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Objectives: Real-world data (RWD) from the clinical care of patients captured through Electronic Health Records (EHRs) is a valuable resource for research. Understanding the relationship between characteristics and outcomes of patients treated in the real world and in oncology clinical trials by producing evaluable trial-like populations from RWD can advance clinical and regulatory knowledge. Methods: RWD from the Flatiron Health EHR-derived, de-identified, longitudinal database were compared with pooled patient-level data from the three randomized controlled trials (RCTs) supporting regular approval of CDK4/6 inhibitors for patients with previously untreated hormone receptor-positive, HER- metastatic breast cancer (mBC). The RCT group included patients who received aromatase inhibitor (AI) monotherapy (RCT-control), and an experimental group (RCT-experimental) that received a cyclin dependent kinase 4/6 (CDK4/6) inhibitor + AI. The real-world control group (rwCG) of patients initiating AI monotherapy was selected using the key eligibility criteria across the RCTs. Patients from the rwCG were matched to the RCT-control and the RCT-experimental patients, respectively. Matching (1:1) was performed through the propensity score (PS) method adjusting for baseline covariates of age, race, site of disease, ECOG PS, and metastatic disease (recurrent, De novo). Multiple imputation (MI) was adopted to impute missing ECOG PS in the rwCG due to the high percentage of missingness. Progression-free survival (PFS) and overall survival (OS) were analyzed for the following groups: A) rwCG and RCT- control B) rwCG and RCT-experimental and C) RCT-control and RCT-experimental. To assess the feasibility of RCT control arm replication, we assessed whether the trial replication hazard ratio (HR) estimates from analysis B were within the published trial estimates’ 95% confidence intervals (CIs). HR and their 95% CIs were estimated using Cox proportional hazard model. Results: A total of 1292 patients were selected from the EHR-derived database to comprise the rwCG and 1827 patients were pooled across the RCTs (1106 for RCT-experimental and 721 patients for RCT-control). With MI, 520 rwCG patients were matched to the RCT-control for analysis A, and 658 rwCG patients were matched to the RCT-experimental for analysis B. The results are summarized in Table 1. The point estimate of the PFS HR comparing the rwCG to the RCT-experimental was within the 95% CIs for three RCTs. For OS, the point estimate of the HR was within the 95% CI for MONALESSA-2 but not for PALOMA-2. Conclusion: PFS and OS appeared longer in the RCT-control than in the rwCG, and the difference was more pronounced in OS. While it appears that there is greater similarity for PFS than for OS based on the results of the matched analysis of RCT- experimental vs. rwCG, evaluation of PFS results are limited by substantial differences in assessment and outcome definitions for progression between RCT-control (RECIST) and rwCG. Despite PS matching, there are apparent differences between patients treated in RCTs and routine practice, highlighting the importance of clinical setting, trial selection, study design, and use of randomization. There are still outstanding feasibility questions on the evaluation of OS and further research is required to understand factors potentially impacting the outcomes between RCTs and RWD. Table 1: Estimated Treatment Effects in PFS and OS, rwCG vs RCT-control vs RCT-experimental Citation Format: Christy Osgood, Jiaxin Fan, Xin Gao, Catherine Keane, Jonathan Bryan, James P. Roose, Erik Bloomquist, Aracelis Torres, Shrujal Baxi, Nathan Nussbaum, Fatima Rizvi, Shenghui Tang, Irene Nunes, Julia Beaver, Donna R. Rivera, Lynn Howie, Prashni Paliwal, Laleh Amiri-Kordestani. Feasibility of generating an external control comparator using RWD by matching with previously conducted RCTs: CDK4/6 Inhibitors for the treatment of Metastatic Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-13-03.

The liver field has been debating for decades the contribution of the plasticity of the two epithelial compartments in the liver, hepatocytes and biliary epithelial cells (BECs), to derive each other as a repair mechanism. The hepatobiliary plasticity has been first observed in diseased human livers by the presence of biphenotypic cells expressing hepatocyte and BEC markers within bile ducts and regenerative nodules or budding from strings of proliferative BECs in septa. These observations are not surprising as hepatocytes and BECs derive from a common fetal progenitor, the hepatoblast, and, as such, they are expected to compensate for each other's loss in adults. To investigate the cell origin of regenerated cell compartments and associated molecular mechanisms, numerous murine and zebrafish models with ability to trace cell fates have been extensively developed. This short review summarizes the clinical and preclinical studies illustrating the hepatobiliary plasticity and its potential therapeutic application.

