Lactose as an inexpensive starting material for the preparation of aldohexos-5-uloses: synthesis of L-ribo and D-lyxo derivatives

SUMMARY: Partially protected derivatives of L-ribo- and D-lyxo-aldohexos-5-ulose have been prepared starting from triacetonlactose dimethyl acetal derivatives. Key steps of the synthetic sequences are a) the synthesis of 4'-deoxy-4'-eno- and 6'-deoxy-5'-eno lactose derivatives, and b) the epoxidation-methanolysis of the above enol ethers to give 1,5-bis-glycopyranosides, masked form of the target 1,5-dicarbonyl hexoses

Depression and adult neurogenesis: Positive effects of the antidepressant fluoxetine and of physical exercise

Of wide interest for health is the relation existing between depression, a very common psychological illness, accompanied by anxiety and reduced ability to concentrate, and adult neurogenesis. We will focus on two neurogenic stimuli, fluoxetine and physical exercise, both endowed with the ability to activate adult neurogenesis in the dentate gyrus of the hippocampus, known to be required for learning and memory, and both able to counteract depression. Fluoxetine belongs to the class of selective serotonin reuptake inhibitor (SSRI) antidepressants, which represent the most used pharmacological therapy; physical exercise has also been shown to effectively counteract depression symptoms in rodents as well as in humans. While there is evidence that the antidepressant effect of fluoxetine requires its pro-neurogenic action, exerted by promoting proliferation, differentiation and survival of progenitor cells of the hippocampus, on the other hand fluoxetine exerts also neurogenesis-independent antidepressant effects by influencing the plasticity of the new neurons generated. Similarly, the antidepressant action of running also correlates with an increase of hippocampal neurogenesis and plasticity, although the gene pathways involved are only partially coincident with those of fluoxetine, such as those involved in serotonin metabolism and synapse formation. We further discuss how extra-neurogenic actions are also suggested by the fact that, unlike running, fluoxetine is unable to stimulate neurogenesis during aging, but still displays antidepressant effects. Moreover, in specific conditions, fluoxetine or running activate not only progenitor but also stem cells, which normally are not stimulated; this fact reveals how stem cells have a long-term, hidden ability to self-renew and, more generally, that neurogenesis is subject to complex controls that may play a role in depression, such as the type of neurogenic stimulus or the state of the local niche. Finally, we discuss how fluoxetine or running are effective in counteracting depression originated from stress or neurodegenerative diseases

New totally intracorporeal reconstructive approach after robotic total gastrectomy. Technical details and short-term outcomes

AIM: To show outcomes of our series of patients that underwent a total gastrectomy with a robotic approach and highlight the technical details of a proposed solution for the reconstruction phase. METHODS: Data of gastrectomies performed from May 2014 to October 2016, were extracted and analyzed. Basic characteristics of patients, surgical and clinical outcomes were reported. The technique for reconstruction (Parisi Technique) consists on a loop of bowel shifted up antecolic to directly perform the esophago-enteric anastomosis followed by a second loop, measured up to 40 cm starting from the esojejunostomy, fixed to the biliary limb to create an enteroenteric anastomosis. The continuity between the two anastomoses is interrupted just firing a linear stapler, so obtaining the Roux-en-Y by avoiding to interrupt the mesentery. RESULTS: Fifty-five patients were considered in the present analysis. Estimated blood loss was 126.55 ± 73 mL, no conversions to open surgery occurred, R0 resections were obtained in all cases. Hospital stay was 5 (3-17) d, no anastomotic leakage occurred. Overall, a fast functional recovery was shown with a median of 3 (3-6) d in starting a solid diet. CONCLUSION: Robotic surgery and the adoption of a tailored reconstruction technique have increased the feasibility and safety of a minimally invasive approach for total gastrectomy. The present series of patients shows its implementation in a western center with satisfying short-term outcomes

Total or near-total thyroidectomy versus subtotal thyroidectomy for multinodular non-toxic goitre in adults

