Environmentally friendly protocol for the determination of sitagliptin phosphate in pharmaceutical preparations and biological fluids using l-tyrosine as a fluorescence probe.

A responsive spectrofluorometric method was developed for the determination of sitagliptin phosphate using l-tyrosine as a fluorescence probe. The fluorescence intensity of l-tyrosine was quenched with sitagliptin phosphate. The fluorescence intensity was recorded at 307 nm using a 272 nm excitation wavelength. The calibration plot between fluorescence intensity and the concentration of drug was linear in the range of 0.1 to 2.0 mM with a good correlation value of 0.997. The limit of detection and quantification were established to be 3.7 × 10-4 and 1.23 × 10-3  mM, respectively. Commonly used excipients did not interfere with sitagliptin phosphate measurement. The proposed method was used to measure the sitagliptin phosphate in its standard type, dosage form, and biological samples. The percent recovery ranged from 97.41-103.36%. The static quenching was shown to be responsible for quenching as indicated by the Stern-Volmer plot. The method was validated using ICH guidelines and profitably applied for the content uniformity test, resulting in a high percent recovery and small relative standard deviation. The proposed approach is effortless, susceptible, selective, economic, and provides a high precision and accuracy, and can be used to determine sitagliptin phosphate in the pharmaceutical industry.

Formation of 3-Aminophenols from Cyclohexane-1,3-diones.

meta-Aminophenols are formed by the action of DBU on 3-amino-2-chlorocyclohex-2-en-1-ones at room temperature in MeCN. The chloro compounds are generated by treating 3-aminocyclohex-2-en-1-ones with the easily prepared halogenating agent BnNMe3·ICl2 in MeOH-CH2Cl2. The amino group must carry two substituents, either two aryl, one aryl and one alkyl, or two alkyl groups; 3-aminocyclohex-2-en-1-ones of this type are readily made from cyclohex-2-en-1-one and a primary or secondary amine.

Determination of cefixime in pure form, in pharmaceutical products and biological samples through fluorescence quenching of eosin Y.

A simple, economic and validated spectrofluorimetric method was developed to assay cefixime (CFX). The technique relies on the quenching effect of CFX on the fluorescence intensity of eosin Y in the presence of acetate buffer pH 3.4 to produce an ion-pair complex that is measured at 549 nm using an excitation wavelength of 300 nm. Reaction-influencing factors were carefully investigated and optimized. The fluorescence quenching value was linear to the CFX concentration in the range 0.2-40 µg/ml with a correlation coefficient of 0.992. The calculated limit of detection and limit of quantification were found to be 0.00242 and 0.0080 µg ml-1 , respectively. The selectivity of the method was confirmed by studying the effects of excipients and no interference was distinguished. The developed method was used to determine CFX in marketable products and in biological samples. To validate the method, directives of the International Conference on Harmonization were applied and per cent recoveries obtained ranged from 95.30 to 102.50% for pharmaceutical products and from 97.00 to 103.00% for biological fluids.

Identification of a novel homozygous TRAPPC9 gene mutation causing non-syndromic intellectual disability, speech disorder, and secondary microcephaly.

TRAPPC9 gene mutations have been linked recently to autosomal recessive mental retardation 13 (MRT13; MIM#613192) with only eight families reported world-wide. We assessed patients from two consanguineous pedigrees of Pakistani descent with non-syndromic intellectual disability and postnatal microcephaly through whole exome sequencing (WES) and cosegregation analysis. Here we report six further patients from two pedigrees with homozygous TRAPPC9 gene mutations, the novel nonsense mutation c.2065G>T (p.E689*) and the previously identified nonsense mutation c.1423C>T (p.R475*). We provide an overview of previously reported clinical features and highlight common symptoms and variability of MRT13. Common findings are intellectual disability and absent speech, and frequently microcephaly, motor delay and pathological findings on MRI including diminished cerebral white matter volume are present. Mutations in TRAPPC9 should be considered in non-syndromic autosomal recessive intellectual disability with severe speech disorder.

Driving Under the Influence: An Unusual Case of Basal Ganglia Stroke Misdiagnosed as Intoxication.

