Toxic metals (Pb and Cd) and their respective antagonists (Ca and Zn) in infant formulas and milk marketed in Brasilia, Brazil

In non-ideal scenarios involving partial or non-breastfeeding, cow's milk-based dairy products are mainstream in infant feeding. Therefore, it is important to study the concentrations of potentially neurotoxic contaminants (Pb and Cd) and their respective counteracting elements (Ca and Zn) in infant dairy products. Fifty-five brands of infant formulas and milk sold in Brasilia, Brazil were analyzed. The dairy products came from areas in the central-west (26%), southeast (29%) and south of Brazil (36%) extending as far as Argentina (7%) and the Netherlands (2%). For toxic Pb and Cd, median concentrations in powdered samples were 0.109 mg/kg and 0.033 mg/kg, respectively; in fluid samples median Pb concentration was 0.084 mg/kg, but median Cd concentration was below the limit of detection and overall values were below reference safety levels. However, 62% of these samples presented higher Pb concentration values than those established by FAO/WHO. Although the inverse correlation between Cd and Zn (Spearman r = -0.116; P = 0.590) was not statistically significant, the positive correlation between Ca and Pb was (Spearman r = 0.619; P < 0.0001). Additionally, there was a significant correlation between Pb and Cd. Furthermore, the study also revealed that provision of the essential trace element Zn in infant formulas can provide adequate amounts of the recommended daily requirements. Infant formulas and milk sold for consumption by infants and children can be an efficient tool to monitor neurotoxic metal risk exposure among young children.     

Infliximab does not increase colonic cancer risk associated to murine chronic colitis

AIM To explore the influence of Infliximab(IFX) on cancer progression in a murine model of colonic cancer associated to chronic colitis.METHODS AOM/DSS model was induced in C57BL/6 mice. Mice were injected with IFX(5 mg/kg) during each DSS cycle while control mice received saline. Body weight, occult blood test and stool consistency were measured to calculate the disease activity index(DAI). Mice were sacrificed at week 10 and colons were analyzed macroscopically and microscopically for number of cancers and degree of inflammation. MTT assay was performed on CT26 to evaluate the potential IFX role on metabolic activity and proliferation. Cells were incubated with TNF-α or IFX or TNF-α plus IFX, and cell vitality was evaluated after 6, 24 and 48 h. The same setting was used after pre-incubation with TNF-α for 24 h.RESULTS IFX significantly reduced DAI and body weight loss in mice compared with controls, preserving also colon length at sacrifice. Histological score was also reduced in treated mice. At macroscopic analysis, IFX treated mice showed a lower number of tumor lesions compared to controls. This was confirmed at microscopic analysis, although differences were not statistically significant. In vitro, IFX treated CT26 maintained similar proliferation ability at MTT test, both when exposed to IFX alone and when associated to TNF-α.CONCLUSION IFX did not increase colonic cancer risk in AOM-DSS model of cancer on chronic colitis nor influence directly the proliferation of murine colon cancer epithelial cells.     

Evolution of incidental branch-duct intraductal papillary mucinous neoplasms of the pancreas: A study with magnetic resonance imaging cholangiopancreatography

AIM To investigate the type and timing of evolution of incidentally found branch-duct intraductal papillary mucinous neoplasms(bd-IPMN) of the pancreas addressed to magnetic resonance imaging cholangiopancreatography(MRCP) follow-up.METHODS We retrospectively evaluated 72 patients who underwent, over the period 2006-2016, a total of 318 MRCPs(mean 4.4) to follow-up incidental, presumed bdIPMN without signs of malignancy, found or confirmedat a baseline MRCP examination. Median follow-up time was 48.5 mo(range 13-95 mo). MRCPs were acquired on 1.5T and/or 3.0T systems using 2D and/or 3D technique. Image analysis assessed the rates of occurrence over the follow-up of the following outcomes:(1) imaging evolution, defined as any change in cysts number and/or size and/or appearance; and(2) alert findings, defined as worrisome features and/or high risk stigmata(e.g., thick septa, parietal thickening, mural nodules and involvement of the main pancreatic duct). Time to outcomes was described with the Kaplan-Meir approach. Cox regression model was used to investigate clinical or initial MRCP findings predicting cysts changes.RESULTS We found a total of 343 cysts(per-patient mean 5.1) with average size of 8.5 mm(range 5-25 mm). Imaging evolution was observed in 32/72 patients(44.4%; 95%CI: 32-9-56.6), involving 47/343 cysts(13.7%). There was a main trend towards small( 10 mm) increase and/or decrease of cysts size at a median time of 22.5 mo. Alert findings developed in 6/72 patients(8.3%; 95%CI: 3.4-17.9) over a wide interval of time(13-63 mo). No malignancy was found on endoscopic ultrasound with fine-needle aspiration(5/6 cases) or surgery(1/6 cases). No clinical or initial MRCP features were significantly associated with changes in bd-IPMN appearance(P 0.01).CONCLUSION Changes in MRCP appearance of incidental bd-IPNM were frequent over the follow-up(44.4%), with relatively rare(8.3%) occurrence of non-malignant alert findings that prompted further diagnostic steps. Changes occurred at a wide interval of time and were unpredictable, suggesting that imaging followup should be not discontinued, though MRCPs might be considerably delayed without a significant risk of missing malignancy.     

