RESUMO
In this study, we identified miRNAs and their potential mRNA targets that are intricately linked to primary chemotherapy response in patients with invasive ductal carcinomas. A cohort of individuals diagnosed with advanced invasive breast ductal carcinoma who underwent primary chemotherapy served as the cornerstone of our study. We conducted a comparative analysis of microRNA expression among patients who either responded or did not respond to primary systemic therapy. To analyze the correlation between the expression of the whole transcriptome and the 24 differentially expressed (DE) miRNAs, we harnessed the extensive repository of The Cancer Genome Atlas (TCGA) database. We mapped molecular mechanisms associated with these miRNAs and their targets from TCGA breast carcinomas. The resultant expression profile of the 24 DE miRNAs emerged as a potent and promising predictive model, offering insights into the intricate dynamics of chemotherapy responsiveness of advanced breast tumors. The discriminative analysis based on the principal component analysis identified the most representative miRNAs across breast cancer samples (miR-210, miR-197, miR-328, miR-519a, and miR-628). Moreover, the consensus clustering generated four possible clusters of TCGA patients. Further studies should be conducted to advance these findings.
Assuntos
Biomarcadores Tumorais , Neoplasias da Mama , Carcinoma Ductal de Mama , MicroRNAs , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Feminino , MicroRNAs/análise , Biomarcadores Tumorais/análise , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/patologia , Pessoa de Meia-Idade , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Adulto , Idoso , TranscriptomaRESUMO
In this study, we identified miRNAs and their potential mRNA targets that are intricately linked to primary chemotherapy response in patients with invasive ductal carcinomas. A cohort of individuals diagnosed with advanced invasive breast ductal carcinoma who underwent primary chemotherapy served as the cornerstone of our study. We conducted a comparative analysis of microRNA expression among patients who either responded or did not respond to primary systemic therapy. To analyze the correlation between the expression of the whole transcriptome and the 24 differentially expressed (DE) miRNAs, we harnessed the extensive repository of The Cancer Genome Atlas (TCGA) database. We mapped molecular mechanisms associated with these miRNAs and their targets from TCGA breast carcinomas. The resultant expression profile of the 24 DE miRNAs emerged as a potent and promising predictive model, offering insights into the intricate dynamics of chemotherapy responsiveness of advanced breast tumors. The discriminative analysis based on the principal component analysis identified the most representative miRNAs across breast cancer samples (miR-210, miR-197, miR-328, miR-519a, and miR-628). Moreover, the consensus clustering generated four possible clusters of TCGA patients. Further studies should be conducted to advance these findings.
RESUMO
OBJECTIVES: SARS-CoV-2 is a highly contagious virus that causes coronavirus disease 2019 (COVID-19) and can affect people of any age with potential for serious symptoms. Since the start of the COVID-19 pandemic, global infection rates have been on the rise with world leaders looking to slow and stop viral transmission. This study is looking at suburban cohabitation/familial infection to compare to similar studies from other countries. STUDY DESIGN: A retrospective review of medical records was collected using the Connecticut Electronic Disease Surveillance System. METHODS: A total of 406 cases who tested positive for SARS-COV-2 from February to June 2020 were reviewed from three towns located in Connecticut, USA. Cohabitation infection rates were identified using the home addresses of those with confirmed SARS-CoV-2 test results, with the first documented case being the index case, and additional home members being the secondary cases. RESULTS: Secondary transmission of SARS-CoV-2 developed in 126 of 406 household contacts (31%). Linear regression indicated positive relationship between cohabitation and age. CONCLUSIONS: The cohabitation infection attack rate of SARS-CoV-2 is significantly higher than previously reported. Age of household contacts and spousal relationship to the index case are risk factors for transmission of SARS-CoV-2 within a household.
