Inorganic nitrate benefits contrast-induced nephropathy after coronary angiography for acute coronary syndromes: the NITRATE-CIN trial.

BACKGROUND AND AIMS: Contrast-induced nephropathy (CIN), also known as contrast-associated acute kidney injury (CA-AKI) underlies a significant proportion of the morbidity and mortality following coronary angiographic procedures in high-risk patients and remains a significant unmet need. In pre-clinical studies inorganic nitrate, which is chemically reduced in vivo to nitric oxide, is renoprotective but this observation is yet to be translated clinically. In this study, the efficacy of inorganic nitrate in the prevention of CIN in high-risk patients presenting with acute coronary syndromes (ACS) is reported. METHODS: NITRATE-CIN is a double-blind, randomized, single-centre, placebo-controlled trial assessing efficacy of inorganic nitrate in CIN prevention in at-risk patients presenting with ACS. Patients were randomized 1:1 to once daily potassium nitrate (12 mmol) or placebo (potassium chloride) capsules for 5 days. The primary endpoint was CIN (KDIGO criteria). Secondary outcomes included kidney function [estimated glomerular filtration rate (eGFR)] at 3 months, rates of procedural myocardial infarction, and major adverse cardiac events (MACE) at 12 months. This study is registered with ClinicalTrials.gov: NCT03627130. RESULTS: Over 3 years, 640 patients were randomized with a median follow-up of 1.0 years, 319 received inorganic nitrate with 321 received placebo. The mean age of trial participants was 71.0 years, with 73.3% male and 75.2% Caucasian; 45.9% had diabetes, 56.0% had chronic kidney disease (eGFR <60 mL/min) and the mean Mehran score of the population was 10. Inorganic nitrate treatment significantly reduced CIN rates (9.1%) vs. placebo (30.5%, P < .001). This difference persisted after adjustment for baseline creatinine and diabetes status (odds ratio 0.21, 95% confidence interval 0.13-0.34). Secondary outcomes were improved with inorganic nitrate, with lower rates of procedural myocardial infarction (2.7% vs. 12.5%, P = .003), improved 3-month renal function (between-group change in eGFR 5.17, 95% CI 2.94-7.39) and reduced 1-year MACE (9.1% vs. 18.1%, P = .001) vs. placebo. CONCLUSIONS: In patients at risk of renal injury undergoing coronary angiography for ACS, a short (5 day) course of once-daily inorganic nitrate reduced CIN, improved kidney outcomes at 3 months, and MACE events at 1 year compared to placebo.

Peripheral intravenous catheter-induced phlebitis in a tertiary hospital of Karachi: a cohort study.

PURPOSE: This study aimed to determine the incidence of peripheral intravenous catheter (PIVC)-induced phlebitis and its predictors among adult patients hospitalized at Dow University Hospital, Karachi, Pakistan. METHODS: A sample of 258 adult patients admitted in the selected wards and planned for peripheral intravenous catheter insertion were recruited through consecutive sampling during March to May 2019. Daily follow-ups were performed to observe signs of phlebitis using a validated tool. The cohort was followed until discharge, removal of peripheral intravenous catheter, or study conclusion. RESULTS: Of 258 patients studied, 139 (53.9%) were females. A significant number of the participants 104 (40.3%) were young adults of age 20-40 years. The incidence of phlebitis was 39.1%. Tuberculosis (TB), peripheral intravenous catheter dwell time before initial assessment, administration of IV fluids, and dissatisfactory nursing care at Day 1 were associated significantly with the development of phlebitis. There was a doseresponse relationship between the catheter dwell time in hours before initial assessment and the development of phlebitis. CONCLUSION: This study found an increased incidence (39.1%) in three months of PIVC-induced phlebitis among adult patients. In addition to patient-related and PIVC-related risk factors considered in this study, PIVC-induced phlebitis is found to be significantly associated with the level of PIVC care provided by nurses. Continuous nursing education, developing standard care plans for PIVCs, and proper documentation of care are recommended.

Gender and its association with cardiac defects in down syndrome population at Children Hospital & Institute of Child Health, Lahore, Pakistan.

