Thyroidectomy without Radioiodine in Patients with Low-Risk Thyroid Cancer.

BACKGROUND: In patients with low-risk differentiated thyroid cancer undergoing thyroidectomy, the postoperative administration of radioiodine (iodine-131) is controversial in the absence of demonstrated benefits. METHODS: In this prospective, randomized, phase 3 trial, we assigned patients with low-risk differentiated thyroid cancer who were undergoing thyroidectomy to receive ablation with postoperative administration of radioiodine (1.1 GBq) after injections of recombinant human thyrotropin (radioiodine group) or to receive no postoperative radioiodine (no-radioiodine group). The primary objective was to assess whether no radioiodine therapy was noninferior to radioiodine therapy with respect to the absence of a composite end point that included functional, structural, and biologic abnormalities at 3 years. Noninferiority was defined as a between-group difference of less than 5 percentage points in the percentage of patients who did not have events that included the presence of abnormal foci of radioiodine uptake on whole-body scanning that required subsequent treatment (in the radioiodine group only), abnormal findings on neck ultrasonography, or elevated levels of thyroglobulin or thyroglobulin antibodies. Secondary end points included prognostic factors for events and molecular characterization. RESULTS: Among 730 patients who could be evaluated 3 years after randomization, the percentage of patients without an event was 95.6% (95% confidence interval [CI], 93.0 to 97.5) in the no-radioiodine group and 95.9% (95% CI, 93.3 to 97.7) in the radioiodine group, a difference of -0.3 percentage points (two-sided 90% CI, -2.7 to 2.2), a result that met the noninferiority criteria. Events consisted of structural or functional abnormalities in 8 patients and biologic abnormalities in 23 patients with 25 events. Events were more frequent in patients with a postoperative serum thyroglobulin level of more than 1 ng per milliliter during thyroid hormone treatment. Molecular alterations were similar in patients with or without an event. No treatment-related adverse events were reported. CONCLUSIONS: In patients with low-risk thyroid cancer undergoing thyroidectomy, a follow-up strategy that did not involve the use of radioiodine was noninferior to an ablation strategy with radioiodine regarding the occurrence of functional, structural, and biologic events at 3 years. (Funded by the French National Cancer Institute; ESTIMABL2 ClinicalTrials.gov number, NCT01837745.).

In vitro conjugation of IncB/O-plasmid: Minimum inhibitory concentration of ß-lactams increases 16-fold in Salmonella enterica compared with Escherichia coli.

The use of antimicrobials in poultry leaves residues in the litter, favoring the emergence of antimicrobial-resistant pathogens and making it a source of contamination. An in vitro 4 × 4 factorial trial was performed to investigate the influence of four treatments, consisting of antimicrobial sub-concentrations, on the transference of IncB/O-plasmid through conjugation in four groups. Each group was composed of one plasmid donor bacterium (Escherichia coli H2332) and a recipient bacterium (Escherichia coli J62 or Salmonella enterica serovars, Enteritidis, Typhimurium, or Heidelberg). Our results showed a little decrease in the conjugation frequency in almost all treatments between the two bacterial species, which varied according to each strain. The MIC test revealed an increase of up to 4096-fold in resistance to beta-lactams in Salmonella serovars after plasmid acquisition. This finding suggests that some genetic apparatus may be involved in increased antimicrobial resistance in Salmonella serovars after the acquisition of primary resistance determinants.

Current practice in intermediate risk differentiated thyroid cancer - a review.

