bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimization of the antimicrobial peptide Bac7 by deep mutational scanning
Authors: Koch Philipp , Schmitt Steven , Heynisch Alexander , Gumpinger Anja , Wüthrich Irene , Gysin Marina , Shcherbakov Dimitri , Hobbie Sven N. , Panke Sven , Held Martin
Published: May 2022

Background

Intracellularly active antimicrobial peptides are promising candidates for the development of antibiotics for human applications. However, drug development using peptides is challenging as, owing to their large size, an enormous sequence space is spanned. We built a high-throughput platform that incorporates rapid investigation of the sequence-activity relationship of peptides and enables rational optimization of their antimicrobial activity. The platform is based on deep mutational scanning of DNA-encoded peptides and employs highly parallelized bacterial self-screening coupled to next-generation sequencing as a readout for their antimicrobial activity. As a target, we used Bac71-23, a 23 amino acid residues long variant of bactenecin-7, a potent translational inhibitor and one of the best researched proline-rich antimicrobial peptides.

Results

Using the platform, we simultaneously determined the antimicrobial activity of >600,000 Bac71-23 variants and explored their sequence-activity relationship. This dataset guided the design of a focused library of ~160,000 variants and the identification of a lead candidate Bac7PS. Bac7PS showed high activity against multidrug-resistant clinical isolates of E. coli, and its activity was less dependent on SbmA, a transporter commonly used by proline-rich antimicrobial peptides to reach the cytosol and then inhibit translation. Furthermore, Bac7PS displayed strong ribosomal inhibition and low toxicity against eukaryotic cells and demonstrated good efficacy in a murine septicemia model induced by E. coli.

Conclusion

We demonstrated that the presented platform can be used to establish the sequence-activity relationship of antimicrobial peptides, and showed its usefulness for hit-to-lead identification and optimization of antimicrobial drug candidates.
Atypical chorioretinal lesions in Siberian Husky dogs with primary angle-closure glaucoma: a case series
Authors: Park Shin Ae , Sledge Dodd , Monahan Colleen F. , Teixeira Leandro , Boyd Ryan , Freeman Katie , Koehl Kristin , Harman Christine , Munoz Kirk , Occelli Laurence M. , Pirie Chris G. , Davidson Harriet , Petersen-Jones Simon , Komáromy András M.
Published: May 2022

Background

A number of etiologies for different canine chorioretinal lesions have been proved or suggested but some fundic lesions remain unclear in terms of an etiologic diagnosis, treatment options and prognosis. The purpose of this case series is to describe atypical chorioretinal lesions observed in dogs with primary angle-closure glaucoma (PACG).

Case presentation

Two spayed-female Siberian Huskies (3- and 4-year-old) and one Siberian Husky/Australian Shepherd mixed breed dog (11-month-old) that had multifocal depigmented retinal lesions and PACG were included. Procedures: Ophthalmic examination, gross, and histopathologic examination findings are described. One of the dogs underwent further clinical diagnostics. Advanced clinical diagnostics on the fellow, presumed to be non-glaucomatous eye of a dog revealed: pectinate ligament dysplasia by gonioscopy, retinal thinning in the depigmented area and wedge shaped retinal thinning with delayed choroidal vascular perfusion by optical coherence tomography, confocal scanning laser ophthalmoscopy, fluorescein and indocyanine green angiography. Quantifiable maze testing for the same eye revealed mild nyctalopia but the full-field electroretinogram showed no generalized decrease of retinal function. Genetic testing for mutations within theretinitis pigmentosa GTPase regulatorgene causing X-linked progressive retinal atrophy in Siberian Huskies was negative. Histopathologic evaluations on enucleated eyes in two dogs confirmed goniodysgenesis, PACG with optic nerve head cupping, and diffuse inner retinal atrophy. In addition, segmental profound retinal atrophy, loss of retinal pigment epithelium, and adhesion of the retina to Bruch’s membrane was observed and coincided with multifocal depigmented lesions noted on fundic examination.

Conclusions

To our knowledge, this is the first case series with clinical and histopathologic data of chorioretinal lesions, most likely caused by severely impaired choroidal perfusion. Further studies are warranted to elucidate the etiology and pathophysiology, including its possible association with PACG.
Surgical management of a Salter-Harris type I proximal physeal fracture of the tibia in a foal: a case report
Authors: Mazaheri-Khameneh Ramin , Azizi Saeed , Davoodi Farshid , Gooran Mohammad Mahdi
Published: May 2022

Background

One of the traumatic fractures occurring in the hindlimb of the foals is physeal fractures of the tibia. The most common type of proximal tibial fracture in foals is reported to be Salter-Harris type II.

Case presentation

This case report describes the history, clinical signs, radiographic findings, and surgical management of a proximal physeal fracture of the tibia due to the kick trauma in a 2-weeks-old Kurdish female foal, with signs of left pelvic limb lameness, valgus deviation with non-weight-bearing, non-mobility in stifle region and crepitation in the affected area. In this case, radiography was utilized to confirm the fracture and detect the exact location of the fracture fragments. The Salter-Harris type I accompanied by tibial tuberosity fracture was diagnosed. In this case, a size 4.5 mm seven-hole, T-plate, and cortical bone screws were employed to fix the physeal fracture, and a cortical bone screw was utilized to fix the tibial tuberosity in the normal position. Case follow-up during two months showed no significant complications, and the patient was fully recovered (no lameness anymore).

