Relationship Between Resilience Factors and Caregiving Status of Families of Patients with Amyotrophic Lateral Sclerosis (ALS) in Japan.

PURPOSE: To identify innate and acquired factors leading to amyotrophic lateral sclerosis (ALS) caregivers' resilience, the relationships among these factors, and caregiving situations. DESIGN: Cross-sectional study. METHODS: Questionnaires measuring resilience, caregiver burden, and family functioning were mailed to caregivers of ALS patients in Japan. FINDINGS: The 370 responses showed that increases in both innate and acquired factors were related to having an ALS association membership, while decreases were associated with reduced family function. Increases in innate factors were related to employment and those consenting to ventilators, while decreases were associated with being male and having a sense of the care burden. Decreases in acquired factors were related to the presence of an alternative caregiver. CONCLUSIONS: By identifying the caregiving situation based on innate and acquired factors, we were able to identify the significance and direction of specific caregiving support. CLINICAL EVIDENCE: Community health nurses should focus on improving family function and creating a supportive environment. Further, support for male and non-working caregivers should be strengthened and consultation on the use of respiratory equipment promoted to reduce the caregiving burden.

A report on a modified protocol for flow cytometry-based assessment of blood group erythrocyte antigens potentially suitable for analysis of weak ABO subgroups.

BACKGROUND: Flow cytometry (FC) has proven its utility in scrutinizing AB antigen expression in red blood cells (RBCs), cooperating with serological tests for accurate blood group typing. However, technical difficulties may impair the characterization of weak ABO subtypes when background noises appear at non-negligible levels. STUDY DESIGN AND METHODS: We sought to establish an FC method that could prevent antibody-induced hemagglutination and an increase in cellular autofluorescence, two major issues inherent to RBC-FC analysis of AB expression. We optimized fixatives, multicolor-staining protocols, and sequential gating strategies. Blood samples from weak ABO subtype cases, Bm and Ael , were analyzed with the established protocol. RESULTS: The optimized mixture of glutaraldehyde and formaldehyde successfully generated fixed RBCs resistant to agglutination while maintaining low autofluorescence. These features allowed co-staining of leukocyte- and erythrocyte-markers, which enabled sequential gating strategies facilitating the precise AB antigen analysis in purely single RBCs with minimum background noises. By the established FC analysis, we could detect in the Bm sample a small RBC population exhibiting weak B antigen expression. The assay also proved it feasible to identify a small population (0.04%) of RBCs weakly expressing the A antigen in the Ael sample confirmed as harboring a rare c.816dupG ABO variant allele. CONCLUSION: The RBC-FC analysis described here allows the detection of AB antigens weakly expressed in RBCs while achieving minimum background noise levels in negative control samples. Overall, the modified protocol provides a quick and reliable assay valuable in transfusion medicine and is potentially applicable to the characterization of rare weak ABO variants.

Integrating network pharmacology and experimental verification to decipher the immunomodulatory effect of Bu-Zhong-Yi-Qi-Tang against poly (I:C)-induced pulmonary inflammation.

