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Examining the subchronic (28-day) effects of aqueous Cd-BaP co-exposure on detoxification capacity and cardiac function in adult zebrafish (Danio rerio)

The present study aimed to examine the effects of environmentally relevant concentrations of cadmium (Cd) and Benzo[a]Pyrene (BaP) in the adult zebrafish (Danio rerio). To this end, fish were exposed to either 1 or 10 μg/L Cd or 0.1 or 1 μg/L BaP in isolation, or a co-exposure containing a mixture of the two toxicants. Our results showed extensive modulation of the expression of key antioxidant genes (GPx, SOD1, catalase), detoxifying genes (MT1, MT2, CYP1A1) and a stress biomarker (HSP70) differing between control, single toxicant groups and co-exposure groups. We additionally carried out histopathological analysis of the gills, liver, and hearts of exposed animals, noting no differences in tissue necrosis or apoptosis. Finally, we carried out ultrasonographic analysis of cardiac function, noting a significant decrease of E-wave peak velocity and end diastolic volume in exposed fish. This in turn was accompanied by a decrease in stroke volume and ejection fraction, but not cardiac output in co-exposed fish. The present study is the first to demonstrate that a subchronic aqueous exposure to a Cd-BaP mixture can extensively modulate detoxification capacity and cardiac function in adult zebrafish in a tissue-specific manner.

Defining Mitochondrial Cristae Morphology Changes Induced by Aging in Brown Adipose Tissue.

Mitochondria are required for energy production and even give brown adipose tissue (BAT) its characteristic color due to their high iron content and abundance. The physiological function and bioenergetic capacity of mitochondria are connected to the structure, folding, and organization of its inner-membrane cristae. During the aging process, mitochondrial dysfunction is observed, and the regulatory balance of mitochondrial dynamics is often disrupted, leading to increased mitochondrial fragmentation in aging cells. Therefore, it is hypothesized that significant morphological changes in BAT mitochondria and cristae will be present with aging. A quantitative 3D electron microscopy approach is developed to map cristae network organization in mouse BAT to test this hypothesis. Using this methodology, the 3D morphology of mitochondrial cristae is investigated in adult (3-month) and aged (2-year) murine BAT tissue via serial block face-scanning electron microscopy (SBF-SEM) and 3D reconstruction software for manual segmentation, analysis, and quantification. Upon investigation, an increase is found in mitochondrial volume, surface area, and complexity and decreased sphericity in aged BAT, alongside significant decreases in cristae volume, area, perimeter, and score. Overall, these data define the nature of the mitochondrial structure in murine BAT across aging.

Discovery and optimization of 2,3-diaryl-1,3-thiazolidin-4-one-based derivatives as potent and selective cytotoxic agents with anti-inflammatory activity

Several studies have indicated the potential therapeutic outcomes of combining selective COX-2 inhibitors with tubulin-targeting anticancer agents. In the current study, a novel series of thiazolidin-4-one-based derivatives (7a–q) was designed by merging the pharmacophoric features of some COXs inhibitors and tubulin polymerization inhibitors. Compounds 7a–q were synthesized and evaluated for their cytotoxic activity against MCF7, HT29, and A2780 cancer cell lines (IC50 = 0.02–17.02 μM). The cytotoxicity of 7a–q was also assessed against normal MRC5 cells (IC50 = 0.47–13.46 μM). Compounds 7c, 7i, and 7j, the most active in the MTT assay, significantly reduced the number of HT29 colonies compared to the control. Compounds 7c, 7i, and 7j also induced significant decreases in the tumor volumes and masses in Ehrlich solid carcinoma-bearing mice compared to the control. The three compounds also exhibited significant anti-HT29 migration activity in the wound-healing assay. They have also induced cell cycle arrest in HT29 cells at the S and G2/M phases. In addition, they induced significant increases in both early and late apoptotic events in HT29 cells compared to the control, where 7j showed the highest effect. On the other hand, compound 7j (1 μM) displayed weak inhibitory activity against tubulin polymerization compared to colchicine (3 μM). On the other hand, compounds 7a–q inhibited the activity of COX-2 (IC50 = 0.42–29.11 μM) compared to celecoxib (IC50 = 0.86 μM). In addition, 7c, 7i, and 7j showed moderate inhibition of inflammation in rats compared to indomethacin, with better GIT safety profiles. Molecular docking analysis revealed that 7c, 7i, and 7j have higher binding free energies towards COX-2 than COX-1. These above results suggested that 7j could serve as a potential anticancer drug candidate.

