Publications by authors named "Sunil Shah"

136 Publications

Outcomes following tacrolimus systemic immunosuppression for penetrating keratoplasty in infants and young children.

Eye (Lond) 2021 Nov 27. Epub 2021 Nov 27.

Department of Ophthalmology, Birmingham Children's Hospital, Birmingham, UK.

Objective: To report outcomes of tacrolimus immunosuppression after penetrating keratoplasty (PK) in very young children.

Methods: Retrospective, consecutive, cohort study of children undergoing PK at a tertiary children's hospital between 2005 and 2016. Oral tacrolimus immunosuppression was given for 2 years, followed by topical tacrolimus.

Results: Fourteen children (20 eyes) had 24 PKs; nineteen eyes had primary PKs, five eyes had repeat PKs. Mean age at primary graft was 95 days (3.1 months) for anterior segment dysgenesis (ASD), 430 days (14.3 months) for non-ASD children. Eleven children (15 eyes) had ASD. Three children (five eyes) had non-ASD: two children (three eyes) had glaucoma-related corneal opacity and one child (two eyes) had congenital hereditary endothelial dystrophy (CHED). One-year rejection-free survival rates following primary PK was 80% for ASD (n = 15) and 100% for non-ASD (n = 4). At final review, 5/15 of primary grafts for ASD were clear. 10/15 failed after a mean of 19 months, specifically attributable to infection (n = 2), rejection (n = 2) and glaucoma (n = 2). 4/4 primary non-ASD grafts are clear at final review (mean follow-up = 77 months). All repeat grafts (n = 5), failed after a mean of 38.25 months. Considering all grafts, 15/24 (62.5%) failed: 5/15 due to infection, 2/15 due to rejection, 8/15 due to glaucoma, phthisis, perforation or vascularised with no rejection. At last review (mean = 58.1 months, range 28-84), overall cohort survival is 37.5%. Final visual acuities range between 0.86 and 2.4 LogMAR.

Conclusion: We compare our results to published literature: 1-year graft survival was higher than previously reported, with lower failure due to rejection. Overall infection rates did not increase, however, proportionally, severe infections were higher. Overall graft survival is at least comparable to reported literature.
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http://dx.doi.org/10.1038/s41433-021-01855-wDOI Listing
November 2021

Diagnostic Scores and Treatment Options for Acute Disseminated Intravascular Coagulation in Children.

Cureus 2021 Sep 3;13(9):e17682. Epub 2021 Sep 3.

Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, California, USA.

Disseminated intravascular coagulation (DIC) is a thrombo-hemorrhagic condition that commonly accompanies life-threatening illnesses in children and is associated with significant morbidity and mortality. Treatment of underlying conditions, hemodynamic support, and replacement therapy with blood components is the mainstay of DIC management. Limited research studies have supported the use of antithrombin (AT), recombinant thrombomodulin (rTM), and protein C concentrates (PrCC). Although there have been several studies and advancements in the DIC treatment in adults, data in pediatric patients are limited, and the consensus is lacking. Evidence validating the use of diagnostic scoring systems in the pediatric population is also limited. Since the hemostatic system differs significantly in children, especially in neonates, management of DIC is also different in children from that of adults, and there is a dire need for good quality research studies in this aspect. We reviewed more than 100 articles in PubMed, Cochrane database, and Google Scholar. This traditional review article discusses different scoring systems for diagnosing DIC in pediatric patients, and different pharmacological treatment options for acute DIC in this population. This study mainly focuses on papers published from 1990 to 2021 and includes papers in all languages involving humans only.
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http://dx.doi.org/10.7759/cureus.17682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415803PMC
September 2021

Medulloblastoma in an Adult Female Patient: A Rare Presentation.

Cureus 2021 Jul 29;13(7):e16713. Epub 2021 Jul 29.

Hematology and Oncology, Guthrie Robert Packer Hospital, Sayre, USA.

Medulloblastoma (MB) is an aggressive malignant tumor of the posterior fossa of the CNS that mainly affects children younger than 15 years of age. It is uncommon in the adult population compared to children. Any adult patient presenting with cerebellar mass must be evaluated with brain tissue biopsy to rule out MB. Our patient is a 27-year-old female who presented with sudden onset of frontal headache and was diagnosed with MB.
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http://dx.doi.org/10.7759/cureus.16713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405177PMC
July 2021

Pure Autonomic Failure: A Case Report of Recurrent Orthostatic Hypotension.

JNMA J Nepal Med Assoc 2021 Jul 1;59(238):589-592. Epub 2021 Jul 1.

Universal College of Medical Sciences, Bhairahawa, Nepal.

Pure autonomic failure is a neurodegenerative disorder affecting the autonomic nervous system which clinically presents with orthostatic hypotension. It is a diagnosis of exclusion after detailed clinical examinations and relevant investigations. Here, we discuss a case of 68 years old male who had complaints of multiple episodes of loss of consciousness on standing from a sitting position for the last 3 years. The diagnosis was considered by clinical examinations revealing autonomic dysfunctions with normal appropriate investigations. The patient was treated successfully with midodrine, fludrocortisone, and other non-pharmacological interventions. We focused on doing various autonomic dysfunction tests in the evaluation of a patient with recurrent orthostatic hypotension. We suspect that pure autonomic failure might not have been considered in the differential diagnosis of recurrent orthostatic hypotension and suggest that it is to be kept as a differential in such a scenario. Midodrine has an effective role in syncope due to sympathetic vasoconstrictor failure.
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http://dx.doi.org/10.31729/jnma.6480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369549PMC
July 2021

Wellens Syndrome: An Atypical Presentation With Burning Chest and Epigastric Pain.

Cureus 2021 Jul 7;13(7):e16241. Epub 2021 Jul 7.

Pediatrics, Ministry of Health, Malé, MDV.

