bluuebunny/crossref_metadata_2025 huggingface dataset:
Early-life undernutrition induces enhancer RNA remodeling in mice liver
Authors: Wang Yinyu , Mao Yiting , Zhao Yiran , Yi Xianfu , Ding Guolian , Yu Chuanjin , Sheng Jianzhong , Liu Xinmei , Meng Yicong , Huang Hefeng
Published: March 2021

Background

Maternal protein restriction diet (PRD) increases the risk of metabolic dysfunction in adulthood, the mechanisms during the early life of offspring are still poorly understood. Apart from genetic factors, epigenetic mechanisms are crucial to offer phenotypic plasticity in response to environmental situations and transmission. Enhancer-associated noncoding RNAs (eRNAs) transcription serves as a robust indicator of enhancer activation, and have potential roles in mediating enhancer functions and gene transcription.

Results

Using global run-on sequencing (GRO-seq) of nascent RNA including eRNA and total RNA sequencing data, we show that early-life undernutrition causes remodeling of enhancer activity in mouse liver. Differentially expressed nascent active genes were enriched in metabolic pathways. Besides, our work detected a large number of high confidence enhancers based on eRNA transcription at the ages of 4 weeks and 7 weeks, respectively. Importantly, except for ~ 1000 remodeling enhancers, the early-life undernutrition induced instability of enhancer activity which decreased in 4 weeks and increased in adulthood. eRNA transcription mainly contributes to the regulation of some important metabolic enzymes, suggesting a link between metabolic dysfunction and enhancer transcriptional control. We discovered a novel eRNA that is positively correlated to the expression of circadian gene Cry1 with increased binding of epigenetic cofactor p300.

Conclusions

Our study reveals novel insights into mechanisms of metabolic dysfunction. Enhancer activity in early life acts on metabolism-associated genes, leading to the increased susceptibility of metabolic disorders.
Clinical features and relapse risks of IgG4-related ophthalmic disease: a single-center experience in China
Authors: Zhao Zhen , Mou Dapeng , Wang Ziqiao , Zeng Qiaozhu , Wang Zhenfan , Xue Jimeng , Ren Limin , Liu Yanying , Su Yin
Published: March 2021

Background

IgG4-related ophthalmic disease (IgG4-ROD) is one of the phenotypes of IgG4-related disease (IgG4-RD), and its lesions are mainly located in the ocular. Currently, there are few studies on IgG4-ROD and no study has compared the phenotypic differences between IgG4-ROD and non IgG4-ROD (nIgG4-ROD). Thus, it is difficult to establish the optimal treatment strategy for IgG4-ROD. The aim of this study was to identify the disparities between the two groups and to clarify the risk factors for IgG4-ROD relapse.

Methods

434 IgG4-RD patients met comprehensive diagnostic criteria and diagnosed at Peking University People’s Hospital between January 2009 and January 2020 were recruited in this study. Patients were divided into IgG4-ROD and nIgG4-ROD group according to the ophthalmic involvement. Demographic, clinical, and laboratory data of two groups were collected and compared. Cox regression analysis was used to identify the independent risk factors for IgG4-ROD relapse.

Results

255 IgG4-ROD patients were identified in this study. IgG4-ROD group had almost equal sex ratio, younger age of disease onset and diagnosis comparing with nIgG4-ROD patients. As compared to nIgG4-ROD group, higher percentage of IgG4-ROD patients met the 2019 American College of Rheumatology/European League Against Rheumatism classification criteria (AECC) for IgG4-RD; moreover, IgG4-ROD patients had higher AECC scores and IgG4-RD responder index (RI). Allergic diseases and multiorgan involvement were more common in IgG4-ROD group. IgG4-ROD was frequently associated with salivary gland, paranasal sinus, lung, and lymph node involvement, while retroperitoneal fibrosis and biliary system lesions were more common in nIgG4-ROD. IgG4-ROD patients had higher serum IgG4 levels, IgG4/IgG ratio, IgE levels, and lower CRP levels. The initial glucocorticoid plus immunosuppressant was a protective factor for IgG4-ROD relapse. IgG4-ROD patients treated with initial glucocorticoid plus immunosuppressant had longer relapse-free survival time than patients treated with initial glucocorticoid monotherapy.

Conclusions

IgG4-ROD patients had distinctive clinical features compared with nIgG4-ROD patients. The initial glucocorticoid plus immunosuppressant was a protective factor for IgG4-ROD relapse, which could prolong the relapse-free survival time of IgG4-ROD patients. These findings may have important implications for understanding and management of IgG4-ROD.
Associations between childhood family emotional health, fronto-limbic grey matter volume, and saliva 5mC in young adulthood
Authors: Pfeiffer J. R. , Bustamante Angela C. , Kim Grace S. , Armstrong Don , Knodt Annchen R. , Koenen Karestan C. , Hariri Ahmad R. , Uddin Monica
Published: March 2021

Background

Poor family emotional health (FEH) during childhood is prevalent and impactful, and likely confers similar neurodevelopmental risks as other adverse social environments. Pointed FEH study efforts are underdeveloped, and the mechanisms by which poor FEH are biologically embedded are unclear. The current exploratory study examined whether variability in 5-methyl-cytosine (5mC) and fronto-limbic grey matter volume may represent pathways through which FEH may become biologically embedded.

