RS 2247911 polymorphism of GPRC6A gene and serum undercarboxylated-osteocalcin are associated with testis function.

PURPOSE: Undercarboxylated-Osteocalcin (ucOCN), acting on its putative receptor GPRC6A, was shown to stimulate testosterone (T) production by Leydig cells in rodents, in parallel with the hypothalamus-pituitary-gonadal axis (HPG) mediated by luteinizing hormone (LH). The aim of this cross-sectional study was to evaluate the association among serum ucOCN, rs2247911 polymorphism of GPRC6A gene and the endocrine/semen pattern in a cohort of infertile males, possibly identifying an involvement of the ucOCN-GPRC6A axis on testis function. METHODS: 190 males, including 74 oligozoospermic subjects, 58 azoosperminc patients and 58 normozoospermic controls, were prospectively recruited at the Orient Hospital for Infertility, Assisted Reproduction and Genetics in Syria (Study N. 18FP), from July 2018 to June 2020. Outpatient evaluation included the clinical history, anthropometrics and a fasting blood sampling for hormonals, serum OCN (both carboxylated and undercarboxylated), glycemic and lipid profile and screening for rs2247911 GPRC6A gene polymorphism. RESULTS: Higher serum ucOCN associated with higher T and HDL-cholesterol (respectively: r = 0.309, P < 0.001 and r = 0.248, P = 0.001), and with lower FSH (r = - 0.327, P < 0.001) and LDL-cholesterol (r = - 0.171; P = 0.018). Patients bearing the GG genotype of rs2247911 had higher sperm count compared to GA genotype (P = 0.043) and, compared to both AG and AA genotypes, had higher serum T (P = 0.004, P = 0.001) and lower triglycerides levels (P = 0.002, P < 0.001). Upon normalization for LH levels and body mass index, rs2274911 and ucOCN were significantly associated with higher serum T at linear stepwise regression analysis (P = 0.013, P = 0.007). CONCLUSIONS: Our data suggest the involvement of ucOCN-GPRC6A axis in the regulation of T production by the testis, subsidiary to HPG.

Gender susceptibility to COVID-19: a review of the putative role of sex hormones and X chromosome.

BACKGROUND: The recent emergence of COVID-19 poses a global health emergency. One of the most frequently reported data is sex-related severity and mortality: according to the last available analysis on 239,709 patients in Italy, lethality is 17.7% in men and 10.8% in women, with 59% of total deaths being men. Interestingly, the infection rate is lower in males than in females, with 45.8% and 54.2% of positive cases, respectively, suggesting that gender-related factor may worsen disease evolution. A tentative hypothesis to explain these findings is the role of angiotensin-converting enzyme 2 (ACE2) and serine protease TMPRSS2 involved in viral infection. PURPOSE: In this review, we summarize the available evidence pointing to gender-related differences in ACE2 and TMPRSS2 expression, from both genetic and endocrine points of view. RESULTS: Altogether, available evidence points toward two not-mutually exclusive mechanisms in gender susceptibility to COVID-19 by sex hormonal regulation of ACE2 and TMPRSS2. On one hand, ACE2 expression could be increased in women, either by estrogens or constitutively by X chromosome inactivation escape or by reduced methylation, providing a larger reservoir of ACE2 to maintain the fundamental equilibrium of RAS regulatory axis. On the other, low levels of androgens in women may keep at low levels TMPRSS2 expression, representing a further protective factor for the development of COVID-19 infection, despite the increased expression of ACE2, which represents the Trojan horse for SARS-CoV-2 entry. CONCLUSIONS: Both mechanisms consistently point to the role of sex hormones and sex chromosomes in the differential severity and lethality of COVID-19 in men and women.

Fatigue in multiple sclerosis patients with different clinical phenotypes: a clinical and magnetic resonance imaging study.

