Dunn's Multiple Comparison Test Research Articles

Nonverbal Cognitive Skills in Children With Aicardi Goutières Syndrome.

Aicardi Goutières syndrome (AGS) is type I interferonopathy characterized by severe neurologic impairment. Although many children with AGS demonstrate motor and expressive language deficits, the magnitude of receptive language impairment is uncharacterized. We sought to characterize cognitive function in AGS-affected children using assessment tools with reduced dependence on motor abilities and compare cognitive testing outcomes with overall severity and parental assessment of adaptive behavior. We performed a cross-sectional study. Children were recruited as part of the Myelin Disorders Biorepository Project at the Children's Hospital of Philadelphia. We included individuals with a confirmed diagnosis of AGS. We administered the Leiter International Performance Scale, third edition (Leiter-3), and the Vineland Adaptive Behavior Scale, third edition (VABS-3), in the context of research encounters. Motor skills were categorized by AGS Severity Scale mobility levels. Descriptive statistics and Spearman's rank correlation were used to compare assessments. Mann-Whitney and Kruskal-Wallis tests with correction with Dunn's multiple comparison test were used to compare test performance between mobility groups. Cognitive and adaptive behavior performance was captured in 57 children. The mean age at encounters was 8.51 (SD 5.15) years. The median (IQR) Leiter-3 score was 51 (interquartile range [IQR] 60), with administration failure in 20 of 57 (35%) individuals. On the VABS-3, the Motor Domain (median 29, IQR 36.25) was more impacted than the Communication (median 50, IQR 52), Daily Living Skills (median 52, IQR 31), and Socialization (median 54, IQR 40) Domains (p < 0.0001). The AGS Scale correlated with VABS-3 (r = 0.86, p < 0.0001) and Leiter-3 (r = 0.87, p < 0.0001). There was correlation between VABS-3 Domains and Leiter-3 (r-range 0.83-0.97). Gross motor and fine motor categories, respectively, correlated with VABS-3 (H = 39.37, p < 0.0001; U = 63, p < 0.0001) and Leiter-3 (H = 40.43, p < 0.0001; U = 66, p < 0.0001). Within each gross motor and fine motor category of the AGS Scale, a subset of children scored within normal IQ range. Parental assessment of function by the VABS-3 correlated with directly assessed performance measures. Our data underscore the potential value of VABS-3 and Leiter-3 as tools to assess psychometric function in AGS. With a deeper understanding of our patients' abilities, we can better guide clinicians and families to provide appropriate support and personalized interventions to empower children with leukodystrophies to maximize their communication and educational potential.

Free-Breathing Functional Pulmonary Proton MRI: A Novel Approach Using Voxel-Wise Lung Ventilation (VOLVE) Assessment in Healthy Volunteers and Patients With Chronic Obstructive Pulmonary Disease.

In respiratory medicine, there is a need for sensitive measures of regional lung function that can be performed using standard imaging technology, without the need for inhaled or intravenous contrast agents. To describe VOxel-wise Lung VEntilation (VOLVE), a new method for quantifying regional lung ventilation (V) and perfusion (Q) using free-breathing proton MRI, and to evaluate VOLVE in healthy never-smokers, healthy people with smoking history, and people with chronic obstructive pulmonary disease (COPD). Prospective pilot. Twelve healthy never-smoker participants (age 30.3 ± 12.5 years, five male), four healthy participants with smoking history (>10 pack-years) (age 42.5 ± 18.3 years, one male), and 12 participants with COPD (age 62.8 ± 11.1 years, seven male). Single-slice free-breathing two-dimensional fast field echo sequence at 3 T. A novel postprocessing was developed to evaluate the MR signal changes in the lung parenchyma using a linear regression-based approach, which makes use of all the data in the time series for maximum sensitivity. V/Q-weighted maps were produced by computing the cross-correlation, lag and gradient between the respiratory/cardiac phase time course and lung parenchyma signal time courses. A comparison of histogram median and skewness values and spirometry was performed. Kruskal-Wallis tests with Dunn's multiple comparison tests to compare VOLVE metrics between groups; Spearman correlation to assess the correlation between MRI and spirometry-derived parameters; and Bland-Altman analysis and coefficient of variation to evaluate repeatability were used. A P-value <0.05 was considered significant. Significant differences between the groups were found for ventilation between healthy never-smoker and COPD groups (median XCCV, LagV, and GradV) and perfusion (median XCCQ, LagQ, and GradQ). Minimal bias and no significant differences between intravisit scans were found (P range = 0.12-0.97). This preliminary study showed that VOLVE has potential to provide metrics of function quantification. 2 TECHNICAL EFFICACY: Stage 1.

