Conditions influencing the in vitro antifungal activity of lactoferrin combined with antimycotics against clinical isolates of Candida. Impact on the development of buccal preparations of lactoferrin

Lactoferrin, an iron-binding glycoprotein, is a potential agent for the treatment of oropharyngeal Candidiasis. The aim of the present study was to test the capability of lactoferrin, combined or not combined with conventional antifungal agents, to inhibit the growth of different Candida species under various experimental conditions to be of guidance in the development of a suitable pharmaceutical formulation containing lactoferrin. The anti-Candida activities of lactoferrin were considerably higher using RPMI instead of SLM as assay medium. They were moreover increased by raising the medium pH from 5.6 to 7.5. With the 'standard' antifungal agent fluconazole similar results were found as for lactoferrin, but the medium type and pH did not affect MIC values of amphotericin B. The addition of saliva to medium did not reduce the antifungal activities of the individual compounds. Synergistic inhibitory effects on Candida growth were found for combinations of lactoferrin and fluconazole or amphotericin B, irrespective of the medium type and pH, or the addition of saliva. This indicates that for treatment of oral Candidiasis a formulation containing lactoferrin seems appropriate; results may be optimized if the formulation is provided with buffer capacity to attain pH 7.5 in the mucosal fluid. The synergistic effects between lactoferrin and 'standard' antifungals indicate that combinations should be considered in such a formulation.     

Neurovegetative symptoms in multiple sclerosis: relationship to depressed mood, fatigue, and physical disability.

Some authors have suggested that when evaluating depression in multiple sclerosis (MS) patients, neurovegetative symptoms should be discounted and/or not considered, given the ostensibly high overlap between symptoms of MS (e.g., sleep disturbance, fatigue) and neurovegetative symptoms of depression. A further assertion is that inclusion of items assessing neurovegetative symptoms may artificially inflate overall depression scores and that mood scales may provide more accurate indices of depression in MS patients. The current study investigated the possibility that some neurovegetative symptoms may be specifically related to MS patients' depressed mood and are not simply indicators of physical disability and/or fatigue. Seventy-six clinically definite MS patients in the northwestern United States were administered two depression inventories and measures of physical disability and fatigue as part of a larger study. Results revealed that one neurovegetative symptom--disinterest in sex--was uniquely associated with depressed mood, and other neurovegetative symptoms were associated with both depression and fatigue but not physical disability. The present findings suggest that certain neurovegetative symptoms are differentially associated with depression, fatigue, and physical disability in MS. Routinely discounting all neurovegetative symptoms when assessing depression in MS patients may thus be unwarranted.     

Association of clinical outcome assessments of mobility capacity and incident disability in community-dwelling older adults - a systematic review and meta-analysis

The objective of the present review is to synthesize all available research on the association between mobility capacity and incident disability in non-disabled older adults. MEDLINE, EMBASE and CINAHL databases were searched without any limits or restrictions until February 2021. Published reports of longitudinal cohort studies that estimated a direct association between baseline mobility capacity, assessed with a standardized outcome assessment, and subsequent development of disability, including initially non-disabled older adults were included. The risk of bias was assessed using the Quality in Prognosis Studies (QUIPS) tool. Random-effect models were used to explore the objective. The certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. The main outcome measures were the pooled relative risks (RR) per one conventional unit per mobility assessment for incident disability. A total of 40 reports (85,515 participants at baseline) were included. For usual and fast gait speed, the RR per −0.1 m/s was 1.23 (95% CI: 1.18–1.28; 26,638 participants) and 1.28 (95% CI: 1.19–1.38; 8161 participants), respectively. Each point decrease in Short Physical Performance Battery score increased the risk of incident disability by 30% (RR = 1.30, 95% CI: 1.23–1.38; 9183 participants). The RR of incident disability by each second increase in Timed Up and Go test and Chair Rise Test performance was 1.15 (95% CI: 1.09–1.21; 30,426 participants) and 1.07 (95% CI: 1.04–1.10; 9450 participants), respectively. The review concludes that among community-dwelling non-disabled older adults, poor mobility capacity is a potent modifiable risk factor for incident disability. Mobility impairment should be mandated as a quality indicator of health for older people.     

