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Natural killer (NK) cells play a key role in innate immunity by detecting alterations in self and non-self ligands via paired NK cell receptors (NKRs). Despite identification of numerous NKR-ligand interactions, physiological ligands for the prototypical NK1.1 orphan receptor remain elusive. Here, we identify a viral ligand for the inhibitory and activating NKR-P1 (NK1.1) receptors. This murine cytomegalovirus (MCMV)-encoded protein, m12, restrains NK cell effector function by directly engaging the inhibitory NKR-P1B receptor. However, m12 also interacts with the activating NKR-P1A/C receptors to counterbalance m12 decoy function. Structural analyses reveal that m12 sequesters a large NKR-P1 surface area via a "polar claw" mechanism. Polymorphisms in, and ablation of, the viral m12 protein and host NKR-P1B/C alleles impact NK cell responses in vivo. Thus, we identify the long-sought foreign ligand for this key immunoregulatory NKR family and reveal how it controls the evolutionary balance of immune recognition during host-pathogen interplay.
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Células Matadoras Naturais/imunologia , Muromegalovirus/imunologia , Receptores de Células Matadoras Naturais/imunologia , Proteínas Virais/metabolismo , Animais , Antígenos Ly/metabolismo , Linhagem Celular , Células HEK293 , Interações Hospedeiro-Patógeno , Humanos , Evasão da Resposta Imune , Imunidade Inata , Camundongos , Células NIH 3T3 , Subfamília B de Receptores Semelhantes a Lectina de Células NK/metabolismo , RatosRESUMO
We report an optical method for particle velocity measurement that is suitable for the measurement of particle velocities within dense particle-laden flows with high spatial resolution. The technique is based on particle shadow velocimetry with the use of a long-distance microscopic lens for images collection. The narrow depth of field of the lens allows particles within the focal plane to have much higher pattern intensities than those outside it on the collected images. Data processing was then employed to remove particles from outside the focal plane based on the gradient of the signal and a threshold. Following this, particle velocity was calculated from two successive images in the usual way. The technique was successfully demonstrated in a free-falling particle curtain with volume fractions in the four-way coupling regime of near-spherical micro-particles falling under gravity. The method was successfully employed to measure the transverse velocity profile through the curtain, which is the first time that such a measurement has been performed. Other highly-fidelity experimental data, which is also well suited to model development and validation, include the particle mass flow rate, curtain thickness and opacity.
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In this Letter, we present a particle image/tracking velocimetry (PIV/PTV) technique for simultaneous velocity measurement of both fluid and particle phases, adopting newly developed optical phase discrimination methods and novel optical particles. Spherical acrylic (PMMA) particles of diameter â¼O(100µm) were used as the particle phase, while fine BAM:Eu2+ phosphors of diameter â¼O(1µm) were used as the fluid tracer. Under Nd:YAG 355 nm laser excitation, both the laser-induced fluorescence (LIF) from PMMA and laser-induced phosphorescence (LIP) from BAM:Eu2+ provided sufficiently strong signals for PIV imaging with two non-intensified cameras and were clearly separable for phase discrimination using spectral filters and temporal profiles. The advantages of the PIV/PTV method include the relatively low cost of BAM:Eu2+ phosphors, high sphericity and narrow size distribution of PMMA particles with LIF emission, and direct optical discrimination eliminating artifacts, while requiring much less computational capacity for PIV/PTV processing of complex particle-laden flows.
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OBJECTIVE: There is emerging evidence that electroconvulsive therapy (ECT) can help with the behavioral and psychological symptoms of dementia. One of the most distressing behavioral symptoms of dementia is disruptive vocalization. Previous small case series have suggested that antidepressants and ECT can be beneficial for this distressing condition. The aim of this study was to describe the successful use of ECT in treating 5 patients with disruptive vocalization. METHODS: A retrospective chart review of 5 patients with dementia of mixed etiologies was conducted comparing pretreatment and posttreatment scores on the Cohen-Mansfield Agitation Inventory. All 5 patients had unsuccessful treatments with nonpharmacological methods and pharmacotherapy including antidepressants. RESULTS: After completion of a series of ECT, the mean verbal agitation score decreased from 6.8 (95% confidence interval, 6.3-7.3) to 2.3 (95% confidence interval, 1.3-3.3), with both clinical and statistical significance (P < 0.001). CONCLUSIONS: Although further research is needed, these findings support considering the use of ECT for disruptive vocalization in dementia.
