Post-diagnosis serum 25-hydroxyvitamin D concentrations in women treated for breast cancer participating in a lifestyle trial in Italy.

OBJECTIVE: To report cross-sectionally serum levels of 25-hydroxyvitamin D [25(OH)D] in women living in Italy within 12 months from breast cancer (BC) diagnosis. METHODS: Baseline data were obtained from 394 women diagnosed with primary BC, enrolled from 2016 to 2019 in a lifestyle trial conducted in Italy. Subjects' characteristics were compared between two 25(OH)D concentrations (hypovitaminosis D<20 and ≥20 ng/mL) with the Chi-squared test or Fisher's exact test for small-expected counts. Using multiple logistic regression-adjusted models, we estimated odds ratios (ORs) of hypovitaminosis D with 95% confidence intervals (CIs) in the total sample and in the unsupplemented subgroup. RESULTS: Hypovitaminosis D was found in 39% of all subjects, 60% in unsupplemented subjects, and 10% in supplemented subjects. Increasing ORs of hypovitaminosis D were found with increasing body mass index, 25-30, >30, and ≥35 versus <25 kg/m2 (ORs: 2.50, 4.64, and 5.81, respectively, in the total cohort and ORs: 2.68, 5.38, and 7.08 in the unsupplemented); living in the most southern Italian region (OR 2.50, 95%CI 1.22-5.13); and with hypertriglyceridemia (OR 2.46; 95%CI 1.16-5.22), chemotherapy history (OR 1.86, 95%CI 1.03-3.38), and inversely with anti-estrogenic therapy (OR 0.43, 95%CI 0.24-0.75) in the total sample. CONCLUSIONS: Hypovitaminosis D in women recently diagnosed with BC and participating in a lifestyle trial in Italy was widespread and highest with obesity, hypertriglyceridemia, and chemotherapy use. Considering that hypovitaminosis D is a risk factor for lower efficacy of bone density treatments and possibly BC mortality, our results suggest the need to promptly address and treat vitamin D deficiency.

Understanding the risk of emerging bacterial resistance to over the counter antibiotics in topical sore throat medicines.

AIMS: The aims of this study were to explore the development of bacterial resistance and cross-resistance in four common human pathogens following realistic exposure to antibiotics found in over-the-counter (OTC) sore throat medicines: gramicidin, neomycin, bacitracin and tyrothricin. METHODS AND RESULTS: Bacterial exposure to in-use (concentration in the product before use) and diluted concentration (i.e. during use) of antibiotic where conducted in broth for 24 h or until growth was visible. The changes in bacterial susceptibility profile before and after exposure was determined using standardized ISO microdilution broth. Antibiotic testing was performed according to EUCAST guidelines. We demonstrated that test bacteria were able to survive exposure to the in-use concentrations of some antibiotics used in OTC medicines. Exposure to during use concentrations of bacitracin resulted in stable increase in minimal inhibitory concentration (MIC) (>8-fold) in Staphylococcus aureus and Acinetobacter baumannii. Exposure to tyrothricin resulted in a stable increase in MIC (2·4-fold) in Klebsiella pneumoniae, and exposure to neomycin resulted in a stable increase MIC (5000-fold higher than the baseline) in Streptococcus pyogenes. Clinical cross-resistance to other antibiotics (ciprofloxacin, fusidic acid, gentamicin, cefpodoxime, amoxicillin/clavulanic acid and cefotaxime) was also demonstrated following exposure to bacitracin or tyrothricin. Bacitracin exposure lead to a stable bacterial resistance after 10 passages. CONCLUSIONS: Our results indicate that OTC antibiotic medicines have the potential to drive resistance and cross-resistance in vitro. SIGNIFICANCE AND IMPACT OF THE STUDY: Tackling antibiotic resistance is a high worldwide priority. It is widely accepted that the overuse and misuse of antibiotics increase the risk of the development and spread of antibiotic resistance within communities. A number of OTC sore throat products, widely available across the world for topical use in respiratory indications, contain locally delivered antibiotics. Our findings showed that these antibiotics in OTC medicines present a risk for emerging cross-resistance in a number of bacterial respiratory pathogens.

