Double Myelomeningocele Repair by Fetal Surgery with a Single Micro-Hysterotomy.

INTRODUCTION: Open spina bifida (OSB) is the most common congenital anomaly of the central nervous system. It is associated with severe neurodevelopmental delay, motor impairment, hydrocephalus, and bowel and bladder dysfunction. In selected cases, intrauterine spina bifida repair has been shown to improve neonatal outcomes. Rarely, the spine can have a double defect compromising two different segments and there is a lack of evidence on the feasibility and benefits of intrauterine repair in these cases. CASE PRESENTATION: We present a case with both cervicothoracic and lumbosacral myelomeningocele, Arnold-Chiari malformation type II and bilateral ventriculomegaly, that was treated successfully at 25 weeks with open micro-neurosurgery. Double myelomeningocele was successfully treated through a single 2-cm micro-hysterotomy, by performing external versions to sequentially expose and repair both defects. Weekly postoperative follow-up showed no progression of ventriculomegaly or complications attributable to the procedure. Preterm rupture of membranes prompted a conventional cesarean delivery at 32 weeks of gestation. Neurodevelopmental outcome at 20 months was within normal ranges, having achieved ambulation without orthopedic support and with no need for ventriculoperitoneal shunting. CONCLUSION: This report demonstrates for the first time the feasibility of double OSB repair through a single 2-cm micro-hysterotomy, suggesting that selected isolated cases of double myelomeningocele could be candidates for fetal intervention. Further prospective studies should be carried out to assess the potential benefit of double OSB intrauterine open repair.

Cultural context and self-care impact on medical students' quality of life. A mixed-methods approach.

BACKGROUND: Medical education can make it difficult for students to take actions to improve their health. OBJECTIVE: To evaluate the influence of the university context on self-care behaviors and quality of life. MATERIAL AND METHODS: A mixed-methods approach was used, with surveys being combined to assess self-care and quality of life, with in-depth interviews to explore cultural influences and perceptions. Statistical analysis and qualitative data coding were carried out, with methods being integrated through network analysis. RESULTS: Self-care scores exceeded 50 points, and quality of life scores exceeded 60 points. Medical students' context is shaped by motivations, expectations, skills, and goals that influence identity formation and contribute to the medical profession. CONCLUSIONS: There is a positive connection between self-care practices and quality of life. However, academic stress can potentially disrupt self-care routines. Furthermore, an association between obesity and a decrease in quality of life stands out, which emphasizes the need for health promotion actions.

ANTECEDENTES: La educación médica puede dificultar que los estudiantes realicen acciones para mejorar su salud. OBJETIVO: Evaluar la influencia del contexto universitario en los comportamientos de autocuidado y la calidad de vida. ­. MATERIAL Y MÉTODOS: Se empleó un enfoque de métodos mixtos, combinando encuestas para evaluar el autocuidado y la calidad de vida, con entrevistas en profundidad para explorar influencias culturales y percepciones. Se llevaron a cabo análisis estadísticos y codificación de datos cualitativos; los métodos se integraron a través del análisis de redes. RESULTADOS: Las puntuaciones de autocuidado superaron los 50 puntos y las de calidad de vida, los 60 puntos. El contexto de los estudiantes de medicina está moldeado por motivaciones, expectativas, habilidades y metas que influyen en la formación de la identidad y contribuyen a la profesión médica. CONCLUSIONES: Existe una conexión positiva entre prácticas de autocuidado y la calidad de vida; sin embargo, el estrés académico pueden interrumpir potencialmente las rutinas de autocuidado. Además, se destaca la asociación entre la obesidad y la afectación en la calidad de vida, lo que enfatiza la necesidad de acciones de promoción de la salud.

Management of Late Twin-to-Twin Transfusion Syndrome beyond 26 Weeks: Comparison between Fetoscopic Laser Therapy versus Traditional Management.