BACKGROUND AND PURPOSE: The prevalence of fatigue and its relation with clinical, neuropsychological and brain magnetic resonance imaging (MRI) variables in a large cohort of multiple sclerosis (MS) patients was investigated. METHOD: The Modified Fatigue Impact Scale and its subdomains were collected from 725 healthy controls and 366 MS patients [238 relapsing-remitting (RRMS) and 128 progressive (PMS)]. For the Modified Fatigue Impact Scale global and subdomains, MS patients were classified as fatigued (F-MS) or non-fatigued (NF-MS) according to cut-off values provided by logistic regression models with a specificity of 90% (i.e. a 10% false-positive rate in classifying healthy controls). MS patients underwent neurological, neuropsychological and MRI evaluations. Clinical and MRI measures were compared between F-MS and NF-MS patients using age-, sex- and phenotype-adjusted linear models. Heterogeneities between phenotypes were tested with specific interaction terms. RESULTS: Global fatigue affected 174 (47.5%) MS patients, being more prevalent in PMS (PMS 64.1% vs. RRMS 38.7%, P < 0.001). For all dichotomizations, F-MS were older (P from <0.001 to 0.012) and more depressed (P < 0.001) than NF-MS patients. Compared to NF-MS, cognitive F-MS patients had lower education (P = 0.035). Compared to NF-MS, patients with global and physical fatigue had higher Expanded Disability Status Scale only for RRMS (P < 0.001). Only RRMS patients with physical fatigue had lower brain (P = 0.05), white matter (P = 0.039) and thalamic volumes (P = 0.022) compared to NF-MS patients. CONCLUSIONS: In MS, fatigue is associated with older age, lower education and higher depression. Only in RRMS, fatigue is associated with Expanded Disability Status Scale and brain atrophy. A plateauing effect of disability and structural damage can explain the lack of associations in PMS.

Structural and functional brain connectomes in patients with systemic lupus erythematosus.

BACKGROUND AND PURPOSE: Systemic lupus erythematosus (SLE) is an immune-mediated disease that may affect the nervous system. We explored the topographical organization of structural and functional brain connectivity in patients with SLE and its correlation with neuropsychiatric (NP) involvement and autoantibody profiles. METHODS: Graph theoretical analysis was applied to diffusion tensor magnetic resonance imaging (MRI) and resting-state functional MRI data from 32 patients with SLE and 32 age- and sex-matched healthy controls. Structural and functional connectivity matrices between 116 cortical/subcortical brain regions were estimated using a bivariate correlation analysis, and global and nodal network metrics were calculated. RESULTS: Structural, but not functional, global network properties (strength, transitivity, global efficiency and path length) were abnormal in patients with SLE versus controls (P < 0.0001), especially in patients with anti-double-stranded DNA (ADNA) autoantibodies (P = 0.03). No difference was found according to NP involvement or anti-phospholipid autoantibody status. Patients with SLE and controls shared identical structural hubs and the majority of functional hubs. In patients with SLE, all structural hubs showed reduced strength and clustering coefficient compared with controls (P from 0.001 to <0.0001), especially in patients with ADNA autoantibodies. Only a few differences in functional hub properties were found between patients with SLE and controls. Structural and functional hub measures did not differ according to NP involvement or anti-phospholipid autoantibody status. Significant correlations were found between clinical, MRI and network measures (r from -0.56 to 0.60, P from 0.0003 to 0.05). CONCLUSIONS: Abnormalities of global and nodal structural connectivity occur in patients with SLE, especially with ADNA autoantibodies, with a diffuse disruption of structural integrity. Functional network integrity may contribute to preserve clinical functions.

Fronto-temporal vulnerability to disconnection in paediatric moderate and severe traumatic brain injury.

