bluuebunny/crossref_metadata_2025 huggingface dataset:
Towards sex-specific osteoarthritis risk models: evaluation of risk factors for knee osteoarthritis in males and females
Authors: Szilagyi Ingrid A , Waarsing Jan H , Schiphof Dieuwke , van Meurs Joyce B J , Bierma-Zeinstra Sita M A
Published: April 2021

Objectives

The aim of this study was to identify sex-specific prevalence and strength of risk factors for the incidence of radiographic knee OA (incRKOA).

Methods

Our study population consisted of 10 958 Rotterdam Study participants free of knee OA in one or both knees at baseline. One thousand and sixty-four participants developed RKOA after a median follow-up time of 9.6 years. We estimated the association between each available risk factor and incRKOA using sex stratified multivariate regression models with generalized estimating equations. Subsequently, we statistically tested sex differences between risk estimates and calculated the population attributable fractions (PAFs) for modifiable risk factors.

Results

The prevalence of the investigated risk factors was, in general, higher in women compared with men, except that alcohol intake and smoking were higher in men and high BMI showed equal prevalence. We found significantly different risk estimates between men and women: high level of physical activity [relative risk (RR) 1.76 (95% CI: 1.29–2.40)] or a Kellgren and Lawrence score 1 at baseline [RR 5.48 (95% CI: 4.51–6.65)] was higher in men. Among borderline significantly different risk estimates was BMI ≥27, associated with higher risk for incRKOA in women [RR 2.00 (95% CI: 1.74–2.31)]. The PAF for higher BMI was 25.6% in women and 19.3% in men.

Conclusion

We found sex-specific differences in both presence and relative risk of several risk factors for incRKOA. Especially BMI, a modifiable risk factor, impacts women more strongly than men. These risk factors can be used in the development of personalized prevention strategies and in building sex-specific prediction tools to identify high risk profile patients.
Distinct morpho-physiological and biochemical features of arid and hyper-arid ecotypes of Ziziphus nummularia under drought suggest its higher tolerance compared with semi-arid ecotype
Authors: Sivalingam P N , Mahajan Mahesh M , Satheesh Viswanathan , Chauhan Sarita , Changal Harish , Gurjar Karun , Singh Dhurendra , Bhan Chander , Sivalingam Anandhan , Marathe Ashish , Ram Chet , Dokka Narasimham , More T A , Padaria J C , Bhat K V , Mohapatra T
Published: April 2021

Tree species in the arid and semi-arid regions use various strategies to combat drought stress. Ziziphus nummularia (Burm. f.) Wight et Arn., native to the Thar Desert in India, is highly drought-tolerant. To identify the most drought-tolerant ecotype of Z. nummularia, one ecotype each from semi-arid (Godhra, annual rainfall >750 mm), arid (Bikaner, 250–350 mm) and hyper-arid (Jaisalmer, <150 mm) regions was selected along with two other Ziziphus species, Ziziphus mauritiana Lamk. and Ziziphus rotundifolia Lamk., and screened for parameters contributing to drought tolerance. Among these, Z. nummularia (Jaisalmer) (CIAHZN-J) was the most drought - tolerant. The tolerance nature of CIAHZN-J was associated with increased membrane stability, root length and number, length of hairs and thorns, root dry/fresh weight ratio, seed germination (at −0.5 MPa), proline content (31-fold), catalase and sugar content (two- to three-fold). Apart from these characteristics, it also exhibited the longest duration to reach highest cumulative drought stress rating, maintained higher relative water content for a longer period of time with reduced leaf size, leaf rolling and falling of older leaves, and displayed sustained shoot growth during drought stress. To determine drought tolerance in Ziziphus, we developed a morphological symptom-based screening technique in this study. Additionally, transcriptome profiling of CIAHZN-J in response to drought revealed the up-regulation of genes involved in sugar metabolism and transport, abscisic acid biosynthesis, osmoregulation, reactive oxygen species homeostasis and maintaining water potential. Expression profiles and semi-quantitative reverse transcription PCR results further correlated with the physiological and biochemical mechanisms. In conclusion, CIAHZN-J is an excellent genetic stock for the identification of drought-responsive genes and can also be deployed in crop improvement programs for drought tolerance.
Evolution of nuptial-gift-related male prosomal structures: taxonomic revision and cladistic analysis of the genus Oedothorax (Araneae: Linyphiidae: Erigoninae)
Authors: Lin Shou-Wang , Lopardo Lara , Uhl Gabriele
Published: April 2021

Sexual selection has been shown to drive speciation. In dwarf spiders (erigonines), males possess diverse, sexually selected prosomal structures with nuptial-gift-producing glands. The genus Oedothorax is suitable for investigating the evolution of these features due to high structural variation. We have re-delimited this genus based on a phylogenetic analysis. Ten species are Oedothorax s.s.; five are transferred back to their original generic placement; 25 remain unplaced as ‘Oedothorax’. Four junior synonymies are proposed: Callitrichia simplex to Ca. holmi comb. nov.; Gongylidioides kougianensis to G. insulanus comb. nov.; Ummeliata ziaowutai to U. esyunini comb. nov.; Oe. kathmandu to Mitrager unicolor comb. nov. Oedothorax seminolus is a junior synonym of Soulgas corticarius and the transfer of Oe. alascensis to Halorates is confirmed. The replacement name Ca. hirsuta is proposed for Ca. pilosa. The male of Callitrichia longiducta comb. nov. and the female of ‘Oedothorax’ nazareti are newly described. Thirty-eight Oedothorax species are transferred to other genera. Callitrichia spinosa is transferred to Holmelgonia. Three genera are erected: Cornitibia, Emertongone and Jilinus. Ophrynia and Toschia are synonymized with Callitrichia. Character optimization suggests multiple origins of different prosomal modification types. Convergent evolution in these traits suggests that sexual selection has played an important role in erigonine diversification.
Measuring Auditory Fitness in Locomotive Engineers: Development and Validation of a Signal Detection Test
Authors: van der Hoek-Snieders Hanneke E.M. , Houben Rolph , Dreschler Wouter A.
Published: April 2021

