Surgical Lip Repositioning in Search of Aesthetics - A Case Series.

INTRODUCTION: The gummy smile (GS) or excessive gum visibility (EGV) is an aesthetic concern that affects an individual's attractiveness and personality. TREATMENT PLANNING: Lip Repositioning surgery (LRP) is a less invasive surgery that can be attributed to treating EGV due to hypermobile lip muscles or mild-to-moderate vertical maxillary excess (VME). Three patients went through LRP surgery by stripping overlying mucosa from the buccal vestibule, followed by suturing the lip mucosa to the mucogingival junction (MGJ), creating shallow vestibule and restricted muscle pull and reducing gingival visibility (GV) during a smile. FOLLOWUP: Three months of follow-up showed a satisfactory result with 3.67 ± 0.58 mm mean reduction in GV.

The Concerted Function of a Novel Class of Transcription Factors, ZBFs, in Light, Jasmonate and Abscisic Acid Signaling Pathways.

Several classes of transcription factors have been investigated in light signaling pathways that bind to the Light Responsive Elements (LREs) present in the promoters of light regulatory genes for transcriptional regulation. Some of these transcription factors have been shown to be binding to numerous promoters through genome-wide ChIP-on-chip (ChIP-chip) studies. Furthermore, through the integration of ChIP-seq and RNA-seq techniques, it has been demonstrated that a transcription factor modifies the expression of numerous genes with which it interacts. However, the mode of action of these transcription factors and their dependency on other regulators in the pathway has just started to be unraveled. In this review article, we focus on a particular class of transcription factors, ZBF (Z-box Binding Factor), and their associated partners within the same or other classes of transcription factors and regulatory proteins during photomorphogenesis. Moreover, we have further made an attempt to summarize the cross talk of these transcription factors with jasmonic acid, abscisic acid and salicylic acid mediated defense signaling pathways. This review offers an in-depth insight into the manner in which ZBFs and their interactors reshape cellular functions and plant behavior. The underlying principles not only contribute to a comprehensive understanding but also establish a framework for analyzing the interplay between early developmental events and hormone signaling, a regulation orchestrated by the ZBF family.

A critical evaluation of contents, labeling, and cost of hand sanitizers marketed in India during COVID-19 pandemic.

Background: Antiseptics were introduced a long time ago, but their significance was noteworthy during the COVID-19 pandemic. Hand sanitizer plays a pivotal role as a preventive measure. Multiple national authorities have advocated for the application of Alcohol-Based Hand Sanitizers (ABHS). During the pandemic, a surge in demand and limited supply prompted numerous manufacturers to ramp up production. Consequently, it is imperative to scrutinize the composition, labeling, and price of hand sanitizers. Aims and Objective: To assess the contents, labeling, and price of hand sanitizers available in the Indian market. Methodology: Hand sanitizers, both online and offline, marketed in India between May 2019 and May 2022 were included. Hand sanitizers by local manufacturers without labeling were excluded. Contents and labeling of hand sanitizers were evaluated as per World Health Organization (WHO) recommendations. Price was assessed as a percentage cost variation. Result: Out of 79, the majority (98.73%) were ABHS, and 28.20% of them met the recommended criteria for "Adequate" alcohol concentration. Ethyl alcohol emerged as the most prevalent (69.23%), often accompanied by emollients, humectants, fragrances, and color additives. Notably, 69.62% of the hand sanitizers featured comprehensive labeling, while incomplete labels lacked essential details under "Warning and Cautions." The average price of hand sanitizers was Rs 505.11 ± 255.36. Conclusion: Choosing ABHS with appropriate alcohol concentrations in line with recommendations is crucial. To ensure the proper and safe use of hand sanitizers, individuals should follow the instructions provided on the product labels; both manufacturers and regulators are responsible for adhering to standards for hand sanitizers made available to the public.

A Systematic Analysis of COVID-19 Clinical Trials Registered in the Clinical Trials Registry of India.

