Observational cohort study of highly functioning community-dwelling older adults to assess their sarcopenic status, leisure physical activity, and quality of life over 12-months.

Background: The prevalence of sarcopenia varies depending on the cohort evaluated, and the diagnostic criteria used. Older adults with sarcopenia report lower quality of life than their non-sarcopenic peers. Leisure physical activity is reported to have a variable effect on sarcopenic status. Most studies to date, have been done in "vulnerable" populations, with fewer done on independent community-dwelling older adults. None have been done in an Alberta, Canada population. Objectives: To prospectively evaluate the sarcopenic status of independent community-dwelling older Albertan adults; whether this changed over 12-months; and any association with self-reported leisure activity or quality of life. Methods: Independent community-dwelling older adults were invited to participate in a 12-month observational study. Assessments were done at baseline, 6 and 12-months for physical function (TUG, SPPB, gait speed, Tinetti, grip strength), muscle mass (DXA, arm and calf circumference), body fat (skinfold, DXA), reported daily exercise (aerobic, resistance), quality of life (EQ5D), and laboratory parameters. European Working Group on Sarcopenia in Older People (EWGSOP) definitions of sarcopenic status were used. Results: All 50 participants (11 male), were independent of all basic activities of daily living at baseline, and most instrumental activities (some needed assistance with driving or finances). They had an average age of 75.8 (67-90) years, with average MMSE and MoCA cognitive scores of 28.1/30 (20-30) and 24.8/30 (14-30) respectively. Eight participants dropped out prior to their first DXA test. Of the remaining 42, 17 participants (5 male) fulfilled the EWGSOP revised criteria for probable, pre-sarcopenia, or sarcopenia, giving a rate of baseline total sarcopenia of 40.5% in this community-dwelling sample. The majority were pre-sarcopenic (28.6%), and sarcopenia was present only in 7.1%. The total sarcopenia group had a lower BMI (25.6 ± 5.1 versus 29 ± 5, p = 0.01), less body fat by skinfold measurement (36.4 ± 6.5 versus 39.3 ± 8.1, p = 0.01) and lower mid-calf (35.6 ± 3.2 versus 37.6 ± 3.4, p = 0.04) and mid-arm (29.1 ± 2.5 versus 31.9 ± 3.5, p = 0.02) circumferences when compared to their non-sarcopenic peers. After 12-months, 39 participants remained in the study. Of these, the sarcopenic status of 7 improved, 10 declined, with the remaining 56% not changing. There were no statistically significant differences in baseline laboratory parameters between the groups, including 25(OH)D status. But, of the status decliners, 40% had suboptimal 25(OH)D at baseline. Self-reported leisure activity (both total time and frequency) was not associated with sarcopenic status at 12-months. EuroQol -5D was not associated with sarcopenic status. Conclusions: The rate of sarcopenia was 7.1%, but the total rate of pre, probable and sarcopenia in this highly functioning, community-dwelling older adult cohort was 40.5%. In the majority (75%), there was either no change, or an improvement, in their sarcopenic status over 12-months. There was no association identified with self-reported leisure activity or quality of life in this cohort.

Very Elevated IgE, Atopy, and Severe Infection: A Genomics-Based Diagnostic Approach to a Spectrum of Diseases.

Elevated IgE has been long recognized as an important clinical marker of atopy but can be seen in a myriad of conditions. The discovery of autosomal dominant STAT3 deficiency marked the first recognition of hyper-IgE syndrome (HIES) and the first primary immunodeficiency linked to elevated IgE. Since then, genomic testing has increased the number of defects with associated mutations causing hyper-IgE syndrome and atopic diseases with FLG, DOCK8, SPINK5, and CARD11, among others. A spectrum of recurrent infections and atopy are hallmarks of elevated IgE with significant phenotypic overlap between each underlying condition. As treatment is predicated on early diagnosis, genomic testing is becoming a more commonly used diagnostic tool. We present a 6-year-old male patient with markedly elevated IgE and severe atopic dermatitis presenting with staphylococcal bacteremia found to have a heterozygous variant in FLG (p.S3247X) and multiple variants of unknown significance in BCL11B, ZAP70, LYST, and PTPRC. We review the genetic defects underpinning elevated IgE and highlight the spectrum of atopy and immunodeficiency seen in patients with underlying mutations. Although no one mutation is completely causative of the constellation of symptoms in this patient, we suggest the synergism of these variants is an impetus of disease.

