bluuebunny/crossref_metadata_2025 huggingface dataset:
Tailoring services in opioid treatment programs for patients involved in America’s criminal justice system: national associations and variation by state and Medicaid expansion status
Authors: Pro George , Montgomery Brooke E. E. , Zaller Nickolas
Published: June 2021

Background

Opioid treatment programs (OTPs) are the primary source of medication-assisted treatment (MAT) for many individuals with opioid use disorder, including poor and uninsured patients and those involved in the criminal justice (CJ) system. Substance use treatment services that are tailored to the unique needs of patients often produce better outcomes, but little national research has addressed characteristics associated with whether OTPs offer services specifically tailored to community members involved in the CJ system. Medicaid expansion under the Affordable Care Act has broadly strengthened MAT services, but the role of expansion in supporting MAT services that are specifically tailored towards CJ-involved populations remains unknown. Moreover, it is unknown whether the availability of tailored services varies between Medicaid expansion states.

Methods

We used the 2019 National Survey of Substance Abuse Treatment Services to identify OTPs in the US (n = 1679) and whether they offered services specifically tailored for CJ-involved patients. We used logistic regression to model the association between OTPs offering tailored services and state Medicaid expansion status, adjusted for state-level opioid overdose and community supervision rates.

Results

Nationally, only a quarter of OTPs offered services tailored to CJ populations, and the majority of OTPs (73%) were located in Medicaid expansion states. Compared to OTPs in non-expansion states, OTPs in expansion states demonstrated nearly double the odds of offering tailored services (adjusted odds ratio = 1.90, 95% confidence interval = 1.41–2.57, p < 0.0001). The predicted probability of offering tailored services varied by state; probability estimates for all expansion states were above the national mean, and estimates for all non-expansion states were below the national mean.

Conclusion

Our findings reiterate the role of Medicaid in promoting the adoption of comprehensive OTP services for CJ-involved populations. However, the proportion of OTPs that offered tailored services was relatively low, pointing to the need to continually strengthen Medicaid services and coverage.
Risk factors for anastomotic complications after one-stage anastomosis for oesophageal atresia
Authors: Huang Jin-Xi , Hong Song-Ming , Chen Qiang , Wang Zeng-Chun , Wu Dian-Ming , Hong Jun-Jie , Zhou Chaoming
Published: June 2021

Background

Oesophageal atresia is a congenital malformation of the oesophagus and a serious malformation of the digestive system, postoperative complications include acute respiratory failure, pneumonia, anastomotic fistula, anastomotic stenosis, tracheal stenosis, gastroesophageal reflux and eosinophilic oesophagitis, anastomotic fistula is one of the important causes of postoperative death. The objective of this study is to identify the risk factors for anastomotic complications after one-stage anastomosis for oesophageal atresia.

Methods

A retrospective analysis was performed on the clinical data of 107 children with congenital oesophageal atresia who underwent one-stage anastomosis in our hospital from January 2013 to December 2018. Single-factor and multivariate logistic regression analyses were performed to determine the risk factors for anastomotic fistula and anastomotic stenosis.

Results

A total of 107 children with oesophageal atresia underwent one-stage anastomosis, and the incidence of anastomotic fistula was 26.2%. The probability of anastomotic stenosis in the long term was 52.3%, and the incidence of refractory stenosis (dilation ≥5 times) was 13.1%. Analysis of the clinical count data in the anastomotic fistula group and non-anastomotic fistula group showed that preoperative albumin (F = 4.199, P = 0.043), low birth weight (F = 7.668, P = 0.007) and long gap defects (F = 6.107, P = 0.015) were risk factors for postoperative anastomotic fistula. Further multivariate logistic regression analysis showed that low birth weight (Wald2 = 4.499, P = 0.034, OR = 2.775) and long gap defects (Wald2 = 6.769, P = 0.009, OR = 4.939) were independent risk factors for postoperative anastomotic fistula. Premature delivery (F = 5.338, P = 0.023), anastomotic fistula (F = 11.381, P = 0.001), endoscopic surgery (F = 6.343, P = 0.013), preoperative neutrophil count (F = 8.602, P = 0.004), preoperative low albumin (F = 8.410, P = 0.005), and a preoperative prognostic nutritional index < 54 (F = 5.54, P = 0.02) were risk factors for refractory anastomotic stenosis in children. Further multivariate logistic regression analysis showed that postoperative anastomotic fistula (Wald2 = 11.417, P = 0.001, OR = 8.798), endoscopic surgery (Wald2 = 9.633, P = 0.002, OR = 4.808), and a prognostic nutritional index < 54 (Wald2 = 4.540, P = 0.002, OR = 2.3798) were independent risk factors for refractory anastomotic stenosis.

Conclusion

Low birth weight and long gap defects are important predictors of postoperative anastomotic fistula, and the possibility of refractory anastomotic stenosis should be considered. The long-term risk of anastomotic stenosis was increased in children undergoing endoscopic surgery and in those with a preoperative prognostic nutritional index < 54.
Giant coronary artery aneurysms involving more than one coronary artery: case report
Authors: Khouzam Matthew S , Khouzam Nayer
Published: June 2021

Background

Coronary artery aneurysms are rare findings in patients undergoing coronary angiography. The presence of multiple coronary artery aneurysms located in more than one coronary artery is even more uncommon. The pathophysiology of such aneurysms is unknown, but the majority are often due to atherosclerosis, congenital heart disease, or vasculitis.

