Optical spectra and exciton radiative lifetimes in bulk transition metal dichalcogenides.

The optical response of layered transition metal dichalcogenides (TMDCs) exhibits remarkable excitonic properties which are important from both fundamental and device application viewpoints. One of these phenomena is the observation of intralayer/interlayer excitons. While much effort has been done to characterize excitons in monolayer TMDCs and their heterostructures, a quite limited number of works have addressed the exciton spectra of their bulk counterparts. In this work, we employ ab initio many-body perturbation calculations to investigate the exciton dynamics and spectra of bulk 2H-MX2 (M = Mo, W, and X = S, Se). For molybdenum-based systems, we find the presence of interlayer excitons at energies higher than the first bright exciton (XA), with non-negligible strength intensity. Our results also show that interlayer excitons in tungsten-based systems are almost degenerate in energy with XA and possess very small oscillator strengths when compared with molybdenum-based systems. At room temperature, and considering the thermal exciton fine-structure population for the XA-exciton, we estimate effective radiative lifetimes in the range of ∼4-14 ns. For higher energy excitons we predict longer effective lifetimes of tens of nanoseconds.

Treatment-related mortality in children with cancer in low-income and middle-income countries: a systematic review and meta-analysis.

BACKGROUND: Approximately 90% of children with cancer live in low-income and middle-income countries (LMICs), where 5-year survival is lower than 20%. Treatment-related mortality in high-income countries is approximately 3-5%; however, in LMICs, treatment-related mortality has been reported in up to 45% of children with cancer. This study aimed to systematically explore the burden of treatment-related mortality in children with cancer in LMICs and to explore the association between country income level and treatment-related mortality. METHODS: For this systematic review and meta-analysis we identified articles published between Jan 1, 2010, and June 22, 2021, describing treatment-related mortality in paediatric patients (aged 0-21 years) with cancer in LMICs. We searched PubMed, Trip, Web of Science, Embase, and the WHO Global Metric Index databases. The search was limited to full-text articles and excluded case reports (<10 patients) and haematopoietic stem-cell transplantation recipients. Two reviewers independently screened studies for eligibility, extracted data from included publications, and evaluated data quality. Random and mixed-effects models were used to estimate treatment-related mortality burden and trends. The Cochran-Q statistic was used to assess heterogeneity between studies. This study is registered on PROSPERO (CRD42021264849). FINDINGS: Of 13 269 identified abstracts, 501 studies representing 68 351 paediatric patients with cancer were included. The treatment-related mortality estimate was 6·82% (95% CI 5·99-7·64), accounting for 30·9% of overall mortality (4437 of 14 358 deaths). Treatment-related mortality was inversely related to country income. Treatment-related mortality was 14·19% (95% CI 9·65-18·73) in low-income countries, 9·21% (7·93-10·49) in lower-middle-income countries, and 4·47% (3·42-5·53) in upper-middle-income countries (Cochran-Q 42·39, p<0·0001). In upper-middle-income countries, the incidence of treatment-related mortality decreased over time (slope -0·002, p=0·0028); however, outcomes remained unchanged in low-income (p=0·21) and lower-middle-income countries (p=0·16). INTERPRETATION: Approximately one in 15 children receiving cancer treatment in LMICs die from treatment-related complications. Although treatment-related mortality has decreased in upper-middle-income countries over time, it remains unchanged in LMICs. There is an urgent need for targeted supportive care interventions to reduce global disparities in childhood cancer survival. FUNDING: American Lebanese Syrian Associated Charities and National Cancer Institute.

Resilient health care in global pediatric oncology during the COVID-19 pandemic.

BACKGROUND: In the face of unprecedented challenges because of coronavirus disease 2019, interdisciplinary pediatric oncology teams have developed strategies to continue providing high-quality cancer care. This study explored factors contributing to health care resilience as perceived by childhood cancer providers in all resource level settings. METHODS: This qualitative study consisted of 19 focus groups conducted in 16 countries in 8 languages. Seven factors have been previously defined as important for resilient health care including: 1) in situ practical experience, 2) system design, 3) exposure to diverse views on the patient's situation, 4) protocols and checklists, 5) teamwork, 6) workarounds, and 7) trade-offs. Rapid turn-around analysis focused on these factors. RESULTS: All factors of health care resilience were relevant to groups representing all resource settings. Focus group participants emphasized the importance of teamwork and a flexible and coordinated approach to care. Participants described collaboration within and among institutions, as well as partnerships with governmental, private, and nonprofit organizations. Hierarchies were advantageous to decision-making and information dissemination. Clinicians were inspired by their patients and explained creative trade-offs and workarounds used to maintain high-quality care. CONCLUSIONS: Factors previously described as contributing to resilient health care manifested differently in each institution but were described in all resource settings. These insights can guide pediatric oncology teams worldwide as they provide cancer care during the next phases of the pandemic. Understanding these elements of resilience will also help providers respond to inevitable future stressors on health care systems.

