Daylight Saving Time and Spontaneous Deliveries: A Case–Control Study in Italy

(1) Background: Although the current literature shows that daylight saving time (DST) may play a role in human health and behavior, this topic has been poorly investigated with reference to Obstetrics. The aim of this case–control study was to evaluate whether DST may influence the number of spontaneous deliveries. (2) Methods: A low-risk pregnancy cohort with spontaneous onset of labor (n = 7415) was analyzed from a single Italian region for the period 2016–2018. Primary outcome was the number of spontaneous deliveries. Secondary outcomes were: gestational age at delivery, type and time of delivery, use of analgesia, birth weight, and 5-min Apgar at delivery. We compared the outcomes in the two weeks after DST (cases) to the two weeks before DST (controls). (3) Results: Data showed no significant difference between the number of deliveries occurring before and after DST (Chi-square = 0.546, p = 0.46). Vaginal deliveries at any gestational age showed no statistical difference between the two groups (Chi-square = 0.120, p = 0.73). There were no significant differences in the secondary outcomes, as well. (4) Conclusions: DST has neither a significant impact on the number of deliveries nor on the obstetric variables investigated by this study

Caratterizzazione molecolare e funzionale di una bevanda simil-Kombucha

Il Kombucha è una bevanda fermentata, di origini asiatiche conosciuta fin dall’antichità, tradizionalmente ottenuta dalla fermentazione del tè nero o verde (addolcita con il 5-8% di zucchero) promossa da un consorzio microbico simbiotico (Symbiotic Culture of Bacteria and Yeasts, SCOBY), composto principalmente da batteri acetici e lieviti osmofili. I microrganismi sono intrappolati in una matrice di cellulosa galleggiante prodotta dai batteri acetici. Questo biofilm, utilizzato nelle successive fermentazioni come starter naturale, mantiene le condizioni aerobie essenziali per le attività metaboliche dei batteri acetici, microrganismi strettamente aerobi. La lunghezza della fermentazione, la temperatura, la qualità del tè, la concentrazione di saccarosio e i consorzi microbici fermentanti, influenzano le proprietà chimiche e antiossidanti del prodotto finale. In particolare, la bevanda fermentata risultante è caratterizzata da un basso pH, contenuto in acidi organici (acetico, gluconico e glucoronico), CO2, vitamine, e contenuto in tracce di etanolo, glicerolo e composti fenolici. Tali composti conferiscono alla bevanda importanti proprietà funzionali, come attività antiossidante, antinfiammatoria, anticancerogena, immunomodulatoria. La presente tesi ha riguardato la caratterizzazione microbiologica e funzionale di una bevanda fermentata simil-kombucha a base di infusi di erbe aromatiche, prodotta in Toscana. In particolare, una prima fase ha previsto la valutazione della shelf-life della bevanda durante il periodo di maturazione (3, 20, 45 e 90 giorni) a due diverse temperature (ambiente e frigo), mediante l’analisi dei principali gruppi microbici “starter naturali” di interesse bio-tecnologico, quali batteri acetici e lieviti, e la determinazione della sua acidità. La carica dei lieviti ritrovata durante tutto il periodo di maturazione è rimasta costante sia per i campioni conservati a temperatura ambiente che per quelli conservati in frigo, mostrando valori compresi tra 7.00±0.02 e 6.26±0.50 Log UFC/mL. Per quanto riguarda i batteri acetici, la carica è rimasta costante nei campioni mantenuti in frigo (nel range di 4.66±0.08 – 3.45±0.16 Log UFC/mL), mentre è diminuita in quelli a temperatura ambiente. Il decremento di alcune popolazioni di lieviti e dei batteri acetici osservato tra 20 e 45 giorni di maturazione nei campioni mantenuti a temperatura ambiente suggerisce la conservazione del prodotto a 4 °C ai fini dell’estensione della sua shelf-life fino a 90 gg. Allo scopo di selezionare ceppi con caratteri funzionali da utilizzare come starter per la produzione di alimenti e bevande fermentati con alto valore salutistico, da campioni della bevanda a fine fermentazione non filtrata, sono stati isolati in coltura pura 68 batteri acetici e 58 lieviti. Tali ceppi sono stati inseriti nella collezione IMA (International Microbial Archives) del Dipartimento di Scienze Agrarie, Alimentari e Agroambientali (DISAAA-a) dell’Università di Pisa, a costituire la Banca del germoplasma della bevanda fermentata simil-kombucha. I lieviti sono stati preliminarmente caratterizzati da un punto di vista morfo-fisiologico e successivamente, identificati a livello di genere e specie, mediante metodi molecolari, quali: PCR specie-specifica, analisi di restrizione della regione ITS e sequenziamento del dominio D1/D2 del 26S rDNA. I risultati ottenuti hanno permesso di identificare i lieviti Dekkera anomala, Saccharomyces cerevisiae, Zygosaccharomyces bailii e Zygosaccharomyces lentus come le specie predominanti del microbiota naturale associato a questa bevanda. Infine, i lieviti isolati sono stati caratterizzati da un punto di vista funzionale, allo scopo di valutare la loro capacità di produrre acidi organici, esopolisaccaridi e di idrolizzare le proteine (attività proteasica), mediante screening qualitativi su mezzo solido. I risultati ottenuti hanno mostrato che tutti gli isolati erano capaci di produrre acidi organici, il 61% di produrre esopolisaccaridi e il 36% degli isolati è risultato essere in grado di idrolizzare le proteine

