Ga2O3-on-SiC Composite Wafer for Thermal Management of Ultrawide Bandgap Electronics.

ß-phase gallium oxide (Ga2O3) is an emerging ultrawide bandgap (UWBG) semiconductor (EG ∼ 4.8 eV), which promises generational improvements in the performance and manufacturing cost over today's commercial wide bandgap power electronics based on GaN and SiC. However, overheating has been identified as a major bottleneck to the performance and commercialization of Ga2O3 device technologies. In this work, a novel Ga2O3/4H-SiC composite wafer with high heat transfer performance and an epi-ready surface finish has been developed using a fusion-bonding method. By taking advantage of low-temperature metalorganic vapor phase epitaxy, a Ga2O3 epitaxial layer was successfully grown on the composite wafer while maintaining the structural integrity of the composite wafer without causing interface damage. An atomically smooth homoepitaxial film with a room-temperature Hall mobility of ∼94 cm2/Vs and a volume charge of ∼3 × 1017 cm-3 was achieved at a growth temperature of 600 °C. Phonon transport across the Ga2O3/4H-SiC interface has been studied using frequency-domain thermoreflectance and a differential steady-state thermoreflectance approach. Scanning transmission electron microscopy analysis suggests that phonon transport across the Ga2O3/4H-SiC interface is dominated by the thickness of the SiNx bonding layer and an unintentionally formed SiOx interlayer. Extrinsic effects that impact the thermal conductivity of the 6.5 µm thick Ga2O3 layer were studied via time-domain thermoreflectance. Thermal simulation was performed to estimate the improvement of the thermal performance of a hypothetical single-finger Ga2O3 metal-semiconductor field-effect transistor fabricated on the composite substrate. This novel power transistor topology resulted in a ∼4.3× reduction in the junction-to-package device thermal resistance. Furthermore, an even more pronounced cooling effect is demonstrated when the composite wafer is implemented into the device design of practical multifinger devices. These innovations in device-level thermal management give promise to the full exploitation of the promising benefits of the UWBG material, which will lead to significant improvements in the power density and efficiency of power electronics over current state-of-the-art commercial devices.

Thermal Conductivity of ß-Phase Ga2O3 and (AlxGa1-x)2O3 Heteroepitaxial Thin Films.

Heteroepitaxy of ß-phase gallium oxide (ß-Ga2O3) thin films on foreign substrates shows promise for the development of next-generation deep ultraviolet solar blind photodetectors and power electronic devices. In this work, the influences of the film thickness and crystallinity on the thermal conductivity of (2̅01)-oriented ß-Ga2O3 heteroepitaxial thin films were investigated. Unintentionally doped ß-Ga2O3 thin films were grown on c-plane sapphire substrates with off-axis angles of 0° and 6° toward ⟨112̅0⟩ via metal-organic vapor phase epitaxy (MOVPE) and low-pressure chemical vapor deposition. The surface morphology and crystal quality of the ß-Ga2O3 thin films were characterized using scanning electron microscopy, X-ray diffraction, and Raman spectroscopy. The thermal conductivities of the ß-Ga2O3 films were measured via time-domain thermoreflectance. The interface quality was studied using scanning transmission electron microscopy. The measured thermal conductivities of the submicron-thick ß-Ga2O3 thin films were relatively low as compared to the intrinsic bulk value. The measured thin film thermal conductivities were compared with the Debye-Callaway model incorporating phononic parameters derived from first-principles calculations. The comparison suggests that the reduction in the thin film thermal conductivity can be partially attributed to the enhanced phonon-boundary scattering when the film thickness decreases. They were found to be a strong function of not only the layer thickness but also the film quality, resulting from growth on substrates with different offcut angles. Growth of ß-Ga2O3 films on 6° offcut sapphire substrates was found to result in higher crystallinity and thermal conductivity than films grown on on-axis c-plane sapphire. However, the ß-Ga2O3 films grown on 6° offcut sapphire exhibit a lower thermal boundary conductance at the ß-Ga2O3/sapphire heterointerface. In addition, the thermal conductivity of MOVPE-grown (2̅01)-oriented ß-(AlxGa1-x)2O3 thin films with Al compositions ranging from 2% to 43% was characterized. Because of phonon-alloy disorder scattering, the ß-(AlxGa1-x)2O3 films exhibit lower thermal conductivities (2.8-4.7 W/m·K) than the ß-Ga2O3 thin films. The dominance of the alloy disorder scattering in ß-(AlxGa1-x)2O3 is further evidenced by the weak temperature dependence of the thermal conductivity. This work provides fundamental insight into the physical interactions that govern phonon transport within heteroepitaxially grown ß-phase Ga2O3 and (AlxGa1-x)2O3 thin films and lays the groundwork for the thermal modeling and design of ß-Ga2O3 electronic and optoelectronic devices.

