Miracle-dz/UniFAR-FTUs huggingface dataset:
Proteinase expression during differentiation of human osteoclasts in vitro

Osteoclasts are macrophage‐derived polykaryons that degrade bone in an acidic extracellular space. This differentiation includes expression of proteinases and acid transport proteins, cell fusion, and bone attachment, but the sequence of events is unclear. We studied two proteins expressed at high levels only in the osteoclast, cathepsin K, a thiol proteinase, and tartrate‐resistant acid phosphatase (TRAP), and compared this expression with acid transport and bone degradation. Osteoclastic differentiation was studied using human apheresis macrophages cocultured with MG63 osteosarcoma cells, which produce cytokines including RANKL and CSF‐1 that mediate efficient osteoclast formation. Immunoreactive cathepsin K appeared at 3–5 days. Cathepsin K activity was seen on bone substrate but not within cells, and cathepsin K increased severalfold during further differentiation and multinucleation from 7 to 14 days. TRAP also appeared at 3–5 d, independently of cell fusion or bone attachment, and TRAP activity reached much higher levels in osteoclasts attached to bone fragments. Two proteinases that occur in the precursor macrophages, cathepsin B, a thiol proteinase related to cathepsin K, and an unrelated lysosomal aspartate proteinase, cathepsin D, were also studied to determine the specificity of the differentiation events. Cathepsin B occurred at all times, but increased two‐ to threefold in parallel with cathepsin K. Cathepsin D activity did not change with differentiation, and secreted activity was not significant. In situ acid transport measurements showed increased acid accumulation after 7 days either in cells on osteosarcoma matrix or attached to bone, but bone pit activity and maximal acid uptake required 10–14 days. We conclude that TRAP and thiol proteinase expression begin at essentially the same time, and precede cell fusion and bone attachment. However, major increases in acid secretion and proteinases expression continue during cell fusion and bone attachment from 7 to 14 days. J. Cell. Biochem. 78:627–637, 2000. © 2000 Wiley‐Liss, Inc.
The Effect of Adherence to Dietary Tracking on Weight Loss: Using HLM to Model Weight Loss over Time

The role of dietary tracking on weight loss remains unexplored despite being part of multiple diabetes and weight management programs. Hence, participants of the Diabetes Prevention and Management (DPM) program (12 months, 22 sessions) tracked their food intake for the duration of the study. A scatterplot of days tracked versus total weight loss revealed a nonlinear relationship. Hence, the number of possible tracking days was divided to create the 3 groups of participants: rare trackers (<33% total days tracked), inconsistent trackers (33–66% total days tracked), and consistent trackers (>66% total days tracked). After controlling for initial body mass index, hemoglobin A1c, and gender, only consistent trackers had significant weight loss (−9.99 pounds), following a linear relationship with consistent loss throughout the year. In addition, the weight loss trend for the rare and inconsistent trackers followed a nonlinear path, with the holidays slowing weight loss and the onset of summer increasing weight loss. These results show the importance of frequent dietary tracking for consistent long-term weight loss success.
Genetic Diversity of Norovirus among Children with Gastroenteritis in São Paulo State, Brazil

ABSTRACT Norovirus (NoV) is one of the most common causes of acute gastroenteritis in children and adults. To study the prevalence and genetic variability of NoV in children with acute gastroenteritis in São Paulo State, Brazil, we examined 234 stool samples from children with or without gastroenteritis during a 5-year period (1995 to 1999). NoV RNA was detected by reverse transcription-PCR and confirmed by DNA sequence analysis. We used two different oligonucleotide primer sets targeting the 3′ end of the RNA polymerase gene (region B), as well a partial capsid region at the 3′ end of the VP1 gene (region D). A total of 78 (33.3%) of the samples tested positive for NoV, and in region B, of the 66 strains sequenced, 4 (6.1%) belonged to GI, 52 (78.7%) belonged to GII, and five samples (7.6%) contained a mixture of the GI and GII genotypes. Phylogenetic analysis showed that the majority (40 of 66 [60.6%]) of the strains belonged to genotype GII.4. The nucleotide sequence identity of three strains was lower than 77.9% compared to a region B reference sequence database but showed 85.3 to 88.8% identity with GII.2 Melksham strain in region D, indicating the circulation of a possible recombinant NoV strain. One sample (GII.3) was sequenced only in region D. In conclusion, we have a total of 67 sequenced strains. This is the first report that describes the predominance of GII.4 NoV strains in children visiting the ambulatory of different hospitals in São Paulo State, Brazil, and we show that mixtures of different strains can be found in individual samples, including some possible new recombinant strains.
Effect of vibration on antagonist muscle coactivation during progressive fatigue in humans.