Nanogap-based all-electronic DNA sequencing devices using MoS2 monolayers.

The realization of nanopores in atom-thick materials may pave the way towards electrical detection of single biomolecules in a stable and scalable manner. In this work, we theoretically study the potential of different phases of MoS2 nanogaps to act as all-electronic DNA sequencing devices. We carry out simulations based on density functional theory and the non-equilibrium Green's function formalism to investigate the electronic transport across the device. Our results suggest that the 1T'-MoS2 nanogap structure is energetically more favorable than its 2H counterpart. At zero bias, the changes in the conductance of the 1T'-MoS2 device can be well distinguished, making possible the selectivity of the DNA nucleobases. Although the conductance fluctuates around the resonances, the overall results suggest that it is possible to distinguish the four DNA bases for energies close to the Fermi level.

Phase transition and electronic structure investigation of MoS2-reduced graphene oxide nanocomposite decorated with Au nanoparticles.

In this work a simple approach to transform MoS2 from its metallic (1T' to semiconductor 2H) character via gold nanoparticle surface decoration of a MoS2 reduced graphene oxide (rGO) nanocomposite is proposed. The possible mechanism to this phase transformation was investigated using different spectroscopy techniques, and supported by density functional theory theoretical calculations. A mixture of the 1T'- and 2H-MoS2 phases was observed from the Raman and Mo 3d high resolution x-ray photoelectron spectra analysis in the MoS2-rGO nanocomposite. After surface decoration with gold nanoparticles the concentration of the 1T' phase decreases making evident a phase transformation. According to Raman and valence band spectra analyzes, the Au nanoparticles (NPs) induce a p-type doping in MoS2-rGO nanocomposite. We proposed as a main mechanism to the MoS2 phase transformation the electron transfer from Mo 4d xy,xz,yz in 1T' phase to AuNPs conduction band. At the same time, the unoccupied electronic structure was investigated from S K-edge near edge x-ray absorption fine structure spectroscopy. Finally, the electronic coupling between unoccupied electronic states was investigated by the core hole clock approach using resonant Auger spectroscopy, showing that AuNPs affect mainly the MoS2 electronic states close to Fermi level.

Ab initio modelling of spin relaxation lengths in disordered graphene nanoribbons.

The spin-dependent transport properties of armchair graphene nanoribbons in the presence of extrinsic spin-orbit coupling induced by a random distribution of nickel adatoms is studied. By combining a recursive Green's function formalism with density functional theory, we explore the influence of ribbon length and metal adatom concentration on the conductance. At a given length, we observed a significant enhancement of the spin-flip channel around resonances and at energies right above the Fermi level. We also estimate the spin-relaxation length, finding values on the order of tens of micrometers at low Ni adatom concentrations. This study is conducted at singular ribbon lengths entirely from fully ab initio methods, providing indirectly evidence that the Dyakonov-Perel spin relaxation mechanism might be the dominant at low concentrations as well as the observation of oscillations in the spin-polarization.

Spin-orbit coupling prevents spin channel suppression of transition metal atoms on armchair graphene nanoribbons.

We investigate the spin-dependent electronic and transport properties of armchair graphene nanoribbons including spin-orbit coupling due to the presence of nickel and iridium adatoms by using ab initio calculations within the spin-polarized density functional theory and non-equilibrium Green's function formalism. Our results indicate that the intensity of the spin-flip precession is a direct consequence of the relaxed adsorption sites of the adatoms. We point out that d orbitals of Ni and Ir result in strong dependence on the spin-conserved and spin-flip transmission probabilities. In particular, we show that the presence of spin-orbit coupling can lead to an enhancement of the transmission probabilities especially around resonances arising due to weak coupling with specific orbitals.