INTRODUCTION: A proportion of monochorionic diamniotic (MCDA) twin pregnancies complicated by twin-to-twin transfusion syndrome (TTTS) can present after 26 weeks of gestation. The aim of this study was to compare perinatal outcomes of late TTTS treated by fetoscopic laser coagulation versus traditional management with amniodrainage and/or emergency preterm cesarean delivery (CD). METHODS: Retrospective cohort from January 2012 to January 2023 of consecutive MCDA twin pregnancies complicated by TTTS after 26 weeks and evaluated in our referring centers. We analyzed perinatal outcomes of cases treated with fetoscopic laser surgery at our national referral fetal surgery center in Queretaro, Mexico, and compared them with those managed with traditional management (amniodrainage and/or emergency preterm CD). The primary outcome was survival at discharge and the secondary outcome was gestational age (GA) at birth. RESULTS: Among the study population, 46 TTTS cases were treated by fetoscopy at 27+6 (26+0-31+0) weeks+days and were compared with a group of 39 cases who underwent emergency preterm CD. In comparison to the group who underwent traditional management, the group treated by laser fetoscopy showed a significantly higher GA at birth (32+3 vs. 29+1 weeks+days, p < 0.001), lower frequency of preterm delivery below 37 weeks (91.3% vs. 100%, p = 0.06), 34 weeks (63.0% vs. 100%, p < 0.001), 32 weeks (50% vs. 74.4%, p = 0.02), or 30 weeks (28.3% vs. 53.8%, p = 0.01), and significantly higher perinatal survival (89.1% vs. 71.8%, p < 0.05 of at least one twin; and 65.2% vs. 38.5%, p = 0.01 of both twins, respectively). CONCLUSION: MCDA twins complicated with TTTS can be treated with fetoscopic laser surgery between 26 and 31 weeks of gestation, which is a feasible and safe option, and such cases are associated with a higher GA at birth and better perinatal survival than those managed with amniodrainage and/or emergency preterm CD.

Work from home-related musculoskeletal pain during the COVID-19 pandemic: A rapid review.

Objective: This rapid review explores the prevalence of musculoskeletal pain symptoms associated with work from home conditions during the COVID-19 pandemic. Methods: We conducted a rapid review across three databases (i.e., PubMed, Medline, and CINAHL) for observational studies that report on the musculoskeletal functions among individuals placed in a work from home setup due to the COVID-19 pandemic, published between December 2019-August 2021. Two independent review authors searched, appraised, and extracted data from the articles included in the final review. A descriptive approach was used to synthesize the narrative evidence. Results: Forty-four articles were initially identified. A total of six (n = 6) studies met the full inclusion criteria and were included. Among them, there were five cross-sectional studies and one case-control study. The highest prevalence reported were neck pain (20.3-76.9%), low back pain (19.5-74.1%), and shoulder pain (3.0-72.9%). The most common instrument used was the Nordic Musculoskeletal Questionnaire. One of the common professions that report musculoskeletal pain symptoms associated with work from home conditions were individuals working in the academic sector. Conclusion: The increased prevalence of musculoskeletal pain symptoms associated with work from home conditions during the COVID-19 pandemic is a concern that should be addressed to prevent negative neuromusculoskeletal outcomes. Systematic review registration: This review is in the Open Science Framework registry (osf.io/vxs4w) and the PROSPERO database (CRD42021266097). Implications for practice: •A system in the workplace should be developed for the early detection of musculoskeletal pain.•Apart from standard occupational safety and proper ergonomic, sustainable policies and programs that address the mental health issues of employees should also be addressed.•Programs addressing musculoskeletal pain should be available online for employees to address accessibility and ubiquity.

Work-from-home-related musculoskeletal pain during the COVID-19 pandemic: A rapid review protocol.