Contrasting ecological impacts of geographically close invasive populations.

Intraspecific trait variability is now well recognized as a key component of biodiversity explaining how individuals within a species can differentially interact with their environment. To date, however, this concept has rarely been incorporated in the study of biological invasions, despite its provision of new insights into invasive species management. Here, we used an experimental approach to investigate how invasive red swamp crayfish (Procambarus clarkii) derived from geographically close ecosystems can differentially impact prey community structure and relevant ecosystem processes. We also compared the magnitude of the effects induced by invasive species introduction with those induced by intraspecific variability. Our results showed that effects of intraspecific variability can be strong for direct interactions such as resource (e.g., leaf litter, snails) consumption and of similar magnitude to the effects induced by the introduction of the invasive species when considering indirect interactions (e.g., primary production, ecosystem metabolism). Overall, these results highlighted that invasive populations of the same species are not ecologically equivalent, with each population acting differently on their recipient ecosystem.

Scale-dependent patterns of intraspecific trait variations in two globally invasive species.

Animal species often show substantial intraspecific trait variability (ITV), yet evidence for its flexibility across multiple ecological scales remains poorly explored. Gaining this knowledge is essential to better understand the different processes maintaining ITV in nature. Due to their broad geographic ranges, widespread invasive species are expected to display strong phenotypic variations across their distribution. Here, we quantified the scale-dependent patterns of morphological variability among invasive populations of two global freshwater invaders-red swamp crayfish Procambarus clarkii and pumpkinseed sunfish Lepomis gibbosus-both established in American and European lakes. We quantified patterns in body morphology across different ecological (Individual and Population) and spatial scales (Region). We then analyzed the scale-dependency of morphological variations among lake populations that span a diversity of abiotic and biotic conditions. Next, we used stable isotope analyses to test the existence of ecomorphological patterns linking morphology and trophic niche of individuals. We found that trait variations mainly accounted for at the regional and individual levels. We showed that populations of both species strongly differed between United States and Europe whereas habitat characteristics had a relatively minor influence on morphological variations. Stable isotope analyses also revealed that ecomorphological pattern for the trophic position of L. gibbosus was region-dependent, whereas no ecomorphological patterns were observed for P. clarkii. Overall, our study strongly supports the notion that the patterns of phenotypic variability among invasive populations are likely to modulate the ecological impacts of invasive species on recipient ecosystems.

Insights on early response to acute heat shock of bovine mammary epithelial cells through a multimethod approach.

Heat stress is a significant challenge in dairy cattle herds, affecting milk production and quality, and generating important changes at the cellular level. Most in vitro research on heat shock (HS) effects on dairy cow mammary cells was focused on medium-long-term effects. In recent years, Fourier transform-infrared (FT-IR) micro-spectroscopy has been increasingly used to study the effects of several external stresses on different cell lines, down to the level of single cellular components, such as DNA/RNA, lipids, and proteins. In this study, the possible changes at the biochemical and molecular level induced by acute (30 min-2 h) HS in bovine mammary epithelial (BME-UV1) cells were investigated. The cells were exposed to different temperatures, thermoneutral (TN, 37 °C) and HS (42 °C), and FT-IR spectra were acquired to analyse the effects of HS on biochemical characteristics of BME-UV1 cellular components (proteins, lipids, and DNA/RNA). Moreover, cell viability assay, reactive oxygen species production, and mRNA expression of heat shock proteins (HSPA1A, HSP90AA1, GRP78, GRP94) and antioxidant genes (SOD1, SOD2) by RT-qPCR were also analysed. The FT-IR results showed a change already at 30 min of HS exposure, in the content of long-chain fatty acids, which probably acted as a response to a modification of membrane fluidity in HS cells compared with TN cells. After 2 h of HS exposure, modification of DNA/RNA activity and accumulation of aggregated proteins was highlighted in HS cells. The gene expression analyses showed the overexpression of HSPA1A and HSP90AA1 starting from 30 min up to 2 h in HS cells compared with TN cells. At 2 h of HS exposure, also the overexpression of GRP94 was observed in HS cells. Acute HS did not affect cell viability, reactive oxygen species level, and SOD1 and SOD2 gene expression of BME-UV1 cells. According to the results obtained, cells initiate early defence mechanisms in case of acute HS and probably this efficient response capacity may be decisive for tolerance to heat stress of dairy cattle.

