Clinical characteristics and outcome of omphalocele and gastroschisis: a 20-year multicenter regional experience.

Omphalocele and gastroschisis are the most common types of abdominal wall defects. Comprehensive local experience helps parents to make decisions on the pregnancy and foresee the disease journey. A retrospective review of abdominal wall defect patients in all three pediatric surgical centers in Hong Kong between January 2003 and February 2023 was conducted. All patients consecutively diagnosed with omphalocele and gastroschisis were included, excluding other forms. Data of demographics and short- and long-term outcome parameters were collected. A total of 99 cases were reviewed and 85 patients met the inclusion criteria. Diagnoses include omphalocele major (n = 49, 57.6%), omphalocele minor (n = 22, 25.9%) and gastroschisis (n = 14, 16.5%), with mean gestational age 37 weeks (SD 2.2) and birth weight 2.7 kg (SD 0.6). Omphalocele is most commonly associated with cardiovascular (n = 28, 39.4%) and chromosomal defects (n = 11, 15.5%). Surgical procedures including primary repair (n = 38, 53.5%), staged closure (n = 30, 42.3%) with average 8.6 days (SD 4.7) of silo reduction, and conservative management (n = 3, 4.2%) were performed. The mortality rate was 14.1% (n = 10) and the complication rate was 36.6% (n = 26). The majority of patients had normal intellectual development (92.5%) and growth (79.2%) on the latest follow-up. For gastroschisis, one patient (7.1%) had intestinal atresia. Surgical procedures included primary repair (n = 9, 64.3%) and staged closure (n = 5, 35.7%) with average 8 days (SD 3.5) of silo reduction. Complication rate was 21.4% (n = 3), with one mortality (7.1%). All patients had normal intellectual development and growth. The mean follow-up time of this series is 76.9 months (SD 62.9). Most abdominal wall defects in our series were managed surgically with a good overall survival rate and long-term outcome. This information is essential during antenatal and postnatal counseling for parents.

Case report: Regression of in-transit metastases of cutaneous squamous cell carcinoma with combination pembrolizumab and topical diphencyprone.

While typically low-risk, cutaneous squamous cell carcinoma (cSCC) can infrequently progress to metastatic disease with in-transit lesions, localized to the dermis or subcutaneous tissue between the primary tumor and draining regional lymph nodes. These lesions are associated with poor prognostic values, including decreased survival rates and increased risk of recurrence. We present the case of a 75-year-old male with cSCC and in-transit metastases on his scalp treated with the immune checkpoint inhibitor (ICI) pembrolizumab in conjunction with diphencyprone (DPCP), a topical hapten that induces a delayed-type hypersensitivity reaction in the skin. The patient was enrolled in a clinical trial (NCT05481658) that involved the twice-weekly application of DPCP 0.04% ointment to four of the in-transit metastases on his frontal scalp, concurrent with pembrolizumab 300 mg administered every three weeks. Following effective sensitization and a twelve-week treatment course, complete clearance of all lesions, DPCP-treated and non-DPCP treated, was achieved, with no adverse events. The immunologic profiles of the post-treatment biopsies were analyzed by TaqMan Low Density Array quantitative real-time polymerase chain reaction to measure immune marker gene expression. Relative to the non-DPCP-treated lesion, the DPCP-treated lesion demonstrated increased pro-inflammatory genetic markers and T-cell activation. This case represents the first reported instance of in-transit metastases of cSCC successfully treated with DPCP and an ICI. It highlights the potential safety and efficacy of DPCP with systemic immunotherapy for the management of in-transit metastases of cSCC in patients for whom surgery and radiation may be contraindicated.

Efficacy and safety of tretinoin 0.025%/clindamycin phosphate 1.2% gel in combination with benzoyl peroxide 6% cleansing cloths for the treatment of facial acne vulgaris.