Wellens syndrome is a pre-infarction stage due to the critical stenosis of the proximal left anterior descending artery. It is characterized by intermittent chest pain with classical ECG changes. The cardiac biomarker is within the normal limit or only slightly elevated in this condition. Early recognition and cardiac intervention are important to prevent adverse cardiac outcomes. We report this rare case of Wellens syndrome in a 70-year-old male with intermittent chest and epigastric pain associated with belching for five days. The patient presented characteristic T-wave changes, symmetric deeply inverted T-waves, in precordial leads (V2-V4). Cardiac biomarkers, including troponin, were negative. He underwent cardiac catheterization and found a clot in the proximal left anterior descending coronary artery, which required a catheter-directed thrombectomy and drug-eluting stent placement. It is important to recognize this condition early and referred on time from primary health centers to higher centers, especially in developing countries like the Maldives, since delays in transfer may lead to a serious outcome.
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http://dx.doi.org/10.7759/cureus.16241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345899PMC
July 2021

A Case Report on Primary Central Nervous System Lymphoma in Immunocompetent Individual.

Cureus 2021 Jun 28;13(6):e15990. Epub 2021 Jun 28.

Hematology and Oncology, Guthrie Robert Packer Hospital, Sayre, USA.

Primary central nervous system lymphoma (PCNSL) is a rare form of CNS tumor. Immunosuppression is the most important risk factor of PCNSL, but few immunocompetent individuals are also affected. The most common clinical feature of PCNSL includes dizziness and ataxia. Our patient was a 71-year-old immunocompetent female who presented with progressive ataxia, imbalance, and dizziness for one year. A homogenous enhancing lesion was found in magnetic resonance imaging (MRI) of the head. One month later, on a follow-up MRI, a significant increase in the tumor size with surrounding edema was seen. The patient underwent craniotomy and resection of the mass. Subsequently, a diagnosis of diffuse large B cell lymphoma was made on pathology examination. Guideline-directed treatment options were discussed. This case highlights that the prognosis of patients with PCNSL highly depends on the factors such as age and physical status. Early diagnosis by accurate interpretation of imaging and management is crucial for better health outcomes.
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http://dx.doi.org/10.7759/cureus.15990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318614PMC
June 2021

Shark Fin Electrocardiogram: A Deadly Electrocardiogram Pattern in ST-Elevation Myocardial Infarction (STEMI).

Cureus 2021 Jun 28;13(6):e15989. Epub 2021 Jun 28.

Medicine, Ministry of Health, Male', MDV.

Shark fin electrocardiographic (ECG) pattern, also known as 'Lambda-wave', 'giant R waves', or 'triangular QRS-ST-T waveform' is a dangerous ECG pattern associated with ST-elevation myocardial infarction (STEMI). It is formed by the fusion of QRS, ST, and T waves and predicts the high risk of mortality due to cardiogenic shock and ventricular fibrillation. The management should be aggressive with reperfusion via thrombolysis or percutaneous intervention, ideally in the intensive care unit with ventricular assist devices. This ECG pattern may be misdiagnosed as wide complex tachycardia or the ECG changes of hyperkalemia. Thus, differentiating it from other conditions causing similar ECG changes and prompt management is highly important to save the patient from serious complications. Here we have presented a case of STEMI with shark fin ECG associated with pulmonary edema (Killip class III acute myocardial infarction).
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http://dx.doi.org/10.7759/cureus.15989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317974PMC
June 2021

Food insecurity during COVID-19 pandemic: A genuine concern for people from disadvantaged community and low-income families in Province 2 of Nepal.

PLoS One 2021 21;16(7):e0254954. Epub 2021 Jul 21.

Department of Allied Health Professions, Sports and Exercise, School of Human and Health Sciences, University of Huddersfield, Huddersfield, United Kingdom.

Background: Food insecurity is a serious social and public health problem which is exacerbated by the COVID-19 pandemic especially in resource-poor countries such as Nepal. However, there is a paucity of evidence at local levels. This study aims to explore food insecurity among people from the disadvantaged community and low-income families during the COVID-19 pandemic in Province-2 of Nepal.

Methods: The semi-structured qualitative interviews were conducted virtually among purposively selected participants (n = 41) from both urban and rural areas in eight districts of Province 2 in Nepal. All the interviews were conducted in the local language between July and August 2020. The data analysis was performed using thematic network analysis in Nvivo 12 Pro software.

Results: The results of this study are grouped into four global themes: i) Impact of COVID-19 on food security; ii) Food insecurity and coping strategies during the COVID-19 pandemic, iii) Food relief and emergency support during the COVID-19 pandemic, and iv) Impact of COVID-19 and food insecurity on health and wellbeing. Most participants in the study expressed that families from low socioeconomic backgrounds and disadvantaged communities such as those working on daily wages and who rely on remittance had experienced increased food insecurity during the COVID-19 pandemic. Participants used different forms of coping strategies to meet their food requirements during the pandemic. Community members experienced favouritism, nepotism, and partiality from local politicians and authorities during the distribution of food relief. The food insecurity among low-income and disadvantaged families has affected their health and wellbeing making them increasingly vulnerable to the COVID-19 infection.

Conclusion: Food insecurity among low-income and disadvantaged families was found to be a serious problem during the COVID-19 pandemic. The study suggests that the relief support plan and policies should be focused on the implementation of immediate sustainable food security strategies to prevent hunger, malnutrition, and mental health problems among the most vulnerable groups in the community.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254954PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294479PMC
July 2021

A Systematic Review of Effects of Vitamin E on the Cardiovascular System.

Cureus 2021 Jun 12;13(6):e15616. Epub 2021 Jun 12.

Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA.

