mtDNA Single-Nucleotide Variants Associated with Type 2 Diabetes.

Type 2 diabetes (T2D) is a chronic systemic disease with a complex etiology, characterized by insulin resistance and mitochondrial dysfunction in various cell tissues. To explore this relationship, we conducted a secondary analysis of complete mtDNA sequences from 1261 T2D patients and 1105 control individuals. Our findings revealed significant associations between certain single-nucleotide polymorphisms (SNPs) and T2D. Notably, the variants m.1438A>G (rs2001030) (controls: 32 [27.6%], T2D: 84 [72.4%]; OR: 2.46; 95%CI: 1.64-3.78; p < 0.001), m.14766C>T (rs193302980) (controls: 498 [36.9%], T2D: 853 [63.1%]; OR: 2.57, 95%CI: 2.18-3.04, p < 0.001), and m.16519T>C (rs3937033) (controls: 363 [43.4%], T2D: 474 [56.6%]; OR: 1.24, 95%CI: 1.05-1.47, p = 0.012) were significantly associated with the likelihood of developing diabetes. The variant m.16189T>C (rs28693675), which has been previously documented in several studies across diverse populations, showed no association with T2D in our analysis (controls: 148 [13.39] T2D: 171 [13.56%]; OR: 1.03; 95%CI: 0.815-1.31; p = 0.83). These results provide evidence suggesting a link between specific mtDNA polymorphisms and T2D, possibly related to association rules, topological patterns, and three-dimensional conformations associated with regions where changes occur, rather than specific point mutations in the sequence.

In vivo evaluation of the genotoxicity and oxidative damage in individuals exposed to 10% hydrogen peroxide whitening strips.

OBJECTIVE: This study assessed the impact of 10% hydrogen peroxide whitening strip exposure on the genotoxicity and oxidative damage by means of the buccal micronucleus cytome assay by counting nuclear abnormalities (NAs) in buccal mucosa and attached gingiva cells and by analyzing in whole saliva the molecule 8-hydroxy-2'-deoxyguanosine (8-OHdG). MATERIALS AND METHODS: The study was conducted on 113 subjects divided into two groups: group 1 or control (n = 53), non-whitening strip exposed, and group 2 (n = 60), whitening strip exposed (Crest® 3D Whitestrips® premium plus, 10% hydrogen peroxide). Oral epithelial cells and whole saliva samples were taken at the beginning and 30 days later for group 1 and immediately before bleaching and 15 and 30 days after the end of the bleaching for group 2. RESULTS: An increased frequency of NAs (p < 0.05) and higher levels of 8-OHdG (p < 0.05) were observed after bleaching exposure. Also, a positive correlation exists between oxidative stress produced by hydrogen peroxide and micronuclei was found. CONCLUSION: Individuals exposed to 10% hydrogen peroxide whitening strips exhibit NAs increased in oral epithelial cells and 8-OHdG in saliva, which is directed related to nuclear and oxidative DNA damage, respectively. CLINICAL SIGNIFICANCE: Hydrogen peroxide is the active agent of tooth whitening and this compound induced DNA damage. Individuals exposed to whitening strips with 10% hydrogen peroxide exhibit increased genotoxic and oxidative damage. Therefore, self-application of bleaching agents should be handled carefully since it could be a risk to human health.

[Practical considerations for high resolution anoscopy in patients infected with human immunodeficiency virus]. / Consideraciones prácticas de la anoscopia de alta resolución en pacientes infectados por el virus de la inmunodeficiencia humana.

Anal cancer is uncommon in the general population, however its incidence is increasing significantly in certain risk groups, mainly in men who have sex with men, and particularly those infected with human immunodeficiency virus. High resolution anoscopy technique is currently considered the standard in the diagnosis of anal intraepithelial neoplasia, but at present there is no agreed standard method between health areas. High resolution anoscopy is an affordable technique that can be critical in the screening of anal carcinoma and its precursor lesions, but is not without difficulties. We are currently studying the most effective strategy for managing premalignant anal lesions, and with this article we attempt to encourage other groups interested in reducing the incidence of an increasing neoplasia.

Role of Histone Deacetylase Inhibitor in Diabetic Painful Neuropathy.