Background Total thyroidectomy (TT) and subtotal thyroidectomy (ST) are worldwide treatment options for multinodular non-toxic goitre in adults. Near TT, defined as a postoperative thyroid remnant less than 1 mL, is supposed to be a similarly effective but safer option than TT. ST has been shown to be marginally safer than TT, but it may leave an undetected thyroid cancer in place. Objectives The objective was to assess the effects of total or near-total thyroidectomy compared to subtotal thyroidectomy for multinodular non-toxic goitre. Search methods We searched the Cochrane Library, MEDLINE, PubMed, EMBASE, as well as the ICTRP Search Portal and ClinicalTrials.gov. The date of the last search was 18 June 2015 for all databases. No language restrictions were applied. Selection criteria Two review authors independently scanned the abstract, title or both sections of every record retrieved to identify randomised controlled trials (RCTs) on thyroidectomy for multinodular non-toxic goitre for further assessment. Data collection and analysis Two review authors independently extracted data, assessed studies for risk of bias and evaluated overall study quality utilising the GRADE instrument. We calculated the odds ratio (OR) and corresponding 95% confidence interval (CI) for dichotomous outcomes. A random-effects model was used for pooling data. Main results We examined 1430 records, scrutinized 14 full-text publications and included four RCTs. Altogether 1305 participants entered the four trials, 543 participants were randomised to TT and 762 participants to ST. A total of 98% and 97% of participants finished the trials in the TT and ST groups, respectively. Two trials had a duration of follow-up between 12 and 39 months and two trials a follow-up of 5 and 10 years, respectively. Risk of bias across studies was mainly unknown for selection, performance and detection bias. Attrition bias was generally low and reporting bias high for some outcomes. In the short-term postoperative period no deaths were reported for both TT and ST groups. However, longer-term data on all-cause mortality were not reported (1284 participants; 4 trials; moderate quality evidence). Goiter recurrence was lower in the TT group compared to ST. Goiters recurred in 0.2% (1/425) of the TT group compared to 8.4% (53/632) of the ST group (OR 0.05 (95% CI 0.01 to 0.21); P < 0.0001; 1057 participants; 3 trials; moderate quality evidence). Re-intervention due to goitre recurrence was lower in the TT group compared to ST. Re-intervention was necessary in 0.5% (1/191) of TT patients compared to 0.8% (3/379)of ST patients (OR 0.66 (95% CI 0.07 to 6.38); P = 0.72; 570 participants; 1 trial; low quality evidence). The incidence of permanent recurrent laryngeal nerve palsy was lower for ST compared with TT. Permanent recurrent laryngeal nerve palsy occurred in 0.8% (6/741) of ST patients compared to 0.7% (4/543) of TT patients (OR 1.28, (95% CI 0.38 to 4.36); P = 0.69; 1275 participants; 4 trials; low quality evidence). The incidence of permanent hypoparathyroidism was lower for ST compared with TT. Permanent hypoparathyroidism occurred in 0.1% (1/741) of ST patients compared to 0.6% (3/543) of TT patients (OR 3.09 (95% CI 0.45 to 21.36); P = 0.25; 1275 participants: 4 trials; low quality evidence). The incidence of thyroid cancer was lower for ST compared with TT. Thyroid cancer occurred in 6.1% (41/669) of ST patients compared to 7.3% (34/465)of TT patients (OR 1.32 (95% CI 0.81 to 2.15); P = 0.27; 1134 participants; 3 trials; low quality evidence). No data on health-related quality of life or socioeconomic effects were reported in the included studies. Authors' conclusions The body of evidence on TT compared with ST is limited. Goiter recurrence is reduced following TT. The effects on other key outcomes such as re-interventions due to goitre recurrence, adverse events and thyroid cancer incidence are uncertain. New long-term RCTs with additional data such as surgeons level of experience, treatment volume of surgical centres and details on techniques used are needed

Altered cerebellum development and impaired motor coordination in mice lacking the Btg1 gene: Involvement of cyclin D1

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Erectile dysfunction in hyperuricemia: A prevalence meta‐analysis and meta‐regression study

AbstractBackgroundWhether and to what extent an association exists between hyperuricemia and erectile dysfunction (ED) has not yet been fully determined.ObjectiveTo define pooled prevalence estimates and correlates of erectile dysfunction in men with hyperuricemic disorders.Materials and methodsA thorough search of Medline, Scopus, and Cochrane Library databases was performed. Data were combined using random‐effects models and the between‐study heterogeneity was assessed by Cochrane's Q and I2 tests. A funnel plot was used to assess publication bias.ResultsOverall, 8 studies included gave information about 85,406 hyperuricemic men, of whom 5023 complained of erectile dysfunction, resulting in a pooled erectile dysfunction prevalence estimate of 33% (95% Confidence Interval: 13–52%; I² = 99.9%). The funnel plot suggested the presence of a publication bias. At the meta‐regression analyses, among the available covariates that could affect estimates, only type 2 diabetes mellitus was significantly associated with a higher prevalence of erectile dysfunction (β = 0.08; 95% Confidence Interval: 0.01, 0.15, p = 0.025). At the sub‐group analysis, the pooled erectile dysfunction prevalence decreased to 4% (95% Confidence Interval: 0%–8%) when only the largest studies with the lowest prevalence of type 2 diabetes mellitus were included and increased up to 50% (95% Confidence Interval: 17%–84%) when the analysis was restricted to studies enrolling smaller series with higher prevalence of type 2 diabetes mellitus.ConclusionsA not negligible proportion of men with hyperuricemia can complain of erectile dysfunction. While a pathogenetic contribution of circulating uric acid in endothelial dysfunction cannot be ruled out, the evidence of a stronger association between hyperuricemia and erectile dysfunction in type 2 diabetes mellitus points to hyperuricemia as a marker of systemic dysmetabolic disorders adversely affecting erectile function