Association between pulmonary embolism and COVID-19 severe pneumonia: Experience from two centers in the core of the infection Italian peak.

PURPOSE: Pulmonary embolism (PE) in COVID-19 patients can play a key role in precipitating clinical conditions. We aimed to evaluate PE distribution on CTA and to investigate any possible association with D-dimer (DD), pulmonary stage of disease and prognosis. METHOD: COVID-19 patients of two affiliated Hospitals, undergone a CTA examination for PE suspicion, were retrospectively enrolled. Comorbidities, laboratory tests and clinical outcomes (hospitalization, discharge, death) were assessed. A parenchymal stage (early, progressive, peak, absorption) for lung involvement was assigned. RESULTS: A cohort of 114 patients (mean age 61 years; 26.3 % females) with severe COVID-19 pneumonia were evaluated. At last follow-up 25 (21.9 %) were hospitalized, 72 (63.2 %) discharged, 17 (14.9 %) dead. Eighty-eight patients (77.2 %) had at least one comorbidity, being cardiovascular ones the most frequent (44.7 %). CTA revealed PE in 65 patients (57 %), with concomitant pulmonary trunk and/or main arteries involvement in 16.9 %. PE defects were ubiquitous in 18.5 % of cases. The predominant parenchymal stages were the progressive (24.6 %) and peak (67.7 %). DD levels showed a significant correlation with PE occurrence and extent in pulmonary branches, despite anticoagulant therapies; trend of correlation with pulmonary stages was also noted. CONCLUSIONS: PE is a frequent complication in severe COVID-19 patients, particularly during central parenchymal stages and despite ongoing anticoagulant therapy. CTA and DD levels play a crucial role in the assessment of suspected PE, despite anticoagulant therapies, along with proper information about lung involvement extent.

Effects of the Interfacial Modeling Approach on Equilibrium Calculations of Slip Length for Nanoconfined Water in Carbon Slits.

In this investigation, equilibrium molecular dynamics simulations were conducted to assess the influence of the interface modeling approach on the calculation of hydrodynamic slip in carbon nanochannels. A Green-Kubo formalism was implemented for the calculation of the slip length in water confined by graphite layers. The nonbonded interactions between solid and liquid atoms (interface models) were modeled using parameters optimized to represent the wetting behavior and adsorption energy curves from electronic structure calculations. Conventional carbon-oxygen-only interaction models were compared against comprehensive models able to represent the molecular-orientation-dependent energy of interaction. Quasi-universal relationships built under the premise of the slip length dependence on the water-graphite affinity and characterized by macroscopic wettability were critically assessed. It was found that the wetting behavior cannot fully characterize the hydrodynamic slip because interface models that produced the same surface wettability yielded different values of the friction coefficient. Alternatively, the density depletion length, used to characterize the interfacial liquid structuring and the availability of momentum carriers (interfacial water molecules), was able to accurately represent the slip length trends independently of the interface model. These findings reassert the importance of physically sound interface models to study interfacial transport properties and the need of reliable parameters and characterization procedures to support theoretical models that seek to unveil the inconsistencies in hydrodynamic slip calculations.

The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade.

In 2019, a new coronavirus (2019-nCoV) infecting Humans has emerged in Wuhan, China. Its genome has been sequenced and the genomic information promptly released. Despite a high similarity with the genome sequence of SARS-CoV and SARS-like CoVs, we identified a peculiar furin-like cleavage site in the Spike protein of the 2019-nCoV, lacking in the other SARS-like CoVs. In this article, we discuss the possible functional consequences of this cleavage site in the viral cycle, pathogenicity and its potential implication in the development of antivirals.