Assuntos
COVID-19/transmissão , Características da Família , Vigilância em Saúde Pública/métodos , SARS-CoV-2/isolamento & purificação , Adulto , COVID-19/epidemiologia , Infecções Comunitárias Adquiridas/transmissão , Busca de Comunicante/estatística & dados numéricos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Retrospectivos , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
Donkeys have been used as working animals for transport and farm activities worldwide. Recently, in European countries, there has been an increasing interest in donkeys due to their use as pets, onotherapy or milk production. During 2014-2016, a countrywide survey was conducted to determine prevalence and risk factors of principal helminth infections in 1775 donkeys in 77 Italian farms. A questionnaire on management and parasite control practices was filled out for each farm. Faecal samples were examined using a modified McMaster technique, a centrifugation/flotation method and a sedimentation technique. Pooled coprocultures were performed for differentiation of strongylid eggs. Strongyles were the most common parasites detected (84.9%), followed by Dictyocaulus arnfieldi (6.9%), Oxyuris equi (5.8%), Parascaris spp. (3.6%), Anoplocephala spp. (1.0%), Strongyloides westeri (0.3%). Coprocultures revealed an omnipresence of cyathostomins (100%), followed by Strongylus vulgaris (31.0%), Poteriostomum spp. (25.0%), Triodontophorus spp. (9.0%), Strongylus edentatus (7.0%), Strongylus equinus (5.0%). Logistic regression analysis identified breed, co-pasture with horses, living area, herd size and number of treatments as significantly associated with strongyles. Sex, age, living area and herd size were significantly associated with Parascaris spp. Dictyocaulus arnfieldi was significantly associated with sex, grass, co-pasture with horses, living area and herd size. Strongylus vulgaris was significantly associated with living area and herd size. The mean number of anthelmintic treatments/year was 1.4; most of the donkeys (71.8%) were dewormed using an ivermectin drug. It is important to design parasite programs to specifically address both D. arnfieldi and S. vulgaris in donkeys, and this is especially important if donkeys co-graze with horses.
Assuntos
Dictyocaulus , Equidae/parasitologia , Helmintíase Animal/epidemiologia , Strongylus , Animais , Itália , Contagem de Ovos de ParasitasRESUMO
Mycoplasma haemocanis (Mhc) and "Candidatus Mycoplasma haematoparvum" (CMhp) are the main haemoplasma species known to infect dogs. The aim of this study was to determine the prevalence of haemoplasma species infections in hunting dogs from southern Italy and assess related risk factors. 1,433 hunting dogs living in Campania region were tested by qPCR assay. The prevalence was 19.9 %; 13.1 % for Mhc and 11.4 % for CMhp; 4.6 % showed a coinfection with both haemoplasma species. Statistical analysis revealed living in Salerno province (Mhc: OR 3.72; CMhp: OR 2.74), hound (Mhc: OR 5.26; CMhp: OR 8.46) and mixed breed (Mhc: OR 3.38; CMhp: OR 2.80), rural environment (Mhc: OR 12.58; CMhp: OR 10.38), wild mammal hunting (Mhc: OR 8.73; CMhp: OR 8.32), cohabitation with other animals (Mhc: OR 2.82; CMhp: OR 2.78) and large pack size (Mhc: OR 2.96; CMhp: OR 1.61) as risk factors for haemoplasmas. Male gender (OR 1.44) and tick infestation history (OR 1.40) represented risk factors only for Mhc, while adult age (2-7 years - OR 2.01; > 7 years - OR 1.84) and large body size (OR 1.48) were associated only to CMhp. Mhc infection was significantly associated to Babesia vogeli (p < 0.05) and Hepatozoon canis (p < 0.001), while CMhp with H. canis (p < 0.001). This study adds information on haemoplasma species distribution in hunting dogs in southern Italy. Outdoor lifestyle and contact with wild fauna, through greater exposure to tick infestation, or possibly wounds acquired during hunting or fighting, could be factors contributing to haemoplasma infections.
Assuntos
Doenças do Cão/epidemiologia , Infecções por Mycoplasma/epidemiologia , Infecções por Mycoplasma/veterinária , Mycoplasma/genética , Mycoplasma/isolamento & purificação , Infestações por Carrapato/veterinária , Cães Trabalhadores/microbiologia , Animais , DNA Bacteriano/genética , Doenças do Cão/microbiologia , Cães , Feminino , Itália/epidemiologia , Masculino , Mycoplasma/classificação , Mycoplasma/patogenicidade , Prevalência , RNA Ribossômico 16S/genética , Fatores de RiscoRESUMO
Hepatozoon canis is a hemoprotozoan organism that infects domestic and wild carnivores throughout much of Europe. The parasite is mainly transmitted through the ingestion of infected ticks containing mature oocysts. The aims of the present survey were to determine the prevalence of H. canis in hunting dogs living in Southern Italy and to assess potential infection risk factors. DNA extracted from whole blood samples, collected from 1433 apparently healthy dogs living in the Napoli, Avellino, and Salerno provinces of Campania region (Southern Italy), was tested by a quantitative real-time polymerase chain reaction (qPCR) assay to amplify H. canis. Furthermore, the investigated dog population was also screened by qPCR for the presence of Ehrlichia canis, a major tick-borne pathogen in Southern Italy, in order to assess possible co-infections. Two hundred dogs were H. canis PCR-positive, resulting in an overall prevalence of 14.0% (CI 12.2-15.9). Breed category (P < 0.0001), hair coat length (P = 0.015), and province of residence (P < 0.0001) represented significant risk factors for H. canis infection. The presence of H. canis DNA was also significantly associated with E. canis PCR positivity (P < 0.0001). Hunting dogs in Campania region (Southern Italy) are frequently exposed to H. canis, and the infection is potentially associated with close contact with wildlife. Further studies are needed to assess the pathogenic potential of H. canis, as well as the epidemiological relationships between hunting dogs and wild animal populations sharing the same habitats in Southern Italy.
