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[EN] Due to electrical features of the tissue, such as impedance, which have a significant impact on irreversible electroporation (IRE) function, the administration of glucose solution 5% (GS5%) through the hepatic artery would focus IRE on scattered liver tumors. By creating a differential impedance between healthy and tumor tissue. This study aimed to determine the effects of the GS5% protocol on healthy liver tissue and its safety. 21 male Athymic nude rats Hsd: RH-Foxn1mu were used in the study. Animals were split into two groups. In group 1, a continuous infusion through the gastroduodenal artery of GS5% was performed to measure the impedance with a dose of 0.008 mL/g for 16 min. In group 2, the animals were divided into two subgroups for infusions of GS5%. Group 2.1, at 0.008 mL/g for 16 min. Group 2.2 at 0.03 mL/g for 4 min. Blood samples were collected after anesthesia has been induced. The second sample, after catheterization of the artery, and the third after the GS5% infusion. All the animals were sacrificed to collect histological samples. The survival rate during the experiment was 100%. A considerable impact on the impedance of the tissue was noticed, on average up to 4.31 times more than the baseline, and no side effects were observed after GS5% infusion. In conclusion, impedance alteration by Glucose solution infusion may focus IRE on tumor tissue and decrease IRE¿s effects on healthy tissue., This research was supported by the Spanish government (Ministry of Economy and Competitiveness) under Grants RTI2018-094357-B-C21, RTI2018-094357-B-C22 and Carlos III Health Institute under Grant PI17/0048 and also PI21/00440 from the same institution.

Pulmonary tuberculosis (PTB) and diabetes mellitus (DM) remain high morbidity and mortality, especially when they are comorbid with each other. Screening for diabetes mellitus in tuberculosis is essential as the incidence and mortality of DM in the population with PTB are higher than in the general people. We aimed to examine the gradient association of tuberculosis on developing DM, the additional yield and the number needed to screen (NNS) to find a new diabetes case. A cross-sectional study was conducted on 801 tuberculosis cases and 972 household contacts in Guizhou, China, from April 2019 to October 2020. After screening for PTB among contacts, all participants were screened for DM and interviewed. Kendall’s tau-b test and proportional odds logistic regression analysis were applied to identify the gradient associations. Among the 1773 subjects, the additional yield of screening was 21.8%. The NNSs of the non-PTB group, the sputum-culture negative and positive groups were 50, 60 and 113, respectively. The gradient incremental establishment of DM and PTB were positively correlated. The general trend on the gradient of DM significantly increased with the gradient increase of PTB. Age 35 years and over, excessive edible oil intake and DM family history were identified as significant predictors of diabetes. Integrated screening for DM targeted to different gradients of PTB combined with associated factors is necessitated to achieve a higher additional yield.

Diabetes is a serious metabolic disorder with high rate of prevalence worldwide; the disease has the characteristics of improper secretion of insulin in pancreas that results in high glucose level in blood. The disease is also associated with other complications such as cardiovascular disease, retinopathy, neuropathy and nephropathy. The development of computer aided decision support system is inevitable field of research for disease diagnosis that will assist clinicians for the early prognosis of diabetes and to facilitate necessary treatment at the earliest. In this research study, a Traditional Chinese Medicine based diabetes diagnosis is presented based on analyzing the extracted features of panoramic tongue images such as color, texture, shape, tooth markings and fur. The feature extraction is done by Convolutional Neural Network (CNN)—ResNet 50 architecture, and the classification is performed by the proposed Deep Radial Basis Function Neural Network (RBFNN) algorithm based on auto encoder learning mechanism. The proposed model is simulated in MATLAB environment and evaluated with performance metrics—accuracy, precision, sensitivity, specificity, F1 score, error rate, and receiver operating characteristics (ROC). On comparing with existing models, the proposed CNN based Deep RBFNN machine learning classifier model outperformed with better classification performance and proving its effectiveness.

One of the most cost-effective strategies for fighting the spread of COVID-19 is the use of facial masks. Despite health officials’ strong efforts to communicate the importance or wearing a mask, compliance has been low in many countries. In the present paper we propose a novel behavior-intervention strategy to encourage people to wear facial masks. Three studies show that the personalization of a mask, as a form of identity expression, increases mask wearing intentions and, by extension, the percentage of individuals who wear facial masks. Given that mask wearing remains a necessity after deployment of the first vaccines, novel approaches to encouraging mask wearing are essential. Linking facial mask wearing to an individual’s identity is a promising strategy.

The similarities between horizontal and vertical Optical Coherence Tomography (OCT) scans for the individual retinal layer thickness measurements in the macula was evaluated. Two volumetric scans (B-scans oriented horizontally and vertically) were performed in 64 multiple sclerosis subjects with history of unilateral optic neuritis and 64 healthy controls. The agreement between the thickness measurements with horizontal and vertical OCT scans was evaluated in 3 groups of eyes: healthy controls, eyes with history of optic neuritis and the fellow eyes. The mean difference in individual layer thickness between the scans was smaller than the instrument’s axial resolution in all 3 groups. The limit of agreement (LoA) varied among the different layers and sectors analyzed and this trend was similar in all the groups. For the inner retinal layers (retinal nerve fiber layer to inner nuclear layer), the inner macular sectors had a larger LoA compared to the corresponding outer sectors. In the outer plexiform and nuclear layers, the central and inner sectors (except inner temporal) had LoA larger than the other sectors and layers. The larger LoA seen for different layers and sectors suggests that the scan direction must be same for the follow-up OCT measurements and in clinical studies.

