bluuebunny/crossref_metadata_2025 huggingface dataset:
Hospital safety preparedness during the COVID-19 pandemic: Lessons learned from Vietnam
Authors: Thu Nguyen Thi Hoai , Anh Bui Thi My , Khanh Luong Bao , Anh Pham Tran , Luong Duong Huy
Published: October 2022

Introduction

The rapid spread of SARS-CoV-2, the varying vaccine coverage, and the appearance of new variants posed a significant threat during the pandemic, especially in LMIC countries. Hospitals in Vietnam at both central and local levels have had cross-infection of patients and healthcare workers. Therefore, providing a safe and secure environment for staff and patients was a major focus for all healthcare institutions.

Methods

We conducted a cross-sectional study, using both quantitative and qualitative methods, to answer the question of how hospital safety during the COVID-19 pandemic in Vietnamese hospitals was implemented and what the challenges were. Secondary data from a recent national survey of safety in 1,398 hospitals conducted by the Vietnam Ministry of Health (MOH) were extracted and analyzed. In-depth interviews of key health managers and health staff in four selected hospitals were performed to further explore challenges in implementing Decision 3088/QD-BYT.

Results

The proportion of hospitals classified as “safe hospital”, “safe hospital with moderate level”, and “unsafe hospital” was 91.7%, 7.3%, and 1.0%, respectively. The rate of “safe hospital” was highest in the central level hospitals (96.1%), followed by private hospitals (94.4%), provincial hospitals (94.2%), specialized hospitals (93.1%), regional hospitals (93.0%), and district hospitals (89.9%), while “safe hospital” rates were lowest in the ministerial level hospital group (82.2%). Challenges in ensuring hospital safety in public and private hospitals related to COVID-19 transmission, such as lack of preparedness before COVID-19 and other pandemics, limited hospital facility, limited space and equipment, shortage of human resources, inadequate training and knowledge transfer, poor patient compliance in declaring health conditions, and lack of patient understanding of infection prevention methods, were explored.

Conclusion

Most hospitals in Vietnam successfully met the classification of “safe hospitals” according to Decision 3088/QD-BYT, a key tool for hospitals to self-assess preparedness and responsiveness to the COVID-19 pandemic. The MOH should adapt the criteria in Decision 3088/QD-BYT to be more suitable for the new phase of the pandemic as we move towards “living with COVID”. Furthermore, we recommend that the MOH work to develop mechanisms or regulations that require hospitals to regularly report on disease preparation and responses for future pandemic preparedness.
Cataloguing environmental influences on the spatiotemporal variability of Adriatic anchovy early life stages in the eastern Adriatic Sea using an artificial neural network
Authors: Džoić Tomislav , Zorica Barbara , Matić Frano , Šestanović Marija , Čikeš Keč Vanja
Published: October 2022

The anchovy (Engraulis encrasicolus, Linnaeus, 1758), one of the most important small pelagic fish species in the Adriatic, is currently described as a species that can be considered overfished. From 2013 to 2020, samples of anchovy eggs and larvae were collected through scientific surveys during the summer months. The collected ichthyoplankton data were combined with environmental data (measured satellite sea surface temperature and chlorophyll data, numerically simulated salinity, maps of primary production) to identify anchovy spawning habitats and environmental conditions affecting the anchovy early life stages. For this large dataset, a nonlinear method called Growing Neural Gas Network analysis was used to explain the multiple dependencies between anchovy and the explanatory environmental variables and represent them in 9 patterns called Best Matching Unit (BMU). Obtained values of anchovy early life stages abundances (eggs/m2; larvae/m2) showed a clear negative trend, which was easily observed both in the time series and in the annual spatial distributions. Among all measured environmental parameters that were previously mentioned, salinity showed a significant increase, which can be attributed to the cyclonic phase of the bimodal oscillatory system of the Adriatic and Ionian Seas. The calculated BMUs showed several interesting results that shed new light on previous findings: (a) there is a split between the richer northern and poorer southern parts of the Adriatic in terms of anchovy eggs and larvae abundances, (b) the Kvarner Bay, the west coast of Istria and the area around Dugi otok are consistently rich spawning grounds, (c) decreased abundance in the southern areas is a result of the influence of salinity, (d) an increase in chlorophyll can lead to an increase in egg count, (e) the positive effects of upwelling can be negated by an increase in salinity, (f) increased primary production is followed by increased egg count. Upwelling, as one of the factors that can influence larval and egg abundance by bringing nutrients up from the seafloor, showed increased spatial and temporal variability during the investigated period, which depended on the wind regime. Our analysis showed that neural network analysis can successfully describe the effects and interplay of environmental factors on the abundance of anchovy early life stages.
Depression in patients with inflammatory bowel disease is associated with increased risk of dementia and Parkinson’s disease: A nationwide, population-based study
Authors: Choi Kookhwan , Lee Hyun Jung , Han Kyungdo , Koh Seong-Joon , Im Jong Pil , Kim Joo Sung
Published: October 2022

Background

Inflammatory bowel disease (IBD) may be associated with depression which is considered an important cause of dementia and Parkinson’s disease (PD). In the present study, the effects of depression on the development of dementia and/or PD in patients with IBD were evaluated.

Materials and methods

A nationwide population-based cohort study was conducted using claims data from the Health Insurance Review and Assessment Service in Korea. The incidence of dementia and PD were analyzed based on the presence of depression in patients with IBD.

