Altered phagocytic capacity due to acute exposure and long-term post-exposure to pesticides used for vector-borne disease as dengue.

Spinosad and temefos are widely used pesticides for chemical control of dengue vector-borne disease (Aedes aegypti). The aim of this study was to compare the effect of acute exposure (7 days) to spinosad (0.5 mg A.I. L-1) and temefos (10 mg A.I. L-1), concentrations used by the Mexican Ministry of Health, on phagocytic capacity (PC) of mononuclear cells of guppies fish (Poecilia reticulata), as well as to assess PC in fish, at 96 days after exposure to those pesticides. Obtained results indicated that spinosad did not alter PC, while an acute exposure to temefos significantly affected phagocytosis and this parameter was maintained downed even 96 days after the acute exposure, suggesting that the immunotoxic effects of temefos may be chronic.

Death of guppy fish (Poecilia reticulata) leukocytes induced by in vivo exposure to temephos and spinosad.

Temephos and spinosad are pesticides used for control of vector-borne diseases such as dengue, chikungunya and zika. However, the inadequate use of these substances has affected the health of non-target organisms. The aim of this study was to evaluate and compare, the effects of temephos and spinosad on leukocyte viability and death, using guppy fish (Poecilia reticulate) as a model organism. Guppies were exposed to temephos (10 mg/L) and spinosad (0.5 mg/L) for 7, 14, and 21 days. Afterwards, they were placed in pesticide-free fish tanks (7, 35, and 70 days) for recovery. The results showed that exposure to temephos caused leukocyte death, even at 35 days of recovery. Contrarily, the exposure to spinosad did not cause leukocyte death. This research show, for the first time, that a single dose of temephos causes apoptosis up to 56 days post-exposition, indicating that this pesticide induces chronic effects on immune response cells.

Ex vivo treatment with fucoidan of mononuclear cells from SARS-CoV-2 infected patients.

COVID-19 is a worldwide health emergency, therapy for this disease is based on antiviral drugs and immunomodulators, however, there is no treatment to effectively reduce the COVID-19 mortality rate. Fucoidan is a polysaccharide obtained from marine brown algae, with anti-inflammatory, antiviral, and immune-enhancing properties, thus, fucoidan may be used as an alternative treatment (complementary to prescribed medical therapy) for the recovery of COVID-19.  This work aimed to determine the effects of ex-vivo treatment with fucoidan on cytotoxicity, apoptosis, necrosis, and senescence, besides functional parameters of calcium flux and mitochondrial membrane potential (ΔΨm) on human peripheral blood mononuclear cells isolated from SARS-CoV-2 infected, recovered and healthy subjects. Data suggest that fucoidan does not exert cytotoxicity or senescence, however, it induces the increment of intracellular calcium flux. Additionally, fucoidan promotes recovery of ΔΨm in PBMCs from COVID-19 recovered females. Data suggest that fucoidan could ameliorate the immune response in COVID-19 patients.

Phonological complexity in intervention for Spanish-speaking children with speech sound disorder.

The efficiency of intervention for children with speech sound disorder may be influenced by linguistic complexity of the phonological intervention target. Complex targets, particularly, later-acquired, less-known consonants and consonant clusters, have been linked to greater post-intervention generalization to untargeted phonological structures. Yet there is little direct evidence to support target selection based on linguistic complexity for Spanish-speaking children with speech sound disorder. This intervention study utilizes an experimental single-case design to examine the efficacy of intervention in Spanish using different complex targets (i.e. /ɡɾ/, /bɾ/, and /l/). For each of the four Spanish-speaking children with speech sound disorder, sounds at 0% accuracy during baseline were monitored across the baseline period, during and post-intervention, and at one- and two-month follow-up visits. Over the course of intervention, only one participant achieved mastery of the targeted structure in practiced words. However, all participants demonstrated some amount of broad phonological generalization to untargeted consonants or clusters. Variable learning trajectories and broad phonological generalization are discussed as they relate to participant characteristics and linguistic complexity.

