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Identification of mutations in I LAMB3 i indicates that both had JEB, the rarest form of EB.4 For generalized EB caused by mutations in I LAMB3 i which account for 80% of all laminin-322 mutations, having at least one missense mutation tends to be associated with the less severe intermediate non-Herlitz type. Dear Editor, Epidermolysis bullosa (EB) is a group of heterogeneous disorders involving fragility of epithelial tissues. [Extracted from the article]

Background: CHILD syndrome is an X‐linked dominant disorder associated with pathogenic mutations in the NSDHL gene. The condition is predominantly found in females as it is lethal in males. Most cases present at birth with extensive unilateral ichthyosiform erythroderma involving the trunk and limbs. Milder and less extensive presentations have been reported, leading to misdiagnosis especially during early childhood. Methods and Results: We report an adult female of Malay ancestry who presented with minimal skin and limb involvement. She was only diagnosed in adulthood when she presented with gastrointestinal symptoms and worsening of skin manifestations. The clinical diagnosis was suspected after a combination of clinical, pathological and immunohistochemistry correlation, and molecularly confirmed with the discovery of a frameshift variant in NSDHL. The novel variant was inherited from her mother who had some linear hypopigmented patches over the medial aspects of both her arms and right forearm. Conclusion: We uncovered a novel frameshift variant associated with presentations that cast a new light on the clinical features of CHILD syndrome. [ABSTRACT FROM AUTHOR]

Integrated optical sensors have garnered much interest for lab‐on‐chip applications such as chemical and biological sensing and detection. Among various ways for detection schemes, spectral analysis performed by a spectrometer has shown great promise. Typically, such spectrometry is carried out in a relatively large device, owing to the fact that spectral resolution is often dictated by large optical path length. Here, a high‐resolution compact spectrometer utilizing random scattering events in a disordered medium is demonstrated. The spectrometer is inverse designed by objective‐first method and fabricated using two‐photon polymerization technique. The compact spectrometer consists of a disordered photonic structure and an inversed‐designed mode decomposer. A spectral resolution of 0.25 nm with a bandwidth of 30 nm in the near‐infrared regime is realized from a spectrometer occupying a relatively small footprint of 30 × 12.8 µm2. The proposed platform has a great potential to be used as a versatile lightweight and compact spectrometer for various applications including on‐chip spectrometer and sensing. [ABSTRACT FROM AUTHOR]

Self‐improving dystrophic epidermolysis bullosa is a rare subtype of dystrophic epidermolysis bullosa (DEB) characterized by significant improvement in skin fragility within the first few years of life. Genetic inheritance has previously been reported as autosomal dominant or recessive with both forms harboring mutations in COL7A1. To date, there have been no reports of this rare clinical entity from various Southeast Asian ethnicities. Here, we describe the clinical and molecular features of five patients from the Southeast Asia region who presented with predominantly acral‐distributed blisters and erosions in the first few days of life. Blistering resolved over several months, without appearance of new blisters. By immunofluorescence, intraepidermal retention of Type VII collagen was observed in all patient skin biopsies when investigated with antibody staining. Genetic analysis of four patients revealed pathogenic variants in COL7A1 which have not been previously reported. The clinical diagnosis in these rare patients is confirmed with molecular histology and genetic characterization. [ABSTRACT FROM AUTHOR]

Haim–Munk syndrome (HMS) and Papillon–Lefevre syndrome (PLS) are phenotypic variants of palmoplantar keratoderma (PPK) with progressive early‐onset periodontitis and dental caries. HMS and PLS have been associated with homozygous or compound heterozygous mutations in the lysosomal protease gene Cathepsin C (CTSC). There have been only a few documented cases of CTSC mutations in patients from South‐East Asia. We report the clinical findings of two Cambodian brothers who presented with diffuse, demarcated PPK with transgrediens extending to the elbows and knees, as well as pachyonychia and dental caries. Arachnodactyly and periodontitis were also found in the older brother. Next‐generation sequencing unveiled a homozygous missense variant in CTSC (NM_001814.5: c.1337AC: p.(Asp446Ala)) in both brothers. Both parents were heterozygous for the variant, while an unaffected older brother was homozygous for the wild‐type allele. Our study adds to the spectrum of mutations and associated clinical presentations for this rare genodermatosis. [ABSTRACT FROM AUTHOR]

CARD14‐associated papulosquamous eruption (CAPE) is a rare autosomal dominant dermatosis that presents classically in early childhood with clinical features of both psoriasis and pityriasis rubra pilaris (PRP). The disease is known to be refractory to topical and systemic therapies classically used for psoriasis, with the majority of reported cases requiring treatment with biologics, such as ustekinumab and secukinumab. We present a toddler with a clinical presentation consistent with CAPE and found to have a novel heterozygous variant of the CARD14 gene. She was refractory to treatment with topical emollients and topical corticosteroids, but responsive to oral acitretin. [ABSTRACT FROM AUTHOR]