BACKGROUND: The Clinical Trials Registry - India (CTRI) database is a registry of various trials conducted in India and this study scrutinized the studies registered for COVID-19 from the database to detect patterns in trial design, appraising the target regions of therapies and comprehending the terrain of research endeavors. METHOD: This was a cross-sectional study that analyzed the registered trials for COVID-19 between March 2020 and September 2023. A trial search was conducted on the CTRI database to include all types of studies registered for COVID-19 with keywords like "COVID" and "coronavirus" and studies conducted on conditions other than COVID-19 were excluded. The data regarding study characteristics were noted under various sections in a preformed proforma. RESULTS: A total of 807 trials were taken for final analysis and there were about 344 prospective and 260 retrospective interventional trials, 35 prospective and 165 retrospective observational studies, and two prospective and one retrospective post-marketing surveillance study. The majority of the studies had duration under 12 months (91%). The maximum number of studies were registered from AYUSH (Ayurveda, Yoga and Naturopathy, Unani, Siddha, and Homeopathy) and allied therapies (n = 283), with about 104 types of interventions, followed by the drug category having 119 trials registered and about 57 types of interventions. Kabasura Kudineer and yoga in the AYUSH category, molnupiravir, colchicine, and favipiravir in the drug category, and tocilizumab and convalescent plasma among biologics were some common interventions used. The majority of trials did not mention the trial phase and declared it as not applicable (54%), whereas 15% were registered as phase 2 and 13% as phase 3. About 54% of the studies were randomized and randomized parallel-group design (20%) was the most common study design. Only 6% of the trials were post-graduate thesis and the majority of the trials (n = 535) denied sharing their individual participant data. Only 0.86% and 0.61% of the trials were terminated and suspended, respectively, denoting proper design and conduct of the trials. CONCLUSION: In the CTRI database, the majority of trials were prospective interventional studies, with a predominance of AYUSH therapies and drug interventions. Common interventions included Kabasura Kudineer and yoga in AYUSH, and molnupiravir, colchicine, and favipiravir in drugs. Most studies had durations under 12 months and randomized parallel-group design was the most common study design. The intention to use and promote an indigenous system of medicine looks promising in the absence of any definite therapy. A minute number of registered suspended and terminated trials might be a positive picture of meticulously designed and executed trials even during a pandemic situation in India.

Impact of positive airway pressure therapy on intraocular pressure in obstructive sleep apnea: A systematic review.

BACKGROUND: Positive airway pressure (PAP) therapy has been reported to have variable effect on intraocular pressure (IOP) in patients with obstructive sleep apnea (OSA) . The objective of this review is to present a qualitative assessment of available literature on impact of PAP on IOP in patients of OSA.Method: Online databases were searched for relevant articles up to September 2023. It included randomized control trial (RCT), prospective observational study, case control study, cross-sectional study, published abstract having relevant information. The comparator group consisted of OSA patients not receiving the PAP therapy or the pre-PAP IOP. Studies reporting change in IOP immediately after PAP use, at 1 month and at 1 year of PAP use were included. For quality assessment Cochrane Risk of Bias tool version 2 and NIH study quality assessment tool for Before-After (Pre-Post) Studies with No Control Group was used.Result: In this systematic review of ten clinical studies with 191 patients of OSA, use of continuous positive airway pressure (CPAP) therapy led to an immediate increase in IOP but it was not significantly different from non-CPAP users. One month and 1 year of CPAP use led to a significant increase in IOP from the baseline value. CONCLUSION: The available albeit limited evidence suggests that CPAP use, particularly at higher pressures, is linked to an elevation in IOP. However, high quality evidence from well-designed RCTs is needed to confirm or refute this findings.

A systematic review and meta-analysis of tolerability, cardiac safety and efficacy of inclisiran for the therapy of hyperlipidemic patients.

