Fat mass as an important predictor of persistent hypertension in patients with primary aldosteronism after adrenalectomy.

Aldosterone excess is present in obesity and is associated with involvement in the pathogenesis of obesity. We evaluate the impact of body obesity as measured by body composition monitor (BCM) on clinical outcomes in patients with unilateral primary aldosteronism (uPA) after adrenalectomy. The BCM device was used to assess body composition before and after adrenalectomy. We used fat mass (FM) and body mass index (BMI) to classify obesity and divided obesity into three groups: clinical overweight (BMI (kg/m2) ≥25); normal weight obesity (NWO, FM (%) ≥ 35 for women, >25 for men & BMI < 25); and no obesity (FM < 35 for women, <25 for men & BMI < 25). A total of 130 unilateral PA (uPA) patients received adrenalectomy, and 27 EH patients were identified; uPA patients with hypertension remission were found to have lower FM (p = 0.046), BMI (p < 0.001), and lower prevalence of overweight (p = 0.001). In the logistic regression model, patients with clinical overweight (OR = 2.9, p = 0.007), NWO (OR = 3.04, p = 0.041) and longer HTN duration (years, OR = 1.065, p = 0.013) were at the risk of persistent hypertension after adrenalectomy. Obesity status was strongly associated with persistent hypertension in uPA patients after adrenalectomy. However, patients in the NWO group also carried higher risk of persistent hypertension. Therefore, assessment of pre-obesity and overweight in uPA patients are extremely important, especially in those who have normal BMI.

IgE-neutralizing UB-221 mAb, distinct from omalizumab and ligelizumab, exhibits CD23-mediated IgE downregulation and relieves urticaria symptoms.

Over the last 2 decades, omalizumab is the only anti-IgE antibody that has been approved for asthma and chronic spontaneous urticaria (CSU). Ligelizumab, a higher-affinity anti-IgE mAb and the only rival viable candidate in late-stage clinical trials, showed anti-CSU efficacy superior to that of omalizumab in phase IIb but not in phase III. This report features the antigenic-functional characteristics of UB-221, an anti-IgE mAb of a newer class that is distinct from omalizumab and ligelizumab. UB-221, in free form, bound abundantly to CD23-occupied IgE and, in oligomeric mAb-IgE complex forms, freely engaged CD23, while ligelizumab reacted limitedly and omalizumab stayed inert toward CD23; these observations are consistent with UB-221 outperforming ligelizumab and omalizumab in CD23-mediated downregulation of IgE production. UB-221 bound IgE with a strong affinity to prevent FcԑRI-mediated basophil activation and degranulation, exhibiting superior IgE-neutralizing activity to that of omalizumab. UB-221 and ligelizumab bound cellular IgE and effectively neutralized IgE in sera of patients with atopic dermatitis with equal strength, while omalizumab lagged behind. A single UB-221 dose administered to cynomolgus macaques and human IgE (ε, κ)-knockin mice could induce rapid, pronounced serum-IgE reduction. A single UB-221 dose administered to patients with CSU in a first-in-human trial exhibited durable disease symptom relief in parallel with a rapid reduction in serum free-IgE level.

Sinularin Induces Oxidative Stress-Mediated Apoptosis and Mitochondrial Dysfunction, and Inhibits Angiogenesis in Glioblastoma Cells.