Combination therapy using medications with complementary mechanisms of action is the standard of care in treating acne. We report results of a clinical trial evaluating the use of a fixed-dose tretinoin 0.025%/clindamycin phosphate 1.2% (T/CP) gel in combination with a benzoyl peroxide 6% foaming cloth compared with T/CP alone for facial acne. At week 12, the combination therapy group showed a trend toward greater efficacy compared with T/CP alone. There was a high success rate observed in the study, which may be attributable to the large percentage of adult female acne patients enrolled. Cutaneous adverse events were not statistically different in using combination therapy compared with T/CP alone.

Efficacy and safety of a ceramide containing moisturizer followed by fixed-dose clindamycin phosphate 1.2%/benzoyl peroxide 2.5% gel in the morning in combination with a ceramide containing moisturizer followed by tretinoin 0.05% gel in the evening for the treatment of facial acne vulgaris.

Combination therapy addressing multiple pathogenic factors should be used to achieve optimal outcomes in treating acne. The following study demonstrated both safety and efficacy of fixed-dose clindamycin phosphate 1.2%/benzoyl peroxide 2.5% in the morning with micronized tretinoin 0.05% gel in the evening. Both products were applied to the skin following the use of a ceramide containing moisturizing lotion.

Progressive impairments in executive function in the APP/PS1 model of Alzheimer's disease as measured by translatable touchscreen testing.

Executive function deficits in Alzheimer's disease (AD) occur early in disease progression and may be predictive of cognitive decline. However, no preclinical studies have identified deficits in rewarded executive function in the commonly used APPSwe/PS1∆E9 (APP/PS1) mouse model. To address this, we assessed 12-26 month old APP/PS1 mice on rewarded reversal and/or extinction tasks. 16-month-old, but not 13- or 26-month-old, APP/PS1 mice showed an attenuated rate of extinction. Reversal deficits were seen in 22-month-old, but not 13-month-old APP/PS1 animals. We then confirmed that impairments in reversal were unrelated to previously reported visual impairments in both AD mouse models and humans. Age, but not genotype, had a significant effect on markers of retinal health, indicating the deficits seen in APP/PS1 mice were directly related to cognition. This is the first characterisation of rewarded executive function in APP/PS1 mice, and has great potential to facilitate translation from preclinical models to the clinic.

Biochemical responses and accumulation properties of long-chain perfluorinated compounds (PFOS/PFDA/PFOA) in juvenile chickens (Gallus gallus).

One-day-old male chickens were exposed via oral gavage to mixtures of perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), and perfluorodecanoate (PFDA) at either a low dose (0.1 mg/kg body weight [b.w.]) or a high dose (1.0 mg/kg b.w.), or a saline/ethanol vehicle control, three times a week for 3 weeks. After 3 weeks of exposure, half of the chicks were sacrificed and the other half were allowed to depurate for a further 3 weeks. No dose-dependent statistically significant differences in body/organ weights were observed among treatment and control groups after 3 weeks of exposure or after three 3 of depuration. Neither 15 histological nor 14 measured plasma biochemical parameters were significantly different in chicks from the exposed groups and vehicle controls. PFOS, PFDA, and PFOA concentrations in blood/liver/kidney samples were measured throughout the exposure and depuration periods at different time intervals. PFOS and PFDA accumulated at much higher concentrations than PFOA during the experimental periods. Interestingly, PFOS and PFDA accumulation patterns in the blood were similar during the exposure and depuration periods. The half-lives for each PFC at the 0.1 and 1.0 mg/kg doses were, respectively, approximately 15 and 17 days for PFOS, 11 and 16 days for PFDA, and 3.9 and 3.9 days for PFOA. PFDA accumulation in organs was greater than or similar to that of PFOS: the liver was the main target during exposure and the blood was the main reservoir during depuration. These results indicate that exposure to a 1.0-mg mixture of PFOS/PFDA/PFOA/kg b.w. has no adverse effect on juvenile chickens.

Identification of 5-fluorouracil response proteins in colorectal carcinoma cell line SW480 by two-dimensional electrophoresis and MALDI-TOF mass spectrometry.

