bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and bacteriology of culture-positive urinary tract infection among pregnant women with suspected urinary tract infection at Mbarara regional referral hospital, South-Western Uganda
Authors: Johnson Bahati , Stephen Bawakanya Mayanja , Joseph Ngonzi , Asiphas Owaraganise , Musa Kayondo , Taseera Kabanda
Published: February 2021

Background

Urinary tract infections (UTIs) in pregnant women contribute about 25% of all infections and are among the most frequent clinical bacterial infections. Pregnancy changes in women that include anatomical, physiological and hormonal make them susceptible to develop UTI. Left untreated, UTI in pregnancy is associated with grave complications to the mother and fetus. These complications can be decreased by prompt and proper diagnosis and appropriate treatment that also reduces the emergency of drug resistance. Antimicrobial resistance is a major health problem in the treatment of UTI. We determined the prevalence, bacteriology and antimicrobial susceptibility of symptomatic urinary tract infection among pregnant women at Mbarara Regional Referral Hospital.

Methods

We conducted a cross-sectional study from November 2019 to February 2020 involving 400 pregnant women with symptomatic UTI. Patient information was obtained using a structured questionnaire. We collected clean-catch midstream urine specimens for culture and performed antimicrobial susceptibility testing following Clinical and Laboratory Standards Institute standards. Data was entered into RED-cap Version 8.2 software and then exported to Stata Version 14.1 for analysis.

Results

The proportion of culture-positive UTI was 140/400 (35%). Gram-negative bacteria were more prevalent (73%):Klebsiella pneumoniae52(37.41%),Escherichia coli40(28.78%),Pseudomonas aeruginosaandProteus mirabilis7(5.04% each), Citrobacter freundii 1(1%).Staphylococcus aureus33(23.57%) was the only gram-positive isolate. All the isolates were resistant to ampicillin, amoxicillin, amoxicillin/clavulanic acid and ceftazidime/clavulanic acid (95.7, 95.0, 72.9 and 50.7% respectively). Prevalence of extended-spectrum beta-lactamases producing Enterobacteriaceae was 29.0% while that of methicillin-resistantStaphylococcus aureuswas 33.3%. All cultures demonstrated resistance to more than one drug. Majority of the bacterial isolates were sensitive to ciprofloxacin, ceftriaxone, nitrofurantoin, cefotaxime and gentamicin at 82.9, 81.4, 79.3, 78.6, 66.4 and 65.7% respectively.

Conclusions

Klebsiella pneumoniaewas the most prevalent isolate followed byE. coli. These two organisms were highly resistant to the commonly used antibiotics. Our study recorded a higher prevalence of culture-positive UTI in pregnancy than all the studies in Uganda. Empirical treatment of UTI should be minimized as sensitivity varies for each organism, for each drug and over time.
How perceived Australian sexual norms shape sexual practices of East Asian and sub-Saharan African international students in Sydney
Authors: Okeke Sylvester R.
Published: February 2021

Introduction

Sexual norms, real or perceived, shape young people’s sexual behaviour and may constitute one of the greatest challenges in HIV/STIs prevention among this population. This study used sexual script theory to explore how international students in Sydney, Australia – from traditional cultures of East Asian and sub-Saharan African countries – construct home backgrounds and Australian sexual norms and how this may shape their sexual practices during their studies in Australia.

Methods

The study involved face-to-face and telephone semi-structured in-depth interviews. Data were provided by 20 international students who are enrolled in various universities in Sydney. Interviews were audio-recorded, transcribed, coded into NVivo and analysed using reflexive thematic analysis.

Results

Identified patterns in the data showed three themes through which participants perceive sexual norms in Australia as distinctly different from their home country norms. First, participants stated that unlike their home country norms, sexual norms in Australia are permissive. Second, participants hold the view that compared to their home country norms, sex in Australia is largely casual as it is not always attached to love. Some participants revealed that this could shape their own sexual practices during their studies in Australia. Finally, participants noted that compared to their home countries’ norm of sex talk taboo, Australia has an open sexual communication norm; which they believe, enables young people in western societies to easily acquire sexual health information.

Conclusions

Findings provide evidence to support a need for contextualized and effective sexual health services for international students that take account of perceptions around sexual norms and how they can be modified to ensure that sexual practices which these students may engage in, will be managed in a safe and responsible manner.
Pain perception and dental anxiety during periodontal probing in patients visiting community oral health programme: a cross sectional study
Authors: Singh Abanish , Shrestha Ashish , Bhagat Tarakant
Published: February 2021

Background

Periodontal probing is one of the basic clinical oral examination procedures. It is carried out to assess the severity of gingival and periodontal disease. The experience of pain during probing may discourage patients. So, this study was conducted to estimate the pain perception and dental anxiety experienced during periodontal probing in patients visiting the community oral health programmes of B. P. Koirala Institute of Health Sciences (BPKIHS).

Methods

A cross-sectional study was conducted among 100 participants of community oral health programmes of BPKIHS. Demographic profile, WHO modified Community Periodontal Index (CPI) 2013, Pain perception via Visual Analogue Scale (VAS Scores) and Short Version of Spielberger State-Trait Anxiety Inventory (STAI) Self-evaluation Questionnaire (Y-6 item) were assessed. Mean ± SD and Spearman correlation for pain and anxiety were computed.

