The first-year course of urine MCP-1 and its association with response to treatment and long-term kidney prognosis in lupus nephritis.

OBJECTIVES: The present study aims to assess the course of uMCP-1 and its association with response to therapy and long-term kidney function in a prospective cohort of adults who received a kidney biopsy for suspicion of active lupus nephritis (LN). METHODS: Subjects were segregated into a histologically active LN group and a histologically chronic LN group. Both groups were followed for > = 36 months and urine were collected at flare, 3, 6, and 12 months of follow-up. The association between the course of uMCP-1, response to treatment, and progression to 30% loss of the eGFR was evaluated by linear mixed models for repeated measures. RESULTS: A kidney biopsy was performed on 125 subjects. In 114, the report was consistent with histologically active LN; in 11, with histologically chronic LN. Urine MCP-1 levels were significantly higher in the active LN than in the chronic LN group. Urine MCP-1 levels correlated with the histological findings of cellular crescents, endocapillary hypercellularity, interstitial inflammation, glomerular sclerosis, interstitial fibrosis, and tubular atrophy. The mean estimates of uMCP-1 at flare were higher in the non-response group than in the complete response group, and decreased in the complete/partial response groups by the third month, while they remained elevated in the non-response group. The mean estimates for uMCP-1 were higher at LN flare and remained elevated in patients who progressed to loss of 30% of the eGFR, while they decreased in patients with stable kidney function. CONCLUSION: The first-year course of uMCP-1 is associated with response to therapy and kidney survival in LN. Key Points •Urine MCP-1 levels differentiate histologically-active lupus nephritis from histologically-chronic lupus nephritis •Urine MCP-1 levels decrease by 3 months of therapy in subjects with a favorable response whose kidney function remains stable long-term •Urine MCP-1 levels remain elevated during the first year of therapy in subjects the will later lose kidney function.

Exclusive breastfeeding promotion policies: whose oxygen mask are we prioritizing?

Provision of human milk is crucial for maternal and infant health. However, exclusive breastfeeding may exacerbate mood disorders in women unable to achieve this goal. A nuanced approach that considers all aspects of maternal and infant health is needed. In this paper, we bring attention to the potentially negative consequences on maternal and infant health that may be associated with exclusive breastfeeding in the setting of significant challenges. We discuss recent literature exploring the relationship between breastfeeding and maternal mental health, and contextualize it with our first-hand experiences as healthcare professionals who aimed to exclusively breastfeed and encountered difficulties. Given existing evidence and our collective anecdotal experience, we advocate for a balanced approach when supporting parents struggling to breastfeed. Timely recommendations are offered for healthcare providers, medical educators and hospital administrators seeking to balance maternal and infant child health considerations while continuing to promote breastfeeding. PRéCIS STATEMENT: Exclusively promotion of breastfeeding impacts maternal mental health and consequently, infant health. We advocate for balanced considerations of maternal and infant child health while promoting breastfeeding. CLINICAL IMPLICATIONS: Singular promotion of exclusive breastfeeding may exacerbate adverse maternal mental health outcomes. A balanced consideration of maternal and infant child health is vital as breastfeeding is encouraged. Clinicians who provide front-line support to breastfeeding parents must be taught and expected to provide nuanced breastfeeding support that anticipates both physical and mental health challenges.

Prevalence and temporal trends of anemia in patients with heart failure.