Accumulation of Ambient Black Carbon Particles Within Key Memory-Related Brain Regions

Ambient air pollution is a worldwide problem, not only related to respiratory and cardiovascular diseases but also to neurodegenerative disorders. Different pathways on how air pollutants could affect the brain are already known, but direct evidence of the presence of ambient particles (or nanoparticles) in the human adult brain is limited. To examine whether ambient black carbon particles can translocate to the brain and observe their biodistribution within the different brain regions. In this case series a label-free and biocompatible detection technique of nonincandescence-related white light generation was used to screen different regions of biobanked brains of 4 individuals from Belgium with neuropathologically confirmed Alzheimer disease for the presence of black carbon particles. The selected biological specimens were acquired and subsequently stored in a biorepository between April 2013 and April 2017. Black carbon measurements and data analysis were conducted between June 2020 and December 2022. The black carbon load was measured in various human brain regions. A Kruskal-Wallis test was used to compare black carbon loads across these regions, followed by Dunn multiple comparison tests. Black carbon particles were directly visualized in the human brain of 4 individuals (3 women [75%]; mean [SD] age, 86 [13] years). Screening of the postmortem brain regions showed a significantly higher median (IQR) number of black carbon particles present in the thalamus (433.6 [289.5-540.2] particles per mm3), the prefrontal cortex including the olfactory bulb (420.8 [306.6-486.8] particles per mm3), and the hippocampus (364.7 [342.0-448.7] particles per mm3) compared with the cingulate cortex (192.3 [164.2-277.5] particles per mm3), amygdala (217.5 [147.3-244.5] particles per mm3), and the superior temporal gyrus (204.9 [167.9-236.8] particles per mm3). This case series provides evidence that ambient air pollution particles are able to translocate to the human brain and accumulate in multiple brain regions involved in cognitive functioning. This phenomenon may contribute to the onset and development of neurodegenerative disorders.

Design of a Stem Cell-Based Therapy for Ependymal Repair in Hydrocephalus Associated With Germinal Matrix Hemorrhages.

In preterm birth germinal matrix hemorrhages (GMHs) and the consequent posthemorrhagic hydrocephalus (PHH), the neuroepithelium/ependyma development is disrupted. This work is aimed to explore the possibilities of ependymal repair in GMH/PHH using a combination of neural stem cells, ependymal progenitors (EpPs), and mesenchymal stem cells. GMH/PHH was induced in 4-day-old mice using collagenase, blood, or blood serum injections. PHH severity was characterized 2 weeks later using magnetic resonance, immunofluorescence, and protein expression quantification with mass spectrometry. Ependymal restoration and wall regeneration after stem cell treatments were tested in vivo and in an ex vivo experimental approach using ventricular walls from mice developing moderate and severe GMH/PHH. The effect of the GMH environment on EpP differentiation was tested in vitro. Two-tailed Student t or Wilcoxon-Mann-Whitney U test was used to find differences between the treated and nontreated groups. ANOVA and Kruskal-Wallis tests were used to compare >2 groups with post hoc Tukey and Dunn multiple comparison tests, respectively. PHH severity was correlated with the extension of GMH and ependymal disruption (means, 88.22% severe versus 19.4% moderate). GMH/PHH hindered the survival rates of the transplanted neural stem cells/EpPs. New multiciliated ependymal cells could be generated from transplanted neural stem cells and more efficiently from EpPs (15% mean increase). Blood and TNFα (tumor necrosis factor alpha) negatively affected ciliogenesis in cells committed to ependyma differentiation (expressing Foxj1 [forkhead box J1] transcription factor). Pretreatment with mesenchymal stem cells improved the survival rates of EpPs and ependymal differentiation while reducing the edematous (means, 18% to 0.5% decrease in severe edema) and inflammatory conditions in the explants. The effectiveness of this therapeutical strategy was corroborated in vivo (means, 29% to 0% in severe edema). In GMH/PHH, the ependyma can be restored and edema decreased from either neural stem cell or EpP transplantation in vitro and in vivo. Mesenchymal stem cell pretreatment improved the success of the ependymal restoration.

Transcranial electrical stimulation during functional magnetic resonance imaging in patients with genetic generalized epilepsy: a pilot and feasibility study.

A third of patients with epilepsy continue to have seizures despite receiving adequate antiseizure medication. Transcranial direct current stimulation (tDCS) might be a viable adjunct treatment option, having been shown to reduce epileptic seizures in patients with focal epilepsy. Evidence for the use of tDCS in genetic generalized epilepsy (GGE) is scarce. We aimed to establish the feasibility of applying tDCS during fMRI in patients with GGE to study the acute neuromodulatory effects of tDCS, particularly on sensorimotor network activity. Seven healthy controls and three patients with GGE received tDCS with simultaneous fMRI acquisition while watching a movie. Three tDCS conditions were applied: anodal, cathodal and sham. Periods of 60 s without stimulation were applied between each stimulation condition. Changes in sensorimotor cortex connectivity were evaluated by calculating the mean degree centrality across eight nodes of the sensorimotor cortex defined by the Automated Anatomical Labeling atlas (primary motor cortex (precentral left and right), supplementary motor area (left and right), mid-cingulum (left and right), postcentral gyrus (left and right)), across each of the conditions, for each participant. Simultaneous tDCS-fMRI was well tolerated in both healthy controls and patients without adverse effects. Anodal and cathodal stimulation reduced mean degree centrality of the sensorimotor network (Friedman's ANOVA with Dunn's multiple comparisons test; adjusted p = 0.02 and p = 0.03 respectively). Mean degree connectivity of the sensorimotor network during the sham condition was not different to the rest condition (adjusted p = 0.94). Applying tDCS during fMRI was shown to be feasible and safe in a small group of patients with GGE. Anodal and cathodal stimulation caused a significant reduction in network connectivity of the sensorimotor cortex across participants. This initial research supports the feasibility of using fMRI to guide and understand network modulation by tDCS that might facilitate its clinical application in GGE in the future.