Assuntos
Coccidiose/veterinária , Doenças do Cão/parasitologia , Eucoccidiida/isolamento & purificação , Animais , Coccidiose/parasitologia , Coccidiose/transmissão , Doenças do Cão/sangue , Doenças do Cão/epidemiologia , Doenças do Cão/transmissão , Cães , Eucoccidiida/genética , Eucoccidiida/fisiologia , Feminino , Itália/epidemiologia , Masculino , Reação em Cadeia da Polimerase , Fatores de Risco , Carrapatos/parasitologia , Carrapatos/fisiologiaRESUMO
AIM: The study aimed at evaluating the concentration levels of organochlorine pollutants in donkey milk and their modulation on the intestinal strongyle infection. Risk evaluation for consumer health was also investigated. METHODS: We analyzed milk of grazing donkeys living in areas of Southern of Italy affected by organochlorine compounds environmental pollution and parasite infection. The presence of pollutants was assessed through summary statistics; regression analysis of intestinal strongyle on pollutant concentration was performed to investigate the relationship between the two variables. RESULTS: PCB concentrations (mainly non-dioxin-like (ndl)-PCBs) were higher than OCP ones. Mean values of ndl-PCBs across areas ranged from 93.13 to 263.64 ng g-1. In all sample units we detected the six indicator PCBs with the prevalence of the PCB 153, followed by the PCB 28 and the PCB 101. Among the dioxin-like (dl)-PCBs, non-ortho PCB 169, 77 and 126 were assessed in some milk samples; in all areas we detected the mono-ortho PCB 118 and PCB 105. Positive correlation between infection level and six indicator PCBs as well as between the former and HCB, on WW and LW, were observed (at least statistically significant at 5 percent). In some cases, Dl-PCB concentrations emerged as dangerous given the EU maximum residue limit for PCDD/Fs and dl-PCBs. CONCLUSION: Evidence supports the hypothesis of an immunosuppressive role of organochlorine pollutants; risk evaluation reveals the potential health impact of dl-PCB intake, particularly for major donkey milk consumers such as infants, children with cow milk and multiple food intolerance, and elders.
Assuntos
Contaminação de Alimentos/análise , Hidrocarbonetos Clorados/análise , Leite/química , Praguicidas/antagonistas & inibidores , Idoso , Animais , Criança , Dibenzofuranos/análise , Exposição Dietética , Equidae , Feminino , Humanos , Lactente , Enteropatias Parasitárias/veterinária , Itália , Praguicidas/análise , Bifenilos Policlorados/análise , Dibenzodioxinas Policloradas/análise , Medição de RiscoRESUMO
BACKGROUND: As first responders, police officers may be exposed to infectious agents such as hepatitis viruses and human immunodeficiency virus. Their risk of infection by these viruses can be reduced with training, monitoring and, with some viruses, vaccination. AIMS: To examine infection prevention policies and practices among police departments and determine provision of vaccination and infection prevention education programmes. METHODS: A questionnaire sent to all police departments in five counties of south-eastern Pennsylvania to capture information about department size, immunization policies and practices, record keeping, infection prevention education and monitoring of exposures. RESULTS: Ninety-six of 168 departments responded (57%). Among these, policies requiring pre-employment physical examinations were almost universal (95%). Vaccination policies were less common with <15% requiring and 50% recommending hepatitis, tetanus or influenza vaccination for officers. Few departments took action to provide (2%) or cover the cost (21%) of vaccination. Fewer than 12% maintained vaccination records. Education about the risk of infectious agents was offered by 60% of the responding departments, but often just once at the start of employment. Fewer than half of the departments had systems to collect exposure information. CONCLUSIONS: Police departments have opportunities to improve policies and practices for infection prevention and control. Accurate documentation of vaccination status is essential to ensure provision of appropriate post-exposure assessment and treatment. Better reporting of exposure will improve understanding of the infection transmission risk, enhancing the ability to offer targeted education and services to officers.