Prevalence, correlates, co-morbidity, and comparative disability of DSM-IV generalized anxiety disorder in the USA: results from the National Epidemiologic Survey on Alcohol and Related Conditions

BACKGROUND: This study addressed the prevalences, correlates, co-morbidity and disability of DSM-IV generalized anxiety disorder (GAD) and other psychiatric disorders in a large national survey of the general population, the National Institute on Alcohol Abuse and Alcoholism's (NIAAA) National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). The study presents nationally representative data, for the first time, on prevalence, correlates, co-morbidity, and comparative disability of DSM-IV GAD.METHOD: Data are taken from a large (n=43093) representative sample of the adult USA population.R: Prevalences of 12-month and lifetime GAD were 2.1% and 4.1%. Being female, middle-aged, widowed/separated/divorced, and low income increased risk, while being Asian, Hispanic, or Black decreased risk. GAD was highly co-morbid with substance use, and other anxiety, mood, and personality disorders. Co-morbidity in GAD was not substantially greater than for most other Axis I and II disorders. Disability and impairment in pure GAD were equivalent to pure mood disorders, but significantly greater than in pure substance use, and other anxiety and personality disorders. Individuals co-morbid for GAD and each mood disorder were more disabled than those with pure forms of GAD or each mood disorder. When co-morbid with GAD, nicotine dependence and other anxiety and personality disorders were not associated with increased disability over that associated with pure GAD, but GAD did show increased disability over that due to each of these disorders in pure form.Conclusions. Associations between GAD and Axis I and II disorders were strong and significant, with variation among specific disorders. Results strongly support GAD as an independent disorder with significant impairment and disability.     

Immune depression in African trypanosomiasis: the role of antigenic competition.

The capacity of trypanosome-infected cattle to mount an immune response to a simultaneous or subsequent challenge with other trypanosomes was investigated using various clones of Trypanosoma congolense and T. brucei. In animals infected simultaneously with equal numbers of trypanosomes of two different clones, the variant-specific antibody response to one clone was severely depressed while the response to the other was not affected. In cattle infected with one clone and then subsequently challenged severely depressed depending on the time interval between the two inoculations. These observations were consistent regardless of whether the clones of trypanosomes used were derived from the same or different species. The characteristics of these responses would suggest that the inability of trypanosome-infected cattle to respond well to a simultaneous or subsequent challenge with other trypanosomes or other antigens may be due to antigenic competition.     

A Review of Cognitive Outcomes in Children Following Perinatal Stroke

Perinatal stroke is a significant cause of congenital neurological disability. Although motor deficits and epilepsy are relatively easy to identify, developmental and behavioral co-morbidities are more complex and challenging to define. We provide an overview of perinatal stroke syndromes and theories relating injury in the developing brain to long-term outcomes. We present a comprehensive overview of the effects on intelligence and other specific cognitive domains, as well as investigations relating clinical features and neuroimaging to deficits. Better understanding of the impact of early stroke has potential to elucidate processes of brain development, in addition to providing guidance for prognosis and rehabilitation.     

Determinants of immunogenicity and mechanisms of protection by virulent and mutant Vibrio cholerae O1 in rabbits.

The colonizing capacities of 16 Vibrio cholerae strains, including nine genetically and/or phenotypically defined parent-mutant pairs, were determined in unobstructed adult rabbit small bowel. There were marked interstrain differences in colonizing capacity, which was enhanced by bacterial motility and the production of cholera holotoxin but was unrelated to production of cholera toxin B-subunit or hemolysin or to bacterial serotype or biotype. The role of colonizing capacity and other bacterial features in determining the immunizing efficiency of live V. cholerae was studied by determining the efficiency with which graded inocula of each strain immunized against attempted recolonization of the ileum or induction of choleralike diarrhea by the RITARD (removable intestinal tie-adult rabbit diarrhea) challenge technique using standard inocula of virulent V. cholerae. Mucosal colonizing capacity was the only quantitative predictor of bacterial immunizing capacity; none of the other bacterial features cited above influenced bacterial immunogenicity against either type of challenge, except as they affected colonizing capacity. Live V. cholerae immunized much more efficiently than Formalin-killed bacteria; the former caused marked protection after a single inoculum of 10(2) CFU, whereas the latter gave only partial protection after three inoculations of 10(11) killed organisms. Protection induced by live bacteria was due largely to resistance to colonization and included marked inhibition of bacterial growth within the bowel lumen. These findings strongly suggest that an optimally efficient oral cholera vaccine would be composed of avirulent live V. cholerae selected for their capacity to colonize the small-bowel mucosa.     