Objectives:

To perform their job safely and effectively, locomotive engineers are required to detect auditory warning signals in the noisy work setting of a train cabin. Based on audio recordings of Dutch train cabins, we have developed a task and job-specific test for assessing the engineer’s ability to detect the two acoustic warning signals for the Dutch situation. The aim of this study was to evaluate the reliability, agreement, and construct validity of this test.

Design:

Two experiments were performed. In the first experiment, reliability and agreement of the signal detection test were assessed. Normally hearing individuals (N = 12) completed a signal detection test twice in 12 driving conditions. In the second experiment, construct validity was assessed. We retrospectively identified locomotive engineers, suspected of being hearing impaired, who were referred to the Amsterdam UMC for an auditory fitness for job assessment. All included engineers (N = 83) performed the signal detection test in four driving conditions, underwent tone audiometry and two speech perception in noise tests, and rated the effort and concentration it takes to detect the auditory signals. Seven a priori formulated hypotheses were tested.

Results:

In the first experiment, sufficient reliability and agreement were found in nine driving conditions (ICC = 0.54–0.81; standard error of measurement = 1.15–1.92), poor reliability in two driving conditions (ICC < 0.50), and poor agreement in one driving condition (standard error of measurement = 2.67 dBA). In the second experiment, the results of the signal detection test correlated moderately with the pure-tone thresholds, speech reception threshold in fluctuating noise, and engineer’s subjective rating of effort and concentration, but not with the speech reception threshold in continuous noise. According to the hypotheses, poorer test scores were obtained by hearing aid users compared with nonhearing aid users.

Conclusions:

The signal detection test has sufficient reliability and agreement in all but three driving conditions. This study provides evidence supporting the construct validity of the signal detection test in locomotive engineers. The moderate associations with conventional hearing tests show that the conventional hearing tests did not cover the whole construct measured with the signal detection test. The results, therefore, underpin the importance of evaluating the ability to detect auditory warning signals separately from other hearing-critical job tasks.
Bone Metabolism in the Healing Process of Lumbar Interbody Fusion: Temporal Changes of Bone Turnover Markers
Authors: Hyakkan Ryota , Kanayama Masahiro , Takahata Masahiko , Oha Fumihiro , Hashimoto Tomoyuki , Iwasaki Norimasa
Published: April 2021

Study Design.

Prospective longitudinal study.

Objective.

The aim of this study was to evaluate temporal changes of bone turnover markers (BTMs) after lumbar spinal fusion in patients without osteoporosis.

Summary of Background Data.

Radiological studies are the standard method to monitor bony fusion, but they do not allow a timely assessment of bone healing. BTMs react rapidly to changes in bone metabolism during fusion process and could be an additional tool to monitor this process.

Methods.

A total of 78 nonosteoporosis patients who had undergone one- or two-level transforaminal lumbar interbody fusion were included. Fusion status was assessed using computed tomography sagittal and coronal images. Serum levels of bone-specific alkaline phosphatase (BAP), procollagen type 1 amino-terminal propeptide (P1NP), and osteocalcin (OC) were measured to assess bone formation, and tartrate-resistant acid phosphatase 5b (TRACP-5b) was measured to assess bone resorption. Serum samples were obtained before surgery and at 1, 2, 4, 8, 13, 26, 39, and 52 weeks after surgery.

Results.

A solid fusion was achieved in 71 of 78 patients (91%), and seven patients resulted in pseudarthrosis. In the fusion group, the level of all BTMs once decreased at 1 postoperative week. Then, BAP and P1NP reached a peak at 4 weeks after surgery, and TRACP-5b and OC peaked at 8 weeks. Thereafter, the level of P1NP and TRACP-5b gradually got closer to the baseline over a year, and BAP kept high until 52 postoperative weeks. In the pseudarthrosis group, peak level of BTMs was significantly higher and the increased level of BAP and P1NP was kept until 52 weeks.

Conclusion.

The present study demonstrated dynamics of BTMs after lumbar spinal fusion in patients without osteoporosis. These normal population data contribute as a baseline to evaluate the effect of osteogenic agents on bone metabolism after spinal fusion.

Level of Evidence: 2
Tranexamic Acid in Pediatric Scoliosis Surgery
Authors: Hasan Mohd Shahnaz , Yunus Siti Nadzrah , Ng Ching Choe , Chan Chris Yin Wei , Chiu Chee Kidd , Kwan Mun Keong
Published: April 2021

Study Design.

Prospective randomized double-blinded trial

Objective.

The objective of this study is to determine the efficacy of high-dose versus low-dose tranexamic acid (TXA) in adolescent idiopathic scoliosis (AIS) corrective surgery.

Summary of Background Data.

