bluuebunny/crossref_metadata_2025 huggingface dataset:
“Examining The Gratification Of Women From Health Communication On Social Media By Women”
Authors: Pawar Sushma , Kakade Prof. Onkaragouda
Published: October 2024

In the digital age, social media has emerged as a crucial platform for health communication; significantly influencing how health information is disseminated and consumed. This study examines the gratification that women experience from health communication on social media. In the contemporary digital landscape, social media has become an essential platform for health communication, particularly for women. This medium provides a valuable space for sharing health information, fostering community support, and promoting wellbeing. Health communication on social media has the potential to significantly influence women’s health behaviors, attitudes, and knowledge. This study aims to examine the gratification of women from health communication on social media, focusing on main objectives like studying the socio-demographics characteristics of the women, identifying their usage patterns of social media, to investigate the gratification derived by women from engaging with health related content on social media. As well as to identify the types of health information that is most influential and trusted by women on social media platforms. For this study, the descriptive research design was adopted, and the primary data of 130 respondents were selected randomly for the collection of primary data through a structured questionnaire
Academic Essay On Equitable Access To Mental Health Services In Brazil
Authors: Júnior Mario Angelo Cenedesi , Sakman Rosângela , Calderaro Kelly Lene Lopes , Faria José Geraldo De
Published: October 2024

Equitable access to mental health services in Brazil faces complex and interconnected challenges. Among the main issues are regional inequalities, socioeconomic barriers, and the stigma associated with mental disorders. Regional inequality results in significant differences in the quality and availability of mental health services between urban and rural areas. While large cities such as São Paulo and Rio de Janeiro have advanced infrastructure and qualified professionals, rural areas and urban outskirts suffer from a lack of resources and professionals, limiting access to necessary care. Socioeconomic barriers also play a crucial role. Low-income populations face additional difficulties, such as lack of transportation and inadequate health insurance, which restrict access to mental health services. The lack of information and the stigmatization of mental disorders worsen the situation, discouraging individuals from seeking treatment due to fear of discrimination and prejudice. To address these challenges, it is essential to adopt integrated strategies. Expanding mental health infrastructure in underserved areas and creating integrated care networks are fundamental. Public policies should reduce socioeconomic inequalities by providing financial support and improving transportation. Awareness campaigns about mental health can overcome informational barriers and stigma. Continuous training of health professionals and community participation are also crucial to ensure inclusive and locally adapted care. With a coordinated effort, it is possible to promote more just and comprehensive access to mental health services in Brazil.
Dengue In Brazil: Challenges And Strategies For Public Health Management
Authors: Júnior Mario Angelo Cenedesi , Ferreira Maria Cristina De Moura- , Da Silva Joana Darc Ferreira , Resende Tatiana Carneiro De , Araújo Maria Aparecida De Almeida
Published: October 2024

This academic essay explores the complex landscape of dengue in Brazil, a viral arbovirus transmitted by the Aedesaegypti mosquito, with significant impacts due to its high incidence and frequent epidemic outbreaks, especially during warm and rainy periods conducive to vector reproduction. The symptoms range from high fever and muscle pain to severe forms such as dengue hemorrhagic fever, requiring urgent medical intervention. The country's dengue control strategies include eliminating breeding sites, using insecticides, and conducting public awareness campaigns. The disease not only strains healthcare services but also adversely affects the economy and social well-being, underscoring the importance of robust epidemiological surveillance systems and coordinated responses. Initiatives such as the Health in Schools Program (PSE) and the roles played by Community Health Agents (ACS) and Endemic Disease Control Agents (ACE) are crucial in prevention and control efforts. Collaborative efforts across health, education, and community sectors are essential to address the challenges of dengue comprehensively. Therefore, Brazil must continue investing in research, vaccines, and innovative strategies to sustainably and effectively reduce the burden of dengue and safeguard public health.
Survival Rate Of Composite Veneer - A Review
Authors: Emmanuel Dr.Minu Anna
Published: October 2024

Composite veneers are a minimally invasive and increasingly popular choice for aesthetic dental restorations. Their clinical durability and success are determined by multiple factors, including material composition, patient habits, and the technical expertise of the dental practitioner. This review evaluates the existing research on the lifespan of composite veneers, with a focus on the key elements that affect their durability, clinical performance, and patient satisfaction. These elements include adhesive bonding methods, patient oral hygiene practices, and mechanical stressors that influence the long-term success of composite veneers.
Elbow Tuberculosis: A Radiological Dilemma
Authors: Karisaiyappanavar Ravi N. , Mohan Keerthi , Vinnakota Avinash , Pattanashetty Adivemma , Pratap Surya Madadi
Published: October 2024

