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Abstract Background Acute cerebellitis (AC) and acute cerebellar ataxia (ACA) are the principal causes of acute cerebellar dysfunction in childhood. Nevertheless. there is no accepted consensus regarding the best management of children with AC/ACA: the aim of the study is both to assess clinical, neuroimaging and electrophysiologic features of children with AC/ACA and to evaluate the correlation between clinical parameters, therapy and outcome. Methods A multicentric retrospective study was conducted on children ≤ 18 years old admitted to 12 Italian paediatric hospitals for AC/ACA from 01/01/2003 to 31/12/2013. A score based on both cerebellar and extracerebellar signs/symptoms was computed for each patient. One point was given for each sign/symptom reported. Severity was divided in three classes: low, moderate, severe. Results A total of 124 children were included in the study. Of these, 118 children received a final diagnosis of ACA and 6 of AC. The most characteristic finding of AC/ACA was a broad-based gait disturbance. Other common symptoms included balance disturbances, slurred speech, vomiting, headache and fever. Neurological sequelae were reported in 6 cases (5%) There was no correlation among symptoms, cerebrospinal fluid findings, clinical outcome. There was no correlation between clinical manifestations and clinical score on admission and length of hospital stay, sex, age and EEG findings with sequelae (P > 0.05). Children with pathological magnetic resonance imaging (MRI) or computed tomography (CT) had a higher probability of having clinical sequelae. Treatment was decided independently case by case. Patients with a higher clinical score on admission had a higher probability of receiving intravenous steroids. Conclusions We confirmed the literature data about the benign course of AC/ACA in most cases but we also highlighted a considerable rate of patients with neurological sequelae (5%). Pathological MRI or CT findings at admission correlate to neurological sequelae. These findings suggest the indication to perform an instrumental evaluation in all patients with AC/ACA at admission to identify those at higher risk of neurological outcome. These patients may benefit from a more aggressive therapeutic strategy and should have a closer follow-up. Randomized controlled trials are needed to confirm these observations. The ultimate goal of these studies could be to develop a standardized protocol on AC/ACA. The MRI/CT data, associated with the clinical manifestations, may allow us to define the class risk of patients for a neurological outcome.

Abstract We describe the purification of xenon from traces of the radioactive noble gas radon using a cryogenic distillation column. The distillation column was integrated into the gas purification loop of the XENON100 detector for online radon removal. This enabled us to significantly reduce the constant $$^{222}$$ 222 Rn background originating from radon emanation. After inserting an auxiliary $$^{222}$$ 222 Rn emanation source in the gas loop, we determined a radon reduction factor of $$R\,>\,27$$ R > 27 (95% C.L.) for the distillation column by monitoring the $$^{222}$$ 222 Rn activity concentration inside the XENON100 detector.

Abstract The XENON1T experiment aims for the direct detection of dark matter in a detector filled with 3.3 tons of liquid xenon. In order to achieve the desired sensitivity, the background induced by radioactive decays inside the detector has to be sufficiently low. One major contributor is the $$\beta $$ β -emitter $$^{85}$$ 85 Kr which is present in the xenon. For XENON1T a concentration of natural krypton in xenon $$\mathrm {^{nat}\mathrm{Kr/Xe}\,

This study examined the relationship of weather conditions, together with sex and country of origin, with running performance in the Boston Marathon from 1972 to 2018. A total of 580,990 observations from 382,209 different finishers were analyzed using Generalized Additive Mixed Models. Different groups and subgroups were considered such as all runners, near elite 101:200 finishers, near elite 21:100, annual top ten finishers and annual winners. Weather conditions, over the hours of the event, were average air temperature (°C), total precipitations (mm), wet-bulb globe temperature (WBGT) (°C), wind speed (km/h), wind direction (head wind, side wind, tail wind) and barometric pressure (hPa). These effects were examined in a multi-variable model, together with: sex, country of origin, calendar year, an interaction term country:sex and a spline smooth term in function of calendar year and sex. The average temperature, when increasing by 1°C, was related to worsened performance (by 00:01:47 h:min:sec for all finishers and by 00:00:20 h:min:sec for annual winners). Also, the pressure and wet-bulb globe temperature, when increasing, were related to worsened performances. Tail wind improved performances of all groups. Increasing precipitation was significantly (p

