Miracle-dz/UniFAR-FTUs huggingface dataset:
Zinc metalloproteinase ZmpC suppresses experimental pneumococcal meningitis by inhibiting bacterial invasion of central nervous systems

ABSTRACT Streptococcus pneumoniae is a leading cause of bacterial meningitis. Here, we investigated whether pneumococcal paralogous zinc metalloproteases contribute to meningitis onset. Findings of codon-based phylogenetic analyses indicated 3 major clusters in the Zmp family; ZmpA, ZmpC, and ZmpB, with ZmpD as a subgroup. In vitro invasion assays of human brain microvascular endothelial cells (hBMECs) showed that deletion of the zmpC gene in S. pneumoniae strain TIGR4 significantly increased bacterial invasion into hBMECs, whereas deletion of either zmpA or zmpB had no effect. In a mouse meningitis model, the zmpC deletion mutant exhibited increased invasion of the brain and was associated with increased matrix metalloproteinase-9 in plasma and mortality as compared with the wild type. We concluded that ZmpC suppresses pneumococcal virulence by inhibiting bacterial invasion of the central nervous system. Furthermore, ZmpC illustrates the evolutional theory stating that gene duplication leads to acquisition of novel function to suppress excessive mortality.
Improvement of Coronary Microvascular Function After Angiotensin Receptor Blocker Treatment With Irbesartan in Patients With Systemic Hypertension

Patients with hypertension exhibit changes in vessel conductance and resistance. The aim of this study was to evaluate the effect of the angiotensin receptor blocker irbesartan on coronary microvascular function. Thirty‐six hypertensive patients without coronary artery or systemic disease were examined. Coronary flow velocity reserve (CFR) was measured using transthoracic Doppler echocardiography in 18 men (54±9 years) before and after 3 months of treatment with 600 mg/d of irbesartan and in 18 controls (55±11 years). Carotid intima‐media thickness (IMT) was evaluated with high‐resolution echocardiography. Baseline CFR did not differ between groups. CFR significantly improved in the irbesartan group (from 2.87±.42 to 3.78±.32; P<.001), but remained unchanged in controls (from 2.94±.61 to 3.06±.72; P=not significant). CFR improved with treatment independent of associated risk factors. BP decreased from 150±18 mm Hg to 129±25 mm Hg (P<.001) during treatment, whereas IMT and left ventricular mass index showed no significant differences at the end of the follow‐up period in both groups. Three‐month irbesartan treatment significantly increased CFR in patients with hypertension. This improvement is attributed to blockade of the renin‐angiotensin system. Coronary microvascular function was shown to improve independent of hypertrophy regression. Patients with lower baseline CFR tended to show a more pronounced CFR response. J Clin Hypertens (Greenwich). 2011;13:155–161. © 2010 Wiley Periodicals, Inc.
Immunomodulatory properties of Brucella melitensis lipopolysaccharide determinants on mouse dendritic cells in vitro and in vivo

ABSTRACT The lipopolysaccharide (LPS) is a major virulence factor of Brucella, a facultative intracellular pathogenic Gram-negative bacterium. Brucella LPS exhibits a low toxicity and its atypical structure was postulated to delay the host immune response, favouring the establishment of chronic disease. Here we carried out an in-depth in vitro and in vivo characterisation of the immunomodulatory effects of Brucella LPS on different dendritic cell (DC) subpopulations. By using LPSs from bacteria that share some of Brucella LPS structural features, we demonstrated that the core component of B. melitensis wild-type (Bm-wt) LPS accounts for the low activation potential of Brucella LPS in mouse GM-CSF-derived (GM-) DCs. Contrary to the accepted dogma considering Brucella LPS a poor TLR4 agonist and DC activator, Bm-wt LPS selectively induced expression of surface activation markers and cytokine secretion from Flt3-Ligand-derived (FL-) DCs in a TLR4-dependent manner. It also primed in vitro T cell proliferation by FL-DCs. In contrast, modified LPS with a defective core purified from Brucella carrying a mutated wadC gene (Bm-wadC), efficiently potentiated mouse and human DC activation and T cell proliferation in vitro. In vivo, Bm-wt LPS promoted scant activation of splenic DC subsets and limited recruitment of monocyte- DC like cells in the spleen, conversely to Bm-wadC LPS. Bm-wadC live bacteria drove high cytokine secretion levels in sera of infected mice. Altogether, these results illustrate the immunomodulatory properties of Brucella LPS and the enhanced DC activation ability of the wadC mutation with potential for vaccine development targeting Brucella core LPS structure.
Oncogenic Ras: A double-edged sword for human epidermal stem and transient amplifying cells

