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1.
J Hosp Infect ; 127: 1-6, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35671861

ABSTRACT

BACKGROUND: The COVID-19 (SARS-CoV-2) pandemic has increased infection control vigilance across several modes of patient contact. However, it is unknown whether hygiene pertaining to stethoscopes, which carry the potential for pathogenic contamination, has also shifted accordingly. AIM: To characterize pandemic-related changes in stethoscope hygiene. METHODS: We surveyed healthcare providers at three major medical centres. Questions quantitatively (Likert scale and frequency) assessed stethoscope hygiene beliefs and practices with two components: before and during COVID-19. Participants were grouped based on performance of optimal stethoscope hygiene (after every patient) before and during COVID-19. Groups were compared using χ2 and analysis of variance (ANOVA). FINDINGS: Of the 515 (10%) who completed the survey, 55 were excluded (N = 460). Optimal hygiene increased from 27.4% to 55.0% (P < 0.001). There were significant increases in Likert scores for all questions pertaining to knowledge of stethoscope contamination (P < 0.001). Belief in stethoscope contamination increased (P < 0.001) despite no change in perceived hygiene education. Resident physicians were less likely compared with attending physicians and nurses to have adopted optimal hygiene during COVID-19 (P < 0.001). CONCLUSION: Despite a positive shift in stethoscope hygiene during COVID-19, optimal hygiene was still only performed by around half of providers. Educational interventions, particularly targeting early-career providers, are encouraged.


Subject(s)
COVID-19 , Stethoscopes , COVID-19/prevention & control , Cross-Sectional Studies , Disinfection , Humans , Hygiene , SARS-CoV-2
3.
Neurourol Urodyn ; 38(8): 2194-2199, 2019 11.
Article in English | MEDLINE | ID: mdl-31532853

ABSTRACT

OBJECTIVES: Limited data exist on the risks of complications associated with a suprapubic catheter (SPC) insertion. Bowel injury (BI) is a well-recognized albeit uncommon complication. Guidelines on the insertion of SPC have been developed by the British Association of Urological Surgeons, but there remains little evidence regarding the incidence of this complication. This study uses contemporary UK data to assess the incidence of SPC insertion and the rate of BI and compares to a meta-analysis of available papers. METHODS: National Hospital Episodes Statistics data were searched on all SPC insertions over an 18-month period for operating procedure codes, Code M38.2 (cystostomy and insertion of a suprapubic tube into bladder). Patients age, 30-day readmission rates, 30-day mortality rate, and catheter specific complication rate were collected. To estimate the BI rate, we searched patients who had undergone any laparotomy or bowel operation within 30 days of SPC insertion. Trusts were contacted directly and directed to ascertain whether there was SPC-related BI. PubMed search to identify papers reporting on SPC related BI was performed for meta-analysis RESULTS: 11 473 SPC insertions took place in the UK in this time period. One hundred forty-one cases had laparotomy within 30 days. Responses from 114 of these cases reported one BI related to SPC insertion. Meta-analysis showed an overall BI rate of 11/1490 (0.7%). CONCLUSIONS: This is the largest dataset reported on SPC insertions showing a lower than previously reported rate of BI. We recommend clinicians use a risk of BI of less than 0.25% when counseling low-risk patients.


Subject(s)
Cystostomy/adverse effects , Digestive System Surgical Procedures/statistics & numerical data , Intestines/injuries , Urinary Catheterization/adverse effects , Colectomy/statistics & numerical data , Colostomy/statistics & numerical data , Humans , Intestines/surgery , Medical Audit , Mortality , Patient Readmission/statistics & numerical data , Proctectomy/statistics & numerical data , United Kingdom , Urinary Bladder
4.
J Cancer Epidemiol ; 2019: 5072506, 2019.
Article in English | MEDLINE | ID: mdl-30804999

