bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychometric evaluation of the subjective well-being measure GP-CORE in a group of older adults in Sweden
Authors: Hochwälder Jacek , Gustafsson Lena-Karin , Östlund Gunnel , Zander Viktoria , Elfström Magnus L.
Published: November 2022

Background

The world’s growing population of older adults is one population that needs to be focused more regarding subjective well-being. It is therefore important to evaluate self-report instruments that measures general well-being for this specific group - older adults. The aim of the present study was to investigate psychometric properties of the Swedish translation of the GP-CORE (general population – Clinical Outcomes in Routine Evaluation) in a group of older adults (> 65 years).

Methods

In this study, a psychometric evaluation of the GP-CORE is presented for 247 Swedish older adults (> 65 years), 184 women and 63 men who applied for home care assistance for the first time.

Results

The psychometric evaluation showed high acceptability; provided norm values in terms of means, standard deviations and quartiles; showed satisfactory reliability in terms of both internal consistency and stability; showed satisfactory validity in terms of convergent and discriminant validity; provided a very preliminary cut-off value and quite low sensibility and sensitivity and showed results which indicated that this scale is sensitive to changes. One gender difference was identified in that women without a cohabitant had a higher well-being than men without a cohabitant (as measured by GP-CORE).

Conclusions

The GP-CORE showed satisfactory psychometric properties to be used to measure and monitor subjective well-being in older adults (> 65 years) in the general population of community dwelling. Future studies should establish a cut-off value in relation to another well-being measure relevant for mental health in older adults.
Neutrophil CD64 index as a superior indicator for diagnosing, monitoring bacterial infection, and evaluating antibiotic therapy: a case control study
Authors: Gao Yanting , Lin Lihui , Zhao Jinyan , Peng Xia , Li Li
Published: November 2022

Background

Neutrophil CD64 (nCD64) index has been widely studied as an indication of bacteria-infected diseases, but the exact usage of nCD64 index in monitoring infections remains debated. So this study aims to investigate the functionality of nCD64 index in tracking infections’ progression and evaluating antibiotic therapy.

Methods

160 participants (36 healthy controls, 34 culture-negative patients, 56 respiratory tract infected patients, and 34 bloodstream infected patients) were recruited and divided into groups. Data on nCD64 index, T lymphocyte subsets, and conventional indicators, including white blood cell count, neutrophil to lymphocyte ratio, procalcitonin, and C-reactive protein, were tested and compared.

Results

Bacteria-infected patients had significantly higher nCD64 indexes (p < 0.05), especially patients with both bloodstream and respiratory tract infections. The nCD64 index could identify infected patients from culture-negative patients or controls, which conventional indicators cannot achieve. We followed up with 24 infected patients and found that their nCD64 indexes were promptly down-regulated after effective antibiotic therapy (3.16 ± 3.01 vs. 1.20 ± 1.47, p < 0.001).

Conclusion

The nCD64 index is a sensitive indicator for clinical diagnosis of bacterial infection, especially in monitoring infection and evaluating antibiotics’ efficacy. Therefore, nCD64 has the potential to improve diagnostic accuracy and provide rapid feedback on monitoring disease progression in infected patients.
Frequency and functional profile of circulating TCRαβ+ double negative T cells in HIV/TB co-infection
Authors: Tan Yuting , Zou Shi , Guo Wei , Xiang Yanni , Dong Yu , Zhu Qi , Wu Songjie , Luo Mingqi , Shen Ling , Liang Ke
Published: November 2022

Background

Increased frequency of circulating double negative T (DNT, CD4−CD8−CD3+) cells with protective immune function has been observed in human immunodeficiency virus (HIV) infection and tuberculosis (TB). Here the role of circulating TCRαβ+ DNT cells was further investigated in HIV/TB co-infection.

Methods

A cross-sectional study was conducted to investigate the frequency and functional profiles of peripheral TCRαβ+ DNT cells including apoptosis, chemokine and cytokine expression among healthy individuals and patients with TB, HIV infection and HIV/TB co-infection by cell surface staining and intracellular cytokine staining combined with flow cytometry.

Results

Significantly increased frequency of TCRαβ+ DNT cells was observed in HIV/TB co-infection than that in TB (p < 0.001), HIV infection (p = 0.039) and healthy controls (p < 0.001). Compared with TB, HIV/TB co-infection had higher frequency of Fas expression (p = 0.007) and lower frequency of Annexin V expression on TCRαβ+ DNT cells (p = 0.049), and the frequency of Annexin V expression on Fas+TCRαβ+ DNT cells had no significant difference. TCRαβ+ DNT cells expressed less CCR5 in HIV/TB co-infection than that in TB (p = 0.014), and more CXCR4 in HIV/TB co-infection than that in HIV infection (p = 0.043). Compared with healthy controls, TB and HIV/TB co-infection had higher frequency of TCRαβ+ DNT cells secreting Granzyme A (p = 0.046; p = 0.005). In TB and HIV/TB co-infection, TCRαβ+ DNT cells secreted more granzyme A (p = 0.002; p = 0.002) and perforin (p < 0.001; p = 0.017) than CD4+ T cells but similar to CD8+ T cells.

