Miracle-dz/UniFAR-FTUs huggingface dataset:
Tenofovir Renal Toxicity: Evaluation of Cohorts and Clinical Studies—Part 2

Tenofovir is a nucleotide reverse transcriptase inhibitor used as part of antiretroviral regimens. It is well tolerated with relative toxicological effects but recent reports have linked it with renal toxicity which is of clinical concern. This study reviews literary work on tenofovir renal toxicity with more light on case reports. Tenofovir renal toxicity manifests as Fanconi’s syndrome, nephrogenic diabetes insipidus and acute renal failure. Fanconi’s syndrome is characterised by acidosis, protenuria, albuminuria, aminoaciduria, hyperchloremic, metabolic acidosis, hypouricemia, hypophosphatemia and glycosuria. The presence of urine osmolality, polydipsia and polyuria could give credence totenofovir induced nephrogenic diabetes insipidus. In some cases of tenofovir renal toxicity, renal biopsy revealed sclerosed glomeruli with ischemic injury including portal collapse of capillary loops. Histopathological changes in glumeruli include mild mesangial proliferation, increased mesangial matrix and thickened capillary loops. Moderate degenerative tubular changes, loss of tubular mass, interstitial scarring and scattered cellular infiltrates. Pharmacodynamic and pharmacokinetic interactions may occur with the co administration of tenofovir with non steroidal anti-inflammatory drugs, aminoglycosides and some protease inhibitors which may potentiate renal toxicity. Tenofovir renal toxicity is associated with some risk factors including genetic polymorphism as supported by dichotomy in renal toxicity among different race and the association between ABCC2 gene and tenofovir kidney tubular dysfunction. The pharmacology of tenofovir renal toxicity is unclear but it is attributed to the interaction between tenofovir and theorganic anion transporters (hOAT1, and to a lesser extent, OAT3) favoring intracellular accumulation in renal proximal tubule cells. This may lead to ultrastructural mitochondrial abnormalities and decreased mtDNA levels which could stimulate reactive oxygen species production, depletion of antioxidants and antioxidant enzymes. These processes can stimulate the destruction of biomolecules such as DNA, proteins, and lipids, thus causing the deregulation of redox-sensitive metabolic pathways, signaling pathways, and cell death. Despite tenofovir renal toxicity it has achieved notable therapeutic success nevertheless patients on tenofovir containing regimens should be monitored for renal function parameters. Co administration with potential nephrotoxic drugs should be avoided except when benefit outweighs risk.
Salivary cortisol levels in children adopted from Romanian orphanages

Six and a half years after adoption, 6- to 12-year-old children reared in Romanian orphanages for more than 8 months in their first years of life (RO, n = 18) had higher cortisol levels over the daytime hours than did early adopted (EA, ≤ 4 months of age, n = 15) and Canadian born (CB, n = 27) children. The effect was marked, with 22% of the RO children exhibiting cortisol levels averaged over the day that exceeded the mean plus 2 SD of the EA and CB levels. Furthermore, the longer beyond 8 months that the RO children remained institutionalized the higher their cortisol levels. Cortisol levels for EA children did not differ in any respect from those of CB comparison children. This latter finding reduces but does not eliminate concerns that the results could be due to prenatal effects or birth family characteristics associated with orphanage placement. Neither age at cortisol sampling nor low IQ measured earlier appeared to explain the findings. Because the conditions in Romanian orphanages at the time these children were adopted were characterized by multiple risk factors, including gross privation of basic needs and exposure to infectious agents, the factor(s) that produced the increase in cortisol production cannot be determined. Nor could we determine whether these results reflected effects on the limbic–hypothalamic–pituitary– adrenal axis directly or were mediated by differences in parent–child interactions or family stress occasion by behavioral problems associated with prolonged orphanage care in this sample.
Non-Lethal Candida Albicans CPH1/CPH1 EFG1/EFG1 Transcription Factor Mutant Establishing Restricted Zone of Infection in a Mouse Model of Systemic Infection