Diabetic painful neuropathy (DPN) is one of the most detrimental complications of diabetes. Alterations in neuroinflammatory mediators play significant roles in the development of DPN. Infiltration of the neutrophils and monocyte/macrophages contributes substantial role in the degenerative process of the distal sciatic nerve by forming neutrophil extracellular traps (NETs) under diabetic condition. Citrullination of histones due to increase in protein arginine deiminase (PAD) enzyme activity under hyperglycemia may promote NET formation, which can further increase the cytokine production by activating macrophages and proliferation of neutrophils. This study reveals that the increase in histone deacetylases (HDAC) is crucial in DPN and inhibition of HDAC using HDAC inhibitor (HDACi) FK228 would suppress NETosis and alleviate diabetic nerve degeneration and pain. FK228, also known as romidepsin, is FDA approved for the treatment of cutaneous T-cell lymphoma yet the molecular mechanisms of this drug are not completely understood in DPN. In this study, type 2 diabetic (T2D) mice with pain were treated with HDACi, FK228 1 mg/kg; I.P. 2 × /week for 3 weeks. The results demonstrate that FK228 treatment can alleviate thermal hyperalgesia and mechanical allodynia significantly along with changes in the expression of HDACs in the dorsal root ganglia (DRG) and spinal cord dorsal horn neurons of diabetic animals. The results also indicate that FK228 treatment can alter the expression of neutrophil elastase (NE), extracellular or cell free DNA (cfDNA), citrullinated histone-3 (CitH3), PADI4, growth-associated protein (GAP)-43, and glucose transporter (GLUT)-4. Overall, this study suggests that FK228 could amend the expression of nerve regeneration markers and inflammatory mediators in diabetic animals and may offer an alternative treatment approach for DPN.

Sleeve Gastrectomy Reduces Oxidative Stress and Reverses Mitochondrial Dysfunction Associated with Metabolic Syndrome.

INTRODUCTION: Previous studies have detected mitochondrial alterations in tissues of individuals with obesity and type 2 diabetes mellitus (T2DM). Metabolic surgery could be an effective treatment to improve mitochondrial morphology and reduce oxidative stress (OS). METHODS: An experimental study was carried out using 48 male Wistar rats, divided into 6 groups (n = 8): control (C), induced Metabolic Syndrome (MS); intervention with sleeve gastrectomy (SG), MS + SG with 6 weeks postoperatively (MS + SG6), MS + SG with 12 weeks postoperatively (MS + SG12), and MS + SG with 24 weeks postoperatively (MS + SG24). Biochemical markers indicative of MS (glycemia, cholesterol, and triglyceride levels) and oxidative stress markers (nitric oxide levels, Superoxide dismutase and Myeloperoxidase activity) were determined. To study mitochondrial morphology, tissue sections of the thoracic aorta, stomach, liver, heart, and kidney were observed by electron microscopy. RESULTS: MS group exhibited elevated glycemic values and dyslipidemia. SG and MS + SG groups showed improvements in glycemia and lipid profiles compared to MS. OS biomarkers indicated reduced oxidative stress in SG and MS + SG groups compared to MS. Electron microscopy revealed mitochondrial alterations in MS. SG group showed no changes compared to the control. MS + SG6 and MS + SG12 groups showed a recovery of mitochondrial morphology until reaching images similar to the control in MS + SG24. CONCLUSION: Metabolic surgery could improve mitochondrial function by restoring mitochondrial morphology and architecture and, consequently, reducing systemic oxidative stress and remitting associated metabolic alterations.

Restorative Parental Discipline and Types of Defending Bystander Intervention in Cyberbullying: The Mediate Role of Justice Sensitivity.

Parental socialization strategies are critical in explaining adolescents' online behavior. This study examined the relationships between parental restorative discipline, observed justice sensitivity, and cyber-bystander defender intervention (constructive and aggressive) in cyberbullying. The sample comprised 900 Mexican adolescents (40.2% male and 58.8% female), of which 450 were from secondary school (M age = 13.6, SD = 0.8) and 450 were from high school (M age = 15.4, SD = 1.3). Structural equation modeling with latent variables was performed. Overall, the results indicate that parental restorative discipline positively relates to the observer's justice sensitivity and the adoption of constructive interventions by cyber-bystander defenders. However, restorative discipline had no significant direct relationship with aggressive intervention. Observers' justice sensitivity mediates the association between restorative parenting discipline and aggressive or constructive defender interventions. Gender does not moderate the relationship proposed in the structural model. These findings suggest that parental restorative discipline explains constructive and aggressive cyber-bystander defender interventions in cyberbullying.