Study of the diversity and short-chain fatty acids production by the bacterial community in overweight and obese Mexican children.

Obesity and overweight are health problems of multifactorial etiology, which may include changes in the microbiome. In Mexico, more than 30 % of the child population between 5 and 11 years of age suffer from being overweight or are obese, which makes it a public health issue in progress. The purpose of this work was to measure the short-chain fatty acid concentration by high-performance liquid chromatography (HPLC), and to characterize the bacterial diversity by ion torrent semiconductor sequencing, of 16S rDNA libraries prepared from stools collected from a sample of well-characterized Mexican children for normal weight, overweight, and obese conditions by anthropometric and biochemical criteria. We found that triglyceride levels are increased in overweight and obese children, who presented altered propionic and butyric acid concentrations in feces. In addition, although the colon microbiota did not show a clear bacterial dysbiosis among the three conditions, the abundance of some particular bacteria was changed with respect to normal controls. We conclude from our results that the imbalance in the abundance of at least nine different bacteria as well as altered short-chain fatty acid concentration in feces is associated to the overweight and obese conditions of Mexican children.

Cathodoluminescence evaluation of defect structure in hydrothermally grown ZnO:Sb nanorods.

Cathodoluminescence emission of hydrothermally grown antimony doped ZnO nanostructures with different antimony doping (2.5, 4.8, and 11.8 at%) was studied in a scanning electron microscope (CL-SEM). Incorporation of antimony results in formation of mostly nanorods with low aspect ratio together with some Sb-rich nanoparticles. Transmissibn electron microscopy (TEM) of the Sb-doped samples revealed delaminated {10-10} planes produced by antimony surface segregation. CL spectra of the as-grown samples revealed well defined emission bands centered at 3.2, 2.74 and 2.0 eV, attributed to excitonic recombination, and the so-called blue and yellow emissions, respectively. It was observed that the intensity of the blue emission depends strongly on antimony content, suggesting the formation of point defects on Sb doping. While the yellow emission red-shifted after thermal annealing, either in argon or oxygen atmosphere, the intensity of the blue band decreases considerably; such behavior is explained through the reduction of the population of Zn(i) defects.

Risk factors for Giardia infection among hospitalized children in Cuba.

The risk factors associated with Giardia infection, in children hospitalized in Havana, Cuba, were recently explored. Children aged ≥5 years were more likely to be positive for Giardia infection than the younger children, with an odds ratio (OR) of 3·41 [95% confidence interval (CI) = 1·36-9·69]. The risk factors found to be associated with Giardia infection in univariate analyses were rural residence (OR = 3·01; CI = 1·23-7·35), belonging to a household that did not receive water from an aqueduct (OR = 3·27; CI = 1·21-8·91), drinking unboiled water (OR = 3·64; CI = 2·14-6·26), nail biting (OR = 3·47; CI = 1·97-6·08), eating unwashed vegetables raw (OR = 4·84; CI = 2·33-10·14), and a personal (OR = 3·23; CI = 1·58-6·59) or family history (OR = 3·96; CI = 1·53-10·47) of previous parasitic infection. In multivariate analyses, however, only two (modifiable) risk factors were found to be independently and significantly associated with Giardia infection: nail biting and eating unwashed vegetables raw. It therefore seems that, at least at the individual level, giardiasis-prevention activities in Havana should be focussed on health education to improve personal hygiene and food-related practices. If appropriately managed, the surveillance of drinking water and foodstuffs, for Giardia and other parasites, might also help to reduce the hospitalization of Cuban children.

Hospitalization of Cuban children for giardiasis: a retrospective study in a paediatric hospital in Havana.

