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Interventional cardiology is on the cusp of a significant transformation as we approach 2050, driven by emerging trends and groundbreaking technological innovations. This mini review explores the pivotal developments shaping the field, focusing on three key areas: Emerging Trends in Interventional Cardiology, Technological Innovations: The Next Frontier, and the Future Era of Intervention Cardiology from 2024 to 2050. Emerging trends, including advancements in imaging and artificial intelligence, are revolutionizing diagnosis and treatment, allowing for more precise and personalized interventions. Technological innovations, such as robotic-assisted procedures and bioresorbable stents, are redefining the landscape, enhancing procedural accuracy, and expanding access to care through remote interventions. Looking ahead to 2050, we anticipate a future where interventional cardiology is increasingly driven by minimally invasive techniques, AI-driven decision-making, and personalized medicine, offering unprecedented improvements in patient outcomes and reshaping the way cardiovascular diseases are managed., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests that can influence the work reported in this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Infective endocarditis (IE) poses significant clinical challenges, often necessitating surgical intervention for improved patient outcomes. The choice between mitral valve repair (MVP) and mitral valve replacement (MVR) is crucial in managing IE. This systematic review and meta-analysis aims to compare the effectiveness of MVP and MVR in treating IE, focusing on outcomes such as postoperative bleeding, mortality, recurrent endocarditis, and stroke., Main Text: A comprehensive literature search was conducted following PRISMA guidelines. Studies directly comparing MVP and MVR in IE patients were included. Data extraction and quality assessment were performed, and meta-analysis was conducted using RevMan software. Thirty-two studies involving 82,123 patients were included. MVP was associated with significantly lower rates of postoperative bleeding (OR: 0.58, 95% CI: 0.40-0.84) and reduced long-term mortality (OR: 0.40, 95% CI: 0.32-0.51) compared to MVR. However, MVR showed lower rates of recurrent endocarditis. MVP was also associated with a decreased likelihood of postoperative stroke (OR: 0.52, 95% CI: 0.40-0.68).2, 4 CONCLUSIONS: MVP demonstrates advantages over MVR in reducing postoperative bleeding, long-term mortality, and stroke risk in IE patients. However, individual patient factors and surgical expertise must be considered in treatment decisions. Further research, including randomized controlled trials, is needed to validate these findings and refine treatment algorithms for IE management., (© 2024. The Author(s).)

The current study aimed to determine the safety and efficacy of Coag-A through in vivo analysis in CFA induced mice model. Treatment of CFA induced arthritis in mice with Coagulansin-A (10 mg/kg i.p. daily for 28 days), a withanolide obtained from Withania coagulans, as well as standard drug treatment with Dexamethasone (5 mg/kg i.p) was provided. The effect of Coag-A on body weight, relative organ weight, hematology, serum biochemistry, survival rate, oxidative stress markers, and antioxidant enzymes was evaluated. The liver and kidney histopathology were also assessed to ascertain its safety profile. Treatment of arthritic mice with Coag-A considerably improved body weight, relative organ weight of liver, kidney, and spleen, ameliorated hematology and serum biochemistry, and increased survival and antioxidant potential. Coag-A was found to be safer with fewer adverse effects showing hepato-protective, nephroprotective, and anti-inflammatory effect. It also significantly (p < 0.001) improved histopathology of CFA-induced mice when compared with Dexa. In conclusion, compared to dexamethasone, Coag-A has demonstrated a greater therapeutic benefit and fewer side effects in the treatment of arthritis against the CFA-induced model., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This study investigates the impact of public-private partnerships investment in energy and FDI on environmental quality in global investment countries during 1995-2018. Economic growth, technological innovations and consumption of clean energy are also considered as additional determinants of environmental quality. The study applied advanced panel econometric models. Our empirical results affirm the evidence of a long-run association between environmental quality and its determinants. Specifically, economic growth as well as clean energy use improves quality of environment by lowering carbon emissions. Public-private partnerships investment in energy, FDI and technological innovations decrease carbon emissions. Energy consumption (generated from fossil fuel) increases carbon emissions. Heterogeneous causality evidence indicates the presence of a unidirectional causality relation from carbon emissions to public-private partnerships investment in energy and a feedback causality occurs between consumption of clean energy and CO 2 emissions. This empirical evidence provides new insights for both policymakers and governments to support public-private partnership investments in energy for the improvement of quality of environment in global investment countries., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

A nulligravid woman in her mid-20s with colchicine-intolerant, steroid-dependent recurrent idiopathic pericarditis was in remission for 2 years on anakinra monotherapy when she had an unplanned pregnancy. Due to very limited and conflicting data, European Alliance of Associations for Rheumatology and American College of Rheumatology guidelines are equivocal on the use of anakinra in pregnancy, emphasising an individualised approach. Anakinra was discontinued but a month later, in the second month of gestation, the patient had an acute pericarditis flare. A multidisciplinary, patient-centred discussion about the competing risks of infection, obstetric complications and fetal malformations with anakinra versus suboptimally managed recurrent acute pericarditis guided the patient to choosing improved symptom control. Chest pain resolved and CRP normalised after daily anakinra injections were resumed. In the second trimester, the patient had mild COVID-19 infection and streptococcal pharyngitis on anakinra. At 34 weeks gestation, the patient went into preterm labour and had a spontaneous vaginal delivery of a healthy neonate., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Breast cancer (BC) continues to be the most common cancer in the women worldwide. Since estrogen receptor (ER)-positive BC accounts for the majority of newly diagnosed cases, endocrine therapy is advised to utilize either tamoxifen (Tam) or aromatase inhibitors. The use of Tam as a monotherapy or in conjunction with an aromatase inhibitor following two or three years of endocrine therapy has long been recommended. When used adjuvantly, Tam medication reduces BC mortality and relapses, while it extends survival times in metastatic BC when used in conjunction with other treatments. Unfortunately, the efficiency of Tam varies considerably. This study was conducted to explore the influence of genetic polymorphisms in CYP2C19 gene on Tam's pharmacogenetics and pharmacokinetics in estrogen-positive BC patients. Data from healthy, unrelated individuals ( n = 410; control group) and ER-positive BC patients ( n = 430) receiving 20 mg of Tam per day were recruited. Steady-state plasma concentrations of Tam and its three metabolites were quantified using the high-performance liquid chromatography in the patients. The CYP2C19 polymorphisms were genotyped using an Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR) approach. More than 65% of healthy individuals were extensive metabolizers (*1/*1) for CYP2C19, whereas more than 70% of ER-positive BC patients were rapid and ultrarapid metabolizers (*1/17*, *17/17*). The polymorphism CYP2C19*17 is significantly associated with higher 4-hydroxytamoxifen (4-OH-Tam). Patients with the *17/*17 genotype exhibited 1- to 1.5-fold higher 4-OH-Tam, which was also high in patients with the *1/*2 and *2/*2 genotypes., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