IntroductionFollowing years of controversy regarding screening for prostate cancer using prostate-specific antigen, evidence evolves towards a more restrained and preference-based use. This study reports the impact of landmark trials and updated recommendations on the incidence rate of prostate cancer screening by Swiss general practitioners.MethodsWe performed a retrospective analysis of primary care data, separated in 3 time periods based on dates of publications of important prostate-specific antigen screening recommendations. 1: 2010-mid 2012 including 2 updates; 2: mid 2012-mid 2014 including a Smarter Medicine recommendation; 3: mid-2014-mid-2017 maintenance period. Period 2 including the Smarter Medicine recommendation was defined as reference period. We further assessed the influence of patient's age and the number of prostate-specific-antigen (PSA) tests, by the patient and within each time period, on the mean PSA concentration. Uni- and multivariable analyses were used as needed.Results36,800 men aged 55 to 75 years were included. 14.6% had ≥ 2 chronic conditions, 11.7% had ≥ 1 prostate-specific antigen test, (mean 2.60 ng/ml [SD 12.3]). 113,921 patient-years were covered. Data derived from 221 general practitioners, 33.5% of GP were women, mean age was 49.4 years (SD 10.0), 67.9% used prostate-specific antigen testing. Adjusted incidence rate-ratio (95%-CI) dropped significantly over time periods: Reference Period 2: incidence rate-ratio 1.00; Period 1: incidence rate-ratio 1.74 (1.59-1.90); Period 3: incidence rate-ratio 0.61 (0.56-0.67). A higher number of chronic conditions and a patient age between 60-69 years were significantly associated with higher screening rate. Increasing numbers of PSA testing per patient, as well as increasing age, were independently and significantly associated with an increase in the PSA value.ConclusionSwiss general practitioners adapted screening behavior as early as evidence of a limited health benefit evolved, while using a risk-adapted approach whenever performing multiple testing. Updated recommendations might have helped to maintain this decrease. Further recommendations and campaigns should aimed at older patients with multimorbidity, to sustain a further decline in prostate-specific antigen screening practices.

Antibiotic resistance (ABR) is a major threat to public health, and the majority of antibiotics are prescribed in the outpatient setting, especially in primary care. Monitoring antibiotic consumption is one key measure in containing ABR, but Swiss national surveillance data are limited. We conducted a retrospective cross-sectional study to characterise the patterns of antibiotic prescriptions, assess the time trends, and identify the factors associated with antibiotic prescribing in Swiss primary care. Using electronic medical records data, we analysed 206,599 antibiotic prescriptions from 112,378 patients. Based on 27,829 patient records, respiratory (52.1%), urinary (27.9%), and skin (4.8%) infections were the commonest clinical indications for antibiotic prescribing. The most frequently prescribed antibiotics were broad-spectrum penicillins (BSP) (36.5%), fluoroquinolones (16.4%), and macrolides/lincosamides (13.8%). Based on the WHO AWaRe classification, antibiotics were 57.9% Core-Access and 41.7% Watch, 69% of which were fluoroquinolones and macrolides. Between 2008 and 2020, fluoroquinolones and macrolides/lincosamides prescriptions significantly declined by 53% and 51%; BSP prescriptions significantly increased by 54%. Increasing patients’ age, volume, and employment level were significantly associated with antibiotic prescribing. Our results may inform future antibiotic stewardship interventions to improve antibiotic prescribing.

The determination of small highly polar metabolites at low concentrations is challenging when reverse-phase (RP) chromatography is used for multiclass analysis. A mixed cationic-RP column coupled to high-resolution tandem MS (HR-MS/MS) was tested for highly polar compounds in biological fluids, i.e., trimethylamine N-oxide (TMAO) and the isobaric molecules beta-methylamino-L-alanine (BMAA) and 2,4-diaminobutyric acid (DAB). The efficient retention and separation of the above compounds were obtained with common and MS-friendly RP conditions, reaching high selectivity and sensitivity. The method was firstly assessed in plasma and urine, showing good linearity in the range 50–1000 µg/L and 500–10,000 µg/L for TMAO and both BMAA and DAB, respectively. Excellent precision (RDS < 3%) and good accuracies (71–85%) were observed except for BMAA in plasma, whose experimental conditions should be specifically optimized. Preliminary tests performed on compounds with biological relevance and a wider range of polarities proved the effectiveness of this chromatographic solution, allowing the simultaneous analysis of a larger panel of metabolites, from very small and polar compounds, like trimethylamine, to quite lipophilic molecules, such as corticosterone. The proposed LC-HRMS protocol is an excellent alternative to hydrophilic interaction liquid chromatography and ion-pairing RP chromatography, thus providing another friendly analytical tool for metabolomics.

