From comfort zone to front-line care: perspectives and reflections of community pharmacists entering home-based palliative care.

BACKGROUND: Palliative care requires a multidisciplinary team to assist patients and their families to obtain good quality care at the end of life. Typically, community pharmacists have fewer opportunities to provide services for patients with palliative care needs than hospital pharmacists. Moreover, home-based palliative care (HBPC) by pharmacists remains low and there is a lack of research regarding HBPC provided by pharmacists. Therefore, this study sought to understand the views and reflections of community pharmacists in the clinical frontline providing palliative home services. METHODS: Purposive sampling was used to recruit six community pharmacists for one-on-one, in-depth, semi-structured interviews and the data were analysed using thematic analysis. RESULTS: Five major themes emerged: [1] Engagement, [2] Challenge, [3] Mission, [4] Career metamorphosis, and [5] Outlook. The pharmacists described how they engaged in HBPC and faced the challenges. They regarded opioid management as a burden. Moreover, some mentioned that reimbursement for palliative home care is low or non-profitable. They suggested building a platform to exchange advice and legislation adjustments so that they could pass on their experiences to less experienced pharmacists in HBPC. CONCLUSIONS: The involvement of pharmacists is crucial to provide better palliative care. Although the present study was small and might not fully represent the whole situation, the findings could still inform future education, training, and policy planning to promote pharmacists' participation in palliative care to generalise community palliative care.

FcγRIIB modulates splenic germinal center response against immune subversion during acute influenza A virus infection.

BACKGROUND: B cells are essential for providing humoral protection against acute influenza A virus (IAV) infection. FcγRIIB, a regulator of antibody (Ab) production, influences immune responses during pathogen infections, but its specific impact on humoral protection and B cell-mediated responses against IAV remains unclear. METHODS: To investigate FcγRIIB's role in host defense and B cell function during acute IAV infection, we generated mice with systemic FcγRIIB deficiency, functional impairment, and B cell-specific FcγRIIB deletion. We infected these mice with PR8 (H1N1) or Hkx31 (H3N2) IAVs and evaluated body weight preservation, survival rates, Ab production, viral neutralization, Ab affinity maturation, and germinal center B cell development. RESULTS: Mice lacking FcγRIIB or with impaired function showed improved protection, preserved body weight, and increased survival rates during IAV infection. Notably, mice with haploinsufficient FcγRIIB function displayed protective effects. Selective deficiency of FcγRIIB in B cells led to enhanced Ab production, resulting in elevated IAV-specific Abs in the serum with superior viral neutralizing potency. However, the impact on the affinity maturation index of virus-specific Abs was modest. Accordingly, FcγRIIB-deficient B cells maintained normal germinal center B cell development during IAV infection, whereas wild-type mice exhibited delayed differentiation. CONCLUSION: Our research underscores the pivotal role of FcγRIIB in host defense and B cell-mediated immunity during acute IAV infection. Additionally, our discoveries hold implications for antiviral treatments, particularly during the initial stages of IAV infection, aimed at enhancing the host's humoral immune response.

Correlates of the Veterans Visiting Emergency Departments in Taiwan: A Comparison Before and After the Coronavirus Disease 2019 Pandemic.

BACKGROUND: Taiwan has a substantial number of veterans, but knowledge regarding their emergency department (ED) visits during the coronavirus disease 2019 (COVID-19) pandemic remains limited. This study examined the characteristics of veterans' ED visits during Taiwan's COVID-19 epidemic. METHODS: This was a cross-sectional study conducted at the ED of a large veteran medical center located in Taipei, Taiwan, from May 2018 to October 2021. We analyzed the numbers and features of visits in summer and autumn according to the first wave of the COVID-19 epidemic in Taiwan in 2021. RESULTS: Medical institutions were positively associated with veteran status. Emergency department complaints of trauma (adjusted odds ratio [AOR] = 1.15, 95% CI: 1.06-1.25; summer P < .01) and chest pain/tightness (AOR = 1.65, 95% CI: 1.45-1.87; summer P < .01; AOR = 1.4, 95% CI: 1.26-1.55; P < .01) were associated with increased odds of being a veteran. Triage levels above 2 were positively associated with veteran status in the autumn model (AOR = 1.14, 95% CI: 1.07-1.22; P < .01). Patients hospitalized after ED visits were associated with reduced odds of veteran status (P < .01). Those who spent a long time in the ED were more likely to be veterans than those who spent a shorter time in the ED (P < .01). Veterans were less likely to visit the ED regardless of the time frame of the study period (P < .01), except during the COVID-19 outbreak in the autumn (2019-2020). CONCLUSIONS: The distinctions in ED visits highlighted the individuality of veterans' medical needs. Our findings suggest that the veteran medical system can add to the focus on improving senior-friendly care, fall prevention, quality of life of institutionalized veterans, access for homeless veterans, and care for ambulatory care-sensitive conditions.

