bluuebunny/crossref_metadata_2025 huggingface dataset:
To the Question of Vitamin D Network in Type 1 Diabetes and Diabetic Nephropathy in Children Nursed in Ukrainian Endocrinology Unit
Authors: Burlaka Ievgeniia , Mityuryayeva I.O.
Published: December 2022

Background

Vitamin D deficiency is a great problem worldwide. Vitamin D plays an essential role in calcium and bone metabolism. Diabetic nephropathy (DN) is a dangerous kidney-related complication of type 1 diabetes (T1D).

Aim of the study

To evaluate levels of Vitamin D3 in pediatric patients with T1D and DN; to study the dependence between the Vitamin D level and main clinical and laboratory parameters of the disease, that is, duration, complications episodes, albuminuria levels, glomerular filtration rate (GFR).

Material and methods

A survey of 72 children with T1D and DN aged 3–17 years was done. Complex examination including conventional methods (physical examination, blood pressure measurement, blood tests, study of urinary sediment, renal ultrasound, etc.) was done for all patients. Data was processed using GraphPad Prism 9.0 Software for Windows (USA, San Diego, CA). p-values <.05 were considered statistically significant.

Results

Majority of patients from T1D group have normal value of Vitamin D, only 27.7% of children have Vitamin D insufficiency. In contrast, in children from DN group only 16.7% of children have Vitamin D insufficiency and 83.3% have Vitamin D deficiency. Vitamin D serum level negatively correlates with disease duration and albuminuria level in the group with DN. Serum levels of Vitamin D positively correlate with GFR in patients with T1D. Patients with DN who had a duration of T1D for 10 years and more have a higher progression rate to Vitamin D deficiency as compared to those who have a T1D duration of less than 10 years.

Conclusions

The authors conclude that Vitamin D has a direct relationship with functional disorders with DN, that is, albuminuria, GFR, kidney function. Further investigations of Vitamin D supplementation on different stages of the ND development and progression are needed.
LOTUS suppresses amyloid β-induced dendritic spine elimination through the blockade of amyloid β binding to PirB
Authors: Kawaguchi Yuki , Matsubayashi Junpei , Kawakami Yutaka , Nishida Ryohei , Kurihara Yuji , Takei Kohtaro
Published: December 2022

Background

Alzheimer’s disease (AD) is the most common neurodegenerative disease worldwide but has no effective treatment. Amyloid beta (Aβ) protein, a primary risk factor for AD, accumulates and aggregates in the brain of patients with AD. Paired immunoglobulin-like receptor B (PirB) has been identified as a receptor of Aβ and Aβ–PirB molecular interactions that cause synapse elimination and synaptic dysfunction. PirB deletion has been shown to suppress Aβ-induced synaptic dysfunction and behavioral deficits in AD model mice, implying that PirB mediates Aβ-induced AD pathology. Therefore, inhibiting the Aβ–PirB molecular interaction could be a successful approach for combating AD pathology. We previously showed that lateral olfactory tract usher substance (LOTUS) is an endogenous antagonist of type1 Nogo receptor and PirB and that LOTUS overexpression promotes neuronal regeneration following damage to the central nervous system, including spinal cord injury and ischemic stroke. Therefore, in this study, we investigated whether LOTUS inhibits Aβ–PirB interaction and Aβ-induced dendritic spine elimination.

Methods

The inhibitory role of LOTUS against Aβ-PirB (or leukocyte immunoglobulin-like receptor subfamily B member 2: LilrB2) binding was assessed using a ligand-receptor binding assay in Cos7 cells overexpressing PirB and/or LOTUS. We assessed whether LOTUS inhibits Aβ-induced intracellular alterations and synaptotoxicity using immunoblots and spine imaging in a primary cultured hippocampal neuron.

Results

We found that LOTUS inhibits the binding of Aβ to PirB overexpressed in Cos7 cells. In addition, we found that Aβ-induced dephosphorylation of cofilin and Aβ-induced decrease in post-synaptic density-95 expression were suppressed in cultured hippocampal neurons from LOTUS-overexpressing transgenic (LOTUS-tg) mice compared with that in wild-type mice. Moreover, primary cultured hippocampal neurons from LOTUS-tg mice improved the Aβ-induced decrease in dendritic spine density. Finally, we studied whether human LOTUS protein inhibits Aβ binding to LilrB2, a human homolog of PirB, and found that human LOTUS inhibited the binding of Aβ to LilrB2 in a similar manner.

Conclusions

This study implied that LOTUS improved Aβ-induced synapse elimination by suppressing Aβ-PirB interaction in rodents and inhibited Aβ–LilrB2 interaction in humans. Our findings revealed that LOTUS may be a promising therapeutic agent in counteracting Aβ-induced AD pathologies.
CGRP-dependent sensitization of PKC-δ positive neurons in central amygdala mediates chronic migraine
Authors: Chou Tse-Ming , Lee Zhung-Fu , Wang Shuu-Jiun , Lien Cheng-Chang , Chen Shih-Pin
Published: December 2022

Background

To investigate specific brain regions and neural circuits that are responsible for migraine chronification.

Methods

We established a mouse model of chronic migraine with intermittent injections of clinically-relevant dose of nitroglycerin (0.1 mg/kg for 9 days) and validated the model with cephalic and extracephalic mechanical sensitivity, calcitonin gene-related peptide (CGRP) expression in trigeminal ganglion, and responsiveness to sumatriptan or central CGRP blockade. We explored the neurons that were sensitized along with migraine chronification and investigated their roles on migraine phenotypes with chemogenetics.

