THE RETROSPECTIVE ANALYSIS OF TRIGEN INTERTAN NAIL IN THE TREATMENT OF UNSTABLE INTERTROCHANTERIC FEMORAL FRACTURES AT HOSPITAL FOR TRAUMATOLOGY AND ORTHOPAEDICS.

Background: Intertrochanteric fractures are highly prevalent among the elderly population, with approximately 90% occurring in individuals aged over 65. These geriatric fractures are associated with elevated mortality rates and significant functional impairment. Common treatment modalities for unstable intertrochanteric fractures include proximal femoral nail antirotation (PFNA) and the InterTan nail (IT). PFNA and IT are frequently employed due to their lower failure rates and favorable biomechanical properties, resulting in positive clinical outcomes for the management of unstable intertrochanteric fractures. The unique design of the IT nail, featuring two cephalocervical screws within an integrated mechanism, permits linear intraoperative compression and rotational stability of the neck and head fragment. In this study, we assess the clinical outcomes of IT nail utilization in the treatment of intertrochanteric fractures at the Hospital for Traumatology and Orthopedics. Methods: This study comprises a retrospective analysis and case series report. Between February 2021 and August 2021, we retrospectively evaluated 35 patients who underwent treatment with the IT nail for unstable intertrochanteric fractures. Epidemiological data, operative duration, intraoperative blood loss, intraoperative blood transfusion requirements, length of hospital stay, bone healing rates, and IT nail-related complications were recorded. Results: The mean age of the patients was 70.97 ± 16.97 years, with a mean operative time of 60 minutes, mean intraoperative blood loss of 160.86 ± 72.8 ml, mean intraoperative blood transfusion volume of 203.43 ± 189.29 ml, and a mean hospital stay of 7 days. Bone healing was observed in 97.14% of cases. Conclusions: The treatment of unstable intertrochanteric fractures using the IT nail in elderly patients was successful. Our findings indicate favorable clinical outcomes in terms of surgical duration, intraoperative blood loss, hospitalization duration, and union rates for elderly patients. Further investigations are warranted to validate these early results.

Implementation of pharmacist-led services for sexual and gender minorities: A multisite descriptive report.

PURPOSE: This paper compares and contrasts the implementation of pharmacist-led services for 3 different sexual and gender minority populations across California, Mississippi, and Florida. SUMMARY: Implementation of pharmacist-led services tailored to sexual and gender minorities may be a potential mechanism to address health disparities in these populations. Clinical pharmacists have the potential to provide care with cultural humility and improve health outcomes by optimizing medication regimens, reducing adverse drug events, enhancing medication acquisition, and improving medication adherence. CONCLUSION: The services provided by clinical pharmacists varied across sites and included management of gender-affirming hormone therapy, HIV antiretroviral medication adherence programming, primary care and chronic disease state management, and involvement in care related to mental health, psychiatry, and substance use as well as sexual health. Various legislative and regulatory barriers and differences in scope of practice for pharmacists were also identified. This paper advocates for the expansion of pharmacy-led services and the adoption of a culturally humble approach to patient care.

Born This Way: Integrating LGBTQIA+ Identities as Pharmacy Practitioners.

Progression through the profession of pharmacy is filled with many milestones that can contribute to feelings of stress, rejection, and isolation. For Lesbian, Gay, Bisexual, Transgender, Queer, Intersex, and Asexual+(LGBTQIA+) students and practitioners, these feelings can be compounded by similar issues experienced by their sexual orientation or gender identity. Historically, LGBTQIA+ students, new practitioners, and seasoned professionals alike have lacked visible role models for how to intersect personal and professional identity in the pharmacy profession. In this paper, the authors describe experiences of intersecting personal queer identities with professional pharmacy identities; exploring barriers to integration and developing solutions to overcome these barriers. The authors also share how the formation of a collective of LGBTQIA+ practitioners and educators has led to a unified voice to advocate for the advancement of LGBTQIA+ healthcare in pharmacy education and practice. This manuscript will provide readers with a guide to navigate and address issues with the integration of personal and professional identity to lead to practice that validates personal identity as important, valuable, and affirmed.

