Determinants of trabecular bone score and prevalent vertebral fractures in women with fragility fractures: a cross-sectional sub-study of NoFRACT.

Determinants of trabecular bone score (TBS) and vertebral fractures assessed semiquantitatively (SQ1-SQ3) were studied in 496 women with fragility fractures. TBS was associated with age, parental hip fracture, alcohol intake and BMD, not SQ1-SQ3 fractures. SQ1-SQ3 fractures were associated with age, prior fractures, and lumbar spine BMD, but not TBS. INTRODUCTION: Trabecular bone score (TBS) and vertebral fractures assessed by semiquantitative method (SQ1-SQ3) seem to reflect different aspects of bone strength. We therefore sought to explore the determinants of and the associations between TBS and SQ1-SQ3 fractures. METHODS: This cross-sectional sub-study of the Norwegian Capture the Fracture Initiative included 496 women aged ≥ 50 years with fragility fractures. All responded to a questionnaire about risk factors for fracture, had bone mineral density (BMD) of femoral neck and/or lumbar spine assessed, TBS calculated, and 423 had SQ1-SQ3 fracture assessed. RESULTS: Mean (SD) age was 65.6 years (8.6), mean TBS 1.27 (0.10), and 33.3% exhibited SQ1-SQ3 fractures. In multiple variable analysis, higher age (ßper SD = - 0.26, 95% CI: - 0.36,- 0.15), parental hip fracture (ß = - 0.29, 95% CI: - 0.54,- 0.05), and daily alcohol intake (ß = - 0.43, 95% CI - 0.79, - 0.08) were associated with lower TBS. Higher BMD of femoral neck (ßper SD = 0.34, 95% CI 0.25-0.43) and lumbar spine (ßper SD = 0.40, 95% CI 0.31-0.48) were associated with higher TBS. In multivariable logistic regression analyses, age (ORper SD = 1.94, 95% CI 1.51-2.46) and prior fragility fractures (OR = 1.71, 95% CI 1.09-2.71) were positively associated with SQ1-SQ3 fractures, while lumbar spine BMD (ORper SD = 0.75 95% CI 0.60-0.95) was negatively associated with SQ1-SQ3 fractures. No association between TBS and SQ1-SQ3 fractures was found. CONCLUSION: Since TBS and SQ1-SQ3 fractures were not associated, they may act as independent risk factors, justifying the use of both in post-fracture risk assessment.

The influence of different implant surfaces on osseointegration in diabetes: a systematic review of the literature.

AIM: The aim of this study was to evaluate, through a systematic review of the literature, the effects of different implant surface modifications on osseointegration in diabetic subjects. METHODS: A search was performed of the PubMed database, using a combination of the following keywords: "Implant surface" OR "Dental implants" AND "Diabetes" OR "Hyperglycemia". Papers published in English between January 1960 and November 2013 were selected. All experimental models were considered in this search, but case reports and in vitro studies were excluded from this review. RESULTS: The initial search identified 182 articles. After reading the titles and abstracts, 39 articles were selected for full reading. Finally, 4 papers were selected after evaluation of all the papers, and these papers are discussed in this review. Due to the methodological heterogeneity of the selected studies, it was not possible to perform a meta-analysis of the data. CONCLUSION: It can be concluded that although the benefits of surface modifications present in individuals with diabetes have biological plausibility, there is little evidence of the benefits of these modifications.

Multi-omics network model reveals key genes associated with p-coumaric acid stress response in an industrial yeast strain.

