Miracle-dz/UniFAR-FTUs huggingface dataset:
Pattern and Predictors of Immunologic Recovery in Human Immunodeficiency Virus-Infected Children Receiving Non-Nucleoside Reverse Transcriptase Inhibitor-Based Highly Active Antiretroviral Therapy

Background: Non-nucleoside reverse transcription inhibitor (NNRTI)-based highly active antiretroviral therapy (HAART) is the recommended first-line regimen for children in Thailand. This study was aimed to assess pattern and predictors of immune recovery in antiretroviral-naive Thai children starting NNRTI-based HAART. Methods: Records were extracted from clinical databases of 2 treatment cohorts in Thailand. The inclusion criteria were HIV-infected naive children who initiated NNRTI-based HAART when CD4 <25%. Immune recovery was defined as achieving a target CD4% of 25. The impact of age, gender, baseline clinical category, CD4 and HIV RNA titer, and regimen on immune recovery to weeks 96 was assessed using multiple logistic regression. Results: There were 274 patients (52% females) with a median baseline age of 7 (Interquartile range [IQR]: 4–9) years and a median CD4% of 5 (IQR: 1–12) who started treatment with nevirapine (66%) or efavirenz (34%) based HAART. Median duration of follow-up was 168 (IQR: 120–192) weeks. The median CD4% increase from baseline was 7% (IQR: 5–11) and 18% (IQR: 12–23) at weeks 24 and 96, respectively. The probability of reaching target CD4% was 51% (95% confidence interval: 45%–57%) by week 96. The predictors of immune recovery at week 96 were younger age, female gender, higher baseline CD4%, and sustained virologic suppression after week 24. Conclusion: In this cohort of children with low baseline CD4, half achieved immune recovery after 96 weeks of HAART. The predictors for immune recovery are younger children, female gender, high baseline CD4%, and long-term virologic suppression.
Temperature-sensitive mutants of influenza virus. 3. Further characterization of the ts-1(E) influenza A recombinant (H3N2) virus in man.

The potential of live, attenuated influenza A virus vaccine strain (ts-1[E]) to safely evoke immunity in man was studied. Virus grown in eggs, like virus grown in bovine kidney culture, exhibited an acceptable balance between attenuation and immunogenicity. The attenuation of this virus was evident by its large 50% infectious dose for man (105 TCID-,) and by the failure of a large quantity of virus (107 TCID-,) to cause influenzal illness. The ts-1[E] virus replicated well in the nasopharynx and was genetically stable in man. Moderate levels of neutralizing antibodies were induced in serum and nasal wash, and there was a suggestion that the latter antibody was associated with resistance to wild-type influenza A virus. However, the ts-1[E] virus was a poor stimulator of antibody to neuraminidase. Overall the pattern of infection produced by the ts-l[E] recombinant virus was comparable to that seen with wild-type virus but was of shorter duration and lesser magnitude. These features make the ts-1[E] virus suitable for use as a live influenza A vaccine in man.
A pivotal involvement of IFN-gamma in the pathogenesis of acetaminophen-induced acute liver injury.

In wild-type BALB/c mice, i.p. administration of acetaminophen (APAP; 750 mg/kg) induced intrahepatic IFN-gamma mRNA expression and a marked increase in serum transaminase levels, leading to acute lethality of approximately 45%. Histopathological examination showed centrilobular hepatic necrosis with leukocyte infiltration and a large number of apoptotic hepatocytes 10 and 24 h after APAP challenge. mRNA expression of intercellular adhesion molecule 1, vascular cell adhesion molecule 1, interleukin (IL) 1alpha, IL-1beta, IL-6, tumor necrosis factor alpha, monocyte chemoattractant protein 1, macrophage inflammatory protein (MIP) 1alpha, MIP-2, KC, IP-10, Mig, Fas, and inducible nitric oxide synthase was enhanced in the liver of wild-type mice injected with APAP. To clarify the role of IFN-gamma in this process, IFN-gamma-deficient mice were treated in the same manner. All IFN-gamma-deficient mice survived with reduced serum transaminase elevation and attenuated hepatic necrosis, leukocyte infiltration, and hepatocyte apoptosis. The gene expression of all molecules was significantly attenuated in IFN-gamma-deficient mice. Administration of an anti-IFN-gamma neutralizing antibody even 2 or 8 h after APAP challenge to wild-type mice alleviated APAP-induced liver injury, and all mice survived. Thus, IFN-gamma is responsible for APAP-induced liver injury by mediating leukocyte infiltration, hepatocyte apoptosis, and NO production as well as cytokine and chemokine production. Moreover, immunoneutralization of IFN-gamma may be therapeutically effective for developing APAP-induced liver injury.
Sensitization of Dopamine‐Stimulated Adenylyl Cyclase in the Striatum of 1‐Methyl‐4‐Phenyl‐1,2,3,6‐Tetrahydropyridine‐Treated Rhesus Monkeys and Patients with Idiopathic Parkinson's Disease