Glioblastoma multiforme (GBM) is a cancer of largely unknown cause that leads to a 5-year survival rate of approximately 7% in the United States. Current treatment strategies are not effective, indicating a strong need for the development of novel therapies. In this study, the outcomes of sinularin, a marine-derived product, were evaluated against GBM. Our cellular studies using GBM cells revealed that sinularin induces cell death. The measured half maximal inhibitory concentrations (IC50) values ranged from 30 to 6 µM at 24-72 h. Cell death was induced via the generation of ROS leading to mitochondria-mediated apoptosis. This was evidenced by annexin V/propidium iodine staining and an upregulation of cleaved forms of the pro-apoptotic proteins caspase 9, 3, and PARP, and supported by CellROXTM Green, MitoSOXTM Red, and CM-H2DCFDA staining methods. In addition, we observed a downregulation of the antioxidant enzymes SOD1/2 and thioredoxin. Upon treatment with sinularin at the ~IC50 concentration, mitochondrial respiration capacities were significantly reduced, as shown by measuring the oxygen consumption rates and enzymatic complexes of oxidative phosphorylation. Intriguingly, sinularin significantly inhibited indicators of angiogenesis such as vessel tube formation, cell migration, and cell mobility in human umbilical vein endothelial cells or the fusion cell line EA.Hy926. Lastly, in a transgenic zebrafish model, intersegmental vessel formation was also significantly inhibited by sinularin treatment. These findings indicate that sinularin exerts anti-brain cancer properties that include apoptosis induction but also antiangiogenesis.

An Augmented Reality (AR) App Enhances the Pulmonary Function and Potency/Feasibility of Perioperative Rehabilitation in Patients Undergoing Orthopedic Surgery.

Perioperative rehabilitation is crucial for patients receiving surgery in order to reduce complications and mortality. Conventional methods such as verbal instructions and pre-recorded video are commonly used, but several disadvantages exist. Therefore, we developed an augmented reality (AR) app that includes respiration training, resistance muscle training, and walking training for surgery preparation. The aim of this pilot study was to compare the effects of AR-based training rehabilitation programs with conventional (non-AR-based) programs considering the objective pulmonary function and subjective feasibility and potency in orthopedic patients. This prospective study was conducted in a medical center in Taiwan between 2018 to 2021. Sixty-six patients undergoing elective orthopedic surgery were allocated with a 1:1 ratio to non-AR or AR groups according to their wishes. After training, the inspiratory flow rate of the AR group was higher than that of the non-AR group pre-operatively. As for the subjective assessment, the feasibility (level of confidence and anxiety reduction) and potency (cooperation and educative effect) were superior in AR-based training, compared with the conventional training model. Our study showed that patients using our AR app had better subjective and objective outcomes compared with a conventional model for perioperative rehabilitation.

Inequality-Related Health and Social Factors and Their Impact on Well-Being during the COVID-19 Pandemic: Findings from a National Survey in the UK.

Background: Lower socioeconomic groups and disadvantaged populations across the world suffer disproportionately from the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to examine the impact of health- and social-inequality-related factors on well-being in order to further distinguish each of their effects during the pandemic. Methods: A nationally-representative sample of 5077 UK respondents aged 18 years or older was recruited through an online survey panel during the COVID-19 pandemic. Their subjective well-being was measured using the 11-point Cantril Ladder of Life Scale. The impact of inequality-related health and social factors (pre-existing medical conditions, household size and occupation), as well as COVID-19-related risk factors (symptoms, confirmed infections, and social distancing behaviours) on well-being were analysed using multiple linear regression models. The associations between the COVID-19-related risk factors and well-being according to the respondents' household size and occupation were modelled in order to test the differences by their socioeconomic profile. Results: We identified inverted V-shaped associations between household size and subjective well-being during the COVID-19 pandemic. Compared to single-person households, respondents from households of two to four persons showed better well-being (ß = 0.57; CI (0.44, 0.72)), whereas living in crowded households of five persons or more was associated with decreased well-being (ß = -0.48; CI (-0.71, -0.25)). Furthermore, lower-skilled occupations (elementary occupations: ß = -0.31; CI (-0.58, -0.03); logistics and transport services: ß = -0.37; CI (-0.74, -0.01)) and chronic medical conditions (cardiometabolic or respiratory diseases: ß = -0.25; CI (-0.41, -0.1); and mental health conditions: ß = -1.12; CI (-1.28, -0.96)) were factors associated with reduced well-being during the pandemic. Interactions between a positive COVID-19 diagnosis, symptoms, and crowded households were identified (ß = -0.95; CI (-1.76, -0.14) and ß = -4.74; CI (-9.87, -1.61), respectively). Conclusions: In a national sample, the levels of general subjective well-being during the COVID-19 pandemic and lockdowns were disproportionately distributed across different groups within society. Preventive policies should explicitly focus on reaching lower socioeconomic groups; more emphasis should be placed on the coordination of multisectoral support in order to tackle existing health and social inequalities.