Results

Only 10% of the study participants had healthy gingiva and 12% had periodontal pockets. Pain perception and dental anxiety was present in the participants. The participants experienced very little pain (6.75 ± 10.65) during periodontal probing. The overall anxiety score was 13.37 ± 1.81. There was a very weak correlation between the VAS Scores and the anxiety scores of the participants.

Conclusion

This study concludes that pain perception and anxiety are low during periodontal probing. There was no correlation between bleeding on probing with pain and anxiety among the people visiting community oral health programmes of BPKIHS.
Antimicrobial activity of medicinal plants used for urinary tract infections in pastoralist community in Ethiopia
Authors: Gadisa Eshetu , Tadesse Elazar
Published: February 2021

Background

Medicinal plants have wide medicament application used to prevent and management of many ailments. These plants are used for primary health care in pastoralist communities who are deprived of modern medical care. They possess extensive therapeutics bioactive coupled with varied chemical structures. However, scientific validation of efficacy and safety of plants used to treat the urinary tract infections haven’t been fully exploited. The aim of this study was to evaluate antimicrobial activity and screening phytochemicals of medicinal plants used to treat urinary tract infections.

Methods

In-vitro experimental study was carried out to evaluate the antimicrobial effect and screening phytochemical of Rumex abyssinicus, Cucumis pustulatus, Discopodium penninervium, Lippia adoensis, Euphorbia depauperata, and Cirsium englerianum. Against drug resistance microbes. 80% methanol was used for extraction of the plant parts. The susceptibility tests were investigated using disc diffusion and broth micro-dilution methods.

Results

The majority of tested extracts showed antimicrobial activity on two or more drug-resistant bacteria with MIC value (1.0–128.0 μg/ml) and 9–27 mm inhibition zone in diameter. Extracts obtained from C.englerianum and E. depauperate showed more potent antibacterial activity on MRSA and Enterococcus faecalis with IZ 25 and 27 mm respectively. E. coli and K. pneumoniae were inhibited by those extracts with IZ ranging 9–25 mm and 11–27 mm respectively. E.faecalis and K. pneumoniae were more susceptible bacteria to the respective extracts. R. abyssinicus showed promising antifungal effect with had 21 mm IZ and MIC range 16-32 μg/ml on C.albicans. Alkaloids, flavonoids, phenolic and terpenoid were common phytochemical characterized in majority of screened plants.

Conclusion

Tested extracts exhibited significant antibacterial and antifungal activity. Hence, further structural elucidation of bioactive that inhibited the growth of microbes aforementioned plants may be used as precursors for the synthesis of new antibiotics in the future.
Acute pharmacodynamic effects of pimobendan in client-owned cats with subclinical hypertrophic cardiomyopathy
Authors: Oldach Maureen S. , Ueda Yu , Ontiveros Eric S. , Fousse Samantha L. , Visser Lance C. , Stern Joshua A.
Published: February 2021

Background

Prior studies have suggested that pimobendan is associated with several positive effects in cats, including improved survival in cats with congestive heart failure and improved left atrial function in research colony cats with hypertrophic cardiomyopathy (HCM) and normal cats. However, there is still a paucity of pharmacodynamic data refuting or supporting the use of pimobendan in a clinical cat population. This clinical trial aimed to evaluate the pharmacodynamic effects and tolerability of a single dose of pimobendan in cats with HCM. Echocardiograms and Doppler-derived systolic blood pressures were performed in 21 client-owned cats with subclinical HCM at baseline and 90-min after oral administration of 1.25 mg of pimobendan (Vetmedin). Seven additional cats were evaluated post-placebo administration to account for intra-day variability.

Results

Heart rate, systolic blood pressure, and murmur grade were not significantly different between baseline and post-pimobendan evaluations. Left auricular blood flow velocity, left atrial size, and left ventricular fractional shortening were not significantly different between baseline and post-pimobendan evaluations.

Mean (± standard deviation) tissue Doppler peak systolic velocity of the mitral annulus was significantly higher following pimobendan (7.4 cm/s ± 1.5 vs 8.5 ± 1.6; p = 0.02). Median (min, max) left-ventricular outflow tract maximum velocity was significantly higher following pimobendan [1.9 m/sec (1.5, 3.4) vs 2.6 m/sec (2.0, 4.0); p = 0.01]. Mean right-ventricular outflow tract maximum velocity was also significantly higher following pimobendan (1.5 m/s ± 0.51 vs 2.0 ± 0.53; p = 0.004). Mean left atrial fractional shortening was significantly higher following pimobendan (28% ± 6 vs 32% ± 7; p = 0.02).

No adverse events were observed following pimobendan administration.

Right ventricular outflow tract velocity was significantly higher following placebo in control cats (1.02 ± 0.21 versus 1.31 ± 0.31; p = 0.01). No other significant differences were detected.

Conclusions

In client-owned cats with HCM, pimobendan acutely increased left atrial function and mildly increased left ventricular systolic function. Left ventricular outflow tract velocity was increased after pimobendan. Pimobendan was well tolerated in the acute setting in cats with HCM. The findings of this prospective, acute-dosing study confirm previous findings in research animals and retrospective analyses and suggest that chronic dosing studies are safe and warranted.
The similarity of inherited diseases (I): clinical similarity within the phenotypic series
Authors: Gamba Alessio , Salmona Mario , Bazzoni Gianfranco
Published: February 2021

Background

Mutations of different genes often result in clinically similar diseases. Among the datasets of similar diseases, we analyzed the ‘phenotypic series’ from Online Mendelian Inheritance in Man and examined the similarity of the diseases that belong to the same phenotypic series, because we hypothesize that clinical similarity may unveil shared pathogenic mechanisms.