Bilateral Wunderlich syndrome causing Page kidney during pregnancy: a rare case report.

The patient presented with complaints of left flank pain and breathlessness. After stabilization, an emergency lower cesarean delivery was performed, and a percutaneous drainage procedure was carried out to alleviate the compression on the left kidney. The patient was treated with blood transfusion, methyldopa, and perindopril. Follow-up examinations performed 3 months later revealed a significant decrease in fluid volume surrounding the left kidney. Lenk's triad provides the primary description of the classical manifestations of this syndrome. Some instances have been connected to the Page kidney phenomenon. The relationship between pregnancy and Wunderlich syndrome has not been extensively studied, primarily because the symptoms can resemble other complications related to pregnancy. Due to the scarcity of evidence in the literature, there is no definitive guideline for managing Wunderlich syndrome during pregnancy. Consequently, each patient is treated on an individual basis. Conservative treatment is recommended once malignancy has been ruled out. The case highlights the importance of considering Wunderlich syndrome as a differential diagnosis in pregnant patients with abdominal or flank pain, a palpable mass, and hypovolemia. Furthermore, the case illustrates the successful management of Wunderlich syndrome during pregnancy.

Association between Childhood Asthma Control Test scores and lung pathophysiologic indicators in longitudinal measurements.

Childhood Asthma Control Test (C-ACT) is a well-validated questionnaire for asthma controls among 4-11 years old children. This study aims to examine if longitudinal C-ACT score changes could also reflect lung pathophysiologic changes. Thirty-seven children (43% female) aged 5 to 10 years old with mild or moderate asthma were followed up for 6 weeks with bi-weekly assessments of C-ACT, airway mechanics, lung function and respiratory inflammation. Associations of longitudinal changes in C-ACT score with lung pathophysiologic indicators were evaluated using linear mixed-effects models. A two-point worsening of total C-ACT score (sum of child and caregiver-reported) was associated with significant decreases in forced expiratory volume during the 1st second (FEV1) by 1.7% (P=0.04) and forced vital capacity (FVC) by 1.6% (P=0.01) and increased total airway resistance [airway resistance at 5 Hz (R5)] by 3.8% (P=0.05). A two-point worsening in child-reported score was significantly associated with 3.1% and 2.5% reductions in FEV1 and FVC, respectively, and with increases in R5 by 6.5% and large airway resistance [airway resistance at 20 Hz (R20)] by 5.5%. In contrast, a two-point worsening of caregiver-reported score was associated with none of the concurrent lung pathophysiologic measurements. Worsening of total C-ACT score was significantly associated with increased respiratory inflammation [fractional exhaled nitric oxide (FeNO)] in a subset (n=23) of children without eosinophilic airway inflammation. C-ACT scores were associated with none of the small airway measures. In children with mild or moderate asthma, longitudinal C-ACT score changes could reflect acute changes in large airway resistance and lung function. Measures of small airway physiology would provide valuable complementary information for asthma control. Asthma phenotype may affect whether C-ACT score could reflect respiratory inflammation.

Application of a Negative Intrauterine Pressure Suction Device for Prophylactic Management of Atonic Postpartum Hemorrhage: A Quality Improvement Study.