Background: Tuberculosis is considered to affect approximately one third of the world population. Being an airborneinfection the percentage of skeletal tuberculosis is found to be very low compared to pulmonary tuberculosis. The incidence of musculoskeletal tuberculosis affecting elbow joint is extremely rare. Materials and Methods: We present a case of a 21 year old male residing in India presented with complaints of progressive left elbow pain for 6 months with restriction of movement later. On examination, the left elbow was in fixed flexion deformity with 40degree with diffuse swelling around the joint. There is fullness in the para olecranon fossa with doughy feeling of the joint which suggests synovial hypertrophic over posterior joint line and anconeus triangle. Range of movement on flexion was 40 to 90degree; supination 0 to 70 degree and pronation 0-30 degree. Inflammatory markers on examination were elevated and revealed C-reactive protein of 29.8mg/L and Erythrocyte Sedimentation rate (ESR) of 40mm/hr. Plain radiograph of left elbow joint shows multifocal geographical areas of lytic destruction involving proximal end of ulna predominantly in olecranon process and cortical irregularity at the head of radius. Computed tomography showed multifocal lytic areas involving the olecranon process of ulna, head of radius and lateral condyle of humerus with synovial thickening around the elbow joint. Magnetic resonance imaging of elbow joint showed homogeneously enhancing diffuse synovial thickening in and around the elbow joint with resultant widening of the joint space. The hypertrophic synovium is extending within the olecranon process of ulna through multiple cortical defects. A differential diagnosis of monoarticular rheumatoid arthritis and possibility of granulomatous lesion was given. Results: The patient was admitted and a synovial biopsy was taken. The histopathology report was suggestive of granulomatous lesion with possibility of tuberculosis. Patient was conservatively managed with anti-tubercular treatment. On further follow up the patient had better mobility of the joint. Conclusion: TB of the joint should be considered in the differential diagnosis of monoarticular arthropathy or arthritis due to its indolent course. This case highlights the diagnostic challenges of TB in an appendicular joint, non-specific imaging findings, and resultant joint dysfunction. It also underscores systemic flaws in healthcare, particularly the lack of drug susceptibility testing and the limited availability of GeneXpert in endemic regions, exacerbating the practice of empirical treatment amidst the rising tide of MDR-TB
Biomimetic Regeneration Of Enamel Using SelfAssembling Peptides: A Systematized Review
Authors: Pandian Dr.Nagendran Jayavel , Devaraj Dr.Karthika , M Dr.Narmatha , Gopalakrishnan Dr.Priyatharsini
Published: October 2024

Background: Noninvasive methods of treating initial caries lesions have been a widely researched topic in this scientific era. Various biomimetic materials are available on the market. Self-assembling peptides focus on the biomimetic regeneration of enamel and stand out from the others due to their ability to restore the enamel matrix Data: This systematized review was conducted on articles with the remineralization effects of SAP on initial enamel lesions published between 2019 January to 2024 September. Sources: The search of this review was carried out in the electronic databases PUBMED, COCHRANE, EMBASE, and Google Scholar. Only primary researches were included Results: Out of 122 articles obtained, 28 articles were included in this review after screening. The studies demonstrate the effect of SAP on reversing WSLs and its efficacy in comparing and combining with other remineralizing agents such as fluorides, and CPP-ACP. Conclusion: With the limited evidence, SAP can be used as a promising solution for WSLs in permanent as well as primary teeth
Etiology, Epidemiology And Methods Of Preventing Sudden Death Of Cardiac Origin In Sports
Authors: De Brito Bruna Estefani Rocha , Silva Matheus Guedes Fernandes , Nascimento Rafael Pinheiro Do , Paschoal Juliana Fontes Beltran , Bezerra Thiago A. Rochetti
Published: October 2024

Introduction: Numerous epidemiological studies have consistently shown an association between moderate aerobic exercise and decreased risk of coronary heart disease (CHD) and death, and even a small amount of exercise provides a significant reduction in risk compared to a sedentary lifestyle Objective: The aim of this study was to identify the etiology, epidemiology and prevention of sudden cardiac death in sports. Methodology: The methodology used was a literature review. The research was carried out by means of an electronic search for scientific articles published on the Scielo (Scientific Electronic Library Online) and Lilacs (Latin American Health Sciences Literature) and Pubmed websites. The health terminologies consulted in the Health Sciences descriptors (DeCS/BIREME) were used; the etiology, epidemiology and ways of preventing sudden cardiac death in sports practices. Discussion: An important distinction must be made between hypertrophic cardiomyopathy and “athlete's heart syndrome”. In this syndrome, intense physical training leads to various morphological and physiological alterations, especially left ventricular hypertrophy. Conclusion: The complete health safety of athletes consists of periodic pre-participation clinical assessment as well as emergency measures, mainly in competition venues, consisting of the availability of health professionals
Diabetic Mastopathy – A Case Report
Authors: Sakthivel Dr.Vijay , Yadav Dr. Dharmendra , Samson Dr. Sandeep , Cherian Dr. Jeenu Elizabeth , Manoharan Dr.Peter
Published: October 2024

Introduction: Diabetic mastopathy is a rare benign condition that can occur in patients with long standing Type I or II diabetes mellitus male or female of any age. Diabetic mastopathy is a fibroinflammatory condition that resembles carcinoma of breast. Here, we report a case of Type II Diabetic female patient with suspicious breast lump in right breast Case presentation: A 62 year old female presented with complaints of lump in right breast for 10 days. Clinically, hard lump of size 8x6 cm was palpable in upper outer quadrant. Trucut biopsy showed features of Diabetic mastopathy. Patient undergone wide local excision and biopsy confirmed the diagnosis. Post operative period was uneventful. Discussion: Diabetic mastopathy is an uncommon tumor-like proliferation of fibrous tissue of the breast, clinically and radiologically mimicking breast cancer. Histopathologically, it involves periductal, perilobular and perivascular lymphocytic infiltration. Primary excision with adequate normal tissue margins is the treatment of choice Conclusion: Diabetic mastopathy is a rare clinical entity, however due to increase in prevalence of Diabetes, diagnosis of Diabetic mastopathy should be considered in patients with breast lumps
Interesting Case Of Congenital Tuberculosis
Authors: Barsaiyan Dr. Sakshi , Nikhra Dr Ankur , Balan Dr Saroja , Gupta Dr Vidya , K Pooja
Published: October 2024

