bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical outcomes of implantation of posterior chamber phakic intraocular lens for pathologic and non-pathologic myopia
Authors: Caixia Lin , Yawen Bai , Yuxin Fang , Xiaoxia Li , Yuhan Wang , Ke Yang , Liya Qiao
Published: April 2023

Background

To compare the clinical outcomes of posterior chamber phakic intraocular lens (pIOL) implantation for non-pathological myopia and pathological myopia.

Methods

This retrospective case series study which were conducted in Beijing Tongren Eye Center between July 2017 and Oct 2021 comprised 192 eyes of 100 consecutive patients undergoing pIOL implantation. Eyes were divided into two groups based on having pathological myopia or not. Predictability, efficacy, safety, and adverse events were compared at 6 months after pIOL implantation.

Results

Our study included 86 non-pathological myopes (171 eyes, group1) and 14 pathological myopes (21eyes, group2) to analysis. The average ages were 25.5 and 33.0, respectively, and the spherical equivalent (SE) were -9.31D and -17.50D pre-operation. Six months after pIOL implantation, the SE were 0.00 and -0.50, respectively, and the refraction changes were statistically significant (P ≤ 0.05). Six months after surgery, 76.92% and 80.41% were within ± 0.50 D of the target and 92.31% and 95.88% were within ± 1.00 D. All eyes had unchanged BCVA or gained 1 or more lines in both groups and mean BCVA both improved a line 6m after operation. The efficacy index in the two groups were 0.95 and 0.88 and the safety index were 1.20, 1.33, respectively which was significantly different (P ≤ 0.05). Over the 6-month follow-up, no cataract, pigment dispersion glaucoma, pupillary block, or other vision-threatening complications happened, either.

Conclusions

The pIOL performed well for the correction of both non-pathological and pathological myopia throughout the 6-month observation period. The clinical outcomes of pIOL implantation for non-pathological myopia are essentially equivalent to those for pathological myopia.
Multicolored MIS-C, a single-centre cohort study
Authors: Varga Petra , Balajthy András , Biró Erika , Bíró Bernadett , Reiger Zsolt , Szikszay Edit , Mogyorósy Gábor , Káposzta Rita , Szabó Tamás
Published: April 2023

Background

The aim of this study was to investigate the clinical and laboratory parameters that can predict the severity of Multisystem Inflammatory Syndrome in Children (MIS-C) at admission.

Methods

We conducted a single-center, partly retrospective, partly prospective, observational cohort study between November 1, 2020 and December 31, 2021, which included patients aged from 1 month to 19 years, meeting the diagnostic criteria of MIS-C. We categorized the patients into three subgroups based on clinical and laboratory markers and assessed the predictive value of these factors in terms of ICU administration and cardiac abnormalities.

Results

53 patients were classified in the following subgroups: Kawasaki-like disease (group 1) (47.2%, n = 25), shock with or without acute cardiac dysfunction (group 2) (32%, n = 17), fever and inflammation (group 3) (20.8%, n = 11). Subgroup analysis revealed that patients with shock and KD at initial presentation had significantly more severe manifestation of MIS-C requiring intensive care unit (ICU) treatment. Of the initial laboratory values, only CRP showed a significant difference between the 3 clinical groups, being lower in group 3. 52.6% of patients were admitted to the ICU. The median length of ICU stay was 3 days (range 3–20). ICU admission was more likely in patients with shortness of breath, renal failure (AKI) and patients with significantly increased concentrations of ferritin, D-dimer, INR and significantly milder increase concentration of fibrinogen. We found that fibrinogen and ferritin levels are independent risk factors for ICU admission. Cardiac abnormalities were found in 56.6% of total (30/53), with the following findings: decreased left ventricular function (32%), coronary abnormality (11.3%), pericardial effusion (17%), arrhythmia (32.1%) and mitral regurgitation (26.6%). Diarrhea and conjunctivitis at the initial presentation with significantly elevated CRP, Pro-BNP and blood pH concentrations were found to be a potential predisposing factor for decreased cardiac function while Pro-BNP and pH were independent risk factors for MIS-C. Regardless of the initial symptoms of MIS-C, the outcome was generally favorable.

Conclusions

Clinical characteristics and baseline laboratory values ​​may help identify patients at increased risk for severe disease outcome, such as need for intensive care, presence of shock and decreased cardiac function.

Trial registration

Participation consent was not reqired and ethical considerations were unnecessary, since we did not perform any extra interventions, only the necessary and usual therapeutic and diagnostic methods were used.
Determinants of pediatrics emergency mortality at comprehensive specialized hospitals of South nation nationalities and people region, Ethiopia, 2022: unmatched case-control study
Authors: Tsegaye Hiwot , Demelash Alebachew , Aklilu Dawit , Girma Bekahegn
Published: April 2023

Background

Globally, child mortality is remaining high, especially in sub-Saharan African countries like Ethiopia. Mortality which happens within 24 hours of admission is preventable. However, in Ethiopia little is known regarding pediatric emergency mortality. Therefore, this study was aimed to identify determinants of pediatric emergency mortality at compressive specialized hospitals found in South Nation Nationalities and people region, Southern Ethiopia.

Methods

A facility-based unmatched case-control study was conducted on 344 children (115 cases and 229 controls) at comprehensive specialized hospitals of South Nation Nationalities and people region, Ethiopia. The data collection checklist was checked for its consistency. Data were entered and cleaned for missed values by using Epi Data3.1, then exported to Stata version 14.1 for analysis. Logistic regression was done to identify the significant determinants for pediatric emergency mortality. Finally, AORs at 95% CI and P-value < 0.05 were used to declare statistical significance.