BACKGROUND: Dyslipidaemia is a crucial risk factor for cardiovascular morbidity and mortality. A short interfering RNA called inclisiran diminishes circulating levels of PCSK9 and LDL-C by hindering PCSK9 translation in the liver. METHODS: RCTs were electronically searched on PubMed, Cochrane Central, and Clinicaltrials.gov to assess the safety and efficacy of inclisiran. Cochrane Review Manager 5 was used to conduct the pooled analysis. Risk of bias was assessed and GRADE pro-GDT was utilized, respectively, to estimate the methodological quality and overall quality of evidence. RESULTS: Of 218 records screened, four studies were included with 2203 participants in inclisiran and 1949 participants in the placebo group. Inclisiran was related to non-significant elevated risk of total adverse events[RR = 1.05(0.98,1.12), p = 0.16; I2 = 53%], non-serious adverse events[RR = 1.09(0.97,1.22),p = 0.15;I2 = 61%] and all-cause mortality[RR = 1.01(0.60,1.70),p = 0.97;I2 = 0%] whereas a lower risk of serious adverse events[RR = 0.94(0.70,1.25),p = 0.67;I2 = 73%], cardiac disorders [RR = 0.87(0.66,1.15),p = 0.33;I2 = 42%] and Major adverse cardiovascular events(MACE)[RR = 0.79(0.62,1.00),p = 0.05; I2 = 0%] as compared to placebo. Inclisiran was also linked to a substantial decline in the percentage of LDL-C, PCSK9, total cholesterol, and Apo B. CONCLUSION: The pooled analysis of the existing evidence shows that inclisiran showed reduced risk of MACE along with excellent efficacy in managing dyslipidemia. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifiers are NCT03399370, NCT03397121, NCT03400800, and NCT02597127.

Elevated cholesterol levels have been found to be associated with a high risk of heart disease and associated deaths. There are various classes of drugs used to control high low-density lipoprotein cholesterol (LDL-C) levels in blood yet appropriate control and patient compliance, to regular cholesterol-lowering drugs have been an issue. Inclisiran, a novel drug for reducing the LDL-C levels in serum can be given every six months as an effective therapy to minimize the levels of LDL-C in serum. This study was designed to assess the safety and effectiveness of inclisiran in patients with hyperlipidemia. Inclisiran was found to have a non-significant elevated risk of total adverse events, non-serious adverse events, and all-cause mortality. The majority of the adverse events seem to be non-serious and tolerable. There was an observed non-significant lower risk of serious adverse events, cardiac disorders, and significantly reduced risk of major adverse cardiovascular events when compared to placebo. Inclisiran was also linked to a significant decline in the percentage of LDL-C, PCSK9, total cholesterol, and Apo B in patients with hyperlipidemia. With the evidence available at present, inclisiran seems an efficacious and well-tolerated therapeutic strategy to manage elevated cholesterol and LDL-C levels. However, long-term, large cardiovascular outcome trials are required to conclude on the drug's cardiovascular and overall safety.

Effectiveness of ayurvedic formulation, NAOQ19 along with standard care in the treatment of mild-moderate COVID-19 patients: A double blind, randomized, placebo-controlled, multicentric trial.

BACKGROUND: Medicines in indigenous systems such as Ayurveda have strong antimicrobial activity but double-blind randomized control trials are infrequent in this system of medicine. The efficacy of a new ayurvedic formulation was evaluated during the pandemic. METHODS: 150 mild-moderate COVID-19 patients were enrolled and randomized in 1:1 to NAOQ19 and placebo group. RT-PCR was done on Day 3, 5 and 7. CBC, CRP, LFT, and KFT were assessed at baseline and exit. Duration of hospital stay was noted and clinical assessment was also performed. RESULT: The results demonstrated more people turning RT-PCR negative in the NAOQ19 group compared to the placebo group on day 3 (p-value = 0.033). The mean time duration to turn RT-PCR negative was significantly lower in the NAOQ19 group (4.6 days) compared to placebo group (5.2 days) (p-value = 0.018). There was significant reduction in hospital stay among patients in the NAOQ19 arm who were discharged earlier (5.6 days) compared to placebo group (6.4 days) (p-value = 0.046). Patients in NAOQ19 arm did not show any adverse life-threatening events. CONCLUSION: The ayurvedic preparation given along with standard of care therapy reduced the duration of hospital stay and there was earlier conversion to RT-PCR negative.The integrated approach can help to reduce patient workload in the hospitals as well as limit the transmission of the virus in the community. STUDY REGISTRATION: CTRI/2021/05/033790.

Bexagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, for improvement of glycemia in type 2 diabetes mellitus: a systematic review and meta-analysis.

OBJECTIVES: This study assessed the clinical safety and efficacy of bexagliflozin, a sodium-glucose cotransporter 2(SGLT2) inhibitor, in managing glycemia among patients with type 2 diabetes mellitus (T2DM). AREAS COVERED: We examined RCTs with T2DM comparing the clinical effectiveness and safety of 20 mg once daily oral dose of bexagliflozin with placebo for managing glycemia till 28 May 2023, published on databases like ClinicalTrials.gov, PubMed, Embase, and Cochrane Library. Furthermore, reduction of body weight, fasting plasma sugarr(FPG), systolic blood pressure (SBP) and the percentage of individuals who achieved glycated hemoglobin (HbA1c) of < 7% from baseline were also evaluated. The Review Manager 5 was utilized to investigate the retrieved data. EXPERT OPINION: We involved eight RCTs. Bexagliflozin was significantly superior in reducing HbA1c[least squares mean difference(LSMD) = -0.45,95% confidence interval (CI =-0.55 to -0.34,p < 0.00001], FPG [LSMD= -1.37, 95%CI =-1.73 to -1.00, p < 0.00001], body weight (LSMD= -1.77, 95%CI =-2.44 to-1.10, p < 0.00001), and SBP(LSMD= -4.11,95%CI = -6.18 to -2.03,p = 0.0001) in comparison to placebo. The safety outcomes of bexagliflozin were consistent with the placebo arm. This study concluded that bexagliflozin seems to be a promising oral anti-diabetic drug for enhancing glycemic management in adult patients with T2DM.

Bexagliflozin, a novel hypoglycemic agent, is an extremely effective SGLT2 inhibitor developed by TheracosBio to manage glycemia in T2DM. The United States Food and Drug Administration (USFDA) granted first approval of bexagliflozin on 20 January 2023, for usage as an adjunctive therapy agent alongside lifestyle changes and exercise in T2DM. All included RCTs have investigated the therapeutic efficacy and safety of bexagliflozin 20 mg concerning glycemic and extra-glycemic effects in T2DM. Bexagliflozin 20 mg significantly reduces HbA1c, FPG (glycemic effect), body weight, and SBP (extra-glycemic effect) compared to the placebo arm in T2DM. Safety data show that bexagliflozin was comparable to placebo arm and polyuria, urinary tract infection (UTI), nasopharyngitis or upper respiratory tract infection (URTI), hypoglycemia, nausea, and diarrhea were the most common non-serious adverse effects. Bexagliflozin 20 mg seems to be an effective SGLT2 inhibitor compared to the placebo arm to manage glycemia in patients with T2DM along with favorable extra-glycemic effects.

Are we providing complete drug information to its users? Status of information adequacy of package insert in India.

