Nutritional Ketosis and photobiomodulation remediate mitochondria warding off Alzheimer's disease in a diabetic, ApoE4+ patient with mild cognitive impairment: A case report.

Alzheimer's Disease (AD) is a neurodegenerative progressive disorder for which there is currently no cure. Recent research demonstrates a robust correlation between type-2 diabetes mellitus (T2DM) and the development of MCI and AD, now referred to as type-3 diabetes. Both AD and T2DM, as metabolic pathologies, can be traced to the level of mitochondrial function. The metabolic hypothesis suggests that the cause of AD might be rooted in mitochondrial dysfunction accompanied by fuel shortage in the brain. Although glucose is known to be the deferred source of fuel for cells, ketone bodies have been observed to provide metabolically compromised brain cells with an alternative fuel source, bypassing deficiencies in GLUT transport due to increased insulin resistance. By keeping glucose and insulin levels low to allow for the production of ketones, there is evidence that mitochondrial function will be restored and cognition/memory improved. Further, visible red or near-infrared (NIR) light has been shown to heal and stimulate damaged tissue by interacting with the mitochondria to restore function. This case study evaluates the effects of a 10-week clinically prescribed ketogenic nutrition protocol combined with transcranial photobiomodulation (PBM) with a 59-year-old male, heterozygous ApoE4 carrier, with a dual diagnosis of mild AD and an 11 year history of insulin dependent type 2 diabetes (T2DM). Statistically significant results reflect an 83% reduction in HOMA-IR; 64% decrease in the triglyceride/HDL ratio; HgA1c reduction from 9.44% to 6.4%; 57% decrease in VLDL and triglycerides; and normalized cognition as measured via the MoCA (Montreal Cognitive Assessment), 26/30 post intervention.

Prevalence and short-term changes of cognitive dysfunction in young ischaemic stroke patients.

BACKGROUND AND PURPOSE: Information on the prevalence and course of post-stroke cognitive impairment in young stroke patients is limited. The aim was to assess a consecutive sample of acute young ischaemic stroke patients (18-55 years) for the presence and development of neuropsychological deficits. METHODS: Patients prospectively underwent a comprehensive clinical and cognitive assessment, examining general cognitive function, processing speed, attention, flexibility/executive function and word fluency within the first 3 weeks after hospital admission (median assessment at day 6) and at a 3 months' follow-up (FU). Cognitive dysfunction was defined in comparison to age-standardized published norms. RESULTS: At baseline (N = 114), deficits were highly prevalent in processing speed (56.0%), flexibility/executive function (49.5%), attention (46.4%) and general cognitive function (42.1%). These frequencies were comparable for those with FU assessment (N = 87). In most domains, cognitive performance improved within 3 months, except for word fluency. However, in about one-third of patients, cognitive deficits (as defined by 1.5 standard deviations below the standardized mean) were still present 3 months after stroke. At FU, 44.0% were impaired in the domain flexibility/executive function, 35.0% in processing speed and 30.0% in attention. CONCLUSIONS: The high prevalence of cognitive deficits in acute young patients with ischaemic stroke highlights the importance of early post-stroke cognitive assessment to capture a patient's dysfunction in a comprehensive manner and to offer adequate rehabilitation. The role of factors which promote neuropsychological deficits needs further exploration.

Evaluation of a vaccine passport to improve vaccine coverage in people living with HIV.