LPA1 receptor and chronic stress: Effects on behaviour and the genes involved in the hippocampal excitatory/inhibitory balance.

The LPA1 receptor, one of the six characterized G protein-coupled receptors (LPA1-6) through which lysophosphatidic acid acts, is likely involved in promoting normal emotional behaviours. Current data suggest that the LPA-LPA1-receptor pathway may be involved in mediating the negative consequences of stress on hippocampal function. However, to date, there is no available information regarding the mechanisms whereby the LPA1 receptor mediates this adaptation. To gain further insight into how the LPA-LPA1 pathway may prevent the negative consequences of chronic stress, we assessed the effects of the continuous delivery of LPA on depressive-like behaviours induced by a chronic restraint stress protocol. Because a proper excitatory/inhibitory balance seems to be key for controlling the stress response system, the gene expression of molecular markers of excitatory and inhibitory neurotransmission was also determined. In addition, the hippocampal expression of mineralocorticoid receptor genes and glucocorticoid receptor genes and proteins as well as plasma corticosterone levels were determined. Contrary to our expectations, the continuous delivery of LPA in chronically stressed animals potentiated rather than inhibited some (e.g., anhedonia, reduced latency to the first immobility period), though not all, behavioural effects of stress. Furthermore, this treatment led to an alteration in the genes coding for proteins involved in the excitatory/inhibitory balance in the ventral hippocampus and to changes in corticosterone levels. In conclusion, the results of this study reinforce the assumption that LPA is involved in emotional regulation, mainly through the LPA1 receptor, and regulates the effects of stress on hippocampal gene expression and hippocampus-dependent behaviour.

Magnetism in cold subducting slabs at mantle transition zone depths.

The Earth's crust-mantle boundary, the Mohorovicic discontinuity, has been traditionally considered to be the interface between the magnetic crust and the non-magnetic mantle1. However, this assumption has been questioned by geophysical observations2,3 and by the identification of magnetic remanence in mantle xenoliths4, which suggest mantle magnetic sources. Owing to their high critical temperatures, iron oxides are the only potential sources of magnetic anomalies at mantle depths5. Haematite (α-Fe2O3) is the dominant iron oxide in subducted lithologies at depths of 300 to 600 kilometres, delineated by the thermal decomposition of magnetite and the crystallization of a high-pressure magnetite phase deeper than about 600 kilometres6. The lack of data on the magnetic properties of haematite at relevant pressure-temperature conditions, however, hinders the identification of magnetic boundaries within the mantle and their contribution to observed magnetic anomalies. Here we apply synchrotron Mössbauer source spectroscopy in laser-heated diamond anvil cells to investigate the magnetic transitions and critical temperatures in Fe2O3 polymorphs7 at pressures and temperatures of up to 90 gigapascals and 1,300 kelvin, respectively. Our results show that haematite remains magnetic at the depth of the transition zone in the Earth's mantle in cold or very cold subduction geotherms, forming a frame of deep magnetized rocks in the West Pacific region. The deep magnetic sources spatially correlate with preferred paths of the Earth's virtual geomagnetic poles during reversals8 that might not reflect the geometry of the transitional field. Rather, the paths might be an artefact caused by magnetized haematite-bearing rocks in cold subducting slabs at mid-transition zone depths. Such deep sources should be taken into account when carrying out inversions of the Earth's geomagnetic data9, and especially in studies of planetary bodies that no longer have a dynamo10, such as Mars.

Pre-Bötzinger complex: Generation and modulation of respiratory rhythm. / El complejo pre-Bötzinger: generación y modulación del ritmo respiratorio.

INTRODUCTION: In mammals, the preBötzinger complex (preBötC) is a bilateral and symmetrical neural network located in the brainstem which is essential for the generation and modulation of respiratory rhythm. There are few human studies about the preBötC and, its relationship with neurological diseases has not been described. However, the importance of the preBötC in neural control of breathing and its potential participation in neurological diseases in humans, has been suggested based on pharmacological manipulation and lesion of the preBötC in animal models, both in vivo and in vitro. METHOD: In this review, we describe the effects of some drugs on the inspiratory activity in vitro in a transverse slice that contains the preBötC, as well as some in vivo experiments. Drugs were classified according to their effects on the main neurotransmitter systems and their importance as stimulators or inhibitors of preBötC activity and therefore for the generation of the respiratory rhythm. CONCLUSION: Clinical neurologists will find this information relevant to understanding how the central nervous system generates the respiratory rhythm and may also relate this information to the findings made in daily practice.

