Clinical characteristics, management, outcome, and cost of stings and bites in patients admitted to a tertiary care teaching hospital.

AIM: The objective of this study was to identify the clinical epidemiology and medical cost of stings and bites at a tertiary care hospital in South India. SUBJECTS AND METHODS: The medical records of hospitalized patients in the tertiary care unit between 2016 and 2020 with the history of either being stung or bitten by insects were reviewed retrospectively. The patient's demographic details, clinical symptoms, treatment chart, expenditure details, and outcomes were collected in pre-structured case report forms. The data were analyzed using SPSS Version 20.0. RESULTS: A total of 66 patients were enrolled, with a mean age of 45.86 ± 23.37 years. The majority of the incidence was due to bee stings (61%). Anaphylaxis was reported in 38% of the cases, followed by acute kidney injury (10.6%). The cost of hospitalization was found to be higher for spider bites at 896.73 ± 1414.95 USD, followed by wasp stings at 989.81 ± 1185.57 USD. In patients with complications, the average cost of stings and bites was 438.81 ± 685.81 USD. Most of the patients received antibiotics (75.8%), followed by steroids (62.1%). CONCLUSION: Stings and bite injuries may appear harmless initially, but they can cause severe complications in unidentified cases and for those who do not seek urgent medical attention. Antibiotics and corticosteroids can help in the management of envenomation.

Analysis of time-domain indices, frequency domain measures of heart rate variability derived from ECG waveform and pulse-wave-related HRV among overweight individuals: an observational study.

Background: Research on the compatibility of time domain indices, frequency domain measurements of heart rate variability obtained from electrocardiogram (ECG) waveforms, and pulse wave signal (pulse rate variability; PRV) features is ongoing. The promising marker of cardiac autonomic function is heart rate variability. Recent research has looked at various other physiological markers, leading to the emergence of pulse rate variability. The pulse wave signal can be studied for variations to understand better changes in arterial stiffness and compliance, which are key indicators of cardiovascular health. Methods: 35 healthy overweight people were included. The Lead II electrocardiogram (ECG) signal was transmitted through an analog-to-digital converter (PowerLab 8/35 software, AD Instruments Pty. Ltd., New South Wales, Australia). This signal was utilized to compute Heart Rate Variability (HRV) and was sampled at a rate of 1024 Hz. The same AD equipment was also used to capture a pulse signal simultaneously. The right index finger was used as the recording site for the pulse signal using photoplethysmography (PPG) technology. Results: The participants' demographic data show that the mean age was 23.14 + 5.27 years, the mean weight was 73.68 +  7.40 kg, the mean body fat percentage was 32.23   +  5.30, and the mean visceral fat percentage was 4.60   +  2.0. The findings revealed no noticeable difference between the median values of heart rate variability (HRV) and PRV. Additionally, a strong correlation was observed between HRV and PRV. However, poor agreement was observed in the measurement of PRV and HRV. Conclusion: All indices of HRV showed a greater correlation with PRV. However, the level of agreement between HRV and PRV measurement was poor. Hence, HRV cannot be replaced with PRV and vice-versa.

Factors contributing to the adverse drug reactions associated with the dipeptidyl peptidase-4 (DPP-4) inhibitors: A scoping review.

BACKGROUND AND AIM: Adverse drug reactions are one of the contributors to increased hospital admission and length of hospital stay. Among the various antidiabetic agents prescribed, dipeptidyl peptidase-4 (DPP-4) inhibitors have gained wide recognition and shown more persistence than other novel hypoglycemic agents. We performed a scoping review to identify the risk factors contributing to the adverse drug reactions with DPP-4 inhibitors. METHODOLOGY: We followed Preferred Reporting Items for Scoping Review (PRISMA-ScR) Guidelines for reporting the findings. Data sources such as PubMed/MEDLINE, Scopus, Embase, and Cochrane were assessed. We included studies that reported the risk factors contributing to the DPP-4 inhibitor-associated adverse drug reactions. The Joanna Briggs Institute (JBI) critical appraisal checklist was used to assess the methodological quality of the studies. RESULTS: Of the 6406 studies retrieved, 11 studies met our inclusion criteria. Of these 11 studies, seven were post-marketing surveillance studies, one nested case-control study, one comparator cohort study, one food and drug administration (FDA) adverse event reporting system (FAERS)-based observational study, and one questionnaire-based cross-sectional survey study. A total of eight factors were identified that contributed to the DPP-4 inhibitor-associated adverse drug reactions. CONCLUSION: The included studies suggested age >65 years, females, grade 4 and 5 renal impairment, concomitant drugs, disease and drug therapy duration, liver disease, non-smokers, and non-hypertension as risk factors. Further studies should be conducted to provide insight into these risk factors so that the appropriate use of DPP-4 inhibitors in the diabetic population can be encouraged to improve the health-related quality of life. PROSPERO REGISTRATION: CRD42022308764.