BACKGROUND: Anemia is an important comorbidity in heart failure (HF), and it is associated with increased adverse disease experience and mortality. Previous reports have focused mainly on HF presenting in healthcare settings. We, therefore, set out to establish the nationwide prevalence and temporal trends of anemia in community-based patients with HF in the US. AIM: To establish the nationwide prevalence and temporal trends of anemia in community-based patients with HF in the US. DESIGN: The NHANES dataset, conducted by the CDC National Center for Health Statistics was used to collect nationally representative data on the health and nutritional status of the non-institutionalized US population. METHODS: We utilized the National Health and Nutrition Examination data collected over five survey cycles (2007-16). Included were participants aged 20-80 years with self-reported diagnosis of HF. Anemia was defined using 2 sex specific cut offs of 13 and 12 g/dl (cutoff 1), and 12 and 11 g/dl (cutoff 2), for men and women, respectively. The Chi square test was used to compare prevalence across different categories and survey cycles. Data analysis was done using STATA 16 with P-values < 0.05 considered statistically significant. RESULTS: The median hemoglobin in all HF patients was 13.5 g/dl (IQR 12.4-14.5). The prevalence of anemia among community-based patients with HF in the US was 21.34% (cutoff 1) and 9.03% (cutoff 2) and has been stable from 2007 to 2016. The burden of anemia was disproportionately higher in NH Blacks (34.48%, 95% CI 27.12-42.67) and those with BMI < 25 Kg/m2 (17.4%, 95% CI 10.9-26.64). CONCLUSION: The prevalence of anemia in patients with HF in the US is at least 9% and has remained stable over the past decade. This high persistent burden with limited proven interventions should spur further efforts aimed at identifying impactful ways of addressing anemia in patients with HF.

Mycobacterium chimaera in heater-cooler devices: an experience in a tertiary hospital in Spain.

The aim of the study was to describe the Mycobacterium chimaera contamination in heater-cooler devices after the application of a protocol of cleaning and disinfection in a tertiary hospital. It was an observational study at the La Paz-Cantoblanco-Carlos III University Hospital, Madrid, Spain. Seven heater-cooler devices are used in our hospital: five 3T Sorin (LivaNova) and two Maquet. We followed the manufacturers' instructions for cleaning and disinfection of the different heater-cooler devices. Environmental testing was developed monthly from January 2017 to July 2019. Samples were obtained from both cardioplegia and patient circuits and before and after the disinfection process and were cultured in appropriate media for non-tuberculous mycobacteria and heterotrophic bacteria (coliforms and Pseudomonas aeruginosa). A total of 320 samples were taken. Mycobacterium chimaera grew in four water samples (1.25%) from three different heater-cooler devices, with two positive results occurring after disinfection. The heterotrophic bacteria Delftia acidovorans and Stenotrophomonas maltophilia were also found. There has not been a case of M. chimaera infection in patients after cardiac surgery in our hospital. In March 2019, we decided to move the heater-cooler device outside the operating room. Mycobacterium chimaera contamination is not always eradicated by disinfection processes. We believe that placing 3T heater-cooler devices outside the operating room is the best option in preventing M. chimaera infection during cardiac surgery.

Comparative in vitro study of the accuracy of impression techniques for dental implants: Direct technique with an elastomeric impression material versus intraoral scanner.

BACKGROUND: The aim of this study was to compare a conventional technique (elastomeric impression material - EIM) and a digital technique (scanner digital model - SDM) on a six-analog master model (MM) to determine which was the most exact. MATERIAL AND METHODS: Twenty impressions were taken of a master model (EIM) and twenty scanned impressions (SDM) (True Definition). A coordinate measuring machine (CMM) was used to measure the distances between adjacent analogues (1-2, 2-3, 3-4, 4-5, 5-6), intermittently positioned analogues (1-4, 3-6) and the most distal (1-6). Reference values were established from the master model, which were compared with the two impression techniques. The significance level was established as 5% (p<0.05). RESULTS: The precision of each technique was compared with MM. For adjacent analogues (1-2), no significant differences were found between EIM-MM (p=0,146). For intermittently positioned analogues (1-4), SDM did not show significant differences with MM (p=0.255). For the distance between distal analogues (1-6), significant differences were found between both techniques and MM (p=0.001). CONCLUSIONS: In a clinical situation with < three implants, EIM is more exact than SDM, but in cases of four implants SDM is more exact. For rehabilitations (> four implants), neither technique can be considered accurate although error falls within the tolerance limits established in the literature (30-150µm).

Cervical consistency index and risk of Cesarean delivery after induction of labor at term.