Thermal Transport across SiC-Water Interfaces.

Thermal transport across interfaces made of 3C-type silicon carbide (SiC) and water was investigated by means of nonequilibrium classical molecular dynamics. The effects of different crystallographic planes and atomic surface terminations were studied, as it pertains to interfacial heat transfer. Hydrophilic and hydrophobic conditions were analyzed by modifying the interfacial bonding strength between the solid and liquid phases. The formation of structures in the liquid molecules close to the solid substrate was observed and found that such structures are sensitive to the uppermost atomic layer termination, the wettability condition, and the temperature of the system. It was found that the interfacial heat transfer and the wetting properties are not universally related and to obtain a more comprehensive description, it is required to include the structuring observed in the liquid phase at the interface. A reconciliation of the thermal boundary conductance calculations was found after the density depletion length was utilized as the descripting parameter.

Can the use of an inclinometer improve the positioning of the acetabular component in total hip arthroplasty?

Aims: Accurate placement of the acetabular component is essential in total hip arthroplasty (THA). The purpose of this study was to determine if the ability to achieve inclination of the acetabular component within the 'safe-zone' of 30° to 50° could be improved with the use of an inclinometer. Patients and Methods: We reviewed 167 primary THAs performed by a single surgeon over a period of 14 months. Procedures were performed at two institutions: an inpatient hospital, where an inclinometer was used (inclinometer group); and an ambulatory centre, where an inclinometer was not used as it could not be adequately sterilized (control group). We excluded 47 patients with a body mass index (BMI) of > 40 kg/m2, age of > 68 years, or a surgical indication other than osteoarthritis whose treatment could not be undertaken in the ambulatory centre. There were thus 120 patients in the study, 68 in the inclinometer group and 52 in the control group. The inclination angles of the acetabular component were measured from de-identified plain radiographs by two blinded investigators who were not involved in the surgery. The effect of the use of the inclinometer on the inclination angle was determined using multivariate regression analysis. Results: The mean inclination angle for the THAs in the inclinometer group was 42.9° (95% confidence interval (CI) 41.7° to 44.0°; range 29.0° to 63.8°) and 46.5° (95% CI 45.2° to 47.7°; range 32.8° to 63.2°) in the control group (p < 0.001). Regression analysis identified a 9.1% difference in inclination due to the use of an inclinometer (p < 0.001), and THAs performed without the inclinometer were three times more likely to result in inclination angles of > 50° (odds ratio (OR) 2.8, p = 0.036). The correlation coefficient for the interobserver reliability of the measurement of the two investigators was 0.95 (95% CI 0.93 to 0.97). Conclusion: The use of a simple inclinometer resulted in a significant reduction in the number of outliers compared with a freehand technique. Cite this article: Bone Joint J 2018;100-B:862-6.

Validation of the Complexity INdex in SARComas prognostic signature on formalin-fixed, paraffin-embedded, soft-tissue sarcomas.

Background: Prediction of metastatic outcome in sarcomas is challenging for clinical management since they are aggressive and carry a high metastatic risk. A 67-gene expression signature, the Complexity INdex in SARComas (CINSARC), has been identified as a better prognostic factor than the reference pathological grade. Since it cannot be applied easily in standard laboratory practice, we assessed its prognostic value using nanoString on formalin-fixed, paraffin-embedded (FFPE) blocks to evaluate its potential in clinical routine practice and guided therapeutic management. Methods: A code set consisting of 67 probes derived from the 67 genes of the CINSARC signature was built and named NanoCind®. To compare the performance of RNA-seq and nanoString (NanoCind®), we used expressions of various sarcomas (n = 124, frozen samples) using both techniques and compared predictive values based on CINSARC risk groups and clinical annotations. We also used nanoString on FFPE blocks (n = 67) and matching frozen and FFPE samples (n = 45) to compare their level of agreement. Metastasis-free survival and agreement values in classification groups were evaluated. Results: CINSARC strongly predicted metastatic outcome using nanoString on frozen samples (HR = 2.9, 95% CI: 1.23-6.82) with similar risk-group classifications (86%). While more than 50% of FFPE blocks were not analyzable by RNA-seq owing to poor RNA quality, all samples were analyzable with nanoString. When similar (risk-group) classifications were measured with frozen tumors (RNA-seq) compared with FFPE blocks (84% agreement), the CINSARC signature was still a predictive factor of metastatic outcome with nanoString on FFPE samples (HR = 4.43, 95% CI: 1.25-15.72). Conclusion: CINSARC is a material-independent prognostic signature for metastatic outcome in sarcomas and outperforms histological grade. Unlike RNA-seq, nanoString is not influenced by the poor quality of RNA extracted from FFPE blocks. The CINSARC signature can potentially be used in combination with nanoString (NanoCind®) in routine clinical practice on FFPE blocks to predict metastatic outcome.

