Human Cytomegalovirus Infection and Neurocognitive and Neuropsychiatric Health.

A common infection, human cytomegalovirus (HCMV) has been associated with a variety of human diseases, including cardiovascular disease and possibly certain cancers. HCMV has also been associated with cognitive, psychiatric, and neurological conditions. Children with congenital or early-life HCMV are at risk for microcephaly, cerebral palsy, and sensorineural hearing loss, although in many cases sensorineural loss may resolve. In addition, HCMV can be associated with neurodevelopmental impairment, which may improve with time. In young, middle-aged, and older adults, HCMV has been adversely associated with cognitive function in some but not in all studies. Research has linked HCMV to Alzheimer's and vascular dementia, but again not all findings consistently support these associations. In addition, HCMV has been associated with depressive disorder, bipolar disorder, anxiety, and autism-spectrum disorder, although the available findings are likewise inconsistent. Given associations between HCMV and a variety of neurocognitive and neuropsychiatric disorders, additional research investigating reasons for the considerable inconsistencies in the currently available findings is needed. Additional meta-analyses and more longitudinal studies are needed as well. Research into the effects of antiviral medication on cognitive and neurological outcomes and continued efforts in vaccine development have potential to lower the neurocognitive, neuropsychiatric, and neurological burden of HCMV infection.

A Wireless Wearable Patch for Remote Monitoring of Respiratory and Cardiac Rhythm in Children.

Remote patient monitoring (RPM) is an innovative strategy to promote health and improve patient management and care. Recent advances in healthcare technologies have seen the emergence of wearable sensors allowing longitudinal physiological measurements in any environment. This paper introduces a wireless wearable patch 'Leo' for continuous remote monitoring of physiological data at home and healthcare settings. This includes single lead ECG, chest impedance, heart rate (HR), respiration rate (RR) and body posture. To test Leo's ability to capture longitudinal physiological data at home, 15 children experiencing acute severe asthma exacerbations were recruited during their emergency department (ED) visits. Participants wore the Leo device for 7 (+/-2) days post-hospital discharge. Nocturnal RR and HR and variability were higher during the first half of the night on Day1 compared to Day7 (p<0.005). Participants also completed a usability questionnaire and reported the patch wear to be comfortable (average score of 3.3 out of 5) and easy to wear during the night (average score of 3.5 out of 5) with 5/15 (33%) reported very slight barely perceptible skin irritation/redness and 2 (13%) reported well defined skin irritation and redness.Clinical Relevance- These results highlight the potential use of the Leo device in clinical practice for continuous un-obstructive monitoring of diseased populations, such as asthma.

My Deep Sea, My Backyard: a pilot study to build capacity for global deep-ocean exploration and research.

The deep ocean is the largest ecosystem on the planet, constituting greater than 90% of all habitable space. Over three-quarters of countries globally have deep ocean within their Exclusive Economic Zones. While maintaining deep-ocean function is key to ensuring planetary health, deficiencies in knowledge and governance, as well as inequitable global capacity, challenge our ability to safeguard the resilience of this vast realm, leaving the fate of the deep ocean in the hands of a few. Historically, deep-ocean scientific exploration and research have been the purview of a limited number of nations, resulting in most of humankind not knowing the deep ocean within their national jurisdiction or beyond. In this article, we highlight the inequities and need for increased deep-ocean knowledge generation, and discuss experiences in piloting an innovative project 'My Deep Sea, My Backyard' toward this goal. Recognizing that many deep-ocean endeavours take place in countries without deep-ocean access, this project aimed to reduce dependency on external expertise and promote local efforts in two small island developing states, Trinidad and Tobago and Kiribati, to explore their deep-sea backyards using comparatively low-cost technology while building lasting in-country capacity. We share lessons learned so future efforts can bring us closer to achieving this goal. This article is part of the theme issue 'Nurturing resilient marine ecosystems'.

Coronary CT Angiography and 5-Year Risk of Myocardial Infarction.

