The application of human pluripotent stem cells to model the neuronal and glial components of neurodevelopmental disorders.

Cellular models of neurodevelopmental disorders provide a valuable experimental system to uncover disease mechanisms and novel therapeutic strategies. The ability of induced pluripotent stem cells (iPSCs) to generate diverse brain cell types offers great potential to model several neurodevelopmental disorders. Further patient-derived iPSCs have the unique genetic and molecular signature of the affected individuals, which allows researchers to address limitations of transgenic behavioural models, as well as generate hypothesis-driven models to study disorder-relevant phenotypes at a cellular level. In this article, we review the extant literature that has used iPSC-based modelling to understand the neuronal and glial contributions to neurodevelopmental disorders including autism spectrum disorder (ASD), Rett syndrome, bipolar disorder (BP), and schizophrenia. For instance, several molecular candidates have been shown to influence cellular phenotypes in three-dimensional iPSC-based models of ASD patients. Delays in differentiation of astrocytes and morphological changes of neurons are associated with Rett syndrome. In the case of bipolar disorders and schizophrenia, patient-derived models helped to identify cellular phenotypes associated with neuronal deficits (e.g., excitability) and mutation-specific abnormalities in oligodendrocytes (e.g., CSPG4). Further we provide a critical review of the current limitations of this field and provide methodological suggestions to enhance future modelling efforts of neurodevelopmental disorders. Future developments in experimental design and methodology of disease modelling represent an exciting new avenue relevant to neurodevelopmental disorders.

Damping of Josephson Oscillations in Strongly Correlated One-Dimensional Atomic Gases.

We study Josephson oscillations of two strongly correlated one-dimensional bosonic clouds separated by a localized barrier. Using a quantum-Langevin approach and the exact Tonks-Girardeau solution in the impenetrable-boson limit, we determine the dynamical evolution of the particle-number imbalance, displaying an effective damping of the Josephson oscillations which depends on barrier height, interaction strength, and temperature. We show that the damping originates from the quantum and thermal fluctuations intrinsically present in the strongly correlated gas. Because of the density-phase duality of the model, the same results apply to particle-current oscillations in a one-dimensional ring where a weak barrier couples different angular momentum states.

Evaluation of ultraviolet-C and spray-drying processes as two independent inactivation steps on enterotoxigenic Escherichia coli K88 and K99 strains inoculated in fresh unconcentrated porcine plasma.

The objectives of this study were to assess the effectiveness of an ultraviolet (UV-C, 254 nm) irradiation system and the spray-drying method as two independent safety steps on inactivation of Escherichia coli K88 and K99 spiked in porcine plasma at 6·46 ± 0·04 log10  ml-1 and 6·78 ± 0·67 log10  ml-1 respectively for UV-C method, and at 7·31 ± 0·39 log10  ml-1 and 7·66 ± 0·11 log10  ml-1 , respectively for the spray-drying method. The UV-C method was performed at different UV light doses (from 750 to 9000 J l-1 ) using a pilot plant UV-C device working under turbulent flow. Spray-drying treatment was done at inlet temperature 220 ± 1°C and two different outlet temperatures, 80 ± 1°C or 70 ± 1°C. Results indicated that UV-C treatment induced a 4 log10 viability reduction for both E. coli at 3000 J l-1 . Full inactivation of both E. coli strains was achieved in all spray-dried samples dehydrated at both outlet temperatures. The special UV-C system design for turbid liquid porcine plasma is a novel treatment that can provide an additional redundant biosafety feature that can be incorporated into the manufacturing process for spray-dried animal plasma. SIGNIFICANCE AND IMPACT OF THE STUDY: The safety of raw materials from animal origin such as spray-dried porcine plasma (SDPP) may be a concern for the swine industry. Ultraviolet treatment at 254 nm (UV-C) of liquid plasma has been proposed as an additional biosafety feature in the manufacturing process of SDPP. We found that UV-C exposure in the liquid plasma at 3000 J l-1 reduces about 4 log10 ml-1 for E. coli K88 and K99. Full inactivation of both E. coli strains was achieved in all spray-dried samples. The incorporation of UV-C treatment to liquid plasma improves the robustness of the SDPP manufacturing process.

Combined effects of spray-drying conditions and postdrying storage time and temperature on Salmonella choleraesuis and Salmonella typhimurium survival when inoculated in liquid porcine plasma.