Assessing the Impact of Factors that Influence the Ketogenic Response to Varying Doses of Medium Chain Triglyceride (MCT) Oil.

Objectives, Design, Setting: The ketogenic effect of medium chain triglyceride (MCT) oil offers potential for Alzheimer's disease prevention and treatment. Limited literature suggests a linear B-hyroxybutyrate (BHB) response to increasing MCT doses. This pharmacokinetic study evaluates factors affecting BHB response in three subject groups. PARTICIPANTS: Healthy subjects without cognitive deficits <65years, similarly healthy subjects >=65years, and those with Alzheimer's Disease were assessed. INTERVENTION: Different doses (0g,14g, 28g, 42g) of MCT oil (99.3% C8:0) were administered, followed by fasting during the study period. MEASUREMENTS: BHB measured by finger prick sampling hourly for 5 hours after ingestion. Each subject attended four different days for each ascending dose. Data was also collected on body composition, BMI, waist/hip ratio, grip strength, gait speed, nutrient content of pre-study breakfast and side effects. RESULTS: Twenty-five participants: eight healthy; average age of 44yr (25-61), nine healthy; 79yr (65-90) and eight with AD; 78.6yr (57-86) respectively. Compiled data showed the expected linear dose response relationship. No group differences, with baseline corrected area under the blood vs. time curve (r2=0.98) and maximum concentrations (r2=0.97). However, there was notable individual variability in maximum BHB response (42g dose: 0.4 -2.1mM), and time to reach maximum BHB response both, within and between individuals. Variability was unrelated to age, sex, sarcopenic or AD status. Visceral fat, BMI, waist/hip ratio and pretest meal CHO and protein content all affected the BHB response (p<0.001). CONCLUSION: There was a large inter-individual variability, with phenotype effects identified. This highlights challenges in interpreting clinical responses to MCT intake.

Arthroscopic diagnosis and medical management of calcium pyrophosphate deposition disease in the temporomandibular joint.

Calcium pyrophosphate deposition disease (CPPD) is a crystal arthropathy that can involve the temporomandibular joint. It is known to accelerate the osteoarthritic process, often initially presenting with advanced level of disease. The management of CPPD in the rheumatology and orthopedic literature is one of early diagnosis and medical management of acute attacks. The cases of three patients who presented with initial complaints of joint pain and limited mouth opening are presented. Preoperative imaging identified calcifications in two of these patients. Definitive diagnosis was achieved through arthroscopic-assisted biopsy. Rheumatology referrals revealed chondrocalcinosis of the knee in one patient. All patients had improved mouth opening and pain.

New technique for removing bone covering miniplates and screws.

Miniplate osteosynthesis has revolutionised the treatment of open reduction and internal fixation in craniomaxillofacial procedures. However, when complications arise necessitating the removal of previously placed miniplates, bony overgrowth may be present and must be eliminated before removal of the hardware is possible. Osteogenesis over the screws prevents proper engagement of the screwdriver with the screw drives. If bone remains embedded in the screw drive during attempted removal of the screw, the contact interference increases the risk of the screwdriver slipping and the screw drive being stripped. There remains a lack of adequate techniques to clear bony overgrowth from miniplates and screws to allow for easy removal, as conventional methods are ineffective, time-consuming, and may damage the screw drives. Herein, we describe a new laser-assisted miniplate removal technique to eliminate bone that has grown over miniplates and screws before the miniplate is removed. This technique is efficient, safe, and simple and, compared with conventional methods, may decrease the complications associated with the removal of miniplates and screws.

Risk factors for community-associated Clostridioides difficile infection in young children.