Results

After repetitive nitroglycerin injections, mice displayed sustained supraorbital and hind paw mechanical hyperalgesia, which lasted beyond discontinuation of nitroglycerin infusion and could be transiently reversed by sumatriptan. The CGRP expression in trigeminal ganglion was also upregulated. We found the pERK positive cells were significantly increased in the central nucleus of the amygdala (CeA), and these sensitized cells in the CeA were predominantly protein kinase C-delta (PKC-δ) positive neurons co-expressing CGRP receptors. Remarkably, blockade of the parabrachial nucleus (PBN)-CeA CGRP neurotransmission by CGRP8–37 microinjection to the CeA attenuated the sustained cephalic and extracephalic mechanical hyperalgesia. Furthermore, chemogenetic silencing of the sensitized CeA PKC-δ positive neurons reversed the mechanical hyperalgesia and CGRP expression in the trigeminal ganglion. In contrast, repetitive chemogenetic activation of the CeA PKC-δ positive neurons recapitulated chronic migraine-like phenotypes in naïve mice.

Conclusions

Our data suggest that CeA PKC-δ positive neurons innervated by PBN CGRP positive neurons might contribute to the chronification of migraine, which may serve as future therapeutic targets for chronic migraine.

Graphical Abstract
Genetic analysis of the ATP11B gene in Chinese Han population with cerebral small vessel disease
Authors: Yu Wen-Kai , Wang Yun-Chao , Gao Yuan , Shi Chang-He , Fan Yu , Yu Lu-Lu , Zhao Zi-Chen , Li Shan-Shan , Xu Yu-Ming , Li Yu-Sheng
Published: December 2022

Background

A loss-of-function mutation in ATPase phospholipid transporting 11-B (putative) (ATP11B) gene causing cerebral small vessel disease (SVD) in vivo, and a single intronic nucleotide polymorphism in ATP11B: rs148771930 that was associated with white matter hyperintensities burden in European patients with SVD, was recently identified. Our results suggest that ATP11B may not play an essential role in SVD in the Chinese population.

Results

We performed target region sequencing including ATP11B gene in 182 patients with sporadic SVD, and identified five rare variants and two novel variants of ATP11B. A case–control study was then performed in 524 patients and matched 550 controls to investigate the relationship between ATP11B and sporadic SVD in the Chinese Han population. Although none of these variants were significantly associated with SVD in our samples, it is important to mention that we identified a novel variant, p. G238W, which was predicted to be pathogenic in silico. This variant was present in our cohort of patients with an extremely low frequency and was absent in the controls.

Conclusion

Our results suggest that ATP11B may not play an essential role in SVD in the Chinese population.
Yield stability and economic heterosis analysis in newly bred sunflower hybrids throughout diverse agro-ecological zones
Authors: Chakraborty Nihar Ranjan , Lakshman Shyam Sundar , Debnath Sandip , Rahimi Mehdi
Published: December 2022

Exploration of heterosis is a strategy for enhancing sunflower yield and productivity. In India, the greatest constraints on sunflower production are stagnant and inconsistent yields. By raising them in a variety of ecological conditions, stableper-seperformance with the highest yielding potential sunflower hybrids were selected. Sustainable agriculture requires the use of desirable hybrids with high seed yields and oil content too. By making three distinct crossing sets from 32 sunflower genotypes, 11 cytoplasmic male sterility (CMS), and 21 restorer lines, a total of 124 hybrids were developed (comprising both lines and tester). After extensive field evaluation of all hybrids, only eight superior F1s belonging to all three sets, as well as the three national control hybrids KBSH-53, LSFH-171, and DRSH-1, were selected for stability analysis in four agro-ecological regions of West Bengal, India viz., Nimpith, Baruipur, Bankura, and Berhapore. The genetic stability of several phenotypic characters was assessed using statistical models that examine genotype-environment interaction (G × E) in multi-locational yield trials. In this experiment, the performance of hybrids under various environmental circumstances over two-year periods was measured using regression coefficient (bi) and deviations from regression (S2di). With the exception of genotypes CMS-852A × EC-601751 for volume weight (0.9335) and CMS-302A × EC-623011 for head diameter (0.0905) and volume weight (0.6425), all sunflower genotypes for all concerned traits had extremely minor and negligible deviations from regression (S2di), which showed significant values. The genotypes having insignificant values of S2diwere more stable. The economic heterosis of these novel hybrids was also quantified. CMS-302A × EC-623011 in which seed yield was recorded 20.90, 20.91, 20.95 and 20.90% higher than DRSH-1 at Nimpith, Baruipur, Bankura and PORS (Berhampur), respectively. The research revealed that CMS-302A × EC-623011, CMS-853A × EC-623027 and P-2–7-1A × EC-512682 exhibited good seed production and stability for critical agronomic parameters in addition to oil content. As a result, the current researches enlighten to find out how stable the expression of important economic traits in sunflower hybrids is.
Measuring the quality of life of long-term care service users in Japan: a cross-sectional questionnaire study
Authors: Hara Koji , Nakabe Takayo , Tanaka Masayuki , Imanaka Yuichi
Published: December 2022

Background

In Japan’s super-aging society, the number of long-term care service providers is increasing, and the quality of care is a matter of concern. One aspect of the quality of care is the user’s quality of life. The questionnaires EQ-5D and WHO-5 are representative indicators of quality of life. Herein, we aimed to measure the quality of life in long-term care service users in Japan and to clarify the relationship between quality of life and the level of care required.

