bluuebunny/crossref_metadata_2025 huggingface dataset:
Adolescent Sjogren’s syndrome presenting as psychosis: a case series
Authors: Hammett Erin K. , Fernandez-Carbonell Cristina , Crayne Courtney , Boneparth Alexis , Cron Randy Q. , Radhakrishna Suhas M.
Published: February 2020

Background

Neurological involvement has been reported in up to 80% of adults with Primary Sjogren’s syndrome (pSS) with psychiatric abnormalities including anxiety, depression, and cognitive dysfunction being common. Psychosis due to pSS has been reported in adult patients but has never been previously reported in the adolescent/pediatric literature. Here we describe for the first time four cases of adolescent Sjogren’s syndrome that presented with psychotic symptoms. Rituximab treatment was followed by improvement of psychiatric symptoms in all patients.

Case presentation

1: 16 year old female without significant past medical history presented to the emergency department with 4 days of abnormal behavior, tremors, insomnia, polyphagia, polyuria, and suicidal ideation.

2: 16 year old female with a 4 year history of severe anxiety, OCD, and tic disorder treated with fluoxetine with partial benefit presented with an abrupt and severe worsening of anxiety, OCD and new auditory hallucinations.

3: 19 year old female without significant past medical history presented with a 3 day history of progressively altered behavior, incoherent speech, insomnia, headache, and tangential thoughts.

4: 17 year old female without significant past medical history presented with new onset suicidal ideation, paranoia, confusion, and emotional lability.

Conclusion

Psychosis is more common in autoimmune disease than previously known. To our knowledge, the four teenage women described above are the first reported patients with adolescent pSS manifesting as psychosis. pSS should be considered in the differential diagnosis of young patients with new psychiatric disorders, even in the absence of sicca symptoms. Psychiatric symptoms improved with rituximab infusions in all 4 of our patients, which suggests rituximab may be an effective treatment option that should be considered early after the diagnosis of pSS-associated psychiatric disturbance.
Aquaporin 1 and the Na+/K+/2Cl− cotransporter 1 are present in the leptomeningeal vasculature of the adult rodent central nervous system
Authors: Li Qianliang , Aalling Nadia N. , Förstera Benjamin , Ertürk Ali , Nedergaard Maiken , Møllgård Kjeld , Xavier Anna L. R.
Published: February 2020

Background

The classical view of cerebrospinal fluid (CSF) production posits the choroid plexus as its major source. Although previous studies indicate that part of CSF production occurs in the subarachnoid space (SAS), the mechanisms underlying extra-choroidal CSF production remain elusive. We here investigated the distributions of aquaporin 1 (AQP1) and Na+/K+/2Cl− cotransporter 1 (NKCC1), key proteins for choroidal CSF production, in the adult rodent brain and spinal cord.

Methods

We have accessed AQP1 distribution in the intact brain using uDISCO tissue clearing technique and by Western blot. AQP1 and NKCC1 cellular localization were accessed by immunohistochemistry in brain and spinal cord obtained from adult rodents. Imaging was performed using light-sheet, confocal and bright field light microscopy.

Results

We determined that AQP1 is widely distributed in the leptomeningeal vasculature of the intact brain and that its glycosylated isoform is the most prominent in different brain regions. Moreover, AQP1 and NKCC1 show specific distributions in the smooth muscle cell layer of penetrating arterioles and veins in the brain and spinal cord, and in the endothelia of capillaries and venules, restricted to the SAS vasculature.

Conclusions

Our results shed light on the molecular framework that may underlie extra-choroidal CSF production and we propose that AQP1 and NKCC1 within the leptomeningeal vasculature, specifically at the capillary level, are poised to play a role in CSF production throughout the central nervous system.
Quantitatively relating brain endothelial cell–cell junction phenotype to global and local barrier properties under varied culture conditions via the Junction Analyzer Program
Authors: Gray Kelsey M. , Jung Jae W. , Inglut Collin T. , Huang Huang-Chiao , Stroka Kimberly M.
Published: February 2020

Background

The endothelial cell–cell junctions of the blood–brain barrier (BBB) play a pivotal role in the barrier’s function. Altered cell–cell junctions can lead to barrier dysfunction and have been implicated in several diseases. Despite this, the driving forces regulating junctional protein presentation remain relatively understudied, largely due to the lack of efficient techniques to quantify their presentation at sites of cell–cell adhesion. Here, we used our novel Junction Analyzer Program (JAnaP) to quantify junction phenotype (i.e., continuous, punctate, or perpendicular) in response to various substrate compositions, cell culture times, and cAMP treatments in human brain microvascular endothelial cells (HBMECs). We then quantitatively correlated junction presentation with barrier permeability on both a “global” and “local” scale.

Methods

We cultured HBMECs on collagen I, fibronectin, collagen IV, laminin, fibronectin/collagen IV/laminin, or hyaluronic acid/gelatin for 2, 4, and 7 days with varying cAMP treatment schedules. Images of immunostained ZO-1, VE-cadherin, and claudin-5 were analyzed using the JAnaP to calculate the percent of the cell perimeter presenting continuous, punctate, or perpendicular junctions. Transwell permeability assays and resistance measurements were used to measure bulk (“global”) barrier properties, and a “local” permeability assay was used to correlate junction presentation proximal to permeable monolayer regions.