Contribution of CACNA1H Variants in Autism Spectrum Disorder Susceptibility

Autism Spectrum Disorder (ASD) is a highly heterogeneous neuropsychiatric disorder with a strong genetic component. The genetic architecture is complex, consisting of a combination of common low-risk and more penetrant rare variants. Voltage-gated calcium channels (VGCCs or Cav) genes have been implicated as high-confidence susceptibility genes for ASD, in accordance with the relevant role of calcium signaling in neuronal function. In order to further investigate the involvement of VGCCs rare variants in ASD susceptibility, we performed whole genome sequencing analysis in a cohort of 105 families, composed of 124 ASD individuals, 210 parents and 58 unaffected siblings. We identified 53 rare inherited damaging variants in Cav genes, including genes coding for the principal subunit and genes coding for the auxiliary subunits, in 40 ASD families. Interestingly, biallelic rare damaging missense variants were detected in the CACNA1H gene, coding for the T-type Cav3.2 channel, in ASD probands from two different families. Thus, to clarify the role of these CACNA1H variants on calcium channel activity we performed electrophysiological analysis using whole-cell patch clamp technology. Three out of four tested variants were shown to mildly affect Cav3.2 channel current density and activation properties, possibly leading to a dysregulation of intracellular Ca2+ ions homeostasis, thus altering calcium-dependent neuronal processes and contributing to ASD etiology in these families. Our results provide further support for the role of CACNA1H in neurodevelopmental disorders and suggest that rare CACNA1H variants may be involved in ASD development, providing a high-risk genetic background

Estimating SARS-CoV-2 transmission in educational settings: a retrospective cohort study

Background School closures and distance learning have been extensively adopted to counter the COVID-19 pandemic. However, the contribution of school transmission to the spread of SARS-CoV-2 remains poorly quantified. Methods We analyzed transmission patterns associated with 976 SARS-CoV-2 exposure events, involving 460 positive individuals, as identified in early 2021 through routine surveillance and an extensive screening conducted on students, school personnel, and their household members in a small Italian municipality. In addition to population screenings and contact-tracing operations, reactive closures of class and schools were implemented. Results From the analysis of 152 clear infection episodes and 584 exposure events identified by epidemiological investigations, we estimated that approximately 50%, 21%, and 29% of SARS-CoV-2 transmission was associated with household, school, and community contacts, respectively. We found substantial transmission heterogeneities, with 20% positive individuals causing 75% to 80% of ascertained infection episodes. A higher proportion of infected individuals causing onward transmission was found among students (46.2% vs. 25%, on average), who also caused a markedly higher number of secondary cases (mean: 1.03 vs. 0.35). By reconstructing likely transmission chains from the entire set of exposures identified during contact-tracing operations, we found that clusters originated from students or school personnel were associated with a larger average cluster size (3.32 vs. 1.15) and a larger average number of generations in the transmission chain (1.56 vs. 1.17). Conclusions Uncontrolled SARS-CoV-2 transmission at school could disrupt the regular conduct of teaching activities, likely seeding the transmission into other settings, and increasing the burden on contact-tracing operations

Estimating SARS-CoV-2 transmission in educational settings: a retrospective cohort study

Background School closures and distance learning have been extensively adopted to counter the COVID-19 pandemic. However, the contribution of school transmission to the spread of SARS-CoV-2 remains poorly quantified. Methods We analyzed transmission patterns associated with 976 SARS-CoV-2 exposure events, involving 460 positive individuals, as identified in early 2021 through routine surveillance and an extensive screening conducted on students, school personnel, and their household members in a small Italian municipality. In addition to population screenings and contact-tracing operations, reactive closures of class and schools were implemented. Results From the analysis of 152 clear infection episodes and 584 exposure events identified by epidemiological investigations, we estimated that approximately 50%, 21%, and 29% of SARS-CoV-2 transmission was associated with household, school, and community contacts, respectively. We found substantial transmission heterogeneities, with 20% positive individuals causing 75% to 80% of ascertained infection episodes. A higher proportion of infected individuals causing onward transmission was found among students (46.2% vs. 25%, on average), who also caused a markedly higher number of secondary cases (mean: 1.03 vs. 0.35). By reconstructing likely transmission chains from the entire set of exposures identified during contact-tracing operations, we found that clusters originated from students or school personnel were associated with a larger average cluster size (3.32 vs. 1.15) and a larger average number of generations in the transmission chain (1.56 vs. 1.17). Conclusions Uncontrolled SARS-CoV-2 transmission at school could disrupt the regular conduct of teaching activities, likely seeding the transmission into other settings, and increasing the burden on contact-tracing operations