Corrective surgery for AIS is associated with significant blood loss. Evidence on the optimum TXA dose to reduce bleeding in pediatric population is scarce.

Methods.

A total of 166 AIS patients aged between 10 and 21 years, of American Society of Anesthesiologists (ASA) physical status I and II, preoperative hemoglobin >10 g/dL, platelet count >150,000 cells/L and Cobb angle of >45° scheduled for elective single-stage posterior spinal fusion (PSF) surgery by two attending surgeons were included between March 2017 and November 2018. Patients were randomized into Group A (High Dose, 30 mg/kg TXA loading dose followed by 10 mg/kg/h infusion) and Group B (Low Dose, 10 mg/kg TXA loading dose followed by 1 mg/kg/h infusion). The primary outcome was total surgical blood loss between both groups. Secondary outcomes were transfusion requirement, perioperative changes in hemoglobin and coagulation profiles, adverse events, and factors that influence total blood loss.

Results.

The mean total surgical blood loss between the two groups was not significant (Group A: 928.8 ± 406.1 mL [range: 348–1857 mL]; Group B: 918.1 ± 406.2 mL [range: 271–2000 mL], P = 0.865). The median duration of surgery was 120 minutes. One patient in each group received allogenic blood transfusion during the perioperative period. There were no significant changes in hemoglobin and coagulation profile at pre-operation, post-operation 0 hour and 48 hours. Sex, number of vertebral levels fused, and duration of surgery were independently associated with total surgical blood loss. No adverse events were observed perioperatively.

Conclusion.

Low-dose TXA was as efficacious as high-dose TXA in reducing blood loss and allogenic blood transfusion for AIS patients undergoing PSF surgery.

Level of Evidence: 1
Anal squamous cell carcinoma: standards of care, new data and ongoing clinical trials
Authors: Giunta Emilio Francesco , Bregni Giacomo , Hendlisz Alain , Sclafani Francesco
Published: April 2021

Purpose of review

To summarize current standards of care, discuss results of recent studies and present ongoing clinical trials for anal squamous cell carcinoma (ASCC).

Recent findings

Over the last year, no practice changing studies have been reported in the setting of localised ASCC. A number of retrospective analyses, however, have provided practice-informing data, such as those confirming the negative impact of low compliance to chemoradiotherapy (CRT) on patient outcomes. In contrast, and for the first time, randomized evidence has become available to inform the management of advanced tumours. The InterAACT trial represents a key milestone in the evidence-building process for this disease, establishing carboplatin plus paclitaxel as a new standard of care for treatment-naïve advanced ASCC patients. Furthermore, more data have accumulated about the value of triplet chemotherapy in the first-line setting and of immune checkpoint inhibitors (either as single agents or in combination with other agents) in the refractory setting.

Recent findings have the potential to improve the treatment quality standards and overall outcome of patients with either localised or advanced ASCC. Results from ongoing clinical trials will hopefully provide useful insights into the management of this disease and further shape current treatment paradigms.
Being Simultaneously Curious and Stressed, Precipitants to Methamphetamine Initiation Among Chinese Men Who Have Sex With Men: Findings From a Qualitative Study
Authors: Zhou Jing , Li Xianhong , Li Fei , Shoptaw Steve , Wang Honghong , Heilemann MarySue V. , Koniak-Griffin Deborah
Published: April 2021

The cultural context and precipitants for initiating methamphetamine (MA) using among Chinese men who have sex with men (MSM) are unclear. This qualitative descriptive study, which explores the specific precipitants of MA initiation within a cultural context among MSM in China, was conducted with data from semistructured, face-to-face interviews with 24 MA-using MSM (8 HIV positive). Two themes were identified, internal precipitants included the following: (a) curiosity, (b) desire for maximum sexual pleasure, (c) experience with other drugs, and (d) strong sense of self-control capacity. External precipitants included (a) Xiao [

JOURNAL/janac/04.03/00001782-202110000-00017/17FFU1/v/2023-08-29T005718Z/r/image-tiff

] (filial piety), (b) peer pressure, (c) negative life events, (d) parental emotional neglect, and (e) experiences of homophobia. Internal precipitants to MA initiation for Chinese MSM are consistent with past research. External precipitants were more culture specific. This exacerbates the vulnerability of MSM to MA initiation and keeps it hidden among this population. Future drug use prevention interventions for MSM should address external precipitants and integrate culture-specific strategies.
Pulmonary toxicity associated with occupational and environmental exposure to pesticides and herbicides
Authors: Bast Aalt , Semen Khrystyna O. , Drent Marjolein
Published: April 2021

Purpose of review

Critical review on the notion that exposure to pesticides and herbicides lead to adverse effects in pulmonary health.

Recent findings

The lung effects of several chemical classes of pesticides and herbicides is biologically plausible. However, the studies that describe the association between exposure and toxic lung effects have numerous limitations. Critical evaluation of the studies that are performed shows that assessment of occupational or environmental exposure to pesticides and herbicides is cumbersome. Moreover, the health effects are not always clearly established due to the use of questionnaires and self-reported data instead of lung function measurements or diagnostic work-up by physicians.

Future studies should preferably better characterize the exposure. Genetic phenotyping should be included to understand and strengthen possible (individual) associations between exposure and health outcome. It should be realized that combined exposure to multiple environmental chemicals may lead to different health effects than exposure to individual chemicals.