Results

Substrate composition was found to play little role in junction presentation, while cAMP supplements significantly increased the continuous junction architecture. Increased culture time required increased cAMP treatment time to reach similar ZO-1 and VE-cadherin coverage observed with shorter culture, though longer cultures were required for claudin-5 presentation. Prolonged cAMP treatment (6 days) disrupted junction integrity for all three junction proteins. Transwell permeability and TEER assays showed no correlation with junction phenotype, but a local permeability assay revealed a correlation between the number of discontinuous and no junction regions with barrier penetration.

Conclusions

These results suggest that cAMP signaling influences HBMEC junction architecture more than matrix composition. Our studies emphasized the need for local barrier measurement to mechanistically understand the role of junction phenotype and supported previous results that continuous junctions are indicative of a more mature/stable endothelial barrier. Understanding what conditions influence junction presentations, and how they, in turn, affect barrier integrity, could lead to the development of therapeutics for diseases associated with BBB dysfunction.
Choroid plexus LAT2 and SNAT3 as partners in CSF amino acid homeostasis maintenance
Authors: Dolgodilina Elena , Camargo Simone M. , Roth Eva , Herzog Brigitte , Nunes Virginia , Palacín Manuel , Verrey Francois
Published: February 2020

Background

Cerebrospinal fluid (CSF) is mainly produced by the choroid plexus (CP) located in brain ventricles. Although derived from blood plasma, it is nearly protein-free (~ 250-fold less) and contains about 2–20-fold less free amino acids, with the exception of glutamine (Gln) which is nearly equal. The aim of this study was to determine which amino acid transporters are expressed in mouse CP epithelium in order to gain understanding about how this barrier maintains the observed amino acid concentration gradient.

Methods

Expression of amino acid transporters was assessed in isolated choroid plexuses (CPs) by qRT-PCR followed by localization studies using immunofluorescence with specific antibodies. The impact of LAT2 (Slc7a8) antiporter deletion on CSF amino acids was determined.

Results

The purity of isolated choroid plexuses was tested on the mRNA level using specific markers, in particular transthyretin (Ttr) that was enriched 330-fold in CP compared to cerebral tissue. In a first experimental round, 14 out of 32 Slc amino acid transporters tested on the mRNA level by qPCR were selected for further investigation. Out of these, five were considered highly expressed, SNAT1 (Slc38a1), SNAT3 (Slc38a3), LAT2 (Slc7a8), ASC1 (Slc7a10) and SIT1 (Slc6a20b). Three of them were visualized by immunofluorescence: SNAT1 (Slc38a1), a neutral amino acid-Na+ symporter, found at the blood side basolateral membrane of CP epithelium, while SNAT3 (Slc38a3), an amino acid-Na+ symporter and H+ antiporter, as well as LAT2 (Slc7a8), a neutral amino acid antiporter, were localized at the CSF-facing luminal membrane. In a LAT2 knock-out mouse model, CSF Gln was unchanged, whereas other amino acids normally 2–20-fold lower than in plasma, were increased, in particular the LAT2 uptake substrates leucine (Leu), valine (Val) and tryptophan (Trp) and some other amino acids such as glutamate (Glu), glycine (Gly) and proline (Pro).

Conclusion

These results suggest that Gln is actively transported by SNAT1 from the blood into CP epithelial cells and then released luminally into CSF via SNAT3 and LAT2. Its efflux via LAT2 may drive the reuptake from the CSF of essential amino acid substrates of this antiporter and thereby participates to maintaining the amino acid gradient between plasma and CSF.
Predominance of the c.648G > T G6PC gene mutation and late complications in Korean patients with glycogen storage disease type Ia
Authors: Kim Yoo-Mi , Choi Jin-Ho , Lee Beom-Hee , Kim Gu-Hwan , Kim Kyung-Mo , Yoo Han-Wook
Published: February 2020

Background

Glycogen storage disease (GSD) Ia, caused by mutations in the glucose-6-phosphatase (G6PC) gene, is characterized by hepatomegaly, hypoglycemia, lactic acidosis, dyslipidemia, and hyperuricemia. This study aimed to investigate clinical and molecular features and late complications in Korean patients with GSD Ia.

Results

Fifty-four Korean patients (33 males and 21 females) from 47 unrelated families, who were diagnosed with GSD Ia, based on genetic and biochemical data, between 1999 and 2017, were included in this study. The median age at diagnosis was 3.9 years (range: 5 months to 42 years), and the follow-up period was 8.0 ± 6.8 years. Most patients presented with hepatomegaly during infancy, but hypoglycemic symptoms were not predominant. Genetic analysis showed that all the patients had at least one c.648G > T allele. Homozygous c.648G > T mutations in the G6PC gene were identified in 34 families (72.3%), and compound heterozygotes with c.648G > T were found in the other families. The allele frequency of c.648G > T was 86.2% (81/94), and p.F51S, p.R83H, p.G122D, p.Y128*, p.G222R, and p.T255A were identified. Of 26 adult patients, 14 had multiple hepatic adenomas, and two were diagnosed with hepatocellular carcinoma. Thirteen patients showed renal complications, and seven patients presented gout, despite preventive allopurinol treatment. Twelve patients had osteoporosis, and two patients had pulmonary hypertension. The final heights were 157.9 cm (standard deviation score: − 3.1) in males and 157.8 cm (standard deviation score: − 0.6) in females.