Methods

A questionnaire study was conducted in 106 facilities of 22 corporations. In addition to the EQ-5D and WHO-5, sex, age, and the level of care required were assessed by descriptive statistics. Bonferroni’s multiple comparison test was used to analyze each quality of life score, and the differences by sex and age were analyzed multiple regression analyses, with each quality of life score as the objective variable.

Results

Of 4647 cases collected, 2830 were analyzed, with no missing data. Both indicators tended to be lower than the general older population. Those scores tended to be higher in females than males (EQ-5D: males, 0.58 ± 0.26; females, 0.60 ± 0.24; P = 0.06 and WHO-5: males, 13.8 ± 5.92; females 14.9 ± 5.70; P < 0.001). In terms of age, those under 65 years old with specific diseases had lower EQ-5D scores than those in other age groups (P < 0.001); however, WHO-5 scores did not differ by age. Multiple regression analysis showed a significant association between the EQ-5D score and level of care required, except for support-required level 1, which tended to worsen as the level of care required increased. Conversely, the WHO-5 score was significantly lower for care need levels 2, 4, and 5.

Conclusions

The quality of life of long-term care service users was worse than that of the general older population, it tended to be low among males and those under 65 years old with specific diseases. Furthermore, it gradually decreased as the level of care required increased. It is important to monitor users’ quality of life as a quality indicator of care, to improve and manage it.
Hematologic and inflammatory parameters for determining severity of odontogenic infections at admission: a retrospective study
Authors: Kusumoto Junya , Iwata Eiji , Huang Wensu , Takata Naoki , Tachibana Akira , Akashi Masaya
Published: December 2022

Background

Severe odontogenic infections in the head and neck region, especially necrotizing soft tissue infection (NSTI) and deep neck abscess, are potentially fatal due to their delayed diagnosis and treatment. Clinically, it is often difficult to distinguish NSTI and deep neck abscess in its early stage from cellulitis, and the decision to perform contrast-enhanced computed tomography imaging for detection is often a challenge. This retrospective case–control study aimed to examine the utility of routine blood tests as an adjunctive diagnostic tool for NSTI in the head and neck region and deep neck abscesses.

Methods

Patients with severe odontogenic infections in the head and neck region that required hospitalization were classified into four groups. At admission, hematologic and inflammatory parameters were calculated according to the blood test results. In addition, a decision tree analysis was performed to detect NSTI and deep neck abscesses.

Results

There were 271 patients, 45.4% in Group I (cellulitis), 22.5% in Group II (cellulitis with shallow abscess formation), 27.3% in Group III (deep neck abscess), and 4.8% in Group IV (NSTI). All hematologic and inflammatory parameters were higher in Groups III and IV. The Laboratory Risk Indicator for Necrotizing Fasciitis score, with a cut-off value of 6 and C-reactive protein (CRP) + the neutrophil-to-lymphocyte ratio (NLR), with a cut-off of 27, were remarkably useful for the exclusion diagnosis for Group IV. The decision tree analysis showed that the systemic immune-inflammation index (SII) of ≥ 282 or < 282 but with a CRP + NLR of ≥ 25 suggests Group III + IV and the classification accuracy was 89.3%.

Conclusions

Hematologic and inflammatory parameters calculated using routine blood tests can be helpful as an adjunctive diagnostic tool in the early diagnosis of potentially fatal odontogenic infections. An SII of ≥ 282 or < 282 but with a CRP + NLR of ≥ 25 can be useful in the decision-making for performing contrast-enhanced computed tomography imaging.
Association between uric acid level and contrast-induced acute kidney injury in patients with type 2 diabetes mellitus after coronary angiography: a retrospective cohort study
Authors: Tang Haixia , Chen Haoying , Li Zuolin , Xu Shengchun , Yan Gaoliang , Tang Chengchun , Liu Hong
Published: December 2022

Background

This study assessed the predictive value of uric acid (UA) for contrast-induced acute kidney injury (CI-AKI) in patients with type 2 diabetes mellitus (T2DM) who underwent coronary angiography (CAG). A nomogram to aid in the prediction of CI-AKI was also developed and validated, and the construction of a prognostic nomogram combined with clinical features was attempted.

Methods

This study retrospectively enrolled T2DM patients who underwent CAG between December 2019 and December 2020 at the Affiliated Zhongda Hospital of Southeast University. Multivariable logistic regression analysis was used for the analysis of clinical outcomes. Receiver operating characteristic (ROC) analyses were performed to determine the area under the ROC curve (AUC) and the cut-off points for continuous clinical data. The prediction accuracies of models for CI-AKI were estimated through Harrell’s concordance indices (C-index). Nomograms of the prognostic models were plotted for individualized evaluations of CI-AKI in T2DM patients after CAG.

Results

A total of 542 patients with T2DM who underwent CAG were included in this study. We found that a high UA level (≥ 425.5 µmol/L; OR = 6.303), BUN level (≥ 5.98 mmol/L; OR = 3.633), Scr level (≥ 88.5 µmol/L; OR = 2.926) and HbA1C level (≥ 7.05%; OR = 5.509) were independent factors for CI-AKI in T2DM patients after CAG. The nomogram model based on UA, BUN, Scr and HbA1C levels presented outstanding performance for CI-AKI prediction (C-index: 0.878). Decision curve analysis (DCA) showed good clinical applicability in predicting the incidence of CI-AKI in T2DM patients who underwent CAG.