Methods

Specifically, for each pair of diseases, we quantified their similarity, based on both number and information content of the shared clinical phenotypes. Then, we assembled the disease similarity network, in which nodes represent diseases and edges represent clinical similarities.

Results

On average, diseases have high similarity with other diseases of their own phenotypic series, even though about one third of diseases have their maximal similarity with a disease of another series. Consequently, the network is assortative (i.e., diseases belonging to the same series link preferentially to each other), but the series differ in the way they distribute within the network. Specifically, heterophobic series, which minimize links to other series, form islands at the periphery of the network, whereas heterophilic series, which are highly inter-connected with other series, occupy the center of the network.

Conclusions

The finding that the phenotypic series display not only internal similarity (assortativity) but also varying degrees of external similarity (ranging from heterophobicity to heterophilicity) calls for investigation of biological mechanisms that might be shared among different series. The correlation between the clinical and biological similarities of the phenotypic series is analyzed in Part II of this study1.
Identification of major depressive disorder disease-related genes and functional pathways based on system dynamic changes of network connectivity
Authors: Geng Ruijie , Huang Xiao
Published: February 2021

Background

Major depressive disorder (MDD) is a leading psychiatric disorder that involves complex abnormal biological functions and neural networks. This study aimed to compare the changes in the network connectivity of different brain tissues under different pathological conditions, analyzed the biological pathways and genes that are significantly related to disease progression, and further predicted the potential therapeutic drug targets.

Methods

Expression of differentially expressed genes (DEGs) were analyzed with postmortem cingulate cortex (ACC) and prefrontal cortex (PFC) mRNA expression profile datasets downloaded from the Gene Expression Omnibus (GEO) database, including 76 MDD patients and 76 healthy subjects in ACC and 63 MDD patients and 63 healthy subjects in PFC. The co-expression network construction was based on system network analysis. The function of the genes was annotated by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Human Protein Reference Database (HPRD,http://www.hprd.org/) was used for gene interaction relationship mapping.

Results

We filtered 586 DEGs in ACC and 616 DEGs in PFC for further analysis. By constructing the co-expression network, we found that the gene connectivity was significantly reduced under disease conditions (P = 0.04 in PFC andP = 1.227e−09 in ACC). Crosstalk analysis showed that CD19, PTDSS2 and NDST2 were significantly differentially expressed in ACC and PFC of MDD patients. Among them, CD19 and PTDSS2 have been targeted by several drugs in the Drugbank database. KEGG pathway analysis demonstrated that the function of CD19 and PTDSS2 were enriched with the pathway of Glycerophospholipid metabolism and T cell receptor signaling pathway.

Conclusion

Co-expression network and tissue comparing analysis can identify signaling pathways and cross talk genes related to MDD, which may provide novel insight for understanding the molecular mechanisms of MDD.
Olodaterol exerts anti-inflammatory effects on COPD airway epithelial cells
Authors: Yang Nan , Singhera Gurpreet K. , Yan Yi Xuan , Pieper Michael P. , Leung Janice M. , Sin Don D. , Dorscheid Delbert R.
Published: February 2021

Background

Airway inflammation is a key feature of chronic obstructive pulmonary disease (COPD) and inhaled corticosteroids (ICS) remain the main treatment for airway inflammation. Studies have noted the increased efficacy of ICS and long-acting beta 2 agonist (LABA) combination therapy in controlling exacerbations and improving airway inflammation than either monotherapy. Further studies have suggested that LABAs may have inherent anti-inflammatory potential, but this has not been well-studied.

Objective

We hypothesize that the LABA olodaterol can inhibit airway inflammation resulting from exposure to respiratory syncytial virus (RSV) via its binding receptor, the β2-adrenergic receptor.

Methods

Human bronchial epithelial brushing from patients with and without COPD were cultured into air–liquid interface (ALI) cultures and treated with or without olodaterol and RSV infection to examine the effect on markers of inflammation including interleukin-8 (IL-8) and mucus secretion. The cell line NCI-H292 was utilized for gene silencing of the β2-adrenergic receptor via siRNA as well as receptor blocking via ICI 118,551 and butaxamine.

Results

At baseline, COPD-ALIs produced greater amounts of IL-8 than control ALIs. Olodaterol reduced RSV-mediated IL-8 secretion in both COPD and control ALIs and also significantly reduced Muc5AC staining in COPD-ALIs infected with RSV. A non-significant reduction was seen in control ALIs. Gene silencing of the β2-adrenergic receptor in NCI-H292 negated the ability of olodaterol to inhibit IL-8 secretion from both RSV infection and lipopolysaccharide stimulus, as did blocking of the receptor with ICI 118,551 and butaxamine.