Traditionally, strokes are characterized by negative symptoms, including contralateral hemiparesis, facial paralysis, and sensory loss in the upper face and upper extremities. Strokes rarely cause movement disorders such as ballismus, a severe chorea characterized by brief, sudden dance-like movements. Early identification of non-traditional stroke symptoms and risk factors for cerebrovascular disease is vital in providing timely treatment and improving patient outcomes. Our case highlights an uncommon complication of stroke and the need to use advanced imaging modalities, including MRI, to identify brain lesions when other testing is negative. This report adds to the body of literature highlighting ballismus, a rare presentation of stroke, and the lessons learned from managing this case.

Prodromal Symptoms in Patients Presenting With Myocardial Infarction.

Background Prodromal symptoms are warning signs of an impending acute myocardial infarction (AMI). However, they are often overlooked by both patients and primary clinicians, and little is known about them. Therefore, this study aims to assess the frequency and types of prodromal symptoms in patients with AMI. Methodology This descriptive cross-sectional study was conducted at a tertiary care cardiac center. Consecutive patients diagnosed with AMI within the last week were evaluated for prodromal symptoms. The prodromal symptoms included chest pain, chest heaviness, chest burning, palpitations, fatigue, sleep disturbance, shortness of breath (SOB), dizziness, anxiety, sudden heat or cold, back pain, and vomiting. Results In a sample of 242 patients, 79.6% were males, with a mean age of 54.7 ± 12.2 years, and 179 (74%) were diagnosed with ST-segment elevation myocardial infarction (STEMI). Among the participants, 142 (58.7%) showed no prodromal symptoms. Among those with prodromal symptoms, chest pain was the predominantly reported prodromal symptom with a frequency of 68%, followed by chest heaviness at 44%, palpitations at 42%, shortness of breath at 34%, and chest burning at 27%. Unusual fatigue in 23% and sleep disturbance in 22% of the patients were also reported. Conclusion The findings from this study revealed that prodromal symptoms were present in a significant proportion of acute myocardial infarction (MI) cases, with more than four in 10 patients reporting these early warning signs. The most commonly observed prodromal symptoms were chest pain, chest heaviness, palpitations, shortness of breath, and chest burning. The timely identification of these symptoms can help prevent infarction, thereby reducing the burden of heart failure and other related mortalities.

Anticoccidial activity of herbal complex in broiler chickens challenged with Eimeria tenella.

The objective of the present study was to evaluate the anticoccidial effect of different concentrations of the herbal complex of 4 plants (leaves of Azadirachta indica and Nicotiana tabacum, flowers of Calotropis procera and seeds of Trachyspermum ammi) in broiler chickens in comparison with amprolium anticoccidial. Three concentrations (2 g, 4 g and 6 g) of herbal complex were given to the experimental groups once a day and amprolium (at the dose rate of 125 ppm) was given orally in drinking water from the 14th to the 21st days of age. One group was kept as infected, non-medicated control and one as non-infected, non-medicated control. All groups were inoculated orally with 75,000 sporulated oocysts on the 14th day of age except the non-infected, non-medicated control. Among herbal complex medicated groups, the maximum anticoccidial effect was seen in the group medicated with 6 g herbal complex followed by 4 g and 2 g herbal complex medicated groups. Treatment with 6 g of the herbal complex significantly reduced the negative performance and pathogenic effects associated with Eimeria tenella challenge at a level that was comparable with amprolium when using a largely susceptible recent field isolate. In summary, concentration-dependent anticoccidial activity of the studied herbal complex suggests its use as an alternative anticoccidial agent to chemotherapeutic drugs for Eimeria tenella control.

Early complications after biliary enteric anastomosis for benign diseases: a retrospective analysis.

