Attention-based deep convolutional neural network for classification of generalized and focal epileptic seizures.

Epilepsy affects over 50 million people globally. Electroencephalography is critical for epilepsy diagnosis, but manual seizure classification is time-consuming and requires extensive expertise. This paper presents an automated multi-class seizure classification model using EEG signals from the Temple University Hospital Seizure Corpus ver. 1.5.2. 11 features including time-based correlation, time-based eigenvalues, power spectral density, frequency-based correlation, frequency-based eigenvalues, sample entropy, spectral entropy, logarithmic sum, standard deviation, absolute mean, and ratio of Daubechies D4 wavelet transformed coefficients were extracted from 10-second sliding windows across channels. The model combines multi-head self-attention mechanism with a deep convolutional neural network (CNN) to classify seven subtypes of generalized and focal epileptic seizures. The model achieved 0.921 weighted accuracy and 0.902 weighted F1 score in classifying focal onset non-motor, generalized onset non-motor, simple partial, complex partial, absence, tonic, and tonic-clonic seizures. In comparison, a CNN model without multi-head attention achieved 0.767 weighted accuracy. Ablation studies were conducted to validate the importance of transformer encoders and attention. The promising classification results demonstrate the potential of deep learning for handling EEG complexity and improving epilepsy diagnosis. This seizure classification model could enable timely interventions when translated into clinical practice.

Seasonal Trends with the Comparison of Venous and Capillary Blood for Diagnosis of Malaria among Children in Karachi, Pakistan.

Background: More than 250 million people are infected by malaria parasites annually while around one million children less than 5 years of age die every year due to malaria. We aimed to assess the seasonal trends and usefulness of capillary and venous blood for rapid diagnosis of malaria. Methods: This cross-sectional study of 18 months duration was conducted at the National Institute of Child Health (NICH), Karachi. All patients reporting fever as chief complaint were recruited as study subjects. A semi-structured questionnaire was used to collect demographic information, presenting complaints, awareness of caregivers regarding malaria, preventive measures and history of malaria fever. Three ml Venous (2-3ml) as well as peripheral blood (3-4 drops) samples of all patients were collected for microscopy and rapid diagnostic tests (RDTs). Results: Out of total 477 patients with fever Venous and Capillary Blood RDTs methods detected 33(6.9%) and 30(6.3%) as the malaria positive while Venous and Capillary Blood Microscopy detected 30(6.1%) and 32(6.7%) cases respectively. Plasmodium Vivax infection was the most prevalent (87.9%) and majority (39.39%) of the cases occurred in the quarter, July to September. Conclusion: July to September is the peak season for malaria and P. Vivax (87.9%) is the predominant strain in Karachi. Venous and capillary blood are equally useful for malaria diagnosis however, convenience and less invasiveness may justify the preference of capillary blood over venous blood for early diagnosis of malaria.

Fortifying Smart Home Security: A Robust and Efficient User-Authentication Scheme to Counter Node Capture Attacks.

In smart home environments, the interaction between a remote user and devices commonly occurs through a gateway, necessitating the need for robust user authentication. Despite numerous state-of-the-art user-authentication schemes proposed over the years, these schemes still suffer from security vulnerabilities exploited by the attackers. One severe physical attack is the node capture attack, which allows adversaries to compromise the security of the entire scheme. This research paper advances the state of the art by conducting a security analysis of user-authentication approaches regarding their vulnerability to node capture attacks resulting in revelations of several security weaknesses. To this end, we propose a secure user-authentication scheme to counter node capture attacks in smart home environments. To validate the effectiveness of our proposed scheme, we employ the BAN logic and ProVerif tool for verification. Lastly, we conduct performance analysis to validate the lightweight nature of our user-authentication scheme, making it suitable for IoT-based smart home environments.