Zinc Deficiency in Nursing Infants

Zinc deficiency during nursing can occur even in breast-fed infants. Zinc reserves accumulated during fetal development modulate the infant’s susceptibility to zinc deficiency. Improvement of maternal zinc nutrition during pregnancy is the key for infant’s zinc nutritional support and prevention of low-for-lactation-age zinc concentrations of breast-milk.     

Total and methyl-mercury in hair and milk of mothers living in the city of Porto Velho and in villages along the Rio Madeira,Amazon, Brazil

High fish consumption and extended breastfeeding are hallmarks of traditional lifestyle in Western Amazonia. We studied sources of mercury exposure, fish-methylmercury (meHg) and dental-amalgam filling, in 75 urban and 82 rural lactating mothers. Total mercury was determined in all samples while meHg concentrations were determined in subsamples of milk (45) and hair (27) of urban mothers living in Porto Velho (PV) and in hair (46) and milk (37) of mothers living in traditional communities (TC) of the Rio Madeira. The TC mothers showed significantly higher median hair-Hg concentrations (8.2 μg g⁻¹) than PV mothers (1.3  μg g⁻¹). Median total Hg in milk of PV mothers (0.36 ng g⁻¹) was significantly lower (p = 0.0000) than that found in milk of TC mothers (2.30 ng g⁻¹). The median meHg concentrations in milk of TC mothers were also significantly higher (1.0 ng g⁻¹) than in milk of PV mothers (0.07 ng g⁻¹). For urban mothers with low fish consumption rates (and relatively higher dental amalgam fillings) the proportion of inorganic Hg in milk was higher (85%) than in TC (62%). In TC mothers 51% of breast milk Hg concentrations were above 2 ng g⁻¹ (world median concentrations), contrasting with 8% in PV mothers. Despite this, there was no significant correlation between total Hg concentrations in milk and either amalgam filling or daily fish consumption. Socioeconomic changes occurring in Western Amazonia are causing changes in fish-eating habits of urban mothers. However, traditional lifestyle and attendant high fish consumption in riverine populations can still impact total Hg and methylmercury concentrations in mothers’ milk and hair.     

Helium-neon laser irradiation induces effects on cytokine production at the protein and the mRNA level

Abstract The construction of an in vitro model allowed an investigation of the basic functions of immunocompetent cells after laser irradiation. Among low-energy laser sources, the helium-neon (He-Ne) laser, with a wavelength of 632.8 nm, has often been found to produce photobiological effects including evidence of interference with immunological functions. Previous experiments revealed an influence of He-Ne laser irradiation on concentrations of interleukin-lα (IL-lα. tumor necrosis factor-α (TNF-α, interleukin-2 (IL-2), and interferon-γ (IFN-γ) in supernatants of cultures of human peripheral blood mononuclear cells (PBMC) with increased cytokine concentrations after irradiation of 18.9 J/cm² and decreased concentrations after irradiation of 37.8 J/cm². Now, the mechanisms involved were studied. Results showed that cytokine production of cells stimulated with phytohemagglutinin (PHA), concanavalin A (Con A), or bacterial lipopolysaccharide (LPS) was altered significantly after laser irradiation but not after stimulation with staphylococcus aureus enterotoxin B (SEB). In situ hybridization of IFN-γ mRNA producing PBMC revealed that the number of positive cells was modulated similarly. The results were identical in cultures of enriched monocytic (Mφ) or enriched T cells. Cells of the human monocytic cell line Mono Mac 6 were also influenced after LPS stimulation, whereas constitutively 1L-2-producing Jurkat cells were not influenced by laser irradiation at any energy density. Analysis of the IL-2 receptor (IL-2R) and intercellular adhesion molecule-1 (ICAM-I) expression in PBMC showed partial down-regulation of both receptors at 37.8 J/cm², but only after stimulation with PHA. Collected data demonstrated that He-Ne laser irradiation induces functional changes of stimulated PBMC both on protein production and at the mRNA level.     