The production of ethanol from lignocellulosic sources presents increasingly difficult issues for the global biofuel scenario, leading to increased production costs of current second-generation (2G) ethanol when compared to first-generation (1G) plants. Among the setbacks encountered in industrial processes, the presence of chemical inhibitors from pre-treatment processes severely hinders the potential of yeasts in producing ethanol at peak efficiency. However, some industrial yeast strains have, either naturally or artificially, higher tolerance levels to these compounds. Such is the case of S. cerevisiae SA-1, a Brazilian fuel ethanol industrial strain that has shown high resistance to inhibitors produced by the pre-treatment of cellulosic complexes. Our study focuses on the characterization of the transcriptomic and physiological impact of an inhibitor of this type, p-coumaric acid (pCA), on this strain under chemostat cultivation via RNAseq and quantitative physiological data. It was found that strain SA-1 tend to increase ethanol yield and production rate while decreasing biomass yield when exposed to pCA, in contrast to pCA-susceptible strains, which tend to decrease their ethanol yield and fermentation efficiency when exposed to this substance. This suggests increased metabolic activity linked to mitochondrial and peroxisomal processes. The transcriptomic analysis also revealed a plethora of differentially expressed genes located in co-expressed clusters that are associated with changes in biological pathways linked to biosynthetic and energetical processes. Furthermore, it was also identified 20 genes that act as interaction hubs for these clusters, while also having association with altered pathways and changes in metabolic outputs, potentially leading to the discovery of novel targets for metabolic engineering toward a more robust industrial yeast strain.

Transmission of infection from non-isolated patients with COVID-19 to healthcare workers.

Insufficiently protected healthcare workers (HCWs), defined as high-risk contacts of patients with coronavirus disease 2019 (COVID-19), are routinely quarantined. This study evaluated the transmission of infection from a symptomatic patient with COVID-19 to 60 HCWs exposed at ≤2 m for ≥15 min or during aerosol-generating procedures. Following ≥106 unique high-risk contacts, none of the HCWs tested positive for severe acute respiratory syndrome coronavirus-2 RNA or developed antibodies. The HCWs reported adherence to basic infection control procedures. These results are in accordance with other reports, and should reassure HCWs and further stimulate broader evaluation of the foundation for the current practice of home quarantining non-symptomatic HCWs.

Reactive oxygen species and autophagy play a role in survival and differentiation of the phytopathogen Moniliophthora perniciosa.

The hemibiotrophic basidiomycete Moniliophthora perniciosa causes "witches' broom disease" in cacao (Theobroma cacao). During plant infection, M. perniciosa changes from mono to dikaryotic life form, an event which could be triggered by changes in plant nutritional offer and plant defense molecules, i.e., from high to low content of glycerol and hydrogen peroxide. We have recently shown that in vitro glycerol induces oxidative stress resistance in dikaryotic M. perniciosa. In order to understand under which conditions in parasite-plant interaction M. perniciosa changes from intercellular monokaryotic to intracellular dikaryotic growth phase we studied the role of glycerol on mutagen-induced oxidative stress resistance of basidiospores and monokaryotic hyphae; we also studied the role of H(2)O(2) as a signaling molecule for in vitro dikaryotization and whether changes in nutritional offer by the plant could be compensated by inducible fungal autophagy. Mono-/dikaryotic glycerol or glucose-grown cells and basidiospores were exposed to the oxidative stress-inducing mutagens H(2)O(2) and Paraquat as well as to pre-dominantly DNA damaging 4-nitroquinoline-1-oxide and UVC irradiation. Basidiospores showed highest resistance to all treatments and glycerol-grown monokaryotic hyphae were more resistant than dikaryotic hyphae. Monokaryotic cells exposed to 1microM of H(2)O(2) in glycerol-media induced formation of clamp connections within 2 days while 1mM H(2)O(2) did not within a week in the same medium; no clamp connections were formed in H(2)O(2)-containing glucose media within a week. Lower concentrations of H(2)O(2) and glycerol, when occurring in parallel, are shown to be two signals for dikaryotization in vitro and may be also during the course of infection. Q-PCR studies of glycerol-grown dikaryotic cells exposed to oxidative stress (10mM H(2)O(2)) showed high expression of MpSOD2 and transient induction of ABC cytoplasmic membrane transporter gene MpYOR1 and autophagy-related gene MpATG8. Expression of a second ABC transporter gene MpSNQ2 was 14-fold induced after H(2)O(2) exposure in glucose as compared to glycerol-grown hyphae while MpYOR1 did not show strong variation of expression under similar conditions. Glucose-grown dikaryotic cells showed elevated expression of MpATG8, especially after exposure to H(2)O(2) and 4-nitroquinoline-1-oxide. During different stages preceding basidiocarp formation MpATG8 and the two catalase-encoding genes MpCTA1 and MpCTT1 were expressed continuously. We have compiled our results and literature data in a model graph, which compares the in vitro and in planta development and differentiation of M. perniciosa with the help of physiological and morphological landmarks.