Case presentation

We present a rare case of a 78-year-old female patient who presented with unstable angina and non-ST segment elevation myocardial infarction. On coronary angiography, she was found to have three separate 1 cm saccular aneurysms involving the proximal left anterior descending coronary artery. The right coronary artery could not be visualized. Computed chest tomography revealed a 6.6 × 6.3 cm saccular aneurysm of the right coronary artery, and a 4.4 cm fusiform aneurysm of the ascending aorta. The patient gave no history of percutaneous coronary intervention or cardiac surgical procedures. She had a previous history of endovascular stenting of an abdominal aortic aneurysm. The sizable right coronary artery aneurysm showed extrinsic compression of both the right atrium and ventricle with right ventricular hypokinesis. Serological studies for vasculitis were all negative. Pathology of the aneurysm wall revealed calcific atherosclerosis without evidence of vasculitis. The patient underwent subtotal resection of the right coronary aneurysm with ligation of the proximal and distal ends of the right coronary artery and double bypass surgery to the left anterior descending and right posterior descending coronary arteries.

Conclusion

The presence of multiple, large coronary artery aneurysms is very rare. Treatment can be challenging and should be individualized. Surgical treatment is recommended for giant coronary artery aneurysms to prevent potential complications.
Effects of ginsenoside Rb1 on second-degree burn wound healing and FGF-2/PDGF-BB/PDGFR-β pathway modulation
Authors: Zhang Li , Hu Qin , Jin Haonan , Yang Yongzhao , Yang Yan , Yang Renhua , Shen Zhiqiang , Chen Peng
Published: June 2021

Background

Panax notoginseng(Burk.) F. H. Chen (P. notoginseng) is a traditional Chinese medicine that has been used therapeutically for cardiovascular diseases, inflammatory diseases and traumatic injuries as well as for external and internal bleeding due to injury. Ginsenoside Rb1, a crucial monomeric active constituent extracted fromP. notoginseng, has attracted widespread attention because of its potential anti-inflammatory, bacteriostatic, and cell growth-promoting effects. In this study, the therapeutic effects of ginsenoside Rb1 on second-degree burn in rats and the potential underlying mechanisms were explored.

Methods

A rat model of second-degree burn injury was established, and skin wound healing was monitored at different time points after ginsenoside Rb1 treatment. HE staining was performed to identify burn severity, and biological tissues were biopsied on days 0, 7, 14, and 24 after treatment. Skin wound healing at different time points was monitored by macroscopic observation. Furthermore, IHC, WB, and RT-PCR were utilized to determine the protein and mRNA expression levels of PDGF-BB, PDGFR-β, and FGF-2 in wound tissues after treatment.

Results

HE staining showed that after 24 days of ginsenoside Rb1 treatment, skin tissue morphology was significant improved. Macroscopic observation demonstrated that in ginsenoside Rb1-treated rats, the scab removal time and fur growth time were decreased, and the wound healing rate was increased. Collectively, the results of IHC, WB and RT-PCR showed that PDGF-BB, PDGFR-β, and FGF-2 expressions peaked earlier in ginsenoside Rb1-treated rats than in model rats, consistent with the macroscopic observations.

Conclusion

Collectively, these findings  indicated that ginsenoside Rb1 promotes burn wound healing via a mechanism possibly associated with upregulation of FGF-2/PDGF-BB/PDGFR-β gene and protein expressions.
Human papillomavirus self-sampling versus standard clinician-sampling for cervical cancer screening in sub-Saharan Africa: a systematic review and meta-analysis of randomized controlled trials
Authors: Tesfahunei Hanna Amanuel , Ghebreyesus Michael Solomon , Assefa Dawit Getachew , Zeleke Eden Dagnachew , Acam Joan , Joseph Michele , Getachew Emnet , Kajogoo Violet Dismas , Bekele Delayehu , Manyazewal Tsegahun
Published: June 2021

Background

Human papillomavirus (HPV) infection remains a major health threat in sub-Saharan Africa (SSA). HPV self-sampling could help find and treat cervical cancer at an early stage. We aimed to evaluate the effectiveness of HPV self-sampling over the standard health facility-based clinician-sampling for cervical cancer screening through a systematic review and meta-analysis of available randomized controlled trials.

Method

We searched PubMed, Cochrane Central Register of Controlled Trials, ClinicalTrial.gov, and the WHO Global Health Library for articles in SSA published as of 31 May 2020. We followed the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) 2015 guidelines for the design and reporting of the results. We included randomized control trials that compared HPV self-sampling with the standard of care. The primary endpoint was uptake of cervical cancer screening service. The secondary endpoints were linkage to care, acceptability, screening frequency, and adverse events. We used RevMan V.5.3 software for statistical analysis. We computed random-effect model to provide pooled estimates of available data and I-squared (I2) test to assess heterogeneity.

Result

Of 77 citations, we included four trials from Nigeria, Ethiopia, Kenya, and Uganda, encompassing 8200 participants with age ranging from 25 to 65 years. The pooled analysis showed significantly higher uptake of cervical cancer screening in women who used HPV self-sampling (risk ratio [RR] 1.72, 95% CI 1.58–1.87; p = 0.01), while this had a considerable heterogeneity as explained by subgroup analysis. Uptake was higher in women who were offered sampling kit at home or work (RR 2.05, 95% CI 1.80–2.33) and those who’s kit was mailed to or invited to a nearby health center (RR 1.65, 95% CI 1.58–1.72, I2 = 0%) than those screened with the standard of care. There was no difference between the two groups in the rate of linkage to care of positive cases (RR 1.30, 95% CI 0.90–2.74, I2 = 91%). HPV self-sampling was acceptable and easy to use. None of the trials compared the frequency of screening or adverse events.