Background: Package inserts (PIs) serve detailed information on drug products to the users and primary care physicians, so information should be accurate, reliable, and as per the regulatory guidelines. The study aims to analyze the information adequacy of the PIs available in the Indian market as per Drug and Cosmetic Rule 1945 and US Food and Drug Administration criteria. Materials and Methods: A cross-sectional study was conducted on PIs collected from accessible pharmacy stores. Information provided was recorded as per criteria, and total information adequacy score (IAS) and information deficiency (IDS) score were calculated. The association of factors like single-drug/FDCs, a company of origin Indian/multinational, and route of administration (ROA) with IDS was statistically analyzed. Results: Of 120 PIs, 60%, 86.66%, and 73% were single-drug, prescription-drug, and drugs by Indian manufacturers, respectively. Most PIs provided generic names, ROA, and indications for use. 85%, 12%, 29.16%, and 3.33% provided information on PIs on the ability to drive, drug-food interactions, drug-drug interactions, and addiction potential, respectively. Lacking area was information on use in pediatrics-geriatrics (30%), excipients (28.3%), preclinical (15.83%), post-surveillance data (18.33%), and approval date (2.5%). There was a statistically significant difference between pharmaceutical score (3.22 vs 4.12), therapeutic score (11.5 vs 13.18), and total IAS (14.78 ± 3.39 vs 17.31 ± 2.33) of Indian and multinational companies. IDS was statistically significantly different in both pharmaceutical and therapeutic categories for single-drug vs FDCs (P = 0.00001), OTC vs prescription drugs (P < 0.05), and Indian vs multinational companies' PIs (P = 0.00001). Conclusion: Numerous facets of information are lacking in PIs, and they do not impart whole information, especially of Indian origin, as per objective IDS.

Daridorexant as a novel pharmacotherapeutic approach in insomnia: a systematic review and meta-analysis.

BACKGROUND: Insomnia is a multi-factorial disorder with conventional treatment options that are not satisfactory for many patients. This metaanalysis analyzed the safety and efficacy of daridorexant. METHODS: An electronic database search for RCTs was conducted on Medline via PubMed, Cochrane, and Clinicaltrials.gov using the terms 'Daridorexant,' 'RCT,' 'Insomnia' trials evaluating the efficacy and/or safety of daridorexant for insomnia were included. The data were synthesized using Cochrane review manager version 5.4.1. Cochrane risk of bias 2.0 tool and GRADEpro-GDT were used to assess the methodological and evidence quality, respectively. RESULTS: Of 109 searched studies, four trials were included. The risk of treatment-emergent adverse events with 25 mg daridorexant [risk ratio (RR) = 1.12 (0.88, 1.43), p = 0.36; I2 = 0%] and 50 mg daridorexant [RR = 1.25 (0.88, 1.79), p = 0.22; I2 = 28%] and serious adverse events with 25 mg [RR = 0.86 (0.23, 3.19), p = 0.82, I2 = 56%] and 50 mg [RR = 1.32 (0.29, 6.08), p = 0.72, I2 = 52%] was comparable to placebo [Moderate quality evidence]. Risk of nasopharyngitis was also comparable to placebo. The efficacy parameters like wake after sleep onset, latency to persistent sleep, and subjective total sleep time showed significant improvement with daridorexant. The risk of bias is low for three studies and some concern for one. CONCLUSION: Daridorexant is a safer and efficacious agent for induction and maintenance of sleep for chronic insomnia. PROSPERO: The registration number is CRD42022335233. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifiers are NCT03575104, NCT03545191, NCT03679884, and NCT02839200).

Detection of Protein-Protein Interactions Utilizing the Split-Ubiquitin Membrane-Based Yeast Two-Hybrid System.

Identifying the interactors of a protein is a key step in understanding its possible cellular function(s). Among the various methods that can be used to study protein-protein interactions (PPIs), the yeast two-hybrid (Y2H) assay is one of the most standardized, sensitive, and cost-effective in vivo methods available. The most commonly used GAL4-based Y2H system utilizes the yeast transcription factor GAL4 to detect interactions between soluble proteins. By virtue of involving a transcription factor, the protein-protein interactions occur in the nucleus. The split-ubiquitin Y2H system offers an alternative to the traditional GAL4-based Y2H system and takes advantage of the reconstitution of split-ubiquitin in the cytosol to identify interactions between two proteins. Moreover, new membranous and soluble interacting partner(s) can be identified by screening a target protein against proteins produced from a cDNA library using this system.