This article attempts to examine the role of creativity on carbon intensity in case of Organization of the Petroleum Exporting Countries (OPEC) countries. The panel estimation techniques are used for annual data for the period of 1990-2018. The empirical evidence affirms that patent rights and innovation act as a policy factor in controlling carbon intensity, i.e. creativity leads to energy-efficient and environment friendly society. However, innovations have higher magnitude compared to patent. Contrarily, urbanization and economic growth are the key determinants in enhancing carbon intensity, while renewable energy has insignificant impact on carbon intensity. The empirical analysis, especially for creativity, can add practical implications for related authorities in controlling carbon intensity and improving energy efficiency., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction and Importance: Mix epithelial and stromal tumor (MEST) is a benign biphasic renal lesion composed of solid as well as cystic components lining tubular and cystic spaces of kidney. There are very few cases of such variety have been reported with perspective to renal involvement. Herein we have reported a rare case of MEST involving left renal tissue and sparing surrounding tissues., Case Presentation: A 20 years old female presented to surgical outpatient department with complaint of amenorrhea and left flank pain as well as heaviness for 1 year. Patient was vitally stable and cooperative. On physical examination left flank mass was palpated and ultrasound and CT scan imaging was also showing left renal mass confined to upper, middle and lower portion of the kidney while renal capsule, adrenal gland and ureter were spared. On histological examination showed multi-cystic structures with variably sized simple cysts lined by hobnailed epithelium with clear cells. Septa show ovarian type fibrous stroma with variable inflammation and immature nephrogenic elements. A final diagnosis of MEST was made. Therefore, radical nephrectomy with trans-peritoneal approach was done., Clinical Discussion: MEST is a benign tumor of renal tissue that is confined to the renal parenchyma rather than involvement of surrounding structures as occurred in our case. Due to benign nature of the disease involvement of renal capsule and adrenal gland is less likely. The choice of treatment is radical nephrectomy through transperitoneal approach., Conclusion: MEST is a rare diagnosis thought case now start reporting since last decade, however, it's still a rare entity to be reported. USG and CT scan are investigating modalities along with histopathological correlation to reach the diagnosis., Competing Interests: Declaration of competing interest N/A., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: This study was designed to explore the antihyperlipidemic effects of amino acid derivatives of 2-mercaptobenzimidazole (4J and 4K) in high-fat diet (HFD)-fed rats., Methods: Male Sprague-Dawley rats were divided into nine groups which received either standard diet or HFD for 28 days. Blood samples were taken on 27th day from HFD-fed rats to ensure hyperlipidemia. HFD-induced hyperlipidemic rats later received daily dosing of either vehicle or simvastatin (SIM; 20 mg/kg) or 4J/4K compounds (10, 20, and 30 mg/kg) for 12 consecutive days. On 40th day, animals were sacrificed, and blood samples were collected for the determination of serum lipid profile and liver function parameters. Liver samples were harvested for histopathological, antioxidant, and qPCR analyses. Molecular docking of tested compounds with HMGCR was also performed to assess the binding affinities., Results: 4J and 4K dose dependently decreased serum total cholesterol, triglycerides, low-density lipoprotein, very low-density lipoproteins, alanine transaminase (ALT), and aspartate aminotransferase (AST) levels while significantly alleviated high-density lipoproteins. However, SIM failed to reduce AST and ALT levels. Moreover, tested compounds displayed antioxidant effects by inducing superoxide dismutase and glutathione levels. Histopathology data also displayed protective effects of 4J and 4K against HFD-induced fatty changes and hepatic damage. In addition, 4J and 4K downregulated transcript levels of HMGCR , APOB , PCSK 9, and VCAM 1, and molecular docking analysis also supported the experimental data., Conclusion: It is conceivable from this study that 4J and 4K exert their antihyperlipidemic effects by modulating multiple targets regulating lipid levels., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Traditional medicine has employed the plant Fagonia bruguieri DC. to alleviate inflammation, fever and pain. The goal of this study was to test the anti-inflammatory, analgesic and antipyretic properties of the methanol extract of whole plant of Fagonia bruguieri (F. bruguieri). The writhing test and Eddy's hot plate test were used to assess the analgesic potential of F. bruguieri at three different doses. Carrageenan-induced rat paw edema was applied to investigate anti-inflammatory activity, whereas antipyretic activity was estimated in Brewer's yeast induced pyrexia model. Flavonoids, alkaloids, saponins, tannins and glycosides were found in F. bruguieri's phytochemical analysis. F. bruguieri at 750 mg/kg reduced writhing count by 62.23 percent, while F. bruguieri enhanced latency in Eddy's hot plate test. In carrageenan-induced edema, F. bruguieri at 750 mg/kg exhibited considerable anti-inflammatory effect (41.11 percent) after 2 nd , 3 rd and 4 th hours of therapy. F. bruguieri was also found to show antipyretic properties. The anti-inflammatory, analgesic and antipyretic properties of F. bruguieri were confirmed in this study, which might be attributable to the presence of several phyto-constituents.

This study aims to investigate blockchain technology for agricultural supply chains during the COVID-19 pandemic. Benefits and solutions are identified for the smooth conduction of agricultural supply chains during COVID-19 using blockchain. This study uses interviews with agricultural companies operating in Pakistan. The findings discover the seven most commonly shared benefits of applying blockchain technology, four major challenges, and promising solutions. About 100% of the respondents mentioned blockchain as a solution for tracking the shipment during COVID-19, data retrieval and data management, product and transaction frauds, and an Inflexible international supply chain. Roughly 75% of the respondents mentioned the challenge of lack of data retrieval and data management and the Inflexible international supply chain in COVID-19 besides their solutions. This study can expand existing knowledge related to agricultural supply chains. The experiences shared in this study can serve as lessons for practitioners to adopt the blockchain technology for performing agricultural supply chain during pandemic situations such as COVID-19., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Elsevier Ltd. All rights reserved.)