Globally, malaria is the major public health disease caused by plasmodium species and transmitted by the bite of the female anopheles mosquito. Assessment of the trend of malaria prevalence is important in the control and prevention of the disease. Therefore, the objective of this study was to assess the six year trend of malaria prevalence at the University of Gondar Comprehensive Specialized Hospital, northwest Ethiopia, from 2014 to 2019. A retrospective laboratory registration logbook review study was conducted on the malaria blood film examination results at the University of Gondar Comprehensive Specialized Hospital. The data was collected by using a data extraction tool and entered into SPSS version 20 for analysis. Descriptive statistics were used to summarize the socio-demographic characteristics of study participants and presented by graphs, tables and texts. The binary logistic regression was also used to test the association the trend of malaria prevalence and different factors like sex, age, year, and season. From a total of 17,500 malaria blood film examinations, 1341 (7.7%) were confirmed for malaria parasites. Of the confirmed malaria cases, 47.2%, 45.6% and 7.2% were P. vivax, P. falciparum and mixed infection, respectively. The proportion of P. vivax was the predominant species in the first three study years (2014–2016) and P. falciparum became the predominant species in the last three study years (2017–2019). The odds of malaria prevalence was lower by 68%, 60% and 69% in the year 2017, 2018 and 2019 compared to 2014, respectively. It was also 1.41 times higher in males than in females. Moreover, the odds of malaria prevalence were 1.60, 1.64, 2.45 and 1.82 times higher in the age group of 54 years old), respectively. Even there was a significant declining in prevalence trend; malaria is still a major public health problem. The study showed that there was high seasonal fluctuation from year to year. Moreover, males and the younger age groups were more affected than females and old age groups, respectively. Therefore, malaria prevention and control activities should be strengthened and require extra efforts by considering these variability.

Background: Purulia is a malaria-prone district in West Bengal, India, with approximately half of the jurisdictional blocks defined as malaria endemic. Methods: We examined the malaria incidence in each block of the district of Purulia for the period between January 1, 2016 and December 31, 2020. Per the Annual Parasite Incidence (API), 20 blocks of Purulia district were assigned to four different categories (0-3) and mapped using ArcGIS software version 10.8. An exponential decay model was fitted to forecast the trend of malaria cases for each block of the district for the 2021-2025 timeline. Findings: There was a sharp decrease in total malaria cases and API from 2016 to 2020. Plasmodium vivax (Pv) cases were decreased by 96.43%, Plasmodium falciparum (Pf) by 90.34%, and mixed infection cases by 92.78%. The majority of cases (72.63%) were found in the 15 year and older age group. Males were more prone to malaria (60.09%) than females. Malaria was highly prevalent among Scheduled Tribes (ST) (48.44%). Six blocks were reported in Category 3 (high risk) and none in Category 0 (no risk) in 2016 while no blocks were determined to be in Category 3 and three blocks were in Category 0 in 2020. The exponential decay model prediction is oriented towards gaining malaria-free status in thirteen blocks of the Purulia district by 2025. Interpretation: By efficiently diagnosing malaria, implementing a GIS system to track malaria incidences, fair usage of Long-lasting insecticidal nets (LLINs), and conducting effective awareness campaigns, malaria control could be possible. Nevertheless, consistent funding is needed to avoid reappearance and sustain eradication goals. Funding Information: None. Declaration of Interests: We declare no competing interests. Ethics Approval Statement: This study was permitted by Zilla Swasthya Bhawan, Purulia, Govt. of West Bengal (Memo No. 2041; Dated: 03.11.2020).

Body mass index (BMI) and dyslipidemia are indicators of human health and are often associated with high blood pressure. In this study,we explored the relationship between BMI or dyslipidemia and the risk of hypertension and further verified the possible interacting influences of BMI with dyslipidemia on the risk of hypertension. The aim is to explore the possible risk factors of hypertension and to provide scientific basis for the prevention and treatment of hypertension. Eligible subjects were selected from a cross-sectional survey in Changsha City, and we collected relevant data and clinical indicators for each participant. Body mass index (BMI) was calculated as weight (kg)/height2 (m2), and divided into four categories according to the Chinese standard. Dyslipidemia is defined according to Chinese guideline. Unconditional logistic regression models were used for dichotomous variables to determine the risk or protective factors of dependent variables. Multivariate Logistic model was used to study the influence of BMI and dyslipidemia on hypertension. The following indicators were used to assess the interaction effects: (1) Relative excess risk due to interaction (RERI); (2) Attributable proportion due to interaction(AP); (3) Synergy index (SI). SPSS software was used for statistical analysis. A total of 2740 eligible participants were enrolled in the cross-sectional study, of which 765 subjects (27.9%) were diagnosed with hypertension. Multivariate Logistic model showed that overweight (OR: 1.70, 95%CI: 1.39–2.09) or obese (OR: 2.60, 95%CI: 1.84–3.66) subjects had a significantly higher risk of hypertension than normal weight people, and underweight was a protective factor for hypertension(OR: 0.52, 95%CI: 0.29–0.93). People with dyslipidemia have a higher risk of hypertension than those with normal lipids (OR: 3.05, 95%CI: 2.36–3.90). In addition,there was a significant potentiating interaction effect between overweight or obesity and dyslipidemia(overweight: RERI (1.91, 95%CI: 0.17–3.66), AP (0.40, 95%CI:0.14–0.66), SI (2.03, 95%CI:1.11–3.74) and obesity: RERI (2.20, 95%CI:1.01–3.40), AP (0.38, 95%CI:0.18–0.58), SI (1.84, 95%CI:1.18–2.89), while no interaction was found between underweight and dyslipidemia. Low body weight is an independent protective factor for hypertension, but overweight, obesity and dyslipidemia are risk factors for hypertension, and dyslipidemia significantly shared interactions with overweight and obesity that influenced the risk of hypertension.