The majority of paediatric Clostridioides difficile infections (CDI) are community-associated (CA), but few data exist regarding associated risk factors. We conducted a case-control study to evaluate CA-CDI risk factors in young children. Participants were enrolled from eight US sites during October 2014-February 2016. Case-patients were defined as children aged 1-5 years with a positive C. difficile specimen collected as an outpatient or ⩽3 days of hospital admission, who had no healthcare facility admission in the prior 12 weeks and no history of CDI. Each case-patient was matched to one control. Caregivers were interviewed regarding relevant exposures. Multivariable conditional logistic regression was performed. Of 68 pairs, 44.1% were female. More case-patients than controls had a comorbidity (33.3% vs. 12.1%; P = 0.01); recent higher-risk outpatient exposures (34.9% vs. 17.7%; P = 0.03); recent antibiotic use (54.4% vs. 19.4%; P < 0.0001); or recent exposure to a household member with diarrhoea (41.3% vs. 21.5%; P = 0.04). In multivariable analysis, antibiotic exposure in the preceding 12 weeks was significantly associated with CA-CDI (adjusted matched odds ratio, 6.25; 95% CI 2.18-17.96). Improved antibiotic prescribing might reduce CA-CDI in this population. Further evaluation of the potential role of outpatient healthcare and household exposures in C. difficile transmission is needed.

Food allergies developing after solid organ transplant.

The development of food allergy is an increasingly recognized form of morbidity after solid organ transplant. It occurs more commonly in liver transplant recipients, although it has also been reported in heart, lung, kidney, and intestinal transplants. Pediatric transplant recipients are more likely to develop symptoms compared to adults, and reports of frequency vary widely from 5% to 38% in pediatric liver transplant recipients. Multiple mechanisms have been proposed in the literature, although no single mechanism can yet account for all reported observations. As food allergy can have at worst potentially fatal consequences, and at best require lifestyle adjustment through food avoidance, it is important for recipients to be aware of the donor's food allergies and particularly in pediatrics, the possibility of completely de novo allergies. This review explores the recent reports surrounding food allergy after solid organ transplant, including epidemiology, proposed mechanisms, and implications for practice.

Mechanism of the sex difference in neuronal ischemic cell death.

BACKGROUND: Stroke risk and outcome are different in men and women. We hypothesized that this is partly due to an inherent difference in susceptibility to ischemia between neurons from male vs. female brains. We tested whether neurons from male rodents are more susceptible to in-vitro ischemia than cells from females, and if this is related to increased expression of soluble epoxide hydrolase (sEH). sEH contributes to neuronal cell death by inactivating neuroprotective epoxyeicosatrienoic acids (EETs). METHODS: Rodent cortical neurons were cultured, and exposed to oxygen-glucose deprivation (OGD); then cell death was measured. EETs levels were determined by LC-MS/MS. Expression of sEH-encoding ephx2 was determined by qRT-PCR. Western blotting, immunocytochemistry, and hydrolase activity assay assessed protein expression and activity. RESULTS: Cell death after OGD was higher in neurons from males vs. females, which correlated with higher ephx2 mRNA and stronger sEH immunoreactivity. However, EETs levels were similar in both sexes and pharmacological inhibition of the hydrolase domain of sEH did not abolish the sex difference in cell death. Genetic knockout of sEH in mice abolished the sex difference observed in neurons isolated from these mice after OGD. CONCLUSIONS: Cultured cortical neurons from females are more resistant to ischemia than neurons from males. Neurons from females have less sEH activity compared to neurons from males at baseline, although sEH levels were not measured after OGD. While pharmacological inhibition of the hydrolase domain of sEH does not affect cell death, knockout of the gene encoding sEH eradicates the sex difference seen in wild-type neurons, suggesting a role for further study of the lesser-known phosphatase domain of sEH and its role in sexual dimorphism in neuronal sensitivity to ischemia.

Presentation of atopic disease in a large cohort of pediatric liver transplant recipients.

Atopic disease occurs in solid organ transplant recipients with an increasingly recognized frequency. The time course for the development of these atopic diseases in liver transplantation has not been described. The objective was to characterize the atopic manifestations of children receiving chronic immunosuppression after orthotopic liver transplantation (OLT). Chart review and follow-up questionnaire were utilized for 176 OLT pediatric recipients at a single institution for manifestations of allergic disease. Atopic disease was present in 25 (14.2%) patients. Median age at transplant was 16 months with a median follow-up of 63 months. Food allergy and non-food related atopic symptoms presented at a median of 11.5 (IQR, 6-28) and 19 (IQR, 5-41) months post-transplantation, respectively. The median age at transplant of the non-atopic children was 72 months, higher than patients with atopy (p < 0.001). Food allergy and atopic skin disease symptoms were present in 40% and 56% of cases, respectively. Asthma, allergic rhinitis, or both were found in 66% of cases. The onset of symptoms of food allergy and eczema (median, 12 months post-transplantation) preceded symptoms of allergic rhinitis and asthma. (median of 27 and 30 months post-transplantation, respectively). Atopy occurs in ∼14% of pediatric liver transplant recipients, with manifestations including food allergy, eczema, allergic rhinitis, and asthma.