Ultrafast charge transfer dynamics pathways in two-dimensional MoS2-graphene heterostructures: a core-hole clock approach.

Two-dimensional van der Waals heterostructures are attractive candidates for optoelectronic nanodevice applications. The charge transport process in these systems has been extensively investigated, however the effect of coupling between specific electronic states on the charge transfer process is not completely established yet. Here, interfacial charge transfer (CT) in the MoS2/graphene/SiO2 heterostructure is investigated from static and dynamic points of view. Static CT in the MoS2-graphene interface was elucidated by an intensity quenching, broadening and a blueshift of the photoluminescence peaks. Atomic and electronic state-specific CT dynamics on a femtosecond timescale are characterized using a core-hole clock approach and using the S1s core-hole lifetime as an internal clock. We demonstrate that the femtosecond electron transfer pathway in the MoS2/SiO2 heterostructure is mainly due to the electronic coupling between S3p-Mo4d states forming the Mo-S covalent bond in the MoS2 layer. For the MoS2/graphene/SiO2 heterostructure, we identify, with the support of density functional calculations, new pathways that arise due to the high density of empty electronic states of the graphene conduction band. The latter makes the transfer process time in the MoS2/graphene/SiO2/Si twice as fast as in the MoS2/SiO2/Si sample. Our results show that ultrafast electron delocalization pathways in van der Waals heterostructures are dependent on the electronic properties of each involved 2D material, creating opportunities to modulate their transport properties.

Anomalous Temperature Dependence of the Band Gap in Black Phosphorus.

Black phosphorus (BP) has gained renewed attention due to its singular anisotropic electronic and optical properties that might be exploited for a wide range of technological applications. In this respect, the thermal properties are particularly important both to predict its room temperature operation and to determine its thermoelectric potential. From this point of view, one of the most spectacular and poorly understood phenomena is indeed the BP temperature-induced band gap opening; when temperature is increased, the fundamental band gap increases instead of decreases. This anomalous thermal dependence has also been observed recently in its monolayer counterpart. In this work, based on ab initio calculations, we present an explanation for this long known and yet not fully explained effect. We show that it arises from a combination of harmonic and lattice thermal expansion contributions, which are in fact highly interwined. We clearly narrow down the mechanisms that cause this gap opening by identifying the peculiar atomic vibrations that drive the anomaly. The final picture we give explains both the BP anomalous band gap opening and the frequency increase with increasing volume (tension effect).

Two-dimensional exciton properties in monolayer semiconducting phosphorus allotropes.

Excitons play a key role in technological applications since they have a strong influence on determining the efficiency of photovoltaic devices. Recently, it has been shown that the allotropes of phosphorus possess an optical band gap that can be tuned over a wide range of values including the near-infrared and visible spectra, which would make them promising candidates for optoelectronic applications. In this work we carry out ab initio many-body perturbation theory calculations to study the excitonic effects on the optical properties of two-dimensional phosphorus allotropes: the case of blue and black monolayers. We elucidate the most relevant optical transitions, exciton binding energy spectrum as well as real-space exciton distribution, particularly focusing on the absorption spectrum dependence on the incident light polarization. In addition, based on our results, we use a set of effective hydrogenic models, in which the electron-hole Coulomb interaction is included to estimate exciton binding energies and radii. Our results show an excellent agreement between the many-body methodology and the effective models.

Impaired oxidative metabolism and calcium mishandling underlie cardiac dysfunction in a rat model of post-acute isoproterenol-induced cardiomyopathy.

