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A major industry badly affected by the spread of COVID-19 is the education sector. With the abrupt transition from traditional classrooms to online learning, several obstacles arose, particularly for more senior teachers who had less time to plan for and adjust to the new model of instruction. This study was conducted to explore the challenges and successes of senior teachers from Pampanga, Philippines in the delivery of online learning. Banking on their wisdom and experiences, this qualitative-exploratory study is guided by Kolb’s Experiential Learning Cycle (1984) and Bandura’s Social Learning Theory (1968). In-depth interviews were conducted with eight senior teachers ranging in age from 55 to 78. Their accounts, experiences, and methods were transcribed, recorded, and classified after undergoing manual qualitative analysis. The major findings highlighted the difficulties, modifications, and countermeasures that experienced educators use when delivering online classes. These results can be used to strengthen educational institutions' ability to provide and support teachers from older generations, whose knowledge and comfort with technology is limited. Most importantly, it focused on filling the gap on the dearth of research publications that have examined the difficulties and triumphs of senior teachers in the context of the new normal in Philippine education.

Background: Xylitol is a five-carbon sugar alcohol that has numerous beneficial health properties. It has almost the same sweetness as sucrose but has lower energy value compared to the sucrose. Metabolism of xylitol is insulin independent and thus it is an ideal sweetener for diabetics. It is widely used in food products, oral and personal care, and animal nutrition as well. Here we present a two-stage strategy to produce bio-xylitol from D-xylose using a recombinant Pichia pastoris expressing a heterologous xylose reductase gene. The recombinant P. pastoris cells were first generated by a low-cost, standard procedure. The cells were then used as a catalyst to make the bio-xylitol from D-xylose.Results: P. pastoris expressing XYL1 from P. stipitis and gdh from B. subtilis demonstrated that the biotransformation was very efficient with as high as 80% (w/w) conversion within two hours. The whole cells could be re-used for multiple rounds of catalysis without loss of activity. Also, the cells could directly transform D-xylose in a non-detoxified hemicelluloses hydrolysate to xylitol at 70% (w/w) yield.Conclusions: We demonstrated here that the recombinant P. pastoris expressing xylose reductase could transform D-xylose, either in pure form or in crude hemicelluloses hydrolysate, to bio-xylitol very efficiently. This biocatalytic reaction happened without the external addition of any NAD(P)H, NAD(P)+, and auxiliary substrate as an electron donor. Our experimental design & findings reported here are not limited to the conversion of D-xylose to xylitol only but can be used with other many oxidoreductase reactions also, such as ketone reductases/alcohol dehydrogenases and amino acid dehydrogenases, which are widely used for the synthesis of high-value chemicals and pharmaceutical intermediates.

Background Multinational clinical trials commonly include different language versions of patient-reported outcomes (PRO) instruments without considering the question of their cross-cultural validity. The inclusion of a PRO instrument, the Adult AIDS Clinical Trial Group Symptom Distress Module (SDM), in an multinational clinical trial in HIV-1 antiretroviral-naive patients offered an opportunity to explore the methods to assess cross-cultural validity of PRO instruments in the context of clinical trials.Purpose To assess the cross-cultural validity of the SDM across seven cultural groups in the setting of a multinational HIV clinical trial.Methods Twenty-five language versions of the SDM were included in a Phase IIb/III trial comparing maraviroc with efavirenz (each in combination with zidovudine/ lamivudine) conducted in 12 countries to assess symptoms perceived by HIV-1-infected antiretroviral-naive patients. Differential item functioning (DIF) detection and the STATIS method were combined in a pragmatic approach to assess the cross-cultural validity of the SDM using pre-antiretroviral treatment data from 759 patients.Results Statistically significant DIF between cultural groups was observed for four items: fatigue; fevers; anxiety; and headache. However, examination of these items by linguists did not lead to meaningful explanations for the statistical differences. With the STATIS approach, the Bantu and European Germanic groups were the furthest from the Occidental English group.Limitations The assessment of cross-cultural validity had to be performed on some very small samples and on data aggregated by cultural groups, which suggests the need for a cautious interpretation of the results.Conclusions Given the heterogeneity of cultures considered, the absence of meaningful explanations for statistically significant differences between cultural groups supports the cross-cultural validity of the SDM versions included in this trial. Thus, this study demonstrated that it is feasible to conduct assessment of crosscultural validity of PRO instruments using data collected in the setting of multinational clinical trials. Clinical Trials 2009; 6: 574—584. http://ctj.sagepub.com

