Conformational changes of a chemically modified HRP

Horseradish peroxidase is an all alpha-Helical enzyme, which widely used in biochemistry applications mainly because of its ability to enhance the weak signals of target molecules. This monomeric heme-containing plant peroxidase is also used as a reagent for the organic synthesis, biotransformation, chemiluminescent assays, immunoassays, bioremediation, and treatment of wastewaters as well. Accordingly, enhancing stability and catalytic activity of this protein for biotechnological uses has been one of the important issues in the field of biological investigations in recent years. In this study, pH-induced structural alterations of native (HRP), and modified (MHRP) forms of Horseradish peroxidase have been investigated. Based on the results, dramatic loss of the tertiary structure and also the enzymatic activity for both forms of enzymes recorded at pH values lower than 6 and higher than 8. Ellipticiy measurements, however, indicated very slight variations in the secondary structure for MHRP at pH 5. Spectroscopic analysis also indicated that melting of the tertiary structure of MHRP at pH 5 starts at around 45° C, which is associated to the pKa of His 42 that has a serious role in keeping of the heme prostethic group in its native position through natural hydrogen bond network in the enzyme structure. According to our data, a molten globule like structure of a chemically modified form of Horseradish peroxidase at pH 5 with initial steps of conformational transition in tertiary structure with almost no changes in the secondary structure has been detected. Despite of some conformational changes in the tertiary structure of MHRP at pH 5, this modified form still keeps its catalytic activity to some extent besides enhanced thermal stability. These findings also indicated that a molten globular state does not necessarily preclude efficient catalytic activity

Trichomoniasis prevalence among women admitted to public health centers of Chaharmahal and Bakhtiari province for annual Pap smear test, 1995-96

در این مطالعه 19530 زن که از مهر ماه 1374 تا پایان شهریور ماه 1375 به منظور اجرای برنامه مراقبت برای معاینات دوره ای به مراکز بهداشتی درمانی در استان چهارمحال و بختیاری مراجعه کرده با بهره گیری از روش پاپ اسمیر مورد آزمایش قرار گرفتند. در مطالعه حاضر علاوه بر بررسی اسمیرهای تهیه شده از مخاط واژن و گردن رحم برای ارزیابی فرآیندهای التهابی دستگاه تناسلی و تغییرات احتمالی سلول های ناحیه، ابتلاء به عفونت هایی نظیر تریکومونیازیس و کاندیدیازیس نیز مورد بررسی قرار گرفت. بخشی از نتایج بدست آمده از این مطالعه بیانگر آن است که میزان شیوع تریکومونیازیس در کل زنان مراجعه کننده به مراکز بهداشتی درمانی در استان چهارمحال و بختیاری 1.37 می باشد و این درحالی است که بیشترین میزان ابتلاء زنان به تریکومونیازیس در شهرستان لردگان با 3.4 و کمترین میزان در شهرستان شهرکرد با 0.46 مشاهده می گردد. همچنین پژوهش حاضر نشانگر آن است که در جمعیت مورد مطالعه شیوع تریکومونیازیس در نقاط مختلف استان متفاوت بوده و این تفاوت بین برخی از نواحی از نظر آماری شاخص است، به گونه ای که میزان شیوع تریکومونیازیس در زنان مورد مطالعه شهرستان لردگان با زنان سایر شهرستان ها بطور محسوسی متفاوت است (

Is Albumin-based Resuscitation in Severe Sepsis and Septic Shock Justifiable? An Evidence from a Cost-effectiveness Evaluation

BACKGROUND: Fluid and antimicrobial therapy are the essential parts of sepsis management. The type of fluid to resuscitate with is an unsettled issue in the treatment of severe sepsis and septic shock. The objective of this study was to evaluate the cost effectiveness of albumin-based resuscitation over crystalloids.METHODS: A cost-effectiveness analysis was conducted by extracting data from a database of Sina Hospital, Islamic Republic of Iran. A decision tree was constructed by using Tree Age Pro2011. The patients were grouped based on the types of fluids used for resuscitation into crystalloid alone or crystalloid + albumin groups at the initial decision node. The patients were followed from the onset of severe sepsis and septic shock upto 28 days. The healthcare payers’ perspective was considered in constructing the model. The cost was measured in US dollars and the effectiveness was measured by life years gained.RESULTS: The addition of albumin during resuscitation of patients with severe sepsis and septic shock has an effectiveness gain of 0.09 life years and cost increment of 495.00 USD. The estimated ICER for this analysis was 5500.00 USD per life year gained. The probability that albumin is cost-effective at one GDP per capita is 49.5%.CONCLUSION: Albumin-based resuscitation is not cost-effective in Iran when a GDP per capita was considered for a life year gain. The cost-effectiveness was insensitive to the cost of standard care. We recomend the caustious use albumin as per the Surviving Sepsis Campaign guideline.