Effect of physical activity promotion on adiponectin, leptin and other inflammatory markers in prediabetes: a systematic review and meta-analysis of randomized controlled trials.

AIMS: Inflammatory stage in prediabetes is associated with increase in level of adipokines and pro-inflammatory cytokines. Physical activity promotion considered as a first-line therapeutic strategy to treat prediabetes. We have conducted the systematic review and meta-analysis to strengthen the evidence on the impact of physical activity promotion on inflammatory markers in prediabetes. METHODS: Studies were identified using electronic search and manual search techniques by choosing keywords for prediabetes, physical activity and inflammatory marker. Randomized controlled trials on individuals diagnosed with prediabetes and provided intervention in the form of physical activity were included in this review. Adiponectin, leptin, C-reactive protein, interleukin-6 and tumour necrosis factor-α were the considered outcome measures. RESULTS: Our search retrieved 1,688 citations, 31 full-text articles assessed for eligibility of inclusion. Nine studies satisfied the pre-specified criteria for inclusion. Meta-analysis found that physical activity with or without dietary or lifestyle modification reduces level of leptin (MD-2.11 ng/mL, 95% CI -3.81 - -0.42) and interleukin-6 (MD -0.15 pg/mL, 95% CI -0.25--0.04). It has no effect on level of adiponectin (MD 0.26 µg/mL, 95% CI -0.42- 0.93), C-reactive protein (MD -0.05 mg/L, 95% CI -0.33-0.23) and tumour necrosis factor-α (MD 0.67 pg/mL, 95% CI -2.56-3.89). CONCLUSIONS: This review suggests that physical activity promotion with dietary and lifestyle modification may reduce the level of leptin and interleukin-6 but are uncertain if there is any effect on levels of adiponectin, C-reactive protein and tumour necrosis factor-α in the individuals with prediabetes.

Intra-Arterial Chemotherapy for Retinoblastoma in Infants ≤10 kg: 74 Treated Eyes with 222 IAC Sessions.

BACKGROUND AND PURPOSE: Intra-arterial chemotherapy for retinoblastoma has dramatically altered the natural history of the disease. The remarkable outcomes associated with a high safety profile have pushed the envelope to offer treatment for patients weighing ≤10 kg. The purpose was to determine the efficacy and safety of IAC infusions performed in infants weighing ≤10 kg with intraocular retinoblastoma. MATERIALS AND METHODS: A retrospective chart review was performed for patients diagnosed with retinoblastoma and managed with intra-arterial chemotherapy. RESULTS: The total study cohort included 207 retinoblastoma tumors of 207 eyes in 196 consecutive patients who underwent 658 intra-arterial chemotherapy infusions overall. Of these, patient weights were ≤10 kg in 69 (35.2%) and >10 kg in 127 (64.8%) patients. Comparison (≤10 kg versus >10 kg) revealed that the total number of intra-arterial chemotherapy infusions was 222 versus 436. Periprocedural complications were not significantly different (2 [0.9%] versus 2 [0.5%]; P = .49). Cumulative radiation exposure per eye was significantly lower in infants weighing ≤10 kg (5.0 Gym2 versus 7.7 Gym2; P = .01). Patients weighing ≤10 kg had a greater frequency of complete tumor regression (82.6% versus 60.9%; P = .02). Mean fluoroscopy time was not significantly different (7.5 versus 7.2; P = .71). There was a significant difference in the frequency of enucleation (16 [21.6%] versus 52 [39.1%]; P = .01). Patients weighing ≤10 kg had greater number of aborted procedures (12 [5.4%] versus 7 [1.6%]; P = .01). On multivariate analysis, weight ≤10 kg was not an independent predictor of complications or procedure failure. CONCLUSIONS: Intra-arterial chemotherapy in patients weighing ≤10 kg is a safe and effective treatment.