Results

During a mean follow-up of 8 years, IBD patients with depression experienced dementia (6.7 vs. 2.0%; p < 0.001) and PD (1.1 vs. 0.3%; p < 0.001) significantly more than IBD patients without depression. Compared with IBD patients without depression, the risk of developing dementia was significantly higher in IBD patients with depression [adjusted hazard ratio (aHR) for IBD, Crohn’s disease (CD), and ulcerative colitis (UC), 2.03, p < 0.001; 1.68, p = 0.033; 2.13, p < 0.001, respectively]. Compared with IBD patients without depression, the risk of developing PD was significantly higher in IBD patients with depression (aHR for IBD, CD, and UC, 2.54, p < 0.001; 1.93, p = 0.470; 2.75, p < 0.001, respectively). The cumulative incidence of dementia and PD in IBD patients with depression was significantly higher than in IBD patients without depression and showed a steady increase after a diagnosis of depression.

Conclusion

The risk of dementia and/or PD increased after a diagnosis of depression in patients with IBD.
Isolation and structure of the fibril protein, a major component of the internal ribbon for Spiroplasma swimming
Authors: Sasajima Yuya , Kato Takayuki , Miyata Tomoko , Kawamoto Akihiro , Namba Keiichi , Miyata Makoto
Published: October 2022

Spiroplasma, which are known pathogens and commensals of arthropods and plants, are helical-shaped bacteria that lack a peptidoglycan layer. Spiroplasma swim by alternating between left- and right-handed helicity. Of note, this system is not related to flagellar motility, which is widespread in bacteria. A helical ribbon running along the inner side of the helical cell should be responsible for cell helicity and comprises the bacterial actin homolog, MreB, and a protein specific to Spiroplasma, fibril. Here, we isolated the ribbon and its major component, fibril filament, for electron microscopy (EM) analysis. Single-particle analysis of the fibril filaments using the negative-staining EM revealed a three-dimensional chain structure composed of rings with a size of 11 nm wide and 6 nm long, connected by a backbone cylinder with an 8.7 nm interval with a twist along the filament axis. This structure was verified through EM tomography of quick-freeze deep-etch replica sample, with a focus on its handedness. The handedness and pitch of the helix for the isolated ribbon and fibril filament agreed with those of the cell in the resting state. Structures corresponding to the alternative state were not identified. These results suggest that the helical cell structure is supported by fibril filaments; however, the helical switch is caused by the force generated by the MreB proteins. The isolation and structural outline of the fibril filaments provide crucial information for an in-depth clarification of the unique swimming mechanism of Spiroplasma.
Occurrence and distribution of Salmonella serovars in carcasses and foods in southern Italy: Eleven-year monitoring (2011–2021)
Authors: Peruzy Maria Francesca , Proroga Yolande Thérèse Rose , Capuano Federico , Mancusi Andrea , Montone Angela Michela Immacolata , Cristiano Daniela , Balestrieri Anna , Murru Nicoletta
Published: October 2022

Salmonella is one of the most common agents of foodborne illness. The genus Salmonella includes two species (Salmonella bongori and S. enterica) and six subspecies (enterica I, salamae II, arizonae IIIa, diarizonae IIIb, houtenae IV, and indica VI), each of which contains multiple serotypes associated with animal and human infections. The aim of the study was to evaluate the presence of Salmonella spp. in carcasses of food-producing animals and foods in southern Italy and the serovar distribution among different sources. From 2011 to 2021, a total of 12,246 foods and 982 samples from animal carcasses were collected and analyzed. The overall percentage of positive samples was 5.84% (N = 773) and a significant increase in prevalence was observed by comparing the years 2011–2015 (257, 3.27%) and 2016–2021 (516, 9.61%; p < 0.05). The highest percentage of positive food samples was observed in “Meat and Meat Products” (N = 327/2,438, 13.41%) followed by “Fish and fishery products” (N = 115/1,915, 6.01%). In carcasses, the highest percentage of positive samples was reported from broilers (N = 42/81, 51.85%) followed by buffalo (N = 50/101, 49.50%) and pork (N = 140/380, 36.84%). After typing, the isolates were assigned to the species S. enterica and to the subspecies: enterica (N = 760, 98.32%), diarizonae (N = 8, 1.03%), salamae (N = 3, 0.39%) and houtenae (N = 2, 0.26%). S. Infantis was the most frequently detected (N = 177, 24.76%), followed by S. Derby (N = 77, 10.77%), monophasic S. Typhimurium (N = 63, 8.81%), S. Typhimurium (N = 54, 7.55%), and S. Rissen (N = 47, 6.57%). By comparing the sampling period 2011–2015 with that of 2016–2021, an increase in the prevalence of S. Infantis and monophasic S. Typhimurium and a decrease of S. Typhimurium were recorded (p < 0.05). Thus, present data suggest that, despite the implementation of national and European control strategies to protect against Salmonella, the prevalence of this pathogen in southern Italy is still increasing and a change of national control programs to protect against Salmonella are necessary.
Genetic improvement of non-conventional Torulaspora delbrueckii for traditional sparkling winemaking by mixing for eventual hybridization with Saccharomyces cerevisiae
Authors: Martínez Alberto , Zamora Emiliano , Álvarez María L. , Bautista-Gallego Joaquín , Ramírez Manuel
Published: October 2022