The objective of this study was to determine the effectiveness of the spray-drying process on the inactivation of Salmonella choleraesuis and Salmonella typhimurium spiked in liquid porcine plasma and to test the additive effect of immediate postdrying storage. Commercial spray-dried porcine plasma was sterilized by irradiation and then reconstituted (1:9) with sterile water. Aliquots of reconstituted plasma were inoculated with either S. choleraesuis or S. typhimurium, subjected to spray-drying at an inlet temperature of 200°C and an outlet temperature of either 71 or 80°C, and each spray-drying temperature combinations were subjected to either 0, 30 or 60 s of residence time (RT) as a simulation of residence time typical of commercial dryers. Spray-dried samples were stored at either 4·0 ± 3·0°C or 23·0 ± 0·3°C for 15 days. Bacterial counts of each Salmonella spp., were completed for all samples. For both Salmonella spp., spray-drying at both outlet temperatures reduced bacterial counts about 3 logs at RT 0 s, while there was about a 5·5 log reduction at RT 60 s. Storage of all dried samples at either 4·0 ± 3·0°C or 23·0 ± 0·3°C for 15 days eliminate all detectable bacterial counts of both Salmonella spp. SIGNIFICANCE AND IMPACT OF THE STUDY: Safety of raw materials from animal origin like spray-dried porcine plasma (SDPP) may be a concern for the swine industry. Spray-drying process and postdrying storage are good inactivation steps to reduce the bacterial load of Salmonella choleraesuis and Salmonella typhimurium. For both Salmonella spp., spray-drying at 71°C or 80°C outlet temperatures reduced bacterial counts about 3 log at residence time (RT) 0 s, while there was about a 5.5 log reduction at RT 60 s. Storage of all dried samples at either 4.0 ± 3.0°C or 23.0 ± 0.3°C for 15 days was effective for eliminating detectable bacterial counts of both Salmonella spp.

[Pediatric traumatic brain injury due to civil gunshot wounds at a General Hospital in Cali, Colombia]. / Traumatismo craneoencefálico pediátrico secundario a heridas por arma de fuego en un Hospital General en Cali, Colombia.

OBJECTIVES: Traumatic brain injury (TBI) due to gunshot-wounds (GSW) is a critical situation in the pediatric population. The aim of this study is to characterize TBI in this population since there are few reports that describe it especially in Colombia where its incidence is high, also to determine which were the main mortality predictor within our population. MATERIAL AND METHODS: We conducted a retrospective cross-sectional study in which we reviewed pediatric medical records of patients that had consulted at the Fundacion Valle del Lili pediatric Emergency Room between January of 2011 and December of 2015 because of TBI due to GSW. A descriptive statistical analysis was performed. RESULTS: In our sample of 32 patients the average age was of 13.3 (SD ± 5.4) and with 75% male patients. In our sample the Glasgow Coma Scale (GCS) at entry was less than 8 in 59.38%, a 15.6% needed craniotomy and 81.2% were admitted to the Intensive Care Unit (ICU). Death occurred in 43.75% of cases. The following mortality predictors were obtained: GCS at entry, pupillary exam and light reflexes, ISS, Marshal Score, absence of basal cisterns and presence of subarachnoid hemorrhage in CT scan, and APACHE II. CONCLUSIONS: TBI due to GSW is a devastating entity, especially in the pediatric population, they are responsible of high mortality and disability rates. There were no significant findings regarding infection rates and the use of surgery as a preventive method, therefore there's a chance it might not be indicated.