Background: Mycobacterium tuberculosis (TB) is a global public health problem and is the causative organism of TB. There were 234,000 deaths of children due to tuberculosis. Since most of the pregnant women who have active TB are symptomless, diagnosis of TB is usually delayed2,3. It is difficult to differentiate between true congenital TB and postnatally acquired TB. High suspicion is needed for early diagnosis and treatment. Case: A 30-day-old girl had abdominal distension 1 week before admission and refusal to feed appeared on the 30th day. Clinically, sepsis, TORCH infection was suspected. USG abdomen showed multiple hypoechoic lesions in liver. Ct chest and abdomen showed multiple discrete non-calcified nodules in bilateral lung fields and liver. Gastric aspirate for AFB was negative. Mother was screened for TB; the TSTwas positive and TB QuantiFERON gold came positive. Hence, Tru-cut Liver biopsy was done for neonate and Biopsy for Genexpert showed low level Mycobacterium TB detected. Cerebrospinal fluid analysis for acid-fast bacilli was negative. 4 drug ATT regimen was started. Two weeks after anti-TB medication, the distension completely disappeared. Conclusion: Early diagnosis and treatment is the key for the survival of neonatal TB
Study Of Incidence And Risk Factors In Surgical Site Infections Post LSCS At Tertiary Care Centre In Western Rajasthan
Authors: Sharma Dr Shweta , Shaheen Dr Rizwana , Saxena Dr Ayushi
Published: October 2024

Background: Surgical site infection post LSCS leads to increasing patient morbidity and increase the duration of patient hospitalization, hospital costs and raise the burden on our healthcare system. The incidence of SSI after caesarean section ranges from 3% to 5%. Objective of current investigation was to study the incidence&risk factors responsible for SSI in LSCS. Methods: This prospective study was done among pregnant women undergoing LSCS who developed SSI at department of Obstetrics and Gynaecology in Umaid Hospital, Jodhpur during June 2023 to August 2023. All patients were following up to 7thpostoperative day.SSI was defined by CDC criteria. Results: The incidence of SSI noted in present study was 2.5%. Almost 30.8% cases had BMI ≥25 kg/m2 , 55% multipara, 67.3% resided in rural area. Anemia, PROM, LSCS in emergency, multiple vaginal examination (>5), prolonged labornoted in participants of SSI was 51.9%, 26.9%, 75, 34.6%, 38.4% respectively. Silk suture material was used in 71% of cases who developed SSI. Conclusions: Incidence of SSI in present is 2.5%. BMI, Anemia, PROM, LSCS in emergency, multiple vaginal examination (>5), prolonged labor, silk suture material were noted higher among the participants who developed SSI. Keywords: Cesarean delivery, Incidence of SSI, Risk factor, Surgical site infection
Knowledge Assessment Of COVID-19 Among Outpatients In Dhaka
Authors: Khanam Tahmina Israt , Islam ABM Mir Mubinul , Uddin Md. Mojib
Published: October 2024

Background: The COVID-19 pandemic has exposed significant gaps in public knowledge and adherence to preventive measures, particularly in low- and middle-income countries. This study aimed to assess the knowledge, attitudes, and preventive practices regarding COVID-19 among outpatients at the Combined Military Hospital (CMH), Dhaka Cantonment. Methods: This descriptive cross-sectional study included 71 outpatients attending the CMH OPD from July 1, 2020, to December 31, 2021. Participants were selected through informed consent and were aged between 18 and 89 years. Data were collected via face-to-face interviews using a semi-structured, pretested questionnaire and were analyzed using SPSS version 23.0. The questionnaire captured participants' knowledge of COVID-19, preventive practices, and comorbidity status. Results: The mean age of the participants was 35.18 years. Females comprised 59.15% of the sample, with 76.06% residing in urban areas. Regarding comorbidities, 16.90% had a history of COVID-19, while 15.49% had hypertension or diabetes mellitus. Although 88.7% of participants knew that wearing a face mask could prevent infection, only 39.4% recognized coughing and sneezing as transmission routes, and just 36.6% acknowledged the importance of social distancing. In terms of overall knowledge, 35.21% had "Good" knowledge, while 8.45% exhibited "Poor" knowledge. Conclusion: Significant gaps in knowledge and adherence to preventive measures were identified, particularly regarding COVID-19 transmission and social distancing. Targeted health education efforts are needed to improve knowledge and practices, particularly among vulnerable groups with comorbidities
Exploring the Association of Serum Lipids, Plasma Glucose, Obesity and Demographic Factors on Breast Cancer Risk in Bangladeshi Female: A Case Control Study
Authors: Nahar Sabekun , Nizam Quazi Sumaiya Bint , Sultana Rebaka , Badhan Raisa Enayet , Banu Laila Anjuman
Published: October 2024