Results

In 98 university students aged 18–22 years, retrospective self-reported childhood FEH was associated with right hemisphere hippocampus (b = 10.4,p = 0.005), left hemisphere amygdala (b = 5.3,p = 0.009), and right hemisphere amygdala (b = 5.8,p = 0.016) volumes. After pre-processing and filtering to 5mC probes correlated between saliva and brain, analyses showed that childhood FEH was associated with 49 5mC principal components (module eigengenes; MEs) (prange = 3 × 10–6to 0.047). Saliva-derived 5mC MEs partially mediated the association between FEH and right hippocampal volume (Burlywood ME indirect effectb = − 111,p = 0.014), and fully mediated the FEH and right amygdala volume relationship (Pink4 ME indirect effectb = − 48,p = 0.026). Modules were enriched with probes falling in genes with immune, central nervous system (CNS), cellular development/differentiation, and metabolic functions.

Conclusions

Findings extend work highlighting neurodevelopmental variability associated with adverse social environment exposure during childhood by specifically implicating poor FEH, while informing a mechanism of biological embedding. FEH-associated epigenetic signatures could function as proxies of altered fronto-limbic grey matter volume associated with poor childhood FEH and inform further investigation into primarily affected tissues such as endocrine, immune, and CNS cell types.
Autoantibodies to speckled protein family in primary biliary cholangitis
Authors: Granito Alessandro , Muratori Luigi , Tovoli Francesco , Muratori Paolo
Published: March 2021

The autoantibody profile of primary biliary cholangitis (PBC) includes antinuclear antibodies (ANA) which are detectable by indirect immunofluorescence in more than 50% of PBC patients. One of the two immunofluorescence patterns which are historically considered “PBC-specific” is the so-called “multiple nuclear dots” (MND) targeting nuclear body proteins such as Sp100, Sp140, Sp140L proteins, promyelocytic leukemia protein (PML) and small ubiquitin-related modifier proteins (SUMO). It has been hypothesized a role of nuclear body protein alterations in immune disorders such as PBC, thus suggesting novel and more refined therapeutic approaches.
Microbleeds show a characteristic distribution in cerebral fat embolism
Authors: Giyab Omar , Balogh Bendegúz , Bogner Péter , Gergely Orsi , Tóth Arnold
Published: March 2021

This systematic review aims to test the hypothesis that microbleeds detected by MRI are common and show a characteristic pattern in cerebral fat embolism (CFE). Eighty-four papers involving 140 CFE patients were eligible for this review based on a systematic literature search up to 31 January 2020. An additional case was added from hospital records. Patient data were individually scrutinised to extract epidemiological, clinical and imaging variables. Characteristic CFE microbleed pattern resembling a “walnut kernel” was defined as punctuate hypointensities of monotonous size, diffusely located in the subcortical white matter, the internal capsule and the corpus callosum, with mostly spared corona radiata and non-subcortical centrum semiovale, detected by susceptibility- or T2* weighted imaging. The presence rate of this pattern and other, previously described MRI markers of CFE such as the starfield pattern and further diffusion abnormalities were recorded and statistically compared. The presence rate of microbleeds of any pattern, the “walnut kernel microbleed pattern”, diffusion abnormality of any pattern, the starfield pattern, and cytotoxic edema in the corpus callosum was found to be 98.11%, 89.74%, 97.64%, 68.5%, and 77.27% respectively. The presence rate between the walnut kernel and the starfield pattern was significantly (p < 0.05) different. Microbleeds are common and mostly occur in a characteristic pattern resembling a “walnut kernel” in the CFE MRI literature. Microbleeds of this pattern in SWI or T2* MRI, along with the starfield pattern in diffusion imaging appear to be the most important imaging markers of CFE and may aid the diagnosis in clinically equivocal cases.
Clinical presentation of congenital syphilis in a rotavirus vaccine cohort study in Lusaka: a case series
Authors: Sukwa Nsofwa , Simuyandi Michelo , Chirwa Masuzyo , Kumwimba Yvonne Mutombo , Chilyabanyama Obvious N. , Laban Natasha , Koyuncu Aybüke , Chilengi Roma
Published: March 2021

Background

Despite an otherwise robust national antenatal clinic program, maternal and congenital syphilis remains an important public health issue in Zambia. This case series reports the clinical presentation of seven infants diagnosed with congenital syphilis in Lusaka, Zambia.

Case presentations

The cases in this series were incidental findings from a cohort of infants enrolled in a rotavirus vaccine immunogenicity study recruiting infants at 6 weeks of age. As part of clinical care for enrolled participants, we screened mothers of children who presented with adverse events of (i) repeated upper respiratory tract infections/coryza, (ii) skin lesions, and (iii) poor weight gain, for syphilis using rapid plasma reagin test. From a cohort of 214 mother–infant pairs enrolled between September and December 2018, a total of 115 (44.4%) of the mothers reported to have not been screened during antenatal care. Of these, four (3.5%) reported to have tested positive; and only two received treatment. Seven out of 57 (26.6%) children meeting the screening criteria had a positive rapid plasma reagin test result. The mean age at diagnosis was 4.5 months (1.3 months standard deviation), and the common presenting features included coryza (6/7), skin lesions (4/7), conjunctivitis (3/7), pallor/anemia (5/7), wasting (2/7), and underweight (5/7). Three of the seven infants were exposed to human immunodeficiency virus. Following diagnosis, all seven cases received standard treatment according to national treatment guidelines. That is, 6/7 cases received inpatient care with benzylpenicillin for 10 days, while 1/7 was treated as an outpatient and received daily procaine penicillin for 10 days.