BACKGROUND: In patients with moderate and severe paediatric traumatic brain injury (TBI), we investigated the presence and severity of white matter (WM) tract damage, cortical lobar and deep grey matter (GM) atrophies, their interplay and their correlation with outcome rating scales. METHODS: Diffusion tensor (DT) and 3D T1-weighted MRI scans were obtained from 22 TBI children (13 boys; mean age at insult = 11.6 years; 72.7% in chronic condition) and 31 age-matched healthy children. Patients were tested with outcome rating scales and the Wechsler Intelligence Scale for Children (WISC). DT MRI indices were obtained from several supra- and infra-tentorial WM tracts. Cortical lobar and deep GM volumes were derived. Comparisons between patients and controls, and between patients in acute (<6 months from the event) vs. chronic (≥6 months) condition were performed. RESULTS: Patients showed a widespread pattern of decreased WM FA and GM atrophy. Compared to acute, chronic patients showed severer atrophy in the right frontal lobe and reduced FA in the left inferior longitudinal fasciculus and corpus callosum (CC). Decreased axial diffusivity was observed in acute patients versus controls in the inferior fronto-occipital fasciculus and CC. Chronic patients showed increased axial diffusivity in the same structures. Uncinate fasciculus DT MRI abnormalities correlated with atrophy in the frontal and temporal lobes. Hippocampal atrophy correlated with reduced WISC scores, whereas putamen atrophy correlated with lower functional independence measure scores. CONCLUSIONS: The study isolated a distributed fronto-temporal network of structures particularly vulnerable to axonal damage and atrophy that may contribute to cognitive deficits following TBI.

Statistical Mechanics-Based Schrödinger Treatment of Gravity.

The entropic gravity conception proposes that what has been traditionally interpreted as unobserved dark matter might be merely the product of quantum effects. These effects would produce a novel sort of positive energy that translates into dark matter via E = m c 2 . In the case of axions, this perspective has been shown to yield quite sensible, encouraging results [DOI:10.13140/RG.2.2.17894.88641]. Therein, a simple Schrödinger mechanism was utilized, in which his celebrated equation is solved with a potential function based on the microscopic Verlinde's entropic force advanced in [Physica A 511 (2018) 139]. In this paper, we revisit this technique with regards to fermions' behavior (specifically, baryons).

Basal vitamin D levels and disease activity in multiple sclerosis patients treated with fingolimod.

BACKGROUND: Several studies have shown an association between 25-hydroxyvitamin D (25[OH]D) levels and multiple sclerosis (MS) susceptibility and/or level of disease activity in patients treated with first line drugs. AIMS: To investigate whether baseline 25[OH]D values could influence disease activity also during treatment with the second-line drug fingolimod (FTY). PATIENTS AND METHODS: We enrolled 176 MS patients who started FTY at the San Raffaele Hospital (OSR) MS center with available 25[OH]D measurement at the time of treatment start. We then prospectively followed them for 2 years with periodic clinical examinations and MRI scans. RESULTS: We found no linear correlation between baseline 25[OH]D levels and annualized relapse rate (ARR) or time to first relapse. However, we observed that patients with serum 25[OH]D ≥ 100 nmol/l showed a lower number of Gd+ and combined unique activity (CUA) lesions at baseline compared to patients with the lowest 25[OH]D levels (less than 50 nmol/l, p value < 0.05). Moreover, they showed fewer CUA lesions at 2-year follow-up also when accounting for baseline level of disease activity (p value < 0.05). CONCLUSIONS: In patients treated with FTY, those with the highest baseline 25(OH)D levels had a significantly lower number of active lesions at baseline; the same effect, even if weaker, was observed also at 2-year follow-up when adjusting for baseline disease activity. Given Vitamin D supplementation safety profile, also if a causal effect has not yet been shown, most of MS patients could probably benefit from 25[OH]D levels above those currently considered to be sufficient.

A randomized, double-blind, placebo-controlled, multicenter study of a ginger extract in the management of chemotherapy-induced nausea and vomiting (CINV) in patients receiving high-dose cisplatin.

