Miracle-dz/UniFAR-FTUs huggingface dataset:
Familial acampomelic form of campomelic dysplasia caused by a 960 kb deletion upstream of SOX9

Campomelic dysplasia (CD) is a rare autosomal dominant osteochondrodysplasia with or without XY disorders of sexual development (DSD). Campomelia is absent in about 10% of the cases, referred to as the acampomelic form of CD (ACD). Most CDs are caused by mutations within the SOX9 coding region. Several CD patients with balanced chromosome rearrangements involving the 17q24 region have been reported suggesting the presence of cis‐regulatory elements upstream and/or downstream of the gene. Deletions upstream of SOX9 represent a third mechanism of mutation. To date, a 1.5 Mb de novo deletion in the SOX9 upstream region has been identified in a single 46,XY patient with ACD and DSD. We report here for the first time on a familial ACD caused by an inherited deletion mapping upstream of the SOX9 gene. Using high‐density oligoarray comparative genomic hybridization (CGH), we showed that the size of the deletion was 960 kb in the XY‐DSD child and her mother, both affected. The deletion lying from 517 kb to 1.477 Mb upstream of SOX9 remove several highly conserved elements and reduce the minimum critical size and therefore the number of highly conserved sequence elements responsible for ACD. © 2009 Wiley‐Liss, Inc.
[The preparation of nano-hydroxyapatite and preliminary observation on its effects on the occlusion of dentinal tubule].

OBJECTIVE To synthesize nano-hydroxyapatite (nano-HA) and evaluate its effect on the occlusion of dentinal tubules in vitro, and therefore provide evidence for the clinical application. METHODS (NH(4))(2)HPO(4) and Ca(NO3)2 were used to form nano-HA, which was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectrometer (FTIR) and X-ray diffractometer (XRD) respectively. Twenty-four dentin slabs were obtained from 8 healthy third molars and randomly divided into 3 groups, which were control group, casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) group, and nano-HA group. After the CPP-ACP and nano-HA were topically applied to the slabs of two study groups twice a day for 7 days, the surface of slab dentin was observed using SEM. RESULTS SEM, TEM, FTIR, and XRD tests showed that nano-HA was synthesized successfully. SEM observations revealed that the sealing of dentinal tubules of nano-HA group was extremely high when compared with those of control and CPP-ACP group. CONCLUSIONS In comparison with CPP-ACP, nano-HA could occlude dentinal tubules more effectively in vitro.
Nightmare in Red: The McCarthy Era in Perspective

This is a well-researched, and frequently entertaining, account of the rise and fall of the House Committee on Un-American activities. Fried describes the growth of the kind of paranoid and xenophobic anti-communism which characterized the HUAC and traces its origins from the New Deal to the post-war periods. Along the way we meet important actors in the Red-baiting drama, including Presidents Roosevelt, Truman, Eisenhower, the young Richard Nixon, Alger Hiss, the Rosenbergs, the Hollywood Ten, and, of course, Wisconsin Senator Joseph McCarthy. Fried, however, also documents the more sweeping and less public effects of McCarthyism on thousands of people, from teachers and lawyers to washroom attendants forced to take loyalty tests. As Fried shows, these 'insignificant' stories are perhaps the strongest testament to the social and political climate which terrorized many ordinary citizens during the McCarthy years.
Antibiotics for asymptomatic bacteriuria.