Stress-induced cardiomyopathy, triggered by acute catecholamine discharge, is a syndrome characterized by transient, apical ballooning linked to acute heart failure and ventricular arrhythmias. Rats receiving an acute isoproterenol (ISO) overdose (OV) suffer cardiac apex ischemia-reperfusion damage and arrhythmia, and then undergo cardiac remodeling and dysfunction. Nevertheless, the subcellular mechanisms underlying cardiac dysfunction after acute damage subsides are not thoroughly understood. To address this question, Wistar rats received a single ISO injection (67 mg/kg). We found in vivo moderate systolic and diastolic dysfunction at 2 wk post-ISO-OV; however, systolic dysfunction recovered after 4 wk, while diastolic dysfunction worsened. At 2 wk post-ISO-OV, cardiac function was assessed ex vivo, while mitochondrial oxidative metabolism and stress were assessed in vitro, and Ca(2+) handling in ventricular myocytes. These were complemented with sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA), phospholamban (PLB), and RyR2 expression studies. Ex vivo, basal mechanical performance index (MPI) and oxygen consumption rate (MVO2) were unchanged. Nevertheless, upon increase of metabolic demand, by ß-adrenergic stimulation (1-100 nM ISO), the MPI versus MVO2 relation decreased and shifted to the right, suggesting MPI and mitochondrial energy production uncoupling. Mitochondria showed decreased oxidative metabolism, membrane fragility, and enhanced oxidative stress. Myocytes presented systolic and diastolic Ca(2+) mishandling, and blunted response to ISO (100 nM), and all these without apparent changes in SERCA, PLB, or RyR2 expression. We suggest that post-ISO-OV mitochondrial dysfunction may underlie decreased cardiac contractility, mainly by depletion of ATP needed for myofilaments and Ca(2+) transport by SERCA, while exacerbated oxidative stress may enhance diastolic RyR2 activity.

Communication transforms the impact of the COVID-19 pandemic on children with cancer and their families.

BACKGROUND: The COVID-19 pandemic altered healthcare systems globally, causing delays in care delivery and increased anxiety among patients and families. This study examined how hospital stakeholders and clinicians perceived the global impact of the COVID-19 pandemic on children with cancer and their families. METHODS: This secondary analysis examined data from a qualitative study consisting of 19 focus groups conducted in 8 languages throughout 16 countries. A codebook was developed with novel codes derived inductively from transcript review. In-depth analysis focused on the impact of the COVID-19 pandemic on children with cancer and their families. RESULTS: Eight themes describing the impact of the pandemic on patients and their families were identified and classified into three domains: contributing factors (COVID-19 Policies, Cancer Treatment Modifications, COVID-19 Symptoms, Beliefs), patient-related impacts (Quality of Care, Psychosocial impacts, Treatment Reluctance), and the central transformer (Communication). Participants described the ability of communication to transform the effect of contributing factors on patient-related impacts. The valence of impacts depended on the quality and quantity of communication among clinicians and between clinicians and patients and families. CONCLUSIONS: Communication served as the central factor impacting whether the COVID-19 pandemic positively or negatively affected children with cancer and families. These findings emphasize the key role communication plays in delivering patient-centered care and can guide future development of communication-centered interventions globally.

Evaluation of factors leading to poor outcomes for pediatric acute lymphoblastic leukemia in Mexico: a multi-institutional report of 2,116 patients.

Background and aims: Pediatric acute lymphoblastic leukemia (ALL) survival rates in low- and middle-income countries are lower due to deficiencies in multilevel factors, including access to timely diagnosis, risk-stratified therapy, and comprehensive supportive care. This retrospective study aimed to analyze outcomes for pediatric ALL at 16 centers in Mexico. Methods: Patients <18 years of age with newly diagnosed B- and T-cell ALL treated between January 2011 and December 2019 were included. Clinical and biological characteristics and their association with outcomes were examined. Results: Overall, 2,116 patients with a median age of 6.3 years were included. B-cell immunophenotype was identified in 1,889 (89.3%) patients. The median white blood cells at diagnosis were 11.2.5 × 103/mm3. CNS-1 status was reported in 1,810 (85.5%), CNS-2 in 67 (3.2%), and CNS-3 in 61 (2.9%). A total of 1,488 patients (70.4%) were classified as high-risk at diagnosis. However, in 52.5% (991/1,889) of patients with B-cell ALL, the reported risk group did not match the calculated risk group allocation based on National Cancer Institute (NCI) criteria. Fluorescence in situ hybridization (FISH) and PCR tests were performed for 407 (19.2%) and 736 (34.8%) patients, respectively. Minimal residual disease (MRD) during induction was performed in 1,158 patients (54.7%). The median follow-up was 3.7 years. During induction, 191 patients died (9.1%), and 45 patients (2.1%) experienced induction failure. A total of 365 deaths (17.3%) occurred, including 174 deaths after remission. Six percent (176) of patients abandoned treatment. The 5-year event-free survival (EFS) was 58.9% ± 1.7% for B-cell ALL and 47.4% ± 5.9% for T-cell ALL, while the 5-year overall survival (OS) was 67.5% ± 1.6% for B-cell ALL and 54.3% ± 0.6% for T-cell ALL. The 5-year cumulative incidence of central nervous system (CNS) relapse was 5.5% ± 0.6%. For the whole cohort, significantly higher outcomes were seen for patients aged 1-10 years, with DNA index >0.9, with hyperdiploid ALL, and without substantial treatment modifications. In multivariable analyses, age and Day 15 MRD continued to have a significant effect on EFS. Conclusion: Outcomes in this multi-institutional cohort describe poor outcomes, influenced by incomplete and inconsistent risk stratification, early toxic death, high on-treatment mortality, and high CNS relapse rate. Adopting comprehensive risk-stratification strategies, evidence-informed de-intensification for favorable-risk patients and optimized supportive care could improve outcomes.

