Leptin and ghrelin dynamics: unraveling their influence on food intake, energy balance, and the pathophysiology of type 2 diabetes mellitus.

Purpose: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance and impaired glucose homeostasis. In recent years, there has been growing interest in the role of hunger and satiety hormones such as ghrelin and leptin in the development and progression of T2DM. In this context, the present literature review aims to provide a comprehensive overview of the current understanding of how ghrelin and leptin influences food intake and maintain energy balance and its implications in the pathophysiology of T2DM. Methods: A thorough literature search was performed using PubMed and Google Scholar to choose the studies that associated leptin and ghrelin with T2DM. Original articles and reviews were included, letters to editors and case reports were excluded. Results: This narrative review article provides a comprehensive summary on mechanism of action of leptin and ghrelin, its association with obesity and T2DM, how they regulate energy and glucose homeostasis and potential therapeutic implications of leptin and ghrelin in managing T2DM. Conclusion: Ghrelin, known for its appetite-stimulating effects, and leptin, a hormone involved in the regulation of energy balance, have been implicated in insulin resistance and glucose metabolism. Understanding the complexities of ghrelin and leptin interactions in the context of T2DM may offer insights into novel therapeutic strategies for this prevalent metabolic disorder. Further research is warranted to elucidate the molecular mechanisms underlying these hormone actions and to explore their clinical implications for T2DM prevention and management.

Inflammaging in Multidrug-Resistant Sepsis of Geriatric ICU Patients and Healthcare Challenges.

Multidrug-resistant sepsis (MDR) is a pressing concern in intensive care unit (ICU) settings, specifically among geriatric patients who experience age-related immune system changes and comorbidities. The aim of this review is to explore the clinical impact of MDR sepsis in geriatric ICU patients and shed light on healthcare challenges associated with its management. We conducted a comprehensive literature search using the National Center for Biotechnology Information (NCBI) and Google Scholar search engines. Our search incorporated keywords such as "multidrug-resistant sepsis" OR "MDR sepsis", "geriatric ICU patients" OR "elderly ICU patients", and "complications", "healthcare burdens", "diagnostic challenges", and "healthcare challenges" associated with MDR sepsis in "ICU patients" and "geriatric/elderly ICU patients". This review explores the specific risk factors contributing to MDR sepsis, the complexities of diagnostic challenges, and the healthcare burden faced by elderly ICU patients. Notably, the elderly population bears a higher burden of MDR sepsis (57.5%), influenced by various factors, including comorbidities, immunosuppression, age-related immune changes, and resource-limited ICU settings. Furthermore, sepsis imposes a significant economic burden on healthcare systems, with annual costs exceeding $27 billion in the USA. These findings underscore the urgency of addressing MDR sepsis in geriatric ICU patients and the need for tailored interventions to improve outcomes and reduce healthcare costs.

Correlation between the middle phalanx of the third finger skeletal maturation staging system and insulin-like growth factor-1 levels among Indian children - A 3-year longitudinal study.

INTRODUCTION: Tracking insulin-like growth factor-1 (IGF-1) level alongside the middle phalanx of the third finger (MP3) staging modification could provide valuable insights into the relationship between hormonal factors and skeletal maturation during different stages of growth. Longitudinal studies indeed play a crucial role in understanding these complex relationships over time, allowing for a more comprehensive assessment of how IGF-1 might serve as a marker for pubertal growth stages. METHODOLOGY: The present longitudinal prospective cohort study was done among 26 boys and 26 girls. For each child, once in every 6 months for 3 years, blood samples (to estimate IGF-1 level) and X-rays of the left hand middle finger were taken. DRG IGF-1 600 Human Enzyme-Linked Immunosorbent Assay kit was used for the quantitative measurement of IGF1 from serum. The MP3 stages of the middle phalanx of the middle finger were evaluated using a modified MP3 system. The collected data were subjected to suitable descriptive and inferential statistics. RESULTS: The mean IGF1 levels were significantly higher in girls compared to boys across all the stages of MP3 skeletal maturity indicators. However, in both boys and girls, IGF-1 levels showed increasing trends from Stage F to H where it peaked and showed deceleration to Stage I (P < 0.05). CONCLUSION: The observed increase in serum IGF-1 levels during pubertal stages, followed by a decline in late puberty, aligning with the stages of skeletal maturation, suggests a close relationship between hormonal changes and bone development.

