism. To the best of our information this is a novel report, which shows a direct association between subclinical hypothyroidism and hypoandrogenaemia. Testosterone deficiency and its symptoms should be kept in view while managing subclinical hypothyroidism in male patients. Further studies are needed in order to reveal the physiological and molecular mechanisms leading to hypoandrogenaemia in subclinical hypothyroidism (TSH < 10 mIU/L).

Adult↗

Molecular dissection of an hCG-beta epitope using single-step solid phase radioimmunoassay.

BACKGROUND: Peptides and proteins have both sequence-specific (contiguous) and conformation-specific (discontiguous) epitopes. Sequence-specific epitopes are delineated by peptide approach and other robust methods like competition assays, gene expression assays, synthetic peptide library based assays etc. Available methods for delineation of conformation-specific epitopes are cumbersome (X-ray crystallography etc.), time-consuming and require costly sophisticated equipments. Hence, there is a need to develop a simple method for identification and mapping of conformation-specific epitopes. METHOD: In the single-step solid phase radioimmunoassay (SS-SPRIA), an immunochemical bridge of 'mouse IgG-anti-mouse IgG' was prepared in the polypropylene wells followed by adsorption with hCG specific monoclonal antibody (MAb) G(1)G(10).1. The extent of competitive inhibition in binding ability of (125)IhCG-beta with chemically or enzymatically modified hCG-beta to immobilized MAb G(1)G(10).1 in comparison to hCG-beta standards was utilized to identify the epitopic amino acid involved in epitope-paratope interaction. RESULTS: Data clearly suggest that the epitope under investigation consisted of Arg (94, 95) and Asp (99) at the core region with a Lys (104) and a His (106) in the proximity and absence of chymotrypsin susceptible Phe or Tyr in this region. CONCLUSION: The data of SS-SPRIA revealed the 93-100 loop of amino acid sequence, as the core region of conformation-specific epitope of hCG-beta at or near the receptor-binding region. Hence, SS-SPRIA seems to be a simple method for identification and mapping of conformation-specific epitopes.

Amino Acid Sequence↗

Improved outcomes in cleft patients with severe maxillary deficiency after Le Fort I internal distraction.

BACKGROUND: Correction of severe maxillary deficiency in cleft lip-cleft palate patients often results in undercorrection, relapse, and need for secondary corrective procedures. Le Fort I internal distraction osteogenesis offers an alternative to one-step orthognathic advancement, with advantages of gradual lengthening through scar and earlier treatment in growing patients. METHODS: Patients with cleft lip-cleft palate deformities and maxillary deficiency were divided into three groups treated by Le Fort I advancement: group 1, mild to moderate deficiency (< 10 mm) with conventional orthognathic procedure; group 2, severe deficiency (> or = 10 mm) with conventional orthognathic procedure; and group 3, distraction procedure for severe deficiency (> or = 10 mm) (n = 51). Preoperative, postoperative, and follow-up (> 1 year) lateral cephalogram measurements were compared including angular (SNA and SNB) and linear (Deltax = horizontal and Deltay = vertical) changes. The Pittsburgh Speech Score was used to assess for velopharyngeal insufficiency (score > 3). RESULTS: Results demonstrated that group 1 patients had a mean SNA change from preoperatively (78.7) to postoperatively (83.8), and a horizontal change of 5.0 mm, with no relapse. Group 2 patients had a mean SNA change from preoperatively (76.3) to postoperatively (82.0) and a horizontal change of 7.2 mm, with 63 percent relapse. Group 3 patients had a mean SNA change from preoperatively (74.1) to postoperatively (84.9) and a horizontal change of 16.5 mm, with 15 percent relapse. Thus, for severe maxillary deficiency, the distraction group had 48 percent less relapse than the conventional Le Fort I group. Postoperative speech evaluation showed velopharyngeal insufficiency in the following: group 1, four of 20 patients (20 percent); group 2, nine of 11 patients (82 percent); and group 3, nine of 20 patients (45 percent). CONCLUSION: These data suggest that Le Fort I internal distraction for severe cleft maxillary deficiency leads to better dental occlusion, less relapse, and better speech results.

Cleft Lip↗

Perspectives on depression, mild cognitive impairment, and cognitive decline.

CONTEXT: The public health implications of depression and cognitive impairment in late life are enormous. Cognitive impairment and late-life depression are associated with increased risk for subsequent dementia; however, investigations of these phenomena appear to be proceeding along separate tracks. OBJECTIVES AND DATA SOURCE: The National Institute of Mental Health organized the conference "Perspectives on Depression, Mild Cognitive Impairment, and Cognitive Decline" to consider how the varied perspectives might be better integrated to examine the associations among depression, mild cognitive impairment, and cognitive decline and to illuminate the common or distinct mechanisms involved in these associations. DATA SYNTHESIS: The following 2 broad questions were addressed: (1) What gaps in our knowledge have the greatest public health significance? (2) Can we more efficiently use our research dollars and participant resources to fill these gaps? Meeting participants included grantees from the National Institute of Mental Health and the National Institute on Aging and program staff from the National Institute of Mental Health, the National Institute on Aging, and the National Institute of Neurological Disorders and Stroke. CONCLUSIONS: One of the most important recommendations to emerge from the meeting discussions is for increased collaboration among clinical and epidemiological investigators whose work focuses in the area of depression with those working primarily in the area of memory disorders. Directions for future research were identified.