Dual antiplatelet therapy is associated with favorable outcome in acute minor stroke with an onset-to-door time beyond 24 h.

BACKGROUND/PURPOSE: In patients with noncardioembolic acute minor ischemic stroke (AMIS), dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel within 24 h after stroke onset was more effective than aspirin alone. This study investigated the efficacy and safety of DAPT in AMIS patients with an onset-to-door time (OTDT) of more than 24 h. METHODS: This was a retrospective analysis of a prospective stroke registry from 2015 to 2021. Patients with AMIS and an OTDT within seven days were classified into the Early (≤24 h) and Late groups (>24 h) according to the time of antiplatelet administration after stroke onset. RESULTS: In total, 691 patients were identified. Of these, 446 (64.5%) and 245 (35.5%) patients were classified into the Early and Late groups, respectively. The rates of recurrent infarction and symptomatic intracranial hemorrhage at 90 days were similar between the single antiplatelet therapy (SAPT) and DAPT subgroups in both the Early and Late groups. More patients in the DAPT subgroup had a favorable outcome (modified Rankin scale of 0-1) at 90 days in both Early (84.2% versus 75.0%, p = 0.016) and Late (88.2% versus 76.9%, p = 0.040) groups. DAPT was independently associated with a favorable outcome in both the Early (odds ratio, 1.95; 95% CI, 1.15-3.32; p = 0.013) and Late (odds ratio, 2.72; 95% CI, 1.14-6.48; p = 0.024) groups. CONCLUSION: In patients with AMIS and an OTDT of more than 24 h, DAPT was associated with a favorable outcome at 90 days.

Patent foramen ovale closure in non-elderly and elderly patients with cryptogenic stroke: a hospital-based cohort study.

Introduction: The efficacy of patent foramen ovale (PFO) closure in the elderly population is unclear. We aimed to investigate the efficacy and safety of PFO closure in non-elderly and elderly patients. Methods: Patients over 18 years of age with cryptogenic stroke (CS) or transient ischemic attack and PFO were prospectively enrolled and classified into two groups according to treatment: (1) closure of PFO (the PFOC group) and (2) medical treatment alone (the non-PFOC group). The primary outcome was a composite of recurrent cerebral ischemic events and all-cause mortality during the follow-up period. A modified Ranking Scale [mRS] at 180 days was recorded. The safety outcomes were procedure-related adverse events and periprocedural atrial fibrillation. The results between the PFOC and non-PFOC groups in non-elderly (<60 years) and elderly (≥60 years) patients were compared. Results: We enrolled 173 patients, 78 (45%) of whom were elderly. During a mean follow-up of 2.5 years, the incidence of primary outcome was significantly lower in the PFOC group (6.2% vs. 17.1%, hazard ratio[HR] = 0.35, 95% CI 0.13-0.97, p = 0.043) in adjusted Cox regression analysis. Compared with the non-PFOC group, the PFOC group had a numerically lower risk of the primary outcome in both the elderly (HR 0.26, 95% CI 0.07-1.01, p = 0.051) and the non-elderly (HR 0.61, 95% CI 0.11-3.27, p = 0.574) groups. In addition, patients with PFO closure in the elderly group had a lower median mRS at 180 days (p = 0.002). The rate of safety outcome was similar between the non-elderly and elderly groups. Discussion: PFO closure was associated with a reduced risk of the primary outcome in patients with PFO and CS in our total cohort, which included non-elderly and elderly patients. Compared to those without PFO closure, elderly patients with PFO closure had a better functional outcome at 180 days. PFO closure might be considered in selected elderly patients with PFO.

