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Equitable social determinants of health (SDOH) screening has been recommended by the Centers for Medicare & Medicaid Services and the Joint Commission; however, little is known about Spanish-speaking caregiver preferences on how they would like to be screened. We conducted a cross-sectional study at 3 pediatric clinics (October-December 2019). Caregivers completed (in English or Spanish) an SDOH screening preferences survey. Three hundred eighty-two of 443 caregivers approached (response rate = 86.2%) completed the survey. Most were female, preferred Spanish, and completed only high school. Spanish-speaking caregivers had greater odds of preferring verbal SDOH screening (odds ratio: 4.1; 95% confidence interval, 1.8-9.2) than English-speaking caregivers. Verbal SDOH screening should be a consideration in families who speak Spanish. Future studies should utilize qualitative methods to further explore Spanish-speaking caregiver preferences for SDOH screening.
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Cuidadores , Hispânico ou Latino , Programas de Rastreamento , Determinantes Sociais da Saúde , Humanos , Feminino , Masculino , Cuidadores/psicologia , Cuidadores/estatística & dados numéricos , Determinantes Sociais da Saúde/estatística & dados numéricos , Estudos Transversais , Inquéritos e Questionários , Programas de Rastreamento/estatística & dados numéricos , Programas de Rastreamento/métodos , Programas de Rastreamento/psicologia , Hispânico ou Latino/estatística & dados numéricos , Hispânico ou Latino/psicologia , Adulto , Pessoa de Meia-IdadeRESUMO
The limited number and diversity of resident physicians pursuing careers as physician-scientists in medicine has been a concern for many decades. The Anesthesia Research Council aimed to address the status of the anesthesiology physician-scientist pipeline, benchmarked against other medical specialties, and to develop strategic recommendations to sustain and expand the number and diversity of anesthesiology physician-scientists. The working group analyzed data from the Association of American Medical Colleges and the National Resident Matching Program to characterize the diversity and number of research-oriented residents from US and international allopathic medical schools entering 11 medical specialties from 2009 to 2019. Two surveys were developed to assess the research culture of anesthesiology departments. National Institutes of Health (NIH) funding information awarded to anesthesiology physician-scientists and departments was collected from NIH RePORTER and the Blue Ridge Medical Institute. Anesthesiology ranked eighth to tenth place of 11 medical specialties in the percent of "research-oriented" entering residents, defined as those with advanced degrees (Master's or PhDs) in addition to the MD degree or having published at least 3 research publications before residency. Anesthesiology ranked eighth of 11 specialties in the percent of entering residents who were women but ranked fourth of 11 specialties in the percent of entering residents who self-identified as belonging to an underrepresented group in medicine. There has been a 72% increase in both the total NIH funding awarded to anesthesiology departments and the number of NIH K-series mentored training grants (eg, K08 and K23) awarded to anesthesiology physician-scientists between 2015 and 2020. Recommendations for expanding the size and diversity of the anesthesiology physician-scientist pipeline included (1) developing strategies to increase the number of research intensive anesthesiology departments; (2) unifying the diverse programs among academic anesthesiology foundations and societies that seek to grow research in the specialty; (3) adjusting American Society of Anesthesiologists metrics of success to include the number of anesthesiology physician-scientists with extramural research support; (4) increasing the number of mentored awards from Foundation of Anesthesia Education and Research (FAER) and International Anesthesia Research Society (IARS); (5) supporting an organized and concerted effort to inform research-oriented medical students of the diverse research opportunities within anesthesiology should include the specialty being represented at the annual meetings of Medical Scientist Training Program (MSTP) students and the American Physician Scientist Association, as well as in institutional MSTP programs. The medical specialty of anesthesiology is defined by new discoveries and contributions to perioperative medicine which will only be sustained by a robust pipeline of anesthesiology physician-scientists.