Lentiviral transduction of human T-lymphocytes with a RANTES intrakine inhibits human immunodeficiency virus type 1 infection.

Intrakines, modified intracellular chemokines, offer a novel strategy to prevent cellular entry of HIV-1 by blocking the surface expression of HIV-1 co-receptors. To investigate potential clinical applications of the RANTES-intrakine, we explored the use of HIV-1-based lentiviral vectors for therapeutic gene transfer into T-lymphocytes. RANTES-intrakine genes can be efficiently transduced into primary human T-lymphocytes by lentiviral vectors, especially when human T-lymphocytes were stimulated with CD3 and CD28 antibodies. The transduced T cells showed decreased surface expression of the chemokine receptor CCR-5, as well as CCR-1 and CCR-3. This lentivirus-mediated approach to intrakine gene transfer protected human T-lymphocytes from infection by a variety of R5-tropic HIV-1 strains. A quantitative real-time PCR assay, developed to monitor cells for HIV entry and persistence, revealed persistent low copy numbers of proviral HIV DNA in RANTES intrakine-transduced T-lymphocytes during 3-week culture, suggesting that viruses produced from infected untransduced cell populations were unable to infect the surrounding transduced T-lymphocytes. We conclude that targeting HIV-1 co-receptors to block virus entry with lentiviral vectors is an attractive approach to the control of HIV-1 infection.

Mechanics of solid tissue invasion by the mammalian pathogen Pythium insidiosum.

The relative significance of mechanical penetration versus the action of substrate-degrading enzymes during solid tissue invasion has not been established for any fungal disease. Pythium insidiosum is an oomycete fungus (or stramenopile) that causes a rare, but potentially lethal infection in humans and other mammalian hosts. Experiments with miniature strain gauges showed that single hyphal apices of this pathogen exert forces of up to 6.9 microN, corresponding to maximum pressures of 0.3 microN microm(-2) or MPa. Samples of cutaneous and subcutaneous tissue from fresh human cadavers displayed a mean strength (resistance to needle puncture) of 24 microN microm(-2), and a mean pressure of 30 microN microm(-2) was necessary to penetrate skin strips from slaughtered horses. These experiments demonstrate that P. insidiosum does not exert sufficient pressure to penetrate undamaged skin by mechanics alone, but must effect a decisive reduction in tissue strength by proteinase secretion.

Prevalence and incidence studies of pressure ulcers in two long-term care facilities in Canada.

A study was initiated to determine the prevalence and incidence of pressure ulcers in two long-term care facilities in Canada, one with 95 residents and the other with 92 residents. The prevalence study was conducted at both facilities on a single day. The incidence study was completed after 41 and 42 days, respectively, at each facility. Data were collected on demographics, medical information, and possible contributing factors. Each resident was assessed for the presence of a pressure ulcer. Each ulcer was staged and anatomical location was noted. The prevalence of pressure ulcers in the two long-term care facilities was 36.8% and 53.2%, respectively. The incidence of pressure ulcers in the two long-term care facilities was 11.7% and 11.6%, respectively. In conclusion, the pressure ulcer prevalence is higher than published figures for the long-term care setting. However, a pressure ulcer incidence of less than 12% in each facility suggests an equal and acceptable level of nursing care in both facilities. The disparity of pressure ulcer prevalence between the two facilities may be explained by a difference of case mix.

Radiation-induced cytogenetic instability in vivo.

Radiation-induced cytogenetic instability has been well documented in a number of laboratories, and we have hypothesized that such instability is the initiating event in the process leading to radiation-induced cancer. To date most studies of radiation-induced instability have used systems in which cells are rapidly dividing. For this phenomenon to have significance for radiation carcinogenesis, it must be established that instability can be induced in vivo in less rapidly dividing fully differentiated tissues known to be at risk. In the present study, we have examined the kinetics of radiation-induced cytogenetic instability in mammary epithelial cells after irradiation in vivo. Having established that instability could arise in vivo in intact mammary tissue, we subsequently demonstrated a dose-response relationship both in vitro and in vivo and demonstrated a lower frequency of instability after fractionated exposures.

