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1.
Nat Commun ; 15(1): 778, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38278803

RESUMO

Organic matter in extraterrestrial samples is a complex material that might have played an important role in the delivery of prebiotic molecules to the early Earth. We report here on the identification of nitrogen-containing compounds such as amino acids and N-heterocycles within the recent observed meteorite fall Winchcombe by high-spatial resolution spectroscopy techniques. Although nitrogen contents of Winchcombe organic matter are low (N/C ~ 1-3%), we were able to detect the presence of these compounds using a low-noise direct electron detector. These biologically relevant molecules have therefore been tentatively found within a fresh, minimally processed meteorite sample by high spatial resolution techniques conserving the overall petrographic context. Carbon functional chemistry investigations show that sizes of aromatic domains are small and that abundances of carboxylic functional groups are low. Our observations demonstrate that Winchcombe represents an important addition to the collection of carbonaceous chondrites and still preserves pristine extraterrestrial organic matter.

2.
Artigo em Inglês | MEDLINE | ID: mdl-37623193

RESUMO

People on buprenorphine maintenance treatment (BMT) commonly present cognitive deficits that have been associated with illicit drug use and dropout from buprenorphine treatment. This study has compared cognitive responses to the Stroop Task and the Continuous Performance Task (CPT) among individuals on BMT, with recent drug use, and healthy controls and explored the associations between cognitive responses and drug use, craving, and buprenorphine use among participants on BMT. The participants were 16 individuals on BMT and 23 healthy controls. All participants completed a 60 min laboratory session in which they completed the Stroop Task and the CPT, a saliva drug test, a brief clinical history that collected substance-use- and treatment-related information, and the Opioid Craving Scale. The results showed that the BMT participants presented more commission errors (MBMT participants = 2.49; Mhealthy controls = 1.38; p = 0.048) and longer reaction times (MBMT participants = 798.09; Mhealthy controls = 699.09; p = 0.047) in the Stroop Task than did the healthy controls. More days on buprenorphine were negatively associated with reaction time in the CPT (-0.52) and the number of commission errors (-0.53), simple reaction time (-0.54), and reaction time correct (-0.57) in the Stroop Task. Neither drug use nor craving was significantly associated with the results for the cognitive tasks. Relative to the control participants, the BMT individuals performed worse in terms of longer reaction times and more commission errors in the Stroop Task. Within the BMT participants, longer times on buprenorphine were associated with better cognitive results in terms of faster reaction times for both tasks and lower commission errors for the Stroop Task.


Assuntos
Buprenorfina , Transtornos Relacionados ao Uso de Opioides , Humanos , Buprenorfina/uso terapêutico , Projetos Piloto , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Analgésicos Opioides , Cognição
3.
J Marital Fam Ther ; 49(3): 654-674, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37403806

RESUMO

Therapists report significant countertransference reactions when treating clients with eating disorders (EDs). Countertransference may be pronounced among therapists with eating disorder lived experience (EDLE). Minimal research examines how therapists with EDLE negotiate their experiences while treating ED clients. Informed by the person-of-the-therapist philosophy, this study sought to understand how therapists use and manage their EDLE when working with ED clients. Using constructivist grounded theory methodology, semistructured interviews (Mtime = 89 min) were conducted with 22 therapists with EDLE. Results revealed that therapists engaged in two interconnected systems. The Central System helps therapists transform their lived experiences into clinical guidance. The Checks and Balances System allows therapists to find a balance between connecting with the client and allowing for differences in experiences to emerge. Lastly, three personal processes existing outside of these systems were found to impact therapists' use of self. Findings provide novel ways that therapists can use their EDLE.


Assuntos
Transtornos da Alimentação e da Ingestão de Alimentos , Humanos , Transtornos da Alimentação e da Ingestão de Alimentos/terapia , Relações Profissional-Paciente , Psicoterapia/métodos
4.
World Neurosurg ; 178: e24-e33, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37268187