Voltage-driven ring confinement in a graphene sheet: assessing conditions for bound state solutions.

We have systematically studied the single-particle states in quantum rings produced by a set of concentric circular gates over a graphene sheet placed on a substrate. The resulting potential profiles and the interaction between the graphene layer and the substrate are considered within the Dirac Hamiltonian in the framework of the envelope function approximation. Our simulations allow microscopic mapping of the character of the electron and hole quasi-particle solutions according to the applied voltage. General conditions to control and operate the bound state solutions are described as functions of external and controllable parameters that will determine the optical properties ranging from metallic to semiconductor phases. Contrasting behaviors are obtained when comparing the results for repulsive and attractive voltages as well as for variation of the relative strength of the graphene-substrate coupling parameter.

Utilizing Multilingual Methods and Rapid Analysis for Global Qualitative Research During a Pandemic.

Historically, qualitative research has complemented quantitative biologic and epidemiologic studies to provide a more complete understanding of pandemics. The COVID-19 pandemic has generated unique and novel challenges for qualitative researchers, who have embraced creative solutions including virtual focus groups and rapid analyses to continue their work. We present our experience conducting a multilingual global qualitative study of healthcare resilience among teams of pediatric oncology professionals during the COVID-19 pandemic. We provide an in-depth description of our methodology and an analysis of factors we believe contributed to our study's success including our use of technology, engagement of a large multilingual team, global partnerships, and framework-based rapid analysis. We hope these techniques may be useful to qualitative researchers conducting studies during the current pandemic, as well as for all pediatric oncology studies including multiple languages or geographically disparate subjects.

Reliability and validity of a Spanish-language measure assessing clinical capacity to sustain Paediatric Early Warning Systems (PEWS) in resource-limited hospitals.

BACKGROUND: Paediatric Early Warning Systems (PEWSs) improve identification of deterioration, however, their sustainability has not been studied. Sustainability is critical to maximise impact of interventions like PEWS, particularly in low-resource settings. This study establishes the reliability and validity of a Spanish-language Clinical Sustainability Assessment Tool (CSAT) to assess clinical capacity to sustain interventions in resource-limited hospitals. METHODS: Participants included PEWS implementation leadership teams of 29 paediatric cancer centres in Latin America involved in a collaborative to implement PEWS. The CSAT, a sustainability assessment tool validated in high-resource settings, was translated into Spanish and distributed to participants as an anonymous electronic survey. Psychometric, confirmatory factor analysis (CFA), and multivariate analyses were preformed to assess reliability, structure and initial validity. Focus groups were conducted after participants reviewed CSAT reports to assess their interpretation and utility. RESULTS: The CSAT survey achieved an 80% response rate (n=169) with a mean score of 4.4 (of 5; 3.8-4.8 among centres). The CSAT had good reliability with an average internal consistency of 0.77 (95% CI 0.71 to 0.81); and CFAs supported the seven-domain structure. CSAT results were associated with respondents' perceptions of the evidence for PEWS, its implementation and use in their centre, and their assessment of the hospital culture and implementation climate. The mean CSAT score was higher among respondents at centres with longer time using PEWS (p<0.001). Focus group participants noted the CSAT report helped assess their centre's clinical capacity to sustain PEWS and provided constructive feedback for improvement. CONCLUSIONS: We present information supporting the reliability and validity of the CSAT tool, the first Spanish-language instrument to assess clinical capacity to sustain evidence-based interventions in hospitals of variable resource levels. This assessment demonstrates a high capacity to sustain PEWS in these resource-limited centres with improvement over time from PEWS implementation.