CpG-SNP site methylation regulates allele-specific expression of MTHFD1 gene in type 2 diabetes.

The interaction of genetic and epigenetic mechanisms is one of the underlying causes of phenotypic variability in complex diseases such as type 2 diabetes (T2D). To explore the influence of genetic and epigenetic changes in T2D, we examined the effect of methylation of CpG-SNP sites on allele-specific expression (ASE) in one-carbon metabolism pathway genes in T2D. Case-control study was conducted on 860 individuals (430 T2D and 430 controls). CpG-SNPs shortlisted through in silico analysis were genotyped using tetra ARMS PCR and validated using Sanger DNA sequencing. Global DNA methylation was carried out using RP-HPLC. Promoter DNA methylation and CpG site-specific methylation were carried out using bisulfite sequencing. mRNA expression and ASE were examined by SYBR green and TaqMan assay, respectively. Four exonic CpG-SNPs of MTHFD1, MTRR, and GGH genes were identified in folate pathway genes. Among these, MTHFD1 rs2236225 showed significant association with T2D independent of obesity, displayed ASE, and correlated with CpG-SNP site-specific methylation when compared with controls. Our results demonstrate that SNP rs2236225 in the CpG site of MTHFD1, which regulates allele-specific gene expression in PBMCs is methylation dependent and may perturb one-carbon metabolism pathway in T2D subjects.

Incidence of neurosensory disturbance in mandibular implant surgery - A meta-analysis.

AIM: Implantology has been widely accepted as the mainstay treatment for rehabilitating complete and partial edentulism. However, it is associated with some failures and complications, the most concerning being neurosensory disturbance. Although neurosensory disturbance has been extensively studied, the incidence and cause remains largely variable. Thus, the aim of this systematic review and meta-analysis was to evaluate the incidence, distribution, and recovery rate of neurosensory disturbance. SETTINGS AND DESIGN: This systematic review was conducted as per the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. A structured literature review was conducted using the following databases: PubMed, Science Direct, Cochrane, Ovid, and Google Scholar for reports related to neurosensory disturbance experienced after implant placement in the mandible. STATISTICAL ANALYSIS USED: Incidence and recovery rate for 100 person-years was calculated using the Poisson regression model. The risk difference of incidence between anterior and posterior implants was calculated with a random effects model. RESULTS: Electronic database search yielded 1589 articles; a total of nine articles were selected for the meta-analysis. The risk of neurosensory disturbance was estimated at 13.50/100 person-years (95% confidence interval (CI): 10.98-16.03), with a greater risk with anteriorly placed implants: -0.02 (95% CI: -0.21-0.16) (P = 0.05). The overall recovery rate was estimated at 51.30/100 person-years (95% CI: 31.2-71.4). CONCLUSIONS: Within the limitations of the study, it can be concluded that mandibular implant placement is associated with a considerable risk of neurosensory disturbance. A large proportion of these patients present with spontaneous recovery; however, clinicians must take necessary precautions to avoid such complications. More randomized controlled trials are required to quantify the effect of factors leading to altered sensation during implant placement.

Efficacy of a mouthwash containing essential oils and curcumin as an adjunct to nonsurgical periodontal therapy among rheumatoid arthritis patients with chronic periodontitis: A randomized controlled trial.

PURPOSE: The purpose of this study was to assess the efficacy of mouthwash containing essential oils and curcumin (MEC) as an adjunct to nonsurgical periodontal therapy on the disease activity of rheumatoid arthritis (RA) among RA patients with chronic periodontitis (CP). MATERIALS AND METHODS: A triple-blinded controlled trial was conducted among 45 female RA patients with CP randomized into three treatment groups as follows: Group A: scaling and root planing (SRP) with 0.2% chlorhexidine mouthwash as an adjunct (n = 15), Group B: SRP with MEC as an adjunct (n = 15), and Group C: SRP alone (n = 15). RA disease activity was assessed using erythrocyte sedimentation rate, serum C-reactive protein, serum anti-citrullinated protein antibody, and serum rheumatoid factor. Periodontal disease activity was assessed using plaque index, clinical attachment level (CAL), and pocket depth (PD). All parameters were recorded at baseline and 6 weeks thereafter. Data were assessed using one-way ANOVA and paired t-test. RESULTS: A significant reduction in periodontal and RA disease activity parameters was observed from baseline to 6 weeks following intervention (P < 0.05). The highest percentage of mean reduction in plaque index and RA parameters from baseline to 6 weeks was observed in Group B followed by Groups A and C. The highest percentage of mean reduction in PD and CAL was observed in Group A followed by Groups B and C (P < 0.001). CONCLUSION: This study reveals that MEC as an adjunct to SRP is effective in reducing the disease activity of RA and CP, thereby warranting the use of the same.

