Miracle-dz/UniFAR-FTUs huggingface dataset:
Gut and blood differ in constitutive blocks to HIV transcription, suggesting tissue-specific differences in the mechanisms that govern HIV latency

Latently-infected CD4+ T cells are widely considered to be the major barrier to a cure for HIV. Much of our understanding of HIV latency comes from latency models and blood cells, but most HIV-infected cells reside in lymphoid tissues such as the gut. We hypothesized that tissue-specific environments may impact the mechanisms that govern HIV expression. To assess the degree to which different mechanisms inhibit HIV transcription in the gut and blood, we quantified HIV transcripts suggestive of transcriptional interference (U3-U5; "Read-through"), initiation (TAR), 5' elongation (R-U5-pre-Gag; "Long LTR"), distal transcription (Nef), completion (U3-polyA; "PolyA"), and multiple splicing (Tat-Rev) in matched peripheral blood mononuclear cells (PBMCs) and rectal biopsies, and matched FACS-sorted CD4+ T cells from blood and rectum, from two cohorts of ART-suppressed individuals. Like the PBMCs, rectal biopsies showed low levels of read-through transcripts (median = 23 copies/106 cells) and a gradient of total (679)>elongated(75)>Nef(16)>polyadenylated (11)>multiply-spliced HIV RNAs(<1) [p<0.05 for all], demonstrating blocks to HIV transcriptional elongation, completion, and splicing. Rectal CD4+ T cells showed a similar gradient of total>polyadenylated>multiply-spliced transcripts, but the ratio of total to elongated transcripts was 6-fold lower than in blood CD4+ T cells (P = 0.016), suggesting less of a block to HIV transcriptional elongation in rectal CD4+ T cells. Levels of total transcripts per provirus were significantly lower in rectal biopsies compared to PBMCs (median 3.5 vs. 15.4; P = 0.008) and in sorted CD4+ T cells from rectum compared to blood (median 2.7 vs. 31.8; P = 0.016). The lower levels of HIV transcriptional initiation and of most HIV transcripts per provirus in the rectum suggest that this site may be enriched for latently-infected cells, cells in which latency is maintained by different mechanisms, or cells in a "deeper" state of latency. These are important considerations for designing therapies that aim to disrupt HIV latency in all tissue compartments.
Periodontal regenerative effect of enamel matrix derivative in diabetes

The present study aimed to investigate the periodontal regenerative effect of enamel matrix derivative (EMD) in diabetes. Thirty-six rats were assigned to streptozotocin-induced diabetes or control (non-diabetic) groups. Three-wall intrabony defects were surgically generated in the bilateral maxilla molar, followed by application of EMD or saline. Primary wound closure and defect fill were evaluated via histomorphological analysis and micro-computed tomography. mRNA expression levels of inflammatory and angiogenic factors in the defects were quantified via real-time polymerase chain reaction. Gingival fibroblasts were isolated from control animals and cultured in high-glucose (HG) or control medium. The effects of EMD on insulin resistance and PI3K/Akt/VEGF signaling were evaluated. The achievement rate of primary closure and the parameters of defect fill were significantly higher at EMD-treated site than at EMD-untreated sites in both diabetic and non-diabetic rats, although defect fill in the diabetic groups was significantly lower in the control groups on two-way repeated-measures analysis of variance (for both, p<0.05). Newly formed bone and cementum were significantly increased at EMD-treated sites in diabetic rats than at EMD-untreated sites in control rats (for both, p<0.05). Vegf was significantly upregulated at EMD-treated sites in both diabetic and non-diabetic rats (for both, p<0.05). In vitro, insulin or EMD-induced Akt phosphorylation was significantly lower in cells cultured in HG medium (p<0.05). EMD-mediated Vegf upregulation was suppressed by the Akt inhibitor wortmannin, although the effect was significantly lower in HG medium (p<0.01). In conclusion, EMD might promote periodontal tissue regeneration via Akt/VEGF signaling, even in a diabetic condition.
Discriminative learning of similar objects enhances memory for the objects and contexts