1. Biceps femoris antagonist coactivation increases during progressive fatigue. Our purpose was to determine if the mechanism that increases coactivation during fatigue is susceptible to vibration. Vibration drives alpha‐motoneurons via the Ia loop, producing force without descending motor drive, and thus uncoupling antagonist and agonist activation. Evidence that vibration increases coactivation disproportionately from its ‘common drive’ would suggest the possibility that some of the effects of fatigue are mediated through a segmental reflex loop. 2. Ten male subjects performed repeated maximal voluntary isometric contractions (MVCs) of the knee extensors of one leg. Paired submaximal test contractions (50% of MVC), without visual feedback, were performed when MVC reached 85, 70 and then 50% of its initial value. Vibration was applied to the patellar tendon during one test contraction in each pair. 3. Vibration reduced test contraction force below control values. However, coactivation increased at the same rate in both conditions. Biceps femoris coactivation was greater during vibration, but did not change during fatigue in either condition. 4. Our observations suggest that agonist‐antagonist muscle pairs are controlled as a single motor unit pool by a common central drive. Vibrating the agonist increases antagonist coactivity, but does not alter the rate at which coactivation increases during fatigue. This supports the idea that agonist coactivation is controlled by a central mechanism.
Effect of systemic clarithromycin and prednisolone on histamine-induced otitis media in guinea pigs

Abstract Conclusion: The results of the study showed that clarithromycin has anti-inflammatory and antioxidant effects and, when it is combined with prednisolone, those effects gain strength. Objectives: The present study aims to investigate the effects that the antioxidant and anti-inflammatory activities of clarithromycin and/or prednisolone have on experimental otitis media in effusion-induced guinea-pigs. Method and results: In this study, 35-male guinea pigs were randomly divided into five-groups. For the experimental otitis media, intra-tympanic histamine (0.1 ml) was injected into the guinea pigs in all of the groups except the control group. Then, 24-h after the intra-tympanic injections, clarithromycin (15 mg/kg/day) and/or prednisolone (1 mg/kg/day) were applied intraperitoneally to the guinea-pigs for 7-days. The biochemical analysis showed an increase in antioxidant capacity and a decrease in oxidant status and malondialdehyde (MDA) levels in the clarithromycin group and the prednisolone group and especially in the clarithromycin+prednisolone group, as compared to the experimental group (p < 0.05). In the cytokine analysis, lower levels of interleukin (IL)-6 and IL-17A and higher IL-10 were found in the clarithromycin, prednisolone, and clarithromycin+prednisolone groups than in the experimental group (p < 0.05). Furthermore, the histologic analyses showed histopathologic changes in the middle ear mucosa of the experimental group, but comparatively fewer-histopathologic changes were observed in the clarithromycin, prednisolone, and clarithromycin+prednisolone groups.
Frequency of Gastroenteritis and Gastroenteritis-Associated Mortality With Early Weaning in HIV-1-Uninfected Children Born to HIV-Infected Women in Malawi

Background:We assessed gastroenteritis (GE) burden in 2 randomized trials conducted in Malawi to reduce postnatal HIV transmission before and after World Health Organization recommendations regarding exclusive breastfeeding for HIV-exposed infants were adopted. The 2 trials were the nevirapine/AZT (NVAZ, 2000-2003 with prolonged breastfeeding) and the Postexposure Prophylaxis to the Infant (PEPI, 2004-2007 with breastfeeding cessation by 6 months). Methods:From NVAZ and PEPI trials data, GE frequency through age 12 months among HIV-negative exposed infants was evaluated. Overall and GE-related cumulative mortality rates were estimated using Kaplan-Meier curves. Results:The frequency of at least one GE-related hospitalization was greater in PEPI vs. NVAZ after age 6 months (respectively, 2.9% vs. 0.1%, at 7-9 months and 1.6% vs. 0.2% at 10-12 months, P < 0.001). Cumulative GE-related mortality was significantly higher in PEPI than in NVAZ after age 6 months; at ages 9 and 12 months GE-related mortality was 19 and 24 per 1000 infants in PEPI vs. 7 and 12 per 1000 infants in NVAZ (P = 0.0002). Conclusions:Early weaning was associated with increased risk of severe GE and GE-related mortality among HIV-exposed infants. Strategies are urgently needed which allow longer breastfeeding while reducing the risk of HIV breast milk transmission in resource-limited settings.
Pattern and flicker detection analysed by subthreshold summation.