Prevalence of Foot Complications in People With Type 2 Diabetes Mellitus: A Community-Based Survey in Rural Udupi.

The objective of the study was to determine the prevalence of foot complications among people with type 2 diabetes mellitus in the rural part of Udupi district, Karnataka, India. A cross-sectional observational study design was conducted in the rural area of Udupi district. In the study, accredited social health activists were trained to screen people with type 2 diabetes mellitus for diabetic foot complications at a community level. Adults over 35 years of age were screened for the presence of type 2 diabetes mellitus by accredited social health activists who reside in the rural part of Udupi district. Participants with type 2 diabetes mellitus were included in the study. Blood glucose level was measured using a glucometer. Foot examination was done by visual inspection, monofilament, tuning fork, and pedal pulse. In the present study, 2110 among the total participants were found to have type 2 diabetes mellitus. The prevalence of musculoskeletal foot complications was 1218 (58%), vascular problem 466 (22.2%), sensory neuropathy 634 (30.2%), autonomic neuropathy 1729 (81.9%), ulcer 134 (6.38%), and infection 561 (26.7%) among people with type 2 diabetes mellitus. In the current study, we found 84.7% of people residing in rural Udupi had type 2 diabetes mellitus. Hence, there is a strong need to create awareness about diabetic foot care in these people.

Carbamazepine Induced Thrombocytopenia.

Antiepileptic Drugs (AEDs) are commonly associated with haematological disorders, including anaemia, thrombocytopenia, neutropenia and even bone marrow failure. Fatal disorders like aplastic anaemia are uncommon. On exploring through the literature, older AEDs are more associated with haematological alterations than newer AEDs, and careful monitoring is warranted especially with phenytoin, carbamazepine and valproate. The exact cause of these alterations is not established, though immune mechanisms and pharmacology of individual drugs are the proposed mechanisms, a further research along this path is underway. Of worth mentioning here, this predilection of older AEDs towards haematological disorders is pronounced in children compared to adults. We present here a case of congenital heart disease with history of brain abscess and seizures, on carbamazepine who presented to our hospital with toothache. Routine screening prior to tooth extraction revealed thrombocytopenia. Further evaluation revealed the association of carbamazepine and thrombocytopenia, which mandated discontinuation of drug and switching patient to alternative AED.

Barrier against water loss: relationship between epicuticular wax composition, gene expression and leaf water retention capacity in banana.

In the present study we examined 13 banana (Musa spp.) genotypes belonging to different genomic groups with respect to total leaf cuticular wax concentration, chemical composition, carbon chain length and their relationship with leaf water retention capacity (LWRC). A positive correlation between epicuticular wax content and LWRC clearly indicated that the cuticular wax plays an important role in maintaining banana leaf water content. The classification of hexane soluble cuticular wax components into different classes based on functional group and their association with LWRC showed that alcohol and ester compounds have a positive correlation. Further, the compounds with >C28 carbon chain length had a positive correlation with LWRC, indicating the role of longer carbon chain length in maintaining the water status of banana leaves. Also, the gene expression analysis showed higher expression of the wax biosynthetic genes FATB and KCS11 in higher wax load genotypes whereas lower expression was seen in low wax banana genotypes. Here, we report for the first time the compositional variations of cuticular wax in different banana genotypes, followed by their association with leaf water retention capacity. The results were also supported by variation in gene expression analysis of cuticular wax biosynthetic genes - FATB and KCS11.

