bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of the COVID-19 pandemic on symptoms of anxiety and depression and health-related quality of life in older patients with chronic kidney disease
Authors: Voorend C. G. N. , van Oevelen M. , Nieberg M. , Meuleman Y. , Franssen C. F. M. , Joosten H. , Berkhout-Byrne N. C. , Abrahams A. C. , Mooijaart S. P. , Bos W. J. W. , van Buren M. ,   on behalf of the POLDER investigators, van Alphen Arjan , Berkhout-Byrne Noeleen , van Breda G. F. , van Buren Marjolijn , Boom Henk , Bos Willem Jan , Diepenbroek Adry , Emmelot-Vonk Marielle , Franssen Casper , Gaillard Carlo A. J. M. , Groeneweg-Peeters Nel , Hoekstra Bettie , Hommes Nienke , Hoornaar Francoise , Joosten Hanneke , Lagro Joep , Litjens Elisabeth , Molenaar Femke , Mooijaart Simon P. , Neradova Aegida , Peters Mike , Veldman Wilma , Voorend Carlijn , Westerbos Lidwien , Westerman-van der Wijden Carlijne , Wierdsma Judith
Published: November 2021

Background

Older patients with advanced chronic kidney disease are at increased risk for a severe course of the coronavirus disease-2019 (COVID-19) and vulnerable to mental health problems. We aimed to investigate prevalence and associated patient (demographic and clinical) characteristics of mental wellbeing (health-related quality of life [HRQoL] and symptoms of depression and anxiety) before and during the COVID-19 pandemic in older patients with advanced chronic kidney disease.

Methods

An ongoing Dutch multicentre prospective cohort study enrols patients of ≥70 years with an eGFR < 20 mL/min/1.73m2 from October 2018 onward. With additional questionnaires during the pandemic (May–June 2020), disease-related concerns about COVID-19 and general anxiety symptoms were assessed cross-sectionally, and depressive symptoms, HRQoL, and emotional symptoms longitudinally.

Results

The 82 included patients had a median age of 77.5 years (interquartile range 73.9–82.1), 77% were male and none had tested positive for COVID-19. Cross-sectionally, 67% of the patients reported to be more anxious about COVID-19 because of their kidney disease, and 43% of the patients stated that their quality of life was reduced due to the COVID-19 pandemic. Compared to pre-COVID-19, the presence of depressive symptoms had increased (11 to 22%; p = .022) and physical HRQoL declined (M = 40.4, SD = 10.1 to M = 36.1, SD = 10.4; p < .001), particularly in males. Mental HRQoL (M = 50.3, SD = 9.6 to M = 50.4, SD = 9.9; p = .913) and emotional symptoms remained similar.

Conclusions

Older patients with advanced chronic kidney disease suffered from disease-related anxiety about COVID-19, increased depressive symptoms and reduced physical HRQoL during the COVID-19 pandemic. The impact of the pandemic on this vulnerable patient group extends beyond increased mortality risk, and awareness of mental wellbeing is important.

Trial registration

The study is registered at the Netherlands Trial Register (NTR), trial number NL7104. Date of registration: 06-06-2018.
Factors associated with mobility decrease leading to disability: a cross-sectional nationwide study in Japan, with results from 8681 adults aged 20-89 years
Authors: Yamada Keiko , Yamaguchi Satoshi , Ito Yoichi M. , Ohe Takashi
Published: November 2021

Background

Mobility decrease leading to disability can gradually develop during early life, however, its related factors are not well clarified. Therefore, we investigate the related factors of mobility decrease at various levels, using nationwide data in Japan.

Methods

In total, 8681 independent community dwellers aged 20-89 years were analysed (average age, 51.6 years; 58.5% women). Three stages of mobility decrease were based on the locomotive syndrome risk test: Stage 1, emerging; Stage 2, progressing; Stage 3, progressed to restrict social engagement. Age was analysed using a simple quadratic function model.

Results

The prevalence of Stages 1-3 was 31.6% (n = 2746), 5.8% (n = 504), and 3.2% (n = 278), respectively. On the multivariable logistic regression, increased age in participants aged ≥40 years (stage 1: odds ratio[OR] 1.05-1.20, stage 2: OR 1.04-1.22, stage 3: OR 1.05-1.22), female (stage 1: OR 2.28, 95% confidence interval [CI] 1.99-2.61, stage 2: OR 2.40, 95% CI 1.77-3.25, stage 3: OR 1.80, 95% CI 1.19-2.72), overweight status (stage 1: OR 1.56, 95% CI 1.34-1.82, stage 2: OR 3.19, 95% CI 2.38-4.27, stage 3: OR 2.87, 95% CI 1.90-4.32), hypertension (stage 1: OR 1.20, 95% CI 1.01-1.41, stage 2: OR 1.99, 95% CI 1.49-2.64, stage 3: OR 2.10, 95% CI 1.44-3.05), and diabetes mellitus (stage 1: OR 1.62, 95% CI 1.17-2.24, stage 2: OR 1.57, 95% CI 0.93-2.66, stage 3: OR 2.10, 95% CI 1.13-3.90) were positively associated. The frequency of physical activity/sports, even a few per month, was inversely associated with all stages (stage 1: OR 0.59-0.72, stage 2: OR 0.50-0.67, stage 3: 0.36-0.53). A one-year increase in age had a stronger impact on mobility decrease in older adults than in younger ones. Increased age in participants aged < 40 years and smoking were associated with Stage 1, while intake of various foods was inversely associated with Stages 1 and 2.