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Anestesia , Anestesiologia , Distinções e Prêmios , Médicos , Estados Unidos , Feminino , Humanos , Masculino , BenchmarkingRESUMO
The implementation of chlorine disinfection in low-income countries reduces the risk of waterborne illness but initiates exposure to disinfection byproducts (DBPs). Like high-income countries, low-income countries typically are adopting regulations focusing on trihalomethanes (THM4) as an indicator of overall DBP exposure. However, the use of impaired water sources can decouple the formation of THM4 from other DBP classes that are more potent toxins. The documentation of DBP species other than THM4 is rare in low-income countries, where water sources may be degraded by inadequate sanitation infrastructure and other uncontrolled wastewater discharges. We measured THM4 and 21 unregulated DBPs in tap waters and laboratory-treated source waters from two cities in northwestern India. The contribution of each DBP class to the cumulative toxicity was estimated by weighting each species by metrics of toxic potency; haloacetonitriles typically were the dominant contributor, while the contribution of THM4 was negligible. THM4 concentrations did not correlate with the total toxic potency-weighted DBP concentrations. Although THM4 rarely exceeded international guidelines, DBPs of greater toxicological concern were observed in high concentrations. The total toxic potency-weighted DBP concentrations in some waters were elevated compared to conventional drinking waters in high-income countries and more closely resembled chlorine-disinfected wastewater effluents. Artificial sweeteners confirmed widespread contamination of both surface and groundwaters by domestic sewage. The results suggest that THM4 may not be an adequate indicator of overall DBP exposure in impaired water supplies prevalent in some low-income nations.
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Desinfetantes , Poluentes Químicos da Água , Purificação da Água , Desinfecção , Halogenação , Índia , TrialometanosRESUMO
Aicardi syndrome (AS) is a rare neurodevelopmental disorder, predominantly seen in female individuals, which appears to have an increased risk of both benign and malignant neoplasia. We report the case of a child with AS who presented with metastatic malignant sacrococcygeal tumor (with yolk sac elements) which recurred and then was treated with 3 cycles of high-dose chemotherapy with autologous stem cell rescue. The patient tolerated therapy with acceptable toxicity and remains in clinical remission 3 months after the completion of therapy. Her neurological status remains similar to that before diagnosis with the exception of chemotherapy induced hearing loss. This is the first description a sacrococcygeal teratoma in a patient with Aicardi, as well as the first use of intensified consolidation chemotherapy in a patient with Aicardi, which was well tolerated and resulted in remission. The use of chemotherapy should be considered for all patients with AS and malignancy.
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Síndrome de Aicardi/complicações , Região Sacrococcígea , Teratoma/terapia , Pré-Escolar , Quimioterapia de Consolidação/métodos , Feminino , Humanos , Indução de Remissão/métodos , Teratoma/etiologiaRESUMO
OBJECTIVE: Children of caregivers with limited health literacy are at risk of poorer health outcomes. Thus, health literacy-informed communication tools are critical to achieving a more equitable health system. However, there is no agreement on the health literacy skills pediatric residents should attain. We used Delphi methodology to establish consensus on health literacy objectives to inform development of a pediatric resident curriculum. METHODS: Our Delphi panel participated in three rounds of anonymous surveys to rank the importance of health literacy objectives in pediatric resident education. Consensus was defined as ≥70% of panelists identifying an objective as essential or 100% agreeing an objective was recommended or essential. RESULTS: Thirteen pediatric health literacy experts comprised a racially, geographically, and professionally-diverse panel. After three survey rounds, 27 of the initial 65 objectives met consensus. All final objectives aligned with Accreditation Council for Graduate Medical Education (ACGME) core competencies. CONCLUSIONS: A panel of pediatric health literacy experts established consensus on health literacy objectives specific to pediatric resident training. These prioritized objectives align with ACGME core competencies, as well as evidence-based strategies like teach-back, and newer considerations like addressing organizational health literacy. They should inform future health literacy curricula and assessment within pediatric residency programs.
