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Objective: The objective of the study was to compare and analyze the emotional intelligence, occupational stress, and coping characteristics of three groups of newly hired oncology nurses. Methods: Data for this secondary analysis were collected from a larger study of 114 newly hired nurses at a cancer center in the Northeastern United States. Survey data were collected using the EQi-2.0™, the Nursing Stress Scale, and the Ways of Coping Questionnaire. Dimensions of study measures were analyzed based on new graduates, 1–5 years, and >5 years of nursing experience. Analysis of variance was conducted among the three groups followed by Tukey pairwise comparisons analysis when P = 0.05. Results: New graduates scored significantly lower on the self-expression dimension (mean = 96.88; standard deviation [SD] = 13.27) than nurses with >5 years nursing experience (mean = 106.12; SD 15.02) (P = 0.04), and the subdimension, assertiveness (mean = 94.73; SD = 13.87) compared to nurses with >5-year nursing experience (mean = 103.94; SD = 14.86) (P = 0.03). Significantly higher sources of stress for new graduates were death and dying (mean = 16.45; SD = 3.37), and for the associations between the three nursing groups (P = 0.001). New graduate nurses used the problem-focused coping strategy of accepting responsibility (mean = 14.06; SD = 7.28) significantly (P = 0.006) more often than nurses with >5-year experience (mean = 8.54; SD = 4.25), and planful problem solving (mean = 16.76; SD = 5.27) significantly less often (P =.001) than nurses with 1–5-year experiences (mean = 20.12; SD = 7.31). Conclusions: Dimension scores highlight the characteristics of nurses with varying levels of nursing experience onboarding at the same time. Findings may inform model-development for improving nurse-recruitment practices and retention strategies.

Objective: This article describes how one comprehensive cancer center in the Northeast United States reorganized their nursing research fellowship (NRF) with the goals of engaging nurses in research processes, developing a culture of inquiry, building nursing research capacity, and sustaining infrastructures for facilitating high-quality, nurse-led oncology research studies. Methods: The basis for the curriculum, course work, and research practicum is derived from academic courses taught at the undergraduate, graduate, and doctoral levels. Evidence from the current literature, expertise of nurse-scientists, and feedback from former fellows provided the background for a fellowship model that included: (1) amending curriculum timeframes; (2) incorporating protected time; (3) improving access to resources; (4) enhancing the protection, data sharing, and accessibility of data; and (5) involving nurse-scientists as mentors and facilitators of research processes. These factors were incorporated over 3 years. Metrics included individual class and overall course evaluations and ongoing assessments. Results: In three cohorts from 2016 to 2019, a total of 21 nurses were accepted, and 18 (86%) nurses completed the NRF. In cohort 1 through cohort 3, 17 fellows presented their research findings internally, and a total of nine projects were presented at external forums. There were seven fellows whose manuscript submissions resulted in 21 journal publications. Of the 18 fellows, 15 (83%) conducted institutional review board-approved studies and three (17%) fellows developed studies involving one concept analysis and two systematic reviews. Conclusions: Utilizing technology, the fellowship improved access beyond the classroom setting. Improved application processes, the inclusion of protected time for nurses, and mentoring from nurse-scientists demonstrate a commitment to fostering a culture supporting new knowledge and innovation for improving patient care.

Rapid detection of bloodstream infections (BSIs) can be lifesaving. We investigated the sample processing and assay parameters necessary for highly-sensitive detection of bloodstream bacteria, using Staphylococcus aureus as a model pathogen and an automated fluidic sample processing-polymerase chain reaction (PCR) platform as a model diagnostic system.We compared a short 128 bp amplicon hemi-nested PCR and a relatively shorter 79 bp amplicon nested PCR targeting the S. aureus nuc and sodA genes, respectively. The sodA nested assay showed an enhanced limit of detection (LOD) of 5 genomic copies per reaction or 10 colony forming units (CFU) per ml blood over 50 copies per reaction or 50 CFU/ml for the nuc assay. To establish optimal extraction protocols, we investigated the relative abundance of the bacteria in different components of the blood (white blood cells (WBCs), plasma or whole blood), using the above assays. The blood samples were obtained from the patients who were culture positive for S. aureus. Whole blood resulted in maximum PCR positives with sodA assay (90% positive) as opposed to cell-associated bacteria (in WBCs) (71% samples positive) or free bacterial DNA in plasma (62.5% samples positive). Both the assays were further tested for direct detection of S. aureus in patient whole blood samples that were contemporaneous culture positive. S. aureus was detected in 40/45 of culture-positive patients (sensitivity 89%, 95% CI 0.75-0.96) and 0/59 negative controls with the sodA assay (specificity 100%, 95% CI 0.92-1).We have demonstrated a highly sensitive two-hour assay for detection of sepsis causing bacteria like S. aureus directly in 1 ml of whole blood, without the need for blood culture.

This paper proposes a complete satellite access network solution for multimedia broadcast multicast service (MBMS) delivery based on T-UMTS standards. First, the benefits of MBMS delivery via satellite (SAT-MBMS) for both S/T-UMTS network operators are shown with market and business analysis. A new integrated S/T-UMTS architecture for MBMS delivery is proposed featuring an intermediate module repeater (IMR) for coverage of urban areas. The architectural options of IMR and terminals are discussed considering the relevant cost and complexity. The IMR propagation channel conditions are investigated and a new propagation channel model is proposed. The potential of advanced coding schemes such as the layered coding technique to tackle the channel variations in broadcast/multicast environment is outlined. The functional and protocol architecture are defined along with the interface between the satellite access network and the UMTS core network. Required modifications on the terrestrial access scheme sub-layers to support MBMS data are investigated and the relevant logical, transport and physical channels are selected. Based on the channel selection and the point-to-multipoint service nature, we define a generic radio resource management (RRM) strategy that takes into account both QoS and GoS requirements. The efficiency of the proposed solutions is evaluated in the presented simulation results, advocating the feasibility of the overall approach. Copyright © 2004 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Despite the care provided, some newborns, who are perfectly healthy, show functional alterations that impair a good breast attack in the first few days. This situation often leads to the early failure of lactation. We conducted a randomized single-blind controlled trial to evaluate whether four weeks of osteopathic treatment can normalize the sucking score in a group of neonates with impaired lactation ability. Forty-two healthy full-term neonates were enrolled in this study. On the basis of the sucking score and the assessment of the infant's breastfeeding skills, infants who had intrinsic breastfeeding difficulties were selected. The inclusion criteria were healthy infants born > 37 weeks, a suction score ≤ 6, and any breast milk at enrolment. At the end of the study, the sucking score was significantly greater in the osteopathic group than in the untreated group; the median sucking score in the treated group was in the normal range, while it remained lower in the untreated group. At the end of the follow-up, the percentage of exclusively breastfeeding infants in the treatment group increased by +25%. This pilot study demonstrates the efficacy of early osteopathic intervention to relieve breastfeeding difficulties in newborns in the first few weeks of life.

