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Context: Osteopathy and morphometric vertebral fractures (VFs) are emerging complications in acromegaly. However, the prediction of VFs in this clinical setting is still a matter of uncertainty, and it is debated whether they are an early event in the natural history of the disease., Objective: We aimed to evaluate the prevalence and determinants of morphometric VFs in patients with recently diagnosed acromegaly., Methods: We enrolled 92 patients (43 men/49 women) on admission to the neurosurgery unit before transsphenoidal surgery, and compared them with control individuals without secondary forms of osteoporosis and pituitary disorders. We performed a VF assessment on preoperative chest x-ray images and collected biochemical, demographic, and clinical data., Results: We detected a significantly higher prevalence of VFs (33.7%) in patients with acromegaly than in controls (P = .001). Among the patients with acromegaly and VFs, 12 (38.7%) showed multiple VFs, and 5 (16.1%) showed moderate/severe VFs. Patients with VFs had higher random serum growth hormone (GH) levels than those with no VFs (P = .03), but there was no difference in insulin-like growth factor-1 (IGF-1) (P = .07) and IGF-1/Upper Normal Limit ratio (P = .08). Free 3,5,3'-triiodothyronine was slightly lower in patients with acromegaly and VFs than in those without VFs (P = .05). In multiple logistic analysis, GH was independently associated with risk for VFs (P = .003). The preoperative serum GH cutoff value that predicted VFs was 12 ng/mL., Conclusion: For the first time, high prevalence of radiological VFs is reported in patients with recent diagnosis of acromegaly. Therefore, we can hypothesize that VFs are an early phenomenon of acromegaly and related to GH levels. VF assessment should be included in the workup at the diagnosis of acromegaly., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Storytelling is an effective information source when coupled with technical-scientific evidence. It can promote a structured relationship between evidence-based knowledge and field experience of workplace safety and prevention services (WSPS) inspectors. This is key to identifying the causes of workplace injuries and to set priorities for prevention strategies., Aims: The main aim was to describe and report how story collection can be used for deriving validated indications for injury prevention. The specific objectives were to report the results of the creation and dissemination on the web of the story collection and the experience of setting up a community of practice (CoP) to develop preventive recommendations., Methods: WSPS inspectors from local health boards in Piedmont (northwest Italy) were asked to write injury stories. They identified the key elements of their stories and developed a narrative of witness accounts to explore the critical issues identified during the investigation. In sessions with the CoP, the inspectors validated the indications for prevention elaborated in each story to reduce bias and standardize recommendations., Results: Between 2012 and 2017, 60 WSPS inspectors wrote 53 injury stories which were collected and published on the institutional website. Twenty-two stories were selected for discussion during peer review sessions in the CoP and the indications for prevention were transformed as preventive solutions., Conclusions: Occupational safety and health prevention can benefit from a narrative-based approach that provides a more comprehensive look at health and safety by facilitating knowledge improvement and sharing., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Climate change affects distribution and persistence of species. However, forecasting species' responses to these changes requires long-term data series that are often lacking in ecological studies. We used 15 years of small mammal trapping data collected between 1978 and 2015 in 3 areas at Doñana National Park (southwest Spain) to (i) describe changes in species composition and (ii) test the association between local climate conditions and size of small mammal populations. Overall, 5 species were captured: wood mouse Apodemus sylvaticus , algerian mouse Mus spretus , greater white-toothed shrew Crocidura russula , garden dormouse Eliomys quercinus , and black rat Rattus rattus . The temporal pattern in the proportion of captures of each species suggests that the small mammal diversity declined with time. Although the larger species (e.g., E. quercinus ), better adapted to colder climate, have disappeared from our trapping records, M. spretus , a small species inhabiting southwest Europe and the Mediterranean coast of Africa, currently is almost the only trapped species. We used 2-level hierarchical models to separate changes in abundance from changes in probability of capture using records of A. sylvaticus in all 3 areas and of M. spretus in 1. We found that heavy rainfall and low temperatures were positively related to abundance of A. sylvaticus , and that the number of extremely hot days was negatively related to abundance of M. spretus . Despite other mechanisms are likely to be involved, our findings support the importance of climate for the distribution and persistence of these species and raise conservation concerns about potential cascading effects in the Doñana ecosystem.