Result

A total of 344 charts were reviewed, of which 333 (97%) (112 cases and 221 controls) charts fulfilled the inclusion criteria.. In multivariable analysis, delayed diagnosis and treatment [AOR = 2.088, 95% of CI (1.128, 3.864)], acute respiratory distress syndrome [AOR = 2.804, 95% of CI (1.487, 5.250)], dehydration [AOR = 3.323, 95% of CI (1.260, 8.761)], meningitis [AOR = 5.282, 95% of CI (2.707, 10.310)], sepsis [AOR = 4.224, 95% of CI (2.220, 8.040)], accidental injury [AOR = 3.603, 95% of CI (1.877, 6.916)] and duration of sign/symptoms [AOR = 5.481, 95% of CI (2.457, 12.230)] were significantly associated with pediatric emergency mortality.

Conclusion

In the current study, delayed diagnosis and treatment, acute respiratory distress syndrome, dehydration, sepsis, meningitis, accidental injury and duration of signs/symptoms were significantly associated with pediatric emergency mortality. Healthcare professionals should identify and treat patients early at an emergency department and provide attention to patients with the above diseases. Furthermore, quality care should be provided.
Evaluating the feasibility of implementing a prescription drug misuse prevention intervention in the community: a mixed methods study
Authors: Al Rawwad Tamara , Tata Vaishnavi , Wanat Matthew A. , Campbell Danielle , Thornton Douglas
Published: April 2023

Background

This study is part of a state-wide effort to promote the safe disposal of prescription medications and mitigate prescription drug misuse. The objective of this study was to evaluate the implementation of a two-component prevention intervention through Community Prevention Organizations (CPOs) in Texas. The first component involved the distribution of in-home disposal products (IHDP) and the second focused on providing education of the risks of prescription drug misuse.

Methods

This study followed a mixed methods sequential explanatory study design. In the quantitative phase, the extent to which CPOs carried out the intervention was determined by the distribution rate – a proportion representing the number of IHDP distributed to end users from the amount of IHDP the CPO was shipped. This measure was used to organize the CPOs in to one of three performance categories. In the qualitative arm of the study, stratified random sampling was used to select five CPOs from each performance strata to participate in an in-depth, semi-structured interview about their distribution activity. The interview guide and the data analysis were guided by Bowen’s Feasibility Framework. The interviews were transcribed and analyzed using a content analysis approach by two research team members. All qualitative analyses were conducted in ATLAS.ti© V7.

Results

There was a total of 47 CPOs contacted and asked to be part of this study. Of them, 44 CPOs participated in the quantitative phase of the study. This phase revealed that all CPOs had existing relationships with organizations throughout the community such as pharmacies and schools that could act as points of distribution. Following the quantitative phase, 15 CPOs were selected for more in-depth interviews about their distribution practices. In the qualitative phase, this finding was reinforced through the theme “partnerships with local institutions and ability to implement the intervention at community events”. Similarly, education promotion efforts were unanimously emphasized as a strategy to increase utilization of IHDP among end users. All CPOs indicated that the intervention was supplemental to their overall goals.

Conclusion

CPOs have unparalleled access to community events, local institutions, and the general population they serve, thus, they have the potential to be active facilitators in implementing prevention interventions.
Epidemiology and prevalence of tobacco use in Tehran; a report from the recruitment phase of Tehran cohort study
Authors: Shafiee Akbar , Oraii Alireza , Jalali Arash , Alaeddini Farshid , Saadat Soheil , Masoudkabir Farzad , Tajdini Masih , Ashraf Haleh , Omidi Negar , Heidari Amirhossein , Shamloo Alireza Sepehri , Sadeghian Saeed , Boroumand Mohamamdali , Vasheghani-Farahani Ali , Karimi Abbasali , Franco Oscar H.
Published: April 2023

Introduction

Tobacco use is a major health concern worldwide, especially in low/middle-income countries. We aimed to assess the prevalence of cigarette smoking, waterpipe, and pipe use in Tehran, Iran.

Methods

We used data from 8272 participants of the Tehran Cohort Study recruitment phase. Tobacco use was defined as a positive answer to using cigarettes, waterpipes, or pipes. Participants who did not report tobacco use during the interview but had a previous smoking history were categorized as former users. Age- and sex-weighted prevalence rates were calculated based on the national census data, and characteristics of current and former tobacco users were analyzed.

Results

Age- and sex-weighted prevalence of current tobacco users, cigarette smokers, waterpipe, and pipe users in Tehran was 19.8%, 14.9%, 6.1%, and 0.5%, respectively. Current tobacco use was higher in younger individuals (35–45 years: 23.4% vs. ≥ 75 years: 10.4%, P < 0.001) and men compared to women (32.9% vs. 7.7% P < 0.001). The prevalence of tobacco use increased with more years of education (> 12 years: 19.3% vs. illiterate: 9.7%, P < 0.001), lower body mass index (< 20 kg/m2: 31.3% vs. ≥ 35 kg/m2: 13.8%, P < 0.001), higher physical activity (high: 23.0% vs. low: 16.4%, P < 0.001), opium (user: 66.6% vs. non-user: 16.5%, P < 0.001), and alcohol use (drinker: 57.5% vs. non-drinker: 15.4%, P < 0.001). Waterpipe users were younger (46.1 vs. 53.2 years) and had a narrower gender gap in prevalence than cigarette smokers (male/female ratio in waterpipe users: 2.39 vs. cigarette smokers: 5.47). Opium (OR = 5.557, P < 0.001) and alcohol consumption (OR = 4.737, P < 0.001) were strongly associated with tobacco use. Hypertension was negatively associated with tobacco use (OR = 0.774, P = 0.005).