Conclusion

HPV self-sampling is an effective and feasible alternative to the standard health facility-based clinician-sampling for cervical cancer screening in SSA. It could improve the uptake of cervical cancer screening and harness the global strategy towards elimination of cervical cancer by 2030.
Commonly diagnosed mental disorders in a general hospital system
Authors: Scott George , Beauchamp-Lebrón Alessandra M. , Rosa-Jiménez Ashley A. , Hernández-Justiniano Javier G. , Ramos-Lucca Axel , Asencio-Toro Gloria , Jiménez-Chávez Julio
Published: June 2021

Background

Considering many patients receive care from general hospitals, these healthcare institutions are uniquely situated to address mental and physical health needs. Little is documented, however, on the common current mental disorders diagnosed in patients receiving care in general hospital settings, especially in Puerto Rico. The objective of this study was to characterize the five most common current DSM-5 mental disorder diagnoses made in patients receiving non-psychiatric medical and surgical care from a general hospital system in southern Puerto Rico between January 2015 and December 2019.

Methods

Our clinical health psychology team provides integrated psychology consultation-liaison services to select clinical units in general hospitals across the southwestern region of Puerto Rico. The clinical team conducted routine standardized psychological evaluations at patients' bedside, arrived at a current DSM-5 diagnosis if warranted, and documented the diagnosis and other select variables. A retrospective study of cross-sectional data generated from the clinical team’s standardized evaluations of 5494 medical patients was implemented. Multinomial logistic regression analyses were used to assess the odds of being diagnosed with a current DSM-5 mental disorder during hospitalization.

Results

Overall, 53% of the entire sample was diagnosed with a mental disorder during hospitalization. Major depressive, neurocognitive, anxiety, substance-related and schizophrenia-spectrum disorders were the most frequently diagnosed. Interestingly, females were 23% less likely to have been diagnosed with major depressive disorder than males (aOR: 0.769, CI [0.650, 0.909], p = 0.002). This is to say males evidenced 1.30 higher odds of being diagnosed with depression compared to their female counterpart. Age, biological sex, civil status, employment status, monthly household income, previous mental disorder and history substance use/abuse history was differentially associated with receiving a current DSM-5 disorder.

Conclusion

The integration of clinical health psychology services within a general hospital facilitated our team’s work of identifying and treating co-occurring mental disorders among hospitalized patients receiving medical and surgical care. Future studies examining the opportunities and barriers of integrating clinical health psychology services within a general hospital’s administrative and clinical infrastructure for rapid identification and treatment of co-occurring mental disorders among medical patients is encouraged.
Using adalimumab serum concentration to choose a subsequent biological DMARD in rheumatoid arthritis patients failing adalimumab treatment (ADDORA-switch): study protocol for a fully blinded randomised superiority test-treatment trial
Authors: Wientjes Maike H. M. , Atiqi Sadaf , Wolbink Gerrit Jan , Nurmohamed Michael T. , Boers Maarten , Rispens Theo , de Vries Annick , van Vollenhoven Ronald F. , van den Bemt Bart J. F. , den Broeder Alfons A.
Published: June 2021

Background

A substantial proportion of rheumatoid arthritis (RA) patients discontinues treatment with tumour necrosis factor inhibitors (TNFi) due to inefficacy or intolerance. After the failure of treatment with a TNFi, treatment can be switched to another TNFi or a bDMARD with a different mode of action (non-TNFi). Measurement of serum drug concentrations and/or anti-drug antibodies (therapeutic drug monitoring (TDM)) may help to inform the choice for the next step. However, the clinical utility of TDM to guide switching has not been investigated in a randomised test-treatment study.

Methods

ADDORA-switch is a 24-week, multi-centre, triple-blinded, superiority test-treatment randomised controlled trial. A total of 84 RA patients failing adalimumab treatment (treatment failure defined as DAS28-CRP > 2.9) will be randomised in a 1:1 ratio to a switching strategy to either TNFi or non-TNFi based on adalimumab serum trough level (intervention group) or random allocation (control group). The primary outcome is the between-group difference in mean time-weighted DAS28 over 24 weeks.

Discussion

The trial design differs in many aspects from previously published and ongoing TDM studies and is considered the first blinded test-treatment trial using TDM in RA. Several choices in the design of this trial are described, and overarching principles regarding test-treatment trials and clinical utility of TDM are discussed in further detail.

Trial registration

Dutch Trial Register NL8210. Registered on 3 December 2019 (CMO NL69841.091.19).
Modular biosynthesis of plant hemicellulose and its impact on yeast cells
Authors: Robert Madalen , Waldhauer Julian , Stritt Fabian , Yang Bo , Pauly Markus , Voiniciuc Cătălin
Published: June 2021

Background

The carbohydrate polymers that encapsulate plants cells have benefited humans for centuries and have valuable biotechnological uses. In the past 5 years, exciting possibilities have emerged in the engineering of polysaccharide-based biomaterials. Despite impressive advances on bacterial cellulose-based hydrogels, comparatively little is known about how plant hemicelluloses can be reconstituted and modulated in cells suitable for biotechnological purposes.

Results

Here, we assembled cellulose synthase-like A (CSLA) enzymes using an optimized Pichia pastoris platform to produce tunable heteromannan (HM) polysaccharides in yeast. By swapping the domains of plant mannan and glucomannan synthases, we engineered chimeric CSLA proteins that made β-1,4-linked mannan in quantities surpassing those of the native enzymes while minimizing the burden on yeast growth. Prolonged expression of a glucomannan synthase from Amorphophallus konjac was toxic to yeast cells: reducing biomass accumulation and ultimately leading to compromised cell viability. However, an engineered glucomannan synthase as well as CSLA pure mannan synthases and a CSLC glucan synthase did not inhibit growth. Interestingly, Pichia cell size could be increased or decreased depending on the composition of the CSLA protein sequence. HM yield and glucose incorporation could be further increased by co-expressing chimeric CSLA proteins with a MANNAN-SYNTHESIS-RELATED (MSR) co-factor from Arabidopsis thaliana.