BACKGROUND Asymptomatic bacteriuria is commonly detected in women aged up to 60 years, patients with diabetes, and the elderly. The benefit of antibiotic treatment for this condition is controversial. OBJECTIVES To assess the effectiveness and safety of antibiotics treatment for asymptomatic bacteriuria in adults. Specific objectives were to assess 1) the effectiveness of antibiotics for preventing development of symptomatic UTI, UTI-related complications, overall mortality, UTI-related mortality, and resolution of bacteriuria; 2) the development of resistance to antibiotic treatment by comparing resistance of grown bacteria in urine before and after therapy; and 3) the frequency of adverse events. SEARCH METHODS We searched the Cochrane Renal Group's Specialised Register up to 24 February 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review. SELECTION CRITERIA Randomised controlled trials (RCTs) and quasi-RCTs comparing antibiotics to placebo or no treatment for asymptomatic bacteriuria in adults were included. The outcomes of interest were the development of symptomatic urinary tract infection (UTI), complications, death, any adverse event, development of antibiotic resistance, bacteriological cure, and decline in kidney function. DATA COLLECTION AND ANALYSIS Two authors independently extracted the data and assessed study quality. Statistical analyses were performed using the random effects model and the results expressed as risk ratios (RR) with 95% confidence intervals (CI). MAIN RESULTS We included nine studies (1614 participants) in this review. Symptomatic UTI (RR 1.11, 95% CI 0.51 to 2.43), complications (RR 0.78, 95% CI 0. 35 to 1.74), and death (RR 0.99, 95% CI 0.70 to 1.41) were similar between the antibiotic and placebo or no treatment arms. Antibiotics were more effective for bacteriological cure (RR 2.32, 95% CI 1.11 to 4.83) but also more adverse events developed in this group (RR 3.77, 95% CI 1.40 to 10.15). No decline in the kidney function was observed across the studies; minimal data were available on the emergence of resistant strains after antimicrobial treatment.The included studies were of medium and high quality, used different treatments for different durations of treatment and follow-up, different populations, but this did not appear to influence the results of review. AUTHORS' CONCLUSIONS No differences were observed between antibiotics versus no treatment of asymptomatic bacteriuria for the development of symptomatic UTI, complications or death. Antibiotics were superior to no treatment for the bacteriological cure but with significantly more adverse events. There was no clinical benefit from treating asymptomatic bacteriuria in the studies included in this review.
The role of anterior cingulate cortex and precuneus in the coordination of motor behaviour

Behavioral studies in humans have shown that bimanual coordination imposes specific demands on the central nervous system that exceed unimanual task control. In the present study we used functional magnetic resonance imaging to investigate the neural correlate of this additional coordination effort, i.e. regions responding more strongly to bimanual movements than inferred from summing up the responses to the unimanual subtasks. Subjects were scanned while performing movements along different directions, either uni‐ or bimanually. During the bimanual condition, trajectories of movement of the left and right hand were spatially incompatible, such that additional effort was required to break away from intrinsically favored mirror‐movements and to integrate movements of both limbs into a new spatial pattern. Our main finding was that the execution of spatially complex bimanual coordination as compared with the unimanual subtasks activated the anterior cingulate cortex (posterior part) as well as the dorso‐anterior precuneus. We hypothesize that the anterior cingulate exerts its modulatory effect on other motor areas, such as the primary motor cortex and the supplementary motor area, in order to suppress intrinsically favored coordination tendencies. Conversely, the precuneus is likely to be involved in shifting attention between different locations in space, which was necessary for monitoring the trajectories of the left and right wrist when both limbs moved in parallel. Our findings suggest that the coordination effort during bimanual and perhaps other modes of coordinated behavior is mediated by regions contributing to higher order functions, which form an interface between cognition and action.
Differential clinical characteristics of acute liver failure caused by hemophagocytic lymphohistiocytosis in children

Children with acute liver failure (ALF) caused by hemophagocytic lymphohistiocytosis (HLH) may be at risk of undergoing unnecessary liver transplantation (LT). The aim of this study was to compare the characteristics of ALF caused by HLH with those of ALF of unknown etiology in children.
Measurement of maternal perceptions of support and control in birth (SCIB).

BACKGROUND High control and support during labor are associated with improved birth outcomes and increased maternal satisfaction with the birth experience, but measures of control and support are varied and often unidimensional. This paper reports the development and validation of a questionnaire measure of support and control in birth for use in research on birth experience and outcomes. METHODS Study 1 interviewed women after birth (n = 10) to identify important dimensions of control and support. In study 2 (n = 402), the Support and Control in Birth (SCIB) questionnaire was developed, with three dimensions of internal control, external control, and support, which was completed by women who had given birth. RESULTS Principal components analysis identified a 33-item, three-component solution, which accounted for 55% of the variance and had good reliability (Cronbach's alpha 0.86-0.93). CONCLUSIONS Overall, these studies suggest the SCIB provides a reliable and comprehensive measure of support and control in birth.
Collagen sandwich culture affects intracellular polyamine levels of human hepatocytes