Conclusion

In our Korean patients with GSD Ia, the most common mutation in the G6PC gene was c.648G > T, suggesting a founder effect. Because of only mild hypoglycemia, the patients tended to be diagnosed late. Thus, adult patients with GSD Ia eventually developed diverse and serious complications, which indicates a need for careful monitoring and proper management of this disease.
A radiological severity scale to measure the impact of Charcot's Neuroarthropathy: an observational study
Authors: Bergin Shan , Naidoo Parm , Williams Cylie M.
Published: February 2020

Background

Charcot's Neuroarthropathy (Charcot foot) is a debilitating and destructive disorder resulting from neurological changes in the foot. Whilst the majority of cases are painless, as a result of disruption to sensory function, a common outcome is severe deformity that impacts considerably on foot function. The purpose of this study was to develop and validate a radiological severity scale to quantify resultant damage from acute mid foot Charcot's. This in turn can be used to evaluate clinical outcomes related to different degrees of offloading.

Methods

A four round Delphi process was used to develop five tool items. Level of consensus and agreement was set at 80%. Inter‐rater and intra‐rater reliability was evaluated using 3 raters and 24 plain x‐rays of chronic mid‐foot Charcot's. Strength of agreement of individual items and overall scores was calculated using weighted Kappa coefficients (S.E). Cronbach's α was used to determine internal consistency. Floor (> 15% score 0) and ceiling (> 15% score 11) effects were examined at each time point. Spearman's correlation coefficient was used to assess construct validity using Mobility and Usual Activity scores taken from the EQ‐5D‐5 L.

Results

Twenty two patients participated. The five item severity scale demonstrated a Cronbach's α of 0.91. Intra‐rater Kappa coefficients (SE) for total scores ranged from 0.84 (0.20) to 0.86 (0.20). Inter rater coefficients (SE) ranged from 0.72 (0.14) to 0.83 (0.14). Distribution was normal and no floor or ceiling effects were identified.

Conclusion/interpretation

This study suggests it may be possible to quantify resultant damage from mid foot Charcot's. Given the physical and emotional impacts from long periods of complete immobilisation defining a minimum standard would be an important development in the management of Charcot foot.
Treating impulsivity with probiotics in adults (PROBIA): study protocol of a multicenter, double-blind, randomized, placebo-controlled trial
Authors: Arteaga-Henríquez Gara , Rosales-Ortiz Silvia Karina , Arias-Vásquez Alejandro , Bitter Istvan , Ginsberg Ylva , Ibañez-Jimenez Pol , Kilencz Tünde , Lavebratt Catharina , Matura Silke , Reif Andreas , Rethelyi Janos , Richarte Vanesa , Rommelse Nanda , Siegl Anne , Ramos-Quiroga J. Antoni
Published: February 2020

Background

Impulsivity and compulsivity are related to emotional and social maladjustment and often underlie psychiatric disorders. Recently, alterations in microbiota composition have been shown to have implications for brain development and social behavior via the microbiota–gut–brain axis. However, the exact mechanisms are not fully identified. Recent evidence suggests the modulatory effect of synbiotics on gut microbiota and the contribution of these agents in ameliorating symptoms of many psychiatric diseases. To date, no randomized controlled trial has been performed to establish the feasibility and efficacy of this intervention targeting the reduction of impulsivity and compulsivity. We hypothesize that supplementation with synbiotics may be an effective treatment in adults with high levels of impulsivity and/or compulsivity.

Methods/design

This is a prospective, multicenter, double-blind, randomized controlled trial with two arms: treatment with a synbiotic formula versus placebo treatment. The primary outcome is the response rate at the end of the placebo-controlled phase (response defined as a Clinical Global Impression–Improvement Scale score of 1 or 2 = very much improved or much improved, plus a reduction in the Affective Reactivity Index total score of at least 30% compared with baseline). A total of 180 participants with highly impulsive behavior and a diagnosis of attention deficit/hyperactivity disorder (ADHD) and/or borderline personality disorder, aged 18–65 years old, will be screened at three study centers. Secondary outcome measures, including changes in general psychopathology, ADHD symptoms, neurocognitive function, somatic parameters, physical activity, nutritional intake, and health-related quality of life, will be explored at assessments before, during, and at the end of the intervention. The effect of the intervention on genetics, microbiota, and several blood biomarkers will also be assessed. Gastrointestinal symptoms and somatic complaints will additionally be explored at 1-week follow-up.

Discussion

This is the first randomized controlled trial to determine the effects of supplementation with synbiotics on reducing impulsive and compulsive behavior. This clinical trial can contribute to explaining the mechanisms involved in the crosstalk between the intestinal microbiome and the brain. If effects can be established by reducing impulsive and compulsive behavior, new cost-effective treatments might become available to these patients.

Trial registration

ClinicalTrials.gov, NCT03495375. Registered on 26 February 2018.
Antiparasitic activity of furanyl N-acylhydrazone derivatives against Trichomonas vaginalis: in vitro and in silico analyses
Authors: Alves Mirna Samara Dié , das Neves Raquel Nascimento , Sena-Lopes Ângela , Domingues Micaela , Casaril Angela Maria , Segatto Natália Vieira , Nogueira Thaís Cristina Mendonça , de Souza Marcus Vinicius Nora , Savegnago Lucielli , Seixas Fabiana Kömmling , Collares Tiago , Borsuk Sibele
Published: February 2020

Background

Trichomonas vaginalisis the causative agent of trichomoniasis, which is one of the most common sexually transmitted diseases worldwide. Trichomoniasis has a high incidence and prevalence and is associated with serious complications such as HIV transmission and acquisition, pelvic inflammatory disease and preterm birth. Although trichomoniasis is treated with oral metronidazole (MTZ), the number of strains resistant to this drug is increasing (2.5–9.6%), leading to treatment failure. Therefore, there is an urgent need to find alternative drugs to combat this disease.

