Primary immunodeficiency and chronic mucocutaneous candidiasis: pathophysiological, diagnostic, and therapeutic approaches.

Chronic mucocutaneous candidiasis (CMC) is characterized by a chronic or recurrent non-invasive infection, mainly due to Candida albicans, in skin, nails, and mucous membranes, associated in some cases with autoimmune manifestations. The key immune defect is a disruption of the action of cytokine IL-17, whose most common genetic etiology is STAT1 gene gain-of-function (GOF) mutations. The initial appropriate treatment for fungal infections is with azoles. However, the frequent occurrence of drug resistance is the main limitation. Therefore, identification of the underlying inborn error if immunity in CMC may allow to widen therapeutic options aimed at restoring immunological function. Type I and II Janus kinase-inhibitors have been shown to control CMC in cases associated with STAT1 GOF. In this review, we delve into the pathogenesis of CMC and the underlying immune mechanisms. We describe the reported genetic defects in which CMC is the main manifestation. Diagnostic and therapeutic approaches for these patients are also offered.

Assessment and accumulation of microplastics in sewage sludge at wastewater treatment plants located in Cádiz, Spain.

Sludge from Wastewater treatment plants (WWTPs) have been determined as a sink of microplastics (MP) removed from wastewater. The aim of this research work has been to evaluate the presence of these pollutants in the sludge of seven WWTPs (five urban and two industrial), located in southern Spain. Samples were collected in the primary, secondary and digested sludge matrixes, MPs were extracted following wet peroxide oxidation and the removal of cellulose, finally the samples were analyzed according to their abundance, size (from 100 µm to 5 mm), shape, colour, and polymer type. Subsequently, the data obtained on the WWTPs were compared, the main difference among the WWTPs and different sample points showed high heterogeneity in terms of abundance of microplastics, due to the differences in the sludge loaded, the processes and the type of sludge. The results from this study established that the most abundant shape was fibers; regarding the size, 100-355 µm fraction was the most abundant, showing that the amount of MPs increased when the size decreased. Regarding the type of polymers, 23 were identified by ATR-FTIR. Further, Acrylate, PE, EAA and PP were the most abundant found polymers. The presence of MPs in the digested sludge varied from 0.02 ± 0.006 MP g DW-1 to 57.18 ± 20.69 MP g DW-1 in the WWTP 6 (food industry) and WWTP 3 (urban city over 212,000 inhabitants), respectively; higher abundance of MPs found in the primary sludge in respect to secondary sludge; in concordance with the removal from wastewater line reported in other studies. The results obtained showed that MPs were widely present in sludge, becoming a sink of these pollutants, estimating that among 8.05 · 104 and 1.77 · 109 MPs · day-1 were loaded to sludge; therefore, these facilities act as a significant source of MPs into agriculture when sludge is used as soil amendment.

Kinetics of humoral deficiency in CART19-treated children and young adults with acute lymphoblastic leukaemia.

CD19-CAR T-cell therapy (CART19) causes B-cell aplasia (BCA) and dysgammaglobulinemia but there is a lack of information about the degree of its secondary immunodeficiency. We conducted a prospective study in children and young adults with acute lymphoblastic leukaemia treated with CART19, analysing the kinetics of BCA and dysgammaglobulinemia during therapy, as well as the B-cell reconstitution in those with CART19 loss. Thirty-four patients were included (14 female) with a median age at CART19 infusion of 8.7 years (2.9-24.9). Median follow-up after infusion was 7.1 months (0.5-42). BCA was observed 7 days after infusion (3-8), with persistence at 24 months in 60% of patients. All patients developed a progressive decrease in IgM and IgA: 71% had undetectable IgM levels at 71 days (41-99) and 13% undetectable IgA levels at 185 days (11-308). Three of 12 patients had protective levels of IgA in saliva. In two of three patients who lost CART19, persistent B-cell dysfunction was observed. No severe infections occurred. In conclusion, BCA occurs soon after CART19 infusion, with a progressive decrease in IgM and IgA, and with less impairment of IgA, suggesting the possibility of an immune reservoir. A persistent B-cell dysfunction might persist after CART19 loss in this population.

Moderate caloric restriction during gestation results in lower arcuate nucleus NPY- and alphaMSH-neurons and impairs hypothalamic response to fed/fasting conditions in weaned rats.