Conclusion

High UA levels are associated with an increased incidence of CI-AKI in T2DM patients after CAG. The developed nomogram model has potential predictive value for CI-AKI and might serve as an economic and efficient prognostic tool in clinical practice.
Bilateral mydriasis as first manifestation of Hodgkin’s lymphoma: a case report
Authors: Baki Enayatullah , Scheidhauer Klemens , Schmidt-Graf Friederike
Published: December 2022

Background

Bilateral mydriasis is usually associated with severe brain stem damage or drug-induced sympathomimetic stimulation.

Herein we report it as a unique neurologic complication of Hodgkin’s lymphoma.

Case presentation

A 23-year-old woman presented at our emergency department with dilated pupils unresponsive to light stimuli. MRI and CT scans showed bilaterally enlarged lymph nodes in the mediastinum and supraclavicular compressing the carotid artery on both sides. The histologic examination of lymph node biopsy specimens confirmed the diagnosis of Hodgkin’s lymphoma.

Conclusion

Pathologies around the carotid artery causing oculosympathetic spasm should be considered among the possible causes of a mydriasis, especially when other common causes like brain stem impairment are excluded.
Case report: radiation-induced lumbosacral plexopathy – a very late complication of radiotherapy for cervical cancer
Authors: Krkoska Peter , Kazda Tomas , Vlazna Daniela , Adamova Blanka
Published: December 2022

Background

Lumbosacral plexopathy caused by radiotherapy is a rare but severe consequence of cancer treatment. This condition often leads to varying degrees of sensory and motor impairment. Neurological complications, which are typically permanent, manifest a long period after irradiation.

Case presentation

We describe a case of progressive lower extremity weakness and sensory impairment in a woman who had been effectively treated with radiotherapy for cervical cancer with development 36 years after irradiation. The electrophysiological assessment revealed a subacute bilateral axonal lesion of the lumbosacral plexus. None of the clinical manifestations, serology, cerebrospinal fluid or imaging data discovered an explanation other than radiation-induced lumbosacral plexopathy (RILP).

Conclusions

This case demonstrates that RILP may emerge more than 30 years after the radiotherapy.
A phase II single arm study of Nivolumab with stereotactic Ablative radiation Therapy after induction chemotherapy in CHOlangiocarcinoma (NATCHO)
Authors: Elias Charbel , Zeidan Youssef H. , Bouferraa Youssef , Mukherji Deborah , Temraz Sally , Charafeddine Maya , Al Darazi Monita , Shamseddine Ali
Published: December 2022

Background

Intrahepatic cholangiocarcinoma (CCA) is amongst the most common primary liver tumors worldwide. CCA carries a bad prognosis prompting research to establish new treatment modalities other than surgery and the current chemotherapeutic regimens adopted. Hence, this trial explores a new therapeutic approach, to combine stereotactic body radiation therapy (SBRT) and immunotherapy (Nivolumab), and asses its clinical benefit and safety profile after induction chemotherapy in CCA.

Methodology

This is a Phase II open-label, single-arm, multicenter study that investigates Nivolumab (PD-1 inhibitor) treatment at Day 1 followed by SBRT (30 Gy in 3 to 5 fractions) at Day 8, then monthly Nivolumab in 40 patients with non-resectable locally advanced, metastatic or recurrent intrahepatic or extrahepatic CCA. Eligible patients were those above 18 years of age with a pathologically and radiologically confirmed diagnosis of non-resectable locally advanced or metastatic or recurrent intrahepatic or extrahepatic CCA, following 4 cycles of cisplatin-based chemotherapy with an estimated life expectancy of more than 3 months, among other criteria. The primary endpoint is the progression free survival (PFS) rate at 8 months and disease control rate (DCR). The secondary endpoints are overall survival (OS), tumor response rate (TRR), duration of response, evaluation of biomarkers: CD3 + , CD4 + and CD8 + T cell infiltration, as well as any change in the PD-L1 expression through percutaneous core biopsy when compared with the baseline biopsy following 1 cycle of Nivolumab and SBRT.

Discussion

SRBT alone showed promising results in the literature by both inducing the immune system locally and having abscopal effects on distant metastases. Moreover, given the prevalence of PD-L1 in solid tumors, targeting it or its receptor has become the mainstay of novel immunotherapeutic drugs use. A combination of both has never been explored in the scope of CCA and that is the aim of this study.

Trial registration

ClinicalTrials.gov NCT04648319,
April 20, 2018.
Markers associated with genomic instability, immunogenicity and immune therapy responsiveness in Metaplastic carcinoma of the breast: Expression of γH2AX, pRPA2, P53, PD-L1 and tumor infiltrating lymphocytes in 76 cases
Authors: Voutilainen S. , Heikkilä P. , Bartkova J. , Nevanlinna H. , Blomqvist C. , Bartek J. , Mattson J.
Published: December 2022

Background

Metaplastic breast cancer (MpBC) is an aggressive subtype of breast carcinoma that is often resistant to conventional chemotherapy. Therefore, novel treatment strategies are urgently needed. Immune check point inhibitors have shown activity in programmed death-ligand 1 (PD-L1) – positive metastatic triple negative breast carcinoma (TNBC), which raises the possibility that immunotherapy may also be effective in MpBC as most of the MpBCs are triple negative. The aim of the present study was to assess genomic instability and immunogenicity in tumor specimens of patients with MpBC.