Unlike 2-dimensional (2D) images, direct 3-dimensional (3D) point cloud processing using deep neural network architectures is challenging, mainly due to the lack of explicit neighbor relationships. Many researchers attempt to remedy this by performing an additional voxelization preprocessing step. However, this adds additional computational overhead and introduces quantization error issues, limiting an accurate estimate of the underlying structure of objects that appear in the scene. To this end, in this article, we propose a deep network that can directly consume raw unstructured point clouds to perform object classification and part segmentation. In particular, a Deep Feature Transformation Network (DFT-Net) has been proposed, consisting of a cascading combination of edge convolutions and a feature transformation layer that captures the local geometric features by preserving neighborhood relationships among the points. The proposed network builds a graph in which the edges are dynamically and independently calculated on each layer. To achieve object classification and part segmentation, we ensure point order invariance while conducting network training simultaneously-the evaluation of the proposed network has been carried out on two standard benchmark datasets for object classification and part segmentation. The results were comparable to or better than existing state-of-the-art methodologies. The overall score obtained using the proposed DFT-Net is significantly improved compared to the state-of-the-art methods with the ModelNet40 dataset for object categorization.

Air quality is a social, economical, and health issue for fast-developing countries such as China. Due to the overuse of nonrenewable energy, industrialization, and the population put pressure on air quality, which seriously threatens public health and economic growth. This study focuses on air quality and also aims to investigate the short-and long-run correlation between foreign direct investment, energy consumption, domestic credit, and financial development. The Autoregressive distributed lag model and the Granger non-causality test were carried out over the period from 1985 to 2018. The main findings of this study show a positive and significant long-run impact of energy consumption on air quality. In addition, domestic credit and financial development similarly show a significant positive short-run association with air quality. Moreover, the unidirectional causality correlation running from foreign direct investment and domestic credit to air quality was concluded by the Granger non-causality test. Considering the empirical analysis, this study suggests that domestic financial institutions should offer credit to industries at a low-interest rate in order to help them to switch from non-renewable to renewable energy consumption towards the promotion of sustainable and healthy air quality., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Multiple myeloma is a progressive and incurable hematologic malignancy. It is predominantly a disease of older individuals, with a third of these patients considered to be elderly. In recent years, there has been a focus and emphasis on identifying and stratifying patients based on their functional status and frailty. There are several hallmark complications of the disease-hypercalcemia, renal insufficiency, anemia, bone pain-along with thromboembolism and compromised immunity that are common in patients with multiple myeloma. Due to the wide range of patient ages and functional status, there are, accordingly, different considerations for management of the above complications based on numerous factors, including frailty status. This review focuses on considerations and management of common complications of multiple myeloma in elderly patients. These include renal failure, skeletal complications, anemia, thromboembolism, and infectious complications., Competing Interests: Disclosure The authors have no conflicts of interest to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

After signing the Regional Comprehensive Economic Partnership trade agreement, China became a proposed signatory to another important trilateral free-trade agreement - the China-Japan-South Korea Free Trade Agreement. In the context of the agreement, we explore the potential effect and internal influencing mechanism of trade openness on this region's carbon emissions from 1970 to 2019. We further detect the impact of the agreement by splitting the full sample into two subsamples, one subperiod before the agreement was signed and the other after it was signed. Then we separately analyze the impacts of imports and exports on carbon emissions and find that: (i) Trade openness positively affects the greenhouse effect, and the signing of the agreement can reduce the promotion effect of trade openness on carbon emissions; (ii) imports contribute to increased carbon emissions while exports significantly reduce carbon emissions in a country; and (iii) expanding trade openness not only directly affects carbon emissions directly, but also has indirect impacts by affecting three main effects (i.e., scale effect, technical effect, and structure effect). Finally, several important policy suggestions are provided to mitigate the greenhouse effect and promote high-quality trade openness., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Immunization hesitancy is a delay in acceptance or refusal of vaccines despite availability of vaccination services. If people are not engaged appropriately via communication and social mobilization, doubts about the trade-offs between the benefits and potential side effects persist. The objective of this study was to explore strategies for improved social mobilization to reduce immunization hesitancy., Methods: Mix of quantitative and qualitative approaches was applied to collect data from a diverse group of respondents in Sargodha and Khushab districts. Quantitative data were collected from 329 community health workers, including vaccinators, lady health workers and lady health supervisors, and school health and nutrition supervisors. In addition, qualitative data were collected from top management of Expanded Programme on Immunization (EPI) through key informant interviews (KIIs) and focus group discussions (FGDs) were conducted with parents. Analysis has been done using SPSS software and detailed transcriptions., Results: Advocacy meetings with local influencers, community group sessions, door-to-door visits by community health workers and mosque announcements are considered the most relevant and appropriate interventions for social mobilization. Community Health Workers (CHWs), cognizant of local culture, are being trusted, though optimum performance is achievable with adequate redressal of hesitancy concerns. However, in some cases negative attitudes of people towards immunization hinder trust towards mobilizers or CHWs. Hence, they leverage active participation of local influencers, teachers and health department officials to convince such stubborn parents. Active community involvement through leveraging support from local religious and non-religious influencers in social mobilization activities increases its acceptance. Community engagement is most effective in rural and hard-to-reach areas when community health workers are skilled in interpersonal communication and information education communication., Conclusions: Communication committees as oversight mechanism should be established or reactivated to regularly monitor and support mobilization activities through managing affairs like speedy liaison with local administration and local influencers, mobilizers' service related concerns, community-specific hurdles, and deficiencies of awareness-material provision that eventually improves mobilization performance. Resistant community's needs can be redressed through rigorous conduct of men's and women's education sessions by CHWs while giving more time and space to mobilizers to take on board local religious and non-religious influencers to convince conservative/illiterate parents. Higher management should fix policy implementation slippages like training needs assessment of mobilizers and Civil Society Organizations' involvement framework., Competing Interests: Competing interests: The authors completed the ICMJE Unified Competing Interest form (available upon request from the corresponding author) and declare no conflicts of interest., (Copyright © 2020 by the Journal of Global Health. All rights reserved.)

This study investigates the effect of foreign direct investment and education on environmental quality for Asian countries by controlling income, energy consumption, and urbanization for the period of 1990-2018. We have applied panel cointegration techniques to probe for long-run associations among the variables. The empirical results indicate the existence of cointegration between the variables. Dynamic ordinary least square and fully modified least square methods are applied to estimate long-run elasticities. The empirical results confirm that environmental quality is sensitive to foreign direct investment, education, and urbanization. Income and energy consumption deteriorate environmental quality by increasing CO 2 emissions. In the long-run, bidirectional causal associations are found for emissions- foreign direct investment, emissions-energy use, income- emissions, foreign direct investment -income, and energy-income nexus. Furthermore, there is a unidirectional causality running from education and urbanization to emissions, foreign direct investment, income, and energy use. Policymakers in Asian economies are encouraged to establish policies that increase the education budget, promote the use of green energy, attract foreign direct investment with green technology, and expand cities to limit the urbanization effects on environmental quality., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Multiple myeloma (MM) is a hematological malignancy characterized by an abnormal clone of plasma cells in the bone marrow. MM and its therapy increase the risk of complications like anemia, osteolytic lesions, pain, infections, and renal abnormalities in MM patients. Supportive care for MM patients improves the quality of life. Treatment with bisphosphonates decreases skeletal-related events. Vertebroplasty and kyphoplasty are done in cases of vertebral compression fractures. Prophylactic antibiotics and antivirals can decrease infections related to morbidity. Plasmapheresis in patients with renal dysfunctions decreases dialysis dependency and improve quality of life., Competing Interests: No potential conflict of interest was reported by the authors., (© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of Greater Baltimore Medical Center.)

