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Inflammatory bowel diseases (IBD) are gastrointestinal tract pathologies of unknown etiology; they have an alternating trend, with active and silent phases. IBD are classified in two main forms: ulcerative colitis (UC) and Crohn’s disease (CD). Both have chronic and recurrent course, gastrointestinal symptoms, and extraintestinal manifestations. The altered immune response role seems to be important both in UC and CD. In the majority of cases, CD begins with abdominal pain, diarrhea, decrease in appetite, and weight loss; there can be also perianal fistulas, rhagades, and perianal recurrent abscesses. In addition, retarded growth and delayed puberty can precede the development of the disease or can even be predominant at onset. Growth retardation is found in 40% of IBD patients, but the underlying mechanism of this and other extra-intestinal manifestations are partially known: the main hypotheses are represented by malnutrition and inflammatory response during the active phase of the disease. The increased level of pro-inflammatory cytokines can influence growth, but also the onset of puberty and its progression. In addition, it could be essential to clarify the role and the possible effects of all the currently used treatments concerning growth failure and delayed puberty.

The association between type 1 diabetes (T1D) and coeliac disease (CD) is well known. Metabolic control of thirty-seven patients aged between 1 and 18 years, with coexisting T1D and CD were evaluated. The control group includes 37 patients affected only by diabetes. All data relating to the metabolic control of all patients were acquired through examination of medical records and CMG reports available on dedicated online platforms. Glucose variability was expressed as Coefficient of Variation (CV) and Standard Deviation of blood glucose values (SD). The formula used for CV computation is: CV (%) = 100 × SD (daily glycemia)/Mean (daily glycemia). Patients with T1D and CD showed a significant reduction in rapid pre-prandial insulin. The same reduction was present if we consider only patients using CGM. In patients without CGM, there was no difference in the doses of basal, pre-prandial and total insulin. Indicators of metabolic control were overlapping between the two groups in patients who used CGM. On the contrary, diabetic and coeliac patients without CGM had increased levels of glycaemic variability indicators and HbA1c. Finally, the percentage of target glycaemic values and >250 mg/dL glycaemic values were significantly decreased and increased, respectively in T1D and CD patients without CGM. With this study we wanted to demonstrate if CGM could improve metabolic control of patients with coexisting T1D and CD. Our data show a worse metabolic control in patients with T1D and CD who did not use CGM. Instead, patients who use CGM, regardless of the concomitant CD, manage to achieve the same glycaemic targets through an adjustment of titration of pre-prandial insulin doses.

IntroductionThere are many techniques to treat congenital concealed penis (CP). Skin resurfacing is the most difficult step in severe cases. We aim to show medium-term results of coronal sulcus–based triangular ventral mucosal flap (CBVMF) as a treatment of prepubertal severe CP, a recently reported technique. We aim to determine whether results are durable and if the technique is associated with persistent mucosal redundancy or with a permanent unequal penile color pattern.MethodsCP cases reconstructed with CBVMF were reviewed. Preoperative complaints, degree of motivation of the child/parent to surgery, satisfaction of parent/child with results, and surgical complications were described.ResultsSeven patients (6 months to 6 years old) were treated with CBVMP. Two patients showed megaprepuce and another was submitted to a limited postectomy 3 years before. One family was not fully satisfied (expected “bigger penis”), but acknowledged that the penis was now well exposed. No child talked about the problem preoperatively, but all of the boys were fully satisfied with the results of the surgery and verbalized this in the interviews. Flap edema resolved after 3 months in all but one patient. The flaps assumed the color of penile skin in the medium term.ConclusionsCBMVP results were satisfactory. Serious complications did not occur. Flap edema does not persist in the medium term, and redundancy was not a problem. The color of the flap tended to evolve into a pattern similar to the penile skin.