Severe lupus flare is associated with a much higher risk of stroke among patients with SLE.

BACKGROUND AND AIM: There are few data on the influence of lupus flare on stroke risk in systemic lupus erythematosus (SLE). In this study, we examined whether a severe lupus flare further increases the risk of stroke among SLE patients. METHODS: Using the Taiwan's National Health Insurance Research Database, we conducted a retrospective population-based cohort study from 2000 to 2016. Each patient with SLE was matched to a non-SLE subject in age, sex, and index date. A severe flare of lupus was identified when an SLE patient was admitted for pulse therapy with intravenous methylprednisolone greater than 250 mg in a single hospitalization. SLE patients were divided into severe flare and non-severe flare groups. RESULTS: In total, 334 of 10,006 patients with SLE had a severe lupus flare, and the remaining 9672 patients were assigned to the non-severe flare group. Ischemic stroke occurred in 29 (8.7%), 485 (5%), and 384 (3.8%) of the patients in the severe flare, non-severe flare, and control groups, respectively. Hemorrhagic stroke occurred in 9 (2.7%), 123 (1.3%), and 37 (0.4%) of patients in the severe flare, non-severe flare, and control groups, respectively. Compared with patients in the non-severe flare group, patients with severe flare had a significantly higher risk of ischemic stroke (adjusted hazard ratio (aHR) = 7.44, 95% confidence interval (CI): 4.93-11.25 vs aHR = 1.52, 95% CI: 1.26-1.83) and hemorrhagic stroke (aHR = 22.49, 95% CI: 10.09-50.12 vs aHR = 4.47, 95% CI: 2.90-6.90). CONCLUSION: Severe lupus flare is associated with a much higher risk of ischemic and hemorrhagic strokes among SLE patients.

The experiences and needs of nurses providing home-based palliative care: A qualitative meta-synthesis.

Objective(s): We conducted a qualitative meta-synthesis of qualitative studies on nurses' experiences when caring for palliative patients to (1) identify the needs of nurses and (2) describe their experiences to provide more in-depth information. Methods: Qualitative articles published in English from 2000 to 2022 were identified from several databases through a searching strategy. Authors screened through the title, abstract, and full text of relevant studies. Articles were read repeatedly and discussed. The thematic analysis methodology was adopted to analyze the data. Results: Of 967 articles, 22 were included in our review. Notions reflecting community nurses providing palliative home care were clustered into four themes: (1) nature of community-based palliative nursing, (2) teamwork, (3) relationship with patient and family, and (4) resources. Findings also suggest establishing a sound support system, strengthening palliative education, and creating more decisive referral criteria and systems. Conclusions: The growing need for palliative home care has become challenging for community health care systems. Our study summarized various aspects of nurses providing home-based palliative care. The findings provide information for health care and education settings to improve home care systems and recruit more staff to meet the needs.

Dihydrocaffeic Acid-Decorated Iron Oxide Nanomaterials Effectively Inhibit Human Calcitonin Aggregation.

To date, more than 30 human peptides or proteins have been found to form amyloid fibrils, most of which are associated with human diseases. However, currently, no cure for amyloidosis exists. Therefore, development of therapeutic strategies to inhibit amyloid formation is urgently required. Although the role of some amyloidogenic proteins has not been identified in certain diseases, their self-assembling behavior largely affects their bioactivity. Human calcitonin (hCT) is a hormone peptide containing 32 amino acids and is secreted by the parafollicular cells of the thyroid gland in the human body. It can regulate the concentration of calcium ions in the blood and block the activity of osteoclasts. Therefore, calcitonin has also been considered a therapeutic peptide. However, the aggregation of hCT hinders this process, and hCT has been replaced by salmon calcitonin in drug formulations. Recently, iron oxide nanomaterials have been developed as potential materials for various applications owing to their high biocompatibility, low toxicity, and ease of functionalization. In this study, nanoparticles (NPs) were prepared using a simple chemical coprecipitation method. We first demonstrated that dopamine-conjugated Fe3O4 inhibited hCT aggregation, similar to what we found when carbon dots were used as core materials in the previous study. Later, we continued to simplify the preparation process, that is, the mixing of dihydrocaffeic acid (DCA) and iron oxide NPs, to maintain their stability and inhibitory effect against hCT aggregation. Furthermore, DCA-decorated Fe3O4 can dissociate preformed hCT amyloid fibrils. This appears to be one of the most promising ways to stabilize hCT in solution and may be helpful for amyloidosis treatment.

