Effects of 12 weeks of Multi-nutrient supplementation on the Immune and Musculoskeletal systems of Older Adults in Aged-Care (The Pomerium Study): Protocol for a Randomised Controlled Trial

IntroductionImmunosenescence leads to increased morbidity and mortality associated with viral infections and weaker vaccine responses. This has been well documented for seasonal influenza and the current pandemic with Sars-Cov2, which disproportionately impact older adults, particularly those in residential aged care facilities. Inadequate nutrient intake associated with impaired immunity, respiratory and muscle function are likely to augment the effects of immunosenescence. In this study, we test whether the effects of inadequate nutrition can be reversed by multi-nutrient supplementation, consequently enhancing vaccine responses, reducing the risk of viral infections, and improving respiratory and muscle function. Methods and analysisThe Pomerium Study is a 12-week, single-blinded, randomised, placebo-controlled trial testing the effects of two daily servings of an oral multi-nutrient supplement (330 kcal, 20g protein, 1.2g CaHMB, 449mg calcium, 520IU vitamin D3, and 25 vitamins and minerals) on the immune system and muscle and respiratory function of older adults in aged-care in Melbourne, Australia. 160 older adults ([≥]75 years old) will be recruited from aged-care facilities and randomised to treatment (multi-nutrient supplement) or control (usual care). Primary outcome is the change in T-cell subsets CD8+ and CD28null counts at 4 and 12 weeks post-intervention. Secondary outcomes measured at baseline and after 12 weeks post-intervention are multiple markers of immunosenescence, body composition (bioimpedance), handgrip strength (dynamometer), physical function (short physical performance battery), respiratory function (spirometry), and quality of life (EQ-5D-3L). Incidence and complications of COVID-19 and/or viral infections (i.e., hospitalisation, complications, or death) will be recorded throughout the trial. DiscussionIf the Pomerium Study demonstrates efficacy and safety of a multi-nutrient supplement on immune, muscle and respiratory function, it may be suitable as a strategy to reduce the adverse outcomes from seasonal influenza and viral infections such as COVID-19 in older adults in aged-care. Funding, Ethics, Registration and DisseminationThe study is funded by the Australian Medical Research Future Fund. It is approved by Melbourne Health Human Research Ethics Committee (Ref No. HREC/73985/MH-2021, ERM Ref No. RMH73985, Melbourne Health Site Ref No. 2021.115), and registered at ANZCTR (12621000420842). Results will be published in peer-reviewed journals and made available to aged-care stakeholders, including providers, residents, and government bodies. Article Summary Strengths and LimitationsO_LIThis is the first study performing a comprehensive immune, respiratory and functional assessment in aged care residents after receiving a multi-nutrient solution that is commercially available. C_LIO_LIOur design and tested intervention assure that the results of the study will be rapidly translated into practice. C_LIO_LIThe main limitation is that any biological effect observed cannot be attributed to one component of the multi-nutrient supplement. C_LIO_LIAnother limitation is that the potential effect of group differences in energy intake on outcomes can only be monitored by assessing regular dietary intake and weight changes during the study period. C_LI

The Progress of Multi-Omics Technologies: Determining Function in Lactic Acid Bacteria Using a Systems Level Approach.

Lactic Acid Bacteria (LAB) have long been recognized as having a significant impact ranging from commercial to health domains. A vast amount of research has been carried out on these microbes, deciphering many of the pathways and components responsible for these desirable effects. However, a large proportion of this functional information has been derived from a reductionist approach working with pure culture strains. This provides limited insight into understanding the impact of LAB within intricate systems such as the gut microbiome or multi strain starter cultures. Whole genome sequencing of strains and shotgun metagenomics of entire systems are powerful techniques that are currently widely used to decipher function in microbes, but they also have their limitations. An available genome or metagenome can provide an image of what a strain or microbiome, respectively, is potentially capable of and the functions that they may carry out. A top-down, multi-omics approach has the power to resolve the functional potential of an ecosystem into an image of what is being expressed, translated and produced. With this image, it is possible to see the real functions that members of a system are performing and allow more accurate and impactful predictions of the effects of these microorganisms. This review will discuss how technological advances have the potential to increase the yield of information from genomics, transcriptomics, proteomics and metabolomics. The potential for integrated omics to resolve the role of LAB in complex systems will also be assessed. Finally, the current software approaches for managing these omics data sets will be discussed.

Evaluating Self-Refraction and Ready-Made Spectacles for Treatment of Uncorrected Refractive Error.