Non-conventional yeasts such as Torulaspora delbrueckii (Td) have been proposed for sparkling winemaking. Unfortunately, this yeast has poor efficiency in completing wine fermentation as compared to Saccharomyces cerevisiae (Sc). New mutants with increased resistance to SO2, ethanol, and high CO2 pressure were previously isolated from spore clones of Td. Although these mutants showed improved capability for base wine fermentation, there is still room for genetic improvement of Td yeasts until the fermentative capacity of Sc is achieved. As an alternative approach, yeast mixture for eventual hybridization of Td with Sc was assayed in this study. The new yeast mixture clones (Sc-mixed Td) showed an intermediate phenotype between both parent yeasts for some relevant biotechnological properties, such as resistance to SO2, ethanol, copper, high CO2 pressure, and high temperature, as well as flocculation potential. These properties varied depending on the specific Sc-mixed Td clone. Several mixture clones showed improved capability for base wine fermentation as compared to the Td parent strain, approaching the fermentation capability of the Sc parent strain. The organoleptic quality of sparkling wine was also improved by using some mixture clones and this improved quality coincided with an increased amount of acetate and ethyl esters. The genetic stability of some Sc-mixed Td clones was good enough for commercial yeast production and winery applications.
Acceptor dependent catalytic properties of GH57 4-α-glucanotransferase from Pyrococcus sp. ST04
Authors: Jung Jong-Hyun , Hong Seungpyo , Jeon Eun Jung , Kim Min-Kyu , Seo Dong-Ho , Woo Eui-Jeon , Holden James F. , Park Cheon-Seok
Published: October 2022

The 4-α-glucanotransferase (4-α-GTase or amylomaltase) is an essential enzyme in maltodextrin metabolism. Generally, most bacterial 4-α-GTase is classified into glycoside hydrolase (GH) family 77. However, hyperthermophiles have unique 4-α-GTases belonging to GH family 57. These enzymes are the main amylolytic protein in hyperthermophiles, but their mode of action in maltooligosaccharide utilization is poorly understood. In the present study, we investigated the catalytic properties of 4-α-GTase from the hyperthermophile Pyrococcus sp. ST04 (PSGT) in the presence of maltooligosaccharides of various lengths. Unlike 4-α-GTases in GH family 77, GH family 57 PSGT produced maltotriose in the early stage of reaction and preferred maltose and maltotriose over glucose as the acceptor. The kinetic analysis showed that maltotriose had the lowest KM value, which increased amylose degradation activity by 18.3-fold. Structural models of PSGT based on molecular dynamic simulation revealed two aromatic amino acids interacting with the substrate at the +2 and +3 binding sites, and the mutational study demonstrated they play a critical role in maltotriose binding. These results clarify the mode of action in carbohydrate utilization and explain acceptor binding mechanism of GH57 family 4-α-GTases in hyperthermophilic archaea.
The evolving role of extracellular vesicles (exosomes) as biomarkers in traumatic brain injury: Clinical perspectives and therapeutic implications
Authors: Khan Naushad Ahmad , Asim Mohammad , El-Menyar Ayman , Biswas Kabir H. , Rizoli Sandro , Al-Thani Hassan
Published: October 2022

Developing effective disease-modifying therapies for neurodegenerative diseases (NDs) requires reliable diagnostic, disease activity, and progression indicators. While desirable, identifying biomarkers for NDs can be difficult because of the complex cytoarchitecture of the brain and the distinct cell subsets seen in different parts of the central nervous system (CNS). Extracellular vesicles (EVs) are heterogeneous, cell-derived, membrane-bound vesicles involved in the intercellular communication and transport of cell-specific cargos, such as proteins, Ribonucleic acid (RNA), and lipids. The types of EVs include exosomes, microvesicles, and apoptotic bodies based on their size and origin of biogenesis. A growing body of evidence suggests that intercellular communication mediated through EVs is responsible for disseminating important proteins implicated in the progression of traumatic brain injury (TBI) and other NDs. Some studies showed that TBI is a risk factor for different NDs. In terms of therapeutic potential, EVs outperform the alternative synthetic drug delivery methods because they can transverse the blood–brain barrier (BBB) without inducing immunogenicity, impacting neuroinflammation, immunological responses, and prolonged bio-distribution. Furthermore, EV production varies across different cell types and represents intracellular processes. Moreover, proteomic markers, which can represent a variety of pathological processes, such as cellular damage or neuroinflammation, have been frequently studied in neurotrauma research. However, proteomic blood-based biomarkers have short half-lives as they are easily susceptible to degradation. EV-based biomarkers for TBI may represent the complex genetic and neurometabolic abnormalities that occur post-TBI. These biomarkers are not caught by proteomics, less susceptible to degradation and hence more reflective of these modifications (cellular damage and neuroinflammation). In the current narrative and comprehensive review, we sought to discuss the contemporary knowledge and better understanding the EV-based research in TBI, and thus its applications in modern medicine. These applications include the utilization of circulating EVs as biomarkers for diagnosis, developments of EV-based therapies, and managing their associated challenges and opportunities.
Early-life maternal deprivation affects the mother-offspring relationship in domestic pigs, as well as the neuroendocrine development and coping behavior of piglets
Authors: Gimsa Ulrike , Brückmann Roberto , Tuchscherer Armin , Tuchscherer Margret , Kanitz Ellen
Published: October 2022