ABSTRACT The human epidermal clonal evolution, i.e. the transition from stem cells (SCs) to transient amplifying (TA)-cells and post-mitotic cells, is a continuous and tightly regulated process that ensures physiologic tissue homeostasis. The Ras family of small GTPases has a key role in skin homeostasis and tumorigenesis. Indeed, activating mutations in Ras genes have been found in human cutaneous squamous cell carcinomas (cSCCs) and in experimentally-induced murine cSCCs. In mouse models, the Ras signaling might lead to hyperproliferative phenotypes, including the development of cSCCs, depending on the nature of the founding cells. Tumor-initiating cells or Cancer Stem Cells (CSCs) have been demonstrated in murine and human cSCCs even if the mechanism of their development from normal SCs or TA-cells is not completely elucidated. Here, the relation between the Ras expression outcome and the clonogenic potential of the target keratinocyte is discussed.
Workplace mobbing and bystanders' helping behaviour towards victims: the role of gender, perceived responsibility and anticipated stigma by association.

We examined victims' perceived responsibility and bystanders' anticipated risk of being victimized themselves when others associate them with the victim (stigma by association, SBA) as possible antecedents of bystanders' helping behaviour towards a victim of workplace mobbing, and explored the effects of gender. Guided by the attribution model of social conduct (Weiner, 2006), a 2 × 2 vignette experiment was conducted. Participants were Dutch regional government employees (N = 161). Path analyses generally supported the hypotheses, but showed different results for women and men. In the strong (Vs. weak) responsibility condition, women reported less sympathy and more anger and men only more anger, which resulted in lower helping intention. Additionally, for men the results showed an unexpected direct positive effect of responsibility on helping intention. Furthermore, in the strong SBA condition, women and men reported more fear and men, unexpectedly, more anger. Consequently, helping intention decreased. The findings on gender are discussed in the context of social role theory, gender and emotion. Our findings suggest that to prevent and tackle mobbing, organizations and professionals should be aware of the attributional and emotional processes and gender differences in bystanders' helping behaviour.
Mycobacterium Smegmatis Infection of a Lumbar Spine Instrumented Fusion

Problem statement: To demonstrate the presentation of atypical mycobacterial postsurgical infections and their management. Approach: Single patient case report. Results: Successful management of atypical mycobacterial post operative infection with preservation of instrumented hardware posterior pedicle screw fixation and interbody cages. Conclusion: This report suggests that these atypical mycobacterial infections can be eradicated with successful outcomes with preservation of spinal instrumentation.
A randomized controlled trial comparing the efficacy of intralesional 5-fluorouracil versus triamcinolone acetonide in the treatment of keloids

Background: Effective keloid management is still a distant dream in spite of many recent modalities being tried for the same. Although many treatment protocols have shown efficacy of varying degrees, there are few systematic randomized trials comparing them. Objective: To compare the efficacy of intralesional 5-Fluorouracil versus Triamcinolone acetonide in the treatment of Keloids. Materials and Methods: This randomized controlled trial was conducted on 30 patients with keloids, randomly divided into two groups of 15 each, treated with intralesional 5-fluorouracil (Group A) or triamcinolone acetonide (Group B). The groups were compared for reduction in the size of keloid, pain relief, and the incidence of adverse effects. Statistical analysis was done using the unpaired student t- test and test of proportion. Results: The reduction in the size of the keloid was found to be significantly better in Group B (71.23%) than in Group A (57.48%) with a P value of 0.04. The difference in the reduction of pain, as assessed by the visual analog scale, between Groups A (18%) and B (24%), was found to be insignificant (P value - 0.47). Although the incidence of complications in Group A was three times higher than those in Group B, the difference was not statistically significant (P value - 0.13). Conclusion: Reduction in the size of the keloid, which was the main aim of this study was significantly better in those treated with triamcinolone acetonide than those treated with 5-fluorouracil. The other parameters like reduction of pain and the incidence of adverse effects were comparable in both the groups.
Frequency and Clinical Correlates of Occlusive Lesions of Cerebral Arteries in Japanese Patients without Stroke

