d aspartate exerts an opposing role upon age dependent nmdar related synaptic plasticity and memory decay

In the present study, we demonstrated that D-aspartate acts as an _in vitro_ and _in vivo_ neuromodulatory molecule upon hippocampal NMDAR transmission. Accordingly, we showed that this D-amino acid, widely expressed during embryonic phase, was able to strongly influence hippocampus-related functions at adulthood. Thus, while up-regulated levels of D-aspartate increased LTP and spatial memory in four-month old adult mice, the prolonged deregulation of this molecule in thirteen-month old animals induced a substantial acceleration of age-dependent decay of synaptic plasticity and cognitive functions. Moreover, we highlighted a role for D-aspartate in enhancing NMDAR-dependent synaptic plasticity through an inducible "turn-on/turn-off-like mechanism". Strikingly, we also showed that D-aspartate, when administered to aged mice, strongly rescued their physiological synaptic decay and attenuated their cognitive deterioration. In conclusion, our data suggest a tantalizing hypothesis for which this in-embryo-occurring D-amino acid, might disclose plasticity windows in the aging brain

Lesions mimicking melanoma at dermoscopy confirmed basal cell carcinoma: evaluation with reflectance confocal microscopy

Background Atypical basal cell carcinoma (BCC), characterized by equivocal dermoscopic features typical of malignant melanoma (MM), can be difficult to diagnose. Reflectance confocal microscopy (RCM) enables in vivo imaging at nearly histological resolution. Objectives To evaluate BCCs mimicking melanoma at dermoscopy according to well-known RCM criteria for typical BCCs, and identify discriminate RCM parameters for superficial (sBCCs) and nonsuperficial BCCs (nsBCCs). Material and Methods A retrospective analysis of consecutive patients, evaluated with RCM, selecting excised lesions classified at dermoscopy with ≥1 score from the revisited seven-point checklist, mimicking melanoma, registered between 2010 - 2016. Lesions without RCM melanocytic parameters, were investigated by operators blinded to histopathology diagnoses. Cluster analysis identified BCC sub-classifications. Results Of 178 atypical lesions, 34 lesions were diagnosed BCC with RCM, and diagnoses were confirmed with histopathology. Dermoscopic features observed atypical network (55.9%), and regressions structures (35.5%) associated with sBCCs, and atypical vascular pattern (58.8%) and irregular blotches (58.8%) with nsBCC. Hierarchical cluster analysis identified 2 clusters: cluster 1 (100% sBCCs) was characterized by the presence of cords connected to the epidermis (90%, p<0.001), tumor islands located in the epidermis (100%, p<0.001), smaller vascular diameter (100%, p<0.001) and solar elastosis (90%, p=0.017) and cluster 2 (nsBCCs 85%) by the dermic location of tumor islands (87.5%, p<0.001) with branch-like structures (70.8%, p= 0.007) and surrounding collagen (83.3%, p=0.012), peripheral palisading (83.3%, p=0.012), and coiled vascular morphology (79.2%, p<0.001) with larger vascular diameter (50%, p<0.001). Conclusions RCM is able to diagnose BCCs mimicking melanoma at dermoscopy and seems able to identify sBCCs and nsBCCs. Therefore, the use of RCM may assist in optimizing therapeutic management of these equivocal lesions

Lesions mimicking melanoma at dermoscopy confirmed basal cell carcinomas: evaluation with reflectance confocal microscopy

