Serious Adverse Events of Inclisiran in Patients With Hypercholesterolemia, a Meta-Analysis of ORION Trials.

BACKGROUND: Several studies have been conducted over the years to find an effective and safe therapeutic agent to treat hypercholesterolemia. Inclisiran is a novel drug being studied for its efficacy and safety in reducing low-density lipoprotein cholesterol levels in patients to reduce the risk of cardiovascular diseases. No previous study was done to review the trials for the serious adverse events of this drug. The primary objective of this research is to investigate the incidence of serious adverse events of this drug. DESIGN: A systematic review and meta-analysis of clinical trials is performed. METHODS: A systematic search of PubMed, Embase, and ClinicalTrials.gov, from their inception till July 3, 2023, was performed for ORION trials, studying the efficacy and safety of inclisiran. The random-effects model was used in the meta-analysis to provide a pooled proportion of serious adverse events. The risk of bias in each study was assessed by the Cochrane Risk of Bias Tool. RESULTS: From 319 studies searched from the databases, only 8 relevant articles remained after a detailed evaluation. These studies, having a total of 4981 patients, were involved in the analysis, with a pooled estimate showing a nonsignificant incidence of serious adverse events. Each adverse event was studied individually, and product issues and endocrine disorders had the highest odds ratio among them. All included studies were classified as moderate quality. CONCLUSION: Following systematic review and meta-analysis, we found no significant differences in any serious adverse events following the administration of inclisiran. However, larger ongoing trials will provide additional data to evaluate the safety profile of this agent.

Antimicrobial drug resistant features of Mycobacterium tuberculosis associated with treatment failure.

Tuberculosis stands as a prominent cause of mortality in developing countries. The treatment of tuberculosis involves a complex procedure requiring the administration of a panel of at least four antimicrobial drugs for the duration of six months. The occurrence of treatment failure after the completion of a standard treatment course presents a serious medical problem. The purpose of this study was to evaluate antimicrobial drug resistant features of Mycobacterium tuberculosis associated with treatment failure. Additionally, it aimed to evaluate the effectiveness of second line drugs such as amikacin, linezolid, moxifloxacin, and the efflux pump inhibitor verapamil against M. tuberculosis isolates associated with treatment failure. We monitored 1200 tuberculosis patients who visited TB centres in Lahore and found that 64 of them were not cured after six months of treatment. Among the M. tuberculosis isolates recovered from the sputum of these 64 patients, 46 (71.9%) isolates were simultaneously resistant to rifampicin and isoniazid (MDR), and 30 (46.9%) isolates were resistant to pyrazinamide, Resistance to amikacin was detected in 17 (26,5%) isolates whereas resistance to moxifloxacin and linezolid was detected in 1 (1.5%) and 2 (3.1%) isolates respectively. Among MDR isolates, the additional resistance to pyrazinamide, amikacin, and linezolid was detected in 15(23.4%), 4(2.6%) and 1(1.56%) isolates respectively. One isolate simultaneously resistant to rifampicin, isoniazid, amikacin, pyrazinamide, and linezolid was also identified. In our investigations, the most frequently mutated amino acid in the treatment failure group was Serine 315 in katG. Three novel mutations were detected at codons 99, 149 and 154 in pncA which were associated with pyrazinamide resistance. The effect of verapamil on the minimum inhibitory concentration of isoniazid and rifampicin was observed in drug susceptible isolates but not in drug resistant isolates. Rifampicin and isoniazid enhanced the transcription of the efflux pump gene rv1258 in drug susceptible isolates collected from the treatment failure patients. Our findings emphasize a high prevalence of MDR isolates linked primarily to drug exposure. Moreover, the use of amikacin as a second line drug may not be the most suitable choice in such cases.

Cryoanesthesia with ethyl chloride spray versus 5% lidocaine gel in alleviating oral local anesthetic injection pain for buccal anaesthesia: A randomized clinical (controlled) trial.

