Bullous pemphigoid in diabetic patients treated by gliptins: the other side of the coin

Bullous pemphigoid (BP) is the most common autoimmune bullous skin disease that affects primarily patients older than 60 years. The majority of BP cases are spontaneous, but BP can also be triggered by certain drugs’ exposures. Since 2011, a growing number of observations has been reporting cases of BP in Type 2 diabetic patients. These forms have been linked to the use of a new category of anti-diabetic drugs called dipeptidyl peptidase inhibitors (DPP-4i) or gliptins, but to date, the exact pathophysiological mechanisms underlying this association are not completely elucidated. Although conventional and gliptin-associated BP are thought to share similar clinical and histopathological features, our thorough review of the most recent literature, shows that these 2 forms are quite distinct: DPP-4-i-associated BP seems to appear at an earlier age than spontaneous BP, it may manifest either as a noninflammatory or inflammatory phenotype, while the conventional form presents with a typical inflammatory phenotype. Additionally, an important distinctive histological feature was recently shown in Gliptin-associated BP: these forms may present a less significant eosinophils infiltrate in the upper dermis of peri-blister lesions compared to the skin of patients with spontaneous BP, and this seems a specific feature of the clinically non-inflammatory forms. In accordance with previous literature, we found that the direct immunofluorescence (DIF) gives identical findings in both DPP-4i-associated and conventional forms of BP which is an IgG and complement C3 deposition as a linear band at the dermal–epidermal junction in perilesional skin. Indirect immunofluorescence shows the presence of IgG circulating autoantibodies in the patient's serum which titer does not differ between spontaneous and DPP-4i-associated BP, while the specificity of these autoantibodies, may be different in spontaneous, induced non-inflammatory and induced inflammatory forms, epitope spreading phenomenon seems to play a role in determining these specificities. Further research, based on integrated epidemiological, clinical, histo-immunological and pharmacogenomic approaches, may give more insight into these forms of BP. This combined approach will allow to better define BP endotypes and to unveil the mechanism of spontaneous or drug-induced breakage of the immunotolerance to skin self-antigens.

Berry paramagnetism in the Dirac semimetal ZrTe5

Dirac matters have attracted a lot of interest due to their unique band structure with linear band dispersions, which have great potential for technological applications. Recently, three-dimensional Dirac and Weyl semimetals have invoked distinctive phenomena originating from a non-trivial Berry phase. In this study, we prepare single crystals of TixZr1-xTe5 with a highly anisotropic Fermi surface. Our detailed electrical transport measurements reveal that the crystals show the Lifshitz transition, and Ti doping induces a band shift. Further quantum oscillation analyses demonstrate that the TixZr1-xTe5 crystals are 3D Dirac semimetals. Additionally, we observed a minimum temperature-dependent magnetic susceptibility, which is close to a peak position of electrical resistivity. This observation is interpreted in terms of the Berry paramagnetism. Our finding paves the way to determine a band topology by magnetism and also provides a platform to apply the Berry magnetism to Dirac semimetals.

Evidence for strong electron correlations in a nonsymmorphic Dirac semimetal

Metallic iridium oxides (iridates) provide a fertile playground to explore new phenomena resulting from the interplay between topological protection, spin-orbit and electron-electron interactions. To date, however, few studies of the low energy electronic excitations exist due to the difficulty in synthesising crystals with sufficiently large carrier mean-free-paths. Here, we report the observation of Shubnikov-de Haas quantum oscillations in high-quality single crystals of monoclinic SrIrO3 in magnetic fields up to 35 T. Analysis of the oscillations reveals a Fermi surface comprising multiple small pockets with effective masses up to 4.5 times larger than the calculated band mass. Ab-initio calculations reveal robust linear band-crossings at the Brillouin zone boundary, due to its non-symmorphic symmetry, and overall we find good agreement between the angular dependence of the oscillations and the theoretical expectations. Further evidence of strong electron correlations is realized through the observation of signatures of non-Fermi liquid transport as well as a large Kadowaki-Woods ratio. These collective findings, coupled with knowledge of the evolution of the electronic state across the Ruddlesden-Popper iridate series, establishes monoclinic SrIrO3 as a topological semimetal on the boundary of the Mott metal-insulator transition.

