Constant vigilance! Managing threats to the skin barrier.

OBJECTIVE: Skin barrier defects are one of the primary causes of atopic dermatitis (AD). The basis of skin barrier defects in AD is due to a deficiency in various barrier proteins including filaggrin, involucrin, claudins, and lipids such as ceramide, fatty acids, and cholesterol. This review updates a more detailed lipid dysregulation in the skin barrier of AD based on recent lipidomic analysis. The clinical implications, treatments, prevention, and predictive capability of skin barrier defects are also reviewed. DATA SOURCES: Published literature obtained through PubMed searches. STUDY SELECTIONS: Studies relevant to the mechanisms, clinical implications, treatments, prevention, and predictors of AD development. RESULTS: Skin barrier defects contribute to transepidermal water loss, infections, IgE sensitizations, and cutaneous inflammation in AD. Preventive treatments include daily hydration and application of moisturizers. Because skin barrier defects precede the development of AD, they provide an opportunity for prediction and intervention. CONCLUSION: Skin barrier defects play an important role in the comorbidities of AD including infectious complications, disease flare, and allergic diathesis. Current research focuses on prevention and prediction of AD development.

High FGF-21 level in a cohort of 22 patients with Dravet Syndrome-Possible relationship with the disease outcomes.

OBJECTIVE: Dravet syndrome (DS) is a severe and intractable form of epilepsy with prolonged seizures which may evolve to other seizure types and associated with mild-to-severe intellectual disabilities. Fibroblast growth factor 21 (FGF-21) is a stress hormone mediating metabolic and oxidative stress and circulating level of FGF-21 had been shown to increase in some patients with impairment of oxidative phosphorylation in muscles. In DS, FGF-21 is of interest for further study as mitochondrial oxidative stress was identified previously in patients. METHODS: Plasma FGF-21 levels were compared between 22 DS patients and 22 normal controls, and their clinical characteristics of DS patients at the time of plasma sampling were studied retrospectively. Besides, the relationships of FGF-21 level with intellectual development, seizure frequency, valproate treatment, and types of SCN1A mutations were analyzed. Logarithmic transformation of FGF-21 levels was performed before comparison and statistical analysis. RESULTS: Mean of log10 FGF-21 level was significantly higher in DS patients when comparing with normal controls (P = .0042). Mean of log10 FGF-21 level was significantly higher in DS patients with normal-to-mild ID versus mild-to-severe ID (P = .0193) and with valproate treatment versus without valproate treatment (P = .015). No significant difference was shown in FGF-21 level in DS patients with missense versus truncating SCN1A variants, and no correlation could be demonstrated between seizure frequency and FGF-21 level. SIGNIFICANCE: Significantly higher level of plasma FGF-21 was identified in DS patients. The high FGF-21 levels were shown to be associated with developmental outcome and valproate treatment. These results support further investigation on the relationship of FGF-21 with the clinical outcomes of DS and other related mechanism which is important for possible therapeutic development for this epileptic encephalopathy.

ARX-associated infantile epileptic-dyskinetic encephalopathy with responsiveness to valproate for controlling seizures and reduced activity of muscle mitochondrial complex IV.

BACKGROUND: ARX genetic defect is associated with a spectrum of neurodevelopmental disorders that exhibit a high degree of phenotypic heterogeneity. METHODS: We studied a family with a 13-year old Chinese boy and his two elder brothers presented with infantile epileptic-dyskinetic encephalopathy and clarified the unknown genetic etiology of the youngest brother by whole exome sequencing. RESULTS: The youngest brother of this family presented with developmental regression, dystonia, epilepsy, microcephaly, visual impairment and oromotor dysfunction. Hyperlactataemia, raised alanine and muscle complex IV deficiency indicated that he had mitochondrial dysfunction. Likely pathogenic hemizygous missense ARX variants (c.989G > A; p.Arg330His) located in conserved nuclear localization sequence was identified. The variant was carried by his asymptomatic mother and not found in his asymptomatic third elder brother. The intractable seizures showed complete but transient responsiveness to pyridoxal phosphate and finally controlled by valproate treatment. CONCLUSION: This is the first case of ARX-associated encephalopathy showing mitochondrial dysfunction and transient responsiveness to pyridoxal phosphate treatment.