Early-life adversity may have programming effects on the psychological and physiological development of offspring. Domestic pigs (Sus scrofa) are an excellent model species for studying these effects because of their many physiological similarities to humans. Piglets from 10 sows were subjected to daily 2-h maternal deprivation on postnatal days (PND) 2–15 alone (DA) or in a group of littermates (DG). Control piglets (C) from 10 sows stayed with their mothers. Mother-offspring interaction, milk oxytocin, and cortisol were analyzed. An open-field/novel-object (OF/NO) test was performed with piglets on PNDs 16 and 40. Plasma cortisol and immune parameters were determined on PND 5 and 16. Two piglets from each group and sow were sacrificed on PND 20 and stress-related gene expression in the limbic system and prefrontal cortex (PFC), as well as splenic lymphocyte proliferative abilities, were examined. The milk cortisol of sows increased during the first separation of mother and offspring on the second day of lactation, whereas milk oxytocin did not change. The increase in cortisol by the OF/NO test on PND 16 was greater in C piglets than in DA and DG ones. DA piglets showed less agitated behavior than DG and C piglets in the OF/NO test at PND 16, but appeared more fearful. On PND 40, DA piglets showed more arousal than DG and C piglets in the OF/NO test. Neither plasma IgA nor N/L ratios in blood nor mitogen-induced proliferation of spleen lymphocytes were affected by deprivation. We found a higher mRNA expression of CRHR1 in the hypothalamus and a higher expression of MR in the hippocampus in DA piglets than in DG ones. The expression of GR, MR, and CRHR1 genes in the PFC was reduced by maternal deprivation, however, the expression of arginine vasopressin and oxytocin receptors was not affected. Repeated maternal deprivation induces sustained effects on stress reactivity and behavior of domestic piglets. Some of these effects were buffered by the presence of littermates. In addition, we found sex-specific differences in behavior and gene expression.
Venous stroke–a stroke subtype that should not be ignored
Authors: Zhou Yifan , Jiang Huimin , Wei Huimin , Liu Lu , Zhou Chen , Ji Xunming
Published: October 2022

Based on the etiology, stroke can be classified into ischemic or hemorrhagic subtypes, which ranks second among the leading causes of death. Stroke is caused not only by arterial thrombosis but also by cerebral venous thrombosis. Arterial stroke is currently the main subtype of stroke, and research on this type has gradually improved. Venous thrombosis, the particular type, accounts for 0.5–1% of all strokes. Due to the lack of a full understanding of venous thrombosis, as well as its diverse clinical manifestations and neuroimaging features, there are often delays in admission for it, and it is easy to misdiagnose. The purpose of this study was to review the pathophysiology mechanisms and clinical features of arterial and venous thrombosis and to provide guidance for further research on the pathophysiological mechanism, clinical diagnosis, and treatment of venous thrombosis. This review summarizes the pathophysiological mechanisms, etiology, epidemiology, symptomatology, diagnosis, and treatment heterogeneity of venous thrombosis and compares it with arterial stroke. The aim is to provide a reference for a comprehensive understanding of venous thrombosis and a scientific understanding of various pathophysiological mechanisms and clinical features related to venous thrombosis, which will contribute to understanding the pathogenesis of intravenous stroke and provide insight into diagnosis, treatment, and prevention.
Upper limb joint coordination preserves hand kinematics after a traumatic brachial plexus injury
Authors: Lustosa Luiggi , Silva Ana Elisa Lemos , Carvalho Raquel de Paula , Vargas Claudia D.
Published: October 2022

Background

Traumatic brachial plexus injury (TBPI) causes a sensorimotor deficit in upper limb (UL) movements.

Objective

Our aim was to investigate the arm–forearm coordination of both the injured and uninjured UL of TBPI subjects.

Methods

TBPI participants (n = 13) and controls (n = 10) matched in age, gender, and anthropometric characteristics were recruited. Kinematics from the shoulder, elbow, wrist, and index finger markers were collected, while upstanding participants transported a cup to their mouth and returned the UL to a starting position. The UL coordination was measured through the relative phase (RP) between arm and forearm phase angles and analyzed as a function of the hand kinematics.

Results

For all participants, the hand transport had a shorter time to peak velocity (p < 0.01) compared to the return. Also, for the control and the uninjured TBPI UL, the RP showed a coordination pattern that favored forearm movements in the peak velocity of the transport phase (p < 0.001). TBPI participants' injured UL showed a longer movement duration in comparison to controls (p < 0.05), but no differences in peak velocity, time to peak velocity, and trajectory length, indicating preserved hand kinematics. The RP of the injured UL revealed altered coordination in favor of arm movements compared to controls and the uninjured UL (p < 0.001). Finally, TBPI participants' uninjured UL showed altered control of arm and forearm phase angles during the deceleration of hand movements compared to controls (p < 0.05).

Conclusion

These results suggest that UL coordination is reorganized after a TBPI so as to preserve hand kinematics.
Ophthalmologic problems correlates with cognitive impairment in patients with Parkinson's disease
Authors: Zhang Chao , Wu Qian-qian , Hou Ying , Wang Qi , Zhang Guang-jian , Zhao Wen-bo , Wang Xu , Wang Hong , Li Wei-guo
Published: October 2022

Objective

Visual impairment is a common non-motor symptom (NMS) in patients with Parkinson's disease (PD) and its implications for cognitive impairment remain controversial. We wished to survey the prevalence of visual impairment in Chinese Parkinson's patients based on the Visual Impairment in Parkinson's Disease Questionnaire (VIPD-Q), identify the pathogens that lead to visual impairment, and develop a predictive model for cognitive impairment risk in Parkinson's based on ophthalmic parameters.