Pulmonary inflammation caused by respiratory tract viral infections is usually associated with acute exacerbation of respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Therefore, maintaining the pulmonary immune homeostasis is particular important for prevention of the acute exacerbation. Bu-Zhong-Yi-Qi-Tang (BZYQT), a traditional Chinese medicine formula, has been broadly used to improve respiratory and gastrointestinal disorders in China for over 700 years. Previously, we have found the regulatory activity of BZYQT on the lower respiratory immune system, while its potential effects during pulmonary inflammation remain unknown. Thus, the current study focused on deciphering its immunomodulatory effect and potential mechanism against pulmonary inflammation by using a viral RNA analogue, poly (I:C), induced murine pulmonary inflammation model and BEAS-2B cell model coupled with network pharmacology. Inflammatory cells in the bronchoalveolar lavage fluid were counted through microscope examination according to the cell's morphology and staining characteristics; protein and gene levels of inflammatory mediators were determined with Elisa and quantitative PCR, respectively; network pharmacology was conducted based on 46 BZYQT-related potential bioactive components, pulmonary inflammation and immune-related targets. Our results indicated that the recruitment of neutrophils and the expression of Adgre1 (encoding the F4/80, which is a macrophage marker) in the lung induced by poly (I:C) were significantly reduced after BZYQT treatment, and these effects were further demonstrated to be related to the interference of leukocyte transendothelial migration from the decreased levels of CXCL10, IL-6, TNF-α, CXCL2, ICAM-1, VCAM-1, and E/P-selectins. Furthermore, BZYQT inhibited the CXCL10, TNF-α, and IFN-ß expression of poly (I:C)-challenged BEAS-2B cells in a dose-dependent manner. Through integrating results from network pharmacology, experiments, and the published literature, isoliquiritigenin, Z-ligustilide, atractylenolide I, atractylenolide III, formononetin, ferulic acid, hesperidin, and cimigenoside were presumed as the bioactive components of BZYQT against pulmonary inflammation. Overall, our findings demonstrated that BZYQT possesses a pronounced immunomodulatory effect on poly (I:C)-induced pulmonary inflammation, which provides a pharmacological basis for BZYQT in the treatment of respiratory disorders.

Coaxial electrospray formulations for improving oral absorption of a poorly water-soluble drug.

Development of oral dosage forms containing poorly water-soluble drugs is a major challenge in the pharmaceutical industry. This paper describes the use of coaxial electrospray deposition as a promising formulation technology for oral delivery of poorly water-soluble drugs. The technology produced core-shell particles composed of griseofulvin and poly(methacrylic acid-co-methyl methacrylate) (Eudragit L-100), with a diameter of around 1 µm. The drug phase was in an amorphous state when the griseofulvin core was coated with the Eudragit L-100 shell. The in vitro dissolution and in vivo oral absorption studies revealed that the core-shell formulation significantly improved dissolution and absorption behaviors, presumably because of a reduction in particle size, improvement in dispersity, and amorphization. Results demonstrated that coaxial electrospray deposition possesses great potential as novel formulation technology for enhancing oral absorption of poorly water-soluble drugs.

Epidermal growth factor promotes glioblastoma cell death under glucose deprivation via upregulation of xCT (SLC7A11).

The cystine/glutamate antiporter xCT (SLC7A11) is frequently overexpressed in many cancers, including glioblastoma. Cystine taken up by the cells via xCT is reduced to cysteine, which is used to synthesize glutathione for antioxidant cellular defense. However, overexpression of xCT causes cell death under glucose-limited conditions. We found that stimulation of glioblastoma cells with epidermal growth factor (EGF) induces the upregulation of xCT and promotes cell death under glucose deprivation. Treatment with the mTOR inhibitor Torin 1 suppressed the EGF-induced upregulation of xCT and cell death. EGF increased xCT mRNA levels, which was suppressed by Torin 1. The lysosome inhibitor bafilomycin A1 increased xCT protein levels in the absence of EGF or in the presence of EGF and Torin 1. Taken together, our study suggests that EGF promotes glioblastoma cell death under glucose-limited conditions via the upregulation of xCT at transcriptional and protein levels in an mTOR-dependent manner.