The higher capability of optical vortex beams of penetrating turbid media (e.g., biological fluids) with respect to the conventional Gaussian beams is, for the first time to our knowledge, demonstrated in the 1.3 µm wavelength range which is conventionally used for optical coherence tomography procedures in endoscopic intravascular scenarios. The effect has been demonstrated by performing transmittance measurements through suspensions of polystyrene microspheres in water with various particulate concentrations and, in reflection, by using samples of human blood with different thicknesses. The reduced backscattering/increased transmittance into such highly scattering media of Laguerre-Gaussian beams with respect to Gaussian ones, in the near infrared wavelength region, could be potentially exploited in clinical applications, leading to novel biomedical diagnoses and/or procedures.

Objective: To assess the learning style preferences of undergraduate medical students and the effect of the preferred learning style on examination outcomes., Methods: The cross-sectional study was conducted from April to September 2018, at Poonch Medical College, Rawlakot, and Azad Jammu and Kashmir Medical College, Muzaffarabad, Pakistan, and comprised students from 2nd to 5th year. Data was collected using 16 item visual, aural, read/write and kinaesthetic questionnaire version 7.0. Data was analysed using SPSS 23., Results: Of the 406 students, 203(50%) belonged to each of the two colleges. None of the students preferred unimodal or bimodal learning styles, while 191(94.1%) at Poonch Medical College and 189(93.1%) at Azad Jammu and Kashmir Medical College preferred quad-modal and the remaining preferred trimodal style. Among the combination of learning styles, aural in different combination was preferred by 201(99.01%) of Poonch Medical College students and 202(99.51%) at the other institution. There was no statistically significant relationship between the preferred learning style and examination outcomes (p>0.05)., Conclusions: Most of the participants preferred multiple sensory modalities for learning.

The practice of choosing the next best therapy for patients with relapsed and/or refractory multiple myeloma (RRMM) is becoming increasingly complex. There is no clear consensus regarding the best treatment sequence for RRMM. With the approval of novel proteasome inhibitors (ixazomib and carfilzomib), immunomodulatory agents (pomalidomide), monoclonal antibodies (daratumumab and elotuzumab), and other targeted therapies, multiple combination regimens utilizing these agents are being studied with the goal of enhancing disease control, prolonging progression-free survival, and improving overall survival. We, herein, describe a review of FDA-approved regimens for RRMM patients and offer a paradigm in selecting subsequent treatment regimens, focusing on patient specific morbidity, treatment toxicity, and disease-specific characteristics., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Tanshinone is a herbal medicinal compound described in Chinese medicine, extracted from the roots of Salvia miltiorrhiza (Danshen). This family of compounds, including Tanshinone IIA and Tanshinone I, have shown remarkable potential as anti-cancer molecules, especially against breast, cervical, colorectal, gastric, lung, and prostate cancer cell lines, as well as leukaemia, melanoma, and hepatocellular carcinoma among others. Recent data has indicated that Tanshinones can modulate multiple molecular pathways such as PI3K/Akt, MAPK and JAK/STAT3, and exert their pharmacological effects against different malignancies. In addition, preclinical and clinical data, together with the safety profile of Tanshinones, encourage further applications of these compounds in cancer therapeutics. In this review article, the effect of Tanshinones on different cancers, challenges in their pharmacological development, and opportunities to harness their clinical potential have been documented., Competing Interests: The authors declare that they have no conflicts of interest., (© The Author(s) 2020.)

[This retracts the article DOI: 10.7759/cureus.4671.]., Competing Interests: No competing interests declared.

[This retracts the article DOI: 10.7759/cureus.4639.]., Competing Interests: No competing interests declared.

Opioid use disorder (OUD) is a rapidly growing challenge worldwide and is characterized by an increase in dependence on opioids up to a point that a person loses control over the drug use. Multiple drugs are approved for its treatment, including methadone, buprenorphine, and diazepam. Although not approved, clonidine is also used for the treatment of OUD. On May 16, 2018, the United States Food and Drug Administration (FDA) approved a new drug lofexidine hydrochloride for the treatment of opioid withdrawal symptoms. Lofexidine is a centrally acting alpha two receptor agonist. It reduces the neurochemical surge by inhibiting the conversion of adenosine triphosphate (ATP) into cyclic adenosine monophosphate (cAMP) which in turn decrease the sympathetic outflow. This results in the improvement of withdrawal symptoms. When compared with methadone and buprenorphine, it is equally effective in controlling withdrawal symptoms. Its efficacy is also similar to clonidine with a better side effects profile. The adverse effects of lofexidine include bradycardia, hypotension, orthostasis, somnolence, sedation, dry mouth, and rebound elevations in blood pressure and prolongation of QT interval. Lofexidine is contraindicated in patients who are on beta-blockers and angiotensin converting enzyme inhibitors (ACE inhibitors). In our review, we have discussed the clinical efficacy and safety profile of lofexidine in treating opioid withdrawal symptoms and its comparison to other available treatment options., Competing Interests: The authors have declared that no competing interests exist.

Introduction Post-operative nausea, vomiting (PONV) and pain are the most frequently encountered complains after thyroid surgery. Steroids effectively reduce pain, nausea, and inflammation, therefore prophylactic administration of steroids improve these outcomes. The aim of our study was to compare the prophylactic administration of dexamethasone with placebo in terms of PONV and pain. Patients and methods We conducted a double-blinded randomized controlled trial including 100 patients who underwent thyroid surgery from January 2017 to December 2017 in Surgical Unit-I of the Holy Family hospital, Pakistan. The outcome in terms of post-operative pain, nausea and vomiting were measured. Results The mean age of the patients was 39.62 ± 12.73 years in group A, while in group B it was 39.06 ± 13.25 years. Out of the 100 patients included in our trial, 52 (52%) patients were males and 48 (48%) patients were females. The mean value of pain in group A patients was 1.60 ± 1.26, while in group B it was 3.60 ± 1.94. A statistically significant difference was found between the study groups with regard to the pain score of the patients i.e. p -value = 0.001. The PONV was found in 28 patients from group A and 19 patients from group B and no significant improvement was seen ( p -value = 0.071). Conclusion A single dose of prophylactic dexamethasone significantly reduces the mean pain score in patients undergoing thyroidectomy; however, insignificant relation was noted in terms of PONV condition., Competing Interests: The authors have declared that no competing interests exist.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare conditions triggered due to a medication that involves the necrosis and desquamation of the skin and mucous membranes. Only one out of 1,000,000 people are affected by the condition. The exact pathophysiology of the disease is still unknown. However, many complications of the disease can occur; pancytopenia and pleural effusion are an even rarer find. Here we present a case of a 17-year-old male who presented with fever and rash for 15 days associated with bleeding per rectum, hemoptysis, and conjunctival hemorrhages. Laboratory investigations showed severe pancytopenia, deranged liver function tests (LFTs), and hypocellular bone marrow. The patient started showing improvement after 10 days post-admission with supportive care and multiple transfusions., Competing Interests: The authors have declared that no competing interests exist.