Background To assess the prevalence of menopausal symptoms among women prescribed hormone therapy (HT) using electronic medical record data from a regional healthcare organization. Methods Retrospective data from the Reliant Medical Group from 1/1/2006-12/31/2011 were assessed for 102 randomly-selected patients. Study eligibility criteria included: females aged 45 to 65; prescribed oral or transdermal HT; no history of breast cancer, venous thromboembolism, stroke, gynecological cancer, or hysterectomy; continuously enrolled in the health plan for 1 year before and after the first observed HT prescription. Prevalence of menopause-related symptoms was analyzed descriptively at both the patient and visit levels. Results Mean age of patients was 54 years. The most common menopausal symptoms were: hot flushes (40 %), night sweats (17 %), insomnia (16 %), vaginal dryness (13 %), mood disorders (12 %), and weight gain (12 %). Among the 102 patients, 163 individual visits listing menopausal symptoms were identified, of which hot flushes (71 visits) were the most common symptom identified. Conclusion Our findings provide recent data on the types of menopausal symptoms experienced by mid-life women prescribed HT. Electronic medical records may be a rich source of data for future studies of menopausal symptoms in this population.

http://www.upjournals.co.za/index.php/SWPR

Since the introduction of highly active antiretroviral therapy (HAART), there has been a dramatic decrease in human immunodeficiency virus type 1 (HIV-1)-related mortality and HIV-1 infection has been transformed from a near-uniformly fatal condition into a chronic or subacute disease in substantial numbers of treated patients (13, 15, 26). Most HAART-treated patients demonstrate “undetectable” levels of HIV-1 RNA in plasma within a few months after the start of therapy. In diverse cohorts, HAART may lead to plasma viral loads (VLs) of less than 500 copies/ml, with the majority of these individuals reaching less than 50 copies of plasma HIV-1 RNA/ml. However, HIV-1 RNA levels at this level do not imply that viral replication has stopped, as evidenced by ongoing viral sequence evolution (14, 39), the expression of viral mRNA species in peripheral blood mononuclear cells (12, 19, 22), and the presence of low but detectable levels of viral RNA in the plasma of infected subjects (6, 9, 38). Failure to completely suppress viral replication with HAART and the presence of the long-lived reservoir of resting latently infected CD4+ T cells are major hurdles to the eradication of HIV-1 infection in vivo (18). Clinical trials in which well-suppressed patients were periodically tested for plasma VL with assays with a lower limit of detection of 50 copies/ml have shown that most of these patients demonstrate intermittent positive plasma HIV-1 RNA determinations (viral blips) (9, 33, 38). The source and the meaning of this episodic low-level viremia in the setting of seemingly effective HAART remain unclear. Nevertheless, achieving low levels of viremia during antiretroviral treatment predicts a sustained virologic response. Kempf et al. reported a strong association between the nadir plasma HIV-1 RNA level and the durability of response to treatment (20). Using a more sensitive PCR assay, Raboud et al. observed that patients whose viremia fell below 20 copies/ml were less prone to virological failure than were those who stayed above this threshold (32). Havlir et al. found an association between viral blips and a higher steady state of viral replication, but not virologic failure over 4.5 years of observation, with virologic failure defined as two consecutive plasma VLs above 200 copies/ml (16). Sklar et al. (36) found that the occurrence of transient viremia did not vary with whether the patient was HAART naive or experienced or was currently taking protease inhibitors or not. Also, these transient episodes of low-level plasma viremia did not appear to affect the risk of developing lasting viremia. Whether the emergence of drug-resistant virions is associated with viral blips during treatment is still controversial (5, 17) and deserves further and prompt investigation. Finally, it has been reported that an increased frequency of blips correlates with slower decay of latently infected cells harboring replication-competent provirus (33). It was recently shown that the variability in the number of viral blips observed in HAART-treated patients during the period of VL suppression cannot be explained by assuming a common probability distribution of blip amplitudes among patients, as would be expected if blips were simply caused by assay variations (28). Thus, this argues against the hypothesis that viral blips represent assay error or variability and suggests that blips have an underlying biological cause. In a more recent study, there was presented an analysis on the dynamics of viral blips with data obtained from 123 patients treated with eight different protease inhibitor-containing regimens. It was shown that viral blips occur substantially at random, viral blip frequency does not change with longer periods of observation, and blip frequency inversely correlates with the baseline CD4+ T-cell counts, i.e., host-specific factors that precede the period of VL suppression (7). Of the 123 patients analyzed, 76 were treated during acute and early infection, within 3 to 157 days from the onset of symptoms (primary HIV infection [PHI]). The remaining 47 patients started therapy during chronic HIV infection (CHI). The aim of this study was to retrospectively analyze the frequency of viral blips during the period of VL suppression and to compare blip frequency as it relates to the status of infection, acute or chronic, and the virologic set point (level of viremia) at the start of therapy.