Conclusions

To our knowledge, this is the first report of Salter-Harris type I fracture in proximal tibia accompanied by tibial tuberosity fracture in a foal treated by a T-plate implant. A cortical screw in lag fashion for tibial tuberosity was utilized in this case for the first time, and the results were satisfying. T-Plate fixation can be recommended as an effective surgical treatment for proximal tibial fractures in foals.
Commensal bacteria-derived extracellular vesicles suppress ulcerative colitis through regulating the macrophages polarization and remodeling the gut microbiota
Authors: Liang Liping , Yang Chenghai , Liu Le , Mai Genghui , Li Haolin , Wu Lele , Jin Ming , Chen Ye
Published: May 2022

Background

The extracellular vesicles (EVs) traffic constitutes an essential pathway of cellular communication. And the molecules in EVs produced by procaryotes help in maintaining homeostasis, addressing microbial imbalance and infections, and regulating the immune system. Despite the fact that Clostridium butyricum (C. butyricum) is commonly used for treating ulcerative colitis (UC), the potential role of C. butyricum-secreted EVs in commensals-host crosstalk remains unclear.

Results

Here, we performed flow cytometry, western blot, immunohistochemistry and 16S rRNA analysis to explore the role of C. butyricum-derived EVs on macrophage polarization and gut microbiota composition in a dextran sulfate sodium (DSS)-induced UC mouse model. The antibiotic cocktail-induced microbiome depletion and faecal transplantations were used to further investigate the mechanisms by which EVs regulate macrophage balance. Our findings showed that C. butyricum-derived EVs improved the remission of murine colitis and polarized the transformation of macrophages to the M2 type. Furthermore, C. butyricum-derived EVs restored gut dysbiosis and altered the relative abundance of Helicobacter, Escherichia-Shigella, Lactobacillus, Akkermansia and Bacteroides, which, in turn, faecal transplantations from EVs-treated mice relieved the symptoms of UC and improved the impact of EVs on the reprogramming of the M2 macrophages.

Conclusion

C. butyricum-derived EVs could protect against DSS-induced colitis by regulating the repolarization of M2 macrophages and remodelling the composition of gut microbiota, suggesting the potential efficacy of EVs from commensal and probiotic Clostridium species against UC.
Exosomal microRNAs shuttling between tumor cells and macrophages: cellular interactions and novel therapeutic strategies
Authors: Xu Wen-Xiu , Wang Dan-Dan , Zhao Zhi-Qiang , Zhang He-Da , Yang Su-Jin , Zhang Qian , Li Lei , Zhang Jian
Published: May 2022

Extracellular vesicles secreted by tumor microenvironment (TME) cells are vital players in tumor progression through transferring nucleic acids and proteins. Macrophages are the main immune cells in TME and tumor associated macrophages (TAM) express M2 phenotype, which induce tumor proliferation, angiogenesis, invasion, metastasis and immune elimination, resulting in the subsequent evolution of malignancies. There are a high number of studies confirmed that tumor cells and TAM interact with each other through extracellular vesicles in various cancers, like pancreatic ductal adenocarcinoma, gastric cancer, breast cancer, ovarian cancer, colon cancer, glioblastoma, hepatocellular cancer, and lung cancer. Herein, this review summarizes the current knowledge on mechanisms of communications between tumor cells and TAM via extracellular vesicles, mainly about microRNAs, and targeting these events might represent a novel approach in the clinical implications of this knowledge into successful anti-cancer strategies.
ANLN and UBE2T are prognostic biomarkers associated with immune regulation in breast cancer: a bioinformatics analysis
Authors: Xiao Yu , Deng Zhiqin , Li Yongshen , Wei Baoting , Chen Xiaoqiang , Zhao Zhe , Xiu Yingjie , Hu Meifang , Alahdal Murad , Deng Zhenhan , Wang Daping , Liu Jianquan , Li Wencui
Published: May 2022

Objectives

To screen and verify differential genes affecting the prognosis of breast cancer.

Methods

Breast cancer gene expression datasets were downloaded from the GEO database, and original data were analyzed in R. The TIMER database was used to analyze the relationship between ANLN and UBE2T and immune cell infiltration.

Results

Ten hub-key genes were identified, and survival analysis showed that UBE2T and ANLN were upregulated in breast cancer and their upregulation was associated with a poor prognosis. ANLN and UBE2T upregulation was associated with the prevalence of Th1 and Th2 cells, shifting the Th1/Th2 balance to Th2 in Basal and Luminal-B breast cancers, which indicates a poor prognosis (P < 0.05).

Conclusion

ANLN and UBE2T are potential biomarkers for predicting the prognosis of breast cancer.
Income inequality and self-rated health status in Colombia
Authors: Góngora-Salazar Pamela , Casabianca María Sofía , Rodríguez-Lesmes Paul
Published: May 2022

Background

The negative association between income inequality and health has been known in the literature as the Income Inequality Hypothesis (IIH). Despite the multiple studies examining the validity of this hypothesis, evidence is still inconclusive, and the debate remains unsolved. In addition, relatively few studies have focused their attention on developing or emerging economies, where levels of inequality tend to be the highest in the world. This work examines the statistical association between income inequality and self-rated health status in Colombia, a highly unequal Latin American country.