Metformin: A Review of Potential Mechanism and Therapeutic Utility Beyond Diabetes.

Metformin has been designated as one of the most crucial first-line therapeutic agents in the management of type 2 diabetes mellitus. Primarily being an antihyperglycemic agent, metformin also has a plethora of pleiotropic effects on various systems and processes. It acts majorly by activating AMPK (Adenosine Monophosphate-Activated Protein Kinase) in the cells and reducing glucose output from the liver. It also decreases advanced glycation end products and reactive oxygen species production in the endothelium apart from regulating the glucose and lipid metabolism in the cardiomyocytes, hence minimizing the cardiovascular risks. Its anticancer, antiproliferative and apoptosis-inducing effects on malignant cells might prove instrumental in the malignancy of organs like the breast, kidney, brain, ovary, lung, and endometrium. Preclinical studies have also shown some evidence of metformin's neuroprotective role in Parkinson's disease, Alzheimer's disease, multiple sclerosis and Huntington's disease. Metformin exerts its pleiotropic effects through varied pathways of intracellular signalling and exact mechanism in the majority of them remains yet to be clearly defined. This article has extensively reviewed the therapeutic benefits of metformin and the details of its mechanism for a molecule of boon in various conditions like diabetes, prediabetes, obesity, polycystic ovarian disease, metabolic derangement in HIV, various cancers and aging.

Association Study of Transforming Growth Factor Beta 1 + 29 T/C exon 1 Polymorphism in Breast Cancer Patients from North Indian Population.

BACKGROUND: TGFB1 cytokine is involved in normal mammary epithelial development as well as in breast tumorigenesis. It has role in both breast tumor suppression and progression. TGFB1 gene has several single nucleotide polymorphisms (SNPs) many of which modulate the activity of TGFB1. Our aim in this study was to analyze TGFB1 + 29 polymorphism in breast cancer individuals from North Indian population. METHODS: TGFB1 + 29 T/C polymorphism was analyzed using Sanger sequencing in 285 breast cancer patients and age matched 363 healthy controls from North Indian population. Next, transcript expression of 13 apoptotic genes, TRAIL, DR4, DR5, DcR1, DcR2, Bcl2, cytochrome c, Casp8L, Casp8, FlipS, FlipL, Casp3s and Casp3 were carried out in 77 breast tumor tissues obtained from 77 individuals. RESULTS: TGFB1 + 29 CC genotype provided protection against the development of breast cancer (P = 0.012). This was mainly attributable to higher age group (> 45 years) women (P = 0.016). Individuals having CC protector genotype showed significantly higher expression of TGFB1 transcript compared to the TT and TC risk genotypes (P = 0.044). Furthermore, we observed that TGFB1 + 29 CC genotype showed increased TRAIL mediated apoptosis via the extrinsic pathway in breast tumor patients with age greater than 45 years (P = 0.027). CONCLUSION: TGFB1 + 29 homozygous mutant CC genotype is related to protection against breast cancer in North Indian women population greater than 45 years of age.

Indian Essential Medicine List for Children: Time to Revisit.

