Enteric viruses replicate in salivary glands and infect through saliva.

Enteric viruses like norovirus, rotavirus and astrovirus have long been accepted as spreading in the population through fecal-oral transmission: viruses are shed into feces from one host and enter the oral cavity of another, bypassing salivary glands (SGs) and reaching the intestines to replicate, be shed in feces and repeat the transmission cycle1. Yet there are viruses (for example, rabies) that infect the SGs2,3, making the oral cavity one site of replication and saliva one conduit of transmission. Here we report that enteric viruses productively and persistently infect SGs, reaching titres comparable to those in the intestines. We demonstrate that enteric viruses get released into the saliva, identifying a second route of viral transmission. This is particularly significant for infected infants, whose saliva directly transmits enteric viruses to their mothers' mammary glands through backflow during suckling. This sidesteps the conventional gut-mammary axis route4 and leads to a rapid surge in maternal milk secretory IgA antibodies5,6. Lastly, we show that SG-derived spheroids7 and cell lines8 can replicate and propagate enteric viruses, generating a scalable and manageable system of production. Collectively, our research uncovers a new transmission route for enteric viruses with implications for therapeutics, diagnostics and importantly sanitation measures to prevent spread through saliva.

Higher serum levels of a cathepsin K-generated periostin fragment are associated with fractures in postmenopausal women with primary hyperparathyroidism: a pilot study.

The only difference between fractured and non-fractured postmenopausal women with PHPT of same sex, age, and BMI was a significantly mean higher serum k-periostin level. K-periostin value was associated with fracture at any site (odds ratio 1.044, 95% CI 1.005-1.091, p = 0.03). INTRODUCTION: To assess serum k-periostin fragment levels in patients with primary hyperparathyroidism (PHPT), fractured and non-fractured matched for sex, age, and body mass index. METHODS: Twenty-five Caucasian fractured postmenopausal women with PHPT (group Fx) and 25 PHPT non-fractured (group NFx) were enrolled. Each patient underwent DXA scan at lumbar, hip, and forearm, spine X-ray, and biochemical evaluation of calcium metabolism. For k-periostin analyses, we utilized a specific ELISA test that detects CatK-generated fragment levels in the bloodstream. RESULTS: We found no difference in mean BMD and bone turnover marker values between Fx and NFx groups. Prevalence of osteoporosis was not significantly different in Fx vs NFx (72% vs 60%, p = 0.55). Among Fx, 16% reported multiple fractures, 28% morphometric vertebral fractures, 4% femoral fractures, 28% non-vertebral non-femoral fractures, and 8% wrist fractures. The only detectable difference between Fx and NFx group was a significantly mean higher k-periostin serum level (46.2 ± 21.4 vs 34.7 ± 13.5 ng/ml, p = 0.02). K-periostin was associated with fracture at any site (odds ratio 1.044, 95% CI 1.005-1.091, p = 0.03). No difference in mean k-periostin values was found between patients with vertebral fracture vs those with non-vertebral fracture, and between those with multiple fractures vs those with single fracture. CONCLUSION: Serum k-periostin is significantly associated with fracture in PHPT. If confirmed by further studies, k-periostin could be considered a new marker of bone fragility in PHPT, independently of BMD.

Lymphomatoid papulosis types D and E: a multicentre series of the French Cutaneous Lymphomas Study Group.

BACKGROUND: Lymphomatoid papulosis (LyP) type D (LyP D) and type E (LyP E) have recently been described in small series of cases or isolated case reports. AIM: To further describe the clinical and histological features of LyP D and E based on a retrospective multicentre study. METHODS: The clinical and histopathological features of 29 patients with an initial diagnosis of LyP D or LyP E were retrospectively assessed using standardized forms. RESULTS: After exclusion of 5 cases, 24 patients (14 LyP D, 10 LyP E) were enrolled in the study. The median follow-up was 2.5 years (range 1 month to 13 years). LyP D was characterized by multiple recurrent self-regressing small papules that developed central erosion or necrosis, whereas LyP E presented as papulonodular lesions that rapidly evolved into necrotic eschar-like lesions > 10 mm in size. Epidermal changes were more frequent in LyP D, whereas dermal infiltrates were deeper in LyP E. Anaplastic cytology was rare and the DUSP22 rearrangement was never observed. Two patients (8%) had an associated cutaneous lymphoma. CONCLUSION: LyP D and E have distinct clinical findings and may be associated with other cutaneous lymphomas.