The cph1/cph1 efg1/efg1 Candida albicans mutant cells were non-lethal in a mouse model of systemic infection. We investigated in vivo proliferation and invasion of C. albicans cells in infected mice to elucidate the interaction between the host and the pathogen. Homogenates of kidneys from the mice infected with the wild-type and the mutant C. albicans cells yielded a mean of 2.1 × 107 CFU/g and 2.2 × 106 CFU/g, respectively. The kidneys from the mice infected with the wild-type cells showed extensive renal cortical necrosis associated with neutrophilic infiltration. There were also wild-type hyphal cells present in abundance. Hence, tubular necrosis leading to renal failure in the mice may be the cause of death. Although the cph1/cph1 efg1/efg1 mutant cells were not lethal, they were capable of establishing restricted zones of infection and colonization near the renal pelvis instead of simply being cleared by the immune system in mice.
Testosterone replacement in hypogonadal men with angina improves ischaemic threshold and quality of life

Background: Low serum testosterone is associated with several cardiovascular risk factors including dyslipidaemia, adverse clotting profiles, obesity, and insulin resistance. Testosterone has been reported to improve symptoms of angina and delay time to ischaemic threshold in unselected men with coronary disease. Objective: This randomised single blind placebo controlled crossover study compared testosterone replacement therapy (Sustanon 100) with placebo in 10 men with ischaemic heart disease and hypogonadism. Results: Baseline total testosterone and bioavailable testosterone were respectively 4.2 (0.5) nmol/l and 1.7 (0.4) nmol/l. After a month of testosterone, delta value analysis between testosterone and placebo phase showed that mean (SD) trough testosterone concentrations increased significantly by 4.8 (6.6) nmol/l (total testosterone) (p = 0.05) and 3.8 (4.5) nmol/l (bioavailable testosterone) (p = 0.025), time to 1 mm ST segment depression assessed by Bruce protocol exercise treadmill testing increased by 74 (54) seconds (p = 0.002), and mood scores assessed with validated questionnaires all improved. Compared with placebo, testosterone therapy was also associated with a significant reduction of total cholesterol and serum tumour necrosis factor α with delta values of −0.41 (0.54) mmol/l (p = 0.04) and −1.8 (2.4) pg/ml (p = 0.05) respectively. Conclusion: Testosterone replacement therapy in hypogonadal men delays time to ischaemia, improves mood, and is associated with potentially beneficial reductions of total cholesterol and serum tumour necrosis factor α.
State-space model generation of distribution networks for model order reduction application

Model order reduction has been the research focus for a long time in large system modeling and simulation field and is also of great significance in distribution grid simulations. However the model formulation requirements of many typical MOR (Model Order Reduction) methods restrict their applications in distribution grids. This paper presents an automated state-space model generation method of large-scale distribution networks for MOR application. The formulation requirements of general MOR methods can be well satisfied with this proposed model. It also shows great advantages over the commonly used MNA (Modified Nodal Analysis) formulation in many aspects. Simulations are performed using the benchmark low voltage test case, proving that the proposed method is feasible as a powerful tool in the modeling and simulation of large-scale distribution grids.
Nested Case-Control Study of One-Carbon Metabolites in Mid-Pregnancy and Risks of Cleft Lip With and Without Cleft Palate

Evidence exists for an association between use of vitamin supplements with folic acid in early pregnancy and reduced risk for offspring with cleft lip with/without cleft palate (CLP). A few observations have been made about nutrients related to one-carbon metabolism other than folate. Our prospective study attempted to extend information on nutrition and CLP by measuring nutrient analytes in mid-pregnancy sera. This study included data from a repository of women's mid-pregnancy serum specimens collected in California from 2003–04. Each woman's specimen was linked with delivery information to determine whether her fetus had CLP or another structural malformation, or was nonmalformed. We identified 89 CLP cases. We randomly selected 409 specimens as controls. Specimens were tested for homocysteine, methylmalonic acid, folate, vitamin B12, pyridoxal phosphate, pyridoxal, pyridoxic acid, riboflavin, choline, betaine, methionine, methionine sulfoxide, cysteine, cystathionine, arginine, and asymmetric and symmetric dimethylarginine. We observed three analytes with odds ratios unlikely to be explained by random variation, i.e., elevated CLP risks were observed for low levels and for high levels of pyridoxal phosphate (vitamin B6), higher levels of choline, and low levels of symmetric dimethylarginine. These data did not show meaningful differences between cases and controls for any other analytes.
Cusp-core transformations in dwarf galaxies: observational predictions