Disparities of health in African Americans.

As a cohort of the vulnerable populations, African Americans have the poorest health status indicators of all ethnic groups. Using a vulnerable populations theoretical framework, the reasons for the disparities are discussed.

Isolation of the PufX protein from Rhodobacter capsulatus and Rhodobacter sphaeroides: evidence for its interaction with the alpha-polypeptide of the core light-harvesting complex.

Using mutant strains of Rhodobacter capsulatus and Rhodobacter sphaeroides in which the pufX gene had been deleted, it was possible to identify by HPLC membrane protein components present in pufX+ cells but absent in pufX- cells. In parallel preparations, membrane proteins soluble in chloroform/methanol containing ammonium acetate were first extracted from lyophilized membrane fractions of the pufX+ cells and separated from pigments and larger protein material by gel-filtration chromatography. Protein-containing fractions were examined by HPLC, and several peaks were collected from pufX+ material that were not present in pufX- material. From N-terminal amino acid sequencing, the PufX protein of Rb. capsulatus was identified, and from positive interaction with a PufX protein antibody, the Rb. sphaeroides PufX protein was identified. Although overall yields were very small, sufficient quantities of these proteins were isolated to evaluate their effect on the reconstitution of the core light-havesting antenna (LH1) and its subunit complex. From the behavior of the PufX protein and the alpha-polypeptide of LH1 on HPLC, qualitative evidence was obtained that the two proteins have a high affinity for each other. In reconstitution assays with bacteriochlorophyll (Bchl) and the LH1 alpha- and beta-polypeptides of Rb. capsulatus, the PufX protein of Rb. capsulatus was inhibitory to LH1 formation at low concentration. A similar inhibition was exhibited by Rb. sphaeroides PufX protein for reconstitution of LH1 with Bchl and the LH1 alpha- and beta-polypeptides of Rb. sphaeroides. In both cases, the ratios of concentrations of the PufX protein to the alpha-polypeptide causing 50% inhibition were approximately 0.5. Formation of the heterologous (alpha beta) subunit-type complex formed with Bchl and the alpha- and beta-polypeptides of LH1 of Rb. capsulatus was also inhibited by low concentrations of the Rb. capsulatus PufX protein (approximately 50% inhibition at PufX:alpha-polypeptide ratios = 0.5). However, neither PufX protein inhibited formation of a homologous (beta beta) subunit-type complex, which indicates that the PufX proteins do not interact with the beta-polypeptides.

Secretory phospholipase A2 cleavage of intravasated bone marrow primes human neutrophils.

BACKGROUND: Recent clinical reports suggest that early femoral intramedullary rod (IMR) fixation in patients with multiple injuries increases the risk of adult respiratory distress syndrome (ARDS). We have shown that lipid-mediated neutrophil (PMN) priming and elevated circulating levels of secretory phospholipase A2 (sPLA2) within the first 24 hours after injury correlate with the development of ARDS. We thus hypothesized that circulating lipid products, generated by sPLA2 cleavage of intravasated bone marrow, prime PMNs for enhanced superoxide anion (O2-) production. METHODS: Isolated PMNs from healthy volunteers were incubated for 5 minutes with buffer or sPLA2-lysed bone marrow (100 U/mL) collected from trauma patients. After formyl-methionyleucylphenylalanine (fMLP) activation, O2- production was quantified by the superoxide dismutase-inhibitable reduction of cytochrome c. Blood samples were also drawn from five injured patients before and 24 hours after femoral IMR fixation. PMNs were isolated and assessed for in vivo priming. RESULTS: PMNs incubated with sPLA2-lysed bone marrow were primed for more than 3.5 times greater fMLP-induced O2- production. Furthermore, in patients with femoral fractures, PMN O2- release in response to fMLP after IMR fixation was more than 2.5 times higher than before fixation. CONCLUSION: Collectively, the findings suggest that bone marrow released from acute fracture sites may become a lipid substrate for the elevated sPLA2 levels found in injured patients. The resultant priming of PMNs may thus render the injured patient at risk for ARDS. Although clearly hypothetical at present, we submit that these observations warrant further investigation because of their clinical implications.