Background: Atypical basal cell carcinoma (BCC), characterized by equivocal dermoscopic features typical of malignant melanoma (MM), can be difficult to diagnose. Reflectance confocal microscopy (RCM) enables in vivo imaging at nearly histological resolution. Objectives: To evaluate BCCs mimicking melanoma at dermoscopy according to well-known RCM criteria for typical BCCs, and identify discriminate RCM parameters for superficial (sBCCs) and nonsuperficial BCCs (nsBCCs). Material and Methods: A retrospective analysis of consecutive patients, evaluated with RCM, selecting excised lesions classified at dermoscopy with ≥1 score from the revisited seven-point checklist, mimicking melanoma, registered between 2010 - 2016. Lesions without RCM melanocytic parameters, were investigated by operators blinded to histopathology diagnoses. Cluster analysis identified BCC sub-classifications. Results: Of 178 atypical lesions, 34 lesions were diagnosed BCC with RCM, and diagnoses were confirmed with histopathology. Dermoscopic features observed atypical network (55.9%), and regressions structures (35.5%) associated with sBCCs, and atypical vascular pattern (58.8%) and irregular blotches (58.8%) with nsBCC. Hierarchical cluster analysis identified 2 clusters: cluster 1 (100% sBCCs) was characterized by the presence of cords connected to the epidermis (90%, p<0.001), tumor islands located in the epidermis (100%, p<0.001), smaller vascular diameter (100%, p<0.001) and solar elastosis (90%, p=0.017) and cluster 2 (nsBCCs 85%) by the dermic location of tumor islands (87.5%, p<0.001) with branch-like structures (70.8%, p= 0.007) and surrounding collagen (83.3%, p=0.012), peripheral palisading (83.3%, p=0.012), and coiled vascular morphology (79.2%, p<0.001) with larger vascular diameter (50%, p<0.001). Conclusions: RCM is able to diagnose BCCs mimicking melanoma at dermoscopy and seems able to identify sBCCs and nsBCCs. Therefore, the use of RCM may assist in optimizing therapeutic management of these equivocal lesions

Genetic and environmental influences on human height from infancy through adulthood at different levels of parental education

Genetic factors explain a major proportion of human height variation, but differences in mean stature have also been found between socio-economic categories suggesting a possible effect of environment. By utilizing a classical twin design which allows decomposing the variation of height into genetic and environmental components, we tested the hypothesis that environmental variation in height is greater in offspring of lower educated parents. Twin data from 29 cohorts including 65,978 complete twin pairs with information on height at ages 1 to 69 years and on parental education were pooled allowing the analyses at different ages and in three geographic-cultural regions (Europe, North America and Australia, and East Asia). Parental education mostly showed a positive association with offspring height, with significant associations in mid-childhood and from adolescence onwards. In variance decomposition modeling, the genetic and environmental variance components of height did not show a consistent relation to parental education. A random-effects meta-regression analysis of the aggregate-level data showed a trend towards greater shared environmental variation of height in low parental education families. In conclusion, in our very large dataset from twin cohorts around the globe, these results provide only weak evidence for the study hypothesis.Peer reviewe

Parental Education and Genetics of BMI from Infancy to Old Age : A Pooled Analysis of 29 Twin Cohorts

Objective The objective of this study was to analyze how parental education modifies the genetic and environmental variances of BMI from infancy to old age in three geographic-cultural regions. Methods A pooled sample of 29 cohorts including 143,499 twin individuals with information on parental education and BMI from age 1 to 79 years (299,201 BMI measures) was analyzed by genetic twin modeling. Results Until 4 years of age, parental education was not consistently associated with BMI. Thereafter, higher parental education level was associated with lower BMI in males and females. Total and additive genetic variances of BMI were smaller in the offspring of highly educated parents than in those whose parents had low education levels. Especially in North American and Australian children, environmental factors shared by co-twins also contributed to the higher BMI variation in the low education level category. In Europe and East Asia, the associations of parental education with mean BMI and BMI variance were weaker than in North America and Australia. Conclusions Lower parental education level is associated with higher mean BMI and larger genetic variance of BMI after early childhood, especially in the obesogenic macro-environment. The interplay among genetic predisposition, childhood social environment, and macro-social context is important for socioeconomic differences in BMI.Peer reviewe

Chronic surgical site infection due to suture-associated polymicrobial biofilm

Background: surgical site infection (SSI) is a common surgical complication; culture-negative SSI presents a particular problem in management.Methods: examination of explanted foreign bodies (sutures) using confocal laser scanning microscopy (CLSM) and fluorescent in situ hybridization (FISH) after surgical exploration of a chronic culture-negative SSI.Results: confocal microscopy (CM) demonstrated bacilli and cocci attached to the surface of the explanted sutures in a mixed biofilm. Florescent in situ hybridization confirmed that Staphylococci were components of the mixed biofilm. Removal of the foreign bodies (sutures) resolved the chronic infection.Conclusion: chronic SSI can arise from underlying bacterial biofilms, which can invest implanted foreign bodies and associated soft tissue surface

Laser disruption and killing of methicillin-resistant Staphylococcus aureus biofilms