How to improve our episodic memory is an important issue in the field of memory. In the present study, we used a discriminative learning paradigm that was similar to a paradigm used in animal studies. In Experiment 1, a picture (e.g., a dog) was either paired with an identical picture, with a similar picture of the same concept (e.g., another dog), or with a picture of a different concept (e.g., a cat). Then, after intervals of 10 min, 1 d, and 1 wk, participants were asked to perform a 2-alternative forced-choice (2AFC) task to discriminate between a repeated and a similar picture, followed by the contextual judgment. In Experiment 2, eye movements were measured when participants encoded the pairs of pictures. The results showed that by discriminative learning, there was better memory performance in the 2AFC task for the “same” and “similar” conditions than for the “different” condition. In addition, there was better contextual memory performance for the “similar” condition than for the other two conditions. With regard to the eye movements, the participants were more likely to fixate on the lure objects and made more saccades between the target and lure objects in the “similar” (versus “different”) condition. The number of saccades predicted how well the targets were remembered in both the 2AFC and contextual memory tasks. These results suggested that with discriminative learning of similar objects, detailed information could be better encoded by distinguishing the object from similar interferences, making the details and the contexts better remembered and retained over time.
The influence of the Community‐based Health Planning and Services (CHPS) program on community health sustainability in the Upper West Region of Ghana

Ghana introduced Community-based Health Planning and Services (CHPS) to improve primary health care in rural areas. The extension of health care services to rural areas has the potential to increase sustainability of community health. Drawing on the capitals framework, this study aims to understand the contribution of CHPS to the sustainability of community health in the Upper West Region of Ghana-the poorest region in the country. We conducted in-depth interviews with community members (n = 25), key informant interviews with health officials (n = 8), and focus group discussions (n = 12: made up of six to eight participants per group) in six communities from two districts. Findings show that through their mandate of primary health care provision, CHPS contributed directly to improvement in community health (eg, access to family planning services) and indirectly through strengthening social, human, and economic capital and thereby improving social cohesion, awareness of health care needs, and willingness to take action at the community level. Despite the current contributions of CHPS in improving the sustainability of community health, there are several challenges, based on which we recommend, that government should increase staffing and infrastructure in order to strengthen and maintain the functionality of CHPS.
Basic patient characteristics predict antimicrobial resistance in E. coli from urinary tract specimens: a retrospective cohort analysis of 5246 urine samples.

BACKGROUND Antimicrobial resistance data from surveillance networks are frequently do not accurately predict resistance patterns of urinary tract infections at the bedside. OJECTIVE To determine simple patient- and institution-related risk factors affecting antimicrobial resistance patterns of Escherichia coli urine isolates. METHODS From January 2012 to May 2015 all consecutive urine samples with significant growth of E. coli (≥103 CFU/ml) obtained from a tertiary care hospital were analysed for antimicrobial susceptibility and related to basic clinical data such a patient age, ward, sample type (catheter vs non-catheter urine). RESULTS Antimicrobial susceptibility testing was available for 5246 E. coli urine isolates from 4870 patients. E. coli was most commonly resistant to amoxicillin (43.1%), cotrimoxazole (24.5%) and ciprofloxacin (17.4%). Resistance rates were low for meropenem (0.0%), fosfomycin (0.9%) and nitrofurantoin (1.5%). Significantly higher rates of resistance to ciprofloxacin (32.8 vs 15.8%) and cotrimoxazole (30.6 vs 23.9%) were found in urological patients compared with patients on other wards (p <0.01). In multivariable analysis, predictors for E. coli resistance against ciprofloxacin and cotrimoxazole were: treatment in the urological unit (odds ratio [OR] 2.04, 95% confidence interval [CI] 1.63-2.54; p <0.001 and OR 1.33, 95% CI 1.07-1.64; p = 0.010, respectively), male sex (OR 1.93, 95% CI 1.630-2.29; p <0.001 and OR 1.22, 95% CI 1.22-1.04; p = 0.015), and only to a lesser extent urine samples obtained from indwelling catheters (OR 1.30, 95% CI 1.05-1.61; p = 0.014 and OR 1.26, 95% CI 1.04-1.53; p = 0.020). Age ≥65 years was associated with higher resistance to ciprofloxacin (OR 1.42, 95% CI 1.21-1.67; p <0.001), but lower resistance to cotrimoxazole (OR 0.76, 95% CI 0.67-0.86; p <0.001). CONCLUSIONS Simple bedside patient data such as age, sex and treating hospital unit help to predict antimicrobial resistance and can improve the empirical treatment of urinary tract infections.
Home-based treatment in Monaghan: the first two years