Conclusion

Increased age (< 40 years) was associated with emerging mobility decrease, while that (≥ 40 years) was associated with any levels of mobility decrease. Female, lifestyle habits, including physical activities and overweight status, were associated with mobility decrease at every level.
Adenocarcinoma in situ and minimally invasive adenocarcinoma in lungs of smokers: image feature differences from those in lungs of non-smokers
Authors: Sugawara Haruto , Watanabe Hirokazu , Kunimatsu Akira , Abe Osamu , Watanabe Shun-ichi , Yatabe Yasushi , Kusumoto Masahiko
Published: November 2021

Purpose

We aimed to examine the characteristics of imaging findings of adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) in the lungs of smokers compared with those of non-smokers.

Materials and methods

We included seven cases of AIS and 20 cases of MIA in lungs of smokers (pack-years ≥ 20) and the same number of cases of AIS and MIA in lungs of non-smokers (pack-years = 0). We compared the diameter of the entire lesion and solid component measured on computed tomography (CT) images, pathological size and invasive component diameter measured from pathological specimens, and CT values of the entire lesion and ground-glass opacity (GGO) portions between the smoker and non-smoker groups.

Results

The diameters of AIS and MIA on CT images and pathological specimens of the smoker group were significantly larger than those of the non-smoker group (p = 0.036 and 0.008, respectively), whereas there was no significant difference in the diameter of the solid component on CT images or invasive component of pathological specimens between the two groups. Additionally, mean CT values of the entire lesion and GGO component of the lesions in the smoker group were significantly lower than those in the non-smoker group (p = 0.036 and 0.040, respectively).

Conclusion

AIS and MIA in smoker’s lung tended to have larger lesion diameter and lower internal CT values compared with lesions in non-smoker’s lung. This study calls an attention on smoking status in CT-based diagnosis for early stage adenocarcinoma.
Patient experience of lasting negative effects of psychological interventions for anxiety and depression in secondary mental health care services: a national cross-sectional study
Authors: McQuaid Aisling , Sanatinia Rahil , Farquharson Lorna , Shah Prisha , Quirk Alan , Baldwin David S. , Crawford Mike
Published: November 2021

Background

Patients who undergo psychological treatment can report both negative and positive effects, but evidence of factors influencing the likelihood of negative effects is limited.

Aims

To identify aspects of the organisation and delivery of secondary care psychological treatment services that are associated with patient experiences of negative effects.

Method

Cross-sectional survey of people with anxiety and depression who ended psychological treatment delivered by 50 NHS trusts in England. Respondents were asked about how their treatment was organised and delivered and whether they experienced lasting negative effects.

Results

Of 662 respondents, 90 (14.1%) reported experiencing lasting negative effects. People over the age of 65 were less likely than younger respondents to report negative effects. There was an association between reporting neutral or negative effects and not being referred at what respondents considered to be the right time (OR = 1.712, 95% CI = 1.078–2.726), not receiving the right number of sessions (OR = 3.105, 95% CI = 1.934–4.987), and not discussing progress with their therapist (OR 2.063, 95% CI = 1.290–3.301).

Conclusions

One in seven patients who took part in this survey reported lasting negative effects from psychological treatment. Steps should be taken to prepare people for the potential for negative experiences of treatment, and progress reviewed during therapy in an effort to identify and prevent negative effects.
How can the utilisation of help for mental disorders be improved? A quasi-experimental online study on the changeability of stigmatising attitudes and intermediate variables in the process of utilisation
Authors: McLaren Thomas , Peter Lina-Jolien , Tomczyk Samuel , Muehlan Holger , Stolzenburg Susanne , Schomerus Georg , Schmidt Silke
Published: November 2021

Background

Epidemiological studies show that even in highly developed countries many people with depression do not seek help for their mental health issues, despite promising prevention approaches encouraging people to seek help and reduce self-stigma. Therefore, an anti-stigma intervention study to support help-seeking behaviour will be developed on the basis of the newly explicated “Seeking Mental Health Care Model”.

Methods

A quasi-experimental online study will be carried out to assess the effect of different intervention variables relevant for the help-seeking process. The study is conceived as a fractional factorial design. Participants will be screened for depressive complaints (PHQ-9 sum score ≥ 8) and current psychiatric/psychotherapeutic treatment. After baseline assessment the participants will be randomly allocated into one of the 24 study groups receiving different combinations of the vignette-based intervention aiming to reduce stigma and support help-seeking. Next, relevant outcome measures will be administered a second time. In a 3- and 6-month follow-up help-seeking behaviour will be measured. Gamified elements and avatar-choice techniques will be used to heighten study immersion and adherence.

Discussion

On the basis of the project results, promising research and intervention perspectives can be developed. Results, firstly, allow for a more detailed empirical investigation and conceptualisation of the stages of mental health care utilisation, as well as an examination of theoretical approaches to stigmatisation. Secondly, our online study could provide insights for an evidence-based design and evaluation of online interventions for people with a mental illness.

Trial registration

German Clinical Trials Register: DRKS00023557. Registered 11 December 2020. World Health Organization, Universal Trial Number: U1111–1264-9954. Registered 16 February 2021.
The wound severity of animal bite victims visiting rabies prevention clinics and the influencing factors in Central China: a cross-sectional investigation
Authors: Li Dandan , Liao Hanlin , Chen Fan , Jiang Qingqing , Wang Tiantian , Lu Zuxun , Liu Qiaoyan , Cao Shiyi
Published: November 2021

Background

Animal bites are a major public health problem. The more serious the bite wound is, the higher the risk of developing rabies is. This study aimed to investigate the severity of wounds among animal bite victims and identify the influencing factors in Wuhan, China.

Methods

A cross-sectional study was conducted among 1015 animal bite victims visiting rabies prevention clinics. We performed a face-to-face interview to collect information on the exposure category of the bite wound, the type of the offending animal, exposure-to-risk situations, etc. Factors associated with exposure categories were identified by multivariate logistic regression analysis.