Methods

Herein, we report thein vitroandin silicoanalysis of 12 furanylN-acylhydrazone derivatives (PFUR 4, a-k) againstTrichomonas vaginalis.Trichomonas vaginalisATCC 30236 isolate was treated with seven concentrations of these compounds to determine the minimum inhibitory concentration (MIC) and 50% inhibitory concentration (IC50). In addition, compounds that displayed anti-T. vaginalisactivity were analyzed using thiobarbituric acid reactive substances (TBARS) assay and molecular docking. Cytotoxicity analysis was also performed in CHO-K1 cells.

Results

The compounds PFUR 4a and 4b, at 6.25 µM, induced complete parasite death after 24 h of exposure with IC50of 1.69 µM and 1.98 µM, respectively. The results showed that lipid peroxidation is not involved in parasite death. Molecular docking studies predicted strong interactions of PFUR 4a and 4b withT. vaginalisenzymes, purine nucleoside phosphorylase, and lactate dehydrogenase, while only PFUR 4b interactedin silicowith thioredoxin reductase and methionine gamma-lyase. PFUR 4a and 4b led to a growth inhibition (< 20%) in CHO-K1 cells that was comparable to the drug of choice, with a promising selectivity index (> 7.4).

Conclusions

Our results showed that PFUR 4a and 4b are promising molecules that can be used for the development of new trichomonacidal agents forT. vaginalis.
Ubiquitin and ubiquitin-like molecules in DNA double strand break repair
Authors: Yu Jia , Qin Bo , Lou Zhenkun
Published: February 2020

Both environmental and endogenous factors induce various forms of DNA damage. DNA double strand break (DSB) is the most deleterious DNA lesion. The swift initiation of a complexed network of interconnected pathways to repair the DNA lesion is essential for cell survival. In the past years, the roles of ubiquitin and ubiquitin-like proteins in DNA damage response and DNA repair has been explored. These findings help us better understand the complicated mechanism of DSB signaling pathways.
Influence of deprivation on initial severity and prognosis of patients admitted to the ICU: the prospective, multicentre, observational IVOIRE cohort study
Authors: Quenot Jean-Pierre , Helms Julie , Labro Guylaine , Dargent Auguste , Meunier-Beillard Nicolas , Ksiazek Elea , Bollaert Pierre-Edouard , Louis Guillaume , Large Audrey , Andreu Pascal , Bein Christophe , Rigaud Jean-Philippe , Perez Pierre , Clere-Jehl Raphaël , Merdji Hamid , Devilliers Hervé , Binquet Christine , Meziani Ferhat , Fournel Isabelle ,   the IVOIRE Trial Investigators and the CRICS TRIGGERSEP Group (Clinical Research in Intensive Care and Sepsis Trial Group for Global Evaluation and Research in Sepsis), Lévy Bruno , Lemarié Jérémie , Cadoz Cyril , Marchalot Antoine , Monnier Alexandra , Rabouel Yannick
Published: February 2020

Background

The influence of socioeconomic status on patient outcomes is unclear. We assessed the impact of socioeconomic deprivation on severity of illness at intensive care unit (ICU) admission, and on the risk of death at 3 months after ICU admission.

Methods

The IVOIRE study was a prospective, observational, multicentre cohort study in the ICU of 8 participating hospitals in France, including patients aged ≥ 18 years admitted to the ICU and receiving at least one life support therapy for organ failure. The primary outcomes were severity at admission (assessed by SAPSII score), and mortality at 3 months. Socioeconomic data were obtained from interviews with patients or family. Deprivation was assessed using the EPICES score.

Results

Among 1294 patents included between 2013 and 2016, 629 (48.6%) were classed as deprived and differed significantly from non-deprived subjects in terms of sociodemographic characteristics and pre-existing conditions. The mean SAPS II score at admission was 50.1 ± 19.4 in deprived patients and 52.3 ± 17.3 in non-deprived patients, with no significant difference by multivariable analysis (β = − 1.85 [95% CI − 3.86; + 0.16, p = 0.072]). The proportion of death was 31.1% at 3 months, without significant differences between deprived and non-deprived patients, even after adjustment for confounders.

Conclusions

Deprivation is frequent in patients admitted to the ICU and is not associated with disease severity at admission, or with mortality at 3 months between deprived and non-deprived patients.