CREB-Regulated Transcriptional Coactivator 2 Proteome Landscape is Modulated by SREBF1.

cAMP response element-binding protein (CREB) regulated transcriptional coactivator 2 (CRTC2) is a critical transcription factor that maintains glucose homeostasis by activating CREB. Energy homeostasis is maintained through multiple pathways; therefore, CRTC2 may interact with other transcription factors, particularly under metabolic stress. CRTC2 liver-specific KO mice were created, and the global proteome, phosphoproteome, and acetylome from liver tissue under high-fat diet conditions were analyzed using liquid chromatography-tandem mass spectrometry and bioinformatics analysis. Differentially regulated proteins (DRPs) were enriched in metabolic pathways, which were subsequently corroborated through animal experiments. The consensus DRPs from these datasets were used as seed proteins to generate a protein-protein interaction network using STRING, and GeneMANIA identified fatty acid synthase as a mutually relevant protein. In an additional local-protein-protein interaction analysis of CRTC2 and fatty acid synthase with DRPs, sterol regulatory element binding transcription factor 1 (SREBF1) was the common mediator. CRTC2-CREB and SREBF1 are transcription factors, and DNA-binding motif analysis showed that multiple CRTC2-CREB-regulated genes possess SREBF1-binding motifs. This indicates the possible induction by the CRTC2-SREBF1 complex, which is validated through luciferase assay. Therefore, the CRTC2-SREBF1 complex potentially modulates the transcription of multiple proteins that fine-tune cellular metabolism under metabolic stress.

P176S Mutation Rewires Electrostatic Interactions That Alter Maspin Functionality.

Maspin is known to regress tumors by inhibiting angiogenesis; however, its roles have been reported to be context- and sequence-dependent. Various proteins and cofactors bind to maspin, possibly explaining its conflicting roles. Moreover, polymorphic forms of maspin have also been linked to tumor regression and survival; for instance, maspin with Ser at 176 (maspin-S176) promotes tumors, while maspin with Pro at 176 (maspin-P176) has opposing roles in cancer pathogenesis. With the help of long molecular dynamics simulations, a possible link between polymorphic forms and tumor progression has been established. First, maspin is dynamically stable with either amino acid at the 176 position. Second, differential contacts have been observed among various regions; third, these contacts have significantly altered the electrostatic energetics of various residues; finally, these altered electrostatics of maspin-S176 and maspin-P176 rewire the polar contacts that abolished the allosteric control of the protein. By combining these factors, the altered electrostatics substantially affect the localization and preference of maspin-binding partners, thus culminating in a different maspin-protein(cofactor)-interaction landscape that may have been manifested in previous conflicting reports. Here, the underlying reason has been highlighted and discussed, which may be helpful for better therapeutic manipulation.

Enhancing Security and Privacy in Healthcare Systems Using a Lightweight RFID Protocol.

Exploiting Radio Frequency Identification (RFID) technology in healthcare systems has become a common practice, as it ensures better patient care and safety. However, these systems are prone to security vulnerabilities that can jeopardize patient privacy and the secure management of patient credentials. This paper aims to advance state-of-the-art approaches by developing more secure and private RFID-based healthcare systems. More specifically, we propose a lightweight RFID protocol that safeguards patients' privacy in the Internet of Healthcare Things (IoHT) domain by utilizing pseudonyms instead of real IDs, thereby ensuring secure communication between tags and readers. The proposed protocol has undergone rigorous testing and has been proven to be secure against various security attacks. This article provides a comprehensive overview of how RFID technology is used in healthcare systems and benchmarks the challenges faced by these systems. Then, it reviews the existing RFID authentication protocols proposed for IoT-based healthcare systems in terms of their strengths, challenges, and limitations. To overcome the limitations of existing approaches, we proposed a protocol that addresses the anonymity and traceability issues in existing schemes. Furthermore, we demonstrated that our proposed protocol had a lower computational cost than existing protocols and ensured better security. Finally, our proposed lightweight RFID protocol ensured strong security against known attacks and protected patient privacy using pseudonyms instead of real IDs.

Lipid kinase PIP5Kα contributes to Hippo pathway activation via interaction with Merlin and by mediating plasma membrane targeting of LATS1.