Itch is thought to represent the peculiar response to stimuli conveyed by somatosensory pathways shared with pain through the activation of specific neurons and receptors. It can occur in association with dermatological, systemic and neurological diseases, or be the side effect of certain drugs. However, some patients suffer from chronic idiopathic itch that is frequently ascribed to psychological distress and for which no biomarker is available to date. We investigated three multigenerational families, one of which diagnosed with joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type (JHS/EDS-HT), characterized by idiopathic chronic itch with predominantly proximal distribution. Skin biopsy was performed in all eight affected members and revealed in six of them reduced intraepidermal nerve fibre density consistent with small fibre neuropathy. Whole exome sequencing identified two COL6A5 rare variants co-segregating with chronic itch in eight affected members and absent in non-affected members, and in one unrelated sporadic patient with type 1 painless diabetic neuropathy and chronic itch. Two families and the diabetic patient carried the nonsense c.6814G>T (p.Glu2272*) variant and another family carried the missense c.6486G>C (p.Arg2162Ser) variant. Both variants were predicted as likely pathogenic by in silico analyses. The two variants were rare (minor allele frequency < 0.1%) in 6271 healthy controls and absent in 77 small fibre neuropathy and 167 JHS/EDS-HT patients without itch. Null-allele test on cDNA from patients' fibroblasts of both families carrying the nonsense variant demonstrated functional haploinsufficiency due to activation of nonsense mediated RNA decay. Immunofluorescence microscopy and western blotting revealed marked disorganization and reduced COL6A5 synthesis, respectively. Indirect immunofluorescence showed reduced COL6A5 expression in the skin of patients carrying the nonsense variant. Treatment with gabapentinoids provided satisfactory itch relief in the patients carrying the mutations. Our findings first revealed an association between COL6A5 gene and familiar chronic itch, suggesting a new contributor to the pathogenesis of neuropathic itch and identifying a new candidate therapeutic target., (© The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: An excess of intracellular beta-catenin protein is triggered by various genetic alterations in melanoma cell lines, and has been suggested to play a role in melanoma tumorigenesis., Objectives: To investigate the role played in vivo by beta-catenin in melanoma tumorigenesis, we compared the cytoplasmic detection of beta-catenin in benign melanocytic cells vs. malignant melanoma cells presumably generated from these benign melanocytic cells. For this purpose, melanocytic naevi occurring in association with melanoma, which were suggested to be melanoma precursors, were compared with their associated melanoma for beta-catenin cytoplasmic immunoreactivity., Methods: Fifty-seven consecutive cases of primary cutaneous melanoma were considered, and 15 of them were found to be associated with a melanocytic naevus portion. The naevus portion showed features of acquired melanocytic naevus (total 12 cases: five dysplastic, seven intradermal) or congenital growth pattern naevus (total three cases: one superficial, two deep). All specimens were immunohistochemically investigated for beta-catenin., Results: Virtually all primary cutaneous melanomas, including those associated with a naevus portion, showed cytoplasmic beta-catenin positivity. However, the intradermal naevus portion was consistently cytoplasmic beta-catenin negative, while both the dysplastic and the congenital naevus portions were cytoplasmic beta-catenin positive., Conclusions: Beta-catenin excess may play a role in melanoma tumorigenesis, because beta-catenin cytoplasmic reactivity was found in primary cutaneous melanoma but not in its associated intradermal naevus precursor. As, however, beta-catenin cytoplasmic reactivity was detected not only in primary cutaneous melanoma but also in its associated dysplastic/congenital naevus precursors, beta-catenin stabilization alone is not sufficient to play a decisive role for melanoma onset.

Aims: Characterize from both genetic and phenotypic standpoints the indigenous strains of Saccharomyces spp. associated with natural fermentation of 'Malvasia delle Lipari'., Methods and Results: A total of 192 yeast isolates were obtained from completed fermentation of a mix of 'Malvasia delle Lipari' (92%) and 'Corinto nero' (8%) grapes in two wineries in Salina Island (Sicily, Italy). Fifty-one Saccharomyces spp. isolates were characterized using ITS-PCR, random amplified polymorphic DNA-PCR and mitochondrial DNA restriction fragment length polymorphism and 12 biotypes were identified. Representative strains of each biotype, tested for their physiological traits, exhibit different killer activity, fermentation vigour, production of hydrogen sulphide and show similar beta-glucosidase and proteolytic activity., Conclusions: It is possible to cluster in different groups naturally occurring indigenous biotypes of Saccharomyces cerevisiae from 'Malvasia delle Lipari' on the basis of molecular profiles., Significance and Impact of the Study: Deeper insight on indigenous wine yeast of a conserved environment. The knowledge gained might offer a contribution to the selection of autochthonous wine yeast as starters for controlled fermentations.