The moment before touchdown: landing manoeuvres of the honeybee Apis mellifera.

Although landing is a crucial part of insect flight, it has attracted relatively little study. Here, we investigate, for the first time, the final moments of a honeybee's (Apis mellifera) landing manoeuvre. Using high-speed video recordings, we analyse the behaviour of bees as they approach and land on surfaces of various orientations. The bees enter a stable hover phase, immediately prior to touchdown. We have quantified behaviour during this hover phase and examined whether it changes as the tilt of the landing surface is varied from horizontal (floor), through sloped (uphill) and vertical (wall), to inverted (ceiling). The bees hover at a remarkably constant distance from the surface, irrespective of its tilt. Body inclination increases progressively as the tilt of the surface is increased, and is accompanied by an elevation of the antennae. The tight correlation between the tilt of the surface, and the orientation of the body and the antennae, indicates that the bee's visual system is capable of inferring the tilt of the surface, and pointing the antennae toward it. Touchdown is initiated by extending the appendage closest to the surface, namely, the hind legs when landing on horizontal or sloping surfaces, and the front legs or antennae when landing on vertical surfaces. Touchdown on inverted surfaces is most likely triggered by a mechanosensory signal from the antennae. Evidently, bees use a landing strategy that is flexibly tailored to the varying topography of the terrain.

Does initial spacing influence crown and hydraulic architecture of Eucalyptus marginata?

Long-term declines in rainfall in south-western Australia have resulted in increased interest in the hydraulic characteristics of jarrah (Eucalyptus marginata Donn ex Smith) forest established in the region's drinking water catchments on rehabilitated bauxite mining sites. We hypothesized that in jarrah forest established on rehabilitated mine sites: (1) leaf area index (L) is independent of initial tree spacing; and (2) more densely planted trees have less leaf area for the same leaf mass, or the same sapwood area, and have denser sapwood. Initial stand densities ranged from about 600 to 9000 stems ha(-1), and trees were 18 years old at the time of sampling. Leaf area index was unaffected by initial stand density, except in the most sparsely stocked stands where L was 1.2 compared with 2.0-2.5 in stands at other spacings. The ratio of leaf area to sapwood area (A(l):A(s)) was unaffected by tree spacing or tree size and was 0.2 at 1.3 m height and 0.25 at the crown base. There were small increases in sapwood density and decreases in leaf specific area with increased spacing. Tree diameter or basal area was a better predictor of leaf area than sapwood area. At the stand scale, basal area was a good predictor of L (r(2) = 0.98, n = 15) except in the densest stands. We conclude that the hydraulic attributes of this forest type are largely independent of initial tree spacing, thus simplifying parameterization of stand and catchment water balance models.

The ROX3 gene encodes an essential nuclear protein involved in CYC7 gene expression in Saccharomyces cerevisiae.

The ROX3 gene was identified during a hunt for mutants with increased expression of the heme-regulated CYC7 gene, which encodes the minor species of cytochrome c in the yeast Saccharomyces cerevisiae. The rox3 mutants caused a 10-fold increase in CYC7 expression both in the presence and absence of heme, had slightly increased anaerobic expression of the heme-activated CYC1 gene, and caused decreases in the anaerobic expression of the heme-repressed ANB1 gene and the aerobic expression of its heme-induced homolog. The wild-type ROX3 gene was cloned, and the sequence indicated that it encodes a 220-amino-acid protein. This protein is essential; deletion of the coding sequence was lethal. The coding sequence for beta-galactosidase was fused to the 3' end of the ROX3 coding sequence, and the fusion product was found to be localized in the nucleus, strongly suggesting that the wild-type protein carries out a nuclear function. Mutations in the rox3 gene showed an interesting pattern of intragenic complementation. A deletion of the 5' coding region complemented a nonsense mutation at codon 128 but could not prevent the lethality of the null mutation. These results suggest that the amino-terminal domain is required for an essential function, while the carboxy-terminal domain can be supplied in trans to achieve the wild-type expression of CYC7. Finally, RNA blots demonstrated that the ROX3 mRNA was expressed at higher levels anaerobically but was not subject to heme repression. The nuclear localization and the lack of viability of null mutants suggest that the ROX3 protein is a general regulatory factor.