AIM: We aimed to characterize the developmental programming effects of moderate caloric restriction during early pregnancy on factors involved in hypothalamic control of energy balance. METHODS: Twenty-five-days-old offspring Wistar rats from 20% caloric restricted dams (from 1 to 12 days of pregnancy) (CR) and from control dams were studied under fed and 12 h fasting conditions. Morphometric studies on arcuate nucleus (ARC) and determinations of circulating parameters and hypothalamic levels of neuropeptide Y (NPY), proopiomelanocortin (POMC), long-form leptin receptor (ObRb), insulin receptor (InsR) and suppressor of cytokine signalling-3 (SOCS-3) mRNA were performed. RESULTS: CR animals did not show different body weight with respect to their controls, but presented higher food intake. They exhibited lower neuropeptide Y- and alpha-melanocyte-stimulating hormone-neurons (decreases of 18 and 13% in males, and 10 and 18% in females respectively) and lower total cells (decrease of 3% in males and 18% in females) in ARC. Under fed conditions, CR animals presented lower circulating leptin and ghrelin levels (decreases of 37 and 43% in males, and 15 and 34% in females respectively); furthermore, hypothalamic POMC, NPY (only in females), ObRb and InsR mRNA levels were reduced (39, 16 and 26% in males, and 112, 33, 61 and 56% in females), and those of SOCS-3 were increased (86% in males and 74% in females). Unlike control animals, under fasting conditions, ObRb, InsR and POMC mRNA levels did not decrease in CR females, and NPY mRNA decreased instead of increase in CR males. CONCLUSIONS: Moderate caloric restriction during gestation affects offspring hypothalamic structure and function, impairing its response to fed/fasting conditions, which suggests a predisposition to insulin and leptin resistance.

Neoplasia in the chimpanzee (Pan spp.).

BACKGROUND: Chimpanzees have over 98% genomic sequence homology with humans and may have a similar host response to malignancy. There is minimal information concerning cancer in the chimpanzee and such information would be valuable to individuals caring for and using them for research. METHODS: Spontaneous neoplasia that was documented in two chimpanzee colonies and in the literature were evaluated statistically. RESULTS: In all, 105 spontaneous and 12 experimental neoplasms were diagnosed. Seventy-four spontaneous tumors occurred in females, 24 in males,and seven in animals of undetermined sex. Of the spontaneous tumors 89 were benign, 14 were malignant, and two were undetermined. Neoplasia was most common in the urogenital system in females. CONCLUSIONS: Neoplasia is not uncommon in the chimpanzee, is generally benign, and occurs primarily in the urogenital system in females.

[Acute cerebellar ataxia in Griscelli syndrome type 2]. / Ataxia cerebelosa aguda en el síndrome de Griscelli de tipo 2.

TITLE: Ataxia cerebelosa aguda en el síndrome de Griscelli de tipo 2.

Obesity, voracity, and short stature: the impact of glutamate on the regulation of appetite.

BACKGROUND: World-wide obesity has risen to alarming levels. We present experimental support for a new and very challenging hypothesis linking obesity, voracity, and growth hormone (GH) deficiency, to the consumption of elevated amounts of the amino-acid glutamate (GLU). Supraphysiological doses of GLU are toxic for neuronal cells. METHODS: Human data were obtained from 807,592 German conscripts born between 1974 and 1978, and from 1,432,368 women of the German birth statistics (deutsche Perinatalerhebung) 1995-1997. The effects of orally administered monosodium glutamate (MSG) were investigated in 30 pregnant Wistar rats and their offspring. Pregnant animals either received no extra MSG, or 2.5 g MSG, or 5 g MSG per day, up to the end of the weaning period. In all, 2.5 g, respectively 5 g, MSG accounted for some 10%, respectively 20%, of dry weight of the average daily food ration. After weaning, MSG feeding was continued in the offspring. FINDINGS: Morbid obesity associates with short stature. Average stature of conscripts progressively declines when body mass index increases above 38 kg/m2. Also morbidly obese young women are shorter than average though to a lesser extent than conscripts. Oral administration of MSG to pregnant rats affects birth weight of the offspring. Maternal feeding with 5 g MSG per day results in severe birth weight reduction (P<0.01). Weight increments remain subnormal when MSG feeding to the mothers is maintained during weaning (P < 0.01). GH serum levels are affected in animals that received MSG during prenatal life via maternal feeding. Animals that are kept on high MSG diet (5 g MSG per day) continue to show serum GH levels that are as low or even lower than those of MSG injected animals (P < 0.05), both at day 30 and at day 90 of life. Animals that were kept on medium MSG diet (2.5 g MSG per day) showed low serum GH levels at day 30 of life (P < 0.01), but seemed to partially recover before day 90. Almost identical results were observed in IGF-1 serum levels. Oral MSG resulted in dose dependent voracity. The animals fed 5 g MSG per day increased water uptake by threefold (P < 0.01), and food uptake by almost two-fold (P < 0.01). The influence of MSG is in general more marked in males than in females. INTERPRETATION: GLU is a widely used nutritional substance that potentially exhibits significant neuronal toxicity. Voracity, and impaired GH secretion are the two major characteristics of parenterally administered GLU-induced neuronal damage. GLU maintains its toxicity in animals even when administered orally. Males appear to be more sensitive than females. The present study for the first time demonstrates, that a widely used nutritional monosubstance--the flavouring agent MSG--at concentrations that only slightly surpass those found in everyday human food, exhibits significant potential for damaging the hypothalamic regulation of appetite, and thereby determines the propensity of world-wide obesity. We suggest to reconsider the recommended daily allowances of amino acids and nutritional protein, and to abstain from the popular protein-rich diets, and particularly from adding the flavouring agents MSG.