This study investigated the relationship between race times and age, in 1-year intervals, by using the world single age records, from 5 km to marathon running (i. e., 5 km, 4 miles, 8, 10, 12, 15 km, 10 miles, 20 km, half-marathon, 25 km, 30 km, and marathon). For each race, a regression model was fitted. Effects of sex, alone and in interaction with age, and the effect of country of origin on performance were examined in a multi-variable model. The relationship between age and race time was modeled through a 4th order-polynomial function. Women achieved their best half-marathon and marathon race time, respectively, 1 year and 3 years earlier in life than men. On the contrary, in the other races, the best women performances were achieved later in life than men (i.e., 4 miles and 30 km: 2 years later, 8 km: 3 years later, 15–20–25 km: 1 year later, 10 miles: 4 years) or at the same age (i.e., 5, 10, 12 km). Moreover, age of peak performance did not change monotonically with the distance of race. For all races, except 12 km, sex differences had an absolute maximum at old ages and a relative maximum near the age of peak performance. From 8 km onward, estimated sex differences were increasing with increasing race distance. Regarding country, runners from Canada were slower than runners from the United States of America in 5 km by 00:10:05 h:min:s (p < 0.001) and in half-marathon by 00:18:43 h:min:s (p < 0.01). On the contrary, in marathon, they were 00:18:43 h:min faster (p < 0.05). Moreover, in 10 miles, runners from Great Britain were 00:02:53 h:min:s faster (p < 0.05) than runners from the United States of America. In summary, differences seem to exist in the age of peak performance between women and men and for nearly all distances sex differences showed an absolute maximum at old ages and relative maximum near the age of peak performance. Thus, these findings highlight the need for sex-specific training programs, especially near the age of peak performance and for elder runners.

The aim of the present study was to compare swimming performances of successful finishers of the 'Triple Crown of Open Water Swimming' from 1875 to 2017, assessing the effects of sex, the place of event and the nationality of swimmers. Data from 535 finishers in 'Catalina Channel Swim', 1,606 finishers in 'English Channel Swim' and 774 finishers in 'Manhattan Island Marathon Swim' were analysed. We performed different analyses and regression model fittings for all swimmers and annual top-5 finishers. Effects (sex, event, time, nationality) and interaction terms (event-time) were examined through a multi-variable spline mixed regression model. Considering all swimmers, we found that (i) women were approximately 0.06 km/h faster than men (p = 0.011) and (ii) Australians were 0.13 km/h faster than Americans (p = 0.004) and Americans were 0.19 km/h faster than British (p

Faces convey many signals (i.e., gaze or expressions) essential for interpersonal interaction. We have previously shown that facial expressions of emotion and gaze direction are processed and integrated in specific combinations early in life. These findings open a number of developmental questions and specifically in this paper we address whether such emotional signals may modulate the behavior in a following gaze context. A classic spatial cueing paradigm was used to assess whether different facial expressions may cause differential orienting response times and modulate the visual response to a peripheral target in adults and in 4-month-old infants. Results showed that both adults and infants oriented towards a peripheral target when a central face was gazing in the direction of the target location. However, in adults this effect occurred regardless of the facial expression displayed by the face. In contrast, in infants, the emotional facial expressions used, at least in the current study, did not facilitate the attention shift but tended to hold infants' attention. (Contains 2 tables and 2 figures.)

A dynamic network loading (DNL) model using a mesoscopic approach is proposed to simulate a multimodal transport network considering en-route change of the transport modes. The classic mesoscopic approach, where packets of users belonging to the same mode move following a path, is modified to take into account multiple modes interacting with each other, simultaneously and on the same multimodal network. In particular, to simulate modal change, functional aspects of multimodal arcs have been developed; those arcs are properly located on the network where modal change occurs and users are packed (or unpacked) in a new modal resource that moves up to destination or to another multimodal arc. A test on a simple network reproducing a real situation is performed in order to show model peculiarities; some indicators, used to describe performances of the considered transport system, are shown.