Abstract Objectives: To describe a home-based treatment (HBT) service. To profile the patient population using HBT. To determine why HBT was used and to record disposal. Method: All patients treated by HBT during the first two years of this new service were identified from the HBT logbook. A checklist recording demographic, diagnostic, presenting complaint data and details of HBT contact was used to analyse the patients' charts. A statistical package JMP was used to analyse the data. Results: Two hundred and six patients (275 episodes) were treated using HBT. These were 101 (49.1 %) males and 105 (50.9%) females. Of these, 89 (43.2%) were single. Forty-eight (19.4%) lived alone and 53 (25.7%) were unemployed. The most common presenting complaint was severe depression (39.3%). A depressive disorder was the most frequent diagnosis (28.7%). Twenty six (13%) episodes of HBT ended in admission. One hundred and eighty five (67.3%) were referred to outpatients and 26 (9.5%) were discharged to the GP. Conclusions: Home-based treatment is feasible for a wide range of patients with an array of presenting complaints. This model of service delivery is viable in a rural setting. Admission will still be required for some patients. Further work is needed to examine its sustainability and its generalisability to other Irish settings.
Small-molecule inhibitor of OGG1 suppresses proinflammatory gene expression and inflammation

DNA binding as an anti-inflammatory Mice that lack the gene encoding 8-oxoguanine DNA glycosylase 1 (OGG1) show resistance to inflammation. This enzyme binds to sites of oxidative DNA damage and initiates DNA base excision repair. Visnes et al. developed a small-molecule drug that acts as a potent and selective active-site inhibitor that stops OGG1 from recognizing its DNA substrate (see the Perspective by Samson). The drug inhibited DNA repair and modified OGG1 chromatin dynamics, which resulted in the inhibition of proinflammatory pathway genes. The drug was well tolerated by mice and suppressed lipopolysaccharide- and tumor necrosis factor–α–mediated neutrophilic inflammation in the lungs. Science, this issue p. 834; see also p. 748 A small-molecule OGG1 glycosylase inhibitor suppresses inflammation by targeting oxidative DNA repair. The onset of inflammation is associated with reactive oxygen species and oxidative damage to macromolecules like 7,8-dihydro-8-oxoguanine (8-oxoG) in DNA. Because 8-oxoguanine DNA glycosylase 1 (OGG1) binds 8-oxoG and because Ogg1-deficient mice are resistant to acute and systemic inflammation, we hypothesized that OGG1 inhibition may represent a strategy for the prevention and treatment of inflammation. We developed TH5487, a selective active-site inhibitor of OGG1, which hampers OGG1 binding to and repair of 8-oxoG and which is well tolerated by mice. TH5487 prevents tumor necrosis factor–α–induced OGG1-DNA interactions at guanine-rich promoters of proinflammatory genes. This, in turn, decreases DNA occupancy of nuclear factor κB and proinflammatory gene expression, resulting in decreased immune cell recruitment to mouse lungs. Thus, we present a proof of concept that targeting oxidative DNA repair can alleviate inflammatory conditions in vivo.
The prevalence of occult hepatitis B infection among the blood donors in a tertiary care hospital, Puducherry

Occult hepatitis B infection (OBI) is a cause of concern while screening the blood donors to prevent transfusion-related transmission of infection. This study was conducted to assess the prevalence of OBI using total anti-HBc by ELISA and DNA detection by real time polymerase chain reaction (PCR). The samples included were negative for HBs Ag by ELISA. Out of 1102 samples tested, 156 were positive for total anti-hepatitis B core antigen and 52/156 by real-time PCR. Overall, the prevalence was found to be 4.71% (52/1102). The results indicate that nucleic acid-based testing should be an essential part of screening procedure to prevent missing of OBI.
Weight-management in children living with asthma: a qualitative study of the experiences of paediatric healthcare professionals