Acid-base transport in Henle's loop: the effects of reduced renal mass and diabetes.

The loop of Henle (LOH) is an important site of renal acidification. Using the in vivo microperfusion technique of LOH combined with quantitative polymerase chain reaction (PCR) performed on isolated thick ascending limbs (TAL), we demonstrated that the Na + -H + exchanger is the main transport mechanism involved, although a small, but significant contribution from the H+-ATPase also occurs. Among the various Na+-H+ exchanger isoforms we have evidenced that NHE3 is expressed and functionally active along the TAL. Since the LOH is exposed to osmotic stress, bicarbonate transport was also measured under medullary hypotonicity conditions, which led to the stimulation of bicarbonate reabsorption. We demonstrated that the LOH can participate in the tubular adaptation to an increased filtered bicarbonate load by increasing net LOH bicarbonate transport. In this setting, at the molecular level, mRNA and protein abundance of NHE3 were also stimulated, and coincided with an increase in NHE3 activity. Finally, NHE3 expression and abundance was highly stimulated in the early phase of diabetes, which is characterized by increased glomerular filtration rate (GFR).

[Glomerulo-tubular balance in diabetes mellitus: molecular evidence and clinical consequences]. / Bilancio glomerulo-tubulare nel diabete mellito: evidenze molecolari e conseguenze cliniche.

Diabetes mellitus is fast becoming a world epidemic. About one-third of individuals with diabetes, after 10 yrs, develop diabetic nephropathy, the first cause of end-stage kidney disease. The evolution of diabetic nephropathy can be considered in three stages: glomerular hyperfiltration, microalbuminuria (30-300 mg/24 hr) and proteinuria (>300 mg/24 hr). This study was designed to investigate the tubular basis of glomerular hyperfiltration in early diabetes mellitus. Diabetes was inducted in rats with i.p. streptozotocin (65 mg/kg bw) for 6 days. At the end of the treatment, the glomerular filtration rate (GFR), measured by inulin clearance, had substantially increased in diabetic rats compared with controls. Quantitative polymerase chain reaction (PCR) and Western blot analysis reveal that in diabetic rats compared with controls, mRNA and protein abundance was higher for type 3 sodium/hydrogen exchanger (NHE3) in proximal tubule and ascending limbs of Henle's loop, and higher for bumetanide-sensitive sodium-potassium-2 chloride cotransporter (NKCC2) in ascending limbs of Henle's loop. Western blot analysis confirmed the PCR results. Finally, the abundance of á -ENaC protein was unchanged in diabetic rats compared to controls. These results show that the primary sodium reabsorption increase in proximal tubule reduces salt concentrations at the macula densa. This elicits a tubuloglomerular feedback-dependent increase in single nephron GFR.

Smads are the central component in transforming growth factor-beta signaling.

Until recently, little was known about how transforming growth factor (TGF)-beta signals are transduced to the nucleus. With the discovery of the Smad proteins initially in Drosophila and C. elegans, the unraveling of the pathway has begun. Nine different vertebrate members also have been reported, indicating that Smads are a conserved component of the TGF-beta pathway. Currently, there are three functional classes of Smads. Class I Smads are phosphorylated by TGF-beta receptors and move to the nucleus. The Class II Smads function with Class I Smads, while Class III Smads antagonize the function of Class I Smads. New evidence shows that Smads bind specific DNA sequences and induce transcription of downstream target genes, thus placing the Smads at the center of the TGF-beta signaling pathway.