Two-year follow-up of 196 interstitial lung disease patients after ICU stay.

OBJECTIVE: Interstitial lung diseases (ILDs) are associated with poor prognosis in the intensive care unit (ICU). We aimed to assess factors associated with hospital mortality in ILD patients admitted to the ICU and to investigate long-term outcome.MATERIAL AND METHODS: This was a retrospective study in a teaching hospital specialised in ILD management. Patients with ILD who were hospitalised in the ICU between 2000 and 2014 were included. Independent predictors of hospital mortality were identified using logistic regression.RESULTS: A total of 196 ILD patients were admitted to the ICU during the study period. Overall hospital mortality was 55%. Two years after ICU admission, 70 (36%) patients were still alive. Of the 196 patients, 108 (55%) required invasive mechanical ventilation, of whom 21 (20%) were discharged alive from hospital. Acute exacerbation of ILD and multi-organ failure were highly associated with hospital mortality (OR 5.4, 95% CI 1.9-15.5 and OR 12.6, 95% CI 4.9-32.5, respectively).CONCLUSION: Hospital mortality among ILD patients hospitalised in the ICU was high, but even where invasive mechanical ventilation was required, a substantial number of patients were discharged alive from hospital. Multi-organ failure could lead to major ethical concerns.

Pregnancy and lactation, a challenge for the skeleton.

In this review we discuss skeletal adaptations to the demanding situation of pregnancy and lactation. Calcium demands are increased during pregnancy and lactation, and this is effectuated by a complex series of hormonal changes. The changes in bone structure at the tissue and whole bone level observed during pregnancy and lactation appear to largely recover over time. The magnitude of the changes observed during lactation may relate to the volume and duration of breastfeeding and return to regular menses. Studies examining long-term consequences of pregnancy and lactation suggest that there are small, site-specific benefits to bone density and that bone geometry may also be affected. Pregnancy- and lactation-induced osteoporosis (PLO) is a rare disease for which the pathophysiological mechanism is as yet incompletely known; here, we discuss and speculate on the possible roles of genetics, oxytocin, sympathetic tone and bone marrow fat. Finally, we discuss fracture healing during pregnancy and lactation and the effects of estrogen on this process.

Millepora platyphylla (Cnidaria, Hydrozoa) range extended back to the Eastern Pacific, thanks to a new record from Clipperton Atoll.

The fire coral Millepora platyphylla Hemprich Ehrenberg, 1834 (Cnidaria, Hydrozoa) has a widespread Indo-Pacific distribution observed from the surface to 40 m (Razak Hoeksema 2003). However, its extirpation from the East Pacific (Gulf of Chiriqui, Panama) was documented after the 1982-1983 bleaching event (Glynn Weerdt 1991). Here, we report the discovery of 5 colonies of M. platyphylla from the eastern Pacific, specifically at Clipperton Atoll, during the TARA Pacific expedition (www.taraexpeditions.org).

[Rhabdomyolysis in patients treated by corticosteroids for acute asthma in intensive care unit]. / La corticothérapie, une cause de rhabdomyolyse chez les asthmatiques en réanimation.

INTRODUCTION: Acute muscle involvement is an infrequent complication of corticosteroids, characterized by muscle weakness and a rhabdomyolysis, rapidly regressive after withdrawal of corticosteroids. CASE REPORT: We report the case of a woman admitted in intensive care unit for acute severe asthma, treated with high doses of methylprednisolone. Serum CPK level raised with a peak at 28,160 UI/L (n<250 UI/L) at day 15, suggesting acute rhabdomyolysis with renal failure. CPK rapidly normalized when corticosteroids were discontinued. Other causes of rhabdomyolysis were ruled out. CONCLUSION: This necrosing myopathy under high doses of corticosteroids has been described in patients with severe acute asthma. The mechanism of the muscle damage results from a combination of corticosteroids toxicity, respiratory acidosis and mechanic ventilation.

T-cell papulosis associated with B-cell malignancy: a distinctive clinicopathologic entity.