Ultrasound-Assisted Lipid Extraction from Chlorella sp.: Taguchi Design and Life Cycle Assessment.

The present study delved into the enhancement of essential oil (EO) extraction process from Chlorella sp. through the implementation of ultrasound-assisted extraction. The Taguchi method was instrumental in determining the ideal parameters for the extraction process, which encompassed ultrasonic amplitude, reaction duration, hexane/ethanol (HE/EtOH) ratio, and processing temperature. The empirical findings indicated that optimal EO yield was realized at an ultrasonic amplitude of 80%, a reaction timeframe of 15 min, a HE/EtOH proportion of 3:1, and a temperature setting of 40 °C. These optimal conditions were further substantiated through additional experimentation, resulting in an EO yield of 18.8 ± 0.2%. A fatty acid profile analysis disclosed that the extracted EO predominantly consisted of long-chain fatty acids (C14-C20), with Palmitic, Heptadecanoic, Oleic, and Linoleic acids featuring as the main components. Nevertheless, a high unsaturation rate of 37.9% in the EO could potentially render it vulnerable to oxidative deterioration during storage, consequently affecting the quality of the ensuing biodiesel. A life cycle assessment of the sonication technique utilized for biodiesel production from Chlorella sp. highlighted that lipid extraction was the principal contributor to global warming and ecotoxicity, as per the CML and TRACI methods. Hence, the ultrasound-assisted extraction of EO from Chlorella sp. appears to be a promising and ecologically viable substitute to conventional techniques employed for biodiesel production.

Pharmacy undergraduate programs: Development of an adaptive curriculum for student success.

Objectives: Applicants for graduate work in Pharmacy on paper appear competitive, but upon entering a Doctor of Pharmacy (PharmD) program many students struggle with course work, course load, and pharmacologic topics in their first-year studies. In addition to math and science, undergraduate candidates need to have skills that enable them to be adaptable and creative learners. The Pharmacy Undergraduate Program (PUP) at the University of Southern California (USC) has been attentive to these educational needs. In this manuscript we will show how our program has been successful in generating well-prepared and successful candidates for graduate programs (pharmaceutical, clinical, medical, and other) and employment in pharmaceutical fields. Methods: A review of current student enrollments (N = 121), graduated student annual survey data (N = 50), student research data (N = 68), and ongoing course surveys have been used to detail information related to PUP. Results: Students who have graduated from PUP have been successful post-graduation. Graduates of PUP have gone on to PharmD programs 44% (22/50); medical school 16% (8/50); PhD programs 24% (12/50); full-time employment 6% (3/50); internship/volunteer positions 10% (5/50); taken a gap year 4% (2/50); and MS/MA program 2% (1/50). Conclusions: PUP has been successful in helping the admission of our students into graduate degree programs related to pharmaceutical sciences and medicine. This success can be attributed to the dynamic nature of the course offerings and the creativity of the teaching faculty, which leads to students being well-prepared to tackle the rigors of their graduate studies after leaving the program.

Beneficial and detrimental effects of non-specific binding during DNA hybridization.

DNA strands have to sample numerous states to find the alignment that maximizes Watson-Crick-Franklin base pairing. This process depends strongly on sequence, which affects the stability of the native duplex as well as the prevalence of non-native inter- and intramolecular helices. We present a theory that describes DNA hybridization as a three-stage process: diffusion, registry search, and zipping. We find that non-specific binding affects each of these stages in different ways. Mis-registered intermolecular binding in the registry search stage helps DNA strands sample different alignments and accelerates the hybridization rate. Non-native intramolecular structure affects all three stages by rendering portions of the molecule inert to intermolecular association, limiting mis-registered alignments to be sampled, and impeding the zipping process. Once in-register base pairs are formed, the stability of the native structure is important to hold the molecules together long enough for non-native contacts to break.