Correlation of the HPV 16 Genotype Persistence in Women Undergoing LEEP for CIN3 with the Risk of CIN2+ Relapses in the First 18 Months of Follow-Up: A Multicenter Retrospective Study.

Specific hr-HPV genotypes have different natural histories and different oncogenic capacity. This study aimed to investigate the risk of CIN2+ recurrence of the individual genotypes and evaluate how the duration of HPV persistence influences the risk of developing recurrent 16 cervical dysplasia of high grade (CIN2+). Data from patients with persistent HPV infection after primary conization were retrospectively extracted. Kaplan-Meier proportional hazards models were used to evaluate associations between the duration of HPV persistence and the risk of developing recurrent CIN2+. Kruskal-Wallis testing with Dunn's multiple comparison test was used to test whether there was a statistically significant difference in the time to development of tumor recurrences between different genotypes. Overall, 333 patients met the inclusion criteria. In 285 cases the HPV infection was persistent, in 48 cases (18%) it was transient, i.e., different genotypes after LEEP. Overall were diagnosed 39 relapses (13.7%), 79.5% (31/39 cases) were due to genotype 16, 20.5% (8/39) were linked to the other genotypes. Persistence of genotype 16 showed a 7-fold increased risk of developing a CIN2+ relapse, OR = 7.08 (95%CI: 3.12-16.08). Furthermore, the majority of relapses (38/39) occurred within 24 months of persistence with a cut-off represented by 18 months (p = 0.001) in which the relapse rate is maximum and the most frequently found genotype was the 16th with 31 (79.5%) cases of recurrence. Kruskal-Wallis test with Dunn's multiple comparisons has shown statistically significant difference in the time of development of CIN2 relapses among HPV16 and other genotypes. (p < 0.05). Kaplan-meier analysis has shown statistically significant difference between the time to CIN2+ relapse onset in patients with HPV 16 infection and patients with other hrHPV genotypes. (p < 0.05) Conclusions: the study results suggest that persistent HPV infection after LEEP with the same HR genotype present before surgery represents one of the most important predictive factors of the risk of CIN2+ recurrence. The persistence of HPV16 for the first 18 months strongly correlates with the risk of developing a CIN2+ recurrence.

HEMŞİRELERE YÖNELİK PSİKOLOJİK ŞİDDET İLE ÇATIŞMA EYLEM STİLLERİ ARASINDAKİ İLİŞKİ: KESİTSEL BİR ÇALIŞMA

Aims: This study aimed to evaluate correlation between psychological violence and conflict action styles against nurses and in order to identify factors affecting.. Materials and Methods: This is a descriptive and correlational study. All registered nurses who communicate with patients and colleagues and work in a hospital setting were included in the study. The data of the study were collected using the "Personal Data Collection Form", "Workplace Psychological Violence Instrument (WPVBI)" and "Conflict Activity Styles Inventory (CASI)". Mann Whitney U test was determined by the Kruskal Wallis H test for independent groups. Dunn's multiple comparison test was used to determine the differences between groups. Extension of Generalized Linear Models (GDM) for assumptions of regression analysis were used. Results:The current study found that the CASI and WPVBI subscale scores of the nurses statistically differ in relation to the clinics they work in, the type of hospital they are in, their working hours, the number of patients they are caring for, the number of nurses working in shifts, the belief in teamwork, manager support, and the level of communication with the clinicians (p&amp;lt;0.05). Further analysis demonstrated that the total score effects of avoidant and compulsive approaches on WPVBI scores were statistically significant (p&amp;lt;0.05). Conclusions: Nurses should be taught to use effective conflict action styles in order not to be exposed to psychological violence.

Early in life stressful events induce chronic visceral pain and changes in bladder function in adult female mice through a mechanism involving TRPV1 and alpha 1A adrenoceptors.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic pain disorder with multiple phenotypes, one of which is associated with an overactive adrenergic system. We investigated if the maternal deprivation model (MDM) in female and male mice mimics IC/BPS phenotype and if the overstimulation of alpha 1A adrenoceptor (A1AAR) and the crosstalk with transient receptor potential vanilloid-1(TRPV1) are involved in the generation of pain and bladder functional changes. C57BL/6 female and male mice were submitted to MDM. TRPV1knockout (KO) mice were used to study TRPV1 involvement. Silodosin administration to MDM mice was used to study A1AAR involvement. The primary outcome was chronic visceral pain measured by Von Frey filaments analysis (effect size: 3 for wild type, 3.9 for TRPV1KO). Bladder changes were secondary outcome measurements. Unpaired T test, Mann-Whitney test, one-way analysis of variance followed by Newman-Keuls multiple comparisons test, and Kruskal-Wallis followed by Dunn's multiple comparisons test were used where appropriate. MDM induces pain behavior in female and not in male mice. Bladder afferents seem sensitize as MDM also increase the number of small volume spots voided, the bladder reflex activity, and urothelial damage. These changes were similarly absent after A1AAR blockade with silodosin or by TRPV1 gene KO. The main limitation is the number/type of pain tests used. MDM induced in female mice is able to mimic IC/BPS phenotype, through mechanisms involving A1AAR and TRPV1. Therefore, the modulation of both receptors may represent a therapeutic approach to treat IC/BPS patients.