Testosterone, progesterone, 17 alpha-hydroxyprogesterone, and 20 alpha-dihydroprogesterone have been measured in the spermatic and peripheral venous blood of 17 prepubertal boys undergoing surgery for undescended testis or inguinal hernia repair. Mean (+/-SE) spermatic testosterone and progesterone (538 +/- 212 and 704 +/- 110 pg/ml, respectively) were significantly higher (P less than 0.005) than peripheral levels (91 +/- 11 and 419 +/- 71 pg/ml, respectively). No significant spermatic-peripheral gradient was found for 17 alpha-hydroxyprogesterone and 20 alpha-dihydroprogesterone. These in vivo studies demonstrate that the secretory pattern of the prepubertal testis is different from the adult testis.

Serum testosterone (T), 17-hydroxyprogesterone (17P), androstenedione (delta 4-dione), dehydroepiandrosterone (DHA), delta 5-androstene-3 beta, 17 beta-diol (delta 5-diol), estradiol (E2), dihydrotestosterone (DHT),5 alpha-androstane-3 alpha,17 beta-diol (3 alpha diol), and 5 alpha-androstane-3 beta,17 beta-diol (3 beta diol) were measured in the peripheral and spermatic venous blood of 21 boys undergoing surgery for idiopathic left varicocele. The boys were divided into 3 groups according to their pubertal development: prepubertal (group 1 or P1; n = 8), pubertal stage 2 (group II or P2; n = 6), and pubertal stages 3-4 (group III or P3-4; n = 7). The testes of the prepubertal boys secreted T, 17P, DHA, delta 5-diol, DHT, and 3 alpha diol, but not delta 4-dione, E2, and 3 beta diol. In pubertal stage P2, the mean spermatic-peripheral secretory gradients of T, 17P, DHA, delta 5-diol, DHT, and 3 alpha diol were significantly higher than those in the prepubertal stage, and there was testicular secretion of delta 4-dione, E2, and 3 beta diol. In pubertal stage P3-4, the mean spermatic-peripheral secretory gradients of most of these steroids, even if increased, were not significantly different from those in stage P2 (with the exception of 17P, delta 5-diol, and DHA). We suggest that after the important modifications of testicular secretion occurring in pubertal stage P2, the testicular secretory pattern of the pubertal testis is similar to the pattern of the adult testis. We suggest also that these results, obtained in boys with idiopathic varicocele, can probably be extended to the secretory activity of the testes of normal pubertal boys.

Spermatic and peripheral plasma concentrations of testosterone (T) and androstenedione (A) have been measured in prepubertal boys affected by inguinal hernia (group I; n = 7) and unilateral undescended testis (group II; n = 18). Mean (+/- SE) spermatic T concentrations (47.7 +/- 14.8 ng/dl in group I; 36.3 +/- 3.4 ng/dl in group II) were significantly different from mean peripheral T concentrations (9.8 +/- 2.1 ng/dl in group I; 9.3 +/- 0.9 ng/dl in group II) in both groups (P less than 0.05 and P less than 0.0005, respectively). Mean spermatic A concentration (59.7 +/- 4.9 ng/dl) was significantly higher than mean peripheral A concentration (49.8 +/- 4.9 ng/dl) in group II (P less than 0.05) but not in group I. Mean spermatic and peripheral T and A values found in boys of group I were not significantly different from those found in group II. The mean spermatic/peripheral T ratio was higher (5.01 in group I; 4.42 in group II) than the corresponding mean spermatic/peripheral A ratio (1.27 in group I; 1.32 in group II) in both groups. Our data suggest that 1) although testicular T secretion is present in all prepubertal boys, A secretion is not constant and often negligible; 2) the contribution of testicular secretion to the circulating T is much more important than the contribution to the circulating A; 3) no significant differences were found between the testicular secretory pattern of prepubertal boys with inguinal hernia and unselected boys with unilateral undescended testis.