Miracle-dz/UniFAR-FTUs huggingface dataset:
Neuropsychopathology in 7 Patients with the 22q13 Deletion Syndrome: Presence of Bipolar Disorder and Progressive Loss of Skills

The 22q13 deletion syndrome is characterised by intellectual disability (ID), delayed or absent speech, autistic-like behaviour and minor, nonspecific dysmorphic features. The deletion of the SHANK3 gene is thought to be responsible for these features. In this study, the clinical data of 7 patients with the 22q13 deletion syndrome are presented, obtained by clinical genetic examination, direct behavioural observation and by interview of family members and/or caregivers, complemented by behavioural questionnaires. The specific focus was on behaviour, psychopathology and the level of functioning during life course in order to determine common features that might contribute to the delineation of the syndrome. Major findings were a high incidence of psychiatric disorders, more in particular bipolar disorder (BPD) and attention deficit hyperactivity disorder (ADHD), and a sudden deterioration after acute events, in addition to a progressive loss of skills over years. Therefore, a deletion of SHANK3 may result in a dysfunctional nervous system, more susceptible to developmental problems and psychiatric disorders on the one hand, less able to recuperate after psychiatric and somatic events, and more vulnerable to degeneration at long term on the other hand. These results are exploratory and need to be confirmed in a larger sample.
Lactate Dehydrogenase Isozymes: Substrate Inhibition in Various Human Tissues

In the report "Lactate dehydrogenase isozymes: substrate inhibition in various human tissues" by E. S. Vesell (17 Dec., p. 1590), the words "LDH-1" and "purified" in the fifth line were transposed; the sentence should have begun, "Based on inhibition at 25�C of isolated, purified LDH-1 by concentrations of pyruvate . " In the legend to Fig. 1, the temperature should have been given as 25�C.
Behavior change techniques used by the English Stop Smoking Services and their associations with short-term quit outcomes.

OBJECTIVE To help identify effective components of behavioral support for smoking cessation, this study identified the behavior change techniques (BCTs) specified in the treatment manuals of 43 English Stop Smoking Services (SSSs) and assessed association between inclusion of specific BCTs and SSS success rates. METHODS SSSs (n = 144) were contacted to request their treatment manuals. BCTs included in the manuals were identified using a previously established taxonomy. Associations between inclusion of specific BCTs and short-term (4-week) quit outcomes were assessed. RESULTS Ninety-eight services responded, of which 43 had suitable treatment manuals. Out of 43 possible BCTs, SSS manuals included a mean of 22 (range 9-37). The number of sessions used for delivery of the smoking cessation intervention differed markedly (range 1-13) across services. Nine of the BCTs were significantly associated with both self-reported and carbon monoxide (CO)-verified 4-week quit rates (e.g., strengthen ex-smoker identity, provide rewards contingent on abstinence, advise on medication, measure CO) and a further 5 were associated with CO-verified 4-week quit rates but not self-reported quit rates (e.g., advise on/facilitate use of social support, provide reassurance). SSSs that scheduled in more sessions had higher quit rates. CONCLUSIONS English SSSs vary widely in how far their treatment manuals include specific behavior change techniques and how many do not have manuals. It is possible to identify BCTs that are reliably associated with better quit outcomes. Behavioral support for smoking cessation could be improved by a more systematic approach to identifying and applying BCTs that are associated with better quit outcomes.
Assessment of the Nasopharyngeal Bacterial Flora of Rhesus Macaques: Moraxella, Neisseria, Haemophilus, and Other Genera

ABSTRACT The nasopharyngeal bacterial flora of healthy rhesus macaques was surveyed for the presence of Neisseria and Haemophilus species, as well as Moraxella catarrhalis. M. catarrhalis was found both in healthy rhesus macaques and in possibly immunocompromised rhesus macaques. Several Haemophilus spp. that are part of the normal nasopharyngeal bacterial flora of humans were found in many animals; these Haemophilus species included H. parahaemolyticus, H. segnis, and H. parainfluenzae. While Haemophilus influenzae was not identified, it is possible that the identification of H. influenzae types may have been thwarted by the growth of less fastidious species. A number of animals harbored Neisseria spp. such as N. sicca. However, Neisseria meningitidis was not found. In summary, it appears as though the rhesus macaque may be used as a model for M. catarrhalis infections. Moreover, in view of the susceptibility of macaques to organisms of the Haemophilus and Neisseria genera, it is possible that these animals may also accurately model nontypeable H. influenzae and N. meningitidis infections.
The comparison of milk production and quality in cows from conventional and automatic milking systems