Background: The therapeutic application of multipotent mesenchymal stem cells (MSCs) encounters significant challenges, primarily stemming from their inadequate growth and limited self-renewal capabilities. Additionally, as MSCs are propagated, their ability to self-renew declines, and the exact cellular and molecular changes responsible for this are poorly understood. This study aims to uncover the complex molecular mechanisms that govern the self-renewal of primitive (p) MSCs., Methods: We grew pMSCs using two types of medium, fetal bovine serum (FM) and xeno-free (XM), at both low passage (LP, P3) and high passage (HP, P20). To evaluate LP and HP pMSCs, we examined their physical characteristics, cell surface markers, growth rate, colony-forming ability, BrdU assays for proliferation, telomerase activity, and potential to differentiate into three lineages. Moreover, we conducted RNA-seq to analyze their transcriptome and MNase-seq analysis to investigate nucleosome occupancies., Results: When grown in FM, pMSCs underwent changes in their cellular morphology, becoming larger and elongated. This was accompanied by a decrease in the expression of CD90 and CD49f, as well as a reduction in CFE, proliferation rate, and telomerase activity. In addition, these cells showed an increased tendency to differentiate into the adipogenic lineage. However, when grown in XM, pMSCs maintained their self-renewal capacity and ability to differentiate into multiple lineages while preserving their fibroblastoid morphology. Transcriptomic analysis showed an upregulation of genes associated with self-renewal, cell cycle regulation, and DNA replication in XM-cultured pMSCs, while senescence-related genes were upregulated in FM-cultured cells. Further analysis demonstrated differential nucleosomal occupancies in self-renewal and senescence-related genes for pMSCs grown in XM and FM, respectively. These findings were confirmed by qRT-PCR analysis, which revealed alterations in the expression of genes related to self-renewal, cell cycle regulation, DNA replication, differentiation, and senescence. To understand the underlying mechanisms, we investigated the involvement of Wnt and TGFβ signaling pathways by modulating them with agonists and antagonists. This experimental manipulation led to the upregulation and downregulation of self-renewal genes in pMSCs, providing further insights into the signaling pathways governing the self-renewal and senescence of pMSCs., Conclusion: Our study shows that the self-renewal potential of pMSCs is associated with the Wnt pathway, while senescence is linked to TGFβ., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: The purpose of the present study was to compare the effectiveness of intrathecal injection of morphine, inserted in the protocols of multimodal analgesia, versus intravenous morphine in the control of postoperative pain and course in women undergoing gynecological surgery., Methods: An observational, single-center, retrospective and case-controlled study was performed. Data were collected in a group of women (N.=80) who underwent to gynecological surgery. Women were divided into two groups: group A (40 patients) laparoscopic hysterectomy and group B (N.=40) performing laparotomic myomectomy. In both groups 20 patients underwent administration of intrathecal morphine (125 mcg in 5 mL) and 20 patients underwent to intravenous morphine (1 mg maximum every 10 minutes). The primary endpoint collected was the mean VAS Score during the first 3 days after surgery, while secondary endpoints were opioid consumed during the same period, nausea, vomitus and pruritus. Among the exploratory objectives, length of hospital stay, canalization and feeding time were collected., Results: In group A, patients performing intrathecal morphine presented a significantly lowest VAS on postoperative day 1 and 3 compared to patients performing intravenous morphine while in group B mean VAS was statistically significant lower only on the first day. The emergence of pruritus was significantly higher in patients performing intrathecal morphine. The day of complete canalization was different in Group A patients in favor of intrathecal morphine as well as the length of stay., Conclusions: The present study showed that intrathecal morphine allows to achieve important management goals with minimal side effects and complications, in particular in case of laparoscopic hysterectomy.

Human mesenchymal stem cells (MSCs) are isolated from various adult and perinatal tissues. Although mesenchymal stem cells from multiple sources exhibit similar morphology and cell surface markers, they differ in their properties. In this study, we determined that the expression of integrin alpha 6 ( ITGA6 ) and ITGA6 antisense RNA ( ITGA6-AS1 ) correlates with the proliferation, cell size, and differentiation potential. The expression of ITGA6 was inversely correlated with ITGA6-AS1 in MSCs. The expression of ITGA6 was higher, but ITGA6-AS1 was lower in MSCs from cord placenta junction, cord tissue, and Wharton's jelly. In contrast, ITGA6 expression was lower, while ITGA6-AS1 was higher in MSCs from the placenta. The bioinformatic analysis showed that ITGA6 genomic DNA transcribes ITGA6-AS1 from the reverse strand, overlapping ITGA6 exon-2. Additionally, we identify several putative promoters (P1-P10) of ITGA6 . ITGA6-P10 is CG rich and contains CGI. EMBOSS Cpgplot software revealed a CGI length of 180 bp that extends from nucleotide 125 to 304 of the P10 sequence. We suggest that the post-transcriptional regulation of the ITGA6 in mesenchymal stem cells is controlled by the ITGA6-AS1, which could be a critical factor responsible for the heterogeneity in function and cell fate of human MSCs. These results may provide further impetus for investigations to unravel the mechanisms of ITGA6 regulation that could help maintain or improve the properties of mesenchymal stem cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Al-Obaide, Ishmakej, Brown, Mazzella, Agosta, Perez-Cruet and Chaudhry.)

Background: The aims of this study were: to investigate the capacity of the rare disease healthcare network in Campania to diagnose patients with rare diseases during the outbreak of Covid-19; and to shed light on problematic diagnoses during this period., Methods: To describe the impact of the Covid-19 pandemic on the diagnosis of patients with rare diseases, a retrospective analysis of the Campania Region Rare Disease Registry was performed. A tailored questionnaire was sent to rare disease experts to investigate major issues during the emergency period., Results: Prevalence of new diagnoses of rare disease in March and April 2020 was significantly lower than in 2019 (117 versus 317, P < 0.001 and 37 versus 349, P < 0.001, respectively) and 2018 (117 versus 389, P < 0.001 and 37 versus 282, P < 0.001, respectively). Eighty-two among 98 rare disease experts completed the questionnaire. Diagnostic success (95%), access to diagnosis (80%) and follow-up (72%), lack of Personal Protective Equipment (60%), lack of Covid-19 guidelines (50%) and the need for home therapy (78%) were the most important issues raised during Covid-19 outbreak., Conclusions: This study describes the effects of the Covid-19 outbreak on the diagnosis of rare disease in a single Italian region and investigates potential issues of diagnosis and management during this period., (© The Author(s) 2021. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: A risk of percutaneous transthoracic needle biopsy (PTNB) is hemoptysis which can range from mild to life-threatening. The reported occurrence of hemoptysis is 1.7-14.5% and the demographic, patient, and procedure characteristics have not been extensively described. The purpose of this study was to assess the associations of demographic, patient, and procedure characteristics with the severity of hemoptysis., Materials and Methods: A single-institution, single group, retrospective, electronic medical record (EMR) review was performed on all hemoptysis events occurring between 2008 and 2018. Demographic, clinical, and procedure variables were extracted from EMRs. Outcome of hemoptysis events was graded using Common Terminology Criteria for Adverse Events (CT-CAE). Mild-moderate and severe hemoptysis were defined as CT-CAE classifications of 1-2 and 3-5, respectively. Associations were generated using logistic regressions and Likelihood Ratio Chi-Square tests., Results: In ten years, 14,665 PTNB resulted in 231 hemoptysis events occurring in 229 patients; 12.7% (n=29) of those were severe. The strongest and statistically significant variables associated with an increased likelihood of a severe event, if an event occurred, were cigarette pack years (OR=1.02, 95% C.I.=1.01-1.04, P=.020); history of chronic obstructive pulmonary disease (COPD) (OR=3.68, 95% C.I. = 1.53-8.82, P=.003); core biopsy technique (OR=8.13, 95% CI=1.07, 61.40, P=.042), and larger diameter needle (20g vs. 18g: OR= 2.60 (1.09, 6.17), P=.031)., Conclusions: PTNB-associated hemoptysis was an uncommon event that was rarely life-threatening. The extent of the patient's smoking history, the diagnosis of COPD, and core biopsy technique were associated with an increased likelihood of severe hemoptysis.