Vitamin E is a fat-soluble vitamin and an antioxidant that prevents the peroxidation of lipid in vitro. The antioxidant role of vitamin E in preventing adverse cardiovascular outcomes is controversial as some studies support it, while others reject it. Therefore, this review aims to determine whether there is an association between vitamin E and cardiovascular diseases (CVDs). An electronic search was done to find out relevant articles. Papers were shortlisted after the initial title and abstract screen. A full-text study was done, and inclusion and exclusion criteria were applied before the quality assessment of each paper was done. Only high-quality papers were selected for analysis. Full-text articles of the last ten years were included, while non-English articles, gray literature, and animal studies were excluded. The majority of the papers, including 75% of the total population in this review, suggested no role of vitamin E in preventing CVD and CVD mortality. Some studies also suggested that a high level of vitamin E can be associated with adverse cardiovascular outcomes. Thus, one should be prudent about taking vitamin E supplementation for cardiovascular risk prevention.
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http://dx.doi.org/10.7759/cureus.15616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275884PMC
June 2021

Kawasaki Disease Shock Syndrome: A Nine-Year-Old Girl With Atypical Presentation of Kawasaki Disease in Emergency Department.

Cureus 2021 Jun 5;13(6):e15471. Epub 2021 Jun 5.

Pediatrics, Ministry of Health, Malé, MDV.

Kawasaki disease (KD) is an acute rheumatological illness usually affecting children between six months and five years of age. It is a vasculitis syndrome of medium-sized vessels that has typical clinical characteristics such as fever, rash, cervical lymphadenopathy, conjunctivitis, and mucosal changes. However, sometimes, it may present with the features of shock when it is known as Kawasaki disease shock syndrome (KDSS). The actual etiology of this disease is still unknown. The primary treatment of this disease is aspirin and intravenous immunoglobulin (IVIG). The most common and serious complication of KD is cardiac complications which can be avoided by IVIG if given on time. KDSS is the other rare but serious early complication that can be presented to the ED as an initial presenting feature. Early diagnosis of KDSS in the ED and its treatment is very important to prevent early and late complications, including cardiac complications of this disease. Although the usual age group for this disease is under five years, here we have presented a rare case of KDSS in a nine-year-old female child.
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http://dx.doi.org/10.7759/cureus.15471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260190PMC
June 2021

The Risks and Benefits of Myopia Control.

Ophthalmology 2021 11 4;128(11):1561-1579. Epub 2021 May 4.

Department of Ophthalmology, Children's University Hospital, Dublin, Ireland; Centre for Eye Research Ireland, School of Physics, Clinical and Optometric Sciences, Technological University Dublin, Dublin, Ireland.

Purpose: The prevalence of myopia is increasing around the world, stimulating interest in methods to slow its progression. The primary justification for slowing myopia progression is to reduce the risk of vision loss through sight-threatening ocular pathologic features in later life. The article analyzes whether the potential benefits of slowing myopia progression by 1 diopter (D) justify the potential risks associated with treatments.

Methods: First, the known risks associated with various methods of myopia control are summarized, with emphasis on contact lens wear. Based on available data, the risk of visual impairment and predicted years of visual impairment are estimated for a range of incidence levels. Next, the increased risk of potentially sight-threatening conditions associated with different levels of myopia are reviewed. Finally, a model of the risk of visual impairment as a function of myopia level is developed, and the years of visual impairment associated with various levels of myopia and the years of visual impairment that could be prevented with achievable levels of myopia control are estimated.

Results: Assuming an incidence of microbial keratitis between 1 and 25 per 10 000 patient-years and that 15% of cases result in vision loss leads to the conclusion that between 38 and 945 patients need to be exposed to 5 years of wear to produce 5 years of vision loss. Each additional 1 D of myopia is associated with a 58%, 20%, 21%, and 30% increase in the risk of myopic maculopathy, open-angle glaucoma, posterior subcapsular cataract, and retinal detachment, respectively. The predicted mean years of visual impairment ranges from 4.42 in a person with myopia of -3 D to 9.56 in a person with myopia of -8 D, and a 1-D reduction would lower these by 0.74 and 1.21 years, respectively.

Conclusions: The potential benefits of myopia control outweigh the risks: the number needed to treat to prevent 5 years of visual impairment is between 4.1 and 6.8, whereas fewer than 1 in 38 will experience a loss of vision as a result of myopia control.
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http://dx.doi.org/10.1016/j.ophtha.2021.04.032DOI Listing
November 2021

Impact of COVID-19 on health services utilization in Province-2 of Nepal: a qualitative study among community members and stakeholders.

BMC Health Serv Res 2021 Feb 24;21(1):174. Epub 2021 Feb 24.

Faculty of Medicine, Health and Social Care, Canterbury Christ Church University, Kent, UK.

Background: The COVID-19 pandemic has posed unprecedented challenges and threats to the health care system, particularly affecting the effective delivery of essential health services in resource-poor countries such as Nepal. This study aimed to explore community perceptions of COVID-19 and their experiences towards health services utilization during the pandemic in Province-2 of Nepal.

Methods: The semi-structured qualitative interviews were conducted among purposively selected participants (n = 41) from a mix of rural and urban settings in all districts (n = 8) of the Province 2 of Nepal. Virtual interviews were conducted between July and August 2020 in local languages. The data were analyzed using thematic network analysis in NVivo 12 Pro.

Results: The findings of this research are categorized into four global themes: i) Community and stakeholders' perceptions towards COVID-19; ii) Impact of COVID-19 and lockdown on health services delivery; iii) Community perceptions and experiences of health services during COVID-19; and iv) COVID-19: testing, isolation, and quarantine services. Most participants shared their experience of being worried and anxious about COVID-19 and reported a lack of awareness, misinformation, and stigma as major factors contributing to the spread of COVID-19. Maternity services, immunization, and supply of essential medicine were found to be the most affected areas of health care delivery during the lockdown. Participants reported that the interruptions in health services were mostly due to the closure of health services at local health care facilities, limited affordability, and involvement of private health sectors during the pandemic, fears of COVID-19 transmission among health care workers and within health centers, and disruption of transportation services. In addition, the participants expressed frustrations on poor testing, isolation, and quarantine services related to COVID-19, and poor accountability from the government at all levels towards health services continuation/management during the COVID-19 pandemic.

Conclusions: This study found that essential health services were severely affected during the COVID-19 pandemic in all districts of Province-2. It is critical to expand and continue the service coverage, and its quality (even more during pandemics), as well as increase public-private sector engagement to ensure the essential health services are available for the population.
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http://dx.doi.org/10.1186/s12913-021-06176-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903406PMC
February 2021

Stability and Visual Outcomes of the Capsulotomy-Fixated FEMTIS-IOL After Automated Femtosecond Laser-Assisted Anterior Capsulotomy.