Objective: The objective of this study was to determine the frequency of different congenital cardiac defects co-existing in karyotypically proved Down syndrome population. It also highlighted the association between gender and pattern of congenital cardiac defects and gender as a risk factor. Methods: A cross sectional comparative study was done in the Department of Genetics, Children Hospital Lahore in the year 2017. A total of 160 patients were subjected to karyotypic analysis through blood test for determining the type of Down Syndrome and Echocardiography of all established cases was performed for determining presence and types of congenital cardiac defects. Results were evaluated in terms of establishing co-existence of various cardiac phenotypes in Down Syndrome cases. Results: In karyotypically proven 160 cases of Down syndrome, 58.1% of Down Syndrome cases and 88.2% of Down Syndrome with Congenital Cardiac Defects presented in infancy. The odds ratio (OR) suggested that females are 1.72 times more likely to experience a cardiac effect compared to males. Female gender was potentially associated (p-value 0.07) with occurrence of Patent Ductus Arteriosus (47.8%), whereas VSD (Ventricular Septal Defects) was most prevalent (41.1%) in males. Patent Ductus Arteriosus + Atrial Septal Defects (44.4%) was the commonest cardiac defect in female cases. The combined data for pattern of cardiac anomalies showed no significant association with gender, as indicated by a p-value of 0.990. Conclusion: The study concluded that most of Down syndrome cases and Down syndrome with congenital cardiac defects present to the hospital in infancy. Female cases are more prone to develop cardiac defects as compared to males. The manifestation of PDA (Patent Ductus Arteriosus) was significantly associated as an isolated anomaly in females and VSD (Ventricular Septal Defects) as isolated anomaly in males. Patent Ductus Arteriosus tend to co-exist most with ASD (Atrial Septal Defects) in female cases. Gender was not established as a risk factor for affecting the pattern of cardiac defects.

A systematic review and meta-analysis of the evidence on inflammation in depressive illness and symptoms in chronic and end-stage kidney disease.

BACKGROUND: Depression affects approximately 27% of adults with chronic kidney disease (CKD) and end-stage kidney failure (ESKF). Depression in this population is associated with impaired quality of life and increased mortality. The extent of inflammation and the impact on depression in CKD/ESKF is yet to be established. Through a systematic literature review and meta-analysis, we aim to understand the relationship between depression and inflammation in CKD/ESKF patients. METHODS: We searched nine electronic databases for published studies until January 2022. Titles and abstracts were screened against inclusion and exclusion criteria. Data extraction and study quality assessment was carried out independently by two reviewers. A meta-analysis was carried out where appropriate; otherwise a narrative review of studies was completed. RESULTS: Sixty studies met our inclusion criteria and entered the review (9481 patients included in meta-analysis). Meta-analysis of cross-sectional associations revealed significantly higher levels of pro-inflammatory biomarkers; C-reactive protein; Interleukin 6 (IL-6) and tumour necrosis factor-alpha in patients with depressive symptoms (DS) compared to patients without DS. Significantly lower levels of anti-inflammatory cytokine IL-10 were found in patients with DS compared to patients without DS. Considerable heterogeneity was detected in the analysis for most inflammatory markers. CONCLUSION: We found evidence for an association of higher levels of pro-inflammatory and lower anti-inflammatory cytokines and DS in patients with CKD/ESKF. Clinical trials are needed to investigate whether anti-inflammatory therapies will be effective in the prevention and treatment of DS in these patients with multiple comorbidities.

Using the artificial bee colony technique to optimize machine learning algorithms in estimating the mature weight of camels.

This paper aims to predict male and female camels' mature weight (MW) through various morphological traits using hybrid machine learning (ML) algorithms. For this aim, biometrical measurements such as birth weight (BW), length of face (FL), length of the neck (NL), a girth of the heart (HG), body length (BL), withers height (WH), and hind leg length (HLL) were used to estimate the mature weight for eight camel breeds of Pakistan. In this study, multivariate adaptive regression splines (MARS), random forest (RF), and support vector machine (SVM) were applied to develop prediction models. Furthermore, the artificial bee colony (ABC) algorithm is employed to optimize ML models' internal parameters and improve prediction accuracy. The predictive performance of ML and hybrid models was evaluated on a testing dataset using goodness-of-fit measures such as mean absolute deviation (MAD), mean absolute percentage error (MAPE), coefficient of determination (R2), and root mean square error (RMSE). The results of the study revealed the ABC-SVM model was the best predictive model. The experimental results of this study showed that the proposed ABC-SVM method could effectively improve the accuracy for MW prediction of camels, thus having a research and practical value.