The relation between exposure to pesticides and herbicides and lung toxicity is less clear than generally assumed. Adverse lung effects seem multifactorial and needs further research. Preventive measures remain key.
The role of magnetic sphincter augmentation in the treatment of gastroesophageal reflux disease
Authors: Bonavina Luigi , Boyle Nick , Schoppmann Sebastian F.
Published: April 2021

Purpose of review

Magnetic sphincter augmentation (MSA) has been designed as a less disruptive and more standardized laparoscopic surgical procedure than fundoplication for patients with early stage gastroesophageal reflux disease (GERD). We analyzed the more recent literature in search of updates regarding indications, technique, perioperative management, and long-term outcomes.

Recent findings

Over the years, the procedure of MSA has evolved to including full hiatus repair rather than relying on the preservation of the phreno-esophageal ligament. Restoring the mechanical synergy between the lower esophageal sphincter and the crural diaphragm has the potential to further enhance the antireflux barrier. The adoption of this approach has led to expand the indications from early stage disease to different scenarios including patients with high esophageal acid exposure, atypical symptoms, large hiatal hernias, Barrett's esophagus, postbariatric surgery, and previously failed fundoplication.

MSA has a favorable side-effect profile and is highly effective in reducing typical reflux symptoms, medication dependency, and esophageal acid exposure. Excellent outcomes have been confirmed over a 12-year follow-up, indicating that the operation has the potential to prevent GERD progression. Further studies are needed to confirm the cost-effectiveness of this procedure in patients with more advanced disease-stage and prior gastric surgery. A randomized control trial comparing MSA with fundoplication could raise the level of evidence and the strength of recommendation.
Kidney cancer management 3.0: can artificial intelligence make us better?
Authors: Lee Matthew , Wei Shuanzeng , Anaokar Jordan , Uzzo Robert , Kutikov Alexander
Published: April 2021

Purpose of review

Artificial intelligence holds tremendous potential for disrupting clinical medicine. Here we review the current role of artificial intelligence in the kidney cancer space.

Recent findings

Machine learning and deep learning algorithms have been developed using information extracted from radiomic, histopathologic, and genomic datasets of patients with renal masses.

Although artificial intelligence applications in medicine are still in their infancy, they already hold immediate promise to improve accuracy of renal mass characterization, grade, and prognostication. As algorithms become more robust and generalizable, artificial intelligence is poised to significantly disrupt kidney cancer care.
An Integrative Review of Organizational Factors Influencing Successful Large-Scale Changes in Healthcare
Authors: Castiglione Sonia Angela , Lavoie-Tremblay Melanie
Published: April 2021

OBJECTIVE

The aim of this study was to review organizational factors influencing successful large-scale change (LSC) in healthcare.

BACKGROUND

LSC is necessary to achieve sustained and meaningful healthcare improvement. However, organizational readiness needs to be considered to promote successful LSC.

METHODS

Four databases were searched for articles published between 2009 and 2018. Thematic analysis was used to identify enabling or hindering factors to LSC.

RESULTS

Seven organizational factors were consistently described as facilitators of or barriers to successful LSC in healthcare: infrastructure support, organizational culture, leadership, change management approach, roles and responsibilities, networks, and measurement and feedback.

CONCLUSION

The factors that emerged from this review are consistent with concepts of implementation but broadened and highlight learning organizations in successful LSC. The results of this review informed the development of a reflective tool on LSC for nurse leaders.
Assessing Evidence-Based Practice Knowledge: An Innovative Approach by a Nursing Research Council
Authors: Maydick-Youngberg Diane , Gabbe Laura , Simmons Grace , Smith Daniel , Quimson Epifania , Meyerson Elaine , Manley-Cullen Catherine , Rosenfeld Peri
Published: April 2021

OBJECTIVE

The aim of this study was to describe the structure and processes implemented by nursing research councils to conduct a nurse-led research study at an urban community teaching hospital.

BACKGROUND

We assessed nurses' knowledge, skills, and attitudes toward evidence-based practice (EBP) to inform development plans.

METHODS

This is an institutional review board–approved single-site cross-sectional anonymous online survey (Evidence-Based Practice Questionnaire [EBPQ]) emailed to 850 participants. Data were analyzed using SPSS v25 (Armonk, New York).

RESULTS

Initial response rate was 11%. Deployment of new strategies achieved an overall response rate of 57.5%. EBPQ subscale scores were highest for “attitude,” followed by “knowledge/skills,” and “practice.” Lowest-scoring items included critical appraisal of literature, converting information needs into a question, time for new evidence, information technology, and research skills.

CONCLUSIONS

Our EBPQ scores were consistent with prior findings. Our strategies provide a framework for other institutions in similar stages of implementing EBP and nurse-led research initiatives.
Effect of Shared Governance on Nurse-Sensitive Indicator and Satisfaction Outcomes: An International Comparison
Authors: Speroni Karen Gabel , Wisner Kirsten , Stafford Amy , Haines Fiona , AL-Ruzzieh Majeda A. , Walters Cynthia , Budhathoki Chakra
Published: April 2021

Objective

Researchers examined associations between Index for Professional Nursing Governance (IPNG) scores and outcomes, by US and international hospitals.

Background

Nursing governance and effects on nurse-related outcomes are not well studied.

Methods

Associations were evaluated using average IPNG scores from 2170 RNs and nurse-sensitive indicators (NSIs) and patient and RN satisfaction outcomes (n = 205 study units, 20 hospitals, 4 countries).