Triazolam impairs delayed recall but not acquisition of various everyday memory tasks in humans.

A double-blind test battery was administered to 24 human subjects (8 control, 16 drug) to assess the effects of 0.125 mg triazolam (oral) on memory encoding and retention across delay intervals ranging from seconds to 1 week after presentation. Although the drug reduced immediate psychomotor performance, it did not impair recall of previously learned information, nor did it significantly impair encoding of new information. The drug enhanced immediate recall of the location and identity of playing cards, without affecting 4-h delayed recall. The drug treatment impaired correct recall of object names after a delay of 20 min. At 4 h delay, the drug impaired olfactory recognition and free-recall of object names. At both 1 day and 1 week delay, the drug impaired recall of biographical information and correct identification of picture-photographer pair associations. The drug also impaired the daily improvement of the drug group as compared with the control group in a geometric puzzle solving task. The time course of these memory impairments compares well with the known effects of triazolam on long-term potentiation (LTP), a candidate biological mechanism underlying telencephalic memory formation and expression.

A profile of the behavioral changes produced by facilitation of AMPA-type glutamate receptors.

A newly developed group of benzoylpiperidine drugs that enhance AMPA-receptor-gated currents ("ampakines") has been shown to improve memory encoding in rats across a variety of experimental paradigms. The present experiments were intended to i) provide a partial profile of the behavioral changes produced by ampakines, ii) test if two ampakines (BDP-12 and BDP-20) that differ significantly in their effects on AMPA receptor kinetics produce similar behavioral profiles, and iii) determine if physiological potency is reflected in behavioral potency. BDP-20 reduced two measures of exploratory activity in aged rats but increased speed of performance in a radial maze; the drug also caused substantially improved retention of spatial information. These results are similar to those obtained with BDP-12, an analog that differs from BDP-20 in its effects on ligand binding to the AMPA receptor and on the physiological responses of the receptors to glutamate. BDP-20 was approximately ten-fold more potent in behavioral effects than BDP-12, which agrees with the relative potencies of the two drugs as assessed with excised patches and excitatory synaptic responses. These findings indicate that ampakines, though differing in their effects on AMPA-receptor-mediated responses, have similar effects at the behavioral level.

Dissemination and implementation of Put Prevention into Family Practice.

INTRODUCTION: The Put Prevention into Practice (PPIP) program was developed and disseminated to address patient, clinician, and office barriers that result in less than optimal delivery of preventive services in the United States. METHODS: To study the dissemination of PPIP by the American Academy of Family Physicians (AAFP), pre- and post-dissemination surveys of knowledge about PPIP and purchase order data were obtained from the AAFP. In addition, a mail questionnaire was sent to a random sample of purchasers to study their use of PPIP. RESULTS: After two years of active promotion, 27% of AAFP members had heard about PPIP, and PPIP components were purchased by 2,004 individuals during its inital dissemination. Flow sheets, health guides, exam room wall charts, and the Clinician's Handbook of Preventive Services were the PPIP items most frequently purchased and used. Excluding the Clinician's Handbook of Preventive Services, 58% of purchasers used one or more parts of the kit with an average of less than four items used per purchaser. CONCLUSIONS: Initial dissemination and implementation of PPIP among family physicians was limited; continued promotion will likely improve dissemination of PPIP. However, this study, and others suggest that the simple availability of a kit of materials is not sufficient to enhance the delivery of preventive services as envisioned by clinicians or policy makers. Additional strategies for dissemination and implementation of preventive services will be required, such as providing external consultation services to practices, incorporation of preventive services into HMO organizations, and training of residents in strategies for change in their future practices.

Evidence that a positive modulator of AMPA-type glutamate receptors improves delayed recall in aged humans.

Elderly subjects (65-76 years) were tested for recall of nonsense syllables prior to and after oral administration of 1-(quinoxalin-6 ylcarbonyl)piperidine (CX516), a centrally active drug that enhances currents mediated by AMPA-type glutamate receptors. A significant and positive drug effect was found for delayed (5 min) recall at 75 min posttreatment; average scores for the highest dose group were more than twofold greater than for the placebo group. The drug had no evident influence on heart rate or self-assessment of several psychological variables.