Hospitalized patients who die from Covid-19 often have pre-existing heart disease. The SARS-CoV-2 virus is dependent on the ACE2 receptor to be able to infect cells. It is possible that the strong link between cardiovascular comorbidities and a poor outcome following a SARS-CoV-2 infection is sometimes due to viral myocarditis. The aim was to examine the expression of ACE2 in normal hearts and hearts from patients with terminal heart failure. The ACE2 expression was measured by global quantitative proteomics and RT-qPCR in left ventricular (LV) tissue from explanted hearts. Immunohistochemistry was used to examine ACE2 expression in cardiomyocytes, fibroblasts and endothelial cells. In total, tissue from 14 organ donors and 11 patients with terminal heart failure were included. ACE2 expression was 2.6 times higher in 4 hearts from patients with terminal heart failure compared with 6 healthy donor hearts. The results were confirmed by immunohistochemistry where more than half of cardiomyocytes or fibroblasts showed expression of ACE2 in hearts from patients with terminal heart failure. In healthy donor hearts ACE2 was not expressed or found in few fibroblasts. A small subpopulation of endothelial cells expressed ACE2 in both groups. Upregulated ACE2 expression in cardiomyocytes may increase the risk of SARS-CoV-2 myocarditis in patients with heart failure.

To assess the spectrum of different etiologies, the intrauterine course, outcome and possible prognostic markers in prenatally detected fetal growth restriction (FGR) combined with polyhydramnios. Retrospective study of 153 cases with FGR combined with Polyhydramnios diagnosed by prenatal ultrasound over a period of 17 years. Charts were reviewed for ultrasound findings, prenatal and postnatal outcome. All cases were categorized into etiological groups and examined for differences. Five etiological groups were identified: chromosomal anomalies (n = 64, 41.8%), complex malformation syndromes (n = 37, 24.1%), isolated malformations (n = 24, 15.7%), musculoskeletal disorders (n = 14, 9.2%) and prenatal non-anomalous fetuses (n = 14, 9.2%). Subgroups showed significant disparities in initial diagnosis of combination of both pathologies, Ratio AFI/ gestational weeks and Doppler ultrasound examinations. Overall mortality rate was 64.7%. Fetuses prenatally assigned to be non-anomalous, showed further complications in 42.9% (n = 6). Fetuses prenatally diagnosed with FGR combined with polyhydramnios are affected by a high morbidity and mortality. Five etiologic groups can be differentiated, showing significant disparities in prenatal and postnatal outcome. Even without recognizable patterns prenatally, long-term-follow up is necessary, as neurodevelopmental or growth delay may occur.

The worldwide spread of the COVID-19 pandemic is a complex and multivariate process differentiated across countries, and geographical distance is acceptable as a critical determinant of the uneven spreading. Although social connectivity is a defining condition for virus transmission, the network paradigm in the study of the COVID-19 spatio-temporal spread has not been used accordingly. Toward contributing to this demand, this paper uses network analysis to develop a multidimensional methodological framework for understanding the uneven (cross-country) spread of COVID-19 in the context of the globally interconnected economy. The globally interconnected system of tourism mobility is modeled as a complex network and studied within the context of a three-dimensional (3D) conceptual model composed of network connectivity, economic openness, and spatial impedance variables. The analysis reveals two main stages in the temporal spread of COVID-19, defined by the cutting-point of the 44th day from Wuhan. The first describes the outbreak in Asia and North America, the second stage in Europe, South America, and Africa, while the outbreak in Oceania intermediates. The analysis also illustrates that the average node degree exponentially decays as a function of COVID-19 emergence time. This finding implies that the highly connected nodes, in the Global Tourism Network (GTN), are disproportionally earlier infected by the pandemic than the other nodes. Moreover, countries with the same network centrality as China are early infected on average by COVID-19. The paper also finds that network interconnectedness, economic openness, and transport integration are critical determinants in the early global spread of the pandemic, and it reveals that the spatio-temporal patterns of the worldwide spreading of COVID-19 are more a matter of network interconnectivity than of spatial proximity.

Stroke individuals’ daily function has been demonstrated to be influenced by their somatosensory capability, cognitive capability, and upper extremity (UE) motor abilities. However, the structural relationships among these abilities on stroke individuals’ independence in daily function remain unclear. We analyzed the pretest measures of 153 stroke individuals in outpatient rehabilitation settings by structural equation modeling to determine the structural relationship among somatosensory capability, UE muscle strength, UE motor function, and cognitive capability that influences independence in daily function. The standardized results indicated somatosensory capability negatively influenced UE muscle strength, but positively influenced UE muscle strength mediated by UE motor function. UE muscle strength, then, positively influenced individuals’ independence in daily function. On the other hand, somatosensory capability positively influenced cognitive capability, which marginally and positively affected the performance of independence in daily function. To the best of our knowledge, this is the first study to demonstrate the influence of somatosensory capability on the daily function is mediated mainly by motor functions and marginally by cognitive capability. This structural model may allow future clinical therapists to design more effective task-related training protocols to promote the independence in daily function for stroke individuals.