North-western Argentinean propolis (NAP), having promising bioactivity, was recently included into the National Food Code. Zuccagnia punctata Cav., a native shrub of north-western Argentina, is one of the prevalent botanical sources of NAPs, but no information on its allergenic constituents was available so far. A liquid chromatography-diode array detector -quadrupole-time of flight system (LC-DAD-QTOF) was used as a screening method for the reliable identification of sensitizing agents belonging to caffeic acid derivatives in Z. punctata and in two NAPs collected in the provinces of Catamarca and Tucumán. Caffeic acid phenethyl ester, one of the most active allergens in propolis, was never detected in either Z. punctata or NAP. Among 31 sensitizers, only geranyl caffeate was alleged in Z. punctata as Z. punctata major constituent), indicating other minor botanical sources. However, the high content of chalcones and flavonoids ascribed to Z. punctata significantly contributes to the antiallergenic and antioxidant character of these NAPs. This peculiar chemical profile depends on the extremophile condition in which this shrub grows and suggests other studies to characterize such raw materials for oral and topical formulations.

A methodology that permits testing the level of integration of the photovoltaic technology in urban areas is presented. The percentage of coverage of the electricity demand of grid-connected photovoltaic systems installed on the roofs of buildings were investigated in a district of the city of Palermo (Sicily). After classifying roofs according to their shape, orientation and pitch by means of satellite images provided by Google Earth, the ratio of the productivity of the PV systems and the consumption of electricity of the households was analysed. The results of the energy assessment have been screened considering the economic feasibility of grid-connected photovoltaic systems: the energy produced by the PV systems whose economic analysis showed disadvantageous values of NPV or IRR was rejected. As a result, it can be concluded that the size of the PV system that may be installed corresponding to the number of floors, and the consequent production of electricity, does not recover the costs for installation and maintenance of the system.

[This corrects the article DOI: 10.1371/journal.pone.0164745.].

T cell maturation takes place within the thymus, a primary lymphoid organ that is commonly targeted during infections. Previous studies showed that acute infection with Paracoccidioides brasiliensis (Pb), the causative agent of paracoccidioidomycosis (PCM), promotes thymic atrophy that is associated with the presence of yeast cells in the organ. However, as human PCM is a chronic infection, it is imperative to investigate the consequences of Pb infection over the thymic structure and function in chronic infection. In this sense, we developed a new experimental model where Pb yeast cells are injected through the intraperitoneal route and mice are evaluated over 120 days of infection. Thymuses were analyzed in chronically infected mice and we found that the thymus underwent extensive morphological alterations and severe infiltration of P. brasiliensis yeast cells. Further analyses showed an altered phenotype and function of thymocytes that are commonly found in peripheral mature T lymphocytes. We also observed activation of the NLRP3 inflammasome in the thymus. Our data provide new information on the severe changes observed in the thymic microenvironment in a model of PCM that more closely mimics the human infection.

This study aimed to evaluate the diagnostic accuracy of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), midregional proatrial natriuretic peptide (MR-proANP) and midregional proadrenomedullin (MR-proADM) to distinguish bacterial from viral community-acquired pneumonia (CAP) and to identify severe cases in children hospitalized for radiologically confirmed CAP. Index test results were compared with those derived from routine diagnostic tests, i.e., white blood cell (WBC) counts, neutrophil percentages, and serum C-reactive protein (CRP) and procalcitonin (PCT) levels.This prospective, multicenter study was carried out in the most important children's hospitals (n = 11) in Italy and 433 otherwise healthy children hospitalized for radiologically confirmed CAP were enrolled. Among cases for whom etiology could be determined, CAP was ascribed to bacteria in 235 (54.3%) children and to one or more viruses in 111 (25.6%) children. A total of 312 (72.2%) children had severe disease.CRP and PCT had the best performances for both bacterial and viral CAP identification. The cut-off values with the highest combined sensitivity and specificity for the identification of bacterial and viral infections using CRP were ≥7.98 mg/L and ≤7.5 mg/L, respectively. When PCT was considered, the cut-off values with the highest combined sensitivity and specificity were ≥0.188 ng/mL for bacterial CAP and ≤0.07 ng/mL for viral CAP. For the identification of severe cases, the best results were obtained with evaluations of PCT and MR-proANP. However, in both cases, the biomarker cut-off with the highest combined sensitivity and specificity (≥0.093 ng/mL for PCT and ≥33.8 pmol/L for proANP) had a relatively good sensitivity (higher than 70%) but a limited specificity (of approximately 55%).This study indicates that in children with CAP, sTREM-1, MR-proANP, and MR-proADM blood levels have poor abilities to differentiate bacterial from viral diseases or to identify severe cases, highlighting that PCT maintains the main role at this regard.