Conclusion

The results provide novel routes for the engineering of polysaccharide-based biomaterials that are needed for a sustainable bioeconomy. The characterization of chimeric cellulose synthase-like enzymes in yeast offers an exciting avenue to produce plant polysaccharides in a tunable manner. Furthermore, cells modified with non-toxic plant polysaccharides such as β-mannan offer a modular chassis to produce and encapsulate sensitive cargo such as therapeutic proteins.

Graphic abstract
Clinical applications of the venous excess ultrasound (VExUS) score: conceptual review and case series
Authors: Rola Philippe , Miralles-Aguiar Francisco , Argaiz Eduardo , Beaubien-Souligny William , Haycock Korbin , Karimov Timur , Dinh Vi Am , Spiegel Rory
Published: June 2021

The importance of functional right ventricular failure and resultant splanchnic venous congestion has long been under-appreciated and is difficult to assess by traditional physical examination and standard diagnostic imaging. The recent development of the venous excess ultrasound score (VExUS) and growth of point-of-care ultrasound in the last decade has made for a potentially very useful clinical tool. We review the rationale for its use in several pathologies and illustrate with several clinical cases where VExUS was pivotal in clinical management.
Selective ablation of cochlear hair cells promotes engraftment of human embryonic stem cell-derived progenitors in the mouse organ of Corti
Authors: Takeda Hiroki , Dondzillo Anna , Randall Jessica A. , Gubbels Samuel P.
Published: June 2021

Background

Hearing loss affects 25% of the population at ages 60–69 years. Loss of the hair cells of the inner ear commonly underlies deafness and once lost this cell type cannot spontaneously regenerate in higher vertebrates. As a result, there is a need for the development of regenerative strategies to replace hair cells once lost. Stem cell-based therapies are one such strategy and offer promise for cell replacement in a variety of tissues. A number of investigators have previously demonstrated successful implantation, and certain level of regeneration of hair and supporting cells in both avian and mammalian models using rodent pluripotent stem cells. However, the ability of human stem cells to engraft and generate differentiated cell types in the inner ear is not well understood.

Methods

We differentiate human pluripotent stem cells to the pre-placodal stage in vitro then transplant them into the mouse cochlea after selective and complete lesioning of the endogenous population of hair cells.

Results

We demonstrate that hair cell ablation prior to transplantation leads to increased engraftment in the auditory sensory epithelium, the organ of Corti, as well as differentiation of transplanted cells into hair and supporting cell immunophenotypes.

Conclusion

We have demonstrated the feasibility of human stem cell engraftment into an ablated mouse organ of Corti.

Graphical abstract
Enhanced HSC-like cell generation from mouse pluripotent stem cells in a 3D induction system cocultured with stromal cells
Authors: Shan Wei , Yu Qin , Long Yan , Luo Qian , Li Honghu , Han Yingli , Xu Yulin , Fu Shan , Zeng Xiangjun , Wei Cong , Gao Yang , Li Xiaoqing , Li Xia , Zhang Lifei , Liu Lizhen , Chen Ming , Qian Pengxu , Huang He
Published: June 2021

Background

Decades of efforts have attempted to differentiate the pluripotent stem cells (PSCs) into truly functional hematopoietic stem cells (HSCs), yet the problems of low differentiation efficiency in vitro and poor hematopoiesis reconstitution in vivo still exist, mainly attributing to the lack of solid, reproduced, or pursued differentiation system.

Methods

In this study, we established an in vitro differentiation system yielding in vivo hematopoietic reconstitution hematopoietic cells from mouse PSCs through a 3D induction system followed by coculture with OP9 stromal cells. The in vivo hematopoietic reconstitution potential of c-kit+ cells derived from the mouse PSCs was evaluated via m-NSG transplantation assay. Flow cytometry analysis, RNA-seq, and cell cycle analysis were used to detect the in vitro hematopoietic ability of endothelial protein C receptor (EPCR, CD201) cells generated in our induction system.

Results

The c-kit+ cells from 3D self-assembling peptide induction system followed by the OP9 coculture system possessed apparently superiority in terms of in vivo repopulating activity than that of 3D induction system followed by the 0.1% gelatin culture. We interestingly found that our 3D+OP9 system enriched a higher percentage of CD201+c-kit+cells that showed more similar HSC-like features such as transcriptome level and CFU formation ability than CD201-c-kit+cells, which have not been reported in the field of mouse PSCs hematopoietic differentiation. Moreover, CD201+ hematopoietic cells remained in a relatively slow cycling state, consistent with high expression levels of P57 and Ccng2. Further, we innovatively demonstrated that notch signaling pathway is responsible for in vitro CD201+ hematopoietic cell induction from mouse PSCs.

Conclusions

Altogether, our findings lay a foundation for improving the efficiency of hematopoietic differentiation and generating in vivo functional HSC-like cells from mouse PSCs for clinical application.
Adipose-derived stem cells therapy effectively attenuates PM2.5-induced lung injury
Authors: Gao Junling , Yuan Juntao , Liu Qun , Wang Yuanli , Wang Huiwen , Chen Yingjie , Ding Wenjun , Ji Guangju , Lu Zhongbing
Published: June 2021

Background

The adverse health effects of fine particulate matter (PM2.5) exposure are associated with marked inflammatory responses. Adipose-derived stem cells (ADSCs) have immunosuppressive effects, and ADSC transplantation could attenuate pulmonary fibrosis in different animal disease models. However, whether ADSCs affect PM2.5-induced lung injury has not been investigated.