Background: The recent COVID-19 pandemic has forced various workforce industries to work from home. The work-from-home set-up has exposed some workers to some office-related work, typically not included in their jobs, consequently exposing them to an increased risk for developing musculoskeletal pain. Methods: We will search PubMed, MEDLINE, and CINAHL for observational studies published between May 2020-June 2021. This review will include published peer-reviewed studies in the English language. We will include studies that recruited adults aged 20-65 from any work industry reporting on outcomes related to musculoskeletal functions (i.e., pain, disorder, condition, etc.). Two independent reviewers will screen the search results. Two independent reviewers will accomplish risk of bias assessment using the JBI-MAStARI critical appraisal tools. Likewise, data extraction will be performed by one reviewer and verified by a second reviewer. Pooled prevalence estimates will be generated using Revman V.5.2.1, where Forest plots will be generated to determine overall estimates of random-effects and confidence intervals. To quantify heterogeneity, we will index the I 2 and X 2 p-value. A narrative synthesis summarised into tables and themes will likewise be used to summarize the extracted data. Discussion: A rapid review methodology was chosen to rapidly synthesize the available literature on the prevalence of musculoskeletal pain associated with work-from-home conditions during the COVID-19 pandemic, which is essential in informing health programs and policies that address both the public and private industry sectors. Systematic review registration: This is registered in the PROSPERO Registry (CRD42021266097).

Fluid dynamic simulation suggests hopping locomotion in the Ordovician trilobite Placoparia.

Colonization of the water column by animals occurred gradually during the early Palaeozoic. However, the morphological and functional changes that took place during this colonization are poorly understood. The fossil record provides clear evidence of animals that were well adapted for swimming near the seafloor or in the open ocean, but recognising transitional forms is more problematic. Trilobites are a good model to explore the colonization of marine ecosystems. Here, we use computational fluid dynamics (CFD) to test between competing functional hypotheses in the Ordovician trilobite Placoparia. The CFD simulations exhibits hydrodynamics that promote detachment from the seafloor but also promote return to the seafloor following detachment, this is compatible with hopping locomotion. The results suggest that Placopara was not able to swim, but its hydrodynamics allowed it to hop long distances. This is consistent with the fossil record, as some ichnofossils show evidence of hopping. This type of locomotion could be useful to avoid predators as an escape mechanism. In addition, CFD simulation shows how the morphology of Placoparia is adapted to protect anterior appendices of the trunk and generate a ventral vortex that send food particles directly to the trilobite mouth. Adaptations in Placoparia allowed the first steps to evolved a new ecological habitat and consequently nektonization during the GOBE.

Mortality and clinical characteristics of multisystem inflammatory syndrome in children (MIS-C) associated with covid-19 in critically ill patients: an observational multicenter study (MISCO study).

BACKGROUND: The clinical presentation and severity of Multisystem Inflammatory Syndrome in Children associated with COVID-19 (MIS-C) is widespread and presents a very low mortality rate in high-income countries. This research describes the clinical characteristics of MIS-C in critically ill children in middle-income countries and the factors associated with the rate of mortality and patients with critical outcomes. METHODS: An observational cohort study was conducted in 14 pediatric intensive care units (PICUs) in Colombia between April 01, 2020, and January 31, 2021. Patient age ranged between one month and 18 years, and each patient met the requirements set forth by the World Health Organization (WHO) for MIS-C. RESULTS: There were seventy-eight children in this study. The median age was seven years (IQR 1-11), 18 % (14/78) were under one year old, and 56 % were male. 35 % of patients (29/78) were obese or overweight. The PICU stay per individual was six days (IQR 4-7), and 100 % had a fever upon arrival to the clinic lasting at least five days (IQR 3.7-6). 70 % (55/78) of patients had diarrhea, and 87 % (68/78) had shock or systolic myocardial dysfunction (78 %). Coronary aneurysms were found in 35 % (27/78) of cases, and pericardial effusion was found in 36 %. When compared to existing data in high-income countries, there was a higher mortality rate observed (9 % vs. 1.8 %; p=0.001). When assessing the group of patients that did not survive, a higher frequency of ferritin levels was found, above 500 ngr/mL (100 % vs. 45 %; p=0.012), as well as more cardiovascular complications (100 % vs. 54 %; p = 0.019) when compared to the group that survived. The main treatments received were immunoglobulin (91 %), vasoactive support (76 %), steroids (70.5 %) and antiplatelets (44 %). CONCLUSIONS: Multisystem Inflammatory Syndrome in Children due to SARS-CoV-2 in critically ill children living in a middle-income country has some clinical, laboratory, and echocardiographic characteristics similar to those described in high-income countries. The observed inflammatory response and cardiovascular involvement were conditions that, added to the later presentation, may explain the higher mortality seen in these children.