Purpose: The current randomized, double-blind, placebo-controlled clinical trial addressed the effects on penile erectile function of relatively high daily oral doses (6 g/day) of L-ARG for 3 months (N = 51) compared to placebo (N = 47), in patients with vasculogenic ED, with comparison between mild-moderate and severe vasculogenic ED., Methods: The outcome measures included IIEF-6 score and cavernous arteries peak systolic flow velocity (PSV) at dynamic penile duplex ultrasonography (PDU)., Results: L-ARG supplementation for 3 months significantly increased IIEF-6 score in the overall cohort (p < 0.0001) and in subgroups of patients with mild-moderate (p < 0.0001) and severe (p = 0.007) vasculogenic ED; PSV was significantly increased in the overall cohort (p < 0.0001) and in patients with mild-moderate (p < 0.0001), but not severe vasculogenic ED. At study completion, 74% of patients improved ED degree category, although only 24% of patients, mainly belonging to the baseline category of mild ED, reached IIEF-6 scores compatible with absence of ED; moreover, 20% of patients, exclusively belonging to the baseline category of mild-moderate vasculogenic ED, reached PSV values compatible with absence of ED., Conclusion: The results of the current study demonstrated that supplementation with relatively high doses of L-ARG as a single compound for 3 months significantly improved penile erectile function, assessed by both IIEF-6 score and PSV at dynamic PDU in patients with mild-moderate, and improved IIEF-6 score, but not PSV, in patients with severe vasculogenic ED, therefore suggesting that L-ARG might be an alternative treatment in mild-moderate vasculogenic ED patients experiencing adverse effects or with contraindications for chronic treatment with PDE5i compounds., (© 2021. The Author(s).)

Aims: To evaluate the role of bisoprolol to control symptoms and left ventricular outflow tract obstruction (LVOTO) in a consecutive cohort of adults with hypertrophic cardiomyopathy (HCM)., Methods and Results: In this retrospective study, patients with HCM with an LVOT gradient ≥50 mmHg after Valsalva manoeuvre and New York Heart Association (NYHA) class II-III symptoms were assigned to receive bisoprolol (starting at 1.25 mg daily). The initial dose was increased every two weeks to achieve the target in LVOT gradient <30 mmHg or the maximum tolerated dose. The primary endpoint was the achievement of a LVOT gradient <30 mmHg and ≥ 1 NYHA class improvement. The secondary endpoints were proportion of patients with LVOT gradient <30 mmHg or < 50 mmHg, proportion of patients with ≥1 NYHA class improvement, and change from baseline in LVOT gradient. Between December 2001 and December 2020, 92 patients were enrolled into the study. Sixteen (17%) patients on bisoprolol met the primary endpoint. Bisoprolol reduced the LVOT gradient to less than 30 mmHg in 33 (36%) patients, to less than 50 mmHg in 57 (62%), and improved NYHA class in 30 (33%). The mean reduction of LVOT gradient on bisoprolol was 28 (±14) mmHg and the percentage reduction was 42 (±21) %. In 35 (38%) patients, bisoprolol did not reduce the gradient to less than 50 mmHg requiring disopyramide and/or myectomy to achieve this goal., Conclusion: Treatment with bisoprolol was well-tolerated and effective in relieving obstruction and improving symptoms in a significant proportion of patients with symptomatic obstructive HCM., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Currently, there is no treatment for retinal degenerative diseases (RDD) such as retinitis pigmentosa (RP). Stem cell-based therapies could provide promising opportunities to repair the damaged retina and restore vision. Thus far, primarily adult mesenchymal stem cells (MSCs) have been investigated in preclinical and clinical studies, and the results have not been convincing. We applied a new approach in which primitive (p) MSC-derived retinal progenitor cells (RPCs) were examined to treat retinal degeneration in an rd12 mouse model of RP., Methods: Well-characterized pMSCs and RPCs labeled with PKH26 were intravitreally injected into rd12 mice. The vision and retinal function of transplanted animals were analyzed using electroretinography. Animals were killed 4 and 8 weeks after cell transplantation for histological, immunological, molecular, and transcriptomic analyses of the retina., Results: Transplanted RPCs significantly improved vision and retinal thickness as well as function in rd12 mice. pMSCs and RPCs homed to distinct retinal layers. pMSCs homed to the retinal pigment epithelium, and RPCs migrated to the neural layers of the retina, where they improved the thickness of the respective layers and expressed cell-specific markers. RPCs induced anti-inflammatory and neuroprotective responses as well as upregulated the expression of genes involved in neurogenesis. The transcriptomic analysis showed that RPCs promoted neurogenesis and functional recovery of the retina through inhibition of BMP and activation of JAK/STAT and MAPK signaling pathways., Conclusions: Our study demonstrated that RPCs countered inflammation, provided retinal protection, and promoted neurogenesis resulting in improved retinal structure and physiological function in rd12 mice., (© 2022. The Author(s).)

Fabry disease (FD, OMIM 301500) is an X-linked lysosomal storage disease caused by pathogenic variants in the GLA gene. Cardiac involvement is common in FD and is responsible for impaired quality of life and premature death. The classic cardiac involvement is a nonobstructive form of hypertrophic cardiomyopathy, usually manifesting as concentric left ventricular hypertrophy, with subsequent arrhythmogenic intramural fibrosis. Treatment of patients with FD should be directed to prevent the disease progression to irreversible organ damage and organ failure. The aim of this review is to describe the current state of knowledge regarding cardiovascular involvement in FD, focusing on clinical and instrumental features, cardiovascular management, and targeted therapy., Competing Interests: Disclosure The authors have nothing to disclose. D.P. Germain is a consultant for Sanofi Genzyme and Takeda., (Copyright © 2021 Elsevier Inc. All rights reserved.)

