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Background Glioblastoma (GBM) is an aggressive primary brain tumor with a high recurrence rate and poor prognosis. Necroptosis, a pathological hallmark of GBM, is poorly understood in terms of its role in prognosis, tumor microenvironment (TME) alteration, and immunotherapy.Methods & Results We assessed the expression of 55 necroptosis-related genes in GBM and normal brain tissues. We identified necroptosis-stratified clusters using Uni-Cox and Least Absolute Shrinkage and Selection Operator (LASSO) regression to establish the 10-gene Glioblastoma Necroptosis Index (GNI). GNI demonstrated significant prognostic efficacy in the TCGA dataset (n = 160) and internal validation dataset (n = 345) and in external validation cohorts (n = 591). The GNI-high subgroup displayed a mesenchymal phenotype, lacking the IDH1 mutation, and MGMT methylation. This subgroup was characterized by significant enrichment in inflammatory and humoral immune pathways with prominent cell adhesion molecules (CD44 and ICAM1), inflammatory cytokines (TGFB1, IL1B, and IL10), and chemokines (CX3CL1, CXCL9, and CCL5). The TME in this subgroup showed elevated infiltration of M0 macrophages, neutrophils, mast cells, and regulatory T cells. GNI-related genes appeared to limit macrophage polarization, as confirmed by immunohistochemistry and flow cytometry. The top 30% high-risk score subset exhibited increased CD8 T cell infiltration and enhanced cytolytic activity. GNI showed promise in predicting responses to immunotherapy and targeted treatment.Conclusions Our study highlights the role of necroptosis-related genes in glioblastoma (GBM) and their effects on the tumor microenvironment and patient prognosis. TheGNI demonstrates potential as a prognostic marker and provides insights into immune characteristics and treatment responsiveness.

Abstract The Yunshang black goat is a renowned mutton specialist breed mainly originating from China that has excellent breeding ability with varying litter sizes. Litter size is an important factor in the economics of goat farming. However, ruminal microbiome structure might be directly or indirectly regulated by pregnancy-associated factors, including litter sizes. Therefore, the current experiment aimed to evaluate the association of different litter sizes (low versus high) with ruminal microbiome structure by 16S rRNA gene sequencing and metabolomic profiling of Yunshang black does. A total of twenty does of the Yunshang Black breed, approximately aged between 3 and 4 years, were grouped (n = 10 goats/group) into low (D-l) and high (D-h) litter groups according to their litter size (the lower group has ≤ 2 kids/litter and the high group has ≧ 3 kids/litter, respectively). All goats were sacrificed, and collected ruminal fluid samples were subjected to 16S rRNA sequencing and LC–MS/MC Analysis for ruminal microbiome and metabolomic profiling respectively. According to PCoA analysis, the ruminal microbiota was not significantly changed by the litter sizes among the groups. The Firmicutes and Bacteroidetes were the most dominant phyla, with an abundance of 55.34% and 39.62%, respectively. However, Ruminococcaceae_UCG-009, Sediminispirochaeta, and Paraprevotella were significantly increased in the D-h group, whereas Ruminococcaceae_UCG-010 and Howardella were found to be significantly decreased in the D-l group. The metabolic profiling analysis revealed that litter size impacts metabolites as 29 and 50 metabolites in positive and negative ionic modes respectively had significant differences in their regulation. From them, 16 and 24 metabolites of the D-h group were significantly down-regulated in the positive ionic mode, while 26 metabolites were up-regulated in the negative ionic mode for the same group. The most vibrant identified metabolites, including methyl linoleate, acetylursolic acid, O-desmethyl venlafaxine glucuronide, melanostatin, and arginyl-hydroxyproline, are involved in multiple biochemical processes relevant to rumen roles. The identified differential metabolites were significantly enriched in 12 different pathways including protein digestion and absorption, glycerophospholipid metabolism, regulation of lipolysis in adipocytes, and the mTOR signaling pathway. Spearman’s correlation coefficient analysis indicated that metabolites and microbial communities were tightly correlated and had significant differences between the D-l and D-h groups. Based on the results, the present study provides novel insights into the regulation mechanisms of the rumen microbiota and metabolomic profiles leading to different fertility in goats, which can give breeders some enlightenments to further improve the fertility of Yunshang Black goats.