Conclusion

These findings suggest that, though screening for syphilis is part of the standard antenatal care in Zambia, it is not offered optimally. There is urgent need to address programmatic shortcomings in syphilis screening and treatment to avoid long-term sequelae. Additionally, clinicians need to raise their index of suspicion and rule out syphilis when confronted with these clinical symptoms, regardless of the mother’s human immunodeficiency virus status.
Exosomes derived from human adipose mesenchymal stem cells attenuate hypertrophic scar fibrosis by miR-192-5p/IL-17RA/Smad axis
Authors: Li Yan , Zhang Jian , Shi Jihong , Liu Kaituo , Wang Xujie , Jia Yanhui , He Ting , Shen Kuo , Wang Yunchuan , Liu Jiaqi , Zhang Wei , Wang Hongtao , Zheng Zhao , Hu Dahai
Published: March 2021

Background

Hypertrophic scar (HS) is a fibro-proliferative disorder of dermis after burn or trauma and usually leads to esthetic disfiguration and functionary impairment for patients. Emerging evidences demonstrated ADSC-Exo could alleviate the visceral fibrosis, but little attention had been paid to its role in skin fibrosis. In the study, we would explore the effect of ADSC-Exo on HS and investigated the exact mechanism underlying the properties.

Methods

ADSC-Exo were isolated, identified, and internalized by HS-derived fibroblasts (HSFs). The effect of ADSC-Exo on the proliferation and migration of HSFs were detected by flow cytometry and Ki67 immunofluorescence staining, or scratch and trans-wells assays, respectively. RT-PCR, immunoblotting, immunofluorescence, and immunohistochemistry staining were used to evaluate the expression of IL-17RA, Col1, Col3, α-SMA, SIP1, and p-Smad2/p-Smad3 in HSFs stimulated with ADSC-Exo, miR-192-5p mimics, or inhibitors, IL-17RA siRNA and their negative controls. Digital morphology, H&E, Masson’s trichrome staining, and immunohistochemistry staining were performed to measure the effect of ADSC-Exo and Lv-IL-17RA shRNA on excisional wound of BALB/c mice.

Results

The verified ADSC-Exo effectively inhibited the proliferation and migration of HSFs, decreased the expression of Col1, Col3, α-SMA, IL-17RA, and p-Smad2/p-Smad3 and increased the levels of SIP1 in HSFs. Besides, the mice in ADSC-Exo-treated group demonstrated faster wound healing and less collagen deposition. Furthermore, miR-192-5p was highly expressed in ADSC-Exo and ADSC-Exosomal miR-192-5p ameliorated hypertrophic scar fibrosis. Meanwhile, miR-192-5p targeted the expression of IL-17RA to decrease the pro-fibrotic proteins levels. Moreover, IL-17RA was overexpressed in HS and HSFs, and knockdown IL-17RA alleviated the expression of Col1, Col3, α-SMA, and p-Smad2/p-Smad3 and increased the expression of SIP1 in HSFs. Most importantly, IL-17RA silence also facilitated wound healing, attenuated collagen production, and modulated Smad pathway in HSFs.

Conclusions

This study illustrated ADSC-Exo attenuated the deposition of collagen, the trans-differentiation of fibroblasts-to-myofibroblasts, and the formation of hypertrophic scar by in vitro and in vivo experiments. ADSC-Exosomal miR-192-5p targeted IL-17RA to regulate Smad pathway in hypertrophic scar fibrosis. ADSC-Exo could be a promising therapeutic strategy for clinical treatment of hypertrophic scar and the anti-fibrotic properties could be achieved by miR-192-5p/IL-17RA/Smad axis.
Setting the mountain ablaze? The Royal Highland Festival in Bhutan from the semi-nomads’ perspective
Authors: Wangdi Jigme , Dorji Tashi , Wangchuk Kesang
Published: March 2021

A study was conducted to assess the effects of the Royal Highland Festival (RHF) from the perspective of yak herders in Laya, Bhutan. Sixty-six respondents were randomly selected from amongst the domicile herders who were regular visitors to the festival. A survey was carried out through a questionnaire with mixed questions. Herders’ opinions suggest good progress of RHF as reflected by improved community vitality and networking with stakeholders. Tourists, both international and domestic, were the major contributors to the income of yak herders during the festival. Livestock products were the biggest income earner, followed by homestays. Herders were encouraged to produce more quantities of livestock products and desired to diversify yak products. Animal shows were adequate and encouraged breed improvement. The grazing resources and the environment were unharmed by the presence of animals in the festival. However, yak herders expressed concerns over the lack of skills and knowledge for yak product diversification and management of festival waste. Herders felt the need to shift the festival venue to benefit highlanders in other areas of Bhutan. The study recommends authorities to consider imparting skills to Laya communities on developing diverse and value-added yak products. Homestay owners require more capacity to manage and maintain farmhouses with proper sanitation. Effective management of festival wastes calls for a farsighted plan. Finally, to inculcate a sense of pride and ownership, the communities of Laya must be empowered to self-organize the festival, while government authorities should consider shifting the festival venue to other highland areas.
Efficacy and safety of human soluble thrombomodulin (ART-123) for treatment of patients in France with sepsis-associated coagulopathy: post hoc analysis of SCARLET
Authors: François Bruno , Fiancette Maud , Helms Julie , Mercier Emmanuelle , Lascarrou Jean-Baptiste , Kayanoki Toshihiko , Tanaka Kosuke , Fineberg David , Vincent Jean-Louis , Wittebole Xavier
Published: March 2021

Background

The phase 3 multinational SCARLET study evaluated the efficacy and safety of a recombinant human soluble thrombomodulin (ART-123) for treatment of sepsis-associated coagulopathy (SAC), which correlates with increased mortality risk in patients with sepsis. Although no significant reduction in mortality was observed with ART-123 compared with placebo in the full analysis set (FAS), an efficacy signal of ART-123 was observed in subgroups of patients who sustained coagulopathy until the first treatment and those not administered concomitant heparin. Post hoc analysis was performed of patients treated in France, the country with the largest enrollment (19% of the FAS) and consistent patient enrollment throughout the study duration.