The medical records of the 185 children who, in 2007, were admitted to the Academic Paediatric Hospital 'Centro Habana', in the Cuban capital of Havana, because of giardiasis were analysed retrospectively. A standardized form was used to collect data on the socio-demographic characteristics, clinical features, laboratory diagnosis, treatment and length of stay of each child. Information on the 15 children who had incomplete medical records was excluded from the data analysis. Of the remaining 170 children, 85 (50·0%) were aged 1-4 years, 97 (57·1%) were male, and 106 (62·4%), 92 (54·1%) and 69 (40·6%) had presented with diarrhoea, vomiting, and/or abdominal pain, respectively. Most (91·2%) of the cases had been diagnosed by the microscopical examination of a duodenal aspirate, and the drugs that had been most used frequently were quinacrine and tinidazole, which had been given to 72 (42·4%) and 62 (36·5%) of the cases, respectively. The mean length of hospital stay was 4·9 days. Such information on the clinical characteristics of giardiasis among children living in an endemic area may be valuable to paediatricians and public-health officials who wish to screen for the disease.

A randomized, controlled, open-label trial evaluating the efficacy and safety of chloroquine in the treatment of giardiasis in children.

BACKGROUND: Giardia duodenalis is among the commonest protozoan parasites in the intestinal tract of humans and may cause significant morbidity worldwide. Although there are several antigiardial agents, treatment failures have been commonly reported. OBJECTIVE: To compare the efficacy and safety of chloroquine (CQ) versus metronidazole (MTZ) in the treatment of children with confirmed G duodenalis mono-infection. METHODS: A randomized, controlled, open-label trial was carried out at the Cuban Institute of Gastroenterology. One hundred and twenty-two children were randomly assigned to receive either CQ (10 mg/Kg bodyweight twice a day for five days) or MTZ [15 mg/Kg bodyweight divided in three daily does for five days]. All children were asked to provide three faecal samples on days 3, 5 and 7 after treatment completion. Children were considered to be cured, if no Giardia trophozoites or cysts were found in any of the three post-treatment faecal specimens evaluated by direct wet mounts and/or after Ritchie concentration techniques. RESULTS: The frequency of cure was a little higher for CQ than for MTZ but the difference was not statistically significant. Headache was more common in patients treated with CQ as was bitter taste. Yellowish colouration of the urine was more frequent in the MTZ treated group. CONCLUSION: Chloroquine, for five days, is as efficacious as the recommended treatment with MTZ in children infected with G duodenalis.

Prevalence, risk factors and clinical features associated with intestinal parasitic infections in children from San Juan y Martínez, Pinar del Río, Cuba.

A cross-sectional study was carried out in 200 children aged 5-15 years, to examine the presence of intestinal parasitic infections (IPIs) and to assess the risk factors and clinical features associated with them in children in San Juan y Martinez (SIM), Cuba. Three fresh faecal samples were collected from each child and were examined by direct wet mount, brine flotation, formalin-ether and Kato-Katz techniques. Data relating to demography, source of drinking water, personal hygiene habits and clinical features were also collected Living in the rural area was significantly associated with the highest infection rates (p < 0.01). According to clinical features and laboratory examinations, children with abdominal pain were about four times more likely to have IPIs (OR 4.05, CI, 1.11, 13.18) especially soil-transmitted helminths (STH). We suggest that IPIs, especially STH, in SJM should be strongly suspected in children with abdominal pain from rural areas. Targeted and frequent interventions to control these infections are needed in this municipality.

Selective inhibitors of the osteoblast proteasome stimulate bone formation in vivo and in vitro.