Methods

A total of 76 patients diagnosed with MpBC over a 15-year period were included in the study. We performed immunohistochemical analyses for tumor cell PD-L1, immune cell PD-L1 and p53 on tissue microarrays (TMAs), analyzed stromal and intratumoral tumor infiltrating lymphocytes (TILs) from hematoxylin and eosin-stained (H&E) slides and scored gamma-H2AX (γH2AX) and phosphorylated-RPA2 (pRPA2) from whole tissue sections. We correlated marker expression with clinicopathologic features and clinical outcome.

Results

All tumors expressed γH2AX and pRPA2 with median expressions of 43% and 44%. P53- (68%), tumor cell PD-L1- (59%) and immune cell PD-L1-positivity (62%) were common in MpBCs. Median stromal TIL and intratumoral TIL counts were 5% and 0. The spindle and squamous cell carcinomas expressed the highest levels of PD-L1 and TILs, and carcinoma with mesenchymal differentiation the lowest.

Conclusions

MpBC appears to be an immunogenic cancer with high genomic instability and frequent PD-L1-positivity, implying that check point inhibitors might be effective in MpBC. Expression levels of PD-L1 and TILs varied across different histologic subtypes, suggesting that immunotherapy might be less effective in carcinoma with mesenchymal differentiation.
The quality of life in children with spinal muscular atrophy: a case–control study
Authors: Zamani Gholamreza , Ashrafi Mahmoud Reza , Ghabeli Homa , Akbari Masood Ghahvechi , Mohammadi Mahmoud , Badv Reza Shervin , Hosseinpour Sareh , Haghighi Roya , Pourbakhtyaran Elham , Khosroshahi Nahid , Heidari Morteza
Published: December 2022

Objectives

This study aimed to analyze the health-related quality of life (HRQoL) of patients with spinal muscular atrophy (SMA) based on the type of SMA, demographic and clinical features and compare HRQoL of these patients with a matched healthy control group. 

Methods

This was a case–control study of Patients with SMA in Iran. Sixty-six patients with SMA type II and III aged 8–18 years and also 264 healthy age, sex, and socio-economic matched individuals were enrolled. To assess the quality of life, we used the Persian version of the KIDSCREEN-27.

Results

The health-related quality of life between children with type II and type III SMA was not significant in all 5 subscales. However, HRQoL in healthy children was significantly higher than in SMA children in all 5 subscales.

Conclusion

The quality of life in children with SMA was lower than the healthy control group in all subscales, and physical well-being and psychosocial aspects are the main domains of life impaired by SMA disease. However, no significant difference between the quality of life in children with SMA type II and type III was observed.
Risky or protective? Online social support’s impact on NSSI amongst Chinese youth experiencing stressful life events
Authors: Xin Moye , Zhang Lijin , Yang Chengxi , Yang Xueyan , Xiang Meiqiu
Published: December 2022

Background

This study was designed to investigate potential gender differences in the interrelations between different types of stressful life events and non-suicidal self injury (NSSI) among Chinese youth, as well as to test the direct and moderating impacts of online social support on Chinese students’ NSSI engagement under the pressure of different types of stressful life events.

Methods

Based on the data of 2200 students from middle - highschools and universities in Northwestern China, gender difference (male/female binary) in stressful life events, online social support, NSSI and their correlations were analyzed in the study.

Results

Among different types of stressful life events, male students were reported to experience a significantly higher impact of punishment and interpersonal relationship than females. Female students only experienced significantly higher learning pressure than males; Gender difference was not indentified in NSSI among youth; Stressful life events related to punishment could significantly predict NSSI engagement among males. Stressful life events related to learning pressures, interpersonal relationships, and adaption were significantly correlated to NSSI engagement among females; Online social support didn’t had a significant direct effect on youth’s NSSI, although it did significantly moderate the relationship between specific types of stressful life events (i.e., loss, interpersonal relationships, adaption among males and all types among females) and their NSSI.

Conclusion

The present study has provided evidence of specified types of stressful life events being risk factors in affecting youth’s NSSI: For male students, the higher impacts of stressful life events related to punishment they experienced, the more likely they were about to engage in NSSI. For female students, stressful life events related to learning pressure, interpersonal relationships and adaption were all proved as significant predictors and risky factors of female youth’s NSSI; Online social support did not impact on individual’s NSSI engagement directly, but moderated it significantly as a protective factor.
Among the swedish generation of adolescents who experience an increased trend of psychosomatic symptoms. Do they develop depression and/or anxiety disorders as they grow older?
Authors: Giannotta F. , Nilsson K. W. , Åslund C. , Larm P.
Published: December 2022

Background

Despite an increase in mental health problems, with psychosomatic symptoms having been observed in new generations of Swedish youth, the extent to which these problems correspond to an increase in adult mental problems is unknown. The present study investigates whether Swedish adolescents with high levels of psychosomatic symptoms are at risk of developing depression and anxiety problems in adulthood and whether sex moderates any association. Moreover, we aim to understand whether different clusters of youth psychosomatic symptoms – somatic, psychological and musculoskeletal – have different impacts on adult mental health.

Methods

One thousand five hundred forty-five Swedish adolescents – aged 13 (49%) and 15 (51%) – completed surveys at baseline (T1) and 3 years later (T2); of them, 1174 (61% females) also participated after 6 years (T3). Multivariate logistic models were run.