BACKGROUND: The activity of ginger in the management of chemotherapy-induced nausea and vomiting (CINV) has been suggested, but design inadequacies, heterogeneity of the population, small numbers and poor quality of tested products limit the possibility to offer generalizable results. PATIENTS AND METHODS: We conducted a randomized, double-blind, placebo-controlled, multicenter study in patients planned to receive ≥2 chemotherapy cycles with high dose (>50 mg/m2) cisplatin. Patients received ginger 160 mg/day (with standardized dose of bioactive compounds) or placebo in addition to the standard antiemetic prophylaxis for CINV, starting from the day after cisplatin administration. CINV was assessed through daily visual-analogue scale and Functional Living Index Emesis questionnaires. The main objective was protection from delayed nausea; secondary end points included intercycle nausea and nausea anticipatory symptoms. RESULTS: In total, 121 patients received ginger and 123 placebo. Lung (49%) and head and neck cancer (HNC; 35%) were the most represented tumors. No differences were reported in terms of safety profile or compliance. The incidence of delayed, intercycle and anticipatory nausea did not differ between the two arms in the first cycle and second cycle. A benefit of ginger over placebo in Functional Living Index Emesis nausea score differences (day 6-day 1) was identified for females (P = 0.048) and HNC patients (P = 0.038). CONCLUSIONS: In patients treated with high-dose cisplatin, the daily addition of ginger, even if safe, did not result in a protective effect on CINV. The favorable effect observed on nausea in subgroups at particular risk of nausea (females; HNC) deserves specific investigation.

Radiation-induced acute dysphagia : Prospective observational study on 42 head and neck cancer patients.

PURPOSE: Acute toxicity in head and neck (H&N) cancer patients treated with definitive radiotherapy (RT) has a crucial role in compliance to treatments. The aim of this study was to correlate doses to swallowing-associated structures and acute dysphagia. METHODS: We prospectively analyzed 42 H&N cancer patients treated with RT. Dysphagia (grade ≥ 3) and indication for percutaneous endoscopic gastrostomy (PEG) insertion were classified as acute toxicity. Ten swallowing-related structures were considered for the dosimetric analysis. The correlation between clinical information and the dose absorbed by the contoured structures was analyzed. Multivariate logistic regression method using resampling methods (bootstrapping) was applied to select model order and parameters for normal tissue complication probability (NTCP) modelling. RESULTS: A strong multiple correlation between dosimetric parameters was found. A two-variable model was suggested as the optimal order by bootstrap method. The optimal model (Rs = 0.452, p < 0.001) includes V45 of the cervical esophagus (odds ratio [OR] = 1.016) and Dmean of the cricopharyngeal muscle (OR = 1.057). The model area under the curve was 0.82 (95% confidence interval 0.69-0.95). CONCLUSION: Our results suggested that the absorbed dose to the cricopharyngeal muscle and cervical esophagus might play a relevant role in the development of acute RT-related dysphagia.

Influence of growing conditions on the reactivity of Ni supported graphene towards CO.

Free standing graphene is chemically inert but, as recently demonstrated, CO chemisorption occurs at low crystal temperature on the single layer grown by ethene dehydrogenation on Ni(111). Such layer is inhomogeneous since different phases coexist, the relative abundance of which depends on the growth conditions. Here we show by X ray photoemission and high resolution electron energy loss spectroscopies that the attained CO coverage depends strongly on the relative weight of the different phases as well as on the concentration of carbon in the Ni subsurface region. Our data show that the chemical reactivity is hampered by the carbon content in the substrate. The correlation between the amount of adsorbed CO and the weight of the different graphene phases indicates that the top-fcc configuration is the most reactive.

The Italian Neuroimaging Network Initiative (INNI): enabling the use of advanced MRI techniques in patients with MS.

Magnetic resonance imaging (MRI) is an important paraclinical tool to diagnose and monitor multiple sclerosis (MS). Conventional MRI measures lack of pathological specificity and are weakly correlated with MS clinical manifestations. Advanced MRI techniques are improving the understanding of the mechanisms underlying tissue injury, repair, and functional adaptation in MS; however, they require careful standardization. The definition of standardized methods for the collection and analysis of advanced MRI techniques is central not only to improve the understanding of disease pathophysiology and evolution, but also to generate research hypotheses, monitor treatment, increase cost-effectiveness and power of clinical trials. We promoted the Italian Neuroimaging Network Initiative (INNI), involving centers and investigators with an International recognized expertise, with the major goal to determine and validate novel MRI biomarkers to be utilized as predictors and/or outcomes in future MS studies. The INNI initiative supported the creation of a centralized repository, where advanced structural and functional MRI scans available at the participating sites, with the related clinical and neuropsychological data, are collected. These data will be used to perform research studies to identify clinical, neuropsychological and imaging biomarkers characteristics of the entire spectrum of MS. INNI will be instrumental to help to define standardized MRI and clinical protocols towards an increasing uptake of personalized interventions for people with MS at a national and international level. Upon approval of the INNI Steering Committee, the data collected in the online database will be shared with any research center detailing specific research proposals on disease pathophysiology or treatment effects.