Type 2 Diabetes with Comorbid Depression in Relation to Cognitive Impairment: an Opportunity for Prevention?

Studies show poor glycemic control is associated with increased risk of dementia among patients with Type 2 diabetes, indicating potential for prevention of dementia with improved glycemia. Emerging evidence suggests that a relationship between short-term glycemic control and cognitive function exists in Type 2 diabetes. However, detailed mechanisms relating diabetic dementia are lacking, as other concurrent conditions, such as depression, may also increase the risk of dementia in Type 2 diabetes. We examined the effects of glycemic control and depression on cognitive function in 88 patients (mean age, 67 ± 4 years) whose A1c (glycosylated hemoglobin) levels, comorbid depression, mini-mental state examination (MMSE) scores were recorded at baseline. Seventeen patients had depression; 14 agreed on anti-depressants. In 6 months, 69 patients reached A1c goal of < 7% (A1c from 9.7 ± 0.8 to 6.4 ± 0.3) while cognition improved significantly (MMSE scored from 20.2 ± 3.5 to 26.2 ± 2.1, p < 0.05). Cognitive increment in controlled diabetes was more consistently observed if their underlying depression was effectively treated (n - 14). Nineteen patients did not reach A1c goal of < 7% (A1c from 9.6 ± 0.9 to 8.9 ± 0.9) while cognitive increment was minimal (MMSE scored from 20.6 ± 4.9 to 21.3 ± 5.1, p > 0.05). Cognitive decrements were observed among depressed diabetics who refused anti-depressants. Multivariate analysis adjusted for age, education, alcohol use, and other variables yielded similar results. We found controlled glycemia and depression prevent cognitive decline. Further research into mechanisms of cognitive impairment in diabetes may allow us to challenge the concept of dementia in those patients as an irremediable disease.

Acupuncture for acute management and rehabilitation of traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) can be life threatening depending on the severity of the insult to the brain. It can also cause a range of debilitating sequelae which require cognitive, motor, communication, emotional, or behavioral rehabilitation of varying intensity and duration. A number of studies conducted and published in China have suggested that acupuncture may be beneficial in the acute treatment and rehabilitation of TBI. OBJECTIVES: To determine the efficacy and safety of acupuncture in the acute management or rehabilitation (or both) of patients with a TBI, including cognitive, neurological, motor, communication, emotional, or behavioral complications, or a combination of such complications. SEARCH METHODS: We searched the Cochrane Injuries Group Specialised Register, Cochrane Central Register of Controlled Trials (The Cochrane Library), MEDLINE, EMBASE, CINAHL, AMED, PsycINFO and others. We also searched the Chinese Acupuncture Studies Register, the Studies Register of the Cochrane Complementary Medicine Field, NCCAM, and NIH Clinical Studies Database. Three major Mainland Chinese academic literature databases (CNKI, VIP and Wang Fang Data) were also searched using keywords in simplified Chinese. We searched all databases through December 2009, and some searches have been updated to October 2012. SELECTION CRITERIA: Randomized controlled studies evaluating different variants of acupuncture and involving participants of any age who had suffered a TBI. Included trials compared acupuncture with placebo or sham treatment, or acupuncture plus other treatments compared with the same other treatments. We excluded trials that only compared different variants of acupuncture or compared acupuncture alone against other treatments alone, as they did not yield the net effect of acupuncture. DATA COLLECTION AND ANALYSIS: Two review authors identified potential articles from the literature search and extracted data independently using a data extraction form. We performed methodological assessment of included studies using the Cochrane Collaboration's tool for assessing risk of bias. We were unable to perform quantitative data analysis due to insufficient included studies and available data. MAIN RESULTS: Four RCTs, including 294 participants, reported outcomes specified by this review. Three investigated electro-acupuncture for TBI while one investigated acupuncture for acute TBI. The results seem to suggest that acupuncture is efficacious for these indications, however the low methodological quality of these studies renders the results questionable. No adverse effects of acupuncture were reported in any of the studies. AUTHORS' CONCLUSIONS: The low methodological quality of the included studies does not allow us to make conclusive judgments on the efficacy and safety of acupuncture in either the acute treatment and/or rehabilitation of TBI. Its beneficial role for these indications remains uncertain. Further research with high quality trials is required.