OBJECTIVE: To evaluate the association between the cervical consistency index (CCI) and the risk of Cesarean delivery after planned induction of labor (IOL) at term. METHODS: This was a prospective observational study of women with a term singleton pregnancy admitted for IOL due to maternal or fetal indication. Ultrasonographic images were obtained before IOL and CCI was calculated offline once recruitment was completed. The main outcome was defined as Cesarean delivery due to failed IOL or arrest of labor. Cesarean deliveries indicated due to maternal or fetal compromise (Van Dillen's grade 1 or 2) were excluded from analysis. Univariate statistical analysis was performed using Fisher's exact test and Student's t-test for categorical and continuous variables, respectively. Multivariate analysis was performed using logistic regression, including CCI and other variables related to the main outcome. Intraclass correlation coefficients were used to estimate intra- and interobserver agreement. RESULTS: Of 510 women admitted for IOL during the study period and for whom image quality was adequate, 46 were excluded due to emergency Cesarean delivery leaving 464 pregnancies for analysis. Cesarean section due to failed IOL or arrest of labor was performed in 100/464 (21.6%) pregnancies. The mean CCI of women who underwent Cesarean delivery was not significantly different from that in those who had vaginal delivery after IOL (70.1 ± 12.3% vs 70.0 ± 13.1%; P = 0.94). Multivariate analysis also showed absence of statistical association between CCI and Cesarean delivery for failed IOL or arrest of labor. Intraclass correlation coefficients for intra- and interobserver agreement were 0.81 (95% CI, 0.66-0.89) and 0.86 (95% CI, 0.75-0.92), respectively. CONCLUSION: CCI does not seem to be associated with the risk of Cesarean delivery after IOL. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Lynx eats cat: disease risk assessment during an Iberian lynx intraguild predation.

Lethal interactions between members of the carnivore guild are well represented in literature. In the Iberian lynx, interspecific killing (without prey consumption) of some mesocarnivores, such as the Egyptian mongoose, genet, and red fox, has been reported. Although vaguely documented, evidence suggests feral cats fall victim to interactions with this apex predator. Here, we describe the first documented case of interspecific killing and partial consumption of a feral cat by an adult male Iberian lynx reintroduced in Southwestern Spain. Ulterior analyses demonstrated that the victim was viremic to feline leukemia virus. To prevent the dissemination of the virus and a potential outbreak in the Iberian lynx population, control measures, including the clinical evaluation of the male Iberian lynx, and intensive monitoring were implemented in order to detect intraspecific interactions. After 3 weeks, the lynx was evaluated, presented good condition and resulted negative to both ELISA and RT-PCR. Thanks to the long-term monitoring, this case could be detected and measures to prevent an outbreak could be implemented.

Response to tocilizumab treatment in Graves' ophthalmopathy by measuring rectus muscle thickness and chemosis using optical coherence tomography. / Evaluación del grosor de los músculos extraoculares y la quemosis tras tocilizumab en oftalmopatía de Graves mediante tomografía de coherencia óptica.

PURPOSE: To assess the extraocular muscle thickness and chemosis after treatment with tocilizumab in patients with active Graves' ophthalmopathy by optical coherence tomography. METHODS: Case series of five patients with active Graves' ophthalmopathy (clinical activity score ≥4/10) treated with 4 doses of tocilizumab. These patients had been previously treated with corticosteroids with no response. Spectral-domain optical coherence tomography was employed to determine lateral and medial rectus muscle thickness and chemosis before and after 4 doses of tocilizumab given monthly. Scanning was performed at 3 and 9 o'clock (nasal and temporal). RESULTS: The study included four women and one man with a median age of 52 years (range: 38-73). Median Graves' ophthalmopathy activity duration was 17 months (12-18). Median medial rectus and determine lateral thicknesses pre-treatment were 249µm (174-366) and 337µm (142-443), respectively. Median chemosis was 409µm (290-610). After tocilizumab treatment, median muscle thicknesses reduced to 157µm (88-187) and 197µm (99-290), respectively (P=.043; Wilcoxon) and chemosis to 59µm (0-78). Median clinical activity score decreased from 5 (4-8) to 1 (0-3). CONCLUSIONS: A reduction in extraocular muscle thickness and chemosis was observed after treatment with tocilizumab in Graves' ophthalmopathy patients using an optical coherence tomography, so this technique could be a useful complementary technique to assess the therapeutic responses.

