Investigation on the transmission rate of carbapenemase-producing carbapenem-resistant Enterobacterales among exposed persons in a tertiary hospital using whole-genome sequencing.

BACKGROUND: To reduce transmission of carbapenemase-producing carbapenem-resistant Enterobacterales (CP-CRE), screening is recommended for patients sharing rooms with CP-CRE-detected patients and healthcare workers caring for them. AIM: The aim of this study was to investigate the transmission rate of CP-CRE among exposed people in a tertiary hospital using whole-genome sequencing. METHODS: This study was conducted in a 1751-bed tertiary teaching hospital from January 2017 to December 2019. Index patients were defined as those with positive results in CP-CRE tests during hospitalization. When an index patient was detected in a shared room, we performed CRE screening tests for patients whose stay overlapped with an index patient's stay for at least one day. Where a second case was found, healthcare worker contacts were also screened. CP-CRE were confirmed, and the carbapenemase type identified, by PCR. Whole-genome sequencing was used to compare isolates from index and exposed patients. RESULTS: During the study period, 47 index patients were identified, and they had been in contact with 152 patients in shared rooms and 54 healthcare workers. None of the healthcare workers had CRE. Among the 152 exposed patients, four patients had the same type of carbapenemases as their CP-CRE index patients and all of them were KPC. Whole-genome sequencing revealed that three of these four pairs showed genotypic accordance between the index and the exposed. CONCLUSION: The CP-CRE transmission rate among the exposed patients was calculated as 2.0% (= 3/152).

Reduction in the acquisition rate of carbapenem-resistant Acinetobacter baumannii (CRAB) after room privatization in an intensive care unit.

BACKGROUND: Acinetobacter baumannii is one of the major pathogens responsible for healthcare-associated infections, especially in intensive care units (ICUs). AIM: To evaluate the effect of room privatization in an ICU on the acquisition of carbapenem-resistant A. baumannii (CRAB). METHODS: Between March and August 2017, a medical ICU was renovated from a multi-bed bay room to single rooms. Acquisition of CRAB was compared between patients admitted to the ICU over 18 months pre-renovation (September 2015 to February 2017) and post-renovation (September 2017 to February 2019). A Cox proportional hazard model was used with adjustment for demographics and comorbidities. FINDINGS: Of the 901 patients, who contributed 8276 patient-days, 95 (10.5%) acquired CRAB during their ICU stay. The CRAB acquisition rate was significantly higher during the pre-renovation period (1.87 per 100 patient-days) than during the post-renovation period (0.39 per 100 patient-days) (P<0.001). In the multi-variable Cox regression model, CRAB acquisition was significantly associated with the presence of a feeding tube (adjusted hazard ratio (aHR), 6.08; 95% confidence interval (CI), 2.46-15.06; P<0.001), continuous renal replacement therapy (aHR, 1.66; 95% CI, 1.09-2.53; P=0.019) and admission after renovation of the ICU to single rooms (aHR, 0.23; 95% CI, 0.12-0.41; P<0.001). CONCLUSIONS: Renovation of ICUs to single rooms is an efficient strategy to prevent transmission of multi-drug-resistant organisms and hospital-acquired infections.

SVD-aided non-orthogonal decomposition (SANOD) method to exploit prior knowledge of spectral components in the analysis of time-resolved data.

Analysis of time-resolved data typically involves discriminating noise against the signal and extracting time-independent components and their time-dependent contributions. Singular value decomposition (SVD) serves this purpose well, but the extracted time-independent components are not necessarily the physically meaningful spectra directly representing the actual dynamic or kinetic processes but rather a mathematically orthogonal set necessary for constituting the physically meaningful spectra. Converting the orthogonal components into physically meaningful spectra requires subsequent posterior analyses such as linear combination fitting (LCF) and global fitting (GF), which takes advantage of prior knowledge about the data but requires that all components are known or satisfactory components are guessed. Since in general not all components are known, they have to be guessed and tested via trial and error. In this work, we introduce a method, which is termed SVD-aided Non-Orthogonal Decomposition (SANOD), to circumvent trial and error. The key concept of SANOD is to combine the orthogonal components from SVD with the known prior knowledge to fill in the gap of the unknown signal components and to use them for LCF. We demonstrate the usefulness of SANOD via applications to a variety of cases.