A scoping review of the minority stress processes experienced by sexual and gender minority individuals in pharmacy settings: Implications for health care avoidance.

BACKGROUND: Sexual and gender minority (SGM) people may avoid or delay health care interactions. The minority stress model describes distal (discrimination, violence) and proximal (expectation of rejection, concealment, internalized self-dislike) stress processes as possible contributors to the health disparities and avoidance behaviors observed when encountered in health care settings. Pharmacies are accessible health care settings, yet the extent to which SGM individuals experience minority stress processes while using services at the pharmacies is unknown. OBJECTIVE: This scoping review aimed to identify distal and proximal minority stress processes experienced by SGM individuals and health care avoidance behaviors related to pharmacies or pharmacists. METHODS: An electronic search of PubMed, Embase, and PsycINFO databases was conducted to search for relevant literature up to September 2022. The search was supplemented with a review of reference lists and contact with experts in the field. Articles were included in the review if they described SGM individuals' perceived experiences within pharmacies or with pharmacists and reported an outcome that could be mapped to a distal or proximal minority stress process. RESULTS: Eleven articles met the eligibility criteria and were included in the review. Of these, 6 reported the presence of distal stress processes, such as perceived stigma, negative pharmacy staff attitudes, and a lack of awareness of population needs. For proximal stress processes, 5 articles reported on concealment, 4 reported on expectation of rejection, and 1 reported on internalized transphobia. Developing rapport and increasing competence were identified as ways to help mediate the impact of minority stress processes. CONCLUSION: Minority stress processes and avoidance behaviors are experienced by SGM individuals that relate to pharmacies and pharmacists. Coordinated efforts between professional stakeholders are required to reduce minority stress processes and ensure pharmacy-based services are accessible to all individuals.

Determinants of mental health among youths and adolescents in the digital era: Roles of cyber and traditional bullying, violence, loneliness, and environment factors.

Introduction: Although the pathogenesis of depressive disorders is not fully elucidated, untreated adolescent depression can lead to serious sequelae such as impaired academic performance and social functioning, substance use disorders, poor self-esteem, and increased risk for suicidal ideation and attempts. Literature on adolescent mental health in Vietnam is limited, despite increased international awareness of this critical issue. This study aimed to investigate the prevalence and associations of depressive symptoms in Vietnamese adolescents. Methods: A cross-sectional, self-administered survey was conducted in five provinces of Vietnam among adolescents aged 14 to 24 years. In addition to collecting participants' demographics, a structured questionnaire was developed to examine depressive symptoms, suicidal ideation, loneliness, and cyberbullying victimization. Depressive symptoms and loneliness were assessed via the PHQ-9 and UCLA Loneliness Scale, respectively. Two-tailed Chi-squared, Mann-Whitney, and Kruskal-Wallis tests were performed to examine associations between variables. Multivariate Logistic regression models were conducted to examine the associations between prior-defined variables and positive depressive symptoms. Results: Among 1,600 respondents, 31.8% of participants reported having mild-moderate or severe depressive symptoms. Participants within the moderate-severe depressive symptom group had significantly lower community cohesion scores than those of participants in normal and mild depressive symptom groups (p < 0.05). Youths living alone were more likely to have moderate-severe depressive symptoms (OR 2.16; 95% CI: 1.09-4.25). Cyberbullying had significant associations with depressive severity (OR 1.93; 95% CI 1.38-2.70). Conclusion: The findings of this study characterize various risk and protective factors for depression in Vietnamese youths and adolescents. The results highlight the importance of raising awareness and increasing access to educational resources for depression and other mental health illnesses. With the rising prevalence of depression, parents, teachers, and community leaders play a vital role in addressing mental health problems in adolescents.

Removal of total nitrogen from wastewater by a combination of Chlorella sp. and audible sound.