Methods

To explore whether this association is present in the general population or whether it is only confined to the bottom of the income distribution, we use data from the 2011–2019 National Quality of Life Survey. Multiple probit estimations are considered for testing the robustness of the IIH.

Results

Evidence favouring the IIH was found, even after controlling for individual income levels, average regional income, and socioeconomic characteristics. The link between income inequality and the probability of reporting poor health seems to be present across all income quintiles. However, the magnitude of such association is considerably smaller when using inequality measures with relatively greater sensitivity to income differences among the rich.

Conclusions

The association between regional income inequality and individual's self-rated health status in Colombia is not only confined to low-income individuals but extends across all socioeconomic strata. This association is robust to the income inequality measure implemented, the income-unit of analysis, and changes in the sample. It is suggested that reducing income disparities can potentially contribute to improving individual's health.
The political economy of priority-setting for health in South Sudan: a case study of the Health Pooled Fund
Authors: Widdig Heloise , Tromp Noor , Lutwama George William , Jacobs Eelco
Published: May 2022

Background

In fragile and conflict affected settings (FCAS) such as South Sudan, where health needs are immense, resources are scarce, health infrastructure is rudimentary or damaged, and government stewardship is weak, adequate health intervention priority-setting is especially important. There is a scarcity of research examining priority-setting in FCAS and the related political economy. Yet, capturing these dynamics is important to develop context-specific guidance for priority-setting. The objective of this study is to analyze the priority-setting practices in the Health Pooled Fund (HPF), a multi-donor fund that supports service delivery in South Sudan, using a political economy perspective.

Methods

A multi-method study was conducted combining document review, 30 stakeholder interviews, and an examination of service delivery. An adapted version of the Walt and Gilson policy analysis triangle guided the study’s design and analysis.

Results

Priority-setting in HPF occurs in a context of immense fragility where health needs are vast, service delivery remains weak, and external funding is essential. HPF's service package gives priority to the health of mothers and children, gender-sensitive programming, immunization services, and a community health initiative. HPF is structured by a web of actors at national and local levels with pronounced power asymmetries and differing vested interests and ideas about HPF’s role. Priority-setting takes place throughout program design, implementing partner (IP) contract negotiation, and implementation of the service package. In practice the BPHNS does not provide adequate guidance for priority-setting because it is too expansive and unrealistic given financial and health system constraints. At the local level, IPs must manage the competing interests of the HPF program and local health authorities as well as challenging contextual factors, including conflict and shortages of qualified health workers, which affect service provision. The resulting priority-setting process remains implicit, scarcely documented, and primarily driven by donors’ interests.

Conclusion

This study highlights power asymmetries between donors and national health authorities within a FCAS context, which drive a priority-setting process that is dominated by donor agendas and leave little room for government ownership. These findings emphasize the importance of paying attention to the influence of stakeholders and their interests on the priority-setting process in FCAS.
Endocrine-disrupting chemicals and the risk of gestational diabetes mellitus: a systematic review and meta-analysis
Authors: Yan Dandan , Jiao Yang , Yan Honglin , Liu Tian , Yan Hong , Yuan Jingping
Published: May 2022

Objective

To conduct a comprehensive systematic review and meta-analysis to estimate the relationship between endocrine-disrupting chemicals (EDCs), including polychlorinated biphenyls (PCBs), poly-brominated diphenyl ethers (PBDEs), phthalates (PAEs), and per- and polyfluoroalkyl substances (PFAS) exposure and risk of gestational diabetes mellitus (GDM).

Methods

Relevant studies from their inception to November 2021 were identified by searching EMBASE, PubMed, and Web of Science. The cohort and case–control studies that reported effect size with 95% confidence intervals (CIs) of EDC exposure and GDM were selected. The heterogeneity among the included studies was quantified by I2 statistic. Publication bias was evaluated through the Begg and Egger tests.

Results

Twenty-five articles with a total of 23,796 participants were found. Results indicated that exposure to PCBs has a significant influence on the incidence of GDM (OR = 1.14; 95% CI = 1.00-–1.31; n = 8). The risk of GDM was found to be associated with PBDE exposure (OR = 1.32; 95% CI = 1.15–1.53; n = 4). PAEs and PFASs exposure were also positively associated with the risk of GDM, with summary ORs of 1.10 (95% CI = 1.03–1.16; n = 7 for PAEs) and 1.09 (95% CI = 1.02–1.16; n = 11 for PFASs), respectively. When only cohort studies were considered, the summary OR between PCBs exposure and the risk of GDM was 0.99 (95% CI = 0.91–1.09; n = 5). Meanwhile, the summary ORs from cohort studies for PBDEs, PAEs, and PFASs exposure were 1.12 (95% CI = 1.00–1.26; n = 2), 1.08 (95% CI = 1.02–1.15; n = 5), and 1.06 (95% CI = 1.00–1.12; n = 8), respectively. The Beggs and Egger tests did not show publication bias, and the sensitivity analyses did not change the results in this meta-analysis.

Conclusion

These results support that exposure to certain EDCs, including PCBs, PBDEs, PAEs, and PFAS, increase the risk of GDM. Further large-sample epidemiologic researches and mechanistic studies are needed to verify the potential relationship and biological mechanisms. These results are of public health significance because the daily EDC exposure is expected to increase the risk of GDM development.