Colorectal cancer (CRC) is the second most prevalent cause of cancer-related deaths in the Western world. 5-Fluorouracil (5-FU) is a standard chemotherapeutic drug to treat CRC. However, the response rate is less than 20% and patients who have responded to 5-FU may become resistant. Therefore there is an urgent need to examine the 5-FU response proteins so that patients with no response to 5-FU can change to other treatment strategies promptly. In this study, the proteomic expression profile in a CRC cell line SW480 before and after 5-FU treatment was examined using 2-dimensional electrophoresis technology. Fourteen proteins with differential expression were identified using mass spectrometry and 7 of them were validated using immunocytochemical (ICC) staining. Protein identification indicated that cyclophilin A, cytokeratin 19 (CK19), cytokeratin 8 (CK8), ras-related nuclear protein, heat shock protein 27 (hsp27) and peroxiredoxin 6 (Prx 6) were upregulated whereas heat shock protein 60 (hsp60), cytokeratin 18 (CK18), cytokeratin 9 (CK9), carbamoylphosphate synthetase I, alpha-enolase, heat shock protein 70 (hsp70), nm23 and beta-actin were down-regulated. Seven of the 14 proteins detected were validated by ICC staining, which showed that the expression of hsp27, Prx 6 and hsp70 correlated with that from proteomics profiling. Our results suggest that hsp27, Prx 6 and hsp70 are potential 5-FU response proteins and they may represent potential targets for further evaluation in other 5-FU-sensitive and -resistant CRC cell lines.

A single-center, double-blind, randomized trial of the atrophogenic effects of fluocinonide cream 0.1% versus clobetasol propionate cream 0.05% in participants with corticosteroid-responsive dermatoses.

To compare the atrophogenic effects of fluocinonide cream 0.1% versus clobetasol propionate cream 0.05%, 20 participants with corticosteroid-responsive dermatoses were randomly assigned to receive fluocinonide cream 0.1% on one arm and clobetasol propionate cream 0.05% on the other arm. Study medications were applied to disease-free target areas on the inner arms twice daily for 2 weeks. The epidermal thickness of pretreatment and posttreatment punch biopsy specimens was measured. Skin examinations were performed evaluating clinical signs of atrophy. No significant reduction in epidermal thickness was observed in the fluocinonide-treated sites (mean, -0.0318 mm; standard deviation, 0.0239; P=.1991). A significant reduction in epidermal thickness was seen in the clobetasol-treated sites (mean, -0.1825 mm; standard deviation, 0.0239; P<.0001). This reduction was significantly greater than results from sites treated with fluocinonide cream 0.1% (difference, -0.1507; standard deviation, 0.0131; P<.0001). Although topical corticosteroids often are the first-line treatment for patients with various dermatoses, a side effect of continuous use is cutaneous atrophy. Our study demonstrated that clobetasol propionate cream 0.05% caused a significantly greater reduction in epidermal thickness compared with fluocinonide cream 0.1% when used twice daily for 2 weeks (P<.001). However, neither drug caused significant clinical signs of atrophy.

An evolutionary route to xylanase process fitness.

Directed evolution technologies were used to selectively improve the stability of an enzyme without compromising its catalytic activity. In particular, this article describes the tandem use of two evolution strategies to evolve a xylanase, rendering it tolerant to temperatures in excess of 90 degrees C. A library of all possible 19 amino acid substitutions at each residue position was generated and screened for activity after a temperature challenge. Nine single amino acid residue changes were identified that enhanced thermostability. All 512 possible combinatorial variants of the nine mutations were then generated and screened for improved thermal tolerance under stringent conditions. The screen yielded eleven variants with substantially improved thermal tolerance. Denaturation temperature transition midpoints were increased from 61 degrees C to as high as 96 degrees C. The use of two evolution strategies in combination enabled the rapid discovery of the enzyme variant with the highest degree of fitness (greater thermal tolerance and activity relative to the wild-type parent).

Impact and efficiency of GH10 and GH11 thermostable endoxylanases on wheat bran and alkali-extractable arabinoxylans.