BACKGROUND: The majority of the under five mortality rate (U5MR) in India were due to treatable causes and could have been prevented by providing quality medicines. Availability and affordability of medicine can be improved by the introduction of essential medicine concepts. PURPOSE: The current study was carried out to compare the latest edition of the WHO essential medicine list for children (EMLc) with that of Indian EMLc to determine the need to update the Indian EMLc. METHODS: A descriptive observational study was carried out in the Department of Pharmacology of a tertiary care hospital. The latest edition of WHO EMLc (8th) was compared with the latest edition of Indian EMLc (1st) in terms of inclusion of categories or subcategories, the number of medicines in each category or subcategories, medicines which are present in WHO EMLc but missing in Indian EMLc and vice versa. RESULTS: In total 134 medicines are present in Indian EMLc as compared to 350 medicines in WHO EMLc. The important categories which are completely missing in Indian EMLc are medicines for reproductive health and perinatal care, peritoneal dialysis solution, medicines for mental and behavioral disorders, and medicines for diseases of joints. The important medicines which are not included in Indian EMLc are bedaquilline, delaminid, cefixime, piperacillin+tazobactum, vancomycin, acyclovir, azathioprine, cisplatin, and filgrastim. Important vaccines including rotavirus, cholera, hepatitis, and typhoid vaccine are not mentioned in Indian EMLc. CONCLUSION: There is an urgent need to update the Indian EMLc in order to promote access to pediatric medicine and facilitate the rational use of medicines.

Multidrug-Resistant TB (MDR-TB) and Extensively Drug-Resistant TB (XDR-TB) Among Children: Where We Stand Now.

Drug-resistant tuberculosis (DR-TB) has continued to be a global health cataclysm. It is an arduous condition to tackle but is curable with the proper choice of drug and adherence to the drug therapy. WHO has introduced newer drugs with all-oral shorter regimens, but the COVID-19 pandemic has disrupted the achievements and raised the severity. The COVID-19 controlling mechanism is based on social distancing, using face masks, personal protective equipment, medical glove, head shoe cover, face shield, goggles, hand hygiene, and many more. Around the globe, national and international health authorities impose lockdown and movement control orders to ensure social distancing and prevent transmission of COVID-19 infection. Therefore, WHO proposed a TB control program impaired during a pandemic. Children, the most vulnerable group, suffer more from the drug-resistant form and act as the storehouse of future fatal cases. It has dire effects on physical health and hampers their mental health and academic career. Treatment of drug-resistant cases has more success stories in children than adults, but enrollment for treatment has been persistently low in this age group. Despite that, drug-resistant childhood tuberculosis has been neglected, and proper surveillance has not yet been achieved. Insufficient reporting, lack of appropriate screening tools for children, less accessibility to the treatment facility, inadequate awareness, and reduced funding for TB have worsened the situation. All these have resulted in jeopardizing our dream to terminate this deadly condition. So, it is high time to focus on this issue to achieve our Sustainable Development Goals (SDGs), the goal of ending TB by 2030, as planned by WHO. This review explores childhood TB's current position and areas to improve. This review utilized electronic-based data searched through PubMed, Google Scholar, Google Search Engine, Science Direct, and Embase.

Chloroplast Engineering: Fundamental Insights and Its Application in Amelioration of Environmental Stress.

Chloroplasts are specialized organelle that are responsible for converting light energy to chemical energy, thereby driving the carbon dioxide fixation. Apart from photosynthesis, chloroplast is the site for essential cellular processes that determine the plant adaptation to changing environment. Owing to the presence of their own expression system, it provides an optimum platform for engineering valued traits as well as site for synthesis of bio-compounds. Advancements in technology have further enhanced the scope of using chloroplast as a multifaceted tool for the biotechnologist to develop stress-tolerant plants and ameliorate environmental stress. Focusing on chloroplast biotechnology, this review discusses the advances in chloroplast engineering and its application in enhancing plant adaptation and resistance to environmental stress and the development of new bioproducts and processes. This is accomplished through analysis of its biogenesis and physiological processes, highlighting the chloroplast engineering and recent developments in chloroplast biotechnology. In the first part of the review, the evolution and principles of structural organization and physiology of chloroplast are discussed. In the second part, the chief methods and mechanisms involved in chloroplast transformation are analyzed. The last part represents an updated analysis of the application of chloroplast engineering in crop improvement and bioproduction of industrial and health compounds.

Clinical efficacy and safety of dasiglucagon in severe hypoglycemia associated with patients of type 1 diabetes mellitus: a systematic review and meta-analysis.