Results

Youth with high levels of psychosomatic symptoms had higher odds of high levels of depressive symptoms at T2 and T3. Moreover, psychosomatic symptoms at T1 predicted a high level of anxiety symptoms and diagnoses of anxiety disorders at T3. When analyzed separately, musculoskeletal symptoms predicted higher odds of having high levels of depressive symptoms at T2 and T3 while somatic symptoms predicted high levels of anxiety symptoms at T2. Moreover, somatic symptoms at T1 predicted diagnoses of depression and anxiety disorders at T3. Sex did not moderate any of the relationships.

Conclusions

The study supports the idea that an increase in mental health problems, such as psychosomatic symptoms, can seriously impact the psychological health of new generations of young adults.
The relationship between mental health and violence toward women during the COVID-19 pandemic
Authors: Shoaei Najmeh Khatoon , Asadi Neda , Salmani Mahin
Published: December 2022

The COVID-19 pandemic has a number of psychological consequences for societies, especially women. This study was conducted to determine the relationship between mental health and violence toward women during the COVID-19 pandemic in Iran.This study was conducted on during late October to November 2020 (N = 400). Demographic information questionnaire, General Health Questionnaire(GHQ-12) and violence toward women inventory(VTWI) were used.The results showed that violence was higher among employed women. Also, the results showed that VTW was higher in women with 3 children, high school degree, family income under 3 million and women over 40 years old. Findings showed that the mean mental health of women at the COVID-19 pandemic was moderate (15.14 ± 8.8). Also, with increasing psychological and economic violence, their mental health decreases. Therefore, it is suggested that policy makers and planners, apart from the physical effects of the COVID-19 pandemic, pay attention to its psychological dimension, especially for women, and try to allocate funds to maintain and promote mental health and family.
Socioeconomic differences in COVID-19 infection, hospitalisation and mortality in urban areas in a region in the South of Europe
Authors: Fernández-Martínez Nicolás F , Ruiz-Montero Rafael , Gómez-Barroso Diana , Rodríguez-Torronteras Alejandro , Lorusso Nicola , Salcedo-Leal Inmaculada , Sordo Luis
Published: December 2022

Background

To analyse differences in confirmed cases, hospitalisations and deaths due to COVID-19 related to census section socioeconomic variables. 

Methods

Ecological study in the 12 largest municipalities in Andalusia (Spain) during the first three epidemic waves of the COVID-19 (02/26/20—03/31/21), covering 2,246 census sections (unit of analysis) and 3,027,000 inhabitants. Incidence was calculated, standardised by age and sex, for infection, hospitalisation and deaths based on average gross income per household (AGI) for the census tracts in each urban area. Association studied using a Poisson Bayesian regression model with random effects for spatial smoothing.

Results

There were 140,743 cases of COVID-19, of which 12,585 were hospitalised and 2,255 died. 95.2% of cases were attributed to the second and third waves, which were jointly analysed. We observed a protective effect of income for infection in 3/12 cities. Almeria had the largest protective effect (smoothed relative risk (SRR) = 0.84 (0.75–0.94 CI 95%). This relationship reappeared with greater magnitude in 10/12 cities for hospitalisation, lowest risk in Algeciras SRR = 0.41 (0.29–0.56). The pattern was repeated for deaths in all urban areas and reached statistical significance in 8 cities. Lowest risk in Dos Hermanas SRR = 0.35 (0.15–0.81).

Conclusions

Income inequalities by geographical area were found in the incidence of COVID-19. The strengths of the association increased when analysing the severe outcomes of hospitalisations and, above all, deaths.
Possible synergic action of non-steroidal anti-inflammatory drugs and glucosamine sulfate for the treatment of knee osteoarthritis: a scoping review
Authors: Veronese Nicola , Ecarnot Fiona , Cheleschi Sara , Fioravanti Antonella , Maggi Stefania
Published: December 2022

Background

Several studies have reported that glucosamine sulfate (GS) can improve knee osteoarthritis (OA) symptomatology. In parallel, the disease-modifying effects of non-steroidal anti-inflammatory drugs (NSAIDs) in knee OA have also been investigated. However, limited literature has reported the combined effect of GS and NSAIDs. The aim of this scoping review is to describe the scope and volume of the literature investigating the potential benefits and synergistic effect of a combination of GS and NSAIDs in patients with knee OA.

Methods

PubMed and Embase were searched for studies published from inception through April 2022, evaluating the effects of the combination of GS and NSAIDs in OA patients, versus either treatment alone. Data are reported narratively.

Results

Five studies were included in this review; 4 were randomized control trials and one was a prospective observational study. The duration of combination treatment was 6 to 12 weeks. The combination was compared to celecoxib in 2 studies, meloxicam in 1, etoricoxib in 1, and a conventional NSAID in 1 (ibuprofen or piroxicam). All 5 studies reported that in patients with knee OA, the combination of GS plus NSAID yielded a significantly greater benefit than single-agent therapy, in terms of outcomes including pain reduction, function, joint stiffness, and markers of inflammatory activity and cartilage degradation.