Assuntos
Infecções/microbiologia , Doenças Profissionais/prevenção & controle , Exposição Ocupacional/efeitos adversos , Saúde Ocupacional , Polícia , Políticas , Vacinação , Infecções por HIV/prevenção & controle , Infecções por HIV/virologia , Hepatite/prevenção & controle , Hepatite/virologia , Humanos , Infecções/etiologia , Influenza Humana/microbiologia , Influenza Humana/prevenção & controle , Doenças Profissionais/etiologia , Doenças Profissionais/microbiologia , Pennsylvania , Tétano/microbiologia , Tétano/prevenção & controleRESUMO
BACKGROUND: The study was aimed to analyze the pattern of bleeding throughout the kidney tissue after renal biopsy and evaluate its relationship with the onset of renal biopsy side effects by using directional power-Doppler sonography. PATIENTS: Eighty-five consecutive subjects with clinical evidence of renal disease underwent to percutaneous renal biopsy using directional power Doppler sonography. In each patient, the pattern of kidney hemorrhage immediately after the renal biopsy was evaluated. RESULTS: Fifty-seven patients, representing 67% of all biopsies performed, evidenced renal bleeding lasting 5.3+/-5.7 min; fifty-five patients, representing 65% of all biopsies, developed a post biopsy hematoma (x = 2.9+/-2.0 cm); 36% of patients developed a perirenal hematoma (x = 1.8+/-2.1 cm). A subcapsular hematoma was experienced by 45% of patients (x = 2.7+/-1.1 cm); 16% of these patients had a combined perirenal-subcapsular hematoma; 5% of hematomas were larger than 5 cm. Hematoma dimensions were related to the length of bleeding (r = 0.6331; p < 0.0001). Hemoglobin and hematocrit levels significantly reduced from 12.7+/-2.3 g/dL to 11.7+/-2.3 g/dL (-7%, p < 0.0001) and 37.6+/-6.5% to 35.4+/-6.5% (-6%, p < 0.0001) respectively, and such variations were related to the hematoma size (Delta Hb: r = -0.5171; p < 0.0001; Delta Htc: r = -0.3465; p < 0.0001). CONCLUSIONS: This study demonstrates that directional power Doppler sonography allows medical personnel to clearly evidence all renal biopsy-related side effects and identify, through the evaluation of renal bleeding immediately after the kidney biopsy, those patients who will develop renal hematomas.
Assuntos
Rim/diagnóstico por imagem , Rim/patologia , Ultrassonografia Doppler , Biópsia por Agulha/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To describe the role of opioid antagonists in the treatment of opioid-induced constipation and pruritus. DATA SOURCES: A MEDLINE search was performed (1966-February 2000) for narcotics and opioid antagonists. Results were limited to English-language and clinical trials. Background information was obtained from pharmacology and pharmacotherapy references and review articles. Hand searching of selected bibliographies yielded several references. STUDY SELECTION AND DATA EXTRACTION: Studies were reviewed that examined the use of naloxone, naltrexone, and methylnaltrexone for opioid-related constipation and pruritus. Selected citations included various clinical trials and case series. DATA SYNTHESIS: Opioid agents are used for cancer and nonmalignant pain. Peripheral opioid receptor stimulation due to endogenous (i.e., endorphins) or exogenous (i.e., morphine) stimulants may result in negative adverse effects, including constipation and pruritus. Adjuvant agents, such as laxatives and antihistamines, are often used to treat these adverse effects, but are themselves associated with adverse effects and are sometimes ineffective. Opioid antagonists have demonstrated reversal of peripheral opioid receptor stimulation. Clinical trials show adequate maintenance of pain control, as well as decreases in opioid-induced constipation and pruritus. CONCLUSIONS: Opioid antagonists offer a therapeutic alternative to conventional adjuvant agents, with the risk of loss of analgesia at higher doses. Methylnaltrexone offers the advantage of peripheral action only, therefore not reversing analgesia. Results are promising; however, larger clinical trials are necessary before opioid antagonists become the standard of care for opioid-induced constipation and pruritus.