Sperm telomere length as a parameter of sperm quality in normozoospermic men.

STUDY QUESTION: Could sperm telomere length (STL) represent a novel parameter and biomarker of sperm quality? SUMMARY ANSWER: STL is associated with standard semen quality parameters and, more importantly, it is significantly associated with levels of DNA fragmentation and sperm protamination. WHAT IS KNOWN ALREADY: Telomeres are fundamental for genome integrity. Recent studies have demonstrated that STL increases with age and men with oligozoospermia have shorter sperm telomeres than normozoospermic men. STUDY DESIGN, SIZE, DURATION: Cohort study conducted from September 2014 to June 2015 on 100 subjects with normal standard semen parameters. PARTICIPANTS/MATERIALS, SETTING, METHODS: STL was measured indirectly by quantitative polymerase chain reaction using telomere/single-copy gene ratio, sperm DNA fragmentation by terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling assay and protamination by aniline blue staining. Data were analyzed for determining the relationships between STL, standard semen parameters and DNA fragmentation and protamination. MAIN RESULTS AND THE ROLE OF CHANCE: Among standard semen parameters, STL was positively associated with progressive motility (P = 0.004) and vitality (P = 0.007). STL was significantly and negatively associated with sperm DNA fragmentation (P = 0.001) and significantly and positively associated with protamination (P = 0.002). The role of chance was limited and the findings have biological relevance and a pathophysiological explanation. LIMITATIONS, REASONS FOR CAUTION: For the present study, we deliberately selected only men with normozoospermia to better analyze whether STL might represent a biomarker of sperm quality beyond traditional sperm parameters. Additional studies in proven fertile men with normal sperm parameters are needed. WIDER IMPLICATIONS OF THE FINDINGS: The measurement of STL is a simple and rapid method that offers further information about the quality of sperm. The results of this study demonstrate that STL could be considered as an additional sperm parameter and opens new perspectives in the evaluation of the infertile male. Additional studies will clarify the significance of this parameter also as a prognostic biomarker in assisted reproduction. STUDY FUNDING/COMPETING INTERESTS: No external funding was either sought or obtained for this study. There are no conflicts of interest to be declared.

Diffusion tensor magnetic resonance imaging in very early onset pediatric multiple sclerosis.

OBJECTIVES: Active myelination during childhood may influence the impact of multiple sclerosis (MS) on brain structural integrity. We studied normal-appearing white matter (NAWM) in children with MS onset before age 12 years using diffusion tensor (DT) magnetic resonance imaging (MRI). METHODS: DT MRI scans were obtained from 22 MS children with their first attack before age 12 years, and 31 healthy controls from two referral centers. Using probabilistic tractography, brain tissue integrity within interhemispheric, intrahemispheric, and projection tracts was compared between patients and site-matched controls. The impact of disease and age at MRI on tract NAWM fractional anisotropy (FA) and mean diffusivity (MD) values was evaluated using linear models. RESULTS: Compared to controls, pediatric MS patients had reduced FA and increased MD of the bilateral superior longitudinal fasciculus and corpus callosum (CC), without center-by-group interaction. CC NAWM average FA was correlated with brain T2 lesion volume. In controls, the majority of the tracts analyzed showed a significant increase of FA and decrease of MD with age. Such a linear correlation was lost in patients. CONCLUSIONS: In very young pediatric MS patients, DT MRI abnormalities affect brain WM tracts differentially, and are only partially correlated with focal WM lesions. Impaired maturation of WM tracts with age may be an additional factor contributing to these findings.

Regional cortical thinning in multiple sclerosis and its relation with cognitive impairment: A multicenter study.