Conclusions

Reduced apoptosis may take part in the mechanism of increased frequency of peripheral TCRαβ+ DNT cells in HIV/TB co-infection. TCRαβ+ DNT cells may play a cytotoxic T cells-like function in HIV/TB co-infection.
Corticosteroid treatment in severe patients with SARS-CoV-2 and chronic HBV co-infection: a retrospective multicenter study
Authors: Meng Mei , Chu Yufeng , Zhang Sheng , Li Xuechuan , Sha Jing , Wang Peng , Cui Yunliang , Han Meihong , Dong Xuan , Sun Wenqing , Zhang Zhongfa , Deng Yunxin , Wang Tao , Annane Djillali , Jia Shouqiang , Chen Dechang
Published: November 2022

Background

The impact of corticosteroids on patients with severe coronavirus disease 2019 (COVID-19)/chronic hepatitis B virus (HBV) co-infection is currently unknown. We aimed to investigate the association of corticosteroids on these patients.

Methods

This retrospective multicenter study screened 5447 confirmed COVID-19 patients hospitalized between Jan 1, 2020 to Apr 18, 2020 in seven centers in China, where the prevalence of chronic HBV infection is moderate to high. Severe patients who had chronic HBV and acute SARS-cov-2 infection were potentially eligible. The diagnosis of chronic HBV infection was based on positive testing for hepatitis B surface antigen (HBsAg) or HBV DNA during hospitalization and a medical history of chronic HBV infection. Severe patients (meeting one of following criteria: respiratory rate > 30 breaths/min; severe respiratory distress; or SpO2 ≤ 93% on room air; or oxygen index < 300 mmHg) with COVID-19/HBV co-infection were identified. The bias of confounding variables on corticosteroids effects was minimized using multivariable logistic regression model and inverse probability of treatment weighting (IPTW) based on propensity score.

Results

The prevalence of HBV co-infection in COVID-19 patients was 4.1%. There were 105 patients with severe COVID-19/HBV co-infections (median age 62 years, 57.1% male). Fifty-five patients received corticosteroid treatment and 50 patients did not. In the multivariable analysis, corticosteroid therapy (OR, 6.32, 95% CI 1.17–34.24, P = 0.033) was identified as an independent risk factor for 28-day mortality. With IPTW analysis, corticosteroid treatment was associated with delayed SARS-CoV-2 viral RNA clearance (OR, 2.95, 95% CI 1.63–5.32, P < 0.001), increased risk of 28-day and in-hospital mortality (OR, 4.90, 95% CI 1.68–14.28, P = 0.004; OR, 5.64, 95% CI 1.95–16.30, P = 0.001, respectively), and acute liver injury (OR, 4.50, 95% CI 2.57–7.85, P < 0.001). Methylprednisolone dose per day and cumulative dose in non-survivors were significantly higher than in survivors.

Conclusions

In patients with severe COVID-19/HBV co-infection, corticosteroid treatment may be associated with increased risk of 28-day and in-hospital mortality.
Epidemiological study of HPV infection in 40,693 women in Putian: a population study based on screening for high-risk HPV infection
Authors: Chen Zhanfei , Lin Hua , Zheng Jinyuan , Cai Lili , Chen Zhonghui , Li Jinqiu , Yu Liumin
Published: November 2022

Background

The infection rate of human papillomavirus (HPV) is high in the coastal regions of China. However, the infection rate among high-risk genotypes of women in Putian City is unknown. Therefore, this study aimed to analyse the epidemiology of high-risk HPV infection among women in Putian and provide a reference for the diagnosis, treatment and vaccination of cervical cancer in this region.

Methods

The data used were obtained from the Chinese government’s public health program (“Cervical and Breast Cancer Screening Project”). A total of 40,693 female cervical cell exfoliation samples screened for high-risk HPV at the Affiliated Hospital of Putian University from July 2020 to December 2021 were enrolled. DNA was extracted using a fully automatic extractor. Then, 14 high-risk genotypes of HPV were detected by polymerase chain reaction. The characteristics of HPV infection, distribution of high-risk genotypes, infection types and thinprep cytologic test (TCT) classification at different age groups were analysed.

Results

Among the 40,693 samples, 3899 were infected with HPV, with an infection rate of 9.6%. Accordingly, HPV infection rates gradually increased with age, and statistically significant differences were observed among age groups (χ2 = 74.03, P < 0.01). The infection rates of high-risk HPV52, HPV58 and HPV16 were in the top three and increased with age. Single infection was dominant (84.7%), followed by double infections (12.7%). The cervical cytology of 3899 HPV-positive people can be classified into negative for intraepithelial lesion and malignancy (NILM, 88.0%), atypical squamous cells of undetermined significance (ASC-US, 6.6%), atypical squamous cells—cannot exclude high-grade squamous intraepithelial lesion (ASC-H, 1.4%), low-grade squamous intraepithelial lesion (LSIL, 3.2%) and high-grade squamous intraepithelial lesion (HSIL, 0.8%). HPV16 infection rate increased with increasing severity of cervical cytology (χ2trend = 43.64, P < 0.01), whereas the infection rates of HPV52 (χ2trend = 13.89, P < 0.01) and HPV58 (χ2trend = 13.50, P < 0.01) showed opposite trends.