Method

C57BL/6 mice were exposed to PM2.5 every other day via intratracheal instillation for 4 weeks. After that, the mice received tail vein injections of ADSCs every 2 weeks.

Results

ADSC transplantation significantly attenuated systemic and pulmonary inflammation, cardiac dysfunction, fibrosis, and cell death in PM2.5-exposed mice. RNA-sequencing results and bioinformatic analysis suggested that the downregulated differentially expressed genes (DEGs) were mainly enriched in inflammatory and immune pathways. Moreover, ADSC transplantation attenuated PM2.5-induced cell apoptosis and pyroptosis in the lungs and hearts.

Conclusion

ADSCs protect against PM2.5-induced adverse health effects through attenuating pulmonary inflammation and cell death. Our findings suggest that ADSC transplantation may be a potential therapeutic approach for severe air pollution-associated diseases.
Embryoid research calls for reassessment of legal regulations
Authors: Hengstschläger Markus , Rosner Margit
Published: June 2021

It is known that in countries, in which basic research on human embryos is in fact prohibited by law, working with imported human embryonic stem cells (hESCs) can still be permitted. As long as hESCs are not capable of development into a complete human being, it might be the case that they do not fulfill all criteria of the local definition of an embryo. Recent research demonstrates that hESCs can be developed into entities, called embryoids, which increasingly could come closer to actual human embryos in future. By discussing the Austrian situation, we want to highlight that current embryoid research could affect the prevailing opinion on the legal status of work with hESCs and therefore calls for reassessment of the regulations in all countries with comparable definitions of the embryo.
Almost absolute weighted summability with index k and matrix transformations
Authors: Sarıgöl M. A. , Mursaleen M.
Published: June 2021

In this paper we generalize the space $\hat{\ell }_{k}$

ℓ
ˆ

k

of absolutely almost convergent series (J. Math. Anal. Appl. 161:50–56, 1991) via weighted mean transformations. We study some inclusion relations and their topological properties. Further we characterize certain matrix transformations.
Three-dimensional niche partitioning between two colonially nesting ardeid species in central China
Authors: Ye Yuanxing , Hu Canshi , Jiang Yiting , Davison Geoffrey W. H. , Ding Changqing
Published: June 2021

Background

Interspecific competition is known to be strongest between those species that are both closely related and sympatric. Egrets are colonially nesting wetland birds that often overlap and can therefore be expected to compete in roosting and nesting habitat as well as in diet. According to the niche partitioning hypothesis, it is to be expected that these similar species would show differentiation in at least one of the main niche dimensions to reduce competition. We tested niche partitioning between the colonially nesting Little Egret (Egretta garzetta) and Cattle Egret (Bubulcus ibis) in temporal, spatial and trophic dimensions.

Methods

Field study was conducted in three mixed egret colonies in Yangxian County, southwest Shaanxi Province, central China. For each nest colony we recorded its spatial location, the height of nesting trees and of nests, the height of roosting trees and of roosting individuals within the trees. We determined the first egg-laying and first hatching dates of the two species. Craw dissection of storm-killed egret nestlings was used to measure the diet. Six transects were surveyed to study foraging habitat selection.

Results

We found that hatching time of Little Egrets peaked earlier (by about 1 month) than that of Cattle Egrets. Cattle Egrets nested and roosted higher than Little Egrets. The foraging habitats used by Little Egrets were dominated by river banks (73.49%), followed by paddy fields (13.25%) and reservoirs (10.84%), whereas Cattle Egret foraging sites were characterized by grasslands (44.44%), paddy fields (33.33%) and river banks (22.22%). Little Egrets consumed more fishes (65.66%) and Odonata larvae (13.69%) than Cattle Egrets, while Cattle Egrets were found feeding mainly on Coleoptera (29.69%) and Orthoptera (23.29%). Little Egrets preyed on larger mean biomasses of food items than Cattle Egrets.

Conclusions

Our results confirm the niche partitioning hypothesis as a mechanism for coexistence among ecologically similar species. In two coexisting egret species, niche partitioning is multidimensional, such that the two coexistent species occupy differing ecological space based on all three temporal, spatial and trophic niche dimensions.
Functional recovery in post-stroke patients on hemodialysis during the convalescent phase: a comparison with those not undergoing hemodialysis
Authors: Ishida Takeki , Kono Kenichi , Nishida Yuusuke , Yoshida Masahiro
Published: June 2021

Background

Low physical fitness is often found in patients undergoing hemodialysis. It may be possible that the recovery of impaired motor function with rehabilitative training might be affected when the patient is on hemodialysis. So far, however, no researcher has clinically investigated this issue in post-stroke patients. The purpose of this study is to clarify the difference of functional recovery during the convalescent phase between post-stroke patients with and without hemodialysis.

Methods

A cohort of 82 post-stroke hemiparetic patients who were admitted to our rehabilitation hospital, were subjected. On the day of admission and discharge, some clinical parameters including Functional Independence Measure (FIM) and Functional Ambulation Category (FAC) were evaluated for each patient. The changes during the hospitalization and the values at the discharge in these parameters were statistically compared between the patients with and without hemodialysis.