Postpartum hemorrhage (PPH) is the leading cause of maternal mortality worldwide. PPH-preventing interventions need to be prioritized and can be integrated with conventional methods of PPH prevention. The introduction of negative intrauterine pressure using a suction cannula can be one of the cheapest modalities to decrease PPH secondary to uterine atonicity. This method has brought a renaissance to practical obstetrics in low-middle income countries (LMIC), where the cost and availability of uterotonics are major health issues. It was a prospective quality improvement (QI) study conducted in the labor and delivery wards of a tertiary care medical institute and teaching center over the duration of one year. We aimed to assess the decrease in the incidence of atonic PPH with a negative intrauterine pressure suction device (NIPSD) integrated with active management of the third stage of labor (AMTSL) in the prevention of atonic PPH following normal vaginal delivery in low-risk antenatal women. In the initial six months, routine AMTSL was instituted for all consenting women (group 1). In the next six months, NIPSD was integrated with AMTSL (group 2). Data pertaining to the amount of blood loss, the incidence of primary PPH, uterine tone, fall in hemoglobin and hematocrit levels post-delivery, need for blood transfusion, and doctor and patient satisfaction were tabulated for all patients. A total of 1324 consenting women were eligible for enrollment during the study time frame. In the initial six months (baseline period, group 1), 715 participants were subjected to routine AMTSL in the third stage of labor. During the intervention phase (group 2), 609 parturient women were recruited. There was no significant difference in baseline parameters between the two groups. With the introduction of NIPSD to routine AMTSL, there was a significant decrease in the average volume of blood loss during vaginal delivery (group 1 = 389.45+65.42 ml, group 2 = 216.66+34.27 ml; p-value = 0.012). The incidence of atonic PPH was reduced by more than 75% (group 1 = 13 women, group 2 = 3 women; p-value = 0.001) after the introduction of NIPSD complementing routine AMTSL. The introduction of NIPSD has also been instrumental in reducing the cost burden on patient and hospital expenditures. The net benefit of its introduction resulted in a reduction of the overall cost burden of blood transfusions by around 70%. PPH is a public health problem, and measures to reduce PPH must be implemented to decrease this health burden. In countries with low resources, complementing routine AMTSL with NIPSD can be instrumental in decreasing the incidence of PPH. Considering its cost-effectiveness and reusability, LMIC can adopt NIPSD as a routine measure in all vaginal deliveries.

Brain MRI segmentation of Zika-Exposed normocephalic infants shows smaller amygdala volumes.

Infants with congenital Zika syndrome (CZS) are known to exhibit characteristic brain abnormalities. However, the brain anatomy of Zika virus (ZIKV)-exposed infants, born to ZIKV-positive pregnant mothers, who have normal-appearing head characteristics at birth, has not been evaluated in detail. The aim of this prospective study is, therefore, to compare the cortical and subcortical brain structural volume measures of ZIKV-exposed normocephalic infants to age-matched healthy controls. We acquired T2-MRI of the whole brain of 18 ZIKV-exposed infants and 8 normal controls on a 3T MRI scanner. The MR images were auto-segmented into eight tissue types and anatomical regions including the white matter, cortical grey matter, deep nuclear grey matter, corticospinal fluid, amygdala, hippocampus, cerebellum, and brainstem. We determined the volumes of these regions and calculated the total intracranial volume (TICV) and head circumference (HC). We compared these measurements between the two groups, controlling for infant age at scan, by first comparing results for all subjects in each group and secondly performing a subgroup analysis for subjects below 8 weeks of postnatal age at scan. ZIKV-exposed infants demonstrated a significant decrease in amygdala volume compared to the control group in both the group and subgroup comparisons (p<0.05, corrected for multiple comparisons using FDR). No significant volume differences were observed in TICV, HC, or any specific brain tissue structures or regions. Study limitations include small sample size, which was due to abrupt cessation of extramural funding as the ZIKV epidemic waned. ZIKV-exposed infants exhibited smaller volumes in the amygdala, a brain region primarily involved in emotional and behavioral processing. This brain MRI finding may lead to poorer behavioral outcomes and warrants long-term monitoring of pediatric cases of infants with gestational exposure to Zika virus as well as other neurotropic viruses.

Cortical thickness, gray-white matter contrast, and intracortical myelin in first-episode schizophrenia patients treated with long-acting paliperidone palmitate versus oral antipsychotics

This longitudinal study evaluated the cortical thickness, gray-to-white matter contrast (GWC), and frontal lobe intracortical myelin (ICM) volume in first-episode schizophrenia (FES) patients treated with oral antipsychotics (OAP) versus a long-acting injectable antipsychotic, paliperidone palmitate (PP). 2D proton density and inversion recovery images, and 3D T1-weighted MPRAGE images were acquired at 3T from 68 FES patients in a randomized clinical trial with PP vs OAP. At baseline, no differences in GWC and ICM were observed between FES patients and HCs, but the thickness of the left precuneus, the right transverse temporal gyrus, and the bilateral superior temporal gyri was found to be thinner in FES patients relative to HCs. Following 9 months of antipsychotics, OAP treatment, compared to PP treatment, resulted in a more widespread cortical thickness reduction including the right lateral occipital and orbitofrontal gyri. No significant ICM and GWC changes were observed in the PP group, whereas OAP treatment led to a significant ICM volume decrease and GWC increase. A negative correlation was found between ICM changes and GWC changes within multiple frontal regions after 9 months of OAP treatment. These preliminary findings suggest that PP treatment might aid preservation of brain morphology.