Histopathological and immunohistochemical characteristics of malignant adenomyoepithelioma in a cat: case report / [Características histopatológicas e imuno-histoquímicas do adenomioepitelioma maligno em gata: relato de caso]

The malignant adenomyoepithelioma is a rare mammary tumor in women and uncommon in cats with only one report in this species. In this case report, the histopathological and immunohistochemical characteristics of six cases of malignant adenomyopithelioma in the feline mammary gland are described. Microscopic evaluation of tumors showed dense cellular neoplastic proliferation, composed of malignant myoepithelial and epithelial cells, formed by varied arrangements and presenting papillary, tubular and solid nest proliferation. Immunohistochemistry was performed for markers Ki67, Cox-2, RE, RP, p63 and HER-2. All cases were positive for p63, confirming the myoepithelial nature of neoplastic cells. The diagnosis of malignant adenomyopithelioma was made possible through the association between histopathological characteristics and immunohistochemical results.(AU)

O adenomioepitelioma maligno é uma neoplasia mamária rara em mulheres e incomum em gatas, possuindo apenas uma descrição nessa espécie. Neste relato de caso, são descritas as características histopatológicas e imuno-histoquímicas de seis casos de adenomioepitelioma maligno na glândula mamária felina. A avaliação microscópica dos tumores demonstrou proliferação neoplásica densamente celular, composta por células mioepiteliais e epiteliais malignas dispostas em padrão papilar, tubular e ninhos sólidos. Foi realizada técnica de imuno-histoquímica para os marcadores Ki67, Cox-2, RE, RP, p63 e HER-2. Todos os casos foram positivos para p63, confirmando a natureza mioepitelial das células neoplásicas. O diagnóstico de adenomioepitelioma maligno foi possível por meio da associação entre as características histopatológicas e os resultados de imuno-histoquímica.(AU)

Variation among pathologists in the histologic grading of canine cutaneous mast cell tumors with uniform use of a single grading reference.

Ten veterinary pathologists independently assigned histologic grades to the same 60 canine cutaneous mast cell tumors using the Patnaik classifications. The degree of agreement in grading among the pathologists was compared with the degree of agreement among the same pathologists in a previous study, in which each pathologist used the reference for grading that he/she uses routinely. Mean agreement improved significantly from 50.3% to 62.1% with uniform use of the Patnaik classifications (P = 0.00001), suggesting that there is value in uniform application of a single grading scheme for canine cutaneous mast cell tumors. Agreement among pathologists was still not 100%, suggesting that a more objective grading scheme should be developed and that other histologic indicators of prognosis should be investigated.

Effects of increasing doses of vigabatrin on platelet gamma-aminobutyric acid-transaminase and brain gamma-aminobutyric acid in rats.

We report the relationship of GABA-transaminase inhibition in platelets and brain with the increase in brain gamma-aminobutyric acid (GABA), as percents of the control, at 24 h after single and after 3 and 8 days of treatment with increasing doses (1, 3, 10, 30, 100 and 300 mg kg(-1) day(-1) of vigabatrin in rats. The inhibition of GABA-transaminase in platelets correlated at least as well as that in brain with the increase in brain GABA after 3 days (r = - 0.87 vs. r = -0.78), and 8 days of treatment (r = -0.77 vs. r = -0.74), and when the data of single and multiple doses were pooled (r = -0.77 vs. r = -0.75). The correlation between platelet GABA-transaminase and brain GABA fitted to a power curve, the increase in brain GABA being significant only when platelet GABA-transaminase was inhibited to less than 50% of the control. Our results suggest that platelet GABA-transaminase could be a peripheral marker of the effect of vigabatrin on brain GABA in rats.