Abstract: Dopamine‐stimulated adenylyl cyclase activity was measured in striatal homogenates of l‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐treated rhesus monkeys and humans with idiopathic Parkinson's disease and compared with the activity in control tissue. No differences between parkinsonian and control tissue were found in the presence of 20 mM NaCl. However, when 120 mM NaCl was included in the assay medium, a significantly higher increase in the Vmax of dopamine‐stimulated adenylyl cyclase activity was observed in the caudate of MPTP‐parkinsonian rhesus monkeys and the putamen of patients with idiopathic Parkinson's disease. No such sensitization was seen in the MPTP‐treated rhesus putamen or human Parkinson's disease caudate tissue. A role of D2 receptors in this sensitization could be ruled out by the concomitant use of the D2 antagonist l‐sulpiride and by [3H]spiperone saturation analysis of the D2 receptor density, which was found at control level in the caudate tissue of MPTP‐treated rhesus monkeys. Similarly, on the basis of saturation binding with the D1 selective ligand 125I‐SCH 23982, there was no difference in caudate nucleus D1 receptor densities between control and MPTP‐treated monkeys. Our results point to a region‐specific functional sensitization of D1 receptors as a consequence of severe dopaminergic denervation of the striatum and suggest the possibility of a therapeutic potential of a D1 agonist with full intrinsic activity in Parkinson's disease.
Endometrial and endocervical secretion: the search for histochemical differentiation.

OBJECTIVE To determine the ideal histochemical stain to differentiate between non-neoplastic and neoplastic endocervix and endometrium. STUDY DESIGN A total of 90 cases representing nonneoplastic cervix, non-neoplastic endometrium, endocervical adenocarcinoma and endometrial adenocarcinoma were stained with toluidine blue (TB); methylene blue (MB); mucicarmine (MUC); periodic acid-Schiff before and after diastase digestion (PAS, PAS-D); Alcian blue, pH 2.5 (AB); and periodic acid-Schiff after Alcian blue, pH 2.5 (PAB). Cases were blinded and randomly divided between two pathologists for evaluation of the staining and the staining distribution of the glandular epithelium by means of a 36-color scheme. RESULTS The majority of non-neoplastic endocervix samples stained blue with MB (57%), fuchsia with MUC (70%), magenta with PAS (77%) and PAS-D (73%) and dark turquoise with AB (70%). The majority of non-neoplastic endometrium samples stained slate blue with TB (60%) and pink with PAS-D (53.3%). There is statistical difference (p < 0.05) in the color of the epithelium and secretions between the non-neoplastic cervix and endometrium. The malignant glands of endocervical origin could be differentiated significantly (p = 0.043) from non-neoplastic endocervical epithelium by MUC. The epithelium of the non-neoplastic endometrium is significantly differentiated from malignant endometrium using TB (p = 0.015) and MB (p = 0.038). Endocervical carcinoma could be significantly differentiated from endometrial carcinoma by MB. The staining in endocervical adenocarcinoma and endometrial carcinoma was predominantly present in both apical and cytoplasmic locations compared to their non-neoplastic counterparts (endocervix, p = 0.003; endometrium, p = 0.049). CONCLUSION This study showed that a panel of histochemical stains could differentiate glandular cells of endocervical epithelium from endometrium.
Impact of oceanic processes on the carbon cycle during the last termination