Conclusion

The concerning prevalence of tobacco use in Tehran and its large gender gap for cigarette and waterpipe use warrant tailored preventive policies.
How do women comply with cancer screenings? A study in four regions of France
Authors: Duchange Nathalie , Poiseuil Marie , Rollet Quentin , Piette Christine , Cosson Mathilde , Quertier Marie-Christine , Moutel Grégoire , Darquy Sylviane
Published: April 2023

Background

This article looks at the behaviour of women facing different cancer screening options available to them from the age of 50 onward. The study was conducted in 2019 in four departments of the French territory with the objective of identifying the factors that influence acceptance of a population-based screening proposal.

Methods

A questionnaire was sent to women who had received three invitations to organised screenings (OS) for both breast and colorectal cancer. The categories of participants in both OS were designed from data from the regional cancer screening coordination centres in each department. Participation in opportunistic cervical cancer screening was evaluated as self-reported data.

Results

4,634 questionnaires were returned out of the 17,194 sent, giving a global return rate of 27%. The highest rate of return (73.5%) was obtained from women who had participated at least once in both breast and colorectal cancer OS. An intermediate rate was obtained from women participating in breast cancer OS only (18.7%). Poor levels of return came from women who had participated in colorectal cancer OS only (3.6%) and from non-participants (4.1%). Our results suggest that women with lower educational levels tend to be the most regular attendants at OS (50.3%), compared to highly educated women (39.7%). 11.8% of women were overdue in their opportunistic cervical cancer screening. This percentage rose to 35.4% in the category of non-participants. In addition, women’s comments provide a better understanding of the reasons for irregular attendance and non-participation.

Conclusion

Overall, similar behaviours towards screening were observed in the four departments. Our analysis suggests that participation in one cancer OS increases the likelihood of participating in others. This adhesion could be an interesting lever for raising women’s awareness of other cancer screenings.
Delay in seeking treatment and associated factors among women with pelvic organ prolapse in Wolaita zone, Southern Ethiopia: Hospital based mixed method study
Authors: Shitu Adisu Worku , Wana Ermias Wabeto , Darebo Tadele Dana , Mune Zewdu Berhanu
Published: April 2023

Background

Despite increasing efforts to improve access to diagnosis and treatment services, women with pelvic organ prolapse tend to stay at home for years before getting treatment. A large number of women, particularly in rural areas do not get early diagnosis and treatment, and they come with an advanced stage; but the reason for this appears unclear. Thus, this study aimed to determine the proportion and associated factors of delay in seeking treatment among women with pelvic organ prolapse (POP) in the Wolaita zone, Southern Ethiopia.

Methods

A hospital-based cross-sectional study mixed with qualitative method was conducted in the Wolaita zone, Southern Ethiopia, from September to October 2021. A total of 422 women with pelvic organ prolapse were selected by systematic random sampling for quantitative data. The women recruited for in-depth interviews were purposefully selected until data saturation reaches via phenomenological study design. The quantitative data were collected by interviewer-administered questionnaire and reviewing clients’ medical records via an open data kit and then exported to and analyzed with a statistical package for social science version 25. The associated variables were determined by conducting a logistic regression model and are presented with the crude odds ratio (COR) and adjusted odds ratio (AOR) with their respective 95% confidence intervals (95%CI). All statistical tests were conducted at a 5% level of significance. The interview was first transcribed, coded, and categories and themes were generated by applying thematic analysis.

Results

The study showed that 82.0% (95% CI: [74.8-89.3%]) of women with POP delayed seeking treatment. The delay to seek treatment was associated with a lack of support (AOR = 4.9; 95% CI [1.8–13.2]), low-income (AOR = 6.4; 95% CI [2.2–19.2]), fear of disclosure (AOR = 5.0; 95% CI [1.3–19.2]) and fear of social stigma (AOR = 4.6; 95% CI [1.5–14.2]). The reasons for the delay were feeling shameful to disclose, fear of stigma and cultural and spiritual beliefs.

Conclusions

More than three-fourths of women with POP delayed seeking treatment, and improving support, improving the economy, raising awareness, and involving influential people in interventions are all necessary to avert it.
Perception versus reality: analysis of time spent on bedside rounds in an academic ICU (Intensive Care Unit)
Authors: Ahmed Haroon , King Austin B. , Mohamed Nada , Mokaya Erica , Chapman Kyle , Leonard Rachel
Published: April 2023

Background

Despite its importance, teaching at the bedside is declining over time. This purported decline has not been quantified. Quantifying bedside teaching is challenging, and we found only one study quantifying bedside teaching on a hospitalist service.

Objective

We conducted a study to understand the prevalence of bedside teaching in our medical intensive care unit.

Methods

We conducted a single-center single-unit study in the medical intensive care unit of an academic tertiary care institution. We used a survey tool to assess perceived time spent on bedside teaching, quality of teaching, and total rounding time. In parallel, independent observers objectively measured time spent on rounds and on bedside teaching. Residents were asked to complete the survey once a week. Independent observers collected data daily and weekly averages were obtained.