ABSTRACT

AIM: We investigated use of mastectomy as treatment for early breast cancer in the US and applied the resulting information to estimate the minimum and maximum rates at which mastectomy could plausibly be undergone by patients with overdiagnosed breast cancer. Little is currently known about overtreatments undergone by overdiagnosed patients. METHODS: In the US, screening is often recommended at ages ≥40. The study population was women age ≥40 diagnosed with breast cancer in the US SEER 9 cancer registries during 2013 (n=26,017). We evaluated first-course surgical treatments and their associations with case characteristics. Additionally, a model was developed to estimate probability of mastectomy conditional on observed case characteristics. The model was then applied to evaluate possible rates of mastectomy in overdiagnosed patients. To obtain minimum and maximum plausible rates of this overtreatment, we respectively assumed the cases that were least and most likely to be treated by mastectomy had been overdiagnosed. RESULTS: Of women diagnosed with breast cancer at age ≥40 in 2013, 33.8% received mastectomy. Mastectomy was common for most investigated breast cancer types, including for the early breast cancers among which overdiagnosis is thought to be most widespread: mastectomy was undergone in 26.4% of in situ and 28.0% of AJCC stage-I cases. These rates are substantively higher than in many European nations. The probability-based model indicated that between >0% and <18% of the study population could plausibly have undergone mastectomy for overdiagnosed cancer. This range reduced depending on the overdiagnosis rate, shrinking to >0% and <7% if 10% of breast cancers were overdiagnosed and >3% and <15% if 30% were overdiagnosed. CONCLUSIONS: Screening-associated overtreatment by mastectomy is considerably less common than overdiagnosis itself but should not be assumed to be negligible. Screening can prompt or prevent mastectomy, and the balance of this harm-benefit tradeoff is currently unclear.

5.
Int J Cancer ; 144(3): 476-488, 2019 02 01.
Article in English | MEDLINE | ID: mdl-30264887

ABSTRACT

Effects of mammography screening in the general population are disputed. Screening rates differ greatly between US counties, providing a natural opportunity to investigate effects of screening. We compared mammography screening rates with the types and outcomes of breast cancers diagnosed in US counties. The county screening rate was defined as the proportion of women age ≥40 with ≥1 mammogram in the past 2 years (range, 34-91%). Two periods were analyzed: 1975-2009 (612,941 breast cancer cases, 195 counties) and 1996-2009 (645,057 cases, 211-547 counties). Multiple signs of overdiagnosis were observed: First, breast cancer incidence increased as screening became common. Second, incidence stopped increasing once screening rates stabilized. Third, the increases in incidence were limited to age groups receiving screening. Fourth, the increases were larger in counties where screening became more common. Fifth, the increases were limited to small and early-stage breast cancers (which are consistent with overdiagnosis). Sixth, compensatory reductions in large and advanced-stage breast cancers were much smaller than the increases. Difference-in-differences regression analysis suggested 31% (95% CI: 28-34%) of breast cancers diagnosed in 1996-2009 were overdiagnosed. Screening rates correlated with increased incidence for all hormone receptor statuses, HER2 statuses, and grades. Reductions in breast cancer mortality during 1975-2009 were similar in screened and unscreened age groups. Overall, we found repeated signs that breast cancer overdiagnosis is widespread in the US, but the biological nature of overdiagnosed tumors remains unclear. Mortality benefits of screening, though they may be present and substantial, could not be detected at the population level.


Subject(s)
Breast Neoplasms/diagnosis , Breast Neoplasms/epidemiology , Early Detection of Cancer/statistics & numerical data , Adult , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Early Detection of Cancer/methods , Female , Humans , Incidence , Mammography/statistics & numerical data , Medical Overuse/statistics & numerical data , Neoplasm Staging , Registries , SEER Program , United States/epidemiology
6.
J Pediatr Rehabil Med ; 11(3): 147-152, 2018.
Article in English | MEDLINE | ID: mdl-29125505

ABSTRACT

Non-nutritive sucking is often used with premature infants by either using a pacifier or an expressed breast nipple to support the introduction and development of early oral feeding. The pattern of non-nutritive sucking is distinct in that it involves two sucks per second in contrast to nutritive sucking which is one suck per second. Although some literature has identified that non-nutritive sucking has some benefit for the premature infant's feeding development, it is not entirely clear why such an approach is helpful as neurologically, activation of non-nutritive and nutritive skills are different. A summary is presented of the main approaches that use non-nutritive sucking with reference to the literature. This paper also considers other factors and beneficial approaches to managing the introduction of infant feeding. These are: the infant's toleration of enteral feeds pre oral trials, overall development and gestational age when introducing oral experiences, developing swallowing skills before sucking, physiological stability, health status, as well as the development and interpretation of infant oral readiness signs and early communication.