Low productivity of ribonucleotide reductase in Saccharomyces cerevisiae increases sensitivity to stannous chloride.

Ribonucleotide reductase (RNR) of the yeast Saccharomyces cerevisiae is a tetrameric protein complex, consisting of two large and two small subunits. The small subunits Y2 and Y4 form a heterodimer and are encoded by yeast genes RNR2 and RNR4, respectively. Loss of Y4 in yeast mutant rnr4Delta can be compensated for by up-regulated expression of Y2, and the formation of a small subunit Y2Y2 homodimer that allows for a partially functional RNR. However, rnr4Delta mutants exhibit slower growth than wild-type (WT) cells and are sensitive to many mutagens, amongst them UVC and photo-activated mono- and bi-functional psoralens. Cells of the haploid rnr4Delta mutant also show a 3- to 4-fold higher sensitivity to the oxidative stress-inducing chemical stannous chloride than those of the isogenic WT. Both strains acquired increased resistance to SnCl2 with age of culture, i.e., 24-h cultures were more sensitive than cells grown for 2, 3, 4, and 5 days in liquid culture. However, the sensitivity factor of three to four (WT/mutant) did not change significantly. Cultures of the rnr4Delta mutant in stationary phase of growth always showed higher frequency of budding cells (budding index around 0.5) than those of the corresponding WT (budding index <0.1), pointing to a delay of mitosis/cytokinesis.

Topical prostaglandin analogues and development of epiretinal membrane. / Análogos de prostaglandinas y desarrollo de membrana epirretinal.

OBJECTIVES: To determine whether patients with glaucoma and epiretinal membrane (ERM) use a greater proportion of prostaglandin analogues (PA) than a control group of patients with glaucoma without ERM. METHOD: A retrospective study of cases and controls was conducted in order to determine whether patients with glaucoma and ERM used a greater proportion of PA than a control group of patients with glaucoma without ERM. The diagnosis of de ERM was made by clinical examination and optical coherence tomography. RESULTS: The mean age of the cases was 77 years (SD: 8.68; 95% CI: 74.3-79.4), compared to the controls with 63 years (SD: 16.6; 95% CI: 70.1-78.5). The cases included 50% (n=26) men and 50% women (n=26), whereas in the controls 25.4% (n=16) of the cases were men and 74.6% (n=47) women. PA treatment was used in 59.6% (n=31) and 60.3% (n=38) of the cases and controls, respectively. There was no statistically significant difference in PA use between the 2groups (P=.939). CONCLUSIONS: In this study, an association between the use of AP and the development of ERM could not be demonstrated.

Germline large genomic alterations on 7q in patients with multiple primary cancers.

Patients with multiple primary cancers (MPCs) are suspected to have a hereditary cancer syndrome. However, only a small proportion may be explained by mutations in high-penetrance genes. We investigate two unrelated MPC patients that met Hereditary Breast and Ovaria Cancer criteria, both presenting triple negative breast tumors and no mutations in BRCA1, BRCA2 and TP53 genes. Germline rearrangements on chromosome 7q, involving over 40 Mb of the same region, were found in both patients: one with mosaic loss (80% of cells) and the other with cnLOH (copy-neutral loss of heterozygosity) secondary to maternal allele duplication. Five children tested had no alterations on 7q. The patients shared 330 genes in common on 7q22.1-q34, including several tumor suppressor genes (TSGs) previously related to breast cancer risk and imprinted genes. The analysis of the triple negative BC from one patient revealed a mosaic gain of 7q translated for over-expressed cancer-related genes. The involvement of TSGs and imprinted genes, mapped on 7q, has the potential of being associated to MPC risk, as well as cancer progression. To our knowledge, this is the first description of patients with MPCs that harbor constitutive large alterations on 7q.