An increased risk of vaccine-preventable infections (VPIs) is seen in people living with HIV (PLWH), and current vaccine coverage and immunity is variable. Vaccine passports have the potential to improve vaccine coverage. The objective was to assess how successful a vaccine passport was in improving vaccine coverage in PLWH. Baseline immunity to VPIs was established in PLWH attending a single HIV clinic and vaccinations required were determined based on the BHIVA Vaccination Guidelines (2015). The passport was completed and the PLWH informed about additional vaccines they should obtain from primary care. After 6-9 months the passport was reviewed including confirmation if vaccines were given. PLWH satisfaction with the system was evaluated by a survey. Seventy-three PLWH provided sufficient data for analysis. At baseline significant proportions of PLWH were not immune/unvaccinated to the main VPIs, especially human papillomavirus, pneumococcus and measles. After the passport was applied immunity improved significantly (56% overall, p < 0.01) for most VPIs; however, full coverage was not achieved. The system was popular with PLWH. The passport was successful in increasing vaccination coverage although full or near-full coverage was not achieved. A more successful service would probably be achieved by commissioning English HIV clinics to provide all vaccines.

Correction: Combination of inverse electron-demand Diels-Alder reaction with highly efficient oxime ligation expands the toolbox of site-selective peptide conjugations.

Correction for 'Combination of inverse electron-demand Diels-Alder reaction with highly efficient oxime ligation expands the toolbox of site-selective peptide conjugations' by S. Hörner, et al., Chem. Commun., 2015, DOI: 10.1039/c5cc03434e.

Combination of inverse electron-demand Diels-Alder reaction with highly efficient oxime ligation expands the toolbox of site-selective peptide conjugations.

A modular approach combining inverse electron-demand Diels-Alder coupling (DARinv) and oxime ligation expands the toolbox of bioorthogonal peptide chemistry. Applicability of versatile site-specific bifunctional building blocks is demonstrated by generation of defined conjugates comprising linear, cystine-bridged and multi-disulfide functional peptides as well as their conjugation with hybrid silsesquioxane nanoparticles.

Comparative evaluation of standardized ileal amino acid digestibility in protein supplements for piglets.

Standardized ileal digestibility (SID) of AA was determined in 6 protein ingredients for piglets. A basal diet based on corn (Zea mays) starch and casein was supplemented with fluid-bed-dried porcine intestinal mucosa hydrolysate, spray-dried porcine intestinal mucosa hydrolysate, soy (Glycine max) protein concentrate, 2 batches of soy protein, or full-fat soybeans. The SID of AA did not differ between the 4 soybean products (P > 0.05). Compared to most SID values in the 4 soybean products, SID of AA were lower in the 2 porcine intestinal mucosa hydrolysates (P ≤ 0.05). In conclusion, although the initial trypsin inhibitor contents in the raw soybeans have not been determined, high SID values in the 4 soybean products indicate that the different processing procedures used to manufacture these products were efficient to inactivate trypsin inhibitors. For most AA in the 2 porcine intestinal mucosa hydrolysates, drying procedure did not affect SID of AA, but SID values were generally lower compared to the 4 soybean products.

Symptomatic stenosis of the vertebrobasilar arteries: results of extra- and intracranial stent-PTA.

BACKGROUND AND PURPOSE: About half of all transient ischaemic attacks (TIAs) or strokes in the posterior circulation are caused by the arterial stenosis. The purposes of this study were to determine the safety of stent-assisted percutaneous transluminal angioplasty (stent-PTA) and its efficacy for the prevention of recurrent stroke in patients with symptomatic artery stenosis in the extra- and intracranial posterior circulation. METHODS: Forty-six patients with a previous stroke or TIA who received balloon-mounted coronary stents for vertebral artery origin stenosis (VAOS; 29 patients) or self-expanding nitinol stents for vertebrobasilar intracranial stenosis (VBIS; 17 patients) were followed-up for a mean of 24.1 (VAOS) and 12.7 (VBIS) months. RESULTS: When all cause morbidity/mortality within 30 days from stent-PTA and stroke or death from stroke in the treated vascular territory during the first 12 months of follow-up are combined, the incidence of periprocedural complications and disease progression for the first year is 10.3% in VAOS patients and 17.6% in the VBIS group. Vessel restenosis >/=50% was found in 52.0% of VAOS and in 32.1% of VBIS patients who completed 6 months follow-up. CONCLUSIONS: We observed a higher periprocedural complication rate for patients with VBIS and a higher rate of restenosis in VAOS patients after stent-PTA for symptomatic artery stenosis.