Acupuncture for hypoxic ischemic encephalopathy in neonates.

BACKGROUND: Hypoxic ischemic encephalopathy (HIE) in the neonate is associated with high mortality and morbidity. Effective treatment options are limited and therefore alternative therapies such as acupuncture are increasingly used. OBJECTIVES: We sought to determine the efficacy and safety of acupuncture on mortality and morbidity in neonates with HIE. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), Cochrane Neonatal Specialized Register, MEDLINE, AMED, EMBASE, PubMed, CINAHL, PsycINFO, WHO International Clinical Trials Registry Platform, and various Chinese medical databases in November 2012. SELECTION CRITERIA: We planned to include randomized or quasi-randomized controlled trials comparing needle acupuncture to a control group that used no treatment, placebo or sham treatment in neonates (less than 28 days old) with HIE. Co-interventions were allowed as long as both the intervention and the control group received the same co-interventions. We excluded trials that evaluated therapy that did not involve penetration of the skin with a needle or trials that compared different forms of acupuncture only. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed trials for inclusion. If trials were identified, the review authors planned to assess trial quality and extract data independently. We planned to use the risk ratio (RR), risk difference (RD), and number needed to benefit (NNTB) or harm (NNTH) with 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) with 95% CI for continuous outcomes. MAIN RESULTS: No trial satisfied our predefined inclusion criteria. Existing trials only evaluated acupuncture in older infants who survived HIE. There are currently no randomized controlled trials evaluating the efficacy of acupuncture for treatment of HIE in neonates. The safety of acupuncture for HIE in neonates is unknown. AUTHORS' CONCLUSIONS: The rationale for acupuncture in neonates with HIE is unclear and the evidence from randomized controlled trial is lacking. Therefore, we do not recommend acupuncture for the treatment of HIE in neonates. High quality randomized controlled trials on acupuncture for HIE in neonates are needed.

A retrospective study on 69 cases of maxillary tooth transposition.

The published literature on tooth transposition includes only a few studies that have involved more than 50 subjects. The aim of the present study was to investigate the prevalence of true maxillary tooth transposition and possible associated dental anomalies in a larger sample of children. The dental records and radiographs of children who had been diagnosed as having true maxillary tooth transposition at a School Dental Clinic in Hong Kong were studied retrospectively. Data were analyzed for sex and side distribution, as well as for associated dental anomalies. Trends of differences were analyzed statistically using the Fisher exact or chi-squared test. A total of 69 cases of true maxillary tooth transposition were identified and studied; its prevalence in Hong Kong Chinese children was 0.81%. More females than males were affected, and the difference between the sexes was statistically significant (P < 0.05). The prevalence of congenitally missing teeth, microdontia of the maxillary lateral incisors or dental impaction was higher in patients with maxillary tooth transposition than in the general population (P < 0.05, P < 0.0005, and P < 0.0001, respectively). The fact that patients with maxillary tooth transposition were more likely to have congenital absence or microdontia of the maxillary lateral incisors lent further support to the contention that a developmental field defect plays a role in the pathogenesis of maxillary tooth transposition.