Background: Numbing the area of oral mucosa with cold application prior to administration of regional anesthesia has been widely used by various dentists in alleviating pain caused by needle prick. Cryoanesthesia using Endo-ice as topical anesthesia has been studied as a replacement to prevail the fallibility of topical anaesthetics. This study aimed to evaluate and compare effectiveness of ethyl chloride spray with 5% lidocaine gel in alleviating buccal anesthesia injection pain. Methods: Total of 90 outpatients were randomly divided into 3 groups as follows: Group 1 - cryotherapy with ethyl chloride at the anesthetic site preceding before administration of local anesthesia; Group 2 - topical application of 5% LIDOCAINE GEL preceding before administration of local anesthesia; and group 3 - control that did not receive any topical agent preceding before administration of local anesthesia. Visual analogue scale (VAS) was used to document pain immediately after injection prick. Results: About comparison of pain scores, significant difference was found between group 1 (ethyl chloride) and group 2 (topical lidocaine) patients (P=0.001). For group 1, about 15 (50%) patients suffered from mild pain, followed by 14 (46.67%) patients suffering from moderate pain. However, majority of the 21 (70%) patients in group 2 suffered from moderate pain. All the patients in group 3 suffered from severe pain. Conclusion: Importance of alleviating fear of needle injection phobia amongst patients is of paramount importance. Ethyl chloride was found to be more effective than topical lidocaine in alleviating needle injection pain before administration of local anesthetic injection.

Surveillance and dietary risk assessment of endocrine-disrupting pesticides in eggplant/brinjal and cauliflower in Pakistan.

Several pesticides (used in vegetable production) have recently been identified as potential endocrine disruptors. The current study aimed to determine the consumer exposure risk associated with eating contaminated vegetables. The European Union-citrate buffered QuEChERS extraction protocol, validated in accordance with the European Union guidelines, was used to monitor selected endocrine-disrupting pesticides in eggplant/brinjal (Solanum melongena L.) and cauliflower (Brassica oleracea) marketed in Rawalpindi/Islamabad, Pakistan. A total of 80 and 69 percent of eggplant/brinjal (n = 25) and cauliflower (n = 26) samples were found contaminated, respectively. Sixty-five percent of cauliflower samples were found non-contaminated with both European Union (EU) and Codex Alimentarius Commission (CAC) maximum residue limits (MRL), while 20 % of brinjal samples were found to be non-compliant with EU-MRL. Both vegetables contained high levels of the androgen antagonist chlorpyrifos and the thyroid hormone inhibitor cyhalothrin-lambda. The estimated acute health risk associated with dietary exposure to chlorpyrifos and cyhalothrin-lambda in cauliflower for both males and females was found to be greater than 200 % of the FAO/WHO Joint Meeting on Pesticide Residues' (JMPR) established acute reference dose. The estimated chronic health risk for all studied endocrine-disrupting pesticides (0-5.27 %) indicates zero to very low health risk for studied population groups.

Carica papaya ameliorates thrombocytopenia through upregulation of Interleukin-11 and modulation of thrombopoietin in mouse model of carboplatin-induced myelosuppression.

INTRODUCTION: Carica papaya L. (C. papaya) is used as a folk medicine for the treatment of various diseases throughout the world. Recently, papaya leaves decoction has been effectively used for the prevention and treatment of thrombocytopenia. The current study was undertaken to evaluate the thrombopoietic and immunomodulatory activities of C. papaya leaves in the mouse model of carboplatin induced myelosuppression. METHODS: Myelosuppression was induced by a single intraperitoneal injection of carboplatin (125 mg/kg b. w.). Aqueous extract of C. papaya leaves (15 mg/kg b. w.) was given orally by feeding tube from day 0-18 to preventive group to see the preventive effect and from day 6-18 to treatment group for treatment effect. RESULTS: The results showed that the C. papaya leaves extract significantly decreased the fall in platelet count in preventive and treatment groups. Extract significantly prevented the fall in total WBCs count on day 12 and 18 in the preventive group, whereas it significantly elevated the WBCs count in treatment group on day 18. Significantly increased RBCs count in both groups was observed on day 18 after treatment with C. papaya leaves extract. Treatment with C. papaya leaves extract significantly upregulated the mRNA expression levels of thrombopoietic cytokine IL-11 in both preventive and treatment groups. It is also observed that restoration of normal platelet count might have been resulted owing to the synergistic effect of upregulated IL-11 which ultimately led to a significantly diminished TPO expression. CONCLUSION: Our data suggest that aqueous extract of C. papaya leaves possesses significant preventive and curative properties against thrombocytopenia.