Conclusions

Olodaterol exhibits inherent anti-inflammatory properties on the airway epithelium, in addition to its bronchodilation properties, that is mediated through the β2-adrenergic receptor and independent of ICS usage.
The association between cannabis use and outcome in pharmacological treatment for opioid use disorder
Authors: Rosic Tea , Kapoor Raveena , Panesar Balpreet , Naji Leen , Chai Darren B. , Sanger Nitika , Marsh David C. , Worster Andrew , Thabane Lehana , Samaan Zainab
Published: February 2021

Background

With the ongoing opioid crisis and policy changes regarding legalization of cannabis occurring around the world, it is necessary to consider cannabis use in the context of opioid use disorder (OUD) and its treatment. We aimed to examine (1) past-month cannabis use in patients with OUD, (2) self-reported cannabis-related side effects and craving, and (3) the association between specific characteristics of cannabis use and opioid use during treatment in cannabis users.

Methods

Participants receiving pharmacological treatment for OUD (n = 2315) were recruited from community-based addiction treatment clinics in Ontario, Canada, and provided information on past-month cannabis use (self-report). Participants were followed for 3 months with routine urine drug screens in order to assess opioid use during treatment. We used logistic regression analysis to explore (1) the association between any cannabis use and opioid use during treatment, and (2) amongst cannabis-users, specific cannabis use characteristics associated with opioid use. Qualitative methods were used to examine responses to the question: “What effect does marijuana have on your treatment?”.

Results

Past-month cannabis use was reported by 51% of participants (n = 1178). Any cannabis use compared to non-use was not associated with opioid use (OR = 1.03, 95% CI 0.87–1.23, p = 0.703). Amongst cannabis users, nearly 70% reported daily use, and half reported experiencing cannabis-related side effects, with the most common side effects being slower thought process (26.2%) and lack of motivation (17.3%). For cannabis users, daily cannabis use was associated with lower odds of opioid use, when compared  with occasional use (OR = 0.61, 95% CI 0.47–0.79, p < 0.001) as was older age of onset of cannabis use (OR = 0.97, 95% CI 0.94, 0.99, p = 0.032), and reporting cannabis-related side effects (OR = 0.67, 95% CI 0.51, 0.85, p = 0.001). Altogether, 75% of cannabis users perceived no impact of cannabis on their OUD treatment.

Conclusion

Past-month cannabis use was not associated with more or less opioid use during treatment. For patients who use cannabis, we identified specific characteristics of cannabis use associated with differential outcomes. Further examination of characteristics and patterns of cannabis use is warranted and may inform more tailored assessments and treatment recommendations.
Sex specific trajectories of central adiposity, lipid indices, and glucose level with incident hypertension: 12 years Follow-up in Tehran lipid and glucose study
Authors: Ahanchi Noushin Sadat , Tamehri Zadeh Seyed Saeed , Khalili Davood , Azizi Fereidoun , Hadaegh Farzad
Published: February 2021

Aims

To identify sex specific trajectories of waist circumference (WC),triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and fasting plasma glucose (FPG) during adulthood and examine their associations with incident hypertension.

Methods

The cohort consisted of 5030 participants (2051 males) with at least 2 repeated measurement during a median of 12 years follow up. We identified trajectory groups using latent class growth mixture model, their association with hypertension was examined using multivariate Cox-regression analysis.

Results

We found 997 cases of hypertension (483 male). For both exposures, three distinct trajectory groups were identified in both genders. For WC, in women: low-increasing, 82.4%; high-stable, 13.4%; high-increasing, 4.2% and in men: stable, 94.6%; low-increasing, 3.6% and for high- increasing, 1.7%. For TG, in women: stable, 91.3%; decreasing, 5.9%; inverse U-shape, 2.8%; in men: stable, 89.7%; inverse U- shape, 6.2% and for decreasing, 4.1%.

Regarding WC, high stable and high-increasing trajectories were associated with hypertension in the multivariate model [(hazard ratio (HR) = 1.66 (95% CI 1.26–2.20) and 2.78(1.79–3.60), respectively]. Among men, this association was shown only for the low-increasing trajectory [2.76: 1.49–5.10]. For TG, among women decreasing and inverse U-shape trajectories were significantly associated with hypertension in the multivariate model [1.32:1.01–1.76] and [2.23:1.58–3.23, respectively].

We did not find any impact of increasing trajectories of FPG and HDL-C on incident hypertension. Considering TC, all individuals followed a stable trajectory.

Conclusion

WC dynamic changes in both gender and TG trajectory among women were significantly associated with incident hypertension.
Development of integration indexes to determine the extent of family planning and child immunization services integration in health facilities in urban areas of Nigeria
Authors: Sheahan Kate L. , Orgill-Meyer Jennifer , Speizer Ilene S. , Curtis Siân , Paul John , Weinberger Morris , Bennett Antonia V.
Published: February 2021

Background

Integrating family planning into child immunization services may address unmet need for contraception by offering family planning information and services to postpartum women during routine child immunization visits. However, policies and programs promoting integration are often based on insubstantial or conflicting evidence about its effects on service delivery and health outcomes. While integration models vary, many studies measure integration as binary (a facility is integrated or not) rather than a multidimensional and varying continuum. It is thus challenging to ascertain the determinants and effects of integrated service delivery. This study creates Facility and Provider Integration Indexes, which measure capacity to support integrated family planning and child immunization services and applies them to analyze the extent of integration across 400 health facilities.