Tsunami of immunotherapy reaches mesothelioma

Malignant pleural mesothelioma (MPM) is the most common type of malignant mesothelioma. It is a rare tumor linked to asbestos exposure and is associated with a poor prognosis. Until very recently, patients with advanced or unresectable disease had limited treatment options, primarily based on doublet chemotherapy with cisplatin and pemetrexed. In 2020 and 2021, after more than a decade with no major advances or new drugs, two phase III clinical trials published results positioning immunotherapy as a promising option for the first- and second-line treatment of MPM. Immunotherapy has revolutionized the treatment of many cancers and is also showing encouraging results in malignant mesothelioma. Both immune checkpoint inhibition and dual cytotoxic T-lymphocyte–associated antigen 4 and programmed death-ligand 1 pathway blockade resulted in significantly improved overall survival in randomized phase III trials. In the CheckMate 743 trial, first-line therapy with nivolumab plus ipilimumab outperformed standard chemotherapy, while in the CONFIRM trial, nivolumab outperformed placebo in patients previously treated with chemotherapy. These two trials represent a major milestone in the treatment of MPM and are set to position immunotherapy as a viable alternative for treatment-naïve patients and patients with progressive disease after chemotherapy.     

Single-fraction stereotactic ablative body radiation therapy for primary and metastasic lung tumor: A new paradigm?

Stereotactic ablative body radiotherapy (SABR) is an effective technique comparable to surgery in terms of local control and efficacy in early stages of non-small cell lung cancer (NSCLC) and pulmonary metastasis. Several fractionation schemes have proven to be safe and effective, including the single fraction (SF) scheme. SF is an option cost-effectiveness, more convenience and comfortable for the patient and flexible in terms of its management combined with systemic treatments. The outbreak of the severe acute respiratory syndrome coronavirus 2 pandemic has driven this not new but underutilized paradigm, recommending this option to minimize patients’ visits to hospital. SF SABR already has a long experience, strong evidence and sufficient maturity to reliably evaluate outcomes in peripheral primary NSCLC and there are promising outcomes in pulmonary metastases, making it a valid treatment option; although its use in central locations, synchronous and recurrencies tumors requires more prospective safety and efficacy studies. The SABR radiobiology study, together with the combination with systemic therapies, (targeted therapies and immunotherapy) is a direction of research in both advanced disease and early stages whose future includes SF.     

Liver transplantation for fulminant hepatic failure in infancy: A single center experience

Abstract:  FHF is characterized by a high percentage of unknown causes leading to acute liver failure and furthermore by an increased morbidity and mortality prior to and post-Ltx. In different transplant centers, the reasons leading to FHF differ significantly as well as outcome. We report our single center experience with 30 pediatric patients receiving a liver transplant for FHF, out of a total of 83 children presenting with FHF. The time to transfer patients to the transplant center after the diagnosis of FHF was long, with a median of 14 days (Ltx group) and 12 days (controls), respectively. In nearly half of the patients (n = 14) in the Ltx group, we were not able to establish an exact diagnosis prior to Ltx: 50% suffered from encephalopathy, and 13 patients were treated in the intensive care unit prior to transplant. Because of the availability of different surgical techniques, all children received a timely transplant [split (n = 18), living donor (n = 9), whole organ (n = 2), and reduced liver (n = 1)]. Patient survival was 93.4%, and graft survival was 83.4% for at least one yr follow-up. Severe complications following Ltx included three cases with aplastic anemia and one child suffering from systemic mitochondrial depletion syndrome. The survival of patients treated medically was 83%. We conclude that a strong focus should be made on early referral to a specialized center and on improvement of diagnostic tools to timely detect the underlying reason for FHF. Results following Ltx for FHF are good.