Abstract Objective: Weight loss has been found to improve the symptoms of asthma in children who are overweight. However, many paediatric weight management programmes do not address the challenges associated with living with asthma. The aim of this study was to explore the views and experiences of paediatric healthcare professionals concerning weight management advice and support offered to families of children living with asthma. Methods: In-depth individual interviews with 10 healthcare professionals who work with a paediatric asthma population (n = 4 Respiratory Consultants, 3 Respiratory Nurses, 3 General Paediatricians). Data were analysed using a Framework approach. Results: Healthcare professionals highlighted that families’ perceptions of weight, their approach to physical activity and nutrition, the family’s social context and perceptions of asthma and asthma treatment all influence weight management in children living with asthma. Initiating weight management conversations and referring to weight management support were perceived as challenging. It was thought that tailoring weight management to the needs of children living with asthma and locating support within the community were important to the success of a family-centred intervention. Conclusions: The results highlight the added complexity of responding to excessive weight in a paediatric population with asthma. Training and referral guidance for healthcare professionals may help overcome weight management support challenges. Addressing family beliefs about the factors influencing paediatric asthma and exploring families’ motivations for behaviour change may enhance engagement with weight management.
Mesenchymal Stem Cells and Transforming Growth Factor-β3 (TGF-β3) to Enhance the Regenerative Ability of an Albumin Scaffold in Full Thickness Wound Healing

Pressure ulcers are one of the most common forms of skin injury, particularly in the spinal cord injured (SCI). Pressure ulcers are difficult to heal in this population requiring at least six months of bed rest. Surgical treatment (grafting) is the fastest recovery time, but it still requires six weeks of bed rest plus significant additional costs and a high recurrence rate. A significant clinical benefit would be obtained by speeding the healing rate of a non-surgical treatment to close to that of surgical treatment (approximately doubling of healing rate). Current non-surgical treatment is mostly inactive wound coverings. The goal of this project was to look at the feasibility of doubling the healing rate of a full-thickness defect using combinations of three treatments, for the first time, each shown to increase healing rate: application of transforming growth factor-β3 (TGF-β3), an albumin based scaffold, and mesenchymal stem cells (MSCs). At one week following surgery, the combined treatment showed the greatest increase in healing rate, particularly for the epithelialization rate. Although the target level of a 100% increase in healing rate over the control was not quite achieved, it is anticipated that the goal would be met with further optimization of the treatment.
Combination therapy for ischemic stroke: Novel approaches to lengthen therapeutic window of tissue plasminogen activator

Tissue plasminogen activator (tPA) thrombolysis continues to be the gold standard therapy for ischemic stroke. Due to the time-limited treatment window, within 4.5 h of stroke onset, and a variety of potentially deadly complications related to delayed administration, particularly hemorrhagic transformation (HT), clinical use of tPA is limited. Combination therapies with other interventions, drug or nondrug, have been hypothesized as a logical approach to enhancing tPA effectiveness. Here, we discuss various potential pharmacological and nondrug treatments to minimize adverse effects, primarily HT, associated with delayed tPA administration. Pharmacological interventions include many that support the integrity of the blood–brain barrier (i.e., atorvastatin, batimastat, candesartan, cilostazol, fasudil, and minocycline), promote vascularization and preserve cerebrovasculature (i.e., coumarin derivative IMM-H004 and granulocyte-colony stimulating factor), employing other mechanisms of action (i.e., oxygen transporters and ascorbic acid). Nondrug treatments are comprised of stem cell transplantation and gas therapies with multi-faceted approaches. Combination therapy with tPA and the aforementioned treatments demonstrated promise for mitigating the adverse complications associated with delayed tPA treatment and rescuing stroke-induced behavioral deficits. Therefore, the conjunctive therapy method is a novel therapeutic approach that can attempt to minimize the limitations of tPA treatment and possibly increase the therapeutic window for ischemic stroke treatment.
Combination of cell transplantation and glial cell line-derived neurotrophic factor-secreting encapsulated cells in Parkinson's disease