Themed issue: Community Development in Africa Host by Department of Social Work, University of Johannesburg Two recent studies have shown that highly effective community practitioners exhibit eight habits that set them apart from the rest. The question arose whether these habits could also be instilled in other, less effective practitioners and if so, what the most appropriate means to do so would be. A quest for answers formed the main thrust of a recent study into the habits of a group of 79 Namibian social workers and the extent to which a specially designed training course would change them. The results proved the intervention to have a practical significant effect on seven of their habits and a medium effect on the eighth. This finding could have far-reaching implications for the direct measurement of existing habits, the continuing education and training of practitioners, and the remedial steps to be taken where some fail to make the grade.

Objective: To assess the efficacy of tenofovir disoproxil fumarate (TDF) monotherapy by following the initial rate of decline in plasma viral load, which is a measure of the efficacy of therapy in blocking viral replication. Design: An open-label, single-site study of TDF monotherapy in 10 antiretroviral drug-naive chronically HIV-1-infected individuals. Methods: Antiviral responses were assessed at baseline and during 21 days of monotherapy with TDF by measuring plasma HIV-1 RNA levels. The rate of change in HIV-1 RNA from baseline was determined both by linear regression and by fitting to a published model. Slopes were compared with those previously determined for ritonavir monotherapy. Results: Over 21 days, mean plasma HIV-1 RNA levels in the TDF-treated patients fell 1.5 log10 copies/ml (range, 0.7–2.0). The initial rates of decline in plasma HIV-1 RNA in the 10 TDF-treated patients and in 25 protease inhibitor-naive subjects treated with ritonavir monotherapy were nearly identical. Conclusions: The reduction in plasma HIV-1 RNA with TDF montherapy was comparable with the decline observed in previous studies of protease inhibitor monotherapy. TDF is a potent antiretroviral agent and has comparable inherent antiviral activity with that of ritonavir, a potent protease inhibitor. These data support further study of TDF-based regimens in simplified combinations of antiviral agents as initial treatment for chronic HIV-1 infection.

Heritage language learners are learners of the primary language of their parents which they might have been exposed to but have not learned it as a language they can fluently use to communicate with other people. Salinlahi, an Interactive Learning Environment, was developed to teach these young Filipino heritage learners about basic Filipino vocabulary while Salinlahi II included a support for collaborative learning. With the aim of teaching learners with basic knowledge in Filipino we developed Salinlahi III to teach higher level lessons focusing on Filipino grammar and sentence construction. An internal evaluation of the system has shown that the user interface and feedback of the tutor was appropriate. Moreover, in an external evaluation of the system, experimental and controlled field tests were done and results showed that there is a positive learning gain after using the system.