During the last termination (from ~18 000 years ago to ~9000 years ago), the climate significantly warmed and the ice sheets melted. Simultaneously, atmospheric CO2 increased from ~190 ppm to ~260 ppm. Although this CO2 rise plays an important role in the deglacial warming, the reasons for its evolution are difficult to explain. Only box models have been used to run transient simulations of this carbon cycle transition, but by forcing the model with data constrained scenarios of the evolution of temperature, sea level, sea ice, NADW formation, Southern Ocean vertical mixing and biological carbon pump. More complex models (including GCMs) have investigated some of these mechanisms but they have only been used to try and explain LGM versus present day steady-state climates. In this study we use a coupled climate-carbon model of intermediate complexity to explore the role of three oceanic processes in transient simulations: the sinking of brines, stratification-dependent diffusion and iron fertilization. Carbonate compensation is accounted for in these simulations. We show that neither iron fertilization nor the sinking of brines alone can account for the evolution of CO2, and that only the combination of the sinking of brines and interactive diffusion can simultaneously simulate the increase in deep Southern Ocean δ13C. The scenario that agrees best with the data takes into account all mechanisms and favours a rapid cessation of the sinking of brines around 18 000 years ago, when the Antarctic ice sheet extent was at its maximum. In this scenario, we make the hypothesis that sea ice formation was then shifted to the open ocean where the salty water is quickly mixed with fresher water, which prevents deep sinking of salty water and therefore breaks down the deep stratification and releases carbon from the abyss. Based on this scenario, it is possible to simulate both the amplitude and timing of the long-term CO2 increase during the last termination in agreement with ice core data. The atmospheric δ13C appears to be highly sensitive to changes in the terrestrial biosphere, underlining the need to better constrain the vegetation evolution during the termination.
Among substituted 9,10-dihydro-9,10-[1,2]benzenoanthracene-1,4,5,8-tetraones, the lead antitumor triptycene bisquinone TT24 blocks nucleoside transport, induces apoptotic DNA fragmentation and decreases the viability of L1210 leukemic cells in the nanomolar range of daunorubicin in vitro

In contrast to their inactive parent compound triptycene (code name TT0), several new synthetic analogs (TT code number) have antileukemic activities and remain effective in daunorubicin (DAU)-resistant tumor sublines in vitro. Among variously substituted 9,10-dihydro-9,10-[1,2]benzenoanthracene-1,4,5,8-tetraones, a total of six lead antitumor compounds have been identified, and their code names are TT2, TT13, TT16, TT19, TT21 and TT24. These active antitumor triptych structures have bisquinone functionality, and various bromo, methoxy, methylamino and/or dimethylamino substitutions with or without longer alkyl chains on the amino function. Like the anthracycline quinone antibiotic DAU, these triptycene (TT) bisquinones also inhibit DNA synthesis and induce DNA cleavage in relation with their cytotoxic activities, but have the additional advantage of blocking the cellular transport of purine and pyrimidine nucleosides, an effect which DAU cannot do. As demonstrated by intact chromatin precipitation and agarose gel electrophoresis, the ability of TT bisquinones and DAU to induce DNA fragmentation is biphasic with a peak that shifts to lower concentrations with increasing times of drug exposure. The most effective lead antitumor compound, TT24, induces DNA cleavage in the same concentration-dependent manner as DAU at 24 h (similar peak in response to 1.6 μ M) and is nearly equipotent to DAU against L1210 tumor cell viability at day 4 (IC50 values of TT24 and DAU: 48 and 25 nM, respectively). The mechanism by which TT24 induces DNA fragmentation is inhibited by actinomycin D, cycloheximide, benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone, benzyloxycarbonyl-Ile-Glu-Thr-Asp-fluoromethyl ketone, N-tosyl-L-phenylalanine chloromethyl ketone and ZnSO4, suggesting that TT bisquinones trigger apoptosis by caspase and endonuclease activation. Since TT24 is cytotoxic in the nanomolar range of DAU, but might have a more versatile mechanism of action than DAU in wild-type and multidrug-resistant tumor cells, this new class of DNA-damaging quinone antitumor drugs inhibiting nucleoside transport might be valuable to develop new means of polychemotherapy.
Hemodialysis Patients with Incidental Hypothyroidism -The Approach to

Aim: This study investigated the effect of L-thyroxine on clinical manifestations and EPO responses, and the approach to L-thyroxine dosage adjustment for HD patients with Incidental hypothyroidism. Methods: Ten cases of Incidental hypothyroidism were diagnosed in 695 HD patients. In this study, L-thyroxine therapy was given only to hypothyroid HD patients with clinical symptoms, hematocrit 30%. The clinical manifestations were found to improve after discontinuation of medications in two of those three patients with medication-induced hypothyroidism. L-thyroxine therapy may not be required for HD patients with hypothyroidism and hematocrit >35%. Conclusions: Adjustment of L-thyroxine dosage according to clinical manifestations, rather than TSH, T4 or FT4 value, is a practical and effective treatment approach for HD patients with hypothyroidism. This approach of L-thyroxine therapy could reduce EPO dosage, and improve both anemia and clinical symptoms. Whether the identified HD patients with hypothyroidism should be treated with L-thyroxine for the action of EPO on the bone marrow or left untreated for energy conservation is worth further investigation. The aim of this study is to investigate the effect of L-thyroxine on clinical manifestations and EPO responses, and the approach to L-thyroxine dosage adjustment for HD patients with Incidental hypothyroidism.
The mammary gland in small ruminants: major morphological and functional events underlying milk production – a review