In developing countries, nitrogen in the traditional market wastewater is a critical environmental problem. In this study, the microalga Chlorella sp., which was isolated from wastewater, was used to remove the total nitrogen (TN) from conventional market wastewater in combination with audible sound (Vietnamese classical music). In addition, effects of sound exposure on removal efficiency at different initial cell densities were analyzed. Results revealed that music sound control demonstrates potential to improve the removal efficiency. TN removal efficiencies of 96%, 69.5%, and 4.3% were observed for treatments with Chlorella sp./audible sound, Chlorella sp., and without Chlorella sp., respectively. The significance of probability value (p-value) (<0.05) on the paired sample t-test confirmed the critical role of audible sound and Chlorella sp. density on the TN removal in screening experiments. The predicted optimal conditions for TN removal were as follows: a Chlorella sp. density of 4%, an audible sound of 52.5 dB, and a cultivation time of 4.6 days. Results based on statistical analysis revealed that the quadratic models for TN removal are significant at a low p-value (<0.05) and a high predicted coefficient of determination (R2 = 0.9452) value. The obtained statistical results also indicated that most of the variables are significant for the abatement of TN from market wastewater using Chlorella sp.

Impacts of COVID-19 on the Life and Work of Healthcare Workers During the Nationwide Partial Lockdown in Vietnam.

Background: Healthcare workers are frontline responders facing a disproportionate increase in occupational responsibilities during the COVID-19 pandemic. Added work-related stress among healthcare personnel may lead to personal and work-related repercussions, such as burnout or decreased quality of care for patients; however, little is known about how the COVID-19 pandemic affects the daily work and life of these workers. This study aimed to evaluate the personal and occupational impacts of the COVID-19 induced partial lockdown in Vietnam among hospital staff. Methods: A cross-sectional web-based study was carried out to collect demographic data and the personal and job impacts of respondents during the second week of national lockdown in April 2020. Snowball sampling technique was applied to recruit 742 hospital staff. The exploratory factor analysis (EFA) was used to examine the validity of the instrument. Results: Of the 742 respondents, 21.2% agreed that "working attitude well-maintained," followed by 16.1% of respondents who reported that there were "enough employees at work." Only 3.2% of respondents agreed that "their work was appreciated by society." Furthermore, healthcare workers in the central region were less likely to have experienced "Avoidance of disclosure and discrimination related to COVID-19" than other areas (Coef. = - 0.25, CI: -0.42 to -0.07). Being women also had a negative association with scores in "Avoidance of disclosure and discrimination related to COVID 19" domain (Coef. = -0.27, CI: -0.43 to -0.12) while having a positive association with "negative attitude towards working conditions" domain (Coef. = 0.19, CI: 0.09 to 0.3). In addition, working in administrative offices (Coef. = 0.20; 95% CI = 0.05 to 0.36) and infectious departments (Coef. = 0.36; 95% CI = 0.09 to 0.63) had a positive association with "Increased work pressure due to COVID 19" domain. Conclusion: These findings revealed marginal impacts of the COVID-19 pandemic on the work and life of hospital staff in Vietnam. Furthermore, this study highlighted the importance of implementing preventive strategies during the nationwide partial lockdown to manage hospital admissions and the burden on healthcare workers. Finally, this study characterizes targeted demographics that may benefit from appreciation by employers and society during a national pandemic.

Thermodynamics of Huntingtin Aggregation.

Amyloid aggregates are found in many neurodegenerative diseases, including Huntington's, Alzheimer's, and prion diseases. The precise role of the aggregates in disease progression has been difficult to elucidate because of the diversity of aggregated states they can adopt. Here, we study the formation of fibrils and oligomers by exon 1 of huntingtin protein. We show that the oligomer states are consistent with polymer micelles that are limited in size by the stretching entropy of the polyglutamine region. The model shows how the sequences flanking the amyloid core modulate aggregation behavior. The N17 region promotes aggregation through weakly attractive interactions, whereas the C38 tail opposes aggregation via steric repulsion. We also show that the energetics of cross-ß stacking by polyglutamine would produce fibrils with many alignment defects, but minor perturbations from the flanking sequences are sufficient to reduce the defects to the level observed in experiment. We conclude with a discussion of the implications of this model for other amyloid-forming molecules.