Subject(s)
Infant, Premature , Pacifiers , Sucking Behavior , Enteral Nutrition , Humans , Infant Nutritional Physiological Phenomena , Infant, Newborn , Infant, Premature/growth & development
7.
Mol Genet Metab ; 117(1): 27-32, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26586473

ABSTRACT

UNLABELLED: Blood ammonia and glutamine levels are used as biomarkers of control in patients with urea cycle disorders (UCDs). This study was undertaken to evaluate glutamine variability and utility as a predictor of hyperammonemic crises (HACs) in UCD patients. METHODS: The relationships between glutamine and ammonia levels and the incidence and timing of HACs were evaluated in over 100 adult and pediatric UCD patients who participated in clinical trials of glycerol phenylbutyrate. RESULTS: The median (range) intra-subject 24-hour coefficient of variation for glutamine was 15% (8-29%) as compared with 56% (28%-154%) for ammonia, and the correlation coefficient between glutamine and concurrent ammonia levels varied from 0.17 to 0.29. Patients with baseline (fasting) glutamine values >900 µmol/L had higher baseline ammonia levels (mean [SD]: 39.6 [26.2]µmol/L) than patients with baseline glutamine ≤ 900 µmol/L (26.6 [18.0]µmol/L). Glutamine values >900 µmol/L during the study were associated with an approximately 2-fold higher HAC risk (odds ratio [OR]=1.98; p=0.173). However, glutamine lost predictive significance (OR=1.47; p=0.439) when concomitant ammonia was taken into account, whereas the predictive value of baseline ammonia ≥ 1.0 upper limit of normal (ULN) was highly statistically significant (OR=4.96; p=0.013). There was no significant effect of glutamine >900 µmol/L on time to first HAC crisis (hazard ratio [HR]=1.14; p=0.813), but there was a significant effect of baseline ammonia ≥ 1.0 ULN (HR=4.62; p=0.0011). CONCLUSIONS: The findings in this UCD population suggest that glutamine is a weaker predictor of HACs than ammonia and that the utility of the predictive value of glutamine will need to take into account concurrent ammonia levels.


Subject(s)
Ammonia/blood , Glutamine/blood , Hyperammonemia/blood , Urea Cycle Disorders, Inborn/blood , Adolescent , Adult , Biomarkers/blood , Child , Child, Preschool , Fasting , Female , Glycerol/analogs & derivatives , Glycerol/therapeutic use , Humans , Hyperammonemia/etiology , Male , Phenylbutyrates/therapeutic use , Predictive Value of Tests , Urea Cycle Disorders, Inborn/drug therapy , Young Adult
8.
J Intellect Disabil Res ; 59(11): 1022-32, 2015 Nov.
Article in English | MEDLINE | ID: mdl-25683670

ABSTRACT

BACKGROUND: Research suggesting that people with intellectual disabilities (ID) have difficulties in recognising emotions provides a rationale for studying alexithymia in this population. A number of studies have found a relationship between alexithymia and challenging behaviours in various populations and this study aims to discover if this is the case for people with ID. METHOD: Cross-sectional data were collected from 96 participants with ID and 95 of their carers. The service user participants completed an alexithymia questionnaire for children while carers completed the checklist for challenging behaviour and the observer alexithymia scale. Correlational analyses were employed to explore relationships between the variables. RESULTS: The relationship between service user and carer-rated alexithymia was very weak. The analysis did show significant associations between observer-rated alexithymia and challenging behaviour frequency, management difficulty and severity, but there was no significant relationship between challenging behaviour and alexithymia as rated by service users themselves. CONCLUSIONS: This study suggests that observer-rated alexithymia is important in understanding challenging behaviour presented by people with ID. Service user-rated alexithymia had no association with challenging behaviour, in contrast to the results from similar research with other challenging populations.


Subject(s)
Affective Symptoms/psychology , Intellectual Disability/psychology , Problem Behavior/psychology , Adolescent , Adult , Affective Symptoms/etiology , Aged , Cross-Sectional Studies , Female , Humans , Intellectual Disability/complications , Male , Middle Aged , Young Adult
9.
Mol Genet Metab Rep ; 5: 12-14, 2015 Dec.
Article in English | MEDLINE | ID: mdl-28649536

ABSTRACT

Urinary phenylacetylglutamine (U-PAGN) concentrations in spot urine samples were analyzed as a dosing biomarker during glycerol phenylbutyrate (GPB) dosing in 68 healthy adults and 66 adult and pediatric patients with urea cycle disorders who participated in GPB clinical trials. Age- and body surface area (BSA)-specific 25th percentile cutoff points for spot U-PAGN concentrations (<~9000 µg/mL for < 2 years old patients, < 7000 µg/mL for > 2 years with BSA ≤ 1.3 m2, and <~5000 µg/mL for > 2 years of age with BSA > 1.3 m2) were determined as an approach to identify patients for whom increased dosing and/or adherence to prescribed dosing should be assessed.