Comparison of various anthropometric indices for the identification of a predictor of incident hypertension: the ARIRANG study.

We compared the predictive capability of weight, waist circumference (WC), waist-to-height ratio (WHtR), waist-to-hip ratio (WHR), body mass index (BMI), body roundness index (BRI), and a body shape index (ABSI) to identify incident hypertension, and to determine whether any of these indices may be used as a better single predictor of incident hypertension. A total of 1718 participants aged 39-72 years were collected  in a longitudinal study. Logistic regression models were used to evaluate various anthropometric indices as significant predictors of hypertension. During 2.8 years of follow-up, 185 new cases of hypertension (10.8%) were reported. The BRI and ABSI were significantly higher in the participants who had developed hypertension than in those who had not (4.15 ± 1.01 vs. 3.57 ± 1.03, 0.80 ± 0.04 vs. 0.78 ± 0.05; respectively, p < 0.001). After adjusting for confounding variables, logistic regression analysis indicated that participants within the highest quartile of WC and WHtR were 4.79 and 4.51 times more likely to have hypertension than those within the lowest quartile (OR 4.79, 95% CI 2.49-9.20 vs. OR 4.51, 95% CI 2.41-8.43, respectively, p < 0.0001); in contrast, no such correlation was found for BMI, WHR, BRI, and ABSI. WC (AUC: 0.672) showed a more powerful predictive ability for hypertension (p < 0.0001) than BMI (AUC: 0.623), and an equal predictive power for hypertension as WHtR (AUC: 0.662) and BRI (AUC: 0.662) in the general population. We concluded that WC and/or WHtR but not BMI, showed superior prediction capability compared to WHR, BRI, and ABSI, for determining the incidence of hypertension in a community-based prospective study.

Simultaneous detection of barrier- and immune-related gene variations in patients with atopic dermatitis by reverse blot hybridization assay.

BACKGROUND: Hereditary factors are involved in the pathogenesis of atopic dermatitis (AD). However, AD-related gene variations are significantly different across ethnicities. AIM: To identify mutations and single-nucleotide polymorphisms (SNPs) in barrier- or immune-related genes from Korean patients with AD and compare the variations with those observed in nonatopic healthy controls (HCs), and to use novel reverse blot hybridization assay (REBA) for AD-related gene variants. METHODS: We carried out REBA to simultaneously detect variations in genes related to barrier or immune function, namely, FLG, SPINK5, KLK7, DEFB1, TNFα, KDR, FCER1A, IL4, IL5,IL5RA, IL9, IL10, IL12, IL12R, IL13 and IL18, from Korean patients with AD, and compared the variation to that in nonatopic healthy controls. RESULTS: The homozygous mutants of KLK7 and SPINK5-2475, and the heterozygous mutants of FLG 3321delA, SPINK5-1156, DEFB1, KDR, IL5RA, IL9 and IL12RB1 were significantly more frequent in AD. It has been predicted that the larger the number of gene variants, the higher the odds ratio of AD prevalence; however, we did not find any significant correlation between the number of gene variants and AD severity. CONCLUSION: Using REBA, we identified more genetic variants that can predict AD occurrence. We also verified that REBA can be used to easily and accurately detect multiple AD-related gene variants simultaneously. In addition, we identified a correlation between KLK7 mutation and AD in Koreans, which is the first such report, to our knowledge.

The relationship between serum ammonia level and neurologic complications in patients with acute glufosinate ammonium poisoning: A prospective observational study.