Outcomes of insulin analogues in pediatric diabetes camps are poorly investigated; no data is available about insulin degludec (IDeg).Our aim was to assess impact of insulin therapy adopted by the participants to a 4-day diabetes camp held in 2017, hypothesizing a possible excess risk of hypoglycemia in patients treated with IDeg. Overall, 40 children with type 1 diabetes (mean age 13.4±3.0 years; 62.5% males) attended the camp (20.0% on continuous subcutaneous insulin infusion and 80.0% on multiple daily injections - MDI). Among children in MDI regimen, 71.9% were treated with IDeg as basal insulin and 28.1% with glargine U100 (IGlar). All patients used Lispro or Aspart as short-acting insulin. Daily plan of the camp included educational sessions, physical exercise, 3 main meals and 2 snacks. At the arrival, IGlar and short-acting insulin doses were revised according to existing guidelines, while IDeg dose was revised based on an empirical individualized approach. At the arrival, insulin doses were reduced in 22 participants (-19.4±10.5%), while doses were increased in 17 children (+17.8±12.7%), based on individual needs. No statistically significant between-group difference emerged in mean blood glucose and glucose variability. No excess risk of hypoglycemia was found in the IDeg group. The study suggests similar effectiveness and safety of different insulin schemes when associated with appropriate diabetes education and management, and flexible dose adjustments. Despite its longer halflife and the lack of a validated algorithm, IDeg was not associated with an excess risk of hypoglycemia.

Background No data exist about the changes induced by the transition from first‐generation long‐acting insulins to second‐generation long‐acting analogues in the paediatric population. Objective To assess changes in insulin/carbohydrate ratio (I:CHO) after the first 6 months of degludec therapy in a paediatric population with type 1 diabetes previously treated with glargine U100. Subjects All patients treated with degludec under routine clinical practice conditions were retrospectively analysed. Methods Nonprofit observational retrospective study. Changes during the follow‐up in mean CHO/I ratio were assessed using longitudinal linear models for repeated measures. Rate of hypoglycaemia, ketoacidosis and adverse events was evaluated. Results Overall, 51 children (mean age 13.8 ± 4.6 years; mean diabetes duration 5.8 ± 3.9 years) started therapy with degludec in the period between April 2017 and April 2018. I:CHO ratio before starting degludec therapy significantly differed among the three meals, being the lowest at breakfast and the highest at dinner. After introducing degludec, I:CHO ratio at lunch (−1.29 95% CI −2.02;−0.57) and at dinner (−3.08 95% CI −4.35;−1.8) significantly decreased, while it slightly increased at breakfast (+1.37 95% CI 0.47;2.28). No episodes of severe hypoglycaemia, ketoacidosis and adverse event were recorded during 6 months. Conclusions Our data show that the use of degludec is associated with a significant change in the I:CHO ratio at the different meals compared to the previous glargine therapy. This could derive from the flat and prolonged pharmacokinetic profile of degludec. This has important clinical implications for daily insulin dose adjustments. No data exist about the changes induced by the transition from first‐generation long‐acting insulins to second‐generation long‐acting analogues in the paediatric population. The study assessed changes in insulin/carbohydrate ratio (I:CHO) after the first 6 months of degludec therapy in a paediatric population with type 1 diabetes previously treated with glargine U100. Our data showed that the use of degludec is associated with a flattening in the I:CHO ratio at the different meals compared to the previous glargine therapy.