Results

Five hundred and sixty-four (55.57%) cases were category III exposures, 418 (41.18%) were category II exposures, and 33 (3.25%) were category I exposures. People who were hurt by their own domestic animals (odds ratio [OR] = 1.55, 95% confidence interval [CI]: 1.14–2.10), and those exposed to animals unvaccinated against rabies (OR = 1.45, 95% CI: 1.08–1.95) had a higher risk for category III exposures. Respondents who did not know the fatality of rabies were more likely to be injured seriously compared to those who knew that rabies is fatal, and the OR was 1.40 (95% CI, 1.05–1.86).

Conclusions

This study showed that factors associated with the severity of bite wounds mainly included types of the offending animal, vaccination status of the animal, and knowledge of rabies fatality. Educational programs and awareness-raising campaigns should be provided to decrease severe animal bites, especially targeting pet owners and those with limited rabies knowledge.
Gallstone disease and nonalcoholic fatty liver disease in patients with type 2 diabetes: a cross-sectional study
Authors: Lu Ye , Hu Lili , Song Jing , Wan Jing , Chen Haibing , Yin Jun
Published: November 2021

Background

Nonalcoholic fatty liver disease (NAFLD) and gallstone disease (GSD) often coexist in the general population owing to shared risk factors. This study explored the relationship between NAFLD and GSD in patients with type 2 diabetes.

Methods

We conducted a retrospective cross-sectional analysis of 4325 patients with type 2 diabetes. GSD and NAFLD were confirmed using ultrasonography. GSD was defined as either asymptomatic gallstones or previous cholecystectomy, and each was analyzed separately.

Result

There was no significant difference in the prevalence of GSD between patients with and without NAFLD (23.8% vs. 21.2%, P = 0.15). After case–control matching (1:1) of baseline data such as age, sex, duration of diabetes, and HbA1c between patients with and without NAFLD, there was still no significant difference in the prevalence of GSD (25.5% vs. 23.6%, P = 0.15). The prevalence of NAFLD in patients with asymptomatic gallstones was lower than that of patients without GSD (38.6% vs. 47.3%, P < 0.001), whereas the prevalence in those who had undergone cholecystectomy was much higher (61.2% vs. 47.3%, P < 0.001). The ratio of cholecystectomy to asymptomatic gallstone in patients with or without NAFLD was 1.97 and 0.79, respectively. The rate of cholecystectomy was higher in the patients with NAFLD than in those without NAFLD (15.8% vs. 9.3%, P < 0.001), consistent with the result after case–control matching (17.3% vs. 11.2%, P < 0.001). Multivariate logistic regression analysis, after adjusting for numerous potential confounding factors, revealed that GSD (OR = 1.241, 95%CI: 1.036–1.488, P = 0.002) and cholecystectomy (OR = 1.946, 95%CI: 1.546–2.445, P < 0.001) were both strongly associated with NAFLD. However, asymptomatic gallstone (OR = 0.663, 95%CI: 0.513–0.856, P = 0.002) seemed to be negatively correlated with NAFLD.

Conclusions

The prevalence of GSD was similar in patients with type 2 diabetes with and without NAFLD. The higher proportion of cholecystectomy and lower proportion of asymptomatic gallstones in patients with NAFLD suggests that NAFLD may increase the risk of complications of GSD.
Impact of cement type and abutment height on pull-off force of zirconia reinforced lithium silicate crowns on titanium implant stock abutments: an in vitro study
Authors: Müller Lisa , Rauch Angelika , Reissmann Daniel R. , Schierz Oliver
Published: November 2021

Background

Pull-off forces of cement-retained zirconia reinforced lithium silicate (ZLS) in implant-supported single crowns on stock titanium abutments with respect to abutment height and implant cement were evaluated and compared.

Methods

Pull-off force of ZLS crowns on stock titanium abutments was evaluated concerning dental cement and abutment height. A total sample size of 64 stock abutments with heights of 3 mm (n = 32) and 5 mm (n = 32) was used. The ZLS crowns were cemented with four different types of cement (one temporary, two semi-permanent, and one permanent). After cementation, water storage, and thermocycling each sample was subjected to a pull-off test using a universal testing machine.

Results

The temporary cement showed the least pull-off force regardless of abutment height (3/5 mm: means 6 N/23 N), followed by the semi-permanent methacrylate-infiltrated zinc oxide cement (28 N/55 N), the semi-permanent methacrylate-based cement (103 N/163 N), and the permanent resin composite cement (238 N/820 N). Results of all types of cement differed statistically significantly from each other (p ≤ .012). The type of implant cement has an impact on the pull-off force of ZLS crowns and titanium abutments.

Conclusions

Permanent cements present higher retention than semi-permanent ones, and temporary cements present the lowest values. The abutment height had a subordinate impact.
Rapidly liver-clearable rare-earth core–shell nanoprobe for dual-modal breast cancer imaging in the second near-infrared window
Authors: Wei Zhuxin , Duan Guangxin , Huang Baoxing , Qiu Shanshan , Zhou Dandan , Zeng Jianfeng , Cui Jiabin , Hu Chunhong , Wang Ximing , Wen Ling , Gao Mingyuan
Published: November 2021

Background

Fluorescence imaging as the beacon for optical navigation has wildly developed in preclinical studies due to its prominent advantages, including noninvasiveness and superior temporal resolution. However, the traditional optical methods based on ultraviolet (UV, 200–400 nm) and visible light (Vis, 400–650 nm) limited by their low penetration, signal-to-noise ratio, and high background auto-fluorescence interference. Therefore, the development of near-infrared-II (NIR-II 1000–1700 nm) nanoprobe attracted significant attentions toward in vivo imaging. Regrettably, most of the NIR-II fluorescence probes, especially for inorganic NPs, were hardly excreted from the reticuloendothelial system (RES), yielding the anonymous long-term circulatory safety issue.