Sensory Behaviours and Resting Parasympathetic Functions among Children with and without ADHD.

Previous studies suggest that parasympathetic functions support sensory behaviours. However, the relationship between sensory behaviours and parasympathetic functions remain inconclusive and inconsistent among children with and without attention-deficit hyperactivity disorder (ADHD). This research aims to examine the sensory behaviours and resting parasympathetic functions among children with and without ADHD. We compared sensory behaviours and baseline parasympathetic functions of 64 participants, with 42 typically developing and 24 ADHD male children aged 7-12 years. Sensory behaviours were evaluated using the sensory profile. Baseline parasympathetic functions were indexed using the normalized unit of heart rate variability high-frequency bands (HF n.u.). Children underwent an experimental protocol consisting of watching a silent cartoon movie while HF n.u. is continuously monitored, within a controlled environment. The results of this research showed significantly lower HF n.u. (t(64) = 7.84, p < 0.01) and sensory processing total score (t(64) = 14.13 = p < 0.01) among children with ADHD compared to their typically developing peers. Likewise, a significant moderate positive correlation (r = 0.36, p < 0.05) was found between the HF n.u. and sensory profile total scores among children with ADHD. Children with ADHD have significantly lower resting state parasympathetic functions compared to their typically developing peers.

Broadly Protective Multivalent OspA Vaccine against Lyme Borreliosis, Developed Based on Surface Shaping of the C-Terminal Fragment.

The development of vaccines for prevention of diseases caused by pathogenic species can encounter major obstacles if high sequence diversity is observed between individual strains. Therefore, development might be restricted either to conserved antigens, which are often rare, or to multivalent vaccines, which renders the production more costly and cumbersome. In light of this complexity, we applied a structure-based surface shaping approach for the development of a Lyme borreliosis (LB) vaccine suitable for the United States and Europe. The surface of the C-terminal fragment of outer surface protein A (OspA) was divided into distinct regions, based primarily on binding sites of monoclonal antibodies (MAbs). In order to target the six clinically most relevant OspA serotypes (ST) in a single protein, exposed amino acids of the individual regions were exchanged to corresponding amino acids of a chosen OspA serotype. Six chimeric proteins were constructed, and, based on their immunogenicity, four of these chimeras were tested in mouse challenge models. Significant protection could be demonstrated for all four proteins following challenge with infected ticks (OspA ST1, OspA ST2, and OspA ST4) or with in vitro-grown spirochetes (OspA ST1 and OspA ST5). Two of the chimeric proteins were linked to form a fusion protein, which provided significant protection against in vitro-grown spirochetes (OspA ST1) and infected ticks (OspA ST2). This article presents the proof-of-concept study for a multivalent OspA vaccine targeting a wide range of pathogenic LB Borrelia species with a single recombinant antigen for prevention of Lyme borreliosis.

Deletion of the Mitochondrial Complex-IV Cofactor Heme A:Farnesyltransferase Causes Focal Segmental Glomerulosclerosis and Interferon Response.