Background and Objective : Medication non-adherence is a preventable reason for treatment failure, poor blood pressure control among hypertensive patients and the geriatric population owing to poor physical activity is more vulnerable strata. The objective of this study is to investigate medication adherence and its associated factors among Pakistani geriatric hypertensive patients. Methods : A cross-sectional survey-based study was conducted at the out-patient department of the cardiac center from May 2018 to August 2018. A universal sampling technique was used to approach patients and 262 eligible consented patients were interviewed to collect information about socio-demographics, health, and disease-related characteristics using a structured questionnaire. The Morisky Levine Green test was used for the assessment of medication adherence. The Barthel index and single item literacy screener (SILS) was used to measure performance in activities of daily living and health literacy respectively. Chi-square tests and multivariate binary logistic regression analysis were performed to find factors by using SPSS version 20. Results: Of the total 262 participants, about 38.9% ( n = 102) were scored 4 and considered adherent while 61.1% ( n = 160) were considered as non-adherent. In logistic regression analysis, self-reported moderate (OR = 3.538, p = 0.009) and good subjective health (OR = 4.249, p = 0.008), adequate health literacy (OR = 3.369, p < 0.001) and independence in performing activities of daily living (OR = 2.968, p = 0.002) were found to be independent predictors of medication adherence among older hypertensive patients. Conclusion : Medication adherence among the older hypertensive population in Pakistan is alarmingly low. This clearly requires patient-centered interventions to overcome barriers and educating them about the importance of adherence., Competing Interests: The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

The small intestine is a relatively privileged organ; primary tumors are uncommon among malignancies of the gastrointestinal tract, with an average annual incidence rate of 9.9 per million people. Among these uncommon tumors, duodenal tumors are even rarer with an average incidence rate of 0.4% only. Histopathological examination mostly shows villous type. Tubulovillous histology is extremely rare with an incidence of less than 1% of all duodenal tumors. These tumors are either found incidentally or during screening for familial disorders such as familial adenomatous polyposis or Gardner's syndrome. Patients usually have symptoms such as diarrhea and abdominal pain along with weight loss over a period of months. Itching over the whole body and progressive yellow discoloration of sclera and skin (jaundice) can also be present when tumor compresses the common bile duct (CBD) and causes obstruction, especially in the region of ampulla of Vater. Examination of the abdomen may or may not reveal a mass lesion. Abdominal radiography and ultrasound show intra- and extra-hepatic biliary dilatation along with distention of CBD and growth at the lower end of CBD. Endoscopic retrograde cholangiopancreatography (ERCP) is, however, the investigation of choice as it not only allows direct visualization of a biliary tree but biopsy specimens can also be taken. Palliative procedures like placing a stent in the common bile duct to relieve obstruction can be done or a drain can be placed to drain bile. The definitive treatment is the Whipple procedure involving gastrojejunostomy, choledochojejunostomy, and cholecystectomy. Our case is unique as the patient had duodenal tubulovillous adenoma, a very rare tumor among the already uncommon duodenal tumors. The patient underwent Whipple procedure, T tube was placed, and feeding jejunostomy was done. An uneventful recovery occurred., Competing Interests: The authors have declared that no competing interests exist.

Problem-based learning is a learner-centered teaching method, which uses real-world scenarios to promote student learning of concepts and principles. The aim of our study is to analyze the consequence of increased problem difficulty on team-based learning and the analytical skills of medical students. In our prospective descriptive study, two problem-based learning scenarios prepared on the topic of hypercortisolism were given to 197 students in two successive sessions. At the end of two sessions, the perceptions of students about team-based learning were documented using a five-point Likert scale on a standardized questionnaire for both scenarios (simple and complex) simultaneously. A written test consisting of multiple-choice questions (MCQs) and short essay questions (SEQs) was given at the end of a complex scenario to test the problem-solving skills and retention of knowledge. No statistically significant difference (p> 0.05) was noted in team-based learning between the simple and complex problem-based learning scenario. MCQs and SEQs of C-2 (interpretation) level were attempted well than C-1 (recall) level and C3 (problem-solving) level. In conclusion, the understanding of the problem by the medical students was improved; however, there was no significant improvement in the problem-solving skills and knowledge retention of the students., Competing Interests: The authors have declared that no competing interests exist.

Biliary cysts are rare cystic dilatations of the biliary tree. Biliary cysts are positively associated with several significant complications, amongst them, cholangiocarcinoma befalls the most dreadful one. The elevated incidence is 20-30% in the unresected cyst and 0.7% in resected cysts. Magnetic resonance imaging (MRI) scan, magnetic resonance cholangiopancreatography (MRCP) or a contrast-enhanced computed tomography (CECT) is applied for the initial diagnostic study but the ultimate diagnosis ordinarily requires the tissue biopsy. Currently, the sole curative option involves the complete surgical resection of the lesion, with standard chemotherapy and active radiation applied as an alternative for the unresectable tumors. Despite the curative surgery the percentage of eternal recurrence of the tumor indefinitely persists, and effective post-surgical surveillance is reasonably demanded. We report a case of 29-year-old female with local recurrence of cholangiocarcinoma in a previously resected biliary cyst type I. The curative resection of the choledochal cyst only minimizes the considerable risk of the possible development of future cholangiocarcinoma but it does not completely prevent it. The appropriate follow-up for potential patients who have been typically treated for a biliary cyst is unclear. The lethal course of cholangiocarcinoma is believed due to its slow asymptomatic growing phase. Therefore, to adequately screen for malignancy, periodic imaging along with annual liver tests represents a reasonable approach to prevent the possible development of this appalling complication., Competing Interests: The authors have declared that no competing interests exist.