BACKGROUND: The Hippo pathway plays a critical role in controlled cell proliferation. The tumor suppressor Merlin and large tumor suppressor kinase 1 (LATS1) mediate activation of Hippo pathway, consequently inhibiting the primary effectors, Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ). Phosphatidylinositol 4,5-bisphosphate (PIP2), a lipid present in the plasma membrane (PM), binds to and activates Merlin. Phosphatidylinositol 4-phosphate 5-kinase α (PIP5Kα) is an enzyme responsible for PIP2 production. However, the functional role of PIP5Kα in regulation of Merlin and LATS1 under Hippo signaling conditions remains unclear. METHODS: PIP5Kα, Merlin, or LATS1 knockout or knockdown cells and transfected cells with them were used. LATS1, YAP, and TAZ activities were measured using biochemical methods and PIP2 levels were evaluated using cell imaging. Low/high cell density and serum starvation/stimulation conditions were tested. Colocalization of PIP5Kα and PIP2 with Merlin and LATS1, and their protein interactions were examined using transfection, confocal imaging, immunoprecipitation, western blotting, and/or pull-down experiments. Colony formation and adipocyte differentiation assays were performed. RESULTS: We found that PIP5Kα induced LATS1 activation and YAP/TAZ inhibition in a kinase activity-dependent manner. Consistent with these findings, PIP5Kα suppressed cell proliferation and enhanced adipocyte differentiation of mesenchymal stem cells. Moreover, PIP5Kα protein stability and PIP2 levels were elevated at high cell density compared with those at low cell density, and both PIP2 and YAP phosphorylation levels initially declined, then recovered upon serum stimulation. Under these conditions, YAP/TAZ activity was aberrantly regulated by PIP5Kα deficiency. Mechanistically, either Merlin deficiency or LATS1 deficiency abrogated PIP5Kα-mediated YAP/TAZ inactivation. Additionally, the catalytic domain of PIP5Kα directly interacted with the band 4.1/ezrin/radixin/moesin domain of Merlin, and this interaction reinforced interaction of Merlin with LATS1. In accordance with these findings, PIP5Kα and PIP2 colocalized with Merlin and LATS1 in the PM. In PIP5Kα-deficient cells, Merlin colocalization with PIP2 was reduced, and LATS1 solubility increased. CONCLUSIONS: Collectively, our results support that PIP5Kα serves as an activator of the Hippo pathway through interaction and colocalization with Merlin, which promotes PIP2-dependent Merlin activation and induces local recruitment of LATS1 to the PIP2-rich PM and its activation, thereby negatively regulating YAP/TAZ activity. Video Abstract.

National Cancer Registry of Pakistan: First Comprehensive Report of Cancer Statistics 2015-2019.

OBJECTIVE: To compile a comprehensive national cancer registry report of Pakistan by merging and analysing cancer registration data received from major functional cancer registries in various parts of Pakistan. STUDY DESIGN: Observational study. Place and Duration of the Study: Health Research Institute (HRI), National Institutes of Health (NIH), Islamabad, from 2015-2019. METHODOLOGY: Data from major cancer registries which included 'Punjab Cancer Registry (PCR), 'Karachi Cancer Registry (KCR)', 'Pakistan Atomic Energy Commission (PAEC) Cancer Registry', Armed Forces Institute of Pathology (AFIP) Cancer Registry, Nishtar Medical University Hospital Multan (NMH), and Shifa International Hospital, Islamabad (SIH) registries were pooled, cleared, and analysed at HRI. RESULTS: A total of 269,707 cancer cases were analysed. Gender-wise 46.7% were males and 53.61% were females. As per province-wise distribution, 45.13% of cases were from Punjab, 26.83% from Sindh, 16.46% from Khyber Pakhtunkhwa (KP), and 3.52% from Baluchistan. Both genders combined, 'breast cancer' 57633 (21.4%) was the most common cancer. In males, the top-5 cancers in order of frequency/percenatages were 'oral' 14477 (11.6%), 'liver' 8398 (6.73%), colorectal 8024 (6.43%), 'lung' 7547 (6.05%) and 'prostate' 7322 (5.87% cancers). In females, causes of the top-5-cancers included 'breast' 56250 (38.8%), 'ovary' 8823 (6.09%), 'oral' 7195 (4.97%), 'cervix' 6043 (4.17%), and 'colorectal' 4860 (3.36%) cancers. In children 'Leukemia' 1626 (14.50%) and in adolescents 'Bone' 880 (14%) were the leading malignancies. CONCLUSION: Breast cancer is the most common cancer in females touching epidemic proportions while 'oral cancer' which is the leading cancer in males ranks third in frequency in females. Like 'oral cancer' which shows a strong correlation with chewing, other common cancers in Pakistan including liver cancer, lung cancer, and cervical cancer are also largely preventable as showed a strong correlation with hepatitis B and C, smoking, and high-risk human papillomavirus. KEY WORDS: National Cancer Registry, Health Research Institute - NIH, Islamabad, Pakistan.