Infected Mosquitoes Have Altered Behavior to Repellents: A Systematic Review and Meta-analysis.

Here we conducted a systematic review and meta-analysis to reach a consensus on whether infected and uninfected mosquitoes respond differently to repellents. After screening 2,316 published studies, theses, and conference abstracts, we identified 18 studies that tested whether infection status modulated the effectiveness of repellents. Thirteen of these studies had outcomes available for meta-analysis, and overall, seven repellents were tested (typically DEET with 62% of outcomes), six mosquito species had repellence behaviors measured (typically Aedes aegypti (L.) (Diptera: Culicidae) mosquitoes with 71% of outcomes), and a broad diversity of infections were tested including Sindbis virus (Togaviridae: Alphavirus) (33% of outcomes), Dengue (Flaviviridae: Flavivirus) (31%), malaria (Plasmodium berghei Vincke & Lips (Haemospororida: Plasmodiidae) or P. falciparum Welch (Haemospororida: Plasmodiidae); 25%), Zika (Flaviviridae: Flavivirus) (7%), and microsporidia (4%). Pooling all outcomes with meta-analysis, we found that repellents were less effective against infected mosquitoes-marking an average 62% reduction in protective efficacy relative to uninfected mosquitoes (pooled odds ratio = 0.38, 95% confidence interval = 0.22-0.66; k = 96). Older infected mosquitoes were also more likely to show altered responses and loss of sensitivity to repellents, emphasizing the challenge of distinguishing between age or incubation period effects. Plasmodium- or Dengue-infected mosquitoes also did not show altered responses to repellents; however, Dengue-mosquito systems used inoculation practices that can introduce variability in repellency responses. Given our findings that repellents offer less protection against infected mosquitoes and that these vectors are the most dangerous in terms of disease transmission, then trials on repellent effectiveness should incorporate infected mosquitoes to improve predictability in blocking vector-human contact.

The effects of AICAR and rapamycin on mitochondrial function in immortalized mitochondrial DNA mutator murine embryonic fibroblasts.

Mitochondrial DNA mutations accumulate with age and may play a role in stem cell aging as suggested by the premature aging phenotype of mitochondrial DNA polymerase gamma (POLG) exonuclease-deficient mice. Therefore, E1A immortalized murine embryonic fibroblasts (MEFs) from POLG exonuclease-deficient and wild-type (WT) mice were constructed. Surprisingly, when some E1A immortalized MEF lines were cultured in pyruvate-containing media they slowly became addicted to the pyruvate. The POLG exonuclease-deficient MEFs were more sensitive to several mitochondrial inhibitors and showed increased reactive oxygen species (ROS) production under standard conditions. When cultured in pyruvate-containing media, POLG exonuclease-deficient MEFs showed decreased oxygen consumption compared to controls. Increased AMP-activated protein kinase (AMPK) signaling and decreased mammalian target of rapamycin (mTOR) signaling delayed aging and influenced mitochondrial function. Therefore, the effects of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), an AMPK activator, or rapamycin, an mTOR inhibitor, on measures of mitochondrial function were determined. Rapamycin treatment transiently increased respiration only in WT MEFs and, under most conditions, increased ATP levels. Short term AICAR treatment transiently increased ROS production and, under most conditions, decreased ATP levels. Chronic AICAR treatment decreased respiration and ROS production in WT MEFs. These results demonstrate the context-dependent effects of AICAR and rapamycin on mitochondrial function.