Background: The fifth most prevalent cause of cancer-related death worldwide and the most frequently diagnosed malignancy is breast cancer. Breast cancer is the second most prevalent neoplasm in Bangladesh and it is rising alarmingly among females. Ignorance and illiteracy are contributing factors to mortality due to delayed presentation. This study was aimed to evaluate the association of obesity, serum lipids, plasma glucose and demographic factors with breast cancer risk in Bangladeshi females. Materials and Methods: This was a case-control study designed using a population of 60 females (30 in each group). The analysis involved a comparison of both the socio-demographic data and the blood samples collected from the participants in the study. Samples were collected over a one-year period from the Department of Surgery at Bangladesh Medical College and Hospital, as well as from the Departments of Surgery and Oncology at Bangabandhu Sheikh Mujib Medical University, Bangladesh. Statistical analysis was performed with SPSS version 26. Results: Mean body mass index (BMI) of case group is 29.4 (± 2.8) and control group is 25.5 (± 3.4) where P value is significant (<0.001). Significant differences (P-value ≤ 0.05) were observed in triglycerides (TG), low density lipoprotein (LDL) cholesterol, and total cholesterol (TC) level between cases and controls. Though there were no significant differences observed between the groups in fasting plasma glucose (FPG), plasma glucose- 2 hours after breakfast (PG-2HABF), haemoglobin A1c (HbA1c), high density lipoprotein (HDL) cholesterol, and serum creatinine level. Conclusion: TC, TG and LDL cholesterol level as well as BMI are independent predictors of breast cancer risk among Bangladeshi females
Endodontic Rescue: A Case Series On Retrieving Separated Instruments With Precision
Authors: Shetty Ashwija , Sultana Hajira Anjum , V Keerthan Bhat , A Srirekha , C Champa
Published: October 2024

Instrument separation is one of the most common undesirable mishaps encountered by endodontists during root canal treatment. The separated instruments hamper endodontic therapy by blocking access to the apical third, inhibiting the proper chemomechanical preparation of the root canals and jeopardizing the prognosis of endodontic therapy. Hence, such fragments should be properly retrieved or an attempt should be made to bypass it. The purpose of this article was to describe, through clinical cases, the technique of retrieval of separated instruments, under dental operating microscope using ultrasonics
Reviving Pulp Vitality Using Strategies For Preserving Pulp Vitality: A Case Series
Authors: . .
Published: October 2024

This case series explores various pulp capping methods, focusing on direct and indirect approaches using tricalcium silicate-based cement. The goal is to maintain pulp vitality while promoting reparative dentin formation. The efficacy of MTA over traditional calcium hydroxide is discussed, emphasizing its superior properties in terms of biocompatibility, sealing ability, and dentin bridge formation. Proper diagnosis, isolation,and follow-up are crucial for successful pulp capping. Clinicians should weigh the benefits of MTA when preserving pulp health
Nuclease‐resistant 63‐bp trimeric siRNAs simultaneously silence three different genes in tumor cells
Authors: Gvozdeva Olga V. , Gladkih Daniil V. , Chernikov Ivan V. , Meschaninova Mariya I. , Venyaminova Alya G. , Zenkova Marina A. , Vlassov Valentin V. , Chernolovskaya Elena L.
Published: December 2017

We designed a multimeric nuclease‐resistant 63‐bp trimeric small‐interfering RNA (tsiRNA) comprising in one duplex the sequence of siRNAs targeting mRNAs of MDR1, LMP2, and LMP7 genes. We show that such tsiRNA is able to suppress the expression of all the target genes independently and with high efficiency, acting via a Dicer‐dependent mechanism. tsiRNA is diced into 42‐ and 21‐bp duplexes inside the cell. tsiRNA‐induced gene silencing is characterized by kinetics similar to that of canonical siRNA, while the silencing efficiency is significantly higher than that of canonical siRNA with the same sequence.
The role of oxidative stress in Friedreich's ataxia
Authors: Lupoli Federica , Vannocci Tommaso , Longo Giovanni , Niccolai Neri , Pastore Annalisa
Published: December 2017

Oxidative stress and an increase in the levels of free radicals are important markers associated with several pathologies, including Alzheimer's disease, cancer and diabetes. Friedreich's ataxia (FRDA) is an excellent paradigmatic example of a disease in which oxidative stress plays an important, albeit incompletely understood, role. FRDA is a rare genetic neurodegenerative disease that involves the partial silencing of frataxin, a small mitochondrial protein that was completely overlooked before being linked to FRDA. More than 20 years later, we now know how important this protein is in terms of being an essential and vital part of the machinery that produces iron‐sulfur clusters in the cell. In this review, we revisit the most important steps that have brought us to our current understanding of the function of frataxin and its role in disease. We discuss the current hypotheses on the role of oxidative stress in FRDA and review some of the existing animal and cellular models. We also evaluate new techniques that can assist in the study of the disease mechanisms, as well as in our understanding of the interplay between primary and secondary phenotypes.
Eurasian Winter Storm Activity at the End of the Century: A CMIP5 Multi‐model Ensemble Projection
Authors: Basu Soumik , Zhang Xiangdong , Wang Zhaomin
Published: December 2017

