Notes

Innate Immunity to be able to Control Ganglion Neuron Reduction: Any Neuroprotective Role regarding Fractalkine Signaling inside Harmed Cochlea.
This defect may serve as a biomarker of PD, and the approach described here may be potentially used for the subclinical detection of PD and to establish a platform to assay disease modifying drugs. ANN NEUROL 2022.
These findings indicate a functional impairment in the handling of amines by SVs in PD patients. This defect may serve as a biomarker of PD, and the approach described here may be potentially used for the subclinical detection of PD and to establish a platform to assay disease modifying drugs. ANN NEUROL 2022.
Prostatic cancers include a diverse microenvironment of tumor cells, cancer-associated fibroblasts, and immune components. This tumor microenvironment (TME) is a known driving force of tumor survival after treatment, but the standard-of-care tissue freezing or fixation in pathology practice limit the use of available approaches/tools to study the TME's functionality in tumor resistance. Thus, there is a need for approaches that satisfy both clinical and laboratory endpoints for TME study. Here we present methods for clinical case identification, tissue processing, and analytical workflow that are compatible with standard histopathology while enabling molecular and functional interrogation of prostate TME components.

We first performed a small retrospective review to identify cases where submission of alternate prostate tissue slices and a parallel live tissue processing protocol complement traditional histopathology and enable viable multicompartment analysis of the TME. Then, we tested its compatibility new predictive and prognostic markers of prostate cancer progression.
To compare overall mortality (OM), cancer-specific mortality (CSM), and other cause mortality (OCM) rates between radical prostatectomy (RP) versus radiotherapy (RT) in clinical node-positive (cN1) prostate cancer (PCa).

Within Surveillance, Epidemiology, End Results (SEER) (2004-2016), we identified 4685 cN1 PCa patients, of whom 3589 (76.6%) versus 1096 (24.4%) were treated with RP versus RT. After 11 propensity score matching (PSM), Kaplan-Meier plots and Cox regression models tested the effect of RP versus RT on OM, while cumulative incidence plots and competing-risks regression (CRR) models addressed CSM and OCM between RP and RT patients. All analyses were repeated after the inverse probability of treatment weighting (IPTW). For CSM and OCM analyses, the propensity score was used as a covariate in the regression model.

Overall, RT patients were older, harbored higher prostate-specific antigenvalues, higher clinical T and higher Gleason grade groups. PSM resulted in two equally sized groups of 894 RP versus 894 RT patients. After PSM, 5-year OM, CSM, and OCM rates were, respectively, 15.4% versus 25%, 9.3%versus 17%, and 6.1% versus 8% for RP versus RT (all p < 0.001) and yielded respective multivariate hazard ratios (HRs) of 0.63 (0.52-0.78, p < 0.001), 0.66 (0.52-0.86, p < 0.001), 0.71 (0.5-1.0, p = 0.05), all favoring RP. After IPTW, Cox regression models yielded HR of 0.55 (95% confidence interval [CI] = 0.46-0.66) for OM, and CRR yielded HRs of 0.49 (0.34-0.70) and 0.54 (0.36-0.79) for, respectively, CSM and OCM, all favoring RP (all p < 0.001).

RP may hold a CSM advantage over RT in cN1 PCa patients.
RP may hold a CSM advantage over RT in cN1 PCa patients.
Prostate cancer (PC) is the most commonly diagnosed malignancy and the second leading cause of cancer-related deaths in males. Volasertib The disease is initially treated with methods that inhibit androgen receptor (AR) signal transduction. Laboratory-based and clinical studies have identified alternative pathways that cause the failure of AR signal inhibition and consequent development of castration-resistant prostate cancer (CRPC). Glucocorticoid receptor (GR) signaling is activated in certain PC patients and promotes the emergence of CRPC, althoughby as yet incompletely understood mechanisms. We have previously demonstrated that ubiquitous βarrestin1 (βArr1) expression levels are linked to PC progression. Here, we consider the possibility that βArr1 interacts with and activates GR in model CRPC cells.

Bioinformatic analysis of tumor xenograft and human PC datasets was used to correlate the expression of βArr1 and GR. Western blot, immunohistochemistryand immunofluorescence microscopy, and subcellular fractionatioease.
βArr1 binds GR that initiates mitogenic signaling cascades involved in the progression of PC to CRPC. The targeting of the βArr1-GR axis may provide a new opportunity to better manage the CRPC disease.
Intraextracardiac Fontan procedure (FP) aimed to combine the advantages of lateral tunnel and extracardiac conduit modifications of the original technique. Herein, we present our early outcomes in patients with intraextracardiac fenestrated FP.

A retrospective analysis was performed to evaluate intraextracardiac fenestrated Fontan patients between 2014 and 2021. Seventeen patients were operated on with a mean age and body weight of 9.1 ± 5.5 years and 28.6 ± 14.6 kg.

Sixteen patients (94%) were palliated as univentricular physiology with hypoplasia of one of the ventricles. One patient (6%) with well-developed two ventricles with double outlet right ventricle and complete atrioventricular septal defect had straddling of the chordae prohibiting a biventricular repair. All of the patients had cavopulmonary anastomosis before Fontan completion, except one case. Fenestration was performed in all cases. Postoperative mean pulmonary artery pressures and arterial oxygen saturation levels at follow-up were 10 ± 2.4 mmHg and 91.3 ± 2.7%, respectively. Mean duration of pleural drainage was 5.4 ± 2.3 days. All of the fenestrations are patent at a mean follow-up period of 4.8 ± 7.7 years, except one case. Any morbidity and mortality were not encountered.