Amelioration of Cytogenotoxic Damage in Drug Abusers Supplemented with Folic Acid.

BACKGROUND: Cytogenotoxic damage caused by the consumption of legal and illegal drugs in drug abusers has been demonstrated, primarily due to alterations in their antioxidant capacity, cellular repair mechanisms, and increased production of free radicals. Folic acid shows antioxidant activity by acting as a reducing agent, neutralizing present free radicals, and reducing genomic damage. METHODS: The intervention involved administering 15 mg of folic acid, divided into three doses per day, to a group of 44 drug abusers. The frequency of nuclear abnormalities (NAs) was determined; micronuclei (MNs), nuclear buds (NBUDs), binucleated cells (BNs), abnormally condensed chromatin (CC), karyorrhexis (KX), pyknotic nuclei (PNs), and karyolysis (KL) were determined at different pre-treatment (baseline) and post-treatment time points at 15 and 30 days. Additionally, a group of 44 healthy individuals was used as the control group. RESULTS: We observed a statistically significant decrease in the frequency of NAs in the drug abuser group (28.45 ± 17.74 before supplementation vs. 11.18 ± 7.42 at 15 days and 9.11 ± 10.9 at 30 days of supplementation). Specifically, it decreased the frequency of NBUDs, BNs, CC, KX, and PNs (p < 0.05). CONCLUSION: Our study demonstrates a clear improvement in cytogenotoxic damage in drug abusers supplemented with folic acid.

Cytogenotoxicity effects in addicts with multidrug consumption.

Drug abuse is considered a global health problem with serious social impact. In recent decades, changes in drug consumption patterns have shown a clear rising trend in the use of multiple drugs. Although the buccal micronucleus cytome (BMCyt) assay has evaluated cytotoxicity in drug abuse, there has not been an approach that takes into account this pattern of multiple drug use. Therefore, in this study, we evaluate for the first time the cytogenotoxic effects in multidrug users, and its correlation with the amount consumed and years of abuse. This study was conducted on 166 individuals by the BMCyt assay. A total of 83 individuals with a history of multiple licit (alcohol and tobacco) and at least one illicit drug abuse (marijuana, methamphetamines, cocaine, and/or inhalants), and 83 healthy individuals, non-drug abusers were analyzed. The results showed that drug abusers had higher frequencies of nuclear abnormalities nuclear buds, binucleated cells, pyknotic nuclei (PNs), karyorrhexis (KX), and abnormally condensed chromatin when compared with healthy controls. Moreover, results suggests that the use of licit and illicit drugs is related to cytogenotoxic damage, as was shown by an upward trend in the frequency of nuclear abnormalities identified in groups 1 (alcohol + tobacco + at least one illicit drug) and 2 (tobacco + at least one illicit drug). Furthermore, a positive correlation was found in the different groups, between the years and the amount of consumption of some drugs (alcohol, methamphetamine, and tobacco) with cytotoxicity markers such as KL, KX, and PNs.

Controlled clinical trial with pirfenidone in the treatment of breast capsular contracture: association of TGF-ß polymorphisms.

BACKGROUND: Breast capsular contracture (BCC) is a commonly adverse event postmammoplastly characterized by an immune response mediated by cytokines and transforming growth factor (TGF)-ß1 resulting in excessive synthesis and deposit of extracellular matrix around the breast implant. Presence of TGF-ß1 polymorphisms has been associated as a risk factor to develop fibroproliferative diseases. METHODS: This open, controlled, prospective, and pilot clinical trial with 6 months duration was carried out to evaluate the efficacy of 1800 mg a day, of oral Pirfenidone (PFD) in the treatment of BCC (Baker Score III/IV) postmammoplasty. Twenty BCC cases received PFD and 14 BCC control cases underwent capsulectomy after 6 months of enrollment. Both groups were followed up for 6 more months up to 12 months to determine the relapse in the absence of PFD. Determination of TGF-ß1 polymorphisms was performed to establish a correlation with capsular contracture. RESULTS: PFD group experienced BCC-reduction in all breasts 6 months after enrollment. Only 1 of 20 cases relapsed after follow-up. In capsulectomy group, 2 of 14 cases presented progression to grade IV during presurgical period. All capsulectomy cases relapsed at end of follow-up. Nearly hundred percent of all patients studied in this protocol had a profibrogenic homozygous TGF-ß1 polymorphism (codon 25; genotype Arg25Arg). CONCLUSIONS: PFD is useful to improve BCC (Baker Score III/IV) postmammoplasty with no relapse after drug administration. There is also an association between capsular contracture and the presence of homozygous G/G TGF-ß1 genotype.