To determine the frequency and clinical correlates of intra- and extracranial arterial occlusive lesions in a stroke-free population, we studied cerebral arteries in 156 subjects with no evidence of stroke who presented at a neurologic clinic with concerns about a possible stroke (104 males ranging in age from 37 to 83 years, with a mean age of 63.0) by using MR angiographies (MRAs). According to a validated rating scheme of MRAs for occlusive lesions, the degree of stenoses in the cervical portion of the carotid artery and of the intracranial arteries including the intracranial portion of the internal carotid artery, the middle cerebral artery stem, and the basilar artery were evaluated. Stenoses (>25% narrowing in diameter) were found in 18 patients (11.5%) in the cervical carotid artery, and in 23 patients (14.7%) in the intracranial arteries. Multiple logistic regression analysis showed that age and hyperlipidemia were significant and independent predictors for cervical carotid artery stenoses, and that age and hypertension were predictors for intracranial artery stenoses. Our data based on this special cohort of stroke-free patients suggested that the risk factors for extra- and intracranial artery lesions were different, and that MRA is possibly efficient in those patients in whom cerebral artery occlusive lesions may be suspected, e.g. in hyperlipidemic or hypertensive elderly. Larger population-based studies are needed to confirm these results.
The mixed lineage leukemia 4 (MLL4) methyltransferase complex is involved in transforming growth factor beta (TGF-β)-activated gene transcription

ABSTRACT Sma and Mad related (SMAD)-mediated Transforming Growth Factor β (TGF-β) and Bone Morphogenetic Protein (BMP) signaling is required for various cellular processes. The activated heterotrimeric SMAD protein complexes associate with nuclear proteins such as the histone acetyltransferases p300, PCAF and the Mixed Lineage Leukemia 4 (MLL4) subunit Pax Transactivation domain-Interacting Protein (PTIP) to regulate gene transcription. We investigated the functional role of PTIP and PTIP Interacting protein 1 (PA1) in relation to TGF-β-activated SMAD signaling. We immunoprecipitated PTIP and PA1 with all SMAD family members to identify the TGF-β and not BMP-specific SMADs as interacting proteins. Gene silencing experiments of MLL4 and the subunits PA1 and PTIP confirm TGF-β-specific genes to be regulated by the MLL4 complex, which links TGF-β signaling to transcription regulation by the MLL4 methyltransferase complex.
The heart of the matter: cardiometabolic care in youth with psychosis

Aim: Weight gain, obesity and metabolic disturbances in youth with psychosis are significant contributors to the health burden of people with psychosis, with a two‐ to threefold increase in rates compared with the general population and a 20% reduction in life expectancy. Several studies have now described cardiometabolic benefits of a range of interventions, including a structured diet and exercise programmes and metformin for patients receiving antipsychotic medications. Despite the development of Australian consensus guidelines and screening algorithms to detect such metabolic abnormalities, there is a lack of guidelines for clinicians to determine appropriate, timely, targeted prevention and intervention to manage these complications in the youth population.
Prevalência da síndrome metabólica e seus fatores associados em área rural de Minas Gerais (MG, Brasil)

OBJETIVO: Estimar a prevalencia da sindrome metabolica (SM) e seus fatores associados em area rural de Minas Gerais. METODOLOGIA: Trata-se de um estudo transversal, de base populacional, conduzido nas comunidades rurais de Virgem das Gracas e Caju, Vale do Jequitinhonha, Minas Gerais. Foram coletas informacoes sobre caracteristicas demograficas, do estilo de vida, antropometricas, bioquimicas e hemodinâmicas de 534 participantes adultos. A SM foi definida segundo criterios estabelecidos pela National Cholesterol Education Program - Adult Treatment Panel III. Associacoes independentes entre as covariaveis e a SM foram avaliadas usando-se a regressao multivariada de Poisson com variâncias robustas. O nivel de significância estatistica foi estabelecido em 5,0%. RESULTADOS: A SM estava presente em 14,9% dos participantes. O sexo feminino, a obesidade, a inflamacao cronica subclinica, a resistencia a insulina, a idade e o consumo moderado de bebida alcoolica permaneceram independentemente associados a SM. CONCLUSOES: Na populacao rural estudada, a SM era problema de Saude Publica, associada a fatores modificaveis. Portanto, medidas preventivas primarias poderiam ser usadas para diminuir a prevalencia deste agravo e o seu impacto na saude das pessoas.
Generating an Engineered Adipose Tissue Flap Using an External Suspension Device.