Aim: To look at anti-cancer effects of a variety of novel drugs on a variety of cancerous cell lines in the quest for a more inexpensive and effective anti-cancer treatment. Methodology: The research was carried out in conjunction with PCMD at JPMC's BMSI Department of Pharmacology. The experiment lasted about eight months (from April to November 2016). Noninvasive estrogen-dependent tumours, invasive estrogen-independent breast cancer, colorectal cancer, and cervical cancer were all depicted using MCF-7, HT-29, MDA-MB-231and HeLa cell lines, in that order. The MTT assay was used to improve the drugs' anticancer or antiproliferative efficacy in vitro. Using the MTT test, we determined the vitality of all treated tumour cell lines as well as the IC50 values of each chemical against all malignant cell lines. Results: This study demonstrated thatMetformin significantly decreased the survivability of MCF7, HT-29, MDA-MB-231, and Hela cell lines when compared to Apricoxib and Mebendazole. As a result, comparing the IC50 values of the studied agents for each of the evaluated treated cells backed up this claim. Hence, for Hela(p=0.386), MCF-7 (p=0.083), and MDA-MB-231 (p=0.083) cell lines but pochoc analysis revealed no significant differences in IC50 values of Metformin and Methotrexate. Conclusion: When compared to Apricoxib and Mebendazole, Metformin has a significant effect on the survivability of the cell lines studied. Metformin, as a result, would have been a wonderful chemotherapeutic addition Keywords: Cell lines, In vitro, MCF-7, Hela, MDA-MB-231

Teletherapy is an emerging and enlarging tool for having treatment in occupational therapy in rehabilitation sciences among occupational therapists all over the world mainly in Pakistan, especially during the era of COVID-19. A lot of studies have been done already highlighting the paramount of teletherapy around the world but it is a new rising mode of treatment in Pakistan coming to light. Therapists and Patients throughout the country making the most of this treatment way respectively and hence this method of treatment while using of technologies is highly being appreciated. The aim of this study is to foster and encourage the use of this technology in third-world countries like Pakistan. It is the most used treatment tool during COVID-19 among occupational therapists all over the country and is highly appreciated in order to cut-down the negative circumstances of a one-to-one session in which therapist and patient is in highly close contact to each other. This course of action has advocate the on-going rehabilitation treatment and has kept away people from COVID-19 expansion to the most extent. In this study, a 5years old boy was included with an under-diagnostic process within the umbrella term of genetic disorder. Having genetic disorder, his sessions were taken in tele-clinic using video call technology during COVID-19. In this process, AOTA Occupational Therapy Tele-Health Decision Guide, AOTA Occupational Profile Template, AOTA Advisory Opinion for the Ethics Commission Teletherapy, i-PiCS-Internet-Based Parent-Implemented Communication Strategies Program, and modeling strategy were followed.

The autophagy mechanism recycles the damaged and long-standing macromolecular substrates and thus maintains cellular homeostatic and proteostatic conditions. Autophagy can be an unavoidable target in cancer therapy because its deregulation leads to cancer formation and progression. Cancer can be controlled by regulating autophagy at different genetic, epigenetic, and post-translational levels. Epigenetics refers to the heritable phenotypic changes that affect gene activity without changing the sequence. Modern biology employs epigenetic alterations as molecular tools to detect and treat a wide range of disorders, including cancer. However, modulating autophagy at the epigenetic level may inhibit cancer growth and progression. Epigenetics-targeting drugs involved in preclinical and clinical trials may trigger antitumor immunity. Here, we have reviewed some experimental evidence in which epigenetics have been used to control deregulated autophagy in cancerous diseases. Furthermore, we also reviewed some current clinical trials of epigenetic therapy against cancer. We hope that this information can be utilized in the near future to treat and overcome cancer.