Results

The FIM motor score at the discharge was significantly lower in hemodialysis patients than non-hemodialysis patients (64.7 ± 21.2 points in hemodialysis patients and 81.8 ± 28.0 points in non-hemodialysis patients, p < 0.05). In addition, the frequency of FAC at the discharge of ≥ 3 was significantly lower in hemodialysis patients than non-hemodialysis patients (40.0% in hemodialysis patients and 72.2% in non-hemodialysis patients, p < 0.05).

Conclusion

In patients undergoing hemodialysis seem to experience a worse functional recovery during the convalescent phase compared to those not undergoing hemodialysis. We might have to modify the rehabilitative program during the convalescent phase after stroke if the patient was on hemodialysis.
The multiplicity of halal standards: a case study of application to slaughterhouses
Authors: Abdallah Ali , Rahem Mohammed Abdel , Pasqualone Antonella
Published: June 2021

Food products suitable for Muslim consumers should behalalcertified, particularly when their origins or production processes are doubtful. However, there is a multiplicity ofhalalstandards. This situation may generate confusion, particularly for producers in Western countries who would like to certify their products in order to export them to Islamic countries. This study analyzed the reasons underlying the multiplicity of standards and reviewed the attempts of harmonization over time. Then, the case study of application to slaughterhouses was considered, by comparing four differenthalalstandards (namely GSO 993:2015, OIC/SMIIC 1:2019, HAS 23103:2012, and MS 1500:2019) representative of different geographic areas. Animal stunning was critically examined, comparing tradition with modernity. The study evidenced that the basic requirements related to slaughtering are common to all thehalalstandards considered, but several differences occur in more specific details. Only a close collaboration between the authorities of all the countries involved in issuinghalalcertifications will lead to a homogeneous regulatory framework with unified certification and accreditation procedures, increasingly required in a globalized market.
Extracellular vesicles (exosomes and ectosomes) play key roles in the pathology of brain diseases
Authors: Meldolesi Jacopo
Published: June 2021

Last century, neurons and glial cells were mostly believed to play distinct functions, relevant for the brain. Progressively, however, it became clear that neurons, astrocytes and microglia co-operate intensely with each other by release/binding of signaling factors, direct surface binding and generation/release of extracellular vesicles, the exosomes and ectosomes, called together vesicles in this abstract. The present review is focused on these vesicles, fundamental in various brain diseases. Their properties are extraordinary. The specificity of their membrane governs their fusion with distinct target cells, variable depending on the state and specificity of their cells of origin and target. Result of vesicle fusion is the discharge of their cargos into the cytoplasm of target cells. Cargos are composed of critical molecules, from proteins (various nature and function) to nucleotides (especially miRNAs), playing critical roles in immune and neurodegenerative diseases. Among immune diseases is multiple sclerosis, affected by extensive dysregulation of co-trafficking neural and glial vesicles, with distinct miRNAs inducing severe or reducing effects. The vesicle-dependent differences between progressive and relapsing-remitting forms of the disease are relevant for clinical developments. In Alzheimer’s disease the vesicles can affect the brain by changing their generation and inducing co-release of effective proteins, such Aβ and tau, from neurons and astrocytes. Specific miRNAs can delay the long-term development of the disease. Upon their traffic through the blood-brainbarrier, vesicles of various origin reach fluids where they are essential for the identification of biomarkers, important for diagnostic and therapeutic innovations, critical for the future of many brain patients.
Checkpoint Kinase 1 (Chk1) inhibition fails to activate the Stimulator of Interferon Genes (STING) innate immune signalling in a human coculture cancer system
Authors: Brooks Teresa , Wayne Joanne , Massey Andrew J.
Published: June 2021

Utilising Checkpoint Kinase 1 (Chk1) inhibitors to increase cytoplasmic DNA may be a potential strategy to increase the sensitivity of tumours to immune checkpoint modulators. The appearance of DNA in the cytoplasm can drive Cyclic GMP-AMP Synthase-2′,3′-Cyclic Guanosine Monophosphate–Adenosine Monophosphate-Stimulator of Interferon Genes (cGAS-cGAMP-STING) inflammatory, anti-tumour T-cell activity via a type I interferon (IFN) and nuclear factor-κB response. In the THP1-Dual reporter cell line, the STING agonist cGAMP activated both reporters, and increased phosphorylation of the innate immune pathway signallers Tank Binding Kinase 1 (TBK1) and Interferon Regulatory Factor (IRF) 3. Inhibition of Chk1 increased TBK1 but not IRF3 phosphorylation and did not induce IRF or NF-κB reporter activation. cGAMP induced a Type I IFN response in THP1 cells whereas inhibition of Chk1 did not. HT29 or HCC1937 cell treatment with a Chk1 inhibitor increased cytoplasmic dsDNA in treated HCC1937 but not HT29 cells and increased IRF reporter activation in cocultured THP1-Dual cells. HT29 cells pre-treated with gemcitabine or camptothecin had elevated cytoplasmic dsDNA and IRF reporter activation in cocultured THP1-Dual cells. Camptothecin or gemcitabine plus a Chk1 inhibitor increased cytoplasmic dsDNA but Chk1 inhibition suppressed IRF reporter activation in cocultured THP1 cells. In THP1-Dual cells treated with cGAMP, Chk1 inhibition suppressed the activation of the IRF reporter compared to cGAMP alone. These results suggest that, in some cellular models, there is little evidence to support the combination of Chk1 inhibitors with immune checkpoint modulators and, in some combination regimes, may even prove deleterious.
Tildacerfont in Adults With Classic Congenital Adrenal Hyperplasia: Results from Two Phase 2 Studies
Authors: Sarafoglou Kyriakie , Barnes Chris N , Huang Michael , Imel Erik A , Madu Ivy-Joan , Merke Deborah P , Moriarty David , Nakhle Samer , Newfield Ron S , Vogiatzi Maria G , Auchus Richard J
Published: June 2021

Context

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21OHD) is typically treated with lifelong supraphysiologic doses of glucocorticoids (GCs). Tildacerfont, a corticotropin-releasing factor type-1 receptor antagonist, may reduce excess androgen production, allowing for GC dose reduction.