Optimizing Outpatient Medication Management: The Impact of Clinical Pharmacists on Identifying and Addressing Drug-Related Problems

Medication Therapy Management Services (MTMS) are effective strategies to reduce Drug-Related Problems (DRPs) and associated healthcare costs. Given the high prevalence of DRPs in outpatient settings and the lack of an effective process to detect such problems in Iran, we decided to evaluate the type and number of DRPs identified by clinical pharmacists in a university-affiliated Pharmacotherapy Clinic in Khuzestan province, South of Iran. In this cross-sectional study, 150 eligible outpatients were included. At a university-affiliated pharmacotherapy clinic, pharmacy students took patients' histories and referred them to clinical pharmacists for DRP evaluation and detection. Appropriate interventions were then implemented in collaboration with patients and their healthcare providers to resolve the problems. Approximately 3.56 DRPs per patient were identified during a nine-month study period. The most prevalent DRPs were lack of education or information (32.40% [174/537]), undertreated indications (17.31% [93/537]), and patient compliance (15.27% [82/537]). Clinical pharmacists detected 537 DRPs, implemented 525 interventions, and performed 0.977 interventions per DRP. The provision of information (57.52% [302/525]) and change of therapy (21.71% [114/525]) were the most frequent types of clinical pharmacist interventions. This study revealed deficiencies and limitations in our healthcare services, resulting in a significant prevalence of DRPs. Implementing pharmaceutical care practice models, such as Pharmacotherapy Clinics, where clinical pharmacists integrate their experience and knowledge in a patient-centered manner, is the most effective method for preventing and managing these issue

Pharmacist-Led Medication Review: Supports for New Role of Pharmacists

In recent decades, by increasing complexity of drug therapy, pharmacists considered as health- care members who can help optimizing drug therapy. We know that medicines do not have the anticipated effects all the times and a vast variability may exist in their behaviors in the body. So, it is very crucial to individualize treatment for every single patient. Nowadays, optimizing drug therapy in patients needs a collaborative interdisciplinary approach to patients care and treatment. Specifically when drug therapy is considered for a condition, pharmacists can enroll as a valuable professional to help for modification of therapy along with other clinicians. Abundant number of studies and reports exist in the literatures which address usefulness of pharmacist engagement in patient care. In this review we have presented some valuable evidences supporting pharmacist role in different clinical settings

Increasing the Number of Adverse Drug Reactions Reporting: the Role of Clinical Pharmacy Residents

Abstract Detection of adverse drug reactions (ADRs) in hospitals provides an important measure of the burden of drug related morbidity on the healthcare system. Spontaneous reporting of ADRs is scare and several obstacles to such reporting have been identified formerly. This study aimed to determine the role of clinical pharmacy residents in ADR reporting within a hospital setting.Clinical pharmacy residents were trained to report all suspected ADRs through ADRreporting yellow cards. The incidence, pattern, seriousness, and preventability of the reported ADRs were analyzed. During the period of 12 months, for 8559 patients, 202 ADR reports were received. The most frequently reported reactions were due to anti-infective agents (38.38%). Rifampin accounted for the highest number of the reported ADRs among anti-infective agents. The gastro-intestinal system was the most frequently affected system (21.56%) of all reactions. Fifty four of the ADRs were reported as serious reactions. Eighteen of the ADRs were classified as preventable. Clinical pharmacy residents involvement in the ADR reporting program could improve the ADR reporting system

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background Disorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021. Methods We estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined. Findings Globally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer. Interpretation As the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed. Funding Bill & Melinda Gates Foundation

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Introduction to Prominent Journals Publishing Pharmaceutical Care Issues

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Prescribing of Potentially Inappropriate Medications to ElderlyPeople by Medical Specialists in Isfahan, Iran: Inappropriate prescription

The goal of this study is to identify the types of potentially inappropriate drugs prescribed by the medical specialists of Isfahan province to elderly patients. A number of 31,254 randomly selected prescriptions from medical specialists of Isfahan province were reviewed for elderly patients who were insured by the Social Security Organization. Three thousand and seven prescriptions were identified and Beers'Criteria was applied to figure out the type of inappropriate medications. The study concluded 49% males and 51% females. Sixty one percent of patients were 65-74 years old and 39% older than 74 years old. Of all the prescriptions reviewed, 24.4% contained inappropriate medications. The ten most common medications detected in the prescriptions were: Naproxen (18.4%), fluoxetine (8.3%), clidinium C (7.2%),indomethacin (7.2%), chlordiazepoxide (5.8%), doxepin (4.76%), dipyridamole (4.4%), amitriptyline (4.27%), methocarbamol (4.15%) and piroxicam (3.88%). Theresults are comparable to what has been reported in the literature. This is also inaccordance with the national drug consumption as NSAIDs are heavily usedthroughout Iran. Due to the extent of inappropriateness of medicine use in the elderly population, we need to define a strategy to curtail this problem including educational classes for physicians and launching national geriatrics residency programs