OBJETIVO: El traumatismo craneoencefálico (TCE) secundario a heridas por arma de fuego (HPAF) es una situación crítica, especialmente en la población pediátrica. El objetivo de este estudio es caracterizar el TCE en esta población dado que existen pocos reportes al respecto, especialmente en Colombia, y determinar cuáles fueron los principales predictores de mortalidad en nuestra población. MATERIALES Y METODOS: Se realizó un estudio descriptivo retrospectivo en el cual se revisaron historias clínicas pediátricas de aquellos pacientes que consultaron al servicio de urgencias de la Fundación Valle del Lili entre enero de 2011 y diciembre de 2015 por TCE debido a HPAF. Se ejecutó un análisis estadístico descriptivo con las variables a considerar. RESULTADOS: Se obtuvo una muestra de 32 pacientes con una edad promedio de 13,3 (SD ± 5,4) y de predominio masculino (75%). Se encontró que el Glasgow Coma Scale (GCS) de ingreso < 8 se presentó en el 59,38% de los casos con un 15,6% que requirieron craniectomía y un 81,2% fue hospitalizado en Unidad de Cuidado Intensivo (UCI). El 43,75% fallecieron. Se obtuvieron los siguientes predictores de mortalidad: GCS de ingreso, examen y reflejos pupilares, ISS, Marshall Score, cisternas basales cerradas y presencia de hemorragia subaracnoidea en la tomografía axial computarizada y APACHE II. CONCLUSIONES: En la presente serie, no se encontró evidencia significativa entre los pacientes tratados quirúrgicamente o no, lo cual podría sugerir que un manejo conservador, individualizando cada caso, es una conducta aceptable y segura.

Intracranial subarachnoid fat and hemorrhage secondary to sacral fracture with spondylopelvic dissociation. / Grasa y hemorragia en el espacio subaracnoideo intracraneal por fractura sacra con disociación espondilopélvica.

We describe a case of fat droplets and blood in the cerebral subarachnoid space secondary in a patient with a complex sacral fracture without associated cranial trauma, a few days after admission. To our knowledge, there is only one published case with similar findings and without any other underlying lesion as cause. We explain the differences in the mechanism of production between this direct fat embolism and brain fat embolism syndrome, which is an intravascular embolism with different radiological appearance. The most important features of sacral fracture with spondylopelvic dissociation are described. Finally, this entity should be taken into account in the differential diagnosis of the few causes of fat in the subarachnoid space. In the context of high-energy trauma fractures of the sacrum or spine must be ruled out as a potential cause of this uncommon intracranial finding.

Inner ear malformations: a practical diagnostic approach. / Malformaciones del oído interno: una aproximación diagnóstica práctica.

Pediatric sensorineural hearing loss is a major cause of disability; although inner ear malformations account for only 20-40% of all cases, recognition and characterization will be vital for the proper management of these patients. In this article relevant anatomy and development of inner ear are surveyed. The role of neuroimaging in pediatric sensorineural hearing loss and cochlear preimplantation study are assessed. The need for a universal system of classification of inner ear malformations with therapeutic and prognostic implications is highlighted. And finally, the radiological findings of each type of malformation are concisely described and depicted. Computed tomography and magnetic resonance imaging play a crucial role in the characterization of inner ear malformations and allow the assessment of the anatomical structures that enable the selection of appropriate treatment and surgical approach.

Inflammatory cytokine receptor blockade in a rodent model of mild traumatic brain injury.

In rodent models of traumatic brain injury (TBI), both Interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNFα) levels increase early after injury to return later to basal levels. We have developed and characterized a rat mild fluid percussion model of TBI (mLFP injury) that results in righting reflex response times (RRRTs) that are less than those characteristic of moderate to severe LFP injury and yet increase IL-1α/ß and TNFα levels. Here we report that blockade of IL-1α/ß and TNFα binding to IL-1R and TNFR1, respectively, reduced neuropathology in parietal cortex, hippocampus, and thalamus and improved outcome. IL-1ß binding to the type I IL-1 receptor (IL-1R1) can be blocked by a recombinant form of the endogenous IL-1R antagonist IL-1Ra (Kineret). TNFα binding to the TNF receptor (TNFR) can be blocked by the recombinant fusion protein etanercept, made up of a TNFR2 peptide fused to an Fc portion of human IgG1. There was no benefit from the combined blockades compared with individual blockades or after repeated treatments for 11 days after injury compared with one treatment at 1 hr after injury, when measured at 6 hr or 18 days, based on changes in neuropathology. There was also no further enhancement of blockade benefits after 18 days. Given that both Kineret and etanercept given singly or in combination showed similar beneficial effects and that TNFα also has a gliotransmitter role regulating AMPA receptor traffic, thus confounding effects of a TNFα blockade, we chose to focus on a single treatment with Kineret.

Radiology of external ear: indications, normal anatomy, and pathological processes. / Radiología del oído externo: indicaciones, anatomía normal y procesos patológicos.