Pharmacological Action of Atorvastatin and Metformin on Non-alcoholic Fatty Liver Disease on an Experimental Model of Metabolic Syndrome.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most frequent cause of chronic liver disease in the world. It is known that there is a pathogenic relation between liver damage and the inflammatory and oxidative environment present in Metabolic Syndrome (MS). OBJECTIVE: To study the pharmacological action of atorvastatin and metformin in an experimental model of MS. METHODS: We used 40 male rats (Wistar) divided into the following groups: Control (A) (n=8), induced MS (B) (n=8), MS + atorvastatin treatment (C)(n=8), MS + metformin treatment (D) (n=8) and MS + combined treatment (E) (n=8). MS was induced by administering 10% fructose in drinking water for 45 days. Atorvastatin 0.035 mg/day/rat, metformin 1.78 mg/day/rat, and a combination of both drugs were administered for 45 days. Metabolic, oxidative (nitric oxide, myeloperoxidase and superoxide dismutase) and inflammatory (fibrinogen) parameters were determined. Histological sections of liver were analyzed by light microscopy. RESULTS: The glycemia, lipid profile and TG/HDL-C index were altered in MS group. After pharmacological treatment, metabolic parameters improve significantly in all treated groups. Inflammatory and oxidative stress biomarkers increase in MS. Treated groups showed an increase in NO bioavailability, no difference in MPO activity and an increase in fibrinogen. Atorvastatin showed a decrease in SOD while Metformin and combination treatment showed an increase in SOD compared to MS. In MS, we observed histological lesions consistent with NAFLD. However, after a combined treatment, we observed total regression of these lesions. CONCLUSION: Our results showed that there is an important synergy between atorvastatin and metformin in improving liver involvement in MS.

A controlled clinical trial with pirfenidone in the treatment of pathological skin scarring caused by burns in pediatric patients.

BACKGROUND: Pathologic skin scarring reversion remains a big challenge for surgeons, as disfiguring scars have a dramatic influence on patient's quality of life. METHODS: A controlled clinical trial was conducted to evaluate 8% pirfenidone (PFD) gel administered topically 3 times a day during 6 months to 33 pediatric patients with hypertrophic scars caused by burns. A total of 30 patients with hypertrophic scars with identical Vancouver Scar Scale values were treated with pressure therapy and included as controls. Improvements were evaluated by Vancouver Scar Scale and a Visual Analog Scale. Safety parameters were determined by the presence of adverse events and monitoring laboratory and hematology parameters. RESULTS: Patients treated with PFD during 6 months presented a continuous monthly statistically significant scar regression in comparison with the initial Vancouver measurement (P = <0.001). PFD group showed a higher improvement of all scar features as compared with control group treated with pressure therapy (P = <0.001). In the PFD group, 9 of 33 patients (27%) had their scores decreased in Vancouver classification by more than 55%, 22 patients (67%) had a 30% to 45% decrease, whereas 2 patients (6%) had a 30% decrease or less. Control group treated with pressure therapy showed a slight improvement in 16% of cases on an average. Patients did not show serious adverse effects or laboratory alterations throughout the study. CONCLUSIONS: Topical administration of 8% PFD gel 3 times a day is more effective and safe in the treatment of hypertrophic scars caused by burns in children, as compared with standard pressure therapy.

Interpretation of cerebrospinal fluid analysis from recumbent cows using different thresholds of red blood cell count.