Multidrug-Resistant Sepsis: A Critical Healthcare Challenge.

Sepsis globally accounts for an alarming annual toll of 48.9 million cases, resulting in 11 million deaths, and inflicts an economic burden of approximately USD 38 billion on the United States healthcare system. The rise of multidrug-resistant organisms (MDROs) has elevated the urgency surrounding the management of multidrug-resistant (MDR) sepsis, evolving into a critical global health concern. This review aims to provide a comprehensive overview of the current epidemiology of (MDR) sepsis and its associated healthcare challenges, particularly in critically ill hospitalized patients. Highlighted findings demonstrated the complex nature of (MDR) sepsis pathophysiology and the resulting immune responses, which significantly hinder sepsis treatment. Studies also revealed that aging, antibiotic overuse or abuse, inadequate empiric antibiotic therapy, and underlying comorbidities contribute significantly to recurrent sepsis, thereby leading to septic shock, multi-organ failure, and ultimately immune paralysis, which all contribute to high mortality rates among sepsis patients. Moreover, studies confirmed a correlation between elevated readmission rates and an increased risk of cognitive and organ dysfunction among sepsis patients, amplifying hospital-associated costs. To mitigate the impact of sepsis burden, researchers have directed their efforts towards innovative diagnostic methods like point-of-care testing (POCT) devices for rapid, accurate, and particularly bedside detection of sepsis; however, these methods are currently limited to detecting only a few resistance biomarkers, thus warranting further exploration. Numerous interventions have also been introduced to treat MDR sepsis, including combination therapy with antibiotics from two different classes and precision therapy, which involves personalized treatment strategies tailored to individual needs. Finally, addressing MDR-associated healthcare challenges at regional levels based on local pathogen resistance patterns emerges as a critical strategy for effective sepsis treatment and minimizing adverse effects.

Redefining the polypill: pros and cons in cardiovascular precision medicine.

Polypill is a multi-drug formulation in a single pill intended to simplify the drug regimen and reduce medication-induced adverse effects. The most common multidrug combinations in a polypill are used to treat cardiovascular diseases and are targeted against key modifiable risk factors such as hypertension and hyperlipidemia. These contain blood-pressure lowering agents, statins, and anti-platelet agents usually in a fixed dose. Polypills can be an affordable therapeutic intervention for treating high-risk patients, as these are proven to increase patients' adherence to medication and improve clinical outcomes. Over the previous years, randomized clinical trials of several polypills have yielded contradictory findings, raising skepticism regarding their widespread use in primary disease prevention. Here, we have reviewed the concept of polypills, the evidence-based strengths, the limitations of this polypharmacy intervention strategy, and discussed future directions for their use in the primary and secondary preventive management of cardiovascular diseases and associated risk factors.

Effect of non surgical periodontal therapy and vitamin C supplementation on total antioxidant capacity in patients with chronic generalised periodontitis - A randomised controlled trial.

Background: Periodontal inflammation are inflammation of supporting tissues of periodontium. The microbial factor can cause infection which is polymicrobial in origin and causes dysbiosis and shift in oxidative stress with compromised antioxidant capacity. This study focused at determination of the effect of nonsurgical periodontal therapy (NSPT) and vitamin C supplementation on total antioxidant capacity (TAOC) in chronic periodontitis patients (ChP). Material & method: A total of 70 ChPand 35 periodontally healthy subjects (control) were recruited in this study. Further, ChP group was subdivided into ChP1 group (n = 35) which received NSPT only and ChP 2 group (n = 35) which received NSPT with vitamin C 500 mg once daily for 3 months. Serum and saliva samples were taken at baseline and at 3 months postNSPT for measurement of TAOC. Clinical parameters measured were measured at 1-, 3-, 6- and 12-month interval. Results: Lower levels of serum and salivary TAOC levels were observed in ChP patients than healthy subjects (p < 0.05). Improvement in Clinical parameters was observed in both the groups ChP1 and ChP 2 group post therapy (p < 0.05). The periodontal treatment showed insignificant changes in serum and salivary TAOC levels (p > 0.05). The supplemental dose of vitamin C didn't have any additional benefits (p > 0.05). Conclusion: There lies an association of oxidative stress with periodontitis, low serum and salivary TAOC levels were seen in chronic periodontitis patients. NSPT improved the periodontal inflammatory status. However, benefits of vitamin C as an adjunct to NSPT remains inconclusive and needs to be further explored by multicentre longitudinal studies.