Anisotropy induced localization of pseudo-relativistic spin states in graphene double quantum wire structures.

We study the single-particle properties of Dirac Fermions confined to a double quantum wire system based on graphene. We map out the spatial regions where electrons in a given subband display the largest occupation probability induced by spatial anisotropic effects associated to the interaction strength between the graphene wires and the substrate. Here, the graphene-substrate interaction is considered as an ad hoc parameter which destroys the zero-gap observed in the relativistic Dirac cone characteristic of graphene electronic energy dispersions. Furthermore, the results indicate that the character of quasi-extended spin states, viewed by multisubband probability density function, is highly sensitive to spatial asymmetries and to the graphene-substrate interaction strength.

Structure-Property-Performance Relationship of Ultrathin Pd-Au Alloy Catalyst Layers for Low-Temperature Ethanol Oxidation in Alkaline Media.

Pd-containing alloys are promising materials for catalysis. Yet, the relationship of the structure-property performance strongly depends on their chemical composition, which is currently not fully resolved. Herein, we present a physical vapor deposition methodology for developing PdxAu1-x alloys with fine control over the chemical composition. We establish direct correlations between the composition and these materials' structural and electronic properties with its catalytic activity in an ethanol (EtOH) oxidation reaction. By combining X-ray diffraction (XRD) and X-ray photelectron spectroscopy (XPS) measurements, we validate that the Pd content within both bulk and surface compositions can be finely controlled in an ultrathin-film regime. Catalytic oxidation of EtOH on the PdxAu1-x electrodes presents the largest forward-sweeping current density for x = 0.73 at ∼135 mA cm-2, with the lowest onset potential and largest peak activity of 639 A gPd-1 observed for x = 0.58. Density functional theory (DFT) calculations and XPS measurements demonstrate that the valence band of the alloys is completely dominated by Pd particularly near the Fermi level, regardless of its chemical composition. Moreover, DFT provides key insights into the PdxAu1-x ligand effect, with relevant chemisorption activity descriptors probed for a large number of surface arrangements. These results demonstrate that alloys can outperform pure metals in catalytic processes, with fine control of the chemical composition being a powerful tuning knob for the electronic properties and, therefore, the catalytic activity of ultrathin PdxAu1-x catalysts. Our high-throughput experimental methodology, in connection with DFT calculations, provides a unique foundation for further materials' discovery, including machine-learning predictions for novel alloys, the development of Pd-alloyed membranes for the purification of reformate gases, binder-free ultrathin electrocatalysts for fuel cells, and room temperature lithography-based development of nanostructures for optically driven processes.

Urticarial Lesions in a Pregnant Woman.