Splenectomy in a child with chronic Mycobacterium avium complex infection and splenic sequestration.

Mycobacterium avium complex infections (MAC) are being reported with increasing frequency in immunocompromised patients. When these infections become resistant to standard antibiotic therapy, treatment with interferon-gamma (IFN-gamma) can be helpful. Pain, fever, splenic enlargement, and cytopenias caused by splenic sequestration developed during IFN-gamma treatment in a 9-year-old boy and were successfully treated by splenectomy. The development of IFN-gamma-induced splenic sequestration and cytopenias in MAC-infected patients represents a new indication for splenectomy.

Statistical consequences of using bone mineral density to pair cadaver femurs in comparative ex vivo hip fracture studies.

OBJECTIVE: In ex vivo hip fracture studies femoral pairs are split to create two comparable test groups. When more than two groups are required, or if paired femurs cannot be obtained, group allocation according to bone mineral density (BMD) is sometimes performed. In this statistical experiment we explore how this affects experimental results and sample size considerations. METHODS: In a hip fracture experiment, nine pairs of human cadaver femurs were tested in a paired study design. The femurs were then re-matched according to BMD, creating two new test groups. Intra-pair variance and paired correlations in fixation stability were calculated. A hypothetical power analysis was then performed to explore the required sample size for the two types of group allocation. RESULTS: The standard deviation (sd) of the mean paired difference in fixation stability increased from 2 mm in donor pairs to 5 mm in BMD-matched pairs. Intra-pair correlation was 0.953 (Pearson's r) in donor pairs and non-significant at -0.134 (Pearson's r) in BMD-matched pairs. Required sample size to achieve a statistical power of 0.8 increased from ten pairs using donor pairs to 54 pairs using BMD-matched pairs. CONCLUSION: BMD cannot be used to create comparable test groups unless sample size is increased substantially and paired statistics are no longer valid. Cite this article: Bone Joint Res 2014;3:317-20.

Análogos de prostaglandinas y desarrollo de membrana epirretinal / Topical prostaglandin analogues and development of epiretinal membrane

OBJETIVOS: Evaluar la posible asociación entre el uso de análogos de prostaglandinas (AP) y el desarrollo de membrana epirretinal (MER) en pacientes con glaucoma. MÉTODO: Mediante el método comparativo se realizó un diseño retrospectivo de casos y controles. Se compararon pacientes que presentaban glaucoma y, a su vez, MER y que utilizaban una mayor proporción de AP con un grupo control de pacientes que presentaban glaucoma pero sin MER. El diagnóstico de MER ha sido realizado mediante un examen clínico y un estudio de tomografía de coherencia óptica. RESULTADOS: La edad media de los casos ha sido de 77 años, con DE de 8,68 (IC 95%: 74,3-79,4) y la de los controles de 63 años, con DE de 16,6 (IC 95%: 70,1-78,5). El 50% de los casos (n = 26) estaba compuesto por hombres y el otro 50% eran mujeres (n = 26), mientras que para los controles el 25,4% eran hombres (n = 16) y el 74,6% eran mujeres (n = 47). El 59,6% de los casos (n = 31) y el 60,3% de los controles (n = 38) fueron tratados con AP. No se ha observado ninguna diferencia de colocación de AP entre ambos grupos (p = 0,939). CONCLUSIONES: En este trabajo no hemos podido demostrar si existe asociación entre el uso de AP y el desarrollo de MER