Mutations in mitochondrial DNA as well as nuclear-encoded mitochondrial proteins have been reported to cause tubulointerstitial kidney diseases and focal segmental glomerulosclerosis (FSGS). Recently, genes and pathways affecting mitochondrial turnover and permeability have been implicated in adult-onset FSGS. Furthermore, dysfunctioning mitochondria may be capable of engaging intracellular innate immune-sensing pathways. To determine the impact of mitochondrial dysfunction in FSGS and secondary innate immune responses, we generated Cre/loxP transgenic mice to generate a loss-of-function deletion mutation of the complex IV assembly cofactor heme A:farnesyltransferase (COX10) restricted to cells of the developing nephrons. These mice develop severe, early-onset FSGS with innate immune activation and die prematurely with kidney failure. Mutant kidneys showed loss of glomerular and tubular epithelial function, epithelial apoptosis, and, in addition, a marked interferon response. In vitro modeling of Cox10 deletion in primary kidney epithelium compromises oxygen consumption, ATP generation, and induces oxidative stress. In addition, loss of Cox10 triggers a selective interferon response, which may be caused by the leak of mitochondrial DNA into the cytosol activating the intracellular DNA sensor, stimulator of interferon genes. This new animal model provides a mechanism to study mitochondrial dysfunction in vivo and demonstrates a direct link between mitochondrial dysfunction and intracellular innate immune response.

Interaction of Photoprotective and Acclimation Mechanisms in Ulva rigida (Chlorophyta) in Response to Diurnal Changes in Solar Radiation in Southern Chile.

Species of the genus Ulva (Chlorophyta) are regarded as opportunistic organisms, which efficiently adjust their metabolism to the prevailing environmental conditions. In this study, changes in chlorophyll-a fluorescence-based photoinhibition of photosynthesis, electron transport rates, photosynthetic pigments, lipid peroxidation, total phenolic compounds, and antioxidant metabolism were investigated during a diurnal cycle of natural solar radiation in summer (for 12 h) under two treatments: photosynthetically active radiation (PAR: 400-700 nm) and PAR+ ultraviolet (UV) radiation (280-700 nm). In the presence of PAR alone, Ulva rigida showed dynamic photoinhibition, and photosynthetic parameters and pigment concentrations decreased with the intensification of the radiation. On the other hand, under PAR+UV conditions a substantial decline up to 43% was detected and an incomplete fluorescence recovery, also, P-I curve values remained low in relation to the initial condition. The phenolic compounds increased their concentration only in UV radiation treatments without showing a correlation with the antioxidant activity. The enzimatic activity of superoxide dismutase (SOD) and ascorbate peroxidase (APX) increased over 2-fold respect at initial values during the onset of light intensity. In contrast, catalase (CAT) increased its activity rapidly in response to the radiation stress to reach maxima at 10 a.m. and decreasing during solar. The present study suggests that U. rigida is capable of acclimating to natural radiation stress relies on a concerted action of various physiological mechanisms that act at different times of the day and under different levels of environmental stress.

Connective Tissue Growth Factor Domain 4 Amplifies Fibrotic Kidney Disease through Activation of LDL Receptor-Related Protein 6.

Connective tissue growth factor (CTGF), a matrix-associated protein with four distinct cytokine binding domains, has roles in vasculogenesis, wound healing responses, and fibrogenesis and is upregulated in fibroblasts and myofibroblasts in disease. Here, we investigated the role of CTGF in fibrogenic cells. In mice, tissue-specific inducible overexpression of CTGF by kidney pericytes and fibroblasts had no bearing on nephrogenesis or kidney homeostasis but exacerbated inflammation and fibrosis after ureteral obstruction. These effects required the WNT receptor LDL receptor-related protein 6 (LRP6). Additionally, pericytes isolated from these mice became hypermigratory and hyperproliferative on overexpression of CTGF. CTGF is cleaved in vivo into distinct domains. Treatment with recombinant domain 1, 1+2 (N terminus), or 4 (C terminus) independently activated myofibroblast differentiation and wound healing responses in cultured pericytes, but domain 4 showed the broadest profibrotic activity. Domain 4 exhibited low-affinity binding to LRP6 in in vitro binding assays, and inhibition of LRP6 or critical signaling cascades downstream of LRP6, including JNK and WNT/ß-catenin, inhibited the biologic activity of domain 4. Administration of blocking antibodies specifically against CTGF domain 4 or recombinant Dickkopf-related protein-1, an endogenous inhibitor of LRP6, effectively inhibited inflammation and fibrosis associated with ureteral obstruction in vivo Therefore, domain 4 of CTGF and the WNT signaling pathway are important new targets in fibrosis.