Conclusion

The 5 studies included in this scoping review all report a significantly greater clinical benefit with a combination of GS plus NSAID compared to either treatment alone. The evidence supports efficacy in reducing pain, improving function, and possibly regulating joint damage. However, further randomized trials with larger sample sizes are warranted to confirm these findings.
A WeChat-based competency and performance checklist in basic surgical skills course for military medical academy undergraduates
Authors: Luo Pengfei , Shui Xianqi , Zhou Yamei , Jiang Xiaoyu , Liu Jia , Sun Yu , Chang Yifan
Published: December 2022

Background

Basic surgical skills (BSS) is a key bridging course for medical students to acquire basic surgical maneuvers and practice animal surgery before clinical rotation, but the complexity of operational procedures and high demands on asepsis may lead to poor performance and frequent error during practice. The current study intended to improve BSS teaching outcomes by implementing smartphone app-based competency and performance checklists for medical academy undergraduates.

Methods

WeChat-based checklists containing competency and performance modules were designed, distributed and collected via smartphone. One hundred seventy-six third-grade undergraduate cadets majoring in clinical medicine or anesthesiology were prospectively enrolled, with 92 set as study group and 84 as control group. Checklists were distributed for self-evaluation before and after each class throughout the semester of autumn 2021-2022. Student age, previous Grade Point Average (GPA), average grades of BSS (including grade-A rate and pass rate), operative time, error rate, and perioperative complications of intestinal anastomosis performed on Beagle dogs between the groups were compared to evaluate the efficacy of the checklists.

Results

The students aged 20.2 ± 0.63 in Group A and 20.3 ± 0.92 in Group B (P = 0.15), with a previous GPA of 2.9 ± 0.61 vs. 2.87 ± 0.58 (P = 0.61). The average operative time on their final lesson of intestinal anastomosis was 192.3 ± 27.18 min vs. 213.8 ± 29.48 min (P < 0.001). All students passed in BSS course, with a final grade of 89.45 ± 4.360 in Group A and 86.64 ± 4.026 in Group B (P < 0.001), in which grade-A rate was 46.7% vs. 26.2% (P = 0.005). For perioperative comorbidities, 4/23 (17.4%) animals in Group A and 5/21 (23.8%) in Group B recorded wound dehiscence or other incision-related complications; no animals died in Group A, and 2 died in Group B due to hemorrhagic shock or sepsis.

Conclusions

The implementation of WeChat-based checklist is a reflection of improved quality of teaching in BSS course that may promote the students’ competency and performance.
The role of Neanderthal introgression in liver cancer
Authors: Taravella Oill Angela M. , Buetow Kenneth H. , Wilson Melissa A.
Published: December 2022

Background

Neanderthal introgressed DNA has been linked to different normal and disease traits including immunity and metabolism—two important functions that are altered in liver cancer. However, there is limited understanding of the relationship between Neanderthal introgression and liver cancer risk. The aim of this study was to investigate the relationship between Neanderthal introgression and liver cancer risk.

Methods

Using germline and somatic DNA and tumor RNA from liver cancer patients from The Cancer Genome Atlas, along with ancestry-match germline DNA from unaffected individuals from the 1000 Genomes Resource, and allele specific expression data from normal liver tissue from The Genotype-Tissue Expression project we investigated whether Neanderthal introgression impacts cancer etiology. Using a previously generated set of Neanderthal alleles, we identified Neanderthal introgressed haplotypes. We then tested whether somatic mutations are enriched or depleted on Neanderthal introgressed haplotypes compared to modern haplotypes. We also computationally assessed whether somatic mutations have a functional effect or show evidence of regulating expression of Neanderthal haplotypes. Finally, we compared patterns of Neanderthal introgression in liver cancer patients and the general population.

Results

We find Neanderthal introgressed haplotypes exhibit an excess of somatic mutations compared to modern haplotypes. Variant Effect Predictor analysis revealed that most of the somatic mutations on these Neanderthal introgressed haplotypes are not functional. We did observe expression differences of Neanderthal alleles between tumor and normal for four genes that also showed a pattern of enrichment of somatic mutations on Neanderthal haplotypes. However, gene expression was similar between liver cancer patients with modern ancestry and liver cancer patients with Neanderthal ancestry at these genes. Provocatively, when analyzing all genes, we find evidence of Neanderthal introgression regulating expression in tumor from liver cancer patients in two genes, ARK1C4 and OAS1. Finally, we find that most genes do not show a difference in the proportion of Neanderthal introgression between liver cancer patients and the general population.

Conclusion

Our results suggest that Neanderthal introgression provides opportunity for somatic mutations to accumulate, and that some Neanderthal introgression may impact liver cancer risk.
Female sex workers and police violence during the Covid-19 health crisis in 2020–2021: results from the EPIC multi-country community-based research program in Argentina
Authors: Aristegui I. , Castro Avila J. , Villes V. , Delabre R. M. , Orellano G. , Aguilera M. , Romero M. , Riegel L. , Kretzer L. , Cardozo N. , Radusky P. D. , Rojas Castro D. ,   EPIC Study Group
Published: December 2022

Background

Female sex workers (FSW) have been disproportionately impacted by the Covid-19 crisis. Data show increases of police violence toward key populations (KP), likely a consequence of their role in enforcing health government measures. This study aimed to identify factors associated with police violence experienced by FSW during the Covid-19 crisis in Argentina.

Methods

EPIC is a multi-country, cross-sectional, community-based research program evaluating the impact of Covid-19 among KP. In Argentina, the study was conducted in collaboration with FSW community-based organizations (CBO). Participants completed an online survey (October 2020–April 2021). Police violence was measured as having experienced episodes of violence (physical, verbal, psychological or sexual) by security forces since the start of the health crisis. Factors associated with police violence were assessed in logistic regression models.

