To assess the screening effectiveness of 3 new noncontact devices, the scanning peripheral anterior chamber depth analyzer (SPAC) (Takagi, Nagano, Japan), which measures peripheral anterior chamber ...depth (ACD); IOLMaster (Carl Zeiss Meditec, Jena, Germany), which measures central ACD; and Visante anterior segment optical coherence tomography (AS-OCT) (Visante, Carl Zeiss Meditec, Dublin, CA), which images the angles, and to compare these instruments with gonioscopy in identifying people with narrow angles (NAs).
Cross-sectional, observational, community-based study.
Phakic subjects aged >or=50 years without ophthalmic symptoms who were recruited from a community polyclinic in Singapore.
All subjects underwent examination with SPAC, IOLMaster, and AS-OCT in the dark by a single operator. Gonioscopy was performed by an ophthalmologist masked to the instruments' findings. The area under the curve (AUC) receiver operating characteristic (ROC) was generated to assess the performance of these tests in detecting people with a NA in either eye.
Eyes were classified as having NAs by gonioscopy if the posterior pigmented trabecular meshwork could be seen for <or=2 quadrants of the angle circumference with or without peripheral anterior synechiae.
A total of 2052 subjects were examined and underwent all 3 tests. The prevalence of a NA in at least 1 eye diagnosed by gonioscopy was 20.4% (422 subjects). The AUC for the SPAC using a numeric grade <5 as a cutoff was 0.83 (95% confidence interval CI, 0.82-0.85), with a sensitivity of 90.0% (95% CI, 86.8-92.7) and a specificity of 76.6% (95% CI, 74.4-78.6). The AUC for the IOLMaster at an ACD cutoff of <2.87 mm was 0.83 (95% CI, 0.81-0.85), with a sensitivity of 87.7% (95% CI, 84.2-90.7) and a specificity of 77.7% (95% CI, 75.6-79.7). The AUC for the AS-OCT was 0.76 (95% CI, 0.74-0.78), with a sensitivity of 88.4% (95% CI, 84.9-91.3) and a specificity of 62.9% (95% CI, 60.5-65.2).
The low specificity found with the SPAC, IOLMaster, and AS-OCT may limit the usefulness of these devices in screening for NAs.
IgG4-related disease is a newly recognized fibro-inflammatory condition characterized by several features: a tendency to form tumefactive lesions in multiple sites; a characteristic histopathological ...appearance; and—often but not always—elevated serum IgG4 concentrations. An international symposium on IgG4-related disease was held in Boston, MA, on 4–7 October 2011. The organizing committee comprising 35 IgG4-related disease experts from Japan, Korea, Hong Kong, the United Kingdom, Germany, Italy, Holland, Canada, and the United States, including the clinicians, pathologists, radiologists, and basic scientists. This group represents broad subspecialty expertise in pathology, rheumatology, gastroenterology, allergy, immunology, nephrology, pulmonary medicine, oncology, ophthalmology, and surgery. The histopathology of IgG4-related disease was a specific focus of the international symposium. The primary purpose of this statement is to provide practicing pathologists with a set of guidelines for the diagnosis of IgG4-related disease. The diagnosis of IgG4-related disease rests on the combined presence of the characteristic histopathological appearance and increased numbers of IgG4+ plasma cells. The critical histopathological features are a dense lymphoplasmacytic infiltrate, a storiform pattern of fibrosis, and obliterative phlebitis. We propose a terminology scheme for the diagnosis of IgG4-related disease that is based primarily on the morphological appearance on biopsy. Tissue IgG4 counts and IgG4:IgG ratios are secondary in importance. The guidelines proposed in this statement do not supplant careful clinicopathological correlation and sound clinical judgment. As the spectrum of this disease continues to expand, we advocate the use of strict criteria for accepting newly proposed entities or sites as components of the IgG4-related disease spectrum.