Enteric fever is a common infectious disease, especially in countries with poor sanitation and in the tropics. It is caused mainly by Salmonella typhi and accounts for nearly 27 million cases worldwide and 200,000 deaths annually. Enteric fever involves the reticuloendothelial system such as bone marrow, spleen, and liver. As it mostly involves the Peyer's patches of the terminal ileum, enteric perforation occurs commonly. However, gallbladder perforation can also occur, though not very often. Ultrasound as well as computerized tomography (CT) abdomen and pelvis lack specificity for detecting gallbladder perforations in enteric fever. Diagnosis is usually confirmed intraoperatively when the gallbladder is visualized and perforation is seen. Gallbladder perforation is usually seen in acute cholecystitis when the gallbladder becomes necrotic and gangrenous. In acalculous cholecystitis, perforation is rare. Enteric fever is one of the rarest causes of acalculous cholecystitis, leading to perforation. Here, we present the case of a 20-year-old man who presented with fever for 10 days along with loose stools, vomiting, and acute abdomen. Labs showed leukopenia, positive Typhidot test but X-ray erect abdomen and ultrasound abdomen and pelvis were nonspecific. Only after resuscitation and exploration of the abdomen was it found that the gallbladder had multiple perforations. The patient was improved after eight days of postoperative intravenous antibiotics. This is a unique and rare presentation of such a common infectious disease., Competing Interests: The authors have declared that no competing interests exist.

Chronic idiopathic constipation (CIC) can be defined as bowel movements that are difficult to pass, are not occurring frequently, or have incomplete evacuation during defecation. A high-fiber diet and laxatives are the commonly used treatments, but in many cases, they do not produce satisfactory results. The first line of treatment is osmotic laxatives. If there is no improvement, the second line is guanylate cyclase-C (GCC) agonists like linaclotide or prokinetic agents such as prucalopride. On December 14, 2018, the United States Food and Drug Administration (US FDA) approved prucalopride for treating chronic idiopathic constipation. Prucalopride is a prokinetic agent which works at the 5-hydroxytryptamine receptor 4 (5-HT4) as an agonist with greater receptor selectivity. Patients on prucalopride reported improved symptoms, quality of life and satisfaction. The most frequent adverse events were headaches and problems related to the gastrointestinal tract. Caution should be taken when using prucalopride in patients with impaired liver and renal function. In Canada, prucalopride has been approved for treatment of female patients with chronic idiopathic constipation who have failed therapy with at least two laxatives from different classes over a six-month period., Competing Interests: The authors have declared that no competing interests exist.

Plasma cell neoplasms are usually associated with normal or decreased platelet count. The association of thrombocytosis and multiple myeloma is exceedingly rare, with only six such cases reported in the literature until now. Differentiating clonal from secondary causes of thrombocytosis can be extremely difficult, yet the distinction has important therapeutic implications. We report the case of a woman presenting with thrombocytosis that led to the diagnosis of multiple myeloma. The possible etiological link between both these entities is also discussed., Competing Interests: The authors have declared that no competing interests exist.

The current practice for diagnosing graft versus host disease (GVHD) includes clinical or endoscopic evaluation of the patient. Clinical diagnosis is limited by an overlapping symptomatic spectrum with infectious causes, a common scenario in the post-transplant setting where an invasive procedure, such as endoscopy, is often impractical. We, therefore, evaluated the role of fecal calprotectin as a diagnostic as well as a prognostic biomarker for gastrointestinal GVHD (GI-GVHD) occurrence and severity in the post-hematopoietic transplant population. Following Prisma guidelines, we performed a systematic search of articles published after 2004 using the PubMed, Embase, Cochrane Library, and Web of Science databases. After a detailed screening, 10 studies involving a total of 494 patients were included. In the cohorts comparing median fecal calprotectin (mFC) level in GI-GVHD vs. non-GI-GVHD patients, the results indicated an increase in the mFC level in patients with GI-GVHD when compared to non-GI-GVHD patients. Similarly, an increase in the mFC level was seen in accordance with the severity of the disease. Moreover, corticosteroid-resistant patients had a higher mFC level as compared to corticosteroid-sensitive patients. Our study indicates that the mFC level can be used for diagnosing as well as predicting the treatment response to GI-GVHD. However, future randomized prospective trials involving larger populations are needed to further explore its significance., Competing Interests: The authors have declared that no competing interests exist.

Immunoglobulin (Ig) D multiple myeloma (MM) is a rare subtype of MM comprising 2% of all the cases. Malignant plasma cell invasion leads to signs and symptoms similar to other subtypes of MM. The synthesis rate of IgD is lower in IgD MM patients, making it very difficult to diagnose compared to other subtypes. As there is no available diagnostic test with 100% accuracy, the diagnosis of IgD MM is based on multiple factors. Recent advances in the treatment have resulted in a better overall survival for IgD MM patients. The aim of this systematic review was to summarize the data on presentation patterns, diagnosis modalities, management strategies, and outcomes in patients with IgD MM., Competing Interests: The authors have declared that no competing interests exist.

Marginal zone B cell lymphomas are divided into nodal, extranodal and splenic types. Renal involvement by extranodal B cell lymphoma is extremely rare with an incidence of about 0.1%. We present a case of a 79-year-old Caucasian male with progressive renal failure and isolated left renal extranodal marginal zone lymphoma. Asymptomatic immunoglobulin (Ig) M monoclonal gammopathy along with bone marrow involvement by lymphoma was observed. Contemporary management options including radiotherapy (RT), chemotherapy, immune-modulating agents and novel chemotherapy-free regimens., Competing Interests: The authors have declared that no competing interests exist.

Light chain multiple myeloma (LCMM) constitutes approximately 15% of patients with multiple myeloma (MM). It has a poorer prognosis when compared to immunoglobulin (Ig) G or IgA variant. We performed a comprehensive literature search on LCMM and identified a total of 390 articles. After a detailed screening, six studies involving a total of 1054 LCMM patients were included. A literature review revealed bone pain and renal failure as the most common initial sign and symptoms while extramedullary disease (EMD) was acquired later during the progression of the disease. Bortezomib has shown superior efficacy in LCMM patients over nonbortezomib regimens as demonstrated by better overall response rate (95.5% vs. 60%), progression-free survival (PFS) (25% vs. 9% at two years), and overall survival (OS) (24% vs. 9% at five years). Moreover, better PFS was seen, when bortezomib was used in combination with bendamustine compared to dexamethasone (95% vs. 25% at two years). Similarly, better OS (90% at two years) was observed with bortezomib in combination with bendamustine. Monitoring of disease should include serum free light chain levels, as literature review revealed that serum assays were more sensitive in indicating the disease and predicting PFS and OS as compared to urine assays. We provide presentation patterns, clinical rarities, management strategies including their efficacy, and disease monitoring in patients with LCMM in our review paper., Competing Interests: The authors have declared that no competing interests exist.