Abstract. Extracellular matrices, like collagen layers, play an important role in preventing dedifferentiation of hepatocytes in long‐term culture experiments. It has also been shown that polyamines are crucial for cell growth and liver differentiation – regeneration. Primary cultured hepatocytes with their low mitotic activity might be a valuable tool in studying the role of polyamines in differentiation. Here, our goal was to investigate whether an extracellular cell culture matrix can influence intracellular polyamine levels in human hepatocytes during long‐term culture. Primary human hepatocytes were isolated from surgical tissue resections and were maintained either in single collagen (SG) or double collagen gel (DG) layer (sandwich) culture systems. Cell viability and function were examined and intracellular polyamine levels were measured using a highly sensitive high performance liquid chromatography (HPLC) method. Hepatocytes showed high viability in both culture systems used, but albumin secretion was diminished in SG cultured hepatocytes after 14 days. In general, total intracellular polyamine levels of hepatocytes decreased markedly in both SG and DG within the first days of culture, but remained constant until day 21 with a SG/DG ratio of about 1.4. Individual polyamines levels were dependent on the culture time and system, where spermine decreased and putrescine increased in both SG and DG over time (day 14), but spermidine increased only in DG. Our results suggest that polyamine levels, in particular putrescine, might be important regulators of hepatocyte specific function in vitro and therefore serve as a marker of differentiation for cultivated human hepatocytes.
Relaxation in rabbit and rat cardiac cells: species‐dependent differences in cellular mechanisms.

The roles of the sarcoplasmic reticulum (SR) Ca(2+)‐ATPase and Na(+)‐Ca2+ exchange in Ca2+ removal from cytosol were compared in isolated rabbit and rat ventricular myocytes during caffeine contractures and electrically stimulated twitches. Cell shortening and intracellular calcium concentration ([Ca2+]i) were measured in indo‐1‐loaded cells. Na(+)‐Ca2+ exchange was inhibited by replacement of external Na+ by Li+. To avoid net changes in cell or SR Ca2+ load during a twitch in 0 Na+ solution, intracellular Na+ (Na+i) was depleted using a long pre‐perfusion with 0 Na+, 0 Ca2+ solution. SR Ca2+ accumulation was inhibited by caffeine or thapsigargin (TG). Relaxation of steady‐state twitches was 2‐fold faster in rat than in rabbit (before and after Na+i depletion). In contrast, caffeine contractures (where SR Ca2+ accumulation is inhibited), relaxed faster in rabbit cells. Removal of external Na+ increased the half‐time for relaxation of caffeine contractures 15‐ and 5‐fold in rabbit and rat myocytes respectively (and increased contracture amplitude in rabbit cells only). The time course of relaxation in 0 Na+, 0 Ca2+ solution was similar in the two species. Inhibition of the Na(+)‐Ca2+ exchange during a twitch increased the [Ca2+]i transient amplitude (delta[Ca2+]i) by 50% and the time constant of [Ca2+]i decline (tau) by 45% in rabbit myocytes. A smaller increase in tau (20%) and no change in delta[Ca2+]i were observed in rat cells in 0 Na+ solution. [Ca2+]i transients remained more rapid in rat cells. Inhibition of the SR Ca(2+)‐ATPase during a twitch enhanced delta[Ca2+]i by 25% in both species. The increase in tau after TG exposure was greater in rat (9‐fold) than in rabbit myocytes (2‐fold), which caused [Ca2+]i decline to be 70% slower in rat compared with rabbit cells. The time course of [Ca2+]i decline during twitch in TG‐treated cells was similar to that during caffeine application in control cells. Combined inhibition of these Ca2+ transport systems markedly slowed the time course of [Ca2+]i decline, so that tau was virtually the same in both species and comparable to that during caffeine application in 0 Na+, 0 Ca2+ solution. Thus, the combined participation of slow Ca2+ transport mechanisms (mitochondrial Ca2+ uptake and sarcolemmal Ca(2+)‐ATPase) is similar in these species. We conclude that during the decline of the [Ca2+]i transient, the Na(+)‐Ca2+ exchange is about 2‐ to 3‐fold faster in rabbit than in rat, whereas the SR Ca(2+)‐ATPase is 2‐ to 3‐fold faster in the rat. (ABSTRACT TRUNCATED AT 400 WORDS)
Directly measured second hand smoke exposure and asthma health outcomes