Background: Renal cell carcinoma (RCC) is considered to be the most frequent form of kidney cancer affecting both men and women worldwide. Monotherapy is not always effective and often results in resistance. Aim: To evaluate cannabidiol and sunitinib combination in human RCC using 786-O cells as an in vitro model. Study Design: Experimental study Place and duration of study: Dow International Medical College, Karachi from 15th November 2021 to 14th May 2022. Methodology: 786-O cells were culture and treated with sunitinib, cannabidiol and the combination of both and the growth inhibition was evaluated using MTT assay, while cell apoptosis was determine using flowcytometry. qPCR was used to analyze the expression of apoptotic genes and STAT3 in sunitinib and cannabidiol treated cells. Results: Sunitinib, cannabidiol and the combination of both drugs showed a dose dependent inhibition on growth of 786-O cells (p

Several clinical practice guidelines (CPGs), consensus statements, and recommendations currently exist for the diagnosis and management of breakthrough cancer pain (BTcP). These documents have considerable variability amongst them, and to date, their quality and methodologic rigor have not been appraised.We aim to identify and perform a quality appraisal of CPGs for the diagnosis and management of BTcP using the Appraisal of Guidelines for Research and Evaluation (AGREE II) tool.A comprehensive literature search was performed in MEDLINE (via PubMed), EMBASE, and SCOPUS databases up until January 1, 2021. Four reviewers independently evaluated each guideline using the AGREE II instrument. Scaled domain scores were generated and the threshold used for satisfactory quality was60%. Additionally, intraclass correlation coefficients (ICC) were calculated to determine level of agreement between reviewers.Eleven guidelines were selected for final evaluation based on inclusion/exclusion criteria. Only one guideline was classified of "average" quality while the rest were classified as "low" quality. The "Editorial Independence" (70.46 ± 35.7) and "Scope and Purpose" (64.78 ± 12.5) domains received the highest mean scores, while the "Applicability" (32.58 ± 13.5) and "Rigor of Development" (35.04 ± 9.0) domains received the lowest mean scores. ICC statistical analysis showed high magnitude of agreement between reviewers with a range of (0.790-0.988).Reflecting upon our quality appraisal, it is evident that the quality and methodologic rigor of BTcP guidelines can be improved upon in the future. Our findings also elucidate the existing variability/discrepancies among guidelines in diagnostic criteria and management of BTcP.

Background and AimsAcetaminophen (APAP) overdose is the leading cause of acute liver failure, with one available treatment, N-acetyl cysteine (NAC). Yet, NAC effectiveness diminishes about ten hours after APAP overdose, urging for therapeutic alternatives. This study addresses this need by deciphering a mechanism of sexual dimorphism in APAP-induced liver injury, and leveraging it to accelerate liver recovery via growth hormone (GH) treatment. GH secretory patterns, pulsatile in males and near-continuous in females, determine the sex bias in many liver metabolic functions. Here, we aim to establish GH as a novel therapy to treat APAP hepatotoxicity.Approach and ResultsOur results demonstrate sex-dependent APAP toxicity, with females showing reduced liver cell death and faster recovery than males. Single-cell RNA sequencing analyses reveal that female hepatocytes have significantly greater levels of GH receptor expression and GH pathway activation compared to males. In harnessing this female-specific advantage, we demonstrate that a single injection of recombinant human GH protein accelerates liver recovery, promotes survival in males following sub-lethal dose of APAP, and is superior to standard-of-care NAC. Alternatively, slow-release delivery of human GH via the safe nonintegrative lipid nanoparticle-encapsulated nucleoside-modified mRNA (mRNA-LNP), a technology validated by widely used COVID-19 vaccines, rescues males from APAP-induced death that otherwise occurred in control mRNA-LNP-treated mice.ConclusionsOur study demonstrates a sexually dimorphic liver repair advantage in females following APAP overdose, leveraged by establishing GH as an alternative treatment, delivered either as recombinant protein or mRNA-LNP, to potentially prevent liver failure and liver transplant in APAP-overdosed patients.

