Losartan rewires the tumor-immune microenvironment and suppresses IGF-1 to overcome resistance to chemo-immunotherapy in ovarian cancer.

BACKGROUND: Ovarian cancer (OvCa) is the most lethal of the gynecologic malignancies. Immune checkpoint inhibitors, which have revolutionized the treatment of multiple malignancies, have had limited efficacy in OvCa patients. This lack of effectiveness is partly due to the abnormal ovarian tumor microenvironment (TME), displaying a desmoplastic, highly fibrotic extracellular matrix. High extracellular matrix deposition leads to a buildup of compressive forces that cause tumor blood vessel collapse, reduced vessel perfusion, poor delivery of drugs, and compromised trafficking of cytotoxic T-cells to these tumors. METHODS: Using two syngeneic OvCa models, we tested the effect of losartan, a widely prescribed anti-hypertensive drug, on reprogramming the TME and chemosensitizing the cancer cells. RESULTS: Losartan treatment (i) reprograms the TME leading to increased vascular perfusion, and thus enhances drug delivery and immune effector cell intratumoral infiltration and function; and (ii) rewires the OvCa cells by suppressing the IGF-1 signaling, resulting in enhanced chemosensitivity. As a result of the combined tumor and stromal effects, losartan treatment enhances the efficacy of chemo-immunotherapy in OvCa models. CONCLUSION: The safety and low cost ( < $1-2/day) of losartan warrant rapid translation of our findings to patients with OvCa.

Novel Bidentate Amine Ligand and the Interplay between Pd(II) and Pt(II) Coordination and Biological Activity.

Pt(II) and Pd(II) coordinating N-donor ligands have been extensively studied as anticancer agents after the success of cisplatin. In this work, a novel bidentate N-donor ligand, the N-[[4-(phenylmethoxy)phenyl]methyl]-2-pyridinemethanamine, was designed to explore the antiparasitic, antiviral and antitumor activity of its Pt(II) and Pd(II) complexes. Chemical and spectroscopic characterization confirm the formation of [MLCl2 ] complexes, where M=Pt(II) and Pd(II). Single crystal X-ray diffraction confirmed a square-planar geometry for the Pd(II) complex. Spectroscopic characterization of the Pt(II) complex suggests a similar structure. 1 H NMR, 195 Pt NMR and HR-ESI-MS(+) analysis of DMSO solution of complexes indicated that both compounds exchange the chloride trans to the pyridine for a solvent molecule with different reaction rates. The ligand and the two complexes were tested for in vitro antitumoral, antileishmanial, and antiviral activity. The Pt(II) complex resulted in a GI50 of 10.5 µM against the NCI/ADR-RES (multidrug-resistant ovarian carcinoma) cell line. The ligand and the Pd(II) complex showed good anti-SARS-CoV-2 activity with around 65 % reduction in viral replication at a concentration of 50 µM.

Influence of diimine bidentate ligand in the nitrosyl and nitro terpyridine ruthenium complex on the HSA/DNA interaction and antiviral activity.

Nitric oxide (NO) acts in different physiological processes, such as blood pressure control, antiparasitic activities, neurotransmission, and antitumor action. Among the exogenous NO donors, ruthenium nitrosyl/nitro complexes are potential candidates for prodrugs, due to their physicochemical properties, such as thermal and physiological pH stability. In this work, we proposed the synthesis and physical characterization of the new nitro terpyridine ruthenium (II) complexes of the type [RuII(L)(NO2)(tpy)]PF6 where tpy = 2,2':6',2″-terpyridine; L = 3,4-diaminobenzoic acid (bdq) or o-phenylenediamine (bd) and evaluation of influence of diimine bidentate ligand NH.NHq-R (R = H or COOH) in the HSA/DNA interaction as well as antiviral activity. The interactions between HSA and new nitro complexes [RuII(L)(NO2)(tpy)]+ were evaluated. The Ka values for the HSA-[RuII(bdq)(NO2)(tpy)]+ is 10 times bigger than HSA-[RuII(bd)(NO2)(tpy)]+. The sites of interaction between HSA and the complexes via synchronous fluorescence suppression indicate that the [RuII(bdq)(NO2)(tpy)]+ is found close to the Trp-241 residue, while the [RuII(bd)(NO2)(tpy)]+ complex is close to Tyr residues. The interaction with fish sperm fs-DNA using direct spectrophotometric titration (Kb) and ethidium bromide replacement (KSV and Kapp) showed weak interaction in the system fs-DNA-[RuII(bdq)(NO)(tpy)]+. Furthermore, fs-DNA-[RuII(bd)(NO2)(tpy)]+ and fs-DNA-[RuII(bd)(NO)(tpy)]3+ system showed higher intercalation constant. Circular dichroism spectra for fs-DNA-[RuII(bd)(NO2)(tpy)]+ and fs-DNA-[RuII(bd)(NO)(tpy)]3+, suggest semi-intercalative accompanied by major groove binding interaction modes. The [RuII(bd)(NO2)(tpy)]+ and [RuII(bd)(NO)(tpy)]3+ inhibit replication of Zika and Chikungunya viruses based in the nitric oxide release under S-nitrosylation reaction with cysteine viral.