Comparative study of 3 methods of crimping in orthodontic hooks with two different types of applied force (elastomeric chains and tie-backs) – in vitro study.

Introduction: the objective of this study was to compare 3 methods of crimping orthodontic hooks with 2 different types of force using tiebacks or elastomeric chains.&#x0D; Methods: 100 crimped hooks, 100 dotted hooks and 100 hooks with a V stop bending on the archwire, divided into 6 groups were put to detachment test in a universal machine SHIMADZU 5000 applying force by means of tiebacks and elastomeric chains, for the use of the machine an accessory base and arm was designed to keep the test stable and standardized. Data were analyzed using GraphPad Prims 8 for Windows. Significance was predetermined at a =0.05. The Shapiro–Wilk test was used to test the data for normality. The data were not normally distributed and therefore the Kruskal Wallis test was used to determine differences between groups, followed by Dunn's multiple comparisons test.&#x0D; Results: The maximum forces obtained for the detachment of an orthodontic hook was up to 2.87kg which was recorded by the group of dotted hooks and with force applied with elastomeric chain and the one with the lowest force was 0.87kg with hooks only crimped. The tie backs showed a more controlled force in all groups and the groups with a “V stop” bend also showed the most stable tests and none displacement of the hook but more eviction and break of the hooks.&#x0D; Conclusions: In the study it was determined that the crimping method is not sufficient for the stability of the hook so pointing it or performing a V stop bend on the wire increases its stability before the maximum force of detachment and clinically gives advantages in the dental movement although it increases the consultation or laboratory time for its realization.

Comparison of Pericapsular Nerve Group (PENG) Block Versus Quadratus Lumborum (QL) Block for Analgesia After Primary Total Hip Arthroplasty Under Spinal Anesthesia: A Retrospective Study.

Total hip arthroplasty (THA) is one of the most common operative procedures performed. Controlling postoperative pain following THA remains a challenge due to the complex innervation of the hip joint and the recent desire to preserve motor function following nerve blockade. Several nerve block techniques have been used for THA in the past, but the quadratus lumborum (QL) block and the blockade of the pericapsular nerve group (PENG) have emerged as opiate-sparing regional anesthesia techniques that preserve motor function. To date, little data comparing thetwo block techniques exists. The purpose of our study was to compare outcomes following these techniques in patients undergoing primary THA. This retrospective analysis utilized data from three distinct groups who underwent primary THA at our institution: 45 patients who received PENG block, 38 patients who received QL block, and 77 control patients. Chart review analysis was performed by authorized personnel to obtain cumulative oral morphine equivalent(OME) data at 24 and 48 hours postoperatively (primary outcomes). In addition, visual analog pain scale (VAS) scores in the post-anesthesia care unit (PACU) and at 12, 24, and 48 hours, ambulation distance, and length of hospital stay data were obtained (secondary outcomes). Group comparisons were conducted using either analysis of variance (ANOVA) with Tukey's multiple comparison test for parametric data or Krustal-Wallis with Dunn's multiple comparison tests for nonparametric endpoints. This study found a statistically significant difference in cumulative OME usage across all groups at 24 and 48 hours. Significant difference in OMEs was found between QL and control and PENG and control; however, no difference was found in OMEs between PENG and QL groups at either time point. There was a statistically significant difference in VAS scores in the PACU across all groups; QL showed significantly lower VAS scores in the PACU compared to PENG and control, while PENG only showed significantly lower VAS scores compared to control. There was a statistically significant difference in VAS scores at 24 hours across all groups; however, only QL showed significantly lower VAS scores compared to control at 24 hours. QL was associated with a statistically significant increase in the length of hospital stay compared to PENG. This study showed no difference between OME usage in patients who received PENG or QL nerve blocks for primary THA. VAS scores were similar between groups with the exception of QL outperforming PENG in the PACU. Optimizing postoperative pain via multi-approach strategies should remain a priority for patients undergoing THA.Future research is warranted in order to provide guidance on best practice for these patients.

Gastric plication surgery changes gastrointestinal and metabolic parameters in an obesity-induced high-fat diet model.