Outcomes of dual mobility components in total hip arthroplasty: a systematic review of the literature.

AIMS: Instability remains a challenging problem in both primary and revision total hip arthroplasty (THA). Dual mobility components confer increased stability, but there are concerns about the unique complications associated with these designs, as well as the long-term survivorship. MATERIALS AND METHODS: We performed a systematic review of all English language articles dealing with dual mobility THAs published between 2007 and 2016 in the MEDLINE and Embase electronic databases. A total of 54 articles met inclusion criteria for the final analysis of primary and revision dual mobility THAs and dual mobility THAs used in the treatment of fractures of the femoral neck. We analysed the survivorship and rates of aseptic loosening and of intraprosthetic and extra-articular dislocation. RESULTS: For the 10 783 primary dual mobility THAs, the incidence of aseptic loosening was 1.3% (142 hips); the rate of intraprosthetic dislocation was 1.1% (122 hips) and the incidence of extra-articular dislocation was 0.46% (41 hips). The overall survivorship of the acetabular component and the dual mobility components was 98.0%, with all-cause revision as the endpoint at a mean follow-up of 8.5 years (2 to 16.5). For the 3008 revision dual mobility THAs, the rate of aseptic acetabular loosening was 1.4% (29 hips); the rate of intraprosthetic dislocation was 0.3% (eight hips) and the rate of extra-articular dislocation was 2.2% (67 hips). The survivorship of the acatabular and dual mobility components was 96.6% at a mean of 5.4 years (2 to 8). For the 554 dual mobility THAs which were undertaken in patients with a fracture of the femoral neck, the rate of intraprosthetic dislocation was 0.18% (one hip), the rate of extra-articular dislocation was 2.3% (13 hips) and there was one aseptic loosening. The survivorship was 97.8% at a mean of 1.3 years (0.75 to 2). CONCLUSION: Dual mobility articulations are a viable alternative to traditional bearing surfaces, with low rates of instability and good overall survivorship in primary and revision THAs, and in those undertaken in patients with a fracture of the femoral neck. The incidence of intraprosthetic dislocation is low and limited mainly to earlier designs. High-quality, prospective, comparative studies are needed to evaluate further the use of dual mobility components in THA. Cite this article: Bone Joint J 2018;100-B:11-19.

Effects of preoperative dexamethasone on postoperative pain, nausea, vomiting and respiratory function in women undergoing conservative breast surgery for cancer: Results of a controlled clinical trial.

The objective was to evaluate whether preoperative administration of dexamethasone improved postoperative nausea and vomiting (PONV), pain and respiratory function tests in women undergoing conservative surgery for breast cancer. This was a controlled clinical trial conducted between June 2013 and October 2014. Eighty patients were evaluated. Patients received a preoperative dose of 8 mg of dexamethasone (n = 40) or placebo (n = 40). The data on PONV and pain intensity was obtained and forced spirometry tests were performed, 1 hr before and at 1, 6, 12 and 24 hr after surgery. Any use of additional analgesic/antiemetic drugs was recorded. Patients were followed until 30 days after surgery for any surgical or medical complications. The pain intensity was lower in the treatment group for all periods; PONV was lower at 6, 12 and 24 hr; Additional analgesics/antiemetics were required less frequently (all p < .05). Both groups exhibited a restrictive ventilatory pattern immediately after surgery, which was reversed in the following hours. However, spirometric values were higher in the dexamethasone group. There were no pulmonary or metabolic complications after surgery. Our conclusions were that dexamethasone significantly reduced the incidences of PONV, pain and improved respiratory parameters, and reduced the need for additional postoperative analgesic and antiemetic drugs.