A silicon-on-insulator microring with three superimposed gratings is proposed and characterized as a device enabling 3×3 optical switching based on orbital angular momentum and wavelength as switching domains. Measurements show penalties with respect to the back-to-back of <1  dB at a bit error rate of 10 -9 for OOK traffic up to 20 Gbaud. Different switch configuration cases are implemented, with measured power penalty variations of less than 0.5 dB at bit error rates of 10 -9 . An analysis is also carried out to highlight the dependence of the number of switch ports on the design parameters of the multigrating microring.

The aim of present study was to evaluate and compare the hypoglycemic activity of different solvents extracts of Thymus serpyllum in rabbits. Diabetes was induced with single intravenous injection of alloxan monohydrate (150mg/kg). Glibenclamide and acarbose were used as standard drugs. The crude powder of Thymus serpyllum (500 mg/kg b.w) significantly reduced blood glucose level in both normal and diabetic rabbits. Various extracts of Thymus serpyllum were compared for their hypoglycemic activity in diabetic rabbits. Ether and aqueous extracts significantly reduced the blood glucose level with maximum effect (p<0.001) produced by aqueous extract, which was selected for further study. Aqueous extract significantly inhibited the rise in glucose level in oral glucose tolerance test. The extract showed synergistic effect with different doses of insulin; however serum insulin level of the diabetic rabbits was not significantly increased by the extract. HbA1c level was significantly (p<0.05) reduced whereas hemoglobin level was significantly increased in three months study. Phytochemical screening of the aqueous extract showed the presence of alkaloids, flavonoids, tannins, terpinoids, reducing sugar and cardiac glycosides. It is concluded that the aqueous extract might be used alone or in combination with insulin to manage diabetes and its associated complications.

The cardiovascular activity of aqueous methanolic extract of Paspalidium flavidum L. was evaluated on isolated rabbit heart and aorta. Heart rates, force of contraction and perfusion pressure were assessed in the presence of different concentrations of extract and adrenaline by using Langendorff's technique. Moreover, the vasoconstriction effects were studied in rabbit aorta using isolated organ bath. The results indicated that the extract (1ng-100 μ g/ml) exhibited a significant increase in heart rate, contractility and perfusion pressure of isolated rabbit's heart; with a maximum effect at 1ng/ml, which was comparable to adrenaline (1 μ g/ml). Similarly, adrenaline at doses from 1-10 μ g/ml produced a significant dose dependant increase in all the cardiac parameters. The cardiotonic effects of the extract were significantly blocked by propranolol (10(-5)M) while an increase in perfusion pressure was completely antagonized by verapamil (10(-6)M). Activity of cardiac marker enzymes was also significantly raised in the perfusate of isolated heart pretreated with the extract. In rabbit aorta, the extract exhibited a dose dependent vasoconstriction effect however it did not increase the tone of aorta when pre-treated with verapamil (10(-6)M). It is conceivable therefore; that the cardiotonic and vasoconstriction effects of the extract might be due to its agonistic actions on β-receptors and Ca(+2) channels.

The present study was conducted to evaluate the analgesic, anti-inflammatory and antipyretic activities of Thymus serphyllum Linn. in mice. Anti-inflammatory activity was evaluated by carrageenan and egg albumin induced paw edema in mice, while analgesic activity was assessed using formalin induced paw licking and acetic acid induced abdominal writhing in mice. For determination of antipyretic activity, pyrexia was induced by subcutaneous injection of 20% yeast. All the extracts produced significant anti-inflammatory effect however, ether extract produced maximum effect 34% inhibition (p < 0.001) against carrageenan and 22% (p < 0.01) inhibition against egg albumin induced paw edema in mice at the end of 3 h. Ether extract produced prominent analgesic effect 77% (p < 0.001) inhibition in acetic acid induced abdominal writhing and 59% inhibition in formalin induced paw licking model in mice, respectively. Ether extract also demonstrated significant (p < 0.001) antipyretic activity against yeast induced pyrexia. The plant showed no sign of toxicity up to the dose of 2000 mg/kg in mice. This study supports the use of Thymus serphyllum in traditional medicine for inflammation accompanied by pain and fever.

Purpose: The arabinoxylan from Ispaghula (Plantago ovata) husk has been proven scientifically as potential excipient. However, toxicity study of the arabinoxylan is still lacking. The present study was done to investigate the acute toxicity of arabinoxylan in two animal species., Methods: The mice were exposed to (1 g/kg, 5 g/kg, 10 g/kg) and rabbits (2.5 g/kg, 5 g/kg) of arabinoxylan orally and observed for a period of 14 days. On day 15 hematology, serum biochemistry and necropsy was performed in mice relative organ weight calculated and histological examination was carried out. Primary dermal and eye irritation tests were carried out. Cardiac effects of isolated arabinoxylan were studied on frog heart., Results: The acute administration of the arabinoxylan did not produce mortality or significant changes in, water and food consumption however body weights of mice and rabbits decreased initially with a gradual increase till day 14. Internal organs relative weights were found to be normal. Hematological biochemical and histopathological examination did not show any significant (p < 0.05) change. Primary dermal and eye irritation was not observed in treated rabbits. No change in heart rate and vascular contraction was observed in frog heart., Conclusion: This study has shown that acute administration of arabinoxylan may be safe.

Traditionally Thymus linearis Benth. have been used for treatment of various diseases including hypertension. The present study was conducted to evaluate the hypotensive and antihypertensive effect of aqueous methanolic extract of aerial parts of Thymus linearis Benth. in normotensive and hypertensive rats. Acute and subchronic studies were also conducted. The aqueous methanolic extract produced a significant decrease in SBP, DBP, MBP and heart rate of both normotensive and hypertensive rats. LDv, of the extract was found to be 3000 mg/kg. The extract also exhibited a reduction in serum ALT, AST, ALP, cholesterol, triglycerides and LDL levels, while a significant increase in HDL level was observed. It is conceivable therefore, that Thymus linearis Benth. contains certain active compound(s) that are possibly responsible for the observed antihypertensive activity. Moreover, these findings further authenticate the traditional use of this plant in folklore medicine.