AATF inhibition exerts antiangiogenic effects against human hepatocellular carcinoma.

Background and aims: Angiogenesis is a key factor in the growth and metastasis of hepatic tumors and thus a potential therapeutic target in hepatocellular carcinoma (HCC). In this study, we aim to identify the key role of apoptosis antagonizing transcription factor (AATF) in tumor angiogenesis and its underlying mechanisms in HCC. Methods: HCC tissues were analyzed for AATF expression by qRT-PCR and immunohistochemistry. Stable clones of control and AATF knockdown (KD) were established in human HCC cells. The effect of AATF inhibition on the angiogenic processes was determined by proliferation, invasion, migration, chick chorioallantoic membrane (CAM) assay, zymography, and immunoblotting techniques. Results: We identified high levels of AATF in human HCC tissues compared to adjacent normal liver tissues, and the expression was found to be correlated with the stages and tumor grades of HCC. Inhibiting AATF in QGY-7703 cells resulted in higher levels of pigment epithelium-derived factor (PEDF) than controls due to decreased matric metalloproteinase activity. Conditioned media from AATF KD cells inhibited the proliferation, migration, and invasion of human umbilical vein endothelial cells as well as the vascularization of the chick chorioallantoic membrane. Furthermore, the VEGF-mediated downstream signaling pathway responsible for endothelial cell survival and vascular permeability, cell proliferation, and migration favoring angiogenesis was suppressed by AATF inhibition. Notably, PEDF inhibition effectively reversed the anti-angiogenic effect of AATF KD. Conclusion: Our study reports the first evidence that the therapeutic strategy based on the inhibition of AATF to disrupt tumor angiogenesis may serve as a promising approach for HCC treatment.

Substantiation of a clopidogrel metabolism-associated gene (CYP2C19) variation among healthy individuals.

BACKGROUND: It is essential to investigate the prevalence of CYP2C19 alleles that affect drug metabolism. This study measures the allelic and genotypic frequencies of CYP2C19 loss-of-function (LoF) alleles CYP2C19∗2, CYP2C19∗3, and gain-of-function (GoF) alleles CYP2C19∗17 in the general population. METHODOLOGY: The study involved 300 healthy subjects between the ages of 18 and 85 recruited by simple random sampling. Allele-specific touchdown PCR was employed to identify the various alleles. The genotype and allele frequencies were calculated and checked for Hardy-Weinberg equilibrium. The phenotypic prediction of ultra-rapid metabolizer (UM = ∗17/∗17), extensive metabolizer (EM = ∗1/∗17, ∗1/∗1), intermediate metabolizer (IM = ∗1/∗2, ∗1/∗3, ∗2/∗17) and poor metabolizer (PM = ∗2/∗2, ∗2/∗3, ∗3/∗3) was made based on their genotype. RESULTS: The allele frequency of CYP2C19∗2, CYP2C19∗3, and CYP2C19∗17 was 0.365, 0.0033, and 0.18, respectively. The IM phenotype predominated with an overall frequency of 46.67%, including 101 subjects with ∗1/∗2, two subjects with ∗1/∗3, and 37 subjects with ∗2/∗17 genotype. This was followed by EM phenotype with an overall frequency of 35%, including 35 subjects with ∗1/∗17 and 70 subjects with ∗1/∗1 genotype. PM phenotype had an overall frequency of 12.67%, including 38 subjects with ∗2/∗2 genotype, and UM phenotype had an overall frequency of 5.67%, including 17 subjects with ∗17/∗17 genotype. CONCLUSION: Given the high allelic frequency of PM in the study population, a pre-treatment test to identify the individual's genotype may be recommended to decide the dosage, monitor the drug response, and avoid adverse drug reactions.