Methods

This study utilizes cross-sectional health facility (N = 400; 58% hospitals, 42% primary healthcare centers) and healthcare provider (N = 1479) survey data that were collected in six urban areas of Nigeria for the impact evaluation of the Nigerian Urban Reproductive Health Initiative. Principal Component Analysis was used to develop Provider and Facility Integration Indexes that estimate the extent of integration in these health facilities. The Provider Integration Index measures provider skills and practices that support integrated service delivery while the Facility Integration Index measures facility norms that support integrated service delivery. Index scores range from zero (low) to ten (high).

Results

Mean Provider Integration Index score is 5.42 (SD 3.10), and mean Facility Integration Index score is 6.22 (SD 2.72). Twenty-three percent of facilities were classified as having low Provider Integration scores, 32% as medium, and 45% as high. Fourteen percent of facilities were classified as having low Facility Integration scores, 38% as medium, and 48% as high.

Conclusion

Many facilities in our sample have achieved high levels of integration, while many others have not. Results suggest that using more nuanced measures of integration may (a) more accurately reflect true variation in integration within and across health facilities, (b) enable more precise measurement of the determinants or effects of integration, and (c) provide more tailored, actionable information about how best to improve integration. Overall, results reinforce the importance of utilizing more nuanced measures of facility-level integration.
“Those are things for married people” exploring parents’/adults’ and adolescents’ perspectives on contraceptives in Narok and Homa Bay Counties, Kenya
Authors: Mwaisaka Jefferson , Wado Yohannes Dibaba , Ouedraogo Ramatou , Oduor Clement , Habib Helen , Njagi Joan , Bangha Martin W.
Published: February 2021

Background

Contraceptive use among adolescent girls is low in many sub-Saharan African countries including Kenya. Attitude and perspectives about contraception of community members including adolescent girls themselves may be likely to limit contraceptive use among adolescent girls. This study was conducted to explore and compare adults’/parents’ and adolescent girls’ narratives and perspectives about contraception in Narok and Homa Bay counties, Kenya.

Methods

Qualitative data from 45 in-depth-interviews conducted with purposively selected consenting adolescent girls aged 15–19 was used. Additionally, twelve focus group discussions were held with 86 consenting adults conveniently recruited from the two counties. All discussions were conducted in the local language and audio recorded following consent of the study participants. Female moderators were engaged throughout the study making it appropriate for the study to solicit feedback from the targeted respondents.

Results

Findings highlighted adults’ perceptions on adolescents’ sexuality and the presence of stringent conceptions about the side-effects of contraception in the study communities. Some participants underscored the need for open contraceptive talk between parents and their adolescent girls. Four main themes emerged from the discussions; (i) Perceptions about adolescents’ sexuality and risk prevention, (ii) Conceptions about contraception among nulligravida adolescents: fear of infertility, malformation and sexual libertinism, (iii) Post-pregnancy contraceptive considerations and (iv) Thinking differently: divergent views regarding contraceptives and parent/adolescent discussion.

Conclusions

Our findings suggest the need for increased attention towards adolescents and their caregivers particularly in demystifying contraceptive misconceptions. Programmatic responses and models which include the provision of comprehensive sexuality education and increased access to and utilization of SRH information, products and services through a well-informed approach need to be well executed. Programmatic efforts like SRH community education should further seek to enhance the capacity of parents to discuss sexuality with their adolescents.
A review of current knowledge of myeloproliferative disorders in the horse
Authors: Satué Katy , Gardon Juan Carlos , Muñoz Ana
Published: February 2021

Myeloid disorders are conditions being characterized by abnormal proliferation and development of myeloid lineage including granulocytes (neutrophils, eosinophils and basophils), monocytes, erythroids, and megakaryocytes precursor cells. Myeloid leukemia, based on clinical presentation and proliferative rate of neoplastic cells, is divided into acute (AML) and myeloproliferative neoplasms (MPN). The most commonly myeloid leukemia reported in horses are AML-M4 (myelomonocytic) and AML-M5 (monocytic). Isolated cases of AML-M6B (acute erythroid leukemia), and chronic granulocytic leukemia have also been reported. Additionally, bone marrow disorders with dysplastic alterations and ineffective hematopoiesis affecting single or multiple cell lineages or myelodysplastic diseases (MDS), have also been reported in horses. MDSs have increased myeloblasts numbers in blood or bone marrow, although less than 20%, which is the minimum level required for diagnosis of AML. This review performed a detailed description of the current state of knowlegde of the myeloproliferative disorders in horses following the criteria established by the World Health Organization.
Increased ribosomal protein levels and protein synthesis in the striatal synaptosome of Shank3-overexpressing transgenic mice
Authors: Jin Chunmei , Lee Yeunkum , Kang Hyojin , Jeong Kwon , Park Joori , Zhang Yinhua , Kang Hyae Rim , Ma Ruiying , Seong Hyunyoung , Kim Yoonhee , Jung Hosung , Kim Jin Young , Kim Yoon Ki , Han Kihoon
Published: February 2021