Abstract Hybrid nanofluids offer higher stability, synergistic effects, and better heat transfer compared to simple nanofluids. Their higher thermal conductivity, lower viscosity, and interaction with magnetic fields make them ideal for various applications, including materials science, transportation, medical technology, energy, and fundamental physics. The governing partial differential equations are numerically solved by employing a finite volume approach, and the effects of various parameters on the nanofluid flow and thermal characteristics are systematically examined from the simulations based on a self-developed MATLAB code. The parameters included magnetic field strength, the Reynolds number, the nanoparticle volume fraction, and the number and position of the strips in which the magnetic field is localized. It has been noted that the magnetized field induces the spinning of the tri-hybrid nanoparticles, which generates the intricate structure of vortices in the flow. The local skin friction (CfRe) and the Nusselt number (Nu) increase significantly when the magnetic field is intensified. Moreover, adding more nanoparticles in the flow enhances both Nu and CfRe, but with different effects for different nanoparticles. Silver (Ag) shows the highest increase in both Nu (52%) and CfRe (110%), indicating strong thermal-fluid coupling. Alumina (Al2O3) and Titanium Dioxide (TiO2) show lower increases in both Nu (43% and 34%) and CfRe (14% and 10%), indicating weaker coupling in the flow. Finally, compared with the localized one, the uniform magnetic field has a minor effect on the flow and temperature distributions.

BackgroundZinc deficiency poses significant health risks, particularly in low-income settings. This study aims to evaluate the impact of agronomically zinc biofortified (fermented and non-fermented) and post-harvest wheat flour flatbread on zinc status and metabolic health in adolescents and adult women in rural Pakistan.MethodsA four-arm triple-blind randomized controlled trial will be conducted in a rural district of Pakistan. Participants (adolescents aged 10-19 and adult women aged 20-40) will be assigned to receive fermented or unfermented high zinc agronomically biofortified wheat flour flatbread, post-harvest zinc-fortified wheat flour flatbread, or low zinc conventional whole wheat flour flatbread. The meal would be served once a day, six days a week for six months. The study aims to enroll 1000 participants and will be analyzed based on the intention-to-treat principle. The trial is registered with number NCT06092515.OutcomesPrimary outcomes will include serum zinc concentration and metabolic markers, while secondary outcomes include anthropometric measurements, blood pressure, and dietary intake.ConclusionThis trial will provide valuable insights into the efficacy of agronomically zinc biofortified wheat flour in improving zinc status and metabolic health. Findings may inform public health strategies to combat zinc deficiency in resource-limited settings.

Objectives: To find out occurrence of ovarian hyperstimulation in patients who were hyper responders in in vitro fertilization cycles. Secondary outcome was to assess number of metaphase II oocyte and fertilization rate, cleavage rate and pregnancy outcome when GnRHa is used for final maturation and triggering ovulation. STUDY DESIGN, SIZE, and DURATION: This is retrospective descriptive analysis of cases managed at single center from June 2017 till May 2018. PATIENTS & METHODS: Twenty patients were identified as hyper responders based on baseline, ovarian reserve characteristics, that is antral follicle count, (AFC) > 25, AMH > 4ng/ml and on day of trigger, follicles >-25 in number of ≥ 11mm were administered GnRHa trigger and 1500IU hCG on oocyte retrieval day while luteal phase was supported with daily vaginal progesterone and twice daily estradiol valerate. Sixteen patients underwent fresh transfer while four patients had their embryos frozen. MAIN RESULTS: Twenty patients were identified as high risk and their baseline characteristics were, mean age 31.7 ± 4.50, mean antral follicle count 25.7 ± 5.01, Anti Mullerian hormone level mean 4.64 ± 2.52 and PCOS was present in 35% cases. Peak estradiol level mean 13455-± 6632pmol/l and mean follicles count of 25.45 ± 8.78 confirmed a high response. Oocyte yield was 11.45+ Metaphase oocyte retrieved were 85.5% and cleavage rate of 93%. No case of early onset OHSS was identified. Only one patient developed moderate OHSS. Pregnancy rate was 31.25%. Miscarriage rate was 6.3% and ongoing pregnancy was 25%. CONCLUSION: This small retrospective descriptive analysis supports the view of current literature that GnRH trigger not only prevents early onset OHSS also achieves increase of M11 oocytes. In addition, pregnancy outcome is not statistically different to those cycles where hCG is used as trigger.