PURPOSE: Uncorrected refractive error is the leading cause of visual impairment worldwide and has significant quality of life and economic implications. Treatment with subjective refraction and custom-made spectacles requires expensive equipment and highly trained personnel. We examine several alternatives. METHODS: Patients were taught to self-refract using two devices: AdSpecs and the I-test Vision Screener. Ready-made spectacles were fit to the self-refraction and visual acuity (VA) was measured. Donated-spectacles were fit to subjective refraction and VA was measured. Self-refraction and donated spectacles spherical equivalent (SE) and VA were compared to subjective refraction SE and VA. RESULTS: About 57 patients (102 eyes) were enrolled in the study. Patients accurately determined refractive power with self-refraction by both AdSpecs and the I-test (compared to subjective refraction SE, r2 = 0.97 and r2 = 0.94, respectively). SE of donated spectacles fit well with self-refraction SE (r2 = 0.91). There was no significant difference between best-corrected VA by subjective refraction and VA treated by ready-made spectacles fit to self-refraction by either device (analysis of variance (ANOVA), p non-significant). Patients fit with donated spectacles had significantly worse VA than best-corrected VA by subjective refraction (ANOVA, p < 0.01), although 80% improved to >20/40. CONCLUSION: Patients accurately self-refract using both devices and ready-made spectacles fit to self-refraction have excellent visual outcomes. Donated spectacles have worse visual outcomes but might be useful in a subset of patients. Ready-made spectacles fit to self-refraction may provide a treatment alternative to uncorrected refractive error.

Prevalence of depression in coronary heart disease in China: a systematic review and meta-analysis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Coronary heart diseases (CHD) have been identified as one of topmost diseases affecting the Chinese population. However, depression in CHD has not been reported and there are limited high quality empirical studies in China focused on the prevalence of the comorbidity. This study aimed to estimate the pooled prevalence of depression with CHD in China.</p><p><b>METHODS</b>Systematic review and meta-analysis of published epidemiologic studies on the depression in CHD patients in China were conducted. The research findings dated before 30 September 2013 were obtained from Ovid Medline, EMBASE and two Chinese electronic publication libraries WANFANG and CNKI. We used "cardiovascular disease", "depression" and "China" as the search themes in Ovid Medline and EMBASE and "cardiovascular disease" and "depression" in WANFANG and CNKI. Random-effects meta-analysis was used to estimate the prevalence of depression in CHD patients.</p><p><b>RESULTS</b>Twenty-seven studies were included in the review. Twenty-three studies had 5 236 participants who were hospitalized and four studies had 1 353 participants from community. The overall prevalence of depression in CHD from hospital was 51% (95% CI: 0.43, 0.58; I-squared = 97%, P = 0.000).The prevalence of depression in CHD from community ranged between 34.6% to 45.8%, and the severe depression was found ranging between 3.1% to 11.2%.</p><p><b>CONCLUSIONS</b>On comparing data with other countries, the prevalence of depression in CHD among admitted patients in China was found to be high. The physicians and healthcare providers should pay more attention to the "physical-mental" health of the CHD patients.</p>

Used glasses versus ready-made spectacles for the treatment of refractive error.

BACKGROUND AND OBJECTIVE: To compare visual outcomes for used glasses versus ready-made spectacles in the treatment of refractive error. PATIENTS AND METHODS: In this prospective, comparative case series, undilated refractive error screening examinations were conducted over a 5-week period. Patients with bilateral refractive error were treated with used glasses and ready-made spectacles powered to match their prescriptions. Snellen visual acuity was measured with no correction, best (manifest) correction, unrefined autorefraction, used glasses, and ready-made spectacles. Main outcome measurements were the mean visual improvement from uncorrected acuity and median final visual acuity after treatment with used and ready-made spectacles. RESULTS: One hundred forty-one patients ages 18 and older with bilateral refractive error were examined. Uncorrected visual acuity in each eye improved an average of 4.5 lines with best correction, 4.0 lines with used glasses, and 3.5 lines with ready-made spectacles, with used glasses demonstrating a statistically significant advantage over ready-made spectacles (P < .001). The median visual acuity in the better eye improved from 20/60 uncorrected to 20/25 with all types of glasses. In patients with less than 1 diopter of anisometropia and greater than 1 diopter of astigmatism in each eye (49%), the ready-made spectacles performed equally as well as the used glasses (P = .95), improving vision an average of 3.9 lines for a median final visual acuity of 20/25 in the better eye. CONCLUSION: Although both were effective, used glasses are better than ready-made spectacles for improving vision loss due to refractive error.

Peripheral retinal vascular abnormalities in primary infantile glaucoma.

Two patients with primary infantile glaucoma were imaged with fluorescein angiography during an examination under anesthesia. Both patients were found to have abnormal peripheral retinal vasculature and non-perfusion. These findings may represent a previously unrecognized retinal vascular component of primary infantile glaucoma.