Professionals' experiences and attitudes toward use of Traditional Chinese Medicine in hospice palliative inpatient care units: A multicenter survey in Taiwan.

BACKGROUND: Medical staff may have difficulties in using conventional medicine to manage symptoms among terminally ill patients, including adverse effects of the treatment. Traditional Chinese medicine (TCM) is regarded as a complementary or alternative medicine, and has been increasingly used in the field of palliative medicine in recent years. This study aimed to investigate the experiences of and attitudes toward using TCM among palliative care professionals, and to provide preliminary information about its use in palliative care. METHODS: This was a cross-sectional survey study conducted in eight inpatient hospice wards in Taiwan between December 2014 and February 2016. The questionnaire was self-administered, and was analyzed with descriptive statistics including Pearson's Chi-square test and Fisher's exact test. RESULTS: A total of 251 palliative care professionals responded to the questionnaire, of whom 89.7% and 88.9% believed that the use of TCM could improve the physical symptoms and quality of life in terminally ill patients, respectively. Overall, 59.8%, of respondents suggested that TCM had rare side effects, and 58.2% were worried that TCM could affect the liver and kidney function of patients. In total, 89.7% and 88.0% of professionals agreed there were no suitable clinical practice guidelines and educational programs, respectively, for TCM use in palliative care. CONCLUSIONS: Most of the respondents agreed there was insufficient knowledge, skills-training, and continuing education on the use of TCM in terminally ill patients in Taiwan. These results show that to address patient safety considerations, guidelines about use of TCM in palliative care should be established.

Smartphone-Enabled, Telehealth-Based Family Conferences in Palliative Care During the COVID-19 Pandemic: Pilot Observational Study.

BACKGROUND: In the palliative care setting, infection control measures implemented due to COVID-19 have become barriers to end-of-life care discussions (eg, discharge planning and withdrawal of life-sustaining treatments) between patients, their families, and multidisciplinary medical teams. Strict restrictions in terms of visiting hours and the number of visitors have made it difficult to arrange in-person family conferences. Phone-based telehealth consultations may be a solution, but the lack of nonverbal cues may diminish the clinician-patient relationship. In this context, video-based, smartphone-enabled family conferences have become important. OBJECTIVE: We aimed to establish a smartphone-enabled telehealth model for palliative care family conferences. Our model integrates principles from the concept of shared decision making (SDM) and the value, acknowledge, listen, understand, and elicit (VALUE) approach. METHODS: Family conferences comprised three phases designed according to telehealth implementation guidelines-the previsit, during-visit, and postvisit phases. We incorporated the following SDM elements into the model: "team talk," "option talk," and "decision talk." The model has been implemented at a national cancer treatment center in Taiwan since February 2020. RESULTS: From February to April 2020, 14 telehealth family conferences in the palliative care unit were analyzed. The patients' mean age was 73 (SD 10.1) years; 6 out of 14 patients (43%) were female and 12 (86%) were married. The primary caregiver joining the conference virtually comprised mostly of spouses and children (n=10, 71%). The majority of participants were terminally ill patients with cancer (n=13, 93%), with the exception of 1 patient with stroke. Consensus on care goals related to discharge planning and withdrawal of life-sustaining treatments was reached in 93% (n=13) of cases during the family conferences. In total, 5 families rated the family conferences as good or very good (36%), whereas 9 were neutral (64%). CONCLUSIONS: Smartphone-enabled telehealth for palliative care family conferences with SDM and VALUE integration demonstrated high satisfaction for families. In most cases, it was effective in reaching consensus on care decisions. The model may be applied to other countries to promote quality in end-of-life care in the midst of the COVID-19 pandemic.