BACKGROUND The tissue-engineering chamber technique can generate large volumes of adipose tissue, which provides a potential solution for the complex reconstruction of large soft-tissue defects. However, major drawbacks of this technique are the foreign-body reaction and the volume limitation imposed by the chamber. METHODS In this study, the authors developed a novel tissue-engineering method using a specially designed external suspension device that generates an optimized volume of adipose flap and avoids the implantation of foreign material. The rabbits were processed using two different tissue-engineering methods, the external suspension device technique and the traditional tissue-engineering chamber technique. RESULTS The adipose flaps generated by the external suspension device had a normal adipose tissue structure that was as good as that generated by the traditional tissue-engineering chamber, but the flap volume was much larger. The final volume of the engineered adipose flap grew between weeks 0 and 36 from 5.1 ml to 30.7 ml in the traditional tissue-engineering chamber group and to 80.5 ml in the external suspension device group. During the generation process, there were no marked differences between the two methods in terms of structural and cellular changes of the flap, except that the flaps in the traditional tissue-engineering chamber group had a thicker capsule at the early stage. In addition, the enlarged flaps generated by the external suspension device could be reshaped into specific shapes by the implant chamber. CONCLUSIONS This minimally invasive external suspension device technique can generate large-volume adipose flaps. Combined with a reshaping method, this technique should facilitate clinical application of adipose tissue engineering.
Topical Amitriptyline-Baclofen Cream for the Treatment of Provoked Vestibulodynia

Objective. To evaluate the effectiveness of amitriptyline 2%/baclofen 2% cream (ABC) in treating provoked vestibulodynia (PV). Materials and Methods. In this retrospective evaluation of patients with PV who received ABC, women who had PV and met entry criteria were identified from a database of women with chronic vulvovaginal disorders. Treatment consisted of a cream containing 2% amitriptyline and 2% baclofen. Response was assessed using verbal report, visual analog scales of discomfort with daily and sexual activities, and 5-point numerical scales rating extent of interference with social activities, intercourse frequency, sexual desire, difficulty in lubrication, frequency and overall level of discomfort during sex, and satisfaction with overall sexual life. Results. Data were available for 38 patients, with a median follow-up of 33 weeks. Overall, 29% patients reported no or little (<30%) improvement, 18% reported moderate (30-60%) improvement, and 53% reported much (>60%) improvement. On self-administered questionnaires, patients reported a decrease in the extent to which the condition interfered with social activities (p =.017), easier lubrication (p =.022), and lower level of pain with intercourse (p =.05). No change was noted in the reported frequency of sexual intercourse, sexual desire, or satisfaction with sexual life. No patients had systemic side effects. Conclusions. Our data are limited by the retrospective study design and the lack of a control group. Nevertheless, given a response rate of 71% in women with refractory symptoms and the overall tolerability of this treatment, we suggest that ABC therapy warrants further investigation as a therapy for PV.
Corpus cavernosum dysfunction in diabetic rats: effects of combined α‐lipoic acid and γ‐linolenic acid treatment

The effects of streptozotocin‐induced diabetes on nitric oxide (NO)‐mediated relaxation of rat corpus cavernosum smooth muscle to neurogenic and endothelial stimulation was examined. The aim was to assess the effects of treatment with low doses of the antioxidant, α‐lipoic acid, and the ω‐6 essential fatty acid, γ‐linolenic acid, either separately or in combination.
Social Ecological Perspectives of Tube-Feeding Older Adults with Advanced Dementia: A Systematic Literature Review