Methods

A total of 205 patients with Parkinson's disease and 200 age-matched controls completed the VIPD-Q and underwent neuro-ophthalmologic examinations, including ocular fundus photography and optical coherence tomography. We conducted nomogram analysis and the predictive model was summarized using the multivariate logistic and LASSO regression and verified via bootstrap validation.

Results

One or more ophthalmologic symptoms were present in 57% of patients with Parkinson's disease, compared with 14% of the controls (χ2-test; p < 0.001). The visual impairment questionnaire showed good sensitivity and specificity (area under the curve [AUC] = 0.918, p < 0.001) and a strong correlation with MoCA scores (Pearson r = −0.4652, p < 0.001). Comparing visual impairment scores between pre- and post-deep brain stimulation groups showed that DBS improved visual function (U-test, p < 0.001). The thickness of the retinal nerve fiber layer and vessel percentage area predicted cognitive impairment in PD.

Interpretation

The study findings provide novel mechanistic insights into visual impairment and cognitive decline in Parkinson's disease. The results inform an effective tool for predicting cognitive deterioration in Parkinson's based on ophthalmic parameters.
Changes in intermuscular connectivity during active elbow extension reveal a functional simplification of motor control after stroke
Authors: Delcamp Célia , Cormier Camille , Chalard Alexandre , Amarantini David , Gasq David
Published: October 2022

Background

Stroke alters muscle co-activation and notably leads to exaggerated antagonist co-contraction responsible for impaired motor function. However, the mechanisms underlying this exaggerated antagonist co-contraction remain unclear. To fill this gap, the analysis of oscillatory synchronicity in electromyographic signals from synergistic muscles, also called intermuscular coherence, was a relevant tool.

Objective

This study compares functional intermuscular connectivity between muscle pairs of the paretic and non-paretic upper limbs of stroke subjects and the dominant limb of control subjects, concomitantly between two muscle pairs with a different functional role, through an intermuscular coherence analysis.

Methods

Twenty-four chronic stroke subjects and twenty-four healthy control subjects were included. Subjects performed twenty elbow extensions while kinematic data and electromyographic activity of both flexor and extensor elbow muscles were recorded. Intermuscular coherence was analyzed in the beta frequency band compared to the assessment of antagonist co-contraction.

Results

Intermuscular coherence was higher in the stroke subjects’ paretic limbs compared to control subjects. For stroke subjects, the intermuscular coherence of the antagonist-antagonist muscle pair (biceps brachii—brachioradialis) was higher than that of the agonist-antagonist muscle pair (triceps brachii—brachioradialis). For the paretic limb, intermuscular coherence of the antagonist-antagonist muscle pair presented a negative relationship with antagonist co-contraction.

Conclusion

Differences in intermuscular coherence between the paretic limbs of stroke subjects and control subjects suggest a higher common central drive during movement. Furthermore, results highlight the association between stroke-related alteration of intermuscular functional connectivity and the alteration of motor function.
Long non-coding RNAs: Potential therapeutic targets for epilepsy
Authors: Liu Sen , Fan Min , Ma Meng-Die , Ge Jin-Fang , Chen Fei-Hu
Published: October 2022

Epilepsy is a common and disastrous neurological disorder characterized by abnormal firing of neurons in the brain, affecting about 70 million people worldwide. Long non-coding RNAs (LncRNAs) are a class of RNAs longer than 200 nucleotides without the capacity of protein coding, but they participate in a wide variety of pathophysiological processes. Alternated abundance and diversity of LncRNAs have been found in epilepsy patients and animal or cell models, suggesting a potential role of LncRNAs in epileptogenesis. This review will introduce the structure and function of LncRNAs, summarize the role of LncRNAs in the pathogenesis of epilepsy, especially its linkage with neuroinflammation, apoptosis, and transmitter balance, which will throw light on the molecular mechanism of epileptogenesis, and accelerate the clinical implementation of LncRNAs as a potential therapeutic target for treatment of epilepsy.
Neuronal toll like receptor 9 contributes to complete Freund’s adjuvant-induced inflammatory pain in mice
Authors: Chen Yu , Chen Hui , Li Xiao-Chen , Mi Wen-Li , Chu Yu-Xia , Wang Yan-Qing , Mao-Ying Qi-Liang
Published: October 2022

Toll like receptor 9 (TLR9) is a critical sensor for danger-associated molecular patterns (DAMPs) and a crucial marker of non-sterile/sterile inflammation among all TLRs. However, the significance of TLR9 in inflammatory pain remains unclear. Here, we subcutaneously injected Complete Freund’s adjuvant (CFA) into the plantar surface of the hind paw, to established a mouse model of inflammatory pain, and we examined expression and distribution of TLR9 in this model. There was a significant increase of TLR9 mRNA and reduction of mechanical paw withdrawal threshold in mice intraplantar injected with CFA. By contrast, mechanical paw withdrawal threshold significantly increased in mice treated with TLR9 antagonist ODN2088. Furthermore, TLR9 is found predominantly distributed in the neurons by immunofluorescence experiment. Accordingly, neuronal TLR9 downregulation in the spinal cord prevented CFA-induced persistent hyperalgesia. Overall, these findings indicate that neuronal TLR9 in the spinal cord is closely related to CFA-induced inflammatory pain. It provides a potential treatment option for CFA-induced inflammatory pain by applying TLR9 antagonist.
A rigorous in silico genomic interrogation at 1p13.3 reveals 16 autosomal dominant candidate genes in syndromic neurodevelopmental disorders
Authors: Ben-Mahmoud Afif , Jun Kyung Ran , Gupta Vijay , Shastri Pinang , de la Fuente Alberto , Park Yongsoo , Shin Kyung Chul , Kim Chong Ae , da Cruz Aparecido Divino , Pinto Irene Plaza , Minasi Lysa Bernardes , Silva da Cruz Alex , Faivre Laurence , Callier Patrick , Racine Caroline , Layman Lawrence C. , Kong Il-Keun , Kim Cheol-Hee , Kim Woo-Yang , Kim Hyung-Goo
Published: October 2022