The objective of this study was to evaluate the effects of two different types of milking systems (conventional parlour vs. automatic milking system) and the season of the year on the composition and hygienic quality of milk from Czech Fleckvieh cows. A total of 500 cows were involved; 200 and 300 in conventional and automatic milking systems, respectively. Bulk milk samples were collected for 12 months from July 2010 to June 2011. The following milk components and quality indicators were determined: % of fat, % of protein, % of lactose, % of fat-free dry matter (FFDM), % of casein, urea content, somatic cell count (SSC), total germ count (TGC) and milk freezing point (FP). The data were processed and evaluated with MS Excel and the statistical software SAS 9.1. Significantly higher (P<0.05 – 0.01) contents of fat, protein, FFDM and casein and increased TGC were observed in the automatic milking system, whereas SCC and FP were significantly lower (P<0.01). The highest contents of fat, protein and casein, and the lowest lactose content were found in the winter season. The highest contents of FFDM, urea and SCC were observed in autumn, whereas TGC was highest in summer (P<0.05 – 0.01). Only FP was not influenced by the season.
Expression and regulation of three lysosomal cysteine protease activities during growth of a differentiating L6 rat myoblast cell line and its nonfusing variant.

The expression of three lysosomal cysteine protease activities, cathepsins B, H, and L, was examined during differentiation of L6 rat myoblasts. Analyses of intracellular levels of these proteases in unfractionated homogenates prepared from cells at different stages of growth and in parallel HPLC-fractionated samples demonstrated a fusion-related increase in all three cathepsins. Analyses of total levels of endogenous inhibitor activity against purified cathepsin B demonstrated a threefold increase in the ratio of protease to inhibitor during myoblast-myotube formation; however, levels of inhibitor activity remained constant. Extracellular levels of cathepsin B, H, and L activities were also examined in the serum-free defined media of differentiating L6 cells. These studies demonstrated a fusion-related increase in extracellular levels of acid/pepsin-activated (i.e., latent) cathepsin L. While increases in intracellular and extracellular levels of cathepsin activities were temporally related to the fusion process, fusion may not be a prerequisite for increased expression, since the nonfusing L6 variant L6-D3 demonstrated high levels of intracellular cathepsins B and L and extracellular latent cathepsin L activities throughout growth. Taken together, these results support the hypotheses that fusion or fusion-related processes play an important role in the controlled expression of cathepsins in L6 myoblasts and that cathepsins, in turn, play an important role in myoblast-myotube differentiation.
Conversion of androgen to estrogen by the human fetal ovary.

The conversion of radiolabeled androgen to estrone and 17 beta-estradiol was assessed in tissues of human embryos that varied from phenotypically indifferent stages (1-3 cm crownrump length) to midgestation (15. 1-20 cm crownrump length). Significant rates of estrogen synthesis were demonstrated only in ovaries, liver, and brain. Estrogen synthesis was undetectable in gonads from 1-3 cm fetuses, but by the 3.1-5-cm stage it had reached an average rate of 1.9 pmol . h-1 . mg protein -1 in ovaries and remained at this level of activity through the latest stages examined. Estrogen formation was undetectable in testes at all stages examined, but the time of appearance of the capacity to form estrogens in the fetal ovary is similar to the onset of the capacity of the fetal testis to synthesize testosterone. The capacity of the fetal ovary to form estrogen develops before histological differentiation of the tissue.
Programming Normal Renal Development and Modeling Disease Pathogenesis Role of the USF 1 transcription factor in diabetic kidney disease

