Another D in MUDPILES? A Review of Diet-Associated Nondiabetic Ketoacidosis.

Ketogenic diet or very-low-carbohydrate diet gained widespread popularity in the 1990s due to their favorable effects on weight loss and diabetes among others with good short-term safety data. People on ketogenic diets exist in a state of dietary ketosis in which the body production of ketone is equal to consumption and no harmful effects of ketonemia occur. However, in face of stress, the harmless dietary ketosis can lead to profound acid-base disturbances due to massive overproduction of ketone bodies that overwhelms the acid buffer system of the body. A handful of case reports have been published on this topic calling the safety of ketogenic diet into question. In this article, we chronicle a unique case of ketogenic (Atkins) diet-associated ketoacidosis, and we present a comprehensive literature review on the etiology of ketoacidosis

Abberent expression analysis of LMNA gene in hutchinson-gilford progeria syndrome

Hutchinson-Gilford progeria syndrome (HGPS) is caused by de novo dominant point mutations of the genes encoding nuclear lamina proteins, leading towards premature aging. A protein sequence is subjected to mutations in nature which can affect the function and folding pattern of the protein by different ways. Mutations involved in HGPS were identified and were substituted in the seed sequence retrieved from the UniProt database to get the mutated versions. Tertiary structure of the Lamin A protein was previously unpredicted so was performed for all the mutated as well as for the seed protein to analyze the effects of mutations on the protein structure, folding and interactions. All the predicted models were refined and validated through multiple servers for multiple parameters. The validated 3D structure of seed protein was then successfully submitted to the Protein Model Database and was assigned with the PMDB ID PM0077829. All the predicted structures were superimposed with a root mean square deviation value of 7.0 Å and a high Dali Z-score of 1.9. It was observed that mutations affected physiochemical properties as well as instability index and thus is affecting the domains in specific and the whole structure in general. It was further analyzed that HGPS is the result of affected Lamin a protein interactions with other integral and binding proteins in the inner nuclear membrane affecting the link in between the nuclear membrane and the network of the lamina

Receptor modification as a therapeutic approach against viral diseases

Poliovirus causes flaccid paralysis through the destruction of motor neurons in the CNS. Susceptibility to its infection is mainly due to the interaction in between the surface capsid proteins and its receptors on the host cell surface, important for binding, penetration and other necessary events during early infection. Receptor modification is a new approach to treat viral diseases by the modification of target proteins structure. Binding domains are modified in an effective way to make it difficult for the virus to recognize it. In this study, tolerant and intolerant induced mutations in the poliovirus receptor, VP1 and VP2 were identified and substituted in the seed sequence to get the modified versions. Substitutions causing changes in initial folding were short listed and further analyzed for high level folding, physiochemical properties and interactions. Highest RMSD values were observed in between the seed and the mutant K90F (3.265 Å) and Q130W (3.270Å) respectively. The proposed substitutions were found to have low functional impact and thus can be further tested and validated by the experimental researchers. Interactions analyses proved most of the substitutions having decreased affinity for both the VP1 and VP2 and thus are of significant importance against poliovirus. This study will play an important role for bridging computational biology to other fields of applied biology and also will provide an insight to develop resistance against viral diseases. It is also expected that same approach can also be applicable against other viruses like HCV, HIV and other in near future

Sequence and structure based assessment of nonsynonymous SNPs in hypertrichosis universalis

Hairs are complex structures, making a protective layer and serves different biological functions. TRPS1, a transcription factor is one of the candidate genes causing congenital hypertrichosis, an excessive hair growth at inappropriate body parts. SNPs of TRPS1 were retrieved from dbSNP which were screened by SIFT and PolyPhen servers based on their functional impacts. Out of the screened SNPs, rs181507248 and rs146506752 were predicted as intolerant and damaging by both the servers. The predicted tertiary structure of the native TRPS1 after refinement and validation was successfully submitted to the Protein Model Database and was assigned with PMDB ID PM0077843, as it was previously unpredicted. It was observed through the structure based analysis that, the SNPs rs181507248 and rs146506752 caused significant changes in the secondary and tertiary structures as well as the physiochemical properties of TRPS1 protein. It can thus be concluded that the changed properties due to these single nucleotide polymorphisms effect the interactions of TRPS1 which result in congenital hypertrichosis