Vibrational predissociation in the bending levels of the à state of C3Ar.

Vibrational predissociation (VP) has been observed in 16 bands of the C3Ar van der Waals complex near the 0 v2 0 - 000 (v2 = 2-, 4-, 2+) and 0 2- 2 - 100 bands of the Ã1Π-X̃1Σ+ g system of C3. New higher resolution wavelength-resolved emission (WRE) spectra covering a wider spectral range have been recorded for many of these C3Ar bands, which show that most of the features observed in fluorescence must be reassigned as emission from the C3 fragment. Two types of VP processes have been recognized. The first type gives rise to vibrationally hot C3 fragments, mostly following |Δv| = 1, |ΔP| = 1 propensity rules, where P is the vibronic angular momentum of C3. The second type gives vibrationally cooled fragments. The VP processes can change abruptly from one type to the other with comparatively small differences in vibrational energy. Although the initial states are associated with both orbital components of the C3, Ã1Πu state, most of the VP fragments belong to the lower orbital component. A dipole-induced dipole model has been used to interpret the observed ΔP- propensities. Ab initio calculations of the binding energies of the ground and excited electronic states of C3Ar have been carried out; the calculated values are consistent with estimates of ≤144 cm-1 and 164 cm-1, respectively, given by the WRE spectra.

First COVID-19 mortality case in Taiwan with bacterial co-infection by national surveillance of critically ill patients with influenza-negative pneumonia.

A 63-year-old diabetic smoker with alcoholism was the first mortality case of coronavirus disease 2019 (COVID-19) in Taiwan. As concurrently infected with Klebsiella pneumoniae and subsequently with Klebsiella aerogenes, he was exposed by a national survey of patients with critically influenza-negative pneumonia. We recommend COVID-19 screening for patients with severe flu-like syndrome and protecting health-care workers from being infected.

Assess the Performance and Cost-Effectiveness of LACE and HOSPITAL Re-Admission Prediction Models as a Risk Management Tool for Home Care Patients: An Evaluation Study of a Medical Center Affiliated Home Care Unit in Taiwan.

The LACE index and HOSPITAL score models are the two most commonly used prediction models identifying patients at high risk of readmission with limited information for home care patients. This study compares the effectiveness of these two models in predicting 30-day readmission following acute hospitalization of such patients in Taiwan. A cohort of 57 home care patients were enrolled and followed-up for one year. We compared calibration, discrimination (area under the receiver operating curve, AUC), and net reclassification improvement (NRI) to identify patients at risk of 30-day readmission for both models. Moreover, the cost-effectiveness of the models was evaluated using microsimulation analysis. A total of 22 readmissions occurred after 87 acute hospitalizations during the study period (readmission rate = 25.2%). While the LACE score had poor discrimination (AUC = 0.598, 95% confidence interval (CI) = 0.488-0.702), the HOSPITAL score achieved helpful discrimination (AUC = 0.691, 95% CI = 0.582-0.785). Moreover, the HOSPITAL score had improved the risk prediction in 38.3% of the patients, compared with the LACE index (NRI = 0.383, 95% CI = 0.068-0.697, p = 0.017). Both prediction models effectively reduced readmission rates compared to an attending physician's model (readmission rate reduction: LACE, 39.2%; HOSPITAL, 43.4%; physician, 10.1%; p < 0.001). The HOSPITAL score provides a better prediction of readmission and has potential as a risk management tool for home care patients.

Continuity of Physicians' Dedication to Inpatient Hospice and Palliative Care: A 14-year Nationwide Survey in Taiwan.