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Patients referred by their general practitioner (GP) with a definite diagnosis, for example, recurrent sore throat for consideration of tonsillectomy in adults, may wait for months without receiving any further clinical information from the hospital until their outpatient consultation. Prompt provision of condition-specific information after referral has received little attention despite considerable potential to enhance patients' understanding, thereby relieving uncertainty and anxiety, and facilitating shared decision-making.This study aimed to report the experience of patients with recurrent tonsillitis who had been sent a booklet outlining the benefits and risks of tonsillectomy immediately after GP referral.Greater Glasgow and Clyde Health Board received 218 referrals of patients aged 16-40 to discuss tonsillectomy between January and August 2022. Every patient was sent a 16-page booklet by post and given the choice to opt in for a consultation.165 (76%) patients opted in, and 53 (24%) did not. Feedback was obtained from 143 patients (66%) from both groups. 99% found the information booklet easy to understand, 97% would recommend it to a friend with recurrent tonsillitis, 93% felt their questions had been answered and 92% believed it helped them to decide whether to proceed with tonsillectomy. Socioeconomic deprivation did not influence the outcome.In conclusion, most patients found provision of clinical information immediately after vetting of the referral to be beneficial, irrespective of whether they opted in for a consultation. This concept has broad applicability across all specialties, and the principles can be readily adopted and adapted by clinicians and managers in local units.
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Encaminhamento e Consulta , Tonsilectomia , Humanos , Tonsilectomia/métodos , Encaminhamento e Consulta/estatística & dados numéricos , Encaminhamento e Consulta/normas , Adulto , Feminino , Masculino , Adolescente , Tonsilite/cirurgia , Satisfação do Paciente/estatística & dados numéricos , Adulto Jovem , Inquéritos e QuestionáriosRESUMO
AIM: The aim of the study was to assess the suitability of an online education package to prepare health professionals to use a new paediatric early warning system. DESIGN: Quasi-experimental mixed methods using co-production. METHODS: Participants completed the Package and participated in up to four clinical scenarios. Data were collected using self-report surveys, and during clinical scenarios; escalation of care, documentation, family involvement, communication handovers were assessed, and recorded debriefings were thematically analysed. Data were integrated using tabulated joint displays. RESULTS: Eleven nurses and three doctors were recruited from three mixed adult and paediatric hospitals. Following completion of the Package and clinical scenarios 13/14 (93%) participants agreed preparedness and confidence to use the ESCALATION System had increased. For 53% handovers, the communication framework was followed, for 79% charts, documentation was complete. Participants engaged with the parent (actor) for 97% scenario interactions. The Package was effective and participation in clinical scenarios appeared to enhance learning. PATIENT OR PUBLIC CONTRIBUTION: Consumers participated in the steering group overseeing the study and in the expert panel who reviewed the education package and clinical scenarios.
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Pessoal de Saúde , Médicos , Adulto , Humanos , Criança , Aprendizagem , Simulação de Paciente , Pesquisa EmpíricaRESUMO
NBU1 is a mobilizable transposon found in Bacteroides spp. Mobilizable transposons require gene products from coresident conjugative transposons for excision and transfer to recipient cells. The integration of NBU1 requires IntN1, which has been identified as a tyrosine recombinase, as well as Bacteroides host factor BHFa. Excision of NBU1 is a more complicated process, involving five element-encoded proteins (IntN1, Orf2, Orf2x, Orf3, and PrmN1) as well as a Bacteroides host factor and a cis-acting DNA sequence. Little has been known about what role the proteins play in excision, although IntN1 and Orf2x have been shown to be the only proteins absolutely required for detectable excision. To determine where IntN1 and Orf2x bind during the excision of NBU1, both proteins were partially purified and tested in DNase I footprinting experiments with the excisive attachment sites attL and attR. The results demonstrate that IntN1 binds to four core-type sites that flank the region of cleavage and strand exchange, as well as six arm-type sites. A unique feature of the system is the location of DR2a and DR2b arm-type sites immediately downstream of the attL core. The DR1a, DR1b, DR3a, and DR3b arm-type sites were shown to be required for in vitro integration of NBU1. In addition, we have identified one Orf2x binding site (O1) on attL as well as a dA+dT-rich upstream element that is required for Orf2x interactions with O1.