Although the overall prognosis for differentiated thyroid cancer (DTC) is excellent, a subset of patients will experience disease recurrence or may not respond to standard treatments. In recent years, DTC management has become more personalized in order to enhance treatment efficacy and avoid unnecessary interventions.In this context, major guidelines recommend post-surgery staging to assess the risk of disease persistence, recurrence, and mortality. Consequently, risk stratification becomes pivotal in determining the necessity of postoperative adjuvant therapy, which may include radioiodine therapy (RIT), the degree of TSH suppression, additional imaging studies, and the frequency of follow-up.However, the intermediate risk of recurrence is a highly heterogeneous category that encompasses various risk criteria, often combined, resulting in varying degrees of aggressiveness and a recurrence risk ranging from 5 to 20%. Furthermore, there is not enough long-term prognosis data for these patients. Unlike low- and high-risk DTC, the available literature is contradictory, and there is no consensus regarding adjuvant therapy.We aim to provide an overview of intermediate-risk differentiated thyroid cancer, focusing on criteria to consider when deciding on adjuvant therapy in the current context of personalized approach, including molecular analysis to enhance the accuracy of patient management.

Causes of death in individuals with lifetime major depression: a comprehensive machine learning analysis from a community-based autopsy center.

BACKGROUND: Depression can be associated with increased mortality and morbidity, but no studies have investigated the specific causes of death based on autopsy reports. Autopsy studies can yield valuable and detailed information on pathological ailments or underreported conditions. This study aimed to compare autopsy-confirmed causes of death (CoD) between individuals diagnosed with major depressive disorder (MDD) and matched controls. We also analyzed subgroups within our MDD sample, including late-life depression and recurrent depression. We further investigated whether machine learning (ML) algorithms could distinguish MDD and each subgroup from controls based on their CoD. METHODS: We conducted a comprehensive analysis of CoD in individuals who died from nontraumatic causes. The diagnosis of lifetime MDD was ascertained based on the DSM-5 criteria using information from a structured interview with a knowledgeable informant. Eleven established ML algorithms were used to differentiate MDD individuals from controls by simultaneously analyzing different disease category groups to account for multiple tests. The McNemar test was further used to compare paired nominal data. RESULTS: The initial dataset included records of 1,102 individuals, among whom 232 (21.1%) had a lifetime diagnosis of MDD. Each MDD individual was strictly paired with a control non-psychiatric counterpart. In the MDD group, the most common CoD were circulatory (67.2%), respiratory (13.4%), digestive (6.0%), and cancer (5.6%). Despite employing a range of ML models, we could not find distinctive CoD patterns that could reliably distinguish individuals with MDD from individuals in the control group (average accuracy: 50.6%; accuracy range: 39-59%). These findings were consistent even when considering factors within the MDD group, such as late-life or recurrent MDD. When comparing groups with paired nominal tests, no differences were found for circulatory (p=0.450), respiratory (p=0.790), digestive (p=1.000), or cancer (p=0.855) CoD. CONCLUSIONS: Our analysis revealed that autopsy-confirmed CoD exhibited remarkable similarity between individuals with depression and their matched controls, underscoring the existing heterogeneity in the literature. Future research should prioritize more severe manifestations of depression and larger sample sizes, particularly in the context of CoD related to cancer.

Competitive exclusion products as an antimicrobial alternative to control Salmonella Heidelberg in broilers.

Intestinal infections caused by non-typhoidal Salmonella spp., along with antimicrobial resistance spread are a major food safety concern worldwide. Here, we evaluate the potential of competitive exclusion products developed by anaerobic or aerobic conditions to control systemic infection, cecal colonization, fecal excretion, and improve the intestinal health in broilers challenged by Salmonella Heidelberg (SH). A total of 105 day-old chickens were randomly distributed into three experimental groups: A (untreated control), B (treated with anaerobic culture), and C (treated with aerobic culture). During 21 days, morphometric parameters of the small intestine were analyzed using microscopy, fecal excretions by cloacal swabs, systemic infection, and cecal colonization by colony-forming unit counts (CFU/g). The results indicated the lowest number of positive swabs (45.33%) recovered from Group C, followed by Group B (71.8%) and Group A (85.33%). The bacterial enumeration revealed the lowest amounts in Group C at the necropsy realized in 5-, 7-, and 14-days post-infection (DPI) (P = 0.0010, P = 0.0048, and P = 0.0094, respectively). Statistical differences between intestinal morphometrics were observed in the Group C at 21 DPI. Our results suggest that the product developed under aerobic conditions can improve intestinal health, protecting birds against SH.