Background: The work continuity of physicians in hospice and palliative medicine (HPM) has a great impact on the quality of care and practice experiences. However, nationwide studies providing a general overview of the work continuity of HPM physicians are scarce. Methods: Data relating to inpatient HPM care provided from July 2000 to December 2013 were obtained from the National Health Insurance Research Database of Taiwan. Specifically, the numbers of hospitals, patients, patient hospitalization days, and physicians involving HPM in each year were calculated. The years of HPM work experience and total HPM workdays of each physician were also computed. Results: Of the 40,965,153 inpatient records during the study, 121,258 (0.3%) records were related to inpatient HPM care, with 60 participating hospitals and 604 attending physicians. The annual number of HPM physicians increased with time from 77 in 2000 to 217 in 2013. The largest percentage (38.4%) of physicians practiced HPM for only one year, while only 23 (3.8%) physicians practiced HPM in each year without interruption. Of the 217 HPM physicians in 2013, 45 (20.7%) were newcomers, 78 (36.0%) had 1-4 years of prior HPM work experience, 54 (24.9%) had 5-9 years, and 40 (18.4%) had at least 10 years. Conclusions: Among HPM physicians in Taiwan, only a small percentage exhibited long-term dedication to the field, whereas most HPM physicians had short practice periods. More strategies are needed to improve work continuity among HPM physicians.

The Provision of Health Care by Family Physicians in Taiwan as Illustrated With Population Pyramids.

Family physicians serve as personal doctors for individuals and their families and also act as gatekeepers of the health care system. If no special status is accorded to family physicians, however, then the rates at which health care recipients utilize their service might be affected. In the present cross-sectional study, representative claims data sets for 2010 from Taiwan's National Health Insurance program, a health care system in which beneficiaries are not required to register with a family physician, were used to investigate the provision of health care to the population by family physicians. Among 919 206 beneficiaries with a total of 13 713 199 ambulatory visits, 49.1% had visited family physicians, 34.1% had visited internists, 24.3% had visited pediatricians, and 38.9% had visited otolaryngologists. Women (χ2(1) = 538, P < .001) and patients aged 65 and above (χ2(1) = 16 000, P < .001) had a higher proportion of visiting family physicians rather than visiting other specialties. The onion-shaped population pyramid with family medicine visits was compatible with the general population, and the proportion of visiting family physicians increased with increasing age. Among 112 289 patients with essential hypertension, 63 379 patients with diabetes mellitus, and 80 090 patients with hyperlipidemia, only 35.3%, 32.0%, and 31.1%, respectively, had visited family physicians. The age and sex distributions of these patients were illustrated with population pyramids for data visualization and direct comparisons. Taken together, the results of this study indicate that the utilization of family physicians in Taiwan and the effectiveness of their associated role in chronic disease management still have room for improvement.

Situation of seven-day service among family medicine clinics in Taiwan: A nationwide survey.

BACKGROUND: General medicine practices in England are required to provide services from 8am to 8pm on weekdays and to also open on Saturdays and Sundays. Internationally, however, the literature regarding the temporal availability of primary health care on national levels is scarce. METHODS: To provide such information regarding Taiwan, in this study, all family medicine clinics within Taiwan's National Health Insurance system were stratified by urbanization level, and the opening hours of the clinics were then analyzed. The opening hours of the clinics were downloaded and the data were extracted cross-sectionally in July 2015. For each clinic, the number of open sessions (in terms of morning, afternoon, and evening sessions) per week was calculated. For each urbanization level, the opening ratios for out-of-hours services and for seven-day services were also analyzed. RESULTS: Among 1621 family medicine clinics, 835 were located in urban areas, 563 were suburban, and 223 were rural. The average numbers of open sessions per week among urban and suburban clinics were higher than among rural clinic (15.7 ± 3.7 and 15.8 ± 3.7 vs. 14.4 ± 4.0). Urban and suburban clinics also had higher opening ratios on weekday evenings and on weekends than rural clinics. Only 53 (3.3%) of all the clinics (29 urban clinics, 18 suburban clinics, and 7 rural clinics) remained open for all 21 sessions of a week. CONCLUSION: The great majority of family medicine clinics in Taiwan voluntarily offered out-of-hours services, but only a small minority remained open in all 21 sessions of a week.