Temporal Changes in Extended Spectrum ß-Lactamase Producing Organisms in Acute Care Surgery.

BACKGROUND: Extended-spectrum ß-lactamase (ESBL) producing organisms are resistant to a wide range of broad-spectrum antibiotics, and their emergence is a significant driving force of antibiotic resistance. Most South-Asian countries have become hotspots for antibiotic resistance, so specifics of ESBL data are critical to tackling antibiotic resistance. We present the temporal changes in ESBL-producing organisms cultured in our tertiary care referral centre. METHODS: Over a year, a historical cohort analysis was carried out at our tertiary care referral centre in Southeast Asia. Samples from patients presenting with acute surgical conditions were sent for culture and sensitivity. The phenotype of all specimens was checked using the combination disc method. Antimicrobial susceptibilities to various antibiotics were also checked as per CLSI (Clinical and Laboratory Standard Institute) guidelines. RESULTS: Specimens from 170 patients were analysed. The mean age was 44.73±19.89 years, and there was a female predominance of 62%. The most common organisms were Escherichia coli (70%), Klebsiella pneumoniae (18%), and Pseudomonas aeruginosa (16%). The percentage of ESBL-producing organisms was 54.7%, which is significantly higher than in previous reports. Widespread resistance was found against commonly used antibiotics, including co-amoxiclav (81.9%), ceftriaxone (75%), ciprofloxacin (47%), and levofloxacin (35.7%). Sensitivities to combination antibiotics like piperacillin-tazobactam (79.2% sensitive), cefoperazone-sulbactam (84.3% sensitive), and imipenem-cilastatin (91.1% sensitive) were also noted to be falling. CONCLUSION: The incidence of ESBL-producing organisms continues to increase at an alarming rate, which mandates strict antibiotic stewardship and amendments to local guidelines.

Immunomodulatory effect of thymoquinone on atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) or atopic eczema is a skin disease characterized with itching, increased serum level of immunoglobulin E, and peripheral eosinophilia. Thymoquinone (TQ) is an important ingredient of Nigella sativa seeds having antioxidant and anti-inflammatory effects. OBJECTIVE: Present study investigates the immunomodulatory effects of Thymoquinone (TQ) in mice model of atopic dermatitis. METHODS: Ear pinnas of mice were sensitized and challenged with DNCB (2-4 di nitro chloro benzene) to induce AD-like lesions. The mice were then treated with TQ and tacrolimus, both orally and topically. Ear thickness and weight were measured along with gross changes. Total and differential leukocyte counts were measured in blood. Total serum IgE levels were measured by enzyme linked immunosorbent assay (ELISA). The mRNA expression levels of IL-4, IL-5, and IFN-γ in ear tissue were measured using reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Both oral and topical thymoquinone showed the potential to improve atopic dermatitis by significantly reducing the inflammatory cells infiltration in the blood (p <  0.001) and improving the dermatitis score (p < 0.001). Significant reduction in ear thickness (p < 0.001) and IgE levels (p < 0.001) were also observed. TQ and tacrolimus also significantly attenuated mRNA expression levels of IL-4, IL-5 and IFN-γ (p <  0.001). CONCLUSIONS & CLINICAL RELEVANCE: Taken together, our results showed that oral and topical application of thymoquinone exerts immunomodulatory effects in animal model of atopic dermatitis, suggesting further studies and clinical trials to establish it as a candidate nutraceutical for the treatment of AD.

Pattern of antimicrobial drug resistance of Salmonella Typhi and Paratyphi A in a Teaching Hospital in Islamabad.

OBJECTIVE: To see the pattern of antimicrobial drug resistance among Salmonella serovars. METHODS: This longitudinal, observational study was conducted at Khan Research Laboratories Hospital, Islamabad, Pakistan, from May 2012 to December 2014. All patients presenting with typhoid fever with positive blood culture were included. Age, gender, salmonella serovar and sensitivity to 9 antimicrobial drugs were taken into account. The tested antimicrobial drugs were ampicillin, trimethoprim/sulphamethoxazole, chloramphenicol, nalidixic acid, ciprofloxacin, ofloxacin, levofloxacin, ceftriaxone and cefixime. SPSS 22 was used for analysis. RESULTS: Of the 197 patients, 118(59.9%) were males and 79(40.1%) were females. Moreover, there were 78(39.6%) children and 119(60.4%) adults. The overall mean age was 19.58±13.82 years. Patients with positive culture for salmonella typhi were 155(78.7%) while patients with positive cultures for salmonella paratyphi A were 42(21.3%). No other serovar was found in this study. Overall percentage of multidrug resistance for both salmonella typhi and paratyphi was 74(37.5%). CONCLUSIONS: The prevalence of multidrug resistance and quinolone resistance among salmonella serovars was high.