Aged↗

Yunis Varon syndrome.

In this communication is reported a neonate with Yunis Varon syndrome, a rare autosomal recessive disorder, born to a consanguineously married couple who had microcephaly, wide cranial sutures, prominent eyes, hypertelorism, dysplastic ears, sparse hairs, cupid bow like upper lip with median pseudocleft and labio-gingival retraction. Bilateral hypoplasia of thumbs, absent great toes, short phalanges were other features. Additional features in this case included median pseudocleft unreported earlier and C.T. findings of underdeveloped gyri, ischemic changes in temperoparietal region and bilateral lacunar infarcts in middle cerebral artery territory.

Abnormalities, Multiple↗

Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock.

OBJECTIVE: To determine the prevalence and impact on mortality of delays in initiation of effective antimicrobial therapy from initial onset of recurrent/persistent hypotension of septic shock. DESIGN: A retrospective cohort study performed between July 1989 and June 2004. SETTING: Fourteen intensive care units (four medical, four surgical, six mixed medical/surgical) and ten hospitals (four academic, six community) in Canada and the United States. PATIENTS: Medical records of 2,731 adult patients with septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main outcome measure was survival to hospital discharge. Among the 2,154 septic shock patients (78.9% total) who received effective antimicrobial therapy only after the onset of recurrent or persistent hypotension, a strong relationship between the delay in effective antimicrobial initiation and in-hospital mortality was noted (adjusted odds ratio 1.119 [per hour delay], 95% confidence interval 1.103-1.136, p<.0001). Administration of an antimicrobial effective for isolated or suspected pathogens within the first hour of documented hypotension was associated with a survival rate of 79.9%. Each hour of delay in antimicrobial administration over the ensuing 6 hrs was associated with an average decrease in survival of 7.6%. By the second hour after onset of persistent/recurrent hypotension, in-hospital mortality rate was significantly increased relative to receiving therapy within the first hour (odds ratio 1.67; 95% confidence interval, 1.12-2.48). In multivariate analysis (including Acute Physiology and Chronic Health Evaluation II score and therapeutic variables), time to initiation of effective antimicrobial therapy was the single strongest predictor of outcome. Median time to effective antimicrobial therapy was 6 hrs (25-75th percentile, 2.0-15.0 hrs). CONCLUSIONS: Effective antimicrobial administration within the first hour of documented hypotension was associated with increased survival to hospital discharge in adult patients with septic shock. Despite a progressive increase in mortality rate with increasing delays, only 50% of septic shock patients received effective antimicrobial therapy within 6 hrs of documented hypotension.

Adult↗

Methylphenidate-enhanced antidepressant response to citalopram in the elderly: a double-blind, placebo-controlled pilot trial.

OBJECTIVE: The authors evaluated the potential of methylphenidate to accelerate and enhance antidepressant response to citalopram in elderly depressed patients. METHODS: Sixteen outpatients with major depression were treated in a 10-week double-blind trial. Response was defined as a score on the Hamilton Depression Rating Scale (24-item) of less than 10. RESULTS: An accelerated response was observed by week 3 in five subjects receiving citalopram (CIT)+methylphenidate (MPH) and in none of those receiving CIT+placebo (PBO). Subjects receiving citalopram and methylphenidate showed a significant improvement in depressive symptoms compared with those on citalopram and placebo. CONCLUSION: Combined treatment with citalopram and methylphenidate appears to be a viable strategy for accelerating and enhancing antidepressant response in elderly depressed patients limited by tolerability and safety.

Aged↗

Towards the use of ontologies for activity-based costing in healthcare organizations.

Activity-based costing is a methodology which provides a basis for healthcare cost optimization. A robust formal representation of such activities is needed in order to be able to draw inferences as to the costs involved in a reliable manner. An introduction to the basic ontological distinctions involved in such a representation and to the complications one faces in carrying out the task is presented in this paper.

Accounting↗

Biomedical ontologies: what part-of is and isn't.

Mereological relations such as part-of and its inverse has-part are fundamental to the description of the structure of living organisms. Whereas classical mereology focuses on individual entities, mereological relations in biomedical ontologies are generally asserted between classes of individuals. In general, this practice leaves some basic issues unanswered: type constraints of mereological relations, e.g., concerning artifacts and biological entities, the relation between parthood and time, inferred parts and wholes as well as a delimitation of parthood against spatial inclusion. Furthermore, mereological relations can be asserted not only between physical objects but also between biological processes and medical procedures. We analyze these ambiguities and make suggestions for a standardization of mereological relations in biomedical ontologies.

Anatomy↗

Bridging the gap between medical and bioinformatics: an ontological case study in colon carcinoma.

Ontological principles are needed in order to bridge the gap between medical and biological information in a robust and computable fashion. This is essential in order to draw inferences across the levels of granularity which span medicine and biology, an example of which include the understanding of the roles of tumor markers in the development and progress of carcinoma. Such information integration is also important for the integration of genomics information with the information contained in the electronic patient records in such a way that real time conclusions can be drawn. In this paper, we describe a large multi-granular datasource built by using ontological principles and focusing on the case of colon carcinoma.

Colonic Neoplasms↗