Histological and immunohistochemical features of carcinomas with pulmonary involvement in cattle.

Primary pulmonary neoplasms in cattle are rare. There are few studies on the pathological findings of these neoplasms in this species. This study aimed to describe the histological and immunohistochemical findings of primary and metastatic pulmonary carcinomas in cattle. We conducted a retrospective study of 19 cases of epithelial neoplasms with pulmonary involvement. Histologically, most of the neoplasms were classified as primary pulmonary neoplasms, including different adenocarcinoma subtypes (4/19, 21%) and adenosquamous carcinomas (3/19, 16%), followed by squamous cell carcinoma (6/19, 32%), metastatic uterine adenocarcinoma (4/19, 21%), metastatic hepatocellular carcinoma (1/19, 5%), and metastatic cholangiocarcinoma (1/19, 5%). By immunohistochemistry, all neoplasms were positive for pancytokeratin, and 4/19 (21%) were positive for vimentin. Primary pulmonary neoplasms had immunoreactivity for thyroid transcription factor-1 (6/7), while only 2 of these cases were positive for napsin A. All cases with squamous differentiation (9/9) had immunoreactivity for cytokeratin (CK) 5/6, while only 7 of these cases were positive for p40. CK20, CK7, and CK8/18 showed varied immunoreactivity in the primary and metastatic pulmonary carcinomas but were important markers to confirm the diagnosis of primary mucinous adenocarcinoma and metastatic cholangiocarcinoma. HepPar-1 was only positive in the metastatic hepatocellular carcinoma. The limited number of cases of metastatic uterine adenocarcinomas in this study precluded identification of a specific immunophenotype for this tumor. Immunohistochemistry proved to be an important tool to confirm the proper classification of these neoplasms.

Characterization of cutaneous lesions caused by natural tick infestation in cattle.

Although tick infestation is a significant health problem in livestock, there are limited studies on the dermatopathological aspects of natural tick infestation in cattle. This study aimed to describe the gross and histologic aspects of cutaneous lesions caused by tick infestation in cattle. Thirteen cases were selected based on necropsy data from a 10-year retrospective study. Predispositions were observed in beef cattle (P = .049) and the Angus breed (P = .012), and lesions occurred mainly in the fall (P = .007). Gross lesions included hypotrichosis (13/13; 100%), scales (12/13; 92%), alopecia (11/13; 85%), ulcers (7/13; 54%), crusts (7/13; 54%), and erosions (2/13; 15%). These gross lesions were mainly located in the thorax (12/13; 92%), head (11/13; 85%), abdomen (10/13; 77%), neck (9/13; 69%), limbs (9/13; 69%), and perineum (9/13; 69%). Histologically, all cases had ticks adhered to the epidermis with erosions (13/13; 100%), ulcers (11/13; 85%), orthokeratotic hyperkeratosis (13/13; 100%), irregular acanthosis (13/13; 100%), intraepidermal pustules (13/13; 100%), crusts (10/13; 77%), and ballooning degeneration (4/13; 31%). In the dermis, just below the tick insertion site, there was coagulation necrosis, fibrin deposition, and inflammatory infiltrate composed of mixed cells (neutrophils, lymphocytes, plasma cells, macrophages, and few eosinophils) (9/13; 69%), neutrophils (3/13; 23%), or eosinophils (1/13; 8%). This study reinforces the different patterns of cutaneous lesions caused by tick infestation in cattle, which should be considered as a potential cause of dermatitis in this species.