Sixteen subjects were treated with highly active antiretroviral therapy within 120 days of the onset of symptoms of newly acquired human immunodeficiency virus type 1 (HIV-1) infection. Eleven of the 16 participated in an adjunctive therapeutic vaccine trial. After a mean of 3.2 years of treatment, they elected to discontinue therapy. Virus rebound occurred in all subjects and was followed by a spontaneous, transient although significant reduction in log plasma HIV-1 RNA level, ranging from 0.3 to 3.1 log(10) copies/mL. Despite evidence of the induction of HIV-1-specific cell-mediated immune responses, plasma viremia was not persistently suppressed to

We have previously described the inhibition of human immunodeficiency virus serotype 1 (HIV-1) using the antimalarial hydroxychloroquine (HCQ), a weak base that inhibits the posttranslational modification of glycoprotein 120 (gp 120) in T cells and monocytes. The mechanism of inhibition of gp 120 production was presumed to be the ability of HCQ to increase endosomal pH and therefore alter enzymes required for gp120 production. To further clarify this action, we have determined the effect of HCQ and its enantiomers on endosomal pH. Pretreatment of cells with HCQ and the levo- and dextro-enantiomers at concentrations demonstrated to suppress anti-HIV-1 activity increased endosomal pH to levels similar to increases seen with chloroquine and ammonium chloride, two other weak bases, and decreased gp 120 production. The dextro- and levo-enantiomers suppressed HIV-1 replication to a similar extent and were no more toxic than racemic HCQ. We next compared the anti-HIV-1 effect of HCQ with zidovudine (ZDV) in both newly and chronically HIV-1-infected T-cell and monocytic cell lines (63 and 63HIV). HCQ suppressed HIV-1 replication in a dose-dependent manner in both recently and chronically infected T-cell and monocytic cell lines. In contrast, ZDV pretreatment had potent anti-HIV-1 activity in the newly infected T and monocytic cells but not in chronically infected cells. An additive effect of HCQ with ZDV was observed in the newly infected T and monocytic cells but not in the chronically infected cells. Although the anti-HIV-1 effect of HCQ was less than that of ZDV, HCQ may still be potentially useful either as an alternative HIV-1 treatment or in combination with other anti-HIV-1 agents, especially in patients who have rheumatic manifestations of HIV-1 infection.

Maraviroc (MVC) is the first approved CCR5 antagonist. The aim of this study was to explore the cost-effectiveness of MVC in treatment-experienced or treatment-resistant HIV-infected adults.The validated HIV microsimulation model ARAMIS was used to predict clinical and economic outcomes of treating patients with optimized background therapy (OBT) alone, as compared to a strategy of testing for the patient's viral tropism and treating with OBT with or without (+/-) MVC in a cohort corresponding to the MOTIVATE screening cohort.Compared to treatment with OBT alone, a treatment strategy of OBT +/- MVC (twice daily) according to tropism test result was predicted to increase CD4+ cell count after 5 years (from mean 249 to 360 cells/microL), undiscounted life expectancy (7.6 to 8.9 years), and quality-adjusted life years (QALYs; from 4.99 to 5.71) for an additional $40,500, giving an incremental cost-effectiveness ratio of $56,400 per QALY gained. The result was relatively insensitive to alternative clinical and cost assumptions within reasonable ranges, but for individuals with HIV susceptible to only two or fewer components of OBT, the ICER decreased to $52,000 per QALY gained.MVC is cost-effective, especially among individuals with few remaining options for active antiretroviral therapy.

Since the introduction of highly active antiretroviral therapy (HAART), there has been a dramatic decrease in human immunodeficiency virus (HIV)-related mortality. In diverse cohorts, most HAART-treated patients attain “undetectable” levels of plasma viral RNA ( 400 copies/ml were three times more likely to experience sustained viral rebound and to have impaired CD4 cell rises relative to those that maintained undetectable viral loads (VLs

Mathematical models provide an understanding of in vivo replication kinetics of human immunodeficiency virus type 1 (HIV-1). With a novel intervention designed for increased potency, we have more accurately deduced the half-lives of virus-producing CD4 + T cells, 0.7 day, and the generation time of HIV-1 in vivo, approximately 2 days, confirming the dynamic nature of HIV-1 replication.

Despite the clinical benefits of combination antiviral therapy, whether maximal antiviral potency has been achieved with current drug combinations remains unclear. We studied the first phase of decay of human immunodeficiency virus type 1 (HIV-1) RNA in plasma, one early indicator of antiviral activity, after the administration of a novel combination of lopinavir/ritonavir, efavirenz, tenofovir disoproxil fumarate, and lamivudine and compared it with that observed in matched cohorts treated with alternative combination regimens. On the basis of these comparisons, we conclude that the relative potency of highly active antiretroviral therapy may be augmented by as much as 25%-30%. However, it is important to emphasize that further study is warranted to explore whether these early measurements of relative efficacy provide long-term virologic and clinical benefits. Nevertheless, we believe that optimal treatment regimens for HIV-1 have yet to be identified and that continued research to achieve this goal is warranted.

