Video-rate nonlinear microscopy of neuronal membrane dynamics with genetically encoded probes

Biological membranes decorated with suitable contrast agents give rise to nonlinear optical signals such as two-photon fluorescence and harmonic up-conversion when illuminated with ultra-short, high-intensity pulses of infrared laser light. Microscopic images based on these nonlinear contrasts were acquired at video or higher frame rates by scanning a focused illuminating spot rapidly across neural tissues. The scan engine relied on an acousto-optic deflector (AOD) to produce a fast horizontal raster and on corrective prisms to offset the AOD-induced dispersion of the ultra-short excitation light pulses in space and time. Two membrane-bound derivatives of the green fluorescent protein (GFP) were tested as nonlinear contrast agents. Synapto-pHluorin, a pH-sensitive GFP variant fused to a synaptic vesicle membrane protein, provided a time-resolved fluorescent read-out of neurotransmitter release at genetically specified synaptic terminals in the intact brain. Arrays of dually lipidated GFP molecules at the plasma membrane generated intense two-photon fluorescence but no detectable second-harmonic power. Comparison with second-harmonic generation by membranes stained with a synthetic styryl dye suggested that the genetically encoded chromophore arrangement lacked the orientational anisotropy and/or dipole density required for efficient coherent scattering of the incident optical field.     

Evidence for linkage of nonsyndromic cleft lip with or without cleft palate to a region on chromosome 2

Results from a genome-wide screen of 10 multiplex families ascertained through probands with nonsyndromic cleft lip with or without cleft palate (CL/P) in Mexico, Argentina, and the United States yielded suggestive evidence of linkage to chromosomes 2, 6, 17 and 18. Fine mapping excluded all regions except chromosome 2. Subsequent analysis was performed on the original 10 families plus an additional 16 families using 31 markers on chromosome 2. This analysis showed intriguing evidence of linkage to 2q (Zlr=2.26, empirical P-value=0.028 in a chromosome-wide analysis). Transmission disequilibrium tests also revealed evidence of linkage and disequilibrium for two markers in this region (D2S168 and D2S1400 with P-values=0.022 and 0.006, respectively). A subset of these 26 families provided additional evidence for a susceptibility gene for CL/P on 2q, suggesting that further studies of genes in this region are warranted.     

Dielectric relaxation properties of linear polythioethers

Values of the dielectric loss tangent were obtained as a function of temperature for poly(pentamethylene sulfide) (P5MS) and poly(1,3-dithiocane) (PDTC). Both P5MS and PDTC exhibit a β absorption, located in the vicinity of their respective glass transition temperatures, ?105°C and ?73°C, which is believed to be associated with micro-Brownian motions in the amorphous phase of the crystalline polymers. The glass-rubber transitions of the polymers are discussed in terms of the flexibility of the chains, as expressed by their conformational partition functions and entropies.     

Cocoa Flavanols Adjuvant to an Oral Nutritional Supplement Acutely Enhances Nutritive Flow in Skeletal Muscle without Altering Leg Glucose Uptake Kinetics in Older Adults

Ageing is associated with postprandial muscle vascular and metabolic dysfunction, suggesting vascular modifying interventions may be of benefit. Reflecting this, we investigated the impact of acute cocoa flavanol (450–500 mg) intake (versus placebo control) on vascular (via ultrasound) and glucose/insulin metabolic responses (via arterialised/venous blood samples and ELISA) to an oral nutritional supplement (ONS) in twelve healthy older adults (50% male, 72 ± 4 years), in a crossover design study. The cocoa condition displayed significant increases in m. vastus lateralis microvascular blood volume (MBV) in response to feeding at 180 and 240-min after ONS consumption (baseline: 1.00 vs. 180 min: 1.09 ± 0.03, p = 0.05; 240 min: 1.13 ± 0.04, p = 0.002), with MBV at these timepoints significantly higher than in the control condition (p < 0.05). In addition, there was a trend (p = 0.058) for MBV in m. tibialis anterior to increase in response to ONS in the cocoa condition only. Leg blood flow and vascular conductance increased, and vascular resistance decreased in response to ONS (p < 0.05), but these responses were not different between conditions (p > 0.05). Similarly, glucose uptake and insulin increased in response to ONS (p < 0.05) comparably between conditions (p > 0.05). Thus, acute cocoa flavanol supplementation can potentiate oral feeding-induced increases in MBV in older adults, but this improvement does not relay to muscle glucose uptake.     

Laparoscopic pyeloplasty as an alternative to nephrectomy in adults with poorly functioning kidneys due to ureteropelvic junction obstruction

International Urology and Nephrology - To evaluate outcomes of laparoscopic pyeloplasty (LP) in adults with poorly functioning kidney due to ureteropelvic junction obstruction (UPJO). A...     

Antimicrobial photodynamic therapy against Propionibacterium acnes biofilms using hypericin (Hypericum perforatum) photosensitizer: in vitro study

Lasers in Medical Science - Acne vulgaris is the most recurring skin condition in the world, causing great harm to the physical and psychological well-being of many patients. Antimicrobial...     