RESUMO

OBJECTIVE: Stereotactic radiosurgery (SRS) is a well-established treatment for vestibular schwannomas (VS). Hearing loss remains a main morbidity of VS and its treatments, including SRS. The effects of radiation parameters of SRS on hearing remain unknown. The goal of this study is to determine the effect of tumor volume, patient demographics, pretreatment hearing status, cochlear radiation dose, total tumor radiation dose, fractionation, and other radiotherapy parameters on hearing deterioration. METHODS: Multicenter retrospective analysis of 611 patients who underwent SRS for VS from 1990-2020 and had pre- and post-treatment audiograms. RESULTS: Pure tone averages (PTAs) increased and word recognition scores (WRSs) decreased in treated ears at 12-60 months while remaining stable in untreated ears. Higher baseline PTA, higher tumor radiation dose, higher maximum cochlear dose, and usage of single fraction resulted in higher post radiation PTA; WRS was only predicted by baseline WRS and age. Higher baseline PTA, single fraction treatment, higher tumor radiation dose, and higher maximum cochlear dose resulted in a faster deterioration in PTA. Below a maximum cochlear dose of 3 Gy, there were no statistically significant changes in PTA or WRS. CONCLUSIONS: Decline of hearing at one year in VS patients after SRS is directly related to maximum cochlear dose, single versus 3-fraction treatment, total tumor radiation dose, and baseline hearing level. The maximum safe cochlear dose for hearingtbrowd preservation at one year is 3 Gy, and the use of 3 fractions instead of one fraction was better at preserving hearing.


Assuntos
Neuroma Acústico , Radiocirurgia , Humanos , Neuroma Acústico/radioterapia , Neuroma Acústico/cirurgia , Estudos Retrospectivos , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos , Seguimentos , Audição , Resultado do Tratamento
5.
J Pediatr Surg ; 58(6): 1170-1177, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36922278

RESUMO

BACKGROUND: Resection-associated liver steatosis, injury, and fibrosis is a devastating complication associated with massive small bowel resection (SBR). Peroxisome proliferator-activated receptor-alpha (PPARα) is a key regulator of intestinal lipid transport and metabolism whose expression is selectively increased after SBR. Here we asked if attenuating intestinal PPARα signaling would prevent steatosis and liver injury after SBR. METHODS: Pparα was deleted selectively in adult mouse intestine using a tamoxifen-inducible Cre-LoxP breeding schema. Mice underwent 50% SBR. At 10 weeks post-operatively, metabolic phenotyping, body composition analysis, in vivo assessment of lipid absorption and intestinal permeability, and assessment of adaptation and liver injury was completed. RESULTS: Pparα intestinal knockout and littermate control mice were phenotypically similar in terms of weight trends and body composition after SBR. All mice demonstrated intestinal adaptation with increased villus height and crypt depth; however, Pparα intestinal knockout mice exhibited decreased villus growth at 10 weeks compared to littermate controls. Liver injury and fibrosis were similar between groups as assessed by serum AST and ALT levels, Sirius Red staining, and hepatic expression of Col1a1 and Acta2. CONCLUSIONS: Inducible intestinal deletion of Pparα influences structural adaptation but does not mitigate liver injury after SBR. These findings suggest that enterocyte PPARα signaling in adult mice is dispensable for resection-induced liver injury. The results are critical for understanding the contribution of intestinal lipid metabolic signaling pathways to the pathogenesis of hepatic injury associated with short bowel syndrome.


Assuntos
Intestino Delgado , PPAR alfa , Animais , Camundongos , Adaptação Fisiológica , Intestino Delgado/cirurgia , Lipídeos , Camundongos Endogâmicos C57BL , Camundongos Knockout , PPAR alfa/genética , PPAR alfa/metabolismo
6.
J Clin Psychol ; 79(1): 201-209, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35751901

RESUMO

AIMS: This exploratory pilot study (N = 3 sessions, 793 speech units) used task analysis to refine an early model of the attachment task in attachment-based family therapy (ABFT). The attachment task aims to repair long-standing parent-adolescent relational ruptures that inhibit parents from being a resource for adolescents recovering from depression and/or suicidality. METHODS: Video recordings of three attachment task sessions with strong adherence to the model were selected for intensive study. Two sessions were rated as successful (i.e., attachment was repaired) and one as unsuccessful (i.e., attachment repair did not occur). Sessions were then coded using Structural Analysis of Social Behavior (SASB). RESULTS: The current SASB analysis provided empirical support for our previous clinical impression that the task involves three parts: (I) adolescent disclosure of attachment rupture, (II) parent disclosure, and (III) a more mutual conversation. SASB also provided insights into more subtle elements of the model. CONCLUSION: Successful attachment sessions were associated with high parent affiliation and autonomy-both while affirming the adolescent's story and when disclosing their own experience. Unsuccessful task attempts were associated with parental enmeshment and hostile belittling, blaming, and distancing. An enhanced model of ideal parent behaviors during the attachment task is offered, including space for parent disclosure-perhaps even apology-that is both warm and independent, leading to a more mutual parent-adolescent conversation. Clinically, the findings support the importance of the therapist focusing on the process and quality of parent-child interactions to facilitate attachment repair.