Glufosinate ammonium poisoning can cause neurological complications even after a symptom-free period. We prospectively investigated the predictors of neurologic complications in acute glufosinate ammonium poisoning and the change of serum ammonia level as a predictor of patient's presence and recovery of neurologic complication. This prospective observational study collected data from consecutive patients diagnosed with acute glufosinate ammonium poisoning between September 2014 and June 2016. Serum ammonia was serially measured. The patients were divided into two groups: the neurologic complication group and the nonneurologic complication group. We also defined 25 other insecticide- or herbicide-poisoned patients as controls. The neurologic complication group included 18 patients (72.0%). The latency period for neurologic complications was within 48-h postingestion. The peak ammonia level was statistically higher in the neurologic complication group than in the control group ( p < 0.001) and the nonneurologic complication groups ( p = 0.001). There was a statistical difference between the nonneurologic complication group and the neurologic complication group ( p = 0.0085) in terms of ingested amount. The peak ammonia was the only predictor for the development of neurologic complications (the optimal cutoff: 90 µg/dL). In patients with mental changes, the mean serum ammonia levels before and after recovery of the mental changes were statistically different ( p = 0.0019). In acute glufosinate ammonium poisoning, serial serum ammonia level measurements are needed and a serum peak ammonia level greater than 90 µg/dL is a predictor of neurologic complications. Also, it is important to treat the hyperammonemia in acute glufosinate ammonium poisoning.

Half-dose ganciclovir preemptive treatment of cytomegalovirus infection after pediatric allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Ganciclovir (GCV) has been widely used as preemptive therapy after hematopoietic stem cell transplantation (HSCT), although bone marrow suppression is a known accompaniment, with secondary infection or bleeding as potential complications. Our aim was to evaluate clinical outcomes in pediatric patients with low cytomegalovirus (CMV) antigenemia levels using half the dosage of GCV generally given preemptively. METHODS: Patients received half doses of intravenous GCV (5 mg/kg once daily, 6 days/week) at CMV antigenemia levels <10/200,000 cells. At higher levels of CMV antigenemia, conventional doses of GCV (5 mg/kg every 12 h) were administered. RESULTS: A total of 130 patients were evaluated, detecting CMV antigenemia in 87 (66.9%). Of these patients, 74 (85.1%) were treated preemptively with half-dose GCV, which proved effective as sole therapy in 51 (68.9%). CMV retinitis developed in 4 patients, 2 of whom initially were given half-dose GCV. All infections resolved successfully, with no CMV-related deaths. CMV seropositivity in recipients was the only significant risk factor for positive CMV antigenemia (hazard ratio [HR] = 10.05, P = 0.046). Compared with half-dose GCV administration, conventional GCV dosing resulted in a higher rate of severe neutropenia, defined as absolute neutrophil count <0.5 × 10(9) /L (HR = 4.30, P = 0.015). CONCLUSION: Half-dose GCV therapy at CMV antigenemia levels <10/200,000 cells is an effective and safe means of preemptively treating pediatric CMV infection after HSCT.

PCR-reverse blot hybridization assay for fast and accurate identification of causative species in superficial fungal infections.

BACKGROUND: Superficial fungal infections are a very common problem in dermatological clinics. The diagnostic method of fungal culture is time-consuming and has inconsistent sensitivity. Therefore, a practical method for rapid and accurate identification of the species causing superficial fungal infections is needed. AIM: To compare PCR-reverse blot hybridization assay (PCR-REBA) with conventional fungal diagnostic methods so as to determine the reliability of PCR-REBA for the diagnosis and species identification in superficial fungal infections. METHODS: Potassium hydroxide (KOH) preparation, fungal culture, conventional real-time PCR and PCR-REBA were used to assess 83 specimens, and the results from each method were compared. RESULTS: Of the 83 specimens, 44 specimens that were positive by fungal culture had 62.7% agreement with PCR-REBA. Compared with real-time PCR, there was 68.7% agreement with fungal culture, but 91.6% agreement with PCR-REBA. When the comparison was made using the 55 specimens that gave positive results in both KOH preparation and fungal culture, there was 85.5% agreement with real-time PCR for fungal culture, but 94.5% agreement with PCR-REBA. CONCLUSIONS: Compared with KOH preparation or fungal culture, PCR-REBA has higher sensitivity and specificity. Therefore, PCR-REBA could be a useful method in clinical settings because it can identify species quickly and accurately, and can also determine the existence of pathogens.