Effects of Organic and Conventional Cultivation on Composition and Characterization of Two Citrus Varieties ‘Navelina’ Orange and ‘Clemenules’ Mandarin Fruits in a Long-Term Study

A transition towards an organic food system is taking place around the world. This process is favored by growing consumer demand, who associate organic crops with being healthier, tastier, and safer for the environment than conventional crops. Citrus is one of the most widely produced crops worldwide and has important socio-economic and cultural significance in the Mediterranean area. The aim of this work is twofold; on the one hand, it reveals the variability of a set of physical–chemical and nutritional quality parameters of two citrus fruit varieties, ‘Navelina’ oranges and ‘Clemenules’ mandarins, from organic and conventional production in a long-term study. On the other hand, taking advantage of the large number of results, a model is proposed that allows the successful differentiation of citrus fruits from organic and conventional production and a tool that allows predicting the production system of citrus fruits. The results suggest that organically produced citrus fruits do not generate differences in terms of external aspects, providing fruits that are acceptable to the market. Organic production techniques influenced the lower peel content and higher pulp and juice content in ‘Navelina’ orange and ‘Clemenules’ mandarin fruits and led to a greater ability to synthesize vitamin C in the juice, more essential oils in the skin, and higher seed numbers, although in all cases, the fruits can be classified as having low seed numbers. Two discriminating equations were obtained that use easy-to-measure parameters to successfully classify organic citrus fruits. The classification and prediction models obtained constitute useful tools to help in the control of the purity/authenticity of organic citrus fruits

Storage time and temperature affect microbial dynamics of yeasts and acetic acid bacteria in a kombucha beverage

Kombucha is a mildly sweet, slightly acidic fermented beverage, commercially available worldwide, that has attracted increasing consumers' interest due to its potential health benefits. Kombucha is commonly prepared using sugared black or green tea, but also other plant substrates are frequently utilised. Kombucha is obtained by fermentation using a symbiotic culture of bacteria and yeasts, whose composition varies depending on inoculum origin, plant substrates and environmental conditions. After fermentation, kombucha drinks are usually refrigerated at 4 ◦C, in order to maintain their biological and functional properties. There are no reports on the fate of microbial communities of kombucha in relation to long-term storage time and temperature. Here, for the first time, we monitored the diversity and dynamics of the microbial communities of a kombucha beverage fermented with different herbs during storage at 4 ◦C and at room temperature, for a period of 90 days, utilising culture dependent and independent approaches. Moreover, cultivable yeasts and acetic acid bacteria (AAB) were isolated from the beverage, inoculated in pure culture, identified by molecular methods, and yeasts assessed for their functional properties. Total yeast counts were not affected by storage temperature and time, although their community composition changed, as Saccharomyces species significantly decreased after 45 days of storage at room temperature, completely disappearing after 90 days. On the other hand, Dekkera anomala (Brettanomyces anomalus), representing 52 % of the yeast isolates, remained viable up to 90 days at both storage temperatures, and was able to produce high levels of organic acids and exopolysaccharides. Data from DGGE (Denaturing Gradient Gel Electrophoresis) band sequencing confirmed that it was the dominant yeast species in all samples across storage. Other yeast isolates were represented by Saccharomyces and Zygosaccharomyces species. Among AAB, Gluconobacter oxydans, Novacetimonas hansenii and Komagataeibacter saccharivorans represented 46, 36 and 18 % of the isolates, whose occurrence remained unchanged across storage at 4 ◦C and did not vary up to 20 days of storage at room temperature. This work showed that the combination of culture-dependent and independent approaches is important for obtaining a complete picture of the distinctive core microbial community in kombucha beverages during storage, elucidating its diversity and composition, and preliminary characterizing yeast strains with putative functional activities