BACKGROUND: A distinctive eruption referred to as 'insect bite-like reaction' or 'eosinophilic dermatosis of haematological malignancy' has been described during the course of haematological B-cell malignancies (BCM). However, its clinical evolution, histopathological features and pathogenesis remain unclear. OBJECTIVES: To characterize this eruption and to investigate its pathogenesis and relationship with the underlying BCM. METHODS: In this multicenter retrospective study of the French Study Group on Cutaneous Lymphomas, 37 patients with a BCM and a cutaneous eruption consisting in chronic and/or recurrent papules, papulo-vesicles and/or nodules were included. Clinical, histopathological, immunohistochemical and molecular data were reviewed. RESULTS: No significant insect bite history or seasonal predominance was recorded. Patients had pruritic papules (81%), papulo-vesicles (43%) and nodules (38%), often predominated in the head and neck region (84%), without complete remission periods in most cases (57%). The predominant associated BCM was chronic lymphocytic leukaemia (73%). Histological and immunohistochemical review showed a dense dermal lymphocytic infiltrate predominantly composed of T lymphocytes (100%), with frequent eosinophils (77.6%); a perivascular and periadnexal (most often folliculotropic) pattern (77.6%), sometimes suggestive of a folliculotropic mycosis fungoides; clusters of tumour B cells were identified in 47% of cases using appropriate phenotyping markers. In 10/14 cases (71.4%) tested for B-cell IgH gene rearrangement, a B-cell clone was identified in skin lesions (identical to the blood clone in nine cases), whereas no T-cell clone was present. CONCLUSION: We propose the denomination 'T-cell papulosis associated with B-cell malignancy' (TCP-BCM) for this distinctive eruption. Although resulting in various histopathological pictures, it can be easily recognized by clinicians and may be identified by informed pathologists relying on some key features. An extravasation of tumour B cells with skin-homing properties associated with a secondary, predominant, T-cell immune reaction could explain the clinicopathologic aspect and the prolonged regressive and recurrent course of the disease.

Interaction between LRP5 and periostin gene polymorphisms on serum periostin levels and cortical bone microstructure.

We investigated the interaction between periostin SNPs and the SNPs of the genes assumed to modulate serum periostin levels and bone microstructure in a cohort of postmenopausal women. We identified an interaction between LRP5 SNP rs648438 and periostin SNP rs9547970 on serum periostin levels and on radial cortical porosity. PURPOSE: The purpose of this study is to investigate the interaction between periostin gene polymorphisms (SNPs) and other genes potentially responsible for modulating serum periostin levels and bone microstructure in a cohort of postmenopausal women. METHODS: In 648 postmenopausal women from the Geneva Retirees Cohort, we analyzed 6 periostin SNPs and another 149 SNPs in 14 genes, namely BMP2, CTNNB1, ESR1, ESR2, LRP5, LRP6, PTH, SPTBN1, SOST, TGFb1, TNFRSF11A, TNFSF11, TNFRSF11B and WNT16. Volumetric BMD and bone microstructure were measured by high-resolution peripheral quantitative computed tomography at the distal radius and tibia. RESULTS: Serum periostin levels were associated with radial cortical porosity, including after adjustment for age, BMI, and years since menopause (p = 0.036). Sixteen SNPs in the ESR1, LRP5, TNFRSF11A, SOST, SPTBN1, TNFRSF11B and TNFSF11 genes were associated with serum periostin levels (p range 0.03-0.001) whereas 26 SNPs in 9 genes were associated with cortical porosity at the radius and/or at the tibia. WNT 16 was the gene with the highest number of SNPs associated with both trabecular and cortical microstructure. The periostin SNP rs9547970 was also associated with cortical porosity (p = 0.04). In particular, SNPs in LRP5, ESR1 and near the TNFRSF11A gene were associated with both cortical porosity and serum periostin levels. Eventually, we identified an interaction between LRP5 SNP rs648438 and periostin SNP rs9547970 on serum periostin levels (interaction p = 0.01) and on radial cortical porosity (interaction p = 0.005). CONCLUSION: These results suggest that periostin expression is genetically modulated, particularly by polymorphisms in the Wnt pathway, and is thereby implicated in the genetic variation of bone microstructure.

Vorinostat and Mithramycin A in combination therapy as an interesting strategy for the treatment of Sézary T lymphoma: a transcriptomic approach.