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Transtornos de Deficit da Atenção e do Comportamento Disruptivo/terapia , Demência/terapia , Eletroconvulsoterapia/métodos , Idoso , Doença de Alzheimer/complicações , Doença de Alzheimer/psicologia , Doença de Alzheimer/terapia , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/etiologia , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/psicologia , Demência/complicações , Demência/psicologia , Demência Vascular/complicações , Demência Vascular/psicologia , Demência Vascular/terapia , Feminino , Humanos , Escalas de Graduação Psiquiátrica , Agitação Psicomotora/tratamento farmacológico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: There is a projected shortage of psychiatrists in Canada in forthcoming years. This study assessed factors in medical school education that are associated with students selecting psychiatry first and matching as a discipline. METHOD: The Canadian Organization of Undergraduate Psychiatry Educators (COUPE) conducted telephone interviews and sent e-mail questionnaires to the 17 medical schools across Canada; all schools provided data for 2012. Relevant data were obtained from the Canadian Resident Matching Service. Statistics were performed using v12 STATA program, and significance was set at a p value of <0.05. RESULTS: Medical student enrollment ranged from 54 to 266 students (mean = 158 ± 16). Of these students, 4.9 ± 0.6 % ranked psychiatry as their first choice for residency. Final match results yielded similar numbers at 5.0 ± 0.6 %. Ten out of 17 programs filled all psychiatry residency positions, whereas the remaining 7 programs had vacancy rates from 5 to 100 % (mean = 43.4 ± 15.1 %). Medical students were exposed to an average of 2.8 ± 0.5 pre-clerkship psychiatry weeks and 6.2 ± 0.3 clerkship weeks. Linear regression analysis demonstrated that the percentage of graduating medical students entering a psychiatry residency program could be predicted from the number of weeks of pre-clerkship exposure (p = 0.01; R(2) = 0.36) but not from the number of clerkship weeks (p = 0.74). CONCLUSIONS: This study indicates that the duration of pre-clerkship exposure to psychiatry predicts the number of students selecting psychiatry as their first choice as a discipline. Thus, increasing the duration of pre-clerkship exposure may increase the enrollment of medical students into psychiatry.
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Escolha da Profissão , Estágio Clínico/estatística & dados numéricos , Currículo/estatística & dados numéricos , Internato e Residência/estatística & dados numéricos , Psiquiatria/estatística & dados numéricos , Adulto , Canadá , Feminino , Humanos , Masculino , Psiquiatria/educação , Adulto JovemRESUMO
Polyembolokoilamania is the act of inserting foreign objects into bodily orifices and can be classified as a paraphilia if done for sexual pleasure. Although problematic sexual behaviors are common in dementia, the majority of case reports of urethral polyembolokoilamania in the elderly have occurred in the absence of dementia or cognitive impairment. Little empirical evidence exists for managing problematic sexual behaviors in the elderly and in dementia. Most evidence in the form of case reports demonstrates that behavioral, environmental, and pharmacological interventions can be effective. In this case report, we describe the management of sexually disinhibited behavior in the form of polyembolokoilamania in a 67-year-old man suffering from treatment-resistant depression, obsessive compulsive disorder, and early signs of frontotemporal dementia. The successful treatment included a course of electroconvulsive therapy.