1. We confirm Keesey's (1972) observation that, when a flickering line is viewed, there are distinct thresholds for detecting flicker (or movement) and for detecting a well localized line (pattern detection). Our measurements of the temporal sensitivity of these two mechanisms are similar to Keesey's. 2. The flicker and pattern detection mechanism have been analysed using subthreshold summation, i.e. by observing the effect of subthreshold flickering stimuli (lines and gratings) on the contrast threshold for a flickering test line. 3. The pattern detector shows linear spatial summation of contrast while the flicker detector is non‐linear in this respect. 4. The receptive field of the (most sensitive) flicker detector is about two to four times broader than that of the pattern detector. 5. The flicker detector has relatively weak surround inhibition and so, unlike the pattern detector, it is sensitive to a uniform flickering field. 6. The spatial arrangement of the pattern detector is the same at all temporal frequencies (including steady presentation); for flicker detection, the width of the receptive field increases with temporal frequency and the strength of lateral inhibition decreases at high frequencies. 7. Flicker detectors of various widths were demonstrated by using different test stimuli (for 12 Hz modulation); surround ingibition was relatively weak for the broadest detector. 8. There is a delay of surround inhibition of about 3 ms for both flicker and pattern detection. 9. By using a broad test stimulus modulated at a high frequency, a detector can be found with no significant surround inhibition. At threshold, this stimulus produces a sensation of flicker without the appearance of lateral motion observed for finer test lines at lower frequencies. 10. The characteristics of pattern and flicker (movement) detection are compared to electrophysiological studies on X (sustained) and Y (transient) neurones respectively, and correlations are described for studies of temporal frequency response, non‐linearity, width of receptive field, strength of the inhibitory surround and motion sensitivity.
Is omitting the 3rd hour measurement in the 100 g oral glucose tolerance test feasible?

Abstract Background: To evaluate the diagnostic value of the 3rd hour plasma glucose level in the 100 g oral glucose tolerance test (OGTT). Methods: Records of all pregnant patients with abnormal 50 g glucose challenge test (GCT) between January 2005 and December 2013 were reviewed (n=1963). The 100 g OGTT results were analyzed separately for both Carpenter & Couston (CC) and National Diabetes Data Group (NDDG) criteria. Results: The number of patients diagnosed with gestational diabetes mellitus (GDM) was 297 (15.1%) according to CC criteria and 166 (8.4%) according to NDDG criteria. The 1st hour plasma glucose level showed the highest correlation with GDM diagnosis (ρ=0.595 for CC and ρ=0.567 for NDDG). However, the 3rd hour plasma glucose level showed the weakest correlation with GDM diagnosis (ρ=0.216 for CC and ρ=0.213 for NDDG). The 3rd hour value of 100 g OGTT was one of the two elevated measurements in 10.8% of patients when CC criteria are used and in 13.8% of patients when NDDG criteria are used. Conclusion: Omitting 3rd hour plasma glucose measurement in 100 g OGTT results in unacceptable rates of underdiagnosed patients.
Protection from experimental autoimmune diabetes in the non‐obese diabetic mouse with soluble interleukin‐1 receptor