Genome-wide chromosomal microarray is extensively used to detect copy number variations (CNVs), which can diagnose microdeletion and microduplication syndromes. These small unbalanced chromosomal structural rearrangements ranging from 1 kb to 10 Mb comprise up to 15% of human mutations leading to monogenic or contiguous genomic disorders. Albeit rare, CNVs at 1p13.3 cause a variety of neurodevelopmental disorders (NDDs) including development delay (DD), intellectual disability (ID), autism, epilepsy, and craniofacial anomalies (CFA). Most of the 1p13.3 CNV cases reported in the pre-microarray era encompassed a large number of genes and lacked the demarcating genomic coordinates, hampering the discovery of positional candidate genes within the boundaries. In this study, we present four subjects with 1p13.3 microdeletions displaying DD, ID, autism, epilepsy, and CFA. In silico comparative genomic mapping with three previously reported subjects with CNVs and 22 unreported DECIPHER CNV cases has resulted in the identification of four different sub-genomic loci harboring five positional candidate genes for DD, ID, and CFA at 1p13.3. Most of these genes have pathogenic variants reported, and their interacting genes are involved in NDDs. RT-qPCR in various human tissues revealed a high expression pattern in the brain and fetal brain, supporting their functional roles in NDDs. Interrogation of variant databases and interacting protein partners led to the identification of another set of 11 potential candidate genes, which might have been dysregulated by the position effect of these CNVs at 1p13.3. Our studies define 1p13.3 as a genomic region harboring 16 NDD candidate genes and underscore the critical roles of small CNVs in in silico comparative genomic mapping for disease gene discovery. Our candidate genes will help accelerate the isolation of pathogenic heterozygous variants from exome/genome sequencing (ES/GS) databases.
Microencapsulated curcumin from Curcuma longa modulates diet-induced hypercholesterolemia in Sprague Dawley rats
Authors: Ashraf Humaira , Butt Masood Sadiq , Iahtisham-Ul-Haq  , Nadeem Muhammad , Aadil Rana Muhammad , Rusu Alexandru Vasile , Trif Monica
Published: October 2022

Hypercholesterolemia is one of the major causes of cardiovascular ailments. The study has been conducted on the hypothesis that hypercholesterolemia can be modulated by microencapsulated curcumin due to its enhanced bioavailability. In this context, curcumin obtained from fresh rhizomes of Curcuma longa by conventional (CSE) and supercritical fluid (SFE) extractions, has been successfully microencapsulated using a mixture of gelatin and maltodextrin. The microencapsulated curcumin CSE&SFE, has been added as supplemented diet and has been resulted in maximum plasma concentration of curcumin at 100 min as 529.31 ± 8.73 and 405.23 ± 7.12 μg/mL, respectively compared to non-encapsulated turmeric powder used as control. During the bio evaluation trial, turmeric powder (3%), microencapsulated curcuminCSE (1%) and microencapsulated curcuminSFE (0.5%) were provided to designate rat groups categorized by normal; N1, N2, and N3 and hypercholesterolemic; H1, H2, and H3 conditions, respectively. The incorporation of microencapsulated curcuminSFE in the supplemented diet caused a reduction in serum cholesterol, low density lipoprotein (LDL) and triglycerides, athrogenic index (AI) and cardiac risk ration (CRR) as 5.42 and 12.81%, 7.25 and 15.42%, 3.17 and 9.38%, 15.38 and 29.28%, and 10.98 19.38% in normo- and hypercholesterolemic rat groups. Additionally, high-density lipoprotein (HDL) and anti-atherogenic index (AAI) indicated a significant increase in all treated rat groups. Conclusively, the inclusion of turmeric and curcumin microencapsulates in the dietary module has been proven effective to alleviate hyperlipidemia. Therefore, the present study is proven that curcumin absorption via the gastrointestinal tract and its stability toward metabolization in the body increased via microencapsulation using maltodextrin and gelatin. Microencapsulated curcumin reaches the target site via oral administration because of sufficient gastrointestinal residence period and stability in the digestive tract.
Effects of lotus seedpod oligomeric procyanidins on the inhibition of AGEs formation and sensory quality of tough biscuits
Authors: Chen Ziting , Tan Jiangying , Qin Jiabin , Feng Nianjie , Liu Qianting , Zhang Chan , Wu Qian
Published: October 2022