Graphical Abstract
Equations for predicting DXA-measured visceral adipose tissue mass based on BMI or weight in adults
Authors: Song Xuan , Wu Hongxia , Zhang Wenhua , Wang Bei , Sun Hongjun
Published: May 2022

Background

Obesity, especially presenting with excessive amounts of visceral adipose tissue (VAT), is strongly associated with insulin resistance (IR), atherosclerosis, metabolic syndrome, and cardiovascular diseases (CVDs).

Aims

To construct a predication equation for estimating VAT mass using anthropometric parameters and validate the models with a validation group.

Methods

Five hundred fifteen subjects (366 for the derivation group and 149 for the validation group) were enrolled in the study. The anthropometric parameters, blood lipid profile, and VAT mass were accessed from medical records. Stepwise regression was applied to develop prediction models based on the dual X–ray absorptiometry (DXA)-measured VAT mass in the derivation group. Bland–Altman plots and correlation analysis were performed to validate the agreements in the validation group. The performance of the prediction equations was evaluated with the Hosmer–Lemeshow test and area under the curve (AUC).

Results

Model 1, which included age, sex, body mass index (BMI), triglyceride (TG), high-density lipoprotein (HDL), and the grade of hepatic steatosis, had a variance of 70%, and model 2, which included age, sex, weight, height, TG, HDL, and the grade of hepatic steatosis, had a variance of 74%. The VAT mass measured by DXA was correlated with age, sex, height, weight, BMI, TG, HDL, and grade of hepatic steatosis. In the validation group, the VAT mass calculated by the prediction equations was strongly correlated with the DXA–VAT mass (r = 0.870, r = 0.875, respectively). The AUC, sensitivity, and specificity of the two prediction equations were not significantly different (both P = 0.933).

Conclusion

The study suggests that prediction equations including age, sex, height, BMI, weight, TG, HDL, and the grade of hepatic steatosis could be useful tools for predicting VAT mass when DXA is not available.
Use of thromboelastography before the administration of hemostatic agents to safely taper recombinant activated factor VII in acquired hemophilia A: a report of three cases
Authors: Hosoi Hiroki , Akagi Yuina , Mushino Toshiki , Takeyama Masahiro , Minoura Naoto , Hiroi Takayuki , Furuya Yoshiaki , Morimoto Masaya , Murata Shogo , Tamura Shinobu , Sonoki Takashi
Published: May 2022

Background

Acquired hemophilia A (AHA) is a rare autoimmune disease characterized by bleeding events. Recombinant activated factor VII (rFVIIa) is a first-line bypassing agent, which is effective against clinically significant bleeding. However, there is no standard way of tapering and discontinuing rFVIIa, mainly because there is no established method for monitoring rFVIIa therapy for AHA.

Case presentation

Here, we report three AHA cases, in which we adjusted the rFVIIa dosing interval based on the results of thromboelastography (TEG) performed just before the administration of the next dose of rFVIIa. The dosing interval of rFVIIa was prolonged based on the reaction rate time (R) according to TEG, which is correlated with coagulation factor activity. The R-value reference range reported by the manufacturer of the TEG system was used as a threshold for making decisions. In these three cases, there was no rebleeding, and the patients’ ability to perform activities of daily living did not decline.

Conclusion

Our cases suggest that conducting TEG-based monitoring just before the administration of the next dose of rFVIIa may be useful for guiding increases in the rFVIIa dosing interval without causing rebleeding events. Further investigations are warranted to examine how TEG could be used to determine the most appropriate rFVIIa dosing interval, e.g., through regular TEG-based monitoring, and the optimal TEG-derived threshold for indicating changes to the rFVIIa dosing interval.
Prevalence and associated factors for workplace violence among general practitioners in China: a national cross-sectional study
Authors: Feng Jing , Lei Zihui , Yan Shijiao , Jiang Heng , Shen Xin , Zheng Yanling , Yu Minyi , Meng Xin , Di Hongkun , Xia Wenqi , Zhou Ying , Yang Tingting , Su Cheng , Cheng Fanjun , Lu Zuxun , Gan Yong
Published: May 2022

Background

General practitioners (GPs) were at risk of violence in their everyday working lives. Workplace violence (WPV) among GPs is a global public health concern. This study aimed to investigate the prevalence and factors associated with WPV among GPs in China.

Methods

A cross-sectional study was conducted among 4376 GPs in eastern, central, and western China between March and May 2021 using a structured self-administered questionnaire. The multivariable stepwise logistic regression model was used to examine the factors associated with WPV among GPs in China.

Results

Among these respondents, 14.26% of them reported exposure to WPV in the past 12 months. GPs who were female, practised in a rural area, made home visits occasionally, worked in a fair or good practice environment or work environment, and had a fair or good relationship with patients were less likely to encounter any type of WPV. In addition, GPs who served patients over 20 per day and worked overtime occasionally or frequently were more likely to be exposed to WPV. The determinants of WPV varied in different types of WPV and sexes.