We have evaluated the effects of a treatment with soluble interleukin‐1 receptor (sIL‐1R) in the accelerated model of autoimmune diabetes induced by cyclophosphamide (CY) in the non‐obese diabetic (NOD) mouse. Prior to the CY challenge (350 mg/kg body weight), female euglycemic NOD mice were randomly divided into three groups (A–C). Groups B and C were treated daily from 1 day before to 13 days after the CY challenge with sIL‐1R at doses of 0.2 and 2 mg/kg body weight. Group A was treated with PBS. By 2 weeks after CY administration, an acute form of autoimmune diabetes with glycosuria, hyperglycemia and severe insulitis occurred in the majority (13/20, 65%) of the control mice (group A). In contrast, repeated injections with sIL‐1R protected NOD mice from insulin‐dependent diabetes mellitus (IDDM) development in a dose‐dependent fashion; the incidence of IDDM was 53.3% (8/15) in the mice treated with 0.2 mg/kg and only 6.7% (1/15) in those treated with 2 mg/kg. However, none of the doses of the sIL‐1R reduced the extent of insulitis in NOD mice. Importantly, the anti‐diabetogenic property of sIL‐1R may not involve major T cell function impairment; accordingly, in parallel experiments, splenic lymphoid cells from NOD mice not challenged with CY, but treated with 2 mg/kg sIL‐1R for 5 consecutive days showed a normal distribution of mononuclear cell subsets and maintained their capacity to secrete interferon‐γ and IL‐2 and to proliferate in response to polyclonal mitogenic stimulation with concanavalin A.
Medical co-morbidities, secondary complications, and mortality in elderly with acute spinal cord injury.

Despite an increasing incidence of spinal cord injury (SCI) in the elderly and evidence that age appears to influence outcome after neurotrauma, surprisingly little is known regarding clinical outcomes and secondary complications in elderly with an acute SCI. This study was undertaken to evaluate the effect of age on clinical outcomes after acute traumatic SCI managed in an acute care unit by a multidisciplinary team. A retrospective chart review of all patients with acute SCI admitted to an acute care unit at a university hospital between 1998 and 2000 was performed. Data on clinical outcomes and secondary complications in younger individuals (group 1: age < 60 years) were compared to elderly subjects (group 2: age > or = 60 years). There were 28 elderly (age 60-89 years) and 30 younger (age 17-56 years) individuals. The severity and level of SCI were similar in both groups (p = 0.11; p = 0.93). Co-morbidities were more frequent in the elderly (p < 0.01). There was a trend, which did not achieve significance, for an increased incidence of secondary complications in the elderly (57.1% versus 33.3%; p = 0.11). The most common secondary complications in both groups were infections, psychiatric disorders, pressure sores, and cardiovascular complications. Mortality rates in elderly and younger individuals with acute SCI (p = 0.41) were not significantly different. Our data suggest that rigorous attention to principles of acute SCI care can minimize previously reported higher susceptibility for secondary complications in the elderly. A multidisciplinary team approach to the management of the elderly with acute SCI is essential to minimize or prevent secondary complications.
Traumatic Brain Injury Patients With a Glasgow Coma Scale Score of ⩽8, Cerebral Edema, and/or a Basal Skull Fracture are More Susceptible to Developing Hyponatremia

Background: Traumatic brain injury (TBI) is a common injury treated at the neurosurgery department. The incidence rate is approximately 3% in the general population and the mortality rate is 25%. The incidence of hyponatremia following TBI is 33%. Hyponatremia is one of the main causes of disability and/or death in TBI patients. This study investigated the epidemiology of hyponatremia following TBI. Methods: Patients who were admitted to our hospital with moderate or severe TBI were analyzed retrospectively. The relationship between the occurrence of hyponatremia and age, sex, type of injury, Glasgow coma scale (GCS) score, whether the patient underwent surgery, and the presence of cerebral edema and basal skull fracture was analyzed statistically using a &khgr;2 test and multivariate logistic regression analysis. Results: Out of the 136 patients recruited for the study (81 males and 55 females; mean±SD age of 48±13 y), 56 suffered from hyponatremia (ie, serum sodium level <135 mmol/L). Univariate analysis indicated that hyponatremia following TBI was not related to age (P>0.05), sex (P=0.347), or surgical history (P=0.492) but that it was related to the type of injury (P=0.031), a GCS score ⩽8 (P<0.001), the presence of cerebral edema (P<0.001), and/or a basal skull fracture (P<0.001). Multivariate logistic regression analysis confirmed a strong association between the occurrence of hyponatremia and a GCS score ⩽8 (P<0.016), the presence of cerebral edema (P<0.001), and a basal skull fracture (P<0.001). Conclusions: TBI patients with a GCS score ⩽8, cerebral edema, and/or a basal skull fracture are particularly prone to developing hyponatremia. These patients require additional treatment that should entail the normalization of serum sodium levels to prevent deterioration of their condition.
Women's health concerns. Is the promotion of hormone replacement therapy for prevention important to women?