Prognostic significance of the blood urea nitrogen to creatinine ratio in in-hospital cardiac arrest after targeted temperature management.

BACKGROUND: Targeted temperature management (TTM) has been reported to improve outcomes in in-hospital cardiac arrest (IHCA) patients but little has been investigated into the relationship between prognoses and the blood urea nitrogen to creatinine ratio (BCR). METHODS: A retrospective analysis of data from IHCA survivors treated with TTM between 2011 and 2018 was conducted based on the Research Patient Database Registry of the Partners HealthCare system in Boston. Serum laboratory data were measured during IHCA and within 24 hours after TTM completion. Intra-arrest and post-TTM BCRs were calculated, respectively. The primary outcome was neurologic status at discharge. The secondary outcome was in-hospital mortality. RESULTS: The study included 84 patients; 63 (75%) were discharged with a poor neurologic status and 40 (47.6%) died. Regarding poor neurological outcome at discharge, multivariate analysis revealed that post-TTM BCR was a significant predictor (adjusted OR, 1.081; 95% CI, 1.002-1.165; p = 0.043) and intra-arrest BCR was a marginal predictor (adjusted OR, 1.067; 95% CI, 1.000-1.138; p = 0.050). Post-TTM BCR had an acceptably predictive ability to discriminate neurological status at discharge, with an area under the receiver-operating characteristic curve of 0.644 (95% CI, 0.516-0.773) and a post-TTM BCR cutoff value of 16.7 had a sensitivity of 61.9% and a specificity of 70.0%. CONCLUSION: Post-TTM BCR was a significant predictor of the neurologic outcome at discharge among IHCA patients receiving TTM. IHCA patients with elevated intra-arrest BCR also had a borderline poor neurological prognosis at discharge.

A 10-year Trend of Sleeping Patterns, Geographical, and Community Disparities Among Chinese Older Adults.

This study examined the trend and geographical/community disparities of sleeping patterns among Chinese older adults. We included older adults from four waves of the Chinese Longitudinal Healthy Longevity Survey (CLHLS; n = 25,672; age ≥65). We used a multivariable logistic regression model to examine sleep quality (not good versus good), and a multinomial logistic regression model to assess daily sleep duration (7-8 hr, <7 hr, >8 hr). Older adults from the Central/South and the West regions were less likely to report good sleep quality (AOR [adjusted odds ratio] = .63, 95% CI: .55, .72 and AOR = .80, 95% CI: .70, .93, respectively) while the Northeastern residents reported better sleep quality (AOR = 1.51, 95% CI: 1.27, 1.79), compared with Northern residents. Older adults from Central/South and West were more likely to obtain less than 7 hr of sleep. Public health interventions are necessary to improve the sleep of Chinese older adults.

The effect of reduction on the properties of the regioselectively oxidized starch granules prepared by bromide-free oxidation system.

Development of intact oxidized starch granules by regioselective oxidation technology is of interest and provides a new research direction for oxidized starch. In this study, new sodium tetrahydridoborate (NaBH4)-treated oxidized starch (OS-BH4) granules were prepared by a one-pot method, where native corn starch (NS) granules were oxidized by 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO)/sodium hypochlorite (NaClO) system followed by reduction with NaBH4. Oxidized starch (OS) granules without NaBH4 reduction were also prepared to investigate the effect of C6 aldehyde groups remained after TEMPO-mediated oxidation on properties of the granules. When degrees of oxidation were controlled to be not higher than 12%, both the OS and OS-BH4 granules had similar morphology to the NS granules with envelopes. Compared to the OS granules, except for lower pasting temperatures and dextrose equivalents, the OS-BH4 granules had higher molecular weights, degrees of polymerization (DP), peak viscosities, final viscosities, and swelling power. Difference of the properties was considered related to (1) repulsive forces formed between the C6 carboxylate groups, (2) C6 aldehyde groups with lower hydrophilicity than the C6 hydroxyl groups, and (3) some hemiacetal linkages formed between the C6 aldehyde groups and the hydroxyl groups. Furthermore, pregelatinized OS-BH4 granules were preliminarily prepared, which showed good swelling behavior with intact granular morphology in alkaline environment.