Concepções de cuidado na visão de doutorandas de Enfermagem / Conceptions of caring held by Nursing PhD students

Trata-se de uma pesquisa exploratória com abordagem qualitativa desenvolvida durante uma disciplina no Curso de Doutorado na Universidade Federal de Santa Catarina, em 2007, com o objetivo de analisar o conceito de cuidado junto a um grupo de doutorandas. Entende-se o cuidado como uma arte em que os seres humanos podem expressar-se e interagir entre si. Na coleta de dados, foi solicitado para 24 doutorandas que descrevessem por escrito o cuidado ontem, hoje e amanhã. Elas o destacaram como ligado à mulher, uma forma de interação e tecnologia. A análise das formas de cuidado apontou aspectos relativos ao referido conceito na enfermagem, na medida em que se apreendem novas perspectivas, buscando mais eficiência, com dignidade e ética, e menor custo humano e político. O caminho a se percorrer em busca de cuidado com qualidade e valorização ainda é árduo e longo.

This qualitative, exploratory study examined the concept of care among a group of PhD students, during a discipline of the PhD nursing program at Santa Catarina Federal University, Brazil, in 2007. Care is understood here as an art in which people can both express themselves and interact with each other. Data were collected by asking 24 PhD students to describe care in the past, today and in the future. Their replies identified care as connected with women, as a form of interaction and as technology. Analysis of the forms of care they described pointed to aspects of this concept in Nursing, in that new outlooks are learned, with a view to greater efficiency, dignity and ethics at lower human and political cost. Achieving quality care and due recognition will demand both hard work and long-term effort.

Se trata de una investigación exploratoria con abordaje cualitativo desarrollada durante una disciplina en el Curso de Doctorado en la Universidad Federal de Santa Catarina – Brasil, en 2007, con el objetivo de analizar el concepto de cuidado junto a un grupo de doctorandas. Se entiende el cuidado como un arte en que los seres humanos pueden expresarse e interactuar entre si. En la recolección de datos, fue solicitado para 24 doctorandas que describiesen por escrito el cuidado ayer, hoy y mañana. Ellas lo destacaron como ligado a la mujer, una forma de interacción y tecnología. El análisis de las formas de cuidado apuntó aspectos relativos al referido concepto en la enfermería, en la medida en que se aprehenden nuevas perspectivas, buscando más eficiencia, con dignidad y ética, y menor coste humano y político. El camino a recorrerse en busca de cuidado con calidad y valorización todavía es arduo y largo.

Short communication: Association analysis of microsatellites and Mycobacterium avium subspecies paratuberculosis antibody response in German Holsteins.

Paratuberculosis in ruminants is characterized by chronic granulomatous enteritis, resulting in persistent diarrhea and progressive wasting of cattle infected with Mycobacterium avium ssp. paratuberculosis (MAP). The disease occurs worldwide with high frequency, leading to growing economic losses in beef and dairy industries. The objective of this study was to investigate associations of microsatellites (BMC9006, BB704, BB705, BB717, BB719, BMS1617, BB702, and BOBT24) located near or within candidate genes involved in response mechanisms to paratuberculosis. Pedigree information existed for 4,686 German Holstein cows that had routinely been screened for MAP status using commercially available serum antibody ELISA test. The immunoglobulin G cutoff level was used to classify all animals as positive or negative for paratuberculosis. A total of 594 (12.7%) cows tested positive for paratuberculosis. The control group comprised 585 animals testing negative for MAP. Microsatellite BMC9006 had only 3 alleles (2 of which occurred at very low frequencies in the present data set) and was therefore not informative; the remaining microsatellites showed 3 to 12 alleles. Fisher's exact and chi2 tests revealed no significant differences in microsatellite allele frequencies between the 2 groups of German Holstein cows testing positive or negative for paratuberculosis.