Assuntos
Apego ao Objeto , Relações Pais-Filho , Adolescente , Humanos , Projetos Piloto , Terapia Familiar , Pais
7.
J Am Acad Audiol ; 2023 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-36070782

RESUMO

BACKGROUND: Vestibular migraine (VM) is one of the common causes of episodic dizziness, but it is underdiagnosed and poorly understood. Previous research suggests that otolith reflex pathway performance is often impaired in this patient group, leading to altered perception of roll plane stimuli. Clinically, this perception can be measured with subjective visual vertical (SVV) testing. PURPOSE: The aim of this study is to compare static SVV performance (absolute mean SVV tilt, variance) in a cohort of patients diagnosed with VM to results obtained from clinically derived normative data. STUDY DESIGN: Retrospective case review. STUDY SAMPLE: Ninety-four consecutive patients between 18 and 65 years of age diagnosed with VM were included in this comparison to clinically derived normative data. DATA COLLECTION AND ANALYSIS: Retrospective chart review was completed. Demographic data, symptom report, and vestibular laboratory results were documented. SVV performance was documented in terms of absolute mean SVV tilt and response variance. RESULTS: Abnormal mean SVV tilt was described in 54% (n = 51) of patients with VM. Including abnormal response variance increased those identified with abnormal presentation to 67% (n = 63). Laboratory findings were insignificant for semicircular canal function, but of those with abnormal ocular vestibular myogenic potential results (n = 30), 77% (n = 23) demonstrated both abnormal SVV and utriculo-ocular reflex performance. There were no associations noted for SVV performance and demographic or other self-report variables. CONCLUSION: Absolute mean SVV tilt and response variance are often abnormal in patients diagnosed with VM. These findings support theories suggesting atypical intralabyrinthine integration within the vestibular nuclei and cerebellar nodular pathways.

8.
Am J Health Promot ; 37(2): 228-232, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36007095

RESUMO

PURPOSE: Information on incentives for COVID-19 testing is needed to understand effective practices that encourage testing uptake. We describe characteristics of those who received an incentive after performing a rapid antigen test. DESIGN: Cross-sectional descriptive analysis of survey data. SETTING: During April 29-May 9, 2021, COVID-19 rapid antigen testing was offered in 2 Maryland cities. SAMPLE: Convenience sample of 553 adults (≥18 years) who tested and received an incentive; 93% consented to survey. MEASURES: Survey questions assessed reasons for testing, testing history, barriers, and demographics. ANALYSIS: Robust Poisson regressions were used to determine characteristic differences based on testing history and between participants who would re-test in the future without an incentive vs participants who would not. RESULTS: The most common reasons for testing were the desire to be tested (n = 280; 54%) and convenience of location (n = 146; 28%). Those motivated by an incentive to test (n = 110; 21%) were 5.83 times as likely to state they would not test again without an incentive, compared to those with other reasons for testing (95% CI: 2.67-12.72, P < .001). CRITICAL LIMITATIONS: No comparative study group. CONCLUSION: Results indicate internal motivation and convenience were prominent factors supporting testing uptake. Incentives may increase community testing participation, particularly among people who have never tested. Keywords COVID-19, pandemic, incentives, health behavior, community testing.


Assuntos
COVID-19 , Motivação , Adulto , Humanos , Maryland , Teste para COVID-19 , Estudos Transversais , COVID-19/diagnóstico
9.
Paediatr Anaesth ; 33(3): 193-200, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36052662