Frailty is Associated With Frontal Cortex-Related Cognitive Function in Patients With Alzheimer Disease.

OBJECTIVE: We compared the cognitive functions of Alzheimer disease (AD) patients who were robust, frail or pre-frail and hypothesized that declines in frontal cortex-related neuropsychological function would be associated with frailty. METHOD: One hundred and sixty outpatients aged 65 years or older with mild AD were enrolled. Cognitive function was assessed using the Cognitive Ability Screening Instrument and further classified into 4 clusters (recent memory, frontal cortex cluster, posterior cortex cluster, and orientation). Other variables included depressive mood, daily activities, body mass index, handgrip strength (HGS), and normal gait speed (NGS). RESULTS: Performance in daily activities, and slower NGS than robust group. Both the frail and pre-frail groups had lower HGS and more depressive symptoms than robust group. Generalized linear with ordinal logistic analysis showed that increment in age, slowing in NGS, and worse frontal cortex cluster function associated with being in a higher level of frailty. The patients with depression symptoms were the odds of being in a higher level of frailty compared to those without depression symptoms. CONCLUSIONS: In addition to physical and psychological symptoms, frailty is associated with specific cognitive domains in patients with AD. A multidimensional approach should be used to assess the impact of intervention programs focusing on frail patients with AD.

Heme oxygenase-1 inhibits DENV-induced endothelial hyperpermeability and serves as a potential target against dengue hemorrhagic fever.

Dengue virus (DENV) is a cause of vascular endothelial dysfunction and vascular leakage, which are characterized as hallmarks of dengue hemorrhagic fever or dengue shock syndrome, which become a severe global health emergency with substantial morbidity and mortality. Currently, there are still no promising therapeutics to alleviate the dengue-associated vascular hemorrhage in a clinical setting. In the present study, we first observed that heme oxygenase-1 (HO-1) expression level was highly suppressed in severe DENV-infected patients. In contrast, the overexpression of HO-1 could attenuate DENV-induced pathogenesis, including plasma leakage and thrombocytopenia, in an AG129 mouse model. Our data indicate that overexpression of HO-1 or its metabolite biliverdin can maintain endothelial integrity upon DENV infection in vitro and in vivo. We further characterized the positive regulatory effect of HO-1 on the endothelial adhesion factor vascular endothelial-cadherin to decrease DENV-induced endothelial hyperpermeability. Subsequently, we confirmed that two medicinal plant-derived compounds, andrographolide, and celastrol, widely used as a nutritional or medicinal supplement are useful to attenuate DENV-induced plasma leakage through induction of the HO-1 expression in DENV-infected AG129 mice. In conclusion, our findings reveal that induction of the HO-1 signal pathway is a promising option for the treatment of DENV-induced vascular pathologies.

Community Nurses' Preparations for and Challenges in Providing Palliative Home Care: A Qualitative Study.

Hospitals have played a leading role in providing palliative care in Taiwan as its care model has developed over the past few decades. However, earlier local studies in Taiwan showed that terminal patients prefer to die at home, highlighting the need to promote community-based palliative care instead of hospital-based care. Along with this shift, how community nurses provide palliative home care merits further exploration. This qualitative descriptive study aims to understand (1) how community nurses implement community-based palliative care, (2) what preparations are needed, and (3) what challenges they may face. Purposive sampling was used for recruiting nurses. We conducted one-on-one, in-depth, semi-structured interviews. Interview recordings were transcribed verbatim and analyzed using thematic analysis. Eight community nurses with a range of experience in palliative home care were interviewed. Four major themes emerged: (1) Opportunities, (2) Qualifications, (3) Support, and (4) Commitments. Psychological preparedness, well-developed professional capabilities, external assistance, and peer support motivate community nurses to offer community-based palliative care. As the requests for palliative home care services increase, community nurses play a critical role in palliative home care. Although the sample size is small and the findings retrieved from a small number of experiences might not be generalized to every region, the study results could inform future experience-sharing and workshop sessions to train more nurses for community-based care, expanding service coverage, and providing optimal palliative care.