Extratropical cyclone activity over Eurasia has exhibited a weakening trend in the recent decade. Extratropical cyclones bring precipitation and hence supply fresh water for winter crops in the mid‐ and high‐latitude regions of Eurasia. Any changes in extratropical cyclone activity over Eurasia in the future may have a critical impact on winter agriculture and the economies of affected communities. However, potential future changes in regional storm activity over Eurasia have not been studied in detail. Therefore, in this study, we investigate anticipated changes in extratropical storm activity by the end of the century through a detailed examination of the historical and future emission scenarios from six different models from CMIP5. A statistical analysis of different parameters of storm activity using a storm identification and tracking algorithm reveals a decrease in the number of storms over mid‐latitude regions. However, intense storms with longer duration are projected over high latitude Eurasia. A further examination of the physical mechanism for these changes reveals that a decrease in the meridional temperature gradient and a weakening of the vertical wind shear over the mid‐latitudes are responsible for these changes in storm activity.
Influence of Rift Superposition on Lithospheric Response to East African Rift System Extension: Lapur Range, Turkana, Kenya
Authors: Boone Samuel C. , Seiler Christian , Kohn Barry P. , Gleadow Andrew J. W. , Foster David A. , Chung Ling
Published: December 2017

The Turkana Depression of northern Kenya lies at the intersection of the NW‐SE trending late Mesozoic‐early Paleogene South Sudan and Anza rifts and the N‐S trending late Paleogene‐Recent East African Rift System (EARS). A low‐temperature thermochronology study in the Lapur Range reveals a complex tectonothermal evolution related to multiple periods of regional and local tectonism. Zircon (U‐Th)/He data from Precambrian basement record rapid Early Cretaceous denudational cooling. Coeval subsidence in the adjacent Anza and South Sudan rifts (Morley, Bosworth, et al., 1999; Schull, 1988) suggests that the northern Turkana region acted as a basement high separating the grabens, as well as an axial source of sediment. Between ~95 and 90 Ma, a period of reheating commenced with burial of Lapur basement beneath ~500 m of Late Cretaceous‐Eocene Lapur Sandstone and ~1.5–3.5 km of latest Eocene‐early Miocene Turkana volcanics. Apatite fission track (AFT) and apatite (U‐Th‐Sm)/He data record a transition to rapid denudational cooling in the mid‐Miocene (~14 Ma) in response to EARS‐related extension in the northern Turkana Basin. Thermal history models indicate that the Lapur Range experienced ~90–100°C of mid‐Miocene to Plio‐Pleistocene cooling, yielding the first Neogene AFT ages reported from Kenya related to EARS exhumation. We attribute the larger magnitude of cooling in the Lapur Range compared to other regions of the EARS to the attenuated crustal thickness and elevated heat flow of the Turkana Depression, crustal properties inherited from earlier Cretaceous‐Paleogene rifting. The resulting low effective elastic thickness of the Turkana lithosphere allowed for increased isostatic footwall uplift in response to EARS extension.
Electrochemically Synthesis of Nickel Cobalt Sulfide for High‐Performance Flexible Asymmetric Supercapacitors
Authors: Zhang Chunyan , Cai Xiaoyi , Qian Yao , Jiang Haifeng , Zhou Lijun , Li Baosheng , Lai Linfei , Shen Zexiang , Huang Wei
Published: December 2017

A lightweight, flexible, and highly efficient energy management strategy is highly desirable for flexible electronic devices to meet a rapidly growing demand. Herein, Ni–Co–S nanosheet array is successfully deposited on graphene foam (Ni–Co–S/GF) by a one‐step electrochemical method. The Ni–Co–S/GF composed of Ni–Co–S nanosheet array which is vertically aligned to GF and provides a large interfacial area for redox reactions with optimum interstitials facilitates the ions diffusion. The Ni–Co–S/GF electrodes have high specific capacitance values of 2918 and 2364 F g−1 at current densities of 1 and 20 A g−1, respectively. Using such hierarchical Ni–Co–S/GF as the cathode, a flexible asymmetric supercapacitor (ASC) is further fabricated with polypyrrple(PPy)/GF as the anode. The flexible asymmetric supercapacitors have maximum operation potential window of 1.65 V, and energy densities of 79.3 and 37.7 Wh kg−1 when the power densities are 825.0 and 16100 W kg−1, respectively. It's worth nothing that the ASC cells have robust flexibility with performance well maintained when the devices were bent to different angles from 180° to 15° at a duration of 5 min. The efficient electrochemical deposition method of Ni–Co–S with a preferred orientation of nanosheet arrays is applicable for the flexible energy storage devices.
Development of a microfluidic platform for high‐throughput screening of non‐viral gene delivery vectors
Authors: Giupponi Elisa , Visone Roberta , Occhetta Paola , Colombo Federica , Rasponi Marco , Candiani Gabriele
Published: December 2017

The grail of gene delivery is the development of delivery vectors as effective and non‐cytotoxic as possible. In this regard, there is an urgent need of new tools for the straightforward and quantitative assessment of transfection efficiency and cytotoxicity simultaneously. We herein reported the development and validation of an easy‐to‐use lab‐on‐chip platform to perform cell transfection assays for unbiased, high‐throughput selection of more and more effective gene delivery vectors by using two commercially sourced lipids, Lipofectamine 2000® and FuGene® 6. A single PDMS‐layer platform was endowed with: i) a chaotic serial dilution generator, designed for the automatic generation of a linear lipoplex dilution (from 100% to 0% with 25% steps) independently delivered to; and ii) the downstream culture and transfection module consisting in five units, each composed of 33 serially connected and fluidically connected culture chambers for trapping small populations of ≈10 cells/chamber. In the absence of any transfectant, cells spread and duplicated up to 2 days. Besides, cells were transfected with EGFP‐encoding reporter gene. The very facile visual inspection of the microdevice by means of a microscope and a semi‐automated analytical method allowed pinpointing the best transfection conditions in terms of efficiency, cytotoxicity, cell doubling rates, and morphological changes at once.
Model for pressure drop and flow deflection in the numerical simulation of stents in aneurysms
Authors: Li Sha , Latt Jonas , Chopard Bastien
Published: December 2017