Comparison of maternal serum lipoproteins in normal pregnancy and primiparous patients with eclampsia.

OBJECTIVE: To evaluate changes in serum lipoproteins in primiparous women with eclampsia and compare it with pregnant women having normal blood pressure. METHODS: This cross sectional study was conducted on 65 primiparous eclamptic patients and 21 normotensive pregnant women in the tertiary care hospitals of Peshawar. History of each woman was recorded on a questionnaire. Blood pressure was measured using standard methods. About 5 ml of venous blood was drawn for the analysis of lipoproteins. The data was analyzed using computer software package SPSS version 10. The P value <0.05 was considered statistically significant. RESULTS: Mean age of hypertensive cases was 23.2 ± 0.52 years while that for controls was 23.9 ± 1.16 years. Significant differences were found in serum lipoproteins. Women having eclampsia had 28.8%, 29.5%, 31.1%, 32.9% and 65.3% higher, low density lipoprotein-cholesterol (LDLC), triglycerides (TG), total cholesterol (TC):high density lipoprotein-cholesterol (HDLC) ratio, LDLC: HDLC ratio and TG: HDLC ratio respectively as compared to the control group. The HDLC concentrations, HDLC: VLDLC ratio and apolipoprotein-A1 level were 26.9%, 56.6% and 27.9% respectively, lower in the patient group as compared to the controls. CONCLUSION: This study suggests that evaluation of lipoprotein concentrations during antenatal period can be helpful in the early detection and prevention of developing eclampsia.

Frequency of ABO blood groups and RhD factor in the female population of District Peshawar.

OBJECTIVE: To determine the frequency of ABO blood group and Rhesus (Rh) D antigen in the females of "District" Peshawar, Khyber Pakhtunkhwa Province, Pakistan. METHODS: This cross-sectional study was conducted on 429 women having pregnancy induced hypertension, admitted in the three teaching hospitals of Peshawar, over a period of one year. Blood sample was collected from each subject after taking informed consent. The antigen antibody agglutination slide test for "blood grouping (ABO)" and RhD factors was done by using IgM and IgG monoclonal reagents. The antisera used were from Biolaboratory, USA. Data was analyzed for percentage calculation. RESULTS: The blood group distribution was 134 (31.2%), 43 (10.1%), 116 (27%), 136 (31.7%) for blood groups A, AB, O and B, respectively. Subjects having blood group B was slightly more dominant, followed by A and O, while blood group AB was rare in these females. Blood group A Rh negative is more in female 12 (37.5%) followed by group O 10 (31.3%), group B 09 (28.1%) and group AB 01 (3.1%). CONCLUSION: Frequency of "Rh-positive blood group" is B, A, O and AB, whereas the frequency of the most common Rh-negative blood group are A, O, B and AB respectively. The determination of the frequency of blood groups in the region would not only help in blood transfusion services, but also reduce the risk of erythroblastosis foetalis in the neonates.

Unique side effects of interferon.

Interferon-alpha, a potent mediator of host immune response, has immunomodulatory properties in addition to its antiviral effects. A wide spectrum of autoimmune diseases can occur in patients treated with interferon-alpha for chronic hepatitis B and D, of which clinical systemic lupus erythematosus (SLE) accounts for less than 1% and hypothyroidism for 2-4 %. We report herein a case of a 16-year-old male who developed antinuclear antibody (ANA)-negative SLE and hypothyroidism after treatment with interferon-alpha for chronic hepatitis. High index of suspicion is therefore necessary in all patients treated with interferon for early diagnosis and treatment.

Hypothyroidism simulating as polymyositis.