The results of a comparative study of two thermostable (1-->4)-beta-xylan endoxylanases using a multi-technical approach indicate that a GH11 xylanase is more useful than a GH10 xylanase for the upgrading of wheat bran into soluble oligosaccharides. Both enzymes liberated complex mixtures of xylooligosaccharides. 13C NMR analysis provided evidence that xylanases cause the co-solubilisation of beta-glucan, which is a result of cell-wall disassembly. The simultaneous use of both xylanases did not result in a synergistic action on wheat bran arabinoxylans, but instead led to the production of a product mixture whose profile resembled that produced by the action of the GH10 xylanase alone. Upon treatment with either xylanase, the diferulic acid levels in residual bran were unaltered, whereas content in ferulic and p-coumaric acids were unequally decreased. With regard to the major differences between the enzymes, the products resulting from the action of the GH10 xylanase were smaller in size than those produced by the GH11 xylanase, indicating a higher proportion of cleavage sites for the GH10 xylanase. The comparison of the kinetic parameters of each xylanase using various alkali-extractable arabinoxylans indicated that the GH10 xylanase was most active on soluble arabinoxylans. In contrast, probably because GH11 xylanase can better penetrate the cell-wall network, this enzyme was more efficient than the GH10 xylanase in the hydrolysis of wheat bran. Indeed the former enzyme displayed a nearly 2-fold higher affinity and a 6.8-fold higher turnover rate in the presence of this important by-product of the milling industry.

Overview on desonide 0.05%: a clinical safety profile.

Desonide (as a cream, ointment, or lotion formulation) is widely used for the treatment of steroid-responsive dermatoses. This paper provides information on its safety record, as determined from adverse event reports and published trial results. A pharmacovigilance program, initiated in 1992 for all countries where desonide is available, collected reports of adverse events associated with topical desonide over nine years. Published accounts of randomized, controlled trials of desonide in comparison with hydrocortisone were reviewed. Sixty-two reports have been collected; most were from consumers and were not medically substantiated. There were no serious reactions directly attributable to desonide treatment and the majority of events reported were classified as expected local reactions, generally mild in nature. This level of reporting is against a background of extensive prescribing of desonide; almost one million packs are dispensed per annum in the US alone. The excellent safety profile of desonide revealed by this pharmacovigilance program is supported by a review of published clinical trial results.

Use and abuse of topical corticosteroids in infections of the skin and related structures.

Topical corticosteroids have improved the management of many inflammatory skin diseases, such as psoriasis and atopic dermatitis. However, these medications are associated with certain adverse effects that are potentially serious. The potent anti-inflammatory actions of these drugs increase susceptibility to bacterial and fungal infections, and therefore may preclude them from use when infection is the known cause of the disease. In addition, children may be more vulnerable than adults to systemic effects of topical corticosteroids because percutaneous absorption is proportionately greater. These are important considerations, and physicians need to weigh and compare the risks and benefits associated with these medications before initiating treatment. This involves an appreciation of which patient populations are at high risk, which skin conditions are incompatible with topical corticosteroid therapy, and which alternative nonsteroidal medications are effective in treating inflammatory skin diseases.

Interocular Shift of Visual Attention Enhances Stereopsis and Visual Acuities of Anisometropic Amblyopes beyond the Critical Period of Visual Development: A Novel Approach.

Aims. Increasing evidence shows that imbalanced suppressive drive prior to binocular combination may be the key factor in amblyopia. We described a novel binocular approach, interocular shift of visual attention (ISVA), for treatment of amblyopia in adult patients. Methods. Visual stimuli were presented anaglyphically on a computer screen. A square target resembling Landolt C had 2 openings, one in red and one in cyan color. Through blue-red goggles, each eye could only see one of the two openings. The patient was required to report the location of the opening presented to the amblyopic eye. It started at an opening size of 800 sec of arc, went up and down in 160 sec of arc step, and stopped when reaching the 5th reversals. Ten patients with anisometropic amblyopia older than age 14 (average age: 26.7) were recruited and received ISVA treatment for 6 weeks, with 2 training sessions per day. Results. Both Titmus stereopsis (z = -2.809, P = 0.005) and Random-dot stereopsis (z = -2.317, P = 0.018) were significantly improved. Average improvement in best corrected visual acuity (BCVA) was 0.74 line (t = 5.842, P < 0.001). Conclusions. The ISVA treatment may be effective in treating amblyopia and restoring stereoscopic function.