BACKGROUND: Although coronary computed tomographic angiography (CTA) improves diagnostic certainty in the assessment of patients with stable chest pain, its effect on 5-year clinical outcomes is unknown. METHODS: In an open-label, multicenter, parallel-group trial, we randomly assigned 4146 patients with stable chest pain who had been referred to a cardiology clinic for evaluation to standard care plus CTA (2073 patients) or to standard care alone (2073 patients). Investigations, treatments, and clinical outcomes were assessed over 3 to 7 years of follow-up. The primary end point was death from coronary heart disease or nonfatal myocardial infarction at 5 years. RESULTS: The median duration of follow-up was 4.8 years, which yielded 20,254 patient-years of follow-up. The 5-year rate of the primary end point was lower in the CTA group than in the standard-care group (2.3% [48 patients] vs. 3.9% [81 patients]; hazard ratio, 0.59; 95% confidence interval [CI], 0.41 to 0.84; P=0.004). Although the rates of invasive coronary angiography and coronary revascularization were higher in the CTA group than in the standard-care group in the first few months of follow-up, overall rates were similar at 5 years: invasive coronary angiography was performed in 491 patients in the CTA group and in 502 patients in the standard-care group (hazard ratio, 1.00; 95% CI, 0.88 to 1.13), and coronary revascularization was performed in 279 patients in the CTA group and in 267 in the standard-care group (hazard ratio, 1.07; 95% CI, 0.91 to 1.27). However, more preventive therapies were initiated in patients in the CTA group (odds ratio, 1.40; 95% CI, 1.19 to 1.65), as were more antianginal therapies (odds ratio, 1.27; 95% CI, 1.05 to 1.54). There were no significant between-group differences in the rates of cardiovascular or noncardiovascular deaths or deaths from any cause. CONCLUSIONS: In this trial, the use of CTA in addition to standard care in patients with stable chest pain resulted in a significantly lower rate of death from coronary heart disease or nonfatal myocardial infarction at 5 years than standard care alone, without resulting in a significantly higher rate of coronary angiography or coronary revascularization. (Funded by the Scottish Government Chief Scientist Office and others; SCOT-HEART ClinicalTrials.gov number, NCT01149590 .).

Activation of Th2 cells downregulates CRTh2 through an NFAT1 mediated mechanism.

CRTh2 (encoded by PTGDR2) is a G-protein coupled receptor expressed by Th2 cells as well as eosinophils, basophils and innate lymphoid cells (ILC)2s. Activation of CRTh2, by its ligand prostaglandin (PG)D2, mediates production of type 2 cytokines (IL-4, IL-5 and IL-13), chemotaxis and inhibition of apoptosis. As such, the PGD2-CRTh2 pathway is considered important to the development and maintenance of allergic inflammation. Expression of CRTh2 is mediated by the transcription factor GATA3 during Th2 cell differentiation and within ILC2s. Other than this, relatively little is known regarding the cellular and molecular mechanisms regulating expression of CRTh2. Here, we show using primary human Th2 cells that activation (24hrs) through TCR crosslinking (αCD3/αCD28) reduced expression of both mRNA and surface levels of CRTh2 assessed by flow cytometry and qRT-PCR. This effect took more than 4 hours and expression was recovered following removal of activation. EMSA analysis revealed that GATA3 and NFAT1 can bind independently to overlapping sites within a CRTh2 promoter probe. NFAT1 over-expression resulted in loss of GATA3-mediated CRTh2 promoter activity, while inhibition of NFAT using a peptide inhibitor (VIVIT) coincided with recovery of CRTh2 expression. Collectively these data indicate that expression of CRTh2 is regulated through the competitive action of GATA3 and NFAT1. Though prolonged activation led to NFAT1-mediated downregulation, CRTh2 was re-expressed when stimulus was removed suggesting this is a dynamic mechanism and may play a role in PGD2-CRTh2 mediated allergic inflammation.

A retrospective multicenter case series evaluating a novel 3.0-mm expanding tapered body implant for the rehabilitation of missing incisors.