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Eletroconvulsoterapia , Demência Frontotemporal/terapia , Transtorno Obsessivo-Compulsivo/terapia , Idoso , Humanos , Masculino , Acetato de Medroxiprogesterona/uso terapêutico , Uretra/lesõesRESUMO
We report a chromosomal-level genome assembly of a male North American wolverine (Gulo gulo luscus) from the Kugluktuk region of Nunavut, Canada. The genome was assembled directly from long-reads, comprising: 758 contigs with a contig N50 of 36.6 Mb; contig L50 of 20; base count of 2.39 Gb; and a near complete representation (99.98%) of the BUSCO 5.2.2 set of 9,226 genes. A presumptive chromosomal-level assembly was generated by scaffolding against two chromosomal-level Mustelidae reference genomes, the ermine and the Eurasian river otter, to derive a final scaffold N50 of 144.0 Mb and a scaffold L50 of 7. We annotated a comprehensive set of genes that have been associated with models of aggressive behavior, a trait which the wolverine is purported to have in the popular literature. To support an integrated, genomics-based wildlife management strategy at a time of environmental disruption from climate change, we annotated the principal genes of the innate immune system to provide a resource to study the wolverine's susceptibility to new infectious and parasitic diseases. As a resource, we annotated genes involved in the modality of infection by the coronaviruses, an important class of viral pathogens of growing concern as shown by the recent spillover infections by severe acute respiratory syndrome coronavirus-2 to naïve wildlife. Tabulation of heterozygous single nucleotide variants in our specimen revealed a heterozygosity level of 0.065%, indicating a relatively diverse genetic pool that would serve as a baseline for the genomics-based conservation of the wolverine, a rare cold-adapted carnivore now under threat.
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COVID-19 , Mustelidae , Animais , Cromossomos , Genômica , Humanos , Masculino , Mustelidae/genética , América do NorteRESUMO
BACKGROUND: Inappropriate sexual behavior (ISB) is an important topic in geriatrics; etiologies remain unclear and evidence for the efficacy of treatment strategies is limited. The aims of this study were to provide a description of the phenomenology of ISB in the geriatric population, to identify potential contributing factors, and to review the efficacy of interventions aimed at reducing ISB. METHODS: A retrospective chart review was conducted of ten patients admitted to an academic inpatient geriatric psychiatry ward because of their ISB (study group) and ten patients matched in age and gender (control group). A comprehensive chart review inventory was done to determine variables that may contribute to ISB. For the study group, effectiveness, adverse effects, and discontinuation due to adverse effects of interventions aimed at reducing ISB were reviewed. RESULTS: A significant finding was the association of a history of right frontal lobe stroke with ISB (Fisher's Exact Probability Test p < 0.05). Also significant was performance on cognitive testing and the presence of dementia (Fisher's Exact Probability Test p < 0.05) in the study group. Citalopram was well tolerated but with minimal reduction of ISB. Atypical antipsychotics olanzapine and risperidone were effective in some cases but also had adverse effects. Medroxyprogesterone acetate was well tolerated and effective in all cases in which it was utilized (n = 5). CONCLUSIONS: This study suggests that ISB in the geriatric population is associated with a history of right frontal lobe stroke and with severity of dementia. Case examples of pharmacologic interventions are reviewed.
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Terapia Comportamental , Demência , Lobo Frontal/patologia , Psicotrópicos , Comportamento Sexual/efeitos dos fármacos , Disfunções Sexuais Psicogênicas , Acidente Vascular Cerebral , Idoso , Idoso de 80 Anos ou mais , Atitude do Pessoal de Saúde , Demência/complicações , Demência/psicologia , Feminino , Avaliação Geriátrica , Instituição de Longa Permanência para Idosos , Humanos , Testes de Inteligência , Masculino , Casas de Saúde , Relações Profissional-Paciente , Psicotrópicos/administração & dosagem , Psicotrópicos/efeitos adversos , Índice de Gravidade de Doença , Comportamento Sexual/psicologia , Disfunções Sexuais Psicogênicas/etiologia , Disfunções Sexuais Psicogênicas/terapia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/psicologia , Resultado do TratamentoRESUMO
OBJECTIVES: To determine whether steroids are effective in treating adults with acute vestibular neuritis. DATA SOURCES: PubMed, Embase, CINAHL, Cochrane CENTRAL, Web of Science, CAB Abstract, ICTRP, LILACS, PEDRO, ClinicalTrials.Gov, Google Scholar, NARIC, and OT Seeker. REVIEW METHODS: A systematic review was undertaken for articles reporting subjective and/or objective outcomes of corticosteroids in adults with acute vestibular neuritis between December 2010 and October 2019. Reports of patient recovery from clinical vestibular outcomes at various time points and adverse effects from corticosteroids were of interest. Statistical analysis included qualitative and quantitative assessments. A limited meta-analysis of the data was performed through a random effects model. RESULTS: Eight studies met the criteria, and 6 were included in the meta-analysis. No significant differences between the groups (corticosteroid vs placebo, corticosteroid vs vestibular exercise, or corticosteroid vs combination of vestibular exercise and corticosteroid) were reported in the proportion of patients with complete recovery at 1, 6, and 12 months. The corticosteroid group had significantly better caloric recover at 1 month (95% CI, -16.33 to -0.32); however, there was no significant difference to the overall effect between the groups across 12 months. Subjective recovery did not differ between the groups. Five of the 8 studies reported on adverse effects from corticosteroids. CONCLUSION: There is insufficient evidence to support the use of corticosteroids in managing acute vestibular neuritis in adults. At present, corticosteroids appear to have short-term benefits in canal paresis but no long-term benefits in canal paresis and symptomatic recovery. Future studies should consider including a wider variety of clinical vestibular tests and frequent acute follow-ups to monitor the effects of corticosteroids.