OBJECTIVE: The aim of the study was to study the efficacy of 2 different lasers in vitro, in disrupting biofilm and killing planktonic pathogenic bacteria. MATERIALS AND METHODS: Biofilms of a stable bioluminescent of Staphylococcus aureus Xen 31 were grown in a 96-well microtiter plate for 3 days. The study included 7 arms: (a) control; (b) ciprofloxacin (3 mg/L, the established minimum inhibitory concentration [MIC]) alone; (c) shock wave (SW) laser alone; (d) near-infrared (NIR) laser alone; (e) SW laser and ciprofloxacin; (f) SW and NIR lasers; (g) SW, NIR lasers, and ciprofloxacin. The results were evaluated with an in vivo imaging system (IVIS) biophotonic system (for live bacteria) and optical density (OD) for total bacteria. RESULTS: Without antibiotics, there was a 43% reduction in OD (P < .05) caused by the combination of SW and NIR suggesting that biofilm had been disrupted. There was an 88% reduction (P < .05) in live biofilm. Ciprofloxacin alone resulted in a decrease of 28% of total live cells (biofilm remaining attached) and 58% of biofilm cells (both P > .05). Ciprofloxacin in combination with SW and SW + NIR lasers caused a decrease of more than 60% in total live biomass and more than 80% of biofilm cells, which was significantly greater than ciprofloxacin alone (P < .05). CONCLUSIONS: We have demonstrated an effective nonpharmacologic treatment method for methicillin-resistant Staphylococcus aureus (MRSA) biofilm disruption and killing using 2 different lasers. The preferred treatment sequence is a SW laser disruption of biofilm followed by NIR laser illumination. Treatment optimization of biofilm is possible with the addition of ciprofloxacin in concentrations consistent with planktonic MIC

Direct demonstration of bacterial biofilms on prosthetic mesh after ventral herniorrhaphy

Background: Prosthetic mesh is employed routinely in the treatment of ventral and parastomal hernias, but its use can lead to major complications, including infection, extrusion, and fistula. Bacterial biofilms have been posited to play a role in mesh-related infection, but although bacteria have been noted to form biofilms on mesh surfaces in vitro, they have never been visualized directly in biofilms on mesh recovered from patients experiencing infectious complications.Methods: Five patients who developed complications after ventral hernia repair with prosthetic mesh were operated on again. Explanted mesh was examined for biofilm with confocal laser scanning microscopy (CLSM) and fluorescence in situ hybridization (FISH). In two cases, a novel molecular assay (the Ibis T5000) was used to characterize the biofilm-forming bacteria.Results: The CLSM examination demonstrated adherent biofilms on mesh surfaces in all five patients. Biofilms also were noted on investing fibrous tissue. The FISH study was able to discriminate between bacterial species in polymicrobial biofilms. In two patients the Ibis T5000 detected more species of constituent biofilm bacteria than did standard culture. Removal of the mesh and reconstruction with autologous tissues or biologic materials resolved the presenting complaints in all cases.Conclusion: Bacterial biofilms should be considered an important contributor to the pathology and complications associated with prosthetic mesh implanted in the abdominal wall. If biofilms are present, complete removal of the mesh and repair of the resulting defect without alloplastic materials is an effective intervention<br/

Bacterial biofilms on implanted suture material are a cause of surgical site infection

Background: Surgical site infection (SSI) has been estimated to occur in up to 5% of all procedures, accounting for up to 0.5% of all hospital costs. Bacterial biofilms residing on implanted foreign bodies have been implicated as contributing or causative factors in a wide variety of infectious scenarios, but little consideration has been given to the potential for implanted, submerged suture material to act as a host for biofilm and thus serve as a nidus of infection. Methods: We report a series of 15 patients who underwent open Roux-en-Y gastric bypass (with musculofascial closure with permanent, multifilament sutures) who developed longstanding and refractory SSIs in the abdominal wall. Explanted suture material at subsequent exploration was examined for biofilm with confocal laser-scanning microscopy (CLSM) and fluorescence in situ hybridization (FISH). Results: All 15 patients at re-exploration were found to have gross evidence of a "slimy" matrix or dense reactive granulation tissue localized to the implanted sutures. Confocal laser-scanning microscopy revealed abundant biofilm present on all sutures examined; FISH was able to identify the presence of specific pathogens in the biofilm. Complete removal of the foreign bodies (and attendant biofilms) resulted in all cases in cure of the SSI. Conclusion: Bacterial biofilms on implanted suture material can manifest as persistent surgical site infections that require complete removal of the underlying foreign body substrata for resolution