Am J Ophthalmol 2021 05 4;225:27-37. Epub 2021 Jan 4.

Department of Ophthalmology, University of Heidelberg, Heidelberg, Germany; Reading Center of Department of Ophthalmology, University of Heidelberg, Heidelberg, Germany.

Purpose: To evaluate stability and performance of a new monofocal anterior capsulotomy-fixated intraocular lens (IOL) (FEMTIS; Teleon Surgical B.V., Spankeren, Netherlands) after femtosecond laser-assisted cataract surgery (FLACS).

Design: Prospective, multicenter, interventional, noncomparative case series.

Methods: FLACS with FEMTIS IOL was performed in 336 eyes of 183 cataract patients with fixation of the IOL to the anterior capsulotomy followed up for 12 months. Examination included uncorrected distance visual acuity (UDVA), best-corrected visual acuity (CDVA), subjective refraction, IOL centration, posterior capsule opacification (PCO), and investigators' satisfaction questionnaire.

Results: At 12 months, mean IOL rotation was 1.50 ± 1.76 degrees and decentration 0.14 ± 0.14 mm from baseline (day of surgery). Mean horizontal IOL tilt was 0.70 ± 0.60 degrees and vertical 1.15 ± 1.06 degrees relative to the baseline (crystalline lens). Mean distance between IOL and iris was 0.32 mm to 0.36 mm for all measured meridians. Mean UDVA was 0.12 ± 0.14 logMAR (range -0.20 to 0.54 logMAR), mean CDVA -0.01 ± 0.09 logMAR (range -0.30 to 0.20 logMAR). Mean spherical equivalent was 0.35 ± 0.53 diopter (D) and 98% of eyes (n = 235) were within ±1.0 D. Median PCO score was 1 with an Nd:YAG laser rate of 3.1% after 12 months. Most surgeons were very satisfied (median score: 1) with surgery and implanted IOL.

Conclusions: Implantation of FEMTIS IOL provided excellent visual and stable refractive outcomes. IOL decentration was very low compared to other published studies and showed an exceptional high in-the-bag stability over a 12-month period. This lens benefits from femtosecond laser capsulotomies. It can be positioned very predictably and offers an optimal platform for toric and multifocal IOL optics.
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http://dx.doi.org/10.1016/j.ajo.2020.12.025DOI Listing
May 2021

Hydroxyapatite coated hip hemiarthroplasty: Morbidity and mortality.

J Clin Orthop Trauma 2020 Jul 8;11(Suppl 4):S568-S572. Epub 2020 May 8.

Department of Trauma & Orthopaedics, Royal Free Hospitals London NHS Foundation Trust, The Ridgeway. Enfield, London, UK.

Background: Use of uncemented femoral stems for treating displaced intra capsular hip fractures in elderly is increasing worldwide. The aim of our study is to evaluate morbidity and mortality of treatment with a modular fully hydroxyapatite-coated collared femoral stem.

Material And Methods: 259 consecutive patients were included in the study. Patients were followed up for12 months. Outcomes were perioperative mortality, perioperative fractures, 30, 120 and 365-day mortality, revision surgery within 30 days and twelve months, length of stay, discharge destination and mobility.

Results: Mean age was 85.4 years. 71.8% were female. 63.3% of patients were ASA grade III and IV. 87.6% of patients were operated within 36 h of attendance to hospital. The mortality rate at 30, 120, and 365 days was 8.2%, 15%, and 18.4% respectively with no peri-operative mortality. 0.8% of the patients sustained a peri-operative fracture below the lesser trochanter. Infection and dislocation were 1.1% and 1.5% respectively. 3.4% of the patient underwent further surgery within thirty days but no further surgery in next twelve months. Mean inpatient acute length of stay was 16.8 days, 41.5% of the patients returned to their own or sheltered accomodation within thirty days. 68% of the patients were mobile outdoors prior to the fracture that dropped to 25% at one year after surgery.

Discussion: Our study demonstrates that treatment of displaced intracapsular femoral neck fractures in elderly with a full hydroxyapatite coated collared stem has satisfactory outcomes, no perioperative mortality, low one-year mortality and low revision hence a dependable option.
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http://dx.doi.org/10.1016/j.jcot.2020.04.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7394800PMC
July 2020

Dietary Risk Factors Associated with Development of Gastric Cancer in Nepal: A Hospital-Based Case-Control Study.

Gastroenterol Res Pract 2020 3;2020:5202946. Epub 2020 Jun 3.

Upendra Devkota Memorial National Institute of Neurological and Allied Sciences, Kathmandu, Nepal.

Objectives: Gastric cancer (GC) is one of the most prevalent neoplasms and a leading cause of mortality globally. To our knowledge, its relationship with dietary factors is not adequately studied and understood in the Nepalese context. This study is aimed at exploring the relationship between the possible dietary risk factors responsible for gastric cancer in Nepal.

Methods: A hospital-based matched case-control study was conducted in two specialized cancer hospitals in Nepal. A total of 237 participants (79 cases and 158 controls) were included in the study. Patients diagnosed within one year (incidence case) with histologically confirmed gastric cancer were taken as cases, and healthy visitors of gastric and nongastric cancer patients without past and present history or not a suspected information of gastric cancer were included as controls. A face-to-face interview was conducted using a semi-structured food frequency questionnaire. Backward stepwise conditional logistic regression was used to estimate the magnitude of the association between the independent variables and gastric cancer. Results were presented as the crude odds ratio (COR) and adjusted odds ratio (AOR) with 95% confidence intervals (CI). A value < 0.05 was considered statistically significant.