Dendritic cell paucity in mismatch repair-proficient colorectal cancer liver metastases limits immune checkpoint blockade efficacy.

Liver metastasis is a major cause of mortality for patients with colorectal cancer (CRC). Mismatch repair-proficient (pMMR) CRCs make up about 95% of metastatic CRCs, and are unresponsive to immune checkpoint blockade (ICB) therapy. Here we show that mouse models of orthotopic pMMR CRC liver metastasis accurately recapitulate the inefficacy of ICB therapy in patients, whereas the same pMMR CRC tumors are sensitive to ICB therapy when grown subcutaneously. To reveal local, nonmalignant components that determine CRC sensitivity to treatment, we compared the microenvironments of pMMR CRC cells grown as liver metastases and subcutaneous tumors. We found a paucity of both activated T cells and dendritic cells in ICB-treated orthotopic liver metastases, when compared with their subcutaneous tumor counterparts. Furthermore, treatment with Feline McDonough sarcoma (FMS)-like tyrosine kinase 3 ligand (Flt3L) plus ICB therapy increased dendritic cell infiltration into pMMR CRC liver metastases and improved mouse survival. Lastly, we show that human CRC liver metastases and microsatellite stable (MSS) primary CRC have a similar paucity of T cells and dendritic cells. These studies indicate that orthotopic tumor models, but not subcutaneous models, should be used to guide human clinical trials. Our findings also posit dendritic cells as antitumor components that can increase the efficacy of immunotherapies against pMMR CRC.

Self-assembled α-lactalbumin nanostructures: encapsulation and controlled release of bioactive molecules in gastrointestinal in vitro model.

BACKGROUND: Implementing encapsulation techniques is pivotal in safeguarding bioactive molecules against environmental conditions for drug delivery systems. Moreover, the food-grade nanocarrier is a delivery system and food ingredient crucial in creating nutraceutical foods. Nano α-lactalbumin has been shown to be a promissory nanocarrier for hydrophobic molecules. Furthermore, the nanoprotein can enhance the tecno-functional properties of food such as foam and emulsion. The present study investigated the nanostructured α-lactalbumin protein (nano α-la) as a delivery and controlled release system for bioactive molecules in a gastric-intestinal in vitro mimic system. RESULTS: The nano α-la was synthesized by a low self-assembly technique, changing the solution ionic strength by NaCl and obtaining nano α-la 191.10 ± 21.33 nm and a spherical shape. The nano α-la showed higher encapsulation efficiency and loading capacity for quercetin than riboflavin, a potential carrier for hydrophobic compounds. Thermal analysis of nano α-la resulted in a ΔH of -1480 J g-1 for denaturation at 57.44 °C. The nanostructure formed by self-assembly modifies the foam volume increment and stability. Also, differences between nano and native proteins in emulsion activity and stability were noticed. The release profile in vitro showed that the nano α-la could not hold the molecules in gastric fluid. The Weibull and Korsmeyer-Peppas model better fits the release profile behavior in the studied fluids. CONCLUSION: The present study shows the possibility of nano α-la as an alternative to molecule delivery systems and nutraceutical foods' formulation because of the high capacity to encapsulate hydrophobic molecules and the improvement of techno-functional properties. However, the nanocarrier is not perfectly suitable for the sustainable delivery of molecules in the gastrointestinal fluid, demanding improvements in the nanocarrier. © 2024 Society of Chemical Industry.

Insights into the role of the cobalt(III)-thiosemicarbazone complex as a potential inhibitor of the Chikungunya virus nsP4.