Chemical profile of Cimicifuga heracleifolia Kom. And immunomodulatory effect of its representative bioavailable component, cimigenoside on Poly(I:C)-induced airway inflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: The dried rhizome of Cimicifuga heracleifolia Kom. (C. heracleifolia) is a popular traditional Chinese medicine, which has been extensively used in Asian countries for its anti-inflammatory, antipyretic and analgesic activities. However, further utilization and application of C. heracleifolia have been hampered due to a lack of full understanding of its active ingredients. AIM OF STUDY: The present study aims for clarification of the systematical chemical profile of C. heracleifolia and the immunomodulatory effect of its main bioavailable component. MATERIALS AND METHODS: Comprehensive chemical profile of C. heracleifolia was systematically analyzed by ultra-performance liquid chromatography hyphenated with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS). Xenobiotics after oral administration of C. heracleifolia extracts were investigated to hunt for bioavailable components. The immunomodulatory activity evaluation of cimigenoside was achieved on poly(I:C)-induced airway inflammation mouse and BEAS-2B cell models from aspects of neutrophil infiltration, lung inflammation by using microscope analysis, quantification of production and expression of inflammatory cytokine and chemokines by using ELISA and quantitative PCR. RESULTS: By UPLC-Q-TOF/MS analysis, 110 compounds (including 81 triterpenoids, 21 cinnamic acid derivatives, and 8 other structure types) were identified or tentatively characterized in ethanolic extract of C. heracleifolia. Based on the data of chemical profile, xenobiotics of C. heracleifolia were subsequently analyzed, and triterpene glycosides were detected as the major bioavailable ingredients. Oral administration of cimigenoside, a representative triterpene glycoside, could prevent neutrophils infiltration in the lung due to suppression of the production of CXCL2 and CXCL10, and the expression of P-selectin, VCAM1 in poly(I:C)-induced airway inflammation model mice. Moreover, cimigenoside also inhibited the productions of inflammatory cytokines and chemokines from human airway epithelial cell line (BEAS-2B cells) induced by poly(I:C). CONCLUSION: Triterpene glycosides were the main components of C. heracleifolia extract, and cimigenoside was considered as the effective component with immunomodulatory effect on the pulmonary immune system by oral administration.

A Rare Case of Palpebral Cellulitis, a Variation of Pott's Puffy Tumor.

A rare case of palpebral cellulitis with simultaneous frontal sinusitis and osteomyelitis is reported. A healthy 45-year-old man presented with left upper eyelid swelling. He was given intravenous meropenem at the local hospital, but he failed to improve. Magnetic resonance imaging showed left frontal and maxillary sinusitis and upper palpebral cellulitis with an abscess. His temperature was 37.6°C, C-reactive protein was 1.36 mg/dL, thyroid hormone was elevated, left best-corrected visual activity was 1.2, and intraocular pressure was 25 mm Hg. He was then given cefazolin intravenously for 3 days but with no improvement. Therefore, the eyelid skin was incised. Postoperatively, the swelling improved significantly. Computed tomography demonstrated osteomyelitis of the left frontal sinus and osteolysis of the inferior wall. This case was considered a variation of Pott's puffy tumor. Bacterial cultures from the cellulitis abscess and sinusitis were negative. As for sinusitis, endoscopic sinusitis surgery (frontal sinus single sinus surgery [Draf III] and Kilian surgery) was performed. During 10 months of follow-up after the skin incision, no signs of recurrent eyelid swelling were observed.

Preparation of fenofibrate solid dispersion using electrospray deposition and improvement in oral absorption by instantaneous post-heating of the formulation.

A coaxial electrospray technique was applied to a poorly soluble drug, fenofibrate (FEN), to increase its bioavailability. A particulate core-shell solid dispersion was designed using poly(methacrylic acid-co-methyl methacrylate) (Eudragit L-100) as a shell material and poly(vinyl pyrrolidone) K12-17 as a dispersant for FEN in the core phase. Although 58% of FEN remained in the crystalline state in the electrosprayed formulation, the dissolution behavior was significantly improved due to decrease in particle size, decrease in crystallinity, and increase in dispersion efficiency. The formulation was subjected to post-heating at 100 °C for 30 s to transform the remaining crystals into the amorphous state to further improve the dissolution behavior. Oral bioavailability was also on the order of: heated formulation>intact formulation>crystalline FEN. Instantaneous heating significantly improved the performance of the formulation despite its simple procedure, and thus can be a powerful step to be incorporated in the formulation manufacturing process.

Surgery information reduces anxiety in the pre-operative period.