The numerical simulation of flow diverters like stents contributes to the development and improvement of endovascular stenting procedures, leading ultimately to an improved treatment of intracranial aneurysms. Due to the scale difference between the struts of flow diverters and the full artery, it is common to avoid fully resolved simulations at the level of the stent porosity. Instead, the effect of stents on the flow is represented by a heuristic continuum model. However, the commonly used porous media models describe the properties of flow diverters only partially, because they do not explicitly account for the deflection of the flow direction by the stent. We show that this deficiency can be circumvented by adopting the theoretical framework of screen models. The article first reviews existing screen models. It then proposes an explicit formula for the drag and the deflection coefficient, as predicted by each model, for both perpendicular and inclined angles. The results of 2D numerical simulations are used to formulate a generalization of these formulas, to achieve best results in the case of stent modeling. The obtained model is then validated, again through 2D numerical simulation.
To Take or Not to Take With Meals? Unraveling Issues Related to Food Effects Labeling for Oral Antineoplastic Drugs
Authors: Deng Jiexin , Brar Satjit S. , Lesko Lawrence J.
Published: December 2017

There has been controversy regarding whether bioavailability of certain oral oncology drugs should be maximized by taking these medications with food, irrespective of label instructions in the dosing and administration section. To provide insight into this controversy, we conducted an in‐depth analysis for oral antineoplastic drugs approved by the Food and Drug Administration in 2000‐2016 and identified important issues influencing food labeling decisions. Furthermore, a case study involving sonidegib, a drug approved for locally advanced basal cell carcinoma with a significant food effect on exposure, was used to demonstrate the consequences of failure to adhere to food label recommendations using drug‐specific population pharmacokinetic and exposure‐toxicity models. In 2000‐2009, 80% (4 out of 5) of all approved oral antineoplastics with increased bioavailability in the fed state were labeled as “take on empty stomach.” In contrast, we found that in 2010‐2016 there is a greater diversity in food recommendations for drugs with increased bioavailability in the fed state. Currently, many oral oncology drugs are given with food to maximize their bioavailability; however, as seen from our case study of sonidegib, failure to fully adhere to label recommendations to either take with food or not could lead to adverse consequences in terms of safety and efficacy.
Pharmacokinetics of Diclofenac and Hydroxypropyl‐β‐Cyclodextrin (HPβCD) Following Administration of Injectable HPβCD‐Diclofenac in Subjects With Mild to Moderate Renal Insufficiency or Mild Hepatic Impairment
Authors: Hamilton Douglas A. , Ernst Cynthia C. , Kramer William G. , Madden Donna , Lang Eric , Liao Edward , Lacouture Peter G. , Ramaiya Atulkumar , Carr Daniel B.
Published: December 2017

Given their established analgesic properties, nonsteroidal anti‐inflammatory drugs (NSAIDs) represent an important postoperative pain management option. This study investigated: (1) the effects of mild or moderate renal insufficiency and mild hepatic impairment on the pharmacokinetics (PK) of diclofenac and hydroxypropyl‐β‐cyclodextrin (HPβCD) following administration of the injectable NSAID HPβCD‐diclofenac; and (2) the PK of HPβCD following administration of HPβCD‐diclofenac and intravenous itraconazole formulated with HPβCD in healthy adults. Diclofenac clearance (CL) and volume of distribution (Vz) tended to increase with decreasing renal function (moderate insufficiency versus mild insufficiency or healthy controls). Regression analysis demonstrated a significant relationship between Vz (but not CL or elimination half‐life, t½) and renal function. HPβCD CL was significantly decreased in subjects with renal insufficiency, with a corresponding increase in t½. There were no significant differences in diclofenac or HPβCD PK in subjects with mild hepatic impairment versus healthy subjects. Exposure to HPβCD in healthy subjects following HPβCD‐diclofenac administration was ∼12% of that with intravenous itraconazole, after adjusting for dosing schedule and predicted accumulation (<5% without adjustment). With respect to PK properties, these results suggest that HPβCD‐diclofenac might be administered to patients with mild or moderate renal insufficiency or mild hepatic impairment without dose adjustment (NCT00805090).
Early postnatal development of electrophysiological and histological properties of sensory sural nerves in male rats that were maternally deprived and artificially reared: Role of tactile stimulation
Authors: Zempoalteca Rene , Porras Mercedes G. , Moreno‐Pérez Suelem , Ramirez‐Funez Gabriela , Aguirre‐Benítez Elsa L. , González del Pliego Margarita , Mariscal‐Tovar Silvia , Mendoza‐Garrido Maria E. , Hoffman Kurt Leroy , Jiménez‐Estrada Ismael , Melo Angel I.
Published: December 2017