Detection of bovine viral diarrhoea virus infected cattle--testing tissue samples derived from ear tagging using an Erns capture ELISA.

A new diagnostic approach testing tissue samples derived from cattle ear tagging for bovine viral diarrhoea virus (BVDV) antigen in a commercially available antigen capture enzyme-linked immunosorbent assay (ACE) was developed. To validate this method, 99 positive and 469 negative samples were tested. With those samples the assay yielded a sensitivity of 100% and specificity of >or=99.6%. Serum and ear tissue samples from 11 persistently infected (PI) BVDV calves were tested. While serum samples were negative after intake of colostrum, the ear tissue samples could be detected positive for BVDV all the time. Testing multiple samples derived from the same ear from PI cattle yielded positive results and low variation. Using cattle ear tags combining the ear tag application with sampling of a small ear tissue plug and testing those tissue samples with an ACE could be a reliable and economic way of BVDV testing.

Neuropathological studies on cycloate-induced neuronal cell death in the rat brain.

The herbicide cycloate (carbamothioic acid, ethyl(cyclohexyl)-S-ethyl ester) given as a single oral dose to rats, caused selective neuronal cell death in two regions in the rat forebrain, the pyramidal neurons of layers II-III throughout the pyriform cortex and in granule cells of the caudal ventro-lateral dentate gyrus. Male Alderley Park rats, 6-8-week-old, were given a single oral dose of either 0 or 2000 mg/kg cycloate and killed for neuropathological investigation 1, 2, 3, 7, 14 or 28 days after dosing, using a regime of perfusion fixation with modified Karnovsky's fixative, followed by routine paraffin embedding. Seven transverse levels of brain were examined from each rat. Cycloate-induced neuronal cell death was seen in the pyriform cortex 1 day after dosing and persisted through to Day 28, the lesion was more marked in the rostral compared to the caudal region of the pyriform cortex. Neuronal cell death was also observed in the ventro-lateral caudal dentate gyrus on Days 1-14, day after dosing. In the early stages, Days 1-3 and to a lesser extent Day 7, the neuronal cell death resembled apoptosis, characterized by condensation of nuclear material, cell shrinkage and strong cytoplasmic eosinophilia. By Days 14 and 28 and to a lesser extent Day 7, the cell death resembled necrosis, i.e. karyorrhectic nuclei with pale irregular cytoplasm. Microglial accumulation was associated with the neuronal cell injury. In control brains, an occasional apoptotic body was seen in both the pyriform cortex and dentate gyrus. Our results demonstrate that cycloate is a novel neurotoxicant, which following a single large oral dose induces a cell specific and highly localized forebrain lesion. The time course data analyzed temporally, suggests that cycloate may cause an up regulation of apoptosis in selected regions of the adult brain.

Asthma management efficacy of school nurses in Taiwan.

As the key health care providers in school settings, the school nurses' asthma management efficacy is crucial to children's health and their continued participation in school learning activities. This article describes the psychometric testing of the asthma management efficacy scale (AMES) for use with school nurses. A cross-sectional survey design was used to assess the asthma management efficacy of 60 school nurses in Taipei, Taiwan. Factor analysis resulted in four factor domains including asthma medication administration, asthma pattern identification, school management behaviour, and monitoring peak expiratory flow rate which explained 76.4% of the variance in school nurses' asthma management efficacy. The school nurses' experience in performing school asthma management activities was positively correlated to their asthma management efficacy (r=0.33, p<0.05). School nurses who had experience with the inhaled asthma medicines had significantly higher efficacy scores on the medication administration subscale (t=-2.89, p<0.01) than did the school nurses who lacked this experience. School nurses who had experience in using peak expiratory flow meters had significantly higher efficacy scores on the total AMES (t=-1.90, p<0.05) and on the monitoring peak expiratory flow rate subscale (t=-5.37, p<0.001) than the school nurses who lacked this experience. Given the need to have nurses who are well prepared to provide asthma care in school settings, implications for nursing education, practice, and further research are discussed.