Buschke Scleredema is a rare connective tissue disorder of unknown aetiology, characterized by thickening of the dermis whose characteristics may mainly to mime systemic sclerosis, eosinophilic fasciitis and cutaneous amyloidosis. Scleredema may be associated with a history of an antecedent febrile illness, diabetes mellitus, or blood dyscrasia. Scleredema can be classified into three clinical groups; each has a different history, course, and prognosis. Each one of these share reduction in chest articular movements and limitation of limbs movements. The skin histology is characterised by thickened dermis and increased spaces between large collagen bundles due to increased deposition of mucopolysaccharide in the dermis. Differential diagnosis can be made considering the typical clinical features and the histologic peculiarity. No therapy has been found effective. The autors describe a case of Buschke Scleredema successfully treated by steroids and colchicines. Clinical evaluation of skin induration and thickness as well as ultrasonography were performed at baseline and after treatment.

Inflammation involving the uveal tract of the eye, termed uveitis, is frequently associated with various rheumatic disease, including seronegative spondylarthropathies, juvenile rheumatoid arthritis, Crohn’s disease and Behçet’s disease. Scleritis and keratitis may be associated with rheumatoid arthritis and systemic vasculitides such as Wegener’s granulomatosis. Immune-mediated uveitis can have a chronic relapsing course and produce numerous possible complications, many of which can result in permanent vision loss. Treatment typically includes topical or systemic corticosteroids with cycloplegic-mydriatic drugs and/or noncorticosteroid immunosuppressants, but often there is an insufficient clinical effectiveness. Anti-TNFα therapy is promising in the treatment of sight threatening uveitis, particularly in patients with Behçet’s disease. However, there have been also reports of new-onset uveitis during treatment of joint disease with TNFα inhibitors. We describe a case of new-onset uveitis in a patient with rheumatoid arthritis during therapy with etanercept at first and infliximab at last. Although we cannot exclude uveitis as linked to rheumatoid arthritis, it is unlike that the uveitis arises when the joint disease is well controlled. The hypothetical paradoxical effect of anti-TNF is here discussed.

The choice of the type of abdominal incision performed in caesarean delivery is made chiefly on the basis of the individual surgeon's experience and preference. A general consensus on the most appropriate surgical technique has not yet been reached. The aim of this systematic review of the literature is to compare the two most commonly used transverse abdominal incisions for caesarean delivery, the Pfannenstiel incision and the modified Joel-Cohen incision, in terms of acute and chronic post-surgical pain and their subsequent influence in terms of quality of life. Electronic database searches formed the basis of the literature search and the following databases were searched in the time frame between January 1997 and December 2013: MEDLINE, EMBASE Sciencedirect and the Cochrane Library. Key search terms included: "acute pain", "chronic pain", "Pfannenstiel incision", "Misgav-Ladach", "Joel Cohen incision", in combination with "Caesarean Section", "abdominal incision", "numbness", "neuropathic pain" and "nerve entrapment". Data on 4771 patients who underwent caesarean section (CS) was collected with regards to the relation between surgical techniques and postoperative outcomes defined as acute or chronic pain and future pregnancy desire. The Misgav-Ladach incision was associated with a significant advantage in terms of reduction of post-surgical acute and chronic pain. It was indicated as the optimal technique in view of its characteristic of reducing lower pelvic discomfort and pain, thus improving quality of life and future fertility desire. Further studies which are not subject to important bias like pre-existing chronic pain, non-standardized analgesia administration, variable length of skin incision and previous abdominal surgery are required.