An overview of biofeedback techniques in mechanical low back pain: effects on sensory integration of balance.

Low back pain is a common musculoskeletal disorder involving the lumbar spine. It affects almost 80% of the world's population and is associated with functional limitations. The reported global prevalence ranges from15-30%. Postural control involves processing the information from sensory stimulus derivative of vestibular, visual, and somatosensory systems in a coordinated manner to precisely regulate center of mass and body positioning. Failure of one or more of these systems, or incorrect processing of sensory information leads to instability or risk of fall. Low back pain can also modify the sensory input for postural control. Biofeedback can be utilized to assist "down-train" elevated muscle activity or to "up-train" weak or inhibited, muscles. Clinicians can use biofeedback to determine if patients are able to relax and evaluate psychophysiological reactions of muscles. Using biofeedback, patients can be educated about physiological processes and how biopsychosocial factors can interact causing recurrent complaints of pain.

Exploring the beliefs and experiences with regard to COVID-19 vaccine hesitancy and acceptance in a slum of Karachi, Pakistan.

The COVID-19-related misinformation and vaccine hesitancy is a widespread global concern and a recognized public health problem in Pakistan. The current research sought to explore the beliefs and experiences with regard to COVID-19, including vaccine hesitancy and acceptance, in a slum of Karachi, Pakistan. This study used an interpretivist epistemological approach for data collection and employed in-depth interviews (IDIs) and focus group discussions (FGDs) to explore the themes of interest. IDIs and FDGs were conducted in the local language (Pashtu) and Urdu, using semi-structured interview guides. A hybrid thematic analysis approach (use of both inductive and deductive coding) was used to analyze the data. We identified two key themes: the first related to vaccine hesitancy and refusal and included the role of personal belief systems, vaccine mistrust and public perceptions in hesitancy; the second related to vaccine acceptance and included knowledge and awareness about the vaccine and trusted sources of information. Religious beliefs and cultural norms influenced attitudes toward COVID-19 and vaccination. This study also found that awareness about the COVID-19 vaccine in this sample was influenced by sex, educational status and socioeconomic status. Participants with good health literacy and those from healthcare backgrounds were more likely to share views that indicated vaccine acceptance. The findings of this study are being used to co-design a comprehensive intervention to dispel COVID-19 misinformation and vaccine hesitancy across a range of stakeholders such as youths, community leaders, family members, faith leaders, schools and community-based local organizations in Pakistan.

This study explored the beliefs and experiences of the COVID-19 vaccine, including hesitancy and acceptance toward vaccinations, in a slum of Karachi, Pakistan. The findings of this study highlight that hesitancy was linked to personal belief systems, vaccine mistrust and public perceptions. In contrast, vaccine acceptance was linked to knowledge and awareness about the vaccine and trusted sources of information. This research identifies a clear need for co-designed health communication for vaccines to design and deliver people-centered interventions to dispel the COVID-19 misconceptions and vaccine hesitancy.

Uninephrectomy and class II PI3K-C2ß inactivation synergistically protect against obesity, insulin resistance and liver steatosis in mice.

Uninephrectomy (UNx) in living kidney donors for transplantation is now routine clinical practice. While chronic kidney disease, due to bilateral kidney dysfunction, is associated with insulin resistance, liver steatosis, and type 2 diabetes, the metabolic impact of UNx remains unclear. To better understand the crosstalk between the kidney and insulin target tissues, we studied the metabolic consequences of UNx and the potential involvement of class II PI3K-C2ß, the inactivation of which has been reported to result in insulin sensitization. Mice underwent UNx or sham operation followed by either normal chow or high-fat diet (HFD). Seventeen weeks post-UNx, mice showed improved glucose tolerance, insulin sensitivity, and decreased HFD-induced liver steatosis. This was associated with an enhanced serum FGF21 and insulin-stimulated Akt signaling in the liver and muscle of both lean and obese mice. Remarkably, the combination of UNx and PI3K-C2ß inactivation protected against HFD-induced obesity and further potentiated the metabolic improvement observed in WT UNx mice correlating with a synergistic increase in metabolic tissues of (1) insulin-stimulated Akt signaling (2) FGFR1 and ßKlotho expression. We demonstrated a potential beneficial effect of kidney donation and more effectively with PI3K-C2ß inactivation to protect against metabolic disorders through a mutual insulin/FGF21 sensitization.