The importance of small ruminants to the dairy industry has increased in recent years, especially in developing countries, where it has a high economic and social impact. Interestingly and despite the fact that the mammary gland is the specialised milk production organ, very few authors studied the modifications occurring in the mammary gland through the lactation period in production animals, particularly in the small ruminants, sheep (Ovis aries) and goat (Capra hircus). Nevertheless, understanding the different mammary gland patterns throughout lactation is essential to improve dairy production. In addition, associating these patterns with different milking frequencies, lactation number or different diets is also of high importance, directly affecting the dairy industry. The mammary gland is commonly composed of parenchyma and stroma, which includes the ductal system, with individual proportions of each changing during the different periods and yields in a lactation cycle. Indeed, during late gestation, as well as during early to mid-lactation, mammary gland expansion occurs, with an increase in the number of epithelial cells and lumen area, which leads to increment of the parenchyma tissue, as well as a reduction of stroma, corresponding macroscopically to the increase in mammary gland volume. Throughout late lactation, the mammary gland volume decreases owing to the regression of the secretory structure. In general, common mammary gland patterns have been shown for both goats and sheep throughout the several lactation stages, although the number of studies is limited. The main objective of this manuscript is to review the colostrogenesis and lactogenesis processes as well as to highlight the mammary gland morphological patterns underlying milk production during the lactation cycle for small ruminants, and to describe potential differences between goats and sheep, hence contributing to a better description of mammary gland development during lactation for these two poorly studied species.
Chiari Type I Malformations in Young Adults: Implications for the College Health Practitioner

Abstract The authors describe 2 cases of Chiari type I malformation (CM-I) in students presenting to a college health center within a 6-month period. A review of CM-I, including epidemiology, typical presentation, evaluation, and management, is followed by a discussion of the clinical and functional implications of the disorder in an emerging adult population.
Effect of Preventive Messages Tailored to Family History on Health Behaviors: The Family Healthware Impact Trial

PURPOSE We wanted to determine the impact of automated family history assessment and tailored messages for coronary heart disease, stroke, diabetes, colorectal, breast, and ovarian cancer on preventive behaviors compared with a standard preventive message. METHODS The study was a cluster-randomized clinical trial that included 41 primary care practices, the majority in the Midwest, using Family Healthware, a self-administered, Web-based tool that assesses familial risk for the diseases and provides personalized risk-tailored messages. Patients in the control group received an age- and sex-specific health message related to lifestyle and screening. Smoking cessation, fruit and vegetable intake, physical activity, aspirin use, blood pressure, and cholesterol and blood glucose screening were assessed at baseline and 6 months after the intervention. RESULTS Of 4,248 participants, 3,344 (78%) completed the study. Participants were white (91%), female (70%), and insured (97%), and had a mean age of 50.6 years (range 35–65 years). Intervention participants were more likely to increase daily fruit and vegetable consumption from 5 or fewer servings a day to 5 or more servings a day (OR = 1.29; 95% confidence interval [CI], 1.05–1.58) and to increase physical activity (OR = 1.47; 95% CI, 1.08–1.98) to 5 to 6 times a week for 30 minutes or more a week. The absolute differences in proportion were 3% and 4%, respectively. Intervention participants were less likely to move from not having cholesterol screening in the last 5 years to having their cholesterol measured within 5 years (OR = 0.34; 95% CI, 0.17–0.67), with an absolute difference of 15%. CONCLUSIONS Messages tailored to an individual’s familial risk for 6 common diseases modestly increased self-reported physical activity and fruit and vegetable intake but reduced the likelihood of receiving cholesterol screening.
Sympathoadrenal and immune system activation during the periparturient period and their association with bovine coliform mastitis. A review