Polymyositis-like syndrome in hypothyroidism is a rare condition characterised by proximal muscle weakness and elevated muscle enzymes. Patients with this condition can initially be misdiagnosed as having polymyositis due to similar characteristics of both diseases; however a response to thyroxine is the main differentiating feature. This report highlights the case of a 30-year-old male who had severe myalgia and proximal muscle weakness. In addition to raised creatinine phosphokinase (CPK) levels, his biochemical profile showed hypothyroidism. Initially thought to be suffering from polymyositis, improvement in both clinical and biochemical profile with thyroxine led to the diagnosis of polymyositis-like syndrome associated with hypothyroidism.

Production of plant cell wall degrading enzymes by monoculture and co-culture of Aspergillus niger and Aspergillus terreus under SSF of banana peels

Filamentous fungi are considered to be the most important group of microorganisms for the production of plant cell wall degrading enzymes (CWDE), in solid state fermentations. In this study, two fungal strains Aspergillus niger MS23 and Aspergillus terreus MS105 were screened for plant CWDE such as amylase, pectinase, xylanase and cellulases (β-glucosidase, endoglucanase and filterpaperase) using a novel substrate, Banana Peels (BP) for SSF process. This is the first study, to the best of our knowledge, to use BP as SSF substrate for plant CWDE production by co-culture of fungal strains. The titers of pectinase were significantly improved in co-culture compared to mono-culture. Furthermore, the enzyme preparations obtained from monoculture and co-culture were used to study the hydrolysis of BP along with some crude and purified substrates. It was observed that the enzymatic hydrolysis of different crude and purified substrates accomplished after 26 h of incubation, where pectin was maximally hydrolyzed by the enzyme preparations of mono and co-culture. Along with purified substrates, crude materials were also proved to be efficiently degraded by the cocktail of the CWDE. These results demonstrated that banana peels may be a potential substrate in solid-state fermentation for the production of plant cell wall degrading enzymes to be used for improving various biotechnological and industrial processes.

Depression among patients with type-II diabetes mellitus.

This study aimed to determine the frequency of depression among patients with type-II diabetes mellitus in Peshawar at Khyber Teaching Hospital, Peshawar, from March to September 2010. Depression was assessed by using Beck Depressive Inventory-II (BDI-II). Out of 140 patients with type-II diabetes, 85 (61%) were women and 55 (39%) were men. Mean age was 45±7.45 years. Eighty four (60%) patients presented with severe depression. Depression was higher in females than males and widows. Depression was high in diabetic patients, especially in females and widows. It is of essence that psychiatric attention may be necessary to be incorporated in diabetes care both for prevention and treatment.

Production of plant cell wall degrading enzymes by monoculture and co-culture of Aspergillus niger and Aspergillus terreus under SSF of banana peels.

Filamentous fungi are considered to be the most important group of microorganisms for the production of plant cell wall degrading enzymes (CWDE), in solid state fermentations. In this study, two fungal strains Aspergillus niger MS23 and Aspergillus terreus MS105 were screened for plant CWDE such as amylase, pectinase, xylanase and cellulases (ß-glucosidase, endoglucanase and filterpaperase) using a novel substrate, Banana Peels (BP) for SSF process. This is the first study, to the best of our knowledge, to use BP as SSF substrate for plant CWDE production by co-culture of fungal strains. The titers of pectinase were significantly improved in co-culture compared to mono-culture. Furthermore, the enzyme preparations obtained from monoculture and co-culture were used to study the hydrolysis of BP along with some crude and purified substrates. It was observed that the enzymatic hydrolysis of different crude and purified substrates accomplished after 26 h of incubation, where pectin was maximally hydrolyzed by the enzyme preparations of mono and co-culture. Along with purified substrates, crude materials were also proved to be efficiently degraded by the cocktail of the CWDE. These results demonstrated that banana peels may be a potential substrate in solid-state fermentation for the production of plant cell wall degrading enzymes to be used for improving various biotechnological and industrial processes.

Histopathological studies on stunting syndrome in broilers, lahore, pakistan.