BACKGROUND: Biliary-enteric anastomosis (BEA) is a common surgical procedure performed for the management of biliary obstruction or leakage that results from a variety of benign and malignant diseases. Complications following BEA are not rare. We aimed to determine the incidence and the factors associated with early complications occurring after BEA for benign diseases. METHODS: We reviewed the medical records of all patients who underwent BEA for benign diseases at our institution between January 1988 and December 2009. The primary outcome was early post operative complication. Logistic regression analysis was done to identify factors predicting the occurrence of complications. RESULTS: Records of 79 patients were reviewed. There were 34 (43%) males and 45 (57% females). Majority (53%) had choledocholithiasis with impacted stone or distal stricture, followed by traumatic injury to the biliary system (33%). Thirty-four patients (43%) underwent a hepaticojejunostomy, 19 patients (24%) underwent a choledochojejunostomy, and choledochoduodenostomy was performed in 26 patients (33%). Early complications occurred in 39 (49%) patients - 41% had local complications and 25% had systemic complications. Most frequent complications were wound infection (23%) and bile leak (10%). Four (5%) patients died. On multivariate analysis, low serum albumin level (odds ratio = 16, 95% CI = 1.14-234.6) and higher ASA levels (odds ratio = 7, 95% CI: 1.22-33.34) were the independent factors predicting the early complications following BEA. CONCLUSIONS: Half of the patients who underwent BEA for benign diseases had complications in our population. This high incidence may be explained by the high incidence of hypoalbuminemia and the high-risk group who underwent operation.

Enhancing Value-Based Care With a Walk-in Clinic: A Primary Care Provider Intervention to Decrease Low Acuity Emergency Department Overutilization.

Background Emergency department overutilization is a known contributor to the high per-capita healthcare cost in the United States. There is a knowledge gap regarding the substitution effect of walk-in clinic availability in primary care provider (PCP) offices and emergency department utilization (EDU). This study evaluates associations between PCP availability and EDU and analyzes the potential cost savings for health systems. Methods A retrospective cohort analysis compared low acuity EDU rates in established patients at a family medicine residency's PCP office before and after walk-in clinic implementation. The practice had 12 providers, 12 residents, and a patient panel of approximately 7,000-8,000. Inclusion criteria were met if patients were: (1) established with the PCP office, (2) had a low acuity emergency department (ED) visit (emergency index score level 4 or 5) OR had a walk-in clinic visit at the family practice. ED visits were tracked from January 2018 to January 2020 and encounters were compared numbers to pre and post-implementation of a walk-in clinic. Cost savings for comparable management was estimated with average price differences for low acuity encounters in the ED versus clinic. Results Over the two-year timeframe, there were 10,962 total visits to the ED by family practice patients, 4,250 of these visits were low acuity. Despite gross monthly increases of EDU from 2018-2020, after implementation of a walk-in clinic in 2019, rates of total EDU decreased by 1.5% and low acuity utilization rates also decreased. The average annual patient census nearly doubled from 5,763 to 8,042. T-tests confirmed statistical significance with p-values <0.05. Average low acuity ED visits ($437) cost 4.9 times more than comparable PCP office visits ($91). Managing 2,387 patients in the walk-in clinic resulted in an estimated annual cost savings of $825,902. Conclusion Extended walk-in availability in primary care offices provides non-ED capacity for low acuity management and might mitigate low acuity ED utilization while providing more cost-effective care. This study supports similarly described pre-hospital diversions in reducing ED over-utilization by increasing access to care. Higher levels of evidence are needed to establish causality.

Application of spore morphology to solve identification problems in certain species of family Dryopteridaceae from Malakand Division, Pakistan.

Here we investigate the morphology of the spores of 12 native taxa of Dryopteridaceae that grow in Malakand division, Pakistan; most of these species not fully described before. This study intends to survey the taxonomic significance of spore morphological features and their variation useful for species identification in 7 species of Polystichum and 5 taxa of Dryopteris. The spores examinations were accomplished utilizing a light microscope (LM), and scanning electron microscope (SEM). The spores are monolete, medium-sized, with variable shapes in both equatorial and polar views. The mean estimation of equatorial diameter ranging from 28.3 to 58.3 µm and the polar diameter varied from 27.6 to 45.8 µm. The exospore thickness ranges between 1.6 to 3.8 µm, and the thickness of perispore is 0.8-6.7 µm. The perispore is perforated, ornamentation elements occur in different ways in the studied taxa of Polystichum. In investigated Dryopteris taxa, rugate perispore type is found. Results of multivariate statistical analysis (UPGMA, and PCA) established on quantitative and qualitative morphological traits of spores demonstrate that the species form distinct groups, not reflecting any phylogenetic relationships. A key to the spores types is provided for species identification, which dependent on the diagnostic characters of spores. The results of this study indicate that variation of spore morphological traits; in particular, the ornamentation and perispore characteristics, which is surface texture, have diagnostic value at the species level. Our data will help in the identification of spores of the family Dryopteridaceae in palynological and taxonomic studies.