RESUMO

BACKGROUND: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy has shown to improve survival in patients with extensive or refractory abdominal tumors of many different histologies. Postoperative pain control can be challenging as the surgical procedure is performed through a midline laparotomy incision from xiphoid to symphysis pubis, and patients are usually nothing by mouth for the first 8-10 postoperative days. AIMS: We present the anesthetic management and postoperative pain control strategies for cytoreductive surgery with hyperthermic intraperitoneal chemotherapy using a multimodal, opioid-sparing, and total intravenous anesthetic technique with a tunneled thoracic epidural. METHODS: A single institution retrospective review of anesthetic management, intraoperative fluid and blood administration, and postoperative pain control for pediatric patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy between July 2018 and December 2020 was conducted. We employed a novel anesthetic and analgesia protocol consisting of premedication with gabapentin followed by intraoperative infusions of propofol, dexmedetomidine, ketamine, and cisatracurium. A tunneled thoracic epidural catheter was placed for management of pain. RESULTS: We reviewed and analyzed the first 25 patient records. The most common diagnosis was desmoplastic small round cell tumor (n = 12). Median age of patients was 14 years (range 21 months-22 years). All patients were extubated in the operating room and no patients required reintubation. There were no incidences of acute kidney injury. Epidural infusions were used for a median of 8 days (range 2-14 days). Median postoperative intravenous opioid use (morphine equivalent) through postoperative day 10 was 0.02 mg/kg/day (range 0-0.86 mg/kg/day) administered for a median of 2 days (range 0-17 days). Nine patients (36%) did not require any intravenous opioids in the postoperative period. CONCLUSIONS: Utilizing a multimodal, opioid-sparing, total intravenous anesthetic technique in conjunction with a tunneled thoracic epidural catheter, we were able to avoid the need for postoperative mechanical ventilation and minimize both intraoperative and postoperative opioid requirements.


Assuntos
Analgesia Epidural , Anestesia , Anestésicos , Hipertermia Induzida , Criança , Humanos , Lactente , Analgesia Epidural/métodos , Analgésicos Opioides/uso terapêutico , Anestésicos/uso terapêutico , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução/métodos , Quimioterapia Intraperitoneal Hipertérmica , Manejo da Dor/métodos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Estudos Retrospectivos , Pré-Escolar , Adolescente , Adulto Jovem
10.
Sci Adv ; 8(46): eabq3925, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36383648

RESUMO

Direct links between carbonaceous chondrites and their parent bodies in the solar system are rare. The Winchcombe meteorite is the most accurately recorded carbonaceous chondrite fall. Its pre-atmospheric orbit and cosmic-ray exposure age confirm that it arrived on Earth shortly after ejection from a primitive asteroid. Recovered only hours after falling, the composition of the Winchcombe meteorite is largely unmodified by the terrestrial environment. It contains abundant hydrated silicates formed during fluid-rock reactions, and carbon- and nitrogen-bearing organic matter including soluble protein amino acids. The near-pristine hydrogen isotopic composition of the Winchcombe meteorite is comparable to the terrestrial hydrosphere, providing further evidence that volatile-rich carbonaceous asteroids played an important role in the origin of Earth's water.

11.
Aging Dis ; 13(5): 1523-1531, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36186125

RESUMO

To measure the association between intravenous administration of monoclonal antibody bamlanivimab (LY-CoV555) to long-term care facility (LTCF) residents recently diagnosed with pre-symptomatic, mild-to-moderate COVID-19 and are considered high risk for disease progression with mortality, hospitalization, and adverse effects. A retrospective analysis of LTCF residents with confirmed COVID-19, pre-symptomatic, mild to moderate disease, who were treated with bamlanivimab (LY-CoV555) were compared to similar LTCF residents who did not receive monoclonal antibody treatment. Dependent variables investigated included mortality and hospitalization as primary outcomes with adverse effects as the secondary outcome. A total of 107 residents from three LTCFs were diagnosed with pre-symptomatic, mild-to-moderate COVID-19 between November 1, 2020, and December 31, 2020. Of the 107 study participants, 44 residents provided consent to treatment, of which 39 received a single intravenous infusion of neutralizing monoclonal antibody, bamlanivimab 700mg, early in the disease, and 5 received an incomplete dose. Of the 39 residents who received the full dose of bamlanivimab, 5 (12.8%) were admitted to the hospital and 4 (10.3%) died. Conversely, of the 63 residents who did not receive the monoclonal antibody, 26 (41.3 %) were admitted to the hospital and 18 (28.6%) died. Relative risk for hospitalization and death were statistically significantly lower for those residents who received the full bamlanivimab treatment. No serious adverse effects were documented on any patient. Intravenous administration of monoclonal antibody bamlanivimab (LY-CoV555) to LTCF residents recently diagnosed with pre-symptomatic, mild to moderate COVID-19 was significantly associated with reduced mortality and hospitalization. The monoclonal antibody was well-tolerated.