Trial registration The IVOIRE cohort is registered with ClinicalTrials.gov under the identifier NCT01907581, registration date 17/7/2013
A type of energy-efficient secure localization algorithm FM based in dynamic sensor networks
Authors: Xue Wei-cheng , Peng Bao , Wang Shan-he , Hua Yu
Published: February 2020

Since dynamic wireless sensor networks are widely used in the military field, the location information is the basis of various applications, because each node in the dynamic sensor network is moving continuously, and it is quite possible to be attacked by various forms of information. Aiming at the problem of secure localization in dynamic sensor networks, a new secure localization algorithm—frequency modulation secure localization (FMSL)—for dynamic sensor networks is proposed with the support of FM signal and Monte Carlo method. The algorithm uses FM signals which are widely covered to locate randomly distributed nodes loaded with FM signal receiving module, filters some malicious attack anchors in the network, and uses the improved Monte Carlo algorithm to locate the nodes, so as to improve the positioning accuracy. Meanwhile, according to the moving path and the localization time, energy consumption of the network could be estimated and also give the sleep scheduling strategy for the node to be localized. The simulation results show that the FMSL algorithm can significantly improve the security performance and positioning accuracy of mobile sensor networks compared with the existing security positioning algorithms such as Monte Carlo and convex programming. In the process of motion, the positioning accuracy can reach less than 10%.
UAV-aided networks with optimization allocation via artificial bee colony with intellective search
Authors: Hu Bing , Sun Zhixin , Hong Hanshu , Liu Jian
Published: February 2020

In this paper, we consider a strong global search algorithm which exhibits strong exploration ability in unmanned aerial vehicle (UAV)-aided networks. UAVs in wireless communication have aroused great interest recently due to its low cost and flexibility in providing wireless connectivity in areas without infrastructure coverage. Artificial bee colony algorithm is a powerful approach for such a scene. However, due to its one-dimensional and greedy search strategy, it still suffers slow convergence speed. In the traditional version, three types of bees, including employed bees, onlooker bees, and scouts, are employed and they cooperate with each other to find the best food source position. Though different roles, these three types of bees play, there is no difference of division within the internal of each type of bees. Considering this phenomenon, this paper proposes a modified artificial bee colony algorithm with intellective search and special division (ABCIS) to enhance its performance, where different employed bees and different onlooker bees use different search strategies to search for food sources. Besides, the greedy selection method is also abandoned and the food sources’ positions are updated at each iteration. Under this circumstance, the whole population’s experience is fully utilized to guide bee’s search. Finally, to testify the proposed algorithms’ competitiveness, a series of benchmarks are adopted, and the experimental results demonstrate its superior performance among other state-of-the-art algorithm in UAV-aided networks.
Assessment of hand hygiene facilities and staff compliance in a large tertiary health care facility in northern Nigeria: a cross sectional study
Authors: Onyedibe Kenneth I. , Shehu Nathan Y. , Pires Daniela , Isa Samson E. , Okolo Mark O. , Gomerep Simji S. , Ibrahim Comfort , Igbanugo Sunday J. , Odesanya Rachel U. , Olayinka Adebola , Egah Daniel Z. , Pittet Didier
Published: February 2020

Background

The burden of healthcare-associated infection (HAI) is 2 to 18 times higher in developing countries. However, few data are available regarding infection prevention and control (IPC) process indicators in these countries. We evaluated hand hygiene (HH) facilities and compliance amongst healthcare workers (HCW) in a 600-bed healthcare facility in Northcentral Nigeria providing tertiary care service for a catchment population of about 20 million.

Methods

An in-house facility assessment tool and the World Health Organization (WHO) direct observation method were used to assess the HH facilities and compliance, respectively. Factors associated with good compliance were determined by multivariate analysis.

Results

The facility survey was carried out in all 46 clinical units of the hospital. 72% of the units had no poster or written policy on HH; 87% did not have alcohol-based hand rubs; 98% had at least one handwash sink; 28% had flowing tap water all day while 72% utilized cup and bucket; and 58% had no hand drying facilities. A total of 406 HH opportunities were observed among 175 HCWs. The overall compliance was 31%, ranging from 18% among ward attendants to 82% among medical students. Based on WHO “5 moments” for HH, average compliance was 21% before patient contact, 23% before aseptic procedure, 63% after body fluid exposure risk, 41% after patient contact and 40% after contact with patients’ surrounding. Being a medical student was independently associated with high HH compliance, adjusted odds ratio: 13.87 (1.70–112.88).

Conclusions

Availability of HH facilities and HCW compliance in a large tertiary hospital in Nigeria is poor. Our findings confirm that HCWs seem more sensitized to their risk of exposure to potential pathogens than to the prevention of HAI cross-transmission. Inadequate HH facilities probably contributed to the poor compliance. Specific measures such as improved facilities, training and monitoring are needed to improve HH compliance.
It's the fiber, not the fat: significant effects of dietary challenge on the gut microbiome
Authors: Morrison Kathleen E. , Jašarević Eldin , Howard Christopher D. , Bale Tracy L.
Published: February 2020

Background

Dietary effects on the gut microbiome play key roles in the pathophysiology of inflammatory disorders, metabolic syndrome, obesity, and behavioral dysregulation. Often overlooked in such studies is the consideration that experimental diets vary significantly in the proportion and source of their dietary fiber. Commonly, treatment comparisons are made between animals fed a purchased refined diet that lacks soluble fiber and animals fed a standard vivarium-provided chow diet that contains a rich source of soluble fiber. Despite the well-established critical role of soluble fiber as the source of short chain fatty acid production via the gut microbiome, the extent to which measured outcomes are driven by differences in dietary fiber is unclear. Further, the interaction between sex and age in response to dietary transition is likely important and should also be considered.