Acupuncture for acute management and rehabilitation of traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) can be life threatening depending on the severity of the insult to the brain. It can also cause a range of debilitating sequelae which require cognitive, motor, communication, emotional, or behavioral rehabilitation of varying intensity and duration. A number of studies conducted and published in China have suggested that acupuncture may be beneficial in the acute treatment and rehabilitation of TBI. OBJECTIVES: To determine the efficacy and safety of acupuncture in the acute management or rehabilitation (or both) of patients with a TBI, including cognitive, neurological, motor, communication, emotional, or behavioral complications, or a combination of such complications. SEARCH METHODS: We searched the Cochrane Injuries Group Specialised Register, Cochrane Central Register of Controlled Trials (The Cochrane Library),MEDLINE, EMBASE, CINAHL, AMED, PsycINFO and others. We also searched the Chinese Acupuncture Studies Register, the Studies Register of the Cochrane Complementary Medicine Field, NCCAM, and NIH Clinical Studies Database.Three major Mainland Chinese academic literature databases (CNKI, VIP and Wang Fang Data) were also searched using keywords in simplified Chinese.We searched all databases through December 2009, and some searches have been updated to October 2012. SELECTION CRITERIA: Randomized controlled studies evaluating different variants of acupuncture and involving participants of any age who had suffered a TBI. Included trials compared acupuncture with placebo or sham treatment, or acupuncture plus other treatments compared with the same other treatments.We excluded trials that only compared different variants of acupuncture or compared acupuncture alone against other treatments alone, as they did not yield the net effect of acupuncture. DATA COLLECTION AND ANALYSIS: Two review authors identified potential articles from the literature search and extracted data independently using a data extraction form. We performed methodological assessment of included studies using the Cochrane Collaboration's tool for assessing risk of bias.We were unable to perform quantitative data analysis due to insufficient included studies and available data. MAIN RESULTS: Four RCTs, including 294 participants, reported outcomes specified by this review. Three investigated electro-acupuncture for TBI while one investigated acupuncture for acute TBI. The results seem to suggest that acupuncture is efficacious for these indications,however the low methodological quality of these studies renders the results questionable. No adverse effects of acupuncture were reported in any of the studies. AUTHORS' CONCLUSIONS: The low methodological quality of the included studies does not allow us to make conclusive judgments on the efficacy and safety of acupuncture in either the acute treatment and/or rehabilitation of TBI. Its beneficial role for these indications remains uncertain.Further research with high quality trials is required.

Acupuncture for acute management and rehabilitation of traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) can be life threatening depending on the severity of the insult to the brain. It can also cause a range of debilitating sequelae which require cognitive, motor, communication, emotional, or behavioral rehabilitation of varying intensity and duration. A number of studies conducted and published in China have suggested that acupuncture may be beneficial in the acute treatment and rehabilitation of TBI. OBJECTIVES: To determine the efficacy and safety of acupuncture in the acute management or rehabilitation (or both) of patients with a TBI, including cognitive, neurological, motor, communication, emotional, or behavioral complications, or a combination of such complications. SEARCH STRATEGY: We searched the Cochrane Injuries Group Specialised Register, Cochrane Central Register of Controlled Trials 2008, Issue 2 (The Cochrane Library), MEDLINE, EMBASE, CINAHL, AMED, PsycINFO and others. We also searched the Chinese Acupuncture Studies Register, the Studies Register of the Cochrane Complementary Medicine Field, NCCAM, and NIH Clinical Studies Database. Three major Mainland Chinese academic literature databases (CNKI, VIP and Wang Fang Data) were also searched using keywords in simplified Chinese. Searches were completed in December 2009. SELECTION CRITERIA: Randomized controlled studies evaluating different variants of acupuncture and involving participants of any age who had suffered a TBI. Included trials compared acupuncture with placebo or sham treatment, or acupuncture plus other treatments compared with the same other treatments. We excluded trials that only compared different variants of acupuncture or compared acupuncture alone against other treatments alone, as they did not yield the net effect of acupuncture. DATA COLLECTION AND ANALYSIS: Two review authors identified potential articles from the literature search and extracted data independently using a data extraction form. We performed methodological assessment of included studies using the Cochrane Collaboration's tool for assessing risk of bias. We were unable to perform quantitative data analysis due to insufficient included studies and available data. MAIN RESULTS: Four RCTs, including 294 participants, reported outcomes specified by this review. Three investigated electro-acupuncture for TBI while one investigated acupuncture for acute TBI. The results seem to suggest that acupuncture is efficacious for these indications, however the low methodological quality of these studies renders the results questionable. No adverse effects of acupuncture were reported in any of the studies. AUTHORS' CONCLUSIONS: The low methodological quality of the included studies does not allow us to make conclusive judgments on the efficacy and safety of acupuncture in either the acute treatment and/or rehabilitation of TBI. Its beneficial role for these indications remains uncertain. Further research with high quality trials is required.

Artefact in a panoral radiograph: a short communication.