The outermost upper quadrant at the right side of the abdomen is right upper quadrant, also acknowledged as epigastrium. Objective: To evaluate of the causes of abdominal right upper quadrant pain using ultrasound. Methods: This was a descriptive cross-sectional study conducted at private medical setup of Gujranwala, Pakistan from January 2022 to March 2022. The information required for this study was collected by using ultrasound equipment TOSHIBA XARIO 100 having probe frequency of 3.5Hz. A sample size of 70 patients was considered having abdominal pain in the right upper quadrant. The data were entered and analyzed using SPSS version 20.0. Results: Highest frequency of RUQ pain was shown in more than 45 years in females 47 (67.1%). The most common diagnosis of patients with RUQ pain was fatty liver disease 27 (38.6%) followed by Cholelithiasis 11(15.7%). Conclusion: Ultrasound is the gold standard modality for diagnosing abdominal organs diseases as it is a cheap, non-invasive and fast modality. Most common diseases diagnosing in patients with RUQ pain is fatty liver (38.6%) in old females (67.1 %).

Nanofluids have already proven great potential in the thermal amplification of several manufacturing industries and have been widely employed in energy technologies in recent times. Therefore, the current framework investigates the characteristics of the Jeffrey nanofluid flow with the influence of activation energy and motile microorganisms over a sheet is considered. The influence of the magnetic field is another important physical parameter in the flow analysis and has been regarded in this review. The remarkable properties of nanofluid are demonstrated by thermophoresis and Brownian motion characteristics. Thermophoresis has relevance in mass transport processes in many higher temperature gradient operating systems. An appropriate similarities transformation is utilized make convenient to partial differential equation into ordinary differential equations. The well-known shooting tactic is utilized to estimate numerical outcomes of obtained ordinary system of flow. The governing dimensionless equations are integrated subject to the aid of the bvp4c scheme in the built-in software of MATLAB to find out the solution. The procedure assumed employing MATLAB. The characteristics of physical parameters against the velocity of fluid, temperature, concentration, and motile microorganisms are elaborated through graphs and tables. The dynamic physical declaration of attained results reveals that buoyancy ratio parameter and bioconvection Rayleigh number plays a vibrant role in the declining flow of Jeffery nanofluid while contrasting nature is analyzed for mixed convection parameter. The increasing behavior of temperature is observed for larger variations of heat sink/source parameters and thermophoresis parameter while it shows conflicting nature for increasing values of Prandtl number. The concentration of nanoparticle is reduced with the advanced values of Prandtl number, Lewis number and Brownian motion, perceived from the results. The mounting valuation of the Peclet number and Bioconvection Lewis number caused a reduction in motile microorganism concentration. The envisaged hypotheses could be beneficial for modifications to extrusion systems, bio-mimetic systems, efficient energy generation, bio-molecules and improved production systems.

Based on the perceptions of the local farmers, this study aims to assess the effects of socioeconomic factors and climatic change on the groundwater livelihood system, with a particular focus on in situ Persian wheels/dug wells. Farmers’ perceptions of climate change and how it is affecting their way of life in the Soan River Basin have also been evaluated to determine the most appropriate adaptive interventions. Information and literature about dug wells was unavailable, which stressed the need to carry out this survey. A structured close-ended questionnaire was designed and administered with as much quantitative data as possible. Random sampling opted for a 5 km buffer zone across the Soan River and its tributaries. Union councils having more than 50% of their area lying in the buffer zone were surveyed, and data was collected. Fifty UCs fell within this criterion, and six dug wells from each Union Council were surveyed. The results of our survey collecting local farmer’s perceptions determined that about 70% of respondents agreed about climate change in the Soan Basin of Pakistan, and 62% of farmers reported that climate change severely impacted their livelihood by affecting agricultural productivity and water availability. Ninety-two percent reported summer becoming hot, 72% highlighted that winters are becoming less cold, and 96% reported that average annual rainfall has decreased compared to 10 years before. About 72% of respondents indicated that available water in their dug wells had decreased, and 80% of respondents explained that their crop yield had decreased compared to 10 years before. Sixty percent preferred drip and 35% sprinkler irrigation as efficient water management practices to cope with water shortages. Ninety-five percent of farmers were ready to use solar pumps for irrigation to tame high pumping costs. The study recommends integrating solar pumping with drip and sprinkler irrigation systems to enhance farmers’ cropped area and productivity. These vulnerable farmers can enhance their resilience and profitability by adopting high-value agriculture (tunnel farming, off-season vegetables, etc.) instead of conventional crops.