Crystal structure of 10-[(3-oxo-3H-benzo[f]chromen-1-yl)meth-yl]-2-tri-fluoro-methyl-9a,10-di-hydro-benz[4,5]imidazo[1,2-a]pyrimidin-4(5aH)-one.

In the title compound, C25H14F3N3O3, the dihedral angle between the planes of the benz[4,5]imidazo[1,2-a]pyrimidine unit (r.m.s. deviation = 0.035 Å) and the benzochromene ring system (r.m.s. deviation = 0.106 Å) is 72.82 (5)°. In the crystal, mol-ecules are linked by C-H⋯O inter-actions, generating [010] C(9) chains. A weak aromatic π-π stacking inter-action [centroid-centroid separation = 3.5376 (15) Å] is also observed.

Crystal structure of 4-azido-methyl-6-tert-butyl-2H-chromen-2-one.

In the title compound, C14H15N3O2, one of the methyl C atoms of the tert-butyl group lies almost in the plane of the chromene ring system [deviation = -0.097 (2) Å], one lies above and one lies below [deviations = 1.460 (3) and 1.006 (3) Å, respectively]. The C-C-N-N torsion angle is 142.33 (17)°. In the crystal, moelcules are linked by weak C-H⋯O hydrogen bonds to generate C(6) chains propagating in the [010] direction.

Crystal structure of 4-azido-methyl-6-isopropyl-2H-chromen-2-one.

In the title mol-ecule, C13H13N3O2, the benzo-pyran ring system is essentially planar, with a maximum deviation of 0.017 (1) Å. In the crystal, weak C-H⋯O hydrogen bonds link mol-ecules into ladders along [010]. In addition, π-π inter-actions between inversion-related mol-ecules, with centroid-centroid distances in the range 3.679 (2)-3.876 (2) Å, complete a two-dimensional network parallel to (001).

Vibrational spectroscopy investigation using M06-2X and B3LYP methods analysis on the structure of 2-Trifluoromethyl-10H-benzo[4,5]-imidazo[1,2-a]pyrimidin-4-one.

In this study, the experimental and theoretical vibrational frequencies of a newly synthesized bioactive agent namely, 2-Trifluoromethyl-10H-benzo[4,5]-imidazo[1,2-a]pyrimidin-4-one (TIP) have been investigated. The experimental FT-IR (4000-400 cm(-1)) and Laser-Raman spectra (4000-100 cm(-1)) of the molecule in solid phase have been recorded. The theoretical vibrational frequencies and the optimized geometric parameters (bond lengths and bond angles) have been calculated using density functional theory (DFT/B3LYP: Becke, 3-parameter, Lee-Yang-Parr) and M06-2X (the highly parametrized, empirical exchange correlation function) quantum chemical methods with 6-311++G(d,p) basis set by Gaussian 09W software, for the first time. The assignments of the vibrational frequencies have been done by potential energy distribution (PED) analysis using VEDA 4 software. The theoretical optimized geometric parameters and vibrational frequencies have been found to be in good agreement with the corresponding experimental data and results in the literature. In addition, the highest occupied molecular orbital (HOMO) energy, the lowest unoccupied molecular orbital (LUMO) energy and the other related molecular energy values of the compound have been investigated using the same theoretical calculations.

2-Tri-fluoro-methyl-10H-benzo[4,5]imidazo[1,2-a]pyrimidin-4-one.

In the mol-ecule of the title compound, C11H6F3N3O, the three fused rings of the benzo[4,5]imidazo[1,2-a]pyrimidine unit are essentially coplanar, the maximum deviation from the mean plane being 0.096 (2) Å. In the crystal, N-H⋯O hydrogen bonds link the mol-ecules into chains running along the b-axis direction.

4-Bromo-methyl-6-tert-butyl-2H-chromen-2-one.

In the crystal structure of the title compound, C14H15BrO2, weak C-H⋯O inter-actions link the mol-ecules into zigzag chains extending along the c-axis direction. These chains are further assembled into (100) layers via π-π stacking inter-actions between inversion-related chromenone fragments [inter-planar distance = 3.376 (2) Å].

Synthesis and antimicrobial studies on novel sulfonamides containing 4-azidomethyl coumarin.