Characterization and differentiation potential of mesenchymal stem cells isolated from multiple canine adipose tissue sources.

BACKGROUND: Mesenchymal stem cells (MSCs) are undifferentiated cells that can give rise to a mesoderm lineage. Adipose-derived MSCs are an easy and accessible source for MSCs isolation, although each source of MSC has its own advantages and disadvantages. Our study identifies a promising source for the isolation and differentiation of canines MSCs. For this purpose, adipose tissue from inguinal subcutaneous (SC), perirenal (PR), omental (OM), and infrapatellar fat pad (IPFP) was isolated and processed for MSCs isolation. In the third passage, MSCs proliferation/metabolism, surface markers expression, in vitro differentiation potential and quantitative reverse transcription PCR (CD73, CD90, CD105, PPARγ, FabP4, FAS, SP7, Osteopontin, and Osteocalcin) were evaluated. RESULTS: Our results showed that MSCs derived from IPFP have a higher proliferation rate, while OM-derived MSCs have higher cell metabolism. In addition, MSCs from all adipose tissue sources showed positive expression of CD73 (NT5E), CD90 (THY1), CD105 (ENDOGLIN), and very low expression of CD45. The isolated canine MSCs were successfully differentiated into adipogenic and osteogenic lineages. The oil-red-O quantification and adipogenic gene expression (FAS, FabP4, and PPARγ) were higher in OM-derived cells, followed by IPFP-MSCs. Similarly, in osteogenic differentiation, alkaline phosphatase activity and osteogenic gene (SP7 and Osteocalcin) expression were higher in OM-derived MSCs, while osteopontin expression was higher in PR-derived MSCs. CONCLUSION: In summary, among all four adipose tissue sources, OM-derived MSCs have better differentiation potential toward adipo- and osteogenic lineages, followed by IPFP-MSCs. Interestingly, among all adipose tissue sources, MSCs derived from IPFP have the maximum proliferation potential. The characterization and differentiation potential of canine MSCs isolated from four different adipose tissue sources are useful to assess their potential for application in regenerative medicine.

ResNet Based Deep Features and Random Forest Classifier for Diabetic Retinopathy Detection.

Diabetic retinopathy, an eye disease commonly afflicting diabetic patients, can result in loss of vision if prompt detection and treatment are not done in the early stages. Once the symptoms are identified, the severity level of the disease needs to be classified for prescribing the right medicine. This study proposes a deep learning-based approach, for the classification and grading of diabetic retinopathy images. The proposed approach uses the feature map of ResNet-50 and passes it to Random Forest for classification. The proposed approach is compared with five state-of-the-art approaches using two category Messidor-2 and five category EyePACS datasets. These two categories on the Messidor-2 dataset include 'No Referable Diabetic Macular Edema Grade (DME)' and 'Referable DME' while five categories consist of 'Proliferative diabetic retinopathy', 'Severe', 'Moderate', 'Mild', and 'No diabetic retinopathy'. The results show that the proposed approach outperforms compared approaches and achieves an accuracy of 96% and 75.09% for these datasets, respectively. The proposed approach outperforms six existing state-of-the-art architectures, namely ResNet-50, VGG-19, Inception-v3, MobileNet, Xception, and VGG16.

Psychometric properties of the Urdu version of the Geriatric Oral Health Assessment Index (GOHAI) and oral health-related quality of life in the elder Pakistani population.

OBJECTIVE: The study aimed to translate the English version of the Geriatric Oral Health Assessment Index, assess its reliability and validity, and demonstrate its psychometric properties with regard to OHRQoL in the elder Pakistani population. MATERIAL AND METHODS: In this cross-sectional study, 408 elder people were randomly recruited from three day-care centres. In the translation process, the translated Urdu version was reviewed by a committee of experts, followed by back-translation into English and re-reviewed by the same committee of experts. The questionnaire sought information about socio-demographic characteristics information and self-perception of oral, general health and treatment needs. OHRQoL was examined using GOHAI-U, and intraoral examination recorded the decayed, missing, and filled teeth. Reliability, internal consistency, convergent and discriminant validity of GOHAI-U were examined. RESULTS: The mean GOHAI-U score was 40.2 (SD = 5.7, range = 20-55). The Cronbach's alpha for GOHAI score was 0.71, item-scale correlation coefficients ranged from 0.63 to 0.76, and test-retest correlation ranged from 0.59 to 0.74. Three factors supported the theoretical construction in the component factor analysis of the index. For convergent validity, there was a significant relationship between the GOHAI score and self-perceived oral, general health and treatment needs (P < .05). For discriminant validity, a significant correlation was found between the GOHAI score and clinical measures of dental health status except with the carious teeth. CONCLUSION: The GOHAI-U has sufficient reliability and constructs validity to be used as an efficient measure of oral health-related quality of life in the Pakistani elder population.