The efficacy and safety of estriol to treat vulvovaginal atrophy in postmenopausal women: a systematic literature review.

OBJECTIVES: To evaluate the efficacy and safety of estriol for the treatment of vulvovaginal atrophy in postmenopausal women. METHODS: A systematic literature review was performed. We searched the following electronic databases: Medline, Cochrane, Embase, Lilacs, CINHAL and Google Scholar. The studies selected included controlled clinical trials and quasi-experimental studies. Selections were made in pairs and independently, first by title and abstract and then complete texts. RESULTS: We identified 188 studies, 22 of which met the inclusion criteria; 13 were controlled clinical trials and nine were quasi-experimental, and 1217 women were included. These studies confirmed the efficacy of local estrogens to treat symptoms of vulvovaginal atrophy with few adverse effects reported. Following treatment, serum estriol levels rose, peaking at 1 h. At the 6-month follow-up, there was no increase in serum estriol in treated women. CONCLUSIONS: The available evidence (of low and moderate quality) shows that, when administered vaginally, estriol preparations appear to be safe for women who have risk factors related to systemic estrogen therapy.

Phenotype in patients with intellectual disability and pathological results in array CGH. / Fenotipo en pacientes con discapacidad intelectual y array-CGH patológico.

INTRODUCTION: Global developmental delay (GDD) and intellectual disability (ID) are frequent reasons for consultation in paediatric neurology departments. Nowadays, array comparative genomic hybridisation (array-CGH) is one of the most widely used techniques for diagnosing these disorders. Our purpose was to determine the phenotypic features associated with pathological results in this genetic test. METHODS: We conducted a blind study of the epidemiological, clinical, anthropometric, and morphological features of 80 patients with unexplained ID to determine which features were associated with pathological results in array-CGH. RESULTS: Pathological results were found in 27.5% of the patients. Factors associated with pathological results in array-CGH were a family history of GDD/ID (OR = 12.1), congenital malformations (OR = 5.33), having more than 3 facial dysmorphic features (OR = 20.9), and hypotonia (OR = 3.25). CONCLUSIONS: Our findings are consistent with those reported by other published series. We therefore conclude that the probability of having pathological results in array-CGH increases with the presence of any of the features mentioned above in patients with ID/GDD.

Sphingomyelin-induced inhibition of the plasma membrane calcium ATPase causes neurodegeneration in type A Niemann-Pick disease.

Niemann-Pick disease type A (NPA) is a rare lysosomal storage disorder characterized by severe neurological alterations that leads to death in childhood. Loss-of-function mutations in the acid sphingomyelinase (ASM) gene cause NPA, and result in the accumulation of sphingomyelin (SM) in lysosomes and plasma membrane of neurons. Using ASM knockout (ASMko) mice as a NPA disease model, we investigated how high SM levels contribute to neural pathology in NPA. We found high levels of oxidative stress both in neurons from these mice and a NPA patient. Impaired activity of the plasma membrane calcium ATPase (PMCA) increases intracellular calcium. SM induces PMCA decreased activity, which causes oxidative stress. Incubating ASMko-cultured neurons in the histone deacetylase inhibitor, SAHA, restores PMCA activity and calcium homeostasis and, consequently, reduces the increased levels of oxidative stress. No recovery occurs when PMCA activity is pharmacologically impaired or genetically inhibited in vitro. Oral administration of SAHA prevents oxidative stress and neurodegeneration, and improves behavioral performance in ASMko mice. These results demonstrate a critical role for plasma membrane SM in neuronal calcium regulation. Thus, we identify changes in PMCA-triggered calcium homeostasis as an upstream mediator for NPA pathology. These findings can stimulate new approaches for pharmacological remediation in a disease with no current clinical treatments.