In this study, the formation of caffeine/dapsone (CAF/DAP) cocrystals by scalable production methods, such as liquid-assisted grinding (LAG) and spray drying, was investigated in the context of the potential use of processed cocrystal powder for pulmonary delivery. A CAF/DAP cocrystal (1:1 M ratio) was successfully prepared by slow evaporation from both acetone and ethyl acetate. Acetone, ethyl acetate, and ethanol were all successfully used to prepare cocrystals by LAG and spray drying. The powders obtained were characterized by X-ray diffractometry (XRD), differential scanning calorimetry (DSC), thermogravimetry (TGA), and Fourier transform infrared spectroscopy (FTIR). Laser diffraction analysis indicated a median particle size (D 50 ) for spray-dried powders prepared from acetone, ethanol, and ethyl acetate of 5.4 ± 0.7, 5.2 ± 0.1, and 5.1 ± 0.0 μm respectively, which are appropriate sizes for pulmonary delivery by means of a dry powder inhaler. The solubility of the CAF/DAP cocrystal in phosphate buffer pH 7.4, prepared by spray drying using acetone, was 506.5 ± 31.5 μg/mL, while pure crystalline DAP had a measured solubility of 217.1 ± 7.8 μg/mL. In vitro cytotoxicity studies using Calu-3 cells indicated that the cocrystals were not toxic at concentrations of 0.1 and of 1 mM of DAP, while an in vitro permeability study suggested caffeine may contribute to the permeation of DAP by hindering the efflux effect. The results obtained indicate that the CAF/DAP cocrystal, particularly when prepared by the spray drying method, represents a possible suitable approach for inhalation formulations with applications in pulmonary pathologies.

Between December 2019 and January 2020, two patients suspected of having severe yellow fever were admitted to a tertiary healthcare facility in São Paulo, Brazil, presenting with acute hemorrhagic syndrome and neurological alterations; both cases had fatal outcomes. Upon admission, both tested negative for yellow fever viral RNA, and Sabiá virus (SABV), a New World arenavirus, was identified as the causative pathogen. To date, only four humans naturally acquired SABV infections have been confirmed, all fatal and linked to rural settings. We applied next-generation sequencing to generate complete and near-complete genomes from two patients (SP17 and SP19). Existing molecular diagnostics failed to detect SABV; therefore, new molecular tests were developed. Genetic analyses of SP17 and SP19 genomes along with other arenaviruses, revealed that the new cases were genetically diverse, showing 93-98.2% amino acid identity at the NP level among SP17, SP19, and the 1990 reference strain (SPH114202). Time-scaled phylogenetic analyses confirmed that SP17 and SP19 were not epidemiologically linked and suggested that SABV has been circulating undetected in Brazil for over a century. Additionally, homology modeling and structure-based mapping provided insights into SABV receptor-binding sequence conservation, suggesting that SABV shares similar receptor binding structure to other clade B arenaviruses, despite some amino acid variation around receptor binding site. Our findings underscore the need for retrospective and prospective surveillance of undiagnosed hemorrhagic fever cases to assess the public health impact of SABV in Brazil.

We evaluated the environmental quality in mangrove areas of the Western Atlantic with different levels and history of contamination, considering biomarkers for the crab Ucides cordatus . For this purpose, specimens were collected in two climatic seasons (rainy and dry seasons) and assays of genotoxicity (MN, micronucleus), cytotoxicity (NRRT, neutral red retention time) and biochemical (MT, metallothionein; and LPO, lipoperoxidation) were conducted. In the most impacted mangroves, there was an increase in the mean of micronucleus (frequency of MN/1000), which was associated with a shorter retention time (minutes of NRRT). In contrast, the most pristine areas showed MN < 3 and NRRT < 100 min, with no seasonal effect, indicating a lower effect of degenerative processes by xenobiotics. The rainy season was more harmful, especially regarding cytogenotoxicity. The use of bioindicator species for environmental monitoring should be guided by an analysis of biomarkers considering the season, because during the period of highest rainfall, biomarkers values can change.