The external ear is accessible to direct examination; the clinical history and otoscopy are sufficient to diagnose and treat most diseases of the external ear. We aim to describe the normal anatomy of the external ear, specify the indications for imaging tests, and review the clinical and radiological manifestations of the most common diseases affecting the external ear. We classify these diseases according to their origin into congenital, inflammatory, infectious, or traumatic disease or benign bone tumors or malignant tumors. Imaging does not play an important role in diseases of the external ear, but in certain clinical scenarios it can be crucial for reaching a concrete diagnosis and establishing the best treatment. Computed tomography is the first-choice technique for most diseases. Magnetic resonance imaging complements computed tomography and makes it possible to differentiate among different tissue types and to evaluate the extension of disease accurately.

Ginkgolide B revamps neuroprotective role of apurinic/apyrimidinic endonuclease 1 and mitochondrial oxidative phosphorylation against Aß25-35 -induced neurotoxicity in human neuroblastoma cells.

Accumulating evidence points to roles for oxidative stress, amyloid beta (Aß), and mitochondrial dysfunction in the pathogenesis of Alzheimer's disease (AD). In neurons, the base excision repair pathway is the predominant DNA repair (BER) pathway for repairing oxidized base lesions. Apurinic/apyrimidinic endonuclease 1 (APE1), a multifunctional enzyme with DNA repair and reduction-oxidation activities, has been shown to enhance neuronal survival after oxidative stress. This study seeks to determine 1) the effect of Aß25-35 on reactive oxygen species (ROS)/reactive nitrogen species (RNS) levels, 2) the activities of respiratory complexes (I, III, and IV), 3) the role of APE1 by ectopic expression, and 4) the neuromodulatory role of ginkgolide B (GB; from the leaves of Ginkgo biloba). The pro-oxidant Aß25-35 peptide treatment increased the levels of ROS/RNS in human neuroblastoma IMR-32 and SH-SY5Y cells, which were decreased after pretreatment with GB. Furthermore, the mitochondrial APE1 level was found to be decreased after treatment with Aß25-35 up to 48 hr, and the level was increased significantly in cells pretreated with GB. The oxidative phosphorylation (OXPHOS; activities of complexes I, III, and IV) indicated that Aß25-35 treatment decreased activities of complexes I and IV, and pretreatment with GB and ectopic APE1 expression enhanced these activities significantly compared with Aß25-35 treatment. Our results indicate that ectopic expression of APE1 potentiates neuronal cells to overcome the oxidative damage caused by Aß25-35 . In addition, GB has been shown to modulate the mitochondrial OXPHOS against Aß25-35 -induced oxidative stress and also to regulate the levels of ROS/RNS in the presence of ectopic APE1. This study presents findings from a new point of view to improve therapeutic potential for AD via the synergistic neuroprotective role played by APE1 in combination with the phytochemical GB.

A rodent model of mild traumatic brain blast injury.

One of the criteria defining mild traumatic brain injury (mTBI) in humans is a loss of consciousness lasting for less than 30 min. mTBI can result in long-term impairment of cognition and behavior. In rats, the length of time it takes a rat to right itself after injury is considered to be an analog for human return to consciousness. This study characterized a rat mild brain blast injury (mBBI) model defined by a righting response reflex time (RRRT) of more than 4 min but less than 10 min. Assessments of motor coordination relying on beam-balance and foot-fault assays and reference memory showed significant impairment in animals exposed to mBBI. This study's hypothesis is that there are inflammatory outcomes to mTBI over time that cause its deleterious effects. For example, mBBI significantly increased brain levels of interleukin (IL)-1ß and tumor necrosis factor-α (TNFα) protein. There were significant inflammatory responses in the cortex, hippocampus, thalamus, and amygdala 6 hr after mBBI, as evidenced by increased levels of the inflammatory markers associated with activation of microglia and macrophages, ionized calcium binding adaptor 1 (IBA1), impairment of the blood-brain barrier, and significant neuronal losses. There were significant increases in phosphorylated Tau (p-Tau) levels, a putative precursor to the development of neuroencephalopathy, as early as 6 hr after mBBI in the cortex and the hippocampus but not in the thalamus or the amygdala. There was an apparent correlation between RRRTs and p-Tau protein levels but not IBA1. These results suggest potential therapies for mild blast injuries via blockade of the IL-1ß and TNFα receptors.

Blue-detuned optical ring trap for Bose-Einstein condensates based on conical refraction.