10.
Infant Behav Dev ; 37(4): 457-64, 2014 Nov.
Article in English | MEDLINE | ID: mdl-24974134

ABSTRACT

Fifty nine premature infants participated in a randomized controlled study to determine the effectiveness of non-nutritive sucking (NNS). It was predicted that NNS would not accelerate the development of full oral feeding or early language skills as sometimes perceived in practice. However, it was predicted that using NNS as a strategy to support parents to identify and respond to early communication and oral readiness signs would increase confidence in infant management and enable quicker discharge home. Infants were aged 26-35 weeks gestation. Infants with no significant difficulties were randomly assigned to one of three groups; Group 1, NNS pre-tube feeding (n=19); Group 2, NNS on onset of tube feeding (n=20) and Group 3, Control (n=20). Follow-up occurred at 6 months. There were no significant differences with number of days to full oral feeding between the groups receiving NNS and the Control group, χ2(2, n=59)=4.33, p=.115. A significant difference in number of days in hospital between the Control group and the other two groups was found χ2 (2, n=59)=7.678, p=.022. Significant changes were noted with the development of more normal sucking patterns in Groups 1-3. At 6 months there were no significant differences in receptive or expressive language skills between all groups. NNS had no significant impact on the transition to full oral feeding or later language development. There was a significant difference in the number of days in hospital between the Control group and the other two groups which involved parents in identification of early communication signs. Possible reasons for this change and future directions are discussed.


Subject(s)
Eating/physiology , Infant Behavior/physiology , Sucking Behavior/physiology , Child Development/physiology , Female , Humans , Infant , Infant, Low Birth Weight , Infant, Newborn , Infant, Premature , Language Development , Male , Pacifiers
11.
Br J Dermatol ; 171(4): 760-70, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24815089

ABSTRACT

BACKGROUND: Dandruff is a common, relapsing and uncomfortable scalp condition affecting a large proportion of the global population. The appearance of flakes on the scalp and in the hair line, and associated itch are thought to be consequences of a damaged skin barrier, altered corneocyte cohesion and abnormal desquamation in dandruff. The balance between skin proteases and protease inhibitors is essential for driving the key events, including corneodesmosome degradation, in the desquamation process and to maintain stratum corneum (SC) barrier integrity. OBJECTIVES: To investigate the distribution of corneodesmosomes, the key component of the SC cohesivity and barrier function, and the protease inhibitors lympho-epithelial Kazal-type-related inhibitor (LEKTI-1) and squamous cell carcinoma antigen (SCCA1) in the scalp of dandruff-affected participants. METHODS: The methods utilized were immunohistochemistry, scanning immunoelectron microscopy, phase-contrast microscopy, Western blotting and serine protease activity assay on tape-stripped SC or scalp skin biopsies. RESULTS: In SC samples from healthy subjects, corneodesmosomes were peripherally located in the corneocytes. In samples of dandruff lesions, corneodesmosomes were located both peripherally and on the entire surface area of the corneocytes. LEKTI-1 and SCCA1 protein levels and parakeratosis were found to be highly elevated in the lesional samples. CONCLUSIONS: The persistence of nonperipheral corneodesmosomes is a characteristic feature of the perturbed desquamation seen in dandruff. The increased expression levels of LEKTI-1 and SCCA1 are consistent with the view that the dandruff condition is characterized by an imbalance in protease-protease inhibitor interaction in the SC.