Increased levels of TAR DNA-binding protein 43 in the hippocampus of subjects with bipolar disorder: a postmortem study.

Bipolar disorder shares symptoms and pathological pathways with other neurodegenerative diseases, including frontotemporal dementia (FTD). Since TAR DNA-binding protein 43 (TDP-43) is a neuropathological marker of frontotemporal dementia and it is involved in synaptic transmission, we explored the role of TDP-43 as a molecular feature of bipolar disorder (BD). Homogenates were acquired from frozen hippocampus of postmortem brains of bipolar disorder subjects. TDP-43 levels were quantified using an ELISA-sandwich method and compared between the postmortem brains of bipolar disorder subjects and age-matched control group. We found higher levels of TDP-43 protein in the hippocampus of BD (n = 15) subjects, when compared to controls (n = 15). We did not find associations of TDP-43 with age at death, postmortem interval, or age of disease onset. Our results suggest that protein TDP-43 may be potentially implicated in behavioral abnormalities seen in BD. Further investigation is needed to validate these findings and to examine the role of this protein during the disease course and mood states.

Cause of Death Determined by Full-body Autopsy in Neuropathologically Diagnosed Dementias: The Biobank for Aging Studies of the University of Sao Paulo (BAS-USP), Brazil.

OBJECTIVE: This study aimed to compare causes of death in the most prevalent neuropathologically diagnosed dementias. METHODS: We analyzed causes of death in a community-based cohort of participants aged 50 or older, submitted to full-body autopsy and a comprehensive neuropathologic examination of the brain. Individuals with Alzheimer disease (AD), vascular dementia (VaD), mixed dementia (AD+VaD), or dementia with Lewy bodies (DLBs) were compared with individuals with no dementia. RESULTS: In a sample of 920 individuals, 456 had no dementia, 147 had AD, 120 had VaD, 53 had DLB, and 37 had AD+VaD. Pneumonia as the cause of death was more frequent in the AD (P=0.023), AD+VaD (P=0.046), and DLB (P=0.043) groups. In addition, VaD (P=0.041) and AD+VaD (P=0.028) groups had a higher frequency of atherosclerosis as detected by full-body autopsy. CONCLUSION: Our findings highlight the importance of preventive measures regarding atherosclerosis and pneumonia in patients with dementia. Moreover, because of cognitive impairment, these patients may not fully account for symptoms to make early detection and diagnosis possible. These results confirm findings from previous studies that were based on clinical data, with added accuracy provided by neuropathologic diagnosis and full-body autopsy reports.

Nitrogen fertilisation impacts greenhouse gas emissions, carbon footprint, and agronomic responses of beet intercropped with arugula.

Although the response of plants to nitrogen (N) in conventional systems has been extensively described in the literature, there is a lack of information available to refine the strategic N fertilisation program required in intercropping systems to match the nutrient supply with crop demands and reduce environmental impacts on greenhouse gas emissions. Therefore, this study aims to investigate the effect of N management on the growth, production, quality, greenhouse gas emissions (GHG) and carbon footprint of a beet-arugula intercropping system during two growing seasons (winter and summer). The efficiency of N fertilisation in each season was assessed by the supply of 20 N doses, varying the amounts applied at planting and as a side dressing (0-80, 0-120, 0-160, 0-200, 0-240, 20-80, 20-120, 20-160, 20-200, 20-240, 40-80, 40-120, 40-160, 40-200, 40-240, 60-80, 60-120,60-160, 60-200 and 60-240 kg N ha-1). GHG emissions and carbon footprint were calculated and converted to CO2 equivalent (CO2 eq) utilising IPCC methodology. The height, total and marketable productivities of beet plants were 33, 31 and 34% higher in winter than in summer, respectively. Arugula plants achieved the highest performance (height, fresh mass and yield) in summer. Considering the environmental impact on global warming/climate change caused by the use of N fertilisers, total GHG emissions may range from 1723.9 to 3369.8 kg CO2eq ha-1 cycle-1 according to the N dose applied. However, based on the carbon footprint, the application of 60-120 kg N ha-1 at planting and as side dressing was the best N dose, since it reduced the carbon footprint (equivalent to 0.134 g CO2eq kcal-1 vegetables) without compromising crop yield.