Background: Because they have chronic airway inflammation, adults with asthma could have symptomatic exacerbation after exposure to second hand smoke (SHS). Surprisingly, data on the effects of SHS exposure in adults with asthma are quite limited. Most previous epidemiological studies used self-reported SHS exposure which could be biased by inaccurate reporting. In a prospective cohort study of adult non-smokers recently admitted to hospital for asthma, the impact of SHS exposure on asthma health outcomes was examined. Methods: Recent SHS exposure during the previous 7 days was directly measured using a personal nicotine badge (n = 189) and exposure during the previous 3 months was estimated using hair nicotine and cotinine levels (n = 138). Asthma severity and health status were ascertained during telephone interviews, and subsequent admission to hospital for asthma was determined from computerised utilisation databases. Results: Most of the adults with asthma were exposed to SHS, with estimates ranging from 60% to 83% depending on the time frame and methodology. The highest level of recent SHS exposure, as measured by the personal nicotine badge, was related to greater asthma severity (mean score increment for highest tertile of nicotine level 1.56 points; 95% CI 0.18 to 2.95), controlling for sociodemographic covariates and previous smoking history. Moreover, the second and third tertiles of hair nicotine exposure during the previous month were associated with a greater baseline prospective risk of hospital admission for asthma (HR 3.73; 95% CI 1.04 to 13.30 and HR 3.61; 95% CI 1.0 to 12.9, respectively). Conclusions: Directly measured SHS exposure appears to be associated with poorer asthma outcomes. In public health terms, these results support efforts to prohibit smoking in public places.
The Difference in Nutrient Intakes between Chinese and Mediterranean, Japanese and American Diets

Across countries, the predominant diets are clearly different and highly related with human health. Therefore, it is necessary to evaluate dietary nutrients between them. This study aimed to evaluate dietary nutrients in China and compare those between Chinese and Mediterranean (Italian), Japanese and American diets. Dietary intakes of 2659 subjects in south-east China, Zhejiang province, from 2010 to 2012, were estimated by three consecutive 24-h dietary recalls. The contribution of carbohydrate to total energy in Chinese subjects was lower than that in Japanese and American subjects, but higher than that in Italian subjects. However, the energy contribution from fat in Chinese subjects was higher than that in Japanese and American subjects, and similar to that in Italian subjects. Moreover, the Chinese diet had lower daily intakes of fiber, calcium, phosphorus, potassium, selenium, vitamin A, vitamin B1, vitamin B2 and vitamin C, compared with the Japanese, American and Italian diets. Nevertheless, intakes of sodium, iron, copper and vitamin E were higher among Chinese people relative to the people of other three countries. The present study demonstrated that the structure of the Chinese diet has been shifting away from the traditional diet toward high-fat, low-carbohydrate and low-fiber diets, and nutrients intakes in Chinese people have been changing even worse than those in American people.
Iron-chelation therapy with oral deferiprone in patients with thalassemia major.