ABSTRACT Dementia is a progressive, debilitating disease that often results in weight loss, malnutrition, and dehydration. Feeding tubes are often prescribed; however, this practice can lead to complications. The purpose of this systematic review was to examine the use of feeding tubes in elderly demented patients from a social ecological perspective. Results indicated that family members often receive inadequate decision-making education. Many health care professionals lack knowledge of evidence-based guidelines pertaining to feeding tube use. Organizational and financial reimbursement structures influence feeding tube use. Feeding practices for patients with advanced dementia is a complex issue, warranting approaches that target each level of the Social Ecological Model.
Prevenção do parto prematuro: emprego do toque vaginal e da ultra-sononografia transvaginal

Objective: to evaluate the uterine cervix by digital and transvaginal ultrasound examinations in pregnant women at high risk of having premature delivery. Methods: during the period between February 1995 and September 1997, 38 pregnant women at high risk of having premature delivery between the 20th and 36th week of gestation were examined. These patients were submitted weekly to both digital and transvaginal ultrasound examinations. The digital examination evaluated the uterine cervix using two parameters: length and dilation. The transvaginal ultrasound studied the length and the anteroposterior diameter of the uterine cervix. The behavior of these cervical measurements was analyzed throughout the pregnancies. The two methods were compared regarding cervical evaluation and accuracy of premature birth diagnosis. Results: the rate of premature deliveries was 18.4% (7/38). Digital examination resulted in cervical evaluations with variation coefficients of 30.3% for length and 193% for dilation. Transvaginal ultrasound resulted in cervical evaluations with variation coefficients of 14.7% and 26.5% for the anteroposterior diameter and length, respectively. The cervical length measures obtained on ultrasound were always greater than those obtained on digital examination. Through analysis with the hypothesis test, an indirect relationship was observed between the cervical length and the gestational period for digital examination and ultrasound study (p<0.05 and p<0.01, respectively), and a direct relationship between the cervical dilation and the gestational age observed on the digital examination (p<0.01). Conclusions: among the parameters studied by means of the digital and transvaginal ultrasound examinations, the ultrasound cervical length presented the best accuracy in the diagnosis of premature birth, proving to be more reliable for the evaluation of cervical alterations in pregnant women at high risk of premature delivery.
Attention and Executive Functions in Children With Epilepsy: What, Why, and What to Do

Abstract Attention and executive function deficits are a common sequelae of many neurological conditions of childhood. Those with epilepsy frequently show such deficits, as executive dysfunction is common in all epilepsy syndromes of childhood. The purpose of this article is to review what is known about attention and executive functions, including the neurological underpinnings of these skills. Then, general cognitive function and dysfunction in childhood epilepsy is discussed with a special focus on attention and executive function impairment. Finally, treatment considerations for children and adolescents with these deficits are reviewed and future directions are discussed.
Sleep-medication for symptomatic insomnia in the general population of Japan

The commercial availability of psychotropic drugs has an important effect on the consumption of medications for the symptomatic treatment of insomnia. Traditional benzodiazepines have been the most frequently prescribed psychotropic medications for promoting sleep in clinical practice in Japan. In recent years, non-diazepine drugs, antidepressant selective serotonin-reuptake inhibitors and over-the-counter sleep aids have been introduced into the Japanese pharmaceutical market. This study aimed therefore to make a poplulation-based assessment of sleep-medication use using the baseline data of a nationally representative sample of 2800 Japanese adults collected in 1997 before such changes. The Pittsburgh Sleep Quality Index was used to measue the symptoms of insomnia and the use of sleep medicine. A total of 1871 subjects participated in our analyses. The overall age-adjusted prevalence of sleep-medication use was 7.4%: 1.3%, 2.0% and 4.1% for <1 time, 1–2 times, and 3+ times per week during the past month, 6.5% and 0.9% for medically prescribed medicine and self-medicated sleeping pills, respectively. Of those with frequent insomniac symptoms, 75% remaied untreated. However, 3% of the users suggests the possibiliy of hypnotic-dependency. Over one-half of the users had multiple illnesses and consulted two or more different medical specialists. Physicians accounted for a disproportionately high percentage of all prescriptions of sleep medicine. Neuropsychiatrists replaced physicians after sociodemographic adjustments. Diabetes mellitus, heart disease, hypertension, and gastroduodenal ulcer represented the most common medical illnesses relating to sleep medication. This study drives the need to further investigate how to manage and treat individuals with insomnia.