Chikungunya virus (CHIKV) is the causative agent of chikungunya fever, a disease that can result in disability. Until now, there is no antiviral treatment against CHIKV, demonstrating that there is a need for development of new drugs. Studies have shown that thiosemicarbazones and their metal complexes possess biological activities, and their synthesis is simple, clean, versatile, and results in high yields. Here, we evaluated the mechanism of action (MOA) of a cobalt(III) thiosemicarbazone complex named [CoIII(L1)2]Cl based on its in vitro potent antiviral activity against CHIKV previously evaluated (80% of inhibition on replication). Furthermore, the complex has no toxicity in healthy cells, as confirmed by infecting BHK-21 cells with CHIKV-nanoluciferase in the presence of the compound, showing that [CoIII(L1)2]Cl inhibited CHIKV infection with the selective index of 3.26. [CoIII(L1)2]Cl presented a post-entry effect on viral replication, emphasized by the strong interaction of [CoIII(L1)2]Cl with CHIKV non-structural protein 4 (nsP4) in the microscale thermophoresis assay, suggesting a potential mode of action of this compound against CHIKV. Moreover, in silico analyses by molecular docking demonstrated potential interaction of [CoIII(L1)2]Cl with nsP4 through hydrogen bonds, hydrophobic and electrostatic interactions. The evaluation of ADME-Tox properties showed that [CoIII(L1)2]Cl presents appropriate lipophilicity, good human intestinal absorption, and has no toxicological effect as irritant, mutagenic, reproductive, and tumorigenic side effects.

An update on the development of antiviral against Mayaro virus: from molecules to potential viral targets.

Mayaro virus (MAYV), first isolated in 1954 in Trinidad and Tobago islands, is the causative agent of Mayaro fever, a disease characterized by fever, rashes, headaches, myalgia, and arthralgia. The infection can progress to a chronic condition in over 50% of cases, with persistent arthralgia, which can lead to the disability of the infected individuals. MAYV is mainly transmitted through the bite of the female Haemagogus spp. mosquito genus. However, studies demonstrate that Aedes aegypti is also a vector, contributing to the spread of MAYV beyond endemic areas, given the vast geographical distribution of the mosquito. Besides, the similarity of antigenic sites with other Alphavirus complicates the diagnoses of MAYV, contributing to underreporting of the disease. Nowadays, there are no antiviral drugs available to treat infected patients, being the clinical management based on analgesics and non-steroidal anti-inflammatory drugs. In this context, this review aims to summarize compounds that have demonstrated antiviral activity against MAYV in vitro, as well as discuss the potentiality of viral proteins as targets for the development of antiviral drugs against MAYV. Finally, through rationalization of the data presented herein, we wish to encourage further research encompassing these compounds as potential anti-MAYV drug candidates.

Insights into enterovirus a-71 antiviral development: from natural sources to synthetic nanoparticles.

Enteroviruses are pathogens responsible for several diseases, being enterovirus A71 (EVA71) the second leading cause of hand, foot, and mouth disease (HFMD), especially in Asia-Pacific countries. HFMD is mostly common in infants and children, with mild symptoms. However, the disease can result in severe nervous system disorders in children as well as in immunosuppressed adults. The virus is highly contagious, and its transmission occurs via fecal-oral, oropharyngeal secretions, and fomites. The EVA71 burdens the healthy systems and economies around the world, however, up to date, there is no antiviral approved to treat infected individuals and the existent vaccines are not available or approved to be used worldwide. In this context, an extensive literature research was conducted to describe and summarize the recent advances in natural and/or synthetic compounds with antiviral activity against EVA71. The summarized data presented here might simply encourage the future studies in EVA71 antiviral development, by encouraging further research encompassing these compounds or even the application of the techniques and technologies to improve or produce new antiviral molecules.

Automatic method based on deep learning to identify and account Rhipicephalus microplus larval hatching.

Reports of Rhipicephalus microplus resistant populations worldwide have increased extensively, making it difficult to control this ectoparasite. The adult immersion test, commonly used to screen for acaricide resistance, produces the results only after 40 days of the tick collection because it needs the eggs to be laid and larvae to hatch. The present study aims to develop an automatic method, based on deep learning, to predict the hatching of R. microplus larva based on egg morphology. Initially, the time course of embryonic development of tick eggs was performed to discriminate between viable and non-viable eggs. Secondly, using artificial intelligence deep learning techniques, a method was developed to classify and count the eggs. The larval hatching rate of three populations of R. microplus was evaluated for the software validation process. Groups of three and six images of eggs with 12 days of embryonic development were submitted to the software to predict the larval hatching percent automatically. The results obtained by the software were compared with the prediction results of the hatching percentage performed manually by the specialist and with the results of the hatching percentage of larvae obtained in the biological assay. The group with three images of each population submitted to the software for automatic prediction of the larval hatching percent presented mean values of 96.35% ± 3.33 (Piracanjuba population), 95.98% ± 3.5 (Desterro population) and 0.0% ± 0.0 (Barbalha population). For groups with six images, the values were 94.41% ± 3.84 (Piracanjuba population), 95.93% ± 2.36 (Desterro population) and 0.0% ± 0.0 (Barbalha population). Biological assays showed the following hatching percentage values: 98% ± 1.73 (Piracanjuba population); 96% ± 2.1 (Desterro population); and 0.14% ± 0.25 (Barbalha population). There was no statistical difference between the evaluated methods. The automatic method for predicting the hatching percentage of R. microplus larvae was validated and proved to be effective, with considerable reduction in time to obtain results.