Objectives: This study aimed to compare the anthropometry and body composition of vegetarian and omnivorous adults living in Portugal, while exploring nutritional and health parameters underlying observed differences. Methods: 425 omnivorous (OMNI), lacto-ovo-vegetarian (LOV), or vegan (VEG) healthy adults were recruited. Anthropometry was measured, and bioelectrical impedance analysis was performed. Participants answered food frequency, sociodemographic, and lifestyle questionnaires. Serum iron, ferritin, and CRP were quantified by spectrophotometry, and serum B12 vitamin and homocysteine were quantified by chemiluminescent microparticle immunoassay. Results: Total protein intake significantly decreased with increasing strictness of vegetarian habits (median (P25; P75) in g/day: 98.6 (79.5; 123.1), 90.4 (65.9; 121.0), and 87.6 (59.8; 118.5) for OMNI, LOV and VEG, respectively; p = 0.020), and carbohydrate intake was the highest in LOV (median (P25; P75) in g/day: 231.5 (178.4; 287.9), 283.9 (227.3; 342.6), and 263.0 (222.0; 348.3) for OMNI, LOV and VEG, respectively; p = 0.001). VEG were the main users of B12 vitamin (93% in VEG vs. 17% in OMNI and 59% in LOV, p = 0.001), and LOV were the main users of iron supplements (29% in LOV vs. 14% in OMNI and 13% in VEG, p = 0.042), respectively. Blood levels of B12 vitamin correlated negatively with blood homocysteine (r(s) = -0.386, p < 0.001) and positively with % muscle mass (r(s) = 0.136, p = 0.005). Participants using iron supplements presented higher C-reactive protein (CRP) (p = 0.014) and they had lower % MM (p = 0.003). Finally, when compared to being OMNI, being LOV independently associated with: (a) having +4.8% (p = 0.002) of fat mass, which could be due to higher carbohydrate intake, and (b) having -2.2% (p = 0.043) of muscle mass. Our data suggest that the association between diet and muscle mass could be attenuated in VEG due to B12 supplementation and/or aggravated in LOV due to iron supplementation-associated inflammation.

Background Studies on functional magnetic resonance imaging (fMRI) have shown that adults with musculoskeletal pain syndromes tolerate smaller amount of pressure (pain) as well as differences in brain activation patterns in areas related to pain.The objective of this study was to evaluate, through fMRI, the brain activation in adolescents with idiopathic musculoskeletal pain (IMP) while performing an experimental paradigm of pain. Methods The study included 10 consecutive adolescents with idiopathic musculoskeletal pain (average age 16.3±1.0) and 10 healthy adolescents age-matched. fMRI exams were performed in a 3 T scanner (Magnetom Trio, Siemens) using an event-related design paradigm. Pressure stimuli were performed in the nondominant hand thumb, divided into two stages, fixed pain and variable pain. The two local Research Ethics Committees (Ethics Committee from Universidade Federal de São Paulo- Brazil, process number 0688/11, on July 1st, 2011 and Ethics Committee from Hospital Israelita Albert Einsten – Brazil, process number 1673, on October 19th, 2011) approved the study. Results The idiopathic musculoskeletal pain (IMP) group showed a reduced threshold for pain (3.7 kg/cm 2 versus 4.45 kg/cm 2 , p  = 0.005). Control group presented increased bain activation when compared to IMP group in the following areas: thalamus ( p  = 0.00001), precentral gyrus ( p  = 0.0004) and middle frontal gyrus ( p  = 0.03). In intragroup analysis, IMP group showed greater brain activation during the unpredictable stimuli of the variable pain stage, especially in the lingual gyrus ( p  = 0.0001), frontal lobe ( p  = 0.0001), temporal gyrus ( p  = 0.0001) and precentral gyrus ( p  = 0.03), when compared to predictable stimulus of fixed pain. The same intragroup analysis with the control group showed greater activation during the unpredictable stimuli in regions of the precentral gyrus ( p  = 0.0001), subcallosal area ( p  = 0.0001), right and left occipital fusiform gyrus ( p  = 0.0001; ( p  = 0.0007), middle gyrus ( p  = 0.01) and precuneus p  = (0.02). Conclusion Adolescents with idiopathic musculoskeletal pain (IMP) tend to request higher brain function in cognitive-emotional areas when interpreting unpredictable sensory-perceptual situations. Therefore, it is assumed that this difference in pain processing in adolescents with IMP make the subjective experience of pain something more intense and unpleasant.