Objective

Assess tildacerfont safety and efficacy.

Design and Setting

Two Phase 2 open-label studies.

Patients

Adults with 21OHD.

Intervention

Oral tildacerfont 200 to 1000 mg once daily (QD) (n = 10) or 100 to 200 mg twice daily (n = 9 and 7) for 2 weeks (Study 1), and 400 mg QD (n = 11) for 12 weeks (Study 2).

Main Outcome Measure

Efficacy was evaluated by changes from baseline at 8 am in adrenocorticotropic hormone (ACTH), 17-hydroxyprogesterone (17-OHP), and androstenedione (A4) according to baseline A4 ≤ 2× upper limit of normal (ULN) or A4 > 2× ULN. Safety was evaluated using adverse events (AEs) and laboratory assessments.

Results

In Study 1, evaluable participants with baseline A4 > 2× ULN (n = 11; 19-67 years, 55% female) had reductions from baseline in ACTH (−59.4% to −28.4%), 17-OHP (−38.3% to 0.3%), and A4 (−24.2% to −18.1%), with no clear dose response. In Study 2, participants with baseline A4 > 2× ULN (n = 5; 26-63 years, 40% female) had ~80% maximum mean reductions in biomarker levels. ACTH and A4 were normalized for 60% and 40%, respectively. In both studies, participants with baseline A4 ≤ 2× ULN maintained biomarker levels. AEs (in 53.6% of patients overall) included headache (7.1%) and upper respiratory tract infection (7.1%).

Conclusions

For patients with 21OHD, up to 12 weeks of oral tildacerfont reduced or maintained key hormone biomarkers toward normal.
Intestinal Flora is a Key Factor in Insulin Resistance and Contributes to the Development of Polycystic Ovary Syndrome
Authors: Yang Yue-Lian , Zhou Wei-Wei , Wu Shan , Tang Wen-Li , Wang Zong-Wei , Zhou Zu-Yi , Li Ze-Wen , Huang Qing-Fa , He Yan , Zhou Hong-Wei
Published: June 2021

Context

The key gut microbial biomarkers for polycystic ovarian syndrome (PCOS) and how dysbiosis causes insulin resistance and PCOS remain unclear.

Objective

To assess the characteristics of intestinal flora in PCOS and explore whether abnormal intestinal flora can affect insulin resistance and promote PCOS and whether chenodeoxycholic acid (CDCA) can activate intestinal farnesoid X receptor (FXR), improving glucose metabolism in PCOS.

Setting and design

The intestinal flora of treatment-naïve PCOS patients and hormonally healthy controls was analyzed. Phenotype analysis, intestinal flora analysis, and global metabolomic profiling of caecal contents were performed on a letrozole-induced PCOS mouse model; similar analyses were conducted after 35 days of antibiotic treatment on the PCOS mouse model, and glucose tolerance testing was performed on the PCOS mouse model after a 35-day CDCA treatment. Mice receiving fecal microbiota transplants from PCOS patients or healthy controls were evaluated after 10 weeks.

Results

Bacteroides was significantly enriched in treatment-naïve PCOS patients. The enrichment in Bacteroides was reproduced in the PCOS mouse model. Gut microbiota removal ameliorated the PCOS phenotype and insulin resistance and increased relative FXR mRNA levels in the ileum and serum fibroblast growth factor 15 levels. PCOS stool-transplanted mice exhibited insulin resistance at 10 weeks but not PCOS. Treating the PCOS mouse model with CDCA improved glucose metabolism.

Conclusions

Bacteroides is a key microbial biomarker in PCOS and shows diagnostic value. Gut dysbiosis can cause insulin resistance. FXR activation might play a beneficial rather than detrimental role in glucose metabolism in PCOS.
Absolute Quantification of Phosphorylated ERβ Amino Acids in the Hippocampus of Women and in A Rat Model of Menopause
Authors: Zhang Mengjie , Flury Sarah , Kim Chun K , Chung Wilson C J , Kirk Jonathan A , Pak Toni R
Published: June 2021

The rapid decline of circulating 17β-estradiol (E2) at menopause leads to negative neurological consequences, although hormone therapy paradoxically has both harmful and positive effects depending on the age at which it is delivered. The inconsistent response to E2 suggests unappreciated regulatory mechanisms for estrogen receptors (ERs), and we predicted it could be due to age-related differences in ERβ phosphorylation. We assessed ERβ phosphorylation using a sensitive mass spectrometry approach that provides absolute quantification (AQUA-MS) of individually phosphorylated residues. Specifically, we quantified phosphorylated ERβ in the hippocampus of women (aged 21-83 years) and in a rat model of menopause at 4 residues with conserved sequence homology between the 2 species: S105, S176, S200, and Y488. Phosphorylation at these sites, which spanned all domains of ERβ, were remarkably consistent between the 2 species, showing high levels of S105 phosphorylation (80%-100%) and low levels of S200 (20%-40%). Further, S200 phosphorylation decreased with aging in humans and loss of E2 in rats. Surprisingly, Y488 phosphorylation, which has been linked to ERβ ligand-independent actions, exhibited approximately 70% phosphorylation, unaltered by species, age, or E2, suggesting ERβ’s primary mode of action may not require E2 binding. We further show phosphorylation at 2 sites directly altered ERβ DNA-binding efficiency, and thus could affect its transcription factor activity. These findings provide the first absolute quantification of ERβ phosphorylation in the human and rat brain, novel insights into ERβ regulation, and a critical foundation for providing more targeted therapeutic options for menopause in the future.
A Pilot Trial: Fish Oil and Metformin Effects on ApoB-Remnants and Triglycerides in Women With Polycystic Ovary Syndrome
Authors: Vine Donna , Proctor Ethan , Weaver Olivia , Ghosh Mahua , Maximova Katerina , Proctor Spencer
Published: June 2021