BACKGROUND To determine whether the orally active iron chelator deferiprone (1,2-dimethyl-3-hydroxy-pyridin-4-one) is efficacious in the treatment of iron overload in patients with thalassemia major, we conducted a prospective trial of deferiprone in 21 patients unable or unwilling to use standard chelation therapy with parenteral deferoxamine. METHODS Hepatic iron stores were determined yearly by chemical analysis of liver-biopsy specimens or magnetic-susceptibility measurements. Detailed clinical and laboratory studies were used to monitor safety and compliance. RESULTS The patients received deferiprone therapy for a mean (+/-SE) of 3.1 +/- 0.3 years. Ten patients in whom previous chelation therapy with deferoxamine had been ineffective had initial hepatic iron concentrations of at least 80 mumol per gram of liver, wet weight -- values associated with complications of iron overload. Hepatic iron concentrations decreased in all 10 patients, from 125.3 +/- 11.5 to 60.3 +/- 9.6 mumol per gram (P < 0.005), with values that were less than 80 mumol per gram in 8 of the 10 patients (P < 0.005). In all 11 patients in whom deferoxamine therapy had previously been effective, deferiprone maintained hepatic iron concentrations below 80 mumol of iron per gram. CONCLUSIONS Oral deferiprone induces sustained decreases in body iron to concentrations compatible with the avoidance of complications from iron overload. The risk of agranulocytosis associated with deferiprone may restrict its administration to patients who are unable or unwilling to use deferoxamine.
Ferritin Mutants of Escherichia coli Are Iron Deficient and Growth Impaired, and fur Mutants are Iron Deficient

ABSTRACT Escherichia coli contains at least two iron storage proteins, a ferritin (FtnA) and a bacterioferritin (Bfr). To investigate their specific functions, the corresponding genes (ftnA and bfr) were inactivated by replacing the chromosomal ftnA and bfr genes with disrupted derivatives containing antibiotic resistance cassettes in place of internal segments of the corresponding coding regions. Single mutants (ftnA::spc andbfr::kan) and a double mutant (ftnA::spc bfr::kan) were generated and confirmed by Western and Southern blot analyses. The iron contents of the parental strain (W3110) and the bfr mutant increased by 1.5- to 2-fold during the transition from logarithmic to stationary phase in iron-rich media, whereas the iron contents of theftnA and ftnA bfr mutants remained unchanged. The ftnA and ftnA bfr mutants were growth impaired in iron-deficient media, but this was apparent only after the mutant and parental strains had been precultured in iron-rich media. Surprisingly, ferric iron uptake regulation (fur) mutants also had very low iron contents (2.5-fold less iron than Fur+ strains) despite constitutive expression of the iron acquisition systems. The iron deficiencies of the ftnA andfur mutants were confirmed by Mössbauer spectroscopy, which further showed that the low iron contents of ftnAmutants are due to a lack of magnetically ordered ferric iron clusters likely to correspond to FtnA iron cores. In combination with thefur mutation, ftnA and bfrmutations produced an enhanced sensitivity to hydroperoxides, presumably due to an increase in production of “reactive ferrous iron. ” It is concluded that FtnA acts as an iron store accommodating up to 50% of the cellular iron during postexponential growth in iron-rich media and providing a source of iron that partially compensates for iron deficiency during iron-restricted growth. In addition to repressing the iron acquisition systems, Fur appears to regulate the demand for iron, probably by controlling the expression of iron-containing proteins. The role of Bfr remains unclear.
Genome-wide screening and identification of antigens for rickettsial vaccine development.

The capacity to identify immunogens for vaccine development by genome-wide screening has been markedly enhanced by the availability of microbial genome sequences coupled to proteomic and bioinformatic analysis. Critical to this approach is in vivo testing in the context of a natural host–pathogen relationship, one that includes genetic diversity in the host as well as among pathogen strains. We aggregate the results of three independent genome-wide screens using in vivo immunization and protection against Anaplasma marginale as a model for discovery of vaccine antigens for rickettsial pathogens. In silico analysis identified 62 outer membrane proteins (Omp) from the 949 predicted proteins in the A. marginale genome. These 62 Omps were reduced to 10 vaccine candidates by two independent genome-wide screens using IgG2 from vaccinates protected from challenge following vaccination with outer membranes (screen 1) or bacterial surface complexes (screen 2). Omps with broadly conserved epitopes were identified by immunization with a live heterologous vaccine, A. marginale ssp. centrale (screen 3), reducing the candidates to three. The genome-wide screens identified Omps that have orthologs broadly conserved among rickettsial pathogens, highlighted the importance of identifying immunologically subdominant antigens, and supported the use of reverse vaccinology approaches in vaccine development for rickettsial diseases.