Online practical assessment in biochemistry designed on Bloom's taxonomy to assess the student's competency: Prior exposure of the students to online tools beneficial.

Online assessments are needed during the prevailing pandemic situation to continue educational activities while ensuring safety. After conducting the online practical assessment (OPrA) in Biochemistry, we analyzed the students' responses. The blueprint of the OPrA was prepared by the faculty, referring to the various levels and domains of Bloom's taxonomy. Four components were chosen for the online assessment: digital spotters, enumerating the steps of objective structured practical examination, interpretation of quantitative estimation, and case discussion. Each faculty assessed about 12-13 students in separate breakout rooms over 15-20 min on all four components. Feedback on the conduct of the examination was collected from the students and faculty anonymously and analyzed. Out of the 200 students who attended the online assessment, only one scored less than 50%, majority of them scored between 71% and 90%. Under the individual exercises, the average score of students in "Spotters" was 9.8 out of 10; in "OSPE," 8.7 out of 10; in "Quantitative experiments," 15.2 out of 20 and in "Case discussion," 22.4 out of 30. Around 20% had previous experience attending the OPrA. They differed in their opinion from the rest of the students on five aspects; time allotted for the assessment (p value = 0.02, χ2  = 5.07), students using unfair means during the online viva (p value = 0.02, χ2  = 5.57), their computing skills (p value = 0.001, χ2  = 19.82), their performance (p value = 0.001, χ2  = 8.84), and overall conduct of the examination (p value = 0.001, χ2  = 15.55). OPrA tools may be designed referring to Bloom's taxonomy, and prior exposure to the online tools may benefit the students.

Therapeutic options in hepatocellular carcinoma: a comprehensive review.

Hepatocellular carcinoma (HCC) is a chronic liver disease that is highly fatal if not detected and treated early. The incidence and death rate of HCC have been increasing in recent decades despite the measures taken for preventive screening and effective diagnostic and treatment strategies. The pathophysiology of HCC is multifactorial and highly complex owing to its molecular and immune heterogeneity, and thus the gap in knowledge still precludes making choices between viable therapeutic options and also the development of effective regimens. The treatment of HCC demands multidisciplinary approaches and primarily depends on tumor stage, hepatic functional reserve, and response to treatment by patients. Although curative treatments are limited but critical in the early stages of cancer, there are numerous palliative treatments available for patients with intermediate and advanced-stage HCC. In recent times, the use of combination therapy has succeeded over the use of monotherapy in the treatment of HCC by achieving effective tumor suppression, increasing survival rate, decreasing toxicity, and also aiding in overcoming drug resistance. This work focuses on reviewing the current and emerging treatment strategies for HCC.

Trends in the Bacterial Prevalence and Antibiotic Resistance Patterns in the Acute Exacerbation of Chronic Obstructive Pulmonary Disease in Hospitalized Patients in South India.

Exacerbation due to antimicrobial-drug-resistant bacteria among chronic obstructive pulmonary disease (AECOPD) patients contributes to mortality and morbidity. We examined the prevalence of the bacterial organisms and trends in drug resistance in AECOPD. In this retrospective study, between January 2016 to December 2020, among 3027 AECOPD patients, 432 (14.3%) had bacteria isolated. The regression and generalized estimating equations (GEE) were used for trends in the resistance patterns over five years, adjusting for age, gender, and comorbidities. Klebsiella pneumoniae (32.4%), Pseudomonas aeruginosa (17.8%), Acinetobacter baumannii (14.4%), Escherichia coli (10.4%), and Staphylococcus aureus (2.5%) were common. We observed high levels of drug resistance in AECOPD patients admitted to ICU (87.8%) and non-ICU (86.5%). A Cox proportional hazard analysis, observed infection with Acinetobacter baumannii and female sex as independent predictors of mortality. Acinetobacter baumannii had 2.64 (95% confidence interval (CI): 1.08−6.43) higher odds of death, compared to Klebsiella pneumoniae. Females had 2.89 (95% CI: 1.47−5.70) higher odds of death, compared to males. A high proportion of bacterial AECOPD was due to drug-resistant bacteria. An increasing trend in drug resistance was observed among females.