A major limitation of cell transplantation for Parkinson's disease (PD) is the mediocre survival of the grafted cells. Facilitating graft survival may improve the functional outcomes of the transplanted cells. Here, we discuss our observations that combination of rat fetal ventral mesencephalic (VM) tissue and encapsulated cells that secrete glial cell line-derived neurotrophic factor (GDNF) enhanced graft function in an animal model of PD. We described significant 2-fold increase in the number of tyrosine hydroxylase immunoreactive (TH-ir) cells per graft, as well as 1.7-fold and 9-fold increments in TH-ir fiber outgrowth into the host brain and toward the capsule with combined transplants and GDNF capsules as opposed to the VM transplants and mock-capsule group. These findings demonstrate that encapsulated GDNF-secreting cells improve graft survival that may optimize functional benefits for the treatment of PD.
Generational Changes in Personality: The Evidence From Corpus Linguistics

According to theory, social change is interconnected with changes in mental phenomena and language. In the present study, secular change in the usage frequencies of common English personality adjectives (n = 336) qualifying the word person was analyzed over the period 1900 to 2002. It was hypothesized that words that represent those personality traits that are advantageous in occupations typical for modern societies have increased in frequency. The results show changes in the frequencies of individual words but stability across the five major categories of trait adjectives in the Google Books English fiction corpus. A modest increase for Extraversion-, Agreeableness-, and Stability-related adjectives was observed in the Google Books English 2012 corpus. Frequency of Intellect-related words increased up to 1960 and then declined. The results suggest that (a) human nature has changed little over the 20th century, (b) generational changes in personality are not strongly reflected in language, or (c) the corpus linguistic method used is not reliable for studying generational changes in personality.
A preliminary study on time-compressed speech recognition in noise among teenage students who use personal listening devices

Abstract Objective: To compare speech perception obtained with different time compression rates in teenagers that do or do not use personal listening devices (PLDs). Design: Teenagers in a high school were recruited to complete questionnaires reporting their recreational noise exposure using PLDs. The dose of individual recreational noise exposure was calculated. The individuals with the most and least doses of recreational noise were selected and grouped into PLD users and non-PLD users. Normal rate and time-compressed (60% and 70%) speech recognition in quiet and noisy conditions was measured. Study sample: PLD user and non-PLD user group each included 20 participants. Results: ANOVA analysis showed that the effect of group, background, compression rate, and interactions between any two factors are significant. Post hoc analysis showed that the speech recognition scores with normal rate in quiet and noise and those obtained from time-compressed speech in the quiet condition were not significantly different between PLD users and non-PLD users. However, differences in the time-compressed speech recognition scores (60% and 70%) in noisy conditions between the two groups were statistically significant. Conclusions: The fast-speed speech recognition in noise decreased significantly in PLD users compared with that in non-PLD users selected by extreme entertainment exposure.
Elisabeth Kübler-Ross and the “Five Stages” Model in a Sampling of Recent American Textbooks

This article examines some aspects of the enduring influence of the work of Dr. Elisabeth Kübler-Ross and especially of her “five stages” model through a sampling of recent textbooks published in the United States in selected academic disciplines and professional fields. The following are the questions to be asked: 1. Does the “five stages” model appear without significant change in the textbooks described here? 2. Is the “five stages” model applied in these textbooks to issues involving loss, grief, and bereavement, as well as to those involving terminal illness and dying? 3. Is the “five stages” model criticized in some or all of these textbooks? 4. If so, is the criticism sufficient to argue that, while the “five stages” model might be presented as an important historical framework, it should no longer be regarded as a sound theory to guide contemporary education and practice?
Radiation-induced lung injury: impact on macrophage dysregulation and lipid alteration – a review

Abstract Lung cancer continues to be the leading cause of cancer deaths and more than one million lung cancer patients will die every year worldwide. Radiotherapy (RT) plays an important role in lung cancer treatment, but the side effects of RT are pneumonitis and pulmonary fibrosis. RT-induced lung injury causes damage to alveolar-epithelial cells and vascular endothelial cells. Macrophages play an important role in the development of pulmonary fibrosis despite its role in immune response. These injury activated macrophages develop into classically activated M1 macrophage or alternative activated M2 macrophage. It secretes cytokines, interleukins, interferons, and nitric oxide. Several pro-inflammatory lipids and pro-apoptotic proteins cause lipotoxicity such as LDL, FC, DAG, and FFA. The overall findings in this review conclude the importance of macrophages in inducing toxic/inflammatory effects during RT of lung cancer, which is clinically vital to treat the radiation-induced fibrosis.