Inflammation is a necessary process to control infection. However, exacerbated inflammation, acute or chronic, promotes deleterious effects in the organism. Violacein (viola), a quorum sensing metabolite from the Gram-negative bacterium Chromobacterium violaceum, has been shown to protect mice from malaria and to have beneficial effects on tumors. However, it is not known whether this drug possesses anti-inflammatory activity. In this study, we investigated whether viola administration is able to reduce acute and chronic autoimmune inflammation. For that purpose, C57BL/6 mice were intraperitoneally injected with 1 μg of LPS and were treated with viola (3.5mg/kg) via i.p. at the same time-point. Three hours later, the levels of inflammatory cytokines in the sera and phenotypical characterization of leukocytes were determined. Mice treated with viola presented a significant reduction in the production of inflammatory cytokines compared with untreated mice. Interestingly, although viola is a compound derived from bacteria, it did not induce inflammation upon administration to naïve mice. To test whether viola would protect mice from an autoimmune inflammation, Experimental Autoimmune Encephalomyelitis (EAE)-inflicted mice were given viola i.p. at disease onset, at the 10th day from immunization. Viola-treated mice developed mild EAE disease in contrast with placebo-treated mice. The frequencies of dendritic cells and macrophages were unaltered in EAE mice treated with viola. However, the sole administration of viola augmented the levels of splenic regulatory T cells (CD4+Foxp3+). We also found that adoptive transfer of viola-elicited regulatory T cells significantly reduced EAE. Our study shows, for the first time, that violacein is able to modulate acute and chronic inflammation. Amelioration relied in suppression of cytokine production (in acute inflammation) and stimulation of regulatory T cells (in chronic inflammation). New studies must be conducted in order to assess the possible use of viola in therapeutic approaches in human autoimmune diseases.

Edible seaweeds have been consumed by Asian coastal communities since ancient times. Fucus vesiculosus and Ascophyllum nodosum extracts have been traditionally used for the treatment of obesity and several gastrointestinal diseases. We evaluated the ability of extracts obtained from these algae to inhibit the digestive enzymes α-amylase and α-glucosidase in vitro, and control postprandial plasma glucose levels in a mouse model of non-alcoholic steatohepatitis (NASH); a liver disease often preceding the development of Type 2 diabetes (T2DM). This model was obtained by the administration of a high-fat diet. Our results demonstrate that these algae only delayed and reduced the peak of blood glucose (p < 0.05) in mice fed with normal diet, without changing the area under the blood glucose curve (AUC). In the model of NASH, the phytocomplex was able to reduce both the postprandial glycaemic peak, and the AUC. The administration of the extract in a diet particularly rich in fat is associated with a delay in carbohydrate digestion, but also with a decrease in its assimilation. In conclusion, our results indicate that this algal extract may be useful in the control of carbohydrate digestion and absorption. This effect may be therapeutically exploited to prevent the transition of NASH to T2DM.

The thymus plays an important role shaping the T cell repertoire in the periphery, partly, through the elimination of inflammatory auto-reactive cells. It has been shown that, during Plasmodium berghei infection, the thymus is rendered atrophic by the premature egress of CD4+CD8+ double-positive (DP) T cells to the periphery. To investigate whether autoimmune diseases are affected after Plasmodium berghei NK65 infection, we immunized C57BL/6 mice, which was previously infected with P. berghei NK65 and treated with chloroquine (CQ), with MOG35-55 peptide and the clinical course of Experimental Autoimmune Encephalomyelitis (EAE) was evaluated. Our results showed that NK65+CQ+EAE mice developed a more severe disease than control EAE mice. The same pattern of disease severity was observed in MOG35-55-immunized mice after adoptive transfer of P. berghei-elicited splenic DP-T cells. The higher frequency of IL-17+- and IFN-γ+-producing DP lymphocytes in the Central Nervous System of these mice suggests that immature lymphocytes contribute to disease worsening. To our knowledge, this is the first study to integrate the possible relationship between malaria and multiple sclerosis through the contribution of the thymus. Notwithstanding, further studies must be conducted to assert the relevance of malaria-induced thymic atrophy in the susceptibility and clinical course of other inflammatory autoimmune diseases.