Subject(s)
Dandruff/enzymology , Desmosomes/enzymology , Protease Inhibitors/metabolism , Adult , Antigens, Neoplasm/metabolism , Desmoglein 1/metabolism , Epidermis/metabolism , Female , Humans , Male , Middle Aged , Parakeratosis/metabolism , Parakeratosis/pathology , Proteinase Inhibitory Proteins, Secretory/metabolism , Serine Peptidase Inhibitor Kazal-Type 5 , Serine Proteases/metabolism , Serpins/metabolism , Young Adult
12.
Mol Genet Metab ; 110(4): 446-53, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24144944

ABSTRACT

BACKGROUND: Phenylacetic acid (PAA) is the active moiety in sodium phenylbutyrate (NaPBA) and glycerol phenylbutyrate (GPB, HPN-100). Both are approved for treatment of urea cycle disorders (UCDs) - rare genetic disorders characterized by hyperammonemia. PAA is conjugated with glutamine in the liver to form phenylacetyleglutamine (PAGN), which is excreted in urine. PAA plasma levels ≥ 500 µg/dL have been reported to be associated with reversible neurological adverse events (AEs) in cancer patients receiving PAA intravenously. Therefore, we have investigated the relationship between PAA levels and neurological AEs in patients treated with these PAA pro-drugs as well as approaches to identifying patients most likely to experience high PAA levels. METHODS: The relationship between nervous system AEs, PAA levels and the ratio of plasma PAA to PAGN were examined in 4683 blood samples taken serially from: [1] healthy adults [2], UCD patients of ≥ 2 months of age, and [3] patients with cirrhosis and hepatic encephalopathy (HE). The plasma ratio of PAA to PAGN was analyzed with respect to its utility in identifying patients at risk of high PAA values. RESULTS: Only 0.2% (11) of 4683 samples exceeded 500 µg/ml. There was no relationship between neurological AEs and PAA levels in UCD or HE patients, but transient AEs including headache and nausea that correlated with PAA levels were observed in healthy adults. Irrespective of population, a curvilinear relationship was observed between PAA levels and the plasma PAA:PAGN ratio, and a ratio>2.5 (both in µg/mL) in a random blood draw identified patients at risk for PAA levels>500 µg/ml. CONCLUSIONS: The presence of a relationship between PAA levels and reversible AEs in healthy adults but not in UCD or HE patients may reflect intrinsic differences among the populations and/or metabolic adaptation with continued dosing. The plasma PAA:PAGN ratio is a functional measure of the rate of PAA metabolism and represents a useful dosing biomarker.


Subject(s)
Glutamine/analogs & derivatives , Hepatic Encephalopathy/blood , Phenylacetates/blood , Urea Cycle Disorders, Inborn/blood , Biomarkers/blood , Drug-Related Side Effects and Adverse Reactions/blood , Drug-Related Side Effects and Adverse Reactions/etiology , Glutamine/administration & dosage , Glutamine/blood , Glycerol/administration & dosage , Glycerol/analogs & derivatives , Hepatic Encephalopathy/etiology , Hepatic Encephalopathy/pathology , Humans , Liver/drug effects , Liver/metabolism , Neoplasms/complications , Neoplasms/drug therapy , Phenylacetates/administration & dosage , Phenylbutyrates/administration & dosage , Randomized Controlled Trials as Topic , Urea Cycle Disorders, Inborn/epidemiology , Urea Cycle Disorders, Inborn/etiology , Urea Cycle Disorders, Inborn/pathology
13.
Ecology ; 94(5): 1142-54, 2013 May.
Article in English | MEDLINE | ID: mdl-23858654

ABSTRACT

Heterothermy plays an important role in lowering the costs of thermoregulation in endotherms by reducing water and energy requirements. We tested predictions that birds in arid habitats should express fine-scale variation in their thermoregulatory patterns as a function of prevailing climatic conditions. We assessed effects of air temperature (Tair) and water vapor pressure deficit (D) on body temperature (Tb) in free-living White-browed Sparrow-Weavers (Plocepasser mahali) during summer in two arid habitats in the Kalahari Desert, South Africa, using data from a dry period at a hot, desert site (n=7 birds), and during a dry period (n=4 birds) and a wet period (n=5 birds) at a milder, semi-desert site. The desert birds maintained a significantly higher set-point Tb (41.5 degrees+/-0.2 degrees C, mean-SD) than semi-desert birds (40.2 degrees+/-0.2 degrees C). During the warmest part of day (12:00-18:00 hours), Tb increased significantly during periods of high Tair and/or high humidity, and mean and maximum Tb were up to 1.40 and 2.3 degrees C, respectively, above normal levels. However, as Tair increased, birds at the desert site maintained Tb at or below set-point levels for a greater proportion of the time than birds at the semi-desert site. Birds at the desert site also expressed a greater magnitude of daily heterothermy (heterothermy index, HI=2.4 degrees+/-0.3 degrees C, mean+/-SD) than birds at the semi-desert site: the latter population showed a greater magnitude of heterothermy during a dry period (HI=2.1 degrees+/-0.3 degrees C) than during a wet period (HI=1.6 degrees+/-0.2 degrees C). Birds continued foraging throughout the warmest part of the day, despite the fact that heat dissipation (percentage of time spent panting and wing-spreading) increased significantly with increasing Tair. Our findings reveal that populations can vary in their thermoregulatory responses in both space and time and suggest that small changes in Tair can have significant effects on thermoregulation in free-ranging desert birds, even when Tair