Nutrient intake, digestibility, feeding behavior, nitrogen balance, and performance of feedlot goat kids fed high-concentrate diets containing licury cake (Syagrus coronata).

The current trial was carried out to evaluate the impacts of adding licury cake (Syagrus coronata) in high-concentrate diets for goat kids feedlot-finished on growth performance and metabolic parameters. Forty crossbred non-castrated Boer goat kids with approximately four months and similar initial live weights (20.15 ± 2.79 kg). The experimental design used in this study was a completely randomized, with four diets (0, 10, 20, and 30% of licury cake inclusion in a dry matter basis (DM)). Licury cake inclusion decreased nutrient intake and digestibility (P < 0.05). Times spent in feeding (P < 0.001) and rumination (P = 0.003) activities, number of events in feeding (P < 0.001) and idling (P = 0.015) increased, whereas a linear reduction occurred in feeding and rumination efficiencies of DM and neutral detergent fiber (P < 0.001). Nitrogen (N) intake, retained N (P < 0.001), triglycerides concentrations (P = 0.002), aspartate-aminotransferase, alanine-aminotransferase, and gamma-glutamyltransferase decreased with the licury cake inclusion (P < 0.05). Final body weight (P = 0.008), average daily gain (P = 0.001), and total weight gain (P = 0.001) decreased linearly when licury cake was included in diets. High-concentrate diets containing increasing levels of licury cake decrease intake and apparent digestibility of nutrients and performance when supplied for goat kids feedlot-finished. Therefore, the inclusion of the studied levels of licury cake in goat kids fed high-concentrate diets is not recommended for feedlot-finished systems.

Diurnal variations and time to reach steady state of external markers used to estimate fecal excretion in sheep.

We executed two studies to investigate time to reach steady state (EXP1) and diurnal variations (EXP 2) of markers, in order to recommend spot fecal sampling in sheep. Eight lambs were used in EXP 1. Each animal has received titanium dioxide (TDOX) and chromium oxide (COX) together during two periods of 15 days. Thirty sheep of the Santa Ines breed were used in EXP 2. Fecal samples were taken with 2-h intervals in the last 5 days of each period, simultaneously to total feces collection. A sine-cosine model was used to evaluate EXP 2, and broken-line model for EXP 1. TDOX could complete its recovery after 2.3 days, and it could accurately promote fecal estimates after 3 days of marker infusion. COX could stabilize after 4.1 days, and it could promote fecal estimates after 5 days. However, estimated fecal excretion became similar to total feces output after 3 days for TDOX and after 6 days for COX. For both markers, a total 6 days of adaptation period could be summed to a 3-day collection period. Spot sampling was similar to total fecal output at 6:00 to 8:00 on morning and between 5:00 and 7:00 on afternoon for TDOX. Also, COX could be sampled at 6:00 to 8:00 on morning and between 5:00 and 7:00 on afternoon. External markers could be evaluated from 3-day fecal spot collection. Fecal collections could be made before the morning feeding, and around 6 p.m. for both markers.

Palm kernel cake in high-concentrate diets for feedlot goat kids: nutrient intake, digestibility, feeding behavior, nitrogen balance, blood metabolites, and performance.