Conclusion

The infection rate of female HPV high-risk screening in this region was 9.6% and mainly involved single infections. In addition, HPV16, HPV52 and HPV58 were closely related to the severity of cervical cytology. Effective screening, vaccination and education are needed. The 9-valent vaccine will be effective in reducing cervical pre-invasive disease. It would also be reasonable to state that the rising trend in HPV infection and high grade cytology with age emphasises the need to target older women with screening. Vaccination of younger women (aged ≤ 25) will lay the foundation for better cancer outcomes in the future.
Benign food-borne type B botulism presenting as unilateral internal ophthalmoplegia: a case report
Authors: Crescenzo Francesco , Del Colle Raffaele , Ajena Domenico , Stecca Matteo , Ferigo Laura , Rossi Francesca , Turazzini Michelangelo
Published: November 2022

Background

Food-borne botulism is a rare neuromuscular junction disorder due to the effect of toxins released from Clostridium botulinum ingested by eating improperly stored food. Its classic manifestation is a rapidly evolving descending symmetrical flaccid paralysis with dysautonomia.

Case presentation

We have described a case of type B food-borne botulism with a benign clinical course characterized by an initially unilateral tonic mydriatic pupil. An extensive neurophysiological evaluation inclusive of pilocarpine eye drop(s) test, facial and limbs nerve stimulation and sudomotor tests, was decisively leading the diagnostic process.

Conclusions

The importance of what has been described here lies in underlining that it is always advisable to consider food-borne botulinum intoxication, even in the case of unilateral/asymmetrical internal ophthalmoplegia without generalized progressive involvement of the voluntary muscles.
Effectiveness of educational intervention on women’s participation to cervical cancer screening: a quasi-experimental study based on PEN-3 model
Authors: Seyrafi Niloofar , Homayuni Atefeh , Hosseini Zahra , Aghamolaei Teamur , Ghanbarnejad Amin , Mouseli Ali
Published: November 2022

Introduction

Cervical cancer is one of the most common cancer types among women in developing countries. Women’s behavior in the early detection of the disease is influenced by sociocultural factors. Thus, the present study aimed to determine the effect of an educational intervention based on PEN-3 model on women’s participation in cervical cancer screening.

Methods

The present quasi-experimental study was conducted with 160 women participants visiting health care centers in Bandar Abbas in 2021. The sampling was as a multi-stage clustering, and the participants were divided into two groups, an intervention and a control (each with 80 participants). The data collection instrument was a researcher-made questionnaire based on the PEN-3 model constructs before and 3 months after an educational intervention (a training course). The intervention involved 30 online sessions of 15–20 minutes for the intervention group while the control group did not receive any training.

Results

After the educational intervention, the mean scores of knowledge, attitude, enablers, nurturers and the Pap smear test behavior in the experimental group increased significantly compared to the control group (P < 0.05). The analysis of covariance results showed that by modulating the effect of pre-test score, there was a statistically significant difference between the intervention and control groups in the post-intervention behavior score.

Conclusion

In the light of the present findings, it can be concluded that interventions based on the PEN-3 model with a focus on knowledge -raising, changing beliefs and identifying sociocultural and environmental factors that affect cervical cancer screening behavior can prevent cervical cancer in women.
Obstructive sleep apnea and nocturnal hypoxemia in adult patients with cystic fibrosis
Authors: Welsner Matthias , Dietz-Terjung Sarah , Stehling Florian , Schulte Tim , Niehammer Ute , Gahbiche Fatma-Ezzahra , Taube Christian , Strassburg Svenja , Schoebel Christoph , Weinreich Gerhard , Sutharsan Sivagurunathan
Published: November 2022

Background

Obstructive sleep apnea (OSA), nocturnal hypoxemia and excessive daytime sleepiness (EDS) are common comorbidities in people with cystic fibrosis (pwCF). Most of the data showing this originates from children and adolescents. The aim of this study was to collect data on sleep parameters, EDS and pulmonary function from a large cohort of adult pwCF.

Methods

Full overnight polysomnography (PSG) was performed. EDS was determined using the Epworth Sleepiness Scale (ESS). Demographic and clinical data (body mass index [BMI], pulmonary function, capillary blood gases) were collected.

Results

A total of 52 adult pwCF were included (mean age 30.7 ± 8.0 years, mean percent predicted forced expiratory volume in 1 s [ppFEV1] of 52.1 ± 14.8). Overall AHI was in the normal range (4.5 ± 4.0/h); 21/52 pwCF (40%) had an apnea-hypopnea index > 5/h. Nocturnal hypoxemia was found in 25% of participants and this was associated with ppFEV1 (p = 0.014), awake oxygen saturation (SpO2; p = 0.021) and awake partial pressure of oxygen (pO2; p = 0.003); there were no significant differences in age, lung function and BMI were found for pwCF with versus without OSA (all p > 0.05). Eight pwCF (15%) had an ESS score > 10 (indicating EDS). OSA was best predicted by awake pO2 (area under the curve [AUC] 0.66, p = 0.048), while nocturnal hypoxemia was best predicted by ppFEV1 (AUC 0.74, p = 0.009), awake pO2 (AUC 0.76, p = 0.006) and awake SpO2 (AUC 0.71; p = 0.025).

Conclusion

OSA, nocturnal hypoxemia and EDS were common in adult pwCF, but no strong predictors were identified. Therefore, we suggest regular PSG and ESS scoring in adult pwCF, regardless of disease severity.
Safety and efficacy of Empagliflozin in Pakistani Muslim patients with type 2 diabetes (SAFE-PAK); a randomized clinical trial
Authors: Aamir Azizul Hasan , Raja Umar Yousaf , Qureshi Faisal Masood , Asghar Ali , Mahar Saeed Ahmed , Ahmed Ibrar , Ghaffar Tahir , Zafar Jamal , Hasan Mohammad Imtiaz , Riaz Amna , Raza Syed Abbas , Khosa Irshad Ahmed , Khan Jahanzeb , Baqar Jaffer Bin
Published: November 2022

Background

Sodium-Glucose-Co-Transporter 2 (SGLT2) inhibitor (Empagliflozin) is an effective drug in controlling blood glucose through predominantly glycosuria. Glycosuria increases the risk of genitourinary infections in diabetes. This study was aimed to establish the safety and efficacy of Empagliflozin (Group-A) versus standard care (Group-B) in Pakistani Muslim individuals with type 2 diabetes.