Early outcomes of intraextracardiac fenestrated FP are encouraging. This procedure may improve the results in a patient population who should be palliated as univentricular physiology, especially in cases with complex cardiac anatomy.
Early outcomes of intraextracardiac fenestrated FP are encouraging. This procedure may improve the results in a patient population who should be palliated as univentricular physiology, especially in cases with complex cardiac anatomy.
The management of incidental findings of FDG-avid tonsils on PET/CT (IFT) is unclear. We aimed to explore the prevalence of malignancy in IFT, identify risk factors for malignancy, and calculate optimal cutoffs of maximum standardized uptake values (SUV
) to discriminate between benign and malignant lesions.

All patients who were tonsillectomized at our institution because of IFT from October 2011 to December 2020 were included. Patients undergoing PET/CT due to suspected tonsillar disease or cancer of unknown primary were excluded.

In total, 77 patients were included, of which 11 (14%) of them had IFT malignancy. Dysphagia (p=0.019) and alcohol abuse (p=0.035) were associated with malignancy. Absolute SUV
cutoff (≥9 sensitivity 100%; specificity 53%) was superior to SUV
side-to-side ratio (≥1.5 sensitivity 64%; specificity 70%) to discriminate between benign and malignant lesions.

We recommend tonsillectomy for patients with IFT displaying SUV
 ≥ 9.0, ratio ≥ 1.5, or symptoms or findings suggesting malignancy.

3 Laryngoscope, 2022.
3 Laryngoscope, 2022.An integrated testing strategy for ecotoxicity assessment (ITS-ECO) was developed to aid in the hazard and fate assessment of engineered nanomaterials (ENMs) deposited in marine environments using the bivalve Mytilus spp. as a test species. The ENMs copper(II) oxide (CuO) and titanium dioxide (TiO2 ), either in pristine form (core) or with functionalized coatings (polyethylene glycol [PEG], carboxyl [COOH], and ammonia [NH3 ]) were selected as case study materials based on their production levels and use. High-throughput in vitro testing in Tier 1 of the ITS-ECO revealed CuO ENMs to elicit cytotoxic effects on lysosomes of hemocytes of mussels, with the hazard potential CuO PEG > CuO COOH > CuO NH3  > CuO core, whereas TiO2 ENMs were not cytotoxic. Genotoxicity in hemocytes as well as gill cells of mussels following in vivo exposure (48 h) to CuO ENMs was also seen. Longer in vivo exposures in Tier 2 (48 h-21 days) revealed subacute and chronic oxidative effects for both CuO and TiO2 ENMs, in some cases leading to lipid peroxidation (core TiO2 ENMs). In Tier 3 bioaccumulation studies, distinct patterns of uptake for Cu (predominantly in gills) and Ti (predominantly in digestive glands) and between the different core and coated ENMs were found. Clear NM-specific and coating-dependent effects on hazard and fate were seen. Overall, using a tiered testing approach, the ITS-ECO was able to differentiate the hazard (acute, subacute, and chronic effects) posed by ENMs of different compositions and coatings and to provide information on fate for environmental risk assessment of these ENMs. Environ Toxicol Chem 2022;411390-1406. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Cervical spinal cord injury (SCI) can lead to dependence on mechanical ventilation (MV) with significant morbidity and mortality. The diaphragm pacing system (DPS) was developed as an alternative to MV.

We conducted a prospective single-arm study of DPS in MV-dependent patients with high SCI and intact phrenic nerves. Following device acclimation, pacing effectiveness to provide ventilation was evaluated. The primary endpoint was the number who could use DPS to breathe for 4 continuous hours without MV. Secondary endpoints included the number of patients that could use DPS 24h/day free of MV and the ability of DPS to maintain clinically acceptable tidal volume (Vt). In addition, we conducted a meta-analysis that included the prospective study along with data from four recently published studies to evaluate DPS hourly use.

Fifty-three patients were implanted in the prospective study. Most were male (77.4%) with a median time from injury to treatment of 28.3 (IQR 12.1, 83.3) months. Four- and 24-h use occurred in 96.2% (95% CI 87.0%, 99.5%) and 58.5% (95% CI 44.1%, 74.9%), respectively. Four and 24-h results in the meta-analysis cohort (n=196) exhibited similar results 92.2% (95% CI 82.6%, 96.7%) and 52.7% (95% CI 36.2%, 68.6%) using DPS for 4 and 24h, respectively. DPS use significantly exceeded the calculated basal tidal volume requirements by a mean of 48.4% (95% CI 37.0, 59.9%; p<0.001).

This study demonstrates that in most ventilator-dependent patients, diaphragm pacing can effectively supplement or completely replace the need for MV and support basal metabolic requirements.
This study demonstrates that in most ventilator-dependent patients, diaphragm pacing can effectively supplement or completely replace the need for MV and support basal metabolic requirements.
To review prenatal diagnosis and outcome of alpha thalassaemia major through universal antenatal screening.

This was a retrospective study on ultrasound features, antenatal diagnosis, in-utero intervention and long term outcome of pregnancies at risk of Haemoglobin Bart's hydrops foetalis syndrome attending prenatal diagnosis from 2000 to 2019 at Tsan Yuk Hospital in Hong Kong.

Among 390 foetuses from 373 at-risk pregnancies, 122 (31%) prenatal invasive procedures were performed and 65 affected foetuses were diagnosed antenatally. For foetuses with ultrasound features of anaemia, the diagnostic yield of BHFS was 73%. Cardiomegaly carried a positive predictive value of 65.2% while its absence had the highest negative predictive value (96.0%). Three women having affected foetuses continued pregnancy and received intrauterine transfusion beginning 20weeks of gestation. All babies were born alive and non-hydropic. They were managed with regular transfusion and cured by haematopoietic stem cell transplantation.
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