This study was conducted to evaluate the effects of including palm kernel cake (PKC) in high-concentrate diets for feedlot goat kids on nutrient intake, digestibility, feeding behavior, nitrogen balance, blood metabolites, and performance. Thirty-two castrated crossbred Boer × mixed breed goat kids with an average age of 4 months and an initial body weight of 19.65 ± 3.00 kg were distributed in a completely randomized design. The diets included one of four levels (0, 12, 24, and 36%) of PKC on a total dry matter basis. The PKC inclusion in the diets promoted quadratic effects in the nutrient intakes (P ≤ 0.05). The digestibility of ether extract increased (P = 0.010), whereas the digestibility of non-fibrous carbohydrates decreased (P = 0.017) with the inclusion of PKC. Palm kernel cake inclusion promoted a quadratic effect on the time spent per episode feeding and decreased the times spent idling and ruminated bolus per day (P ≤ 0.05). The ingested and retained nitrogen decreased with the inclusion of PKC (P ≤ 0.05). The inclusion of PKC in the diets had quadratic effects in the cholesterol concentrations, albumin (A), globulin (G), A:G ratio, and gamma-glutamyltransferase enzyme activity (P ≤ 0.05). The PKC inclusion promoted a quadratic increase in total weight gain (P = 0.026), with the highest value achieved at the inclusion level of 11.68%. The inclusion of up to 12% PKC in high-concentrate diets increases the intake and growth performance without compromising the digestibility of nutrients and feed efficiency.

Factors associated with brain volume in major depression in older adults without dementia: results from a large autopsy study.

OBJECTIVE: We examined brain volume and atrophy in individuals with major depressive disorder (MDD) without dementia that were referred to a large autopsy service. We also examined potential risk factors for brain atrophy, including demographics and clinical variables. METHODS: In this study, 1373 participants (787 male) aged 50 years or older who died from natural causes were included. Participants with no reliable informant, with cognitive impairment or dementia, with a medical history of severe chronic disease, or with prolonged agonal state were excluded. Presence of MDD at least once in their lifetime was defined according to the Structured Clinical Interview for DSM. Brain volume was measured immediately after removal from the skull. RESULTS: Mean age at death was 68.6 ± 11.6, and MDD was present in 185 (14%) individuals. Smaller brain volume was associated with older age (p < 0.001), lower education (years; p < 0.001), hypertension (p = 0.001), diabetes (p = 0.006), and female gender (p < 0.001). In the multivariate analysis adjusted for sociodemographics and cardiovascular risk factors, smaller brain volume was not associated with major depression (ß = -0.86, 95% CI = -26.50 to 24.77, p = 0.95). CONCLUSIONS: In this large autopsy study of older adults, MDD was not associated with smaller brain volumes. Regardless of the presence of MDD, in this sample of older adults without dementia, we found that smaller brain volumes were associated with risk factors for brain neurodegeneration such as older age, diabetes, hypertension, and lower education. Copyright © 2017 John Wiley & Sons, Ltd.

Cyclic lipopeptide signature as fingerprinting for the screening of halotolerant Bacillus strains towards microbial enhanced oil recovery.

Cyclic lipopeptides (CLPs) are non-ribosomal biosurfactants produced by Bacillus species that exhibit outstanding interfacial activity. The synthesis of CLPs is under genetic and environmental influence, and representatives from different families are generally co-produced, generating isoforms that differ in chemical structure and biological activities. This study to evaluate the effect of low and high NaCl concentrations on the composition and surface activity of CLPs produced by Bacillus strains TIM27, TIM49, TIM68, and ICA13 towards microbial enhanced oil recovery (MEOR). The strains were evaluated in mineral medium containing NaCl 2.7, 66, or 100 g L-1 and growth, surface tension and emulsification activity were monitored. Based on the analysis of 16S rDNA, gyrB and rpoB sequences TIM27 and TIM49 were assigned to Bacillus subtilis, TIM68 to Bacillus vallismortis, and ICA13 to Bacillus amyloliquefaciens. All strains tolerated up to 100-g L-1 NaCl, but only TIM49 and TIM68 were able to reduce surface tension at this concentration. TIM49 also showed emulsification activity at concentrations up to 66-g L-1 NaCl. ESI-MS analysis showed that the strains produced a mixture of CLPs, which presented distinct CLP profiles at low and high NaCl concentrations. High NaCl concentration favored the synthesis of surfactins and/or fengycins that correlated with the surface activities of TIM49 and TIM68, whereas low concentration favored the synthesis of iturins. Taken together, these findings suggest that the determination of CLP signatures under the expected condition of oil reservoirs can be useful in the guidance for choosing well-suited strains to MEOR.