BACKGROUND: Hemodilution of the cerebrospinal fluid (CSF) could confound interpretation of results. Accurately predicting total nucleated cells count (TNCC) and total protein concentration (TPC) attributable to hemodilution is difficult. OBJECTIVE: To determine the effects of hemodilution on TPC and TNCC in bovine CSF. METHODS: Retrospective review of CSF analysis results of downer dairy cows treated at Centre hospitalier universitaire vétérinaire between January 2006 and December 2014. Descriptive statistics were performed using 3 scenarios. RESULTS: Among the 235 samples included, red blood cell (RBC) count (RBCC) ranged from 0 to 869 220 RBC/µL (median = 6.6), TPC ranged from 0.04 to 6.51 g/L (median = 0.27), and TNCC ranged from 0 to 7500 cell/µL (median = 1.1). Among the 157 samples that had <30 RBC/µL (a threshold used in other species), TPC and TNCC varied between 0.13 and 1.06 g/L (median = 0.27) and between 0 and 31.4 cell/µL (median = 0.6), respectively. Eighty-four samples had TPC <0.25 g/L and TNCC ≤4.5 cell/µL. Among those 84 samples, RBCC varied between 0 and 1290 RBC/µL (median = 4.7). In 20 samples, TNCC was 0 with a variation in RBCC between 0 and 840 RBC/µL (median = 3.9). No strong correlations between RBCC and TNCC and TPC were found. CONCLUSIONS: A cutoff around 200 RBC/µL is proposed as clinically meaninful in bovine CSF. Results between 200 and 1290 RBC/µL are equivocal.

Class I MHC Polymorphisms Associated with Type 2 Diabetes in the Mexican Population.

Type 2 diabetes (T2D) has been linked to the expression of Human Leukocyte Antigens, principally to the Major Histocompatibility Complex Class II, with only scarce reports of Major Histocompatibility Complex Class I in specific populations. The objective of the present work was to explore the presence of polymorphisms in the MHC Class I related to T2D in the Mexican population using the Genome-Wide Association Studies Slim Initiative in Genomic Medicine of the Americas (GWAS SIGMA) database. This database contains information on 3848 Mexican individuals with T2D and 4366 control individuals from the same population without a clinical or hereditary history of the disease. The searching criteria considered a p-value of <0.005 and an odds ratio (OR) of >1.0. Ten novel, statistically significant nucleotide variants were identified: four polymorphisms associated with HLA-A (A*03:01:01:01) and six with HLA-C (C*01:02:01:01). These alleles have a high prevalence in Latin American populations and could potentially be associated with autoimmunity mechanisms related to the development of T2D complications.

Mitochondrial Control Region Variants Related to Breast Cancer.

Breast cancer has an important incidence in the worldwide female population. Although alterations in the mitochondrial genome probably play an important role in carcinogenesis, the actual evidence is ambiguous and inconclusive. Our purpose was to explore differences in mitochondrial sequences of cases with breast cancer compared with control samples from different origins. We identified 124 mtDNA sequences associated with breast cancer cases, of which 86 were complete and 38 were partial sequences. Of these 86 complete sequences, 52 belonged to patients with a confirmed diagnosis of breast cancer, and 34 sequences were obtained from healthy mammary tissue of the same patients used as controls. From the mtDNA analysis, two polymorphisms with significant statistical differences were found: m.310del (rs869289246) in 34.6% (27/78) of breast cancer cases and 61.7% (21/34) in the controls; and m.315dup (rs369786048) in 60.2% (47/78) of breast cancer cases and 38.2% (13/34) in the controls. In addition, the variant m.16519T>C (rs3937033) was found in 59% of the control sequences and 52% of the breast cancer sequences with a significant statistical difference. Polymorphic changes are evolutionarily related to the haplogroup H of Indo-European and Euro-Asiatic origins; however, they were found in all non-European breast cancers.

Binge drinking and declarative memory in university students.