Retinoblastoma-independent antiproliferative activity of novel intracellular antibodies against the E7 oncoprotein in HPV 16-positive cells

<p>Abstract</p> <p>Background</p> <p>"High risk" Human Papillomavirus strains are the causative agents of the vast majority of carcinomas of the uterine cervix. In these tumors, the physical integration of the HPV genome is a frequent, though not invariable occurrence, but the constitutive expression of the E6 and E7 viral genes is always observed, suggesting key roles for the E6 and E7 oncoproteins in the process of malignant transformation. The "intracellular antibody" technology using recombinant antibodies in single-chain format offers the possibility of targeting a protein in its intracellular environment even at the level of definite domains thus representing a valuable strategy to "knock out" the function of specific proteins.</p> <p>Methods</p> <p>In this study, we investigate the <it>in vitro </it>activity of two single-chain antibody fragments directed against the "high-risk" HPV 16 E7 oncoprotein, scFv 43M2 and scFv 51. These scFvs were expressed by retroviral system in different cell compartments of the HPV16-positive SiHa cells, and cell proliferation was analyzed by Colony Formation Assay and EZ4U assay. The binding of these scFvs to E7, and their possible interference with the interaction between E7 and its main target, the tumor suppressor pRb protein, were then investigated by immunoassays, PepSet™technology and Surface Plasmon Resonance.</p> <p>Results</p> <p>The expression of the two scFvs in the nucleus and the endoplasmic reticulum of SiHa cells resulted in the selective growth inhibition of these cells. Analysis of binding showed that both scFvs bind E7 via distinct but overlapping epitopes not corresponding to the pRb binding site. Nevertheless, the binding of scFv 43M2 to E7 was inhibited by pRb in a non-competitive manner.</p> <p>Conclusions</p> <p>Based on the overall results, the observed inhibition of HPV-positive SiHa cells proliferation could be ascribed to an interaction between scFv and E7, involving non-pRb targets. The study paves the way for the employment of specific scFvs in immunotherapeutic approaches against the HPV-associated lesions.</p

Brivaracetam as add-on treatment in patients with post-stroke epilepsy: real-world data from the BRIVAracetam add-on First Italian netwoRk Study (BRIVAFIRST)

Objective: Post-stroke epilepsy (PSE) is one of the most common causes of acquired epilepsy and accounts for about 10-15% of all newly diagnosed epilepsy cases. However, evidence about the clinical profile of antiseizure medications in the PSE setting is currently limited. Brivaracetam (BRV) is a rationally developed compound characterized by high-affinity binding to synaptic vesicle protein 2A. The aim of this study was to assess the 12-month effectiveness and tolerability of adjunctive BRV in patients with PSE treated in a real-world setting. Methods: This was a subgroup analysis of patients with PSE included in the BRIVAracetam add-on First Italian netwoRk Study (BRIVAFIRST). The BRIVAFIRST was a 12-month retrospective, multicentre study including adult patients prescribed adjunctive BRV. Effectiveness outcomes included the rates of seizure response (≥50% reduction in baseline seizure frequency), seizure-freedom, and treatment discontinuation. Safety and tolerability outcomes included the rate of treatment discontinuation due to adverse events (AEs) and the incidence of AEs. Results: Patients with PSE included in the BRIVAFIRST were 75 and had a median age of 57 (interquartile range, 42-66) years. The median daily doses of BRV at 3, 6, and 12 months from starting treatment were 100 (100-150) mg, 125 (100-200) mg and 100 (100-200) mg, respectively. At 12 months, 32 (42.7%) patients had a reduction in their baseline seizure frequency by at least 50%, and the seizure freedom rates was 26/75 (34.7%). During the 1-year study period, 10 (13.3%) patients discontinued BRV. The reasons of treatment withdrawal were insufficient efficacy in 6 (8.0%) patients and poor tolerability in 4 (5.3%) patients. Adverse events were reported by 13 (20.3%) patients and were rated as mild in 84.6% and moderate in 15.4% of cases. Significance: Adjunctive BRV was efficacious and generally well-tolerated when used in patients with PSE in clinical practice. Adjunctive BRV can be a suitable therapeutic option for patients with PSE