The objectives of this study were to find out women's health concerns for the community and for themselves as they age and whether the promotion of hormone replacement therapy for prevention is important to them. A postal questionnaire was sent to 1649 women aged 20-69 years. The sample was random but stratified for age and taken from the lists of eight general practices in the town of Stockton-on-Tees in north east England. The questionnaire included questions on priorities for health care, fears for personal health with ageing, knowledge about osteoporosis, cardiovascular disease and hormone replacement therapy. A 74.3% response rate was achieved. Cancer was named as deserving highest priority for health care in Britain today by 40.7% of respondents. The promotion of long term hormone replacement therapy was given a relatively low priority. The health problem women named as the one they most fear will affect them as they age was, for 30.2% of women, cancer; for 18.8% of women, dementia; for 11.6% of women, arthritis; for 8.8% of women, heart disease. The role of oestrogen in preventing osteoporosis was known by 74.9% of respondents and its role in prevention of cardiovascular disease by 6.6%. Lack of exercise as a risk factor for osteoporosis was known by 29.0% and as a risk factor for cardiovascular disease by 84.6%. Arthritis-like pain was thought to be a warning sign of osteoporosis by by 55.8% of respondents. The promotion of hormone replacement therapy for prevention does not appear to be a high priority for women. (ABSTRACT TRUNCATED AT 250 WORDS)
Disparate Pathways for the Biogenesis of Cytochrome Oxidases in Bradyrhizobium japonicum*

This work addresses the biogenesis of heme-copper terminal oxidases in Bradyrhizobium japonicum, the nitrogen-fixing root nodule symbiont of soybean. B. japonicum has four quinol oxidases and four cytochrome oxidases. The latter include the aa3- and cbb3-type oxidases. Although both have a CuB center in subunit I, the subunit II proteins differ in having either a CuA center (in aa3) or a covalently bound heme c (in cbb3). Two biogenesis factors were genetically studied here, the periplasmically exposed CoxG and ScoI proteins, which are the respective homologs of the mitochondrial copper-trafficking chaperones Cox11 and Sco1 for the formation of the CuB center in subunit I and the CuA center in subunit II of cytochrome aa3. We could demonstrate copper binding to ScoI in vitro, a process for which the thiols of cysteine residues 74 and 78 in the ScoI polypeptide were shown to be essential. Knock-out mutations in the B. japonicum coxG and scoI genes led to loss of cytochrome aa3 assembly and activity in the cytoplasmic membrane, whereas the cbb3-type cytochrome oxidase apparently remained unaffected. This suggests that subunit I of the cbb3-type oxidase obtains its copper cofactor via a different pathway than cytochrome aa3. In contrast to the coxG mutation, the scoI mutation caused a decreased symbiotic nitrogen fixation activity. We hypothesize that a periplasmic B. japonicum protein other than any of the identified CuA proteins depends on ScoI and is required for an effective symbiosis.
Probucol in the Treatment of Nonalcoholic Steatohepatitis: An Open-Labeled Study

Goals To evaluate the effects of probucol, an agent with strong antioxidant properties, in reversing biochemical changes in nonalcoholic steatohepatitis (NASH). Background There is currently no well-established medical treatment of NASH. It is believed that oxidative stress plays a major role in hepatic damage in these patients. Study Cases of biopsy-proven NASH referring to a referral center in Tehran during a 12-month period were included in the study. Viral, autoimmune and other hepatic diseases were excluded. Alcohol ingestion was excluded by repeated questioning of the patient and at least two family members. Patients were given 500mg of probucol daily for 6 months. Serum levels of liver enzymes, the serum lipid profile, and weight was recorded monthly. Results A total of 17 patients completed the study. The mean age was 37.2 years, 13 patients were male and 4 female. The mean pretreatment value of ALT and AST was 93.5 and 80.4 U/L, and the mean posttreatment value was 41.8 and 35.9 U/L respectively (P = 0.001 and 0.006). Conclusion Probucol, even in the low dose of 500 mg/d, appears to be significantly effective in decreasing the ALT and AST levels in patients with NASH.