During the COVID-19 pandemic, healthcare workers (HW) have faced an extremely difficult work environment, with an increased workload and traumatic events. Our study aimed to investigate the impact of COVID-19 pandemic on HW's mental wellbeing. We analyzed the correlations between levels of burnout and other mental health disorders and we searched for the presence of specific risk factors of post-traumatic symptomatology related to the pandemic. A structured an on-line questionnaire and validated instruments were completed by a sample of HW from some hospitals in Genoa, Italy. Anxious, depressive, post-traumatic and other psychological symptoms were assessed and risk factors, related to the pandemic, were considered. Then, we investigated the correlation between levels of burnout and the risk of developing psychopathology. A total of 731 HW were screened, and we found increased levels of anxiety (61%), depression (62%), PTSD (34%) and high levels of burnout; especially emotional exhaustion (37%). A statistically significant association between burnout and insomnia, depression, anxiety, and post-traumatic symptoms was demonstrated. This study indicates that during the COVID-19 pandemic, HW showed high levels of psychological distress and that burnout is an important predictor of sufferance. These findings support the idea to provide psychological and psychiatric support for HW.

Importance: Attention is being focused on improving mothers' positive experiences of childbirth while reducing the negative ones. Cesarean section is a known factor able to increase maternal anxiety., Objective: To determine whether a new binaural beat-based technique can reduce the preoperative discomfort of the elective surgical patient., Methods: Prospective, randomized double-blind controlled study: 60 women scheduled to undergo elective cesarean section. Women with a low risk pregnancy were recruited and enrolled at the time of the "37 weeks" visit. Exclusion criteria were: psychiatric disorders, neurological impairment, epilepsy, deafness, use of drugs/alcohol during pregnancy, insufficient reading level. Participants will be contestually allocated to one of three groups according to a predetermined computer-generated random sequence: (1) "binaural" group, (2) "normal music" group, and (3) "control" group. Participants of groups 1 and 2 will be unaware of the type of audio heard., Intervention: According to the allocation arm, participants were asked to listen an engineered audio track (binaural beat arm) created with the novel algorithm "Dynamic Spectrum Phase Shift" (DMSPS), or an identical soundtrack without DMSPS in it (music arm), or no specific intervention, representing standard practice. The feeling of anxiety has been measured by the State-Trait Anxiety Inventory (STAI-Y) questionnaire. Conclusions and Relevance: Binaural beat audio created with DMSPS algorithm provides superior changes in reported anxiety in comparison to normal music and above all to standard care.This technique does not need extra staff or extra staying time for the patients, so it could be a cost-effective way to manage preoperative anxiety in women undergoing elective cesarean section, with a potential impact to the mother's positive experiences and care of the newborn. The EudraCT number: 2019-000743-27.

Background: The management of male idiopathic infertility is heterogeneous. Although meta-analyses reported the effectiveness on pregnancy rate, the real clinical impact of follicle-stimulating hormone (FSH) was not evaluated so far. In Italy, FSH is approved by the National Medicines Agency (AIFA) for idiopathic infertile patients with FSH < 8 IU/L, independently of semen parameters., Aim: Primary endpoint was to record the therapeutic approach to the male partner of infertile couples. Secondary aim was to assess changes of semen parameters during FSH treatment., Methods: A multicentre, prospective, observational, clinical practice survey was carried out, enrolling the male partner of infertile couples attending ten Italian participating centres. Inclusion criteria were as follows: couple infertility, age >18 years and FSH serum levels <8 IU/L. Thus, all men in which AIFA allowed the FSH prescription were enrolled. Primary endpoint was the number of infertile patients treated with FSH. Secondary outcomes were semen parameters. The treating physician decided whether to offer FSH therapy and whether to re-evaluate the male partner., Results: A total of 718 infertile couples were enrolled, and 241 patients were re-evaluated (median follow-up: 4.5 months). In 64.9% (466 patients), a treatment was prescribed. FSH was prescribed in 397 patients (85.2% of treated men). Sperm concentration (P = .002) and normal form percentage (P < .001) significantly improved during FSH administration. No correlation was found between these parameters and FSH duration (P = .545 and P = .627, respectively) or dosage (P = .455 and P = .533, respectively). Among patients treated with FSH, the incidence of oligozoospermia decreased from 73.0% to 56.0% (P < .001) and teratozoospermia from 43.6% to 27.7% (P < .001)., Discussion: This first nation-wide survey reveals a FSH prescription rate of 55% in patients qualifying for treatment according to AIFA. Although the study was not designed to highlight FSH efficacy in male infertility, a slight increase in semen parameters was demonstrated in about half of the treated men without adverse events., (© 2019 American Society of Andrology and European Academy of Andrology.)

Background: This study aimed to describe the prevalence of type 2 diabetes and combinations of multiple chronic conditions (MCCs) that are leading causes of death (LCD) and confirm that disparities exist between groups based on race and sex., Materials and Methods: We conducted a retrospective cohort study using 2012 Medicare claims data from beneficiaries with type 2 diabetes over the age of 65 in the state of Michigan., Results: Female beneficiaries have type 2 diabetes and 1 or more MCCs that are LCD more often than males. Most type 2 diabetes patients have diabetes alone without MCCs, while a large proportion have at least 1 additional chronic condition that is a LCD. One in 3 patients have 3 or more chronic conditions. The most prevalent type 2 diabetes coexisting MCCs are congestive heart failure (CHF), chronic obstructive pulmonary disease and chronic kidney disease. Asian/Pacific Islanders have the highest prevalence of type 2 diabetes without MCCs, and the highest prevalence of diabetes plus CHF. While fewer black beneficiaries have diabetes alone or 1 additional MCC, the prevalence of 3 or more MCCs in blacks generally exceeds the prevalence in other races. In beneficiaries with newly diagnosed type 2 diabetes, chronic obstructive pulmonary disease and CHF are the first new chronic conditions to be diagnosed after an initial type 2 diabetes diagnosis., Conclusions: Race and sex disparities occur in the prevalence of type 2 diabetes and MCCs that are LCD in Medicare beneficiaries in the state of Michigan., (Copyright © 2020 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Presently, disparities exist between race, sex, socioeconomic status, hospitals, income, comorbidities, and insurance profiles of patients undergoing DBS surgery. Here, we aim to highlight several variables and their predictive powers of DBS surgery outcomes as measured by dischargelocation, length of hospital stays, and total hospital charges. A retrospective cohort study using discharge data from NIS and HCUP for analyses and regression model statistics is performed. Comparative analyses demonstrate urban patients were more often non-routinely discharged, possessed private insurance, and accrued greater hospital costs compared to rural patients. Moreover, regression analyses predicts urban patients have 70% lower odds of routine discharge while those with a major loss of function prior to surgery also have 81% lower odds of routine discharge compared to those with minor loss of function. Ultimately, our study found urban patients or patients with major illnesses have higher hospital charges, longer hospitalization, and more often non-routinely discharged., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

With advances in technologies that facilitate metabolome-wide analyses, the incorporation of metabolomics in the pursuit of biomarkers of exposure and effect is rapidly evolving in population health studies. However, many analytic approaches are limited in their capacity to address high-dimensional metabolomics data within an epidemiologic framework, including the highly collinear nature of the metabolites and consideration of confounding variables. In this Children's Health Exposure Analysis Resource (CHEAR) network study, we showcase various analytic approaches that are established as well as novel in the field of metabolomics, including univariate single metabolite models, least absolute shrinkage and selection operator (LASSO), random forest, weighted quantile sum (WQS RS ) regression, exploratory factor analysis (EFA), and latent class analysis (LCA). Here, in a Bangladeshi birth cohort (n = 199), we illustrate research questions that can be addressed by each analytic method in the assessment of associations between cord blood metabolites ( 1 H NMR measurements) and birth anthropometric measurements (birth weight and head circumference).