Individual Amino Acid Supplementation Can Improve Energy Metabolism and Decrease ROS Production in Neuronal Cells Overexpressing Alpha-Synuclein.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by alpha-synuclein accumulation and loss of dopaminergic neurons in the substantia nigra (SN) region of the brain. Increased levels of alpha-synuclein have been shown to result in loss of mitochondrial electron transport chain complex I activity leading to increased reactive oxygen species (ROS) production. WT alpha-synuclein was stably overexpressed in human BE(2)-M17 neuroblastoma cells resulting in increased levels of an alpha-synuclein multimer, but no increase in alpha-synuclein monomer levels. Oxygen consumption was decreased by alpha-synuclein overexpression, but ATP levels did not decrease and ROS levels did not increase. Treatment with ferrous sulfate, a ROS generator, resulted in decreased oxygen consumption in both control and alpha-synuclein overexpressing cells. However, this treatment only decreased ATP levels and increased ROS production in the cells overexpressing alpha-synuclein. Similarly, paraquat, another ROS generator, decreased ATP levels in the alpha-synuclein overexpressing cells, but not in the control cells, further demonstrating how alpha-synuclein sensitized the cells to oxidative insult. Proteomic analysis yielded molecular insights into the cellular adaptations to alpha-synuclein overexpression, such as the increased abundance of many mitochondrial proteins. Many amino acids and citric acid cycle intermediates and their ester forms were individually supplemented to the cells with L-serine, L-proline, L-aspartate, or L-glutamine decreasing ROS production in oxidatively stressed alpha-synuclein overexpressing cells, while diethyl oxaloacetate or L-valine supplementation increased ATP levels. These results suggest that dietary supplementation with individual metabolites could yield bioenergetic improvements in PD patients to delay loss of dopaminergic neurons.

Cyclic-AMP regulates postnatal development of neural and behavioral responses to NaCl in rats.

During postnatal development rats demonstrate an age-dependent increase in NaCl chorda tympani (CT) responses and the number of functional apical amiloride-sensitive epithelial Na+ channels (ENaCs) in salt sensing fungiform (FF) taste receptor cells (TRCs). Currently, the intracellular signals that regulate the postnatal development of salt taste have not been identified. We investigated the effect of cAMP, a downstream signal for arginine vasopressin (AVP) action, on the postnatal development of NaCl responses in 19-23 day old rats. ENaC-dependent NaCl CT responses were monitored after lingual application of 8-chlorophenylthio-cAMP (8-CPT-cAMP) under open-circuit conditions and under ±60 mV lingual voltage clamp. Behavioral responses were tested using 2 bottle/24h NaCl preference tests. The effect of [deamino-Cys1, D-Arg8]-vasopressin (dDAVP, a specific V2R agonist) was investigated on ENaC subunit trafficking in rat FF TRCs and on cAMP generation in cultured adult human FF taste cells (HBO cells). Our results show that in 19-23 day old rats, the ENaC-dependent maximum NaCl CT response was a saturating sigmoidal function of 8-CPT-cAMP concentration. 8-CPT-cAMP increased the voltage-sensitivity of the NaCl CT response and the apical Na+ response conductance. Intravenous injections of dDAVP increased ENaC expression and γ-ENaC trafficking from cytosolic compartment to the apical compartment in rat FF TRCs. In HBO cells dDAVP increased intracellular cAMP and cAMP increased trafficking of γ- and δ-ENaC from cytosolic compartment to the apical compartment 10 min post-cAMP treatment. Control 19-23 day old rats were indifferent to NaCl, but showed clear preference for appetitive NaCl concentrations after 8-CPT-cAMP treatment. Relative to adult rats, 14 day old rats demonstrated significantly less V2R antibody binding in circumvallate TRCs. We conclude that an age-dependent increase in V2R expression produces an AVP-induced incremental increase in cAMP that modulates the postnatal increase in TRC ENaC and the neural and behavioral responses to NaCl.

Calorie restriction does not restore brain mitochondrial function in P301L tau mice, but it does decrease mitochondrial F0F1-ATPase activity.