Sanchez AP, Zhao J, You Y, Declèves A-E, Diamond-Stanic M, Sharma K. Role of the USF1 transcription factor in diabetic kidney disease. Am J Physiol Renal Physiol 301: F271–F279, 2011. First published May 4, 2011; doi:10.1152/ajprenal.00221. 2011. —The predominant transcription factors regulating key genes in diabetic kidney disease have not been established. The transcription factor upstream stimulatory factor 1 (USF1) is an important regulator of glucosemediated transforming growth factor (TGF)1 expression in mesangial cells; however, its role in the development of diabetic kidney disease has not been evaluated. In the present study, wild-type (WT; USF1 / ), heterozygous (USF1 / ), and homozygous (USF1 / ) knockout mice were intercrossed with Akita mice (Ins2/Akita) to induce type 1 diabetes. Mice were studied up to 36 wk of age. The degree of hyperglycemia and kidney hypertrophy were similar in all groups of diabetic mice; however, the USF1 / diabetic mice had significantly less albuminuria and mesangial matrix expansion than the WT diabetic mice. TGF1 and renin gene expression and protein were substantially increased in the WT diabetic mice but not in USF1 / diabetic mice. The underlying pathway by which USF1 is regulated by high glucose was investigated in mesangial cell culture. High glucose inhibited AMP-activated protein kinase (AMPK) activity and increased USF1 nuclear translocation. Activation of AMPK with AICAR stimulated AMPK activity and reduced nuclear accumulation of USF1. We thus conclude that USF1 is a critical transcription factor regulating diabetic kidney disease and plays a critical role in albuminuria, mesangial matrix accumulation, and TGF1 and renin stimulation in diabetic kidney disease. AMPK activity may play a key role in high glucose-induced regulation of USF1.
Assessment of cell viability after manipulation with insulator‐based dielectrophoresis

The effects of insulator‐based DEP (iDEP) manipulation on cell viability were investigated by varying operating conditions and the shape of the insulating structures. Experiments were conducted with Escherichia coli, Bacillus subtilis, and Saccharomyces cerevisiae cells by varying the applied potential (300–1000 V), exposure time (1–4 min), and composition of the suspending medium (0–10% glucose); using devices made from polydimethylsiloxane. Cell viability was quantified employing Trypan blue staining protocols. The results illustrated a strong decrease in cell survival at higher applied electric potentials and exposure times; and an increase in cell viability obtained by increasing suspending medium osmolality. The composition and structure of the cell wall also played a major role on cell survival, where prokaryotic Gram‐positive B. subtilis was the most resilient cell strain, while eukaryotic S. cerevisiae had the lowest survival rate. Due to the popularity of iDEP in applications with biological cells, characterizing how iDEP operating conditions affect cell viability is essential.
Critical role of zinc in hardening of Nereis jaws

SUMMARY Hardening of invertebrate jaws and mandibles has been previously correlated to diverse, potentially complex modifications. Here we demonstrate directly, for the first time, that Zn plays a critical role in the mechanical properties of histidine-rich Nereis jaws. Using nanoindentation, we show that removal of Zn by chelation decreases both hardness and modulus by over 65%. Moreover, reconstitution of Zn yields a substantial recovery of initial properties. Modulus and hardness of Zn-replete jaws exceed those attainable by current engineering polymers by a factor of >3. Zn-mediated histidine cross-links are proposed to account for this enhancement in mechanical properties.
The chronic toxicities of technical benzene hexachloride and its alpha, beta and gamma isomers.

In a total of 420 rats fed for a lifetime diets containing the technical benzene hexachloride or the alpha, beta or gamma isomer in dosage levels ranging from 5 to 1600 p.p.m. the following effects were observed: 1. Beta isomer retarded growth rate at 100 p.p.m. , the alpha isomer and the technical benzene hexachloride at 800 p.p.m. and the gamma isomer at 1600 p.p.m. Lower dosages had no effect on growth. 2. All isomers, except dry gamma and the technical benzene hexachloride, increased the mortality rate at 800 p.p.m. 3. All isomers and the technical benzene hexachloride increased the size of the liver. The lowest dosage of each substance which produced a significant effect was 10 p.p.m. beta, 100 p.p.m. alpha, gamma and technical, and 800 p.p.m. dry gamma. 4. Tissue storage was marked with the beta isomer and somewhat less for the alpha and gamma isomers. In a decreasing order these substances were found in fat, kidney, brain, muscle and liver tissues. 5. In a total of 238 animals microscopically sectioned, the chief organ affected was the liver; the kidney was affected to a lesser degree. 6. Grossly, the chief alteration of the liver consisted of enlargement, but changes such as off color and small foci of necrosis also appeared. 7. The microscopic alterations in the liver were of two types, namely, the specific one of certain hepatic cell changes as generally seen in rodents fed various chlorinated compounds and the less specific but sometimes more damaging ones such as diffuse hepatic cell enlargement, hepatic cell atrophy, fatty degeneration and focal necrosis. 8. In descending order of total damage to the liver the dosage levels of the compounds were: 800 p.p.m. beta, 800 p.p.m. technical, 800 p.p.m. alpha, 1600 p.p.m. gamma, 800 p.p.m. dry gamma, 800 p.p.m. gamma, 100 p.p.m. beta, 400 p.p.m. gamma, 100 p.p.m. technical and 100 p.p.m. alpha. Very slight changes only were seen in the groups on 100 p.p.m. gamma, 100 p.p.m. dry gamma, 50 p.p.m. technical, 50 p.p.m. alpha and 10 p.p.m. beta. No effect was observed with 50, 10 and 5 p.p.m. gamma and 10 p.p.m. technical, alpha and dry gamma. 9. Slight to moderate kidney damage occurred in the groups on 800 p.p.m. alpha and 800 p.p.m. dry gamma, and slight damage in the group on 800 p.p.m. technical. 10. A moderate degree of testicular atrophy occurred in the group on 800 p.p.m. technical. 11. In comparison with previous chronic experiments with DDT this experiment indicates that the gamma isomer of benzene hexachloride is about a fourth as toxic as DDT, the beta isomer is two to three times as toxic, and the alpha isomer and the technical benzene hexachloride are of the same order of chronic toxicity as DDT.
Safety and Efficacy of Moxifloxacin Monotherapy for Treatment of Orthopedic Implant-Related Staphylococcal Infections