Subject(s)
Adaptation, Physiological/physiology , Body Temperature Regulation/physiology , Ecosystem , Passeriformes/physiology , Animals , Behavior, Animal , Circadian Rhythm , Demography , Seasons , Temperature
14.
Clin Exp Immunol ; 173(3): 512-22, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23668840

ABSTRACT

In this study, we hypothesized that the granulomatous disorder sarcoidosis is not caused by a single pathogen, but rather results from abnormal responses of Toll-like receptors (TLRs) to conserved bacterial elements. Unsorted bronchoalveolar lavage (BAL) cells from patients with suspected pulmonary sarcoidosis and healthy non-smoking control subjects were stimulated with representative ligands of TLR-2 (in both TLR-2/1 and TLR-2/6 heterodimers) and TLR-4. Responses were determined by assessing resulting production of tumour necrosis factor (TNF)-α and interleukin (IL)-6. BAL cells from patients in whom sarcoidosis was confirmed displayed increased cytokine responses to the TLR-2/1 ligand 19-kDa lipoprotein of Mycobacterium tuberculosis (LpqH) and decreased responses to the TLR-2/6 agonist fibroblast stimulating ligand-1 (FSL)-1. Subsequently, we evaluated the impact of TLR-2 gene deletion in a recently described murine model of T helper type 1 (Th1)-associated lung disease induced by heat-killed Propionibacterium acnes. As quantified by blinded scoring of lung pathology, P. acnes-induced granulomatous pulmonary inflammation was markedly attenuated in TLR-2(-/-) mice compared to wild-type C57BL/6 animals. The findings support a potential role for disordered TLR-2 responses in the pathogenesis of pulmonary sarcoidosis.


Subject(s)
Sarcoidosis, Pulmonary/metabolism , Toll-Like Receptor 2/metabolism , Adolescent , Adult , Aged , Animals , Bronchoalveolar Lavage Fluid/cytology , Bronchoalveolar Lavage Fluid/immunology , Case-Control Studies , Cytokines/biosynthesis , Disease Models, Animal , Female , Gene Expression , Humans , Ligands , Male , Mice , Mice, Knockout , Middle Aged , Pneumonia/genetics , Pneumonia/immunology , Propionibacterium acnes/immunology , Protein Multimerization , Sarcoidosis, Pulmonary/genetics , Sarcoidosis, Pulmonary/immunology , Toll-Like Receptor 2/antagonists & inhibitors , Toll-Like Receptor 2/genetics , Toll-Like Receptor 4/agonists , Toll-Like Receptor 4/metabolism , Toll-Like Receptors/chemistry , Toll-Like Receptors/genetics , Toll-Like Receptors/metabolism , Young Adult
15.
Int J Cosmet Sci ; 35(5): 412-23, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23517450

ABSTRACT

Profilaggrin (proFLG) and its processing products are critical to the health and appearance of skin. The recent identification of loss-of-function filaggrin (FLG) mutations as a predisposing factor in ichthyosis vulgaris and atopic dermatitis has lead to a resurgent interest in this enigmatic protein. Here, we review the literature on the structure and many functions of proFLG, from its role as a filament-aggregating protein and a source of natural moisturizing factor (NMF), to the more recent discoveries of its role in epidermal barrier formation and its more speculative functions as an antimicrobial and sunscreen. Finally, we discuss the relationship of proFLG with dry skin, the influence of moisturizers on NMF generation and speculate on next generation of FLG research.