A Novel Framework for Qualification of a Composite-Based Main Landing Gear Strut of a Lightweight Aircraft.

The determination of suitable testing and qualification procedures for fiber-reinforced polymer matrix composite structures is an active area of research due to the increased demand, especially in the field of aerospace. This research illustrates the development of a generic qualification framework for a composite-based main landing gear strut of a lightweight aircraft. For this purpose, a landing gear strut composed of T700 carbon fiber/epoxy material was designed and analyzed for a given lightweight aircraft having mass of 1600 kg. Computational analysis was performed on ABAQUS CAE® to evaluate the maximum stresses and critical failure modes encountered during one-point landing condition as defined in the UAV Systems Airworthiness Requirements (USAR) and Air Worthiness Standards FAA FAR Part 23. A three-step qualification framework including material, process and product-based qualification was then proposed against these maximum stresses and failure modes. The proposed framework revolves around the destructive testing of specimens initially as per ASTM standards D 7264 and D 2344, followed by defining the autoclave process parameters and customized testing of thick specimens to evaluate material strength against the maximum stresses in specific failure modes of the main landing gear strut. Once the desired strength of the specimens was achieved based on material and process qualifications, qualification criteria for the main landing gear strut were proposed which would not only serve as an alternative to drop test the landing gear struts as defined in air worthiness standards during mass production, but would also give confidence to manufacturers to undertake the manufacturing of main landing gear struts using qualified material and process parameters.

A Multicenter Study of Clinical Presentations and Outcomes of Multiple Myeloma in Pakistan: The Real-World Analysis in a Resource-Constrained Country.

This is the first multicenter study from Pakistan exploring the prevalence, clinical presentations and treatment outcomes of Multiple Myeloma patients. This retrospective study involved data collection from hospital record system of four tertiary care referral hospitals of Pakistan including all patients diagnosed as having Multiple Myeloma from January 2014 to December 2018. The demographic details, clinical presentations, laboratory findings, treatment responses, and mortalities were evaluated. The progression-free survival and overall survival were analyzed considering relapse and mortality as the end points, respectively. For the progression-free survival, the Kaplan-Meier survival analysis and the log rank test were used to compare the survival function for chemotherapy followed by autologous stem cell transplant (ASCT) as opposed to chemotherapy alone (non-ASCT). The overall survival analysis was assessed by Kaplan-Meier survival analysis. This study identified 403 Multiple Myeloma patients in five years. The median age at presentation was 55 years. Bortezomib based drug regimens were the most commonly used initial treatments (57.5%). Forty three patients received ASCT. The progression-free survival median for ASCT and non-ASCT patients were 50 months (95% CI, 42-57.9 months) and 26 months (95% CI, 21.5-30.5 months), respectively. The cumulative probability of survival rate at 60 months was 80%. This study identified 403 Multiple Myeloma patients over 5 years in four tertiary care hospitals of Pakistan. It underscores the importance of autologous stem cell transplant in Myeloma patients and advocates improving its facilities in Pakistan.