Results

Here, we develop a facile strategy for the fabrication of Nd3+-doped rare-earth core–shell nanoparticles (Nd-RENPs), NaGdF4:5%Nd@NaLuF4, with strong emission in the NIR-II window. What’s more, the Nd-RENPs could be quickly eliminated from the hepatobiliary pathway, reducing the potential risk with the long-term retention in the RES. Further, the Nd-RENPs are successfully utilized for NIR-II in vivo imaging and magnetic resonance imaging (MRI) contrast agents, enabling the precise detection of breast cancer.

Conclusions

The rationally designed Nd-RENPs nanoprobes manifest rapid-clearance property revealing the potential application toward the noninvasive preoperative imaging of tumor lesions and real-time intra-operative supervision.

Graphical abstract
Cell-derived extracellular vesicles and membranes for tissue repair
Authors: Ding Yuan , Li Yanjie , Sun Zhongquan , Han Xin , Chen Yining , Ge Yao , Mao Zhengwei , Wang Weilin
Published: November 2021

Humans have a limited postinjury regenerative ability. Therefore, cell-derived biomaterials have long been utilized for tissue repair. Cells with multipotent differentiation potential, such as stem cells, have been administered to patients for the treatment of various diseases. Researchers expected that these cells would mediate tissue repair and regeneration through their multipotency. However, increasing evidence has suggested that in most stem cell therapies, the paracrine effect but not cell differentiation or regeneration is the major driving force of tissue repair. Additionally, ethical and safety problems have limited the application of stem cell therapies. Therefore, nonliving cell-derived techniques such as extracellular vesicle (EV) therapy and cell membrane-based therapy to fulfil the unmet demand for tissue repair are important. Nonliving cell-derived biomaterials are safer and more controllable, and their efficacy is easier to enhance through bioengineering approaches. Here, we described the development and evolution from cell therapy to EV therapy and cell membrane-based therapy for tissue repair. Furthermore, the latest advances in nonliving cell-derived therapies empowered by advanced engineering techniques are emphatically reviewed, and their potential and challenges in the future are discussed.

Graphical Abstract
Cargo proteins in extracellular vesicles: potential for novel therapeutics in non-alcoholic steatohepatitis
Authors: Kim Jimin , Lee Seul Ki , Jeong Seon-Yeong , Cho Hye Jin , Park Joonghoon , Kim Tae Min , Kim Soo
Published: November 2021

Background

Extracellular vesicles (EVs) are recognized as novel cell-free therapeutics. Non-alcoholic steatohepatitis (NASH) remains a critical health problem. Herein, we show that EVs from pan peroxisome proliferator-activated receptor agonist-primed induced mesenchymal stem cell (pan PPAR-iMSC-EVs) has unique cargo protein signatures, and demonstrate its therapeutic function in NASH.

Results

A unique protein signatures were identified in pan PPAR-iMSC-EVs against those from non-stimulated iMSC-EVs. NASH mice receiving pan PPAR-iMSC-EVs showed reduced steatotic changes and ameliorated ER stress and mitochondiral oxidative stress induced by inflammation. Moreover, pan PPAR-iMSC-EVs promoted liver regeneration via inhibiting apoptosis and enhancing proliferation.

Conclusions

We conclude that our strategy for enriching unique cargo proteins in EVs may facilitate the development of novel therapeutic option for NASH.

Graphical Abstract
Engineered extracellular vesicles derived from primary M2 macrophages with anti-inflammatory and neuroprotective properties for the treatment of spinal cord injury
Authors: Zhang Chuanjie , Li Daoyong , Hu Hengshuo , Wang Zhe , An Jinyu , Gao Zhanshan , Zhang Kaihua , Mei Xifan , Wu Chao , Tian He
Published: November 2021

Background

Uncontrollable inflammation and nerve cell apoptosis are the most destructive pathological response after spinal cord injury (SCI). So, inflammation suppression combined with neuroprotection is one of the most promising strategies to treat SCI. Engineered extracellular vesicles with anti-inflammatory and neuroprotective properties are promising candidates for implementing these strategies for the treatment of SCI.

Results

By combining nerve growth factor (NGF) and curcumin (Cur), we prepared stable engineered extracellular vesicles of approximately 120 nm from primary M2 macrophages with anti-inflammatory and neuroprotective properties (Cur@EVs−cl−NGF). Notably, NGF was coupled with EVs by matrix metalloproteinase 9 (MMP9)-a cleavable linker to release at the injured site accurately. Through targeted experiments, we found that these extracellular vesicles could actively and effectively accumulate at the injured site of SCI mice, which greatly improved the bioavailability of the drugs. Subsequently, Cur@EVs−cl−NGF reached the injured site and could effectively inhibit the uncontrollable inflammatory response to protect the spinal cord from secondary damage; in addition, Cur@EVs−cl−NGF could release NGF into the microenvironment in time to exert a neuroprotective effect against nerve cell damage.

Conclusions

A series of in vivo and in vitro experiments showed that the engineered extracellular vesicles significantly improved the microenvironment after injury and promoted the recovery of motor function after SCI. We provide a new method for inflammation suppression combined with neuroprotective strategies to treat SCI.