Performance of the Real Fungus-ID kit based on multiplex RT-PCR assay for the rapid detection and identification of Trichophyton spp. and Microsporum spp. in clinical specimens with suspected dermatophyte infection.

AIMS: The aim of this study was to evaluate the performance of a commercially available multiplex RT-PCR assay for the rapid detection and identification of dermatophytes directly from clinical samples and cultures. METHODS AND RESULTS: The multiplex RT-PCR assay was used to evaluate 118 clinical isolates from various specimen types and a total of 140 known specimens were compared with both conventional methods, commercially available PCR-REBA, and ITS sequence analysis. In this study, multiplex RT-PCR assay yield significantly more positive results than culture (91·9 vs 39·5%) and conventional methods including KOH microscopy (91·9 vs 71·3%). Although the results among the multiplex RT-PCR, PCR-REBA and ITS sequence analysis were concordant (100%) in 118 clinical isolates, concordant results between multiplex RT-PCR assay and culture were at 66% (78/118). The overall positive rates for the PCR-REBA, multiplex RT-PCR assay and ITS sequence analysis were 98·8, 91·9, and 52·9% respectively. In addition, the concordance rate of multiplex RT-PCR assay and the PCR-REBA assay was 93% (95% confidence interval (CI), 89·9-96·1, P < 0·0001), 93·7% (95% CI, 90·5-96·4, P < 0·0001) sensitivity, 100% (95% CI, 80·0-100, P < 0·0001) specificity, and 99·6% positive and 81% negative predictive values, respectively. Among the 258 samples, the most frequently identified dermatophyte species were Trichophyton rubrum (n = 199, 77·1%) and Trichophyton mentagrophytes (n = 28, 10·9%). CONCLUSIONS: The entire multiplex RT-PCR procedure takes about 3 h, while results from culture can take up to 2-3 weeks. The use of the multiplex RT-PCR molecular diagnostic assay was rapid and reliable for detecting pathogen infections. SIGNIFICANCE AND IMPACT OF THE STUDY: Even though the use of molecular diagnostic technology is more expensive than conventional methods, the clinical and economic benefit of saving time relative to expense remains to be elucidated. Therefore, the multiplex RT-PCR assay may provide the essential information to accelerate therapeutic decisions for earlier and adequate antibiotic treatment in the acute phase of fungal pathogen infections.

Preferential killing of human lung cancer cell lines with mitochondrial dysfunction by nonthermal dielectric barrier discharge plasma.

The distinctive cellular and mitochondrial dysfunctions of two human lung cancer cell lines (H460 and HCC1588) from two human lung normal cell lines (MRC5 and L132) have been studied by dielectric barrier discharge (DBD) plasma treatment. This cytotoxicity is exposure time-dependent, which is strongly mediated by the large amount of H2O2 and NOx in culture media generated by DBD nonthermal plasma. It is found that the cell number of lung cancer cells has been reduced more than that of the lung normal cells. The mitochondrial vulnerability to reactive species in H460 may induce distinctively selective responses. Differential mitochondrial membrane potential decrease, mitochondrial enzymatic dysfunction, and mitochondrial morphological alteration are exhibited in two cell lines. These results suggest the nonthermal plasma treatment as an efficacious modality in lung cancer therapy.

Automicroneedle therapy system combined with topical tretinoin shows better regenerative effects compared with each individual treatment.