Several studies highlight that testosterone deficiency is associated with, and predicts, an increased risk of developing metabolic disorders, and, on the other hand, is highly prevalent in obesity, metabolic syndrome and type-2 diabetes mellitus. Models of gonadotropin releasing hormone deficiency, and androgen deprivation therapy in patients with prostate cancer, suggest that hypogonadotropic hypogonadism might contribute to the onset or worsening of metabolic conditions, by increasing visceral adiposity and insulin resistance. Nevertheless, in functional hypogonadism, as well as in late onset hypogonadism, the relationship between hypogonadotropic hypogonadism and metabolic disorders is bidirectional, and a vicious circle between the two components has been documented. The mechanisms underlying the crosstalk between testosterone deficiency and metabolic disorders include increased visceral adipose tissue and insulin resistance, leading to development of metabolic disorders, which in turn contribute to a further reduction of testosterone levels. The decrease in testosterone levels might be determined by insulin resistance-mediated and, possibly, pro-inflammatory cytokine-mediated decrease of sex hormone binding globulin, resulting in a temporary increased free testosterone available for aromatization to estradiol in visceral adipose tissue, followed by a subsequent decrease in free testosterone levels, due to the excess of visceral adipose tissue and aromatization; by a direct inhibitory effect of increased leptin levels on Leydig cells; and by a reduced gonadotropin secretion induced by estradiol, inflammatory mediators, leptin resistance, and insulin resistance, with the ultimate determination of a substantial hypogonadotropic hypogonadism. The majority of studies focusing on the effects of testosterone replacement therapy on metabolic profile reported a beneficial effect of testosterone on body weight, waist circumference, body mass index, body composition, cholesterol levels, and glycemic control. Consistently, several interventional studies demonstrated that correction of metabolic disorders, in particular with compounds displaying a greater impact on body weight and insulin resistance, improved testosterone levels. The aim of the current review is to provide a comprehensive overview on the relationship between hypogonadotropic hypogonadism and metabolism, by clarifying the independent role of testosterone deficiency in the pathogenesis of metabolic disorders, and by describing the relative role of testosterone deficiency and metabolic impairment, in the context of the bidirectional relationship between hypogonadism and metabolic diseases documented in functional hypogonadotropic hypogonadism. These aspects will be assessed by describing metabolic profile in men with hypogonadotropic hypogonadism, and androgenic status in men with metabolic disorders; afterwards, the reciprocal effects of testosterone replacement therapy and corrective interventions on metabolic derangements will be reported.

Medullary thyroid carcinoma (MTC) represents 3-5% of thyroid cancers. 75% is sporadic and 25% is the dominant component of the hereditary multiple endocrine neoplasia (MEN) type 2 syndromes. Three different subtypes of MEN2, such as MEN2A, MEN2B, and Familial MTC (FMTC) have been defined, based on presence or absence of hyperparathyroidism, pheocromocytoma and characteristic clinical features. Mutations of the RET proto-oncogene are implicated in the pathogenesis of MTC, but there are many other mutational patterns involved. In MEN2A, Codon 634 in exon 11 (Cys634Arg), corresponding to a cysteine in the extracellular cysteine-rich domain, is the most commonly altered codon. Many other mutations include codons 611, 618, 620. In the genetical testing of RET mutations in MTCs, Next-Generation Sequencing (NGS) is taking an increasingly important role. One of the most important benefit is the comprehensive analysis of molecular alterations in MTC, which allows rapidly to select patients with different risk levels. There is a difference in miRNA expression pathway between sporadic and hereditary MTCs. Among sporadic cases, expression of miR-127 was significantly lower in those who harbor somatic RET mutations than those with wild-type RET. CDKN1B mutations are associated with many clinical pictures of cancers, such as MEN4. V109G polymorphism is associated with sporadic MTCs negative for RET mutations, and might influence the clinical course of the patients affected by MTC. Although surgery (i.e. total thyroidectomy with neck lymph node dissection) is the elective treatment for MTCs, about 80% of patients have distant metastases at diagnosis and in this cases surgery is not enough and an additional treatment is needed. Interesting results come from two large phase III clinical trials with two targeted tyrosine kinase inhibitors (TKIs), vandetanib and cabozantinib., Conclusions: New genetical testings and therapeutical approaches open new perspectives in MTC management., (Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Rapid technological advances for the frequent monitoring of health parameters have raised the intriguing possibility that an individual's genotype could be predicted from phenotypic data alone. Here we used a machine learning approach to analyze the phenotypic effects of polymorphic mutations in a mouse model of Huntington's disease that determine disease presentation and age of onset. The resulting model correlated variation across 3,086 behavioral traits with seven different CAG-repeat lengths in the huntingtin gene (Htt). We selected behavioral signatures for age and CAG-repeat length that most robustly distinguished between mouse lines and validated the model by correctly predicting the repeat length of a blinded mouse line. Sufficient discriminatory power to accurately predict genotype required combined analysis of >200 phenotypic features. Our results suggest that autosomal dominant disease-causing mutations could be predicted through the use of subtle behavioral signatures that emerge in large-scale, combinatorial analyses. Our work provides an open data platform that we now share with the research community to aid efforts focused on understanding the pathways that link behavioral consequences to genetic variation in Huntington's disease.

Huntington's Disease (HD) is a progressive neurodegenerative disorder that causes motor, cognitive, and psychiatric symptoms. In these experiments, we tested if operant training at an early age affected adult cognitive deficits in the zQ175 KI Het (zQ175) mouse model of HD. In Experiment 1 we trained zQ175 mice in a fixed-ratio/progressive ratio (FR/PR) task to assay learning and motivational deficits. We found pronounced deficits in response rates and task engagement in naïve adult zQ175 mice (32-33 weeks age), while deficits in zQ175 mice trained from 6-7 weeks age were either absent or less severe. When those mice were re-tested as adults, FR/PR performance deficits were absent or otherwise less severe than deficits observed in naïve adult zQ175 relative to wild type (WT) mice. In Experiment 2, we used a Go/No-go operant task to assess the effects of early cognitive testing on response inhibition deficits in zQ175 mice. We found that zQ175 mice that began testing at 7-8 weeks did not exhibit deficits in Go/No-go testing, but when re-tested at 28-29 weeks age exhibited an initial impairment that diminished with training. These transient deficits were nonetheless mild relative to deficits observed among adult zQ175 mice without prior testing experience. In Experiment 3 we trained mice in a two-choice visual discrimination test to evaluate cognitive flexibility. As in prior experiments, we found performance deficits were mild or absent in mice that started training at 6-9 weeks of age, while deficits in naive mice exposed to training at 28-29 weeks were severe. Re-testing mice at 28-29 weeks age, were previously trained starting at 6-9 weeks, revealed that deficits in learning and cognitive flexibility were absent or reduced relative to effects observed in naive adults. In Experiment 4, we tested working memory deficits with a delayed non-match to position (DNMTP) test. Mice with prior experience exhibited mild working memory deficits, with males zQ175 exhibiting no deficits, and females performing significantly worse than WT mice at a single delay interval, whereas naive zQ175 exhibited severe delay-dependent deficits at all intervals exceeding 1 s. In sum, these experiments indicate that CAG-dependent impairments in motivation, motor control, cognitive flexibility, and working memory are sensitive to the environmental enrichment and experience. These findings are of clinical relevance, as HD carrier status can potentially be detected at an early age.