Integrative study of cell damage and cancer risk in gas station attendants.

Gas station attendants are potentially exposed to carcinogenic substances. This study aimed to evaluate chronic occupational exposed gas station attendant's according to genetic parameters and its relationship with cancer predisposition. Forty gas station attendants were recruited and paired with 40 control subjects. Thousand cells from each subject were analyzed counting the number of pyknotic (PYC), karyolitic (KYL), karyorrhetic (KHC), condensed chromatin (CC), binucleated (BN), basal cells (BC), Nuclear buds (Nbud), and differentiated cells (DIFF). More 2.000 differentiated cells were analyzed counting micronucleated (MNi) and nuclear buds (NBud). We observed a statistical increase in BC and decrease in DIFF (p < 0.05). PYC, CC, KYL, MN, NBud were statistically increased (p < 0.05). All in all, our data showed elevated DNA damage, chromosomal instability, and cell cycle disturbing in our group of gas station attendants. It is a clear risk for their health in future and could be classified as a cancer predisposition.

Locus coeruleus volume and cell population changes during Alzheimer's disease progression: A stereological study in human postmortem brains with potential implication for early-stage biomarker discovery.

INTRODUCTION: Alzheimer's disease (AD) progression follows a specific spreading pattern, emphasizing the need to characterize those brain areas that degenerate first. The brainstem's locus coeruleus (LC) is the first area to develop neurofibrillary changes (neurofibrillary tangles [NFTs]). METHODS: The methods include unbiased stereological analyses in human brainstems to estimate LC volume and neuronal population in controls and individuals across all AD stages. RESULTS: As the Braak stage increases by 1 unit, the LC volume decreases by 8.4%. Neuronal loss started only midway through AD progression. Age-related changes spare the LC. DISCUSSION: The long gap between NFT accumulation and neuronal loss suggests that a second trigger may be necessary to induce neuronal death in AD. Imaging studies should determine whether LC volumetry can replicate the stage-wise atrophy observed here and how these changes are specific to AD. LC volumetry may develop into a screening biomarker for selecting high-yield candidates to undergo expensive and less accessible positron emission tomography scans and to monitor AD progression from presymptomatic stages.

GRN and MAPT Mutations in 2 Frontotemporal Dementia Research Centers in Brazil.

BACKGROUND: Mutations in GRN (progranulin) and MAPT (microtubule-associated protein tau) are among the most frequent causes of monogenic frontotemporal dementia (FTD), but data on the frequency of these mutations in regions such as Latin America are still lacking. OBJECTIVE: We aimed to investigate the frequencies of GRN and MAPT mutations in FTD cohorts from 2 Brazilian dementia research centers, the University of Sao Paulo and the Federal University of Minas Gerais medical schools. METHODS: We included 76 probands diagnosed with behavioral-variant FTD (n=55), semantic-variant Primary Progressive Aphasia (PPA) (n=11), or nonfluent-variant PPA (n=10). Twenty-five percent of the cohort had at least 1 relative affected with FTD. RESULTS: Mutations in GRN were identified in 7 probands, and in MAPT, in 2 probands. We identified 3 novel GRN mutations (p.Q130X, p.317Afs*12, and p.K259Afs*23) in patients diagnosed with nonfluent-variant PPA or behavioral-variant FTD. Plasma progranulin levels were measured and a cutoff value of 70 ng/mL was found, with 100% sensitivity and specificity to detect null GRN mutations. CONCLUSIONS: The frequency of GRN mutations was 9.6% and that of MAPT mutations was 7.1%. Among familial cases of FTD, the frequency of GRN mutations was 31.5% and that of MAPT mutations was 10.5%.