The present study assessed the prevalence, patterns and determinants of dyslipidaemia among South African adults with multi-morbidities. In this study, 614 individuals with DM and hypertension were recruited. Dyslipidaemia was defined as elevated levels of total cholesterol (TC) ≥ 5.2 mmol/L and/or low-density lipoprotein cholesterol (LDL-C) ≥ 2.6 mmol/L, triglycerides (TG) ≥ 1.8 mmol/L and low high-density lipoprotein cholesterol (HDL-C)

The third isoform of the Na+–Ca2+ exchanger (NCX3) is crucial for a physiological fine-tuning of the Ca2+ fluxes in excitable tissues. In this view, the NCX3 accounts for the aberrant Ca2+ influx seen during neuronal excitotoxicity, such as in Alzheimer’s disease (AD). However, little is known about NCX3 regulation and functional properties. Withania somnifera (L.) Dunal (W. somnifera), a traditional indigenous plant widely recognized for having numerous medicinal values, was undertaken to determine its potential therapeutic benefit against aggregated Aβ1–42-induced NCX3 dysregulation and the thereof cognition impairment in 5xFAD mice. The undertaken sourced dried roots of authenticated W. somnifera physicochemical compositional tests satisfied standards of pharmacognostic quality, and further phytochemical analysis of the roots methanol extract revealed the roots constitute several antioxidants. Following an intra-gastric gavage administration of synthesized W. somnifera roots methanolic extract from postnatal day 30 (P30) to P75, in vivo cognitional studies and then neurochemical examinations of the NCX3 expression level, Aβ plaque deposition, and antioxidant activities in the AD-associated brain regions of 4-month-old 5xFAD mice suggests that the oxidative stress normalizing effects of W. somnifera constituents, operating on the NCX3, may have a therapeutic role in the improvement of cognition in AD.

Several epidemiological studies investigated the relation of Ca intake with type 2 diabetes mellitus (T2DM), but there were inconsistencies in their findings. So, we conducted a systematic review and dose–response meta-analysis to quantify the relation of dietary Ca intake with the risk of T2DM/hyperglycemia in adults. A systematic search was conducted up to May 2021, in MEDLINE (Pubmed), Web of Science (WOS), Scopus electronic databases and Google Scholar, for epidemiological studies that investigated the relation of dietary Ca intake (as the exposure) and T2DM/hyperglycemia (as the outcome) in adults, without restriction in publication date and language. Finally, 8 cohort and 9 cross-sectional studies were included in the analysis. The body of evidence was assessed by the GRADE approach. Combining effect sizes from prospective cohort studies included 255,744 general adult population illustrated that highest level of dietary Ca intake, compared to lowest category, was related to an 18% reduced risk of T2DM (RR: 0.82; 95% CI 0.74–0.92). Based on linear dose–response analysis (including 255,744 healthy individuals and 13,531 patients with T2DM), each 300, 600 and 1000 mg/day increment in dietary Ca intake was respectively associated to 7, 14 and 23% reduced risk of T2DM. There was a steeper reduction in risk of T2DM when dietary Ca intake increased from low levels to 750 mg/day. Nevertheless, meta-analysis of cross-sectional studies revealed an inverse significant association between dietary Ca intake and T2DM/hyperglycemia only in the female population (OR: 0.66; 95% CI 0.50–0.88). This meta-analysis illustrated an inverse association between dietary Ca intake and risk of T2DM in general adult populations in prospective cohort studies, in a dose–response manner. It seems that increasing dietary Ca intake from low levels to around 750 mg/day was inversely related to risk of T2DM. In cross-sectional studies, an inverse relation between dietary Ca intake and T2DM/hyperglycemia was found only in females.

The aim of this study was to determine the prevalence, antimicrobial susceptibility pattern and associated factors of urinary tract infection (UTI) among pregnant women attending Hargeisa Group Hospital (HGH), Hargeisa, Somaliland. A cross-sectional study was conducted at HGH, Hargeisa, Somaliland and participants were selected by systematic random sampling technique. Clean catch midstream urine samples were collected from 422 participants and cultured and antimicrobial susceptibility pattern was determined for the isolates. Univariable and multivariable logistic regression analyses were utilized to identify the independent risk factors for UTI. The prevalence of UTI was 16.4% (95% CI 13.3–19.9). The predominant bacteria isolate was E. coli (43.5%) followed by Coagulase negative staphylococcus (CoNS) 11(16%), S. aureus 9(13%), K. pneumonia 6(8.7%), Pseudomonas aeruginosa 5(7.2%), Proteus mirabilis 4(5.8%), Citrobacter spp 3(4.4%) and M. morganii 1(1.5%) Gram negative bacilli were resistant to ampicillin (96%) and tetracycline (71.4%) and Gram-positive cocci were also resistant to ampicillin (90%), tetracycline (55%). Multidrug resistance was observed in 85.5% of bacterial isolated. No formal education participants, previous history of catheterization and previous history of UTI had 3.18, 3.22 and 3.73 times respectively more likely to develop UTI than their counterparts. Culture and susceptibility test is vital for appropriate management of UTI in the study area.

In a retrospective study we tested our hypothesis that the subjective postural vertical ratio (SPV ratio), i.e., the subjective postural vertical measured in relation to the lateral flexion axis, is predictive of lateral trunk flexion in patients with Parkinson's disease (PD). Twenty-five patients were included. The SPV angle, i.e., the subjective perception of a vertical position with reference to the vertical axis, and the SPV ratio, i.e., the SPV angle with reference to the axis of lateral flexion, were calculated. The SPV ratio (r = 0.698, P = 0.001) and LTF angle (r = − 0.601, P = 0.001) correlated with change in the LTF angle at 1 year. The SPV ratio was significantly smaller in patients for whom lateral trunk flexion improved (n = 12) than in those for whom it did not improve (n = 13) (0.99 ± 0.78 vs 1.66 ± 0.71, P = 0.011). The AUC under the ROC curve of the SPV ratio for discrimination of improvement was 0.795 (95% confidence interval: 0.61–0.98). We found that the SPV ratio is associated with change in the LTF and that it can conceivably be used to predict the likelihood of improvement in PD-associated lateral trunk flexion.