12.
ACS Chem Biol ; 17(5): 1239-1248, 2022 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-35467845

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) is a major threat to human health, as the US mortality rate outweighs those from HIV, tuberculosis, and viral hepatitis combined. In the wake of the COVID-19 pandemic, antibiotic-resistant bacterial infections acquired during hospital stays have increased. Antibiotic adjuvants are a key strategy to combat these bacteria. We have evaluated several small molecule antibiotic adjuvants that have strong potentiation with ß-lactam antibiotics and are likely inhibiting a master regulatory kinase, Stk1. Here, we investigated how the lead adjuvant (compound 8) exerts its effects in a more comprehensive manner. We hypothesized that the expression levels of key resistance genes would decrease once cotreated with oxacillin and the adjuvant. Furthermore, bioinformatic analyses would reveal biochemical pathways enriched in differentially expressed genes. RNA-seq analysis showed 176 and 233 genes significantly up- and downregulated, respectively, in response to cotreatment. Gene ontology categories and biochemical pathways that were significantly enriched with downregulated genes involved carbohydrate utilization, such as the citrate cycle and the phosphotransferase system. One of the most populated pathways was S. aureus infection. Results from an interaction network constructed with affected gene products supported the hypothesis that Stk1 is a target of compound 8. This study revealed a dramatic impact of our lead adjuvant on the transcriptome that is consistent with a pleiotropic effect due to Stk1 inhibition. These results point to this antibiotic adjuvant having potential broad therapeutic use in combatting MRSA.


Assuntos
COVID-19 , Staphylococcus aureus Resistente à Meticilina , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Proteínas de Bactérias/metabolismo , Carbazóis/farmacologia , Humanos , Staphylococcus aureus Resistente à Meticilina/genética , Testes de Sensibilidade Microbiana , Pandemias , Staphylococcus aureus , Transcriptoma
13.
ACS Med Chem Lett ; 13(3): 483-491, 2022 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-35295086

RESUMO

Antibiotic-resistant infections are a pressing global concern, causing millions of deaths each year. Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of nosocomial infections in healthcare settings and is increasingly responsible for community-acquired infections that are often more difficult to treat. Antibiotic adjuvants are small molecules that potentiate antibiotics through nontoxic mechanisms and show excellent promise as novel therapeutics. Screening of low-molecular-weight compounds was employed to identify novel antibiotic adjuvant scaffolds for further elaboration. Brominated carbazoles emerged from this screening as lead compounds for further evaluation. Lead carbazoles were able to potentiate several ß-lactam antibiotics in three medically relevant strains of MRSA. Gene expression studies determined that these carbazoles were dampening the transcription of key genes that modulate ß-lactam resistance in MRSA. The lead brominated carbazoles represent novel scaffolds for elaboration as antibiotic adjuvants.

14.
Nurs Forum ; 57(4): 694-702, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35187672

RESUMO

INTRODUCTION: Nurse well-being is at the forefront of nursing leadership's focus, particularly with the impact of the ongoing COVID-19 pandemic. Nurse managers, as authentic leaders, should understand their role in supporting the spectrum of nurse well-being. At the negative end of well-being, leaders must address staff burnout as it increases nurse turnover, shortage of nurses, and poor patient outcomes. PURPOSE: The specific aim for this quality improvement (QI) project was to implement a program that could guide a nurse manager of a single inpatient unit on how to improve well-being in their nursing staff as measured by: (a) improved well-being scores to a composite score of 3.5 or greater as indicated by follow-up Culture Pulse surveys distributed in 2021; and (b) reduced absenteeism among nursing staff by 18%. RESULTS: Five surveys identical to the organization's work culture survey, that measures well-being, were sent to staff each month starting in January 2021 and ending in May 2021. The average composite score from all five surveys was 2.8, indicating an overall improvement. Absenteeism was reduced during implementation by 39%. DISCUSSION: This QI project guides nurse managers in the evidence-based interventions that can promote well-being in their staff.