Methods

Adult patients with SAC (international normalized ratio > 1.4; platelets > 30 × 109/L to < 150 × 109/L or platelet decrease > 30% within 24 h) and evidence of bacterial infection were included. The primary efficacy outcome was 28-day all-cause mortality. Safety outcomes included adverse, serious adverse, and major bleeding events. This analysis assessed patient characteristics and efficacy and safety outcomes in France compared with the rest of the world (ROW; excluding France). Mortality rates were assessed in patients in France or the ROW with characteristics previously associated with ART-123 efficacy.

Results

Baseline characteristics were similar between France and the ROW, but some measurements of disease severity were higher in patients in France. The 28-day all-cause mortality absolute risk reductions (ARRs) with ART-123 were 8.3% in France and 1.1% in the ROW. The greater ARR in France may be related to a higher rate of sustained coagulopathy and lower rate of heparin use. In France and the ROW, 84.6% and 78.0% of patients sustained coagulopathy from the time of initial SAC diagnosis to first treatment with the study drug, and 65.8% and 43.9% did not receive heparin, respectively. The ARRs for these subgroups of patients in France were 13.4% and 16.6%, respectively. Safety of ART-123 was comparable between France and the ROW.

Conclusions

Results from this exploratory analysis suggest that patients with sustained SAC not receiving concomitant heparin may benefit from ART-123, a fact that should be confirmed in future studies with more restrictive inclusion criteria.
Surveillance of antimicrobial resistance in low- and middle-income countries: a scattered picture
Authors: Iskandar Katia , Molinier Laurent , Hallit Souheil , Sartelli Massimo , Hardcastle Timothy Craig , Haque Mainul , Lugova Halyna , Dhingra Sameer , Sharma Paras , Islam Salequl , Mohammed Irfan , Naina Mohamed Isa , Hanna Pierre Abi , Hajj Said El , Jamaluddin Nurul Adilla Hayat , Salameh Pascale , Roques Christine
Published: March 2021

Data on comprehensive population-based surveillance of antimicrobial resistance is lacking. In low- and middle-income countries, the challenges are high due to weak laboratory capacity, poor health systems governance, lack of health information systems, and limited resources. Developing countries struggle with political and social dilemma, and bear a high health and economic burden of communicable diseases. Available data are fragmented and lack representativeness which limits their use to advice health policy makers and orientate the efficient allocation of funding and financial resources on programs to mitigate resistance. Low-quality data means soaring rates of antimicrobial resistance and the inability to track and map the spread of resistance, detect early outbreaks, and set national health policy to tackle resistance. Here, we review the barriers and limitations of conducting effective antimicrobial resistance surveillance, and we highlight multiple incremental approaches that may offer opportunities to strengthen population-based surveillance if tailored to the context of each country.
Androgen receptor splice variant 7 detected by immunohistochemical is an independent poor prognostic marker in men receiving adjuvant androgen-deprivation therapy after radical prostatectomy
Authors: Ouyang Wei , Zhang Yucong , Long Gongwei , Sun Guoliang , Liu Man , Li Fan , Yang Chunguang , Zeng Xing , Yang Jun , Yu Xiao , Wang Zhihua , Liu Zheng , Guan Wei , Hu Zhiquan , Wang Shaogang , Liu Xiaming , Li Heng , Xu Hua , Ye Zhangqun
Published: March 2021

Background

To evaluate the predictive value of AR-V7 expression detected by immunohistochemical (IHC) in the prognosis of prostate cancer patients receiving adjuvant hormonal therapy (AHT) following radical prostatectomy (RP).

Methods

We retrospectively collected data of 110 patients with prostate cancer receiving RP, followed by AHT, from Tongji hospital. IHC analysis of AR-V7 expression was performed in a retrospective cohort.

Results

In total, 110 patients were enrolled, of whom 21 patients (19.1%) were AR-V7-positive and 89 patients (80.9%) were AR-V7-negative. No significant differences in baseline characteristics were found between the two groups. AR-V7-positive patients had shorter progression-free survival (PFS) (HR: 4.26; 95% CI, 1.55 to 11.68; P = 0.003), shorter cancer-special survival (CSS) (HR: 22.47; 95% CI, 2.912 to 173.4; P = 0.003) and shorter overall survival (OS) (HR: 6.61; 95% CI, 1.40 to 31.20; P = 0.017) compared to AR-V7-negative patients. In multivariate analysis, AR-V7 is an independent risk factor for shorter PFS (HR, 3.76; 95% CI, 1.63 to 8.70; P = 0.002), shorter CSS (HR: 9.17; 95% CI, 1.48 to 55.56; P = 0.017) and shorter OS (HR: 4.81; 95% CI, 1.28 to 17.86; P = 0.020).