Examining the Consequences of Change Fatigue in Healthcare Providers

Background and Objective: By making new changes in organizations, organizations are looking for various innovations to maintain their level of performance in the existing competitive environment. However, these frequent changes can lead to change fatigue and its negative consequences for employees. Therefore, the present study was conducted to evaluate change fatigue and its related consequences in healthcare providers. Materials and Methods: This cross-sectional study was conducted in health centers in western Iran. In this study, 803 people were selected using the available method. The change fatigue scale, Parker and Decotis’ Job Stress Questionnaire, Ruth and Field’s Job Satisfaction Questionnaire, Maslash and Jackson’s Burnout Questionnaire, Turnover Intention Questionnaire, and Standard Questionnaire of Organizational Commitment of Mowday et al. were used. All analyses were performed using SPSS (version 23) and AMOS (version 18) softwares. Results: The results of the present study showed that with the increase of change fatigue, the intention to leave, stress, and burnout increased significantly, and job satisfaction decreased significantly; however, no significant relationship was observed between change fatigue and organizational commitment. In addition, a significant relationship was observed between marital status, age, work experience, type of employment, type of job, and education with change fatigue. Conclusion: In environments associated with rapid and continuous changes, it is important to consider change fatigue and its consequences because it can increase job stress and burnout, reduce job satisfaction and organizational commitment, and provide a reason for leaving the job

Predictors of Acute Stent Thrombosis After Primary Percutaneous Coronary Intervention

OBJECTIVES To identify the specific predictors of acute stent thrombosis in patients after primary percutaneous coronary intervention.METHODOLOGY This retrospective study was carried out at the Department of Cardiology Hayatabad Medical Complex Peshawar from 1st January to 30th June 2022. All consecutive patients with an angiographically confirmed stent thrombosis were enrolled. Patients gave informed consent for the inclusion of data in this registry. Stent thrombosis was categorized according to the timing of the event as acute (occurrence within the first 24 hours after the index procedure).RESULTSA total of 400 patients were included in the study. Age ranged between 35-70 years, with a mean age of 52.5. There were 260(65%) males and 140(35%) females, with male to female ratio of 1.8:1. All patients underwent primary PCI with stent implantation. According to the elapsed time since stent implantation, 42(10.5%) patients presented with acute stent thrombosis after primary percutaneous coronary intervention. The mean time to develop acute stent thrombosis after primary PCI was ±4.5 hours (range 3-6 hours). In most STEMI patients, 340(85%) received a loading dose of clopidogrel at the time of the index PCI. In 23(54.7%) patients, acute stent thrombosis occurred within 6 hours, 10(23.8%) within 12 hours, 6(14.2%) within 18 hours and 3(7.1%) after clopidogrel loading.CONCLUSIONInadequate stent expansion or mal-opposition, diabetes mellitus, chronic kidney disease, and female gender were the strong predictors of acute stent thrombosis

Changes in Lipid Profile of Rat Plasma after Chronic Administration of Laghobanondo Rosh (LNR)—An Ayurvedic Formulation

Abstract In this study, the lipid profile of rats' plasma was measured after chronic administration of LNR usually used in the treatment of pandu (anaemia).The animal used for this research work was albino rats (Rattus novergicus: Sprague-Dawley strains) and LNR was administered per oral route at a dose of 100mg/kg body weight, once daily, up to 45 days for all the experiments. Forty rats, equally of both sexes, were randomly grouped into four where one male and one female group were used as control and other groups were used as test. LNR remarkably decreased plasma triglycerides in both male and female rats and it was statistically very highly significant (p=0.001***). Similar trend of result was noticed incase of total cholesterol in both sexes of the animal but it was not statistically significant (male, p=0.296, female, p=0.511). On the other hand, a reverse trend in the result was observed in case of VLDL, LDL and HDL. In case of LDL, the increase in male rats was statistically significant (p=0.047*) but in female rats it was statistically insignificant (p=0.506). The increase in VLDL and HDL was statistically insignificant in the both male and female rats

Optimiranje podloge za pojačanu proizvodnju glukoamilaze fermentacijom na krutoj podlozi s pomoću gljive Fusarium solani