Results

43 responses were collected over a 4-month period. Most respondents (73%) reported a total rounding time of either 90–120 min or greater than 120 min. Median reported bedside teaching time was 16–20 min with 16 respondents (37%) reporting less than 15 min and 27 respondents (63%) reporting 16 min or more. The amount of time spent on bedside teaching was reported as adequate or more than adequate by 77% (33) of respondents with 58% (25) reporting that bedside teaching was very or extremely effective in helping them learn. Mean census reported by the independent observers was 12.75 patients per team. Bedside teaching represented an average of 12% of total rounding time, 16.85 min per day. While total rounding time increased with increasing census, there was no decline in bedside teaching time.

Conclusion

It is reported that bedside teaching has decreased over time. Our study has demonstrated that bedside teaching occurs in our Medical ICU, and though it represents a minority of the time spent on rounds, residents still reported teaching in the ICU to be adequate.
De novo variation in EP300 gene cause Rubinstein-Taybi syndrome 2 in a Chinese family with severe early-onset high myopia
Authors: Huang Xiaoyu , Rui Xue , Zhang Shuang , Qi Xiaolong , Rong Weining , Sheng Xunlun
Published: April 2023

Background

Rubinstein-Taybi syndrome (RSTS) is characterized by distinctive facial features, broad and often angulated thumbs and halluces, short stature, and moderate-to-severe intellectual disability, classified into two types RSTS1 (CREBBP-RSTS) and RSTS2 (EP300-RSTS). More often, the clinical features are inconclusive and the diagnosis of RSTS is established in a proband with identification of a heterozygous pathogenic variant in CREBBP or EP300 to confirm the diagnosis.

Methods

In this study, to describe an association between the clinical phenotype and the genotype of a RSTS2 patient who was initially diagnosed with severe early-onset high myopia (eoHM) from a healthy Chinese family, we tested the proband of this family by whole exome sequencing (WES) and further verified among other family members by Sanger sequencing. Real-time quantitative PCR was used to detect differences in the relative mRNA expression of candidate genes available in the proband and family members. Comprehensive ophthalmic tests as well as other systemic examinations were also performed on participants with various genotypes.

Results

Whole-exome sequencing revealed that the proband carried the heterozygous frameshift deletion variant c.3714_3715del (p.Leu1239Glyfs*3) in the EP300 gene, which was not carried by the normal parents and young sister as verified by Sanger sequencing, indicating that the variant was de novo. Real-time quantitative PCR showed that the mRNA expression of EP300 gene was lower in the proband than in other normal family members, indicating that such a variant caused an effect on gene function at the mRNA expression level. The variant was classified as pathogenic as assessed by the interpretation principles of HGMD sequence variants and ACMG guidelines. According to ACMG guidelines, the heterozygous frameshift deletion variant c.3714_3715del (p.Leu1239Glyfs*3) in the EP300 gene was more likely the pathogenic variant of this family with RSTS2.

Conclusions

Therefore, in this paper, we first report de novo heterozygous variation in EP300 causing eoHM-RSTS. Our study extends the genotypic spectrums for EP300-RSTS and better assists physicians in predicting, diagnosis, genetic counseling, eugenics guidance and gene therapy for EP300-RSTS.
Early events marking lung fibroblast transition to profibrotic state in idiopathic pulmonary fibrosis
Authors: Jia Minxue , Rosas Lorena , Kapetanaki Maria G. , Tabib Tracy , Sebrat John , Cruz Tamara , Bondonese Anna , Mora Ana L. , Lafyatis Robert , Rojas Mauricio , Benos Panayiotis V.
Published: April 2023

Background

Idiopathic Pulmonary Fibrosis (IPF) is an age-associated progressive lung disease with accumulation of scar tissue impairing gas exchange. Previous high-throughput studies elucidated the role of cellular heterogeneity and molecular pathways in advanced disease. However, critical pathogenic pathways occurring in the transition of fibroblasts from normal to profibrotic have been largely overlooked.

Methods

We used single cell transcriptomics (scRNA-seq) from lungs of healthy controls and IPF patients (lower and upper lobes). We identified fibroblast subclusters, genes and pathways associated with early disease. Immunofluorescence assays validated the role of MOXD1 early in fibrosis.

Results

We identified four distinct fibroblast subgroups, including one marking the normal-to-profibrotic state transition. Our results show for the first time that global downregulation of ribosomal proteins and significant upregulation of the majority of copper-binding proteins, including MOXD1, mark the IPF transition. We find no significant differences in gene expression in IPF upper and lower lobe samples, which were selected to have low and high degree of fibrosis, respectively.

Conclusions

Early events during IPF onset in fibroblasts include dysregulation of ribosomal and copper-binding proteins. Fibroblasts in early stage IPF may have already acquired a profibrotic phenotype while hallmarks of advanced disease, including fibroblast foci and honeycomb formation, are still not evident. The new transitional fibroblasts we discover could prove very important for studying the role of fibroblast plasticity in disease progression and help develop early diagnosis tools and therapeutic interventions targeting earlier disease states.
Overcoming insecticide resistance in Anopheles mosquitoes by using faster-acting solid forms of deltamethrin
Authors: Carson Jessica , Erriah Bryan , Herodotou Stephania , Shtukenberg Alexander G. , Smith Leilani , Ryazanskaya Svetlana , Ward Michael D. , Kahr Bart , Lees Rosemary Susan
Published: April 2023

Background

Controlling malaria-transmitting Anopheles mosquitoes with pyrethroid insecticides is becoming increasingly challenging because of widespread resistance amongst vector populations. The development of new insecticides and insecticidal formulations is time consuming and costly, however. A more active crystalline form of deltamethrin, prepared by heating the commercial crystalline form, previously was reported to be 12-times faster acting against susceptible North American Anopheles quadrimaculatus mosquitoes. Herein the potential for heat-activated deltamethrin dispersed on chalk to overcome various resistance mechanisms amongst five West African Anopheles strains is investigated, and its long-term sustained lethality evaluated.