Fluorescence Quenching of the Probes L-Tryptophan and Indole by Anions in Aqueous System.

A fluorescence quenching study of the fluorescent probes L-tryptophan and indole by anions (NO3-, Cl-, SO42-) was carried out in an aqueous system. The ions NO3-, Cl- and SO42- showed very good quenching of both the probes. Quenching of L-tryptophan by all the anions studied was higher as compare to the quenching of indole. The data was fitted with the Stern-Volmer equation. Stern-Volmer constants were observed in the order NO3- > Cl- > SO42-. Stern-Volmer constants reflect the sensitivity of the method for the studied anions. Limit of detection (LOD) was calculated as three times the standard deviation of the blank for n = 10 (3 × SD) while the limit of quantification (LOQ) was calculated as ten times the standard deviation of the blank for n = 10 (10 × SD). In the case of L-tryptophan LOD and LOQ varied from 4.08 × 10-5 - 4.56 × 10-4 mol L-1, while in the case of indole the values ranged from 3.87 × 10-5 - 6.59 × 10-4 respectively. Fluorescence quenching of L-tryptophan and indole by the studied anions showed good reproducibility and the method could be very effective for the determination of anions.

Partial Annuloplasty Rings in the Repair of Functional Ischemic Mitral Regurgitation.

Background Acute myocardial infarction (MI) is the leading cause of worldwide cardiac morbidities and mortalities. Mitral regurgitation (MR) is a common complication of MI. The severity of ischemic MR (IMR) can range widely, both clinically and hemodynamically. Mitral valve (MV) repair by lifting annuloplasty is a surgical procedure used to correct the pathology of IMR. The immediate outcomes of this technique have not yet been determined. The present study, therefore, evaluated the immediate results of MV annuloplasty performed to complement MV repair in patients with IMR. Methodology All adult patients with IMR who underwent lifting posterior mitral annuloplasty (LPMA) plus concomitant coronary artery bypass grafting (CABG) were included. Immediate outcomes were evaluated by transesophageal color Doppler echocardiography. The frequency of successful outcomes was compared in patients with different baseline characteristics. Results Posterior mitral annuloplasty was successful in 93.1% of patients, including in 92.8% of men and 94.1% of women. The percentages of successful immediate outcomes differed significantly in patients with and without diabetes and hypertension, and in patients with two- and three-vessel disease. Conclusion LPMA resulted in a high percentage of successful immediate outcomes in patients with IMR. Further studies should compare rates of immediate, intermediate, and late outcomes of this technique.

Multivessel Coronary Artery Disease and Subsequent Thrombolysis in Myocardial Infarction Flow Grade After Primary Percutaneous Coronary Intervention.