Context

Women with polycystic ovary syndrome (PCOS) have increased incidence of atherogenic dyslipidemia and cardiovascular disease (CVD). Interventions targeting atherogenic dyslipidemia to reduce CVD risk are limited in women with PCOS.

Objective

This pilot study was conducted to determine the effect of 12 weeks of high dose fish oil (FO), metformin, and FO as an adjunct to metformin (FO-metformin) therapy on fasting and nonfasting plasma lipids and ApoB-remnants in young women with the metabolic syndrome (MetS) and PCOS.

Methods

In this open-label parallel pilot trial, women with MetS and PCOS (18-30 years of age) were randomized into 1 of 3 interventions: (1) FO; (2) metformin; and (3) FO-metformin. Plasma lipids and ApoB (48 and 100)-lipoproteins and triglycerides (TG) were measured in the fasted and postprandial state following a high-fat meal at baseline and postintervention.

Results

FO-metformin significantly lowered fasting plasma TG by >40% compared with FO and metformin treatments. Fasting plasma apoB48 was lowered 40% in FO-metformin and 15% in the FO groups from baseline to postintervention. ApoB48 area under the curve (ApoB48AUC), ApoB48 incremental AUC (ApoB48iAUC), ApoB100AUC, and ApoB100iAUC decreased in all groups from baseline to postintervention; however, these findings did not reach statistical significance.

Conclusion

The findings of this pilot trial show that high dose FO and FO-metformin combination therapy tend to lower fasting and postprandial plasma TG and ApoB-lipoprotein remnants compared with metformin; however, the study is limited by small sample size. These results may be clinically significant in individuals with PCOS for management of atherogenic dyslipidemia.
A Novel Liver-targeted Testosterone Therapy for Sarcopenia in Androgen Deprived Men With Prostate Cancer
Authors: Rhee Handoo , Navaratnam Anojan , Oleinikova Irina , Gilroy Deborah , Scuderi Yolanda , Heathcote Peter , Nguyen Tuan , Wood Simon , Ho Ken K Y
Published: June 2021

Objective

Androgen deprivation therapy (ADT) reduces muscle and bone mass, increasing frailty in men with prostate cancer. The liver mediates the whole body anabolic effects of testosterone. Based on first-pass metabolism, liver-targeted testosterone treatment (LTTT) entails oral delivery of a small dose of testosterone that does not raise peripheral blood testosterone levels. LTTT reduces blood urea and stimulates protein anabolism in hypogonadal men and postmenopausal women. We investigated whether LTTT prevents loss of lean and bone mass during ADT.

Method

A 6-month, double-blind, placebo-controlled study of testosterone 40 mg/day in 50 men. Primary outcome measures were lean mass and bone mineral content (BMC). Testosterone, urea and prostate-specific antigen (PSA) were monitored. Patients were withdrawn if PSA exceeded 4 ng/mL.

Results

42 patients completed the study. Mean (95% CI) testosterone rose during LTTT but not placebo treatment [∆ 2.2 (1.3-3.0) vs −0.7 (−1.5 to 0.2) nmol/L; P < 0.01]. Mean PSA level did not change significantly during either treatment. Blood urea fell [∆ −0.4 (−0.9 to −0.1) mmol/L] during LTTT but not placebo [∆ 0.05 (−0.8 to 0.9) mmol/L]. BMC [∆ 49 (5 to 93) g; P < 0.02] and lean mass [∆ 0.8 (−0.1 to 1.7) kg; P = 0.04) increased compared to placebo. Five patients on LTTT withdrew from increased PSA levels, all returning to baseline levels.

Conclusion

LTTT shows promise as a simple therapy for preventing sarcopenia and bone loss during ADT. LTTT may induce reversible PSA rise in some patients. Further studies are required to optimize LTTT dose in ADT. LTTT has potential application in other catabolic states in men and women.
Siblings with megalencephalic leukoencephalopathy with subcortical cysts van der Knaap disease
Authors: M P Saanida , Varghese Lin , Thomas Rinu Susan , Prasad Sandeep Govindan
Published: June 2021

Cerebral leukoencephalopathy and megalencephaly with subcortical cysts (also known as van der Knaap disease) is an autosomal recessive condition. The disease was initially described in India and Netherlands independently and seems to have highest incidence in Indian Agrawal community and Turkish population. 1 The objective of this study is to document the case of two siblings with this condition, from a non-Agrawal Indian community and briefly describe the imaging features of this condition. Two siblings, born out of a third-degree consanguineous marriage, with simple focal seizures were subjected to MRI with diffusion-weighted imaging and spectrometry. The findings were compared to diseases with similar clinical presentation. Subcortical cysts initially involving anterior temporal lobes and subsequently frontal and parietal lobes, sparing of central white mater, small N acetyl aspartate peak and diffusion facilitation were the imaging findings. The imaging findings were consistent with the diagnosis of the rare genetic disorder- Cerebral leukoencephalopathy and megalencephaly with subcortical cysts.