Artefacts in dental radiographs are not uncommon findings. In some cases, however, such film faults might lead to difficult or even wrong diagnoses. In this brief report, the authors present a case where a small piece of paper cast a foreign body-like image onto a panoral radiograph. The importance of proper techniques and film handling when taking radiographs cannot be over-emphasised.

An audit of concomitant dental anomalies with maxillary talon cusps in a group of children from Hong Kong.

AIM: To investigate the prevalence of various concomitant dental anomalies in Hong Kong children with true talon cusps on the permanent maxillary incisors. METHODS: Dental records and radiographs of a group of Hong Kong Chinese primary schoolchildren with true talon cusps (half crown height or more) on one or more permanent maxillary incisors were selected and studied retrospectively. The prevalence of various dental anomalies in this group of children was compared with that of the general population of Hong Kong Chinese children of similar age. RESULTS: A total of 11,537 records were reviewed and 58 children with true talon cusps on one or more permanent maxillary incisors were identified. A total of 69 permanent maxillary incisors were affected, of which all except one were lateral incisors. Dens evaginatus on premolars, supernumerary teeth in the anterior maxilla, and hypodontia were found in 5 (8.6%), 5 (8.6%), and 5 (8.6%) cases respectively. The prevalence of supernumerary teeth was significantly higher in children with true talon cusps as compared with the results of two previous general studies of Chinese children of similar age (P<0.05, Fisher's exact test). CONCLUSION: Children with true talon cusps on the permanent maxillary incisors were more frequently affected by supernumerary teeth in the anterior maxilla. Further studies with a larger sample are needed to confirm a true association.

Molar incisor hypomineralization in Hong Kong Chinese children.

BACKGROUND: Most prevalence studies on molar incisor hypomineralization (MIH) were carried out in European countries, and data from the East-Asian populations were lacking. AIM: This study aimed to investigate the prevalence of MIH in Hong Kong Chinese children. DESIGN: Since 2006, charting of teeth with MIH was included into the routine dental examination in a school dental clinic. The dental records of grade 6 primary school children who attended annual check-up in this clinic in 2006 were subsequently reviewed retrospectively. The records were selected for this study if the charting indicated that the children were affected by MIH. RESULTS: A total of 2635 records were reviewed and 73 cases of MIH were identified. The prevalence of MIH in this group of children was 2.8%. Their mean age was 12, and the male-to-female ratio was 1 : 1.2. The mean decayed, missing, or filled permanent teeth value of those affected was 1.5, which was higher than that of the general Hong Kong Chinese children aged 12 years old (0.8). A total of 192 teeth were affected. The most commonly affected teeth were permanent maxillary first molars, followed by mandibular first molars and maxillary central incisors. Dental fillings and fissure sealants were found in 52 (38%) and 65 (47%) permanent first molars with hypomineralization, respectively. Medical histories were unremarkable in 60 children, whereas early childhood diseases were reported in 13 cases. CONCLUSIONS: The prevalence of MIH in the permanent dentition of Hong Kong Chinese children was 2.8%. Children with MIH showed higher caries experience in the permanent dentition than the general population of similar age.

Impaction of permanent mandibular second molars in ethnic Chinese schoolchildren.

OBJECTIVE: To investigate the prevalence of impaction of permanent mandibular second molars and associated dental and radiographic characteristics of Chinese children in Hong Kong. MATERIALS AND METHODS: Dental and radiographic records of a group of Chinese schoolchildren were studied retrospectively. Cases of impaction of 1 or both permanent mandibular second molars were selected. Demographic data and dental and radiographic findings were recorded and analyzed. The angle of the impacted second molars was measured on panoramic radiographs. RESULTS: Among the 3,053 records reviewed, 32 cases of impaction of permanent mandibular second molars were identified and studied. Mesial impaction was found in all but 1 case. The angle of the mesially impacted teeth ranged from 13 degrees to 75 degrees . Mandibular crowding and the presence of third molars were common. Dens evaginatus, taurodontism and Class III malocclusions were significantly more prevalent in the study group than in the general population of Chinese children of similar age. CONCLUSIONS: The prevalence of impaction of permanent mandibular second molars in Chinese children was estimated to be 1%. Thorough and regular examination of the child"s developing dentition is recommended to diagnose dental impaction promptly.