Outcomes of Philadelphia Positive Acute Lymphoblastic Leukemia in Adolescent and Young Adults.

Background Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) accounts for 25% of acute lymphoblastic leukemia cases in the adolescent and young adult (AYA) age subgroup. It is associated with poor outcomes and is considered a standard indication for allogeneic stem cell transplant (Allo-SCT). Improved outcomes have been reported with addition of tyrosine kinase inhibitors (TKIs) to chemotherapy in children and the role of Allo-SCT is now being debated in the first remission. Complete response (CR) at three months is associated with improved survival even without Allo-SCT in first CR. In this study, we have analyzed disease-free survival (DFS), overall survival (OS), and factors affecting survival outcomes of Ph+ ALL in the AYA subgroup, in resource-limited settings treated with chemotherapy and TKIs. Materials and methods This is a retrospective, multicenter cohort study of Ph+ ALL AYA patients, aged 18-40 years, and registered between January 2015 and December 2020. Primary objectives are to calculate disease-free survival (DFS) and overall survival (OS). Secondary objectives are to identify prognostic factors affecting response rates and outcomes. List of cases was obtained from hospital information system (HIS) and data were collected from patient case notes and electronic medical records. Data analysis was done utilizing the SPSS statistical program (Armonk, NY: IBM Corp.). Results Forty-nine patients were identified with Ph+ ALL with a median age of 23 years (range: 18-40 years) and a male-to-female ratio of 2.5:1. None of the patients had central nervous system (CNS) disease. White cell count was >30,000 per mm3 in 26% of patients, while 13% had additional cytogenetic abnormalities. Thirty-three percent patients received adult (hyper-cyclophosphamide, vincristine, Adriamycin, and dexamethasone {CVAD}) protocols while 67% received pediatric-inspired (Berlin-Frankfurt-Munster {BFM} 2000 or UK-ALL 2003/2011) protocols. TKI therapy was received by 66% of patients during treatment (early: 37%; late: 29%) and 34% did not receive TKIs due to financial constraints. CR after induction was achieved in 69% cases. Induction mortality was 16%. The median DFS for the entire cohort was 27 months (0.93-53.06) and the median OS was 29 months (8.89-49.10). The median OS in Allo-SCT group was not reached vs 8.0±8.8 months (p=0.05) with chemotherapy only. The OS was significantly better in patients with no additional cytogenetic abnormalities, pediatric-inspired chemotherapy protocols, early use of TKIs in induction phase, Allo-SCT, and post-Allo-SCT use of TKIs. Conclusion Addition of TKIs to pediatric-inspired chemotherapy protocols in Ph+ ALL AYA patients and Allo-SCT results in better overall survival. TKI availability remains a significant issue in low-income countries due to significant financial burden on the patients. Allo-SCT continues to be an attractive option, particularly in low-income countries providing an option for cure in Ph+ ALL.

Diagnosis and Management of Diffuse Large B-Cell Lymphoma: Society of Medical Oncology, Pakistan Society of Hematology, and Pakistan Society of Clinical Oncology Joint Clinical Practice Guideline.

Diffuse large B-cell lymphoma (DLBCL) is the commonest non-Hodgkin lymphoma encountered by hematopathologists and oncologists. Management guidelines for DLBCL are developed and published by countries with high income and do not cater for practical challenges faced in resource-constrained settings. This report by a multidisciplinary panel of experts from Pakistan is on behalf of three major national cancer societies: Society of Medical Oncology Pakistan, Pakistan Society of Hematology, and Pakistan Society of Clinical Oncology. The aim is to develop a practical and standardized guideline for managing DLBCL in Pakistan, keeping in view local challenges, which are similar across most of the low- and middle-income countries across the globe. Modified Delphi methodology was used to develop consensus guidelines. Guidelines questions were drafted, and meetings were convened by a steering committee to develop initial recommendations on the basis of local challenges and review of the literature. A consensus panel reviewed the initial draft recommendations and rated the guidelines on a five-point Likert scale; recommendations achieving more than 75% consensus were accepted. Resource grouping initially suggested by Breast Health Global Initiative was applied for resource stratification into basic, limited, and enhanced resource settings. The panel generated consensus ratings for 35 questions of interest and concluded that diagnosis and treatment recommendations in resource-constrained settings need to be based on available resources and management expertise.