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Corticosteroides/uso terapêutico , Neuronite Vestibular/tratamento farmacológico , Doença Aguda , Adulto , HumanosRESUMO
BACKGROUND: A central tenet in biochemistry for over 50 years has held that microorganisms, plants and, more recently, certain apicomplexan parasites synthesize essential aromatic compounds via elaboration of a complete shikimic acid pathway, whereas metazoans lacking this pathway require a dietary source of these compounds. The large number of sequenced bacterial and archaean genomes now available for comparative genomic analyses allows the fundamentals of this contention to be tested in prokaryotes. Using Hidden Markov Model profiles (HMM profiles) to identify all known enzymes of the pathway, we report the presence of genes encoding shikimate pathway enzymes in the hypothetical proteomes constructed from the genomes of 488 sequenced prokaryotes. RESULTS: Amongst free-living prokaryotes most Bacteria possess, as expected, genes encoding a complete shikimic acid pathway, whereas of the culturable Archaea, only one was found to have a complete complement of recognisable enzymes in its predicted proteome. It may be that in the Archaea, the primary amino-acid sequences of enzymes of the pathway are highly divergent and so are not detected by HMM profiles. Alternatively, structurally unrelated (non-orthologous) proteins might be performing the same biochemical functions as those encoding recognized genes of the shikimate pathway. Most surprisingly, 30% of host-associated (mutualistic, commensal and pathogenic) bacteria likewise do not possess a complete shikimic acid pathway. Many of these microbes show some degree of genome reduction, suggesting that these host-associated bacteria might sequester essential aromatic compounds from a parasitised host, as a 'shared metabolic adaptation' in mutualistic symbiosis, or obtain them from other consorts having the complete biosynthetic pathway. The HMM results gave 84% agreement when compared against data in the highly curated BioCyc reference database of genomes and metabolic pathways. CONCLUSIONS: These results challenge the conventional belief that the shikimic acid pathway is universal and essential in prokaryotes. The possibilities that non-orthologous enzymes catalyse reactions in this pathway (especially in the Archaea), or that there exist specific uptake mechanisms for the acquisition of shikimate intermediates or essential pathway products, warrant further examination to better understand the precise metabolic attributes of host-beneficial and pathogenic bacteria.
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Genes Bacterianos/genética , Interações Hospedeiro-Patógeno/genética , Redes e Vias Metabólicas/genética , Ácido Chiquímico/metabolismo , Archaea/genética , Archaea/metabolismo , Bactérias/enzimologia , Bactérias/genética , Bases de Dados Genéticas , Cadeias de Markov , Células Procarióticas/metabolismo , Proteoma/genética , Análise de Sequência de DNA , Ácido Chiquímico/química , Moldes GenéticosRESUMO
We describe a method to simulate on macroscopic time scales the stress relaxation in an atomistic nanocrystal model under an imposed strain. Using a metadynamics algorithm for transition state pathway sampling we follow the full evolution of a classical anelastic relaxation event, with relaxation times governed by the nanoscale microstructure imperfections in the solid. We show that probing this sensitive variation leads to mechanistic insights that reveal a direct correlation between system-level relaxation behavior and localized atomic displacements in the vicinity of the nanostructured defects, in turn implying a unit mechanism for self-organized plastic response. This suggests a new class of measurements in which the microstructure imperfections are characterized and matched to predictive simulations enabled by the present method.