Perceptions regarding team-based learning among undergraduate physical therapy students.

Team-based learning (TBL) is a strategy where teams work together to develop concepts and apply them towards problem-solving. This latest learning approach has not been tried in the educational environment of Rehabilitation Sciences. Hence, this study aimed to assess the knowledge and practices regarding TBL among undergraduate physical therapy students. A descriptive cross sectional survey was conducted involving 222 undergraduate physical therapy students who were selected via non-probability convenience sampling from Foundation University Institute of Rehabilitation Sciences over a period of three months (May 2018 - July 2018). Data was collected using questionnaire in the light of literature review, developed by Wright States University's Department of Communication based on the Minnesota satisfaction questionnaire. It contained questions regarding knowledge, practices and satisfaction with team-based learning, assessed via 19 statements on 5-point Likert scale. The sample consisted of 208 (93.7%) females and 14 (6.3%) males with mean age of 20.07±1.18 years. Regarding familiarity with TBL, 189 (85.1 %) students had understanding of TBL. 182 (82%) participants had practiced team-based learning whereas 40 (18%) had never practiced TBL in their lives. Majority of the students agreed on the positive effects of TBL on quality of learning, clinical reasoning abilities and professional development (median=4.00). TBL could be a highly useful, active learning strategy inculcating multiple skills among undergraduate students and should be introduced as supplementary to traditional lecture-based teaching.

Spectrum of external genital anomalies in disorders of Sex Development at Children Hospital & Institute of Child Health, Lahore, Pakistan.

OBJECTIVE: To describe the mode of presentation and frequency of external genital anomalies in disorder of sex development (DSD). METHODS: This cross-sectional study was conducted at Children Hospital & Institute of Child Health, Lahore from January to December, 2016 on Children with DSD above 10 years of age. A detailed history and physical examination were done. Positive findings were recorded on a predesigned proforma and analyzed by SPSS 21. Karyotyping on blood samples was done to determine their genetic sex. RESULTS: Out of 83 DSD children, 67% (n=56) were assigned a female sex at birth of which 9% (n=5) had ambiguous genitalia. Male sex at birth was given to 33% (n=27) of which 96% (n=26) had genital ambiguity. Mode of presentation other than ambiguous genitalia were delayed puberty, amenorrhea, hirsuitism, gynaecomastia, cyclic hematuria etc. Clitoromegaly was the main finding in 62.5% (n=5) and micropenis in 45% (n=9). Karyotypic sex of 56 female sex of rearing was 46XX 80% (n=45), 45X0 13% (n=7), XXX 2% (n=1) and 46 XY in 5% (n=3). Karyotypic sex of 27 male sex of rearing was 46XY in 78% (n=21), 46XX in 15% (n=4) and 47XXY in 7% (n=2). CONCLUSION: Disorders of sex development presented with a wide spectrum of external genital anomalies ranging from clitoromegaly in females to micropenis and hypospadias in males. There was also an extreme diversity in mode of presentation of these cases including pubertal delay, amenorrhea in females and gender confusion disorders.

Generation of High Dose Inhalable Effervescent Dispersions against Pseudomonas aeruginosa Biofilms.

PURPOSE: Novel particle engineering approach was used in this study to generate high dose inhalable effervescent particles with synergistic effects against Pseudomonas aeruginosa biofilms. METHODS: Spray dried co-amorphous salt of ciprofloxacin (CFX) and tartaric acid (TA) was prepared and coated with external layer of sodium bicarbonate and silica coated silver nanobeads. Design of experiments (DOE) was used to optimize physicochemical properties of particles for enhanced lung deposition. RESULTS: Generated particles were co-amorphous CFX/TA showing that CFX lost its zwitterionic form and exhibiting distinct properties to CFX/HCl as assessed by FTIR and thermal analysis. Particles exhibited mass mean aerodynamic diameter (MMAD) of 3.3 µm, emitted dose of 78% and fine particle dose of 85%. Particles were further evaluated via antimicrobial assessment of minimum inhibitory concentrations (MIC) and minimum biofilm eradication concentration (MBEC). MIC and MBEC results showed that the hybrid particles were around 3-5 times more effective when compared to CFX signifying that synergistic effect was achieved. Diffusing wave spectroscopy results showed that the silver containing particles had a disruptive effect on rheological properties as opposed to silver free particles. CONCLUSIONS: Overall, these results showed the potential to use particle engineering to generate particles that are highly disruptive of bacterial biofilms.