Summary Increased incidence of clinical mastitis in high‐yielding cows during early lactation has been attributed to a depressed functional capacity of the immune system. Sympathoadrenal factors are known to play an important role in modulating the host susceptibility and resistance to infectious diseases. Of primary importance in combating acute intramammary infections are polymorphonuclear leukocytes (PMN), as they represent one of the early lines of immunological defense. The release of stress hormones at parturition and during the first weeks of lactation has been proposed to partly contribute to the impaired function of PMN. Here, we summarize the current understanding of the stress‐induced peripheral effectors, i.e. the limbs of the sympathetic system and the hypothalamic‐pituitary‐adrenal axis, on PMN function around parturition and during coliform mastitis. The questions as to whether and how stress induced secretion of glucocorticoids and catecholamines might affect the lactating dairy cow's udder health will be addressed.
Homer Regulates Gain of Ryanodine Receptor Type 1 Channel Complex*

Homer proteins form an adapter system that regulates coupling of group 1 metabotropic glutamate receptors with intracellular inositol trisphosphate receptors and is modified by neuronal activity. Here, we demonstrate that Homer proteins also physically associate with ryanodine receptors type 1 (RyR1) and regulate gating responses to Ca2+, depolarization, and caffeine. In contrast to the prevailing notion of Homer function, Homer1c (long form) and Homer1-EVH1 (short form) evoke similar changes in RyR activity. The EVH1 domain mediates these actions of Homer and is selectively blocked by a peptide that mimics the Homer ligand. 1B5 dyspedic myotubes expressing RyR1 with a point mutation of a putative Homer-binding domain exhibit significantly reduced (∼33%) amplitude in their responses to K+depolarization compared with cells expressing wild type protein. These results reveal that in addition to its known role as an adapter protein, Homer is a direct modulator of Ca2+ release gain. Homer is the first example of an “adapter” that also modifies signaling properties of its target protein. The present work reveals a novel mechanism by which Homer directly modulates the function of its target protein RyR1 and excitation-contraction coupling in skeletal myotubes. This form of regulation may be important in other cell types that express Homer and RyR1.
Complete Inhibition of Streptococcus pneumoniae RecA Protein-catalyzed ATP Hydrolysis by Single-stranded DNA-binding Protein (SSB Protein)

The ATP-dependent three-strand exchange activity of the Streptococcus pneumoniae RecA protein (RecA(Sp)), like that of the Escherichia coliRecA protein (RecA(Ec)), is strongly stimulated by the single-stranded DNA-binding protein (SSB) from either E. coli (SSB(Ec)) or S. pneumoniae (SSB(Sp)). The RecA(Sp) protein differs from the RecA(Ec) protein, however, in that its ssDNA-dependent ATP hydrolysis activity is completely inhibited by SSB(Ec) or SSB(Sp) protein, apparently because these proteins displace RecA(Sp) protein from ssDNA. These results indicate that in contrast to the mechanism that has been established for the RecA(Ec) protein, SSB protein does not stimulate the RecA(Sp) protein-promoted strand exchange reaction by facilitating the formation of a presynaptic complex between the RecA(Sp) protein and the ssDNA substrate. In addition to acting presynaptically, however, it has been proposed that SSB(Ec) protein also stimulates the RecA(Ec) protein strand exchange reaction postsynaptically, by binding to the displaced single strand that is generated when the ssDNA substrate invades the homologous linear dsDNA. In the RecA(Sp) protein-promoted reaction, the stimulatory effect of SSB protein may be due entirely to this postsynaptic mechanism. The competing displacement of RecA(Sp) protein from the ssDNA substrate by SSB protein, however, appears to limit the efficiency of the strand exchange reaction (especially at high SSB protein concentrations or when SSB protein is added to the ssDNA before RecA(Sp) protein) relative to that observed under the same conditions with the RecA(Ec) protein.
Bronchial Challenge with Serotonin in Asthmatics

Bronochial challenge with serotonin creatinine in phosphate buffer was performed in 20 stable asthmatics. In contrast to some earlier studies we observed no changes in FEV1 or FVC 0 and 2 min after provocation with increasing conecntrations of serotonin (maximal conecntration 20 mg/ml). In the first eight patients the PC20 histamine was 0.125–0.65 mg/ml, performed on a separate day. In three other asthmatics serotonin chloride 20 mg/ml did not affect lung function or produce any subjective symptoms. Serotonin can not be used to evaluate non‐specific bronchial hyperreactivity in asthmatics.