Methods

The more active deltamethrin form was generated in a commercial dust containing deltamethrin by heating the material as purchased. Tarsal contact bioassays were conducted to investigate its efficacy, potency, and speed of action against resistant Anopheles populations compared to the commercially available form of deltamethrin dust.

Results

In all cases, D-Fense Dust heated to generate the more active form of deltamethrin was substantially more effective than the commercially available formulation. 100% of both Banfora M and Kisumu populations were knocked down 10 min post-exposure with no recovery afterwards. Gaoua-ara and Tiefora strains exhibited 100% knockdown within 15 min, and the VK7 2014 strain exhibited 100% knockdown within 20 min. In all cases, 100% mortality was observed 24 h post-exposure. Conversely, the commercial formulation (unheated) resulted in less than 4% mortality amongst VK7 2014, Banfora, and Gaoua-ara populations by 24 h, and Tiefora and Kisumu mosquitoes experienced 14 and 47% mortality by 24 h, respectively. The heat-activated dust maintained comparable efficacy 13 months after heating.

Conclusions

The heat-activated form of commercial deltamethrin D-Fense Dust outperformed the material as purchased, dramatically increasing efficacy against all tested pyrethroid-resistant strains. This increase in lethality was retained for 13 months of storage under ambient conditions in the laboratory. Higher energy forms of commonly used insecticides may be employed to overcome various resistance mechanisms seen in African Anopheles mosquitoes through more rapid uptake of insecticide molecules from their respective solid surfaces. That is, resistant mosquitoes can be killed with an insecticide to which they are resistant without altering the molecular composition of the insecticide.
Stability of different fixation methods after reduction malarplasty under average and maximum masticatory forces: a finite element analysis
Authors: Al-Watary Mohammed Qasem , Gao Heyou , Song Libin , He Yingyou , Wei Yiyuan , Li Jihua
Published: April 2023

Background

Although titanium plates/screws are effective fixation methods (FM) after L-shaped osteotomy reduction malarplasty (LORM), the ideal FM remains controversial. This first finite element analysis (FEA) aimed to study the effect of various zygomatic body/zygomatic arch FM combinations and their placement vectors on the zygoma complex stability after virtual LORM under the effect of both average (150 N/mm2) and maximum (750 N/mm2) forces and three-dimensional (3D) mapping of stress and strain parameters distribution over the zygomatic bone, fixation methods, and total model.

Results

The fixation methods about the short-arm of the L-shaped osteotomy showed lower stress, strain, and displacement values than those across the long-arm osteotomy site. Combined with any zygomatic arch fixation methods (ZAFm), the two bicortical screws group (2LS) on the zygomatic body osteotomy site resulted in smaller displacements and the lowest zygoma bone stress and displacement when combined with Mortice–Tenon structure (MT) as zygomatic arch fixation method. Applied forces caused statistically significant differences in zygomatic bone stress (P < 0.001 and P = 0.001) and displacement (P = 0.001 and P = 0.002).

Conclusion

All FMs both on the zygomatic body and zygomatic arch provide adequate zygomatic complex stability after LORM. The 2LS group showed better resistance than rectangular plate (RP) and square plate (SP) with lower stress concentrations. The L-shaped plate with short-wing on the maxilla (LPwM) is more stable than having the short-wing on the zygoma bone (LPwZ). Future prospective clinical studies are required to validate the current findings.
Application of next-generation sequencing on diagnosis of bloodstream infection caused by Mycoplasma hominis in a patient with ANCA-associated vasculitis
Authors: Chen Yili , Chen Hengxin , Huang Hao , Zhong Yinyin , Lin Xiaoshu , Chen Peisong , Liao Kang , Yang Juhua , Liu Min , Hong Mengzhi , Wang Ruizhi
Published: April 2023

Background

Mycoplasma hominis is one of the main opportunistic pathogenic mycoplasmas in humans which has a major impact on patients with bloodstream infections. Because it is difficult to detect or isolate, rapid and accurate diagnosis using improved methods is essential and still challenging for patients with bloodstream infection.

Case presentation

In this case, we reported the application of next -generation sequencing for the diagnosis of bloodstream infection caused by Mycoplasma hominis in a patient with Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. After 9 days of combined treatment with levofloxacin, polymyxin B and meropenem, the patient’s condition was gradually controlled and he was discharged without further complications. During the three-month outpatient follow-up, no recurrence of symptoms or clinical signs was reported.

Conclusions

This successful application of next generation sequencing assisted the rapid diagnosis of Mycoplasma hominis bloodstream infection, provided a new perspective in the clinical approach and highlighted the potential of this technique in rapid etiological diagnosis.
PP1γ regulates neuronal insulin signaling and aggravates insulin resistance leading to AD-like phenotypes
Authors: Yadav Yamini , Sharma Medha , Dey Chinmoy Sankar
Published: April 2023

Background

PP1γ is one of the isoforms of catalytic subunit of a Ser/Thr phosphatase PP1. The role of PP1γ in cellular regulation is largely unknown. The present study investigated the role of PP1γ in regulating neuronal insulin signaling and insulin resistance in neuronal cells. PP1 was inhibited in mouse neuroblastoma cells (N2a) and human neuroblastoma cells (SH-SY5Y). The expression of PP1α and PP1γ was determined in insulin resistant N2a, SH-SY5Y cells and in high-fat-diet-fed-diabetic mice whole-brain-lysates. PP1α and PP1γ were silenced by siRNA in N2a and SH-SY5Y cells and effect was tested on AKT isoforms, AS160 and GSK3 isoforms using western immunoblot, GLUT4 translocation by confocal microscopy and glucose uptake by fluorescence-based assay.