Background In underdeveloped countries, coronary artery disease (CAD) has developed into a serious health issue due to the high rates of risk factors such as obesity and smoking amongst the population. This study has been performed to find the rate of multivessel CAD (MVD) and subsequent thrombolysis in myocardial infarction (TIMI) flow grade III in patients undergoing primary percutaneous coronary intervention (PCI). Methods This transverse study was carried out involving 110 patients from the emergency department of the National Institute of Cardiovascular Diseases, Karachi, Pakistan, from August 2015 to March 2016. All patients were diagnosed as ST-segment elevation myocardial infarction (STEMI) and had gone through primary PCI. Pre-procedure angiographic findings regarding the number of vessels involved and post-procedure TIMI flow grade were assessed and analysed. Results The average age of the study sample was 56.3 ± 11.4 years. The proportion of male patients was 81.8% (n=90), and hypertension was the most prevalent risk factor followed by type II diabetes with a frequency of 67.3% (n=74) and 40.0% (n=44), respectively. Coronary angiography showed MVD in 50.0% (n=55) of the patients, of whom 34 patients had two-vessel disease, and the remaining 21 had three-vessel disease. Ninety percent (n=99) of the patients exhibited TIMI flow grade III after the procedure with no significant difference between patients with MVD and those with single-vessel disease with a rate of 87.3% (n=48/55) versus 92.7% (n=51/55, P=0.527), respectively. Conclusion Post-procedure TIMI flow grade III was accomplished in almost 90% of the subjects with or without MVD. It can be concluded that primary PCI has a significant role in the early restoration of myocardial blood flow following STEMI regardless of the vessels involved.

Coronary Artery Anomalies in Tetralogy of Fallot Patients Undergoing CT Angiography at a Tertiary Care Hospital.

Background The aim of this study was to determine the frequency of coronary artery anomalies (CAAs) in Tetralogy of Fallot (TOF) patients undergoing computed tomography (CT)-angiography in a tertiary care hospital. Methodology In this observational study, we included consecutive TOF patients undergoing CT-angiography without prior history of cardiac surgery or congenital heart disease. CAAs were defined based on either origin or course of the artery. Results Out of 441 TOF patients, the prevalence of CCAs was 3.6% (16), of which 13 were below 18 years of age. Anomalous left main artery was observed in six (1.4%) patients, followed by left anterior descending artery and right coronary artery, observed in four (0.9%) patients each, and two (0.5%) patients had a single coronary artery originating from the left coronary cusp with an interarterial course. Conclusions CAAs were observed in a significant number (3.6%) of TOF patients. A CT-angiographic assessment before surgical correction would help identify the exact anatomy for better surgical planning to minimize complications.

Outcome at Six Months After Primary Percutaneous Coronary Interventions Performed at a Rural Satellite Center of Sindh Province of Pakistan.

Introduction Primary percutaneous coronary intervention (PPCI) is now a well-established treatment of acute ST-elevation myocardial infarction (STEMI). For the first time in Pakistan, various off-site satellite centers are established to perform PPCI 24-hours. Our population mainly resides in the rural area with low literacy rate and poor socioeconomic conditions. The majority of the patients who are presented in the satellite center had either never received any long-term treatment plan or were non-compliant to their medication. The objective of this study was to determine the outcome of patients at six months who underwent primary PCI at a rural satellite center of Sindh, Pakistan. Methods This study was conducted at Larkana satellite center of National Institute of Cardiovascular Diseases, Karachi. Patients who underwent PPCI for STEMI from October 2017 to March 2018 were enrolled in the study. In case of death of the patient, data were obtained from the attendant of the deceased. Patients, on follow-up visits, were interrogated for post-procedure symptoms. Results A total of 271 patients were enrolled in the study. The mean age ± standard deviation of patients was 54.84 ± 10.64 years. The most common culprit artery was left anterior descending (LAD) artery with 161 (59.4%) patients, followed by right coronary artery (RCA) with 98 (36.2%) patients. Only 41 (15%) patients had a three-vessel disease, while 141 (52%) patients had single-vessel disease. On follow-up, 70 (25.8%) patients complained of chest pain grade II, 20 (7.4%) complained of shortness of breath (SOB) grade II, 44 (16.2%) complained of vertigo, and 16 (5.9%) complained of nonspecific weakness. The mortality rate of 6.3% (17) was observed after six months of PPCI. The mortality rate was found to be lower for patients with LAD disease (p = 0.036) and higher among patients with RCA as the culprit artery (p = 0.045). The mortality rate was significantly associated with the number of diseased vessels and the type of stent deployed. Conclusion Primary PCI, at a rural satellite center, has an overall positive outcome. Steps should be taken to provide free medication along with encouragement towards compliance of dual antiplatelet medication. Furthermore, the facility for subsequent procedures should be provided at the same set-up.