Results: In the adjusted multivariable conditional logistic regression model, an increased risk of gastric cancer was more likely to have higher odds among those respondents who had a high consumption of processed meat (AOR = 3.99, 95% CI: 0.90-17.66), preferences of a high amount of fats/oil (AOR = 4.64, 95% CI: 1.56-13.72), and preferences of high amounts of salts (AOR = 4.18, 95% CI: 1.30-13.44). Conversely, those respondents who consumed higher amounts of fruits (AOR = 0.21, 95% CI: 0.07-0.65) were seen to have lower odds of gastric cancer.

Conclusions: Our study found an increased risk of gastric cancer with frequent consumption of red meat, processed meat, high preferences of salt, fats/oil, and condiments. Regular consumption of fruits had a protective effect against gastric cancer. Providing nutrition education, public awareness, and lifestyle modification are primary steps to promote the avoidance of risk factors and change unhealthy dietary habits to prevent gastric cancer in Nepal.
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http://dx.doi.org/10.1155/2020/5202946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290904PMC
June 2020

Distribution of Pathogenic Yeasts in Different Clinical Samples: Their Identification, Antifungal Susceptibility Pattern, and Cell Invasion Assays.

Infect Drug Resist 2020 20;13:1133-1145. Epub 2020 Apr 20.

National Centre for Microbial Resource (NCMR), National Centre for Cell Science, NCCS Complex, S.P. Pune University, Pune 411 007, Maharashtra, India.

Introduction: Species of genus are part of the common microbiota of humans; however, some of the species are known opportunistic pathogens. Formation of biofilms, resistance to antifungal drugs, and increase in asymptomatic infections demands more studies on isolation, identification and characterization of from clinical samples.

Methods: The present manuscript deals with assessment of authentic yeast identification by three methods viz., DNA sequencing of gene, protein profiles using MALDI-TOF MS, and colony coloration on chromogenic media. Antifungal susceptibility and in vitro cell invasion assays were performed to further characterize these isolates.

Results: Comparison of three methods showed that DNA sequence analysis correctly identified more than 99.4% of the isolates up to species level as compared to 89% by MALDI-TOF MS. In this study, we isolated a total of 176 yeasts from clinical samples and preliminary morphological characters indicated that these yeast isolates belong to the genus . The species distribution of isolates was as follows: 75 isolates of (42.61%), 50 of (28.40%), 22 of (12.5%), 14 of (7.95%) and 4 of (2.27%). Other species like sp., and were less than 2%. Antifungal susceptibility assay performed with 157 isolates showed that most of the isolates were resistant to the four azoles viz., clotrimazole, fluconazole, itraconazole, and ketoconazole, and the frequency of resistance was more in non-albicans isolates. The susceptibility to azole drugs ranged from 7% to 48%, while 75% of the tested yeasts were susceptible to nystatin. Moreover, 88 isolates were also tested for their capacity to invade human cells using HeLa cells. In vitro invasion assay showed that most of the isolates showed epithelial cell invasion as compared to isolates belonging to and .

Discussion: The identification of yeasts of clinical origin by sequencing of gene performed better than MALDI-TOF MS. The present study reiterates the world scenario wherein there is a shift from strains to emerging opportunistic pathogens which were earlier regarded as environmental strains. The present study enlightens the current understanding of identification methods for clinical yeast isolates, increased antifungal drug resistance, epithelial cell invasion as a virulence factor, and diversity of yeasts in Indian clinical samples.
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http://dx.doi.org/10.2147/IDR.S238002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7182453PMC
April 2020

Increased risk of ocular injury seen during lockdown due to COVID-19.

Cont Lens Anterior Eye 2020 06 27;43(3):216. Epub 2020 Apr 27.

Prof. Sunil Shah Consultant Ophthalmologist, Birmingham and Midland Eye Centre, Birmingham, United Kingdom. Electronic address:

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http://dx.doi.org/10.1016/j.clae.2020.04.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184015PMC
June 2020

Polyamide Backbone Modified Cell Targeting and Penetrating Peptides in Cancer Detection and Treatment.

Front Chem 2020 31;8:218. Epub 2020 Mar 31.

Department of Chemistry and Biochemistry, Seton Hall University, South Orange, NJ, United States.

Cell penetrating and targeting peptides (CPPs and CTPs) encompass an important class of biochemically active peptides owning the capabilities of targeting and translocating within selected cell types. As such, they have been widely used in the delivery of imaging and therapeutic agents for the diagnosis and treatment of various diseases, especially in cancer. Despite their potential utility, first generation CTPs and CPPs based on the native peptide sequences are limited by poor biological and pharmacological properties, thereby restricting their efficacy. Therefore, medicinal chemistry approaches have been designed and developed to construct related peptidomimetics. Of specific interest herein, are the design applications which modify the polyamide backbone of lead CTPs and CPPs. These modifications aim to improve the biochemical characteristics of the native peptide sequence in order to enhance its diagnostic and therapeutic capabilities. This review will focus on a selected set of cell penetrating and targeting peptides and their related peptidomimetics whose polyamide backbone has been modified in order to improve their applications in cancer detection and treatment.
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http://dx.doi.org/10.3389/fchem.2020.00218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136562PMC
March 2020

Bifunctional Au-templated RNA nanoparticles enable direct cell uptake detection and GRP75 knockdown in prostate cancer.

J Mater Chem B 2020 03;8(10):2169-2176

Department of Chemistry and Biochemistry, Seton Hall University, 400 South Orange Avenue, South Orange, New Jersey 07079, USA.