Huntington's disease (HD) is an autosomal dominant, progressive neurodegenerative disorder caused by expansion of CAG repeats in the huntingtin gene. Tissue transglutaminase 2 (TG2), a multi-functional enzyme, was found to be increased both in HD patients and in mouse models of the disease. Furthermore, beneficial effects have been reported from the genetic ablation of TG2 in R6/2 and R6/1 mouse lines. To further evaluate the validity of this target for the treatment of HD, we examined the effects of TG2 deletion in two genetic mouse models of HD: R6/2 CAG 240 and zQ175 knock in (KI). Contrary to previous reports, under rigorous experimental conditions we found that TG2 ablation had no effect on either motor or cognitive deficits, or on the weight loss. In addition, under optimal husbandry conditions, TG2 ablation did not extend R6/2 lifespan. Moreover, TG2 deletion did not change the huntingtin aggregate load in cortex or striatum and did not decrease the brain atrophy observed in either mouse line. Finally, no amelioration of the dysregulation of striatal and cortical gene markers was detected. We conclude that TG2 is not a valid therapeutic target for the treatment of HD.

Background: Bromelain (BR) is a cysteine protease with inhibitory effects on intestinal secretion and inflammation. However, its effects on intestinal motility are largely unexplored. Thus, we investigated the effect of this plant-derived compound on intestinal contractility and transit in mice., Methods: Contractility in vitro was evaluated by stimulating the mouse isolated ileum, in an organ bath, with acetylcholine, barium chloride, or electrical field stimulation. Motility in vivo was measured by evaluating the distribution of an orally administered fluorescent marker along the small intestine. Transit was also evaluated in pathophysiologic states induced by the pro-inflammatory compound croton oil or by the diabetogenic agent streptozotocin., Key Results: Bromelain inhibited the contractions induced by different spasmogenic compounds in the mouse ileum with similar potency. The antispasmodic effect was reduced or counteracted by the proteolytic enzyme inhibitor, gabexate (15 × 10(-6)  mol L(-1) ), protease-activated receptor-2 (PAR-2) antagonist, N(1) -3-methylbutyryl-N(4) -6-aminohexanoyl-piperazine (10(-4) mol L(-1) ), phospholipase C (PLC) inhibitor, neomycin (3 × 10(-3) mol L(-1) ), and phosphodiesterase 4 (PDE4) inhibitor, rolipram (10(-6)  mol L(-1) ). In vivo, BR preferentially inhibited motility in pathophysiologic states in a PAR-2-antagonist-sensitive manner., Conclusions & Inferences: Our data suggest that BR inhibits intestinal motility - preferentially in pathophysiologic conditions - with a mechanism possibly involving membrane PAR-2 and PLC and PDE4 as intracellular signals. Bromelain could be a lead compound for the development of new drugs, able to normalize the intestinal motility in inflammation and diabetes., (© 2011 Blackwell Publishing Ltd.)

Background: Acne vulgaris is a complex, chronic, and common skin disorder of pilosebaceous units. The major pathogenic factors involved are ductal hyperkeratinization, obstruction of sebaceous follicles resulting from abnormal keratinization of the infundibular epithelium, stimulation of sebaceous gland secretion by androgens, and microbial colonization of pilosebaceous units by Propionibacterium acnes, which promotes perifollicular inflammation., Aim: The aim of the study was to investigate the therapeutic effects of resveratrol, a natural phytoalexin produced by some spermatophytes, such as grapes and other plants, on acneic skin., Methods: Resveratrol was incorporated in a carboxymethylcellulose-based gel. The chemical stability of resveratrol after storage at 4°C for 30 days was investigated by high-performance liquid chromatography (HPLC). The resveratrol-containing hydrogel was administered to 20 patients affected by acne vulgaris enrolled in this single-blind study. The resveratrol-containing formulation was applied daily as a solo treatment on the right side of the face for 60 days, while the hydrogel vehicle was applied to the left side of the face as a control. To objectively evaluate the results, a digital photographic database was used to collect images. The number and type of lesions were recorded for each patient, to compare the Global Acne Grading System (GAGS) score before treatment with that obtained at the end of the study. Moreover, with the innovative technique of follicular biopsy, areas of acneic skin were prepared for histopathology. The average area occupied by microcomedones at baseline was compared with that at the end of treatment., Results: HPLC analysis demonstrated that resveratrol, upon incorporation into the gel, did not convert to its cis-isomer when stored at 4°C for 30 days. All patients were satisfied with the active treatment and none experienced adverse effects. Clinical evaluation showed a 53.75% mean reduction in the GAGS score on the resveratrol-treated sides of the face compared with 6.10% on the vehicle-treated sides of the face. These data were supported by histologic analysis, which showed a 66.7% mean reduction in the average area of microcomedones on the resveratrol-treated sides of the face. The comparison with the vehicle-treated side of the face (9.7% reduction) showed a clinically relevant and statistically significant decrease of lesions in areas treated with resveratrol-containing hydrogel., Conclusion: This pilot study showed positive results for resveratrol gel in acne, and should be considered a valid starting point for further testing of the effectiveness of this molecule in different concentrations and formulations and in a larger group of patients.

Familial Danish dementia (FDD) is a progressive neurodegenerative disease with cerebral deposition of Dan-amyloid (ADan), neuroinflammation, and neurofibrillary tangles, hallmark characteristics remarkably similar to those in Alzheimer's disease (AD). We have generated transgenic (tg) mouse models of familial Danish dementia that exhibit the age-dependent deposition of ADan throughout the brain with associated amyloid angiopathy, microhemorrhage, neuritic dystrophy, and neuroinflammation. Tg mice are impaired in the Morris water maze and exhibit increased anxiety in the open field. When crossed with TauP301S tg mice, ADan accumulation promotes neurofibrillary lesions, in all aspects similar to the Tau lesions observed in crosses between beta-amyloid (Abeta)-depositing tg mice and TauP301S tg mice. Although these observations argue for shared mechanisms of downstream pathophysiology for the sequence-unrelated ADan and Abeta peptides, the lack of codeposition of the two peptides in crosses between ADan- and Abeta-depositing mice points also to distinguishing properties of the peptides. Our results support the concept of the amyloid hypothesis for AD and related dementias, and suggest that different proteins prone to amyloid formation can drive strikingly similar pathogenic pathways in the brain.