Rox3 and Rts1 function in the global stress response pathway in baker's yeast.

Yeast respond to a variety of stresses through a global stress response that is mediated by a number of signal transduction pathways and the cis-acting STRE DNA sequence. The CYC7 gene, encoding iso-2-cytochrome c, has been demonstrated to respond to heat shock, glucose starvation, approach-to-stationary phase, and, as we demonstrate here, to osmotic stress. This response was delayed in a the hog1-delta 1 strain implicating the Hog1 mitogen-activated protein kinase cascade, a known component of the global stress response. Deletion analysis of the CYC7 regulatory region suggested that three STRE elements were each capable of inducing the stress response. Mutations in the ROX3 gene prevented CYC7 RNA accumulation during heat shock and osmotic stress. ROX3 RNA levels were shown to be induced by stress through a novel regulatory element. A selection for high-copy suppressors of a ROX3 temperature-sensitive allele resulted in the isolation of RTS1, encoding a protein with homology to the B' regulatory subunit of protein phosphatase 2A0. Deletion of RTS1 caused temperature and osmotic sensitivity and increased accumulation of CYC7 RNA under all conditions. Over-expression of this gene caused increased CYC7 RNA accumulation in rox3 mutants but not in wild-type cells.

Nuclear phosphoinositide specific phospholipase C (PI-PLC)-beta 1: a central intermediary in nuclear lipid-dependent signal transduction.

Several studies have demonstrated the existence of an autonomous intranuclear phospho-inositide cycle that involves the activation of nuclear PI-PLC and the generation of diacylglycerol (DG) within the nucleus. Although several distinct isozymes of PI-PLC have been detected in the nucleus, the isoform that has been most consistently highlighted as being nuclear is PI-PLC-beta1. Nuclear PI-PLC-beta1 has been linked with either cell proliferation or differentiation. Remarkably, the activation mechanism of nuclear PI-PLC-beta1 has been shown to be different from its plasma membrane counterpart, being dependent on phosphorylation effected by p44/42 mitogen activated protein (MAP) kinase. In this review, we report the most up-dated findings about nuclear PI-PLC-beta1, such as the localization in nuclear speckles, the activity changes during the cell cycle phases, and the possible involvement in the progression of myelodisplastic syndrome to acute myeloid leukemia.

Effect of subtle neurological dysfunction on response to haloperidol treatment in schizophrenia.

OBJECTIVE: The primary purpose of this study was to assess whether an interaction between subtle neurological impairment and haloperidol plasma level affects treatment response and, if so, the impact on negative symptoms in particular. METHOD: Forty-three schizophrenic and two schizoaffective inpatients diagnosed according to Research Diagnostic Criteria were given, at the end of a 1-week placebo period, a baseline evaluation consisting of the Brief Psychiatric Rating Scale (BPRS), Scales for the Assessment of Positive and Negative Symptoms, Quantified Neurological Scale, and the Simpson-Angus Scale for extrapyramidal side effects. Subjects were randomly assigned to one of three haloperidol plasma ranges and treated for 6 weeks. At the end point the BPRS, Scales for the Assessment of Positive and Negative Symptoms, and Simpson-Angus Scale were readministered. Multiple linear regressions were used to assess the extent to which the interaction between neurological abnormality and haloperidol plasma level predicted the end-point symptoms once the baseline symptoms, neurological abnormality, and haloperidol plasma level were accounted for. RESULTS: Those patients with higher levels of overall abnormality on the Quantified Neurological Scale at baseline and with frontal dysfunction in particular, had, with increasing haloperidol plasma levels, more severe negative symptoms at end point. Neurological dysfunction was not related to end-point positive symptoms. The effect was specific to end-point negative symptoms and was independent of extrapyramidal side effects. CONCLUSIONS: If confirmed, these findings may indicate that relatively intact frontal function is needed for improvement in negative symptoms and that those patients with schizophrenia who have subtle neurological dysfunction should be treated with lower doses of neuroleptics.