Conclusion

The presence of AR-V7 in prostate cancer tissue is independently associated with an unfavorable prognosis for PFS, OS and CSS in patients who received AHT.
Perception of quality of life by children and adolescents with cleft lip/palate after orthodontic and surgical treatment: gender and age analysis
Authors: Ruiz-Guillén Ana , Suso-Ribera Carlos , Romero-Maroto Martín , Gallardo Carmen , Peñacoba Cecilia
Published: March 2021

Background

The quality of life (QoL) of children and adolescents with cleft lip/palate (CL/P) has been shown to be a predictor of good psychosocial functioning in this population group. This study aimed to measure QoL, from the patient´s perception of change produced by the different surgical and orthodontic treatments carried out since early childhood, and if gender and age are modulating the outcome variables results.

Materials and methods

A cross-sectional research study was carried out. The study included 60 patients with cleft lip, cleft palate, or cleft lip/palate, aged between 8 and 18, who were in orthodontic treatment and had undergone at least one surgery. They were asked to complete the Quality-of-Life Adolescent Cleft Questionnaire (QoLAdoCleft), which allows the assessment of the QoL through self-perception of improvement after surgical and orthodontic interventions. In particular, this questionnaire (administered only once), allows the evaluation of self-perception of QoL at the present time and before orthodontic and surgical treatment. This double assessment was carried out for the domains of physical, psychological, and social health. The results were analysed by looking at the interaction of gender and age.

Results

Statistically significant differences were found in the perception of the current QoL in comparison to the retrospective perception in all the dimensions considered. The perception of QoL improved in all cases. The results also showed a moderation of gender in the relation between perception of previous behaviour and social function and actual behaviour and social function.

Conclusion

The results indicated that patients perceived their quality of life had improved as a result of the treatments received, with the highest effect sizes found in the physical health domain. Specifically, the improvement in QoL in behaviour and social function tended to be influenced to a greater extent by perception of previous QoL. In this sense, personalized preventative measures from holistic and biopsychosocial approaches are necessary.
Does atorvastatin have augmentative effects with sodium valproate in prevention of migraine with aura attacks? A triple-blind controlled clinical trial
Authors: Ganji Reza , Majdinasab Nastaran , Hesam Saeed , Rostami Nazanin , Sayyah Mehdi , Sahebnasagh Adeleh
Published: March 2021

Background

Migraine is a painful and disabling nervous disorder which negatively affects the quality of life. Migraineurs may suffer from a generalized vasomotor dysfunction. Statins improve vasomotor and vascular function, with their pleiotropic effects. We aimed to assess efficacy and safety of adding Atorvastatin to prophylactic regimen in better control of migraine with aura.

Methods

This triple-blind controlled clinical trial was on 68 patients with migraine with aura. An interval of at least 1 month was given to evaluate vitamin D3 level and eligibility. In patients with vitamin D3 deficiency, the correction with vitamin D supplementation was provided. The patients were randomly assigned to receive atorvastatin 20 mg plus sodium valproate 500 mg or placebo plus sodium valproate 500 mg once a day for 2 months. The patients were evaluated based for the number of attacks and pain severity based on Visual Analogue Scale.

Results

There was a significant (p = 0.0001) improvement in severity of pain and number of migraine attacks by adding Atorvastin to the prophylactic regimen of patients with migraine with aura. After controlling for variable parameters, the differences between two arms of the study was yet statistically significant (p = 0.0001). A significant number of participants in intervention group were satisfied by their treatment (p = 0.001) with no remarkable side effects (P = 0.315).

Conclusions

Adding atorvastatin to migraine with aura preventive regimen may help reduce the number of acute attacks and pain severity without causing considerable side effects and led to a better patient satisfaction.

Trial registration

IRCT20180106038242N1. Registered: 7 February 2018.
Effect of antipsychotics on breast tumors by analysis of the Japanese Adverse Drug Event Report database and cell-based experiments
Authors: Maeshima Tae , Iijima Ryosuke , Watanabe Machiko , Yui Satoru , Itagaki Fumio
Published: March 2021

Background

Since antipsychotics induce hyperprolactinemia via the dopamine D2 receptor, long-term administration may be a risk factor for developing breast tumors, including breast cancer. On the other hand, some antipsychotic drugs have been reported to suppress the growth of breast cancer cells in vitro. Thus, it is not clear whether the use of antipsychotics actually increases the risk of developing or exacerbating breast tumors. The purpose of this study was to clarify the effects of antipsychotic drugs on the onset and progression of breast tumors by analyzing an adverse event spontaneous reporting database and evaluating the proliferation ability of breast cancer cells.

Methods

Japanese Adverse Drug Event Report database (JADER) reports from April 2004 to April 2019 were obtained from the Pharmaceuticals and Medical Devices Agency (PMDA) website. Reports of females only were analyzed. Adverse events included in the analysis were hyperprolactinemia and 60 breast tumor-related preferred terms. The reporting odds ratio (ROR), proportional reporting ratio (PRR), and information component (IC) were used to detect signals. Furthermore, MCF-7 cells were treated with haloperidol, risperidone, paliperidone, sulpiride, olanzapine and blonanserin, and cell proliferation was evaluated by WST-8 assay.

Results

In the JADER analysis, the IC signals of hyperprolactinemia were detected with sulpiride (IC, 3.73; 95% CI: 1.81–5.65), risperidone (IC, 3.69; 95% CI: 1.71–5.61), and paliperidone (IC, 4.54; 95% CI: 2.96–6.12). However, the IC signal of breast tumors was not observed with any antipsychotics. In cell-based experiments, MCF-7 cells were treated with six antipsychotics at concentrations of 2 and 32 μM, and none of the drugs showed any growth-promoting effects on MCF-7 cells. On the other hand, blonanserin markedly suppressed the growth of MCF-7 cells at a concentration of 32 μM, and the effect was concentration dependent.