BACKGROUND AND AIMS: This study was carried out to analyze the clinical safety and efficacy of dasiglucagon for the treatment of severe hypoglycemia in patients with type 1 diabetes mellitus (T1DM). METHODS: We searched PubMed, Cochrane Library, Embase, and ClinicalTrials.gov for randomized controlled trials (RCTs) investigating the safety and efficacy of dasiglucagon in the treatment of hypoglycemia in patients with T1DM. Furthermore, time required for the recovery of blood glucose or to elevate blood glucose levels ≥20.0 mg/dL from baseline was analyzed. The data was analyzed in version 5.4 of review manager 5 (RevMan). RESULTS: We included five published RCTs with a total of 347 patients . Dasiglucagon was significantly better at reducing the recovery time of blood glucose or increasing blood glucose levels 20.0 mg/dL from baseline compared to glucagon [pooled mean difference (PMD): 1.08%, 95% confidence interval (CI): 1.96 to 0.21, p = 0.02] and placebo (PMD: - 23.30%, 95% CI: 23.97 to 22.63, p < 0.00001). Overall, the safety outcome results of dasiglucagon were comparable with the native glucagon. CONCLUSIONS: Dasiglucagon appears to be a promising human glucagon analog peptide for the safe and effective treatment of severe hypoglycemia in T1DM.

Therapeutic Application of Lithium in Bipolar Disorders: A Brief Review.

Bipolar affective disorder includes Bipolar Disease (BD) and Bipolar Spectrum Disorder (BSD). The prevalence of BSD, BD-I, BD-II, and subthreshold BD globally is estimated to be about 3.1%, 1.5%,0.03%, and 1.6%, respectively. BD is a multidimensional disease that exhibits a range of moods of mania, hypomania, and depression. The disease is chronic, complex, and fatal, with a high possibility of reappearance, infirmity, social incompetence, and felo-de-se. Managing emotional disruption, negative neuropsychology, physiology, and immunology is a challenge. This review focuses on therapeutic benefits, adverse drug reactions, and pharmacological intervention for BD and BSD, in particular lithium. Long-term management of BD with a single medication is ineffective and therefore, not recommended. It is advised to use multiple agents for treatment instead. Medications include mood stabilizers (lithium and anticonvulsants), atypical antipsychotics, and antidepressants. Along with medication provision, psychotherapy is of great significance for BD patients. The review was conducted on recent available scientific literature through the electronic database like Embase, ScienceDirect, Google Scholar, and PubMed using keywords like 'Bipolar Disease,' 'Bipolar Disease Therapeutics,' 'Bipolar Disease and Psychotherapy' to highlight the possible effective means of management of this disease of mood instability.

A systematic review of mucormycosis cases in COVID-19: Is it an unholy trilogy of COVID-19, diabetes mellitus, and corticosteroids?

Background: A significant surge of cases of mucormycosis is seen in individuals with COVID-19 with presence of diabetes mellitus (DM) and usage of corticosteroids. We aim to conduct a systematic analysis of the cases involving presence of mucormycosis and to find out its association with COVID-19, diabetes mellitus, and corticosteroids. Method: The electronic records of PubMed, Google Scholar, and Science Direct were searched for the case reports and case series that reported mucormycosis in association of COVID-19. The particulars of each case report and case series were retrieved, stored and analyzed. Results: In this study, 476 cases of mucormycosis were reported. In 346 cases of mucormycosis, the patients were found to be COVID-19 positive. The incidence of diabetes Mellitus (DM) was 67.01%. Corticosteroid was administered in 57.77% of the cases. Mortality was reported in 36.34% of the cases. Conclusion: An immunosuppressive environment created due to the COVID-19, diabetes mellitus, and extensive use of corticosteroid provide a suitable background for the increased incidence of mucormycosis. The COVID task force should adopt an aggressive multidisciplinary approach to optimize the use of corticosteroids and maintain glucose in the optimal range.