Graphical Abstract
Impact of oral anticoagulation therapy on postoperative atrial fibrillation outcomes: a systematic review and meta-analysis
Authors: Fragão-Marques Mariana , Teixeira Francisco , Mancio Jennifer , Seixas Nair , Rocha-Neves João , Falcão-Pires Inês , Leite-Moreira Adelino
Published: November 2021

Background

Post-operative atrial fibrillation (POAF) is the most common complication after cardiac surgery. Recent studies had shown this phenomenon is no longer considered transitory and is associated with higher risk of thromboembolic events or death. The aim of this study was to systematically review and analyze previous studies comparing oral anticoagulation therapy with no anticoagulation, regarding these long-term outcomes.

Methods

PubMed/MEDLINE, EMBASE, Web of Science and Cochrane Database were systematically searched to identify the studies comparing the risk of stroke, or thromboembolic events or mortality of POAF patients who received anticoagulation compared with those who were not anticoagulated. Incidence of stroke, thromboembolic events and all-cause mortality were evaluated up to 10 years after surgery. Time-to-event outcomes were collected through hazard ratio (HR) along with their variance and the early endpoints using frequencies or odds ratio (OR). Random effect models were used to compute statistical combined measures and 95% confidence intervals (CI). Heterogeneity was evaluated through Q statistic-related measures of variance (Tau2, I2, Chi-squared test).

Results

Eight observational cohort studies were selected, including 15,335 patients (3492 on Oral Anticoagulants (OAC) vs 11,429 without OAC) that met the inclusion criteria for qualitative synthesis. Patients had a wide gender distribution (38.6–82.3%), each study with a mean age above 65 years (67.5–85). Vitamin K antagonists were commonly prescribed anticoagulants (74.3–100%). OAC was associated with a protective impact on all-cause mortality at a mean of 5.0 years of follow-up (HR is 0.85 [0.72–1.01]; p = 0.07; I2 = 48%). Thromboembolic events did not differ between the two treatment arms (HR 0.68 [0.40–1.15], p = 0.15).

Conclusion

Current literature suggests a possibly protective impact of OAC therapy for all-cause mortality in patients with new-onset atrial fibrillation after cardiac surgery. However, it does not appear to impact thromboembolism rate.
Overexpression of E3 ubiquitin ligase Cbl attenuates endothelial dysfunction in diabetes mellitus by inhibiting the JAK2/STAT4 signaling and Runx3-mediated H3K4me3
Authors: Jin Qingsong , Lin Liangyan , Zhao Tiantian , Yao Xiaoyan , Teng Yaqin , Zhang Dongdong , Jin Yongjun , Yang Meizi
Published: November 2021

Background

Diabetes mellitus (DM), a most common chronic disease, is featured with impaired endothelial function and bioavailability of nitric oxide (NO), while E3 ubiquitin ligase appears to alleviate endothelial dysfunction as a promising option for DM treatment. Herein, we aimed to determine whether E3 ubiquitin ligase casitas B-lineage lymphoma (Cbl) alleviates endothelial dysfunction in DM rats by JAK2/STAT4 pathway.

Methods

A rat model of DM was developed through intraperitoneal injection of streptozotocin, followed by collection of aortic tissues to determine the expression of Cbl, JAK2, runt-related transcription factor 3 (Runx3) and STAT4. Human umbilical vein endothelial cells (HUVECs) were cultured in high glucose (HG) condition to induce DM as an in vitro model. With gain- and loss-function method, we assessed the aberrantly expressed Cb1 on endothelial dysfunction, NO production and apoptosis of HUVECs.

Results

Cbl was reduced in DM rat tissues and HG-induced HUVECs, where JAK2, Runx3 and STAT4 were elevated. It was found that overexpression of Cbl alleviated endothelial dysfunction by increasing NO production and restoring vasodilation and suppressing apoptosis of HUVECs. Mechanistically, Cb1 enhanced JAK2 ubiquitination and decreased JAK2 and STAT4 expression, where STAT4 improved Runx3 expression by regulating histone H3 lysine 4 trimethylation level. Overexpression of JAK2 and STAT4, or Runx3 increased apoptosis of HUVECs, abrogating the effect of Cb1 on endothelial function.

Conclusion

In conclusion, Cbl alleviates endothelial dysfunction by inactivation of the JAK2/STAT4 pathway and inhibition of Runx3 expression in DM. These evidence might underlie novel Cbl-based treatment against DM in the future.
CD4+ effector T cells accelerate Alzheimer’s disease in mice
Authors: Machhi Jatin , Yeapuri Pravin , Lu Yaman , Foster Emma , Chikhale Rupesh , Herskovitz Jonathan , Namminga Krista L. , Olson Katherine E. , Abdelmoaty Mai Mohamed , Gao Ju , Quadros Rolen M. , Kiyota Tomomi , Jingjing Liang , Kevadiya Bhavesh D. , Wang Xinglong , Liu Yutong , Poluektova Larisa Y. , Gurumurthy Channabasavaiah B. , Mosley R. Lee , Gendelman Howard E.
Published: November 2021

Background

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by pathological deposition of misfolded self-protein amyloid beta (Aβ) which in kind facilitates tau aggregation and neurodegeneration. Neuroinflammation is accepted as a key disease driver caused by innate microglia activation. Recently, adaptive immune alterations have been uncovered that begin early and persist throughout the disease. How these occur and whether they can be harnessed to halt disease progress is unclear. We propose that self-antigens would induct autoreactive effector T cells (Teffs) that drive pro-inflammatory and neurodestructive immunity leading to cognitive impairments. Here, we investigated the role of effector immunity and how it could affect cellular-level disease pathobiology in an AD animal model.