Bioinformatic Tools for the Identification of MicroRNAs Regulating the Transcription Factors in Patients with ß-Thalassemia.

ß-thalassemia is a significant health issue worldwide, with approximately 7% of the world's population having defective hemoglobin genes. MicroRNAs (miRNAs) are short noncoding RNAs regulating gene expression at the post-transcriptional level by targeting multiple gene transcripts. The levels of fetal hemoglobin (HbF) can be increased by regulating the expression of the γ-globin gene using the suppressive effects of miRNAs on several transcription factors such as MYB, BCL11A, GATA1, and KLF. An early step in discovering miRNA:mRNA target interactions is the computational prediction of miRNA targets that can be later validated with wet-lab investigations. This review highlights some commonly employed computational tools such as miRBase, Target scan, DIANA-microT-CDS, miRwalk, miRDB, and micro-TarBase that can be used to predict miRNA targets. Upon comparing the miRNA target prediction tools, 4 main aspects of the miRNA:mRNA target interaction are shown to include a few common features on which most target prediction is based: conservation sites, seed match, free energy, and site accessibility. Understanding these prediction tools' usage will help users select the appropriate tool and interpret the results accurately. This review will, therefore, be helpful to peers to quickly choose a list of the best miRNAs associated with HbF induction. Researchers will obtain significant results using these bioinformatics tools to establish a new important concept in managing ß-thalassemia and delivering therapeutic strategies for improving their quality of life.

Evaluation of injectable platelet-rich fibrin effect on the rate of canine retraction and alkaline phosphatase levels: An in-vivo study.

INTRODUCTION: With time, the treatment protocol has changed, and currently, there is a new school of treatment called accelerated orthodontics, wherein the goal is to shorten the time. In this study, a liquid formulation of platelet-rich fibrin such as injectable platelet-rich fibrin (i-PRF), was used, and its effect on the rate of canine retraction and the crevicular alkaline phosphatase (ALP) levels were studied. METHODS: Thirteen patients were recruited for this study with a mean age of 20.6 ± 3.2 years. A split-mouth type of study design was used in which the maxillary arch of each subject was divided into an experimental and control group. I-PRF was injected in the labial and lingual attached gingiva of the canine in the experimental group. The gingival crevicular fluid collection was done from the distal aspect of the canine before canine retraction, 24 hours after retraction, and 28 days after retraction from both sites (ie, control and experimental sites). ALP activity was analyzed using a semiautomated analyzer, and the rate of canine retraction was measured on stone casts with the help of a digital vernier caliper. RESULTS: The individual canine retraction was 1.8-fold faster in the i-PRF group than in the control group. The ALP activity was significantly greater at 24 hrs and 28 days after retraction in the experimental group. CONCLUSIONS: These results suggest that i-PRF is an innovative, noninvasive approach to accelerating tooth movement. ALP activity in gingival crevicular fluid reflects the biological changes in the periodontium, and the steep increase in the activity indicates increased bone remodeling within the experimental group.

Supernumerary derivative 22 chromosome resulting from novel constitutional non-Robertsonian translocation: t(20;22)-Case Report.

BACKGROUND: Maternal non-Robertsonian translocation-t(20;22)(q13;q11.2) between chromosomes 20 and 22resulting in an additional complex small supernumerary marker chromosome as derivative (22)inherited to the proband is not been reported yet. CASE PRESENTATION: A 4 years old boy with a history of developmental delay, low set ears, and facial dysmorphism was presented to the genetic clinic. Periauricular pit, downward slanting eyes, medially flared eyebrows, downturned mouth corners, and micrognathia were observed. He had congenital heart defect with atrial septal defect (ASD), ventricular septal defect (VSD), and central nervous system (CNS) anomalies with the gross cranium. Karyotype analysis, Fluorescent in-situ hybridization analysis (FISH), and Chromosomal microarray analysis (CMA) were used to determine the chromosomal origin and segmental composition of the derivative 22 chromosome. Karyotype and FISH analyses were performed to confirm the presence of a supernumerary chromosome, and Microarray analysis was performed to rule out copy number variations in the proband's 22q11.2q12 band point. The probands' karyotype revealed the inherited der(22)t(20;22)(q13;q11.2)dmat. Parental karyotype confirmed the mother as the carrier, with balanced non-Robertsonian translocation-46,XX,t(20;22)(q13;q11.2). CONCLUSION: The mother had a non-Robertsonian translocation t(20;22)(q13;q11.2) between chromosomes 20 and 22, which resulted in Emanuel syndrome in the proband. The most plausible explanation is 3:1 meiotic malsegregation, which results in the child inheriting derivative chromosome. The parental karyotype study aided in identifying the carrier of the supernumerary der(22), allowing future pregnancies with abnormal offspring to be avoided.