Abstract Background & Aims Histamine sensitizes the nociceptor TRPV1 and has been shown to contribute to visceral hypersensitivity in animals. We investigated the role of TRPV1 in irritable bowel ...syndrome (IBS) and evaluated if an antagonist of histamine receptor H1 (HRH1) could reduce symptoms of patients in a randomized placebo controlled trial. Methods Using live calcium imaging, we compared activation of submucosal neurons by the TRPV1 agonist capsaicin in rectal biopsies collected from 9 patients with IBS (ROME 3 critera) and 15 healthy subjects. Sensitization of TRPV1 by histamine, its metabolite imidazole acetaldehyde, and supernatants from biopsies was assessed by calcium imaging of mouse dorsal root ganglion neurons. We then performed a double-blind trial of patients with IBS (mean age, 31 years; range, 18–65 years; 34 female). After a 2 week run-in period, subjects were randomly assigned to groups given either the HRH1 antagonist ebastine (20 mg/day; n=28) or placebo (n=27) for 12 weeks. Rectal biopsies were collected, barostat studies were performed, and symptoms were assessed (using the validated gastrointestinal symptom rating scale) before and after the 12 week period. Patients were followed for an additional 2 weeks. Abdominal pain, symptom relief, and health-related quality of life were assessed on a weekly basis. The primary endpoint of the study was the effect of ebastine on the symptom score evoked by rectal distension. Results TRPV1 responses of submucosal neurons from patients with IBS were potentiated compared to those of healthy volunteers. Moreover, TRPV1 responses of submucosal neurons from healthy volunteers could be potentiated by their pre-incubation with histamine; this effect was blocked by the HRH1 antagonist pyrilamine. Supernatants from rectal biopsies from patients with IBS, but not from the healthy volunteers, sensitized TRPV1 in mouse nociceptive dorsal root ganglion neurons via HRH1; this effect could be reproduced by histamine and imidazole acetaldehyde. Compared to subjects given placebo, those given ebastine had reduced visceral hypersensitivity, increased symptom relief (ebastine 46% vs placebo 13%; P=.024) and reduced abdominal pain scores (ebastine 39±23 vs placebo 62±22, P=.0004). Conclusion In studies of rectal biopsies from patients, we found that HRH1-mediated sensitization of TRPV1 is involved in IBS. Ebastine, an antagonist of HRH1, reduced visceral hypersensitivity, symptoms, and abdominal pain in patients with IBS. Inihbitors of this pathway might be developed as a new treatment approach for IBS. ClinicalTrials.gov no: NCT01144832
We have provided an overview on the profound impact of COVID‐19 upon older people with Alzheimer's disease and other dementias and the challenges encountered in our management of dementia in ...different health‐care settings, including hospital, out‐patient, care homes, and the community during the COVID‐19 pandemic. We have also proposed a conceptual framework and practical suggestions for health‐care providers in tackling these challenges, which can also apply to the care of older people in general, with or without other neurological diseases, such as stroke or parkinsonism. We believe this review will provide strategic directions and set standards for health‐care leaders in dementia, including governmental bodies around the world in coordinating emergency response plans for protecting and caring for older people with dementia amid the COIVD‐19 outbreak, which is likely to continue at varying severity in different regions around the world in the medium term.
X-linked acrogigantism (X-LAG) is a new syndrome of pituitary gigantism, caused by microduplications on chromosome Xq26.3, encompassing the gene GPR101, which is highly upregulated in pituitary ...tumors. We conducted this study to explore the clinical, radiological, and hormonal phenotype and responses to therapy in patients with X-LAG syndrome. The study included 18 patients (13 sporadic) with X-LAG and microduplication of chromosome Xq26.3. All sporadic cases had unique duplications and the inheritance pattern in two families was dominant, with all Xq26.3 duplication carriers being affected. Patients began to grow rapidly as early as 2–3 months of age (median 12 months). At diagnosis (median delay 27 months), patients had a median height and weight standard deviation scores (SDS) of >+3.9 SDS. Apart from the increased overall body size, the children had acromegalic symptoms including acral enlargement and facial coarsening. More than a third of cases had increased appetite. Patients had marked hypersecretion of GH/IGF1 and usually prolactin, due to a pituitary macroadenoma or hyperplasia. Primary neurosurgical control was achieved with extensive anterior pituitary resection, but postoperative hypopituitarism was frequent. Control with somatostatin analogs was not readily achieved despite moderate to high levels of expression of somatostatin receptor subtype-2 in tumor tissue. Postoperative use of adjuvant pegvisomant resulted in control of IGF1 in all five cases where it was employed. X-LAG is a new infant-onset gigantism syndrome that has a severe clinical phenotype leading to challenging disease management.
Background
New Zealand's (NZ) complete absence of community transmission of influenza and respiratory syncytial virus (RSV) after May 2020, likely due to COVID‐19 elimination measures, provided a ...rare opportunity to assess the impact of border restrictions on common respiratory viral infections over the ensuing 2 years.
Methods
We collected the data from multiple surveillance systems, including hospital‐based severe acute respiratory infection surveillance, SHIVERS‐II, ‐III and ‐IV community cohorts for acute respiratory infection (ARI) surveillance, HealthStat sentinel general practice (GP) based influenza‐like illness surveillance and SHIVERS‐V sentinel GP‐based ARI surveillance, SHIVERS‐V traveller ARI surveillance and laboratory‐based surveillance. We described the data on influenza, RSV and other respiratory viral infections in NZ before, during and after various stages of the COVID related border restrictions.