Background: Now, a days myofascial trigger points are tremendously occurring and become a stressful part of nearly any person at any time in a lifetime. This study compares the effects of ischemic compression pressure with spray and stretch technique to treat active myofascial trigger points of the trapezius muscle in patients with neck pain. Methodology: A comparative interventional study was conducted at Dow University of Health Sciences from December 2016 and May 2017. Seventy patients (35 in each group) with active myofascial trigger points of trapezius were randomly assigned to group A (ischemic compression pressure) and group B (vapocoolant spray and stretch technique). Baseline and last session assessment of pain intensity, pain pressure tolerance, cervical range of motion and functional disability were measured through numerical pain-rating scale, algometer, goniometer and neck disability index, respectively. Results: Both groups showed significant improvement in all dependent variables of study which were neck pain, cervical range of motion and pain pressure tolerance (p-value

Objective: To describe the demographic, clinical, serological and radiological scores in patients with rheumatoid arthritis (RA) presenting in a tertiary hospital in Pakistan. Study Design: Cross sectional study. Place and Duration of Study: Department of Rheumatology, Fauji Foundation Hospital (FFH), Rawalpindi, from Sep 2018 to Feb 2019. Methodology: The study included 52 female patients with RA between the ages of 18 and 80 years. Data were obtained from FFH Rawalpindi's outpatient department. Demographic details, reference data, and serological status were recorded. The joints involved in the onset of the disease, joint deformities, clinical disease activity index (CDAI) and overall functional status were evaluated. Extra-articular manifestations of rheumatoid arthritis have also been examined during a detailed physical examination. The patient's bone mineral density was calculated by the use of dual energy absorptiometry (DEXA scan). Radiological scores were evaluated using modified sharp score. Results: Mean age of the patient was 55.08 ± 8.79 and mean duration of disease 9 .73 ± 7.54. The most common co-morbidity in rheumatoid arthritis patients was hypertension 20 (38.5%). Twenty four (11.7%) patients had osteoporosis. Wrist was the first joint involved in 17 (32.7%) patients. Ulnar deviation was the most common deformity in 12 (23.1%) patients. Sharp score for joint space narrowing was 61.09 ± 36.90 and sharp score joint erosions were 36.90 ± 42.41. Most common extra articular manifestation was anemia. Conclusion: Rheumatoid arthritis as a variable spectrum of disease with different manifestations. Patients had radiological damage as demonstrated by high sharp score even before starting.................

Abstract Background Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit upon the host. Knowledge and attitudes of health professionals have been reported to be at a medium level for probiotics. The objective was to evaluate the knowledge and practice styles about probiotics among pediatricians working in different regions of Saudi Arabia. Methods This cross-sectional study was conducted at pediatric hospitals in Saudi Arabia. A national survey of 550 pediatric providers (PPs) was conducted between January and March 2020 anonymously on their knowledge and practice styles regarding probiotics, and it was completed by pediatric residents (PRs), pediatric specialist (PSs), pediatric consultants (PCs), and pediatric gastroenterologists (PGs). Results The survey had a response rate of 82%. Among the respondents, 57.7% were aware of the probiotic’s definition. There were significant differences in the percentage of participants who had little knowledge of probiotics (P

Objective(s): This study was designed to investigate the effect of AgNPs (10 nm and 30 nm) on different phenotypes of Staphylococcus aureus biofilm consortia.Materials and Methods: A total of eighteen biofilm-producing isolates of Methicillin-Resistant S. aureus (MRSA) were used in the present study. Tube methods, Congo-red agar method, and scanning electron microscopy (SEM) were used to study biofilm phenotypes. Population analysis assay on a tryptone agar (TSA) plate was applied to study the different phenotypes of biofilm consortia. The effect of AgNPs was evaluated by broth dilution assay. Results: Results showed that biofilm consortia harbor different phenotypes, i.e., planktonic, metabolically inactive cells, and small colony variants (SCVs) or persister cells. The focus of the present study is the effect of AgNPs on biofilm consortia of MRSA, particularly on the SCVs population. Large size AgNPs (30 nm) were unable to diffuse through extracellular matrix material coverings of the biofilm consortia; they were only active against the planktonic population that occupies the outer surface of consortia. The smaller AgNPs (10 nm), on the other hand, were found to diffuse through the matrix material and hence were effective against planktonic as well as metabolically inactive population of consortia. Moreover, 30 nm AgNPs take 6 hr to disperse off and kill planktonic and upper surface indwellers. The 10 nm AgNPs disperse and kill the majority of biofilm indwellers within 20 min. Conclusion: The present study showed that 10 nm AgNPs can easily penetrate inside the biofilm and are active against all of the indwellers of consortia.