Calorie restriction (CR) has been shown to increase lifespan and delay aging phenotypes in many diverse eukaryotic species. In mouse models of Alzheimer's disease (AD), CR has been shown to decrease amyloid-beta and hyperphosphorylated tau levels and preserve cognitive function. Overexpression of human mutant tau protein has been shown to induce deficits in mitochondrial electron transport chain complex I activity. Therefore, experiments were performed to determine the effects of 4-month CR on brain mitochondrial function in Tg4510 mice, which express human P301L tau. Expression of mutant tau led to decreased ADP-stimulated respiratory rates, but not uncoupler-stimulated respiratory rates. The membrane potential was also slightly higher in mitochondria from the P301L tau mice. As shown previously, tau expression decreased mitochondrial complex I activity. The decreased complex I activity, decreased ADP-stimulated respiratory rate, and increased mitochondrial membrane potential occurring in mitochondria from Tg4510 mice were not restored by CR. However, the CR diet did result in a genotype independent decrease in mitochondrial F0F1-ATPase activity. This decrease in F0F1-ATPase activity was not due to lowered levels of the alpha or beta subunits of F0F1-ATPase. The possible mechanisms through which CR reduces the F0F1-ATPase activity in brain mitochondria are discussed.

Regulatory Effects of Ca2+ and H+ on the Rat Chorda Tympani Response to NaCl and KCl.

Modulatory effects of pHi and [Ca(2+)]i on taste receptor cell (TRC) epithelial sodium channel (ENaC) were investigated by monitoring chorda tympani (CT) responses to NaCl and KCl at various lingual voltages, before and after lingual application of ionomycin and with 0-10mM CaCl2 in the stimulus and rinse solutions adjusted to pHo 2.0-9.7. 0.1 and 0.5M KCl responses varied continuously with voltage and were fitted to an apical ion channel kinetic model using the same parameters. ENaC-dependent NaCl CT response was fitted to the same channel model but with parameters characteristic of ENaC. A graded increase in TRC [Ca(2+)]i decreased the ENaC-dependent NaCl CT response, and inhibited and ultimately eliminated its pH sensitivity. CT responses to KCl were pHi- and [Ca(2+)]i-independent. Between ±60 mV applied lingual potential, the data were well described by a linear approximation to the nonlinear channel equation and yielded 2 parameters, the open-circuit response and the negative of the slope of the line in the CT response versus voltage plot, designated the response conductance. The ENaC-dependent NaCl CT response conductance was a linear function of the open-circuit response for all pHi-[Ca(2+)]i combinations examined. Analysis of these data shows that pHi and [Ca(2+)]i regulate TRC ENaC exclusively through modulation of the maximum CT response.

Novel antigens in non-small cell lung cancer: SP17, AKAP4, and PTTG1 are potential immunotherapeutic targets.

Lung cancer is the leading cause of cancer deaths in both genders worldwide, with an incidence only second to prostate cancer in men and breast cancer in women. The lethality of the disease highlights the urgent need for innovative therapeutic options. Immunotherapy can afford efficient and specific targeting of tumor cells, improving efficacy and reducing the side effects of current therapies. We have previously reported the aberrant expression of cancer/testis antigens (CTAs) in tumors of unrelated histological origin. In this study we investigated the expression and immunogenicity of the CTAs, Sperm Protein 17 (SP17), A-kinase anchor protein 4 (AKAP4) and Pituitary Tumor Transforming Gene 1 (PTTG1) in human non-small cell lung cancer (NSCLC) cell lines and primary tumors. We found that SP17, AKAP4 and PTTG1 are aberrantly expressed in cancer samples, compared to normal lung cell lines and tissues. We established the immunogenicity of these CTAs by measuring CTA-specific autoantibodies in patients' sera and generating CTA-specific autologous cytotoxic lymphocytes from patients' peripheral blood mononuclear cells. Our results provide proof of principle that the CTAs SP17/AKAP4/PTTG1 are expressed in both human NSCLC cell lines and primary tumors and can elicit an immunogenic response in lung cancer patients.

Culture, acculturation and smoking use in Hmong, Khmer, Laotians, and Vietnamese communities in Minnesota.