The advanced glycation end products (AGEs) are formed in baked products through the Maillard reaction (MR), which are thought to be a contributing factor to chronic diseases such as heart diseases and diabetes. Lotus seedpod oligomeric procyanidins (LSOPC) are natural antioxidants that have been added to tough biscuit to create functional foods that may lower the risk of chronic diseases. The effect of LSOPC on AGEs formation and the sensory quality of tough biscuit were examined in this study. With the addition of LSOPC, the AGEs scavenging rate and antioxidant capacity of LSOPC-added tough biscuits were dramatically improved. The chromatic aberration (ΔE) value of tough biscuits containing LSOPC increased significantly. Higher addition of LSOPC, on the other hand, could effectively substantially reduced the moisture content, water activity, and pH of LSOPC toughen biscuits. These findings imply that using LSOPC as additive not only lowers the generation of AGEs, but also improves sensory quality of tough biscuit.
Quercetin improves lacrimal gland function through its anti-oxidant actions: Evidence from animal studies, and a pilot study in healthy human volunteers
Authors: Inaba Takaaki , Ohnishi-Kameyama Mayumi , Liu Ying , Tanaka Yasuhisa , Kobori Masuko , Tamaki Shusaku , Ito Tomotaka , Higa Kazunari , Shimazaki Jun , Tsubota Kazuo
Published: October 2022

Anti-oxidant properties of polyphenols have been gaining medical attention as a preventive factor against aging and/or lifestyle diseases. In this study, we examined the anti-oxidant activity of quercetin improved tear function through its effects on the lacrimal gland in mice and humans. Six week-old diabetic mice, a model for decreased tear production, were fed for 12 weeks ad libitum with an experimental diet containing 0.5% quercetin. As a result, the tear volume was significantly improved compared to the control, despite no changes in body weight, food intake, lacrimal gland morphology or biochemical serum parameters. Moreover, significantly higher SOD-1 and SOD-2 protein levels were detected in the lacrimal glands of quercetin-treated mice by western blot. In addition, quercetin treatment of mouse corneal cell lines exposed to oxidative stress resulted in dose-dependent inhibition of ROS production and enhanced cell survival. Finally, we examined quercetin pharmacokinetics, specifically its presence in serum and tears subsequent to onion consumption in healthy volunteers, and found that the distribution of quercetin and its metabolite shifted from serum to tear following onion intake. An improvement in tear film stability also resulted following the intake by these healthy volunteers of a new, quercetin-rich onion cultivar (”Quergold”) in powder form. These results suggested that quercetin improved tear function through its effects on the lacrimal gland in mice and humans.
The impact of diet and lifestyle on wellbeing in adults during COVID-19 lockdown
Authors: Muth Anne-Katrin , Losecaat Vermeer Annabel , Terenzi Damiano , Park Soyoung Q.
Published: October 2022

A healthy diet and lifestyle may protect against adverse mental health outcomes, which is especially crucial during stressful times, such as the COVID-19 pandemic. This preregistered longitudinal online study explored whether diet and lifestyle (physical activity, sleep, and social interactions) were associated with wellbeing and mood during a light lockdown in Germany. Participants (N = 117, 72 males; 28 ± 9 years old) answered mental health and lifestyle questionnaires (social connections, sleep, activity) followed by submitting 1 week of food and mood-lifestyle diary (food intake, positive and negative mood, mental wellbeing, sleep quality, physical activity level, quantity and quality of social interactions) via a smartphone app. We used multivariate linear and mixed-effects models to associate mood and wellbeing with dietary components and lifestyle factors. Interindividual analyses revealed that sleep and social interaction significantly impacted mood and wellbeing. Interestingly, fruit and vegetable intake correlated with wellbeing, even when controlling for all lifestyle factors. Fruit and vegetable intake also significantly correlated with daily fluctuations in wellbeing within individuals next to sleep, physical activity, and social interactions. We observed gender differences in fruit and vegetable intake and anxiety levels. Our results emphasize the importance of diet contributing to individual wellbeing, even in the challenging times of a pandemic. Future research is necessary to test if our findings could extend to other populations.
Clinical significance of polyunsaturated fatty acids in the prevention of cardiovascular diseases
Authors: Kotlyarov Stanislav , Kotlyarova Anna
Published: October 2022

Cardiovascular diseases are one of the most important problems of modern medicine. They are associated with a large number of health care visits, hospitalizations and mortality. Prevention of atherosclerosis is one of the most effective strategies and should start as early as possible. Correction of lipid metabolism disorders is associated with definite clinical successes, both in primary prevention and in the prevention of complications of many cardiovascular diseases. A growing body of evidence suggests a multifaceted role for polyunsaturated fatty acids. They demonstrate a variety of functions in inflammation, both participating directly in a number of cellular processes and acting as a precursor for subsequent biosynthesis of lipid mediators. Extensive clinical data also support the importance of polyunsaturated fatty acids, but all questions have not been answered to date, indicating the need for further research.
Novel serum proteomic biomarkers for early diagnosis and aggressive grade identification of prostate cancer
Authors: Wang Ce , Liu Guangming , Liu Yehua , Yang Zhanpo , Xin Weiwei , Wang Meng , Li Yang , Yang Lan , Mu Hong , Zhou Chunlei
Published: October 2022

Background

Prostate cancer (PCa) is one of the most common tumors and the second leading cause of cancer-related death in men. The discovery of novel biomarkers for PCa diagnosis in the early stage, as well as discriminating aggressive PCa from non-aggressive PCa continue to pose a challenge. The aim of this study was to identify serum proteins that were sensitive and specific enough to detect early-stage and aggressive PCa.