The cross-sectional study assessed knowledge, attitudes, and preventive practices toward COVID-19 disease of incarcerated people. A total of 685 subjects were surveyed. 94% were aware that respiratory droplets are involved in the transmission of COVID-19, and 77.2% that patients with chronic conditions are at risk of a more severe disease. Overall, 92.7% of respondents considered COVID-19 a more severe disease compared to influenza, and 85.4% believed that COVID-19 could cause serious consequences in their institution. Only 22.6% were self-confident about their ability to protect themselves from SARS-CoV-2 infection. This attitude was significantly higher in those who were involved in working activities in the institution, who did not report at least one common symptom compatible with COVID-19 in the previous 3 months, who did not show generalized anxiety symptoms, and did not need additional information. 63.9% of incarcerated people expressed willingness to receive COVID-19 vaccination. Older subjects, who knew that a COVID-19 vaccination is available, believed that COVID-19 is more serious than influenza, and were self-confident about their ability to protect themselves from SARS-CoV-2 infection, were significantly more willing to undergo COVID-19 vaccination. Public health response to COVID-19 in prisons should address vaccine hesitancy to increase vaccine confidence among incarcerated people.

This study aims to assess the effects of central and general adiposity on development of cardiovascular diseases (CVDs) mediated by cardiometabolic risk factors and to analyze their degree of dependency for mediating their effects. To this end, data from the the Tehran Lipid and Glucose Study cohort with 6280 participants were included in this study. The hazard ratios were calculated using a 2-stage regression model in the context of a survival model. Systolic blood pressure (BP), total serum cholesterol, and fasting plasma glucose were designated as mediators. Assessing the interactions revealed that BP was the most important mediator for general ( (HRNIE: 1.11, 95% CI 1.17–1.24) and central obesity (CO) (HRNIE: 1.11, 95% CI 1.07–1.15) with 60% and 36% proportion of the effects mediated in the total population, respectively. The proportion of mediated risk for all three metabolic risk factors was 46% (95% CI 31–75%) for overweight, 66% (45–100%) for general obesity and 52% (39–87%) for central obesity. BP was the most important mediator for overweight and central obesity in men, comprising 29% and 36% of the risk, respectively. The proportion of the risk mediated through all three metabolic risk factors in women was 23% (95% CI 13–50%) for overweight, 36% (21–64%) for general obesity and 52% (39–87%) for central obesity. Based on the results of this study, cardiometabolic mediators have conciliated more than 60% of the adverse effects of high BMI on CVDs in men. Controlling the metabolic risk factors in women does not efficiently contribute to decreasing CVDs as effectively.

Herpes simplex virus (HSV) usually produces cytopathic effect (CPE) within 24-72 h post-infection (P.I.). Clinical isolates from recurrent HSV infections in patients on Acyclovir therapy were collected between 2016 and 2019 and tested in cell cultures for cytopathic effects and further in-depth characterization. Fourteen such isolates did not show any CPE in A549 or Vero cell lines even at 120 h P.I. However, these cultures remained positive for HSV-DNA after several passages. Sequence analysis revealed that the non-CPE isolates were all HSV-1. Analysis of the thymidine kinase gene from the isolates revealed several previously reported and two novel ACV-resistant mutations. Immunofluorescence and Western blot data revealed a low-level expression of the immediate early protein, ICP4. Late proteins like ICP5 or capsid protein, VP16 were almost undetectable in these isolates. AFM imaging revealed that the non-CPE viruses had structural deformities compared to wild-type HSV-1. Our findings suggest that these strains are manifesting an unusual phenomenon of being non-CPE herpesviruses with low level of virus protein expressions over several passages. Probably these HSV-1 isolates are evolving towards a more “cryptic” form to establish chronic infection in the host thereby unraveling yet another strategy of herpesviruses to evade the host immune system.

The current study was performed to evaluate the effects of alpha-lipoic acid (ALA) supplementation on lactate, nitric oxide (NO), vascular cell adhesion molecule-1 (VCAM-1) levels, and clinical symptoms in women with episodic migraines. Considering the inclusion and exclusion criteria, ninety-two women with episodic migraines participated in this randomized, double-blind, placebo-controlled, parallel-design trial. The participants were randomly assigned to receive either 300 mg/day ALA or placebo, twice per day for 12 weeks. The primary outcomes included headache severity, headache frequency per month, and duration of attacks and the secondary outcomes included lactate (a marker of mitochondrial function), NO, and VCAM-1 serum levels were measured at baseline and the end of the intervention. At the end of the study, there was a significant decrease in lactate serum levels (− 6.45 ± 0.82 mg/dl vs − 2.27 ± 1.17 mg/dl; P = 0.039) and VCAM-1 (− 2.02 ± 0.30 ng/ml vs − 1.21 ± 0.36 ng/ml; P = 0.025) in the ALA as compared to the placebo group. In addition, the severity (P

Coenzyme Q10 (CoQ10) is a naturally produced organic molecule which acts as an antioxidant agent, including in skin anti-ageing, and plays a major role in the social determinants of health. However, its level in the body will decrease during ageing. Therefore, an external supplement is required to repair damaged skin, especially the skin dermis layer. This study aims to evaluate the use of a protransfersomal emulgel to improve the skin delivery and stability of CoQ10 which demonstrates low water solubility, poor permeability and instability. CoQ10 was initially dissolved in oleic acid at a weight ratio of 1:56. Protransfersome was then loaded with CoQ10 (Protransf-CoQ10) and prepared using a composition of L-α-Phosphatidylcholine and Tween 80 at a molar ratio of 85:15. The Protransf-CoQ10 was dispersed in an emulgel base consisting of Tween 80 and Span 80 to produce Protransf-CoQ10 emulgel. The in vivo studies of anti-aging activity and irritability were further evaluated by applying daily 200 mg of emulgels twice a day to a 4 cm2 section on the back of a UV-ray aging-induced male Balb/c mouse 20 min before irradiation. The results showed that Protransf-CoQ10 could transform into transfersomal vesicles with particle sizes of approximately 201.5 ± 6.1 nm and a zeta potential of − 11.26 ± 5.14 mV. The dispersion of Protransf-CoQ10 into emulgel base resulted in stable Protransf-CoQ10 Emulgel during 28 days of observation at low temperatures. Moreover, the in vivo study revealed that Protransf-CoQ10 Emulgel successfully increases the collagen density and number of fibroblast cells in UV radiation skin-aged induced-mice which reflects its potential for repairing the skin ageing process. In addition, the 24-h topical application of Protransf-CoQ10 Emulgel showed that no erythema or skin rash was observed during the study. In conclusion, loading CoQ10 into protransfersomal Emulgel successfully enhanced the stability and anti-ageing efficacy enabling its potential use as anti-ageing cosmetics.