BACKGROUND: Regenerative therapy is a relatively new dermatological field. However, the currently available topical agents are unsuitable for transdermal drug delivery because of their high molecular weight and low liposolubility. Therefore, a more effective transdermal drug delivery system is needed in order to achieve better therapeutic effects with these agents. A recently introduced microneedle therapy system (MTS), which is a mechanical method for making minute holes in the skin, improves transdermal delivery. A recently developed refinement of this technique, the automicroneedle therapy system (AMTS), has several advantages over the traditional MTS, as it can achieve consistent results because of its automatic punching method. AIM: To evaluate the cutaneous effects of an AMTS in combination with topical tretinoin. METHODS: Twelve hairless mice were divided into two groups, and the dorsal skin of each mouse was marked down the centre. The first group was treated with the AMTS plus 0.025% tretinoin on one side of the back, and with 0.025% tretinoin only on the other side. The other group was treated with the AMTS and vehicle on one side, while the other side was left untreated. The effects on cutaneous regeneration and the treatment side-effects were evaluated by functional assessment including transepidermal water loss and skin hydration, and by histopathology including epidermal and dermal thickness, and density of collagen fibres. Western blotting and real-time reverse transcriptase PCR were also performed to determine protein and mRNA expression of procollagen type 1 and matrix metalloproteinase-13. RESULTS: Compared with the individual treatments (the AMTS alone or tretinoin alone) the combination of tretinoin plus the AMTS produced greater dermal regeneration as a result of increased proliferation of collagen fibres. This combination therapy did not result in treatment-related adverse effects. CONCLUSIONS: An AMTS combined with topical tretinoin is a safe and effective method for skin regeneration, which works by increasing collagen production, and might be a new therapeutic option for regenerative therapy.

Topical calcitriol restores the impairment of epidermal permeability and antimicrobial barriers induced by corticosteroids.

BACKGROUND: The active form of vitamin D(3) , calcitriol, is widely used for the treatment of psoriasis, with or without topical corticosteroids. Topical corticosteroids are known to disrupt permeability and antimicrobial barriers, even with short-term use. Yet, the effect of topical calcitriol on epidermal permeability and antimicrobial barriers disrupted by topical corticosteroids has not been determined. OBJECTIVES: To examine the effect of calcitriol on epidermal permeability and antimicrobial barrier function that has been impaired by corticosteroids, as well as to elucidate the mechanism of improvement. MATERIAL AND METHODS: Topical calcitriol or the control vehicle was applied to each flank of hairless mice 20 min after treatment with topical clobetasol propionate and repeated every 12 h for 3·5 days. Barrier function assessment, Nile red staining, electron microscopy, immunohistochemistry, Western blotting, and real-time reverse transcriptase-polymerase chain reaction studies were performed 24 h after the last application. RESULTS: Epidermis co-treated with topical calcitriol showed an improvement of stratum corneum integrity and barrier recovery, more intense fluorescence staining with Nile red, and an increase in lamellar body (LB) maturation and density, as well as upregulation of major epidermal lipid synthesis-related enzymes (3-hydroxy-3-methylglutaryl-CoA, serine-palmitoyl transferase and fatty acid synthase), mouse beta-defensin 3, cathelin-related antimicrobial peptide and vitamin D receptor. CONCLUSIONS: We found that topical calcitriol restored both the epidermal permeability and antimicrobial barrier that had been impaired by corticosteroids. This restoration was mediated by both an activation of the cutaneous vitamin D pathway and an increase of epidermal lipids and antimicrobial peptides, promoted by the formation of the LB and the activity of epidermal lipid synthesis-related enzymes.

Stimulation of epidermal calcium gradient loss increases the expression of hyaluronan and CD44 in mouse skin.

BACKGROUND: Hyaluronan (HA), a major extracellular matrix component in epidermis, has been found to accumulate in the epidermis after disruption of the epidermal barrier; however, the precise mechanisms underlying this process are not yet clear. Alterations in the epidermal calcium gradient are an important signal for permeability-barrier homeostasis. Thus, we hypothesized that epidermal calcium-ions might regulate HA expression. AIM: To investigate whether changes in the epidermal calcium gradient and subsequent induction of cytokines regulate HA, HA synthase (HAS) and HA receptor (CD44) expression in mouse epidermis, and to clarify the mechanisms of HA induction. METHODS: Sonophoresis of 1.5 mmol/L Ca(2+)-containing gel or Ca(2+)-free gel was performed to manipulate the epidermal Ca(2+) content without disrupting the permeability barrier. We also manipulated the Ca(2+) gradient by tape-stripping with or without 2 h immersion in 1.2 mmol/L Ca(2+)-containing solutions. Next we inhibited cytokine activity using tumour necrosis factor (TNF)-alpha or interleukin (IL)-1 inhibitors before sonophoresis. Six hours after each treatment, the expression of HA, HAS and CD44 were analysed using reverse transcription PCR and immunohistochemical stains. RESULTS: Sonophoresis of Ca(2+)-free gel significantly increased HA, HAS3 and CD44 expression in epidermis and in tape-stripped skin. However, the inhibition of Ca(2+) decrease in the upper epidermis by sonophoresis of Ca(2+)-containing gel or immersion of barrier-disrupted skin into a Ca(2+)-containing solution attenuated these inductions. Specific inhibitors of TNF-alpha and IL-1 specific inhibitors also abolished the sonophoresis-induced expression of HA, HAS3 and CD44. CONCLUSIONS: These results suggest that modulations in epidermal calcium regulate HA and CD44 expression directly or via induction of cytokines.