Conclusions

The prevalence of WPV among GPs is low in China. Our findings could inform the measures to reduce the WPV among GPs.
Rapid scale-up of COVID-19 training for frontline health workers in 11 African countries
Authors: Tsiouris Fatima , Hartsough Kieran , Poimboeuf Michelle , Raether Claire , Farahani Mansoor , Ferreira Thais , Kamanzi Collins , Maria Joana , Nshimirimana Majoric , Mwanza Job , Njenga Amon , Odera Doris , Tenthani Lyson , Ukaejiofo Onyekachi , Vambe Debrah , Fazito Erika , Patel Leena , Lee Christopher , Michaels-Strasser Susan , Rabkin Miriam
Published: May 2022

Background

The global spread of the SARS-CoV-2 virus highlights both the importance of frontline healthcare workers (HCW) in pandemic response and their heightened vulnerability during infectious disease outbreaks. Adequate preparation, including the development of human resources for health (HRH) is essential to an effective response. ICAP at Columbia University (ICAP) partnered with Resolve to Save Lives and MOHs to design an emergency training initiative for frontline HCW in 11 African countries, using a competency-based backward-design approach and tailoring training delivery and health facility selection based on country context, location and known COVID-19 community transmission.

Methods

Pre- and post-test assessments were conducted on participants completing the COVID-19 training. Parametric and non-parametric methods were used to examine average individual-level changes from pre- to post-test, and compare performance between countries, cadres, sex and facility types. A post-evaluation online training survey using Qualtrics was distributed to assess participants’ satisfaction and explore training relevance and impact on their ability to address COVID-19 in their facilities and communities.

Results

A total of 8797 HCW at 945 health facilities were trained between June 2020 and October 2020. Training duration ranged from 1 to 8 days (median: 3 days) and consisted of in person, virtual or self guided training. Of the 8105 (92%) HCW working at health facilities, the majority (62%) worked at secondary level facilities as these were the HF targeted for COVID-19 patients. Paired pre- and post-test results were available for 2370 (25%) trainees, and 1768 (18%) participants completed the post-evaluation training survey. On average, participants increased their pre- to post-test scores by 15 percentage points (95% CI 0.14, 0.15). While confidence in their ability to manage COVID-19 was high following the training, respondents reported that lack of access to testing kits (55%) and PPE (50%), limited space in the facility to isolate patients (45%), and understaffing (39%) were major barriers.

Conclusion

Ongoing investment in health systems and focused attention to health workforce capacity building is critical to outbreak response. Successful implementation of an emergency response training such as this short-term IPC training initiative in response to the COVID-19 pandemic, requires speed, rigor and flexibility of its design and delivery while building on pre-existing systems, resources, and partnerships.
Development of a scale to evaluate negative menstrual attitudes among Nepalese women
Authors: Kawata Rina , Endo Masayuki , Rai Shiba Kumar , Ohashi Kazutomo
Published: May 2022

Background

Menstrual attitudes include negative and positive perceptions of menstruation and are associated with reproductive health, underscoring the importance of its evaluation in women. Given that social and cultural factors affect menstrual attitudes, developing evaluation methods specific to distinct societal cultures is necessary.

Methods

We developed a scale based on the menstrual attitude questionnaire, which is the most widely used measure of menstrual attitudes, to evaluate negative menstrual attitudes among Nepalese women in consideration of Nepalese cultural backgrounds and literacy. In total, 352 Nepalese women aged 20–45 years living in urban or suburban areas in Nepal were enrolled in the study. Participants were randomly divided into two groups using the permuted block method. Using the prototype, Group 1 (n = 176) was evaluated with an exploratory factor analysis to develop a reliable scale, and Group 2 (n = 176) was evaluated with a confirmatory factor analysis to confirm the structure of negative menstrual attitudes. Further, we preliminarily examined the relationship of negative menstrual attitudes with the frequency of traditional menstrual practices and intensity of menstrual pain, which are significant reproductive health issues in Nepal, in Group 2.

Results

We developed a 15-item, 3-factor scale to evaluate negative menstrual attitudes among Nepalese women using exploratory factor analysis. The first, second, and third factors were “Natural event” (α = 0.82), “Debilitating event” (α = 0.76), and “Bothersome event” (α = 0.69), respectively. Confirmatory factor analysis revealed that negative menstrual attitudes comprised a 3-factor structure. Participants who performed three traditional menstrual practices (“stay in their own house”, “go to public spaces”, and “contact with others generally”) demonstrated significantly higher scores for negative menstrual attitudes than did non-performers. Negative menstrual attitudes were positively correlated with the intensity of menstrual pain (r = 0.558).

Conclusions

This study is the first to evaluate menstrual attitudes and analyse its factor structure among Nepalese women. In the future, the relationship between accurately evaluated negative menstrual attitudes and reproductive health issues should be examined more comprehensively.
Competitive motivation increased home use and improved prosthesis self-perception after Cybathlon 2020 for neuromusculoskeletal prosthesis user
Authors: Earley Eric J. , Zbinden Jan , Munoz-Novoa Maria , Mastinu Enzo , Smiles Andrew , Ortiz-Catalan Max
Published: May 2022

Background

Assistive technologies, such as arm prostheses, are intended to improve the quality of life of individuals with physical disabilities. However, certain training and learning is usually required from the user to make these technologies more effective. Moreover, some people can be encouraged to train more through competitive motivation.