Results
We observed that border closure to most people, and mandatory government‐managed isolation and quarantine on arrival for those allowed to enter, appeared to be effective in keeping influenza and RSV infections out of the NZ community. Border restrictions did not affect community transmission of other respiratory viruses such as rhinovirus and parainfluenza virus type‐1. Partial border relaxations through quarantine‐free travel with Australia and other countries were quickly followed by importation of RSV in 2021 and influenza in 2022.
Conclusion
Our findings inform future pandemic preparedness and strategies to model and manage the impact of influenza and other respiratory viral threats.
The aim of this study was to determine how attitudes toward the return of genomic research results vary internationally.
We analyzed the “Your DNA, Your Say” online survey of public perspectives on ...genomic data sharing including responses from 36,268 individuals across 22 low-, middle-, and high-income countries, and these were gathered in 15 languages. We analyzed how participants responded when asked whether return of results (RoR) would motivate their decision to donate DNA or health data. We examined variation across the study countries and compared the responses of participants from other countries with those from the United States, which has been the subject of the majority of research on return of genomic results to date.
There was substantial variation in the extent to which respondents reported being influenced by RoR. However, only respondents from Russia were more influenced than those from the United States, and respondents from 20 countries had lower odds of being partially or wholly influenced than those from the United States.
There is substantial international variation in the extent to which the RoR may motivate people’s intent to donate DNA or health data. The United States may not be a clear indicator of global attitudes. Participants’ preferences for return of genomic results globally should be considered.
Dengue is a major public health problem in Singapore. Age-specific dengue morbidity rates are highest in the young adult population, unlike in many other Southeast Asian countries where dengue is ...mainly a paediatric disease. Hence, the World Health Organization (WHO) guidelines on dengue diagnosis and management which were developed using the paediatric experiences, may not be suitable for the management of adult dengue infections.
The Early DENgue (EDEN) infection and outcome study is a collaborative longitudinal study to investigate epidemiological, clinical, viral and host-specific features of early dengue-infected adults, in an effort to identify new early markers for prognostication. Patients presenting with early undifferentiated fever were included in the study. We carried out an interim analysis to look for early indicators of severe disease.
During the period of this interim study analysis, 455 febrile patients were recruited. Of these, 133 were confirmed as acute dengue cases based on dengue-specific polymerase chain reaction (PCR) results. There were significant clinical and epidemiological differences between dengue and febrile non-dengue cases. Nine per cent of the dengue cases experienced persistent tiredness, drowsiness and loss of appetite beyond 3 weeks of illness. Quantitation of viral loads using the crossover (Ct) value of real-time RT-PCR correlated with the duration of symptoms. More than half of both primary and secondary dengue cases were hospitalised. There was no dengue-related mortality in this study.
The duration of illness and prolonged symptom duration in 9% of the subjects indicate that the burden of dengue illness is substantially different from other non-dengue febrile illness in our study cohort. Our study also highlights the paucity of early prognostic markers for dengue fever in adults.
Progressive cerebral amyloid β-protein (Aβ) deposition is believed to play a central role in the pathogenesis of Alzheimer's disease (AD). Elevated levels of Aβ(42) peptide formation have been linked ...to early-onset familial AD-causing gene mutations in the amyloid β-protein precursor (AβPP) and the presenilins. Sequential cleavage of AβPP by the β- and γ-secretases generates the N- and C-termini of the Aβ peptide, making both the β- and γ-secretase enzymes potential therapeutic targets for AD. The identity of the AβPP γ-secretase and the mechanism by which the C-termini of Aβ are formed remain uncertain, although it has been suggested that the presenilins themselves are novel intramembrane-cleaving γ-secretases of the aspartyl protease class Wolfe, M. S., Xia, W., Ostaszewski, B. L., Diehl, T. S., Kimberly, W. T., and Selkoe, D. J. (1999) Nature 398, 513−517. In this study we report the identification of L-685,458 as a structurally novel inhibitor of AβPP γ-secretase activity, with a similar potency for inhibition of Aβ(42) and Aβ(40) peptides. This compound contains an hydroxyethylene dipeptide isostere which suggests that it could function as a transition state analogue mimic of an aspartyl protease. The preferred stereochemistry of the hydroxyethylene dipeptide isostere was found to be the opposite to that required for inhibition of the HIV-1 aspartyl protease, a factor which may contribute to the observed specificity of this compound. Specific and potent inhibitors of AβPP γ-secretase activity such as L-685,458 will enable important advances toward the identification and elucidation of the mechanism of action of this enigmatic protease.
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