Subject(s)
Intermediate Filament Proteins/metabolism , Skin Diseases/metabolism , Skin/metabolism , Animals , Epidermis/metabolism , Filaggrin Proteins , Humans
17.
Mol Genet Metab ; 107(3): 308-14, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22958974

ABSTRACT

UNLABELLED: We have analyzed pharmacokinetic data for glycerol phenylbutyrate (also GT4P or HPN-100) and sodium phenylbutyrate with respect to possible dosing biomarkers in patients with urea cycle disorders (UCD). STUDY DESIGN: These analyses are based on over 3000 urine and plasma data points from 54 adult and 11 pediatric UCD patients (ages 6-17) who participated in three clinical studies comparing ammonia control and pharmacokinetics during steady state treatment with glycerol phenylbutyrate or sodium phenylbutyrate. All patients received phenylbutyric acid equivalent doses of glycerol phenylbutyrate or sodium phenylbutyrate in a cross over fashion and underwent 24-hour blood samples and urine sampling for phenylbutyric acid, phenylacetic acid and phenylacetylglutamine. RESULTS: Patients received phenylbutyric acid equivalent doses of glycerol phenylbutyrate ranging from 1.5 to 31.8 g/day and of sodium phenylbutyrate ranging from 1.3 to 31.7 g/day. Plasma metabolite levels varied widely, with average fluctuation indices ranging from 1979% to 5690% for phenylbutyric acid, 843% to 3931% for phenylacetic acid, and 881% to 1434% for phenylacetylglutamine. Mean percent recovery of phenylbutyric acid as urinary phenylacetylglutamine was 66.4 and 69.0 for pediatric patients and 68.7 and 71.4 for adult patients on glycerol phenylbutyrate and sodium phenylbutyrate, respectively. The correlation with dose was strongest for urinary phenylacetylglutamine excretion, either as morning spot urine (r = 0.730, p < 0.001) or as total 24-hour excretion (r = 0.791 p<0.001), followed by plasma phenylacetylglutamine AUC(24-hour), plasma phenylacetic acid AUC(24-hour) and phenylbutyric acid AUC(24-hour). Plasma phenylacetic acid levels in adult and pediatric patients did not show a consistent relationship with either urinary phenylacetylglutamine or ammonia control. CONCLUSION: The findings are collectively consistent with substantial yet variable pre-systemic (1st pass) conversion of phenylbutyric acid to phenylacetic acid and/or phenylacetylglutamine. The variability of blood metabolite levels during the day, their weaker correlation with dose, the need for multiple blood samples to capture trough and peak, and the inconsistency between phenylacetic acid and urinary phenylacetylglutamine as a marker of waste nitrogen scavenging limit the utility of plasma levels for therapeutic monitoring. By contrast, 24-hour urinary phenylacetylglutamine and morning spot urine phenylacetylglutamine correlate strongly with dose and appear to be clinically useful non-invasive biomarkers for compliance and therapeutic monitoring.


Subject(s)
Ammonia/urine , Glutamine/analogs & derivatives , Glycerol/analogs & derivatives , Phenylacetates/urine , Phenylbutyrates/urine , Urea Cycle Disorders, Inborn/drug therapy , Urea Cycle Disorders, Inborn/urine , Adolescent , Adult , Ammonia/blood , Biomarkers, Pharmacological/blood , Biomarkers, Pharmacological/urine , Child , Cross-Over Studies , Drug Administration Schedule , Female , Glutamine/blood , Glutamine/urine , Glycerol/blood , Glycerol/pharmacokinetics , Glycerol/urine , Humans , Male , Phenylacetates/blood , Phenylbutyrates/blood , Phenylbutyrates/pharmacokinetics , Urea Cycle Disorders, Inborn/blood
18.
Int J Cosmet Sci ; 34(4): 298-306, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22515370

ABSTRACT

Dandruff is characterized by a flaky, pruritic scalp and affects up to half the world's population post-puberty. The aetiology of dandruff is multifactorial, influenced by Malassezia, sebum production and individual susceptibility. The commensal yeast Malassezia is a strong contributory factor to dandruff formation, but the presence of Malassezia on healthy scalps indicates that Malassezia alone is not a sufficient cause. A healthy stratum corneum (SC) forms a protective barrier to prevent water loss and maintain hydration of the scalp. It also protects against external insults such as microorganisms, including Malassezia, and toxic materials. Severe or chronic barrier damage can impair proper hydration, leading to atypical epidermal proliferation, keratinocyte differentiation and SC maturation, which may underlie some dandruff symptoms. The depleted and disorganized structural lipids of the dandruff SC are consistent with the weakened barrier indicated by elevated transepidermal water loss. Further evidence of a weakened barrier in dandruff includes subclinical inflammation and higher susceptibility to topical irritants. We are proposing that disruption of the SC of the scalp may facilitate dandruff generation, in part by affecting susceptibility to metabolites from Malassezia. Treatment of dandruff with cosmetic products to directly improve SC integrity while providing effective antifungal activity may thus be beneficial.