Introduction: The significance of written feedback in students’ learning is well established in the literature; however, it is contingent on several factors, particularly the quality of written feedback. Many teachers are not formally trained to give feedback that could affect the student learning. Objective: This study was designed to investigate whether teachers modify their written feedback in response to a formal training workshop on written feedback. Methodology: Using a quasi-experimental design with pre and post within subject design, 94 teachers participated in this study. As a pre-test, participants were made to provide written feedback on a sample script at the beginning of the workshop. This was followed by a two-day interventional workshop that included discussions and hands on exercises on multiple aspects of written feedback. At the end of the workshop, the participants were again asked to provide feedback on the same script. Results: Comparisons between the pre- and post-intervention data revealed several differences. The quantity of feedback increased subsequent to the intervention. A rise in feedback on form and writing style was observed after the workshop, as opposed to a slight drop in feedback on content, leading to a more balanced focus. Although some of the desired differences, such as avoiding vague comments and criticism, were statistically insignificant, most of the other, differences in the pre-test and post-test were statistically significant. Conclusion: This study affirms that a formal training workshop could improve the quality of teachers’ written feedback.

The contamination of agroecosystems by microplastics (MPs) has raised great concerns recently. Plastic mulching has contributed a lot in the building of MP pollution in farmlands. This technique has been in use for decades worldwide because of its immense advantages, preferably in drier and colder regions. The physical extraction of plastic mulches at the end of the growing season is very laborious and ineffective, and thus small pieces of mulches are left in the field which later convert into MP particles after aging, weathering, or on exposure to solar radiation. MPs not only influence physical, chemical, or biological properties of soils but also reduce crop productivity which could be a threat to our food security. They also interact with and accumulate other environmental contaminants such as microbial pathogens, heavy metals, and persistent organic pollutants on their surfaces which increase their risk of toxicity in the environment. MPs also transfer from one trophic level to the other in the food chain and ultimately may impact human health. Because of the ineffectiveness of the recovery of plastic film fragments from fields, researchers are now mainly focusing on alternative solutions to conventional plastic mulch films such as the use of biodegradable mulches. In this review, we have discussed the issue of plastic mulch films in agroecosystems and tried to link already existing knowledge to the current limitations in research on this topic from cropland soils and future prospects have been identified and proposed.

Heavy metal pollution is a great hazard to the environment that enters the ecosystem through different natural and anthropogenic sources. A study was performed to evaluate concentrations of Cd and Pb in selected plants, Ricinus communis and Parthenium hysterophorus, and soils from different functional sites in Sialkot. Maximum fresh and dry weights of R. communis were recorded from control and field sites. Highest concentrations of Cd in P. hysterophorus (33.5 mg kg−1) and R. communis (24.36 ± 2.83 mg kg−1) were recorded at residential and industrial sites, respectively. However, road site samples showed maximum concentrations of Pb both in R. communis (9.06 ± 0.35 mg kg−1) and P. hysterophorus (7.90 ± 0.36 mg kg−1). Soil from the road site were found to be highly acidic (pH 4.75 ± 0.04), while the field site showed highest EC (494 ± 3.60) and TDS (509 ± 3.00) values. Generally, there were reductions in chlorophyll a and carotenoids, but an increase in chlorophyll b was observed in both plants at all sites compared to the control.