We investigated global and regional effects of myocardial transplantation of human induced pluripotent stem cell (i PSC)-derived mesenchymal stem cells (i MSCs) in infarcted myocardium. Acute myocardial infarction ( MI) was induced by ligation of left coronary artery of severe combined immunodeficient mice before 2 × 105 i MSCs or cell-free saline were injected into peri-infarcted anterior free wall. Sham-operated animals received no injection. Global and regional myocardial function was assessed serially at 1-week and 8-week by segmental strain analysis by using two dimensional (2D) speckle tracking echocardiography. Early myocardial remodelling was observed at 1-week and persisted to 8-week with global contractility of ejection fraction and fractional area change in saline- (32.96 ± 14.23%; 21.50 ± 10.07%) and i MSC-injected (32.95 ± 10.31%; 21.00 ± 7.11%) groups significantly depressed as compared to sham control (51.17 ± 11.69%, P < 0.05; 34.86 ± 9.82%, P < 0.05). However, myocardial dilatation was observed in saline-injected animals (4.40 ± 0.62 mm, P < 0.05), but not i MSCs (4.29 ± 0.57 mm), when compared to sham control (3.74 ± 0.32 mm). Furthermore, strain analysis showed significant improved basal anterior wall strain (28.86 ± 8.16%, P < 0.05) in the i MSC group, but not saline-injected (15.81 ± 13.92%), when compared to sham control (22.18 ± 4.13%). This was corroborated by multi-segments deterioration of radial strain only in saline-injected (21.50 ± 5.31%, P < 0.05), but not i MSC (25.67 ± 12.53%), when compared to sham control (34.88 ± 5.77%). Improvements of the myocardial strain coincided with the presence of interconnecting telocytes in interstitial space of the infarcted anterior segment of the heart. Our results show that localized injection of i MSCs alleviates ventricular remodelling, sustains global and regional myocardial strain by paracrine-driven effect on neoangiogenesis and myocardial deformation/compliance via parenchymal and interstitial cell interactions in the infarcted myocardium. [ABSTRACT FROM AUTHOR]

Cardiac fibroblasts are crucial in pathophysiology of the myocardium whereby their aberrant proliferation has significant impact on cardiac function. Hydrogen sulphide ( H2S) is a gaseous modulator of potassium channels on cardiomyocytes and has been reported to attenuate cardiac fibrosis. Yet, the mechanism of H2S in modulating proliferation of cardiac fibroblasts remains poorly understood. We hypothesized that H2S inhibits proliferative response of atrial fibroblasts through modulation of potassium channels. Biophysical property of potassium channels in human atrial fibroblasts was examined by whole-cell patch clamp technique and their cellular proliferation in response to H2S was assessed by BrdU assay. Large conductance Ca2+-activated K+ current ( BKCa), transient outward K+ current (Ito) and inwardly rectifying K+ current ( IKir) were found in human atrial fibroblasts. Current density of BKCa ( IC50 = 69.4 μM; n = 6), Ito ( IC50 = 55.1 μM; n = 6) and IKir ( IC50 = 78.9 μM; n = 6) was significantly decreased ( P < 0.05) by acute exposure to NaHS (a H2S donor) in atrial fibroblasts. Furthermore, NaHS (100-500 μM) inhibited fibroblast proliferation induced by transforming growth factor-β1 ( TGF-β1; 1 ng/ml), Ang II (100 nM) or 20% FBS. Pre-conditioning of fibroblasts with NaHS decreased basal expression of Kv4.3 (encode Ito), but not KCa1.1 (encode BKCa) and Kir2.1 (encode IKir). Furthermore, H2S significantly attenuated TGF-β1-stimulated Kv4.3 and α-smooth muscle actin expression, which coincided with its inhibition of TGF-β-induced myofibroblast transformation. Our results show that H2S attenuates atrial fibroblast proliferation via suppression of K+ channel activity and moderates their differentiation towards myofibroblasts. [ABSTRACT FROM AUTHOR]

Abstract: The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are known to inhibit leukocyte recruitment to endothelium but the mechanism is less understood. Platelet endothelial cell adhesion molecule-1 (PECAM-1) is an endothelial junction protein involved in leukocyte diapedesis. We hypothesize that in endothelial cells, statins may well recruit PECAM-1 to exert their inhibitory effect on leukocyte trans-endothelial migration (TEM). In lovastatin-treated resting human umbilical vein endothelial cells (HUVECs), increased levels of mRNA and protein of PECAM-1 as well as its bio-synthesis (all ∼2-fold) were observed by real-time PCR, Western blotting and 35S-labeled methionine incorporation assay, respectively. Moreover, in lovastatin treated resting cells as well as TNF-α activated endothelial cells, unanimously decreased Triton X-100 insoluble and soluble PECAM-1 ratio was observed. Such changes were accompanied by decreased TEM of U-937 cells (a promonocyte cell line). All lovastatin’s effects were abrogated by mevalonic acid. In resting HUVECs, geranylgeranyl pyrophosphate (GGPP), but not farnesyl pyrophosphate (FPP) (both are isoprenoid intermediates in the cholesterol biosynthesis pathway) compromised the effect of lovastatin on PECAM-1 expression, whereas C3 toxin, an inhibitor of small G proteins, exerted statin-like effect. Conclusion: Statin-reduced endothelial permeability could be attributed to altered intracellular distribution of PECAM-1 in endothelial cells. We speculate that lovastatin regulates PECAM-1 expression in HUVECs through the mevalonate-GGPP pathway by inhibiting of Rho small GTPase. [Copyright &y& Elsevier]

This paper presents an inverse‐designed 3D‐printed polymer‐based broadband free‐form polarization beamsplitter in the near‐infrared. A computational inverse‐design method is used to design a thin free‐form meta‐grating to split normally incident light with different polarizations to different diffraction orders, one toward the left first order and one toward the right first order. The grating is 3D‐printed using two‐photon direct laser writing. Polarization splitting behavior is experimentally observed in the near‐infrared region for wavelengths of 1.3 and 1.55 µm, and with performance metrics close to the simulation values. The proposed platform combining inverse‐design and 3D‐printing can be extended to the design, fabrication, and integration of multiple broadband photonic structures to build devices with complex functionalities. [ABSTRACT FROM AUTHOR]