Evaluation of wastewater characterization methods.

Wastewater contains various organic components with different physical and biochemical characteristics. ASM No. 1 distinguishes two categories of biodegradable organic matter in wastewater, rapidly and slowly biodegradable. In general there are two methods for wastewater characterization: based on filtration in combination with a long-term BOD test or based on a respirogram. By comparing both approaches, we showed that in wastewater three categories of organic compounds with different biodegradation rates can be distinguished. These categories are referred to as readily biodegradable, rapidly hydrolysable and slowly hydrolysable organic matter. The total biodegradable COD can be found from a long-term BOD-test combined with a curve-fit and the readily biodegradable and rapidly hydrolysable from a respirogram. The slowly hydrolysable is the difference between total biodegradable COD and the sum of readily biodegradable and rapidly hydrolysable COD. Simulation with characterization based on filtration for a pre-anoxic reactor with a certain N-removal compared with the N-removal of the same plant with wastewater according to the modified characterization shows different results of each wastewater, especially with regard to the effluent nitrate concentration.

25 Hydroxyvitamin D 1 alpha-hydroxylase is required for optimal epidermal differentiation and permeability barrier homeostasis.

Keratinocytes express high levels of 25OHD 1alpha-hydroxylase (1OHase). The product of this enzyme, 1,25-dihydroxyvitamin D (1,25(OH)(2)D), promotes the differentiation of keratinocytes in vitro suggesting an important role for this enzyme in epidermal differentiation. To test whether 1OHase activity is essential for keratinocyte differentiation in vivo we examined the differentiation process in mice null for the expression of the 1alphaOHase gene (1alphaOHase(-/-)). Heterozygotes for the null allele were bred, and the progeny genotyped by PCR. The epidermis of the 1alphaOHase(-/-) animals and their wild-type littermates (1alphaOHase(+/+)) were examined by histology at the light and electron microscopic level, by immunocytochemistry for markers of differentiation, and by function examining the permeability barrier using transepidermal water loss (TEWL). No gross epidermal phenotype was observed; however, immunocytochemical assessment of the epidermis revealed a reduction in involucrin, filaggrin, and loricrin-markers of differentiation in the keratinocyte and critical for the formation of the cornified envelope. These observations were confirmed at the electron microscopic level, which showed a reduction in the F (containing filaggrin) and L (containing loricrin) granules and a reduced calcium gradient. The functional significance of these observations was tested using TEWL to evaluate the permeability barrier function of the epidermis. Although TEWL was normal in the basal state, following disruption of the barrier using tape stripping, the 1alphaOHase(-/-) animals displayed a markedly delayed recovery of normal barrier function. This delay was associated with a reduction in lamellar body secretion and a failure to reform the epidermal calcium gradient. Thus, the 25OHD 1OHase is essential for normal epidermal differentiation, most likely by producing the vitamin D metabolite, 1,25(OH)(2)D, responsible for inducing the proteins regulating calcium levels in the epidermis that are critical for the generation and maintenance of the barrier.

The characterization of molecular organization of multilamellar emulsions containing pseudoceramide and type III synthetic ceramide.