We present a novel approach for the optical manipulation of neutral atoms in annular light structures produced by the phenomenon of conical refraction occurring in biaxial optical crystals. For a beam focused to a plane behind the crystal, the focal plane exhibits two concentric bright rings enclosing a ring of null intensity called the Poggendorff ring. We demonstrate both theoretically and experimentally that the Poggendorff dark ring of conical refraction is confined in three dimensions by regions of higher intensity. We derive the positions of the confining intensity maxima and minima and discuss the application of the Poggendorff ring for trapping ultra-cold atoms using the repulsive dipole force of blue-detuned light. We give analytical expressions for the trapping frequencies and potential depths along both the radial and the axial directions. Finally, we present realistic numerical simulations of the dynamics of a 87Rb Bose-Einstein condensate trapped inside the Poggendorff ring which are in good agreement with corresponding experimental results.

Early-life dietary spray-dried plasma influences immunological and intestinal injury responses to later-life Salmonella typhimurium challenge.

Increasing evidence supports the concept that early-life environmental influences, including nutrition and stress, have an impact on long-term health outcomes and disease susceptibility. The objective of the present study was to determine whether dietary spray-dried plasma (SDP), fed during the first 2 weeks post-weaning (PW), influences subsequent immunological and intestinal injury responses to Salmonella typhimurium challenge. A total of thirty-two piglets (age 16-17 d) were weaned onto nursery diets containing 0, 2·5 % SDP (fed for 7 d PW) or 5 % SDP (fed for 14 d PW), and were then fed control diets (without SDP), for the remainder of the experiment. At 34 d PW (age 50 d), pigs were challenged with 3 × 109 colony-forming units of S. typhimurium. A control group (non-challenged) that was fed 0 % SDP in the nursery was included. At 2 d post-challenge, the distal ileum was harvested for the measurement of inflammatory, histological and intestinal physiological parameters. S. typhimurium challenge induced elevated ileal histological scores, myeloperoxidase (MPO), IL-8 and TNF, and increased intestinal permeability (indicated by reduced transepithelial voltage (potential difference) and elevated 4 kDa fluorescein isothiocyanate dextran (FD4) flux rates). Compared with S. typhimurium-challenged controls (0 % SDP), pigs fed the 5 % SDP-14 d diet exhibited reduced ileal histological scores, MPO levels, IL-8 levels and FD4 flux rates. Pigs fed the 5 % SDP-14 d nursery diet exhibited increased levels of plasma and ileal TNF-α in response to the challenge, compared with the other treatments. These results indicate that inclusion of SDP in PW diets can have an influence on subsequent immunological and intestinal injury responses induced by later-life S. typhimurium challenge.

Hematologic neoplasms: interpreting lung findings in chest computed tomography.

Lung disease is very common in patients with hematologic neoplasms and varies in function of the underlying disease and its treatment. Lung involvement is associated with high morbidity and mortality, so it requires early appropriate treatment. Chest computed tomography (CT) and the analysis of biologic specimens are the first line diagnostic tools in these patients, and sometimes invasive methods are necessary. Interpreting the images requires an analysis of the clinical context, which is often complex. Starting from the knowledge about the differential diagnosis of lung findings that radiologists acquire during training, this article aims to explain the key clinical and radiological aspects that make it possible to orient the diagnosis correctly and to understand the current role of CT in the treatment strategy for this group of patients.

Preparations for colon capsule endoscopy. Prospective and randomized comparative study between two preparations for colon capsule endoscopy: PEG 2 liters + ascorbic acid versus PEG 4 liters.

INTRODUCTION: PillCam© colon capsule endoscopy (CCE) enables the study of colonic diseases in a safe and non-invasive way, although there are aspects that need to be improved. Current methods of bowel preparation lead to discordant rates of adequate cleansing and CCE excretion. AIMS: To compare the efficacy of colon cleansing using two different regimes (2L PEG plus ascorbic acid versus 4L PEG alone) for PillCam Colon (C2) capsule endoscopy. METHODS: Fifty eight patients included in this prospective study and randomized to: Group A, PEG plus ascorbic acid regimen (n = 28, 12 F/16 M) or group B, PEG alone regimen (n = 30, 14 F/16 M). The degree of cleansing was categorized into "excellent-good" or "fair-poor", according to Leighton´s recently published preparation scale. CCE excretion rate and colon cleansing were assessed. Patients underwent to PillCam colon of second generation (C2). RESULTS: Cleansing was considered to be excellent-good in 78 % of cases in group A and in 64 % of cases in group B, with no significant difference between the groups (p = 0.252). Nevertheless, when the grade of cleansing was analyzed in segments, a significant difference was found in the cecum and transverse colon. No differences were observed in the bubble effect between preparations. The excretion rate was 93 % in group A versus 70 % in group B (p = 0.043). CONCLUSIONS: These results suggest that a 2L PEG plus ascorbic acid regimen is at least as effective as a 4L PEG regimen. This regimen may be considered an effective alternative which would improve compliance because a smaller volume is required.