Regulation of quackery amid unprecedented HIV outbreak in Sindh, Pakistan.

OBJECTIVE: To assess the problem of unlicensed practitioners and quacks in Sindh, Pakistan. METHODS: A cross-sectional study was conducted in 29 districts of Sindh province in Pakistan from December 2019 to January 2020. Initial data available with Sindh Health Department about locations where quacks were practicing was used to identify unlicensed practitioners. A structured questionnaire was developed which contained information about certification of practitioners and an observational checklist was developed to assess infection prevention and control practices (IPC) and injection safety. RESULTS: A total of 4315 private practitioners were inspected out of which 3022 (70%) were unlicensed health practitioners belonging to different categories. Within the six surveyed divisions of Sindh, the highest proportion of unlicensed practitioners were documented in Shaheed Benazirabad division (n=739; 24.5%) followed by Hyderabad (n=599; 19.8%). In Mirpur Khas, there were 510 (16.9%), in Karachi 310 (10.3%), in Sukkur 484 (16%) and in Larkana there were 380 (12.6%) unlicensed practitioners. Poor IPC was observed in 89.4% (3861/4315) of all health providers. Reuse of syringes and intravenous drip sets was observed among 78.7% (1916/2432) of the untrained providers across the province. It was also found that 155 MBBS doctors had given their names on rent to be used as a signboard outside the clinics of some of the unlicensed practitioners. CONCLUSION: The problem of quackery is widespread in the Sindh province. It can be proactively addressed by shutting down all unlicensed practitioners and educating the community to avoid visiting them in order to reduce the probability of exposure to unsafe healthcare practices.

Polyubiquitin gene Ubb is required for upregulation of Piwi protein level during mouse testis development.

Testis development, including early embryonic gonad formation and late postnatal spermatogenesis, is essential for the reproduction of higher metazoans to generate fertile gametes, called sperm. We have previously reported that the polyubiquitin gene Ubb is required for fertility in both male and female mice. In particular, the Ubb-null male mice showed an azoospermia phenotype due to arrest of spermatogenesis at the pachytene stage. Here, we analyzed the whole testis proteome at postnatal day 20 to define the molecular mediators of the male-infertility phenotype caused by Ubb knockout. From the identified proteome, 564 proteins were significantly and differentially expressed in Ubb-knockout testes and, among these, 36 downregulated proteins were involved at different stages of spermatogenesis. We also found that levels of piRNA metabolic process-related proteins, including Piwil2 and Tdrd1, were downregulated in Ubb-null testes through functional gene ontology analysis. Further, protein-protein interaction mapping revealed that 24 testis development-related proteins, including Hsp90aa1, Eef1a1, and Pabpc1, were directly influenced by the depletion of ubiquitin. In addition, the reduced mRNA levels of these proteins were observed in Ubb-knockout testes, which closely resembled the global downregulation of piRNA-metabolic gene expression at the transcriptional and post-transcriptional levels. Together with proteomic and transcriptional analyses, our data suggest that Ubb expression is essential for the maintenance of testicular RNA-binding regulators and piRNA-metabolic proteins to complete spermatogenesis in mice.

Primary Mediastinal B-Cell Lymphoma: A 2021 Update on Genetics, Diagnosis, and Novel Therapeutics.