Diabetes conversation map - a novel tool for diabetes management self-efficacy among type 2 diabetes patients in Pakistan: a randomized controlled trial.

BACKGROUND: This study aimed to measure the effect of diabetes education using the novel method of "diabetes conversation map (DCM)" as compared to routine counselling (RC) on diabetes management self-efficacy (DMSE) among patients living with type 2 diabetes in Karachi, Pakistan. METHODS: A parallel arm randomized controlled trial among patients with type 2 diabetes aged 30-60 years, with HbA1c > 7%, diagnosed for at least 5 yrs., was conducted at the national institute of diabetes and endocrinology in Karachi, Pakistan. A total 123 type 2 diabetes patients were randomized into DCM (n = 62) or RC (n = 61). Four weekly diabetes control sessions of 40 min each using the DCM or RC was provided. DMSE was measured using a validated Urdu language DMSE tool at baseline and after three months of the randomization. Change in DMSE and HbA1c levels within groups (pre-post) and between the groups after 3 months of enrollment was compared. RESULTS: Baseline characteristics except HbA1c were similar between the two arms. After 3 months of enrollment, there was no change in the DMSE score in the RC arm however, significant increase in DMSE score was noted in the DCM arm (P = < 0.001). The average difference (95% confidence interval) in DMSE score between the DCM and RC arm was 33.7(27.3, 40.0; p = < 0.001) after 3 months of the enrollment. Difference in HbA1c within groups was not significant. CONCLUSIONS: DCM significantly improved DMSE among type 2 diabetes patients in a developing country setting like Pakistan. Healthcare workers caring for type 2 diabetes patients need to be trained on DCM to effectively utilize this novel tool for educating diabetes patients. TRIAL REGISTRATION: This trial was prospectively registered. ClinicalTrials.gov Identifier: NCT03747471. Date of registration: Nov 20. 2018.

The MEK Inhibitor Trametinib Ameliorates Kidney Fibrosis by Suppressing ERK1/2 and mTORC1 Signaling.

BACKGROUND: During kidney fibrosis, a hallmark and promoter of CKD (regardless of the underlying renal disorder leading to CKD), the extracellular-regulated kinase 1/2 (ERK1/2) pathway, is activated and has been implicated in the detrimental differentiation and expansion of kidney fibroblasts. An ERK1/2 pathway inhibitor, trametinib, is currently used in the treatment of melanoma, but its efficacy in the setting of CKD and renal fibrosis has not been explored. METHODS: We investigated whether trametinib has antifibrotic effects in two mouse models of renal fibrosis-mice subjected to unilateral ureteral obstruction (UUO) or fed an adenine-rich diet-as well as in cultured primary human fibroblasts. We also used immunoblot analysis, immunohistochemical staining, and other tools to study underlying molecular mechanisms for antifibrotic effects. RESULTS: Trametinib significantly attenuated collagen deposition and myofibroblast differentiation and expansion in UUO and adenine-fed mice. We also discovered that in injured kidneys, inhibition of the ERK1/2 pathway by trametinib ameliorated mammalian target of rapamycin complex 1 (mTORC1) activation, another key profibrotic signaling pathway. Trametinib also inhibited the ERK1/2 pathway in cultured primary human renal fibroblasts stimulated by application of TGF-ß1, the major profibrotic cytokine, thereby suppressing downstream mTORC1 pathway activation. Additionally, trametinib reduced the expression of myofibroblast marker α-smooth muscle actin and the proliferation of renal fibroblasts, corroborating our in vivo data. Crucially, trametinib also significantly ameliorated renal fibrosis progression when administered to animals subsequent to myofibroblast activation. CONCLUSIONS: Further study of trametinib as a potential candidate for the treatment of chronic renal fibrotic diseases of diverse etiologies is warranted.