To investigate the molecular organization and phase behavior of physiologic lipid mixtures that contain either newly synthesized pseudoceramide or type III synthetic ceramide, various analytical techniques were used. The phase transition temperatures detected in differential scanning calorimetry analysis were 51.19 and 50.52 for the pseudoceramide-containing physiologic lipid mixture and synthetic type III ceramide-containing lipid mixture, respectively. From the small angle XRD patterns, the multilamellar emulsion-pseudoceramide showed 11.5 nm and 7.61 nm lamellar phases, while the multilamellar emulsion-synthetic ceramide showed only a 7.61 nm lamellar phase. The nonceramide containing lipid mixture did not show any distinct repeat pattern. Lateral packing distances of multilamellar emulsion-pseudoceramide and multilamellar emulsion-synthetic ceramide were measured as 0.4119 and 0.4110 nm at 30, respectively, which indicated the presence of hexagonal lattice. On the contrary, non-multilamellar emulsion did not show any definite repeat pattern. Transmission electron microscopy observation showed nearly comparable lamellar structures in all of the tested emulsions compared to the structure of human stratum corneum intercellular lipid. Decrease of water contents resulted in phase transition into liquid phase for all the tested emulsions, whereas phase transition into orthorhombic phase was observed only in multilamellar emulsion-pseudoceramide. From these results, we concluded that the molecular organization of multilamellar emulsion-pseudoceramide was characterized as the lateral hexagonal phase and both the long and short periodicity lamellar phases, which showed structural similarity with the native human stratum corneum intercellular lipid.

The skin barrier state of aged hairless mice in a dry environment.

BACKGROUND: Many elderly people have chronic xerosis, and frequently experience an exacerbation during winter. OBJECTIVES: To investigate the barrier state of aged murine skin with or without barrier disruption in a dry environment. METHODS: Aged and young hairless mice were kept separately in dry and normal conditions for 9 days. Acetone treatment was used to perturb the skin barrier. Skin barrier function was measured as transepidermal water loss (TEWL), and morphological changes in the epidermis were studied by electron microscopy. RESULTS: The baseline TEWL was not higher in the dry environment. The number of stratum corneum (SC) layers and the epidermal thickness of aged mice increased in the dry environment. The recovery rate of the aged skin barrier was neither accelerated nor delayed in the dry environment. In the normal environment, aged mice recovered more slowly than young mice. After barrier perturbation in the aged mice, changes in SC layers and in epidermal thickness were similar in the two environments. The secretion and number of lamellar bodies did not differ between the two environments. CONCLUSIONS: We confirmed that a dry environment induces epidermal proliferation and scaling in both aged and young mice. However, no remarkable difference was found in the skin barrier recovery of aged hairless mice in a dry environment.

Evolution of TEM-related extended-spectrum beta-lactamases in Korea.

TEM-52, differing from TEM-1 by having the substitutions Glu-104-->Lys, Met-182-->Thr, and Gly-238-->Ser, has previously been described as the most prevalent extended-spectrum beta-lactamase (ESBL) in Korea. In a further survey, we discovered the ESBLs TEM-15, which is like TEM-52 but lacks the substitution at residue 182, and TEM-88, which is like TEM-52 with an additional Gly-196-->Asp substitution. TEM-88 retained the activity of TEM-52 against moxalactam. Otherwise, the kinetic properties of the three ESBLs failed to show an advantage to this evolution.

Using genetic variation to study human disease.

The generation of a draft sequence of the human genome has spawned a unique opportunity to investigate the role of genetic variation in human diseases. The difference between any two human genomes has been estimated to be less than 0.1% overall, but still, this means that there are at least several million nucleotide differences per individual. The study of single nucleotide polymorphisms (SNPs), the most common type of variant, is likely to contribute substantially to deciphering genetic determinants of common and rare diseases. The effort to identify SNPs has been accelerated by three developments: the availability of sequence data from the genome project, improved informatic tools for searching the former and high-throughput genotype platforms. With these new tools in hand, dissecting the genetics of disease will rapidly move forward, although a number of formidable challenges will have to be met to see its promise realized in clinical medicine.