Methods

A multicenter, randomized clinical trial was conducted in five cities across Pakistan from July 2019 to August 2020. Patients of both genders aged 18–75 years, body mass index (BMI) ≤ 45 kg/m2, glycosylated hemoglobin (HbA1c) 7–10% (53 mmol/mol to 86 mmol/mol) and treatment-naive to Empagliflozin were included. Treatment was given for 24 weeks, and allocation was done through randomization.

Results

Out of 745 screened patients, 333 met the eligibility criteria, and a total of 244 (73.3%) patients were enrolled. More hypoglycemic events were reported in the standard care group, whereas positive urine culture, fungal infection, dehydration, and hypotension occurrence were comparable between the two groups. The 6 months mean HbA1c reduction was significant in both groups; (Group-A: 0.91 ± 0.15; p < 0.001 vs. Group-B2: 0.79 ± 0.14; p < 0.001). Efficacy comparison at 6 months revealed a significant reduction in weight and systolic blood pressure (SBP) in Group A only (Group-A: 1.4 ± 0.4 kg; p < 0.002 vs. Group-B: 0.01 ± 0.5 kg; p < 1.00), (Group-A: 5.1 ± 1.7 mmHg; p < 0.012 vs. Group-B: 2.3 ± 1.7 mmHg; p < 0.526).

Conclusions

Empagliflozin was a safe drug compared to standard care in Pakistani Muslim patients with diabetes. It was as effective as standard care in the clinical setting but achieved glycemic control by reducing weight and SBP in type 2 diabetes patients.

Trial registration

This study was registered in the NIH US National Library of Medicine clinical trials registry at Clinicaltrials.gov with the registration number: NCT04665284 on 11/12/2020.
Bullet screen in pre-clinical undergraduate pharmacology education: a survey study
Authors: Chen Yaoxing , Qi Hong , Qiu Yu , Li Juan , Zhu Liang , Wang Hao , Gao Xiaoling , Jiang Gan
Published: November 2022

Background

The lack of interaction and communication in pharmacology courses, especially since the onset of the coronavirus disease 2019 (COVID-19) pandemic, which required a fast shift to remote learning at medical schools, leads to an unsatisfactory learning outcome. New interactive teaching approaches are required to improve pharmacology learning attention and interaction in remote education and traditional classrooms.

Methods

We introduced bullet screens to pharmacology teaching. Then, a survey was distributed to first-, second- and third-year pre-clinical undergraduate medical and nursing students at the Shanghai Jiao Tong University School of Medicine from November 2020 to March 2022. We evaluated the essential features, instructional effectiveness, and entertainment value of bullet screens. Responses to structured and open-ended questions about the strengths and weaknesses of the bullet screen and overall thoughts were coded and compared between medical and nursing students.

Results

In terms of essential features, bullet screens have a high degree of acceptability among students, and this novel instructional style conveniently increased classroom interaction. Considering instructional effectiveness, bullet screen may stimulate students’ in-depth thinking. Meanwhile, students tended to use bullet-screen comments as a way to express their support rather than to make additional comments or to express their different viewpoints. The entertainment value of bullet screen was noteworthy. The lack of ideas might lead to relative differences between medical and nursing students, indicating that guiding the appropriate use of bullet screen is necessary.

Conclusions

The bullet screen may be popularized as an auxiliary teaching approach to promote interaction between teachers and students in the classroom as well as during remote education. It is an interesting and beneficial tool in pharmacology courses, yet there are several aspects of this device that should be improved for popularization.
Quality of care in the last year of life: adaptation and validation of the German “Views of Informal Carers’ Evaluation of Services – Last Year of Life – Cologne”
Authors: Dust Gloria , Schippel Nicolas , Stock Stephanie , Strupp Julia , Voltz Raymond , Rietz Christian ,   On behalf of the CoRe-Net Co-applicants
Published: November 2022

Background

To inform quality improvement and strengthen services provided in the last year of life, measuring quality of care is essential. For Germany, data on care experiences in the last year of life that go beyond diagnoses and care settings are still rare. The aim of this study was to develop and validate a German version of the ‘Views of Informal Carers’ Evaluation of Services – Short Form (VOICES-SF)’ suitable to assess the quality of care and services received across settings and healthcare providers in the German setting in the last year of life (VOICES-LYOL-Cologne).

Methods

VOICES-SF was adapted and translated following the ‘TRAPD’ team approach. Data collected in a retrospective cross-sectional survey with bereaved relatives in the region of Cologne, Germany were used to assess validity and reliability.

Results

Data from 351 bereaved relatives of adult decedents were analysed. The VOICES-LYOL-Cologne demonstrated construct validity in performing according to expected patterns, i.e. correlation of scores to care experiences and significant variability based on care settings. It further correlated with the PACIC-S9 Proxy, indicating good criterion validity. The newly added scale “subjective experiences of process and outcome of care in the last year of life” showed good internal consistency for each given care setting, except for the homecare setting. Test-retest analyses revealed no significant differences in satisfaction ratings according to the length of time since the patient’s death. Overall, our data demonstrated the feasibility of collecting patient care experiences reported by proxy-respondents across multiple care settings.