The photoinduced synthesis of zinc oxide nanoparticles (ZnO NPs) was carried out to unveil the effects of change in wavelength of photons. ZnO NPs were synthesized by the coprecipitation technique exposed to different light regimes [dark environment, daylight, and blue-, green-, yellow-, and red-colored light-emitting diodes (LEDs)] at room temperature. X-ray diffractogram (XRD) revealed the wurtzite structure of ZnO NPs. A small change in the size of ZnO NPs (17.11-22.56 nm) was observed with the variation in wavelength of lights from 350 to 700 nm. Spherical to hexagonal disks and rodlike surface morphologies were observed by scanning electron microscopy (SEM). The elemental composition and surface chemistry of NPs were studied by energy-dispersive X-ray diffractive (EDX) and Fourier transform infrared (FTIR) spectra. Maximum free radical quenching activity, cation radical scavenging, and total antioxidant capacity were found in ZnO NPs synthesized under green light (28.78 ± 0.18, 30.05 ± 0.21%, and 36.55 ± 2.63 μg AAE/mg, respectively). Daylight-synthesized NPs (DL-ZNPs) showed the greatest total reducing potential (15.81 ± 0.33 μg AAE/mg) and metal-chelating activity (37.77 ± 0.31%). Photoinduced ZnO NPs showed significant enzyme inhibitory effects on amylase, lipase, and urease by red-light NPs (87.49 ± 0.19%), green-light NPs (91.44 ± 0.29%), and blue-light NPs (92.17 ± 0.34%), respectively. Photoinduced ZnO NPs have been employed as nanozymes and found to exhibit intrinsic peroxidase-like activity as well. Blue-light-synthesized ZnO NPs displayed the strongest antibacterial activity (23 mm) against methicillin-resistant Staphylococcus aureus (MRSA). This study can be considered as a novel step toward the synthetic approach using LEDs to synthesize ZnO NPs with specific physicochemical properties and extends a great prospect in the environmental chemistry, food safety, and biomedical fields as nanozyme, antioxidant, antibacterial, anti-α-amylase, antiurease, and antilipase agents.

Some nanoparticles (NPs) have photocatalytic and photodynamic properties that change on variation in wavelength of light carrying different energies. To access photo-dynamic toxicity of CuO NPs, Brassica nigra seeds were in vitro grown on CuO NPs supplemented media under the exposure of five different spectral lights (white, blue, red, yellow and green). Light wavelength significantly affected shoot and root length and fresh weight of B. nigra and CuO NPs exerted different level of toxicity under these lights. Noteworthy variations were observed in free radical scavenging activity, total antioxidantive response and total reducing power potential when plants were grown in presence of NPs and spectral lights. Significant variations in total phenolics and flavonoids contents were observed in shoots as compared with roots. HPLC analysis presented variation in phenolics in shoots extracts under synergistic influence of NPs and light regime. The study shows that nanoparticles exert different level of toxicity under different wavelengths of lights. Resultantly plants show variations in morphological and biochemical responses. Consequently secondary metabolites produce in plants at varying concentrations to mitigate nanotoxicity under photodynamic response. Phenolics and flavonoid production enhance in plant grown in presence of CuO NPs and different wavelength of striking light.

Background Under-reporting of clinical trial results can lead to negative consequences that include inhibiting propagation of knowledge, limiting the understanding of how devices work, affecting conclusions of meta-analyses, and failing to acknowledge patient participation. Therefore clinical trial transparency, through publication of trial results on ClinicalTrials.gov or in manuscript form, is important. We aimed to examine clinical trial transparency in endoscopic clinical trials. Methods The ClinicalTrials.gov database was searched for endoscopy trials up to October 2019. Adherence to the reporting of results to the database or in publication form was recorded for each trial. Results The final analysis included 923 trials, of which 801 were completed and 122 were either terminated or suspended. Results were available either on ClinicalTrials.gov or in publication for 751/923 trials (81.4 %). Other fields have reported a publication rate of 40 %–63 %. Results were available on ClinicalTrials.gov for 168 trials (18.2 %) and in the form of a publication for 720 trails (78.0 %). Conclusions Compared with other fields in medicine, endoscopy clinical trials have a high rate of clinical trial transparency. However, there is room for improvements as close to one-fifth of trials fail to report results and 81.8 % do not report results to ClinicalTrials.gov.

On June 29, 2020, the FDA approved pertuzumab, trastuzumab, and hyaluronidase-zzxf subcutaneous injection (Phesgo) for the treatment of patients with HER2-positive early-stage and metastatic breast cancer. Patients should be selected for therapy based on an FDA-approved companion diagnostic test. Approval was primarily based on the FeDeriCa trial, a randomized, open-label, multicenter comparability study of pertuzumab, trastuzumab, and hyaluronidase-zzxf subcutaneous injection compared with intravenous pertuzumab and intravenous trastuzumab administered in the neoadjuvant and adjuvant settings with chemotherapy for the treatment of patients with early breast cancer. The pharmacokinetic endpoints were, first, to demonstrate that the exposure of subcutaneous pertuzumab was not inferior to that of intravenous pertuzumab, and then to demonstrate that the exposure of subcutaneous trastuzumab was not inferior to that of intravenous trastuzumab. The primary endpoints were met with the observed lower limit of the two-sided 90% confidence intervals above the prespecified noninferiority margins. The most common adverse reactions were alopecia, nausea, diarrhea, anemia, and asthenia. The totality of the evidence demonstrated comparability of the subcutaneous product to intravenous, allowing for extrapolation and approval of all breast cancer indications for which intravenous trastuzumab and pertuzumab are approved.