ABSTRACT The rifampin-ciprofloxacin combination is recommended for treatment of orthopedic implant-related staphylococcal infections to avoid the emergence of ciprofloxacin resistance; however, the efficacy of this combination is limited by the tolerability problems associated with the use of rifampin. Moxifloxacin is a quinolone up to 10 times more active against staphylococci than ciprofloxacin and the risk of resistance development during monotherapy against staphylococci is theoretically lower for moxifloxacin, but information regarding its use in bone infections is lacking. The aim of the present study was to evaluate the safety and clinical efficacy of moxifloxacin monotherapy in patients with orthopedic implant-related staphylococcal infections. From June 2006 to April 2009, all patients with culture-proven infection by quinolone-sensitive staphylococcal strains associated with orthopedic implants at our institution were included in a management protocol that mostly included specific surgery, 1 to 2 weeks of an intravenous course of cloxacillin-cefazolin or vancomycin, and long-term therapy with moxifloxacin (400 mg/day for 3 months). Cure was defined as (i) a lack of clinical signs and symptoms of infection, (ii) a C-reactive protein level less than 5 mg/liter, and (iii) absence of radiological signs of loosening or infection at the latest follow-up visit. Failure was defined as (i) persisting clinical and/or laboratory signs of infection or (ii) persisting or new isolation of the initial microorganism. A total of 48 patients with a median follow-up of 716 days (range, 102 to 1,613 days) were included in the study. Complete drug compliance was achieved in all but two patients (4.2%), who required drug discontinuation because of side effects (diarrhea and dizziness). No moxifloxacin-induced arrhythmia was reported. Twenty patients had joint prosthesis infections (5 acute-onset infections and 15 chronic infections), and 28 patients had osteosynthesis material infections (4 acute-onset infections and 24 chronic infections). The etiologies were methicillin-sensitive Staphylococcus aureus in 33 patients and a coagulase-negative staphylococcus (CoNS) in 15. Surgical management was performed for the majority of patients (37/48; 77%), and the implant was retained in 21 patients (43.8%). The global cure rate was 38/46 (82.6%), and the cure rate for patients with implant retention was 15/21 (71.4%). The global cure rate for the 32 patients with a minimum follow-up of 2 years was 80%. Of the eight cases of relapse, we obtained microbiological confirmation in six cases, and all bacteria recovered were quinolone susceptible. Monotherapy with moxifloxacin seems to be an effective, safe, and easy alternative for the long-term treatment of orthopedic implant-related staphylococcal infections by quinolone-sensitive strains. Comparative studies with rifampin-containing regimens are warranted.
Management of diabetes in primary care: A structured-care approach