Conclusion

VOICES-LYOL-Cologne is the first German instrument to analyse care experiences in the last year of life in a comprehensive manner and encourages further research in German-speaking countries. This instrument enables the comparison of quality of care between settings and may be used to inform local and national quality improvement activities.

Trial registration

This study was registered in the German Clinical Trials Register (DRKS00011925; Date of registration: 13/06/2017).
Social risks and social needs in a health insurance exchange sample: a longitudinal evaluation of utilization
Authors: Lewis Cara C. , Jones Salene M. W. , Wellman Robert , Sharp Adam L. , Gottlieb Laura M. , Banegas Matthew P. , De Marchis Emilia , Steiner John F.
Published: November 2022

Background

Health systems are increasingly attempting to intervene on social adversity as a strategy to improve health care outcomes. To inform health system efforts to screen for social adversity, we sought to explore the stability of social risk and interest in assistance over time and to evaluate whether the social risk was associated with subsequent healthcare utilization.

Methods

We surveyed Kaiser Permanente members receiving subsidies from the healthcare exchange in Southern California to assess their social risk and desire for assistance using the Accountable Health Communities instrument. A subset of initial respondents was randomized to be re-surveyed at either three or six months later.

Results

A total of 228 participants completed the survey at both time points. Social risks were moderate to strongly stable across three and six months (Kappa range = .59-.89); however, social adversity profiles that included participants’ desire for assistance were more labile (3-month Kappa = .52; 95% CI = .41-.64 & 6-month Kappa = .48; 95% CI = .36-.6). Only housing-related social risks were associated with an increase in acute care (emergency, urgent care) six months after initial screening; no other associations between social risk and utilization were observed.

Conclusions

This study suggests that screening for social risk may be appropriate at intervals of six months, or perhaps longer, but that assessing desire for assistance may need to occur more frequently. Housing risks were associated with increases in acute care. Health systems may need to engage in screening and referral to resources to improve overall care and ultimately patient total health.
Personalized management of dyslipidemias in patients with diabetes—it is time for a new approach (2022)
Authors: Banach Maciej , Surma Stanisław , Reiner Zeljko , Katsiki Niki , Penson Peter E. , Fras Zlatko , Sahebkar Amirhossein , Paneni Francesco , Rizzo Manfredi , Kastelein John
Published: November 2022

Dyslipidemia in patients with type 2 diabetes (DMT2) is one of the worst controlled worldwide, with only about 1/4 of patients being on the low-density lipoprotein cholesterol (LDL-C) target. There are many reasons of this, including physicians’ inertia, including diabetologists and cardiologists, therapy nonadherence, but also underusage and underdosing of lipid lowering drugs due to unsuitable cardiovascular (CV) risk stratification. In the last several years there is a big debate on the risk stratification of DMT2 patients, with the strong indications that all patients with diabetes should be at least at high cardiovascular disease (CVD) risk. Moreover, we have finally lipid lowering drugs, that not only allow for the effective reduction of LDL-C and do not increase the risk of new onset diabetes (NOD), and/or glucose impairment; in the opposite, some of them might effectively improve glucose control. One of the most interesting is pitavastatin, which is now available in Europe, with the best metabolic profile within statins (no risk of NOD, improvement of fasting blood glucose, HOMA-IR, HbA1c), bempedoic acid (with the potential for the reduction of NOD risk), innovative therapies—PCSK9 inhibitors and inclisiran with no DMT2 risk increase, and new forthcoming therapies, including apabetalone and obicetrapib—for the latter one with the possibility of even decreasing the number of patients diagnosed with prediabetes and DMT2. Altogether, nowadays we have possibility to individualize lipid lowering therapy in DMT2 patients and increase the number of patients on LDL-C goal without any risk of new onset diabetes and/or diabetes control worsening, and in consequence to reduce the risk of CVD complications due to progression of atherosclerosis in this patients’ group.
Combined evaluation of arterial stiffness, glycemic control and hypertension for macrovascular complications in type 2 diabetes
Authors: Wu Zhiyuan , Yu Siqi , Zhang Haiping , Guo Zheng , Zheng Yulu , Xu Zongkai , Li Zhiwei , Liu Xiangtong , Li Xia , Chen Shuo , Zhang Jingbo , Tao Lixin , Guo Xiuhua
Published: November 2022

Background

Arterial stiffness, glycemic control and blood pressure are risk factors of macrovascular complications in type 2 diabetes. This study aimed to investigate the combined association of arterial stiffness, glycemic control and hypertension status with the occurrence of diabetic macrovascular complication.

Methods

A total of 1870 patients of diabetes were enrolled from Beijing Health Management Cohort between 2008 and 2018 as baseline, and then followed for macrovascular complication onset. We proposed a composite risk score (0–4) by arterial stiffness severity, pool glycemic control and hypertension status. Cox model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI).

Results

The mean age (SD) of this population was 59.90 (12.29) years. During a median follow-up of 4.0 years, 359 (19.2%) patients developed macrovascular complication. Compared to the normal arterial stiffness and good glycemic control group, patients with severe arterial stiffness and pool glycemic control had the highest risk of macrovascular complications (HR: 2.73; 95% CI: 1.42–5.25). Similarly, those of severe arterial stiffness and hypertension had the highest risk (HR: 2.69; 95% CI: 1.61–4.50). Patients of the composite score > 2 had a significantly increased risk of macrovascular complication.