Objective: To make an estimate of magnitude of cerebrospinal fluid rhinorrhea patients presenting in Otorhinolaryngology department of CMH Lahore and further elaboration of our experience of different techniques of endonasal endoscopic repair of cerebrospinal fluid leak. Study Design: Cross-sectional analytical study. Place and Duration of Study: Combined Military Hospital Lahore, from Jan 2017 to Dec 2017. Methodology: For this analytical study last one year’s data of cerebrospinal fluid rhinorrhea patients as well as all endoscopic surgeries was collected retrospectively from ENT department registers. Both male and female patients of all ages undergoing functional endoscopic sinus surgery were included in study to calculate the magnitude of cerebrospinal fluid rhinorrhea. Results: During the last one year, 832 ENT surgeries were performed out of which 234 (28%) were functional endoscopic sinus surgeries. Total 10 cerebrospinal fluid rhinorrhea patients presented in ENT department of CMH Lahore in the last one year and all these underwent endonasal endoscopic repair surgery in operation theatre. Out of these 3 were males and 7 females. Age range was 43 to 67 years (average age was 53.2 years). Out of 10 cases of cerebrospinal fluid rhinorrhea treated endoscopically, 4 (40%) were iatrogenic, 3 (30%) were traumatic and 3 (30%) had spontaneous cerebrospinal fluid leakage. Conclusion: Cerebrospinal fluid leakage is quite rare happening and its surgical management is also difficult to master. In our study use of facialata (alone or with septal cartilage) to endoscopically repair the leak has proved to be successful in 90% of cases.

Objective: To evaluate the usefulness of residual cholesteatoma wall as a lining of mastoid cavity in achieving a dry mastoid cavity after a canal wall down (CWD) mastoidectomy. Study Design: Experimental study. Place and Duration of Study: Combined Military Hospital Lahore, from May 2015 to Oct 2016. Methodology: Both adults and children (58 cases) undergoing canal wall down mastoidectomies were included in the study. While removing the cholesteatoma, medial wall of fundus was left intact and wide opening was ensured to leave it saucer shaped. Post operatively all patients were observed to see that when their mastoid cavities become dry and asymptomatic. Results: Out of total 58 patients operated 11 were children and 47 adults. Age range was 11 to 67 years. Thirty patients were males and 28 were females. Following Canal Wall Down mastoidectomies all the mastoid cavities were managed regularly and at the end of four months 27 (47%) cavities became dry. At six months 49 (84%) became dry and one was still wet after one year of surgery. Conclusion: At 12 month follow up, 98% percent of mastoid cavities were dry and asymptomatic with our technique of leaving part of cholesteatoma wall. However longer follow-up and larger sample is required for better outcome assessment.

Background and Objective: COVID-19 can cause severe acute respiratory distress syndrome. With deteriorating disease, most of the patients may require intensive care admission. This study was carried out to determine and evaluate the response of Tocilizumab with special reference to C-reactive protein (CRP) in critically ill patients presented to Farooq Hospital, West Wood Lahore.Methods: This retrospective study included the data of 55 critically ill COVID-19 patients (respiratory rate ≥30, SpO2Results: Out of 55 patients who were administered Tocilizumab, 72.7% survived whereas 27.3% died. There was higher median reduction of CRP levels in patients who survived (77.5 to 34.9 mg/L) as compared to those who died (65.5 to 45.3 mg/L). There was a statistically significant difference between CRP levels at the time of admission, 72 hours after Tocilizumab was administered (PConclusion: Tocilizumab administration might be helpful in reducing the complications of cytokine storm in patients with severe COVID-19 pneumonia.

BACKGROUND & OBJECTIVE: Many polio cases have been reported in recent years, which strongly affect the Global Polio Eradication Initiative campaign. This study aimed to determine the global trends in polio research during the last fifty years. METHODOLOGY: An online search was conducted utilizing the Web of Science Core Collection database. The key term used was “Polio*" and the retrieved documents were assessed for several attributes. The required graphs were generated using OriginPro 2018. Furthermore, the data were plotted for co-authorship organizations, co-authorship countries, and co-occurrence author keywords network visualization mapping using VOSviewer software for windows. RESULTS: A total of 2,345 publications were included, cited 22,872 times. The year 2017 was the most frequent year with 162 (6.91%) publications. The paper authored by Nomoto and colleagues published in 1977 was the leading paper with 237 citations. In total, Vaccine was the leading journal with 168 (7.16%) publications, followed by Journal of Infectious Diseases 106 (4.52%), and Lancet 77 (3.28%). The included publications were published from 132 countries, of which 44 countries contributed ≥10 publications. The United States of America was the leading country with the highest number of publications (n=740, 31.56%), followed by India (n=215, 9.17%), and England (n=180, 7.68%). CONCLUSION: This study provide researchers and policy makers with a comprehensive list of the key bibliometric characteristics and major contribution in polio research. Majority of the studies were published in developed countries. The developing countries need to make strong research collaborations with developed countries.