OBJECTIVES: The objectives of this paper are to compare in a multicenter setting patterns of regional cortical thickness in patients with relapsing-remitting multiple sclerosis (RRMS) and cognitive impairment (CI) and those cognitively preserved (CP), and explore the relationship between cortical thinning and cognitive performance. METHODS: T1-weighted isotropic brain scans were collected at 3T from seven European centers in 60 RRMS patients and 65 healthy controls (HCs). Patients underwent clinical and neuropsychological examinations. Cortical thickness (CTh) measures were calculated using FreeSurfer (failing in four) and both lobar and vertex-based general linear model (GLM) analyses were compared between study groups. RESULTS: Twenty (36%) MS patients were classified as CI. Mean global CTh was smaller in RRMS patients compared to HCs (left 2.43 vs. 2.53 mm, right 2.44 vs. 2.54 mm, p < 0.001). Multivariate GLM regional analysis showed significantly more temporal thinning in CI compared to CP patients. Verbal memory scores correlated to regional cortical thinning in the insula whereas visual memory scores correlated to parietal thinning. CONCLUSIONS: This multicenter study showed mild global cortical thinning in RRMS. The extent of thinning is less pronounced than previously reported. Only subtle regional differences between CI and CP patients were observed, some of which related to specific cognitive domains.

Searching for the neural basis of reserve against memory decline: intellectual enrichment linked to larger hippocampal volume in multiple sclerosis.

BACKGROUND AND PURPOSE: Active engagement in intellectually enriching activities (e.g. reading, hobbies) builds 'reserve' against memory decline in elders and persons with multiple sclerosis (MS), but the neural basis for this protective influence of enrichment is unknown. Herein the neuroanatomical basis of reserve against memory decline in MS patients is investigated. METHODS: Relapse-onset MS patients (N = 187) underwent 3.0 T magnetic resonance imaging of the brain to quantify T2 lesion volume (T2LV) and normalized volumes of total brain, total white, total grey (using SIENAX) and thalamus, caudate, putamen, pallidum, amygdala and hippocampus (using FIRST). Patients completed a survey quantifying their engagement in early life intellectual enrichment (i.e. reading, hobbies). Verbal and visuospatial episodic memory was assessed with neuropsychological tasks in a representative subsample (N = 97). RESULTS: Controlling for demographics and T2LV, intellectual enrichment was specifically linked to larger normalized hippocampal volume (r(p) = 0.213, P = 0.004), with no link to other brain volumes/structures. Moreover, greater intellectual enrichment moderated/attenuated the negative relationship between normalized total brain volume (i.e. overall cerebral atrophy) and normalized hippocampal volume (i.e. hippocampal atrophy; P = 0.001) whereby patients who engaged in more early life intellectual enrichment better maintained hippocampal volume in the face of worse overall cerebral atrophy. Finally, the link between greater intellectual enrichment and better memory was partially mediated through larger hippocampal volume. CONCLUSIONS: These findings support larger hippocampal volume as one key component of the neuroanatomical basis of reserve against memory decline in MS. These findings are consistent with previous literature on experience-dependent neuroplasticity within the hippocampus.

Functional MRI in investigating cognitive impairment in multiple sclerosis.

There is increasing evidence that the severity of the clinical manifestations of multiple sclerosis (MS) does not simply result from the extent of tissue destruction, but it rather represents a complex balance between tissue damage, tissue repair, and cortical reorganization. Functional magnetic resonance imaging (fMRI) provides information about the plasticity of the human brain. Therefore, it has the potential to provide important pieces of information about brain reorganization following MS-related structural damage. When investigating cognitive systems, fMRI changes have been described in virtually all patients with MS and different clinical phenotypes. These functional changes have been related to the extent of brain damage within and outside T2-visible lesions as well as to the involvement of specific central nervous system structures. It has also been suggested that a maladaptive recruitment of specific brain regions might be associated with the appearance of clinical symptoms in MS, such as fatigue and cognitive impairment. fMRI studies from clinically (and cognitively) impaired MS patients may be influenced by different task performances between patients and controls. As a consequence, new strategies have been introduced to assess the role, if any, of brain reorganization in severely impaired patients, including the analysis of resting-state networks. The enhancement of any beneficial effects of this brain adaptive plasticity should be considered as a potential target of therapy for MS.