BACKGROUND: The modulation of inflammatory processes is a necessary step, mostly orchestrated by regulatory T (Treg) cells and suppressive Dendritic Cells (DCs), to prevent the development of deleterious responses and autoimmune diseases. Therapies that focused on adoptive transfer of Treg cells or their expansion in vivo achieved great success in controlling inflammation in several experimental models. Chloroquine (CQ), an anti-malarial drug, was shown to reduce inflammation, although the mechanisms are still obscure. In this context, we aimed to access whether chloroquine treatment alters the frequency of Treg cells and DCs in normal mice. In addition, the effects of the prophylactic and therapeutic treatment with CQ on Experimental Autoimmune Encephalomyelitis (EAE), an experimental model for human Multiple Sclerosis, was investigated as well. METHODOLOGY/PRINCIPAL FINDINGS: EAE was induced in C57BL/6 mice by immunization with myelin oligodendrocyte glycoprotein (MOG35-55) peptide. C57BL/6 mice were intraperitoneally treated with chloroquine. Results show that the CQ treatment provoked an increase in Treg cells frequency as well as a decrease in DCs. We next evaluated whether prophylactic CQ administration is capable of reducing the clinical and histopathological signs of EAE. Our results demonstrated that CQ-treated mice developed mild EAE compared to controls that was associated with lower infiltration of inflammatory cells in the central nervous system CNS) and increased frequency of Treg cells. Also, proliferation of MOG35-55-reactive T cells was significantly inhibited by chloroquine treatment. Similar results were observed when chloroquine was administrated after disease onset. CONCLUSION: We show for the first time that CQ treatment promotes the expansion of Treg cells, corroborating previous reports indicating that chloroquine has immunomodulatory properties. Our results also show that CQ treatment suppress the inflammation in the CNS of EAE-inflicted mice, both in prophylactic and therapeutic approaches. We hypothesized that the increased number of regulatory T cells induced by the CQ treatment is involved in the reduction of the clinical signs of EAE.

Women with type 2 diabetes were less likely to have diabetes related complications than women with type 1. Women with type 1 diabetes had a high prepregnancy care and showed a worse glycemic control than women with type 2 both in the preconception period and during pregnancy. Obstetrical outcomes showed that preeclampsia and stillbirth rate is almost doubled in type 1 patients while perinatal deaths and SGA importantly increased in type 2 diabetes. In modern obstetrical care it is mandatory to maintain glucose levels as close to normal as possible particularly in diabetic population. HbA1C no higher than 6% before pregnancy and during the first trimester seems to decrease the risk of adverse obstetrical outcomes. Both the preconceptional counseling and glycemic profile optimization represent a fundamental step to improve pregnancy outcomes in women with preexisting diabetes. A systematic approach to family planning and the availability of preconception care for all diabetic women who desire pregnancy could be an essential step for diabetic management program.

Models for photovoltaic (PV) cells and panels, based on the diode equivalent circuit, have been widely used because they are effective tools for system design. Many authors have presented simplified one-diode models whose three or four parameters are calculated using the data extracted from the datasheets issued by PV panel manufactures and adopting some simplifying hypotheses and numerical solving techniques. Sometimes it may be difficult to make a choice among so many models. To help researchers and designers working in the area of photovoltaic systems in selecting the model that is fit for purpose, a criterion for rating both the usability and accuracy of simplified one-diode models is proposed in this paper. The paper minutely describes the adopted hypotheses, analytical procedures and operative steps to calculate the parameters of the most famous simplified one-diode equivalent circuits. To test the achievable accuracy of the models, a comparison between the characteristics of some commercial PV modules issued by PV panel manufacturers and the calculated current-voltage (I-V) curves, at constant solar irradiance and/or cell temperature, is carried out. The study shows that, even if different usability ratings and accuracies are observed, the simplified one-diode models can be considered very effective tools.

In July 2013, the Italian photovoltaic (PV) support policies changed the feed-in tariff (FIT) mechanism and turned to a tax credits program, which is currently in force. The aim of this paper is to investigate how such a radical change has influenced the electricity demand coverage of the PV systems installed in urban contexts. A methodology, which connects the economic assessment to a detailed architectural and energy suitability analysis, was applied to some case studies to analyse the relationships between the physical parameters related to multi-storey buildings (roof shapes, number of floors and area of flats) and the most relevant economic and financial features affecting the viability of rooftop PV systems. The study, which considers only the electricity produced by the PV systems that are economically profitable, highlighted that the tax credits scheme is even more effective in covering the electrical consumption of densely urbanised Italian city districts. The results, which are significantly influenced by the latitude of the analysed districts, underline the opportunity for governments to adopt PV promoting policies that are more sensitive to the amount of solar energy available in the different regions of their national territory.