SAHA (vorinostat) is a histone deacetylase inhibitor approved by the USA Food and Drug Administration (FDA) for treating advanced refractory cutaneous T cell lymphomas. As SAHA alters the expression of many genes under control of the Sp1 transcription factor, we examined the effect of its association with the FDA-approved anticancer antibiotic Mithramycin A (MTR, plicamycin), a competitive inhibitor of Sp1 binding to DNA. Sézary syndrome (SS) cells, expanded ex vivo from peripheral blood mononuclear cells of 4 patients, were tested for their sensitivity to the drugs regarding cytotoxicity and differential responsive gene expression. Multivariate statistical methods were used to identify genes whose expression is altered by SAHA, MTR, and the synergist effect of the two drugs. MTR, like SAHA, induced the apoptosis of SS cells, while the two drugs in combination showed clear synergy or potentiation. Expression data stressed a likely important role of additive or synergistic epigenetic modifications in the combined effect of the two drugs, while direct inhibition of Sp1-dependent transcription seemed to have only limited impact. Ontological analysis of modified gene expression suggested that the two drugs, either independently or synergistically, counteracted many intertwined pro-survival pathways deregulated in SS cells, resistance of these tumors to intrinsic and extrinsic apoptosis, abnormal adhesion migration, and invasive properties, as well as immunosuppressive behavior. Our findings provide preliminary clues on the individual and combined effects of SAHA and MTR in SS cells and highlight a potential therapeutic interest of this novel pair of drugs for treatment of SS patients.

Seroprevalence of seven pathogens transmitted by the Ixodes ricinus tick in forestry workers in France.

In order to assess the level of occupational exposure to the main pathogens transmitted by the Ixodes ricinus tick, a seroprevalence study was performed on serum samples collected in 2003 from 2975 forestry workers of northeastern France. The global seroprevalence estimated for the seven pathogens studied was 14.1% (419/2975) for Borrelia burgdorferi sl, 5.7% (164/2908) for Francisella tularensis, 2.3% (68/2941) for tick-borne encephalitis virus, 1.7% (50/2908) for Anaplasma phagocytophilum and 1.7% (48/2908) for Bartonella henselae. The seroprevalences of Babesia divergens and Babesia microti studied in a subgroup of participants seropositive for at least one of these latter pathogens were 0.1% (1/810) and 2.5% (20/810), respectively. Borrelia burgdorferi sl seroprevalence was significantly higher in Alsace and Lorraine and F. tularensis seroprevalence was significantly higher in Champagne-Ardenne and Franche-Comté. The results of this survey also suggest low rates of transmission of Bartonella henselae and F. tularensis by ticks and a different west/east distribution of Babesia species in France. The frequency and potential severity of these diseases justify continued promotion of methods of prevention of I. ricinus bites.

Additive Genetic Effects on Circulating Periostin Contribute to the Heritability of Bone Microstructure.

CONTEXT: Genetic factors account for 60-80% of the areal bone mineral density (aBMD) variance, whereas the heritability of bone microstructure is not clearly established. aBMD and microstructure are under the control of osteocytes, which regulate bone formation through the expression of molecules such as sclerostin (SOST) and periostin (POSTN). OBJECTIVE: We hypothesized that additive genetic effects contribute to serum levels of SOST and POSTN and thereby to the individual variance of bone microstructure. SUBJECTS AND METHODS: In a retrospective analysis of 432 subjects from the Geneva Retiree Cohort age 64.9 ± 1.4 years and 96 of their offspring age 37.9 ± 5.7 years, we measured serum SOST (sSOST) and serum POSTN (sPOSTN), distal radius and tibia microstructure, hip and lumbar spine aBMD, and bone turnover markers, Heritability (h(2), %) was calculated as twice the slope of the regression (ß) between parents and offspring. RESULTS: cPOSTN levels were significantly higher in men than women and in offspring than parents. h(2) values for bone microstructural traits ranged from 22-64% depending on the envelope (trabecular [Tb] or cortical [Ct]) and skeletal site (radius or tibia), whereas h(2) for sPOSTN and sSOST was 50% and 40%, respectively. sPOSTN was positively associated with Tb bone volume on total volume and Ct thickness, and negatively with Ct porosity. The associations for Ct parameters remain significant after adjustment for propetide of type-I procollagen, cross-linked telopeptide of type I collagen, femoral neck aBMD, sex or age. After adjustment of bone traits for sPOSTN, h(2) values decreased for several Tb and Ct bone parameters, but not for aBMD. In contrast, adjusting for sSOST did not alter h(2) values for bone traits. CONCLUSIONS: Additive genetic effects account for a substantial proportion of the individual variance of bone microstructure, sPOSTN, and sSOST. sPOSTN is largely inherited as a sex-related trait and carries an important contribution to the heritability of bone microstructure, indicating that these traits are at least partly determined by common genetic effects.

[Papular mycosis fungoides]. / Mycosis fongoïde papuleux.