Dear Editor, Gestational pemphigoid (GP) is a rare autoimmune bullous dermatosis in pregnancy. GP usually occurs during the second or third month of pregnancy. It clinically manifests as the development of either early-onset urticarial lesions or late-onset subepidermal blisters that may linger for weeks or even months. Herein we report the case of a 45-year-old woman with the distinctive clinical onset of GP. A forty-five-year-old woman, gravida I, para 0, at 27 weeks gestation, was referred for evaluation to our Department with an extensive pruritic eruption that had developed over the previous 7 days. The lesions had first appeared on the proximal thighs and extended progressively to the abdomen. On physical examination, numerous round urticarial plaques of approximately 1 cm in diameter were noted on her abdomen, involving the periumbilical area. Her thighs and back were also affected (Figures 1 and 2). The palms and soles were spared. No mucosal involvement was seen. The patient medical history was unremarkable, and she denied use of any other medications or herbal remedies at the time the symptoms started or since. No other symptoms but pruritus were referred. Laboratory studies, including complete blood cell count, coagulation tests, and renal and hepatic function were all normal. A punch biopsy was taken from an urticarial plaque and stained with hematoxylin and eosin. Histological examination found spongiosis in combination with an intraepidermal eosinophilic infiltrate, without the development of blisters (Figure 3). Direct immunofluorescence of perilesional skin showed linear deposition of complement (C3) along the basement membrane zone (Figure 4). Serum antibody titers for BP180NC16a were detected by enzyme-linked immunosorbent assay (ELISA). We established a diagnosis of gestational pemphigoid. Our patient was treated with systemic glucocorticoids, no blisters developed, and lesions cleared 8 weeks after delivery. The newborn girl did not developed neonatal gestational pemphigoid. Gestational pemphigoid, originally misnamed herpes gestationis, is a rare autoimmune bullous dermatosis in pregnancy. Single cases have been also described in patients with molar pregnancies and trophoblastic tumors (1). Its etiology is based in the development of autoantibodies against the fetoplacental unit, triggering an autoimmune response against both skin and amnion hemidesmosomal proteins, mainly BP180, but also BP230 and type VII collagen. An association with HLA-DR3 and HLA-DR4 has been described (2). GP usually occurs during the second or third month of pregnancy, but it may appear at any time during pregnancy or puerperium. In the vast majority of cases, symptoms alleviate a few weeks before delivery, but they reemerge at the time of delivery. Recurrences are frequent in following pregnancies, with an earlier onset and more severe symptoms, and may occur during subsequent menstruations or hormonal contraceptive use (1). GP clinically consists of the development of either early-onset urticarial lesions or late-onset subepidermal blisters that mat linger for weeks or even months. They generally appear on the abdomen, specifically in the periumbilical area, with posterior widespread extension to proximal limbs. Facial and mucosal lesions are uncommon (1). Histopathological studies are necessary to establish the diagnosis. These findings vary depending on the stage and severity of the disease and include subepidermal blisters, papillary dermal edema, eosinophilic spongiosis, and a polymorphous perivascular inflammatory cell infiltrate with a predominance of eosinophils. Direct immunofluorescence of perilesional skin shows a linear deposition of C3 along the basement membrane zone in all cases. IgG deposits can also be seen (3). These deposits are located within the lamina lucida and localized to the proximal part of anchoring filaments of the epidermal fragment of salt-split skin (4). Moreover, immunoblot and ELISA of the NC16a domain of BP180 RP are highly sensitive diagnostic methods in GP (5). The aim of treatment is to alleviate the pruritus and prevent formation of new blisters. Topical corticosteroids and oral antihistamines may be used in mild cases. Systemic corticosteroids are the treatment of choice in moderate to severe cases. Other treatments that have been used are cyclophosphamide, dapsone, gold, methotrexate, and plasmapheresis (5).

Ex Vivo Cardiotoxicity of Antineoplastic Casiopeinas Is Mediated through Energetic Dysfunction and Triggered Mitochondrial-Dependent Apoptosis.

Casiopeinas are a group of copper-based antineoplastic molecules designed as a less toxic and more therapeutic alternative to cisplatin or Doxorubicin; however, there is scarce evidence about their toxic effects on the whole heart and cardiomyocytes. Given this, rat hearts were perfused with Casiopeinas or Doxorubicin and the effects on mechanical performance, energetics, and mitochondrial function were measured. As well, the effects of Casiopeinas-triggered cell death were explored in isolated cardiomyocytes. Casiopeinas III-Ea, II-gly, and III-ia induced a progressive and sustained inhibition of heart contractile function that was dose- and time-dependent with an IC50 of 1.3 ± 0.2, 5.5 ± 0.5, and 10 ± 0.7 µM, correspondingly. Myocardial oxygen consumption was not modified at their respective IC50, although ATP levels were significantly reduced, indicating energy impairment. Isolated mitochondria from Casiopeinas-treated hearts showed a significant loss of membrane potential and reduction of mitochondrial Ca2+ retention capacity. Interestingly, Cyclosporine A inhibited Casiopeinas-induced mitochondrial Ca2+ release, which suggests the involvement of the mitochondrial permeability transition pore opening. In addition, Casiopeinas reduced the viability of cardiomyocytes and stimulated the activation of caspases 3, 7, and 9, demonstrating a cell death mitochondrial-dependent mechanism. Finally, the early perfusion of Cyclosporine A in isolated hearts decreased Casiopeinas-induced dysfunction with reduction of their toxic effect. Our results suggest that heart cardiotoxicity of Casiopeinas is similar to that of Doxorubicin, involving heart mitochondrial dysfunction, loss of membrane potential, changes in energetic metabolites, and apoptosis triggered by mitochondrial permeability.