OBJECTIVE: Narrow-diameter implants are indicated for narrow sites, small interdental/interimplant spaces, or sites with congenitally missing teeth. They also offer a substitute for invasive augmentation procedures. The authors retrospectively evaluated the performance of a new 3.0-mm diameter implant for rehabilitating small anterior spaces. METHOD AND MATERIALS: This observational multicenter retrospective case series included consecutive patients needing single-unit restoration for mandibular and lateral maxillary incisors. The outcome variables were: implant survival, Plaque Index, pocket probing depth (PPD), Jemt's papilla index, bleeding on probing (BOP), and marginal bone remodeling. RESULTS: In total, 45 patients received 58 3.0-mm implants placed in healed sites (n = 22), extraction sockets (n = 16), or sites with congenitally missing teeth (n = 20). Average follow-up time was 15.1 ± 5.2 months. Prosthetic loading was immediate (n = 23), early (n = 16), or delayed (n = 19). Two implants were lost, and two prosthetic complications occurred. One-year bone remodeling averaged -0.36 ± 0.85 mm (n = 44). PPD averaged 1.75 ± 0.58 mm. Neither BOP nor plaque was detected around implants. CONCLUSIONS: At 1-year follow-up, narrow 3.0-mm diameter implants placed in mandibular and lateral maxillary incisor sites demonstrate a high survival rate and support stable marginal bone levels and healthy soft tissue.

Initial hospital-related cost comparison of total ankle replacement and ankle fusion with hip and knee joint replacement.

BACKGROUND: Total hip and knee arthroplasty (THA and TKA) are accessible to patients with end-stage hip and knee arthritis in most health care systems. The availability of total ankle arthroplasty (TAA) to patients with end-stage ankle arthritis is often restricted because of prosthesis cost. Ankle fusion (AF) is often offered as the only alternative. Patients should have equal access to procedures that are equivalent in total cost. We compared total costs of TAA, AF, THA, and TKA for similar cohorts in a government-funded teaching hospital. METHODS: A subset of 13 TAA and 13 AF patients were selected from the Canadian Orthopaedic Foot and Ankle Society Prospective Ankle Reconstruction Database, and 13 THA and 13 TKA patients were randomly selected from the Canadian Joint Replacement Registry. Total cost was estimated from operating room time, hospital stay, surgeon billing, and equipment used. RESULTS: Mean total cost associated with TAA was $13,500 ± 1000 and was the same as THA ($14,500 ± 1500) and TKA ($12,500 ± 1000). Mean total cost associated with AF was significantly less at $5500 ± 500. Mean operating room time was longer, but mean hospital stay was shorter for the ankle procedures compared with THA and TKA. CONCLUSION: All arthroplasties had similar total costs. Total ankle arthroplasty should not be denied based on prosthetic cost alone, as total procedure cost is equivalent to THA and TKA. We believe ankle fusion is a less expensive and preferable alternative for some patient groups.

Effect of basic fibroblast growth factor on the cellular repopulation of decellularized anterior cruciate ligament allografts.

The use of decellularized anterior cruciate ligament (ACL) allografts in ACL replacement surgery may allow for the native structure of the ligament to be retained, thereby recapturing the function of the ligament post-injury. Our previous work has focused on repopulating decellularized allograft ACL tissue with ACL fibroblasts in order to prevent destructive remodelling of the implanted tissue by extrinsic host cells. In this study, the use of basic fibroblast growth factor (bFGF) to improve the cellular repopulation of decellularized ACL tissue was assessed. A concentration of 6 ng/ml bFGF was demonstrated to be effective in increasing cellular growth in the absence of tissue; however, this concentration, as well as reduced and increased levels of bFGF (0.1 and 60 ng/ml, respectively), failed to increase cellular repopulation of ACL fibroblast-seeded decellularized tissue after 28 days of culture. Mean repopulation levels of 11-19% of fresh tissue [3200-5300 cells/mg dry weight (dwt) tissue] were achieved after 28 days in culture. Qualitative observation of histological samples suggested that different repopulation characteristics exist at various concentrations of bFGF and, in particular, that bFGF may be stimulating a catabolic pathway resulting in matrix destruction. Significant differences in the effects of bFGF observed between cell-only and cell-and-tissue studies serve to reinforce the concept that cells respond to stimuli in a different manner, depending on the surrounding environment. As a result, caution should be used when information obtained from studies utilizing cells alone is applied to the development of tissue-engineered constructs.