The SH3 and multiple ankyrin repeat domains 3 (Shank3) protein is a core organizer of the macromolecular complex in excitatory postsynapses, and its defects cause numerous synaptopathies, including autism spectrum disorders. Although the function of Shank3 as a postsynaptic scaffold is adequately established, other potential mechanisms through which Shank3 broadly modulates the postsynaptic proteome remain relatively unexplored. In our previous quantitative proteomic analysis, six up-regulated ribosomal proteins were identified in the striatal synaptosome of Shank3-overexpressing transgenic (TG) mice. In the present study, we validated the increased levels of RPLP1 and RPL36A in synaptosome, but not in whole lysate, of the TG striatum. Moreover, protein synthesis and extracellular signaling-regulated kinase (ERK) activity were enhanced in the TG striatal synaptosome. To understand the potential contribution of increased protein synthesis to the proteomic change in the TG striatal synaptosome, we performed RNA-sequencing analyses on both whole synaptosomal and synaptic polysome-enriched fractions. Comparative analyses showed a positive correlation only between the polysome-associated transcriptome and up-regulated proteome in the TG striatal synaptosome. Our findings suggest a novel mechanism through which Shank3 may remodel the postsynaptic proteome by regulating synaptic protein synthesis, whose dysfunction can be implicated inSHANK3-associated synaptopathies.
Correction to: Tumor-derived exosomal miR-934 induces macrophage M2 polarization to promote liver metastasis of colorectal cancer
Authors: Zhao Senlin , Mi Yushuai , Guan Bingjie , Zheng Binbin , Wei Ping , Gu Yanzi , Zhang Zhengxiang , Cai Sanjun , Xu Ye , Li Xinxiang , He Xuefeng , Zhong Xinyang , Li Guichao , Chen Zhiyu , Li Dawei
Published: February 2021

An amendment to this paper has been published and can be accessed via the original article.
Urban Growth and urban need to fair distribution of healthcare service: a case study on Shiraz Metropolitan area
Authors: Rezaee Rita , Rahimi Fatemeh , Goli Ali
Published: February 2021

Objective

(1) To analyze urbanization development pattern in Shiraz after the year 1977; (2) To analyze hospital development model in Shiraz after the year 1977; (3) To review and prioritize location-allocation criteria for hospitals; and (4) To specify appropriate locations for the establishment of potential future general hospitals in Shiraz based on selected criteria.

Results

Although a significant expansion is seen from different geographical directions (particularly northwest and southeast of the city) in the urbanization model after the year 1977, the construction of hospitals has been limited to the central parts of the city and the areas around the city lack any hospitals. The “open access path to the hospital during incidents and disasters and a light traffic” criterion has enjoyed the highest priority amongst the 24 selected hospital location-allocation criteria. Appropriate locations for establishment of new hospitals in the future have been marked as colored maps. The present study has been able to determine and prioritize a comprehensive list of hospital location-allocation criteria. Moreover, the achieved maps from this study can be used by policy makers to develop new hospitals.
Effects of a gratitude intervention program on work engagement among Japanese workers: a protocol for a cluster randomized controlled trial
Authors: Komase Yu , Watanabe Kazuhiro , Kawakami Norito
Published: February 2021

Background

Work engagement is one of the most important outcomes for both employees and employers. Although the findings to date, integrated 40 intervention studies aiming to improve work engagement, consistent results have not yet been produced, suggesting the importance of further intervention studies. This study aims to investigate the effects of gratitude intervention programs focused on two important work engagement factors among Japanese workers: personal and job resources.

Methods

This study will be a two-arm, parallel-group cluster (organization) randomized control trial. Japanese organizations and nested employees will be recruited through the first author’s acquaintances using snowball sampling. Organizations that meet the inclusion criteria will be randomly allocated to intervention or control groups in a 1:1 ratio within the company unit. The intervention groups will be provided with a 1-month long gratitude intervention program, which aims to promote reciprocal gratitude exchanges within the same organization. The program consists of psychoeducation, gratitude lists, and behavioral gratitude expression. The control groups will not receive any intervention. The primary outcome will be work engagement measured by the Japanese version of the Utrecht Work Engagement Scale at baseline and after 1 (immediate post-survey), 3, and 6 months. Multilevel latent growth modeling will be conducted to examine the effectiveness of the intervention program.

Discussion

This study will be the first cluster randomized controlled trial applied to the investigation of gratitude intervention aimed at improving work engagement among Japanese workers; to promote reciprocal gratitude exchanges within a given organization; and to include both gratitude lists and behavioral gratitude expression. Gratitude interventions have several strengths in terms of implementation: the objectives of the exercises are easy to understand and implement; it does not require much time or expense; they tend to have lower dropout rates; and they do not require experts in psychology. Although implementation difficulties have been common in previous interventions targeting work engagement, gratitude intervention may be suitable even for workers who have limited time to devote to the tasks.