The presence of a dark matter core in the central kiloparsec of many dwarf galaxies has been a long standing problem in galaxy formation theories based on the standard cold dark matter paradigm. Recent simulations, based on Smooth Particle Hydrodynamics and rather strong feedback recipes have shown that it was indeed possible to form extended dark matter cores using baryonic processes related to a more realistic treatment of the interstellar medium. Using adaptive mesh renement, together with a new, stronger supernovae feedback scheme that we have recently implemented in the RAMSES code, we show that it is also possible to form a prominent dark matter core within the well-controlled framework of an isolated, initially cuspy, 10 billion solar masses dark matter halo. Although our numerical experiment is idealized, it allows a clean and unambiguous identication of the dark matter core formation process. Our dark matter inner prole is well tted by a pseudo-isothermal prole with a core radius of 800 pc. The core formation mechanism is consistent with the one proposed recently by Pontzen & Governato. We highlight two key observational predictions of all simulations that nd cusp-core transformations: (i) a bursty star formation history (SFH) with peak to trough ratio of 5 to 10 and a duty cycle comparable to the local dynamical time; and (ii) a stellar distribution that is hot with v= 1. We compare the observational properties of our model galaxy with recent measurements of the isolated dwarf WLM. We show that the spatial and kinematical distribution of stars and HI gas are in striking agreement with observations, supporting the fundamental role played by stellar feedback in shaping both the stellar and dark matter distribution.
Pattern of Hypocretin (Orexin) Soma and Axon Loss, and Gliosis, in Human Narcolepsy

Human narcolepsy is correlated with a greatly reduced number of hypocretin (orexin) containing neurons and axons, and an elevated level of hypothalamic gliosis. We now report that the percentage loss of Hcrt cells and percentage elevation of GFAP staining are variable across forebrain and brainstem nuclei, and are maximal in the posterior and tuberomammillary hypothalamic region. Regional gliosis and percent loss of hypocretin axons in narcoleptics are not correlated with regional hypocretin cell soma density in normals or with regional percent soma loss in narcoleptics. Rather they are independently and strongly correlated with the regional density of hypocretin axons and the message density for hypocretin receptor 2, as quantified in the rat. These results are consistent with the hypotheses that the loss of hypocretin function in narcolepsy results from a cytotoxic or immunologically mediated attack focused on hypocretin receptor 2 or an antigen anatomically linked to hypocretin receptor 2, and that this process is intensified in regions of high axonal density.
Self-Sampling for Human Papillomavirus in a Community Setting: Feasibility in Hispanic Women

Background: The aim of the study was (a) to assess sensitivity and specificity of self-sampling in a community setting for identifying high-risk human papillomavirus (HPV) infection and abnormal Papanicolaou (Pap) smears and (b) to assess satisfaction with this collection method among Hispanic women. Methods: Lay health workers distributed self-collection kits to Hispanic women in the community. Participants collected an unsupervised vaginal sample at home or in the place and time of their preference. Results: A total of 1,213 Hispanics were included and provided a self-sample for HPV testing and were invited for a Pap smear; 662 (55%) of them had a Pap smear and the first 386 of these also had a physician-collected sample for HPV retesting. Using physician collection as the gold standard, unsupervised self-collection had a sensitivity of 90% and specificity of 88% for identifying high-risk HPV. Compared with physician sampling, self-sampling in a community setting had comparable sensitivity for identifying a low-grade lesions or greater in the Pap smear (50% versus 55%; P = 0.45) but lower specificity (94% versus 79%). Overall experience with self-sampling was reported as excellent or very good by 64% and only 2.6% reported a poor or fair experience. Conclusions: Unsupervised self-collection of vaginal samples for HPV testing in a community setting has a high sensitivity for identifying high-risk HPV and a high satisfaction among Hispanics. This approach may benefit populations with limited access to health care or with cultural barriers to cervical cancer screening. (Cancer Epidemiol Biomarkers Prev 2008;17(8):2163–8)
C9ORF72 repeat expansions in mice cause TDP-43 pathology, neuronal loss, and behavioral deficits