Evaluation of the possible influence of trailing and paradoxical effects on the clinical outcome of patients with candidemia.

OBJECTIVE: Paradoxical growth (PG) and trailing effect (TE) are frequently observed during antifungal susceptibility testing (AFST). These two phenomena interfere with the determination of the minimal inhibitory concentration (MIC). The aim of this study was to assess the clinical impact of TE and PG. METHODS: We analysed the frequency of TE and PG of 690 Candida isolates collected from a population-based study performed in Spain (CANDIPOP) and correlated the results with clinical outcome of the patients. RESULTS: Around 70% (484/690) of the isolates exhibited TE to azoles. Candida tropicalis showed the highest presence of TE (39/53 isolates exhibited residual growth >25% of control). No TE was seen in most of the isolates from the psilosis complex. PG was mainly associated with echinocandins. In patients treated with fluconazole within the first 48 hours after blood sampling (n = 221), the presence of TE to azoles tended to be associated with lower 30-day mortality (odds ratio (OR) 0.55, 95% confidence interval (CI) 0.25-1.00) but not with clinical failure (OR 0.85, 95% CI 0.45-1.54). In the subgroup of 117 patients treated with echinocandins, the presence of PG was not associated with patient's response to antifungal treatment (OR for 30-day mortality 1.63, 95% CI 0.76-4.03; OR for clinical failure 1.17, 95% CI 0.53-2.70). CONCLUSIONS: TE or PG are widely expressed among Candida spp., although they do not seem to influence clinical outcome.

Phenotypical characterization of regulatory T cells in humans and rodents.

Regulatory T cells (Tregs ) constitute a fascinating subpopulation of CD4(+) T cells due to their ability to limit the immune response against self and non-self antigens. Murine models and antibodies directed against surface and intracellular molecules have allowed elucidation of the mechanisms that govern their development and function. However, these markers used to their classification lack of specificity, as they can be expressed by activated T cells. Similarly, there are slight differences between animal models, in steady state and pathological conditions, anatomical localization and strategy of analysis by flow cytometry. Here, we revised the most common markers utilized for Treg typification by flow cytometry such as CD25, forkhead box protein 3 (FoxP3) and CD127, along with our data obtained in different body compartments of humans, mice and rats. Furthermore, we revised and determined the expression of other molecules important for the phenotypical characterization of Treg cells. We draw attention to the drawbacks of those markers used in chronic states of inflammation. However, until a specific marker for the identification of Tregs is discovered, the best combination of markers will depend upon the tissue or the degree of inflammation from which Tregs derive.

Highly Pathogenic Avian Influenza H5N8 Clade 2.3.4.4 Virus: Equivocal Pathogenicity and Implications for Surveillance Following Natural Infection in Breeder Ducks in the United Kingdom.

Since early 2014, several outbreaks involving novel reassortant highly pathogenic avian influenza (HPAI) A(H5N8) viruses have been detected in poultry and wild bird species in Asia, Europe and North America. These viruses have been detected in apparently healthy and dead wild migratory birds, as well as in domestic chickens, turkeys, geese and ducks. In this study, we describe the pathology of an outbreak of H5N8 HPAIV in breeder ducks in the UK. A holding with approximately 6000 breeder ducks, aged approximately 60 weeks, showed a gradual reduction in egg production and increased mortality over a 7-day period. Post-mortem examination revealed frequent fibrinous peritonitis, with severely haemorrhagic ovarian follicles and occasional splenic and pancreatic necrosis and high incidence of mycotic granulomas in the air sacs and lung. Low-to-moderate levels of HPAI H5N8 virus were detected mainly in respiratory and digestive tract, with minor involvement of other organs. Although histopathological examination confirmed the gross pathology findings, intralesional viral antigen detection by immunohistochemistry was not observed. Immunolabelled cells were rarely only present in inflamed air sacs and serosa, usually superficial to granulomatous inflammation. Abundant bacterial microcolonies were observed in haemorrhagic ovaries and oviduct. The limited viral tissue distribution and presence of inter-current fungal and bacterial infections suggest a minor role for HPAIV H5N8 in clinical disease in layer ducks.