Methods

In this study, we investigated if the training for and participation in a competitive event (Cybathlon 2020) could promote behavioral changes in an individual with upper limb amputation (the pilot). We defined behavioral changes as the active time while his prosthesis was actuated, ratio of opposing and simultaneous movements, and the pilot’s ability to finely modulate his movement speeds. The investigation was based on extensive home-use data from the period before, during and after the Cybathlon 2020 competition.

Results

Relevant behavioral changes were found from both quantitative and qualitative analyses. The pilot’s home use of his prosthesis nearly doubled in the period before the Cybathlon, and remained 66% higher than baseline after the competition. Moreover, he improved his speed modulation when controlling his prosthesis, and he learned and routinely operated new movements in the prosthesis (wrist rotation) at home. Additionally, as confirmed by semi-structured interviews, his self-perception of the prosthetic arm and its functionality also improved.

Conclusions

An event like the Cybathlon may indeed promote behavioral changes in how competitive individuals with amputation use their prostheses. Provided that the prosthesis is suitable in terms of form and function for both competition and at-home daily use, daily activities can become opportunities for training, which in turn can improve prosthesis function and create further opportunities for daily use. Moreover, these changes appeared to remain even well after the event, albeit relevant only for individuals who continue using the technology employed in the competition.
Clinical presentation and surgical management of perforated peptic ulcer in a tertiary hospital in Mogadishu, Somalia: a 5-year retrospective study
Authors: Ali Abdihamid Mohamed , Mohamed Abdulkadir Nor , Mohamed Yahye Garad , Keleşoğlu Salim İdris
Published: May 2022

Background

Perforated peptic ulcer is a common surgical emergency condition worldwide, which is associated with significant morbidity and mortality if early diagnosis and immediate surgical management were not carried out. Perforation occurs in roughly 5% of PUD patients during their lifetime; this study aimed to explore the wide range of clinical presentations, associated risk factors, complications, and surgical management of perforated peptic ulcer patients.

Methods

A 5-year retrospective observational study on the clinical presentation and surgical management of perforated peptic ulcer is carried out in a tertiary hospital in Mogadishu, Somalia, Department of General Surgery, from January 2017 to December 2021. We included all patients undergoing operations with an intraoperative confirmed diagnosis of perforated peptic ulcer at the general surgery department. For operated patients, follow-up evaluation was performed in the outpatient department.

Results

Fifty-one patients underwent an emergency operation for perforated peptic ulcer during the study period. The sociodemographic distribution of patients was 45 (88.2%) males and 6 (11.8%) females, giving a male-to-female ratio of 7.5:1. The mean age of patients was 35.5 ± 16.8 years, and the peak frequency was in the third decade. The commonest presenting symptoms were sudden onset of severe epigastric pain in 42 (82.4%) patients. Patients who presented perforated peptic ulcer within 24 h of initiation of symptoms were free from complications. Age-group and delayed presentation > 48 h after onset of symptoms were linked to postoperative complications and were statistically significant (P 0.032 and P 0.005), respectively. Four patients died (mortality rate of 7.8%). Two patients were reoperated because of the failed primary repair, and 4 patients had > 5 cm intra-abdominal abscess image-guided percutaneous drainage, and the rest were given antibiotic therapy according to peritoneal fluid culture and sensitivity results. The most common microorganism isolated was E. coli 22% and Klebsiella 11%. Other rare microorganisms (pseudomonas, Staphylococcus aureus, and Candida spp.) were identified. In half (51%) of the patients with peritoneal fluid culture, no microorganism growth was seen.

Conclusion

The distribution of perforated peptic ulcer is common in the young age-group in the third decades of life. Delayed presentation of the disease is linked because most patients arrived from remote areas where proper facilities of health care and health education are not available and the patient might come to the hospital in an advanced stage of the disease. We suggest conducting further researches, health awareness related to complications over-the-counter drugs self-medication, and bad habit including smoking, and to improve health-seeking behaviors of society.
Birt-Hogg-Dubé syndrome encountered at rare lung disease clinic in Anhui province, China
Authors: Zhang Guofeng , Liu Jinli , Wang Yushuo , Wang Yue , Jiang Xianliang , Peng Yan , Xiao Jun , Wei Wei , Shen Bing , Yi Long , Ryu Jay H. , Hu Xiaowen
Published: May 2022

Background

Diagnosis of rare diseases remains a challenge in China. We describe our experience with Birt-Hogg-Dubé syndrome (BHDS) encountered at a Rare Lung Disease Clinic recently established in China.

Methods

After the first patient with BHDS was recognized in 2017, a Rare Lung Disease Clinic with a multidisciplinary team of specialists was established. We retrospectively analyzed the data of consecutive patients with BHDS encountered from inception to December 2021.

Results

There were 1, 1, 15, 12 and 21 cases with BHDS diagnosed from year 2017 to 2021, respectively. All 50 patients (34 women) were of Han race with a mean age of 47.4 years. The common manifestations were pulmonary cysts (98%), pneumothorax (54%) and skin lesions (68%). Renal cancer was detected in two patients and renal angiomyolipoma in four other patients. The main presentations leading to diagnosis were pneumothorax (42%), family screening (36%), and lung cysts identified on radiologic imaging (20%). The average delay in diagnosis was 8.3 years, and 4.7 years in patients with only pulmonary cysts. The most frequent pathogenic variant was c.1285del/dup on exon 11 (23%) among 44 patients confirmed by genetic testing. Renal cancer has not been found on follow-up surveillance thus far.