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Here we report kinetic Monte Carlo simulations of dislocation climb in heavily deformed, body-centered cubic iron comprising a supersaturation of vacancies. This approach explicitly incorporates the effect of nonlinear vacancy-dislocation interaction on vacancy migration barriers as determined from atomistic calculations, and enables observations of diffusivity and climb over time scales and temperatures relevant to power-law creep. By capturing the underlying microscopic physics, the calculated stress exponents for steady-state creep rates agree quantitatively with the experimentally measured range, and qualitatively with the stress dependence of creep activation energies.
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Synthetic cathinones, commonly referred to as "bath salts," are powerful amphetamine-like psychostimulants, and new derivatives are constantly appearing in the illicit market to evade judicial consequences. To keep up with these new stimulant drugs, a low-sample-size liquid chromatography-tandem mass spectrometry method was validated to quantify 30 synthetic cathinones in postmortem blood including N-ethylpentylone and eutylone. Mixed mode cation exchange solid-phase extraction using 0.25 mL postmortem blood was performed followed by detection using a triple quadrupole mass spectrometer operating electrospray ionization in positive mode. The reversed-phase chromatographic separation was achieved in 16 min, resolving all isobaric compounds. The linear range of the calibration curve was 1-500 ng/mL (R 2 > 0.99) for all compounds. Limit of quantification (LOQ) and limit of detection were determined to be at 1 ng/mL. Both imprecision and bias were evaluated and had met all allowed criteria (CV and bias <20%). No matrix effect was observed with values ranging from -5.1 to 13.3% (CV 11.4-17.5%, n = 10). Extraction efficiency (84.9-91.5%) and process efficiency (86.1-102.6%) were satisfactory, except for 4-chloroethcathinone which was 63 and 64.9%, respectively. No carryover after the upper LOQ was detected. Neither endogenous nor exogenous interferences were observed. Both dilution integrity and stability (24 h) yielded acceptable results. This method was applied to 18 postmortem cases received between 2015 and 2019. Eight different synthetic cathinones were detected in selected postmortem cases within the past 5 years, showing a wide range of concentrations from 1.4 to >500 ng/mL. While ethylone and methylone were detected in 2015, cases between 2016 and 2017 were predominantly butylone, dibutylone, pentylone and N-ethylpentylone which had also exhibited a significant increase in 2018. To our knowledge, this method is the most comprehensive methodology for the determination of up-to-date synthetic cathinones currently available in whole blood.
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Alcaloides/análise , Toxicologia Forense , Detecção do Abuso de Substâncias , Cromatografia Líquida , Humanos , Limite de Detecção , Espectrometria de Massas em TandemRESUMO
A one-pot double galvanic approach was explored for the rational synthesis of metal oxide nanotubes, predictable based on the reduction potential hierarchy of templates and ion precursors (e.g., Ag nanowire substrate is oxidized by MnO4 - ions and it is consecutively reduced by Fe2+ ions to form an Fe2O3 nanotube). This method generated a variety of metal oxide nanotubes via a redox potential landscape.
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As the number of older adults living with chronic conditions continues to rise, they will require assistance with activities of daily living (ADL) and healthcare tasks to continue living independently in their homes. One proposed solution to assist with the care needs of an aging population and a shrinking healthcare workforce is robotic technology. Using a cross-sectional survey design, we purposively sampled adults (≥18 years old) to assess generational acceptance and perceived usefulness of robots to assist with ADLs, healthcare tasks, and evaluate acceptance of robotic healthcare assistance across different settings. A total of 499 adults (age range [years] 18-98, Mean = 38.7, SD = 22.7) responded to the survey. Significant differences were found among young, middle-aged, and older adults on perceived usefulness of robots for cleaning, escorting them around town, acting as companionship, delivering meals, assessing sadness and calling for help, providing medical advice, taking vital sign assessments, and assisting with personal care (p < 0.05). The majority of younger adults reported that they would like a robot to provide healthcare assistance in the hospital, compared to middle-aged and older adults (p < 0.001). Results of this study can guide the design of robots to assist adults of all ages with useful tasks.