Scientific reports 12, 734 (2022). doi:10.1038/s41598-021-04531-x, Published by Macmillan Publishers Limited, part of Springer Nature, [London]

Ketosis often occurs during the postpartum transition period in dairy cows, leading to economic and welfare problems. Previously, ketosis was reported to be associated with hematological and serum biochemical parameters. However, the association between the parameters on the calving date and ketosis during the postpartum transition period remains unclear. This study aimed to investigate this association. Blood samples were collected from the jugular vein of Holstein cows on the calving date and β-hydroxybutyrate was tested once every 3 days (8 times in 21 days). The cows were divided into three groups: non-ketosis, subclinical ketosis, and clinical ketosis. The clinical ketosis group significantly had the highest values of mean corpuscular volume, mean corpuscular hemoglobin, β-hydroxybutyrate, non-esterified fatty acids, and total bilirubin, but the lowest values of red cell distribution width, the counts of white blood cell, monocyte, and eosinophil, albumin, alanine transaminase, lactate dehydrogenase, and amylase. In contrast, the non-ketosis group showed the opposite results (p

We compared quadriceps oxygenation and surface electromyography (sEMG) responses during the 1-min sit-to-stand (1STS) in 14 people with severe COPD and 12 controls, in whom cardiorespiratory response, near-infrared spectroscopy signals (oxy [Hb-Mb], deoxy [Hb-Mb], total [Hb-Mb], and SmO2) and sEMG signals of the quadriceps were recorded. Time duration of each sit-to-stand cycle and the total work performed during the 1STS were measured. The quadriceps oxygenation parameters were normalized by reporting their values according to the total work during 1STS. The rate of sit-to-stand maneuvers decelerated in people with COPD leading to smaller total work compared with controls. The pattern of quadriceps oxygenation response during 1STS was similar between groups. However, in COPD, the recovery after 1STS was characterized by larger overshoots in oxy [Hb-Mb], total [Hb-Mb], and SmO2. When corrected for the cumulative total work, the increase in muscle O2 extraction (deoxy [Hb-Mb]) during the first 30 s of recovery was greater in people with COPD compared to controls. Quadriceps sEMG changes suggestive of a fatiguing contraction pattern was observed only in people with COPD. All together, these results highlighted physiological misadaptation of people with severe COPD to the 1STS.

New predictors that could boost early detection of preeclampsia (PE) and prognosticate its severity are urgently needed. We examined serum miR-17, miR-363, MALAT-1 and HOTAIR as potential biomarkers of PE risk, onset and severity. This prospective study included 160 pregnant females; 82 PE cases and 78 healthy pregnancies. Serum samples were collected between 20 to 40 weeks of gestation. Early-onset PE was defined as developing clinical manifestations at ≤ 34 gestational weeks. Severe PE was defined as systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 110 mmHg and proteinuria (≥ 2 g/24 h or ≥ 2+ dipstick). Selection of PE-related non-coding RNAs and functional target gene analysis were conducted using bioinformatics analysis. Expression profiles were assessed by RT-qPCR. Serum miR-363 and MALAT-1 were downregulated, meanwhile miR-17 was upregulated, and HOTAIR was not significantly altered in PE compared with healthy pregnancies. miR-17 was elevated while miR-363 and MALAT-1 were reduced in severe versus mild PE. miR-363 was lower in early-onset versus late-onset PE. MALAT-1, miR-17 and miR-363 showed diagnostic potential and discriminated severe PE, whereas miR-363 distinguished early-onset PE in the receiver-operating-characteristic analysis. miR-363 and MALAT-1 were significantly associated with early and severe PE, respectively in multivariate logistic analysis. In PE, miR-17 and MALAT-1 were significantly correlated with gestational age (r = − 0.328 and r = 0.322, respectively) and albuminuria (r = 0.312, and r = − 0.35, respectively). We constructed the MALAT-1, miR-363, and miR-17-related protein–protein interaction networks linked to PE. Serum miR-17, miR-363 and MALAT-1 could have utility as new biomarkers of PE diagnosis. miR-363 may be associated with early-onset PE and MALAT-1 downregulation correlates with PE severity.