Methods

The serum proteomic profiling of patients with PCa and benign prostatic hyperplasia (BPH) was comprehensively analyzed using data-independent acquisition mass spectrometry (DIA-MS), and the bioinformatics analysis was performed. The differentially expressed proteins (DEPs) of interest were further verified by enzyme-linked immunosorbent assay (ELISA) and immunoturbidimetry assay.

Results

Statistically significant difference in abundance showed 56 DEPs between early-stage PCa and BPH and 47 DEPs between aggressive and non-aggressive PCa patients. In addition, the verification results showed that serum L-selectin concentration was significantly higher (p<0.05) in Gleason 6 PCa when compared with BPH, and the concentration of osteopontin (SPP1) and ceruloplasmin (CP) increased with higher Gleason score.

Conclusions

DIA-MS has great potential in cancer-related biomarker screening. Our data demonstrated that adding SPP1 and CP to PSA improved the separation of Gleason 7 (4 + 3) or above from Gleason 7 (3 + 4) or below compared with PSA diagnosis alone. Serum SPP1 and CP could be effective biomarkers to differentiate aggressive PCa (especially Gleason 7 (4 + 3) or above) from non-aggressive disease.
Serum lactate is associated with increased illness severity in immunocompromised pediatric hematology oncology patients presenting to the emergency department with fever
Authors: Slatnick Leonora Rose , Miller Kristen , Scott Halden F. , Loi Michele , Esbenshade Adam J. , Franklin Anna , Lee-Sherick Alisa B.
Published: October 2022

Introduction

Determining which febrile pediatric hematology/oncology (PHO) patients will decompensate from severe infection is a significant challenge. Serum lactate is a well-established marker of illness severity in general adult and pediatric populations, however its utility in PHO patients is unclear given that chemotherapy, organ dysfunction, and cancer itself can alter lactate metabolism. In this retrospective analysis, we studied the association of initial serum lactate in febrile immunosuppressed PHO patients with illness severity, defined by the incidence of clinical deterioration events (CDE) and invasive bacterial infection (IBI) within 48 hours.

Methods

Receiver operating characteristic (ROC) curves were reported using initial lactate within two hours of arrival as the sole predictor for CDE and IBI within 48 hours. Using a generalized estimating equations (GEE) approach, the association of lactate with CDE and IBI within 48 hours was tested in univariate and multivariable analyses including covariates based on Quasi-likelihood under Independence Model Criterion (QIC). Additionally, the association of lactate with secondary outcomes (i.e., hospital length of stay (LOS), intensive care unit (PICU) admission, PICU LOS, non-invasive infection) was assessed.

Results

Among 897 encounters, 48 encounters had ≥1 CDE (5%), and 96 had ≥1 IBI (11%) within 48 hours. Elevated lactate was associated with increased CDE in univariate (OR 1.77, 95%CI: 1.48-2.12, p<0.001) and multivariable (OR 1.82, 95%CI: 1.43-2.32, p<0.001) analyses, longer hospitalization (OR 1.15, 95%CI: 1.07-1.24, p<0.001), increased PICU admission (OR 1.68, 95%CI: 1.41-2.0, p<0.001), and longer PICU LOS (OR 1.21, 95%CI: 1.04-1.4, p=0.01). Elevated lactate was associated with increased IBI in univariate (OR 1.40, 95%CI: 1.16-1.69, p<0.001) and multivariable (OR 1.49, 95%CI: 1.23-1.79, p<0.001) analyses. Lactate level was not significantly associated with increased odds of non-invasive infection (p=0.09). The QIC of the model was superior with lactate included for both CDE (305 vs. 325) and IBI (563 vs. 579).

Conclusions

These data demonstrated an independent association of elevated initial lactate level and increased illness severity in febrile PHO patients, suggesting that serum lactate could be incorporated into future risk stratification strategies for this population.
Impact of the COVID-19 pandemic on the regular follow-up and outcomes of patients with chronic myeloid leukemia in chronic-phase
Authors: Yılmaz Umut , Küçükyurt Selin , Tunç Sertaç , Eşkazan Ahmet Emre
Published: October 2022

Introduction

COVID-19 immediately became a major consideration in the management of chronic myeloid leukemia (CML). The influence of such considerations on viral transmission rates and leukemic control remain to be explored. We conducted this study to identify these alterations and to investigate their clinical consequences.

Methods

This was a cross-sectional study, performed at a single institution on CML patients who were interviewed with a survey. We compared variables concerning new attitudes in the pandemic era between the 12-month periods before and after the pandemic onset. Outcome data were attained from the hospital archives.

Findings

The number of patients receiving regular outpatient care for CML in chronic phase was 210, 91% had achieved at least major molecular responses. We assessed survival, progression, number of clinical visits of all, performed the survey on 89% and evaluated molecular responses on 86.6% of these patients. The frequency of clinical and molecular monitoring was significantly reduced during the pandemic deviating significantly from the guidelines. Frequency of death, progression, loss of molecular response was not significantly increased during the pandemic era despite a few cases where the delay in assessment possibly played a role in the unfavorable outcomes. There were no COVID related deaths or disabilities.

Conclusion

The case-based untoward events would have probably been better managed with a more efficient communication web between patients, hematologists, and the laboratory. Therefore, it seems reasonable to consider whether such communicative paths are functional before giving up on the set schedule of CML management at times of uncertainty.