Early adverse experiences disrupt brain development and behavior, but little is known about how such experiences impact on the development of the peripheral nervous system. Recently, we found alterations in the electrophysiological and histological characteristics of the sensory sural (SU) nerve in maternally deprived, artificially reared (AR) adult male rats, as compared with maternally reared (MR) control rats. In the present study, our aim was to characterize the ontogeny of these alterations. Thus, male pups of four postnatal days (PND) were (1) AR group, (2) AR and received daily tactile stimulation to the body and anogenital region (AR‐Tactile group); or (3) reared by their mother (MR group). At PND 7, 14, or 21, electrophysiological properties and histological characteristics of the SU nerves were assessed. At PND 7, the electrophysiological properties and most histological parameters of the SU nerve did not differ among MR, AR, and AR‐Tactile groups. By contrast, at PND 14 and/or 21, the SU nerve of AR rats showed a lower CAP amplitude and area, and a significant reduction in myelin area and myelin thickness, which were accompanied by a reduction in axon area (day 21 only) compared to the nerves of MR rats. Tactile stimulation (AR‐Tactile group) partially prevented most of these alterations. These results suggest that sensory cues from the mother and/or littermates during the first 7–14 PND are relevant for the proper development and function of the adult SU nerve. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 78: 351–362, 2018
Compartment‐specific dynamics and functions of autophagy in neurons
Authors: Kulkarni Vineet Vinay , Maday Sandra
Published: December 2017

Autophagy is a lysosomal degradation pathway that is critical to maintaining neuronal homeostasis and viability. Autophagy sequesters damaged and aged cellular components from the intracellular environment, and shuttles these diverse macromolecules to lysosomes for destruction. This active surveillance of the quality of the cytoplasm and organelles is essential in neurons to sustain their long‐term functionality and viability. Indeed, defective autophagy is linked to neurodevelopmental abnormalities and neurodegeneration in mammals. Here, we review the mechanisms of autophagy in neurons and functional roles for autophagy in neuronal homeostasis. We focus on the compartment‐specific dynamics of autophagy in neurons, and how autophagy might perform non‐canonical functions critical for neurons. We suggest the existence of multiple populations of autophagosomes with compartment‐specific functions important for neural activity and function. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 78: 298–310, 2018
Opposing deer and caterpillar foraging preferences may prevent reductions in songbird prey biomass in historically overbrowsed forests
Authors: Godfrey R. Keating , Yerger Ellen H. , Nuttle Timothy J.
Published: December 2017

Overbrowsing by ungulates decimates plant populations and reduces diversity in a variety of ecosystems, but the mechanisms by which changes to plant community composition influence other trophic levels are poorly understood. In addition to removal of avian nesting habitat, browsing is hypothesized to reduce bird density and diversity through reduction of insect prey on browse‐tolerant hosts left behind by deer. In this study, we excluded birds from branches of six tree species to quantify differences in songbird prey removal across trees that vary in deer browse preference. Early in the breeding season, birds preyed on caterpillars at levels proportional to their abundance on each host. Combining these data with tree species composition data from stands exposed to experimentally controlled deer densities over 30 years ago, we tested whether overbrowsing by white‐tailed deer reduces prey biomass long after deer densities are reduced. Our analysis predicts total prey availability in the canopy of regenerating forests is fairly robust to historic exposure to high deer densities, though distribution of prey available from host species changes dramatically. This predicted compensatory effect was unexpected and is driven by high prey abundance on a single host tree species avoided by browsing deer, Prunus serotina. Thus, while we confirm that prey abundance on host trees can act as a reliable predictor for relative prey availability, this study shows that quantifying prey abundance across host trees is essential to understanding how changes in tree species composition interact with ungulate browse preference to determine prey availability for songbirds.
Development of a genotype‐by‐sequencing immunogenetic assay as exemplified by screening for variation in red fox with and without endemic rabies exposure
Authors: Donaldson Michael E. , Rico Yessica , Hueffer Karsten , Rando Halie M. , Kukekova Anna V. , Kyle Christopher J.
Published: December 2017

Pathogens are recognized as major drivers of local adaptation in wildlife systems. By determining which gene variants are favored in local interactions among populations with and without disease, spatially explicit adaptive responses to pathogens can be elucidated. Much of our current understanding of host responses to disease comes from a small number of genes associated with an immune response. High‐throughput sequencing (HTS) technologies, such as genotype‐by‐sequencing (GBS), facilitate expanded explorations of genomic variation among populations. Hybridization‐based GBS techniques can be leveraged in systems not well characterized for specific variants associated with disease outcome to “capture” specific genes and regulatory regions known to influence expression and disease outcome. We developed a multiplexed, sequence capture assay for red foxes to simultaneously assess ~300‐kbp of genomic sequence from 116 adaptive, intrinsic, and innate immunity genes of predicted adaptive significance and their putative upstream regulatory regions along with 23 neutral microsatellite regions to control for demographic effects. The assay was applied to 45 fox DNA samples from Alaska, where three arctic rabies strains are geographically restricted and endemic to coastal tundra regions, yet absent from the boreal interior. The assay provided 61.5% on‐target enrichment with relatively even sequence coverage across all targeted loci and samples (mean = 50×), which allowed us to elucidate genetic variation across introns, exons, and potential regulatory regions (4,819 SNPs). Challenges remained in accurately describing microsatellite variation using this technique; however, longer‐read HTS technologies should overcome these issues. We used these data to conduct preliminary analyses and detected genetic structure in a subset of red fox immune‐related genes between regions with and without endemic arctic rabies. This assay provides a template to assess immunogenetic variation in wildlife disease systems.
Drivers of advanced stage at breast cancer diagnosis in the multicountryAfrican breast cancer – disparities in outcomes (ABC‐DO) study
Authors: McKenzie Fiona , Zietsman Annelle , Galukande Moses , Anele Angelica , Adisa Charles , Parham Groesbeck , Pinder Leeya , Cubasch Herbert , Joffe Maureen , Kidaaga Frederick , Lukande Robert , Offiah Awa U. , Egejuru Ralph O. , Shibemba Aaron , Schuz Joachim , Anderson Benjamin O. , dos Santos Silva Isabel , McCormack Valerie
Published: December 2017