Conclusions

Analysis of the JADER using the IC did not show breast tumor signals due to antipsychotic drugs. In in vitro experiments, antipsychotics did not promote MCF-7 cell proliferation whereas blonanserin suppressed MCF-7 cell growth. Further research on the effects of blonanserin on the onset and progression of breast tumor is expected.
Association between media exposure and family planning in Myanmar and Philippines: evidence from nationally representative survey data
Authors: Das Pranta , Samad Nandeeta , Al Banna Hasan , Sodunke Temitayo Eniola , Hagan John Elvis , Ahinkorah Bright Opoku , Seidu Abdul-Aziz
Published: March 2021

Background

Although women in South Asia and South-east Asia have developed their knowledge regarding modern contraceptive and other family planning techniques, limited information exists on the influence of mass media exposure on the utilization of contraceptives and family planning. The current study examined the association between media exposure and family planning in Myanmar and Philippines.

Methods

The study analyzed data from the 2017 Philippines National Demographic and Health Survey (NDHS) and 2015–16 Myanmar Demographic and Health Survey (MDHS). Three family planning indicators were considered in this study (i.e., contraceptive use, demand satisfied regarding family planning and unmet need for family planning). A binary logistic regression model was fitted to see the effect of media exposure on each family planning indicator in the presence of covariates such as age group, residence, education level, partner education level, socio-economic status, number of living children, age at first marriage, and working status.

Results

The prevalence of contraception use was 57.2% in the Philippines and 55.7% in Myanmar. The prevalence of demand satisfied regarding family planning was 70.5 and 67.1% in the Philippines and Myanmar respectively. Unmet need regarding family planning was 16.6% and 19.9% in the Philippines and Myanmar respectively. After adjusting for the covariates, the results showed that women who were exposed to media were more likely to use contraception in Philippines (aOR = 2.24, 95% CI = 1.42–3.54) and Myanmar (aOR 1.39, 95% CI = 1.15–1.67). Media exposure also had a significant positive effect on demand satisfaction regarding family planning in the Philippines (aOR = 2.19, 95% CI = 1.42–3.37) and Myanmar (aOR = 1.34, 95% CI = 1.09–1.64). However, there was no significant association between media exposure and unmet need in both countries.

Conclusions

The study established a strong association between mass media exposure and the use and demand satisfaction for family planning among married and cohabiting women in Philippines and Myanmar. Using mass media exposure (e.g., local radio, television- electronic; newspapers) to increase both access and usage of contraceptives as well as other family planning methods in these countries could be pivotal towards the attainment of United Nations Sustainable Development Goal 3 (SDG 3) of improving maternal health.
Improving college students’ fact-checking strategies through lateral reading instruction in a general education civics course
Authors: Brodsky Jessica E. , Brooks Patricia J. , Scimeca Donna , Todorova Ralitsa , Galati Peter , Batson Michael , Grosso Robert , Matthews Michael , Miller Victor , Caulfield Michael
Published: March 2021

College students lack fact-checking skills, which may lead them to accept information at face value. We report findings from an institution participating in the Digital Polarization Initiative (DPI), a national effort to teach students lateral reading strategies used by expert fact-checkers to verify online information. Lateral reading requires users to leave the information (website) to find out whether someone has already fact-checked the claim, identify the original source, or learn more about the individuals or organizations making the claim. Instructor-matched sections of a general education civics course implemented the DPI curriculum (N = 136 students) or provided business-as-usual civics instruction (N = 94 students). At posttest, students in DPI sections were more likely to use lateral reading to fact-check and correctly evaluate the trustworthiness of information than controls. Aligning with the DPI’s emphasis on using Wikipedia to investigate sources, students in DPI sections reported greater use of Wikipedia at posttest than controls, but did not differ significantly in their trust of Wikipedia. In DPI sections, students who failed to read laterally at posttest reported higher trust of Wikipedia at pretest than students who read at least one problem laterally. Responsiveness to the curriculum was also linked to numbers of online assignments attempted, but unrelated to pretest media literacy knowledge, use of lateral reading, or self-reported use of lateral reading. Further research is needed to determine whether improvements in lateral reading are maintained over time and to explore other factors that might distinguish students whose skills improved after instruction from non-responders.
Recurrent spontaneous CSF rhinorrhea: combined endo-nasal endoscopic repair with lumbo-peritoneal shunt insertion
Authors: Soliman Ahmed Y. , Ebeid Kamal , Elfadle Amr Abu
Published: March 2021

Background

Spontaneous cerebrospinal fluid (CSF) leaks are associated with high morbidity and recurrence rates. Most cases had increased intracranial pressure (ICP) on presentation. There is still controversy regarding the use of lumbo-peritoneal shunt to prevent its recurrence.

Aim

This study was conducted to evaluate the impact of lumbo-peritoneal CSF shunt following the initial as well as recurrent repair of spontaneous CSF leaks to avoid recurrence.

Methods

A retrospective cohort study reviewed patients with recurrent spontaneous CSF leaks over a 4-year period. All patients had increased ICP and were subjected to endoscopic repair and lumbo-peritoneal shunt procedure.