Runting stunting syndrome (RSS) is a multifactorial disease with many names and faces that had caused considerable economic losses to poultry through reduced uniformity, reduced livability, decreased body weights, elevated feed conversions, and many secondary diseases. The aim of the current study was to evaluate the effect of stunting syndrome on histopathology in chicks (n = 120) of different ages collected from nine different farms. Grouping was done on the basis of age (G1 = 1-10 days, G2 = 11-20 days, G3 = 21-30 days, and G4 = 31-40 days) including both stunted and normal chicks. Histopathological findings were the intestinal lesions (29%), including degeneration of villi, crypts, epithelial cells and lamina propria. Pancreatic histopathological lesions (16.65%) included the fibrosis, vacuolation, and degeneration of acinar cells. Degeneration of follicles and epithelial cells, of bursa of fabricius (43%) and dilation of glandular cells of proventriculus including lymphocytes infiltration (5.6%) were other histopathological findings. All these changes may interfere with normal digestive processes and normal body functioning resulting in poor weight gain and retarded growth or stunting of chicks.

Abnormal Lipid levels as a risk factor of eclampsia, study conducted in tertiary care Hospitals of Khyber Pakhtunkhwa Province - Pakistan.

OBJECTIVE: To evaluate abnormal lipid metabolism as a risk factor of eclampsia in pregnant women. METHODS: This cross sectional study was conducted in three tertiary care hospitals of Peshawar. Serum total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), triglyceride (TG), apolipoprotein A1 (APO-A1), APO-B100, lipoprotein-a (Lpa) were measured in 110 women with eclampsia and compared with 90 healthy pregnant women. Mean lipid levels in cases and controls were compared using student's t test". RESULTS: Mean systolic/diastolic blood pressure, TC, TG, VLDL-C and Lpa levels were significantly higher (p<0.001) in patients compared to control women. Similarly TC: HDL-C, LDL-C: HDL-C and TG: HDL-C ratio in the patients group were significantly higher (p<0.001) and HDL-C: VLDL-C ratio was significantly lower (p<0.001) in the patients as compared to control group. Undesirable cholesterol were noted in 35.8% patients, HDL-C in 50.5%, borderline high concentration of LDL-C in 23.6%, high triglycerides levels in 73.2%, undesirable cholesterol ratio in 52.3% and undesirable LDL-C ratio were noted in 82.1% patients of eclampsia. CONCLUSION: Serum lipids were found significantly higher thus early assessment may be helpful in prevention of complications in the eclampsia patients.

A feasible method for growing fungal pellets in a column reactor inoculated with mycelium fragments and their application for dye bioaccumulation from aqueous solution.

In the present paper, a feasible method was developed to grow fungal pellets in an air lift column reactor inoculated with mycelium fragments for improving separation effect of biomass from solution and reducing clogging effect of biomass; bioaccumulation of dye by the growing fungal pellets in the case of mycelium fragments inoculation was investigated. The results showed that inoculation with the mycelium fragments without any pre-treatment did not witness the formation of pellets; only pre-treated fragments using maize as both nucleus and carbon source for 72 h incubation guaranteed the formation of pellets in the air lift column reactor. Nearly 100% of dye removal was obtained by bioaccumulation of the growing pellets in successive three batches of dye wastewater treatment. The formation of pellets not only resulted in low clogging effect to promote mass transfer and dye bioaccumulation but also caused quick separation of dye-loaded biomass from treated wastewater.

Bioleaching of zinc and manganese from spent Zn-Mn batteries and mechanism exploration.

In this work, bioleaching was used to extract valuable Zn and Mn from spent Zn-Mn batteries. The results showed that 96% of Zn extraction was achieved within 24h regardless of energy source types and bioleaching bacteria species. However, initial pH had a remarkable influence on Zn release, extraction dose sharply decreased from 2200 to 500mg/l when the initial pH value increased from 1.5 to 3.0 or higher. In contrast to Zn, all the tested factors evidently affected Mn extraction; the maximum released dose of 3020mg/l was obtained under the optimum conditions. The acidic dissolution by biogenic H(2)SO(4) by the non-contact mechanism was responsible for Zn extraction, while Mn extraction was owed to both contact/biological and non-contact mechanisms. The combined action of acidic dissolution of soluble Mn(2+) by biogenic H(2)SO(4) and reductive dissolution of insoluble Mn(4+) by Fe(2+) resulted in 60% of Mn extraction, while contact of microbial cells with the spent battery material and incubation for more than 7days was required to achieve the maximum extraction of Mn.