Cigarettes: a growing problem for Taiwanese adolescents.

An alarming number of Taiwanese teenagers continue to smoke despite the adverse health consequences of cigarette smoking. This research review describes the prevalence and onset of smoking behavior among Taiwanese adolescents and analyzes the risk factors contributing to smoking initiation. The findings of this review suggest that health educators need to target high-risk groups before they initiate smoking. High-risk groups are those who have poor school achievement, have an external locus of control, have a prosmoking attitude, know others who smoke, and are from low socioeconomic status families. These risk factors support the need for nurses to implement an effective smoking prevention program for adolescents.

Stabilization of a fibronectin type III domain by the removal of unfavorable electrostatic interactions on the protein surface.

It is generally considered that electrostatic interactions on the protein surface, such as ion pairs, contribute little to protein stability, although they may play important roles in conformational specificity. We found that the tenth fibronectin type III domain of human fibronectin (FNfn10) is more stable at acidic pH than neutral pH, with an apparent midpoint of transition near pH 4. Determination of pK(a)'s for all the side chain carboxyl groups of Asp and Glu residues revealed that Asp 23 and Glu 9 have an upshifted pK(a). These residues and Asp 7 form a negatively charged patch on the surface of FNfn10, with Asp 7 centrally located between Asp 23 and Glu 9, suggesting repulsive electrostatic interactions among these residues at neutral pH. Mutant proteins, D7N and D7K, in which Asp 7 was replaced with Asn and Lys, respectively, exhibited a modest but significant increase in stability at neutral pH, compared to the wild type, and they no longer showed pH dependence of stability. The pK(a)'s of Asp 23 and Glu 9 in these mutant proteins shifted closer to their respective unperturbed values, indicating that the unfavorable electrostatic interactions have been reduced in the mutant proteins. Interestingly, the wild-type and mutant proteins were all stabilized to a similar degree by the addition of 1 M sodium chloride at both neutral and acidic pH, suggesting that the repulsive interactions between the carboxyl groups cannot be effectively shielded by 1 M sodium chloride. These results indicate that repulsive interactions between like charges on the protein surface can destabilize a protein, and protein stability can be significantly improved by relieving these interactions.

Predominantly BCR-ABL negative myeloid precursors in interferon-alpha treated chronic myelogenous leukemia: a follow-up study of peripheral blood colony-forming cells with fluorescence in situ hybridization.

The mechanism and target cell of the life-prolonging effect of interferon-alpha (IFN-alpha) in chronic myelogenous leukemia (CML) are controversial. We studied the influence of IFN-alpha treatment on the frequency of malignant hematopoietic precursor cells in the peripheral blood (PB) of CML patients during the course of the disease. PB 10-day colony-forming cells (PB-CFCs) were assessed with regard to their quantity, lineage distribution, and BCR-ABL status, as determined by fluorescence in situ hybridization (FISH). PB-CFC numbers were determined in 39 patients (29 in the chronic phase, 6 in an advanced stage, and 4 with progression to an advanced stage during follow-up). Thirty-one patients were evaluated either once or several times to determine the BCR-ABL status of the colonies. BCR-ABL negative PB-CFCs were detectable at diagnosis in 5 of 11 patients. A major reduction of BCR-ABL positive colonies to <25% of PB-CFCs was observed in 10/13 determinable IFN-alpha treated patients in early and late chronic phases, indicating a high proportion of BCR-ABL negativity at the clonogenic cell level. In contrast, only 3 of these patients had a cytogenetic response of <25% Philadelphia chromosome (Ph1)-positive metaphases in bone marrow cytogenetics. Treatment with IFN-alpha and/or hydroxyurea (HU) during chronic phase was accompanied by a reduction of PB-CFCs to subnormal levels (median 24 CFCs/ml) compared to controls (median 207 CFCs/ml), untreated patients in chronic phase (median 25,979 CFCs/ml), and patients with advanced disease (median 6,047 CFCs/ml). In blast crisis (6 patients), all colonies tested were BCR-ABL positive. Our results show that IFN-alpha treatment leads to a marked reduction of malignant myeloid precursor cells in the PB of CML patients, which exceeds the degree of cytogenetic remission. This offers an explanation for the good therapeutic efficacy and even life-prolonging effect of IFN-alpha, which is also observed in cytogenetic non-responders.