Assessing very advanced HIV disease in adolescent girls and young women

Background: South Africa has the largest HIV epidemic globally, with ~7.5 million people living with HIV in 2021. Adolescent girls (AG) and young women (YW), aged 15–19 years and 20–24 years, are twice as likely to be living with HIV as their male counterparts. The national HIV prevalence for young women was 9.1% (2021), with limited data on disease severity.Objectives: This study assessed very advanced HIV disease (CD4 100 cells/μL) in adolescent girls and young women (AGYW) in South Africa.Method: A retrospective descriptive study analysed data collated from the National Health Laboratory Service database for 2017 to 2021 calendar years for AGYW. National and provincial specimen volumes, the percentage of tests with a CD4 100 cells/μL and ≥ 100 cells/μL, and the median and interquartile ranges, were calculated. Logistic regression determined the odds ratio for a CD4 100 cells/μL, controlling for age category.Results: Data for 1 199 010 CD4 specimens indicated a significant decrease in volumes of 34% from 287 410 (2017) to 189 533 (2021). The percentage of samples with a count 100 cells/μL ranged from 4.9% to 5.2% for YW versus 5.6% to 6.1% for AG. Provincial data for a CD4 count 100 cells/μL ranged between 4.5% and 8.3% in AG and 3.6% to 6.3% for YW. Logistic regression indicated a 24% higher likelihood for AG having a CD4 count 100 cells/μL.Conclusion: The study reported a higher proportion of very advanced HIV disease for AG versus YW nationally, with provincial disparity needing further analysis.

Comparative study of anatomical features of primary and accessory maxillary ostia between patients withobstructive sleep apnea and healthy controls.

The purpose of this study was to examine how the size and shape of the maxillary sinus and its ostia (the primary maxillary ostium and accessory maxillary ostium) relate to each other in patients with OSAusing computed tomography (CT) scans. Additionally, the study aimed toexplore whether or not obstructive sleep apnea (OSA) had an effect on these structures. CT images of patients diagnosed with OSAS and healthy participantswere evaluated tocompare the patency, location, dimension, and presence of PMOs and AMOs using the Mann-Whitney U, Student t, and chi-square tests. Also, intragroup correlations were analyzed by Spearman's correlation test. Among 139 patients with OSA and healthy controls, there were significant variations in the average length (p = 0.001) and width (p = 0.008) of PMOs among the study groups. The mean maxillary sinus volume was significantly decreased in the OSA group (p = 0.001). A significant decrease in the maxillary sinus volume was observed in the OSA group (p = 0.001). In the OSA group, a significant correlation was observed between PMO obstruction and the presence of AMO (p = 0.004). The healthy group had significant correlations (r = 0.755, p = 0.000) between the vertical height and the distance between PMO and the maxillary sinus floor. Correlation analyses revealed positive, strong correlations between study variables such as the mean length and width of AMO and the vertical height of the maxillary sinus (r = 0.566, p = 0.000) in the OSA group. The current study indicated significant differences in sinus volume, PMO occlusion, and AMO-related dimensions between patientswith OSA and healthy controls.

Partial vasopressin 1a receptor agonism reduces portal hypertension and hyperaldosteronism and induces a powerful diuretic and natriuretic effect in rats with cirrhosis and ascites

The vasopressin system has emerged as a therapeutic focus for lowering portal hypertension and reducing splanchnic vasodilation in patients with refractory ascites. Clinically available vasopressin agonists are limited by preferential selectivity for V1 receptors that also have steep concentration–response curves with potential risks of excess vasoconstriction and/or complete antidiuretic effects. OCE-205 is a novel, selective, partial V1a receptor agonist with mixed agonist/antagonist activity and no V2 receptor activation at therapeutic doses. We carried out two studies assessing the in vivo effects of OCE-205 in different rat models of cirrhosis and ascites. In a carbon tetrachloride rat cirrhosis model, OCE-205 administration produced a marked reduction in portal hypertension and hyperaldosteronism, along with robust diuretic and natriuretic effects. These effects were accompanied by marked decreases in ascites volume, with three of five animals experiencing total mobilization of ascites. There was no evidence of fluid overload or sodium or water retention, confirming OCE-205′s lack of V2 receptor activity. In a second, corroborative study using a bile duct ligation rat model of ascites, OCE-205 produced significant decreases in ascites volume and body weight and a significant increase in urine volume versus vehicle. Urine sodium excretion increased significantly after the first administration of OCE-205 relative to vehicle; however, repeat administration over 5 days did not lead to hyponatremia. Thus, in separate in vivo models, the mixed agonist/antagonist OCE-205 demonstrated relevant and expected endpoint findings consistent with its known mechanism of action and in vitro pharmacology without apparent unwanted effects or nonspecific toxicities.

