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ABSTRACT The effect of protriptyline on Ca2+ physiology in human hepatoma is unclear. This study explored the effect of protriptyline on [Ca2+]i and cytotoxicity in HepG2 human hepatoma cells. Protriptyline (50-150 μM) evoked [Ca2+]i rises. The Ca2+ entry was inhibited by removal of Ca2+. Protriptyline-induced Ca2+ entry was confirmed by Mn2+-induced quench of fura-2 fluorescence. Except nifedipine, econazole, SKF96365, GF109203X, and phorbol 12-myristate 13 acetate did not inhibit Ca2+ entry. Treatment with the endoplasmic reticulum Ca2+ pump inhibitor 2,5-di-tert-butylhydroquinone (BHQ) inhibited 40% of protriptyline-induced response. Treatment with protriptyline abolished BHQ-induced response. Inhibition of phospholipase C (PLC) suppressed protriptyline-evoked response by 70%. At 20-40 μM, protriptyline killed cells which was not reversed by the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid-acetoxymethyl ester (BAPTA/AM). Together, in HepG2 cells, protriptyline induced [Ca2+]i rises that involved Ca2+ entry through nifedipine-sensitive Ca2+ channels and PLC-dependent Ca2+ release from endoplasmic reticulum. Protriptyline induced Ca2+-independent cell death. [ABSTRACT FROM AUTHOR]

Tricyclic antidepressants (TCA) have been clinically prescribed in the auxiliary treatment of cancer patients. Although protriptyline, a type of TCA, was used primarily in the clinical treatment of mood disorders in cancer patients, the effect of protriptyline on physiology in human osteosarcoma is unknown. This study examined the effect of protriptyline on cytosolic free Ca2+ concentrations ([Ca2+]i) and viability in MG63 human osteosarcoma cells. Protriptyline between 50 and 250 μM evoked [Ca2+]irises concentration-dependently. Protriptyline induced influx of Mn2+, indirectly implicating Ca2+ influx. Protriptyline-evoked Ca2+ entry was inhibited by nifedipine by 20% but was not altered by econazole, SKF96365, GF109203X, and phorbol-12-myristate-13-acetate (PMA). In Ca2+-free medium, treatment with protriptyline inhibited the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin-evoked [Ca2+]irises. Conversely, treatment with thapsigargin inhibited 45% of protriptyline-evoked [Ca2+]irises. Inhibition of phospholipase C (PLC) with U73122 failed to alter protriptyline-evoked [Ca2+]irises. Protriptyline at 50–250 μM decreased cell viability, which was not reversed by pretreatment with the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA/AM). Collectively, our data suggest that in MG63 cells, protriptyline induced [Ca2+]irises by evoking Ca2+ release from the endoplasmic reticulum and other stores in a PLC-independent manner, and Ca2+ entry via a nifedipine-sensitive Ca2+ pathway. Protriptyline also caused Ca2+-independent cell death. [ABSTRACT FROM PUBLISHER]

Objective: People from ethnic minority groups who receive cancer care outside their country of origin may experience poor survival and psychological outcomes relative to that nation's majority groups. This exploratory qualitative study aimed to understand the experience of a large minority group of Mandarin-speaking cancer patients (MSCPs) after diagnosis and treatment of their cancer in Australia, with a view to delineate if cultural or linguistic factors affected the quality of care provided.Method: We employed an exploratory qualitative design involving interviews with 22 MSCPs who were treated during 2009 at the Peter MacCallum Cancer Centre (PMCC) in Melbourne, Australia. Participants were interviewed by a bilingual psychiatrist, audiotaped, transcribed in Mandarin, and then translated into English before being subjected to thematic analysis by two independent researchers.Results: MSCPs experienced notable challenges as a result of both language difficulties and differing cultural approaches, which often limited their understanding of their disease and impeded their ability to access quality care and adequate support. The results call for Australia and other Western nations with increasingly diverse populations to consider how cancer care can be modified to better support people from minority groups to effectively cope with their diagnosis and treatment.Significance Of Results: This study raises several suggestions for service improvement, including the development of bilingual communication aids, improved educational opportunities for clinical staff to aid their mastery of cultural issues and effective interpreter consultations, and improved access to supportive services offering culturally specific strategies. [ABSTRACT FROM AUTHOR]

