Normalization of Calcium Balance in Striatal Neurons in Huntington's Disease: Sigma 1 Receptor as a Potential Target for Therapy.

Huntington's disease (HD) is a neurodegenerative, dominantly inherited genetic disease caused by expansion of the polyglutamine tract in the huntingtin gene. At the cellular level, HD is characterized by the accumulation of mutant huntingtin protein in brain cells, resulting in the development of the HD phenotype, which includes mental disorders, decreased cognitive abilities, and progressive motor impairments in the form of chorea. Despite numerous studies, no unambigous connection between the accumulation of mutant protein and selective death of striatal neurons has yet been established.

Active Reprioritization of the Reading Worklist Using Artificial Intelligence Has a Beneficial Effect on the Turnaround Time for Interpretation of Head CT with Intracranial Hemorrhage.

Purpose: To determine how to optimize the delivery of machine learning techniques in a clinical setting to detect intracranial hemorrhage (ICH) on non-contrast-enhanced CT images to radiologists to improve workflow.

Materials And Methods: In this study, a commercially available machine learning algorithm that flags abnormal noncontrast CT examinations for ICH was implemented in a busy academic neuroradiology practice between September 2017 and March 2019. The algorithm was introduced in three phases: as a "pop-up" widget on ancillary monitors, as a marked examination in reading worklists, and as a marked examination for reprioritization based on the presence of the flag.

Potent Antimalarials with Development Potential Identified by Structure-Guided Computational Optimization of a Pyrrole-Based Dihydroorotate Dehydrogenase Inhibitor Series.

Dihydroorotate dehydrogenase (DHODH) has been clinically validated as a target for the development of new antimalarials. Experience with clinical candidate triazolopyrimidine DSM265 () suggested that DHODH inhibitors have great potential for use in prophylaxis, which represents an unmet need in the malaria drug discovery portfolio for endemic countries, particularly in areas of high transmission in Africa. We describe a structure-based computationally driven lead optimization program of a pyrrole-based series of DHODH inhibitors, leading to the discovery of two candidates for potential advancement to preclinical development.

Silicon Oxynitrophosphide Nanoscale Coating Enhances Antioxidant Marker-Induced Angiogenesis During in vivo Cranial Bone-Defect Healing.

Critical-sized bone defects are challenging to heal because of the sudden and large volume of lost bone. Fixative plates are often used to stabilize defects, yet oxidative stress and delayed angiogenesis are contributing factors to poor biocompatibility and delayed bone healing. This study tests the angiogenic and antioxidant properties of amorphous silicon oxynitrophosphide (SiONPx) nanoscale-coating material on endothelial cells to regenerate vascular tissue in vitro and in bone defects.

Effects of wearing a cloth face mask on performance, physiological and perceptual responses during a graded treadmill running exercise test.

Objectives: To (1) determine if wearing a cloth face mask significantly affected exercise performance and associated physiological responses, and (2) describe perceptual measures of effort and participants' experiences while wearing a face mask during a maximal treadmill test.

Methods: Randomised controlled trial of healthy adults aged 18-29 years. Participants completed two (with and without a cloth face mask) maximal cardiopulmonary exercise tests (CPETs) on a treadmill following the Bruce protocol.

Hedgehog signaling mechanism and role in cancer.

Cell-cell communication through evolutionarily conserved signaling pathways governs embryonic development and adult tissue homeostasis. Deregulation of these signaling pathways has been implicated in a wide range of human diseases including cancer. One such pathway is the Hedgehog (Hh) pathway, which was originally discovered in Drosophila and later found to play a fundamental role in human development and diseases.

Sex differences in prenatal programming of hypertension by dexamethasone.

Prenatal dexamethasone has been shown to increase blood pressure in male offspring but the mechanism for the increase in blood pressure is unclear. The present study examined if prenatal programming by maternal injection of dexamethasone on days 15 and 16 of gestation affected the blood pressure comparably in female and male offspring. Our hypothesis was that males would be affected by prenatal dexamethasone to a greater extent than females and that either an increase in renal tubular transporter abundance or an increase in renin or aldosterone system would be associated with hypertension with prenatal programming.

Lumbar Bracing for Chronic Low Back Pain: A Randomized Controlled Trial.

Purpose: We performed this study to evaluate the effect of back bracing to treat patients with chronic low back pain.

Methods: This was a prospective, unblinded, randomized controlled trial of 61 adults with uncomplicated chronic low back pain (>12 wks) and imaging findings of degenerative spondylosis, to assess the effectiveness of a semirigid back brace. All study participants received back school instruction.

A Rare Pulmonary-Systemic Connection: Levoatriocardinal Vein.

Levoatriocardinal vein is a rare persistent connection between pulmonary and systemic venous circulation that might result in bidirectional shunt and paradoxical embolism.

CLEAR - Medical use of contact lenses.