Inhibition of αvß5 Integrin Attenuates Vascular Permeability and Protects against Renal Ischemia-Reperfusion Injury.

Ischemia-reperfusion injury (IRI) is a leading cause of AKI. This common clinical complication lacks effective therapies and can lead to the development of CKD. The αvß5 integrin may have an important role in acute injury, including septic shock and acute lung injury. To examine its function in AKI, we utilized a specific function-blocking antibody to inhibit αvß5 in a rat model of renal IRI. Pretreatment with this anti-αvß5 antibody significantly reduced serum creatinine levels, diminished renal damage detected by histopathologic evaluation, and decreased levels of injury biomarkers. Notably, therapeutic treatment with the αvß5 antibody 8 hours after IRI also provided protection from injury. Global gene expression profiling of post-ischemic kidneys showed that αvß5 inhibition affected established injury markers and induced pathway alterations previously shown to be protective. Intravital imaging of post-ischemic kidneys revealed reduced vascular leak with αvß5 antibody treatment. Immunostaining for αvß5 in the kidney detected evident expression in perivascular cells, with negligible expression in the endothelium. Studies in a three-dimensional microfluidics system identified a pericyte-dependent role for αvß5 in modulating vascular leak. Additional studies showed αvß5 functions in the adhesion and migration of kidney pericytes in vitro Initial studies monitoring renal blood flow after IRI did not find significant effects with αvß5 inhibition; however, future studies should explore the contribution of vasomotor effects. These studies identify a role for αvß5 in modulating injury-induced renal vascular leak, possibly through effects on pericyte adhesion and migration, and reveal αvß5 inhibition as a promising therapeutic strategy for AKI.

Physiological acclimation of Lessonia spicata to diurnal changing PAR and UV radiation: differential regulation among down-regulation of photochemistry, ROS scavenging activity and phlorotannins as major photoprotective mechanisms.

Intertidal macroalgae are constantly subjected to high variations in the quality and quantity of incident irradiance that can eventually generate detrimental effect on the photosynthetic apparatus. The success of these organisms to colonize the stressful coastal habitat is mainly associated with the complexity of their morphological structures and the efficiency of the anti-stress mechanisms to minimize the physiological stress. Lessonia spicata (Phaeophyceae), a brown macroalga, that inhabits the intertidal zone in central-southern Chile was studied in regard to their physiological (quantum yield, electron transport rate, pigments) and biochemical (phlorotannins content, antioxidant metabolism, oxidative stress) responses during a daily light cycle under natural solar radiation. Major findings were that F v/F m, photosynthetic parameters (ETRmax, alpha, E k) and pigments in L. spicata showed an inverse relationship to the diurnal changes in solar radiation. Phlorotannins levels and antioxidant activity showed their highest values in treatment that included UV radiation. There was an increase in SOD and APX in relation at light stress, with a peak in activity between 5.2 and 10.1 W m-2 of biologically effective dose. The increase in peroxidative damage was proportional to light dose. These results indicated that different light doses can trigger a series of complementary mechanisms of acclimation in L. spicata based on: (i) down-regulation of photochemistry activity and decrease in concentration of photosynthetic pigments; (ii) induction of phenolic compounds with specific UV-screening functions; and (iii) reactive oxygen species (ROS) scavenging activity via complementary repair of the oxidative damage through increased activity of antioxidant enzymes and potentially increased amounts of phenolic compounds.

TWEAK-Fn14 Signaling Activates Myofibroblasts to Drive Progression of Fibrotic Kidney Disease.