Results

Results showed that, in one hand PP1γ, and not PP1α, regulates neuronal insulin signaling and insulin resistance by regulating phosphorylation of AKT2 via AKT2-AS160-GLUT4 axis. On the other hand, PP1γ regulates phosphorylation of GSK3β via AKT2 while phosphorylation of GSK3α via MLK3. Imbalance in this regulation results into AD-like phenotype.

Conclusion

PP1γ acts as a linker, regulating two pathophysiological conditions, neuronal insulin resistance and AD.
Gasdermin E regulates the stability and activation of EGFR in human non-small cell lung cancer cells
Authors: Xu Limei , Shi Feifei , Wu Yingdi , Yao Shun , Wang Yingying , Jiang Xukai , Su Ling , Liu Xiangguo
Published: April 2023

Background

Lung cancer is the most lethal malignancy, with non-small cell lung cancer (NSCLC) being the most common type (~ 85%). Abnormal activation of epidermal growth factor receptor (EGFR) promotes the development of NSCLC. Chemoresistance to tyrosine kinase inhibitors, which is elicited by EGFR mutations, is a key challenge for NSCLC treatment. Therefore, more thorough understanding of EGFR expression and dynamics are needed.

Methods

Human non-small cell lung cancer cells and HEK293FT cells were used to investigate the molecular mechanism of gasdermin E (GSDME) regulating EGFR stability by Western blot analysis, immunoprecipitation and immunofluorescence. GSDME and EGFR siRNAs or overexpression plasmids were used to characterize the functional role of GSDME and EGFR in vitro. EdU incorporation, CCK-8 and colony formation assays were used to determine the proliferation ability of non-small cell lung cancer cells.

Results

GSDME depletion reduced the proliferation of non-small cell lung cancer cells in vitro. Importantly, both GSDME-full length (GSDME-FL) and GSDME-N fragment physically interacted with EGFR. GSDME interacted with cytoplasmic fragment of EGFR. GSDME knockdown inhibited EGFR dimerization and phosphorylation at tyrosine 1173 (EGFRY1173), which activated ERK1/2. GSDME knockdown also promoted phosphorylation of EGFR at tyrosine 1045 (EGFRY1045) and its degradation.

Conclusion

These results indicate that GSDME-FL increases the stability of EGFR, while the GSDME N-terminal fragment induces EGFR degradation. The GSDME-EGFR interaction plays an important role in non-small cell lung cancer development, reveal a previously unrecognized link between GSDME and EGFR stability and offer new insight into cancer pathogenesis.
Spontaneous cancer remission after COVID-19: insights from the pandemic and their relevance for cancer treatment
Authors: Meo Concetta , Palma Giuseppe , Bruzzese Francesca , Budillon Alfredo , Napoli Claudio , de Nigris Filomena
Published: April 2023

Early in the COVID-19 pandemic, it emerged that the risk of severe outcomes was greater in patients with co-morbidities, including cancer. The huge effort undertaken to fight the pandemic, affects the management of cancer care, influencing their outcome. Despite the high fatality rate of COVID-19 disease in cancer patients, rare cases of temporary or prolonged clinical remission from cancers after SARS-CoV-2 infection have been reported. We have reviewed sixteen case reports of COVID-19 disease with spontaneous cancer reduction of progression. Fourteen cases of remission following viral infections and two after anti-SARS-CoV-2 vaccination. The immune response to COVID-19, may be implicated in both tumor regression, and progression. Specifically, we discuss potential mechanisms which include oncolytic and priming hypotheses, that may have contributed to the cancer regression in these cases and could be useful for future options in cancer treatment.
Evaluating key performance indicators of the process of care in juvenile idiopathic arthritis
Authors: Cooper Sarah M. , Currie Gillian R. , Kromm Seija , Twilt Marinka , Marshall Deborah A.
Published: April 2023

Objective

To determine whether and how often the information to measure a set of key performance indicators (KPIs) in juvenile idiopathic arthritis (JIA) is found in data collected routinely in a Pediatric Rheumatology Clinic.

Methods

A retrospective electronic chart review and administrative data analysis was conducted for a cohort of 140 patients with JIA at a tertiary Pediatric Rheumatology Clinic between 2016–2020. The set of KPIs include measuring patient outcomes (joint assessment, physician’s global assessment of disease activity, assessment of functional ability, composite disease activity measurement), access to care (waiting time between referral and first visit, visit with the rheumatologist within the first year of diagnosis, annual follow-up visits with the rheumatologist), and safety (tuberculosis screening, and laboratory monitoring). Documentation was assessed as a binary variable indicating whether the required information was ever found. Documentation frequency for each KPI was assessed with counts and percentages of the number of times the required information was documented for each clinic visit. Compliance with the safety KPI definitions was assessed using administrative databases.

Results

Data for each KPI were found at least once in the cohort and documentation varied in frequency and consistency. Access to care and safety KPIs were documented more frequently than patient outcome KPIs. A joint assessment was documented at every visit for 95% of patients, 46% for an assessment of pain, and none for a physician’s global assessment of disease activity, an assessment of functional ability, or a composite disease activity measurement.