The objective of this study was to optimize the organic selenium (Se) requirements of intensively reared silver carp (Hypophthalmichthys molitrix). A total of n = 300 juveniles silver carp 11.40±0.52 cm long, and average weighing 25.28±0.18 grams were randomly assigned to 15 aquaria (20 fish/100L aquaria) and subjected to five different dietary Se levels in a completely randomized design. The diets were pelleted supplemented with exogenous Se methionine @ 0.0, 0.3, 0.6, 0.9 and 1.2 mg/kg of the diet. The fourteen days of aquaria acclimatization was given to fish and then an 84-day feeding trial was conducted. The group supplemented with 0.9 mg/kg Se had greater feed intake, gain in length, body weight %, and specific growth rate with a better feed conversion ratio as compared to those fed on the rest of the dietary levels or control (P0.05). The proximate analysis showed that dry matter, crude protein, and fat contents of meat were not changed (P>0.05) by dietary treatments. Similarly, values of TBARS, RBCs, Hb, and blood glucose contents were similar (P>0.05) across the treatments. However, the concentration of WBCs, HCT, and MCHC was greater in those groups fed on 0.9 and 1.2 Se levels than in those fed on 0.6, 0.3, and 0.0 Se levels respectively (P

Objective(s): This study was designed to determine the relationship of Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli isolates in multispecies biofilms and their individual phenotypic characters in biofilm consortia. Materials and Methods: The subject isolates were recovered from different food samples and identified on the basis of growth on differential and selective media. Tube methods, Congo-red agar method, and scanning electron microscopy (SEM) were used to study biofilms phenotypes. The hydrophobicity of the strains was evaluated by the adhesion to apolar solvent. Results: The results showed that E. coli dominated the pre-biofilm stage. It has been observed that E. coli adopted biofilm life much before S. aureus and P. aeruginosa. However, after adopting biofilm lifestyle, slowly and gradually, P. aeruginosa dominated the consortia and dispersed other stakeholders. The subject isolates of P. aeruginosa produce cis-2-decanoic acid to disperse or inhibit S. aureus and E. coli biofilms. Gas-chromatography and mass spectrometry results showed that cis-2-decanoic was higher in the co-culture condition and increased at late log-phase or at stationary phase. Although majority of S. aureus were unable to compete with P. aeruginosa, however, a minor population competed, survived, and persisted in biofilm consortia as small colony variants. The survivors showed higher expression of sigB and sarA genes. P. aeruginosa showed comparatively higher hydrophobic surface properties. Conclusion: Comparative analysis showed that cell surface hydrophobicity, growth rate, and small colony variants (SCVs) are correlated in biofilm consortia of the P. aeruginosa, S. aureus, and E. coli.

Objective: To compare efficacy of chemical cautery with silver nitrate along with fucidin ointment versus topical vasoconstrictor spray (xylometazoline 0.05%) and fucidin ointment application in idiopathic pediatric anterior epistaxis. Study Design: Randomized controlled trial. Place and Duration of Study: Study was carried out at Combined Military Hospital (CMH) Bahawalpur from Jan 2016 to Dec 2016. Material and Methods: Total 112 patients fulfilling the inclusion criteria were selected from Ear Nose Throat (ENT) outpatient department at CMH Bahawalpur. They were randomly divided into two groups of 56 cases in each group. Group A individuals were treated by cauterization with 75% silver nitrate followed by fucidic acid ointment. Group-B individuals were treated with topical vasoconstrictor spray (xylometazoline 0.05% twice a day for one week) along with fucidic acid ointment. Efficacy was determined in terms of control of epistaxis, whether the procedure was effective in controlling epistaxis or otherwise i.e. patient again developed bleeding from same side of nose and needed further treatment to control epistaxis. All the cases were followed up for two months after procedure to check their efficacy. Results: There were total 61 (54.46%) males and 51 (45.54%) females among the cases. Mean age of patients was 8.27 (± 2.34) years. Both the groups were comparable as regards the gender (p=0.817) and age (p=0.749). Group-A were treated with silver nitrate cauterization followed by fucidic acid ointmnet application and group-B were treated by vasoconstrictor nasal spray along with fucidic acid ointment. In group A (silver nitrate cautery), 87.5% cases had no rebleed during two months follow up and in group-B, 67.8% children had no rebleed during two months follow up period (p=0.022). Conclusion: Chemical cauterization with silver nitrate along with fucidic acid ointment application was found to be more effective as compared to xylometazoline nasal spray and fucidic Acid ointment application in treating idiopathic pediatric epistaxis.