The medical use of contact lenses is a solution for many complex ocular conditions, including high refractive error, irregular astigmatism, primary and secondary corneal ectasia, disfiguring disease, and ocular surface disease. The development of highly oxygen permeable soft and rigid materials has extended the suitability of contact lenses for such applications. There is consistent evidence that bandage soft contact lenses, particularly silicone hydrogel lenses, improve epithelial healing and reduce pain in persistent epithelial defects, after trauma or surgery, and in corneal dystrophies.

Estimates of brain age for gray matter and white matter in younger and older adults: Insights into human intelligence.

Aging entails a multifaceted complex of changes in macro- and micro-structural properties of human brain gray matter (GM) and white matter (WM) tissues, as well as in intellectual abilities. To better capture tissue-specific brain aging, we combined volume and distribution properties of diffusivity indices to derive subject-specific age scores for each tissue. We compared age-related variance between younger and older adults for GM and WM age scores, and tested whether tissue-specific age scores could explain different effects of aging on fluid (Gf) and crystalized (Gc) intelligence in younger and older adults.

The role of Bcl-2 proteins in modulating neuronal Ca signaling in health and in Alzheimer's disease.

The family of B-cell lymphoma-2 (Bcl-2) proteins exerts key functions in cellular health. Bcl-2 primarily acts in mitochondria where it controls the initiation of apoptosis. However, during the last decades, it has become clear that this family of proteins is also involved in controlling intracellular Ca signaling, a critical process for the function of most cell types, including neurons.

Frequency of ischiofemoral space discrepancy when comparing magnetic resonance images of distinct institutions for the same patient.

Inaccuracy of ischiofemoral space (IFS) measurement may result in radiographic misdiagnosis of ischiofemoral impingement, as well as insufficient or excessive osseous resection when surgery is indicated. This study compared the IFS measured in magnetic resonance imaging (MRI) performed in distinct health services for the same patient. Sixty-five patients (95 hips) who had hip MRI performed at an outside institution (noncontrolled MRI) followed by a hip MRI with lower extremity positioning reproducing the standing position (controlled MRI) were studied.

Balancing ER-Mitochondrial Ca Fluxes in Health and Disease.

Organelles cooperate with each other to control cellular homeostasis and cell functions by forming close connections through membrane contact sites. Important contacts are present between the endoplasmic reticulum (ER), the main intracellular Ca-storage organelle, and the mitochondria, the organelle responsible not only for the majority of cellular ATP production but also for switching on cell death processes. Several Ca-transport systems focalize at these contact sites, thereby enabling the efficient transmission of Ca signals from the ER toward mitochondria.

Near-infrared temperature-switchable fluorescence nanoparticles.

Background: Near infrared (NIR) environment-sensitive fluorophores are highly desired for many biomedical applications because of its non-invasive operation, high sensitivity and specificity, non-ionizing radiation and deep penetration in biological tissue. When the fluorophores are appropriately encapsulated in or conjugated with some thermal-sensitive polymers, they could work as excellent temperature-sensing probes.

Methods: In this study, we synthesized and characterized a series of NIR temperature-switchable nanoparticles based on two series of NIR fluorophores aza-BODIPY (ADP is used for abbreviation in this work) and Zinc phthalocyanine (ZnPc) and four pluronic polymers (F127, F98, F68 and F38).

Solidified glomerulosclerosis, identified using single glomerular proteomics, predicts end-stage renal disease in Chinese patients with type 2 diabetes.

Few histological prognostic indicators for end-stage renal disease (ESRD) have been validated in diabetic patients. This biopsy-based study aimed to identify nephropathological risk factors for ESRD in Chinese patients with type 2 diabetes. Histological features of 322 Chinese type 2 diabetic patients with biopsy-confirmed diabetic nephropathy (DN) were retrospectively analysed.

Prediction of Pathological Upgrading at Radical Prostatectomy in Prostate Cancer Eligible for Active Surveillance: A Texture Features and Machine Learning-Based Analysis of Apparent Diffusion Coefficient Maps.

Objective: To evaluate a combination of texture features and machine learning-based analysis of apparent diffusion coefficient (ADC) maps for the prediction of Grade Group (GG) upgrading in Gleason score (GS) ≤6 prostate cancer (PCa) (GG1) and GS 3 + 4 PCa (GG2).

Materials And Methods: Fifty-nine patients who were biopsy-proven to have GG1 or GG2 and underwent MRI examination with the same MRI scanner prior to transrectal ultrasound (TRUS)-guided systemic biopsy were included. All these patients received radical prostatectomy to confirm the final GG.

An aptamer interacting with heat shock protein 70 shows therapeutic effects and prognostic ability in serous ovarian cancer.

Ovarian cancer (OvCa) is the most lethal gynecologic malignancy owing to its high chemoresistance and late diagnosis, which lead to a poor prognosis. Hence, developing new therapeutic modalities is important for OvCa patient treatment. Our previous results indicated that a novel aptamer, Tx-01, can specifically recognize serous carcinoma cells and tissues.