Conclusions

Increasing number of patients with BHDS are being recognized in China, facilitated by establishment of a Rare Lung Disease Clinic. Pulmonary cysts and pneumothorax were commonly encountered features, but skin lesions appeared to be more prevalent in Chinese subjects than previously reported in other Asian countries.
Termination-of-resuscitation rule in the emergency department for patients with refractory out-of-hospital cardiac arrest: a nationwide, population-based observational study
Authors: Goto Yoshikazu , Funada Akira , Maeda Tetsuo , Goto Yumiko
Published: May 2022

Background

In Japan, emergency medical service (EMS) providers are prohibited from field termination-of-resuscitation (TOR) in out-of-hospital cardiac arrest (OHCA) patients. In 2013, we developed a TOR rule for emergency department physicians (Goto’s TOR rule) immediately after hospital arrival. However, this rule is subject to flaws, and there is a need for revision owing to its relatively low specificity for predicting mortality compared with other TOR rules in the emergency department. Therefore, this study aimed to develop and validate a modified Goto’s TOR rule by considering prehospital EMS cardiopulmonary resuscitation (CPR) duration.

Methods

We analysed the records of 465,657 adult patients with OHCA from the All-Japan Utstein registry from 2016 to 2019 and divided them into two groups: development (n = 231,363) and validation (n = 234,294). The primary outcome measures were specificity, false-positive rate (FPR), and positive predictive value (PPV) of the revised TOR rule in the emergency department for predicting 1-month mortality.

Results

Recursive partitioning analysis for the development group in predicting 1-month mortality revealed that a modified Goto’s TOR rule could be defined if patients with OHCA met the following four criteria: (1) initial asystole, (2) unwitnessed arrest by any laypersons, (3) EMS-CPR duration > 20 min, and (4) no prehospital return of spontaneous circulation (ROSC). The specificity, FPR, and PPV of the rule for predicting 1-month mortality were 99.2% (95% confidence interval [CI], 99.0–99.4%), 0.8% (0.6–1.0%), and 99.8% (99.8–99.9%), respectively. The proportion of patients who fulfilled the rule and the area under the receiver operating curve (AUC) was 27.5% (95% CI 27.3–27.7%) and 0.904 (0.902–0.905), respectively. In the validation group, the specificity, FPR, PPV, proportion of patients who met the rule, and AUC were 99.1% (95% CI 98.9–99.2%), 0.9% (0.8–1.1%), 99.8% (99.8–99.8%), 27.8% (27.6–28.0%), and 0.889 (0.887–0.891), respectively.

Conclusion

The modified Goto’s TOR rule (which includes the following four criteria: initial asystole, unwitnessed arrest, EMS-CPR duration > 20 min, and no prehospital ROSC) witha > 99% predictor of 1-month mortality is a reliable tool for physicians treating refractory OHCAs immediately after hospital arrival.
Impact of prolonged requirement for insulin on 90-day mortality in critically ill patients without previous diabetic treatments: a post hoc analysis of the CONTROLING randomized control trial
Authors: Thouy François , Bohé Julien , Souweine Bertrand , Abidi Hassane , Quenot Jean-Pierre , Thiollière Fabrice , Dellamonica Jean , Preiser Jean-Charles , Timsit Jean-François , Brunot Vincent , Klich Amna , Sedillot Nicholas , Tchenio Xavier , Roudaut Jean-Baptiste , Mottard Nicolas , Hyvernat Hervé , Wallet Florent , Danin Pierre-Eric , Badie Julio , Jospe Richard , Morel Jérôme , Mofredj Ali , Fatah Abdelhamid , Drai Jocelyne , Mialon Anne , Ait Hssain Ali , Lautrette Alexandre , Fontaine Eric , Vacheron Charles-Hervé , Maucort-Boulch Delphine , Klouche Kada , Dupuis Claire
Published: May 2022

Background

Stress hyperglycemia can persist during an intensive care unit (ICU) stay and result in prolonged requirement for insulin (PRI). The impact of PRI on ICU patient outcomes is not known. We evaluated the relationship between PRI and Day 90 mortality in ICU patients without previous diabetic treatments.

Methods

This is a post hoc analysis of the CONTROLING trial, involving 12 French ICUs. Patients in the personalized glucose control arm with an ICU length of stay ≥ 5 days and who had never previously received diabetic treatments (oral drugs or insulin) were included. Personalized blood glucose targets were estimated on their preadmission usual glycemia as estimated by their glycated A1c hemoglobin (HbA1C). PRI was defined by insulin requirement. The relationship between PRI on Day 5 and 90-day mortality was assessed by Cox survival models with inverse probability of treatment weighting (IPTW). Glycemic control was defined as at least one blood glucose value below the blood glucose target value on Day 5.

Results

A total of 476 patients were included, of whom 62.4% were male, with a median age of 66 (54–76) years. Median values for SAPS II and HbA1C were 50 (37.5–64) and 5.7 (5.4–6.1)%, respectively. PRI was observed in 364/476 (72.5%) patients on Day 5. 90-day mortality was 23.1% in the whole cohort, 25.3% in the PRI group and 16.1% in the non-PRI group (p < 0.01). IPTW analysis showed that PRI on Day 5 was not associated with Day 90 mortality (IPTWHR = 1.22; CI 95% 0.84–1.75; p = 0.29), whereas PRI without glycemic control was associated with an increased risk of death at Day 90 (IPTWHR = 3.34; CI 95% 1.26–8.83; p < 0.01).