Results

Eighteen patients were included in this study. Most patients were obese (BMI = 33.6 ± 1.8 kg/m2) women (88.9%), with sleep apnea syndrome (77.8%). All patients presented with headache and visual complaints. Meningitis was recorded in two patients (11.1%). The most common sites of leakage were the cribriform (66.7%), followed by both cribriform and ethmoidal (16.7%), sphenoid (11.1%), and ethmoidal (5.6%) bones. The mean defect size was 5.1 ± 1.1 mm. About one third of cases had multiple defects. Encephalocele and meningocele were encountered in 61.1% and 66.7% of cases, respectively. The mean preoperative CSF pressure was 36.5 ± 1.7 mm H2O. Lumbo-peritoneal shunt was inserted for all our patients. The failure rate of repair was 11.1%.

Conclusion

Success rate is higher in patients with spontaneous CSF leaks and CSF hypertension treated by lumbo-peritoneal shunt. Future prospective studies with larger sample sizes should confirm the efficacy and safety of this management plan.
Motor unit number estimation versus compound muscle action potential in the evaluation of motor unit loss in amyotrophic lateral sclerosis
Authors: Ibrahem Arwa Khalid , Al-Mahdawi Akram Mohammed , Hamdan Farqad Bader
Published: March 2021

Introduction

Motor neuron loss is the primary pathologic feature of amyotrophic lateral sclerosis (ALS). An estimate of the number of surviving motor units (MUs) represents a direct measure of the disease state in ALS. The objective of the study is to compare MU number estimation (MUNE) using the multipoint stimulation method (MPS) and compound muscle action potentials (CMAP) amplitude in patients with ALS.

Methods

Twenty-eight patients with ALS with a disease duration of 3–48 months were studied. Nerve conduction study of the median, ulnar, tibial, common peroneal, and sural nerves were done. Besides, electromyography (EMG) of cranio-bulbar, cervical, thoracic and lumbosacral muscles, and MPS-MUNE.

Results

MUNE is decreased in patients with ALS. MUNE was positively correlated with CMAP amplitude, medical research council (MRC) scale, and ALS functional rating scale (ALS-FRS). On the contrary, MUNE was negatively correlated with MUAP duration. Case detection by the MUNE methods was high as compared to that of CMAP amplitude.

Conclusions

MUNE is highly specific and more sensitive than CMAP amplitude in detecting the neurophysiologic abnormalities in patients with ALS. Case detection by MUNE is three times more than CMAP amplitudes. The rate of decline of motor units using the MPS-MUNE is more sensitive than the MRC score and ALSFRS-R when expressed as the percentage change from baseline.
Closure or medical therapy of patent foramen ovale in cryptogenic stroke: prospective case series
Authors: Poli Sven , Siebert Elisabeth , Mbroh Joshua , Poli Khouloud , Krumbholz Markus , Mengel Annerose , Greulich Simon , Härtig Florian , Müller Karin A. L. , Bocksch Wolfgang , Gawaz Meinrad , Ziemann Ulf , Zuern Christine S.
Published: March 2021

Background

Results of randomized controlled trials (RCT) do not provide definite guidance for secondary prevention after ischemic stroke (IS)/transient ischemic attack (TIA) attributed to patent foramen ovale (PFO). No recommendations can be made for patients > 60 years. We aimed to compare interventional and medical PFO-management in cryptogenic IS/TIA patients, including patients > 60 years.

Methods

Prospective case series including consecutive cryptogenic IS/TIA patients with PFO at Tuebingen university stroke unit, Germany. ‘PFO-closure’ was recommended in patients ≤70 years when featuring high-risk PFO (i.e., with atrial septal aneurysm, spontaneous, or high-grade right-to-left shunt during Valsalva). Primary (recurrent IS/intracranial hemorrhage) and secondary endpoints (e.g., disability) were assessed during ≥1-year follow-up; planned subgroup analyses of patients ≤60/> 60 years.

Results

Among 236 patients with median age of 58 (range 18–88) years, 38.6% were females and median presenting National Institutes of Health Stroke Scale score was 1 (IQR 0–4). Mean follow-up was 2.8 ± 1.3 years. No intracranial hemorrhage was observed. Recurrent IS rate after ‘PFO-closure’ was 2.9% (95%CI 0–6.8%) and 7% (4–16.4) in high-risk PFO patients ≤60 (n = 103) and > 60 years (n = 43), respectively, versus 4% (0–11.5) during ‘medical therapy alone’ MTA (n = 28). 42 low-risk PFO patients treated with MTA experienced no recurrent IS/TIA.

Conclusions

In our real-world study, IS recurrence rate in ‘PFO-closure’ high-risk PFO patients ≤60 years was comparable to that observed in recent RCT. High-risk PFO patients > 60 years who underwent PFO-closure had similar IS recurrence rates than those who received MTA. MTA seems the appropriate treatment for low-risk PFO.

Trial registration

ClinicalTrials.gov, registration number: NCT04352790, registered on: April 20, 2020 – retrospectively registered.
The comparison of serum TGF-beta levels and associated polymorphisms in patients with coronary artery ectasia and normal coronary artery
Authors: Ser Özgür Selim , Çetinkal Gökhan , Kiliçarslan Onur , Dalgıç Yalçın , Batit Servet , Keskin Kudret , Özkara Gulçin , Aslan Ezgi Irmak , Aydoğan Hülya Yilmaz , Yıldız Ahmet , Yiğit Zerrin
Published: March 2021

Background

Coronary artery ectasia (CAE) is described as the enlargement of a coronary artery segment by 1.5 times or more, which is generally associated with the atherosclerotic process. Atherosclerotic changes lead to arterial remodeling result in CAE. In our study, we measured serum transforming growth factor (TGF)-β1 levels, which have a protective role against atherosclerosis. Further, we aimed to assess the TGF-β1 gene variants rs1800469 (–509C>T, c.−1347C>T) and rs1800470 (c.+29T>C, p.Pro10Leu, rs1982073), which might have an effect on TGF production. Overall, 2877 patients were screened including 56 patients with CAE and 44 patients with normal coronary arteries who were included in the study. Serum TGF-β1 levels were measured using ELISA and compared between two groups. Additionally, TGF-β1 rs1800469 and rs1800470 gene variations were determined using TaqMan® SNP Genotyping Assays.