CO chemisorption at vacancies of supported graphene films: a candidate for a sensor?

We investigate CO adsorption at single vacancies of graphene supported on Ni(111) and polycrystalline Cu. The borders of the vacancies are chemically inert but, on the reactive Ni(111) substrate, CO intercalation occurs. Adsorbed CO dissociates at 380 K, leading to carbide formation and mending of the vacancies, thus preventing their effectiveness in sensor applications.

A review of recent literature on functional MRI and personal experience in two cases of definite vestibular migraine.

The pathophysiology of vestibular migraine (VM) is at present poorly understood. Functional magnetic resonance imaging (fMRI), a technique that measures brain activity by detecting changes associated with blood flow oxygenation, has been used to study neural pathways involved in VM pathophysiology. In this study, we summarize results of previous fMRI studies in VM patients, both during and between vertigo attacks. Moreover, we report our experience in two patients with definite VM, who underwent fMRI during a visual stimulation in a vertigo-free period. Compared with 15 matched healthy controls, fMRI demonstrated activation of brain areas related to integration of visual and vestibular cues (increased activation of the paracentral lobule and bilateral inferior parietal lobule and decreased activation of the left superior frontal gyrus, head of the caudate nucleus, left superior temporal gyrus, left parahippocampal gyrus, and right lingual gyrus). Our results partially confirm those of other authors, reporting increased activation of multimodal association brain areas (BA 40, BA 31/5) and decreased activation of occipital regions In addition, we also found a decreased activation of fronto-temporal areas, such as the parahippocampal region, functionally involved in space memory and navigation.

D-Aspartic acid stimulates steroidogenesis through the delay of LH receptor internalization in a mammalian Leydig cell line.

PURPOSE: Recent experimental evidence on non-mammalian animal models showed that D-Aspartic acid (d-Asp) administration increases testosterone levels through upregulation of StAR in Leydig cells. In this study, we aimed to investigate in vitro the signaling pathway associated with d-Asp stimulation in MA-10 murine Leydig cells. METHODS: MA-10 cells were stimulated with different concentrations of d-Asp, in presence or absence of hCG. Then total testosterone (T) levels in the culture medium were evaluated by electrochemiluminescence immunoassay, and StAR and LHR protein expressions were quantified by the means of Western blotting. LHR cellular localization after hormonal stimulation was assessed by immunofluorescence. RESULTS: Stimulation with the sole d-Asp did not induce any relevant increase of T release from cultured cells. On the other hand, stimulation with hCG induced significant increase of T (P = 0.045). Concomitant stimulation with hCG and d-Asp, at the concentration of 0.1 and 1 nM, induced additional and significant increase of released T (P = 0.03 and P = 0.04, respectively). StAR protein levels increased after concomitant stimulation with hCG and d-Asp 0.1 nM, compared with stimulation with the sole hCG (P = 0.02), whereas no variation in LHR protein expression was observed. Finally, d-Asp attenuated displacement of LHR staining, from cell membrane to cytoplasm, subsequent to hCG stimulation. CONCLUSIONS: In this study, we confirmed a steroidogenic role for d-Asp, in concert with hCG, on murine Leydig cells, which is mediated by an increase in StAR protein levels. In addition, we showed that the possible mechanism subtending the effect of d-Asp could rely on the modulation of LHR exposure on the cell membrane.

Anisotropic dispersion and partial localization of acoustic surface plasmons on an atomically stepped surface: Au(788).

Understanding acoustic surface plasmons (ASPs) in the presence of nanosized gratings is necessary for the development of future devices that couple light with ASPs. We show here by experiment and theory that two ASPs exist on Au(788), a vicinal surface with an ordered array of monoatomic steps. The ASPs propagate across the steps as long as their wavelength exceeds the terrace width, thereafter becoming localized. Our investigation identifies, for the first time, ASPs coupled with intersubband transitions involving multiple surface-state subbands.