PURPOSE: Patients preparing to undergo surgery should not suffer needless anxiety. This study aimed to evaluate anxiety levels on the day before surgery as related to the information known by the patient regarding the diagnosis, surgical procedure, or anesthesia. METHOD: Patients reported their knowledge of diagnosis, surgery, and anesthesia. The Spielberger State-Trait Anxiety Inventory (STAI) was used to measure patient anxiety levels. RESULTS: One hundred and forty-nine patients were selected, and 82 females and 38 males were interviewed. Twenty-nine patients were excluded due to illiteracy. The state-anxiety levels were alike for males and females (36.10 +/- 11.94 vs. 37.61 +/- 8.76) (mean +/- SD). Trait-anxiety levels were higher for women (42.55 +/- 10.39 vs. 38.08 +/- 12.25, P = 0.041). Patient education level did not influence the state-anxiety level but was inversely related to the trait-anxiety level. Knowledge of the diagnosis was clear for 91.7% of patients, of the surgery for 75.0%, and of anesthesia for 37.5%. Unfamiliarity with the surgical procedure raised state-anxiety levels (P = 0.021). A lower state-anxiety level was found among patients who did not know the diagnosis but knew about the surgery (P = 0.038). CONCLUSIONS: Increased knowledge of patients regarding the surgery they are about to undergo may reduce their state-anxiety levels.

Surgery information reduces anxiety in the pre-operative period

PROPÓSITO: Pacientes que vão ser operados não devem sofrer ansiedade. Este estudo tem por objetivo comparar o grau de ansiedade no dia anterior à cirurgia entre pacientes que têm informação sobre seu diagnóstico, cirurgia e anestesia. MÉTODOS: Pacientes referiram seu conhecimento sobre o diagnóstico, a cirurgia e a anestesia. O inventário de Spielberger, State-Trait Anxiety Inventory (STAI), mediu a ansiedade. RESULTADOS: Cento e quarenta e nove pacientes foram selecionados, 82 mulheres e 38 homens foram entrevistados. Vinte e nove pacientes foram excluídos do estudo por analfabetismo. A ansiedade-estado foi semelhante para homens e mulheres, (36,10 ± 11,94 vs. 37,61 ± 8,76) (mean ± SD). A ansiedade-traço foi maior entre mulheres (42,55 ± 10,39 vs. 38,08 ± 12,25, P = 0,041). O nível de educação não influenciou a ansiedade-estado mas mostrou-se inversamente relacionado à ansiedade-traço. O diagnóstico fora claro para 91,7 por cento dos pacientes entrevistados, cirurgia para 75 por cento e anestesia para 37,5 por cento. O desconhecimento da cirurgia elevou a ansiedade-estado (P = 0,021) cujo menor índice foi encontrado entre pacientes que não conheciam seu diagnóstico, mas sabiam sobre a cirurgia (P = 0,038). CONCLUSÕES: O conhecimento sobre a cirurgia a ser realizada pode reduzir o estado de ansiedade.

The patient-physician interactions as seen by undergraduate medical students

CONTEXT: The interaction between a physician and his or her patient is complex and occurs by means of technical performance and through a personal relationship. OBJECTIVE: To assess the interaction between the medical professional and his or her patient with the participation of medical students assuming a role as observers and participants in a medical appointment in an outpatient office. DESIGN: Questionnaire interview study. SETTING: General Medicine outpatient offices, Hospital das Clínicas, Faculty of Medicine, University of Säo Paulo. PARTICIPANTS: Medical students performed an ethnographical technique of observation, following 199 outpatient medical appointments with Clinical Medicine Residents. MAIN MEASUREMENTS: A questionnaire filled out by observer students measured the physician's attitudes towards patients, as well as patients' expectations regarding the appointment and his or her understanding after its completion. RESULTS: Patients showed higher enthusiasm after the appointment (4.47 + or - 0.06 versus 2.62 + or - 0.10) (mean + or - SEM), as well as some negative remarks such as in relation to the waiting time. The time spent in the consultation was 24.66 + or - 4.45 minutes (mean + or - SEM) and the waiting time was 123.09 + or - 4.91 minutes. The physician's written orientation was fairly well recalled by the patient when the doctor's letter could be previously understood. CONCLUSION: Patients benefit from physicians who keep the focus on them. In addition, this program stimulated the students for their accomplishment of the medical course