Computational fluid dynamics can detect changes in airway resistance for patients after COVID-19 infection

Infection with COVID-19 can cause severe complication in the respiratory system, which may be related to increased respiratory resistance. Computational fluid dynamics(CFD) was used in this study to calculate the airway resistance based on the airway anatomy and a common air flowrate. The correlation between airway resistance and COVID-19 prognosis was then investigated. A total of 23 COVID-19 patients with 54 CT scans were grouped into the good prognosis and bad prognosis group based on whether the CT scan shows significant decrease in the pneumonia volume after one week treatment and retrospectively analyzed. A baseline group of 8 healthy people with the same age and gender ratio is enrolled for comparison. Results show that the airway resistance at admission is significantly higher for COVID-19 patients with poor prognosis than those with good prognosis and the baseline(0.063 ± 0.055 vs 0.029 ± 0.011 vs 0.017 ± 0.006 Pa/(ml/s),p = 0.01). In the left superior lobe (r = 0.3974,p = 0.01),left inferior lobe (r = 0.4843,p < 0.01), the right inferior lobe (r = 0.5298,p < 0.0001), the airway resistance was significantly correlated with the degree of pneumonia infection. It is concluded that for COVID-19 patients’, airway resistance at admission is closely associated with their prognosis, and has the clinical potential to be used as an index for patients’ diagnosis.

Impact of COVID-19 Pandemic on Pathology Residents/Trainees in North America: A Survey-Based Study.

Background The COVID-19 pandemic has had a significant impact on resident training and education in the field of Pathology. This study aims to identify the tangible effects and resultant changes in education for Pathology trainees that have resulted from the pandemic. Design An electronic survey regarding Pathology trainee perceptions and experiences in relation to COVID-19 was created via Google Forms. The questionnaire was distributed to the pathology trainees via Twitter and email. The survey was also shared with all Pathology residency program coordinators across the USA and Canada. Results One hundred forty-five trainees responded to the questionnaire. 37.6% reported a significant decrease in specimen volume, whereas 43.3% reported a slight decrease in specimen volume. 18.3% reported the cancellation of educational lectures before shifting to a virtual platform for didactic purposes. However, 74.6% reported shifting all educational activities to virtual platforms. 35% cited cancellations of grand rounds, whereas 18.2% reported cancellations of grand rounds led by guest speakers.53.5% took COVID-19 tests, and 22.7% were quarantined. 100% reported a change in sign-out culture. Conclusions This pandemic has significantly impacted pathology training in various aspects, including training, education, and well-being. Residents harbored anxiety and stress regarding board exam delays or uncertainties, inadequate exam preparation time, family separation, and compromised safety. The exact quantification of educational loss varied from program to program. A significant decrease in specimen volume and detrimental changes in sign-out culture are indicators of compromised resident education due to the pandemic. This pandemic has extended the use of digital pathology and virtual platforms to a higher extent. Free virtual educational resources provided by various pathology organizations were critically important interventions during this pandemic, contributing to resident education. The pandemic has shown that developing a comprehensive infrastructure to overcome the loss of educational opportunities is of paramount importance to alleviate stress and anxiety among trainees.

Evaluation of biogas production rate and leachate treatment in Landfill through a water-energy nexus framework for integrated waste management