Is Excessive Polypharmacy a Transient or Persistent Phenomenon? A Nationwide Cohort Study in Taiwan.

Objectives: Target populations with persistent polypharmacy should be identified prior to implementing strategies against inappropriate medication use, yet limited information regarding such populations is available. The main objectives were to explore the trends of excessive polypharmacy, whether transient or persistent, at the individual level. The secondary objectives were to identify the factors associated with persistently excessive polypharmacy and to estimate the probabilities for repeatedly excessive polypharmacy. Methods: Retrospective cohort analyses of excessive polypharmacy, defined as prescription of ≥ 10 medicines at an ambulatory visit, from 2001 to 2013 were conducted using a nationally representative claims database in Taiwan. Survival analyses with log-rank test of adult patients with first-time excessive polypharmacy were conducted to predict the probabilities, stratified by age and sex, of having repeatedly excessive polypharmacy. Results: During the study period, excessive polypharmacy occurred in 5.4% of patients for the first time. Among them, 63.9% had repeatedly excessive polypharmacy and the probabilities were higher in men and old people. Men versus women, and old versus middle-aged and young people had shorter median excessive polypharmacy-free times (9.4 vs. 5.5 months, 5.3 vs. 10.1 and 35.0 months, both p < 0.001). Overall, the probabilities of having no repeatedly excessive polypharmacy within 3 months, 6 months, and 1 year were 59.9, 53.6, and 48.1%, respectively. Conclusion: Although male and old patients were more likely to have persistently excessive polypharmacy, most cases of excessive polypharmacy were transient or did not re-appear in the short run. Systemic deprescribing measures should be tailored to at-risk groups.

Birth Trends among Female Physicians in Taiwan: A Nationwide Survey from 1996 to 2013.

Background: Although more and more women are becoming physicians, their decisions regarding pregnancy may be affected by the lengthy period of medical education and postgraduate training. The aim of this study was to explore the birth trends among female physicians in Taiwan; Methods: Retrospective analyses of maternal ages at delivery from 1996 to 2013, both for physicians and the general population, were conducted using a nationwide dataset called National Health Insurance Research Database; Results: During the study period, 8540 female physicians were identified. The physicians delivered a total of 4940 births in that time, with a rise from 210 in 1996 to 440 in 2013. In addition, the mean maternal age of the physicians at delivery increased from 32.19 years (standard deviations (SD) 2.80) in 1996 to 33.61 (SD 3.21) in 2013, values significantly higher than those for non-physicians of 27.81 (SD 4.74) in 1996 (p < 0.001) and 31.36 (SD 4.78) in 2013 (p < 0.001); Conclusion: Female physicians usually gave birth at an older age than non-physicians, but the discrepancy between the two groups gradually declined over the 18-year course of the study. The establishment of a maternity-friendly environment for female physicians should be considered by those who determine healthcare system policies.

Pattern of Visits to Older Family Physicians in Taiwan.

Many family physicians still practice at an old age. Nevertheless, their practice patterns have scarcely been studied. To address this lack of research, the current study analyzed claims data for a total of 2,018,440 visits to 171 family physicians in 2011 sourced from Taiwan's National Health Insurance Research Database. Family physicians aged 65 years and over had fewer patients (mean: 2330, standard deviation (SD): 2019) and visits (mean: 9220, SD: 8600) than younger physicians had. Furthermore, the average age of the patients who visited physicians aged 65 years and over was 51.9 (SD: 21.5) years, significantly higher than that of patients who visited younger physicians. However, the proportions of visits for upper respiratory tract infections, hypertension, diabetes mellitus, and dyslipidemia did not differ significantly among different age groups of physicians. In the future, the manpower planning of physicians should take into consideration the age structure and work profile of physicians.