Dimethyl sulfoxide (DMSO) is an organic compound widely used as solvent in biological studies and as vehicle for drug administration. DMSO has been shown to possess several biological effects, including antioxidant, anti-inflammatory, antinociceptive effects, and it has been proposed to be therapeutic in several disorders, such as gastrointestinal diseases, rheumatologic diseases, and for the treatment of several manifestations of amyloidosis. To better define the biological profile of DMSO, we investigated its effect on an in vivo model of acute myocardial infarction in rats, caused by left anterior descending coronary artery ligation. Our results show that pretreatment of rats with intraperitoneal (ip) DMSO (500 microL/Kg) for 3 consecutive days before left anterior descending coronary artery ligation significantly (P < 0.05) reduced cardiac damage from 18.75 +/- 4.88% (n = 12) to 4.46 +/- 2.01% (n = 8); serum levels of troponin I from 29.35 +/- 12.32 ng/mL (n = 8) to 2.95 +/- 1.32 ng/mL (n = 4); and serum levels of myoglobin from 46.86 +/- 10.35 ng/mL (n = 7) to 13.75 +/- 0.85 ng/mL (n = 4). Our data demonstrate that DMSO has a protective effect in a model of acute myocardial infarction in rats.

In the last decade, there has been an increased awareness that secondary metabolites produced by marine diatoms negatively impact the reproductive success of their principal predators, the copepods. Several oxylipins, products of the enzymatic oxidation of fatty acids, are produced when these unicellular algae are damaged, as occurs during grazing. In the past, the dinoflagellate Prorocentrum minimum, which does not produce the oxylipin 2-trans,4-trans-decadienal (DD), has been used as a live carrier to calculate daily ingestion rates of this molecule by copepod crustaceans. However, since the interaction between oxylipins and live carriers is unknown, the question as to how much and for how long ingestion of these molecules affects copepod reproduction remains a critical point to understanding the functional role of such compounds at sea. In the investigation presented here we used giant liposomes ( approximately 7 mum) as a delivery system for the oxylipin DD, prepared in the same size range as copepod food and containing known amounts of DD. The aim of this work was to relate the ingestion of DD to the reproductive failure of the copepods Temora stylifera and Calanus helgolandicus. Liposomes were very stable over time and after 10 days of feeding, liposomes encapsulating DD reduced egg hatching success and female survival with a concomitant appearance of apoptosis in both copepod embryos and female tissues. Concentrations of DD inducing blockage were one order of magnitude lower that those used in classical feeding experiments demonstrating that liposomes are a useful tool to quantitatively analyze the impact of toxins on copepods.

Background: Rapid and reliable bed-side determination of blood glucose concentration is very important in the management of acutely ill infants and especially in premature newborns. HemoCue is an easy-to-use glucose analyser. The aim of the present study was to examine the usefulness of the HemoCue glucose analyser compared to a reference plasma glucose method (SYS, BM/Hitachi 747/737) in a neonatal intensive care unit (NICU)., Methods: Seventy-eight consecutive neonates admitted to our NICU were enrolled in the study. At the time of the study all patients were grouped according to nutritional management (parenteral or enteral nutrition), haematocrit values and birth weight. The effects of feeding management, haematocrit values, and birth weight on accuracy and precision of the device were evaluated., Results: Overall data linear regression analysis yielded an r-value of 0.905 and the Bland-Altman method demonstrated that HemoCue overestimates plasma glucose by 0.932 mmol/L. Evaluation of our data by receiver operating characteristic curve demonstrated 100% sensitivity cutoff at 4.1 mmol/L., Conclusions: HemoCue cannot be used satisfactorily in the management of glycaemia in the NICU. In the preterm population, birth weight had a dramatic influence on HemoCue accuracy. Low haematocrit and parenteral feeding further contributed to a decrease in the accuracy of this device.

Background: Recently we demonstrated an increased 2,3-diphosphoglycerate (2,3-DPG) erythrocyte concentration in rat pups subjected to nucleotide-enriched artificial feeding., Design: The present study was carried out to test the hypothesis that a possible increase in 2,3-DPG concentration can also be obtained in human neonates who are fed nucleotide-enriched formula. Preterm neonates born or referred to the neonatal intensive care unit of the G. Gaslini Hospital, Genoa University, with a gestational age >30 weeks and <37 weeks were enrolled in our randomized trial. Recruitment took place within 48-72 hours from birth. Only newborns of mothers deciding not to breast-feed were eligible to be randomized for the supplemented group (FN) or non-supplemented group (RF). Breast-fed newborns were considered the control group (C). The study window (for supplementation and blood samples) was restricted to the first two weeks following birth (from the 2nd (t1) to the 16th (t2) day of life). At the end of our study, only 21 neonates were eligible for statistical analysis., Results: The stimulating action of dietary nucleotides on 2,3-DPG concentration failed to be demonstrated; increases in 2,3-DPG concentration that were observed in newborns fed with nucleotide supplemented formula (FN) were comparable to those observed in newborns fed with regular formula (RF) and breast-fed newborns., Conclusions: The EC recommendation for the amount of nucleotides allowed in formula milk does not seem to be high enough to have positive effects on 2,3-DPG synthesis. Whether this possible 'pharmacological' effect can be achieved by a higher intake of ingested nucleotides and/or a change in the proportions of single nucleotides contained in milk formulas remain interesting end points to be elucidated.

Objectives: The purpose of this research was to compare coronary obstruction between clinically similar African Americans (AA) and white persons undergoing coronary angiography., Background: African Americans have higher rates of coronary death than whites, but are less likely to undergo coronary revascularization. Although differences in coronary anatomy do not explain racial difference in revascularization rates, several studies of clinically diverse persons undergoing coronary angiography have found less obstructive coronary disease in AA than clinically similar whites., Methods: We studied 52 AA and 259 white male veterans who had both a positive nuclear perfusion imaging study and coronary angiography within 90 days of that study in five Department of Veterans Affairs hospitals. We used chart review and patient interview to collect demographics, clinical characteristics, and coronary anatomy results. Before angiography, we asked physicians to estimate the likelihood of coronary obstruction., Results: The treating physicians' estimates of coronary disease likelihood were similar for AA (79.5%) and whites (83.0%); AA were less likely to have any coronary obstruction (63.5% vs. 76.5%, p = 0.05) and had significantly less severe coronary disease (p = 0.01) than whites. African Americans continued to be less likely to have coronary obstruction in analyses controlling for clinical features, including the physician's estimate of the likelihood of coronary obstruction., Conclusions: These results suggest that AA have less coronary obstruction than apparently clinically similar whites. Further studies are required to confirm our findings and better understand the paradox that AA are less likely to have obstructive coronary disease and more likely to suffer mortality from coronary disease.