Obesity treatment includes less invasive procedures such as gastric plication (GP) surgery; however, its effects on gastrointestinal (GI) motility parameters are underestimated. We aimed to verify the metabolic and gastrointestinal effects of GP surgery in the rat obesity model. A high-fat diet-induced obesity was used. Animals were allocated to four experimental groups: control sham (n = 6); control GP (n = 10); obese sham (n = 6); and obese GP (n = 10). Nutritional and murinometric parameters, gastric motility, glucose tolerance, histopathology, fat depots, leptin, and lipoproteins levels were evaluated 30 days after surgery. Data were analyzed by ANOVA followed by post Tukey or Kruskal-Wallis test followed by Dunn's multiple comparisons test. Gastric plication decreased leptin levels, feed efficiency, and body weight gain. GP does not improve lipid profile in obese animals and however, ameliorates glucose tolerance in control and obese rats. GP did not improve the gastric emptying time or normalize the frequency of contractions disturbed by obesity. Surgery provides a remodeling process in the mucosa and muscularis mucosa layers, evidenced by leukocyte infiltration mainly in the mucosa layer. Our study revealed the influence of the gastrointestinal tract on obesity is underestimated with pieces of evidence pointing out its important role as a target for surgical treatment.

Maxillary Sinus-Floor Augmentation by Porcine-Apatite Xenograft: A Prospective Case Series Study.

Bone substitutes sometimes are unsuccessful in replacing the autogenous bone graft, combining the advantages and disadvantages to achieve satisfactory results. The aim of this work was to clinically and histologically evaluate the outcome of porcine-apatite xenograft used to elevate the maxillary sinus floor in severe atrophy ridge. A two-stage crestal window sinus lift protocol was conducted in 24 patients with crestal bone ≤2mm. Highly porous porcine carbonate apatite moistened with saline solution was placed in the elevated sinus cavity as the sole grafting material. Bone core biopsies were taken at 6, 9 and 12 months after the sinus augmentation surgery at the time of implant placement. The treatment outcome was assessed using the μCT (micro computed tomogram) and histological analysis. Statistical analysis was performed using the nonparametric Kruskal-Wallis test, followed by the post-hoc Dunn multiple comparison test. At 6 months after implant placement, all implants achieved good primary stability (≥ 30 Ncm of insertion torque) and successfully osseointegrated. The residual graft amount (m±SE) was low (11.91±1.99%) at 6 months, and further decreased (6.11±2.64%) at 12 months after the sinus augmentation surgery. On the contrary, the amount of new bone detected was 18.94±4.08% at 6 months, and significantly (p<0.05) increased (40.16±5.27%) 12 months after sinus augmentation surgery. Histological assessment revealed existing of osteoclasts in resorbing the graft as well as the osteoblasts in forming the new bone. In the severely atrophic maxilla, the porcine-apatite xenograft promotes new bone formation while being slowly absorbed. In conclusion, within the limited sample size, the porcine-apatite xenograft seems to be a good material to be used as the graft material for crestal window sinus augmentation.

Curbside particulate matter and susceptibility to SARS-CoV-2 infection.

Biologic plausibility for the association between exposure to particulate matter (PM) less than 10 μm in aerodynamic diameter (PM10) and coronavirus disease 2019 (COVID-19) morbidity in epidemiologic studies has not been determined. The upregulation of angiotensin-converting enzyme 2 (ACE2), the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) entry receptor on host cells, by PM10 is a putative mechanism. We sought to assess the effect of PM10 on SARS-CoV-2 infection of cells invitro. PM10 from the curbside of London's Marylebone Road and from exhaust emissions was collected by cyclone. A549 cells, human primary nasal epithelial cells (HPNEpCs), SARS-CoV-2-susceptible Vero-E6 and Calu3 cells were cultured with PM10. ACE2 expression (as determined by median fluorescent intensity) was assessed by flow cytometry, and ACE2 mRNA transcript level was assessed by PCR. The role of oxidative stress was determined by N-acetyl cysteine. The cytopathic effect of SARS-CoV-2 (percentage of infection enhancement) and expression of SARS-CoV-2 genes' open reading frame (ORF) 1ab, S protein, and N protein (focus-forming units/mL) were assessed in Vero-E6 cells. Data were analyzed by either the Mann-Whitney U test or Kruskal-Wallis test with the Dunn multiple comparisons test. Curbside PM10 at concentrations of 10 μg/mL or more increased ACE2 expression in A549 cells (P= .0021). Both diesel PM10 and curbside PM10 in a concentration of 10 μg/mL increased ACE2 expression in HPNEpCs (P= .0022 and P= .0072, respectively). ACE2 expression simulated by curbside PM10 was attenuated by N-acetyl cysteine in HPNEpCs (P= .0464). Curbside PM10 increased ACE2 expression in Calu3 cells (P= .0256). In Vero-E6 cells, curbside PM10 increased ACE2 expression (P= .0079), ACE2 transcript level (P= .0079), SARS-CoV-2 cytopathic effect (P= .0002), and expression of the SARS-CoV-2 genes' ORF1ab, S protein, and N protein (P= .0079). Curbside PM10 increases susceptibility to SARS-COV-2 infection invitro.