Factors associated with do-not-resuscitate document completion among patients hospitalized in geriatric ward.

BACKGROUND: With a rapidly aging population, there is an increasing need for do-not-resuscitate (DNR) and advance care planning (ACP) discussions. This study investigated the factors associated with signing DNR documents of older patients in the geriatric ward. METHODS: We conducted a retrospective cohort study at a geriatric ward in a tertiary hospital in Southern Taiwan. Three hundred and thirty-seven hospitalized older patients aged ≥65 years in the geriatric ward from 2018 to 2019. The Hospital Information System and electronic medical records were accessed to obtain details regarding patients' demographics, daily living activities, serum albumin level, nutrition screening score, intensive care unit transferal, resuscitation procedure, days of hospital stay, and survival status on discharge, and DNR status was recorded retrospectively. Patients were classified into DNR and non-DNR groups, with t-tests and Chi-square tests applied to compare the differences between groups. Logistic regression was performed to predict factors related to the DNR documents. RESULTS: A total of 337 patients were included, 66 of whom had signed a DNR during hospitalization. After multivariate logistic regression, age 85 or more compared to age 65-74 (adjusted odds ratio, aOR 5.94), poor nutrition with screening score two or more (aOR 2.71), albumin level less than 3 (aOR 3.24), Charlson Comorbidity Index higher than 2 (aOR 2.46) and once transferred to ICU (aOR 5.11) were independently associated with DNR documentation during hospitalization. CONCLUSIONS: Several factors related to DNR documents for geriatric patients were identified which could provide clinical information for physicians, patients, and their families to discuss DNR and ACP.

Dynamic Modeling and Experimental Validation of an Impact-Driven Piezoelectric Energy Harvester in Magnetic Field.

In this study, an impact-driven piezoelectric energy harvester (PEH) in magnetic field is presented. The PEH consists of a piezoelectric cantilever beam and plural magnets. At its initial status, the beam tip magnet is attracted by a second magnet. The second magnet is moved away by hand and then the beam tip magnet moves to a third magnet by the guidance of the magnetic fields. The impact occurs when the beam motion is stopped by the third magnet. The impact between magnets produces an impact energy and causes a transient beam vibration. The electric energy is generated by the piezoelectric effect. Based on the energy principle, a multi-DOF (multi-degree of freedom) mathematical model was developed to calculate the displacements, velocities, and voltage outputs of the PEH. A prototype of the PEH was fabricated. The voltages outputs of the beam were monitored by an oscilloscope. The maximum generated energy was about 0.4045 mJ for a single impact. A comparison between numerical and experimental results was presented in detail. It showed that the predictions based on the model agree with the experimental measurements. The PEH was connected to a diode bridge rectifier and a storage capacitor. The charges generated by the piezoelectric beam were stored in the capacitor by ten impacts. The experiments showed that the energy stored in the capacitor can light up the LED.

Risk of Dementia in Patients with Depression or Parkinson's Disease: A Retrospective Cohort Study.

BACKGROUND: This study aimed to clarify whether Parkinson's disease (PD) and depression were independent risk factors or with synergic effects in dementia. METHODS: Newly diagnosed PD (n = 1213) patients and control subjects (n = 4852) were selected from the Taiwan National Health Insurance Research Database from January 2001 through December 2008. Follow-up ended in 2011 with an outcome of dementia occurring or not. This cohort was divided into controls with or without depression, PD only, and PD with depression. The incident rate of dementia and hazard ratio (HR) using Cox's regression analysis were calculated for each group. RESULTS: When compared with controls without depression as HR 1.00, the adjusted HR for dementia was 3.29 (p < 0.001) in the PD only group, 2.77 (p < 0.001) in the PD with depression group, and 1.55 (p=0.024) in the depression only group. The incident rate of dementia was 29.2 (per 1000 person-years) in the PD only group and 13.2 in the PD with depression group. The effect of PD on dementia in the depression group produced a HR of 0.97 (p=0.905). CONCLUSIONS: Parkinson's disease served as a risk factor for dementia. By comparison, depression was not a risk factor for dementia in PD patients, although it did act as a risk factor for dementia.