Objective To assess temporal changes in prevalence of transmitted HIV-1 drug resistance in a homogeneous cohort of newly infected individuals. Methods Pretreatment genotypic and phenotypic drug resistance was tested in 154 subjects with primary HIV-1 infection identified between 1995 and 2001 (group A; n = 76) and 1999 and 2001 (group B; n = 78). Sequence analysis was assessed by population-based sequencing. Virus susceptibility to antiretroviral agents was determined by the PhenoSense assay (ViroLogic). Results The frequency of resistance-associated mutations in protease (PR) and reverse transcriptase (RT) genes increased from 13.2% (1995–1998) to 19.7% (1999–2001). Although the overall prevalence of viruses with phenotypic resistance did not vary (1995–1998, 10.0%; 1999–2001, 10.8%), the distribution of drug classes changed [nucleoside RT inhibitor (NRTI): 8.3% to 2.7%; non-NRTI: 5.0% to 8.1%; protease inhibitors (PI): 1.7% to 5.4%]. The decrease of phenotypic resistance to NRTI in 1999–2001 was caused by the absence of transmitted lamivudine-resistant variants. Phenotypically susceptible variants with aspartic acid or serine residues at position 215 of RT (5.3%;P = 0.04) instead emerged. Hypersusceptibility to PI decreased from 18.3% to 5.4% (P = 0.02) while the amino acid substitutions in PR increased over time: M36I (6.6% to 19.7%) and A71V/T (3.9% to 15.8%). Conclusions There was an increase in the number of HIV-1 variants with both genotypic and phenotypic resistance to non-NRTI and PI over time. Furthermore, viruses with altered genotypes compatible with thymidine analogue or PI exposure but susceptible phenotypes were seen in 1999–2001. The latter findings suggest transmission of viruses from subjects who have either changed or discontinued therapy.

Highly active antiretroviral therapy (HAART) has reduced the morbidity and mortality related to infection with the human immunodeficiency virus-1 (HIV-1) through its ability to suppress viral replication and preserve and reconstitute specific immune responses in many infected individuals. However, the complete eradication of HIV-1 with current HAART regimens is not considered possible by most experts. Moreover, many current antivirals have metabolic complications and limiting side effects. Consequently, the treatment paradigm has shifted from 'hit hard and early' to delaying the initiation of therapy until later in the course of HIV-1-related disease, with corresponding modifications of consensus treatment guidelines. Factors that need to be considered in deciding when to initiate therapy and with what regimen include the patient's risk of disease progression, the possible adverse drug effects, the patient's ability to adhere to the prescribed therapy, and the need to preserve future therapeutic options. In this article, we discuss the issues surrounding the initiation of HAART, and describe the virologic and immunologic milestones that may be achieved with effective antiretroviral therapy.

Alterations in the beta-adrenergic receptor adenylyl cyclase pathway are well known in heart failure. To determine if an alteration in this pathway occurs during the reversible phase of cardiac allograft rejection, we used a rat heterotopic heart transplant model. Lewis rats received either isografts or Lewis Brown Norway allografts. Cardiac grafts and native hearts were explanted 4, 5, or 6 days later. Receptor-mediated modulation of adenylyl cyclase activity was investigated using isoproterenol, forskolin, and the muscarinic and adenosine receptor agonists carbachol and R-N6-(C2-phenyl-isopropyl)-adenosine (R-PIA), respectively. Allografts demonstrated evidence of histological rejection and a significantly impaired response to forskolin and isoproterenol on all days: [table: see text] (% increase in cAMP in response to forskolin or isoproterenol +/- standard error. All results P less than 0.03 except Day 4 forskolin and Day 5 isoproterenol.) No significant difference was noted between isografts and allografts stimulated with carbachol and R-PIA. These data suggest that a primary alteration in adenylyl cyclase activity may be a component of the molecular basis of reversible contractile dysfunction in cardiac allograft rejection.