Objective: To assess the prevalence of various ear, nose and throat diseases in Shangla valley. Study Design: A descriptive cross-sectional study. Place and Duration of Study: Study was carried out in shangla. Duration of study was 3 months, from Jun 2014 to Aug 2014. Material and Methods: All the patients of any age group and both genders who reported with any ENT disorder and emergency were included in this study. Frequency and percentage of various ENT diseases among patients and emergency procedures performed were found. Results: A total of 2725 patients were included. The most common ENT disorder encountered was rhinosinusitis which was seen in 14.2% cases, followed by ear wax (impacted cerumen) in 13.4% and pharyngitis in 12.5% cases. Allergic rhinitis was seen in 10.4% cases, epistaxis in 7.4% and chronic suppurative otitis media in 6.4% cases. Among the emergency ENT procedures performed, anterior nasal packing was the commonest (done in 55 cases) followed by stitching of lacerations and foreign body removal from ear and nose. Conclusion: Ear, nose and throat diseases are very common in Shangla and their spectrum range from rhinosinusitis, impacted cerumen (ear wax) and pharyngitis to less common but potentially dangerous conditions like foreign body impaction in ear and nose.

Objective(s):Staphylococcus aureus is a Gram-positive pathogen, well known for its resistance andversatile lifestyle. Under unfavourable conditions, it adapts biofilm mode of growth. For staphylococcal biofilm formation, production of extracellular polymeric substances (EPS) is a pre-requisite, which is regulated by ica operon-encoded enzymes. This study was designed to know the impact of ascorbic acid on biofilm formation and colony spreading processes of S. aureus and MRSA. Materials and Methods: The isolates of methicillin-resistant S. aureus (MRSA) used in present study, were recovered from different food samples. Various selective and differential media were used for identification and confirmation of S. aureus. Agar dilution method was used for determination of oxacillin and ascorbic acid resistance level. MRSA isolates were re-confirmed by E-test and by amplification of mecA gene. Tube methods and Congo-Red agar were used to study biofilm formation processes. Gene expression studies were carried on real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Results: The results revealed the presence of mecA gene belonging to SCCmecA type IV along with agr type II in the isolates. In vitro studies showed the sub-inhibitory concentration of oxacillin induced biofilm production. However, addition of sub-inhibitory dose of ascorbic acid was found to inhibit EPS production, biofilm formation and augment colony spreading on soft agar plates. The inhibition of biofilm formation and augmentation of colony spreading observed with ascorbic acid alone or in combination with oxacillin. Moreover, gene expression studies showed that ascorbic acid increases agr expression and decreases icaA gene expression. Conclusion:The present study concluded thatascorbic acid inhibits biofilm formation, promotes colony spreading and increases agr gene expression in MRSA.

INTRODUCTION: Medicine budget allocation in health facilities usually focus on past funding levels and the efficiency of health services delivery. Despite the level of allocation to hospitals, there is a growing gap between available and required medicine budget because the health needs have not diminished. This gap has led us for medicine consumption costing of tehsil headquarters hospitals of Punjab. OBJECTIVE: To assess average medicine cost including laboratory investigations for indoor and outdoor patient treated at tehsil headquarter hospital of Punjab, working under Punjab Primary and Secondary Healthcare Department. SETTING: The cost of medicines consumption is estimated both for inpatient as well as outpatients of tehsil headquarter hospitals of Punjab. METHODOLOGY: Ten tehsil headquarter (THQ) hospitals were selected out of 129 THQ hospitals of Punjab through simple random sampling technique; 2 indoor and 2 outdoor patients were again chosen through simple random sampling technique from each ward of selected THQs and free medicine were dispensed to these selected patients.Cross sectional study design is used and cost of medicine consumption is observed from the patients of randomly selected sample hospitals at single point time or time interval. RESULTS: This study provides an estimated medicine cost for treating all indoor and outdoor patients at all THQ hospitals under Primary and Secondary Healthcare Department of Punjab. The average cost per outpatient visit is estimated as Rs. 172.46 and the average cost per admission for inpatient care is Rs. 2992.50.Total medicines consumption estimated cost for 129 tehsil headquarter hospitals is Rs 7.18 billion. CONCLUSION: The current study identified gap between allocated medicines budget and actual medicines needed by the patients. In future this study may provide guidelines to policy maker while calculating actual justified budget allocation for medicines, diagnostic and other supplies to fulfill the patient’s requirement effectively and efficiently.