Background:This study identified possible risk factors for newly diagnosed mood disorders, including depressive and bipolar disorders, in prostate cancer patients.Methods:From 2000 to 2006, two cohorts were evaluated on the occurrence of mood disorder diagnosis and treatment. For the first cohort, data of patients diagnosed with prostate cancer was obtained from the Taiwan National Health Insurance (NHI) Research Database. As the second cohort, a cancer-free comparison group was matched for age, comorbidities, geographic region, and socioeconomic status.Results:Final analyses involved 12,872 men with prostate cancer and 12,872 matched patients. Increased incidence of both depressive (IRR 1.52, 95% CI 1.30–1.79, P <0.001) and bipolar disorder (IRR 1.84, 95% CI 1.25–2.74, P = 0.001) was observed among patients diagnosed with prostate cancer. Multivariate matched regression models show that cerebrovascular disease (CVD) and radiotherapy treatment could be independent risk factors for developing subsequent depressive and bipolar disorders.Conclusion:We observed that the risk of developing newly diagnosed depressive and bipolar disorders is higher among Taiwanese prostate cancer patients. Clinicians should be aware of the possibility of increased depressive and bipolar disorders among prostate cancer patients in Taiwan. A prospective study is necessary to confirm these findings. [ABSTRACT FROM PUBLISHER]

BackgroundDisclosure of HIV serostatus is important for the prevention of HIV infection among men who have sex with men (MSM). However, knowledge of sexual partners’ HIV status among MSM in China is low. As a complement to HIV testing services, HIV self-testing (HIVST) has considerable potential to promote serostatus disclosure. ObjectiveThe primary objective of our trial is to evaluate the effect of HIVST on improving serostatus disclosure to sexual partners. We hypothesize that MSM in an intervention condition will have a higher awareness of the HIV status of their sexual partners compared with MSM in the control condition. The secondary aims are to evaluate (i) changes in sexual behaviors after disclosure of HIV status by sexual partners, (ii) promotion of the frequency of HIV and syphilis testing on participants and their sexual partners, and (iii) factors that restrict the disclosure of HIV infection to sexual partners. We hypothesize that MSM in the intervention condition will exhibit safer sexual decision making and a higher rate of HIV testing uptake compared with MSM in the control condition. MethodsA stepped wedge randomized controlled trial will be conducted throughout China. Study recruitment of 800 MSM will be promoted through advertisements released on WeChat public accounts. Individuals who are born biologically male, aged ≥18 years, HIV negative, and who have not undergone HIV testing in the past 3 months will be recruited. Eligible men will be randomly divided (1:1:1:1) into four groups and randomized. The group cluster will initiate the intervention so that participants will be provided with 2-4 free finger prick–based HIVST kits until trial completion. The intervention period for participants in each of the four groups will be initiated at 3-month intervals. Men in both groups will be required to complete a baseline and four follow-up surveys every 3 months. The primary intervention outcome will evaluate the effect of the distribution of HIVST kits on improvement in the disclosure of sexual partners’ HIV status. The secondary outcomes will be changes in sexual behaviors after disclosure of HIV status from sexual partners, the promotion of the frequency of HIVST on participants and their sexual partners, and the factors that restrict disclosure of HIV status to sexual partners. ResultsSubject recruitment began in August 2018. The first round of follow-up surveys post intervention is complete, with three rounds remaining to be done. Data analysis was scheduled for April 2020 and the results will be disseminated through conferences and peer-reviewed publications. ConclusionsFew studies have evaluated interventions to increase knowledge of sexual partners’ HIV status among MSM. Our trial will provide information on the link between HIVST and HIV serostatus disclosure. The findings of this trial will facilitate the implementation of HIVST services to help control the spread of HIV among MSM in China. Trial RegistrationChinese Clinical Trial Registry ChiCTR1800019453; http://www.chictr.org.cn/showproj.aspx?proj=30158 International Registered Report Identifier (IRRID)DERR1-10.2196/17788

The antidepressant, sertraline, has been shown to have diverse in vitro effects. This study examined whether sertraline altered [Ca2+]i in MG63 human osteosarcoma cells by using fura-2 as a Ca2+-sensitive fluorescent dye. At 50–200 μM, sertraline induced a [Ca2+]i rise in a concentration-dependent manner. Ca2+ response was decreased by removing extracellular Ca2+, suggesting that Ca2+ entry and release contributed to the [Ca2+]i signal. Sertraline-induced Ca2+ entry was inhibited by nifedipine, La3+, Gd3+, and SK&F96365. When extracellular Ca2+ was removed, pretreatment with the endoplasmic reticulum (ER) Ca2+ pump inhibitor, thapsigargin, or 2,5-di-tert-butylhydroquinone (BHQ) abolished the sertraline-evoked [Ca2+]i rise. Incubation with sertraline also abolished the thapsigargin or BHQ-induced [Ca2+]i rise. Inhibition of phospholipase C (PLC) with U73122 abolished the sertraline-induced [Ca2+]i rise. At 20–30 μM, overnight treatment with sertraline killed cells in a concentration-dependent manner. The cytotoxic effect of sertraline was not reversed by chelating cytosolic Ca2+ with 1,2-bis(2-aminophenoxy)ethane-N,N,N’,N’-tetraacetic acid (BAPTA). Annexin V/propidium iodide staining data demonstrate that sertraline (30 μM) evoked apoptosis. Sertraline (20 and 30 μM) also increased levels of reactive oxygen species. Together, in human osteosarcoma cells, sertraline evoked a [Ca2+]i rise by inducing PLC-dependent Ca2+ release from the ER and Ca2+ entry by L-type Ca2+ channels and store-operated Ca2+ channels. Sertraline induced cell death that may involve apoptosis by mitochondrial pathways. [ABSTRACT FROM AUTHOR]