A mouse model for ALS A G4C2 repeat expansion in C9ORF72 is known to be the major genetic cause of frontotemporal dementia and amyotrophic lateral sclerosis (c9FTD/ALS). However, a lack of animal models recapitulating key disease features has hindered efforts to understand and prevent c9FTD/ALS-related neurodegeneration. Until now. Chew et al. describe a mouse model that mimics both neuropathological and clinical phenotypes of c9FTD/ALS. Science, this issue p. 1151 A mouse model mimics the pathological and behavioral abnormalities seen in certain amyotrophic lateral sclerosis or frontotemporal dementia patients. The major genetic cause of frontotemporal dementia and amyotrophic lateral sclerosis is a G4C2 repeat expansion in C9ORF72. Efforts to combat neurodegeneration associated with “c9FTD/ALS” are hindered by a lack of animal models recapitulating disease features. We developed a mouse model to mimic both neuropathological and clinical c9FTD/ALS phenotypes. We expressed (G4C2)66 throughout the murine central nervous system by means of somatic brain transgenesis mediated by adeno-associated virus. Brains of 6-month-old mice contained nuclear RNA foci, inclusions of poly(Gly-Pro), poly(Gly-Ala), and poly(Gly-Arg) dipeptide repeat proteins, as well as TDP-43 pathology. These mouse brains also exhibited cortical neuron and cerebellar Purkinje cell loss, astrogliosis, and decreased weight. (G4C2)66 mice also developed behavioral abnormalities similar to clinical symptoms of c9FTD/ALS patients, including hyperactivity, anxiety, antisocial behavior, and motor deficits.
Uso da terapia não farmacológica, medicina alternativa e complementar na fibromialgia

A fibromialgia e uma sindrome dolorosa cronica que afeta ate 5% da populacao mundial. Pode associar-se com disturbios do sono, do humor e fadiga, e cursar com incapacidade funcional. Sua patogenese envolve disturbio de modulacao central da dor, comprometimento do sistema inibitorio descendente e hiperatividade da substância P. Em funcao da vasta sintomatologia apresentada pelos pacientes e da natureza multifatorial da sua patogenese, seu tratamento ideal requer uma abordagem multidisciplinar incluindo a associacao de terapia farmacologica e nao farmacologica. A terapia farmacologica atualmente preconizada nessa sindrome inclui, entre outros compostos, antidepressivos, moduladores dos canais de calcio, relaxantes musculares e analgesicos. O tratamento nao farmacologico e realizado, na maioria dos casos, por meio de educacao do paciente, atividade fisica aerobica supervisionada e terapia cognitivo-comportamental. No entanto, muitos pacientes nao apresentam respostas satisfatorias ou apresentam efeitos colaterais associados ao uso dos farmacos a longo prazo, alem de referirem dificuldades em permanecer em uma terapia baseada em exercicios e medicina fisica. Ha, portanto, um crescente interesse por parte dos medicos e pacientes por uma terapia alternativa e complementar na fibromialgia. Nesta revisao, os autores discorrem sobre as diversas modalidades terapeuticas empregadas nessa doenca, enfatizando as evidencias da terapia nao farmacologica e do uso de medicina alternativa e complementar nesses pacientes.
Endometrioid stromal sarcomas of the ovary. A clinicopathologic analysis of 23 cases

The clinical and pathologic features of 23 endometrioid stromal sarcomas of the ovary were analyzed. The patients' ages ranged from 20 to 76 years (average, 54 years). The most common presenting symptom was abdominal swelling or pain. In 12 cases the tumors were unilateral and in 11 cases they involved both ovaries. Four of the tumors were Stage I, nine Stage II, and eight Stage III; two were Stage IV because of the presence of pulmonary metastases. In nine of the cases there was a prior, synchronous or subsequent endometrial stromal sarcoma of the uterus. Nineteen tumors with less than 10 mitotic figures (MF) per 10 high power fields (HPF) were classified as low grade and the remaining four tumors with 12 to 30 MF per 10 HPF were designated as high grade. Only 2 of the 19 patients with low‐grade tumors are known to have died of their disease and 9 of those whose tumor had spread beyond the ovary at the time of presentation were alive one or more years postoperatively. Three of the four patients with high‐grade tumors died of their disease within 4 years. Cancer 53:1143‐1155, 1984.
Prism adaptation reduces the disengage deficit in right brain damage patients

Recent research has shown that prism adaptation alleviates some of the symptoms of neglect. Although prism adaptation can aid patients with neglect, the mechanisms underlying these benefits remain largely unknown. One way in which prisms may work is by altering attentional orienting mechanisms known to be impaired in neglect. To investigate this hypothesis, we tested four right brain damaged patients (two with neglect) on a reflexive covert attention task before and after rightward prism adaptation and compared them with a group of healthy controls who underwent sham prism adaptation. Results demonstrated that rightward prism adaptation reduced both the rightward attentional bias, and the disengage deficit in patients with right brain damage irrespective of the presence of neglect.
Temperature dependence of the Kondo resonance in YbAl3.