Results

International units had better IPNG shared governance scores (113.5; US = 100.6; P < 0.001), and outcomes outperforming unit benchmarks (6 of 15, 40.0%; US = 2 of 15, 13.3%). Shared governance significantly outperformed traditional governance for 5 of 20 (25.0%) US outcomes (patient satisfaction = 1, RN satisfaction = 4) and for 3 of 11 (27.3%) international (patient satisfaction = 1, RN satisfaction = 2). Internationally, self-governance significantly outperformed traditional governance and shared governance for 5 of 12 (41.7%) outcomes (NSI = 2, patient satisfaction = 3).

Conclusions

Shared governance is a strategy that can be considered by nurse leaders for improving select outcomes.
Connecting Nursing Students and Older Adults
Authors: Bowling Hilary , Murray Lori , Eichler Timothy , Usher Barbara , Fennimore Laura
Published: April 2021

Background

Aging populations have an increased need for health care services. Nursing students are often introduced to care of older adults through a clinical experience in a skilled nursing facility, which can negatively bias a student's attitudes toward this population.

Purpose

The purpose of this quality improvement project was to improve the attitudes of undergraduate nursing students toward older adults.

Method

Students (N = 104) completed a minimum of 5 visits with an independent community-dwelling older adult. Student attitudes toward older adults were measured before and after the experience using the Polizzi Refined Aging Semantic Differential Scale. Student and older adult participants responded to satisfaction surveys.

Results

Statistical and clinically significant improvements in student attitudes were noted after the service-learning intervention.

Conclusions

Nurse educators can impact the way nursing students view the older adult population by including intergenerational service-learning experiences in the curriculum.
False-Positive Axillary Lymph Nodes on FDG PET/CT Resulting From COVID-19 Immunization
Authors: Nawwar Ayah Adel , Searle Julie , Hopkins Richard , Lyburn Iain Douglas
Published: April 2021

World-wide mass COVID-19 vaccination has been deployed starting with those most vulnerable, including the elderly and cancer patients. A 70-year-old man with right lung cancer underwent staging FDG PET/CT, which demonstrated an avid right lung mass with avid hilar and mediastinal nodes. Avid left axillary nodes of benign configuration were also noted. The patient had the Oxford-AstraZeneca COVID-19 vaccination in the left arm a week earlier. On reflection, the axillary nodes were concluded to be reactive related to this. This is a potential COVID-19 vaccination associated pitfall on PET/CT that should be considered when interpreting FDG PET/CT images.
Increased FDG Uptake of the Pectoral Girdle and Serratus Anterior Due to Wallpaper Stripping on PET/CT—Exquisite Demonstration of the Biomechanics
Authors: Nawwar Ayah Adel , Vekeria Monique , Searle Julie , Singh Rajiv , Lyburn Iain Douglas
Published: April 2021

According to published guidelines and routine procedures, patients are instructed to avoid strenuous exercise for 6 to 24 hours before FDG imaging, avoiding unfavorable muscular uptake. A 40-year-old man with esophageal carcinoma underwent FDG PET/CT for response assessment. Intense uptake was noted in the muscles of the right upper limb and chest. The patient stated he had avoided exercise before scanning. On further questioning, he was found to be a professional painter and decorator and had been working stripping wallpaper. Marked skeletal FDG uptake occurs in subjects who have strenuously exerted themselves before or after the injection of FDG.
Multimodal Imaging in a Patient With Alzheimer Disease and Parkinsonism Because of a Presenilin-1 Mutation
Authors: Lu Jia-Ying , Sun Yi-Min , Yen Tzu-Chen , Zuo Chuan-Tao , Wang Jian
Published: April 2021

A correct clinical diagnosis of motor dysfunction accompanied by cognitive impairment remains challenging. Recent advances in molecular imaging biomarkers hold promise to overcome this issue. A 37-year-old woman presenting with parkinsonism and cognitive impairment underwent both multimodal neuroimaging and genetic testing. Her main findings on PET included diffuse tau accumulation in the cerebral cortex and left putamen, increased cerebellar amyloid deposits, asymmetrically reduced dopamine transporter binding, and mild hypermetabolism in the putamen. Genetic analysis revealed the presence of a presenilin-1 mutation (C.1157T>G). These findings suggested a diagnosis of early-onset autosomal dominant Alzheimer disease accompanied by parkinsonism.
α7 Nicotinic Acetylcholine Receptor Agonists Regulate Inflammation and Growth Hormone Resistance in Sepsis
Authors: Pruekprasert Napat , Meng Qinghe , Gu Raymond , Xie Han , Liu Yu , Liu Chunli , Cooney Robert N.
Published: April 2021