The historical perspective in approaches to the spheno-petro-clival meningiomas

Neurosurgical Review - The current literature regarding surgical treatment for tumors in the sphenopetroclival (SPC) region is merely scarce. Through a comprehensive literature review, we...     

Is Preoperative Staphylococcus aureus Screening and Decolonization Effective at Reducing Surgical Site Infection in Patients Undergoing Orthopedic Surgery? A Systematic Review and Meta-Analysis With a Special Focus on Elective Total Joint Arthroplasty

BackgroundStaphylococcus aureus is a major pathogen implicated in orthopedic infections worldwide. Preoperative decolonization has been promoted but different strategies present mixed results. Thus, the goals of this study are to determine (1) whether S aureus screening and/or decolonization is effective at reducing surgical site infection in orthopedic surgery, (2) with a special focus on elective total joint arthroplasty (TJA), and (3) which preoperative S aureus screening/treatment strategy is most cost-effective for TJA.MethodsPubMed, Ovid MEDLINE, and Cochrane databases were searched on January 1, 2020, using a systematic strategy. We included papers with data comparing surgical site infection and periprosthetic joint infection rate in orthopedic surgery and/or elective total hip and knee arthroplasty patients before/after S aureus screening and/or decolonization protocol and papers evaluating the cost-effectiveness of different S aureus screening/treatment strategies.ResultsA total of 1260 papers were screened, and 32 papers were ultimately included. Results showed an increased risk of developing any infection (relative risk [RR] = 1.71 ± 0.16) and S aureus infection (RR = 2.79 ± 0.45) after orthopedic surgery without previous nares and whole-body decolonization. Focusing exclusively on elective TJA, there was an increased risk of developing any infection (RR = 1.70 ± 0.17) and S aureus infection (RR = 2.18 ± 0.41) if no decolonization is performed. All strategies appeared to be cost-effective, although universal decolonization without screening seemed to be the most advantageous.ConclusionPreoperative S aureus screening/decolonization protocol lowered the risk of infection after elective orthopedic and TJA surgeries. However, further studies are needed to determine optimal clinical and cost-effective methodologies.     

Baseline Assessment of Circulating MicroRNAs Near Diagnosis of Type 1 Diabetes Predicts Future Stimulated Insulin Secretion

Type 1 diabetes is an autoimmune disease resulting in severely impaired insulin secretion. We investigated whether circulating microRNAs (miRNAs) are associated with residual insulin secretion at diagnosis and predict the severity of its future decline. We studied 53 newly diagnosed subjects enrolled in placebo groups of TrialNet clinical trials. We measured serum levels of 2,083 miRNAs, using RNA sequencing technology, in fasting samples from the baseline visit (<100 days from diagnosis), during which residual insulin secretion was measured with a mixed meal tolerance test (MMTT). Area under the curve (AUC) C-peptide and peak C-peptide were stratified by quartiles of expression of 31 miRNAs. After adjustment for baseline C-peptide, age, BMI, and sex, baseline levels of miR-3187-3p, miR-4302, and the miRNA combination of miR-3187-3p/miR-103a-3p predicted differences in MMTT C-peptide AUC/peak levels at the 12-month visit; the combination miR-3187-3p/miR-4723-5p predicted proportions of subjects above/below the 200 pmol/L clinical trial eligibility threshold at the 12-month visit. Thus, miRNA assessment at baseline identifies associations with C-peptide and stratifies subjects for future severity of C-peptide loss after 1 year. We suggest that miRNAs may be useful in predicting future C-peptide decline for improved subject stratification in clinical trials.     

Management of functioning pediatric adrenal tumors

AimThe aim of this study is to present our experience in the management of hormonally active adrenal tumors in children.Material and methodsWe did a retrospective chart review of all children with hormonally active adrenal tumors evaluated at the endocrinology clinic and operated at our institution between 1983 and 2019.ResultsThere were 75 patients included in the study, 58 with adrenocortical tumors (ACTs) and 17 with pheochromocytomas (PCCs). Within the group of patients with ACTs, there were 41 females and 17 males. The mean age was 58.3 (SD: 87.9; range: 9–211) months. The clinical manifestation of the tumor's hormonal activity was virilization in 37 cases, Cushing syndrome in 5, and mixed in 16. A positive family history was present in 11 patients (18.9%). The mean tumor size was 48.2 (SD: 22.4; range: 7–120) mm. The pathological diagnosis was adenoma in 42 cases, carcinoma in 15 cases, and macronodular hyperplasia in 1. Median follow-up was 192 (range: 50–290) months. Tumor recurrence occurred in 6 patients (10.3%), and there were three disease-related deaths (5%). Within the group of patients with PCCs, there were 11 males and 6 females. The mean age was 146.7 (SD: 71.2; range: 60–216) months. A positive family history was present in 7 patients (41.2%). The mean tumor size was 36.6 (SD: 16.7; range: 7–120) mm. The pheochromocytoma was classified as benign in 15 cases and as malignant in 2. During a median follow-up of 180 (range: 127–300) months, recurrence was observed in 6 cases (35.3%) and disease-related death in 1 case (5.9%).ConclusionsProper diagnosis and management at our referral center were associated with a high cure rate, even in cases of malignant tumors. Familial surveillance is highly recommended.Level of evidenceLevel IV.