Conclusion

Although feasible to measure, there is an opportunity for improving the consistency of documentation. Having an active system of monitoring KPIs and tools to simplify measurement is a key step in the process toward improved patient care outcomes. Streamlining the collection of KPI data can increase the likelihood of compliance. Next steps should involve replicating this study in various centres.
Estimating the risk of irreversible post-SSRI sexual dysfunction (PSSD) due to serotonergic antidepressants
Authors: Ben-Sheetrit Joseph , Hermon Yehonathan , Birkenfeld Shlomo , Gutman Yehiel , Csoka Antonei B. , Toren Paz
Published: April 2023

Background

Sexual dysfunction is a common side effect of Serotonergic antidepressants (SA) treatment, and persists in some patients despite drug discontinuation, a condition termed post-SSRI sexual dysfunction (PSSD). The risk for PSSD is unknown but is thought to be rare and difficult to assess. This study aims to estimate the risk of erectile dysfunction (ED) and PSSD in males treated with SAs.

Methods

A 19-year retrospective cohort analysis was conducted using a computerized database of the largest HMO in Israel. ED was defined by phosphodiesterase-5 inhibitors prescriptions. 12,302 males aged 21–49 met the following criteria: non-smokers, no medical or psychiatric comorbidities or medications associated with ED, no alcohol or substance use. Logistic regression was used for estimation of ED risk in SA-treated subjects compared to non-SA-treated controls, assessed with and without the effects of age, body mass index (BMI), socioeconomic status (SES), depression and anxiety, yielding crude and adjusted odds ratios (cOR and aOR, respectively).

Results

SAs were associated with an increased risk for ED (cOR = 3.6, p < 0.000001, 95% CI  2.8–4.8), which remained significant after adjusting for age, SES, BMI, depression and anxiety (aOR = 3.2, p < 0.000001, 95% CI  2.3–4.4). The risk for PSSD was 1 in 216 patients (0.46%) treated with SAs. The prevalence of PSSD was 4.3 per 100,000.

Conclusions

This work offers a first assessment of the small but significant risk of irreversible ED associated with the most commonly prescribed class of antidepressants which should enhance the process of receiving adequate informed consent for therapy.
Hyepereosiniphilic syndrome and COVID-19: 2 case reports
Authors: Sherafati Alborz , Rahmanian Mehrzad , Sattarzadeh Badkoubeh Roya , Khoshavi Meysam , Foroumandi Morteza , Peiman Soheil , Shahi Farhad , Sardari Akram , Pourkia Roghayeh , Larti Farnoosh
Published: April 2023

Background

Nearly half of the patients with hypereosinophilic syndrome (HES) have cardiovascular involvement, a major cause of mortality. COVID-19 infection can lead to cardiac involvement, negatively impacting the clinical course and prognosis. We reported two patients with HES complicated by COVID-19, with cardiac involvement and valve replacement.

Case presentation

Our first patient was a 27-year-old woman admitted due to dyspnea and signs of heart failure. She had severe mitral stenosis and mitral regurgitation on the echocardiogram. Corticosteroid therapy improved her symptoms initially, but she deteriorated following a positive COVID-19 test. A repeated echocardiogram showed right ventricular failure, severe mitral regurgitation, and torrential tricuspid regurgitation and, she underwent mitral and tricuspid valve replacement. Our second patient was a 43-year-old man with HES resulted in severe tricuspid stenosis, which was improved with corticosteroid treatment. He underwent tricuspid valve replacement due to severe valvular regurgitation. He was admitted again following tricuspid prosthetic mechanical valve thrombosis. Initial workups revealed lung involvement in favor of COVID-19 infection, and his PCR test was positive.

Conclusion

COVID-19 infection can change the clinical course of HES. It may result in a heart failure exacerbation due to myocardial injury and an increased risk of thrombosis in prosthetic valves or native vessels due to hypercoagulability.
Gab2 plays a carcinogenic role in ovarian cancer by regulating CrkII
Authors: Yin Yi , Zhang Li , Li Yong , Zhang Can , He Aiqin
Published: April 2023

Objective

To detect the expression of Growth factor binding protein 2 associated binding protein 2 (Gab2) and CT10 regulator of kinase II (CrkII) in ovarian cancer and analyze their clinical significance. To explore the effects of Gab2 and CrkII on the biological behavior of ovarian cancer cells. To analyze the possible molecular mechanism of Gab2 in the development of ovarian cancer.

Methods

Immunohistochemistry was used to detect the expression of Gab2 and CrkII in ovarian cancer. Chi square test was used to analyze the correlation between Gab2, CrkII and clinical parameters. Using Cox regression model to evaluate the risk factors affecting the prognosis. To analyze the correlation between Gab2, CrkII and survival rate by Kaplan–Meier. Cell experiments were preformed to explore the effects of Gab2 and CrkII on the biological behavior of cells. The interaction between Gab2 and CrkII was explored by immunoprecipitation.

Results

Immunohistochemistry revealed that high expression of Gab2 and CrkII in ovarian cancer. Patients with high expression of Gab2 or CrkII had higher International Federation of Gynecology and Obstetrics (FIGO) stage, grade and platinum-resistance recurrence. Multivariate analysis showed that Gab2 and CrkII were independent prognostic factors. Kaplan–Meier curve showed that the higher Gab2 and CrkII were, the poor prognosis the patients had. We observed that the overexpression of Gab2 and CrkII promoted the proliferation, metastasis and reduced chemosensitivity of cells. Conversely, the knockdown of Gab2 and CrkII resulted in the opposite results. In CrkII-knockdown cells, we found that Gab2 mediates biological behavior through CrkII.