Nucleic acids templated on gold (Au) surfaces have led to a wide range of functional materials ranging from microarrays, sensors and probes in addition to drug delivery and treatment. In this application, we describe a simple and novel method for templating amino-functionalized RNA onto Au surfaces and their self-assembly into small, discrete nanoparticles. In our method, sample hybridization with a complementary RNA strand with and without a fatty acid (palmitamide) appendage produced functionalized double-stranded RNA on the Au surface. The resulting Au-functionalized RNA particles were found to be stable under reducing conditions according to UV-Vis spectroscopy. Sample characterization by DLS and TEM confirmed self-assembly into primarily small (∼10-40 nm) spherical shaped nanoparticles expected to be amenable to cell biology. However, fluorescence emission (λexc: 350 nm, λem: 650 nm) revealed radiative properties which limited cell uptake detection. Introduction of FITC within the Au-functionalized RNA particles produced a bifunctional probe, in which FITC fluorescence emission (λexc: 494 nm, λem: 522 nm) facilitated cell uptake detection, in a time-dependent manner. The dual encapsulation-release profiles of the FITC-labeled Au-functionalized RNA particles were validated by time-dependent UV-Vis spectroscopy and spectrofluorimetry. These experiments respectively indicated an increase in FITC absorption (λabs: 494 nm) and fluorescence emission (λem: 522 nm) with increased sample incubation times, under physiological conditions. The release of Au-functionalized siRNA particles in prostate cancer (PC-3) cells resulted in concomitant knockdown of GRP75, which led to detectable levels of cell death in the absence of a transfection vector. Thus, the formulation of stable, small and discrete Au-functionalized RNA nanoparticles may prove to be valuable bifunctional probes in the theranostic study of cancer cells.
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http://dx.doi.org/10.1039/c9tb02438gDOI Listing
March 2020

Size Matters: Arginine-Derived Peptides Targeting the PSMA Receptor Can Efficiently Complex but Not Transfect siRNA.

Mol Ther Nucleic Acids 2019 Dec 23;18:863-870. Epub 2019 Oct 23.

Department of Chemistry and Biochemistry, Seton Hall University, 400 South Orange Avenue, South Orange, NJ 07079, USA. Electronic address:

Oligoarginine sequences conjugated to a short cancer-targeting peptide (CTP) selective for the prostate-specific membrane antigen (PSMA) receptor was developed for selective small interfering RNA (siRNA) delivery to a human metastatic/castration-resistant prostate cancer (PCa) cell line, which expresses PSMA on the surface. The PSMA-R (n = 6 and 9) peptides were synthesized by solid-phase peptide synthesis, characterized by liquid chromatography-mass spectrometry (LC-MS) and condensed with glucose-regulated protein (GRP)-silencing siRNAs. Native gels showed formation of stable CTP:siRNA ionic complexes. Furthermore, siRNA release was effected by heparin competition, supporting the peptides' capabilities to act as condensing and releasing agents. However, dynamic light scattering (DLS) and transmission electron microscopy (TEM) studies revealed large anionic complexes that were prone to aggregation and limited cell uptake for RNAi activity. Taken together, these data support the notion that the development of efficient peptide-based siRNA delivery systems is in part contingent on the formulation of discrete nanoparticles that can effectively condense and release siRNA in cells.
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http://dx.doi.org/10.1016/j.omtn.2019.10.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861565PMC
December 2019

Non-fluorescent filters for fluorescence detection with in-line geometry.

Methods Appl Fluoresc 2019 May 16;7(3):037001. Epub 2019 May 16.

Department of Physics and Astronomy, Texas Christian University, Fort Worth, TX 76129, United States of America.

Intrinsic emission from typical filters can unexpectedly contribute to the total measured signal in a fluorescence system. This emission becomes even more problematic for in-line geometry measurements where the excitation light can directly excite the emission filter. Potassium dichromate has minimal intrinsic fluorescence even with ultra-violet (UV) excitation. We show that a liquid sample can be tuned for its transmission properties by adding a base to the solution. This makes it attractive for use as an optical filter. In addition, when embedded in poly (vinyl alcohol) (PVA) film, potassium dichromate is even less fluorescent. These films can be cut and molded into practically any size or shape. Thus non-fluorescent, modular and cheap filters composed of potassium dichromate embedded in a PVA film is proposed to eliminate this unwanted emission and is suitable for a wide variety of devices and applications.
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http://dx.doi.org/10.1088/2050-6120/ab2034DOI Listing
May 2019

Comparison of surgical parameters using different lens fragmentation patterns in eyes undergoing laser-assisted cataract surgery.

Int Ophthalmol 2019 Nov 4;39(11):2459-2465. Epub 2019 Mar 4.

Birmingham and Midland Eye Centre, Birmingham, UK.

Purpose: To compare surgical parameters among eyes undergoing laser-assisted cataract surgery (LACS) using different lens fragmentation patterns (LFP).

Methods: Prospective, randomized, unmasked clinical trial. One-hundred eyes underwent LACS and were randomly assigned to 1 of 3 LFP treatment groups: (1) laser capsulotomy only; no lens fragmentation (NLF) (n = 34); (2) three-plane chop (TPC) (n = 33); and, (3) pie-cut pattern (PCP) fragmentation (n = 33). Prechop phacoemulsification (PHACO) was performed on all eyes using the same femtosecond (FS) laser and active-fluidics PHACO machine.

Main Outcome Measures: FS laser dock time (s), PHACO time (s), PHACO power (%), cumulative dissipated energy (CDE) (%-s), irrigating fluid volume, and operative time.

Results: The 3 treatment groups were comparable in terms of patient age (P = 0.164) and nuclear density (P = 0.669). FS dock time was higher in the PCP group (184.18 ± 25.86) compared to the TPC (145.09 ± 14.15) group (P < 0.001). PHACO time was significantly shorter in the PCP (23.19 ± 17.20 s) compared to TPC (35.27 ± 17.70) and NLF (46.15 ± 23.72) groups (P < 0.001). PHACO power was lower in the PCP (11.81 ± 3.71) compared to the NLF (14.41 ± 1.88) and TPC (14.04 ± 2.46) groups (P < 0.001). CDE was lower in the PCP (2.85 ± 2.32) compared to NLF (6.55 ± 3.32) and TPC (6.55 ± 5.45) groups (P < 0.001). Fluid volumes and operative times were similar.

Conclusion: LFP can influence PHACO surgical parameters. Extensive fragmentation patterns such as PCP appear to lower PHACO time, power, and CDE and may potentially reduce the risk of PHACO related complications.
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http://dx.doi.org/10.1007/s10792-019-01087-8DOI Listing
November 2019

GRP78 modulates cell adhesion markers in prostate Cancer and multiple myeloma cell lines.