During sepsis the normal induction of circulating insulin-like growth factor-I (IGF-I) by growth hormone (GH) action on liver is attenuated, a phenomenon called hepatic GH resistance. Hepatic GH resistance can be caused by cytokine-mediated activation of the NF-κB pathway which interferes with normal GH-signaling. The afferent and efferent fibers of the vagus nerve are integral to the cholinergic anti-inflammatory pathway (CAP) which attenuates hepatic TNFα production by activating the α7 nicotinic acetylcholine receptor (α7nAChR). We examined the effects of selective afferent vagotomy (SAV) and α7nAChR activation on sepsis-induced mortality, hepatic and systemic inflammation, the GH/IGF system and hepatic GH resistance using Sprague Dawley (SD) rats, C57BL/6 wild type (WT) mice, and α7nAChR knockout (KO) mice. Capsaicin was used to perform SAV and GTS-21 (α7nAChR agonist) was used to activate the α7nAChR. Sepsis-induced mortality, hepatic NF-κB activation, and plasma cytokine levels were increased in SAV rats and reduced in GTS-21-treated mice. The effects of sepsis on the GH/IGF-I system plasma IGF-I, IGF binding protein-1 (IGFBP-1), hepatic IGF-I, IGFBP-1, and GH receptor (GHR) mRNA and rhGH-responsiveness in mice were improved by GTS-21. Collectively these results confirm the protective effects of the anti-inflammatory CAP and α7nAChR activation in sepsis. They also provide evidence the CAP and α7nAChR activation could be used to attenuate hepatic GH resistance and anabolic failure in sepsis.
Factors That Predict the Success of Laparoscopic Common Bile Duct Exploration for Choledocholithiasis: A 10-Year Study
Authors: Kao Chien-Tse , Seagar Rosemary , Heathcock Daniel , Tacey Mark , Lai Jiun Miin , Yong Tuck , Houli Nezor , Bird David , Hodgson Russell
Published: April 2021

Background:

Laparoscopic common bile duct exploration (LCBDE) can be performed to treat choledocholithiasis at the time of laparoscopic cholecystectomy. The aim of this study was to identify factors that predict the success of LCBDE.

Materials and Methods:

A retrospective audit was performed on patients who underwent LCBDE for the management of choledocholithiasis at Northern Health between 2008 and 2018.

Results:

A total of 513 patients were identified with an overall success rate of 90.8%. Most LCBDE were done through a transcystic approach with the remainder through a choledochotomy. When comparing patients with a successful operation to those that were unsuccessful, univariate analysis demonstrated significant differences in preoperative white cell count and number of duct stones found. Age and elevated nonbilirubin liver function tests were found to be significant factors associated with the failure of LCBDE on multivariate analysis. The likelihood of a failed operation in those with multiple stones was observed to be almost halved compared with patients with single stone although this did not reach significance [odds ratio (OR): 0.53, 95% confidence interval (CI): 0.28-1.01, P=0.055]. Multivariate analysis indicated that unsuccessful procedures (OR: 10.13, 95% CI: 4.34-23.65, P<0.001) and multiple duct stones (OR: 3.79, 95% CI: 1.66-8.67, P=0.002) were associated with an increased risk of severe complications.

Conclusions:

A single impacted stone may be more difficult to remove, however complications were more likely to be associated with multiple duct stones. With no other clinically relevant predictive factors, and because of the high success of the procedure and the low morbidity, LCBDE remains an option for all patients with choledocholithiasis.
Estimating SARS-CoV-2 reproduction number by infection location in Japan
Authors: Kurita Junko , Hata Takahide , Sugawara Tamie , Ohkusa Yasushi , Hata Atsuko
Published: April 2021

Background

COVID-19 infectiousness might differ by infection location. Nevertheless, no such study of infectiousness has been reported.

Object

The study objective was estimation of the reproduction number by infection location.

Method

Patients who infected no one were ignored because their reliability might be lower than that of patients who infected more than one person. On the assumption that the histogram follows an exponential distribution, we estimated the reproduction number from the histogram of the number of people infected by the same patient.

Results

Night entertainment venues showed the greatest infectiousness, followed by facilities for elderly people and hospitals. Nursery schools and workplaces were followed by homes, with the lowest infectiousness.

Discussion and Conclusion

Countermeasures under the second declaration of emergency status targeted restaurants. However, infectiousness at restaurants was not high. Comparable to those of universities and karaoke, and not significantly different from homes: the least infectious location studied.
Characterization of the Second Wave of COVID-19 in India
Authors: Ranjan Rajesh , Sharma Aryan , Verma Mahendra K.
Published: April 2021

Abstract

The second wave of COVID-19, which began around 11 February 2021, has hit India very hard with the daily cases reaching nearly triple the first peak value as on April 19, 2021. The epidemic evolution in India is quite complex due to regional inhomogeneities and the spread of several coronavirus mutants. In this paper, we characterize the virus spread in the ongoing second wave in India and its states until April 19, 2021, and also study the dynamical evolution of the epidemic from the beginning of the outbreak. Variations in the effective reproduction number (Rt) are taken as quantifiable measures of the virus transmissibility.Rtvalue for every state, including those with large rural populations, has value greater than the self-sustaining threshold of 1. An exponential fit on recent data also shows that the infection rate is much higher than the first wave. Subsequently, characteristics of the COVID-19 spread are analyzed regionwise, by estimating test positivity rates (TPRs) and case fatality rates (CFRs). Very high TPR values for several states present an alarming situation. CFR values are lower than those in the first wave but recently showing signs of increase as healthcare systems become over-stretched with the surge in infections. Preliminary estimates with a classical epidemiological model suggest that the peak for the second wave could occur around mid-May 2021 with daily count exceeding 0.4 million. The study strongly suggests that an effective administrative intervention is needed to arrest the rapid growth of the epidemic.
Antiretroviral therapy associated lipodystrophy; learning from the past
Authors: Sereke Senai Goitom , Berhe Semhar Eyob , Bongomin Felix
Published: April 2021

Background

With the introduction of effective antiretroviral therapy (ART), descriptions of body shape abnormalities, such as central fat accumulation and peripheral fat loss emerged among persons living with human immunodeficiency virus (HIV). We aimed to determine the prevalence of lipodystrophy and associated risk factors among patients on ART at Orotta National Referral Hospital (ONRH), Asmara, Eritrea.