We have found that the ubiquitin-proteasome pathway exerts exquisite control of osteoblast differentiation and bone formation in vitro and in vivo in rodents. Structurally different inhibitors that bind to specific catalytic beta subunits of the 20S proteasome stimulated bone formation in bone organ cultures in concentrations as low as 10 nM. When administered systemically to mice, the proteasome inhibitors epoxomicin and proteasome inhibitor-1 increased bone volume and bone formation rates over 70% after only 5 days of treatment. Since the ubiquitin-proteasome pathway has been shown to modulate expression of the Drosophila homologue of the bone morphogenetic protein-2 and -4 (BMP-2 and BMP-4) genes, we examined the effects of noggin, an endogenous inhibitor of BMP-2 and BMP-4 on bone formation stimulated by these compounds and found that it was abrogated. These compounds increased BMP-2 but not BMP-4 or BMP-6 mRNA expression in osteoblastic cells, suggesting that BMP-2 was responsible for the observed bone formation that was inhibited by noggin. We show proteasome inhibitors regulate BMP-2 gene expression at least in part through inhibiting the proteolytic processing of Gli3 protein. Our results suggest that the ubiquitin-proteasome machinery regulates osteoblast differentiation and bone formation and that inhibition of specific components of this system may be useful therapeutically in common diseases of bone loss.

Intestinal protozoan and helminth infections in the Municipality San Juan y Martínez, Pinar del Río, Cuba.

A cross-sectional study was carried out to determine the prevalence of intestinal parasitic infections and the intensity of soil-transmitted helminths (STHs) among children who attend the educational centres of San Juan y Martinez, Cuba. Ascaris lumbricoides, Blastocystis hominis and Giardia lamblia were the most common parasites found, with prevalence rates of 40.5%, 38.5% and 25%, respectively. In total, 91% of children harboured at least one type of intestinal parasite. The rates and intensity of intestinal parasitic infections found permit us to speculate that the conditions that predispose to acquire intestinal protozoan and STH infections persist in this municipality.

Outcomes and Surgical Complications in Kidney Transplantation.

BACKGROUND: Kidney transplantation is the most cost-effective therapy for end-stage renal disease. Post-operative complications account for 15%-17% of all cases and are associated with significant morbidity. Currently 4.8% of post-transplantation patients have returned to dialysis. Our center's main transplant origin is cadaveric donation. OBJECTIVE: To review surgical complications of kidney transplantation over the past 5 years. METHODS: This was an observational descriptive study that included all patients from 2011 to 2015. RESULTS: A total of 55 cases were reviewed. Diabetic nephropathy was the etiology in 30.9% of cases. Post-surgical complications occurred in 12.7% of patients with a post-operative mortality of 4%. Graft survival at 1 year was 82.4% with a 91% 1-year patient survival. CONCLUSION: Early identification and treatment of surgical complications are critical for patient and graft survival. Complications are low but significant.

Apoptosis loss and bcl-2 expression: key determinants of lymph node metastases in T1 breast cancer.

The Bcl-2 proto-oncogene extends cell survival but does not confer any proliferative advantage to cells that express it. Thus, the loss of apoptosis may have a role in progression allowing the acquisition of additional mutations. To determine whether apoptosis loss at diagnosis is associated with the metastatic advantage of ductal breast carcinomas and to examine the relationship between Bcl-2 expression, p53, and tumor cell death status, we examined tumor samples from 116 patients diagnosed with T1 (2 cm or less) breast cancer with (n = 49) or without (n = 67) lymph node metastases. Apoptosis loss in histological sections was considered when <1% of tumor nuclei were stained with terminal deoxynucleotidyl transferase labeled with biotin. We studied the expression of Bcl-2 and p53 by immunohistochemistry and in 37 p53 mutations by single-strand conformational polymorphism analysis and cycle sequencing. Multivariate logistic regression modeling was used to estimate prevalence odds ratios (pORs) for apoptosis loss and presence of lymph node metastases. Patients with marked apoptosis loss in their tumor cells were about 5 times more likely to present lymph node metastases than those with no apoptosis loss in their tumor cells (adjusted pOR, 4.7; 95% confidence interval, 1.4-15.6; trend test, P = 0.008). Bcl-2 expression was strongly associated with both apoptosis loss (pOR, 6.9; trend test, P < 0.0001) and presence of lymph node metastases (pOR, 5.7; trend test, P = 0.002). These associations were more evident in histological grade I and II tumors than in poorly differentiated histological grade III tumors and in p53-negative tumors than in p53-positive tumors. This study demonstrates for the first time that the lymphatic progression of T1 human breast cancer is strongly related to apoptosis loss.