Results

Among 173 respondents, median age was 34 [IQR 27–42], 39.3% were transgender women (TW), 78.1% declared sex work as their only income and 71.7% mentioned their financial situation has deteriorated with the health crisis. Nearly half of FSW (44.5%) reported experiencing police violence within the first year of the Covid-19 pandemic, and among them, 76.6% declared more frequent violence episodes since the beginning of the health crisis. After adjustment for age, being a TW (aOR [95% CI] = 2.71 [1.21;6.05]), reporting non-injection drug use (2.92 [1.02;8.36]), having a considerably deteriorated financial situation (3.67 [1.47;9.21]), having had a consultation with a CBO worker for medical care/treatments (5.56 [2.15;14.37]) and declaring fear or experiences of discrimination by physicians/other health workers (2.97 [1.21;7.29]), since the beginning of the Covid-19 health crisis, were independently associated with police violence.

Conclusions

FSW in Argentina have experienced an increase in police violence since the beginning of the health crisis. Belonging to multiple KP (FSW, TW, people who use drugs) increases the likelihood of experiencing police violence, highlighting the need of an intersectional approach to develop interventions to reduce stigma and violence against FSW. CBOs have provided essential support and services during the crisis to FSWs, and other KPs, who may have avoided traditional healthcare structures due to fear or experiences of discrimination.
Analysis of policy responses to COVID-19: a case study in Babol University of Medical Sciences (BUMS), Iran
Authors: Farhadi Zeynab , Salemi Morteza , Jahani Mohammad Ali
Published: December 2022

Background

Preparation and financing of treatments, control of disease by limited resources, are known as the most important challenges encountered by the policy-makers involved in an epidemic outbreak. Therefore, the present study was conducted to analyze the policy responses of Babol University of Medical Sciences (BUMS) to Coronavirus (COVID-19).

Methods

A qualitative study was performed to investigate the policy responses of BUMS to COVID-19 in Babol of January to March, 2021. The statistical population included the experts, pundits, policy-makers and planners involved in four areas of management, treatment, healthcare, and health donation. Data collection was done according to interviews and policy documents, and the obtained data were analyzed based on the Walt and Gilson’s policy triangle.

Results

There are five main themes to names: policy context, policy analysis, policy-making process, actors and stakeholders and 16 sub-themes. After several rounds of revision, the text of the interviews and policy documents were tagged and finally, various issues related to sub-themes were extracted. Also, two sub-themes entitled (improving the policy framework, People’s participation) were obtained from the strategies to reduce the incidence of Covid-19 theme.

Conclusions

(BUMS) was able to use the capacities and skills of experienced physicians, specialists and nurses to respond to patients awaiting treatment. Therefore, most of the policies were aimed at patient care and treatment. The lack of financial resources was compensated by health donors. But the (BUMS) could not use the power of the city government to control traffic and comply with health protocols and prevent infections. It was mainly the formulation and implementation of irregular and unstable policies.
Brain pharmacokinetics of mono- and bispecific amyloid-β antibodies in wild-type and Alzheimer’s disease mice measured by high cut-off microdialysis
Authors: Julku Ulrika , Xiong Mengfei , Wik Elin , Roshanbin Sahar , Sehlin Dag , Syvänen Stina
Published: December 2022

Background

Treatment with amyloid-β (Aβ) targeting antibodies is a promising approach to remove Aβ brain pathology in Alzheimer's disease (AD) and possibly even slow down or stop progression of the disease. One of the main challenges of brain immunotherapy is the restricted delivery of antibodies to the brain. However, bispecific antibodies that utilize the transferrin receptor (TfR) as a shuttle for transport across the blood–brain barrier (BBB) can access the brain better than traditional monospecific antibodies. Previous studies have shown that bispecific Aβ targeting antibodies have higher brain distribution, and can remove Aβ pathology more efficiently than monospecific antibodies. Yet, there is only limited information available on brain pharmacokinetics, especially regarding differences between mono- and bispecific antibodies.

Methods

The aim of the study was to compare brain pharmacokinetics of Aβ-targeting monospecific mAb3D6 and its bispecific version mAb3D6-scFv8D3 that also targets TfR. High cut-off microdialysis was used to measure intravenously injected radiolabelled mAb3D6 and mAb3D6-scFv8D3 antibodies in the interstitial fluid (ISF) of hippocampus in wild-type mice and the AppNL−G−F mouse model of AD. Distribution of the antibodies in the brain and the peripheral tissue was examined by ex vivo autoradiography and biodistribution studies.

Results

Brain concentrations of the bispecific antibody were elevated compared to the monospecific antibody in the hippocampal ISF measured by microdialysis and in the brain tissue at 4–6 h after an intravenous injection. The concentration of the bispecific antibody was approximately twofold higher in the ISF dialysate compared to the concentration of monospecific antibody and eightfold higher in brain tissue 6 h post-injection. The ISF dialysate concentrations for both antibodies were similar in both wild-type and AppNL−G−F mice 24 h post-injection, although the total brain tissue concentration of the bispecific antibody was higher than that of the monospecific antibody at this time point. Some accumulation of radioactivity around the probe area was observed especially for the monospecific antibody indicating that the probe compromised the BBB to some extent at the probe insertion site.

Conclusion

The BBB-penetrating bispecific antibody displayed higher ISF concentrations than the monospecific antibody. The concentration difference between the two antibodies was even larger in the whole brain than in the ISF. Further, the bispecific antibody, but not the monospecific antibody, displayed higher total brain concentrations than ISF concentrations, indicating association to brain tissue.