BMC Cancer 2018 Dec 18;18(1):1263. Epub 2018 Dec 18.

Center for Discovery and Innovation, Hackensack University Medical Center, 340 Kingsland Street, Building 102, Nutley, NJ, 07110, USA.

Background: Glucose regulated protein 78 (GRP78) is a resident chaperone of the endoplasmic reticulum and a master regulator of the unfolded protein response under physiological and pathological cell stress conditions. GRP78 is overexpressed in many cancers, regulating a variety of signaling pathways associated with tumor initiation, proliferation, adhesion and invasion which contributes to metastatic spread. GRP78 can also regulate cell survival and apoptotic pathways to alter responsiveness to anticancer drugs. Tumors that reside in or metastasize to the bone and bone marrow (BM) space can develop pro-survival signals through their direct adhesive interactions with stromal elements of this niche thereby resisting the cytotoxic effects of drug treatment. In this study, we report a direct correlation between GRP78 and the adhesion molecule N-cadherin (N-cad), known to play a critical role in the adhesive interactions of multiple myeloma and metastatic prostate cancer with the bone microenvironment.

Methods: N-cad expression levels (transcription and protein) were evaluated upon siRNA mediated silencing of GRP78 in the MM.1S multiple myeloma and the PC3 metastatic prostate cancer cell lines. Furthermore, we evaluated the effects of GRP78 knockdown (KD) on epithelial-mesenchymal (EMT) transition markers, morphological changes and adhesion of PC3 cells.

Results: GRP78 KD led to concomitant downregulation of N-cad in both tumors types. In PC3 cells, GRP78 KD significantly decreased E-cadherin (E-cad) expression likely associated with the induction in TGF-β1 expression. Furthermore, GRP78 KD also triggered drastic changes in PC3 cells morphology and decreased their adhesion to osteoblasts (OSB) dependent, in part, to the reduced N-cad expression.

Conclusion: This work implicates GRP78 as a modulator of cell adhesion markers in MM and PCa. Our results may have clinical implications underscoring GRP78 as a potential therapeutic target to reduce the adhesive nature of metastatic tumors to the bone niche.
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http://dx.doi.org/10.1186/s12885-018-5178-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6299583PMC
December 2018

Solid phase synthesis and self-assembly of higher-order siRNAs and their bioconjugates.

Chem Biol Drug Des 2019 06 23;93(6):999-1010. Epub 2018 Dec 23.

Department of Chemistry and Biochemistry, Seton Hall University, South Orange, New Jersey.

New methods for the synthesis of higher-order siRNA motifs and their bioconjugates have recently gained widespread attention in the development of new and improved gene therapeutics. Our efforts aim to produce new chemical tools and protocols for the generation of modified siRNAs that screen for important oncogene targets as well as silence their activity for effective gene therapy in cancer models. More specifically, we have developed an efficient solution-phase synthesis for the production of a ribouridine branchpoint synthon that can be effectively incorporated by solid phase synthesis within higher-order RNA structures, including those adopting V-, and Y- and >-< shape RNA templates. Self-assembly of complementary RNA to the template strands produced higher-order siRNA nanostructures that were characterized by a combination of PAGE, DLS, and TEM techniques. In an effort to extend the repertoire of functionally diverse siRNAs, we have also developed solid phase bioconjugation strategies for incorporating bio-active probes such as fatty acid appendages and fluorescent reporters. Taken together, these methods highlight the ability to generate higher-order siRNAs and their bioconjugates for exploring the influence of modified siRNA structure on anti-cancer activity.
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http://dx.doi.org/10.1111/cbdd.13448DOI Listing
June 2019

Endoscopic Goniosynechialysis for Acute Angle Closure Glaucoma Following Descemet's Stripping Automated Endothelial Keratoplasty.

J Curr Glaucoma Pract 2018 May-Aug;12(2):90-93. Epub 2018 Aug 1.

Clinical Lead and Consultant, Department of Ophthalmology, Birmingham and Midland Eye Centre, UK.

We describe a new modified technique to release the peripheral iridocorneal adhesions that formed after Descemet stripping automated endothelial keratoplasty. The usual technique of goniosynechialysis was modified and performed using endoscopic fiber-optic light and camera probe to aid visualization of the adherent iris tissue and carry out uneventful 270 degrees release of adhesions. The iris tissue was gently pulled away using micro forceps. The modified technique was conceptualized, as the view from the cornea was very poor due to recent lamellar surgery and corneal oedema secondary to poorly controlled intraocular pressure. The blocked trabecular meshwork system was successfully recanalized, which allowed an adequate control of intraocular pressure. The graft survived the insult and cornea gained complete clarity giving the patient the desired vision and improved quality of life. Rana M, Shah S, Pandey P, Masood I. Endoscopic Goniosynechialysis for Acute Angle Closure Glaucoma Following Descemet's Stripping Automated Endothelial Keratoplasty. J Curr Glaucoma Pract 2018;12(2):90-93.
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http://dx.doi.org/10.5005/jp-journals-10008-1250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6236120PMC
August 2018

Enhanced Cancer Theranostics with Self-Assembled, Multilabeled siRNAs.

ACS Omega 2018 Oct 10;3(10):12975-12984. Epub 2018 Oct 10.

Department of Chemistry and Biochemistry, Seton Hall University, South Orange, New Jersey 07079, United States.