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Sítios de Ligação Microbiológicos , Bacteroides/enzimologia , Bacteroides/genética , Elementos de DNA Transponíveis , Integrases/metabolismo , Recombinação Genética , Sítios de Ligação , Pegada de DNA , DNA Bacteriano/metabolismo , Ligação ProteicaRESUMO
Introduction: COVID-19 accelerated the use of telemedicine. Subsequently, clinical sites began conducting virtual visits. Academic institutions implemented telemedicine for patient care and simultaneously had to teach residents the logistics and best practices. To meet this need, we developed a training session for faculty focused on telemedicine best practices and teaching telemedicine in the pediatric realm. Methods: We designed this training session based on institutional and society guidelines and faculty experience with telemedicine. Objectives included telemedicine documentation, triage, counseling, and ethical issues in telemedicine. We conducted all sessions in a 60-minute or 90-minute format over a virtual platform for small and large groups using case scenarios with photos, videos, and interactive questions. A novel mnemonic ABLES (awake-background-lighting-exposure-sound) was created to guide providers during the virtual exam. Following the session, participants completed a survey evaluating content and presenter effectiveness. Results: We presented the training sessions between May 2020 and August 2021 to 120 participants. Participants included pediatric fellows and faculty, reaching 75 participants locally and 45 nationally (at Pediatric Academic Society and Association of Pediatric Program Directors meetings). Sixty evaluations (response rate: 50%) showed favorable results for general satisfaction and content. Discussion: This telemedicine training session was well received by pediatric providers and addressed the need for training faculty to teach telemedicine. Future directions include adapting the training session for medical students and developing a longitudinal curriculum that applies telehealth skills learned with patients in real time.
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COVID-19 , Internato e Residência , Telemedicina , Humanos , Criança , COVID-19/epidemiologia , Currículo , DocentesRESUMO
BACKGROUND: Previous studies have indicated that, in patients with multiple myeloma (MM), bortezomib is associated with an increased incidence of herpes zoster, resulting from reactivation of latent varicella zoster virus (VZV). OBJECTIVE: Our objective was to determine whether increased risk of VZV reactivation could be abrogated by using prophylactic acyclovir. METHODS: We retrospectively evaluated 100 consecutive MM patients treated with bortezomib-based therapies at the Roswell Park Cancer Institute for development of herpes zoster. Frontline and relapsed/refractory patients were included, and patients received bortezomib alone or in combination with agents such as doxorubicin, melphalan, or dexamethasone. All patients received >4 weeks of acyclovir prophylaxis (400 mg twice daily), which was initiated prior to starting treatment with bortezomib and discontinued 4 weeks following bortezomib. RESULTS: Median patient age was 62 years, 57% were male, and most (56%) had Durie-Salmon stage IIIA MM. None of the 100 MM patients receiving acyclovir prophylaxis developed herpes zoster during treatment with bortezomib, irrespective of patients receiving a wide variety of concomitant antimyeloma therapies and regardless of response to bortezomib-based therapy. One additional patient, found to be noncompliant with acyclovir therapy, experienced VZV reactivation, having received 3 cycles of bortezomib (3 weeks each cycle) in combination with cyclophosphamide and dexamethasone. LIMITATIONS: Limitations of the study include its small size and retrospective nature. CONCLUSIONS: The increased risk of VZV reactivation observed in previous studies of bortezomib-based therapy was completely abrogated in this series of patients who received prophylaxis with acyclovir.