Methods

In this report, we developed and characterized cloned lines of amyloid beta (Aβ) reactive type 1 T helper (Th1) and type 17 Th (Th17) cells to study their role in AD pathogenesis. The cellular phenotype and antigen-specificity of Aβ-specific Th1 and Th17 clones were confirmed using flow cytometry, immunoblot staining and Aβ T cell epitope loaded haplotype-matched major histocompatibility complex II IAb (MHCII-IAb–KLVFFAEDVGSNKGA) tetramer binding. Aβ-Th1 and Aβ-Th17 clones were adoptively transferred into APP/PS1 double-transgenic mice expressing chimeric mouse/human amyloid precursor protein and mutant human presenilin 1, and the mice were assessed for memory impairments. Finally, blood, spleen, lymph nodes and brain were harvested for immunological, biochemical, and histological analyses.

Results

The propagated Aβ-Th1 and Aβ-Th17 clones were confirmed stable and long-lived. Treatment of APP/PS1 mice with Aβ reactive Teffs accelerated memory impairment and systemic inflammation, increased amyloid burden, elevated microglia activation, and exacerbated neuroinflammation. Both Th1 and Th17 Aβ-reactive Teffs progressed AD pathology by downregulating anti-inflammatory and immunosuppressive regulatory T cells (Tregs) as recorded in the periphery and within the central nervous system.

Conclusions

These results underscore an important pathological role for CD4+ Teffs in AD progression. We posit that aberrant disease-associated effector T cell immune responses can be controlled. One solution is by Aβ reactive Tregs.

Graphical Abstract
Immune reactivity and host modulatory roles of two novel Haemonchus contortus cathepsin B-like proteases
Authors: Bakshi Mariam , Tuo Wenbin , Aroian Raffi V. , Zarlenga Dante
Published: November 2021

Background

Haemonchus contortusis a blood-feeding, gastrointestinal nematode (GIN) that causes significant economic losses to the small ruminant industry worldwide. Despite extensive efforts, our understanding of the molecular mechanisms used by GIN to evade host immune responses is limited. Cathepsin B-like proteins (CBPs) are members of the cysteine protease family and are involved in parasite invasion and thus provide viable vaccine candidates.

Methods

In silico comparative analysis was used to identify conserved proteins among a subset of clade V parasitic nematodes with emphasis on blood-feeding worms, among which CBPs appeared prominently. We identified and characterized two novel CBPs designated Hc-CBP-1 and Hc-CBP-2. Rabbit anti-recombinant (r) Hc-CBP-1 and rHc-CBP-2 were used to detect the presence of native proteins in the excretory secretory products (ESP) and in worm tissues of adultH. contortus. Peptide arrays of rHc-CBP-1 and rHc-CBP-2 were screened with the homologous and heterologous anti-sera and with sera from dexamethasone-treated (Dex+) and non-treated (Dex−)H. contortus-infected animals to identify key immunogenic peptides. Gene transcription of Hc-cbp-1and Hc-cbp-2was also performed onH. contortus-infected animals treated with Dex+. Finally, the mature recombinant proteins were used to assess their abilities to modulate cell functions.

Results

Immunohistochemistry showed that both Hc-CBP-1 and Hc-CBP-2 are present on the brush borders of the intestine; Hc-CBP-2 was also present in the hypodermis of the body wall. Peptide displays screened with rabbit anti-rHc-CBP-1 and anti-rHc-CBP-2 revealed regions within the proteins where dominant and overlapping epitopes prevailed. ELISA results were consistent with only Hc-CBP-1 being present inH. contortusadult ESPs.H. contortusfrom Dex+animals exhibited a threefold increase in Hc-cbp-2transcript while Hc-cbp-1expression did not change. In contrast, comparisons of immunoreactivities of rHc-CBP-1 and rHc-CBP-2 peptide arrays to sera from Dex+and Dex−animals primarily showed changes in Hc-CBP-1 binding. Lastly, rHc-CBP-1 suppressed mRNA expression of bovine peripheral blood mononuclear cell cytokines/activation markers, including TNFα, IL-1, IL-6 and CD86.

Conclusions

These results suggest that as secreted and cryptic proteins, respectively, Hc-CBP-1 and Hc-CBP-2 influence cellular and immunological activities that have interesting dynamics during infection and may provide viable immune-related targets for attenuatingH. contortusinfectivity.

Graphic Abstract
High-frequency oscillations detected by electroencephalography as biomarkers to evaluate treatment outcome, mirror pathological severity and predict susceptibility to epilepsy
Authors: Sun Yueqian , Ren Guoping , Ren Jiechuan , Wang Qun
Published: November 2021

High-frequency oscillations (HFOs) in the electroencephalography (EEG) have been extensively investigated as a potential biomarker of epileptogenic zones. The understanding of the role of HFOs in epilepsy has been advanced considerably over the past decade, and the use of scalp EEG facilitates recordings of HFOs. HFOs were initially applied in large scale in epilepsy surgery and are now being utilized in other applications. In this review, we summarize applications of HFOs in 3 subtopics: (1) HFOs as biomarkers to evaluate epilepsy treatment outcome; (2) HFOs as biomarkers to measure seizure propensity; (3) HFOs as biomarkers to reflect the pathological severity of epilepsy. Nevertheless, knowledge regarding the above clinical applications of HFOs remains limited at present. Further validation through prospective studies is required for its reliable application in the clinical management of individual epileptic patients.
Urban Living Labs: how to enable inclusive transdisciplinary research?
Authors: Laborgne Pia , Ekille Epongue , Wendel Jochen , Pierce Andrea , Heyder Monika , Suchomska Joanna , Nichersu Iulian , Balaican Dragos , Ślebioda Krzysztof , Wróblewski Michał , Goszczynski Wojciech
Published: November 2021

The Urban Living Lab (ULL) approach has the potential to create
enabling environments for social learning and to be a successful arena for innovative local collaboration in knowledge co-creation and experimentation in the context of research and practice in sustainability transitions. Nevertheless, complex issues such as the urban Food-Water-Energy (FWE) Nexus present a challenge to the realization of such ULL, especially regarding their inclusiveness.