Subject(s)
Dermatitis, Seborrheic/microbiology , Epidermis/metabolism , Malassezia/growth & development , Sebum/metabolism , Dermatitis, Seborrheic/metabolism , Epidermis/microbiology , Humans , Water Loss, Insensible
19.
Soc Psychiatry Psychiatr Epidemiol ; 47(11): 1827-35, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22322983

ABSTRACT

PURPOSE: The review aimed to (1) identify measures that assess the recovery orientation of services; (2) discuss how these measures have conceptualised recovery, and (3) characterise their psychometric properties. METHODS: A systematic review was undertaken using seven sources. The conceptualisation of recovery within each measure was investigated by rating items against a conceptual framework of recovery comprising five recovery processes: connectedness; hope and optimism; identity; meaning and purpose; and empowerment. Psychometric properties of measures were evaluated using quality criteria. RESULTS: Thirteen recovery orientation measures were identified, of which six met eligibility criteria. No measure was a good fit with the conceptual framework. No measure had undergone extensive psychometric testing and none had data on test-retest reliability or sensitivity to change. CONCLUSIONS: Many measures have been developed to assess the recovery orientation of services. Comparisons between the measures were hampered by the different conceptualisations of recovery used and by the lack of uniformity on the level of organisation at which services were assessed. This situation makes it a challenge for services and researchers to make an informed choice on which measure to use. Further work is needed to produce measures with a transparent conceptual underpinning and demonstrated psychometric properties.


Subject(s)
Mental Disorders/rehabilitation , Orientation , Outcome Assessment, Health Care , Recovery of Function , Concept Formation , Humans , Mental Health , Mental Health Services , Models, Psychological , Power, Psychological , Psychometrics , Reproducibility of Results , Self Concept , Surveys and Questionnaires
20.
Neurourol Urodyn ; 31(1): 139-42, 2012 Jan.
Article in English | MEDLINE | ID: mdl-21953734

ABSTRACT

INTRODUCTION: The effect of urodynamic catheters on urine flow rate (Q(max) ) is well documented but under-researched. Several studies show reduced Q(max) but methodologies and patient demographics differ. The aims of this study were to further quantify the effect of urodynamic catheters on Q(max) and to explore if this was consistent across different urodynamic diagnoses. METHODS: Four groups of 50 consecutive men attending for urodynamic studies (UDS) were retrospectively analyzed: Group 1 comprised 50 men with normal UDS, Group 2 was 50 men with BOO, and Group 3 contained 50 men with detrusor underactivity. Groups 1-3 had UDS performed using both 10 Fr filling and 4 Fr measuring catheters in situ. Group 4 comprised 50 men who had UDS performed with a smaller catheter assembly (8 Fr dual-lumen). Values of Q(max) with and without catheters present were compared using paired Student's t-tests. Differences between groups were compared using ANOVA. RESULTS: Q(max) measured during UDS in men from Groups 1-3 showed a mean reduction of 38% compared to Q(max) from "free" uroflowmetry. ANOVA indicated this reduction was significantly greater among men with normal UDS. Interestingly the group who underwent UDS with a smaller catheter assembly showed no significant reduction in Q(max) measured with catheters in situ. CONCLUSION: Our findings are in line with previous work suggesting that smaller calibre urethral catheters do not cause a significant obstructive effect during voiding. In addition it would appear that the reduction in Q(max) with larger urethral catheters in situ is greatest in those with normal urodynamics.


Subject(s)
Catheters, Indwelling , Urinary Catheterization/instrumentation , Urination/physiology , Urodynamics/physiology , Adolescent , Adult , Aged , Aged, 80 and over , Humans , Male , Middle Aged , Retrospective Studies , Urinary Bladder/physiology , Urinary Bladder/physiopathology , Urinary Bladder Neck Obstruction/physiopathology , Urination Disorders/physiopathology , Young Adult
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