Treating uncorrected refractive error in adults in the developing world with autorefractors and ready-made spectacles.

BACKGROUND: To evaluate a method for treating uncorrected refractive error in adults in the developing world. DESIGN: Prospective, cross-sectional study in outpatient community health centres. PARTICIPANTS: Eight hundred and forty subjects aged 18 and older from rural villages in Haiti and Belize. METHODS: Undilated refractive error screening exams were conducted over a 5-day period in rural Haiti and Belize using portable autorefractors. Isometropic, spherical, ready-made spectacles were provided to patients with bilateral refractive error, astigmatism ≤ 1 dioptre in each eye and visual acuity worse than 6/9 in each eye. Visual acuity was measured with and without corrective spectacles. MAIN OUTCOME MEASURES: The mean visual improvement and median final visual acuity after treatment with ready-made glasses. RESULTS: Eight hundred and forty patients aged 18 and older were screened with autorefractors. One hundred and eighty-nine subjects (22.5%) were found to have visually significant bilateral refractive error. Fifty-eight per cent (110/189) of these patients met criteria for treatment with ready-made spectacles. Visual acuity improved an average of 4.2 lines in the better eye and 4.1 lines in the worse eye with corrective glasses. The median visual acuity in the better eye was 6/6 after treatment. CONCLUSION: Autorefractors and ready-made spectacles allow for effective treatment of uncorrected refractive error in adults in the developing world.

Bilateral fluorescein angiographic findings in unilateral Coats' disease.

Two patients with clinically unilateral Coats' disease were imaged with fluorescein angiography during an examination under anesthesia. Both patients were found to have abnormal retinal vasculature in their contralateral eye. These findings may represent a previously unrecognized bilateral component of Coats' disease.

Melanopsin-dependent persistence and photopotentiation of murine pupillary light responses.

PURPOSE: To determine the relative contributions of inner and outer retinal photoreception to the pupillary light response. METHODS: Wild-type, retinal degenerate (rd/rd), and melanopsin mutant (opn4(-/-)) mice were tested for pupillary light responsiveness by video pupillometry before, during, and after exposure to supersaturating light intensities. Similar lighting protocols were used to probe responses of intrinsically photosensitive retinal ganglion cells (ipRGCs) recorded with multielectrode arrays ex vivo. RESULTS: Both outer retinal photoreceptors (rods and cones) and inner retinal photoreceptors (intrinsically photosensitive retinal ganglion cells [ipRGCs]) are sufficient to drive the pupillary light response in mice. After supersaturating light exposure, rather than bleaching or adapting, rd/rd mice showed paradoxical potentiation of responses to subsaturating light exposure. opn4(-/-) mice, in contrast, could not sustain pupillary constriction under continuous bright illumination, and showed desensitization after bright-light exposure. Both the intensity of light necessary to induce potentiation and the spectral sensitivity for sustained and potentiated responses differed from that necessary to trigger pupillary constriction, suggesting that photopotentiation is dependent on a pigment-state distinct from that triggering the pupillary light response itself. Multielectrode array recordings of ipRGCs from rd/rd retinas demonstrated persistent cell firing under continuous light exposure but did not show potentiation. CONCLUSIONS: Unique photoreceptive properties of intrinsically photosensitive RGCs confer resistance to bleaching and/or adaptation under continuous bright illumination to the pupillary light response and suggest the presence of a photopigment with multiple absorption states.

Endophthalmitis after ganciclovir implant in patients with AIDS and cytomegalovirus retinitis.

PURPOSE: To describe the incidence, clinical course, and outcomes of endophthalmitis in patients treated with a ganciclovir implant. DESIGN: Retrospective review of cases identified from a clinical survey. METHODS: Cases of endophthalmitis were identified from a survey of 30 clinical practices known to treat a large number of patients with cytomegalovirus retinitis. RESULTS: Twenty-four cases of endophthalmitis were identified from 5185 implants performed (incidence, 0.46%). Final visual acuity ranged from 20/20 to no light perception, with 50% (12/24) seeing light perception or worse. Vitreous cultures revealed Staphylococcus epidermidis in 29% (7/24) of patients, whereas other gram-positive organisms were responsible in 42% (10/24) of cases. In the remaining 29% (7/24) of cases, no organisms were cultured; these cases exhibited a better visual outcome (P =.007). Six of the eight late-onset cases were associated with wound problems such as implant strut or suture exposure. There was no significant relationship between implant removal and final visual acuity. CONCLUSIONS: Endophthalmitis is an infrequent but potentially devastating complication associated with placement of a ganciclovir implant.