Morbimortality associated to acute kidney injury in patients admitted to pediatric intensive care units.

AIM: To describe the morbimortality associated to the development of acute kidney injury (AKI) defined by the pediatric adaptation of the RIFLE criteria in a Pediatric Intensive Care Unit (PICU). DESIGN: A retrospective cohort study was carried out. SETTING: Children admitted to a PICU in a tertiary care hospital. Patients or participants A total of 320 children admitted to a tertiary care hospital PICU during the year 2011. Neonates and renal transplant patients were excluded. Primary endpoints AKI was defined and classified according to the pediatric adaptation to the RIFLE criteria. PICU and hospital stays, use of mechanical ventilation and mortality were used to evaluate morbimortality. RESULTS: A total of 315 children met the inclusion criteria, with a median age of 19 months (range 6-72). Of these patients, 128 presented AKI (73 reached the Risk category and 55 reached the Injury and Failure categories). Children with AKI presented a longer PICU stay (6.0 [4.0-12.5] vs. 3.5 [2.0-7.0] days) and hospital stay (17 [10-32] vs. 10 [7-15] days), and a greater need for mechanical ventilation (61.7 vs. 36.9%). The development of AKI was an independent factor of morbidity, associated with a longer PICU and hospital stay, and with a need for longer mechanical ventilation, with a proportional relationship between increasing morbidity and the severity of AKI. CONCLUSION: The development of AKI in critically ill children is associated with increased morbimortality, which is proportional to the severity of renal injury.

Operational characteristics of ultrasound in the diagnosis of Sjögren's syndrome.

BACKGROUND AND OBJECTIVE: To determine the operational characteristics of salivary gland ultrasound (SGU) in the diagnosis of Sjögren's syndrome (SS) in a population of colombian patients with dry symptoms. MATERIALS AND METHODS: Study of diagnostic tests in patients with dry symptoms who consecutively attended the rheumatology consultation (2018-2020). Sociodemographic and clinical data were obtained through a survey, paraclinical and ophthalmological tests, minor salivary gland biopsy, unstimulated salivary flow and SGU (score 0-6 based on De Vita) were done. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values (Stata 15®) were calculated. The receiver operating characteristics (ROC) curve was developed. RESULTS: 102 patients were included (34 SS and 68 non-SS), mean age 55.69 (±11.93) years, 94% women. Positive ultrasound (score of 2 or more) was more frequent in the SS group, (70.6% vs. 22.1%, P<0.0001). The sensitivity was the same for grade 2 and 3 (70.59%), with a higher specificity (89.71%) for grade 3 (PPV 77.42% NPV 85.92). The ROC curve from the sum of the glands by means of ultrasound was better than those of the independent glands. The ROC curve of the ultrasound presented a greater area under the curve (0.72 [0.61-0.82]) than that of the histological analysis (focus score) (0.68 [0.59-0.78]), P=0.0252. CONCLUSION: Salivary gland ultrasound is a useful and reliable method for the classification of SS. Its use could be considered in the future within the SS classification criteria.

Transplant renal artery stenosis: Study of incidence using doppler ultrasound, risk factors and analysis is effect in graft outcomes.