The effect of the insecticide methoxychlor on the physiology of renal tubular cells is unknown. This study aimed to explore the effect of methoxychlor on cytosolic Ca2+ concentrations ([Ca2+]i) in MDCK renal tubular cells using the Ca2+-sensitive fluorescent dye fura-2. Methoxychlor at 5-20 μM increased [Ca2+]i in a concentration-dependent manner. The signal was reduced by 80% by removing extracellular Ca2+. Methoxychlor-induced Ca2+ entry was not affected by nifedipine and SK&F96365 but was inhibited by econazole and protein kinase C modulators. In Ca2+-free medium, treatment with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin or 2,5-di-tert-butylhydroquinone ( BHQ) partly inhibited methoxychlor-induced [Ca2+]i rise. Incubation with methoxychlor also inhibited thapsigargin- or BHQ-induced [Ca2+]i rise. Inhibition of phospholipase C with U73122 nearly abolished methoxychlor-induced [Ca2+]i rise. At 5-15 μM, methoxychlor slightly increased cell viability, whereas at 20 μM, it decreased viability. The cytotoxic effect of methoxychlor was not reversed by chelating cytosolic Ca2+ with 1,2-bis(2-aminophenoxy)ethane-N,N,N,N-tetraacetic acid/ AM ( BAPTA/ AM). Annexin V- FITC data suggest that 10 μM methoxychlor inhibited apoptosis, while 20 μM methoxychlor enhanced apoptosis. Methoxychlor (10 and 20 μM) increased the production of reactive oxygen species. Together, in renal tubular cells, methoxychlor induced [Ca2+]i rise by inducing phospholipase C-dependent Ca2+ release from multiple stores and Ca2+ entry via protein kinase C- and econazole-sensitive channels. Methoxychlor slightly enhanced or inhibited cell viability in a concentration-dependent, Ca2+-independent manner. Methoxychlor induced cell death that may involve apoptosis via mitochondrial pathways. [ABSTRACT FROM AUTHOR]

1. It has been shown that the antidepressant desipramine is able to induce increases in [Ca2+]i and cell death in MG63 human osteosacroma cells, but whether apoptosis is involved is unclear. In the present study, the effect of desipramine on apoptosis and the underlying mechanisms were explored. It was demonstrated that desipramine induced cell death in a concentration- and time-dependent manner. 2. Cells treated with 100–800 mmol/L desipramine showed typical apoptotic features, including an increase in sub-diploid nuclei and activation of caspase 3, indicating that these cells underwent apoptosis. Immunoblotting revealed that 100 mmol/L desipramine activated extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK). Although pretreatment of cells with 20 mmol/L PD98059 (an ERK inhibitor) or 20 mmol/L SP600125 (an inhibitor of JNK) did not inhibit cell death, the addition of 20 mmol/L SB203580 (a p38 MAPK inhibitor) partially rescued cells from apoptosis. Desipramine-induced caspase 3 activation required p38 MAPK activation. 3. Pretreatment of cells with BAPTA/AM (20 mmol/L) to prevent desipramine-induced increases in [Ca2+]i did not protect cells from death. 4. The results of the present study suggest that, in MG63 human osteosarcoma cells, desipramine causes Ca2+-independent apoptosis by inducing p38 MAPK-associated activation of caspase 3. [ABSTRACT FROM AUTHOR]