OBJECTIVES: To determine whether patients with glaucoma and epiretinal membrane (ERM) use a greater proportion of prostaglandin analogues (PA) than a control group of patients with glaucoma without ERM. METHOD: A retrospective study of cases and controls was conducted in order to determine whether patients with glaucoma and ERM used a greater proportion of PA than a control group of patients with glaucoma without ERM. The diagnosis of de ERM was made by clinical examination and optical coherence tomography. RESULTS: The mean age of the cases was 77 years (SD: 8.68; 95% CI: 74.3-79.4), compared to the controls with 63 years (SD: 16.6; 95% CI: 70.1-78.5). The cases included 50% (n = 26) men and 50% women (n=26), whereas in the controls 25.4% (n = 16) of the cases were men and 74.6% (n = 47) women. PA treatment was used in 59.6% (n = 31) and 60.3% (n = 38) of the cases and controls, respectively. There was no statistically significant difference in PA use between the 2 groups (P = .939). CONCLUSIONS: In this study, an association between the use of AP and the development of ERM could not be demonstrated

Sensitivity to Sn2+ of the yeast Saccharomyces cerevisiae depends on general energy metabolism, metal transport, anti-oxidative defences, and DNA repair.

Resistance to stannous chloride (SnCl(2)) of the yeast Saccharomyces cerevisiae is a product of several metabolic pathways of this unicellular eukaryote. Sensitivity testing of different null mutants of yeast to SnCl(2) revealed that DNA repair contributes to resistance, mainly via recombinational (Rad52p) and error-prone (Rev3p) steps. Independently, the membrane transporter Atr1p/Snq1p (facilitated transport) contributed significantly to Sn(2+)-resistance whereas absence of ABC export permease Snq2p did not enhance sensitivity. Sensitivity of the superoxide dismutase mutants sod1 and sod2 revealed the importance of these anti-oxidative defence enzymes against Sn(2+)-imposed DNA damage while a catalase-deficient mutant (ctt1) showed wild type (WT) resistance. Lack of transcription factor Yap1, responsible for the oxidative stress response in yeast, led to 3-fold increase in Sn(2+)-sensitivity. While loss of mitochondrial DNA did not change the Sn(2+)-resistance phenotype in any yeast strain, cells with defect cytochrome c oxidase (CcO mutants) showed gradually enhanced sensitivities to Sn(2+) and different spontaneous mutation rates. Highest sensitivity to Sn(2+) was observed when yeast was in exponential growth phase under glucose repression. During diauxic shift (release from glucose repression) Sn(2+)-resistance increased several hundred-fold and fully respiring and resting cells were sensitive only at more than 1000-fold exposure dose, i.e. they survived better at 25 mM than exponentially growing cells at 25 microM Sn(2+). This phenomenon was observed not only in WT but also in already Sn(2+)-sensitive rad52 as well as in sod1, sod2 and CcO mutant strains. The impact of metabolic steps in contribution to Sn(2+)-resistance had the following ranking: Resting WT cells > membrane transporter Snq1p > superoxide dismutases > transcription factor Yap1p >or= DNA repair >> exponentially growing WT cells.

Growth in children with chronic renal failure on conservative treatment.

Statural growth and its relationship with degree of renal insufficiency were studied in 42 children and 5 infants with chronic renal failure (CRF). Most of the children had a congenital disease or were already ill in the neonatal period. Average GFR was 34 ml/min/1.73 m2 at the beginning and 16 ml at the end of the follow-up period, which averaged 4.3 years (1 to 12 years). Most patients grew at a normal rate; only 3 out of 42 children (7%) and 3 out of 5 infants lost one standard deviation or more during the follow-up period. No correlation was found between the degree of GFR and growth velocity. Catch-up growth was observed only for a 12-month period in 4 children with a bone age of 7 to 8 years. In 10 out of 11 children who reached puberty while under observation, a normal pubertal growth spurt was observed. Suitable and comprehensive controls and treatment can arrest growth retardation in the great majority of children with CRF after the first few years of life, regardless of their GFR. Achievement of a normal growth pattern in infants with CRF during the first year(s) of life remains a major unsolved problem.