Trial registration: This study was registered at the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR, ID=UMIN000042546):https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000048566on November 25, 2020.
Frontotemporal lobar degeneration proteinopathies have disparate microscopic patterns of white and grey matter pathology
Authors: Giannini Lucia A. A. , Peterson Claire , Ohm Daniel , Xie Sharon X. , McMillan Corey T. , Raskovsky Katya , Massimo Lauren , Suh EunRah , Van Deerlin Vivianna M. , Wolk David A. , Trojanowski John Q. , Lee Edward B. , Grossman Murray , Irwin David J.
Published: February 2021

Frontotemporal lobar degeneration proteinopathies with tau inclusions (FTLD-Tau) or TDP-43 inclusions (FTLD-TDP) are associated with clinically similar phenotypes. However, these disparate proteinopathies likely differ in cellular severity and regional distribution of inclusions in white matter (WM) and adjacent grey matter (GM), which have been understudied. We performed a neuropathological study of subcortical WM and adjacent GM in a large autopsy cohort (n = 92; FTLD-Tau = 37, FTLD-TDP = 55) using a validated digital image approach. The antemortem clinical phenotype was behavioral-variant frontotemporal dementia (bvFTD) in 23 patients with FTLD-Tau and 42 with FTLD-TDP, and primary progressive aphasia (PPA) in 14 patients with FTLD-Tau and 13 with FTLD-TDP. We used linear mixed-effects models to: (1) compare WM pathology burden between proteinopathies; (2) investigate the relationship between WM pathology burden and WM degeneration using luxol fast blue (LFB) myelin staining; (3) study regional patterns of pathology burden in clinico-pathological groups. WM pathology burden was greater in FTLD-Tau compared to FTLD-TDP across regions (beta = 4.21, SE = 0.34, p < 0.001), and correlated with the degree of WM degeneration in both FTLD-Tau (beta = 0.32, SE = 0.10, p = 0.002) and FTLD-TDP (beta = 0.40, SE = 0.08, p < 0.001). WM degeneration was greater in FTLD-Tau than FTLD-TDP particularly in middle-frontal and anterior cingulate regions (p < 0.05). Distinct regional patterns of WM and GM inclusions characterized FTLD-Tau and FTLD-TDP proteinopathies, and associated in part with clinical phenotype. In FTLD-Tau, WM pathology was particularly severe in the dorsolateral frontal cortex in nonfluent-variant PPA, and GM pathology in dorsolateral and paralimbic frontal regions with some variation across tauopathies. Differently, FTLD-TDP had little WM regional variability, but showed severe GM pathology burden in ventromedial prefrontal regions in both bvFTD and PPA. To conclude, FTLD-Tau and FTLD-TDP proteinopathies have distinct severity and regional distribution of WM and GM pathology, which may impact their clinical presentation, with overall greater severity of WM pathology as a distinguishing feature of tauopathies.
Prognostic value of lymphocyte counts in bronchoalveolar lavage fluid in patients with acute respiratory failure: a retrospective cohort study
Authors: Hirasawa Yasutaka , Nakada Taka-aki , Shimazui Takashi , Abe Mitsuhiro , Isaka Yuri , Sakayori Masashi , Suzuki Kenichi , Yoshioka Keiichiro , Kawasaki Takeshi , Terada Jiro , Tsushima Kenji , Tatsumi Koichiro
Published: February 2021

Background

Cellular patterns in bronchoalveolar lavage fluid (BALF) are used to distinguish or rule out particular diseases in patients with acute respiratory failure (ARF). However, whether BALF cellular patterns can predict mortality or not is unknown. We test the hypothesis that BALF cellular patterns have predictive value for mortality in patients with ARF.

Methods

This was a retrospective single-center observational study conducted in a Japanese University Hospital. Consecutive patients (n= 78) with both pulmonary infiltrates and ARF who were examined by bronchoalveolar lavage (BAL) between April 2015 and May 2018 with at least 1 year of follow-up were analyzed. Primary analysis was receiver operating characteristic curve—area under the curve (ROC-AUC) analysis for 1-year mortality.

Results

Among the final sample size of 78 patients, survivors (n= 56) had significantly increased lymphocyte and eosinophil counts and decreased neutrophil counts in BALF compared with non-survivors (n= 22). Among the fractions, lymphocyte count was the most significantly different (30 [12-50] vs. 7.0 [2.9-13]%,P<0.0001). In the ROC curve analysis of the association of BALF lymphocytes with 1-year mortality, the AUC was 0.787 (P<0.0001, cut-off value [Youden index] 19.0%). Furthermore, ≥20% BALF lymphocytes were significantly associated with increased survival with adjustment for baseline imbalances (1-year adjusted hazard ratio, 0.0929; 95% confidence interval, 0.0147–0.323,P<0.0001; 90-dayP=0.0012). Increased survival was significantly associated with ≥20% BALF lymphocytes in both interstitial lung disease (ILD) and non-ILD subgroups (P=0.0052 andP=0.0033, respectively). In secondary outcome analysis, patients with ≥20% BALF lymphocytes had significantly increased ventilator-free days, which represents less respiratory dysfunction than those with <20% BALF lymphocytes.

Conclusions

In the patients with ARF, ≥20% lymphocytes in BALF was associated with significantly less ventilatory support, lower mortality at both 90-day and 1-year follow-ups.
The effects of 12 weeks of functional strength training on muscle strength, volume and activity upon exposure to elevated Gz forces in high-performance aircraft personnel
Authors: Rausch Monika , Weber Frank , Kühn Sven , Ledderhos Carla , Zinner Christoph , Sperlich Billy
Published: February 2021

Background

Technological advancements in modern military and acrobatic jet planes have resulted in extraordinary psychophysiological loads being exerted upon flying personnel, including inducing neck and back pain. The purpose of this study was to examine the effects of 12 weeks of functional strength training on 1) the volume and strength of the neck and shoulder muscles and 2) muscular activity upon exposure to helmets of different masses and elevated Gzforces in a long-arm centrifuge in high-performance aircraft personnel.