BACKGROUND: Binge drinking (BD), which is characterized by sporadic consumption of large quantities of alcohol in short periods, is prevalent among university students. Animal studies have shown that BD is associated with damage to the hippocampus, a region of the brain that plays a key role in learning and memory. The temporal cortex undergoes structural and functional changes during adolescence. The aim of the present study was to examine the association between BD and declarative memory in male and female university students. METHODS: The participants were 122 students (between 18 and 20 years of age): 62 BD (30 women) and 60 non-BD (29 women). The neuropsychological assessment included the Rey Auditory Verbal Learning Test (RAVLT) and Weschler Memory Scale-3rd ed. (WMS-III) Logical Memory subtest, to evaluate verbal declarative memory, and the WMS-III Family Pictures subtest, to measure visual declarative memory. RESULTS: The BD students remembered fewer words in the interference list and displayed greater proactive interference in the RAVLT; they performed worse in the Logical Memory subtest, both on immediate and delayed recall. There were no differences between the groups in performance of the Family Pictures subtest. No significant interactions were observed between BD and sex. CONCLUSIONS: Binge drinking is associated with poorer verbal declarative memory, regardless of sex. The findings are consistent with the vulnerability of the adolescent hippocampus to the neurotoxic effects of alcohol. Longitudinal studies will help determine the nature of this relationship, the neurodevelopmental trajectories for each sex, and the repercussions on academic performance.

[Definition of adolescent binge drinking]. / Definición del concepto de consumo intensivo de alcohol adolescente (binge drinking).

BACKGROUND: Review of the concept of adolescent binge drinking in order to propose an operational definition. METHODS: We conducted a literature review in the databases MEDLINE and PSYCLIT for the period 1980 to 2009. Through the filter "(binge drinking OR heavy-episodic-drinking) AND (adolescence OR university-students OR college-students)" 80 articles were selected for review. RESULTS: Epidemiological studies that have reported the prevalence of binge drinking show a lack of consensus regarding the operational definition. Alternative approaches have been proposed in relation to the number of standard drink units (SDUs) consumed per occasion, frequency of episodes and their duration. CONCLUSIONS: A proper definition of the pattern of intensive alcohol consumption should integrate the quantity and frequency variables, and also take into account the negative consequences associated with it. The criterion most widely accepted by the international scientific community is the consumption of 5 or more SDUs - 4 or more for women - on a single occasion at least once in the last two weeks. However, aspects such as differences in the grams of alcohol of SDUs hinder the establishment of an international definition of the term, making it necessary to adapt this approach to the country in which the study is being carried out.

Unraveling the Role of Shared Vision and Trust in Constructive Conflict Management of Family Firms. An Empirical Study From a Mixed Methods Approach.

Family firms are a unique setting to study constructive conflict management due to the influence of family ties of the owning family imprinting a sense of common purpose and shared destiny, and high levels of trust. We study the relationship between shared vision and trust that intervene in the adoption of constructive conflict management. To achieve our purpose, we carried out a systematic indirect observation using a mixed methods approach. We used the narratives of 17 semi-structured interviews, audio-recorded and transcribed, of family and non-family managers or directors from five Spanish family firms in the siblings' partnership stage, combined with documentary data obtained from different sources. Intra- and inter-observer reliability were confirmed. Results show a dynamic relationship between shared vision and specific components of trust (benevolence and ability) at different levels of conflict management. We also provide evidence of specific processes of concurrence-seeking and open-mindedness in family and ownership forums accounting for the relevance of family governance in these type of organizations. Family firms are a sum of several subsystems which exhibit a particular resources configuration. This study sheds light on constructive conflict management in family firms opening interesting avenues for further research and offering practical implications to managers, owners, and advisors.

Pregnancy Inhibits Mammary Carcinogenesis by Persistently Altering the Hypothalamic-Pituitary Axis.

Early full-term pregnancy is known to reduce the lifetime risk of breast cancer. Although the phenomenon of parity-induced protection is well-established, the physiological mechanisms involved in this protection are not clear. Earlier reports have shown that pregnancy results in alterations of hormone levels. How pregnancy affects hypothalamic hormones and how the change, if any, influences breast cancer is not well understood. Seven-week-old female Lewis rats were given N-methyl-N-nitrosourea. Two weeks post carcinogen exposure, a set of females were housed with males to generate the parous rats and another set of rats served as the nulliparous controls. Mammary tumorigenesis was assessed for 9 months. Hypothalamic and pituitary levels of hormones were measured at various timepoints. Further, animals were also challenged with growth hormone and prolactin secretagogues to test the effect of pregnancy on the hypothalamic-pituitary hormonal axis. Persistent alterations in the level of growth hormone-releasing hormone, thyrotropin releasing hormone, dopamine, and somatostatin in the hypothalamus of parous animals was observed. Further, we also observed that pregnancy had a significant effect on the pituitary gland and its response to growth hormone and prolactin secretagogues. Our studies using the rodent model system demonstrate that pregnancy could be reducing the risk of breast cancer by persistently altering the hypothalamic-pituitary axis, which could have implications for breast cancers in humans as well.