[Dental caries in a group of Carnia children. Epidemiological study]. / Carie dentarie in un campione di bambini della Carnia. Studio epidemiologico.

The purpose of the research is to analyse the prevalence of dental caries of children living in Carnia divided into 2 groups, one of which was treated with fluoride tablets since the first months of life. In the considered area there is a reduction of dental caries even if the problem remains a major one. The prevention programme, based on collaboration with relatives from the first months of their babies, can be considered a valid operative support.

High frequency of empty sella syndrome in children with growth hormone deficiency.

Computer-assisted tomography (CT) with 2 mm axial sections and reconstructions was carried out in 31 children affected by GH deficiency (GHD): 18 with idiopathic complete isolated GHD, 3 with idiopathic partial isolated GHD, 2 with idiopathic panhypopituitarism, 4 with isolated acquired GHD and 4 with acquired panhypopituitarism. Density in the intrasellar area on CT corresponded to that of cerebrospinal fluid in 13/20 cases with idiopathic hypopituitarism and in 2/8 cases with acquired hypopituitarism. The overall incidence of primary empty sella syndrome (PESS) in the GH deficient patients studied was thus over 48%, while in children without endocrine dysfunction, it was only 5/213 (2.4%). It is concluded that PESS is more frequent in childhood than assumed until now and that it is frequently associated with GHD.

Home treatment of seizures as a strategy for the long-term management of febrile convulsions in children.

A cooperative study evaluating compliance and efficacy of Diazepam clisma in home treatment of febrile seizures in children was conducted from January 1979 to June 1981. Parents of 601 children admitted to hospital for a febrile convulsion were taught to use Diazepam clisma in the eventuality of a new seizure and asked to record the length of the episode. Complete follow-up was possible in 564 cases for an average time of 16.7 months. During the research period 109 convulsive episodes were registered in 76 children. Four of these children presented a seizure without fever. Diazepam clisma was administered correctly in 70 episodes (64.2%). In 26 of the remaining 39 cases, therapy was not administered because the seizure ended before the treatment was started. Prolonged seizures (greater than 15 min) have been reported in 8 cases. Six were in the non-treated group and 2 in the treated group. In both these last cases Diazepam was expelled immediately after being administered. The results of the study suggest that home treatment of febrile convulsions by Diazepam clisma represents a well accepted and useful strategy for prevention of prolonged seizures, provided that continuous contact and complete understanding between family and physician can be ensured.

Low productivity of ribonucleotide reductase in Saccharomyces cerevisiae increases sensitivity to stannous chloride

Ribonucleotide reductase (RNR) of the yeast Saccharomyces cerevisiae is a tetrameric protein complex, consisting of two large and two small subunits. The small subunits Y2 and Y4 form a heterodimer and are encoded by yeast genes RNR2 and RNR4, respectively. Loss of Y4 in yeast mutant rnr4delta can be compensated for by up-regulated expression of Y2, and the formation of a small subunit Y2Y2 homodimer that allows for a partially functional RNR. However, rnr4delta mutants exhibit slower growth than wild-type (WT) cells and are sensitive to many mutagens, amongst them UVC and photo-activated mono- and bi-functional psoralens. Cells of the haploid rnr4delta mutant also show a 3- to 4-fold higher sensitivity to the oxidative stress-inducing chemical stannous chloride than those of the isogenic WT. Both strains acquired increased resistance to SnCl2 with age of culture, i.e., 24-h cultures were more sensitive than cells grown for 2, 3, 4, and 5 days in liquid culture. However, the sensitivity factor of three to four (WT/mutant) did not change significantly. Cultures of the rnr4delta mutant in stationary phase of growth always showed higher frequency of budding cells (budding index around 0.5) than those of the corresponding WT (budding index <0.1), pointing to a delay of mitosis/cytokinesis.