Primary mediastinal large B-cell lymphoma (PMBCL) is an aggressive B-cell lymphoma arising from thymic B-cells having clinicopathologic features distinct from systemic diffuse large B-cell lymphoma (DLBCL). PMBCL comprises 2% to 4% of all non-Hodgkin lymphomas (NHL), 7% of DLBCL and seen predominantly in young females with a median age of 35 years at diagnosis. The annual incidence of PMBCL is 0.4 per million with a 5-year survival rate exceeding 70% with improving supportive care and genetic characterization of the disease. Pathogenesis involves dysregulation of Janus kinase-signal transducer and activator of transcription (JAK-STAT), nuclear factor-kB (NF-kB) pathways and amplification of the 9p24.1 region of chromosome 9. PMBCL patients have a prolonged life expectancy necessitating the need for treatment approaches that are based on maximizing cure with minimal long-term toxicity. Due to rarity and its recognition as a distinct entity, therapeutic decisions are guided by clinical presentation, clinician and center experience, and analysis of patients with PMBCL within DLBCL registries. Historically R-CHOP has been the usual first line treatment for PMBCL followed by involved site radiotherapy (ISRT), however clinical practice varies across centers with emerging consensus to avoid upfront RT by utilizing dose intense regimens (DA-EPOCH-R) in younger and fit patients. Prognosis of relapsed refractory PMBCL not responding to salvage chemotherapy is dismal, however there are many emerging options including Brentuximab Vedotin, immune check point inhibitors and chimeric antigen receptor T-cell therapy. In this article, we focus on the pathogenesis, current and evolving treatments, and provide recommendations for optimal management of patients with PMBCL.

A Plum On Thumb: A Rare Presentation Of Synovial Sarcoma.

Synovial sarcoma (SS) is a rare and aggressive mesenchymal tumour accounting for around 5-10% soft tissue neoplasms usually found in joints of upper and lower extremities. A 35years old healthy looking male patient from Afghanistan presented with swelling on palmar side of base of thumb from last one year. Seven months back excisional biopsy was taken report of which showed neurofibroma/dermatofibroma with. No evidence of malignancy seen. From last 5months mass reappeared and gradually increased in size with itching sensation and mild pain. On local examination there was 5×4×5 cm reddish mass on palmar surface of base of thumb with extension into mid thenar eminence with diffuse margins. X-ray showed soft tissue density mass with spikes of calcification. Ultrasound showed 4.2×4×4.5 cm heterogeneous solid lesion on anteromedial surface of root of right thumb without any remarkable intralesional calcification and remarkable intralesional vasculature. MRI reported lobulated well defined soft tissue mass eliciting low to intermediate signal on T1 and WIs and bright signal on T2and STIR Vividly enhancing mass. Case was operated mass was excised and biopsy sent. Post op status was unremarkable. Biopsy reported poorly differentiated biphasic synovial sarcoma. No recurrence seen till 3months.

Effectiveness of Treatment in Children With Cerebral Palsy.

OBJECTIVE:  The objective of this study was to assess the effectiveness of conservative and surgical treatment in cerebral palsy children by evaluating the Medical Research Council (MRC) grading system, modified Ashworth scale, and Barthel Activities of Daily Life (ADL) scale. METHOD: This prospective case series was performed using a non-probability consecutive sampling technique at the Department of Orthopedic Surgery and Traumatology, King Edward Medical University/Mayo Hospital, Lahore from October 2011 to November 2013. Two hundred children of all ages, having cerebral palsy diagnosed on history and clinical examination were enrolled in the study. Children were treated with conservative and surgical treatment. Pre- and post-treatment, all children were classified based on movement disorder (spastic, athetoid, ataxic, and mixed), parts of the body involved (paraplegic, tetraplegic, diplegic, hemiplegic, monoplegic, double hemiplegic, and triplegic), and gross motor function (GMFCS level I-IV). Their muscle power and tone were assessed using the MRC grading system and modified Ashworth scale, respectively. Assessment of disability and daily function was done by ranking disability grading and Barthel ADL, respectively. The range of motion (ROM) of each joint was assessed clinically. Children were divided based on the treatment method as non-surgical versus surgical treatment. RESULTS: Out of a total of 200 children, the mean age of the children was 7.86±4.17year. There were 134 (67.0%) males and 66 (33.0%) female children. Classification on basis of movement disorder, body part involved, and gross motor function at three-month intervals till twelve months was performed. From the first presentation of children till the last follow-up time period, i.e., 12th month there was no change in the movement disorder (a type of CP, body parts involved, and GMFCS). The final rating of overall treatment results shows that there were 84 (42%) patients who had a poor outcome, and only 35 (17.50%) patients had a fair treatment outcome and 81 (40.50%) patients had good treatment outcomes.  Conclusion: The conservative and surgical management showed no effect on movement disorder of the child although, on the final rating scale fair to good treatment outcome was observed in all children. There was an improvement in muscle power grading on the ADL, but no significant improvement was seen on the improvement of type, parts of the body involved, gross motor function classification, modified Ashworth, and ranking disability grading of the children.