Assuntos
COVID-19 , Enfermeiros Administradores , Recursos Humanos de Enfermagem Hospitalar , Humanos , Satisfação no Emprego , Liderança , Pandemias , Melhoria de Qualidade
15.
Ear Hear ; 43(5): 1515-1525, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35075042

RESUMO

OBJECTIVE: The purpose of this study was to provide empirical data describing the relationship between behavioral responses to dynamic visual motion in adults with chronic dizziness symptoms with and without clinically identifiable peripheral vestibular impairment. DESIGN: Prospective, quasi-experimental study including individuals with chronic dizziness symptoms with identified unilateral peripheral vestibular impairment (n=27), and individuals with chronic dizziness symptoms without identified vestibular impairment (n=26). We measured (a) visual perception of verticality in a dynamic background, (b) postural displacement in a dynamic background, (c) eye movement behaviors in various visual contexts, and (d) self-rating degree of anxiety. RESULTS: Status of peripheral vestibular function was not a significant predictor of behavioral responses to visual motion. The data show that the ability to fixate on a visual target was predictive of postural control in a dynamic visual background. Trial-to-trial variability in verticality responses and degree of self-rated anxiety were also associated with postural control. CONCLUSIONS: Apart from vestibular function, oculomotor control is important for maintaining control of whole-body motor responses during exposure to a dynamic visual stimulus. Vertical perception precision-not accuracy-may be more important for understanding real-world consequences of visual motion sensitivity. Traditional diagnostic evaluations focusing exclusively on characterizing the peripheral vestibular system may not provide insight into the behaviors associated with visual motion sensitivity.


Assuntos
Tontura , Doenças Vestibulares , Adulto , Tontura/diagnóstico , Movimentos Oculares , Humanos , Equilíbrio Postural/fisiologia , Estudos Prospectivos , Doenças Vestibulares/diagnóstico
16.
Organometallics ; 40(16): 2844-2851, 2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34483434

RESUMO

We report a variety of rhenium complexes supported by bidentate and tridentate phosphinoamine ligands and their use in the formation of the advanced biofuel isobutanol from methanol and ethanol. Rhenium pincer complexes 1-3 are effective catalysts for this process, with 2 giving isobutanol in 35% yields, with 97% selectivity in the liquid fraction, over 16 h with catalyst loadings as low as 0.07 mol %. However, these catalysts show poorer overall selectivity, with the formation of a significant amount of carboxylate salt solid byproduct also being observed. Production of the active catalyst 1d has been followed by 31P NMR spectroscopy, and the importance of the presence of base and elevated temperatures to catalyst activation has been established. Complexes supported by diphosphine ligands are inactive for Guerbet chemistry; however, complexes supported by bidentate phosphinoamine ligands show greater selectivity for isobutanol formation over carboxylate salts. The novel complex 7 was able to produce isobutanol in 28% yield over 17 h. The importance of the N-H moiety to the catalytic performance has also been established, giving further weight to the hypothesis that these catalysts operate via a cooperative mechanism.

17.
Chem Biol Drug Des ; 98(6): 1038-1064, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34581492

RESUMO

Antibiotic resistance is a global and pressing concern. Our current therapeutic arsenal is increasingly limited as bacteria are developing resistance at a rate that far outpaces our ability to create new treatments. Novel approaches to treating and curing bacterial infections are urgently needed. Bacterial kinases have been increasingly explored as novel drug targets and are poised for development into novel therapeutic agents to combat bacterial infections. This review describes several general classes of bacterial kinases that play important roles in bacterial growth, antibiotic resistance, and biofilm formation. General features of these kinase classes are discussed and areas of particular interest for the development of inhibitors will be highlighted. Small molecule kinase inhibitors are described and organized by phenotypic effect, spotlighting particularly interesting inhibitors with novel functions and potential therapeutic benefit. Finally, we provide our perspective on the future of bacterial kinase inhibition as a viable strategy to combat bacterial infections and overcome the pressures of increasing antibiotic resistance.


Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Proteínas de Bactérias/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Infecções Bacterianas/tratamento farmacológico , Biofilmes/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Histidina Quinase/antagonistas & inibidores , Histidina Quinase/metabolismo , Humanos , Inibidores de Proteínas Quinases/química , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia
18.
Geochim Cosmochim Acta ; 303: 66-91, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34531614

RESUMO

Determining compositional trends among individual minerals is key to understanding the thermodynamic conditions under which they formed and altered, and is also essential to maximizing the scientific value of small extraterrestrial samples, including returned samples and meteorites. Here we report the chemical compositions of Fe-sulfides, focusing on the pyrrhotite-group sulfides, which are ubiquitous in chondrites and are sensitive indicators of formation and alteration conditions in the protoplanetary disk and in small Solar System bodies. Our data show that while there are trends with the at.% Fe/S ratio of pyrrhotite with thermal and aqueous alteration in some meteorite groups, there is a universal trend between the Fe/S ratio and degree of oxidation. Relatively reducing conditions led to the formation of troilite during: (1) chondrule formation in the protoplanetary disk (i.e., pristine chondrites) and (2) parent body thermal alteration (i.e., LL4 to LL6, CR1, CM, and CY chondrites). Oxidizing and sulfidizing conditions led to the formation of Fe-depleted pyrrhotite with low Fe/S ratios during: (1) aqueous alteration (i.e., CM and CI chondrites), and (2) thermal alteration (i.e., CK and R chondrites). The presence of troilite in highly aqueously altered carbonaceous chondrites (e.g., CY, CR1, and some CM chondrites) indicates they were heated after aqueous alteration. The presence of troilite, Fe-depleted pyrrhotite, or pyrite in a chondrite can provide an estimate of the oxygen and sulfur fugacities at which it was formed or altered. The data reported here can be used to estimate the oxygen fugacity of formation and potentially the aqueous and/or thermal histories of sulfides in extraterrestrial samples, including those returned by the Hayabusa2 mission and due to be returned by the OSIRIS-REx mission in the near future.

19.
Otolaryngol Clin North Am ; 54(5): 949-958, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34294433

RESUMO

Vestibular migraine (VM) is one of the most common neurologic causes of vertigo. Symptoms and International Classification of Headache Disorders criteria are used to diagnose VM because no objective tests, imaging or audiologic, have been shown to reliably diagnose this condition. Central auditory, peripheral, and central vestibular pathway involvement has been associated with VM. Although the interaction between migraine and other vestibular disorders can be a challenging scenario for diagnosis and treatment, there are data to show that vestibular rehabilitation and a variety of pharmacologic agents improve reported symptoms and vertigo frequency.


Assuntos
Transtornos de Enxaqueca , Doenças Vestibulares , Humanos , Transtornos de Enxaqueca/diagnóstico , Transtornos de Enxaqueca/epidemiologia , Vertigem/diagnóstico , Vertigem/epidemiologia , Vertigem/etiologia , Doenças Vestibulares/diagnóstico , Doenças Vestibulares/epidemiologia , Doenças Vestibulares/terapia
20.
Sr Care Pharm ; 36(4): 217-222, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33766194

RESUMO

OBJECTIVE: To evaluate the impact of pharmacy interventions on recurrence of falls in older people. DESIGN: Prospective case-crossover study. SETTING: LECOM Health Nursing and Rehabilitation (LNR) and Senior Living Center (SLC) and Millcreek Community Hospital older adult behavioral health and inpatient rehabilitation units (IRU). PARTICIPANTS: Twenty and 15 residents of the SLC and LNR, respectively, and 5 and 2 patients of the older adult behavioral health unit and IRU, respectively, experienced a fall during the 8-week study period. INTERVENTIONS: Medication reviews were conducted by a pharmacist assessing for fall risk-increasing drugs (FRIDs). Adverse effects, drug interactions, and nonpharmacologic causes were evaluated, and recommendations were made to reduce future fall risk. MAIN OUTCOME MEASURES: Recommendation acceptance rate, FRID use, and incidence of recurrent falls. RESULTS: Eighty percent of fall risk-reduction recommendations were accepted and implemented by the medical team. The mean number of potential FRIDs prescribed per participant was reduced from 3.71 to 3.38. There was a 12.4% reduction in recurrent falls after pharmacy intervention (P = 0.0336; odds ratio [95% confidence interval] = 1.783 [1.045-3.112]). CONCLUSION: Pharmacist interventions for older people who experience a fall were associated with a high acceptance rate by health care providers, a reduction in FRID use, and decreased rate of recurrent falls.


Assuntos
Acidentes por Quedas/prevenção & controle , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Conduta do Tratamento Medicamentoso/organização & administração , Farmacêuticos/psicologia , Avaliação de Programas e Projetos de Saúde , Estudantes de Farmácia/psicologia , Acidentes por Quedas/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Cross-Over , Feminino , Humanos , Masculino , Farmácia , Estudos Prospectivos
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