Berberis orhob, otrvs Bien. ex Aitch. (B.o.) has been reported to have antihypertensive effect in different experimental models. The aim of present study was to evaluate the possible antihypertensive mechanism. Aqueous methanolic extract of B.o. roots and its various fractions namely (ethyl acetate, n-butanol or aqueous) in different concentrations (10 ng/mL, 100 ng/mL, I pg/mL, 10 pg/mL, 100 pg/mL ) were evaluated in isolated perfused rabbit heart to assess their effect on force of contraction, HR and perfusion pressure. The crude extract of B.o. and its fractions exhibited a significant decrease in heart rate, contractility and perfusion pressure of isolated rabbit heart, however, butanolic fraction produced more prominent effect and was selected for further study. The effects of butanol fraction were not blocked by atropine (10' M) in isolated perfused heart. However, butanol fraction significantly blocked the effects of adrenaline (10' M). It is therefore conceivable that cardiac depressant activity of B.o. butanol fraction might be due to the presence of certain 3-blocking agents which might be responsible for antihypertensive effect However, further experiments are required to isolate the active compound(s) and elucidate exact mechanism of action.

The cardiac activity of Saussurea lappa roots was evaluated in isolated perfused rabbit heart by the Langendorff's technique. Heart rate, contractility and coronary flow were determined in the presence of different concentrations of methanolic extract of Saussurea lappa, digoxin and diltiazem. The extract exhibited significant (p<0.01) positive inotropic effect at the first three doses (0.5/μg, 2.5/μg and 5.0/μg) while a significant negative chronotropic effect and coronary flow rates were observed at all the doses tested. These effects were comparable to the effects of digoxin and diltiazem. The increase in force of contraction with decrease in heart rate and coronary flow rates were also observed to be dose dependent as increase in the dose of test extract further enhanced the effects except contractility that started decreasing at higher doses. It is conceivable therefore, that Saussurea lappa roots contain certain pharmacologically active compounds that could be involved in the cardiotonic activity of the extract.

Objective: To study the efficacy and safety of cinitapride in the treatment of functional dyspepsia, and to evaluate the improvement of patients' quality of life., Methods: The prospective cross-sectional multi-centre phase IV study was conducted at Jinnah Hospital, Lahore, Ziauddin Medical University, Karachi and Pakistan Railways General Hospital, Rawalpindi, from July 2009 to June 2010 and comprised 121 patients of functional dyspepsia who were given cinitapride 1mg thrice daily 15 minutes before meals and were followed up for four weeks. Primary clinical response was assessed by using the Global Index Score. Secondary response was seen by percentage change of the total score as well as of each dyspepsia symptom compared with baseline and the overall subjective assessment of patients by using the 7-point Likert's scale. Reduction in Nepean Dyspepsia Index-Short Farm was used to evaluate the improvement in quality of life of patients at week 2 and 4. SPSS 15 used for statistical analysis., Results: After 4 weeks of treatment, the Global Index Score showed statistically significant reduction in 58 (48.92%) patients (p<0.01). Similar reduction (p<0.01) was seen in individual dyspepsia symptoms; early satiety, post-prandial fullness, and abdominal distension. The 7 point Likert's scale also showed similar improvement in subjective response (p<0.01).The quality of life also improved significantly at week 2 and 4 (p<0.01). No abnormal results were seen in vital signs, physical and laboratory examination except an unexplained rise in globulin level. Only one adverse event (sore throat) was reported during the study., Conclusion: The drug was effective in minimising dyspepsia symptoms, and improving the quality of life of patients. It was well tolerated and was almost free of side effects.

Introduction: Clostridium difficile-associated diarrhoea (CDAD) is the most common cause of nosocomial diarrhoea in the USA. In this study, we sought to determine the association between chronic kidney disease (CKD) and CDAD., Methods: A case-control study was designed to determine the association between CKD and CDAD in an urban hospital. Over a 2-year period, all patients diagnosed with CDAD (n = 188) were included as cases and the prevalence of CKD was calculated. Age- and sex-matched patients without CDAD were considered as controls with a ratio of 2:1 controls to cases. The prevalence of different stages of advanced CKD (stages 3-5) was determined and compared between groups. Also the calculated odds ratios (OR) were adjusted for multiple possible confounding variables using logistic regression analysis., Results: There was no significant difference in prevalence of advanced CKD between cases and controls (OR = 1.38, 95% confidence intervals (CI) = 0.90-2.12, P = 0.1365). The association between CKD and CDAD remained insignificant in subjects with CKD stages 3-5 who were not on dialysis (OR = 1.07, 95% CI = 0.65-1.77), P = 0.7970). However, the group with end-stage renal disease on dialysis showed a significant association (OR = 2.60, 95% CI = 1.25-5.41, P = 0.0165). Controlling for antibiotics as a possible confounding variable, yielded an OR that was not statistically significant (OR = 2.05, 95% CI = 0.94-4.47, P = 0.07), but still showing a trend towards increased risk., Conclusion: End-stage renal disease may increase the risk of acquiring CDAD through unknown mechanisms. This suggests implementing better surveillance strategies for these patients and eliminating the known risk factors for CDAD.

We have identified a consanguineous Pakistani family where oligodontia is inherited along with short stature in an autosomal-recessive fashion. Increased bone density was present in the spine and at the base of the skull. Using high-density single-nucleotide polymorphism microarrays for homozygosity mapping, we identified a 28 Mb homozygous stretch shared between affected individuals on chromosome 11q13. Screening selected candidate genes within this region, we identified a homozygous nonsense mutation, Y774X, within LTBP3, the gene for the latent TGF-beta binding protein 3, an extracellular matrix protein believed to be required for osteoclast function.

The activity of the heat stable, glycosylated high molecular weight bovine brain neutral protease (HMW protease) is differentially regulated by phospholipids. While phosphatidylcholine (PC), phosphatidylserine (PS) and phosphatidic acid (PA) had only marginal stimulatory effect (40-75%) on the activity of HMW protease, lysophoshatidylcholine (lysoPC) and lysophosphatidic acid (lysoPA) activated the enzyme by more than two-fold. Both lysoPC and lysoPA exhibited concentration-dependent saturation kinetics for the activation of HMW protease. Surprisingly, phosphoinositides (phosphatidylinositol, PI; phosphatidylinositol 4-phosphate, PIP; and phosphatidylinositol 4,5-bisphosphate, PIP2) modulated the activity of protease differently: activation of the enzyme was higher with PIP (90%) as compared to PI (21%), whereas PIP2 inhibited the enzyme (16%). The inhibition of the protease by PIP2 was concentration-dependent. During receptor-coupled cell activation, phospholipase A2 (PLA2) converts PC and PA to lysoPC and lysoPA, respectively; PI is converted to PIP2 by successive enzymatic phosphorylation by PI 4-kinase and PIP 5-kinase; and phospholipase C (PLC) degrades PIP2 to diacylglycerol and inositol 1,4,5-trisphosphate. Therefore, the data suggest that HMW protease may be coupled to cell signal transduction where PLA2, PI 4-kinase, PIP 5-kinase and PLC are involved.