Adolescence represents a period of significant neurodevelopment during which adverse experiences can lead to prolonged effects on disease vulnerability, including effects that can impact future offspring. Adolescence is a common period for the initiation of drug use, including the use of opioids. Beyond effects on central reward, opioids also impact glucose metabolism, which can impact the risk of diabetes. Moreover, recent animal models suggest that the effects of adolescent opioids can effect glucose metabolism in future offspring. Indeed, we demonstrated that the adult male offspring of females exposed to morphine for 10 days during adolescence (referred to as MORF1 males) are predisposed to the adverse effects of an obesogenic diet. As adults, MORF1 males fed a high fat moderate sucrose diet (FSD) for just 6 weeks had increased fasting glucose and insulin levels when compared to age-matched offspring of females exposed to saline during adolescence (SALF1 males). Clinically, a similar profile of impaired fasting glucose has been associated with hepatic insulin resistance and an increased risk of non-alcoholic fatty liver disease. Thus, in the current study, we used RNA sequencing to determine whether adult MORF1 males demonstrate significant alterations in the hepatic transcriptome suggestive of alterations in metabolism. Age-matched SALF1 and MORF1 males were fed either FSD or control diet (CD) for 8 weeks. Similar to our previous observations, FSD-maintained MORF1 males gained more weight and displayed both fasting hyperglycemia and hyperinsulinemia when compared to FSD-maintained SALF1 males, with no significant effect on glucagon. No differences in bodyweight or fasting-induce glucose were observed in control diet (CD)-maintained F1 males, although there was a trend for CD MORF1 males to display elevated levels of fasting insulin. Unexpectedly, transcriptional analyses revealed profound differences in the hepatic transcriptome of CD-maintained MORF1 and SALF1 (1686 differentially expressed genes) with no significant differences between FSD-maintained MORF1 and SALF1 males. As changes in the hepatic transcriptome were not revealed under 8 weeks FSD conditions, we extended the feeding paradigm and conducted a glucose tolerance test to determine whether impaired fasting glucose observed in FSD MORF1 males was due to peripheral insulin resistance. Impaired glucose tolerance was observed in both CD and FSD MORF1 males, and to a more limited extent in FSD SALF1 males. These findings implicate intergenerational effects of adolescent morphine exposure on the risk of developing insulin resistance and associated comorbidities, even in the absence of an obesogenic diet.

EUS-guided transmural endoscopic drainage is commonly used in the treatment of WOPN in the late phase of ANP. The role of endoscopic intervention remains unclear in the early phase of ANP. This study aimed to prospectively evaluate early endoscopic treatment of ANCs compared with endoscopic drainage of WOPN. Overall, 71 patients with ANP who underwent transmural endoscopic drainage for necrotic collections were included. Endoscopic intervention was performed within the first four weeks of ANP in 25 (35.21%) patients with ANC (Group 1) and in 46 (64.79%) patients after four weeks since the onset of ANP with WOPN (Group 2). The overall mean age of patients was 49.9 (22–79) years and 59 of them were males. The mean time of active drainage and duration of total endoscopic treatment was 26.8 and 16.9 days (P = 0.0001) and 270.8 and 164.2 days (P = 0.0001) in Groups 1 and 2, respectively. The average total number of endoscopic interventions was 9.5 and 4.5 in Groups 1 and 2, respectively (P = 0.0001). The clinical success rate, frequency of complications of endoscopic interventions, long-term success rate, and recurrence rate were not significantly different between the groups (P > 0.05 for each). Transmural endoscopic drainage is effective method of treatment of early ANCs within the first four weeks of ANP. However, compared with endoscopic intervention in WOPN, more interventions and longer duration of drainage are required.

Comprehensive screening for non-alcoholic fatty liver disease (NAFLD) may help prompt clinical management of fatty liver disease. A family history, especially of diabetes, has been little studied as a predictor for NAFLD. We characterized the cross-sectional relationship between a family history of type 2 diabetes (FHT2D) and NAFLD probability in 1185 diabetes-free Apulian (Southern-Italy) subjects aged > 20 years with overweight or obesity not receiving any drug or supplementation. Clinical data and routine biochemistry were analysed. NAFLD probability was defined using the fatty liver index (FLI). A first-degree FHT2D was assessed by interviewing subjects and assigning a score of 0, 1, or 2 if none, only one, or both parents were affected by type 2 diabetes mellitus (T2DM). Our study population featured most females (70.9%, N = 840), and 48.4% (N = 574) of the sample had first-degree FHT2D. After dividing the sample by a FHT2D, we found a higher BMI, Waist Circumference (WC), and diastolic blood pressure shared by FHT2D subjects; they also showed altered key markers of glucose homeostasis, higher triglyceride levels, and worse liver function. FLI scores were significantly lower in subjects without a first-degree FHT2D. After running logistic regression models, a FHT2D was significantly associated with the NAFLD probability, even adjusting for major confounders and stratifying by age (under and over 40 years of age). A FHT2D led to an almost twofold higher probability of NAFLD, regardless of confounding factors (OR 2.17, 95% CI 1.63 to 2.89). A first-degree FHT2D acts as an independent determinant of NAFLD in excess weight phenotypes, regardless of the age group (younger or older than 40 years). A NAFLD risk assessment within multidimensional screening might be useful in excess weight subjects reporting FHT2D even in the absence of diabetes.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) belongs to the coronavirus family and is characterized by its high transmission competence. Elderly COVID-19 patients are at significantly higher risk of severe course of disease and death. Therefore, outbreaks in nursing homes are particularly challenging for facility managers and health authorities. Here, we report three outbreaks of COVID-19 related to nursing homes (NH01.a, NH02 and NH03) with almost 1000 affected individuals during the first COVID-19 wave in Berlin, Germany. The occurrence of cases and the measures taken were analyzed retrospectively. In all three outbreaks, the index persons were nursing home employees or volunteers. Measures taken were quarantine of contacts, close-meshed tests, separation of the affected housing unit, suspension of admission, ban on visiting, and equipping staff with personal protective equipment, of which there was a shortage in Germany at the beginning of the pandemic. A court-ordered quarantine became necessary for three residents of NH01.a due to cognitive disabilities. In total, 61 persons were tested positive for SARS-CoV-2 in NH01.a, ten persons in NH02, and sixteen persons in NH03. Seventeen patients (27.9%) of NH01.a and three patients (18.8%) of NH03 were referred to hospital. Of all confirmed cases, thirteen (21.3%) related to NH01.a and four (25.0%) related to NH03 died as a result of the infection. Besides one 82 year old volunteer, all deceased persons were residents aged between 66 and 98. Our results emphasize the importance of a previously developed containment and cluster strategy for nursing homes. Due to the particular vulnerability of the residents, immediate action, close cooperation and communication between the facility management, residents, visitors and the health authorities are essential in the case of confirmed COVID-19 cases in healthcare facilities.