Conclusion

This study suggested the clinical importance of combined evaluation of arterial stiffness, glycemic control and hypertension status for the risk stratification and management of macrovascular complication of type 2 diabetes.
Simultaneous saccharification and ethanologenic fermentation (SSF) of waste bread by an amylolytic Parageobacillus thermoglucosidasius strain TM333
Authors: Ibenegbu Christopher C. , Leak David J.
Published: November 2022

The starch in waste bread (WB) from industrial sandwich production was directly converted to ethanol by an amylolytic, ethanologenic thermophile (Parageobacillus thermoglucosidasius strain TM333) under 5 different simultaneous saccharification and fermentation (SSF) regimes. Crude α-amylase from TM333 was used alone or in the presence of amyloglucosidase (AMG), a starch monomerizing enzyme used in industry, with/without prior gelatinisation/liquefaction treatments and P. thermoglucosidasius TM333 fermentation compared with Saccharomyces cerevisiae as a control. Results suggest that TM333 can ferment WB using SSF with yields of 94–100% of theoretical (based on all sugars in WB) in 48 h without the need for AMG addition or any form of heat pre-treatment. This indicates that TM333 can transport and ferment all of the malto-oligosaccharides generated by its α-amylase. In the yeast control experiments, addition of AMG together with the crude α-amylase was necessary for full fermentation over the same time period. This suggests that industrial fermentation of WB starch to bio-ethanol or other products using an enhanced amylolytic P. thermoglucosidasius strain could offer significant cost savings compared to alternatives requiring enzyme supplementation.
Health effects of Indigenous language use and revitalization: a realist review
Authors: Whalen D. H. , Lewis Melissa E. , Gillson Stefanie , McBeath Brittany , Alexander Bri , Nyhan Kate
Published: November 2022

Background

Indigenous populations across the world are more likely to suffer from poor health outcomes when compared to other racial and ethnic groups. Although these disparities have many sources, one protective factor that has become increasingly apparent is the continued use and/or revitalization of traditional Indigenous lifeways: Indigenous language in particular. This realist review is aimed at bringing together the literature that addresses effects of language use and revitalization on mental and physical health.

Methods

Purposive bibliographic searches on Scopus were conducted to identify relevant publications, further augmented by forward citation chaining. Included publications (qualitative and quantitative) described health outcomes for groups of Indigenous people who either did or did not learn and/or use their ancestral language. The geographical area studied was restricted to the Americas, Australia or New Zealand. Publications that were not written in English, Spanish, French, Portuguese or German were excluded. A realist approach was followed to identify positive, neutral or negative effects of language use and/or acquisition on health, with both qualitative and quantitative measures considered.

Results

The bibliographic search yielded a total of 3508 possible publications of which 130 publications were included in the realist analysis. The largest proportion of the outcomes addressed in the studies (62.1%) reported positive effects. Neutral outcomes accounted for 16.6% of the reported effects. Negative effects (21.4%) were often qualified by such issues as possible cultural use of tobacco, testing educational outcomes in a student’s second language, and correlation with socioeconomic status (SES), health access, or social determinants of health; it is of note that the positive correlations with language use just as frequently occurred with these issues as the negative correlations did.

Conclusions

Language use and revitalization emerge as protective factors in the health of Indigenous populations. Benefits of language programs in tribal and other settings should be considered a cost-effective way of improving outcomes in multiple domains.
UBE2O ubiquitinates PTRF/CAVIN1 and inhibits the secretion of exosome-related PTRF/CAVIN1
Authors: Cen Xiaotong , Chen Qing , Wang Bin , Xu Hongjie , Wang Xu , Ling Yixia , Zhang Xiaofei , Qin Dajiang
Published: November 2022

Background

Exosomes are small vesicles released by cells, which have crucial functions in intercellular communication. Exosomes originated from cell membrane invagination and are released followed by multivesicular bodies (MVBs) fused with the cell membrane. It is known that Polymerase I and Transcript Release Factor (PTRF, also known as Caveolin-associated Protein-1, CAVIN1) plays an important role in caveolae formation and exosome secretion. And PTRF in exosomes has been identified as a potential biomarker in multiple malignancies such as glioma and renal cell carcinoma. However, the mechanisms of how to regulate the secretion of exosome-related PTRF remain unknown.

Methods

We performed exogenous and endogenous immunoprecipitation assays to investigate the interaction between ubiquitin-conjugating enzyme E2O (UBE2O) and PTRF. We identified UBE2O ubiquitinated PTRF using ubiquitination assays. Then, exosomes were isolated by ultracentrifugation and identified by transmission electronic microscopy, western blot and nanoparticle tracking analysis. The effect of UBE2O on the secretion of exosome-related PTRF was analyzed by western blot, and the effect of UBE2O on exosome secretion was evaluated by exosome markers and the total protein content of exosomes.

Results

Here, we showed that UBE2O interacts with PTRF directly and ubiquitinates PTRF. Functionally, we found that UBE2O inhibited the effects of PTRF on exosome secretion via decreasing caveolae formation. Importantly, UBE2O decreased exosome secretion, resulting in downregulating PTRF secretion via exosomes. Our study also identified Serum Deprivation Protein Response (SDPR, also known as Caveolin-associated Protein-2, CAVIN2) interacted with both UBE2O and PTRF. Furthermore, we found that SDPR promotes PTRF expression in exosomes. Interestingly, even in the presence of SDPR, UBE2O still inhibited the secretion of exosome-related PTRF.