Spring water quality monitoring using multiple bioindicators from multiple collection sites.

The aim of this study was to examine the water quality of the Extrema River spring in a Brazilian Cerrado area. Three collection sites (P1 - P3) were sampled in the dry and rainy seasons, which are close to industries from different sectors. In the physicochemical analysis, a decrease in dissolved oxygen levels (<5 mg/L) and pH (< 6) at P3 was detected. An increase in heterotrophic bacteria count was recorded at all sites (> 500 colonies/ml). In ecotoxicological analyses, P2 and P3 exhibited toxicity using Vibrio fischeri (> 20%). In evaluating toxicity, the reduction in seed germination was significant utilizing Lactuca sativa at all locations and with Allium cepa only at P2; rootlet length was decreased at P3 on L. sativa and at all sites with A. cepa. In contrast, loss of membrane integrity and mitochondrial function of meristems was adversely affected at all locations using both L. sativa and A. cepa assays. Principal components analysis (PCA) approach indicated that seasonality apparently did not markedly interfere with the obtained data, but it is important to include more collection locations to be evaluated with multiple bioindicators in the spring region. Our data indicate the urgent need for more rigorous programs to monitor the discharge of effluents into water springs.

Feline pulmonary carcinoma: Gross, histological, metastatic, and immunohistochemical aspects.

Feline pulmonary carcinoma (FPC) is an uncommon neoplasm with unique morphological features. We describe the gross, histological, metastatic, and immunohistochemical aspects of FPC, based on postmortem examinations from an 11-year retrospective study. Thirty-nine cases were selected. Predispositions were observed in senior (P < .001) and Persian (P = .039) cats. There were three gross patterns of the pulmonary tumors: (a) a large nodule and additional smaller nodules, (b) a solitary nodule, and (c) small, multifocal to coalescent nodules. Extrapulmonary metastases were present in 22/39 cases (56.4%), mainly in the regional lymph nodes (17/39, 43.5%), skeletal muscles (9/39, 23%), kidneys (6/39, 15.3%), and parietal pleura (4/39, 10.2%). The primary tumor size was correlated with the occurrence of extrapulmonary metastases (P = .002). Histologically, the tumors were classified as papillary adenocarcinoma (19/39, 48.7%), adenosquamous carcinoma (ADS) (8/39, 20.5%), acinar adenocarcinoma (6/39, 15.3%), solid adenocarcinoma (3/39, 7.6%), lepidic adenocarcinoma (2/39, 5.1%), and micropapillary adenocarcinoma (1/39, 2.5%). By immunohistochemistry, 39/39 cases (100%) were positive for pancytokeratin, 34/39 (87.1%) for thyroid transcription factor-1, and 8/39 (20.5%) for vimentin. Immunoreactivity for p40 was detected in the squamous component of all ADSs (8/8, 100%) and occasionally in the glandular component of adenocarcinomas (10/31, 32.2%). Napsin A expression was absent in all feline tissue tested. The results indicate that a modified and simplified histological classification based on current human and domestic animal systems is appropriate for cats. Additionally, this study highlights the utility of p40 as an immunohistochemical marker for the diagnosis of FPC with squamous differentiation.

Bilateral genital asymmetry in livebearer fishes of the genus Phalloceros Eigenmann, 1907, with description of a new species from coastal drainages of southern Brazil (Cyprinodontiformes: Poeciliidae).