Latent forms of transforming growth factor-beta (TGF beta) derived from bone cultures: identification of a naturally occurring 100-kDa complex with similarity to recombinant latent TGF beta.

Transforming growth factor-beta (TGF beta) is produced by most tissues, including bone, as a complex that is biologically inert. Release of TGF beta homodimer from this latent complex is necessary for TGF beta to exert effects on target cells. Thus, the nature of the latent complex and the mechanisms responsible for TGF beta release are the key to understanding TGF beta actions. We have found that murine calvarial bone cultures secrete multiple latent forms of TGF beta. Using analytical chromatography and Western blot analysis, we have compared bone latent TGF beta with the previously characterized latent complex present in platelets and with simian TGF beta precursor, which is stably expressed in a latent form by Chinese hamster ovarian (CHO) cells. A major component of the bone material appears to be a latent complex of 100 kDa, consisting of mature TGF beta (25-kDa homodimer). Like the recombinant TGF beta precursor, it elutes from a Mono-Q fast pressure liquid chromatography anion exchange column at 0.2 M NaCl and shows a very similar banding pattern on Western blots. Thus, this bone complex closely resembles recombinant TGF beta precursor expressed in a latent form by CHO cells and differs from the naturally occurring platelet complex, which has an additional 135-kDa binding protein that is bound through disulfide bonds to the precursor proregion. Western blot analysis also indicates that, like CHO cells, which express recombinant TGF beta precursor, but unlike other cell types, the bone cultures secrete detectable amounts of uncleaved TGF beta precursor. The bone calvarial culture is the first example of a naturally occurring system that expresses the 100-kDa latent TGF beta complex.

Dose-escalated paclitaxel in 1-hour infusion with a fixed dose of cisplatin in previously untreated advanced ovarian cancer: a phase II trial of the Spanish Group for Ovarian Cancer.

This phase II trial was planned to study the efficacy and toxicity of a fixed dose of cisplatin plus paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) given over 1 hour with intrapatient dose escalation. Patients with advanced epithelial ovarian cancer (stages IIB-IV); Eastern Cooperative Oncology Group performance status < or = 2; normal renal, liver, and bone marrow function; and evaluable residual disease after debulking surgery were accrued. Paclitaxel was given over 1-hour infusion and dose was escalated from 175 to 200 and 225 mg/m2 if nadir neutrophil counts were > or = 1000/microL, platelets were > or = 100,000/microL, and neurotoxicity was less than grade 2. Cisplatin was given after paclitaxel at a fixed dose of 80 mg/m2. Six courses at 3-week intervals were planned. From May 1995 to August 1996, 68 patients were entered. Paclitaxel could not be escalated in six patients, another six received up to 200 mg/m2, and 45 received 225 mg/m2. Three hundred seventy-five courses were given: 27.7% at 175 mg/m2, 19.2% at 200 mg/m2, and 53.1% at 225 mg/m2. All patients were evaluable for toxicity, and 67 were evaluable for response. Thirty-five patients had a complete clinical response (51.4%), 20 had a partial response (29.4%), six had stable disease (8.9%), and six progressed on therapy (8.9%). Overall response rate was 80.8 (95% confidence interval, 71.3% to 90.1%). Second-look laparotomy was performed in 32 patients, and 20 of them (62.5%) had a pathologic complete remission. Grade 3 or 4 neutropenia was seen in 26 patients (38%), but only one had fever. Severe thrombocytopenia was not seen. Peripheral neurotoxicity (grade 1, 39.7%; grade 2, 42.6%; and grade 3, 8.8%) was dose-limiting. It is too early to report on time to progression and survival, and these data are not yet available. This combination of cisplatin with escalating doses of paclitaxel is feasible and very active, but the high incidence of peripheral neurotoxicity may limit its use.