Conclusions

Our study demonstrated that UBE2O downregulated exosome release and controlled the secretion of exosome-related PTRF through ubiquitinating PTRF. Since exosomes play an important role in malignant tumor growth and PTRF included in exosomes is a biomarker for several malignant tumors, increasing UBE2O expression in cells has the potential to be developed as a novel approach for cancer treatment.
Unveiling the transcriptomic landscape and the potential antagonist feedback mechanisms of TGF-β superfamily signaling module in bone and osteoporosis
Authors: Wang Ying-Wen , Lin Wen-Yu , Wu Fang-Ju , Luo Ching-Wei
Published: November 2022

Background

TGF-β superfamily signaling is indispensable for bone homeostasis. However, the global expression profiles of all the genes that make up this signaling module in bone and bone-related diseases have not yet been well characterized.

Methods

Transcriptomic datasets from human bone marrows, bone marrow-derived mesenchymal stem cells (MSCs) and MSCs of primary osteoporotic patients were used for expression profile analyses. Protein treatments, gene quantification, reporter assay and signaling dissection in MSC lines were used to clarify the interactive regulations and feedback mechanisms between TGF-β superfamily ligands and antagonists. Ingenuity Pathway Analysis was used for network construction.

Results

We identified TGFB1 in the ligand group that carries out SMAD2/3 signaling and BMP8A, BMP8B and BMP2 in the ligand group that conducts SMAD1/5/8 signaling have relatively high expression levels in normal bone marrows and MSCs. Among 16 antagonist genes, the dominantly expressed TGF-β superfamily ligands induced only NOG, GREM1 and GREM2 via different SMAD pathways in MSCs. These induced antagonist proteins further showed distinct antagonisms to the treated ligands and thus would make up complicated negative feedback networks in bone. We further identified TGF-β superfamily signaling is enriched in MSCs of primary osteoporosis. Enhanced expression of the genes mediating TGF-β-mediated SMAD3 signaling and the genes encoding TGF-β superfamily antagonists served as significant features to osteoporosis.

Conclusion

Our data for the first time unveiled the transcription landscape of all the genes that make up TGF-β superfamily signaling module in bone. The feedback mechanisms and regulatory network prediction of antagonists provided novel hints to treat osteoporosis.
Evaluating the frequency and the impact of pharmacogenetic alleles in an ancestrally diverse Biobank population
Authors: Verma Shefali S. , Keat Karl , Li Binglan , Hoffecker Glenda , Risman Marjorie ,   Regeneron Genetics Center, Sangkuhl Katrin , Whirl-Carrillo Michelle , Dudek Scott , Verma Anurag , Klein Teri E. , Ritchie Marylyn D. , Tuteja Sony
Published: November 2022

Background

Pharmacogenomics (PGx) aims to utilize a patient’s genetic data to enable safer and more effective prescribing of medications. The Clinical Pharmacogenetics Implementation Consortium (CPIC) provides guidelines with strong evidence for 24 genes that affect 72 medications. Despite strong evidence linking PGx alleles to drug response, there is a large gap in the implementation and return of actionable pharmacogenetic findings to patients in standard clinical practice. In this study, we evaluated opportunities for genetically guided medication prescribing in a diverse health system and determined the frequencies of actionable PGx alleles in an ancestrally diverse biobank population.

Methods

A retrospective analysis of the Penn Medicine electronic health records (EHRs), which includes ~ 3.3 million patients between 2012 and 2020, provides a snapshot of the trends in prescriptions for drugs with genotype-based prescribing guidelines (‘CPIC level A or B’) in the Penn Medicine health system. The Penn Medicine BioBank (PMBB) consists of a diverse group of 43,359 participants whose EHRs are linked to genome-wide SNP array and whole exome sequencing (WES) data. We used the Pharmacogenomics Clinical Annotation Tool (PharmCAT), to annotate PGx alleles from PMBB variant call format (VCF) files and identify samples with actionable PGx alleles.

Results

We identified ~ 316.000 unique patients that were prescribed at least 2 drugs with CPIC Level A or B guidelines. Genetic analysis in PMBB identified that 98.9% of participants carry one or more PGx actionable alleles where treatment modification would be recommended. After linking the genetic data with prescription data from the EHR, 14.2% of participants (n = 6157) were prescribed medications that could be impacted by their genotype (as indicated by their PharmCAT report). For example, 856 participants received clopidogrel who carried CYP2C19 reduced function alleles, placing them at increased risk for major adverse cardiovascular events. When we stratified by genetic ancestry, we found disparities in PGx allele frequencies and clinical burden. Clopidogrel users of Asian ancestry in PMBB had significantly higher rates of CYP2C19 actionable alleles than European ancestry users of clopidrogrel (p < 0.0001, OR = 3.68).