Background: In the Irish Midland Health Service Executive (HSE) Diabetes Structured Care Project, additional resources were targeted at general practice in the absence of a local hospital-based specialized diabetes unit. Objective: We assessed the performance of the Midland HSE Diabetes Structured Care programme in 2003, bench-marked against Primary Care Trust (PCT) data from the 2003/2004 National Diabetes Audit for England. Methods: Data on 947 patients (72% of eligible patients) from all 20 general practices participating in the structured-care programme were collected retrospectively over a 12-month period. The data included demographic and clinical variables as well as key process-of-care and intermediate outcome indicators used in the National Diabetes Audit for England. Results: The level of recording of process-of-care measures was near or above the upper quartile for PCTs in England. The proportion of patients with HbA1c concentrations at target levels (<6.5%) in the Midlands HSE project (26.8%) was virtually identical to the upper quartile level for PCTs in England (27.4%). The proportion of patients reaching target total cholesterol levels (<5.0 mmol/l) (54.6%) was close to the mean for PCTs in England (56.6%), and performance with regard to target blood pressure levels was equally poor in both the Midlands HSE (18.0%) and in PCTs in England (20.8%). Conclusion: Primary-care-led structured care, with relatively limited but well-focused investment, can achieve quality of care for patients with diabetes, comparable to international best practice.
Regulator of G-protein signalling and GoLoco proteins suppress TRPC4 channel function via acting at Gαi/o.

Transient receptor potential canonical 4 (TRPC4) forms non-selective cation channels implicated in the regulation of diverse physiological functions. Previously, TRPC4 was shown to be activated by the Gi/o subgroup of heterotrimeric G-proteins involving Gαi/o, rather than Gβγ, subunits. Because the lifetime and availability of Gα-GTP are regulated by regulators of G-protein signalling (RGS) and Gαi/o-Loco (GoLoco) domain-containing proteins via their GTPase-activating protein (GAP) and guanine-nucleotide-dissociation inhibitor (GDI) functions respectively, we tested how RGS and GoLoco domain proteins affect TRPC4 currents activated via Gi/o-coupled receptors. Using whole-cell patch-clamp recordings, we show that both RGS and GoLoco proteins [RGS4, RGS6, RGS12, RGS14, LGN or activator of G-protein signalling 3 (AGS3)] suppress receptor-mediated TRPC4 activation without causing detectable basal current or altering surface expression of the channel protein. The inhibitory effects are dependent on the GAP and GoLoco domains and facilitated by enhancing membrane targeting of the GoLoco protein AGS3. In addition, RGS, but not GoLoco, proteins accelerate desensitization of receptor-activation evoked TRPC4 currents. The inhibitory effects of RGS and GoLoco domains are additive and are most prominent with RGS12 and RGS14, which contain both RGS and GoLoco domains. Our data support the notion that the Gα, but not Gβγ, arm of the Gi/o signalling is involved in TRPC4 activation and unveil new roles for RGS and GoLoco domain proteins in fine-tuning TRPC4 activities. The versatile and diverse functions of RGS and GoLoco proteins in regulating G-protein signalling may underlie the complexity of receptor-operated TRPC4 activation in various cell types under different conditions.
Relationship between 800-m running performance and accumulated oxygen deficit in middle-distance runners.

PURPOSE To determine whether there is a significant relationship between accumulated oxygen deficit (AOD) and 800-m running performance in a group of runners of homogeneous ability. METHODS Nine well-trained male middle and long distance runners (age = 24.7 +/- 4.5 yr, body mass = 69.4 +/- 8.5 kg, VO2max = 64.8 +/- 4.5 mL.kg-1.min-1) underwent treadmill testing to determine maximum oxygen uptake (VO2max), running economy (RE) at 1% and 10.5% treadmill gradient, and AOD at 1% and 10.5% treadmill gradient; 800-m running performance was determined by time trials on an outdoor 440-yd track, for which the average time was 132 +/- 4 s. For the AOD test, subjects were required to run on the treadmill at supramaximal speeds until volitional exhaustion. The AOD value was calculated using linear (LIN) and curvilinear (CUR) extrapolation procedures. RESULTS Mean AOD values using LIN and CUR were 45.0 +/- 6.9 and 59.3 +/- 10.1 mL.kg-1 at a 1% treadmill gradient and 63.2 +/- 10.6 and 93.6 +/- 19.7 mL.kg-1 at a 10.5% gradient, respectively. No significant relationship was found between 800-m run time and AOD at 1% gradient or 10.5% gradient or when AOD was estimated from a linear or curvilinear fit of the VO2 data. Other variables measured in this study (e.g., VO2max and running economy) were not found to be predictive of 800-m run time. CONCLUSION Among a homogeneous group of well-trained male middle- and long-distance runners, AOD measured at a 1% and 10.5% treadmill gradient is not significantly related to 800-m running performance.