N-terminal PDZ domain is required for NHERF dimerization.

NHERF, a 55 kDa PDZ-containing protein, binds receptors and ion transporters to mediate signal transduction at the plasma membrane. Recombinant NHERF demonstrated an apparent size of 150 kDa on gel filtration, which could be reduced to approximately 55 kDa by protein denaturing agents, consistent with the formation of NHERF dimers. Biosensor studies established the time- and concentration-dependent dimerization of NHERF. Overlays of recombinant NHERF fragments suggested that NHERF dimerization was principally mediated by the N-terminal PDZ-I domain. In PS120 cells, reversible protein phosphorylation modulated NHERF dimerization and suggested a role for NHERF dimers in hormonal signaling.

[New concepts of tubular calcium transport in the kidney: clinical implications]. / Nuove acquisizioni ed implicazioni cliniche del trasporto del calcio a livello del tubulo renale.

The kidney plays an important role in calcium homeostasis. In this review we discuss new concepts in tubular calcium transport, related proteins and the clinical implications of these new findings. Most calcium reabsorption occurs in the proximal tubules via the passive paracellular pathway, but calcium reabsorption also occurs in the thick ascending limb of Henle's loop (50% via the transcellular pathway). Finally, at the level of the distal convoluted tubule and connecting tubule calcium is reabsorbed via the active transcellular route. The Calcium-sensing receptor, localised along the thick ascending limb of Henle's loop, regulates the urinary calcium excretion in response to changes in extracellular calcium concentration. The Epithelial Calcium Channel 1 is a highly Ca2+-sensitive channel that is predominantly present in the connecting tubule. The Calbindin D(28k) is a cytoplasmatic protein expressed in the distal tubule, it is involved both in transcellular calcium diffusion and in the control of intracellular calcium concentration. Heterozygous mutations in the gene for the calcium sensing receptor, which result in a loss of function by the receptor, are associated with familial hypocalciuric hypercalcaemia. Mutations involving a gain of function have been associated with hypocalcaemia with normal serum parathyroid hormone concentration. Bartter's syndrome, caused by a dysfunction of thick ascending limb cells, is associated with calcium wasting. On the contrary, Gitelman's syndrome, caused by a dysfunction of the distal tubule, is characterised by hypocalciuria and hypomagnesemia.

A clinical study of vestibular neuronitis.

By means of clinical and neurotological findings in 38 patients with vestibular Neuronitis, an analysis of the clinical-pathological manifestations, that may be included into this denomination, has been carried out. The probable etiology of this disease and the results of the tests performed have also been analyzed. In the light of these results the vestibular compensatory mechanisms, studied with later periodic tests, are discussed, and the conclusions on the prognosis and treatment of this entity derived.

Treatment for facial neuronitis: a new approach to Bell's palsy.

The presence of sensitive symptoms, symptoms of parasympathetic ganglion's affection, as well as signs of affection of other cranial nerves accompanying to Bell's palsy, led us to consider and treat this disorder as a symptom of motor lesion of a possible primary neuron inflammation. Although we have not found valid statistical correlations between the lesion and location patterns, we have found, however, that continues electromyographic studies, and the early treatment carried out, may be of great interest to avoid sequels. The treatment was focussed to eliminate both the possible cause and the inflammatory process, as to improve neuron regeneration. From 60 patients selected to enter this study, 91,66 percent recovered the motor function.

[Adenoma pleomorphic (mixed tumor) in the nasal septum]. / Adenoma pleomorfo (tumor mixto) en el septum nasal.

A pleomorphic Adenoma was found in the right side of the nasal septum of a 44-year-old female patient. After removal the pathologist's examination could diagnose the mass as a pleomorphic adenoma (mixed tumor) developed from ectopic salivary glands. Early symptoms were nasal obstruction and recurrent spontaneous epistaxis, sometimes preceded by local discomfort. Surgical removal. In this article are discussed some aspects of the these unusual tumors (sitting in the nasal cavity) and the AA. compare their findings with data reported by other publishers.