Enterotoxigenic Escherichia coli (ETEC) producing type Ib heat-stable toxin (STa) are a main cause of children's diarrhea and travelers' diarrhea, thus STa needs to be targeted in ETEC vaccine development. However, because this 19-amino acid STa is poorly immunogenic, attempts to genetically fuse or chemically couple it to carrier proteins have been made to enhance STa immunogenicity. In this study, we selected one genetic fusion and one chemical conjugate to comparatively evaluate STa immunogenicity. The genetic fusion is 3xSTaN12S-mnLTR192G/L211A carrying three toxoid (STaN12S) genetically fused to a double mutant LT monomer (mnLTR192G/L211A); the chemical conjugate is BSA-STaA14T, which has toxoid STaA14T chemically coupled to bovine serum albumin (BSA). We immunized mice with the STa toxoid fusion and chemical conjugates, and examined antibody responses. Furthermore, we immunized pigs and evaluated derived antibodies for efficacy to passively provide protection against ETEC diarrhea using a piglet model. Data showed that mice subcutaneously immunized with BSA-STaA14T or 3xSTaN12S-mnLTR192G/L211A developed a strong anti-STa antibody, and the induced antibodies exhibited equivalent toxin-neutralizing activities. Pigs immunized with 3xSTaN12S-mnLTR192G/L211A or BSA-STaA14T developed similar levels of anti-STa antibodies; piglets with passively acquired antibodies induced by the genetic fusion appeared better protected against STa + ETEC. Results from the current study indicate that the fusion and conjugate approaches are viable options for facilitating STa immunogenicity and developing ETEC vaccines. [ABSTRACT FROM AUTHOR]

Aim The present study aimed to determine whether the Mini-Nutritional Assessment Short-Form (MNA-SF) can predict the 1-year outcome of orthopedic fracture surgery in elderly patients. Methods This 1-year prospective study assessed nutrition using the MNA-SF at baseline, and postoperatively at 6 and 12 months. Repeated measures analysis of covariance was used to examine functional change over time for two MNA-SF categories. Multivariable logistic regression analysis with forward stepwise modeling was carried out to identify risk factors of functional decline, emergency department visit, hospital readmission and mortality at follow up. Results There were 312 participants, 11 of whom died (3.53%) during 1-year follow up. The mean age was 74.04 ± 7.65 years. A total of 88.1% and 11.9% of the participants were well nourished (MNA-SF 12-14 points) or at risk of undernutrition (0-11 points), respectively. For MNA-SF as a continuous variable, lower MNA-SF scores were associated with a significantly higher risk of emergency department visit at 6-month follow up, and mortality at 12-month follow up (emergency room visit, adjusted odds ratio 0.78, 95% CI 0.63-0.96, P < 0.05; mortality, adjusted odds ratio 0.73, 95% CI 0.57-0.94, P < 0.05). No association was found between functional decline and hospital readmission, and MNA-SF scores. For MNA-SF categories, functional decline was more profound in patients at risk of undernutrition than in well-nourished patients, especially 6-12 months postoperatively. Conclusions The MNA-SF could be an effective and non-invasive preoperative screening tool to predict functional decline, emergency department visit and mortality during the year after surgery. Geriatr Gerontol Int 2017; 17: 2361-2368. [ABSTRACT FROM AUTHOR]

The article presents a case-study of 39-year-old female with new-onset hyperprolactinemia-related delusion of pregnancy concurrent with risperidone treatment. It mentions that the patient reported breast pain and galactorrhea after administration of risperidone long-acting injection (LAI). It mentions that aripiprazole was prescribed instead of risperidone LAI and patient showed improvement.

Purpose: The aim of our study was to evaluate the overall cancer risk among patients with the irritable bowel syndrome (IBS) by using a nationwide population-based data set.Methods: We obtained data on newly diagnosed IBS patients (age ≥ 20 years) without antecedent cancer from the Taiwan National Health Insurance Research Database for the period between 2000 and 2010. Standardized incidence ratios (SIRs) were calculated for various types of cancer in the IBS patients.Results: A total of 1,043 people among the 29,838 IBS patients had developed cancer, and the follow-up was 139,185 person-years (median, 4.56 years), leading to a significantly increased SIR (1.18; 95% confidence interval [CI]) = 1.11-1.26) among all cancer types. However, after excluding cancer that developed within the first year after IBS diagnosis, the increased SIR of overall cancer was nonsignificant. In particular, the IBS patients exhibited an increased risk of cancers of the colon and rectum (SIR = 1.51; 95% CI = 1.31-1.73), liver and biliary tract (SIR = 1.40; 95% CI = 1.21-1.62), pancreas (SIR = 1.56; 95% CI = 1.02-2.28), and kidney (SIR = 1.56; 95% CI = 1.10-2.15).Conclusions: An increased SIR in IBS patients was observed only within the first year of IBS diagnosis. The findings of this study might have resulted from detection bias, localized symptoms, or paraneoplastic syndromes associated with IBS-like symptoms. Additional prospective studies are necessary to confirm these findings. [ABSTRACT FROM AUTHOR]