Discovery of Zika Virus NS2B/NS3 Inhibitors That Prevent Mice from Life-Threatening Infection and Brain Damage.

Zika virus (ZIKV) infection, which initially was endemic only in Africa and Asia, is rapidly spreading throughout Europe, Oceania, and the Americas. Although there have been enormous efforts, there is still no approved drug to treat ZIKV infection. Herein, we report the synthesis and biological evaluation of agents with noncompetitive mechanism of the ZIKV NS2B/NS3 protease inhibition through the binding to an allosteric site. Compounds 1 and 2 showed potent activity in both enzymatic and cellular assays. Derivative 1 efficiently reduced the ZIKV protein synthesis and the RNA replication and prevented the mice from life-threatening infection and the brain damage caused by ZIKV infection in a ZIKV mouse model.

Effects of Methyl Terminal and Carbon Bridging Groups Ratio on Critical Properties of Porous Organosilicate-Glass Films.

Organosilicate glass-based porous low dielectic constant films with different ratios of terminal methyl to bridging organic (methylene, ethylene and 1,4-phenylene) groups are spin-on deposited by using a mixture of alkylenesiloxane with organic bridges and methyltrimethoxysilane, followed by soft baking at 120-200 °C and curing at 430 °C. The films' porosity was controlled by using sacrificial template Brij® L4. Changes of the films' refractive indices, mechanical properties, k-values, porosity and pore structure versus chemical composition of the film's matrix are evaluated and compared with methyl-terminated low-k materials. The chemical resistance of the films to annealing in oxygen-containing atmosphere is evaluated by using density functional theory (DFT). It is found that the introduction of bridging groups changes their porosity and pore structure, increases Young's modulus, but the improvement of mechanical properties happens simultaneously with the increase in the refractive index and k-value. The 1,4-phenylene bridging groups have the strongest impact on the films' properties. Mechanisms of oxidative degradation of carbon bridges are studied and it is shown that 1,4-phenylene-bridged films have the highest stability. Methylene- and ethylene-bridged films are less stable but methylene-bridged films show slightly higher stability than ethylene-bridged films.

Sarcopenia in female patients with Alzheimer's disease are more likely to have lower levels of haemoglobin and 25-hydroxyvitamin D.

AIM: Few studies have investigated sarcopenia in patients with cognitive impairment. However, identifying the characteristics and factors associated with sarcopenia in these patients may help to decrease the risk of falls, prevent disabilities, and maintain an independent life, all of which can affect the quality of life of both patient and caregiver. Therefore, the aim of this study was to investigate associated factors of sarcopenia in patients with mild to moderate Alzheimer's disease. METHODS: This cross-sectional study enrolled 125 outpatients aged 65 to 89 years (mean age 79.5 ± 7.9 years) from January 2018 to December 2018. In addition to demographic characteristics, cognitive status, depressive mood, activities of daily living, body mass index (BMI), handgrip strength, gait speed, muscle mass, and serum levels of 25-hydroxyvitamin D (Vit D), haemoglobin (Hb), albumin and creatinine were assessed. Sarcopenia was defined based on the presence of low muscle mass and either low muscle strength or low physical performance. RESULTS: Overall, 29.6% of the patients had sarcopenia. The patients with sarcopenia were mostly male, significantly older, and had a lower BMI and lower levels of Vit D. The female patients with sarcopenia were more likely to have lower levels of Hb. Multiple logistic regression showed that sarcopenia was associated with BMI in both genders. The level of Vit D was associated with sarcopenia in the female patients, whereas age was associated with sarcopenia in the male patients. CONCLUSIONS: A low BMI may be a dementia-related risk factor for sarcopenia. The female patients with sarcopenia were more likely to have lower levels of Hb and Vit D. There may be different risk profiles for sarcopenia in men and women with Alzheimer's disease. Further studies are needed to devise different nutritional support for muscle weakness in patients with cognitive decline by gender.