Results

We compared the impact of transitioning young adult and 1-year aged male and female mice from their standard chow diet to a refined low soluble fiber diet on gut microbiota community composition. Then, to determine the contribution of dietary fat, we also examined the impact of transitioning a subset of animals from refined low-fat to refined high-fat diet. We used a serial sampling strategy coupled with 16S rRNA marker gene sequencing to examine consequences of recurrent dietary switching on gut microbiota community dynamics. Analysis revealed that the transition from a chow diet to a refined diet that lacks soluble fiber accounted for most of the variance in community structure, diversity, and composition across all groups. This dietary transition was characterized by a loss of taxa within the phylum Bacteroidetes and expansion of Clostridia and Proteobacteria in a sex- and age-specific manner. Most notably, no changes to gut microbiota community structure and composition were observed between mice consuming either refined low- or high-fat diet, suggesting that transition to the refined diet that lacks soluble fiber is the primary driver of gut microbiota alterations, with limited additional impact of dietary fat on gut microbiota.

Conclusion

Collectively, our results show that the choice of control diet has a significant impact on outcomes and interpretation related to diet effects on gut microbiota. As the reduction of soluble fiber may influence synthesis of microbial metabolites that are important for regulating metabolic, immune, behavioral, and neurobiological outcomes, additional studies are now needed to fully delineate the contribution of fat and fiber on the gut microbiome.
Machine learning-aided analyses of thousands of draft genomes reveal specific features of activated sludge processes
Authors: Ye Lin , Mei Ran , Liu Wen-Tso , Ren Hongqiang , Zhang Xu-Xiang
Published: February 2020

Background

Microorganisms in activated sludge (AS) play key roles in the wastewater treatment processes. However, their ecological behaviors and differences from microorganisms in other environments have mainly been studied using the 16S rRNA gene that may not truly represent in situ functions.

Results

Here, we present 2045 archaeal and bacterial metagenome-assembled genomes (MAGs) recovered from 1.35 Tb of metagenomic data generated from 114 AS samples of 23 full-scale wastewater treatment plants (WWTPs). We found that the AS MAGs have obvious plant-specific features and that few proteins are shared by different WWTPs, especially for WWTPs located in geographically distant areas. Further, we developed a novel machine learning approach that can distinguish between AS MAGs and MAGs from other environments based on the clusters of orthologous groups of proteins with an accuracy of 96%. With the aid of machine learning, we also identified some functional features (e.g., functions related to aerobic metabolism, nutrient sensing/acquisition, and biofilm formation) that are likely vital for AS bacteria to adapt themselves in wastewater treatment bioreactors.

Conclusions

Our work reveals that, although the bacterial species in different municipal WWTPs could be different, they may have similar deterministic functional features that allow them to adapt to the AS systems. Also, we provide valuable genome resources and a novel approach for future investigation and better understanding of the microbiome of AS and other ecosystems.
Public reporting of IVF outcomes influences medical decision-making and physician training
Authors: Gunderson Stephanie , Jungheim Emily S. , Kallen Caleb B. , Omurtag Kenan
Published: February 2020

Background

Since 1992 ART clinics have been required to report outcome data. Our objective was to assess practitioners’ opinions of the impact of public reporting of assisted reproductive technology (ART) outcomes on treatment strategies, medical decision-making, and fellow training.

Methods

Survey study performed in an academic medical center. Members of the Society of Reproductive Endocrinology and Infertility and the Society of Reproductive Surgery were recruited to participate in an online survey in April 2012.: Categorical survey responses were expressed as percentages. Written responses were categorized according to common themes regarding effects of reporting on participants’ medical management of patients. The study was primarily qualitative and was not powered to make statistical conclusions.

Results

Of 1019 surveys sent, 323 participants (31.7%) responded from around the United States, and 275 provided complete data. Nearly all (273 of 282; 96.8%) participants responded that public reporting sometimes or always affected other providers’ practices, and 264 of 281 (93.9%) responded that other practitioners were motivated to deny care to poor-prognosis patients to improve reported success rates. However, only 121 of 282 (42.9%) indicated that public reporting influenced their own medical management. The majority of respondents agreed that public reporting may hinder adoption of single embryo transfer practices (194 of 299; 64.9%) and contribute to the persistent rate of twinning in in vitro fertilization (187 of 279; 67%). A small majority (153 of 279; 54.8%) felt that public reporting did not benefit fellow training, and 58 (61.7%) of the 94 participants who trained fellows believed that having fellows perform embryo transfers reduced pregnancy rates. A small majority (163 of 277; 58.8%) of respondents reported their ART success rates on clinical websites. However, the majority (200 of 275; 72.7%) of respondents compared their success rates with those of other clinics. Finally, most respondents (211 of 277; 76%) believed that most centers that advertised their success rates did so in ways that were misleading to patients.

Conclusions

Public reporting of ART clinical outcomes is intended to drive improvement, promote trust between patients and providers, and inform consumers and payers. However, providers reported that they modified their practices, felt others denied care to poor-prognosis patients, and limited participation of trainees in procedures in response to public reporting of ART outcomes.
Antivenin plants used for treatment of snakebites in Uganda: ethnobotanical reports and pharmacological evidences
Authors: Omara Timothy , Kagoya Sarah , Openy Abraham , Omute Tom , Ssebulime Stephen , Kiplagat Kibet Mohamed , Bongomin Ocident
Published: February 2020