Liraglutide modulates morpho-functional and inflammatory gastrointestinal responses in rats.

Obesity impairs homeostatic control of energy and is associated with chronic low-grade inflammation. Effects of glucagon-like peptide-1, the target in the gastrointestinal tract for anti-obesity drugs such as Liraglutide, were not properly associated with inflammation markers. This study investigated the effects of Liraglutide on metabolic and gastrointestinal parameters in a rat model of obesity. Twenty-six Wistar rats with obesity were randomly distributed to receive saline (n = 10), 400 μg (n = 8), or 1200 μg of Liraglutide/kg/day (n = 8), subcutaneously for 30 consecutive days, once a day. Weight gain, feeding efficiency, caloric consumption, gastric motility, adiposity, histomorphometric, murinometric, biochemical parameters and cytokines TNF-α and TGF-β1 in duodenal tissue were measured. Data were analysed by ANOVA, followed by Bonferroni post hoc or Kruskal-Wallis test, followed by Dunn's multiple comparison test. Liraglutide-treated animals had better feeding efficiency and higher caloric intake in a dose-dependent manner. Higher doses slowed gastric emptying and diminished the amplitude of gastric contractions. These effects were accompanied by decreases in intestinal muscle layer thickness and crypt depth. Liraglutide significantly reduced retroperitoneal and visceral white adipose tissue depots. High-dose treatment decreased levels of TNF-α and enhanced levels of TGF-β1 in duodenal tissue. Liraglutide treatment provided significant reductions in total cholesterol, triglyceride and hepatic transaminases. Liraglutide reduced fat accumulation, improved metabolic parameters and downregulated levels of inflammatory signalling in duodenal tissue. Liraglutide at high doses controlled obesity-related outcomes, and such effects seemed to be driven by its action on glucagon-like peptide-1 receptors in the gastrointestinal tract slowing gastric motility.

Changes in the Abundances of Cervical and Rectal Mycobiota during Chemoradiotherapy in Cervical Cancer

Globally, cervical cancer is the fourth most frequent cancer in women. The local and gut microbiomes of cervical cancer patients primarily consist of bacteria, viruses, and fungi. Bacterial composition has been previously associated with response to chemoradiotherapy (CRT) and patient outcome. Recently, our group has demonstrated that the HPV virome dynamically shifts during treatment and was associated with treatment response. Although connections between fungi and cervicovaginal health have been established, little is known about the fungal microbiome during treatment of cervical cancer. In this study, we sought to explore changes in fungal distribution throughout CRT for a cohort of cervical cancer patients. This study includes 57 patients diagnosed with cervical cancer at a single institution with samples collected throughout CRT timepoints: baseline, week 1, week 3, and week 5. 170 swab specimens were included in this analysis: 138 cervical swabs from 56 patients and 32 rectal swabs from 9 patients. Whole genome sequencing data was obtained from the swabs using the Illumina HiSeqX platform (2 × 150bp). Fungal reads were log transformed to reduce variability and skewness and normalized to the total library size resulting in log normalized fungal reads per million (RPM). Bacterial reads were normalized with the same methodology. Timepoint analysis was performed using Wilcoxon signed rank tests or Friedman tests (with Dunn's multiple comparisons test) when comparing two or more time points, respectively. All swab samples contained reads mapped to fungi. Of the 3.70 × 109 total reads across all sequenced samples, 19.2% did not map specifically to the human genome: 91.8% of these non-human reads could not be mapped to an individual microbial genome. Of the remaining 8.2% of non-human reads that mapped to a specific microbial genome (1.6% of total), 97.4% were classified as bacterial (1.5% of total), 0.71% as virus (0.011% of total), and 0.44% as fungal (0.0069% of total). Comparison of fungal RPM in the cervical and rectal microbiome revealed a significant decrease during treatment from baseline to week 5 (cervical, P = 0.0002; rectal, P = 0.0273). Distribution of bacterial reads exhibited similar trends as decreases were observed between baseline and week 5 for both cervical (P = 0.0116) and rectal (P = 0.0195) samples. Fungi to bacteria distribution ratios in the rectal microbiome revealed significant differences when comparing across all timepoints (P = 0.0041), baseline vs. week 1 (P = 0.0028), baseline vs. week 3 (P = 0.0389), and baseline vs. week 5 (P = 0.0113) with all three later timepoints higher relative to baseline. The distributions of cervical and gut fungal reads and their relationship to the bacteriome shift during CRT. Further investigation into characterizing fungi and their relationship with other microbiota will be valuable to understanding its potential associations with cervical cancer and treatment response.

Switching from Galenic to Advanced Dressings or Vacuum Assisted Closure Therapy Can Improve Quality of Life of Patients with Chronic Non-Responsive Pressure Skin Ulcers: Preliminary Data with Italian Translation of WOUND-Q.