Time course of the effect of status epilepticus induced in the developing rat on γ-amino butyric acid and glutamate cerebellar concentration. / Evaluación temporal del efecto del status epilepticus inducido en la rata en desarrollo en la concentración cerebelar de ácido γ-aminobutírico y glutamato.

INTRODUCTION: Status epilepticus (SE) is an epileptic condition that can cause cerebellar atrophy and loss of Purkinje cells in both humans and research animals. Cerebellum is a region rich in γ-aminobutyric acid (GABA) and glutamate, and some studies have shown that their concentrations may be altered after convulsions. However, there are no studies showing the effect of seizures on different cerebellar regions in developing rats. Time course of the effect of status epilepticus induced in the developing rat on γ-amino butyric acid and glutamate cerebellar concentration. METHODS: SE was induced using the lithium-pilocarpine model; control rats were injected with saline solution. At 6h, 24h, and 1 month after SE o saline injection, rats were anaesthetised with pentobarbital and decapitated, and cerebella were extracted. The vermis and hemispheres were dissected and homogenised in 0.1M perchloric acid containing 4mM sodium bisulfite. Homogenates were centrifuged and supernatant was used to quantify GABA, and glutamate tissue concentrations by HPLC coupled with fluorometric detection. RESULTS: SE did not alter GABA and glutamate tissue concentration in the cerebellar vermis and hemispheres. CONCLUSION: The developing rat cerebellum is resistant to both short- and long-term neurochemical changes induced by SE.

Do higher-volume hospitals provide better value in revision hip and knee arthroplasty?

AIMS: The purpose of this study is to determine if higher volume hospitals have lower costs in revision hip and knee arthroplasty. MATERIALS AND METHODS: We questioned the Centres for Medicare and Medicaid Services (CMS) Inpatient Charge Data and identified 789 hospitals performing a total of 29 580 revision arthroplasties in 2014. Centres were dichotomised into high-volume (performing over 50 revision cases per year) and low-volume. Mean total hospital-specific charges and inpatient payments were obtained from the database and stratified based on Diagnosis Related Group (DRG) codes. Patient satisfaction scores were obtained from the multiyear CMS Hospital Compare database. RESULTS: High-volume hospitals comprised 178 (30%) of the total but performed 15 068 (51%) of all revision cases, including 509 of 522 (98%) of the most complex DRG 466 cases. While high-volume hospitals had higher Medicare inpatient payments for DRG 467 ($21 458 versus $20 632, p = 0.038) and DRG 468 ($17 003 versus $16 120, p = 0.011), there was no difference in hospital specific charges between the groups. Higher-volume facilities had a better CMS hospital star rating (3.63 versus 3.35, p < 0.001). When controlling for hospital geographic and demographic factors, high-volume revision hospitals are less likely to be in the upper quartile of inpatient Medicare costs for DRG 467 (odds ratio (OR) 0.593, 95% confidence intervals (CI) 0.374 to 0.941, p = 0.026) and DRG 468 (OR 0.451, 95% CI 0.297 to 0.687, p < 0.001). CONCLUSION: While a high-volume hospital is less likely to be a high cost outlier, the higher mean Medicare reimbursements at these facilities may be due to increased case complexity. Further study should focus on measures for cost savings in revision total joint arthroplasties. Cite this article: Bone Joint J 2017;99-B:1611-17.

Spironolactone in Post-Transplant Proteinuria: A Safe Alternative Therapy.