A series of new and novel coumarin-6-sulfonamides with a free C4-azidomethyl group have been synthesized as antimicrobials in three steps starting from 7-methyl-4-bromomethylcoumarin 1. The reaction of 1 with chlorosulfonic acid was found to yield the corresponding 6-sulfonylchloride 2, which when treated with sodium azide led to intermediate 3. The title sulfonamides 5a-y were obtained from the reaction of 3 with various aromatic amines 4 in refluxing benzene. The chemical structures of the compounds were elucidated by IR, NMR and LC-MS spectral data. All the synthesized compounds have been screened for their in vitro anti-bacterial and anti-fungal activities. Some of the compounds have been found to be active against both bacterial species at a concentration of 1 microg/mL.

Development of a bacterial screen for novel hypoxanthine-guanine phosphoribosyltransferase substrates.

The lack of de novo purine biosynthesis in many parasitic protozoans makes the enzymes in the salvage of purines attractive chemotherapeutic targets. Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) is a key enzyme for purine salvage and bacterial complementation screens for HGPRT inhibitors are known. The low KMS for purine bases makes purine analogs unattractive as competitive inhibitors for this enzyme. Despite the availability of many crystal structures of HGPRTs, it is only recently that selective inhibitors of the enzyme have been developed. Therefore, novel purine analogs which act as substrates for the HGPRT reaction and thereby inhibit downstream enzymes or get incorporated into the nucleotide pool are an attractive altenative for drug design. We have used a combination of two E. coli strains Sphi606 (ara, deltapro-gpt-lac, thi, hpt) and Sphi609 (ara, deltapro-gpt-lac, thi, hpt, pup, purH,J, strA) to identify inhibitors and substrates of HGPRT. E. coli Sphi609 is deficient in both de novo synthesis as well as salvage enzymes of purine nucleotide synthesis, while E. coli Sphi606 is deficient in salvage enzymes only. Hence, expression of functional HGPRTs in E. coli Sphi606 grown in minimal medium makes it susceptible to HGPRT substrates, which inhibit downstream processes. Growth of E. coli Sphi609 in minimal medium can be made conditional for the expression of a functional HGPRT and this growth would be susceptible to both HGPRT substrate analogs and inhibitors. A substance that strictly acts as an inhibitor will affect growth of transformed E. coli Sphi609 only. For this purpose, we compared the human and P. falciparum enzymes with known HGPRT substrate analogs. Our data with 6-mercaptopurine, 6-thioguanine and allopurinol show that these compounds act by being substrates for HGPRT. Our results with allopurinol suggest that it is a better substrate for P. falciparum HGXPRT than the human enzyme. Therefore, species-specific substrates can be tested out successfully in E. coli Sphi606. The formation of products from substrates like allopurinol lacking a labile proton at N7 raises the possibility that the deprotonation of substrates might occur at N9 rather than at N7 or a purine anion might be the true substrate for the reaction.

Unusual substrate specificity of a chimeric hypoxanthine-guanine phosphoribosyltransferase containing segments from the Plasmodium falciparum and human enzymes.

Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) catalyzes the phosphoribosylation of hypoxanthine and guanine by transferring the phosphoribosyl moiety from phosphoribosylpyrophosphate (PRPP) on to N9 in the purine base, resulting in the formation of inosine monophosphate (IMP) and guanosine monophosphate (GMP). Xanthine is an additional substrate for the Plasmodium falciparum HGXPRT. Our aim has been to elucidate structural features in HGPRT that govern substrate specificity. We have addressed this problem by engineering chimeric HGPRTs, which contain segments from both the parasite and human enzymes. Four chimeric enzymes were engineered (DS1-DS4), of which the chimeric enzyme, DS1, in which the first 49 residues of human HGPRT were replaced with the corresponding residues from the P. falciparum enzyme, exhibited additional specificity for xanthine. None of the switched residues forms a part of the purine or PRPP binding region in the available crystal structures of HG(X)PRTs. Our data on the chimeric enzyme DS1 provide the first evidence that the N-terminal approximately 50 amino acids, although not proximal to the active site in the crystal structure, can in fact modulate substrate specificity. DS1 exhibits a reduced k(cat) for hypoxanthine and guanine, while its K(m) for these oxopurine bases remains largely unchanged. Its specific activity for xanthine is comparable with hypoxanthine but five times more than that for guanine.