Conclusion

In ICU patients without previous diabetic treatments, only PRI without glycemic control on Day 5 was associated with an increased risk of death. Additional studies are required to determine the factors contributing to these results.
Traditional acupuncture and laser acupuncture in chronic nonspecific neck pain: study protocol for a randomized controlled trial
Authors: Peron Rafaela , Rampazo Érika Patrícia , Liebano Richard Eloin
Published: May 2022

Background

Nonspecific neck pain is a multifactorial and very common condition in adult individuals, traditional acupuncture (TA) and laser acupuncture (LA) may be treatment options for certain individuals in such a condition. However, no reports were found in the literature comparing the effectiveness of TA and LA in cases of chronic nonspecific neck pain. Therefore, the aim of the present study is to investigate the effectiveness of TA and LA therapies in individuals with chronic nonspecific neck pain, noting which one is more efficient for this condition. The result of this research will have direct implications for pain management and, consequently, may benefit individuals suffering from nonspecific chronic neck pain.

Methods/design

This will be a controlled and randomized clinical trial. Eighty-four individuals will be recruited and distributed equally and randomly into 3 groups: TA (which will receive the acupuncture treatment with needles), LA (which will receive the laser acupuncture treatment), and Sham (who will receive the placebo intervention). The acupuncture points (Tianzhu,Fengchi,Jianjing, andJianzhongshu) will be stimulated bilaterally. The primary outcome will be pain intensity, determined using the Numerical Rating Scale. The secondary outcomes will be pressure pain threshold, temporal summation of pain, conditioned pain modulation, use of analgesic medicines after treatment, and the global perceived effect scale. The assessments will be performed immediately before and after the treatment, which will be a single session, at the follow-up and 1 month after the end of the treatments; evaluation will be made of the pain intensity and the global perceived effect. Statistical analysis of the data obtained will consider a significance level ofp< 0.05.

Discussion

This study will provide evidence concerning the effects of LA treatment, in comparison with TA and sham intervention, leading to benefits for individuals suffering from chronic nonspecific neck pain.

Trial registration

Brazilian Registry of Clinical Trials - ReBECRBR-7vbw5gd. Date of registration: August 06th, 2021.
Baricitinib decreases anti-dsDNA in patients with systemic lupus erythematosus: results from a phase II double-blind, randomized, placebo-controlled trial
Authors: Dörner Thomas , van Vollenhoven Ronald F. , Doria Andrea , Jia Bochao , Ross Terres Jorge A. , Silk Maria E. , de Bono Stephanie , Fischer Peter , Wallace Daniel J.
Published: May 2022

Background

Patients with systemic lupus erythematosus (SLE) have substantial unmet medical need. Baricitinib is a Janus kinase (JAK)1 and 2 inhibitor that was shown to have therapeutic benefit in patients with SLE in a phase II clinical trial. The purpose of this study was to evaluate the median change from baseline in conventional serologic biomarkers in subgroups and the overall population of baricitinib-treated patients with SLE, and the SLE Responder Index-4 (SRI-4) response by normalization of anti-dsDNA.

Methods

Data were assessed from the phase II trial I4V-MC-JAHH (NCT02708095). The median change from baseline in anti-dsDNA, IgG, and other conventional serologic markers was evaluated over time in patients who had elevated levels of markers at baseline, and in all patients for IgG. Median change from baseline for baricitinib treatments were compared with placebo. Among patients who were anti-dsDNA positive at baseline, SRI-4 responder rate was compared for those who stayed positive or achieved normal levels by week 24.

Results

Significant decreases of anti-dsDNA antibodies were observed in response to baricitinib 2 mg and 4 mg compared to placebo beginning at weeks 2 (baricitinib 2 mg = − 14.3 IU/mL, placebo = 0.1 IU/mL) and 4 (baricitinib 4 mg = − 17.9 IU/mL, placebo = 0.02 IU/mL), respectively, continuing through week 24 (baricitinib 2 mg = − 29.6 IU/mL, baricitinib 4 mg = − 15.1 IU/mL, placebo=3.0 IU/mL). Significant reductions from baseline of IgG levels were found for baricitinib 4 mg-treated patients compared to placebo at weeks 12 (baricitinib 4 mg = − 0.65 g/L, placebo = 0.09 g/L) and 24 (baricitinib 4 mg = − 0.60 g/L, placebo = − 0.04 g/L). For patients who were anti-dsDNA positive at baseline, no relationship between achieving SRI-4 responder and normalization of anti-dsDNA was observed by week 24.

Conclusions

Baricitinib treatment resulted in a rapid and sustained significant decrease in anti-dsDNA antibodies compared to placebo among those with positive anti-dsDNA antibodies at baseline, as well as a significant decrease in IgG levels in the 4 mg group at weeks 12 and 24. These data suggest that baricitinib may influence B cell activity in SLE. Further studies are needed to evaluate if reductions in anti-dsDNA levels with baricitinib treatment reflect the impact of baricitinib on B cell activity.

Trial registration

NCT02708095.