We present ULL as a frame for a local knowledge co-creation and participation approach based on the project "Creating Interfaces - Building capacity for integrated governance at the Food-Water-Energy-nexus in cities on the water". This project aims at making FWE Nexus linkages better understandable to the stakeholders (citizens and associations, city government, science, businesses), and to facilitate cooperation and knowledge exchange among them. This paper focuses on and discusses inclusiveness as a key aspect and challenge of ULLs and on what literature and our experiences in this regard suggest for the advancement of the concept of ULL towards ULL 2.0. These findings often also relate to framing transdisciplinary research in a wider sense.
Evaluation of cognitive impairment in patients with major depressive disorder in remission
Authors: Ali Mustafa , Fahmy Magda , Haggag Wafaa , El-Tantawy Ashraf , Hassan Haydy
Published: November 2021

Background

Cognitive symptoms are one of the core symptoms of depressive disorders with a bearing effect on functional outcomes. Cognitive symptoms, including poor concentration and difficulty making decisions, are one of the DSM-IV diagnostic criteria for major depressive disorder. This study was designed to evaluate cognitive deficits in a sample of adult patients with major depressive disorder (MDD) in remission. A cross-sectional study was done on 60 patients fulfilling the diagnostic criteria of MDD in remission state. In addition, 60 normal subjects with matched age, sex, and educational level were compared with the patients group. Participants in both patients and control groups were subjected to clinical assessment using Mini-International Neuropsychiatric Interview plus (MINI-plus), assessment of cognitive functions using Wechsler Memory Scale-Revised (WMS-R) short form, and Wisconsin Card Sorting Test (WCST).

Results

There were statistically significant differences between patients and control groups regarding cognitive function. The patients group scored less in visual memory, verbal memory, attention/concentration, and psychomotor speed. They also performed poorly regarding executive functions. But there was no statistically significant difference between the patients and control groups regarding sustained attention and visuospatial function. No significant correlations did exist between age at onset of MDD and the duration of illness with different domains of cognitive function except for figural memory of WMS-R and categories completed of Wisconsin card sorting test.

Conclusion

Patients with MDD in remission experienced deficits in several cognitive functions when compared to matched control subjects. The cognitive functions do not reach normal levels of performance, particularly in visual memory and executive functioning with remission of depressive symptoms.
Cross-legged sitting posture effect on lumbar proprioception in young adults: a cross-sectional study
Authors: Karkousha Rania N. , Mohamed Aseel Rasheed , Ibrahim Amal H. M.
Published: November 2021

Background

The cross-legged sitting posture (CLS) is assumed by young adults’ results in a bent and unbalanced posture. The study purpose was to assess the effect of sitting in a cross-legged position (knee on knee) on lumbar proprioception. Thirty-six participants of both genders aged from 18 to 25 were selected and divided equally into group A who adapt to a cross-legged sitting posture and group B who adapt to erect sitting (not prefer cross-legged sitting). The Biodex System 3 pro isokinetic dynamometer was utilized to assess the lumbar proprioception by testing the lumbar region repositioning accuracy.

Results

The lumbar repositioning error of group A increased statistically significantly as compared to group B (p < 0.05).

Conclusions

Cross-legged sitting posture negatively affects lumbar proprioception compared with participants who adapt to erect sitting, and this effect should be considered in the avoidance of sitting in a cross-legged position and in prevention and intervention programs of lumbar proprioception impairment.
Tramadol, captagon and khat use in the Eastern Mediterranean Region: opening Pandora's box
Authors: Mohaddes Ardabili Hossein , Akbari Abolfazl , Rafei Parnian , Butner JL , Khan Riaz , Khazaal Yasser , Arab Abdulmalik Zuhair , Qazizada Mohammed Rafiq , Al-Ansari Basma , Baldacchino Alexander Mario
Published: November 2021

As defined by the World Health Organization, the Eastern Mediterranean Region (EMR), given its special geopolitical situation and internal/external conflicts, faces an increase in illegal activities such as drug production and trafficking, highlighting the need for a comprehensive understanding of the substance use situation. On the basis of a review of published papers between 2015 and 2021 we briefly review substance use in the EMR with special focus on the emerging drugs pertinent to this region, namely tramadol, captagon and khat.
End-to-End Non–Small-Cell Lung Cancer Prognostication Using Deep Learning Applied to Pretreatment Computed Tomography
Authors: Torres Felipe Soares , Akbar Shazia , Raman Srinivas , Yasufuku Kazuhiro , Schmidt Carola , Hosny Ahmed , Baldauf-Lenschen Felix , Leighl Natasha B.
Published: November 2021

PURPOSE

Clinical TNM staging is a key prognostic factor for patients with lung cancer and is used to inform treatment and monitoring. Computed tomography (CT) plays a central role in defining the stage of disease. Deep learning applied to pretreatment CTs may offer additional, individualized prognostic information to facilitate more precise mortality risk prediction and stratification.

METHODS

We developed a fully automated imaging-based prognostication technique (IPRO) using deep learning to predict 1-year, 2-year, and 5-year mortality from pretreatment CTs of patients with stage I-IV lung cancer. Using six publicly available data sets from The Cancer Imaging Archive, we performed a retrospective five-fold cross-validation using pretreatment CTs of 1,689 patients, of whom 1,110 were diagnosed with non–small-cell lung cancer and had available TNM staging information. We compared the association of IPRO and TNM staging with patients' survival status and assessed an Ensemble risk score that combines IPRO and TNM staging. Finally, we evaluated IPRO's ability to stratify patients within TNM stages using hazard ratios (HRs) and Kaplan-Meier curves.