Abstract Alantolactone (ALT), a sesquiterpene lactone component of Inula helenium, has been reported to exert anticancer activity in various cancers. However, the cellular targets and underlying mechanism of anticancer activity of ALT in various cancers including lung cancer has not been fully defined. In the present study, we found that ALT effectively inhibits proliferation and triggers oxidative stress mediated-apoptosis in A549 lung adenocarcinoma cells by inducing ER stress and mitochondrial dysfunction. This ALT-mediated apoptosis was inhibited by NAC while diamide potentiated it. Moreover, ALT effectively suppressed both constitutive and inducible STAT3 activation, inhibited its translocation into nucleus and decreased its DNA binding activity. Further mechanistic study revealed that ALT abrogated STAT3 activation by promoting STAT3 glutathionylation. ROS scavenger NAC reverted ALT-mediated STAT3 glutathionylation and inhibition of STAT3 phosphorylation. Finally, ALT enhanced chemosensitivity of A549 cells to doxorubicin and reversed doxorubicin resistance in A549/DR cells by inhibiting STAT3 activation and P-glycoprotein expression and increasing intracellular accumulation of doxorubicin. Suppression of STAT3 activation by targeting ROS metabolism with ALT thus discloses a previously unrecognized mechanism underlying the biological activity of ALT. Taken together; ALT induces oxidative stress-dependent apoptosis, inhibits STAT3 activation and augments doxorubicin toxicity in A549 lung cancer cells. These findings provide an in-depth insight into the molecular mechanism of ALT in the treatment of lung cancer.

Background Outcome measures in physiotherapy are multi dimensional hence, may not estimate the individualized goals of patients with varying complaints. To make a quantitative, individual assessment of patients in a community is even more challenging. Therefore, assessment measure such as goal attainment scaling (GAS) acts as a better tool of measurement. Objective To assess feasibility of goal attainment scaling (GAS) as used by physiotherapists in a community based ehabilitation setting. Method This is a quantitative pilot study with pre and post intervention data evaluation using GAS. The author selected 10 consecutive patients, of different diagnosis, from referred patients waiting list and handed over to physiotherapists who gave informed consent to apply GAS scale. Results A total of 10 patients data were collected. The mean age of patients was 80.4 years. Patients with lower quadrant complaints showed a marked improved in GAS scores. A total of 19 goals were identified , out of which 8 goals were achieved at expected level; 6 failed to reach the expected level and 5 were superseded the expected level of performance. Feedback from physiotherapists suggested that GAS is a useful measure for community based rehabilitation (CBR) in a low income setting. Conclusion GAS proves to be a responsive measure in CBR setting. GAS provides clarity of goals for the physiotherapists, patients and hence, their families. GAS seems to have good psychometric properties but the concern with its use is therapist may set goals which are too easy to achieve for the patient. Further research is required to investigate its feasibility of GAS in Pakistan.

To produce unsaturated fatty acids, membrane-bound fatty acid desaturases (FADs) can be exploited to introduce double bonds into the acyl chains of fatty acids. In this study, 19 membrane-bound FAD genes were identified in Gossypium raimondii through database searches and were classified into four different subfamilies based on phylogenetic analysis. All 19 membrane-bound FAD proteins shared three highly conserved histidine boxes, except for GrFAD2.1, which lost the third histidine box in the C-terminal region. In the G. raimondii genome, tandem duplication might have led to the increasing size of the FAD2 cluster in the Omega Desaturase subfamily, whereas segmental duplication appeared to be the dominant mechanism for the expansion of the Sphingolipid and Front-end Desaturase subfamilies. Gene expression analysis showed that seven membrane-bound FAD genes were significantly up-regulated and that five genes were greatly suppressed in G. raimondii leaves exposed to low temperature conditions.