Harlequin Ichthyosis in a Filipino Newborn: Management Pearls in a Resource-limited Setting

Introduction. Harlequin ichthyosis (HI) is a rare type of autosomal recessive congenital ichthyosis. There are approximately 200 documented cases worldwide, with less than five published reports in the Philippines. Despite its rarity, current literature suggests a better prognosis for these patients. Case description. We describe a preterm male newborn who presented at birth enclosed in a thick hyperkeratotic armor-like scale plates with areas of fissures, with associated ectropion, conjunctiva dehiscence, and eclabium. The thickened encasement also covered the hands and feet, causing severe contractures. A diagnosis of harlequin ichthyosis was given based on the clinical features. The patient was managed through a multidisciplinary approach, including referral to the tele-ichthyosis platform of a US-based foundation for patients with ichthyosis. Thermoregulation, nutrition, and hydration were carefully managed. Bland emollients were applied generously following normal saline soaks to improve barrier protection. Acitretin was administered on day 2 of life to facilitate the desquamation of the thickened encasement. A marked decrease in erythema and the thickness of the hyperkeratotic skin, and reduced conjunctival dehiscence were noted after one week of therapy. However, the constrictions on the hands and feet showed bluish discoloration and signs of necrosis. Linear band excision was performed to release the constrictors. Despite aggressive management, the patient succumbed to sepsis on day 12 of life. Conclusion. Improved prognosis amongst HI patients is correlated with optimal quality of care regardless of resource limitations. A multidisciplinary approach and early administration of retinoids cannot be overemphasized. Linear band excision within the first week of life is suggested for constrictions on the extremities that do not improve with retinoids to avoid necrosis and autoamputation.

A study of clinical and Immunofluorescence spectrum of Immunobullous diseases

Background: Immunobullous disorders are a group of disorders involving the formation of a fluid filled cavity within or beneath the epidermis, due to the presence of autoantibodies against adhesion molecules in epidermis and dermis. Accurate diagnosis of these disorders requires clinicopathological correlation along with immunofluorescence study. Aims and Objectives: This study was undertaken to describe the clinical features of immunobullous disorders and to analyse the utility of Direct immunofluorescence (DIF) in the diagnosis of these disorders. Materials and Methods: A total of 42 Patients attending skin OPD between February 2014 and March 2017 who had a provisional diagnosis of immunobullous disease were enrolled in the study. Detailed clinical examination and DIF study were done in all cases. Results: Out of 42 cases studied, 31 were diagnosed as pemphigus vulgaris (PV) and 11 as bullous pemphigoid (BP) that was confirmed by DIF. There were 20 (46.61%) male patients and 22 (52.38%) female patients in the age group of 18 to 81 years with a mean age of 52.64 years. A slightly female preponderance was observed. Mean age of presentation of PV patients is 50.83 years with age group range was between 18 to 77 years. Majority of patients presented at 4th and 5th decade of life. Age group range for BP was between 34 to 81years with mean age of presentation being 57.72 years. Majority of our patients presented at 5th decade or later. DIF was positive in all 42 cases (100%) of immunobullous disease. DIF in all 31 cases of PV showed 100% IgG deposition in intercellular substance (ICS) and 64.51% C3 deposition in ICS. BP showed 100% C3 deposition in all 11 cases, 63.63% IgG in seven of the eleven,18.18% IgA in two and 9% IgM, fibin in one each as a linear band at basement membrane zone (BMZ). Conclusion: Both the clinical findings and the Imunofluorescence features are important in arriving at a definite diagnosis in immunobullous diseases. In all the cases DIF was absolutely essential tool to come to a final diagnosis.

Order-by-disorder from bond-dependent exchange and intensity signature of nodal quasiparticles in a honeycomb cobaltate

Recent theoretical proposals have argued that cobaltates with edge-sharing octahedral coordination can have significant bond-dependent exchange couplings thus offering a platform in 3d ions for such physics beyond the much-explored realisations in 4d and 5d materials. Here we present high-resolution inelastic neutron scattering data within the magnetically ordered phase of the stacked honeycomb magnet CoTiO3 revealing the presence of a finite energy gap and demonstrate that this implies the presence of bond-dependent anisotropic couplings. We also show through an extensive theoretical analysis that the gap further implies the existence of a quantum order-by-disorder mechanism that, in this material, crucially involves virtual crystal field fluctuations. Our data also provide an experimental observation of a universal winding of the scattering intensity in angular scans around linear band-touching points for both magnons and dispersive spin-orbit excitons, which is directly related to the non-trivial topology of the quasiparticle wavefunction in momentum space near nodal points.