In vitro and in vivo efficacies of ivermectin and cypermethrin against the cattle tick Hyalomma anatolicum anatolicum (Acari: Ixodidae).

This study investigated the comparative efficacy of ivermectin and cypermethrin pour-on, for the treatment of Hyalomma anatolicum (a.) anatolicum infestations in bovines. For examining acaricidal efficacy, 480 ticks were exposed in vitro to graded doses of both the acaricides and in vivo efficacy was examined in 360 tick-infested bovines treated at the recommended doses of ivermectin (IVM) and cypermethrin (CYM) pour-on. The comparative quantitative assessment of tick burden was done on days 0, 5, 10, 15, and 20 after treatment using "finger counting." The results of the tick survival assay indicated both compounds were effective in vitro against H. a. anatolicum. The arc transformed mean surviving ticks, 24 h post immersion, was 2.66 and zero in groups treated with the highest dilutions of IVM and CYM, respectively. At 15 days post-treatment, the CYM pour-on showed a higher in vivo efficacy (no surviving ticks) compared to IVM (mean of 20 surviving ticks). A single dose of CYM and IVM was found effective for 20 and 15 days post-treatment, respectively. Additionally, a questionnaire was used to gather information from 30 small holder dairy farms on the farmer's approach toward the control of ticks. The majority (90%) of respondents were using acaricides incorrectly along with poor husbandry practices on their farms. Overuse of IVM in the tested area of Pakistan may be the reason the IVM is not as effective as expected. These results provide useful tools for the decision making in tick control, as well as providing the basis for testing the findings on provincial and national levels in future studies.

Educating the power: HIV/AIDS and parliamentarians of Pakistan.

Increasing rates of HIV have been recorded amongst the Injection Drug User community from all parts of Pakistan. This has mobilized the health authorities into definitive action before there is a general spread of the epidemic into the Pakistani populace. Lacking any formal research as pertains to HIV policy development in Pakistan, international collaborating agencies, including the United Nations, are aiding in the formulation of a national policy to tackle HIV/AIDS. This article discusses the progress and importance of interventions being conducted amongst the Parliamentarians of Pakistan, relatively unchartered waters. The series of Seminars help to appraise the Parliamentarians of the ground situation as pertains to HIV in their constituencies, aiming to ultimately generate federal and provincial governmental policies, and a solid strategy to combat the spread of HIV/AIDS in Pakistan.

Outcomes of Primary Percutaneous Coronary Intervention through a Transradial Approach in a Tertiary Care Cardiac Center.

Background Transradial approach for percutaneous coronary intervention (PCI) is gaining popularity due to lesser bleeding and other access site related complications. This study aims to determine the in-hospital outcomes of primary PCI through a transradial approach in a tertiary care cardiac center. Methods Consecutive patients with ST-segment elevation myocardial infarction presenting within 12 hours with symptoms without a previous history of thrombolytic therapy, coronary angioplasty, or cardiac surgery were included in the study. All patients underwent a diagnostic angiogram followed by primary PCI of the infarct-related artery through a radial route and were kept under observation during the hospital stay for forearm hematoma or mortality. Results A total of 180 patients were included in this study, with a mean age of 52.04±7.31 years. Majority (87.2%) of the patients were male, and diabetes (72.8%) was the most commonly observed co-morbid condition followed by hypertension (67.2%). Hospital mortality rate was 3.9% (7 patients), and post-procedure forearm hematoma was noted in 5.6% (10 patients). An increased mortality rate was found to be associated with age above 50 years (7.1% vs. 0.0%; p=0.012) and non-hypertension (8.5% vs. 1.7%; p=0.026). An increased incidence of forearm hematoma was found to be associated with age above 50 years (10.2% vs. 0.0%; p=0.002), diabetic mellitus (7.6% vs. 0.0%; p=0.047), hyperlipidemia (11% vs. 0.0%; p=0.001), and non-smoking (10.2% vs. 0.0%; p=0.003). Conclusion Our study showed that primary PCI through a transradial approach is a safe option with excellent success rates in terms of both mortality rates and morbidity such as forearm hematoma.