A new species of Phalloceros is described from the Tijucas, Maruim, Aririú, Cubatão do Sul, Rio da Madre, D'Una and Tubarão river basins in southern Brazil. The new species is diagnosed among congeners by the bilateral asymmetry of a hood-like structure located immediately anterior to the urogenital papilla of females. The hood is fused with the urogenital papilla on the right side, but free from the papilla on the left side. This hood is reported for the first time in the genus and is present in six of the 21 valid species of Phalloceros, but its bilateral asymmetry is an exclusive condition of the new species. These species do not constitute a monophyletic group. The new species is likely to be phylogenetically related to P. caudimaculatus, whose females have a symmetrical hood.

Effect of 4 weeks of plyometric training in the pre-competitive period on volleyball athletes' performance.

We aimed to evaluate the effect of 4 weeks of plyometric training (PT), performed in the pre-competitive period, on the vertical jump performance of professional volleyball athletes. We recruited 17 professional female volleyball players (age: 19 ± 3 years; weight: 67.2 ± 5.50 kg; height: 1.81 ± 0.22 m; body fat: 14.4 ± 2.12%; squat 1RM test: 75.5 ± 7.82 kg; training time experience: 6.2 ± 3.4 years) to participate in four weeks of training and assessments. They were divided into an experimental group (EG = 9) and a control group (CG = 8). Both groups were submitted to friendly matches, technical, tactical and resistance training (4 weeks/˜9 sessions per week), and internal load monitoring was carried out. The EG performed PT twice a week. At the beginning and end of the four weeks, jump tests were performed. The main findings are: 1) PT when incorporated into the pre-competitive period can induce greater improvements in jumping performance (EG = 28.93 ± 3.24 cm to 31.67 ± 3.39 cm; CG = 27.91 ± 4.64 cm to 28.97 ± 4.58 cm; when comparing the percentage delta, we found a difference between groups with ES of 1.04 and P = 0.02); 2) this result is observed when the training load is similar between groups and increases over the weeks, respecting the linear progression principle. Therefore, including plyometric training in the preparatory period for volleyball, with low monotony and training strain increment, is an effective strategy for further CMJ performance improvement.

Abortion outbreak in a sheep flock caused by Toxoplasma gondii clonal type III.

Toxoplasma gondii is a major cause of reproductive losses in small ruminants in several countries. We describe here an outbreak of T. gondii-associated abortion in sheep in Southern Brazil. The flock was comprised of 55 adult sheep, and late-term abortions and stillbirths were detected in 15/36 (41.66%) gestating ewes. Serum samples collected from 45 sheep were tested for T. gondii through indirect immunofluorescence assay; IgM and IgG positive results were detected in 44.44% (20/45) and 86.67% (39/45) of the cases, respectively. Four fetuses and two placentas were pathologically evaluated. Gross changes were restricted to fetal membranes and were characterized by multifocal white areas in the cotyledons. Microscopically, these areas corresponded to necrotic foci affecting the chorionic epithelium accompanied by rare cysts of T. gondii. The main histological change in fetal tissues consisted of well-demarked and sparsely distributed necrotic foci in the central nervous system. Tissue samples from all four fetuses and one placenta had positive PCR results for T. gondii. Restriction fragment length polymorphism (RFLP) genotyping using ten markers (SAG1, 5'-3'SAG2, alt.SAG2, SGA3, BTUB, GRA6, c22-8, c29-2, L358, and PK1) was carried out on one sample, and results were consistent with T. gondii clonal type III (ToxoDB-PCR-RFLP genotype #2, TgCpBr4).

Tissue micro-RNAs associated with colorectal cancer prognosis: a systematic review.

Colorectal cancer (CRC) is a multifactorial disease commonly diagnosed worldwide, with high mortality rates. Several studies demonstrate important associations between differential expression of micro-RNAs (miRs) and the prognosis of CRC. The present study aimed to identify differentially expressed tissue miRs associated with prognostic factors in CRC patients, through a systematic review of the Literature. Using the PubMed database, Cochrane Library and Web of Science, studies published in English evaluating miRs differentially expressed in tumor tissue and significantly associated with the prognostic aspects of CRC were selected. All the included studies used RT-PCR (Taqman or SYBR Green) for miR expression analysis and the period of publication was from 2009 to 2018. A total of 115 articles accomplished the inclusion criteria and were included in the review. The studies investigated the expression of 100 different miRs associated with prognostic aspects in colorectal cancer patients. The most frequent oncogenic miRs investigated were miR-21, miR-181a, miR-182, miR-183, miR-210 and miR-224 and the hyperexpression of these miRs was associated with distant metastasis, lymph node metastasis and worse survival in patients with CRC. The most frequent tumor suppressor miRs were miR-126, miR-199b and miR-22 and the hypoexpression of these miRs was associated with distant metastasis, worse prognosis and a higher risk of disease relapse (worse disease-free survival). Specific tissue miRs are shown to be promising prognostic biomarkers in patients with CRC, given their strong association with the prognostic aspects of these tumors, however, new studies are necessary to establish the sensibility and specificity of the individual miRs in order to use them in clinical practice.