High frequency of altered HLA class I phenotypes in invasive breast carcinomas.

We studied 105 tumor samples obtained from patients diagnosed as having breast carcinomas for HLA class I and II (DR) antigen expression, using a panel of mAbs defining HLA-monomorphic, locus-specific and allele-specific determinants. Peripheral blood lymphocytes from patients were also typed for HLA alleles. The results indicated total HLA class I losses in 55 patients (52.3%), HLA-A locus losses in four patients (3.8%), HLA-B locus losses in eight patients (7.6%), and A, B, locus losses in 10 patients (9.5%). The remaining 28 patients whose tissues reacted positively with monomorphic- and locus-specific mAbs were tested for HLA allelic losses using several anti-HLA mAbs defining A2, A3, A9, B8, B12, etc. Of these 28 patients, 16 (57%) showed one or more losses of HLA reactivity. These results indicated that in 88.5% of patients we detected a particular HLA-altered tumor phenotype. The downregulation of HLA class I antigens in breast carcinomas may thus be more frequent than previously reported, and patients without HLA class I downregulation may be the exception rather than the rule. It cannot be ruled out that HLA alterations are present in some of the 12 patients with an apparently normal HLA phenotype, as some HLA alleles could not be studied because of the lack of appropriate mAbs. These HLA alterations could represent an important step associated with tumor invasion, conferring to the tumor cells the ability to escape from T-lymphocyte recognition.

Prevalence of intestinal parasites in Cuban acquired immunodeficiency syndrome (AIDS) patients.

A coproparasitological study was carried out on 67 acquired immunodeficiency syndrome (AIDS) patients admitted at the Institute of Tropical Medicine 'Pedro Kouri'. The results were compared with 136 HIV-seronegative patients (control group) who were also hospitalised in the same period. In both groups monoparasitism was more prevalent than polyparasitism and intestinal protozoa were more prevalent than helminths. At least one intestinal parasite was found in 34 (51%) of the 67 AIDS patients and in 65 (48%) of the control group patients. Intestinal coccidia were only detected in AIDS patients; Cryptosporidium spp. was the most prevalent, with eight cases (11.9%), followed by Cyclospora cayetanensis with two cases (3.0%) and Isospora belli in one case (1.5%). The microsporidia Encephalitozoon (Septata) intestinalis and Enterocytozoon bieneusi were not detected. With regard to the prevalence of other pathogenic intestinal parasites in AIDS patients and the control group, no differences were found.

First-line chemotherapy with intraperitoneal cisplatin and intravenous cyclophosphamide in ovarian carcinoma. A preliminary report.

Between August 1982 and October 1986, the feasibility and activity of five cycles of intraperitoneal (i.p.) cisplatin (CDDP) (90 mg/m2 in 6 h dwelling) and i.v. cyclophosphamide (600 mg/m2) were studied in 24 previously untreated patients with ovarian carcinoma having small or no residual disease after cytoreductive surgery. Six patients (25%) had local complications requiring catheter removal before the end of therapy. Fifteen of the 21 patients (71%) evaluable for activity achieved or maintained a pathologic complete remission. The median disease-free survival was 29+ months (range 18-58+ months). Three patients with tumor progression (two patients previously without evidence of disease, and one patient with minimal residual disease), and three partial responders were documented by laparotomy at the end of therapy. Two patients who achieved pathologic complete response relapsed at 20 and 36 months. All treatment failures (eight cases, 38%) occurred in the peritoneal cavity. Since patients were selected for having the most favorable tumor characteristics to benefit from i.p. treatment, our findings may cast some doubt on the actual contribution of i.p. CDDP at a dose of 90 mg/m2 in the treatment of patients with ovarian carcinoma and small residual disease in the peritoneal cavity.