Snakebite envenomation is a serious public health concern in rural areas of Uganda. Snakebites are poorly documented in Uganda because most occur in rural settings where traditional therapists end up being the first-line defense for treatment. Ethnobotanical surveys in Uganda have reported that some plants are used to antagonize the activity of various snake venoms. This review was sought to identify antivenin plants in Uganda and some pharmacological evidence supporting their use. A literature survey done in multidisciplinary databases revealed that 77 plant species belonging to 65 genera and 42 families are used for the treatment of snakebites in Uganda. The majority of these species belong to family Fabaceae (31%), Euphorbiaceae (14%), Asteraceae (12%), Amaryllidaceae (10%) and Solanaceae (10%). The main growth habit of the species is shrubs (41%), trees (33%) and herbs (18%). Antivenin extracts are usually prepared from roots (54%) and leaves (23%) through decoctions, infusions, powders, and juices, and are administered orally (67%) or applied topically (17%). The most frequently encountered species were Allium cepa, Carica papaya, Securidaca longipedunculata, Harrisonia abyssinica, and Nicotiana tabacum. Species with global reports of tested antivenom activity included Allium cepa, Allium sativum, Basella alba, Capparis tomentosa, Carica papaya, Cassia occidentalis, Jatropa carcus, Vernonia cinereal, Bidens pilosa, Hoslundia opposita, Maytensus senegalensis, Securinega virosa, and Solanum incanum. There is need to identify and evaluate the antivenom compounds in the claimed plants.
Lactobacillus pentosus S-PT84 and Rubus suavissimus leaf extract suppress lipopolysaccharide-induced gut permeability and egg allergen uptake
Authors: Kanouchi Hiroaki , Majumder Kaustav , Shibata Hiroshi , Mine Yoshinori
Published: February 2020

Increased gut permeability facilitates the uptake of food allergens into the bloodstream and triggers allergenic reactions. The present study aimed to evaluate the effect of Lactobacillus pentosus S-PT84 (S-PT84) and Rubus suavissimus leaf extract (RSLE) against egg ovomucoid (OVM)-uptake in lipopolysaccharide (LPS)-induced increased gut-permeability mice model of food allergy. Six-eight weeks old, female C57BL6 mice were continuously fed with LPS (300 μg/kg BW), for 3 months to increase gut permeability. Reduction in the expression of sealing claudin-4, increase in the expression of pore-forming claudin-2, and increase in D-mannitol absorption into the blood plasma in the LPS treated groups suggested the increase in gut permeability after LPS treatment. The oral administration of major egg allergen, OVM, after LPS intervention, significantly increased the plasma mast cell protease-1 and OVM-specific IgE compared to the negative control group. These results indicated that continuous LPS intervention developed OVM-induced food allergy. However, both the treatment of S-PT84 and RSLE suppressed the claudin-2 expression and the gut permeability induced by LPS. Furthermore, S-PT84 and RSLE treatment also reduced the plasma mast cell protease-1 and OVM-specific IgE, indicating the potential beneficial effect against LPS intervention developed OVM-induced food allergy. These findings suggest that S-PT84 and RSLE ameliorated LPS induced gut permeability and food allergic reactions.
Pulmonary bullet embolism following cardiac gunshot wound: case report of a bullet that traversed the heart twice
Authors: Bakir Delan Ahmed , Othman Yad N. , Taha Abdulsalam Y.
Published: February 2020

Background

Cardiac gunshot wounds with bullet embolism (BE) into the pulmonary artery are rare. Most pulmonary BE follow injuries of peripheral veins without concomitant cardiac injury. Herein, we describe a case of cardiac gunshot injury in which the bullet migrated from right atrium through the inferior vena cava down to right internal iliac vein and back to the left pulmonary artery. Such bullet migration is too rare and unusual and to our knowledge not reported before.

Case presentation

On March 4, 2019, a man of 39 had a bullet injury during celebratory gunfire. He was clinically stable with entrance on right posterior chest but no exit. Chest CT scan showed a bullet in the right atrium. The next day, the bullet migrated to the right pelvis as shown by plain chest and pelvic radiographs. CT angiography 3 weeks afterwards displayed the bullet in the right internal iliac vein. Meanwhile, the patient was asymptomatic, thus discharged home. However, 3 months later, he was readmitted because of chest pain, dyspnea, and sweating. A repeat chest CT scan showed the bullet in the left lower lobe pulmonary artery. Hence, pulmonary BE was suspected and eventually a 0.36 bullet was removed via left thoracotomy.

Conclusions

This is a case of symptomatic venous BE with typical diagnostic criteria (a small low-velocity bullet with inlet but no exit located away from anticipated trajectory with migration proven by serial radiographs). Endovascular removal was preferred but was not available. BE of the heart is exceedingly rare. Hence, diagnosis requires a high degree of clinical awareness.
L1–2 minimization for P- and S-impedance inversion
Authors: Nie Wenliang , Wen Xiaotao , Yang Jixin , He Jian , Lin Kai , Yang Longcheng
Published: February 2020