Breast cancer (BC) survival rates in sub‐Saharan Africa (SSA) are low in part due to advanced stage at diagnosis. As one component of a study of the entire journey of SSA women with BC, we aimed to identify shared and setting‐specific drivers of advanced stage BC. Women newly diagnosed in the multicountry African Breast Cancer–Disparities in Outcomes (ABC‐DO) study completed a baseline interview and their stage information was extracted from medical records. Ordinal logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for advanced stage (I, II, III, IV) in relation to individual woman‐level, referral and biological factors. A total of 1795 women were included from Nigeria, Uganda, Zambia, and the multiracial populations of Namibia and South Africa, 1091 of whom (61%) were stage III/IV. Stage was lower in women with greater BC knowledge (OR 0.77 (95% CI: 0.70, 0.85) per point on a 6 point scale). More advanced stage was associated with being black (4.00 (2.79, 5.74)), having attended <secondary education (1.75 (1.42, 2.16)), having never heard of BC (1.64 (1.31, 2.06)), an unskilled job (1.77 (1.43, 2.20)) and pregnancy in the past 3 years (30% of ≤45 year olds) (1.63 (1.15, 2.31)), and were mediated through delays to diagnosis: symptom duration of ≥ 1 year (OR 2.47 (1.93, 3.15)). These findings provide further evidence that late‐stage BC in SSA is largely attributed to modifiable factors and strategies to improve BC education and awareness in women and the health system should be intensified.
DNA methylation‐based biological aging and cancer risk and survival: Pooled analysis of seven prospective studies
Authors: Dugué Pierre‐Antoine , Bassett Julie K. , Joo JiHoon E. , Jung Chol‐Hee , Ming Wong Ee , Moreno‐Betancur Margarita , Schmidt Daniel , Makalic Enes , Li Shuai , Severi Gianluca , Hodge Allison M. , Buchanan Daniel D. , English Dallas R. , Hopper John L. , Southey Melissa C. , Giles Graham G. , Milne Roger L.
Published: December 2017

The association between aging and cancer is complex. Recent studies have developed measures of biological aging based on DNA methylation and called them “age acceleration.” We aimed to assess the associations of age acceleration with risk of and survival from seven common cancers. Seven case–control studies of DNA methylation and colorectal, gastric, kidney, lung, prostate and urothelial cancer and B‐cell lymphoma nested in the Melbourne Collaborative Cohort Study were conducted. Cancer cases, vital status and cause of death were ascertained through linkage with cancer and death registries. Conditional logistic regression and Cox models were used to estimate odds ratios (OR) and hazard ratios (HR) and 95% confidence intervals (CI) for associations of five age acceleration measures derived from the Human Methylation 450 K Beadchip assay with cancer risk (N = 3,216 cases) and survival (N = 1,726 deaths), respectively. Epigenetic aging was associated with increased cancer risk, ranging from 4% to 9% per five‐year age acceleration for the 5 measures considered. Heterogeneity by study was observed, with stronger associations for risk of kidney cancer and B‐cell lymphoma. An associated increased risk of death following cancer diagnosis ranged from 2% to 6% per five‐year age acceleration, with no evidence of heterogeneity by cancer site. Cancer risk and mortality were increased by 15–30% for the fourth versus first quartile of age acceleration. DNA methylation‐based measures of biological aging are associated with increased cancer risk and shorter cancer survival, independently of major health risk factors.
Vaginal discharge concentrations of β‐human chorionic gonadotropin, creatinine, and urea for the diagnosis of premature rupture of membranes
Authors: Bouzari Zinatossadat , Shahhosseini Roza , Mohammadnetaj Meadeh , Barat Shahnaz , Yazdani Shahla , Hajian‐Tilaki Karimollah
Published: December 2017

Objective

To determine the diagnostic value of vaginal discharge concentrations of β human chorionic gonadotropin (β‐hCG), creatinine, and urea to identify premature rupture of membranes (PROM).

Methods

An observational cross‐sectional study was conducted between 12 June, 2014, and 11 June, 2015, among 120 women who were admitted to an Iranian hospital at 28–41 weeks of pregnancy. Women with positive pooling and nitrazine test results were assigned to the PROM group (n=60), whereas those with negative test results were assigned to the control group (n=60). Samples of vaginal discharge were obtained.

Results

Mean concentrations of β‐hCG, urea, and creatinine were all higher in the PROM group than in the control group (all P=0.001). The diagnostic accuracies as defined by area under the curve for creatinine, urea, and β‐hCG were 0.891, 0.895, and 0.908, respectively. The corresponding optimal cutoff values were 20.33 μmol/L, 0.94 mmol/L, and 39.5 IU/L, respectively.

Conclusion

The vaginal discharge concentrations of all three markers exhibited favorable predictive value for the diagnosis of PROM; however, β‐hCG showed greater diagnostic accuracy than either urea or creatinine.