Methods

Eighteen participants underwent 12 weeks of functional strength training (n = 12) or the control protocol (n = 6) without additional strength training. Pre- and post-intervention tests included evaluations of isometric strength of the head extensor muscles, flexion, and lateral flexion and rotation, as well as magnetic resonance imaging (MRI) to measure the volume of them. sternocleidomastoideus,m. trapezius, and deep neck muscles. Furthermore, during a long-arm centrifuge (+ 1.4 and + 3 Gz) protocol, the muscular activity levels of them. sternocleidomastoideus,m. trapeziusandm. erector spinaemuscles were assessed without a flight helmet, with a helmet, and with a helmet and night vision goggles. Each participant’s perception of muscular strain was noted immediately after the long-arm centrifuge protocol.

Results

The maximal isometric strength in all exercises and muscle volumes increased in the training group but not the control group (P < 0.05). Relative muscle activity (%MVC) with a helmet decreased after the intervention in the training but not the control group (P = 0.01). Relative muscle activity while wearing a helmet and night vision goggles was higher after intervention in the control group than in the training group (P < 0.01). The perceived muscular strain of the neck muscles induced by the long-arm centrifuge did not differ between the groups.

Conclusion

Twelve weeks of functional strength training improves the maximal isometric strength and volume of neck and shoulder muscles and leads to lower relative muscle activation upon exposure to elevated Gzforces in a long-arm centrifuge.
ROBUST: A Phase III Study of Lenalidomide Plus R-CHOP Versus Placebo Plus R-CHOP in Previously Untreated Patients With ABC-Type Diffuse Large B-Cell Lymphoma
Authors: Nowakowski Grzegorz S. , Chiappella Annalisa , Gascoyne Randy D. , Scott David W. , Zhang Qingyuan , Jurczak Wojciech , Özcan Muhit , Hong Xiaonan , Zhu Jun , Jin Jie , Belada David , Bergua Juan Miguel , Piazza Francesco , Mócikova Heidi , Molinari Anna Lia , Yoon Dok Hyun , Cavallo Federica , Tani Monica , Yamamoto Kazuhito , Izutsu Koji , Kato Koji , Czuczman Myron , Hersey Sarah , Kilcoyne Adrian , Russo Jacqueline , Hudak Krista , Zhang Jingshan , Wade Steve , Witzig Thomas E. , Vitolo Umberto
Published: February 2021

PURPOSE

Patients with the activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) historically showed inferior survival with standard rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Phase II studies demonstrated that adding the immunomodulatory agent lenalidomide to R-CHOP improved outcomes in ABC-type DLBCL. The goal of the global, phase III ROBUST study was to compare lenalidomide plus R-CHOP (R2-CHOP) with placebo/R-CHOP in previously untreated, ABC-type DLBCL.

METHODS

Histology and cell-of-origin type were prospectively analyzed by central pathology prior to random assignment and study treatment. Patients with ABC-DLBCL received lenalidomide oral 15 mg/d, days 1-14/21 plus standard R-CHOP21 versus placebo/R-CHOP21 for six cycles. The primary end point was progression-free survival (PFS) per independent central radiology review.

RESULTS

A total of 570 patients with ABC-DLBCL (n = 285 per arm) were stratified by International Prognostic Index score, age, and bulky disease, and randomly assigned to R2-CHOP or placebo/R-CHOP. Baseline demographics were similar between arms. Most patients completed six cycles of treatment: 74% R2-CHOP and 84% placebo/R-CHOP. The most common grade 3/4 adverse events for R2-CHOP versus placebo/R-CHOP were neutropenia (60% v 48%), anemia (22% v 14%), thrombocytopenia (17% v 11%), and leukopenia (14% v 15%). The primary end point of PFS was not met, with a hazard ratio of 0.85 (95% CI, 0.63 to 1.14) and P = .29; median PFS has not been reached for either arm. PFS trends favoring R2-CHOP over placebo/R-CHOP were seen in patients with higher-risk disease.

CONCLUSION

ROBUST is the first DLBCL phase III study to integrate biomarker-driven identification of eligible ABC patients. Although the ROBUST trial did not meet the primary end point of PFS in all patients, the safety profile of R2-CHOP was consistent with individual treatments with no new safety signals.
Branch-Cut-and-Price for the Robust Capacitated Vehicle Routing Problem with Knapsack Uncertainty
Authors: Pessoa Artur Alves , Poss Michael , Sadykov Ruslan , Vanderbeck François
Published: February 2021

Capacitated vehicle routing problems are widely studied combinatorial optimization problems, and branch-and-cut-and-price algorithms can solve instances harder than ever before. These models, however, neglect that demands volumes are often not known with precision when planning the vehicle routes, thus incentivizing decision makers to significantly overestimate the volumes for avoiding coping with infeasible routes. A robust formulation that models demand uncertainty through a knapsack polytope is considered. A new branch-and-cut-and-price algorithm for the problem is provided, which combines efficient algorithms for the problem with no uncertainty with profound results in robust combinatorial optimization and includes novel heuristics and new valid inequalities. The numerical results illustrate that the resulting approach is two orders of magnitude faster that the best algorithm from the literature, solving twice as many instances to optimality.