BACKGROUND: Southeast Asian communities in the United States have suffered from high rates of tobacco use and high rates of chronic diseases associated with firsthand and secondhand smoking. Research is needed on how best to reduce and prevent tobacco use and exposure to secondhand smoke in these communities. The objective of this study was to examine how tobacco use patterns in Minnesota's Southeast Asian communities have been shaped by culture, immigration, and adjustment to life in America in order to inform future tobacco control strategies. METHODS: The study consisted of semi-structured interviews with 60 formal and informal leaders from Minnesota's Hmong, Khmer (Cambodian), Lao, and Vietnamese communities and incorporated principles of community-based participatory research. RESULTS: Among Khmer, Lao and Vietnamese, tobacco in the homeland was a valued part of material culture and was used to signify social status, convey respect, and support social rituals among adult men (the only group for whom smoking was acceptable). Among the Hmong, regular consumption of tobacco was unacceptable and rarely seen until the civil war in Laos when a number of Hmong soldiers became smokers. In Minnesota, social norms have begun to shift, with smoking becoming less acceptable. Although older male smokers felt social pressure to quit, smoking functioned to reduce the stress of social isolation, economic hardship, prior trauma, and the loss of power and status. Youth and younger women no longer felt as constrained by culturally-rooted social prohibitions to smoke. CONCLUSIONS: Leaders from Minnesota's Southeast Asian communities perceived key changes in tobacco-related attitudes, beliefs, and behaviors which were embedded in the context of shifting power, status, and gender roles within their communities. This has practical implications for developing policy and interventions. Older Southeast Asians are likely to benefit from culturally-tailored programs (e.g., that value politeness and the importance of acting in ways that benefit the family, community, and clan) and programs that work with existing social structures, as well as initiatives that address smokers' psychological distress and social isolation. Leaders remained uncertain about how to address smoking uptake among youth, pointing to a need for additional research.

Effect of ENaC modulators on rat neural responses to NaCl.

The effects of small molecule ENaC activators N,N,N-trimethyl-2-((4-methyl-2-((4-methyl-1H-indol-3-yl)thio)pentanoyl)oxy)ethanaminium iodide (Compound 1) and N-(2-hydroxyethyl)-4-methyl-2-((4-methyl-1H-indol-3-yl)thio)pentanamide (Compound 2), were tested on the benzamil (Bz)-sensitive NaCl chorda tympani (CT) taste nerve response under open-circuit conditions and under ±60 mV applied lingual voltage-clamp, and compared with the effects of known physiological activators (8-CPT-cAMP, BAPTA-AM, and alkaline pH), and an inhibitor (ionomycin+Ca2+) of ENaC. The NaCl CT response was enhanced at -60 mV and suppressed at +60 mV. In every case the CT response (r) versus voltage (V) curve was linear. All ENaC activators increased the open-circuit response (ro) and the voltage sensitivity (κ, negative of the slope of the r versus V curve) and ionomycin+Ca2+ decreased ro and κ to zero. Compound 1 and Compound 2 expressed a sigmoidal-saturating function of concentration (0.25-1 mM) with a half-maximal response concentration (k) of 0.49 and 1.05 mM, respectively. Following treatment with 1 mM Compound 1, 8-CPT-cAMP, BAPTA-AM and pH 10.3, the Bz-sensitive NaCl CT response to 100 mM NaCl was enhanced and was equivalent to the Bz-sensitive CT response to 300 mM NaCl. Plots of κ versus ro in the absence and presence of the activators or the inhibitor were linear, suggesting that changes in the affinity of Na+ for ENaC under different conditions are fully compensated by changes in the apical membrane potential difference, and that the observed changes in the Bz-sensitive NaCl CT response arise exclusively from changes in the maximum CT response (rm). The results further suggest that the agonists enhance and ionomycin+Ca2+ decreases ENaC function by increasing or decreasing the rate of release of Na+ from its ENaC binding site to the receptor cell cytosol, respectively. Irrespective of agonist type, the Bz-sensitive NaCl CT response demonstrated a maximum response enhancement limit of about 75% over control value.