BACKGROUND: Aldosterone is involved in the process of renal allograft fibrosis, clinically manifest by proteinuria and allograft dysfunction, with increased risk for cardiovascular death. The treatment with aldosterone antagonists appears to be effective in controlling proteinuria, with a protective effect on progression of renal fibrosis. METHODS: This retrospective, cohort study included kidney transplant recipients from January 1993 to June 2015. Inclusion criteria were persistent proteinuria >0.5 g/d, longer than 6 months, and spironolactone therapy. RESULTS: One hundred forty transplant recipients fulfilled the inclusion criteria and were divided into 3 groups, according to proteinuria levels at the beginning of spironolactone therapy: low (<1 g/24 h), intermediate (1-3 g/24 h), and nephrotic (>3 g/24 h). Groups were comparable in demographic data, with a higher incidence of living related donors in the nephrotic group. In patients with proteinuria ≥1 g/d, we observed a significant reduction in proteinuria after 6 months of therapy that persisted over time. Blood pressure and glomerular filtration rate persisted stable over time. Adverse events were not severe to withdrawal therapy. CONCLUSIONS: Spironolactone can be a safe alternative to control post-transplant proteinuria, especially in patients with mild to moderate allograft dysfunction with proteinuria ≥1 g/day.

maLPA1-null mice as an endophenotype of anxious depression.

Anxious depression is a prevalent disease with devastating consequences and a poor prognosis. Nevertheless, the neurobiological mechanisms underlying this mood disorder remain poorly characterized. The LPA1 receptor is one of the six characterized G protein-coupled receptors (LPA1-6) through which lysophosphatidic acid acts as an intracellular signalling molecule. The loss of this receptor induces anxiety and several behavioural and neurobiological changes that have been strongly associated with depression. In this study, we sought to investigate the involvement of the LPA1 receptor in mood. We first examined hedonic and despair-like behaviours in wild-type and maLPA1 receptor null mice. Owing to the behavioural response exhibited by the maLPA1-null mice, the panic-like reaction was assessed. In addition, c-Fos expression was evaluated as a measure of the functional activity, followed by interregional correlation matrices to establish the brain map of functional activation. maLPA1-null mice exhibited anhedonia, agitation and increased stress reactivity, behaviours that are strongly associated with the psychopathological endophenotype of depression with anxiety features. Furthermore, the functional brain maps differed between the genotypes. The maLPA1-null mice showed increased limbic-system activation, similar to that observed in depressive patients. Antidepressant treatment induced behavioural improvements and functional brain normalisation. Finally, based on validity criteria, maLPA1-null mice are proposed as an animal model of anxious depression. Here, for we believe the first time, we have identified a possible relationship between the LPA1 receptor and anxious depression, shedding light on the unknown neurobiological basis of this subtype of depression and providing an opportunity to explore new therapeutic targets for the treatment of mood disorders, especially for the anxious subtype of depression.

Body weight changes after adjuvant chemotherapy of patients with breast cancer: results of a Mexican cohort study.

Weight gain is observed in breast cancer patients receiving chemotherapy and is a well-known complication. Several factors that contributing to weight gain have been identified. However, there is a lack of information about factors associated with weight changes following adjuvant chemotherapy. A retrospective cohort of 200 pre- and post-menopausal Mexican patients treated for breast cancer was made. Anthropometric variables were measured before/after treatment. Biomarkers, cellular differentiation and chemotherapy were similar between groups. Weight gain occurred in 85.6% of pre-menopausal and 72.6% of post-menopausal women (p = .03). At the end of chemotherapy, weight and body mass index (BMI) did not differ significantly between pre-menopausal (69.3 ± 12.6 kg; 26.6 ± 4.8 kg/m2 ) and post-menopausal women (69.5 ± 10.9 kg; 27.3 ± 4.4 kg/m2 ) (p = .91 and 0.34). Dexamethasone doses were higher in pre-menopausal (85.7 ± 39.1 g) than post-menopausal patients (79.2 ± 22.5 g; p = .13). Weight loss was observed in 9.2% of pre-menopausal and 20.2% of post-menopausal patients (p = .04). A multivariate analysis revealed that age (OR = 2.7; 95% CI = 1.26-5.79; p = .01), menopausal status (OR = 2.29; 95% CI = 1.09-4.80; p = .03), dexamethasone dosage (OR = 2.1; 95% CI = 1.04-4.23; p = .03) and daily caloric intake (OR = 2.3; 95% CI = 1.12-5.10; p = .02) were independent variables that inducted weight gain. Pre- and post-menopausal women gained weight, but more pre-menopausal patients showed gain. An effort should be made to administer lower steroid doses to reduce weight gain.