This study aimed to evaluate the sensitivity and prognostic value of arterial spin labeling (ASL) in a large group of status epilepticus (SE) patients and compare them with those of other magnetic resonance (MR) sequences, including dynamic susceptibility contrast (DSC) perfusion imaging. We retrospectively collected data of patients with SE in a tertiary center between September 2016 and March 2020. MR images were visually assessed, and the sensitivity for the detection of SE and prognostication was compared among multi-delay ASL, DSC, fluid-attenuated inversion recovery (FLAIR), and diffusion-weighted imaging (DWI). We included 51 SE patients and 46 patients with self-limiting seizures for comparison. Relevant changes in ASL were observed in 90.2% (46/51) of SE patients, a percentage higher than those for DSC, FLAIR, and DWI. ASL was the most sensitive method for initial differentiation between SE and self-limiting seizures. The sensitivity of ASL for detecting refractory SE (89.5%) or estimating poor outcomes (100%) was higher than those of other MR protocols or electroencephalography and comparable to those of clinical prognostic scores, although the specificity of ASL was very low as 9.4% and 15.6%, respectively. ASL showed a better ability to detect SE and predict the prognosis than other MR sequences, therefore it can be valuable for the initial evaluation of patients with SE.

We previously identified genomic variants that are quantitative trait loci for circulating miR-1908-5p and then showed this microRNA to causally associate with plasma levels of LDL-C, fasting blood glucose and HbA1c. The link to LDL-C was subsequently validated and clarified by the identification of a miR1908-5p-TGFB-LDLR regulatory axis. Here, we continue our investigations on miR1908-5p function by leveraging human primary hepatocytes and HuH-7 hepatoma models. Expression of miR1908-5p was shown to be sensitive to glucose and agents affecting glucose metabolism. Transcriptome-wide changes in primary hepatocytes and HuH-7 cells treated with a miR1908-5p mimic were investigated by enrichment approaches to identify targeted transcripts and cognate pathways. Significant pathways included autophagy and increased mitochondrial function. Reduced activation and/or levels of several key energy and metabolic regulators (AKT, mTOR, ME1, G6PD, AMPK and LKB) were subsequently confirmed in mimic treated HuH-7 cells. These effects were associated with reduced NADPH to NADP+ ratio in HuH-7 cells. LKB1 was validated as a direct target of miR1908-5p, the reintroduction of which was however insufficient to compensate for the impact of the miR1908-5p mimic on AMPK and ACC1. These findings implicate miR1908-5p in metabolic and energy regulation in hepatocyte models via multiple, independent, pathways.

In this paper, we investigate an norovirus (NoV) epidemic model with stochastic perturbation and the new definition of a nonlocal fractal–fractional derivative in the Atangana–Baleanu–Caputo (ABC) sense. First we present some basic properties including equilibria and the basic reproduction number of the model. Further, we analyze that the proposed stochastic system has a unique global positive solution. Next, the sufficient conditions of the extinction and the existence of a stationary probability measure for the disease are established. Furthermore, the fractal–fractional dynamics of the proposed model under Atangana–Baleanu–Caputo (ABC) derivative of fractional order “$${p}$$ p ” and fractal dimension “$${q}$$ q ” have also been addressed. Besides, coupling the non-linear functional analysis with fixed point theory, the qualitative analysis of the proposed model has been performed. The numerical simulations are carried out to demonstrate the analytical results. It is believed that this study will comprehensively strengthen the theoretical basis for comprehending the dynamics of the worldwide contagious diseases.

We compared two and four intra-articular injections of platelet-rich plasma (PRP) in terms of changes of synovial cytokines and clinical outcomes. One hundred twenty-five patients having knee osteoarthritis (OA) underwent PRP injections at a 6-week interval. Before each PRP injection, synovial fluid aspiration was collected for investigation. Patients were divided into two or four intra-articular PRP injections (group A and B, respectively). Changes in synovial biomarkers were compared with the baseline levels of both groups, and clinical outcomes were evaluated until one year. Ninety-four patients who had completed synovial fluid collection were included for final evaluation, 51 in group A and 43 in group B. There were no differences in mean age, gender, body mass index (BMI), and radiographic OA grading. The average platelet count and white blood cell count in PRP were 430,000/µL and 200/ µL, respectively. There were no changes of synovial inflammatory cytokines (IL-1β, IL-6, IA-17A, and TNF-alpha), anti-inflammatory cytokines (IL-4, IL-10, IL-13, and IL-1RA), and growth factors (TGF-B1, VEGF, PDGF-AA, and PDGF-BB) between baseline levels and six weeks in group A, and 18 weeks in group B. Both groups had significantly improved clinical outcomes from six weeks including visual analog scale (VAS), patient-reported outcome measures [PROMs; Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index and Short Form-12 (SF-12)], with a significant delayed improvement of performance-based measures [PBMs; time up and go (TUG), 5-time sit to stand test (5 × SST), and 3-min walk test (3-min WT)]. In conclusion, two- or four-PRP intra-articular injection at a 6-week interval for knee OA demonstrated no changes of synovial cytokines and growth factors but similarly improved clinical outcomes from 6 weeks until 1 year.