The integration of therapy and diagnostics, termed "theranostics", has recently gained widespread utility in the development of new and improved therapeutics that effectively diagnose and treat diseases, such as cancer. In this study, the covalent attachment of multiple fluorescent labels (i.e., fluorescein isothiocyanate (FITC)) to a wide range of siRNAs, including those adopting linear, V- and Y-shape nanostructures, was successfully accomplished by solid-phase bioconjugation for monitoring cell uptake, co-localization, and biological activity in cell culture. The FITC-labeled higher-order V- and Y-shape siRNAs maintained the requisite hybrid stabilities and A-type helical structures for invoking RNAi activity. The FITC-siRNA hybrids with sense-strand modifiers enabled efficient mRNA knockdown (∼50-90%), which also translated to increased cell death (∼20-95%) in a bone metastatic prostate cancer cell line, over a 72 h incubation period. Significantly, the Y-shaped siRNA containing three FITC probes enhanced fluorescent signaling relative to the siRNA constructs containing single and double fluorophores while retaining potent knockdown and cell death effects post-transfection. Taken together, this data highlights the theranostic utility of the multilabeled FITC-siRNA constructs for potential cancer gene therapy applications.
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http://dx.doi.org/10.1021/acsomega.8b01999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6217585PMC
October 2018

Direct Transfection of Fatty Acid Conjugated siRNAs and Knockdown of the Glucose-Regulated Chaperones in Prostate Cancer Cells.

Bioconjug Chem 2018 11 10;29(11):3638-3648. Epub 2018 Oct 10.

Department of Chemistry and Biochemistry , Seton Hall University , South Orange , New Jersey 07079 , United States.

The emerging field of RNAi nanotechnology has led to rapid advances in the applications of siRNAs in chemical biology, medicinal chemistry, and biotechnology. In our RNAi approach, bioconjugation of linear, V-, and Y-shaped RNA templates were designed using a series of saturated and unsaturated fatty acids to improve cell uptake and knockdown efficacy of the oncogenic glucose regulated proteins (GRPs) in prostate (PC-3) cancer cells. An optimized HCTU-coupling procedure was developed for tagging variable saturated and unsaturated fatty acids onto the 5'-ends of linear and V-shaped RNA templates that were constructed by semiautomated solid phase RNA synthesis. Hybridization and self-assembly of complementary strands yielded linear, V-, and Y-shaped fatty acid-conjugated siRNAs which were characterized by native PAGE. CD spectroscopy confirmed their A-type helix conformations. RP IP HPLC provided trends in amphiphilic properties, whereas DLS and TEM confirmed multicomponent self-assembled structures that were prone to aggregation. Subsequently, the fatty acid conjugated siRNA bioconjugates were tested for their RNAi activity by direct transfection within PC-3 cells known to overexpress oncogenic GRP activity. The siRNA bioconjugates with sense strand modifiers provided more potent GRP knockdown relative to the antisense modified siRNAs, but to a lesser extent when compared to the unconjugated siRNA controls that were transfected with the commercial Trans-IT X2 dynamic delivery system. Flow cytometry revealed that the latter may be at least in part attributed to limited cell uptake of the fatty acid conjugated siRNAs. Nonetheless, these new constructs represent an entry point in modifying higher-order siRNA constructs that may lead to the generation of more efficient siRNA bioconjugates for screening important oncogene targets and for cancer gene therapy applications.
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http://dx.doi.org/10.1021/acs.bioconjchem.8b00580DOI Listing
November 2018

Corrigendum to "Drugs - Do we need them? Applications of non-pharmaceutical therapy in anterior eye disease: A review" [Contact Lens Anterior Eye 40 (2017) 360-366].

Cont Lens Anterior Eye 2018 12 18;41(6):547. Epub 2018 Aug 18.

Birmingham and Midland Eye Centre, Sandwell and West Birmingham Hospitals NHS Trust, City Hospital, Dudley Road, Birmingham, B18 7QH, UK; School of Life and Health Sciences, Aston University, Birmingham, B4 7ET, UK. Electronic address:

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http://dx.doi.org/10.1016/j.clae.2018.08.007DOI Listing
December 2018

Evaluation of antifertility potential of (Petiole) on female wistar rats "rising approaches of herbal contraception''.

Biochem Biophys Rep 2018 Sep 14;15:97-102. Epub 2018 Aug 14.

Deparment of Pharmacognosy, College of Pharmacy, Sri Satya Sai University of Technology & Medical Sciences, Sehore, Madhya Pradesh 466001, India.

(Petiole) is used of herbal methods for fertility regulation is widely accepted alternative for the synthetic drugs containing chemical having side effects. (Petiole) is the plant having several medical properties but no reports were available on the antifertility activity. The aim of this study was to investigate the antifertility activity of extracts of (Petiole) on female wistar rats at the doses 500 mg/kg b.wt./day for 30 days. Different parameters were studied in female wistar rats including effect of Reproductive outcome, Anti-implantation, Abortifacient and Estrogenic & Anti-estrogenic activity, were observed. shown positive test for Alkaloids, Steroid, Flavonoids, Terpene, Carbohydrates and Tannin. The extract has anti-fertility effect the control rats showed good number of litters and treatment of animal with different extracts resulted a significant (P < 0.05, P < 0.01). Antifertility activity 51% and 37.2% was exhibited by Alcoholic extracts of (Petiole) APB and Aqueous extracts of (Petiole) WPB respectively. After 21 days of the extracts free period, the antifertility effect of the extracts was reversed. The extract treatment with APB, an increase in the percentage of resorption index indicates the failure in development of embryo. The mean percentage of anti-implantation and abortifacient were found to be highest for APB-38.45%, WPB 13.62, and APB-28.96%, WPB-12.75% respectively. The decrement in implantation caused by the extracts may be due to estrogenic or anti-estrogenic activity. However, along with standard APB exhibiting more potent estrogenic and less potent anti-estrogenic when compared with standard. Female antifertility agents should include acceptability, safety and efficacy during and after the treatment. The above results revealed the potential, reversible female antifertility effect of alcoholic extract (Petiole).
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http://dx.doi.org/10.1016/j.bbrep.2018.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6098191PMC
September 2018

Massive haemorrhagic blister formation following total knee arthroplasty.

JRSM Open 2018 May 4;9(5):2054270418758569. Epub 2018 May 4.

2Royal Free London NHS Foundation Trust, Barnet Hospital, London EN5 3DJ, UK.

Skin blistering following trauma is not uncommon; however, large haemorrhagic bullous blisters following total knee arthroplasty is relatively rare and not widely documented in the literature.
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http://dx.doi.org/10.1177/2054270418758569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5946637PMC
May 2018
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