Postural Tachycardia Syndrome (PoTS) represents a disorder of the autonomic nervous system that results in symptoms of orthostatic intolerance. Despite having a severe impact on the patient’s quality of life, the current treatment options for PoTS are based on limited evidence. Subsequently, this results in clinicians having to utilise a variety of treatment regimens in the hope of successfully providing symptomatic relief. However, the options available for PoTS are not without significant side effects that can worsen an already debilitating condition. Our cases provide a further novel treatment option for clinicians to consider in PoTS refractory to established treatments.

Calcium-dependent protein kinases (CDPKs) are one of the largest protein kinases in plants and participate in different physiological processes through regulating downstream components of calcium signaling pathways. In this study, 41 CDPK genes, from GrCPK1 to GrCPK41, were identified in the genome of the diploid cotton, Gossypium raimondii. The phylogenetic analysis indicated that all these genes were divided into four subgroups and members within the same subgroup shared conserved exon-intron structures. The expansion of GrCPKs family in G. raimondii was due to the segmental duplication events, and the analysis of Ka/Ks ratios implied that the duplicated GrCPKs had mainly undergone strong purifying selection pressure with limited functional divergence. The cold-responsive elements in promoter regions were detected in the majority of GrCPKs. The expression analysis of 11 selected genes showed that GrCPKs exhibited tissue-specific expression patterns and the expression of GrCPKs were induced or repressed by cold treatment. These observations would lay an important foundation for functional and evolutionary analysis of CDPK gene family in Gossypium species.

Background: Awareness of morbidity as a major surgical constraint has led the surgical fraternity to proceed from conventional to the more recent laparoscopic cholecystectomies. But developing countries still lack the availability of infrastructure and expertise for widespread use of minimal access and open cholecystectomy still continues to be the widely used method of cholecystectomy. The objective of this study was to determine the peroperative and early postoperative complications of open cholecystectomy. Material & methods: This descriptive study was carried out at Department of Surgery, Peshawar Institute of Medical Sciences, Hayatabad, Peshawar. A total of 100 cases with symptomatic cholelithiasis were operated by open cholecystectomy from January 2011 to December 2012. Peroperative and early postoperative complications were recorded. Results: Among complications of access; difficulty in identification of anatomy was noted in 10% cases. Among procedure complications; vascular injury was recorded in 6%; bile duct injury in 2%, dropped stones in peritoneal cavity in 2%, and perforation of gallbladder in 2%. Postoperative complications on first day after operation i.e. bile leak in drain was noted in 6% cases, and fever in 4% cases. Postoperative complications on first follow-up visit i.e. wound infection was seen in 6% cases, sub-hepatic collection in 4%, and chest infection in 4% cases. Mean hospital stay was 68 hours. Conclusions: Open cholecystectomy is associated with few per and post-operative complications and we still recommend it in the management of cholelithiasis where facilities for advanced surgery are not available.

2014 marks the 20th anniversary of adipokines. Through the identification of leptin, our perceived understanding of adipose tissue was changed instantaneously. From a simple dormant site of energy storage, adipose tissue is now recognized as an integral hub of various hormones known as adipokines. Although great strides have been made in characterizing these hormones in health, research also shows they are significantly implicated in a series of pathologies. One such condition is obesity. Defined as an excess of adipose tissue, obesity remains one of the greatest healthcare epidemics of the 21st century. With no definitive treatment, attention has shifted to understanding the role of adipokines in obesity. This review provides an introduction to the salient obesity-related adipokines and their possible application as a treatment for obesity.

Alantolactone and isoalantolactone, main bioactive compounds that are present in many medicinal plants such as Inula helenium, L. Inula japonica, Aucklandia lappa, Inula racemosa, and Radix inulae, have been found to have various pharmacological actions including anti-inflammatory, antimicrobial, and anticancer properties, with no significant toxicity. Recently, the anticancer activity of alantolactone and isoalantolactone has been extensively investigated. Here, our aim is to review their natural sources and their anticancer activity with specific emphasis on mechanism of actions, by which these compounds act on apoptosis pathways. Based on the literature and also on our previous results, alantolactone and isoalantolactone induce apoptosis by targeting multiple cellular signaling pathways that are frequently deregulated in cancers and suggest that their simultaneous targeting by these compounds could result in efficacious and selective killing of cancer cells. This review suggests that alantolactone and isoalantolactone are potential promising anticancer candidates, but additional studies and clinical trials are required to determine their specific intracellular sites of actions and derivative targets in order to fully understand the mechanisms of therapeutic effects to further validate in cancer chemotherapy.