Conclusions

Clinically actionable PGx alleles are highly prevalent in our health system and many patients were prescribed medications that could be affected by PGx alleles. These results illustrate the potential utility of preemptive genotyping for tailoring of medications and implementation of PGx into routine clinical care.
A non-destructive approach for measuring rice panicle-level photosynthetic responses using 3D-image reconstruction
Authors: Dharni Jaspinder Singh , Dhatt Balpreet Kaur , Paul Puneet , Gao Tian , Awada Tala , Bacher Harel , Peleg Zvi , Staswick Paul , Hupp Jason , Yu Hongfeng , Walia Harkamal
Published: November 2022

Background

Our understanding of the physiological responses of rice inflorescence (panicle) to environmental stresses is limited by the challenge of accurately determining panicle photosynthetic parameters and their impact on grain yield. This is primarily due to the lack of a suitable gas exchange methodology for panicles and non-destructive methods to accurately determine panicle surface area.

Results

To address these challenges, we have developed a custom panicle gas exchange cylinder compatible with the LiCor 6800 Infra-red Gas Analyzer. Accurate surface area measurements were determined using 3D panicle imaging to normalize the panicle-level photosynthetic measurements. We observed differential responses in both panicle and flag leaf for two temperate Japonica rice genotypes (accessions TEJ-1 and TEJ-2) exposed to heat stress during early grain filling. There was a notable divergence in the relative photosynthetic contribution of flag leaf and panicles for the heat-tolerant genotype (TEJ-2) compared to the sensitive genotype (TEJ-1).

Conclusion

The novelty of this method is the non-destructive and accurate determination of panicle area and photosynthetic parameters, enabling researchers to monitor temporal changes in panicle physiology during the reproductive development. The method is useful for panicle-level measurements under diverse environmental stresses and is sensitive enough to evaluate genotypic variation for panicle physiology and architecture in cereals with compact inflorescences.
Commentary: an industry perspective on the importance of incorporating participant voice before, during, and after clinical trials
Authors: Goodson N. , Wicks P. , Farina C.
Published: November 2022

It is increasingly recognized that involving patients and the public in the design of clinical trials can lead to better recruitment, retention, and satisfaction. A recent scoping review determined that between 1985 and 2018, just 23 articles meeting quality criteria obtained feedback from clinical trial participants after a trial had been completed. In a timespan that presumably included thousands of trials across hundreds of indications, the paucity of the literature seems surprising, if not outright disappointing. By contrast, practitioners in the life sciences industry are increasingly incorporating patient research into their trial design process before, during, and after trial completion. Examples of approaches used include recruitment of “look alike” participant samples through online communities, surveys, and the use of smartphone apps to directly record participants’ spoken reactions to trial materials like recruitment materials, site visit schedules, or informed consent materials. However, commercial organizations tend not to publish their findings, leading to a potential two-tier experience for trial participants depending on whether the trial they participate in will be industry-funded or government-funded. This seems problematic on a number of levels. Increasing regulatory, funder, and publisher interest in improving the inclusivity of clinical trial participants may act as a timely lever to spur patient-centered coproduction of trials. Until continuous feedback processes are the mandated, funded, and published norm, participating in a clinical trial will be more arduous than it needs to be.
Onchocerciasis in the Ntui Health District of Cameroon: epidemiological, entomological and parasitological findings in relation to elimination prospects
Authors: Siewe Fodjo Joseph Nelson , Ngarka Leonard , Njamnshi Wepnyu Yembe , Enyong Peter Ayuk , Zoung-Kanyi Bissek Anne-Cécile , Njamnshi Alfred Kongnyu
Published: November 2022

Background

Despite decades of community-directed treatment with ivermectin (CDTI), onchocerciasis transmission persists in Cameroon and has been associated with increased risk for epilepsy in endemic communities. We investigated the onchocerciasis situation in the Ntui Health District (a known onchocerciasis focus in Cameroon where the Sanaga River constitutes the main source of black fly vectors) using parasitological, entomological and serological parameters.

Methods

In July 2021, community-based surveys were conducted in four villages (Essougli, Nachtigal, Ndjame and Ndowe). Onchocerciasis was diagnosed via microscopic examination of skin snips. Using rapid diagnostic tests, we screened children aged 3–6 years for Ov16 antibodies as a proxy for recent onchocerciasis transmission. Monthly black fly biting rates were obtained from the two riverside villages (Nachtigal and Essougli) for 12 consecutive months (July 2021 to June 2022) using the human landing catch technique. Some black flies were dissected each month to check for infection.

Results

Overall, 460 participants were recruited; mean age was 32.1 (range: 3–85) years with 248 (53.9%) being males. Among skin snipped participants (n = 425), onchocerciasis prevalence was 14.6%. Participants with epilepsy (n = 25) were more often skin snip positive (45.8% vs 12.7%; P < 0.001) and had higher microfilarial loads (9.2 ± 22.0 vs 0.7 ± 3.5 microfilariae/skin snip; P < 0.001) compared to their peers without epilepsy. Eight (6.5%) of the 123 tested children were Ov16 seropositive. The breeding sites we investigated along the Sanaga River during the current study harbored fewer vectors (annual biting rates reaching 530,322 vs 606,370 in the Mbam River) and exhibited lower black fly infection rates (annual transmission potentials reaching 1479 vs 4488 in the Mbam River) when compared to recent entomological reports in Cameroon.

Conclusion

Despite substantial biting rates, black fly infection rates (by microscopy) in the Ntui Health District were rather low resulting in overall low transmission potentials in study villages. Thanks to CDTI, O. volvulus infection in both humans and insects is on the decrease. However, there is evidence that O. volvulus is still endemic in these communities. Reducing the vector population will further accelerate onchocerciasis elimination prospects.

Graphical Abstract