The purpose of this methods paper is to offer pediatricians and nuclear medicine physicians a diagnostic protocol for performing lymphoscintigraphy in newborns that may be useful for enhancing diagnosis and management of newborns with congenital lymphatic abnormalities. Indications for lymphoscintigraphy, choice of tracer, optimal dose, routes of administration, methods of data acquisition, timing, and interpretation of results for newborns are presented and discussed.

We report on three infants with congenital chylothorax (CC) and congenital pulmonary lymphangiectasia (CPL). CPL appears to be a characteristic pathological finding in CC. Through the use of lymphoscintigraphy and computed tomography, this study suggests that CC and CPL are strongly correlated entities and that the dysplasia of the lymphatic system results in a pulmonary lymphatic obstruction sequence. The initial microscopic dilatation of the lymph channels may lead to progressive weeping of lymphatics and, consequently, to pleural effusion. Non-Immune Hydrops Fetalis (NIHF) may be the final consequence of impaired systemic venous return and may help to explain pleural-pulmonary involvement in this generalized lymph-vessel malformation syndrome.

We report a female infant with congenital lymphedema, facial anomalies, intestinal lymphangiectasia consistent with a diagnosis of Hennekam syndrome. At birth the patient presented with severe respiratory distress due to nonimmune hydrops fetalis, a congenital chylothorax (CC), and pulmonary lymphangiectasia. Hydrops fetalis may be present in newborns with the Hennekam syndrome. Lymphoscintigraphy can be useful in explaining pleural-pulmonary involvement of this generalized lymph vessel malformation syndrome., (Copyright 2003 Wiley-Liss, Inc.)

Objective: Assessing updated incidence of type 1 diabetes in 0- to 14-year-old children in Liguria, a Northwest region of Italy., Research Design and Methods: Incident cases were recorded prospectively from 1989 to 1998. Incidence rates (IRs) were standardized to the 1999 world population using the direct method. The independent effect of sex, age, residence, and calendar year was estimated with Poisson regression model. The degree of ascertainment was calculated in accordance to capture/recapture method., Results: During 10 full calendar years, 219 new cases of type 1 diabetes in children were diagnosed in Liguria. The standardized IR over the 10-year period was 12.56 cases per 100,000 per year (95% CI 11.0-14.3). The sex-specific IR among men and women was 14.15 and 10.88, respectively. The age-specific IR was higher in the 10- to 14-year-old age-group (15.01/100,000) than in 0- to 4-year-old age-group (9.01/100,000) and in the 5- to 9-year-old age-group (13.03/100,000)., Conclusions: The IR of type 1 diabetes in Liguria is among the highest in Southern Europe and approaches IRs of Northern European countries. In particular it is much higher than those reported in the surrounding Italian regions except for Sardinia. Therefore, the geographical distribution of type 1 diabetes does not seem to reflect the simple North-South gradient reported in several previous works.

Congenital varicella syndrome refers to the spectrum of fetal anomalies associated with maternal varicella zoster virus (VZV) infection during the first trimester of pregnancy. The syndrome is rare and the risk to the fetus uncertain. We describe an unusual case of congenital varicella syndrome in which hydrocephalus was the main consequence and likely represented VZV reactivation in utero.

In the last few years, a variety of experimental and clinical studies concerning the formation, metabolism, and cellular effects of cholesterol oxidation products (COPs) have been carried out. Nevertheless, a substantial lack of knowledge exists regarding the possible intake of these compounds by the newborn through human and/or adapted formula milk. As far as the pathological role of COPs is concerned, exhaustive studies have shown that since dietary COPs are cytotoxic and atherotoxic, they may lead to adverse effects on health. The aim of this study was to investigate the possible development of cholesterol oxidation in adapted formula and in human milk by comparing the main cholesterol oxidation biomarker (7-ketocholesterol) concentration in both. To do so, the total (bonded and free) 7-ketocholesterol content was measured in ten fresh human mature milk samples and in ten milk adapted formula samples by high performance liquid chromatography and diode array detection. The 7-ketocholesterol human milk content (0.7+/-0.3) was often below the quantifiable limit (0.5 microg/g of extracted lipids) while 7-ketocholesterol adapted milk concentrations were often above (3.6+/-4.0) this limit. The 7-ketocholesterol content of adapted formula samples was significantly higher as compared to human milk samples (P<0.05). This is the first study to provide data concerning the concentrations of cholesterol oxides in human milk and in formula milk. Our results clearly suggest that the manufacturing technologies employed and the nutrient extractive sources play a crucial role in the development of cholesterol oxides in the end product. Careful surveillance has to be paid in order to avoid alteration of bioactive properties of nutrients and/or development of potentially toxic derivative compounds.

We report on a male child with "apple-peel" atresia associated with microcephaly and ocular anomalies. To date, no magnetic resonance imagings have been published. We report on the fourth reported case with this phenotype, but the first to be studied by brain magnetic resonance imaging., (Copyright 2002 Wiley-Liss, Inc.)

Aims/hypothesis: The pathogenesis of permanent diabetes mellitus diagnosed early in life is heterogeneous and, in most cases, not known. We aimed at identifying markers differentiating between non-autoimmune and autoimmune diabetes., Methods: The clinical, genetic and epidemiological features of 111 diabetic patients (62 males) who received insulin within 12 months of life were studied., Results: The epidemic curve by age of diabetes onset revealed two subsets of patients at a cutoff of 180 days. In the group with diabetes onset before 180 days ("early onset" permanent diabetes) the analysis of HLA susceptibility heterodimers (available for 21 individuals) showed that 76% had a "protective" HLA genotype for Type I (insulin-dependent) diabetes mellitus as compared to 11.9% (5/42) of the later onset group. Accordingly, "early onset" children were less likely to have autoimmunity markers (4 out of 26 tested) than children with onset after 180 days (13 out 20 tested) (15.4% vs. 65.0%, p<0.01). Of note, 19 out of 20 (or the 95%) patients who were born on the island of Sardinia, an Italian region where the incidence of Type I diabetes is six times higher than continental Italy (33/100,000/year vs 5/100,000/year), were included in the later onset group (>180 days). Small-for-date birthweight, a possible sign of reduced foetal insulin secretion, was more common in the "early onset" group (OR=9.9, 95%-CI 2.6-38.6)., Conclusion/interpretation: These results, obtained in the largest population-based cohort of diabetic infants hitherto reported, suggest that "early onset" permanent diabetes cases differ from later onset cases and that most of them do not have an autoimmune pathogenesis.

We describe two newborn brothers with a pattern of malformation characterized by the persistence of Müllerian duct derivatives, intestinal lymphangiectasia, hypertrophied alveolar ridges, and early death. Postmortem examination showed the presence of a rudimentary uterus, fallopian tubes, the upper third of a vagina, a prostate of normal shape, a dilated colon, and generalized intestinal and pulmonary lymphangiectasia. The syndrome was first delineated by Urioste and co-workers [1993: Am J Med Genet 47:494-503]. These cases confirm the existence of a definite and distinct entity., (Copyright 2001 Wiley-Liss, Inc.)