Mesenchymal stem cell-derived interleukin-28 drives the selection of apoptosis resistant bone metastatic prostate cancer.

Bone metastatic prostate cancer (PCa) promotes mesenchymal stem cell (MSC) recruitment and their differentiation into osteoblasts. However, the effects of bone-marrow derived MSCs on PCa cells are less explored. Here, we report MSC-derived interleukin-28 (IL-28) triggers prostate cancer cell apoptosis via IL-28 receptor alpha (IL-28Rα)-STAT1 signaling. However, chronic exposure to MSCs drives the selection of prostate cancer cells that are resistant to IL-28-induced apoptosis and therapeutics such as docetaxel. Further, MSC-selected/IL-28-resistant prostate cancer cells grow at accelerated rates in bone. Acquired resistance to apoptosis is PCa cell intrinsic, and is associated with a shift in IL-28Rα signaling via STAT1 to STAT3. Notably, STAT3 ablation or inhibition impairs MSC-selected prostate cancer cell growth and survival. Thus, bone marrow MSCs drive the emergence of therapy-resistant bone metastatic prostate cancer yet this can be disabled by targeting STAT3.

Exposure to aflatoxin B1 and associated risk factors in hepatitis C patients in cosmopolitan city of Pakistan: facility-based study.

INTRODUCTION: population-based follow-up study has been designed to investigate the contributing factors to high exposure to Aflatoxin B1 (AFB1) and the subsequent associated risk factors among hepatitis C-infected patients at a referral centre, Karachi. Pakistan. Hepatitis C infection affects millions of individuals worldwide and confers high morbidity and mortality, especially in lower middle-income countries (LMICs) including Pakistan. A literature review of recent studies has revealed that a number of hepatocellular carcinomas (HCC) cases are markedly increased in Pakistan, where one of the potential causes of HCC is hepatitis C virus. The objectives of this study were to determine frequency of Aflatoxin B1 (AFB1) exposure and other associated characteristics among hepatitis C patients at a referral centre, Karachi, Pakistan. METHODS: a semi-structured pre-coded pro forma designed to collect socio-demographic, Pharmacological, biochemical and clinical information from patients and hospital records. Patient´s pre and post polymerase chain reaction (PCR), serum alanine aminotransferase (ALT) levels and other blood parameters were analysed. AFB1 exposure was determined using an ELISA kit and validated through high-performance liquid chromatography (HPLC). RESULTS: AFB1 exposure was found in 30 (34%) patients. Post treatment responders were 49 (55.6%). More than 37% of study participants had a family history of hepatitis C. About 74% had a history of surgical procedure, and around 36% of study participants had a blood transfusion history. Up to 36% participants were fond of spicy food and around 25% study participants were eating roadside food on daily basis. CONCLUSION: high frequency of AFB1 exposure due to risky dietary habits, low level of formal education and awareness are contributing factors may be responsible for high exposure of AFB1. Effective and multidimensional strategies are needed to prevent advance stage progression of disease and associated complications.