The aim of this study was to investigate the simultaneous biogas generation and leachate treatment using municipal waste and its polluted leachate at Mashhad landfill in northeast Iran. The research focused on examining the kinetic model of CH4, CO2, CO, H2S and O2 production with and without leachate recirculation (LR) through control/test wells. The findings from both wells showed an increase in logarithmic CH4 production rate, with the coefficient related to the rate of increase in methane concentration ranging from 0/52-0/64 in the control well and 0/47-0/55 in the test well, respectively. Under LR conditions, it was observed that the CH4 production rate was slower, taking an average of 120 minutes to reach 50% concentration, compared to just 15 minutes without LR. Using first-order equations, the CH4 production coefficients were measured to be 2/17 h−1 and 0/9 h−1 for the control and test wells, respectively. The analysis of recirculated leachate revealed a significant decrease (∼30%) in the total volume of leachate with 72% COD removal, which could help manage overloaded leachate problems in the landfill. The COD removal coefficient was found to be 0/036 day−1 in the control well, whereas the test well with leachate recirculation showed a more rapid decrease from 50 g.l−1 to about 14 g.l−1 with a removal coefficient of 0/012 day−1, three times higher than the control well. Additionally, nitrogen content analysis indicated that although the amount of ammonia content increased with LR, the increase was relatively low in comparison to conditions without LR, equivalent to 1394 ppm and 1000 ppm in control and test wells, respectively. This study aligns with the water-energy-nexus concept by offering a sustainable solution for waste management and energy generation, while also addressing water management challenges associated with landfill operations.

Decreased gray matter volume in regions associated with affective pain processing in unmedicated individuals with nonsuicidal self-injury

Nonsuicidal self-injury (NSSI) has been consistently associated with a reduced aversion to physical pain. Yet, little research has been done to investigate the brain structures related to pain in individuals with NSSI. This study examined gray matter volume patterns of pain processing regions in participants engaging in NSSI (n = 63) and age-, sex-, and handedness-matched healthy controls (n = 63). Voxel-based morphometry was performed to explore gray matter volume in regions of interest (ROIs) and partial correlation analyses were conducted to identify their associations with the frequency, versatility, duration, functions, and pain intensity of self-injury. As a result, significant volume decreases were found in the right anterior insula, bilateral secondary somatosensory cortex (SII), and left inferior frontal gyrus. Moreover, individuals with smaller anterior insula and SII volume showed a higher likelihood of endorsing affect-regulation and sensation-seeking functions of NSSI, as well as engaging in self-injury with a greater perceived intensity of pain. Our results provide the first empirical evidence that individuals with NSSI may exhibit distinct characteristics in brain regions associated with the affective component of pain processing. These neurobiological changes may be associated with their maladaptive response to noxious and painful NSSI experiences.

Evaluation of hemodynamics in vertebral arteries in case of herniated cervical intervertebral discs using functional tests

Background. Degenerative changes of the vertebral-motor segment occupy an important place among the causes of cervicogenic headache, neck pain with radiation to the shoulder and arm, noise in the head, dizziness. The same symptoms are often found in vertebral artery syndrome, which is a set of disorders of vertebral-basilar dynamics. Dopplerography makes it possible to obtain quantitative parameters of blood flow in the vertebral arteries, thereby assessing the level of pathological changes in blood flow.&#x0D; Purpose. Dopplerographic assessment of blood flow parameters in vertebral arteries in patients with herniated cervical intervertebral discs using functional tests.&#x0D; Materials and methods. An analysis of the results of dopplerography of the vertebral arteries in 42 young patients with herniated cervical intervertebral discs was carried out. Peak systolic velocity (Vs), end-diastolic velocity (Vd), indices of peripheral resistance (RI) and pulsatility (PI), minute volume of blood flow (HOK – Vvol) in the second segment of the VA at the C2-C3 level were determined at functional prob.&#x0D; Results and discussion. With a left-sided hernia, the value of Vs in the left VA during contralateral head rotation was 34.1 ± 2.9 cm/s, RI – 0.71 ± 0.03, PI – 1.04 ± 0.06, HOC – 85 ± 9 ml/min, and in the comparison group – 45.3 ± 3.8 cm/s, 0.59 ± 0.02, 0.85 ± 0.04, 118±13 ml/min, respectively. In patients with a right-sided hernia, Vs in the right VA during contralateral head rotation was 32.6 ± 3.2 cm/s, RI – 0.72 ± 0.03, PI – 1.03 ± 0.06, COC – 83 ± 8 ml/min, and in the comparison group – 44.8 ± 4.1 cm/s, 0.60 ± 0.02, 0.87 ± 0.04, 117 ± 12 ml/min, respectively. The difference between Doppler blood flow parameters obtained during contralateral head rotation in patients with disc herniation and the comparison group (persons without disc herniation) was significant (P &lt; 0.05).&#x0D; Conclusion.Hemodynamically significant disruption of blood flow in the vertebral artery occurs when the paramedian and posterolateral hernia is localized on the side of the same name during head rotation to the opposite side. These violations consist in a significant decrease in systolic speed and minute volume of blood flow, in an increase in indices of resistance and pulsatility compared to persons without disc herniation.