Adjunctive Brivaracetam in Older Patients with Focal Seizures: Evidence from the BRIVAracetam add‑on First Italian netwoRk Study (BRIVAFIRST)

BACKGROUND: The management of epilepsy in older adults has become part of daily practice because of an aging population. Older patients with epilepsy represent a distinct and more vulnerable clinical group as compared with younger patients, and they are generally under-represented in randomized placebo-controlled trials. Real-world studies can therefore be a useful complement to characterize the drug's profile. Brivaracetam is a rationally developed compound characterized by high-affinity binding to synaptic vesicle protein 2A and approved as adjunctive therapy for focal seizures in adults with epilepsy. OBJECTIVE: The aim of this study was to assess the 12-month effectiveness and tolerability of adjunctive brivaracetam in older patients (≥65 years of age) with epilepsy treated in a real-world setting. METHODS: The BRIVAFIRST (BRIVAracetam add-on First Italian netwoRk STudy) was a 12-month retrospective multicenter study including adult patients prescribed adjunctive brivaracetam. Effectiveness outcomes included the rates of seizure response (≥50% reduction in baseline seizure frequency), seizure freedom, and treatment discontinuation. Safety and tolerability outcomes included the rate of treatment discontinuation due to adverse events and the incidence of adverse events. Data were compared for patients aged ≥65 years of age ('older') vs those aged <65 years ('younger'). RESULTS: There were 1029 patients with focal epilepsy included in the study, of whom 111 (10.8%) were aged ≥65 years. The median daily dose of brivaracetam at 3 months was 100 [interquartile range, 100-175] mg in the older group and 100 [100-200] mg in the younger group (p = 0.036); it was 150 [100-200] mg in both groups either at 6 months (p = 0.095) or 12 months (p = 0.140). At 12 months, 49 (44.1%) older and 334 (36.4%) younger patients had a reduction in their baseline seizure frequency by at least 50% (p = 0.110), and the seizure freedom rates were 35/111 (31.5%) and 134/918 (14.6%) in older and younger groups, respectively (p < 0.001). During the 1-year study period, 20 (18.0%) patients in the older group and 245 (26.7%) patients in the younger group discontinued brivaracetam (p = 0.048). Treatment withdrawal because of insufficient efficacy was less common in older than younger patients [older: n = 7 (6.3%), younger: n = 152 (16.6%); p = 0.005]. Adverse events were reported by 24.2% of older patients and 30.8% of younger patients (p = 0.185); the most common adverse events were somnolence, nervousness and/or agitation, vertigo, and fatigue in both study groups. CONCLUSIONS: Adjunctive brivaracetam was efficacious, had good tolerability, and no new or unexpected safety signals emerged when used to treat older patients with uncontrolled focal seizures in clinical practice. Adjunctive brivaracetam can be a suitable therapeutic option in this special population

Sustained seizure freedom with adjunctive brivaracetam in patients with focal onset seizures

The maintenance of seizure control over time is a clinical priority in patients with epilepsy. The aim of this study was to assess the sustained seizure frequency reduction with adjunctive brivaracetam (BRV) in real-world practice. Patients with focal epilepsy prescribed add-on BRV were identified. Study outcomes included sustained seizure freedom and sustained seizure response, defined as a 100% and a >= 50% reduction in baseline seizure frequency that continued without interruption and without BRV withdrawal through the 12-month follow-up. Nine hundred ninety-four patients with a median age of 45 (interquartile range = 32-56) years were included. During the 1-year study period, sustained seizure freedom was achieved by 142 (14.3%) patients, of whom 72 (50.7%) were seizure-free from Day 1 of BRV treatment. Sustained seizure freedom was maintained for >= 6, >= 9, and 12 months by 14.3%, 11.9%, and 7.2% of patients from the study cohort. Sustained seizure response was reached by 383 (38.5%) patients; 236 of 383 (61.6%) achieved sustained >= 50% reduction in seizure frequency by Day 1, 94 of 383 (24.5%) by Month 4, and 53 of 383 (13.8%) by Month 7 up to Month 12. Adjunctive BRV was associated with sustained seizure frequency reduction from the first day of treatment in a subset of patients with uncontrolled focal epilepsy