RESULTS

IPRO showed similar prognostic power (concordance index [C-index] 1-year: 0.72, 2-year: 0.70, 5-year: 0.68) compared with that of TNM staging (C-index 1-year: 0.71, 2-year: 0.71, 5-year: 0.70) in predicting 1-year, 2-year, and 5-year mortality. The Ensemble risk score yielded superior performance across all time points (C-index 1-year: 0.77, 2-year: 0.77, 5-year: 0.76). IPRO stratified patients within TNM stages, discriminating between highest- and lowest-risk quintiles in stages I (HR: 8.60), II (HR: 5.03), III (HR: 3.18), and IV (HR: 1.91).

CONCLUSION

Deep learning applied to pretreatment CT combined with TNM staging enhances prognostication and risk stratification in patients with lung cancer.
Seasonal cellular stress phenomena and phenotypic plasticity in land snail Helix lucorum populations from different altitudes
Authors: Staikou Alexandra , Feidantsis Konstantinos , Gkanatsiou Ourania , Bibos Modestos Nakos , Hatziioannou Marianthi , Storey Kenneth B. , Michaelidis Basile
Published: November 2021

Temperature, a major abiotic environmental factor, regulates various physiological functions in land snails and therefore determines their biogeographical distribution. Thus, species with different distributions may present different thermal tolerance limits. Additionally, the intense reactivation of snail metabolic rate upon arousal from hibernation or estivation may provoke stress. Land snails, Helix lucorum, display a wide altitudinal distribution resulting in populations being exposed to different seasonal temperature variations. The aim of the present study was to investigate the expression of heat shock proteins (Hsps), mitogen activated protein kinases (MAPKs) and proteins that are related to apoptosis (Bcl-2, ubiquitin), that have ‘cytoprotective’ roles and are also considered to be reliable indicators of stress because of their crucial role in maintaining cellular homeostasis. These proteins were assessed in H. lucorum individuals from two different populations, one at Axios (sea level, 0 m) and the other at Kokkinopilos (Olympus, 1250 m), as well as after mutual population exchanges, in order to find out whether the different responses of these stress-related proteins depend solely on the environmental temperature. The results showed seasonally altered levels in all studied proteins in the hepatopancreas and foot of snails, both among different populations and between the same populations exposed to varying altitudes. However, individuals of the same population in their native habitat or acclimatized to a different habitat showed a relatively similar pattern of expression, supporting the induction of the specific proteins according to the life history of each species.
Fe-MOF-235 as an Efficient and Stable Electrocatalyst for the Oxygen Evolution Reaction
Authors: Liu Jiangtao , Fu Lin , Peng Xuegang , Pei Tong , Gao Zhihua , Huang Wei , Zuo Zhijun
Published: November 2021

Oxygen evolution reaction (OER) is studied on four kinds of Fe-based MOFs (Fe-MOF-235, Fe-MIL-101, Fe-MIL-88B and Fe-MIL-53) synthesized by solvothermal method using FeCl3·6H2O and terephthalic acid as precursors. Among them, Fe-MOF-235 exhibited optimal activity with the overpotential of 255 mV at a current density of 10 mA·cm−2, and a small Tafel slope of 33.1 mV·dec−1. However, OER activity of the catalyst decreases, when the skeleton structure of Fe-MOF-235 is destroyed after calcination. It is found that the outstanding OER performance of Fe-MOF-235 may be due to abundant active sites and faster charge transport kinetics afforded by the complete skeleton structure of Fe-MOF-235, and it also shows excellent stability during 70 h electrochemical testing. Therefore, Fe-MOF-235 can be directly used as an efficient OER catalyst.
Health Problems & Barriers to Healthcare Services for the Transgender Community in Lahore, Pakistan
Authors: Manzoor Iram , Khan Zartasha Hanan , Tariq Rafia , Shahzad Rijah
Published: November 2021

Objectives: To find out the major health problems and barriers in getting health care by transgender community in Lahore, Pakistan.

Methods: An analytical cross-sectional study was conducted in transgender community of Lahore from January to October 2020. The study included 214 participants from different areas of Lahore by targeting their “gurus”. Non-probability, snow-ball sampling technique was used to collect required sample size. Data was collected by using a structured questionnaire. Data were analyzed using SPSS version 23. Results were generated in form of tables and graphs. Chi square test and Fischer’s exact test were used to find out associations between health seeking behavior with their transgender status and p value was fixed as ≤ 0.05 as significant.

Results: Among total 214, 78.5% were transgender females and 21.5% were transgender male. Among the common health problems were depression (56%), anxiety (59%) and genital tract ulcers (45%). About 70% transgender seek health care from government hospitals. Among total 214 participants, 70% reported that they receive poor quality of health care. The main reasons of not getting proper care is non acceptance (20.7%), feeling ashamed (28.7%), non-availability of CNIC (44.5%) and un-affordability (6.1%). Significant association of transgender female with consultation with doctors (p=0.013), seeking care at government hospitals (p =0.038) poor experience at health care facility (0.050), neglect during medical treatment (p=0.015) and feeling of discrimination during treatment (p= 0.042).

Conclusion: Transgender community face physical, mental, social and reproductive health issues. About 70% trans-genders receive poor quality of health care services. Non acceptance, feeling ashamed, non-availability of CNIC and non-affordability have been reported as major barriers in getting desired health care.

doi: https://doi.org/10.12669/pjms.38.1.4375

How to cite this:Manzoor I, Khan ZH, Tariq R, Shahzad R. Health Problems & Barriers to Healthcare Services for the Transgender Community in Lahore, Pakistan. Pak J Med Sci. 2022;38(1):138-144. doi: https://doi.org/10.12669/pjms.38.1.4375

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.