Atomic-absorption spectrometric determination of calcium, magnesium and potassium in leaf samples after decomposition with molten sodium hydroxide.

The decomposition of standard leaf samples of varied origin and nature by fusion with sodium hydroxide in an open system has been studied. The use of sodium nitrate as an auxiliary agent facilitated the mineralization of most of the samples. The solutions obtained were analysed for calcium, magnesium and potassium by flame atomic-absorption spectrometry. The method is fast and quite precise, with absolute standard deviations of 0.04-0.13, 0.002-0.03 and 0.04-0.12% for calcium, magnesium and potassium contents of O.8-5.0, 0.13-0.48 and 0.36-2.2% respectively. The limits of detection (mug/ml) in the determination step were 0.10 for calcium, 0.011 for magnesium, and 0.09 for potassium.

Determination of phosphorus in samples of vegetable origin Mineralization with molten alkali and spectrophotometric determination.

For determination of phosphorus in samples of vegetable origin (leaves and wheat flour) decomposition by means of molten alkali is proposed. Two procedures have been studied, one with dry reagents including an auxiliary oxidant, and the other with initially moist alkali with no extra oxidant. The fusion product is easily soluble and produces a solution suitable for elemental analysis. The phosphorus is determined by the molybdenum blue method. The suggested mineralization is rapid, accurate and precise.

Quantitative approximation for the selectivity of analytical spectrophotometric procedures with systems which do not obey Beer's law.

A selectivity index is proposed for defining the selectivity of a spectrophotometric procedure that is subject to interference by species which do not obey Beer's law in the system. The interactions between analyte and interferents which affect the absorbance of an analytical system are studied by means of a simple mathematical model. Theoretical expressions are derived which represent the selectivity as a function of the analyte or interfering species concentration. The treatment is illustrated by a study of the Zr(IV)-chloranilic acid system in presence of thorium as interferent.

[Surgical diagnostic procedures in superior vena cava syndrome]. / Procedimientos quirúrgicos diagnósticos en el síndrome de vena cava superior.

We evaluate surgical risk and efficacy in a series of 29 patients referred to us over a 22-year period with diagnoses of superior vena cava syndrome (SVCS) requiring surgical removal of histology specimens. We did 34 procedures: 23 mediastinoscopies, 6 mediastinotomies, 2 thoracotomies, 2 sternotomies and 1 Daniel's biopsy procedure. Mean surgical time was 88 minutes. There were no serious surgical complications and no deaths. Histological diagnoses (27 malignant and 2 benign) were obtained for all patients. The efficacy of mediastinoscopy was 82.6% whereas the efficacy of mediastinotomy was 66.6%. We believe that diagnostic surgical procedures in patients with SVCS are safe and effective. The use of blind radiation therapy is unjustified, given that some patients present benign processes or malignant ones that are more responsive to chemotherapy. Moreover, subsequent histologic confirmation can be made more difficult after blind radiation.

[Sport injuries and level of anxiety in soccer players]. / Lesiones deportivas y rasgo de ansiedad en los jugadores de fútbol.

BACKGROUND: To study the relationship between psychological factors such as the anxiety trait and the possibility of suffering a sports injury in soccer players. SUBJECTS AND METHOD: In this study we analysed a sample of 149 males soccer players using a classic statistical analysis of case-control design studies, the relationship between the "sports injury" effect and the theoretical risk indicator of "the anxiety trait" measured using the Sixteen Personality Factors (16PF). RESULTS: It was found that there is indeed a relationship (odds ratio [OR] = 3.4; CI 95%; 1.03-11.4) between high levels in the anxiety trait and a proneness to suffering injuries, however, apart from confirming this idea which has been put forward by several authors, our results suggested that a very high or very low anxiety trait score favours the possibility of suffering an injury (OR = 3.2; CI 95%: 1.4-7.5). CONCLUSIONS: In soccer players to minimize the risk of sports injuries an optimum anxiety trait score is important as extreme scores, whether these are high or low, are associated with a greater risk of suffering injuries. Thus, if this individual characteristic is known, then it is possible to identify those persons who are predisposed to suffering sport injuries.