International audience; Resource availability matters the most in health care system-based outcomes. But health spending is highly unequal across the world and presents varying outcomes. This study aims to investigate the missing part that why some countries failed to have reasonable outcomes despite spending more than those countries that spend less. This study intends to include all those factors that are responsible for improving the costeffectiveness of health expenditures. The study took two data sets, one from the developing countries and second of developed countries as per World Bank classification. As anticipated, there are significant differences in health per capita expenditures. Determinants were also found to behave differently both in the short run and long run as well as across the two data sets.

Phytophthora capsici is a notorious fungus which infects many crop plants at their early and late growth stages. In the present study, twelve P. capsici isolates were morphologically characterized, and based on pathogenicity assays; two highly virulent isolates causing post-emergence damping-off on locally cultivated chilli pepper were screened. Two P. capsici isolates, HydPak1 (MF322868) and HydPk2 (MF322869) were identified based on internal transcribed spacer (ITS) sequence homology. Plant growth promoting rhizobacteria (PGPR) play a significant role in disease suppression and plant growth promotion in various crops. Out of fifteen bacterial strains recovered from chilli rhizosphere, eight were found potential antagonists to P. capsici in vitro. Bacterial strains with strong antifungal potential were subjected to biochemical and molecular analysis. All tested bacterial strains, were positive for hydrogen cyanide (HCN), catalase production and indole-3-acetic acid (IAA) production (ranging from 6.10 to 56.23 µg ml−1), while siderophore production varied between 12.5 and 33.5%. The 16S rRNA sequence analysis of tested bacterial strains showed 98–100% identity with Pseudomonas putida, P. libanensis, P. aeruginosa, Bacillus subtilis, B. megaterium, and B. cereus sequences available in the National Center for Biotechnology Information (NCBI) GenBank nucleotide database. All sequences of identified bacteria were submitted to GenBank for accessions numbers (MH796347-50, MH796355-56, MH801129 and MH801071). Greenhouse studies concluded that all tested bacterial strains significantly suppressed the P. capsici infections (52.3–63%) and enhanced the plant growth characters in chilli pepper. Efficacy of many of these tested rhizobacteria is being first time reported against P. capsici from Pakistan. Plant growth promoting rhizobacteria (PGPR) exhibiting multiple traits may be used in the development of new, eco-friendly, and effective bioformulations as an alternative to synthetic fungicides.

Objectives: In search of effective and economical option for prophylaxis of Migraine evaluating the prophylactic role of Metformin in migraine. Study Design: Single blind placebo controlled trial. Setting: Department of Pharmacology BMSI, JPMC, in collaboration with Sindh services Hospital Karachi. Period: April 2017 – August 2018. Material & Methods: A total 105 patients with diagnosed migraine were included in this trial. Total patients were equally divided into 3 groups designated Groups A, B, and C that were representative of Placebo, Metformin and Propranolol groups respectively. Total study duration was 6 months, which were equally divided into 2 phases. First 3 month phase was baseline period and later one was treatment period. The primary parameters for evaluating the prophylactic role of Metformin in Migraine were Migraine integral Burden scale (MIBS), HIT-6, MIDAS, MPQ-5, frequency of migraine attack per month. Results: At baseline there were statistically non-significant differences found for MIBS (F (2,102) = 0.346, p = 0.708), MIDS (F (2,102) =0.248, p=0.781), MPQ (F (2,102) =0.188, p=0.828) and severity of headache (F (2,102) =0.247, p=0.782) among all treated groups. But at final follow up there was highly significant difference were found among all treated groups for all parameters. Pairwise comparison showed significant differences between group A and B and group A and C was recorded for all parameters. Nevertheless there was no difference seen in group B and C (mean difference (MD) = -0.171 ± 0.149, p= 0.485) ,(MD= -0.143±0.132,p=0.526), (MD = - 2.057±0.301, p