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Atividades Cotidianas , Robótica/métodos , Tecnologia Assistiva , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
While circumventing legislative controls, synthetic piperazines are encountered as "legal" alternatives to ecstasy. Unforeseeable challenges may delay quantitative analysis of these compounds in biological fluids. Enzymatic reactions, matrix interferences and limited knowledge of analyte stability further complicate interpretation of calculated concentrations. The objective of this study was to investigate the stability of synthetic piperazines in human blood under various storage conditions over time. All samples were prepared by spiking certified reference standards (Cayman Chemical, MI, U.S.A.) of eight synthetic piperazine into certified drug-free human whole blood (UTAK Laboratories, Inc., CA, U.S.A.) independently at 1000 ng/mL as well as mixtures containing all tested piperazines in this study. Samples were stored at room temperature (~20°C), 4°C and -20°C for 1, 3, 6, 9 and 12 months in dark sealed containers. Solid phase extraction (SPE) was performed using mixed-mode copolymeric cartridges (Clean Screen®, UCT Inc., PA, U.S.A.). Analytes were assessed on their degrees of degradation using a Shimadzu Ultra-Fast Liquid Chromatograph with SCIEX 4000 Q-Trap Electrospray Ionization Tandem Mass Spectrometer (UFLC-ESI-MS/MS) in positive ionization mode. Of the two categories, benzyl piperazines were more stable than phenyl piperazines under all storage conditions, in which 1-(4-methylbenzyl)-piperazine (MBZP) had more than 70% (769-1,047 ng/mL) remaining after 12 months. 1-(4-methoxyphenyl)-piperazine (MeOPP) was not detected under room and refrigerated temperatures after 6 months and was the least stable. Matrix interferences and drug-drug interaction were observed. Storing samples at room temperature should be avoided due to detrimental impacts on stability of piperazine compounds. For backlog situations, case samples suspected to contain synthetic piperazines should be kept frozen or refrigerated even for time periods as short as 30 days for optimal result. Phenyl piperazines stored for more than 6 months showed analyte degradation and loss of parent compounds after extended storage regardless of storage conditions.
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Toxicologia Forense/métodos , Drogas Ilícitas/sangue , Piperazinas/sangue , Psicotrópicos/sangue , Detecção do Abuso de Substâncias/métodos , Cromatografia Líquida de Alta Pressão , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Toxicologia Forense/legislação & jurisprudência , Regulamentação Governamental , Humanos , Manejo de Espécimes , Detecção do Abuso de Substâncias/legislação & jurisprudência , Espectrometria de Massas em TandemRESUMO
INTRODUCTION: Neonatal abstinence syndrome (NAS) is a rapidly growing public health concern that has considerably increased health-care utilization and health-care costs. In an effort to curtail costs, attempts have been made to complete withdrawal as an outpatient. Outpatient therapy has been shown to prolong exposure to medications, which may negatively impact neurodevelopmental and behavioral outcomes. We hypothesized that the implementation of a modified NAS protocol would decrease total drug exposure and length of stay while allowing for complete acute drug withdrawal during the neonatal hospital stay. METHODS: Data were derived retrospectively from medical records of term (≥37 0/7) infants with NAS who were treated with pharmacologic therapy in the University of Louisville Hospital Neonatal Intensive Care Unit from 2005 to 2015. The pharmacologic protocol (SP1) for infants treated between 2005 and March 2014 (n = 146) dosed oral morphine every 4 h and utilized phenobarbital as adjuvant therapy. Protocol 2 (SP2) initiated after March 2014 (n = 44) dosed morphine every 3 h and used clonidine as adjuvant therapy. Charts were reviewed for demographic information and maternal drug history. Maternal and infant toxicology screens were recorded. The length of morphine therapy and need for adjuvant drug therapy were noted. Length of stay was derived from admission and discharge dates. RESULTS: The length of morphine therapy was decreased by 8.5 days from 35 to 26.5 days (95% CI 4.5-12 days) for infants treated with SP2 vs. SP1 (p < 0.001). The need for adjuvant pharmacologic therapy was decreased by 24% in patients treated with SP2 vs. SP1 (p = 0.004). The length of stay was decreased by 9 days from 42 to 33 days (95% CI 5.1-13 days) for infants treated with SP2 vs. SP1 (p < 0.001). The decreased length of stay resulted in an average reduction of hospital charges by $27,090 per patient in adjusted 2015 US Dollars. CONCLUSION: This study demonstrates that total drug exposure and length of stay can be reduced while successfully completing acute withdrawal during the neonatal hospital stay.