Nanoliposomal VEGF-R2 peptide vaccine acts as an effective therapeutic vaccine in a murine B16F10 model of melanoma

BackgroundThe vascular endothelial growth factor receptor-2 (VEGFR-2) plays an important role in melanoma development and progression. Peptide vaccines have shown great potential in cancer immunotherapy by targeting VEGFR-2 as a tumor-associated antigen and boosting the immune response against both tumor cells and tumor endothelial cells. Despite this, the low efficiency of peptide vaccines has resulted in moderate therapeutic results in the majority of studies. Enhancing the delivery of peptide vaccines using nanoliposomes is an important strategy for improving the efficacy of peptide vaccines. In this regard, we designed VEGFR-2-derived peptides restricted to both mouse MHC I and human HLA-A*02:01 using immunoinformatic tools and selected three peptides representing the highest binding affinities. The peptides were encapsulated in nanoliposomal formulations using the film method plus bath sonication and characterized for their colloidal properties.ResultsThe mean diameter of peptide-encapsulated liposomes was around 135 nm, zeta potential of − 17 mV, and encapsulation efficiency of approximately 70%. Then, vaccine formulations were injected subcutaneously in mice bearing B16F10-established melanoma tumors and their efficiency in triggering immunological, and anti-tumor responses was evaluated. Our results represented that one of our designed VEGFR-2 peptide nanoliposomal formulations (Lip-V1) substantially activated CD4+ (p < 0.0001) and CD8+ (P < 0.001) T cell responses and significantly boosted the production of IFN-γ (P < 0.0001) and IL-4 (P < 0.0001). Furthermore, this formulation led to a significant decrease in tumor volume (P < 0.0001) and enhanced survival (P < 0.05) in mice.ConclusionOur findings suggest that the nanoliposomal formulation containing VEGFR-2 peptides could be a promising therapeutic vaccination approach capable of eliciting strong antigen-specific immunologic and anti-tumor responses.

Quantitative analysis and correlative evaluation of video-oculography, micro-computed tomography, and histopathology in Pendrin-null mice

Patients with SLC26A4 mutations exhibit highly variable hearing loss and vestibular dysfunction. Although Slc26a4 mutant mice similarly exhibit vestibular deficits, including circling behavior, head tilting, and torticollis, the underlying pathogenesis of the vestibular symptoms remains unclear, hindering its effective management for patients with SLC26A4 mutations. In this study, we evaluated the equilibrium function using the inspection equipment, which can record eye movements against rotational, gravitational, and thermal stimulations. Moreover, we correlated the degree of functional impairment with the morphological alterations observed in Slc26a4Δ/Δ mice. The rotational stimulus and ice water caloric tests revealed considerable impairment of the semicircular canal, while the tilted gravitational stimulus test showed a severe functional decline of the otolithic system in Slc26a4Δ/Δ mice. Generally, the degree of impairment was more severe in circling Slc26a4Δ/Δ mice than in non-circling Slc26a4Δ/Δ mice. In non-circling Slc26a4Δ/Δ mice, the semicircular canal function was normal. Micro-computed tomography results showed enlargement of the vestibular aqueduct and bony semicircular canals but no correlative relationship between the severity of the caloric response and the size of bony labyrinths. Giant otoconia and a significant decrease in total otolith volume in the saccule and utricle were observed in Slc26a4Δ/Δ mice. However, the giant otoconia were not overly dislocated in the bony otolithic system and ectopic otoconia were absent in the semicircular canal. The number and morphology of the utricular hair cells in Slc26a4Δ/Δ mice were not significantly reduced compared to those in Slc26a4Δ/+ mice. Collectively, we can conclude that vestibular impairments are mainly associated with otoconia formation and morphology rather than hair cell degeneration. In addition, severe disturbances of semicircular canals cause circling behavior in Slc26a4Δ/Δ mice. Our comprehensive morphological and functional assessments apply to mouse models of other genetic diseases with vestibular impairment.