Amplitude variation with offset (AVO) inversion has been widely used in reservoir characterization to predict lithology and fluids. However, some existing AVO inversion methods that use [Formula: see text] norm regularization may not obtain the block boundary of subsurface layers because the AVO inversion is a severely ill-posed problem. To obtain sparse and accurate solutions, we have introduced the [Formula: see text] minimization method as an alternative to [Formula: see text] norm regularization. We used [Formula: see text] minimization for simultaneous P- and S-impedance inversion from prestack seismic data. We first derived the forward problem with multiangles and set up the inversion objective function with constraints of a priori low-frequency information obtained from well-log data. Then, we introduced minimization of the difference of [Formula: see text] and [Formula: see text] norms, denoted as [Formula: see text] minimization, to solve this objective function. The nonconvex penalty function of the [Formula: see text] minimization method is decomposed into two convex subproblems via the difference of convex algorithm, and each subproblem is solved by the alternating direction method of multipliers. Compared to [Formula: see text] norm regularization, the results indicate that [Formula: see text] minimization has superior performance over [Formula: see text] norm regularization in promoting blocky/sparse solutions. Tests on synthetic and field data indicate that our method can provide sparser and more accurate P- and S-impedance inversion results. The overall results confirm that our method has great potential in the detection and identification of fluids.
Quantitative analysis of facies variation using ground-based lidar and hyperspectral imaging in Mississippian limestone outcrop near Jane, Missouri
Authors: Shahtakhtinskiy Aydin , Khan Shuhab
Published: February 2020

Ground-based hyperspectral imaging is useful for geologic mapping because of its high spectral and spatial resolutions at a millimeter to centimeter scale. We have used hyperspectral and terrestrial laser scanner (TLS) data collected in close range to a roadcut near Jane, Missouri, that contains a subvertical outcrop of Lower Mississippian limestone. The outcrop consists of the Compton, Northview, and Pierson Formations, which we evaluated for facies heterogeneity. The sequence near Jane, Missouri, was deposited in shelf margin with high-frequency sea-level fluctuations. These fluctuations introduced lithologic and geometric heterogeneity to the facies, and debris flows brought in carbonate mounds referred to as outrunner blocks. These are important to interpret accurately because of their equivocal depositional origin, which is highly debated by previous workers. We combined hyperspectral data with TLS for an integrated spatial analysis of geometric and compositional variations in facies by accurate, point cloud-registered mineralogical mapping. We mapped several carbonate facies based on spectral signatures of calcite, silt, and clay particles and distinguished pure limestone outrunner blocks from surrounding mud-prone limestone facies with various proportions of silt and clay (a total of approximately 60%). By tracing the classified facies from combined hyperspectral and TLS imagery, we produced a lithostratigraphic framework, which indicates rapid changes in lithology and the presence of shale baffles that vary the character of the Compton through Pierson interval and contribute to heterogeneity in this outcrop. The data suggest a lower energy depositional environment and support the hypothesis of transported outrunner blocks in a distally steepened ramp system. The information that we have evaluated in our study could help to explain reservoir heterogeneity in equivalent carbonate fields.
Cognitive decline and mortality in a community-based sample of homeless and precariously housed adults: 9-year prospective study
Authors: Gicas Kristina M. , Jones Andrea A. , Thornton Allen E. , Petersson Anna , Livingston Emily , Waclawik Kristina , Panenka William J. , Barr Alasdair M. , Lang Donna J. , Vila-Rodriguez Fidel , Leonova Olga , Procyshyn Ric M. , Buchanan Tari , MacEwan G. William , Honer William G.
Published: February 2020

Background

Homeless and precariously housed individuals experience a high burden of comorbid illnesses, and excess mortality. Cross-sectional studies report a high rate of cognitive impairment. Long-term trajectories have not been well investigated in this group.

Aims

To longitudinally assess risks for premature and/or accelerated cognitive ageing, and the relationship with early mortality in homeless and precariously housed people.

Method

This is a 9-year community-based study of 375 homeless and precariously housed individuals from Vancouver, Canada. Annual cognitive testing assessed verbal learning and memory, and inhibitory control. Linear mixed-effects models examined associations between clinical risk factors (traumatic brain injury, psychotic disorders, viral exposure, alcohol dependence) and cognitive change over 9 years. Cox regression models examined the association between cognition and mortality.

Results

Traumatic brain injury and alcohol dependence were associated with decline in verbal memory. Inhibitory control declined, independent of risk factors and to a greater extent in those who died during the study. Better inhibitory control was associated with a 6.6% lower risk of mortality at study entry, with a 0.3% greater effect for each year of life. For each one-point increase in the Charlson Comorbidity Index score at study entry, the risk of mortality was 9.9% higher, and was consistent across age. Adjusting for comorbidities, inhibitory control remained a significant predictor of mortality.

Conclusions

Findings raise the possibility of a premature onset, and accelerated trajectory, of cognitive ageing in this group of homeless and precariously housed people. Traumatic brain injury, alcohol dependence and cognition could be treatment priorities.
Atypical Presentations and Management of Endocrine and Hepatic Immune-Related Adverse Events From Adjuvant Immune Checkpoint Inhibitor Therapy in Stage III Resected Melanoma
Authors: Kottschade Lisa A. , Yan Yiyi
Published: February 2020

Patients diagnosed with stage III melanoma who have undergone curative-intent surgery still remain at relatively high risk of disease recurrence. Recently approved adjuvant therapies with immune checkpoint inhibitors (ICIs) have brought increased relapse-free and overall survival rates. However, they have introduced a new range of side effects that can be difficult to diagnose, are challenging to treat, and may have lifelong consequences for patients. Oncologists and other members of the oncology care team should be aware of these side effects, including atypical presentations, and be prepared to intervene to prevent increased morbidity and mortality. Oncologists also need to have a low threshold for referral to other subspecialists, as many of these immune-related adverse events (irAEs) need to be comanaged using a multidisciplinary approach. Herein, we present a case that illustrates challenging presentations of endocrinopathy and hepatic irAEs in a patient with stage III melanoma receiving ICI therapy in the adjuvant setting.