Objective: A few studies have focused on the quality of life (QoL) of patients with chronic non-responsive pressure skin ulcers. The aim of this study was to assess how correct treatment (advanced wound care [AWC] dressings alone or vacuum assisted closure [VAC] therapy alone) changes the QoL of these patients. Approach: One hundred six patients with chronic non-responsive pressure skin ulcers, who had previously used galenic dressings, applied without proper therapeutic indication, were included in this study. We administered the WOUND-Q, at time 0 and after 1 month of appropriate therapy, to assess patient-reported outcome measures. Group 1 consisted of 30 patients treated with advanced dressings, Group 2: 22 patients treated with VAC therapy, and Group 3: 30 patients continuing conventional galenic dressings (Control group). Statistical analysis allowed us to analyze QoL changes over time and to compare WOUND-Q Group 1 and 2 deltas with those of Group 3. The study followed the STROBE statement. Results and Innovation: In all the scales evaluated (Assessment, Drainage, Smell, Life impact, Psychological, Social, Sleep and Dressing), there were significant improvements in mean values for Groups 1 and 2. Kruskal-Wallis tests with Dunn's multiple-comparisons tests and Brown-Forsythe and Welch Analysis of Variance tests demonstrated significant differences between deltas of Group 1 and Group 2 compared with those of Group 3 for most scales analyzed. Conclusions: Administration of the WOUND-Q demonstrated that the application of advanced dressings alone or VAC therapy alone positively affects the QoL of patients with chronic nonresponsive pressure wounds, in comparison with galenic dressings alone. The WOUND-Q has been shown to be a valid tool in studying changes in QoL of these patients.

Sceletium tortuosum-derived mesembrine significantly contributes to the anxiolytic effect of Zembrin®, but its anti-depressant effect may require synergy of multiple plant constituents

Ethnopharmacology relevanceSceletium tortuosum (L.) N.E.Br. (ST) is an alkaloid-rich succulent plant with various mechanisms of action that infer psychotropic effects. These actions correlate with clinical evidence suggesting efficacy in the treatment of depression and anxiety, in line with its use by indigenous populations. Its low side effect profile suggests potential of ST to improve the overall wellbeing and compliance of millions of patients that experience severe side effects and/or do not respond to current prescription medication. However, to elucidate specific physiological effects of ST extracts, it is necessary to first understand which of its constituents are the major contributors to beneficial effects demonstrated for ST in this context. Aim of the studyTo determine an anxiolytic- and antidepressant-like effective concentration of a ST extract by means of a dose response in zebrafish (ZF) larvae, and to assess relative contributions of equivalent concentrations of isolated alkaloids contained in the effective concentration(s). Materials and methodsA dose response study employing a light-dark transition test (LDTT) was done in ZF larvae (<5 days post fertilization) to track locomotor activity in terms of anxiety-like (hyperlocomotion) and depression-like (hypolocomotion) behaviour. Larvae were treated for 1 h directly before the LDTT with escalating concentrations of a ST extract commercially known as Zembrin® (Zem) ranging from 0.25 to 500 μg/mL and compared to an untreated control group (n = 12 per treatment concentration). LDTT was repeated after 24 h to evaluate long-term exposure toxicity. The concentration that best attenuated hyperlocomotion during the dark phase following light-dark transition was identified as the anxiolytic-like concentration. This concentration, plus one higher and one lower concentration, were used for subsequent tests. The percentage content of each alkaloid (mesembrine, mesembrenone, mesembrenol, and mesembranol) in these concentrations were calculated and applied to additional larvae to identify the most effective anxiolytic-like alkaloid in the LDTT. To identify antidepressant-like therapeutic concentration and equivalent alkaloid concentration, the same treatment concentrations were tested in larvae (n = 12 per treatment concentration) pre-exposed to reserpine for 24 h. Depending on normality of data distribution, Brown-Forsythe and Welch, or Kruskal-Wallis ANOVA were used, with Dunnett or Dunn's multiple comparisons tests. ResultsOnly the extreme concentration of Zem (500 μg/mL) elicited toxicity after treatment for 24 h. Zem 12.5 μg/mL was the most effective anxiolytic-like concentration as it significantly decreased locomotor activity (P = 0.05) in the LDTT. Low (5 μg/mL), optimal (12.5 μg/mL) and high (25 μg/mL) Zem concentrations, as well as treatment solutions of single alkaloids (mesembrine, mesembrenone, mesembranol and mesembrenol), prepared to contain equivalent concentrations of each major alkaloid contained within these three concentrations of Zem, were tested further. Only mesembrine concentrations equal to that contained within the optimal and high dose of Zem (12.5 and 25 μg/mL) showed significant anxiolytic-like effects (P < 0.05). Only the highest Zem concentration (25 μg/mL) reversed the effects of reserpine - indicating antidepressant-like properties (P < 0.05) - while isolated alkaloids failed to induce such effects when administered in isolation. ConclusionsCurrent data provide evidence of both anxiolytic- and antidepressant-like effect of whole extract of Zem, with relatively higher concentrations required to achieve antidepressant-like effect. Of all alkaloids assessed, only mesembrine contributed significantly to the anxiolytic-like effects of Zem. No alkaloid alone could be pinpointed as a contributor to the antidepressant-like activity observed for higher concentration Zem. This may be due to synergistic effects of the alkaloids or may be due to other components not tested here. Current data warrants further investigation into mechanisms of action, as well as potential synergy, of ST alkaloids in suitable mammalian in vivo models.