Methods

A single center, retrospective study was conducted at the ONRH, reviewing records of HIV-infected patients commenced on ART between January 2007 and December 2012.

Results

Records of 250 eligible patients were reviewed. Most were female (59.2%, n=148) with a median age of 35 (IQR-20-63) years. Forty-three (17.2%) participants had body fat abnormalities. 42 (97.6%) had lipoatrophy and 1 (2.4%) buffalo hump. Of the 43 patients with lipodystrophy 34 (79%) were on Stavudine (d4T)/Lamivudine (3TC)/Nevirapine (NVP) regimen, 6 (14%) on Zidovudine (AZT)/3TC/NVP, 2 (4.7%) on d4T/3TC/Efavirenz (EFV) and 1(2.3%) on AZT, 3TC, EFV. EFV-based regimen was significantly associated with lipodystrophy (p< 0.01).

Conclusion

We report a high prevalence of lipodystrophy. Four drug regimens were incriminated in the development of lipodystrophy. EFV-based regimen was significantly associated with the lipodystrophy.
Strategies for COVID-19 vaccination under a shortage scenario: a geo-stochastic modelling approach
Authors: Barreiro N. L. , Ventura C. I. , Govezensky T. , Núñez M. , Bolcatto P. G. , Barrio R. A.
Published: April 2021

In a world being hit by waves of COVID-19, vaccination is a light on the horizon. However, the roll-out of vaccination strategies and their influence on the pandemic are still open problems. In order to compare the effect of various strategies proposed by the World Health Organization and other authorities, a previously developed SEIRS stochastic model of geographical spreading of the virus is extended by adding a compartment for vaccinated people. The parameters of the model were fitted to describe the pandemic evolution in Argentina, Mexico and Spain to analyze the effect of the proposed vaccination strategies. The mobility parameters allow to simulate different social behaviors (e.g. lock-down interventions). Schemes in which vaccines are applied homogeneously in all the country, or limited to the most densely-populated areas, are simulated and compared. The second strategy is found to be more effective. Moreover, under the current global shortage of vaccines, it should be remarked that immunization is enhanced when mobility is reduced. Additionally, repetition of vaccination campaigns should be timed considering the immunity lapse of the vaccinated (and recovered) people. Finally, the model is extended to include the effect of isolation of detected positive cases, shown to be important to reduce infections.
SPOPmutation confers sensitivity to AR-targeted therapy in prostate cancer by reshaping the androgen-driven chromatin landscape
Authors: Grbesa Ivana , Augello Michael A. , Liu Deli , McNally Dylan R. , Gaffney Christopher D. , Huang Dennis , Lin Kevin , Goueli Ramy , Robinson Brian D. , Khani Francesca , Deonarine Lesa D. , Blattner Mirjam , Elemento Olivier , Davicioni Elai , Sboner Andrea , Barbieri Christopher E.
Published: April 2021

The normal androgen receptor (AR) cistrome and transcriptional program are fundamentally altered in prostate cancer (PCa). Here, we show thatSPOPmutations, an early event in prostate tumorigenesis, reshape the chromatin landscape and AR-directed transcriptional program in normal prostate cells. Induction ofSPOPmutation results in DNA accessibility and AR binding patterns found in human PCa. Consistent with dependency on this AR reprogramming, castration ofSPOPmutant mouse models results in the loss of neoplastic phenotypes. Finally, humanSPOPmutant PCa show improved response to AR-targeted therapies. Together, these results show that a single genomic alteration may be sufficient to reprogram the chromatin of normal prostate cells toward oncogenic phenotypes and thatSPOPmutant tumors may be preferentially dependent on AR signaling through this mechanism.
μ-opioid receptor availability is associated with sex drive in human males
Authors: Nummenmaa Lauri , Jern Patrick , Malén Tuulia , Kantonen Tatu , Pekkarinen Laura , Lukkarinen Lasse , Sun Lihua , Nuutila Pirjo , Putkinen Vesa
Published: April 2021

The endogenous mu-opioid receptor (MOR) system modulates a multitude of social and reward-related functions, and exogenous opiates also influence sex drive in humans and animals. Sex drive shows substantial variation across humans, and it is possible that individual differences in MOR availability underlie interindividual of variation in human sex drive. Here we measured healthy male subjects’ (n=52) brain’s MOR availability with positron emission tomography (PET) using an agonist radioligand, [11C]carfentanil, that has high affinity for MORs. Sex drive was measured using self-reports of engaging in sexual behaviour (sex with partner and masturbating). Bayesian hierarchical regression analysis revealed that sex drive was positively associated with MOR availability in cortical and subcortical areas, notably in caudate nucleus, hippocampus, and cingulate cortices. These results were replicated in full-volume GLM analysis. These widespread effects are in line with high spatial autocorrelation in MOR expression in human brain. Complementary voxel-based morphometry analysis (n=108) provided limited evidence for association between sex drive and cortical density in the midcingulate cortex. We conclude that endogenous MOR tone is associated with individual differences in sex drive in human males.
Anxiolytic effects of chronic intranasal oxytocin on neural responses to threat are dose-frequency dependent
Authors: Kou Juan , Zhang Yingying , Zhou Feng , Gao Zhao , Yao Shuxia , Zhao Weihua , Li Hong , Lei Yi , Gao Shan , Kendrick Keith M. , Becker Benjamin
Published: April 2021