Correlates of recent suicide attempts in a triethnic group of adolescents.

PURPOSE: To describe recent self-reported suicide attempts in a triethnic group of adolescents, to analyze differences in the correlates of attempts by ethnicity and gender, and to explore theoretical correlates of recent suicide attempts using a resilience framework. METHODS: Quantitative data were collected from 10,059 students in 7th, 9th, and 11th grades in Connecticut in 1996. Secondary analysis was done to compare respondents of African American, Hispanic Latino, and Caucasian ethnicities. Data were analyzed using bivariate and multivariate procedures. Logistic regression was used to identify the best set of explanatory variables for recent suicide attempts. RESULTS: The percentage of suicide attempts was significantly higher among Hispanic Latina girls (19.3%) than in any other ethnic-gender group. Significant relationships were found between recent suicide attempts and (a) family history of suicide attempt, (b) friend's history of suicide attempt, (c) history of sexual abuse, (d) history of physical abuse, and (e) environmental stress. The significant set of explanatory variables for recent suicide attempts for the three ethnic groups combined were stress, internalizing and externalizing behaviors, physical and sexual abuse, family and friend attempted suicide, social connectedness, and religious influence. CONCLUSIONS: Findings support use of a resilience model for suicide attempts among three ethnic groups. The finding of a significantly higher percentage of recent suicide attempts by Hispanic girls compared to girls in other ethnic-gender groups warrants further investigation along with development and testing of culturally sensitive preventive interventions.

Using focus group methods with middle school children.

Focus group methods are an effective way to clarify middle school children's perceptions of health and illness. Children between 11 and 14 years of age, who are undergoing the developmental transition from child to adolescent, tend to be reticent when talking with adult strangers. However, they are more relaxed and willing to share perceptions when discussions are held with a group of peers. Conducting focus groups involves developing an interview guide, arranging the meeting place, supporting group building, and encouraging participation by the group members while discouraging domination by influential members. Data analysis begins during the focus group session as issues emerge in the context of group discussions.

The association between the diameter of a patent foramen ovale and the risk of embolic cerebrovascular events.

PURPOSE: We sought to determine whether the size of a patent foramen ovale affected the risk of embolic cerebrovascular events of unknown origin. PATIENTS AND METHODS: We ascertained the presence and measured the size of patent foramen ovale using multiplane transesophageal echocardiography in 121 consecutive patients younger than 60 years who had transient ischemic attacks or ischemic strokes and in 123 control subjects. None of the patients had left heart, aortic, or carotid sources of embolism, or echocardiographic signs of elevated left or right atrial pressure. We used multivariate logistic regression to determine whether the size of the patent foramen ovale was an independent risk factor for cerebrovascular events. RESULTS: The mean (+/- SD) diameter of a patent foramen ovale was significantly larger in patients (4 +/- 2 mm) than in control subjects (2 +/- 1 mm, P <0.0001). A patent foramen ovale greater than 4 mm was associated with an increased risk of transient ischemic attacks [odds ratio (OR) = 3.4; 95% confidence interval (CI), 1.0 to 11, P = 0.04], ischemic strokes (OR = 12; 95% CI, 3.3 to 44, P = 0.0001), and, especially, having evidence of two or more strokes (OR = 27; 95% CI, 4.7 to 160, P = 0.0002). CONCLUSION: The diameter of a patent foramen ovale is an independent risk factor for ischemic events, especially recurrent strokes.