Rotational analysis of bands of the à - X̃ transition of the C3Ar van der Waals complex.

Rotational analyses have been carried out for four of the strongest bands of the Ã-X̃ transition of the C3Ar van der Waals complex, at 393 and 399 nm. These bands lie near the 02(-)0-000 and 04(-)0-000 bands of the Ã(1)Πu-X̃(1)Σ(+) g transition of C3 and form two close pairs, each consisting of a type A and a type C band of an asymmetric top, about 4 cm(-1) apart. Only K″ = even lines are found, showing that the complex has two equivalent carbon atoms (I = 0), and must be T-shaped, or nearly so. Strong a- and b-axis electronic-rotational (Coriolis) coupling occurs between the upper states of a pair, since they correlate with a (1)Πu vibronic state of C3, where the degeneracy is lifted in the lower symmetry of the complex. Least squares rotational fits, including the coupling, have given the rotational constants for both electronic states: the van der Waals bond lengths are 3.81 and 3.755 Å, respectively, in the ground and excited electronic states. For the ground state our new quantum chemical calculations, using the Multi-Channel Time-Dependent Hartree method, indicate that the C3 unit is non-linear, and that the complex does not have a rigid-molecule structure, existing instead as a superposition of arrowhead (↑) and distorted Y-shaped (Y) structures.

Fluorescence lifetimes of the Ã1Πu state of C3.

The fluorescence lifetimes of 115 vibrational levels of the Ã1Π(u) state of C3 have been measured under supersonic molecular beam conditions. Of these, ninety-one are Π(u) vibronic levels, for which the lifetimes lie in the range 190-700 ns. The lifetimes of those Π(u) levels where only the bending vibration is excited lie in the range 190-235 ns. There is very little variation with bending quantum number, and the lifetimes of the two orbital components of the 1Π(u) state are essentially the same. When ν1 and ν3 are excited, the lifetimes become longer and/or reach a maximum for levels with v1 + v3 ~ 4. Excitation of the bending vibration in addition to the stretching vibrations shortens the lifetime slightly. Several of the levels show double-exponential decays. Another 23 levels, of Σ(u)+ vibronic symmetry, mostly have lifetimes that are longer than 300 ns. Interaction with nearby "dark" electronic states, such as B1Σ(u)-, B'1Δ(u), C1Π(g), and b3Π(g), is proposed to account for the observed lifetime lengthening. A particularly clear instance of such an interaction is the long lifetime (914 ns) of a perturbing Σ(u)+ level at 30,181 cm(-1), which is confirmed as belonging to the perturbing B'1Δ(u) state. A single level of Δ(u) symmetry at 29,170 cm(-1), which perturbs one of the Π(u) levels, is shown to belong to the à state.

p38 Mitogen-activated protein kinase and extracellular signal-regulated kinase signaling pathways are not essential regulators of formyl peptide-stimulated p47(phox) activation in neutrophils.