Anxiety disorders are prevalent psychiatric conditions characterized by exaggerated anxious arousal and threat reactivity. Animal and human studies suggest an anxiolytic potential of the neuropeptide oxytocin (OT), yet, while a clinical application will require chronic administration protocols previous studies in humans have exclusively focused on single-dose (acute) intranasal OT effects. We aimed at determining whether the anxiolytic effects of OT are maintained with repeated (chronic) administration or are influenced by dose frequency and trait anxiety. A double-blind randomized, placebo-controlled pharmaco-fMRI trial (n=147) determined acute (single-dose) as well as chronic effects of two different dose frequencies of OT (OT administered daily for 5 days or every other day) on emotional reactivity in healthy subjects with high versus low trait anxiety. OT produced valence, dose frequency and trait anxiety specific effects, such that the low-frequency (intermittand) chronic dosage specifically attenuated neural reactivity in amygdala-insula-prefrontal regions in high anxious subjects in response to threatening but not positive stimuli. The present trial provides evidence that low dose frequency chronic oxytocin nasal spray has the potential to alleviate exaggerated neural threat reactivity in subjects with elevated anxiety levels underscoring a treatment potential for anxiety disorders.
rDNA nascent transcripts promote a unique spatial organization during mouse early development
Authors: Chebrout Martine , Kone Maimouna Coura , Jan Habib U. , Cournut Marie , Letheule Martine , Fleurot Renaud , Aguirre-Lavin Tiphaine , Peynot Nathalie , Jouneau Alice , Beaujean Nathalie , Bonnet-Garnier Amélie
Published: April 2021

During the first cell cycles of the early development, the chromatin of the embryo is highly reprogrammed alongside that embryonic genome starts its own transcription. The spatial organization of the genome is a major process that contributes to regulating gene transcription in time and space, however, it is poorly studied in the context of early embryos. To study the cause and effect link between transcription and spatial organization in embryos, we focused on the ribosomal genes, that are first silent and begin to transcribe during the 2-cell stage in mouse. We demonstrated that ribosomal sequences are spatially organized in a very peculiar manner from the 2-cell to the 16-cell stage with transcription and processing of ribosomal RNAs excluding mutually. Using drugs inhibiting the RNA polymerase I, we show that this organization, totally different from somatic cells, depends on an active transcription of ribosomal genes and induces a unique chromatin environment that favors major satellite sequences transcription after the 4-cell stage.
Inversion of asymmetric histone deposition upon replication stress
Authors: Zwinderman Martijn R. H. , Lobo Thamar Jessurun , van der Wouden Petra E. , Spierings Diana C. J. , van Vugt Marcel A. T. M. , Lansdorp Peter M. , Guryev Victor , Dekker Frank J.
Published: April 2021

Following DNA replication, equal amounts of histones are distributed over sister chromatids by re-deposition of parental histones and deposition of newly synthesized histones. Molecular mechanisms balancing the allocation of new and old histones remain largely unknown. Here, we studied the genome-wide distribution of new histones relative to parental DNA template strands and replication initiation zones using double-click-seq. In control conditions, new histones were preferentially found on DNA replicated by the lagging strand machinery. Strikingly, replication stress induced by hydroxyurea or curaxin treatment, and inhibition of ATR or p53 inactivation, inverted the observed histone deposition bias to the strand replicated by the leading strand polymerase in line with previously reported effects on RPA occupancy. We propose that asymmetric deposition of newly synthesized histones onto sister chromatids reflects differences in the processivity of leading and lagging strand synthesis.
Targeted next-generation sequencing of Candidate Regions Identified by GWAS Revealed SNPs Associated with IBD in GSDs
Authors: Peiravan Atiyeh , Salavati Mazdak , Psifidi Androniki , Sharman Mellora , Kent Andrew , Watson Penny , Allenspach Karin , Werling Dirk
Published: April 2021

Canine Inflammatory bowel disease (IBD) is a chronic multifactorial disease, resulting from complex interactions between the intestinal immune system, microbiota and environmental factors in genetically predisposed dogs. Previously, we identified several single nucleotide polymorphisms (SNP) and regions on chromosomes (Chr) 7, 9, 11 and 13 associated with IBD in German shepherd dogs (GSD) using GWAS and FST association analyses. Here, building on our previous results, we performed a targeted next-generation sequencing (NGS) of a two Mb region on Chr 9 and 11 that included 14 of the newly identified candidate genes, in order to identify potential functional SNPs that could explain these association signals. Furthermore, correlations between genotype and treatment response were estimated. Results revealed several SNPs in the genes for canineEEF1A1,MDH2,IL3,IL4,IL13andPDLIM, which, based on the known function of their corresponding proteins, further our insight into the pathogenesis of IBD in dogs. In addition, several pathways involved in innate and adaptive immunity and inflammatory responses (i.e. T helper cell differentiation, Th1 and Th2 activation pathway, communication between innate and adaptive immune cells and differential regulation of cytokine production in intestinal epithelial cells by IL-17A and IL-17F), were constructed involving the gene products in the candidate regions for IBD susceptibility. Interestingly, some of the identified SNPs were present in only one outcome group, suggesting that different genetic factors are involved in the pathogenesis of IBD in different treatment response groups. This also highlights potential genetic markers to predict the response in dogs treated for IBD.