Conclusions

The expression of Gab2 and CrkII increase in ovarian cancer. The higher expression of Gab2 and CrkII predict the poor prognosis of patients. Gab2 and CrkII promote the proliferation and migration and reduce the chemosensitivity of cells. Gab2 regulates the biological behaviors of ovarian cancer cells through CrkII.
TReating Incontinence for Underlying Mental and Physical Health (TRIUMPH): a study protocol for a multicenter, double-blinded, randomized, 3-arm trial to evaluate the multisystem effects of pharmacologic treatment strategies for urgency-predominant urinary incontinence in ambulatory older women
Authors: Huang Alison J. , Walter Louise C. , Yaffe Kristine , Vittinghoff Eric , Kornblith Erica , Schembri Michael , Chang Ann , Subak Leslee L.
Published: April 2023

Background

Urgency-type urinary incontinence affects one in four older community-dwelling women and overlaps with other common aging-associated health syndromes such as cognitive impairment, physical mobility impairment, and depression. Observational studies have raised concern about potentially higher rates of delirium and dementia in older adults taking anticholinergic bladder medications, but few prospective data are available to evaluate the effects of these and other pharmacologic treatments for urgency incontinence on cognition and other multisystem functional domains important to older women.

Methods

The TRIUMPH study is a randomized, double-blinded, 3-arm, parallel-group trial comparing the multisystem effects of anticholinergic versus beta-3-adrenergic agonist bladder therapy and versus no active bladder anti-spasmodic pharmacotherapy in older women with urgency incontinence. Women aged 60 years and older (target N = 270) who have chronic urgency-predominant urinary incontinence and either normal or mildly impaired cognition at baseline are recruited from the community by investigators based in northern California, USA. Participants are randomized in equal ratios to take identically encapsulated oral anticholinergic bladder therapy (in the form of tolterodine 2 mg extended release [ER]), oral beta-3 adrenergic agonist bladder therapy (mirabegron 25 mg ER), or placebo daily for 24 weeks, with the option of participant-directed dose titration (to tolterodine 4 mg ER, mirabegron 50 mg ER, or matching placebo daily). Participants also receive patient-oriented information and instructions about practicing first-line behavioral management strategies for incontinence. The primary outcome is change in composite cognitive function over 24 weeks assessed by a comprehensive battery of cognitive tests, with a secondary exploration of the persistence of change at 36 weeks. Secondary outcomes include changes over 24 and 36 weeks in domain-specific cognitive function; frequency, severity, and impact of urgency-associated urinary symptoms; physical function and balance; sleep quality and daytime sleepiness; psychological function; and bowel function.

Discussion

The TRIUMPH trial addresses the need for rigorous evidence to guide counseling and decision-making for older women who are weighing the potential multisystem benefits and risks of pharmacologic treatments for urgency incontinence in order to preserve their day-to-day functioning, quality of life, and independence in older age.

Trial registration

ClinicalTrials.gov NCT05362292. Registered on May 5, 2022.
Effect of a customized digital adherence tool on retention in care and adherence to antiretroviral treatment in breastfeeding women, children and adolescents living with HIV in Tanzania: a mixed-methods study followed by clinical trials
Authors: Sumari-de Boer I. Marion , Ngowi Kennedy M. , Swai Iraseni U. , Masika Lyidia V. , Maro Rehema A. , Mtenga Alan E. , Mtesha Benson A. , Nieuwkerk Pythia T. , Reis Ria , de Wit Tobias F. Rinke , Aarnoutse Rob E.
Published: April 2023

Background

Adherence to antiretroviral (ARV) treatment for HIV infection is challenging because of many factors. The World Health Organization (WHO) has recommended using digital adherence technologies (DATs). However, there is limited evidence on how DATs improve adherence. Wisepill® is an internet-enabled medication dispenser found feasible and acceptable in several studies. However, limited evidence is available on its effectiveness in improving ART adherence, specifically among children and adolescents. Furthermore, DATs are often developed without involving the target groups. We propose a two-stage project consisting of a formative study to customize an existing Wisepill DAT intervention and a randomized clinical trial to investigate the effectiveness of DAT combined with reminder cues and tailored feedback on adherence to ARV treatment among children and adolescents living with HIV and retention in care among breastfeeding women living with HIV in Kilimanjaro and Arusha Region, Tanzania.

Methods

We will conduct a formative mixed-methods study and three sub-trials in Kilimanjaro and Arusha Regions among (1) children aged 0–14 years and their caregivers, (2) adolescents aged 15–19 years and (3) breastfeeding women and their HIV-negative infants. In the formative study, we will collect and analyse data on needs and contents for DATs, including the contents of short message service (SMS) texts and tailored feedback. The results will inform the customization of the DAT to be tested in the sub-trials. In the trials, participants will be randomized in the intervention arm, where the DAT will be implemented or the control arm, where standard care will be followed. Participants in the intervention arm will take their medication from the Wisepill box and receive daily reminder texts and tailored feedback during clinic visits.

Discussion

If the intervention improves adherence to ART and the devices are acceptable, accurate and sustainable, the intervention can be scaled up within the National Aids Control Programmes.

Trial registration

PACTR202301844164954, date 27 January 2023.