Pharmaceutical evaluation of Graphirine syrup formulated from some common indigenous herbs of Pakistan.

Since ancient times humans have relied on traditional medicine and herbal formulation for the cure of various diseases and disorders. Globally, interest in use of herbal medicine has increased; as drawbacks of modern medicine and have started getting more prominent. Most of the traditional system of medicine; all in their formulations depends on plants. Traditional herbal cough products have considered to be mild, nontoxic, non-sedative and even harmless. As Syrup is commonly taken for the relief of cough; we aimed to formulate a cough syrup (Graphirine) from some common indigenous herbs; Adhatoda vasica, Piper longum and Rosa Damasena and evaluate its physicochemical parameters along with the changes in accelerated stability testing. Preformulation studies, i.e. moisture content, ash, water and ethanol extractive values of all three herbs were defined. Physicochemical factors, quantitative spectral measurement, FTIR spectrum for identification of compounds; along with accelerated stability and possible microbial fungal growth; were also checked for the formulated syrup. Each and every parameter complied with the specifications.

Correction to: Novel mutation G324C in WNT1 mapped in a large Pakistani family with severe recessively inherited Osteogenesis Imperfecta.

In the original publication of this article [1], there are two errors in the article which the cDNA position of the pathogenic variant WNT1 p.Gly324Cys should be c.970G>T instead of c.1168G>T.

Ambiguous genitalia: An overview of 7 years experience at the Children's Hospital & Institute of Child Health, Lahore, Pakistan.

OBJECTIVE: To determine the classification and etiological diagnosis of children presented with ambiguous genitalia/atypical genitalia according to the newer classification system of Disorder of Sex Development (DSD). METHODS: This observational, cross-sectional study was conducted at the Department of Pediatric Endocrinology and Diabetes at The Children's Hospital &Institute of Child Health, Lahore from January, 2007 to December; 2014. Files of all the children with ambiguous genitalia were retrospectively analyzed and relevant data was retrieved. All the information was recorded on predesigned proforma and analyzed accordingly. RESULTS: A total of 300 cases of ambiguous genitalia classified according to the new DSD classification. 46, XX DSD were 54.3% (n=163), 46, XY DSD were 43.7% (n=131), sex chromosome DSD were 2% (n=6). Among 46, XX DSD cases, the most common cause was congenital adrenal hyperplasia (97%, n=158). However, in 46, XY DSD partial androgen insensitivity/5α-reductase deficiency (62%. n=81) constituted the most commonest disorder. Other causes of 46XY DSD include testosterone synthesis defect(23%), congenital adrenal hyperplasia (CAH,12%), testis regression syndrome (1.5%) and persistent mullerian duct syndrome (PMDS,1.5%). Sex chromosome disorder constituted one case of iso-chromosome X turner syndrome, mixed gonadal dysgenesis (n=3), ovotesticular DSD/chimerism (n=2). CONCLUSION: Ambiguous genitalia have varied etiologies, 46; XXDSD found being the commonest of all, showing predominance of CAH especially salt loosing type. The early detection and prompt treatment of cases of ambiguous genitalia plays a pivotal role in the management of acute life threatening condition and gender assignment.

Polymorphism of Interleukin-10 (IL-10, -1082 G/A) and Interleukin-28B (IL-28B, C/T) In Pediatric Acute Lymphoblastic Leukemia (ALL).

We conducted genotypic analyses of interleukin-10 (IL-10) (-1082 G/A; GG, GA, AA) and interleukin-28B (CC, CT, TT) genes polymorphisms in acute lymphoblastic leukemia (ALL) pediatric patients in descriptive study to evaluate the prevalence of these mutations. In amplification refractory mutation system-PCR (ARMS-PCR), one reaction was carried out for each patient's DNA sample. For IL-28B gene, two forward and two reverse primers specific for C-allele and T-allele were used separately. For human IL-10 gene, two different forward primers specific for A and G alleles were used in combination with common reverse primer. IL-10 gene promoter showed highest frequency (n=29, 58%) of heterozygous (GA) allele, while genotypic analysis of IL-28B gene showed highest frequency (n=28, 56%) of homozygous (CC) allele. The IL-10 (AA) genotype related to its protein's less production in body which may be associated with the least survival of ALL's patients, while IL-28b (CT and TT) genotypes may be associated with less IFNλ3 levels and less life expectancy.