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BACKGROUND: Studies suggest that antipsychotic-induced weight gain is not a great concern in the elderly population. This study investigated the weight change in elderly patients with various treatment duration and antipsychotics. Part 1 of the study was to determine whether atypical antipsychotics induced weight change in elderly patients. Part 2 was to determine whether certain atypical antipsychotics induced more weight change in elderly patients. METHODS: In Part 1, a retrospective chart review was done on 115 geriatric inpatients. After exclusion, patients were divided into four groups: control (n = 17), new treatment (n = 18), long-term treatment (n = 13), and medication switch groups (n = 8). In Part 2, a retrospective medication review was performed on 169 geriatric inpatients. After exclusion, patients were divided into three groups: aripiprazole (n = 18), olanzapine (n = 49), and risperidone (n = 57). Body weights were obtained at two different time points. RESULTS: No significant difference in weight change was observed among the control (1.5 kg), new treatment (0.8 kg), long-term treatment (-0.3 kg), and medication switch (1.9 kg) groups. No significant difference in weight change was observed between patients with and without dementia (0.8 and 1.1 kg, respectively). The weight change in the aripiprazole group (-2.0 kg; -2.30% from baseline) was significantly different from the weight change in the olanzapine group (0.7 kg; 1.87% from baseline; p < 0.05), but not from the risperidone group (-0.4 kg; -0.45% from baseline). Clinically significant weight gain (>7% increase in body weight) occurred in 14.3% of the olanzapine patients, a percentage significantly higher than the 3.5% in the risperidone group. CONCLUSION: Although atypical antipsychotics were generally weight neutral in the geriatric population, aripiprazole and olanzapine were associated with significant weight loss and weight gain, respectively.
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For a variety of reasons, researchers and evidence-based clearinghouses synthesizing the results of multiple studies often have very few studies that are eligible for any given research question. This situation is less than optimal for meta-analysis as it is usually practiced, that is, by employing inverse variance weights, which allows more informative studies to contribute relatively more to the analysis. This article outlines the choices available for synthesis when there are few studies to synthesize. As background, we review the synthesis practices used in several projects done at the behest of governmental agencies and private foundations. We then discuss the strengths and limitations of different approaches to meta-analysis in a limited information environment. Using examples from the U.S. Department of Education's What Works Clearinghouse as case studies, we conclude with a discussion of Bayesian meta-analysis as a potential solution to the challenges encountered when attempting to draw inferences about the effectiveness of interventions from a small number of studies.
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We demonstrate that stress differentially regulates glutamate homeostasis in the dorsal and ventral hippocampus and identify a role for the astroglial xCT in ventral dentate gyrus (vDG) in stress and antidepressant responses. We provide an RNA-seq roadmap for the stress-sensitive vDG. The transcription factor REST binds to xCT promoter in co-occupancy with the epigenetic marker H3K27ac to regulate expression of xCT, which is also reduced in a genetic mouse model of inherent susceptibility to depressive-like behavior. Pharmacologically, modulating histone acetylation with acetyl-L-carnitine (LAC) or acetyl-N-cysteine (NAC) rapidly increases xCT and activates a network with mGlu2 receptors to prime an enhanced glutamate homeostasis that promotes both pro-resilient and antidepressant-like responses. Pharmacological xCT blockage counteracts NAC prophylactic effects. GFAP+-Cre-dependent overexpression of xCT in vDG mimics pharmacological actions in promoting resilience. This work establishes a mechanism by which vDG protection leads to stress resilience and antidepressant responses via epigenetic programming of an xCT-mGlu2 network.