Results

Serum TGF-β1 levels were significantly lower in patients with CAE than in controls (p=0.012). However, there was no difference in terms of the genotype and allele distributions of TGF-β1 rs1800469 and rs1800470 polymorphisms. Serum TGF-β1 levels were higher in individuals carrying the TGF-β1 rs1800470 G allele (GG+AG) than in individuals with normal homozygous AA genotype in the CAE group (p=0.012).

Conclusion

Our findings suggest that lower serum TGF-β1 levels are associated with an increased risk for CAE development and that TGF-β1 polymorphisms exert a protective effect. Furthermore, TGF-β1 rs1800470 G allele carriers were shown to have higher TGF-β1 levels in the CAE group. This suggests that having the G allele in the TGF-β1 rs1800470 polymorphism could prevent CAE development.
User Experience With Low-Cost Virtual Reality Cancer Surgery Simulation in an African Setting
Authors: Bing Eric G. , Brown Megan L. , Cuevas Anthony , Sullivan Richard , Parham Groesbeck P.
Published: March 2021

PURPOSE

Limited access to adequate cancer surgery training is one of the driving forces behind global inequities in surgical cancer care. Affordable virtual reality (VR) surgical training could enhance surgical skills in low- and middle-income settings, but most VR and augmented reality systems are too expensive and do not teach open surgical techniques commonly practiced in these contexts. New low-cost VR can offer skill development simulations relevant to these settings, but little is known about how knowledge is gained and applied by surgeons training and working in specific resource-constrained settings. This study addresses this gap, exploring gynecologic oncology trainee learning and user experience using a low-cost VR simulator to learn to perform an open radical abdominal hysterectomy in Lusaka, Zambia.

METHODS

Eleven surgical trainees rotating through the gynecologic oncology service were sequentially recruited from the University Teaching Hospital in Lusaka to participate in a study evaluating a VR radical abdominal hysterectomy training designed to replicate the experience in a Zambian hospital. Six participated in semi-structured interviews following the training. Interviews were analyzed using open and axial coding, informed by grounded theory.

RESULTS

Simulator participation increased participants' perception of their surgical knowledge, confidence, and skills. Participants believed their skills transferred to other related surgical procedures. Having clear goals and motivation to improve were described as factors that influenced success.

CONCLUSION

For cancer surgery trainees in lower-resourced settings learning medical and surgical skills, even for those with limited VR experience, low-cost VR simulators may enhance anatomical knowledge and confidence. The VR simulator reinforced anatomical and clinical knowledge acquired through other modalities. VR-enhanced learning may be particularly valuable when mentored learning opportunities are limited.
Denosumab Reduces Lesional Fluoride Skeletal Burden on Na[18F]F PET-CT in Patients With Fibrous Dysplasia/McCune–Albright Syndrome
Authors: van der Bruggen Wouter , Vriens Dennis , Meier Maartje E , Smit Frits , Winter Elizabeth M , de Geus-Oei Lioe-Fee , Appelman-Dijkstra Natasha M
Published: March 2021

Context

The correlation between fibrous dysplasia/McCune–Albright syndrome (FD/MAS) skeletal disease burden on Na[18F]F positron emission tomography–computed tomography (PET-CT) and serum bone turnover markers (BTMs) was recently described. The effect of treatment on lesional fluoride burden in FD/MAS is unknown.

Objective

To investigate treatment response measurements in patients with FD/MAS who underwent Na[18F]F-PET-CT and treatment with antiresorptives.

Methods

Observational case series at an academic center of expertise for rare bone diseases. Fifteen consecutive patients were observed with FD/MAS with baseline and follow-up Na[18F]F-PET-CT parameters of healthy bone and FD lesions, BTMs, and pain scores at start of denosumab (n = 8) treatment and non-denosumab patients (n = 7). On Na[18F]F-PET-CT the volumetric measures of FD burden (fluoride tumor volume [FTV]) and “fraction affected skeleton” (FAS) represented the portion of the skeleton affected. This was correlated with BTMs and pain.

Results

Disease activity decreased significantly, with FTV 361 cm3 to 97 cm3 (P = .018) in denosumab-treated patients, but not in non-denosumab patients (P = .249). Serum P1NP and alkaline phosphatase (ALP) decreased significantly: 82 ng/mL vs 55 ng/mL (P = .023) and 119 IU/L vs 84 IU/L (P = .020), respectively. In denosumab-treated patients pain scores improved leading to pain medication reduction. This correlated with lesional uptake, but healthy bone activity did not change. BTMs and FTV correlated positively (P1NP r = 0.730, P < .001; and ALP r = 0.406, P = .006), as did change in BTMs and FTV: P1NP (P = 0.032) and ALP (P = 0.024). FAS strongly correlated with treatment-induced decrease in ALP (P = .027) and P1NP (P = .009).

Conclusion

Na[18F]F-PET-CT captured treatment-induced lesional changes which correlated with BTMs and pain reduction. Therefore Na[18F]F-PET-CT can be used as an objective local parameter of response to denosumab treatment in FD/MAS.