Three structurally unrelated p38 mitogen-activated protein kinase (MAPK) inhibitors, (4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)imidazole (SB203580), 1-5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-[4-(2-morpholin-4-yl-ethoxy)naphthalen-1-yl] urea (BIRB 796) and 5-(2,6-dichlorophenyl)-2-[2,4-difluorophenyl]thio]-6H-pyrimido[1,6-b]pyridazin-6-one (VX 745) showed approximately 40% inhibition of formyl-Met-Leu-Phe (fMLP)-stimulated neutrophil superoxide anion (O2(•-)) generation at concentrations that greatly diminished p38 MAPK activity. However, a significant inhibition of p47(phox) activation occurred at concentrations much higher than the corresponding IC50 values of these inhibitors in blocking p38 MAPK activity. 4-Ethyl-2(p-methoxyphenyl)-5-(4'-pyridyl)-IH-imidazole (SB202474), an inactive analogue of SB203580, at a concentration (30µM) which significantly attenuated p38 MAPK activity, had no effect on p47(phox) activation, whereas it inhibited O2(•-) generation with an IC50 value of approximately 16µM. Moreover, both SB203580 and BIRB 796 had no effect on protein kinase B (PKB)/Akt Ser473 phosphorylation and S100A9 protein membrane translocation at concentrations that effectively blocked p38 MAPK activity. Pretreatment of cells with two structurally unrelated MAPK/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitors, 2-(2-amino-3-methoxy-phenyl)-chromen-4-one (PD 98059) and 1,4-diamino-2,3-dicyano-1,4-bis(2-aminophenylthio)butadiene (U0126), at concentrations that effectively blocked MEK activity, attenuated p47(phox) phosphorylation but did not affect the recruitment of p47(phox) to p22(phox) or O2(•-) generation. Both p47(phox) activation and O2(•-) generation were attenuated by a protein kinase C (PKC) inhibitor 2-[1-(3-dimethylaminopropyl)-1H-indol-3-yl]-3-(1H-indol-3-yl)-maleimide (GF 109203X) in the concentration range that effectively blocked PKC activity. Taken together, these results suggest that the ERK-mediated Ser phosphorylation of p47(phox) is not implicated in the assembly of NADPH oxidase or O2(•-) generation, and that O2(•-) generation is partly attributable to p38 MAPK signaling through mechanisms other than p47(phox) activation, Akt activation and S100A9 membrane recruitment in fMLP-stimulated neutrophils.

Syphilis and neurosyphilis in human immunodeficiency virus-infected patients: a retrospective study at a teaching hospital in Taiwan.

BACKGROUND AND PURPOSE: Some studies have reported that the risk factors for neurosyphilis in patients with human immunodeficiency virus (HIV) and syphilis co-infection, include CD4 cell counts ≤350cells/µL and rapid plasma reagin (RPR) titer ≥1:32. However, neurosyphils can develop even in patients with CD4 cell counts >350cells/µL or RPR titer <1:32. In this study, we evaluated the outcome of syphilis to treatment in HIV-infected patients, and analysed the predictors of neurosyphilis in this population. METHODS: We retrospectively reviewed medical records of HIV-infected patients with syphilis who visited the China Medical University Hospital between January 2000 and December 2009. Neurosyphilis was defined by white blood cell (WBC) counts >20cells/µL in the cerebrospinal fluid (CSF) sample or elevated Venereal Disease Research Laboratory (VDRL) titers of the CSF samples. Treatment failure was defined as less than 4-fold decrease in the serum RPR titer at or beyond 12 months post-treatment in case of early syphilis, and, at or beyond 24 months in case of late syphilis. RESULTS: One hundred and twenty-one HIV-infected patients (average age, 32 years) with syphilis were included in this study. Of 63 patients who had follow-up of serologic responses, 30 (47.6%) failed to respond to treatment. CD4 cell counts ≤200cells/µL was the indicator for treatment failure (P=.029). Lumbar puncture was performed in 65 patients, and 14 patients were diagnosed with neurosyphilis. At the time of lumbar puncture, 31 and 19 of the 65 patients showed CD4 cell counts of >350cells/µL and RPR of <1:32, respectively. An HIV viral load (VL) ≥10000copies/mL was found to be associated with the development of neurosyphilis (P=.016). CONCLUSION: In HIV-infected patients with syphilis, RPR titer should be evaluated more frequently when CD4 count ≤200cell/µL is associated with treatment failure. Lumbar puncture for the diagnosis of neurosyphilis should be considered in patients with HIV and syphilis co-infection, even in patients with CD4 cell counts >350cells/µL, and particularly when the HIV VL ≥10000copies/mL.