Solid-state cultivation of Fusarium solani was carried out for enhanced production of glucoamylase (GA) using different substrates like wheat bran, rice bran, green gram bran, black gram bran and maize bran. The SSF medium containing wheat bran as a substrate yielded the highest enzyme activity. The physical and chemical parameters were optimized. Maximum enzyme activity (61.35±3.69) U/g of dry wheat bran was achieved under optimum growth conditions. The optimum conditions were fructose as carbon and energy additive 1 % (by mass), urea as nitrogen additive 1 % (by mass), initial moisture content of solid substrate 70 % (by mass per volume), incubation period 96 h, inoculum size 15 % (by mass per volume) having 10^6–10^7 spores/mL, incubation temperature (35±1) °C and pH=5.0. It was further observed that the addition of surfactants caused a decrease in enzyme biosynthesis by F. solani in SSF of wheat bran under optimum process conditions.Uzgojem gljive Fusarium solani fermentacijom na krutoj podlozi povećana je proizvodnja glukoamilaze (GA) primjenom različitih supstrata kao što su pšenične i rižine posije, te posije zelene soje, crne soje i kukuruza. Najveća aktivnost enzima dobivena je uporabom podloge od pšeničnih posija. Optimirani su fizikalni i kemijski parametri i pri optimalnim uvjetima rasta postignuta je maksimalna aktivnost enzima od (61,35±3,69) U/g suhih pšeničnih posija. Optimalni uvjeti bili su: 1 % (m/V) fruktoze kao izvora ugljika i energije, 1 % (m/m) uree kao izvora dušika, 70 % (m/V) početnog udjela vlage u krutoj podlozi, vrijeme inkubacije u trajanju od 96 h, 15 % inokuluma (m/V) s 10^6-10^7 spora/mL, temperatura inkubacije (35±1) °C i pH=5,0. Dodatkom površinski aktivnih tvari smanjila se biosinteza enzima proizvedenog fermentacijom pri optimalnim uvjetima na podlozi od pšeničnih posija s pomoću gljive F. solani

Evaluation of Three Chitin Metal Silicate Co-Precipitates as a Potential Multifunctional Single Excipient in Tablet Formulations

The performance of the novel chitin metal silicate (CMS) co-precipitates as a single multifunctional excipient in tablet formulation using direct compression and wet granulation methods is evaluated. The neutral, acidic, and basic drugs Spironolactone (SPL), ibuprofen (IBU) and metronidazole (MET), respectively, were used as model drugs. Commercial Aldactone®, Fleximex® and Dumazole® tablets containing SPL, IBU and MET, respectively, and tablets made using Avicel® 200, were used in the study for comparison purposes. Tablets of acceptable crushing strength (>40 N) were obtained using CMS. The friability values for all tablets were well below the maximum 1% USP tolerance limit. CMS produced superdisintegrating tablets (disintegration time < 1 min) with the three model drugs. Regarding the dissolution rate, the sequence was as follow: CMS > Fleximex® > Avicel® 200, CMS > Avicel® 200 > Dumazole® and Aldactone® > Avicel® 200 > CMS for IBU, MET and SPL, respectively. Compressional properties of formulations were analyzed using density measurements and the compression Kawakita equation as assessment parameters. On the basis of DSC results, CMS co precipitates were found to be compatible with the tested drugs. Conclusively, the CMS co-precipitates have the potential to be used as filler, binder, and superdisintegrant, all-in-one, in the design of tablets by the direct compression as well as wet granulation methods

Association between contrast-induced nephropathy and CHA2DS2-VASc score in patient with non-ST elevation myocardial infarction after percutaneous coronary intervention

Background: Contrast-induced nephropathy (CIN) is a recognized complication in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). CHA2DS2-VASc score, commonly employed in clinical settings, shares similar risk factors for CIN development. This cross-sectional observational study investigated the association between CHA2DS2-VASc score and CIN post-PCI in non-ST segment elevated myocardial infarction (NSTEMI) patients. Methods: Over one year (April 2019 to March 2020), 100 NSTEMI patients undergoing PCI at the national institute of cardiovascular diseases (NICVD), Dhaka, were included. Patients were categorized into two groups based on CHA2DS2-VASc scores (≥4, group I; &lt;4, group II). CIN assessment utilized post-procedural serum creatinine within 48 hours, with statistical analysis performed using SPSS version 20.0. Results: Group I exhibited a significantly higher CHA2DS2-VASc score (4.15±1.35 vs. 2.25±0.92 in group II). Post-procedural serum creatinine was notably elevated in CHA2DS2-VASc score ≥4 (1.98±0.46 vs. 1.46±0.27, p&lt;0.001). A CHA2DS2-VASc score cut-off ≥4 predicted CIN with 84.6% sensitivity, 55.2% specificity (AUC 0.83, CI: 0.743-0.90, p&lt;0.001). Conclusions: This study establishes a significant association between CHA2DS2-VASc score and CIN in NSTEMI patients post-PCI, suggesting its potential utility in predicting CIN risk in this population.