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Aciclovir/uso terapêutico , Antineoplásicos/efeitos adversos , Antivirais/uso terapêutico , Ácidos Borônicos/efeitos adversos , Herpesvirus Humano 3/efeitos dos fármacos , Mieloma Múltiplo/tratamento farmacológico , Pirazinas/efeitos adversos , Ativação Viral/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Bortezomib , Feminino , Herpesvirus Humano 3/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/virologia , Estudos RetrospectivosRESUMO
Novel agents have provided a new foundation for multiple myeloma therapies. When combined with other anti-myeloma agents, these compounds significantly enhance clinical efficacy. High-dose steroids are frequently used in anti-myeloma combination regimens; however, the doses employed are often poorly tolerated, especially in patients with concurrent comorbid conditions. We hypothesized that a steroid-independent combination regimen could be developed without significant compromise of efficacy. The availability of such a regimen will be important for patients whose concurrent ailments make them poor candidates for steroid containing anti-myeloma regimens. A phase II single institute, non-randomized clinical trial was conducted to investigate a novel steroid-free three-drug combination of bortezomib (V), pegylated liposomal doxorubicin (D), and thalidomide (T), the VDT regimen. Forty-three newly diagnosed multiple myeloma patients requiring treatment were enrolled on this study. The overall response rate and complete response (CR) + near complete response (nCR) rate was 78% and 35%, respectively. Median time to progression was 29·5 months. Fatigue, rash, neuropathy, constipation and infections were the most common side effects. We concluded that VDT is a tolerable and an effective regimen capable of inducing high response rates and can be employed in patients considered to be poor candidates for steroid-based treatment regimens.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ácidos Borônicos/administração & dosagem , Ácidos Borônicos/efeitos adversos , Bortezomib , Progressão da Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Glucocorticoides/administração & dosagem , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Estadiamento de Neoplasias , Pirazinas/administração & dosagem , Pirazinas/efeitos adversos , Talidomida/administração & dosagem , Talidomida/efeitos adversos , Resultado do TratamentoRESUMO
INTRODUCTION: Learning effective communication, particularly jargon avoidance, is important for medical training. Standardized methods exist to identify jargon but there is room to further refine those methods to define medical jargon and expand categorization. This project aims to classify jargon words as having a plain language alternative or not, to both standardize the definition of jargon and as a foundation for teaching jargon avoidance. METHODS: We analyzed 123 transcribed encounters between standardized patients and medical students to quantify and categorize medical jargon using a stepwise process based on published literature. This process eliminated common words (based on New Dale-Chall list) without distinct medical meaning. Uncommon words and words with distinct medical meanings found in Stedman's Medical Dictionary were considered jargon. Jargon words were cross-referenced with the Plain Language Thesaurus to identify plain language alternatives. RESULTS: This process identified 310 jargon words, 102 with plain language alternative from the 123 encounters. CONCLUSION: We objectively classified jargon into distinct categories with a novel focus on jargon words with and without plain language alternatives. PRACTICE IMPLICATIONS: This objective classification system serves as an important step in gaining a comprehensive understanding of jargon use which is essential to improving and teaching communication skills.
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Comunicação , Estudantes de Medicina , Humanos , Idioma , RegistrosRESUMO
IntDOT is a tyrosine recombinase encoded by the conjugative transposon CTnDOT. The core binding (CB) and catalytic (CAT) domains of IntDOT interact with core-type sites adjacent to the regions of strand exchange, while the N-terminal arm binding (N) domain interacts with arm-type sites distal to the core. Previous footprinting experiments identified five arm-type sites, but how the arm-type sites participate in the integration and excision of CTnDOT was not known. In vitro integration assays with substrates containing arm-type site mutants demonstrated that attDOT sequences containing mutations in the L1 arm-type site or in the R1 and R2 or R1 and R2' arm-type sites were dramatically defective in integration. Substrates containing mutations in the L1 and R1 arm-type sites showed a 10- to 20-fold decrease in detectable in vitro excision, but introduction of multiple arm-type site mutations in attR did not have an effect on the excision frequency. A sixth arm-type site, the R1' site, was also identified and shown to be required for integration and important for efficient excision. These results suggest that intramolecular IntDOT interactions are required for integration, while the actions of accessory factors are more important for excision. Gel shift assays performed in the presence of core- and arm-type site DNAs showed that IntDOT affinity for the attDOT core was enhanced when IntDOT was simultaneously bound to arm-type site DNA.
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Sítios de Ligação Microbiológicos , Bacteroides/enzimologia , DNA Bacteriano/genética , Integrases/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Regulação Bacteriana da Expressão Gênica/fisiologia , Integrases/genética , Mutação , Ligação Proteica , Recombinação GenéticaAssuntos
Anestesiologia , Escolha da Profissão , Médicas , Anestesiologia/educação , Anestesiologia/história , Anestesiologia/tendências , Atitude do Pessoal de Saúde , Educação Médica , Feminino , História do Século XX , História do Século XXI , Humanos , Liderança , Mentores , Médicas/história , Médicas/tendências , Preconceito , SexismoRESUMO
OBJECTIVE: To determine if use of a health literacy low-inference, self-assessment measure (LISAM), promoted behavior change as measured by increased use of health literacy communication skills (HLCS). METHODS: The LISAM is a tool used by educators to self-assess their performances after giving a lecture. The tool is low inference because it self-assesses behaviors that are specific, with little room for subjectivity. Forty-four third-year medical students self-assessed HLCS using a LISAM modified to include health literacy communication skills (LISAM-HLCS). Self-assessment followed participation in an audio recorded, standardized patient encounter and again after listening to the recording. Students also created 3 written goals for improvement. This session was repeated 1 week later. RESULTS: At Session 2, 71.4% of students met at least 2 of their 3 self-created objectives. The 3 most commonly created objectives were using teach-back, asking more open ended questions, and obtaining patient input into the management plan. Use of the LISAM increased HLCS use at Session 2 versus Session 1 as assessed by both students and study investigators (P < .05). CONCLUSIONS: Without faculty present, students met and adjusted objectives, catalyzing changes in HLCS. The LISAM-HLCS has the potential to empower students to improve communication skills and to reduce dependence on faculty observations.