Estimation of the burden of major cancers in Korea

We estimated the burden of diseases in Korea especially caused by major cancers using DALY (disability adjusted life year) measurement. Firstly, the burden of disease due to premature death was estimated by using YLLs (years life lost due to premature death) measurement developed by the global burden of disease study group. Secondly, for the calculation of the YLD (years lived with disability), the following parameters were estimated in the formula; incidence rate, case fatality rate and disability weight of major cancers. Thirdly, we estimated DALY of major cancers by adding YLLs and YLDs. The burden of major cancers for male per 100,000 population was attributed mainly to liver cancer (528.8 person-year), stomach cancer (451.4 person-year), and lung cancer (374.9 person-year). The burden of major cancers for female per 100,000 population was attributed mainly to liver cancer (140.0 person-year), stomach cancer (259.7 person-year), and lung cancer (125.2 person-year). Each of these cancers was responsible for the loss of over 100 person-year per 100,000 population based on our DALY measurement. We found the DALY method employed was appropriate to quantify the burden of disease. Thereby, it would provide a rational bases to plan a national health policy regarding the burden of disease caused by major cancers in Korea.     

Basic overview of method validation in the clinical virology laboratory

Diagnostic virology laboratories are an essential part of the health system and are often relied upon to provide information to clinicians that will inform clinical decision making. It is therefore imperative that diagnostic results produced in the laboratory are reliable. One way of ensuring quality results is by ensuring that all tests are either validated (for tests developed in‐house) or verified (for commercial assays that are FDA‐approved or CE‐labeled). In the diagnostic virology laboratory, these processes can be complex as both qualitative and quantitative measurements for serological and molecular tests are routinely offered. While there are numerous guidelines governing quality assurance in the virology laboratory, all accrediting agencies would insist on tests being validated or verified prior to implementation without providing explicit guidance to the process. As there is no universal guideline on the optimal way to perform validation/verification experiments, this review will provide a basic overview of method validation/verification, specific for clinical virology laboratories, and includes explanation of statistical analysis and acceptance/rejection criteria.     

The functional disability inventory: measuring a neglected dimension of child health status.

Described the development and validation of the Functional Disability Inventory (FDI) for school-age children and adolescents. Results provide support for construct, concurrent, and predictive validity. FDI scores also demonstrated stability over a 3-month period in patients with a chronic condition, and the instrument was sensitive to changes in patient status subsequent to medical treatment. There was some evidence that gender played a role in disability, particularly in adolescence. The instrument may be used (a) in studying individual differences in pediatric disability, (b) in examining the relation of disability to psychosocial functioning in the child and other family members, or (c) as an outcome measure in assessing the impact of interventions on patient functioning.     

An investigative study of the Bender-Gestalt: clinical validation of its use with a reading disabled population.

Investigated usefulness of the Bender-Gestalt in differentiating between primary and secondary reading disability. Research with 50 reading disabled Ss was carried out. The Ss were classified as having a primary or secondary reading disability according to selected criteria; then their Bender protocols were scored. It was hypothesized that developmental scores would differentiate the two diagnostic groups. A second hypothesis was that specific signs would differentiate between primary and secondary reading disabled children. The results supported the latter hypothesis, but not the former. Results also showed that those in the primary group were more reading retarded than secondary reading disability Ss and that Bender-Gestalt scores are not significantly related to reading level in such a group of reading disabled children.     

Occupational exposures as triggers of asthma

The prevalence of occupational asthma is rising, possibly due to the introduction of different chemicals and substances in the workplace. Etiologic agents include organic and inorganic compounds that are encountered in a variety of industries. Early diagnosis, adequate management of inflammation, and prevention of further exposure are essential to occupational asthma management. Reducing complications and disability while providing work rehabilitation should be the ultimate goal of the health care provider. This article discusses these issues and gives guidance to the clinician treating patients with possible occupational asthma.     