We report the observation of a strong temperature dependence of the Kondo resonance in the valence-band photoemission spectrum and of the 3d→4f white line in the x-ray absorption spectrum of YbAl 3 . The asymmetric Kondo resonance has a binding energy of ∼35 meV with a ∼50 meV width. The temperature dependence of the Yb 4f spectral features and valence are well reproduced by Anderson impurity calculations with a Kondo temperature of T K ≃400 K, demonstrating that both spectroscopic and near ground state properties can be described within a unified theoretical framework
Self-concept development and measurement in children with mild intellectual disabilities

Objective: Using a multi-trait–multi-method technique, self-concept was analysed as a function of chronological age in children with mild intellectual disabilities. Also, relations between reading achievement and self-concept were measured. Methods: Participants were assessed on the Woodcock Reading Mastery Test–Revised, the Pictorial Scale of Perceived Competence and Social Acceptance and the Self-Description Questionnaire I–Individual Administration. Results: A median split was run to divide participants into younger and older groups; older participants evidenced coefficients that revealed more multidimensionality, stability and discriminant validity. Also, a significant canonical correlation was found between the Harter Pictorial Scale at Time 1 and WRMT-R at Time 2, χ2(8) = 17.99, r = 0.62, p = 0.02. Conclusion: As a whole, these results suggest that children with intellectual disabilities evince self-concept development similar to what would be expected in typically-developing children.
Clone‐ and Gene‐Specific Aberrations of Parental Imprinting in Human Induced Pluripotent Stem Cells

Genomic imprinting is an epigenetic phenomenon whereby genes are expressed in a monoallelic manner, which is inherited either maternally or paternally. Expression of imprinted genes has been examined in human embryonic stem (ES) cells, and the cells show a substantial degree of genomic imprinting stability. Recently, human somatic cells were reprogrammed to a pluripotent state using various defined factors. These induced pluripotent stem (iPS) cells are thought to have a great potential for studying genetic diseases and to be a source of patient‐specific stem cells. Thus, studying the expression of imprinted genes in these cells is important. We examined the allelic expression of various imprinted genes in several iPS cell lines and found polymorphisms in four genes. After analyzing parent‐specific expression of these genes, we observed overall normal monoallelic expression in the iPS cell lines. However, we found biallelic expression of the H19 gene in one iPS cell line and biallelic expression of the KCNQ10T1 gene in another iPS cell line. We further analyzed the DNA methylation levels of the promoter region of the H19 gene and found that the cell line that showed biallelic expression had undergone extensive DNA demethylation. Additionally we studied the imprinting gene expression pattern of multiple human iPS cell lines via DNA microarray analyses and divided the pattern of expression into three groups: (a) genes that showed significantly stable levels of expression in iPS cells, (b) genes that showed a substantial degree of variability in expression in both human ES and iPS cells, and (c) genes that showed aberrant expression levels in some human iPS cell lines, as compared with human ES cells. In general, iPS cells have a rather stable expression of their imprinted genes. However, we found a significant number of cell lines with abnormal expression of imprinted genes, and thus we believe that imprinted genes should be examined for each cell line if it is to be used for studying genetic diseases or for the purpose of regenerative medicine. STEM CELLS 2009;27:2686–2690
prognostic marker for reduced risk of recurrence in epithelial ovarian cancer

Division of Gynecologic Oncology, Department Materno Infantile e Tecnologie Biomediche, University of Brescia, Brescia, Italy Section of Medical Statistics and Biometry, Department of Biomedical Sciences and Biotechnology, University of Brescia, Brescia, Italy Department of Pathology, University of Brescia, Brescia, Italy Department of Obstetrics & Gynecology, Division of Gynecologic Oncology, Yale University New Haven Hospital, CT, USA