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Letramento em Saúde , Estudantes de Medicina , Comunicação , Docentes , Humanos , Autoavaliação (Psicologia)RESUMO
Background: The American Academy of Pediatrics recommends that pediatricians address the social determinants of health (SDOH) through research, community partnership, and policy development. Objective: This study aimed to identify the unmet SDOH of the patients served by the Pasadena-Pediatric and Adolescent Health Center (PA-PAHC) and to understand provider perspectives on screening for SDOH. Methods: The PA-PAHC is a low-income pediatric clinic in southeast Houston. A cross-sectional survey eliciting potential SDOH concerns was administered to caregivers of children presenting for their well-child exam, along with pediatric residents and staff/faculty. Staff/faculty and residents were asked about their perceptions of SDOH screening. Statistical analysis calculated frequencies for categorical data and mean/median for continuous variables. Secondary data analysis consisted of chi-square test and logistic regression. Results: A total of 110 caregivers, 22 residents, and 21 staff/faculty participated in the study. Caregivers listed health care access the most frequently (15.5%), followed by childcare, school, and immigration status as SDOH concerns. Residents (31.8%) and staff/faculty (23.8%) also identified health care access as a concern. When comparing topic selection by survey role, there was no statistically significant difference among the 3 groups (P = .257). Residents were more likely to indicate that screening was more time-consuming than were faculty/staff (P = .004). Conclusion: Staff/faculty and residents agree that SDOH affect child health and screening is valuable in the patient encounter. There were no differences in the needs identified by the 3 groups. Further evaluation to assess caregiver perspectives on standardized SDOH screening versus obtaining routine social history needs to be undertaken.
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Cuidadores , Pediatria , Adolescente , Criança , Estudos Transversais , Humanos , Programas de Rastreamento , Determinantes Sociais da SaúdeRESUMO
The basis for memory loss in early Alzheimer's disease (AD) seems likely to involve synaptic damage caused by soluble Abeta-derived oligomers (ADDLs). ADDLs have been shown to build up in the brain and CSF of AD patients and are known to interfere with mechanisms of synaptic plasticity, acting as gain-of-function ligands that attach to synapses. Because of the correlation between AD dementia and synaptic degeneration, we investigated here the ability of ADDLs to affect synapse composition, structure, and abundance. Using highly differentiated cultures of hippocampal neurons, a preferred model for studies of synapse cell biology, we found that ADDLs bound to neurons with specificity, attaching to presumed excitatory pyramidal neurons but not GABAergic neurons. Fractionation of ADDLs bound to forebrain synaptosomes showed association with postsynaptic density complexes containing NMDA receptors, consistent with observed attachment of ADDLs to dendritic spines. During binding to hippocampal neurons, ADDLs promoted a rapid decrease in membrane expression of memory-related receptors (NMDA and EphB2). Continued exposure resulted in abnormal spine morphology, with induction of long thin spines reminiscent of the morphology found in mental retardation, deafferentation, and prionoses. Ultimately, ADDLs caused a significant decrease in spine density. Synaptic deterioration, which was accompanied by decreased levels of the spine cytoskeletal protein drebrin, was blocked by the Alzheimer's therapeutic drug Namenda. The observed disruption of dendritic spines links ADDLs to a major facet of AD pathology, providing strong evidence that ADDLs in AD brain cause neuropil damage believed to underlie dementia.