BACKGROUND: Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma. A new form of incipient MF has recently been described: papular MF. Herein, we report a case and propose a literature review. PATIENTS AND METHODS: A 63-year-old man presented with erythematous and non-pruritic papular lesions of the trunk. The general examination was unremarkable. A skin biopsy showed moderately dense epidermotropic lymphocytic infiltration consistent with MF. Screening for CD30 was negative. Treatment with an extremely potent corticosteroid (clobetasol, one application per day) seemed effective, with almost complete disappearance of the lesions. DISCUSSION: Many clinical variants of the initial stages of MF have been described, one of the most recent of which is papular mycosis fungoides (PMF), of which 10 cases are reported in the literature. PMF begins clinically with an erythematous, non-pruritic and chronic papular rash that is not associated with the classic erythematous-squamous lesions of incipient MF. There appears to be no predominance of gender, and the age of onset ranges from 31 to 63 years. Histological examination of the PMF lesions revealed an epidermotropic subepidermal infiltrate composed predominantly of CD4+T-cells. The prognosis appeared good with the treatments conventionally used for incipient MF. PMF is likened to a form of incipient MF with a good prognosis. Associated classic MF lesions comprising erythematous-squamous plaques have been described as the condition progresses. Differential diagnoses include pilotropic MF, pityriasis lichenoides chronica, pityriasis lichenoides varioliformis acuta, and especially type B lymphomatoid papulosis, the histopathological findings of which may be close to PMF. CONCLUSION: Papular MF would appear to be a papular variant of incipient MF with a good prognosis. However, it is necessary to obtain clinical and disease progression data for a greater number of patients in order to better characterize this entity.

Y-autosome translocation interferes with meiotic sex inactivation and expression of autosomal genes: a case study in the pig.

Y-autosome translocations are rare in humans and pigs. In both species, these rearrangements can be responsible for meiotic arrest and subsequent infertility. Chromosome pairing abnormalities on the SSCX, SSCY and SSC1 chromatin domains were identified by analyzing pachytene spermatocytes from a boar carrying a (Y;1) translocation by immunolocalization of specific meiotic protein combined with FISH. Disturbance of the meiotic sex chromosome inactivation (MSCI) was observed by Cot-RNA-FISH and analysis of ZFY gene expression by sequential RNA- and DNA-FISH on spermatocytes. We hypothesized that the meiotic arrest observed in this boar might be due to the silencing of critical autosomal genes and/or the reactivation of some sex chromosome genes.

Combined effects of zoledronate and mechanical stimulation on bone adaptation in an axially loaded mouse tibia.

BACKGROUND: local bisphosphonate delivery may be a solution to prevent periprosthetic bone loss and improve orthopedic implants fixation. In load-bearing implants, periprosthetic bone is exposed to high mechanical demands, which in normal conditions induce an adaptation of bone. In this specific mechanical situation, the modulation of the bone response by bisphosphonate remains uncertain. METHODS: we assessed the combined effects of zoledronate and mechanical loading on bone adaptation using an in-vivo axial compression model of the mouse tibia and injections of zoledronate. Bone structure was quantified with in-vivo microCT before and after the period of stimulation and the mechanical properties of the tibias were evaluated with 3 point-bending tests after sacrifice. FINDINGS: axial loading induced a localized increase of cortical thickness and bone area. Zoledronate increased cortical thickness, bone perimeter, and bone area. At the most loaded site of the tibia, the combined effect of zoledronate and mechanical stimulation was significantly smaller than the sum of the individual effects measured at the same site in the control groups. INTERPRETATIONS: the results of this study suggested that a negative interaction between zoledronate and mechanical loading might exist at high level of strain.

Meiotic studies of a 38,XY/39,XXY mosaic boar.

Klinefelter's syndrome (KS) is the most common sex chromosome abnormality identified in human males. This syndrome is generally associated with infertility. Men with KS may have a 47,XXY or a 46,XY/47,XXY karyotype. Studies carried out in humans and mice suggest that only XY cells are able to enter and complete meiosis. These cells could originate from the XY cells present in mosaic patients or from XXY cells that have lost one X chromosome. In pig, only 3 cases of pure 39,XXY have been reported until now, and no meiotic analysis was carried out. For the first time in pig species we report the analysis of a 38,XY/39,XXY boar and describe the origin of the supplementary X chromosome and the chromosomal constitutions of the germ and Sertoli cells.