INTRODUCTION AND OBJECTIVES: Transplant renal artery stenosis (TRAS) is a vascular complication after kidney transplantation which estimated incidence is 13%. It could cause refractory arterial hypertension, kidney dysfunction and premature death in transplant recipients. METHODS: We carried out a retrospective study including every patient who underwent renal transplantation between 2014 and 2020. They were evaluated with a systematic post-transplant renal Doppler ultrasound. To identify independent risk factors for transplant renal artery stenosis we performed a multivariate analysis. RESULTS: Seven hundred twenty-four kidney transplants were included, 12% ​​were living donors and 88% were deceased donors. The mean age was 54.8 in recipients and 53 in donors. Transplant renal artery stenosis was diagnosed in 70 (10%) recipients, the majority in the first 6 months after surgery. 51% of patients with transplant renal artery stenosis were managed conservatively. The multivariate analysis showed diabetes mellitus, graft rejection, arterial resuture and donor body mass index as independent risk factors for transplant renal artery stenosis. Survival of the grafts with transplant renal artery stenosis was 98% at 6 months and 95% at two years. CONCLUSIONS: The systematic performance of Doppler ultrasound in the immediate post-transplant period diagnosed 10% of transplant renal artery stenosis in our cohort. Despite the above risk factors, an adequate monitoring and treatment could avoid the increased risk of graft loss in patients with transplant renal artery stenosis.

Bax phosphorylation association with nucleus and oligomerization after neonatal hypoxia-ischemia.

Neonatal hypoxia-ischemia (HI) is a common occurrence in preterm and low-birth-weight infants, and the incidence of low-birth-weight and preterm births is increasing. Characterization of brain injury after HI is of critical importance in developing new treatments that more accurately target the injury. After severe HI, neuronal cells undergo necrosis and secondary apoptosis of the surrounding cells as a result of neuroinflammation. We sought to characterize the biochemical pathways associated with cell death after HI. Bax, a cell death signaling protein, is activated after HI and translocates to the nucleus, endoplasmic reticulum, and mitochondria. The translocation patterns of Bax affect the resultant cell death phenotype (necrotic or apoptotic) observed. Although Bax is known to oligomerize once it is activated, less is known about the factors that control its translocation and oligomerization. We hypothesize that Bax kinase-specific phosphorylation determines its oligomerization and intracellular localization. Using well-established in vivo and in vitro models of neonatal HI, we characterized Bax oligomerization and multiorganelle translocation. We found that HI-dependent phosphorylation of Bax determines its oligomerization status and multiorganelle localization, and, ultimately, the cell death phenotype observed. Understanding the mechanisms of Bax translocation will aid in the rational design of therapeutic strategies that decrease the trauma resulting from HI-associated inflammation.

Evaluation of the Brix refractometer to estimate immunoglobulin G concentration in bovine colostrum.

Refractometry using a Brix refractometer has been proposed as a means to estimate IgG concentration in bovine maternal colostrum (MC). The refractometer has advantages over other methods of estimating IgG concentration in that the Brix refractometer is inexpensive, readily available, less fragile, and less sensitive to variation in colostral temperature, season of the year and other factors. Samples of first-milking MC were collected from 7 dairy farms in Maine, New Hampshire, Vermont, and Connecticut (n=84) and 1 dairy farm in California (n=99). The MC was milked from the cow at 6.1 ± 5.6h postparturition and a sample was evaluated for Brix percentage by using an optical refractometer. Two additional samples (30 mL) were collected from the milk bucket, placed in vials, and frozen before analysis of total IgG by radial immunodiffusion (RID) using commercially available plates and by turbidimetric immunoassay (TIA). The second sample was analyzed for total bacterial counts and coliform counts at laboratories in New York (Northeast samples) and California (California samples). The Brix percentage (mean ± SD) was 23.8 ± 3.5, IgG concentration measured by RID was 73.4 ± 26.2g/L, and IgG concentration measured by TIA was 67.5 ± 25.0 g/L. The Brix percentage was highly correlated (r=0.75) with IgG analyzed by RID. The Brix percentage cut point to define high- or low-quality colostrum (50 g of IgG/L measured by RID) that classified more samples correctly given the proportion of high- (86%) and low-quality (14%) samples in this study was 21%, which is slightly lower than other recent estimates of Brix measurements. At this cut point, the test sensitivity, specificity, positive and negative predictive values, and accuracy were 92.9, 65.5, 93.5, 63.3, and 88.5%, respectively. Measurement of IgG by TIA correlated with Brix (r=0.63) and RID (r=0.87); however, TIA and RID methods of IgG measurement were not consistent throughout the range of samples tested. We conclude that Brix measurement of total solids in fresh MC is an inexpensive, rapid, and satisfactorily accurate method of estimating IgG concentration. A cut point of 21% Brix to estimate samples of MC >50 g/L was most appropriate for our data. Measurement of IgG in MC by TIA differed from measurement by RID.