Role of nonsurgical periodontal therapy on leptin levels and total antioxidant capacity in chronic generalised periodontitis patients - A clinical trial.

INTRODUCTION: Periodontitis causes oxidative stress and reduce total antioxidant levels. The aim of this study was to determine the effect of non-surgical periodontal treatment on leptin levels and total antioxidant capacity in chronic periodontitis. MATERIALS AND METHODS: A total of 35 chronic periodontitis (ChP) patients and 35 systemically and periodontal healthy subjects were enrolled in this study. Further, the ChP group received nonsurgical periodontal therapy (NSPT). Leptin and total antioxidant capacity (TAOC) was measured in serum and saliva samples at baseline, 3 months and 6 months after non-surgical periodontal therapy. Clinical parameters measured were measured at baseline, 1, 3 and 6 months interval. RESULTS: The mean serum leptin and TAOC levels in control group were significantly higher compared to chronic periodontitis group (p < 0.05). The control group had lower mean salivary leptin levels and higher mean salivary TAOC levels as compared to periodontitis group(p < 0.05). Clinical parameters were improved in ChP group post therapy (p < 0.05). However, the periodontal treatment showed insignificant changes in serum and salivary leptin and TAOC levels. CONCLUSION: Chronic periodontitis is significantly associated with serum and salivary TAOC and leptin levels. Non surgical periodontal therapy didn't alter the local and systemic TAOC and leptin levels.

Chemopreventive and Anticancer Property of Selenoproteins in Obese Breast Cancer.

Obesity is a significant risk factor for various cancers including breast cancer resulting in an increased risk of recurrence as well as morbidity and mortality. Extensive studies on various pathways have been successful in establishing a biological relationship between obesity and breast cancer. The molecular classification of breast cancer includes five groups each having different responses to treatment. Increased levels of inflammatory cytokines seen in obese conditions drive the pro-proliferative pathways, such as the influx of macrophages, angiogenesis, and antiapoptotic pathways. Increased peripheral aromatization of androgens by aromatase increases the circulating estrogen levels which are also responsible for the association of obesity with breast cancer. Also, increased oxidative stress due to chronic low-grade inflammation in obese women plays an important role in carcinogenesis. Despite the availability of safe and effective treatment options for breast cancer, obese women are at increased risk of adverse outcomes including treatment-related toxicities. In the recent decade, selenium compounds have gained substantial interest as chemopreventive and anticancer agents. The chemical derivatives of selenium include inorganic and organic compounds that exhibit pro-oxidant properties and alter cellular redox homeostasis. They target more than one metabolic pathway by thiol modifications, induction of reactive oxygen species, and chromatin modifications to exert their chemopreventive and anticancer activities. The primary functional effectors of selenium that play a significant role in human homeostasis are selenoproteins like glutathione peroxidase, thioredoxin reductase, iodothyronine deiodinases, and selenoprotein P. Selenoproteins play a significant role in adipose tissue physiology by modulating preadipocyte proliferation and adipogenic differentiation. They correlate negatively with body mass index resulting in increased oxidative stress that may lead to carcinogenesis in obese individuals. Methylseleninic acid effectively suppresses aromatase activation thus reducing the estrogen levels and acting as a breast cancer chemopreventive agent. Adipose-derived inflammatory mediators influence the selenium metabolites and affect the proliferation and metastatic properties of cancer cells. Recently selenium nanoparticles have shown potent anticancer activity which may lead to a major breakthrough in the management of cancers caused due to multiple pathways. In this review, we discuss the possible role of selenoproteins as chemopreventive and an anticancer agent in obese breast cancer.