Survival and prognostic indicators in downer dairy cows presented to a referring hospital: A retrospective study (1318 cases).

BACKGROUND: Downer cow syndrome, a common problem in dairy cattle, represents a diagnostic and therapeutic challenge for the attending veterinarian. Identifying prognostic indicators and assessing the odds of survival may improve the accuracy of the clinician's prognosis at the time of diagnosis. OBJECTIVE: To describe a population of downer dairy cows referred to a hospital and investigate predictors of outcome. ANIMALS: Recumbent adult dairy cows (cows unable or unwilling to stand without help) treated at a referral hospital. METHODS: Data at the time of admission were collected from medical records of downer dairy cows treated at the Centre Hospitalier Universitaire Vétérinaire between 1994 and 2016. Simple and multivariable logistic regression analyses were performed to assess the association of predictors with the outcome. RESULTS: Among 1318 cows included, 727 (55%) cows were discharged, and 591 (45%) cows died or were euthanized. Cows with longer time of recumbency before referral (odds ratio [OR] = 3.6), tachycardia (100-120 beats per minute [bpm], OR = 1.93; >120 bpm, OR = 2.92), tachypnea (OR = 1.76), hypothermia (OR = 2.08), anemia (OR = 3.30), neutropenia (OR = 1.7), high aspartate aminotransferase activity (500-1000 U/L, OR = 2.16; >1000 U/L, OR = 6.69), and increased serum creatinine concentration (OR = 1.75) had higher odds of nonsurvival. CONCLUSIONS AND CLINICAL IMPORTANCE: These findings may help the practitioner to consider treatment options and decide if referral is likely beneficial based on the odds of success. Early recognition of low chance of survival may facilitate an early decision for euthanasia.

Cytogenotoxicity Evaluation of Young Adults Exposed to High Levels of Air Pollution in a Mexican Metropolitan Zone Using Buccal Micronucleus Cytome Assay.

Air pollution has become a serious public health problem globally. Recent studies support the harmful effect of air pollution on human health, in addition to scientific evidence that recognizes it as a human carcinogen. The buccal micronucleus cytome (BMC) assay is employed extensively to measure cytotoxic and genotoxic damage in a population exposed to environmental contamination. The objective of this study was to evaluate the cytotoxic and genotoxic effects in healthy young adults exposed to different levels of air pollution and to identify areas with air pollution rates above the regulatory limits. This study was performed through the BMC assay in oral mucosa samples from 80 healthy young adults from the Guadalajara metropolitan zone. Three highly contaminated areas were taken into account: Tlaquepaque, Miravalle, and Las Pintas. Las Aguilas, a less contaminated area, was used as a reference. The frequencies of nuclear abnormalities in the areas with the highest and lowest levels of air pollution were compared with the Mann-Whitney U test. In addition, an analysis of the concentration of environmental pollutants, particulate matter ≤ 10 µm (PM10), ozone (O3), nitrogen dioxide (NO2), sulfur dioxide (SO2), and carbon monoxide (CO), were carried out in the mentioned areas, in order to identify the events above the regulatory limits in a year period. The results showed that young adults exposed to a higher concentration of pollutants showed higher frequencies of nuclear abnormalities. The individuals from the areas of Tlaquepaque, Miravalle, and Las Pintas showed cytotoxic damage since statistically significant differences were found in the abnormalities of pyknotic nuclei (PNs), condensed chromatin (CC), karyorrhexis (KX), and karyolysis (KL). The individuals who showed the most cytotoxic damage were from the Las Pintas area with higher frequencies in nuclear abnormalities (PNs, CC, KX, and KL) (p < 0.0001). Genotoxic damage was found in individuals from two zones, Miravalle and Las Pintas, with statistically significant differences in the abnormality of nuclear buds (NBUDs) (p < 0.0001). Our results suggest that exposure to high levels of air pollution in healthy young adults has an effect on cellular and nuclear integrity and thus in human health, since areas with higher air pollution showed an increase in cytotoxicity, specifically in early and late markers of cell death (CC, KX, PN, and KL) and genotoxic damage (BUDs).