Unilateral Retinal Vasculitis as the Presenting Manifestation of Parry-Romberg Syndrome (Progressive Hemifacial Atrophy)

Purpose: This work aims to present a case of retinal vasculitis associated with Parry-Romberg syndrome. Method: A case report is presented. Results: A 17-year-old man with new floaters was found to have 20/40 vision with 1+ vitreous cell and retinal vasculitis in the right eye only. Workup for infectious etiologies did not reveal an explanation for the retinal vasculitis. However, magnetic resonance imaging of the head showed areas of linear band-like atrophy and scarring of the scalp and soft tissues as well as areas of gliosis and encephalomalacia in the subcortical white matter, all of which were consistent with Parry-Romberg syndrome. The patient was prescribed oral steroids and methotrexate, and the retinal vasculitis improved. Conclusions: Parry-Romberg syndrome is a rarely reported cause of retinal vasculitis and should be kept in the differential for retinal vasculitis.

Idiopathic linear IgA bullous dermatosis treated with prednisone

We present a case of a 43-year-old man with a medical history of paroxysmal atrial fibrillation that presented with acute onset generalised vesiculobullous rash of 1-week duration. The rash was initially noticed on his groin and then spread to his hands, feet and mucosal surfaces. Laboratory tests were unremarkable, including an extensive infection aetiology work-up. Punch biopsies were obtained of a fresh lesion and were stained with H&E and sent for direct immunofluorescence. Light microscopy and immunofluorescence study demonstrated a subepidermal blister with predominant neutrophilic infiltrates and a linear band of IgA at the dermoepidermal junction, respectively. The patient was diagnosed with linear IgA bullous dermatosis and was subsequently treated with 0.5 mg/kg of prednisone daily following previous case reports. At 1-week follow-up as an outpatient, the bullae became crusted, and the rash was nearly completely regressed.

Beside or by turn? The Buh-Dnister foragers and the Linear Band Pottery farmers on the Southern Buh River (Ukraine)

For a long time, finds of the Linear Band Pottery culture (LBK) on the Southern Buh numbered only two bowls from the Buh-Dnister culture site of Bazkiv Ostriv. After the recent discovery of a few more vessels and four stationary LBK settlements, some scholars have assumed the Neolithic incomers regularly inhabited the most of the region. However new direct AMS dates on the Buh-Dnister pottery have shown the existence of the indigenous hunter-gatherers here from 5300 to 5000 BC. Therefore, today, the cluster of four sites is the only verified area that was settled by the early farmers near the town of Zavallia. The occurrence of the settlements at very this place is explained by the fertile local soil and the desire of the inhabitants to control the huge deposit of graphite, which was a centre of an extensive exchange network for the North-Pontic indigenous groups. This could have given the local LBK community significant social prestige through the active production and exchange of valuable goods.

Mechanisms of Spectrotemporal Modulation Detection for Normal- and Hearing-Impaired Listeners

Spectrotemporal modulations (STM) are essential features of speech signals that make them intelligible. While their encoding has been widely investigated in neurophysiology, we still lack a full understanding of how STMs are processed at the behavioral level and how cochlear hearing loss impacts this processing. Here, we introduce a novel methodological framework based on psychophysical reverse correlation deployed in the modulation space to characterize the mechanisms underlying STM detection in noise. We derive perceptual filters for young normal-hearing and older hearing-impaired individuals performing a detection task of an elementary target STM (a given product of temporal and spectral modulations) embedded in other masking STMs. Analyzed with computational tools, our data show that both groups rely on a comparable linear (band-pass)–nonlinear processing cascade, which can be well accounted for by a temporal modulation filter bank model combined with cross-correlation against the target representation. Our results also suggest that the modulation mistuning observed for the hearing-impaired group results primarily from broader cochlear filters. Yet, we find idiosyncratic behaviors that cannot be captured by cochlear tuning alone, highlighting the need to consider variability originating from additional mechanisms. Overall, this integrated experimental-computational approach offers a principled way to assess suprathreshold processing distortions in each individual and could thus be used to further investigate interindividual differences in speech intelligibility.