Improved prediction of proximal femoral fracture load using nonlinear finite element models.

Hip fracture, which is often due to osteoporosis or other conditions affecting bone strength, can lead to permanent disability, pneumonia, pulmonary embolism, and/or death. Great effort has been directed toward developing noninvasive methods for evaluating proximal femoral strength (fracture load), with the goal of assessing fracture risk. Previously, computed tomographic scan-based, linear finite element (FE) models were used to estimate proximal femoral fracture loads ex vivo in two load configurations, one approximating joint loading during single-limb stance and the other simulating impact from a fall. Measured and computed fracture loads were correlated (stance, r=0.867; fall, r=0.949). However, precision for the stance configuration was insufficient to identify subjects with below average fracture loads reliably. The present study examined whether, for this configuration, nonlinear FE models could be used to identify these subjects. These models were found to predict fracture load within +/-2.0 kN (r=0.962). This level of precision is sufficient to identify 97.5% of femora with fracture loads 1.3 standard deviations below the mean as having below average fracture loads. Accordingly, 20% of subjects with below average fracture loads, i.e. those with the lowest fracture loads and likely to be at greatest risk of fracture, would be correctly identified with at least 97.5% reliability. This FE modeling method will be a powerful tool for studies of hip fracture.     

Independence of synaptic specificity from neuritic guidance

Neuronal circuits are interconnected with a high degree of specificity. While axonal guidance has been demonstrated to be crucial for the choice of the correct target region, its role in specificity at the level of individual cells remains unclear. Specificity of synapse formation may either result from precise guidance of axonal outgrowth onto the target or depend on a molecular "match" between pre- and postsynapse. To distinguish between these possibilities, an in vitro system was used in which neuritic outgrowth of rat cortical neurons is accurately guided along the narrow pathways of a surface micropattern. The micropattern consisted of a blend of extracellular matrix molecules applied to a cell repellent background of polystyrene by microcontact printing. The system reproduces guidance by attractant and repellent surface cues while no other signals that may influence synapse formation, like gradients of trophic factors or accumulations of signaling molecules, are provided. While the number of contact points between neighboring cells was strongly reduced on patterned substrates due to the geometrical restrictions, frequency of synapse formation was not different from homogeneous cultures. Thus it was unaffected by stringent guidance onto the target cell or by the number of cell-cell contacts. Moreover, a statistically significant enrichment of reciprocal contacts between mixed pairs of excitatory and inhibitory neurons over probabilistic predictions was found, which has similarly been shown by others in dissociated neuronal cultures. Our results indicate that precise axonal guidance is insufficient for target-specific synapse formation and suggest that instead recognition between individual cells is required.     

基于脉搏波检测技术的心血管健康评测

脉搏波中蕴含丰富的生理病理信息,能反映心功能参数的早期变化趋势。因此,脉搏波信息的量化对心血管疾病具有重要的参考价值。从脉搏波的形成机制角度,阐述脉搏波与心血管生理病理信息的关系;从脉搏波的波形分析,阐述临床中应用脉搏波技术的心血管无创检测指标;将心血管的生理病理信息和脉搏波理论相结合,建立评测心功能健康状况的评价指标。基于脉搏波理论建立的心血管无创检测方法,有助于全面维护心血管健康,为心血管系统疾病的早发现、早预防、早治疗提供重要医疗手段;其次,可以简化临床检测过程,降低检测成本,实现心血管疾病适时地健康普检,降低心血管疾病的致死率和致残率。     

A newly prepared surface-treated oxystarch for removal of urea

There is an urgent need to develop an efficient technique to remove urea from the blood or gastrointestinal tract of uremic patients. Activated charcoals have a low sorption capacity for urea although they effectively remove other uremic toxic substances. To provide an urea-reactive adsorbent, a chemically modified oxystarch with albumin or gelatin has been prepared. Elemental analysis and Fourier transform infrared (FT-IR) spectroscopic analysis demonstrate that the reaction of a small amount of protein (albumin or gelatin) with oxystarch has taken place possibly by chemical combination. The influence of the dialdehyde content of the oxystarch on urea sorption, its sorption isotherm, and the adsorption rates have been investigated. It was found that the swelling factor of the oxystarch is closely related to the sorption activity under physiological conditions (pH 7.2-7.4 at 37 degrees C). Adsorption studies have shown that sorption capacity is increased by surface treatment and can reach 6-8.2 g urea/kg-dried adsorbent (initial urea concentration was 70 mg/dL). The oxystarch had 49.2% of glucose unit oxidized and was surface treated with albumin. These results suggest that the newly prepared surface-treated oxystarch would be utilized as an effective chemisorbent for urea removal under physiological conditions.     