Papiller Tiroid Karsinomada Tümör Büyüklüğü ve Metastazın Belirticisi Olarak Nötrofil Lenfosit Oranı

Aim: Inflammation plays a critical role in many cancer features such as tumor development and&#x0D; progression. Recently, the neutrophil-lymphocyte ratio (NLR) has been evaluated as a simple and valid&#x0D; systematic marker of inflammatory response. The aim of this study was to investigate the prognostic&#x0D; value of the preoperative neutrophil / lymphocyte ratio.&#x0D; Material and Methods: In this study, archive files of 259 adult cases were evaluated retrospectively.&#x0D; Kolmogorov Smirnov test, Mann Whitney U Test, Kruskal Wallis and Dunn multiple comparison tests&#x0D; were used in the statistical analysis.&#x0D; Results: A statistical correlation was found between the neutrophil/lymphocyte ratio and T staging,&#x0D; lymph node and distant metastases (p2.0906&gt;1,644, the sensitivity to predict papillary&#x0D; thyroid cancers larger than 1 cm, lymph node metastasis and distant metastasis was found to be 85.4%,&#x0D; 73.8%, and 96% respectively.&#x0D; Conclusion: Neutrophil/lymphocyte ratio is associated with tumor size and presence of metastasis.&#x0D; The neutrophil/lymphocyte ratio may help us predict the size of the tumor, lymph node involvement, and&#x0D; distant metastasis when the right cut-off points are established.

Effects of Moringa oleifera Seed Oil on Cultured Human Sebocytes In Vitro and Comparison with Other Oil Types.

The seeds of Moringa oleifera (horseradish tree) contain about 40% of one of the most stable vegetable oils (Moringa seed oil). Therefore, the effects of Moringa seed oil on human SZ95 sebocytes were investigated and were compared with other vegetable oils. Immortalized human SZ95 sebocytes were treated with Moringa seed oil, olive oil, sunflower oil, linoleic acid and oleic acid. Lipid droplets were visualized by Nile Red fluorescence, cytokine secretion via cytokine antibody array, cell viability with calcein-AM fluorescence, cell proliferation by real-time cell analysis, and fatty acids were determined by gas chromatography. Statistical analysis was performed by the Wilcoxon matched-pairs signed-rank test, the Kruskal-Wallis test and Dunn's multiple comparison test. The vegetable oils tested stimulated sebaceous lipogenesis in a concentration-dependent manner. The pattern of lipogenesis induced by Moringa seed oil and olive oil was comparable to lipogenesis stimulated by oleic acid with also similar fatty acid secretion and cell proliferation patterns. Sunflower oil induced the strongest lipogenesis among the tested oils and fatty acids. There were also differences in cytokine secretion, induced by treatment with different oils. Moringa seed oil and olive oil, but not sunflower oil, reduced the secretion of pro-inflammatory cytokines, in comparison to untreated cells, and exhibited a low n-6/n-3 index. The anti-inflammatory oleic acid detected in Moringa seed oil probably contributed to its low levels of pro-inflammatory cytokine secretion and induction of cell death. In conclusion, Moringa seed oil seems to concentrate several desired oil properties on sebocytes, such as high content level of the anti-inflammatory fatty acid oleic acid, induction of similar cell proliferation and lipogenesis patterns compared with oleic acid, lipogenesis with a low n-6/n-3 index and inhibition of secretion of pro-inflammatory cytokines. These properties characterize Moringa seed oil as an interesting nutrient and a promising ingredient in skin care products.

Influence of intravenous 10% amino acids infusion on serum albumin concentration in hypoalbuminemic dogs.

To evaluate the effect of parenteral amino acid application in hospitalized hypoalbuminemic dogs. Medical records of client-owned hypoalbuminemic dogs (albumin ≤ 25 g/L) were analyzed. Dogs receiving amino acids for only 1-2 days, receiving transfusions or surgery, or <6 months of age were excluded. Dogs were grouped as those receiving intravenous amino acids (AA, 80 dogs) over 3 days and longer, and those without additional amino acid treatment (CON, 78 dogs). Duration of hospitalization, albumin, and total protein concentrations were compared between groups by Mann-Whitney U test. Course of albumin and total protein concentration was evaluated by Friedman test and Dunn's multiple comparison test. Significance was set to p ≤ 0.05. Dogs in group AA received 10% amino acid solution intravenously over median 4 days (3-11 days). No significant differences regarding survival and adverse effects were observed between groups. Dogs of group AA had significantly longer duration of hospitalization (median 8 days; 3-33 days) compared to group CON dogs (median 6 days, 3-24 days; p < 0.001). Initial albumin concentration was lower in group AA compared to CON (p < 0.001). This difference was no longer present on day 2 (p = 0.134). Intravenous application of 10% amino acid solution in hypoalbuminemic dogs can improve albumin concentration after 2 days, but does not influence outcome.