Change of functional state in cardiological patients before and after coronoviral infection

Goal — was to assess the quality of life and the functional state of the cardiovascular system of patients who have had COVID-19, to outline the further tactics of recovery of the cardiovascular system. Materials and methods. The study included 131 patients, men (n = 84) and women (n = 47), aged 41–76 years, with the presence of cardiovascular disease. Patients for a long time 4.4 ± 1.3 years, are under outpatient supervision in polyclinic No. 3, Makhachkala. Of the 131 patients included in the study: ischemic heart disease: angina pectoris I-II functional class was in n = 59 (45.0 %), arterial hypertension in n = 72 (55.0 %). All patients filled out the World Health Organization’s quality of life questionnaire, daily monitoring of electrocardiography, blood pressure, echocardiography and other types of examination was performed. The research was carried out in accordance with the norms and principles of the Declaration of Helsinki. Results. After 2 months. after the COVID-19 illness, the survey showed that 62 patients (47.3 %) (p = 0.0026) were dissatisfied with the quality of life, before the illness, this figure was (28.3 %). Another 69 patients (52.7 %) are not satisfied with their state of health (p = 0.0048), against (30.4 %) — before coronavirus disease. Physical pain interferes with life — 48 patients (36.6 %) (p = 0.0019), before illness, only (24.5 %), and so on. Thus, the change in the status of quality of life “before and after” was statistically significant, p &lt; 0.05. After 2 months. after coronavirus disease and discharge from the hospital, the daily monitoring of electrocardiography showed that in patients with exertional angina pectoris I-II functional class, ischemic and arrhythmic indicators were significant compared with the primary data p &lt; 0.05. At the same time, the data of daily monitoring of electrocardiography in patients with arterial hypertension reached the indicators of patients with angina pectoris I-II functional class. The results of 24-hour monitoring of blood pressure before and after coronavirus disease showed that patients with increased numbers of systolic and diastolic blood pressure increased, with grade II arterial hypertension by n = 7, and with grade III. by n = 6. Hypertensive crisis began to be noted, almost every third patient had 16 (22.2 %), only 2 (2.8 %) patients were hospitalized with a stroke. Initial and after COVID-19, echocardiographic parameters were as follows, a significant decrease in left ventricular end-diastolic volume from 133.2 ± 4.2 to 127.0 ± 3.4, end-systolic volume from 77.3 ± 2.6 to 72.4 ± 7.01. The total ejection fraction significantly decreased in comparison with the initial data: from 49.6 ± 4.2 to 41.9 ± 7.3. There was a significant decrease in stroke volume from 61.7 ± 4.1 to 54.0 ± 5.8. Conclusion. After analyzing the laboratory and instrumental data of the patients’ examination, we noticed that the real functional state decreased by a quarter in comparison with the initial indicators. But the survey of the quality of life showed that patients tend to overestimate the problems of their functional state by up to 30–40 %. At the same time, almost one third of our patients have developed post-ovarian syndrome, most of them developed depression, anxiety and fear for their health.

Cardiac fat pat change after laparoscopic sleeve gastrectomy and Roux-en-Y gastric bypass surgery: a systematic review and meta-analysis.

Cardiac fat pad is a metabolically active organ that plays a role in energy homeostasis and cardiovascular diseases and generates inflammatory cytokines. Many studies have shown remarkable associations between cardiac fat thickness and cardiovascular diseases, making it a valuable target for interventions. Our meta-analysis aimed to investigate the effects of the 2 most popular bariatric surgeries (sleeve gastrectomy [SG] and Roux-en-Y gastric bypass [RYGB]) in cardiac fat pad reduction. A systematic review of the literature was done by searching in Scopus, Web of Science, Cochrane, and PubMed for articles published by September 16, 2022. This review followed the meta-analysis rules based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Nineteen studies met the inclusion criteria out of 128 potentially useful studies, including a total number of 822 patients. The results of subgroup analysis on the type of surgery showed that bariatric surgeries decreased the mean fat pad diameter, but the reduction was greater in SG than in RYGB. Epicardial and pericardial fat type showed a significant decrease of fat pad diameter. The results of subgroup analysis indicated RYGB had a significant reduction in mean fat pad volume. Computed tomography scan and cardiac magnetic resonance imaging showed a significant reduction of the mean cardiac fat pad volume. Epicardial and paracardial fat type showed a significant decrease in volume. The cardiac fat pad diameter and volume were significantly reduced after bariatric surgeries. SG showed greater reduction in fat pad diameter in comparison with RYGB, and RYGB had a significant reduction in mean fat pad volume.