Reflexiones en torno a la adherencia a tratamiento de las personas en situación de enfermedad / Reflections about treatment adherence to treatment of people living in illness

La relación profesional- paciente es muy importante para promover una buena adherencia. Sin embargo los pacientes admiten que con relativa frecuencia, abandonan la medicación, la dieta, la práctica de ejercicios, o cualquier otra intervención terapéutica. Esto afecta a largo plazo la calidad de vida. El éxito del tratamiento depende de ambos: médico/ terapeuta y paciente. Para una sólida adherencia, el tratante requiere de competencias técnicas y de herramientas y habilidades comunicacionales...

The relationship with the patient is very important in order to promote good adherence. Nevertheless, patients admit that it's getting more common to stop taking pills, maintaining diets and exercise, or another medical/ therapeutic interventions. This affects the quality of life in the long term. The success of the treatment depends on both the doctor/therapist, and patient. For solid adherence the specialists require technical competence and communicational skills and abilities...

The regulation of neuronal mitochondrial metabolism by calcium.

Calcium signalling is fundamental to the function of the nervous system, in association with changes in ionic gradients across the membrane. Although restoring ionic gradients is energetically costly, a rise in intracellular Ca(2+) acts through multiple pathways to increase ATP synthesis, matching energy supply to demand. Increasing cytosolic Ca(2+) stimulates metabolite transfer across the inner mitochondrial membrane through activation of Ca(2+) -regulated mitochondrial carriers, whereas an increase in matrix Ca(2+) stimulates the citric acid cycle and ATP synthase. The aspartate-glutamate exchanger Aralar/AGC1 (Slc25a12), a component of the malate-aspartate shuttle (MAS), is stimulated by modest increases in cytosolic Ca(2+) and upregulates respiration in cortical neurons by enhancing pyruvate supply into mitochondria. Failure to increase respiration in response to small (carbachol) and moderate (K(+) -depolarization) workloads and blunted stimulation of respiration in response to high workloads (veratridine) in Aralar/AGC1 knockout neurons reflect impaired MAS activity and limited mitochondrial pyruvate supply. In response to large workloads (veratridine), acute stimulation of respiration occurs in the absence of MAS through Ca(2+) influx through the mitochondrial calcium uniporter (MCU) and a rise in matrix [Ca(2+) ]. Although the physiological importance of the MCU complex in work-induced stimulation of respiration of CNS neurons is not yet clarified, abnormal mitochondrial Ca(2+) signalling causes pathology. Indeed, loss of function mutations in MICU1, a regulator of MCU complex, are associated with neuromuscular disease. In patient-derived MICU1 deficient fibroblasts, resting matrix Ca(2+) is increased and mitochondria fragmented. Thus, the fine tuning of Ca(2+) signals plays a key role in shaping mitochondrial bioenergetics.

Monosaccharide production in an acid sulfite process: kinetic modeling.

Spent sulfite liquor is a lignocellulosic waste obtained after the sulfite pulping process. It is mainly formed by sugars and lignosulfonates which are isolated from the pulp during the cooking process. The current work investigates the kinetic modeling of the sulfite process from a biorefinery point of view since monosaccharides present in the spent liquor can be used as a raw material in further biorefinery processes to produce other value-added products. Kinetic parameters of carbohydrate degradation have been determined following sugar and inhibitors from wood to spent liquor, using laboratory scale reactors and different temperatures, 130, 140 and 150 °C. Three types of reaction schemes were developed. Kinetic parameters were obtained for each one using first and n order reactions, using Aspen Custom Modeler. Results show that the best temperature to be used in the process is 130 °C, giving the maximum sugar conversion, 33.91 mol% and obtaining 13.81 mol% of decomposition products.