The identification of the cellular origins of myofibroblasts has led to the discovery of novel pathways that potentially drive myofibroblast perpetuation in disease. Here, we further investigated the role of innate immune signaling pathways in this process. In mice, renal injury-induced activation of pericytes, which are myofibroblast precursors attached to endothelial cells, led to upregulated expression of TNF receptor superfamily member 12a, also known as fibroblast growth factor-inducible 14 (Fn14), by these cells. In live rat kidney slices, administration of the Fn14 ligand, TNF-related weak inducer of apoptosis (TWEAK), promoted pericyte-dependent vasoconstriction followed by pericyte detachment from capillaries. In vitro, administration of TWEAK activated and differentiated pericytes into cytokine-producing myofibroblasts, and further activated established myofibroblasts in a manner requiring canonical and noncanonical NF-κB signaling pathways. Deficiency of Fn14 protected mouse kidneys from fibrogenesis, inflammation, and associated vascular instability after in vivo injury, and was associated with loss of NF-κB signaling. In a genetic model of spontaneous CKD, therapeutic delivery of anti-TWEAK blocking antibodies attenuated disease progression, preserved organ function, and increased survival. These results identify the TWEAK-Fn14 signaling pathway as an important factor in myofibroblast perpetuation, fibrogenesis, and chronic disease progression.

[LACHT association with hypoplasia of the upper airway. Clinical case]. / Asociación LACHT con hipoplasia de la vía aérea superior. Caso clínico.

INTRODUCTION: The Mardini-Nyhan or LACHT association is a clinical condition of low prevalence that presents with pulmonary, cardiac and limb abnormalities, in which genetic etiology is not clearly documented to date. OBJECTIVE: To describe the case of a 4-month-old child and the literature review of cases reported on this association, with the purpose of exposing the alterations found and thus gui de the early diagnosis of this entity. CLINICAL CASE: 4 months old girl, who admitted to intensive care in mixed respiratory failure, with pulmonary, cardiac and limb disorders that meet criteria for LACHT association, additionally documents hypoplasia of the upper airway, which worsens the evolution, increases the difficulty in mechanical ventilation and favors the fatal outcome at 7 days of hospita lization. CONCLUSIONS: LACTH association is a rare pathology in which the clinical findings make it possible to suspect the diagnosis, this is the first case diagnosed in the Americas and the number 11 case in the world literature and brings as a new finding the association with hypoplasia of the upper airway.

MicroRNAs as novel therapeutic targets to treat kidney injury and fibrosis.

MicroRNAs (miRs), a class of small noncoding RNAs that act as post-transcriptional regulators of gene expression, have attracted increasing attention as critical regulators of organogenesis, cancer, and disease. Interest has been spurred by development of a novel class of synthetic RNA oligonucleotides with excellent drug-like properties that hybridize to a specific miR, preventing its action. In kidney disease, a small number of miRs are dysregulated. These overlap with regulated miRs in nephrogenesis and kidney cancers. Several dysregulated miRs have been identified in fibrotic diseases of other organs, representing a "fibrotic signature," and some of these fibrotic miRs contribute remarkably to the pathogenesis of kidney disease. Chronic kidney disease, affecting ∼10% of the population, leads to kidney failure, with few treatment options. Here, we will explore the pathological mechanism of miR-21, whose pre-eminent role in amplifying kidney disease and fibrosis by suppressing mitochondrial biogenesis and function is established. Evolving roles for miR-214, -199, -200, -155, -29, -223, and -126 in kidney disease will be discussed, and we will demonstrate how studying functions of distinct miRs has led to new mechanistic insights for kidney disease progression. Finally, the utility of anti-miR oligonucleotides as potential novel therapeutics to treat chronic disease will be highlighted.

Maintenance of vascular integrity by pericytes is essential for normal kidney function.