Neuropsychological profiles of children diagnosed as specific language impaired with and without hyperlexia.

This study compared the neuropsychological profiles of 46 children with Specific Language Impairment (SLI) and 16 children with SLI and Hyperlexia (SLI + H). The results indicated that the essential feature of Hyperlexia is Specific Language Impairment and not reading disability. Thus, Hyperlexia would be best conceptualized as a subgroup of Developmental Language Disorder rather than as a subgroup of Developmental Dyslexia. Further, the SLI + H group exhibited significantly better developed visual/spatial memory which, along with average visual perceptual skills, appears to be the major contributing factor to their elevated word recognition and spelling ability. Finally, it should be noted that both groups of children exhibited decreasing performance on tasks of immediate auditory/verbal memory as the language/semantic demands of the memory task increased. This finding appears to be the result of a limited capacity for immediate verbal processing and not the result of a deficit in verbal learning and recall.     

Down syndrome as a model of DNA polymerase beta haploinsufficiency and accelerated aging

Down syndrome is a condition of intellectual disability characterized by accelerated aging. As with other aging syndromes, evidence accumulated over the past several decades points to a DNA repair defect inherent in Down syndrome. This evidence has led us to suggest that Down syndrome results in reduced DNA base excision repair (BER) capacity, and that this contributes to the genomic instability and the aging phenotype of Down syndrome. We propose important roles for microRNA and/or folate metabolism and oxidative stress in the dysregulation of BER in Down syndrome. Further, we suggest these pathways are involved in the leukemogenesis of Down syndrome. We have reviewed the role of BER in the processing of oxidative stress, and the impact of folate depletion on BER capacity. Further, we have reviewed the role that loss of BER, specifically DNA polymerase beta, plays in accelerating the rate of aging. Like that seen in the DNA polymerase beta heterozygous mouse, the aging phenotype of Down syndrome is subtle, unlike the aging phenotypes seen in the classical progeroid syndromes and mouse models of aging. As such, Down syndrome may provide a model for elucidating some of the basic mechanisms of aging.     

Central nervous system involvement in arthrogryposis multiplex congenita: Overview of causes,diagnosis, and care

Arthrogryposis or AMC, arthrogryposis multiplex congenita, is defined as multiple congenital joint contractures in more than two joints and in different body areas. The common cause of all AMC is lack of movement in utero, which in turn can have different causes, one of which is CNS involvement. Intellectual disability/CNS involvement is found in approximately 25% of all AMC. AMC with CNS involvement includes a large number of genetic syndromes. So far, more than 400 genes have been identified as linked to AMC, with and without CNS involvement. A number of neonatally lethal syndromes and syndromes resulting in severe disability due to CNS malfunction belong to this group of syndromes. There are several X‐linked disorders with AMC, which are primarily related to intellectual disability. A number of neuromuscular disorders may include AMC and CNS/brain involvement. Careful clinical evaluation by a geneticist and a pediatrician/pediatric neurologist is the first step in making a specific diagnosis. Further investigations may include MRI of the brain and spinal cord, electroencephalogram, blood chemistry for muscle enzymes, other organ investigations (ophtalmology, cardiology, gastrointestinal, and genitourinary systems). Nerve conduction studies, electromyogram, and muscle pathology may be of help when there is associated peripheral nervous system involvement. But most importantly, genetic investigations with targeted or rather whole exome or genome sequencing should be performed. A correct diagnosis is important in planning adequate treatment, in genetic counselling and also for future understanding of pathogenic mechanisms and possible new treatments. A multidiciplinary team is needed both in investigation and treatment.