Early-Life Patterns of Sugar Consumption and Dental Caries in the Permanent Teeth: A Birth Cohort Study.

Early-life family conditions may presage caries development in childhood. The aim of this study was to evaluate associations between patterns of sugar consumption in early childhood and permanent dentition caries at age 6 years. A cohort enrolled women accessing prenatal care at public health clinics in Porto Alegre, Brazil. Sociodemographic, anthropometric, and dietary data were collected during pregnancy and 6-month, 12-month, and 3-year follow-ups. Calibrated dental examinations occurred at ages 3 and 6 years. Multivariable logistic regression analysis was performed in series to quantify associations between early-life variables and permanent dentition caries. At age 6 years, 7.9% of children (21/266) had ≥1 caries lesion on permanent teeth (first molars). In unadjusted models, gestational weight gain, sweet food introduction (age 6 months), household sugar purchases (age 3 years), and caries (age 3 years) were positively associated with permanent dentition caries (age 6 years). In multivariable models, each 1-kg increase in gestational weight gain (odds ratio [OR]: 1.08; 95% confidence interval [CI]: 1.01, 1.16) and each 1-item increase in sweet food consumption at age 6 months (OR: 1.27; 95% CI: 1.02, 1.59) remained statistically significantly associated with permanent molar caries. Findings from this cohort study suggest family and child factors that long predate the permanent dentition, including sugar-related behaviors, predict future dental status, and may inform prevention strategies.

Modified snare technique improves left ventricular lead implant success for cardiac resynchronization therapy.

BACKGROUND: Left ventricular (LV) lead placement is the most challenging aspect of cardiac resynchronization therapy (CRT) device implantation, with a failure rate of up to 10% due to complex coronary anatomies. We describe a modified snare technique for LV lead placement and evaluate its safety and efficacy in cases when standard methods fail. METHODS AND RESULTS: A prospective study was conducted of patients indicated for a CRT implant. When LV lead delivery to the target vessel failed using standard techniques, a modified snare technique was employed. Patients were evaluated every 6 months. From 2015 to 2019, 566 CRTs were implanted (26.1% female, 72 ± 10.2 years old, follow-up duration 18.9 ± 15.8 months). The standard LV implant technique failed in 94 cases (16.6%), of which the modified snare technique was successful in 92 (97.9%). There were no differences between the modified snare and standard techniques in the rates of 30-day postimplant CRT all-cause mortality (3.2% vs. 1.7%, p = .33), 4-year all-cause mortality (15.9% vs. 15.5%, p = .49), or major acute complications (7.4% vs. 3.8%, p = .12). However, the 4-year procedural reintervention rate was lower with the modified snare technique (3.2% vs. 10.2%, p < .05), specifically LV implant failure or dislodgement rates (0% vs. 5.3%, p < .05), improving the response rate (71.8% vs. 55.1%, p < .05). CONCLUSIONS: For challenging coronary sinus anatomies that preclude LV lead placement by standard methods, this modified snare alternative was safe and effective, with comparable mortality and complications, but significantly lower procedural reintervention and higher response rates.

Intestinal T-cell lymphoma in a coati (Nasua nasua) - Short communication.

A 10-year-old female coati (Nasua nasua) was necropsied after an 8-day history of apathy, weight loss and dehydration. Gross changes consisted of multifocal to coalescing nodules ranging from 0.5 to 2.0 cm in diameter in the wall of the small intestine, adjacent to the mesentery and in the mesenteric lymph nodes. Histologically, neoplastic CD3-positive lymphocytes infiltrated all layers of the intestine, as well as the mesenteric adipose tissue and mesenteric lymph nodes. Based on the pathological and immunohistochemical findings, a diagnosis of intestinal T-cell lymphoma was made.