Pericytes are tissue-resident mesenchymal progenitor cells anatomically associated with the vasculature that have been shown to participate in tissue regeneration. Here, we tested the hypothesis that kidney pericytes, derived from FoxD1+ mesodermal progenitors during embryogenesis, are necessary for postnatal kidney homeostasis. Diphtheria toxin delivery to FoxD1Cre::RsDTR transgenic mice resulted in selective ablation of >90% of kidney pericytes but not other cell lineages. Abrupt increases in plasma creatinine, blood urea nitrogen, and albuminuria within 96 h indicated acute kidney injury in pericyte-ablated mice. Loss of pericytes led to a rapid accumulation of neutral lipid vacuoles, swollen mitochondria, and apoptosis in tubular epithelial cells. Pericyte ablation led to endothelial cell swelling, reduced expression of vascular homeostasis markers, and peritubular capillary loss. Despite the observed injury, no signs of the acute inflammatory response were observed. Pathway enrichment analysis of genes expressed in kidney pericytes in vivo identified basement membrane proteins, angiogenic factors, and factors regulating vascular tone as major regulators of vascular function. Using novel microphysiological devices, we recapitulated human kidney peritubular capillaries coated with pericytes and showed that pericytes regulate permeability, basement membrane deposition, and microvascular tone. These findings suggest that through the active support of the microvasculature, pericytes are essential to adult kidney homeostasis.

Short- and long-term acclimation patterns of the giant kelp Macrocystis pyrifera (Laminariales, Phaeophyceae) along a depth gradient.

The giant kelp, Macrocystis pyrifera, is exposed to highly variable irradiance and temperature regimes across its geographic and vertical depth gradients. The objective of this study was to extend our understanding of algal acclimation strategies on different temporal scales to those varying abiotic conditions at various water depths. Different acclimation strategies to various water depths (0.2 and 4 m) between different sampling times (Jan/Feb and Aug/Sept 2012; long-term acclimation) and more rapid adjustments to different depths (0.2, 2 and 4 m; short-term acclimation) during 14 d of transplantation were found. Adjustments of variable Chl a fluorescence, pigment composition (Chl c, fucoxanthin), and the de-epoxidation state of the xanthophyll cycle pigments were responsible for the development of different physiological states with respect to various solar radiation and temperature climates. Interestingly, the results indicated that phlorotannins are important during long-term acclimation while antioxidants have a crucial role during short-term acclimation. Furthermore, the results suggested that modifications in total lipids and fatty acid compositions apparently also might play a role in depth acclimation. In Aug/Sept (austral winter), M. pyrifera responded to the transplantation from 4 m to 0.2 m depth with a rise in the degree of saturation and a switch from shorter- to longer-chain fatty acids. These changes seem to be essential for the readjustment of thylakoid membranes and might, thus, facilitate efficient photosynthesis under changing irradiances and temperatures. Further experiments are needed to disentangle the relative contribution of solar radiation, temperature and also other abiotic parameters in the observed physiological changes.

Prognostic Factors of Recurrence and Survival in Vulvar Melanoma: Subgroup Analysis of the VULvar CANcer Study.

OBJECTIVE: The aim of this study was to analyze the prognostic factors related to the recurrence rate and overall survival of vulval melanoma patients by means of a subgroup analysis of the VULvar CANcer study. METHODS: The international multicenter VULvar CANcer study involved 100 international centers, which contributed 2453 vulvar cancer cases. Of the 1727 patients finally included in the study, 42 were suffering from vulvar melanoma (2.4%). RESULTS: The mean follow-up for vulval melanoma patients was 44.1±35.7 months. Recurrence rate was 50%, and the mean recurrence-free survival was 43.5±6.6 months. For local recurrences, the mean recurrence-free interval was 63.3±8.6 months; for metastasis, 33.5±3.5 months. The 5-year recurrence-free survival rate was 28.6%. The mean overall survival for vulvar melanomas was 45.9±4 months and the 5-year overall survival rate was 78.6%. The only factor with prognostic significance regarding local recurrence of vulvar melanoma was tumor size (P = 0.003). American Joint Committee on Cancer staging was the only prognostic factor associated with metastatic disease at recurrence (P < 0.001). Finally, age of patient was significantly associated with overall survival (P < 0.001). CONCLUSIONS: Tumor size and American Joint Committee on Cancer stage were independent prognostic factors associated with local and distant recurrence, respectively. Patients' age was the only independent prognostic factor associated with overall survival.