Assuntos
Constipação Intestinal/tratamento farmacológico , Antagonistas de Entorpecentes/uso terapêutico , Entorpecentes/efeitos adversos , Prurido/tratamento farmacológico , Ensaios Clínicos como Assunto , Constipação Intestinal/induzido quimicamente , Humanos , Morfina/efeitos adversos , Naloxona/uso terapêutico , Naltrexona/análogos & derivados , Naltrexona/uso terapêutico , Prurido/induzido quimicamente , Compostos de Amônio QuaternárioRESUMO
In order to define the ability of bovine lens aldose reductase (ALR2) to generate polyols from aldoses, the quantitative determination of glycerol in the presence of glyceraldehyde was performed by gas chromatography after derivatization with trifluoroacetic anhydride. The proposed method appears to be useful in quantifying low amounts of glycerol in the presence of relatively high concentrations of glyceraldehyde and in following glycerol formation in enzyme assay conditions. The generation of one equivalent of glycerol in the presence of ALR2, is paralleled by the oxidation of one equivalent of NADPH. A similar result was obtained when S-glutathionyl-modified ALR2 was used, instead of the native enzyme, as a catalyst of glyceraldehyde reduction. Sorbinil, a classical ALR2 inhibitor, present in the enzyme assay mixture, inhibits to the same extent both NADPH oxidation and glycerol formation. The demonstration of the stoichiometric ratio of 1:1 occurring in the presence of bovine lens ALR2 between the synthesis of glycerol from D, L -glyceraldehyde and the oxidation of NADPH, rules out doubts concerning the ability of the enzyme to catalyse the reduction of aldoses to the corresponding polyalcohols. Possible autooxidation processes of glyceraldehyde, in the enzyme assay conditions, appear to be irrelevant with respect to the enzyme-catalysed reduction of the aldose. This would indicate that the spectrophotometric monitoring of NADPH oxidation at 340 nm, in the presence of ALR2, is a reliable method to assay the enzyme activity.
Assuntos
Aldeído Redutase/fisiologia , Gliceraldeído/metabolismo , NADP/metabolismo , Aldeído Redutase/antagonistas & inibidores , Animais , Catálise , Bovinos , Cromatografia Gasosa , Fluoracetatos , Glicerol/metabolismo , Cristalino/enzimologia , Oxirredução , Ácido Trifluoracético/farmacologiaRESUMO
Model smear soft cheeses, prepared with Debaryomyces hansenii and Brevibacterium linens as ripening starters, were ripened under aseptic conditions. Results of the cheese-making trials, in triplicate, were similar and showed similar patterns of protein degradation. In all of the trials, the acid-soluble nitrogen and nonprotein nitrogen (NPN) indexes and NH3 concentrations of the rind were low until d 10. The acid-soluble nitrogen and NPN of the rind then increased to 100 and 18% of total nitrogen, respectively, at d 76. The NH3 concentrations remained low until d 24 and increased until d 70, reaching about 1.8 g of NH3/kg of DM, and then remained constant. The acid-soluble nitrogen and NPN indexes and NH3 concentrations in the inner cheese mass were lower than in the rind. They showed the same evolution, reaching about 18% for acid-soluble nitrogen, 10% for NPN, and 1.5 g of NH3/kg of DM. It was shown that the inner cheese pH and populations of D. hansenii and B. linens have an effect on proteolysis. Viable cell counts of D. hansenii and B. linens were correlated with the environmental conditions and with proteolytic products. The determining role of carbon source and NH3 diffusions on the cheese ripening process were confirmed.
Assuntos
Brevibacterium/metabolismo , Queijo/microbiologia , Proteínas do Leite/metabolismo , Peptídeo Hidrolases/metabolismo , Saccharomycetales/metabolismo , Amônia/análise , Câmaras de Exposição Atmosférica , Brevibacterium/enzimologia , Brevibacterium/crescimento & desenvolvimento , Fermentação , Concentração de Íons de Hidrogênio , Lactatos/análise , Desnaturação Proteica , Reprodutibilidade dos Testes , Saccharomycetales/enzimologia , Saccharomycetales/crescimento & desenvolvimento , Fatores de Tempo , ÁguaRESUMO
A Mu-class glutathione S-transferase purified to electrophoretic homogeneity from bovine lens displayed thioltransferase activity, catalysing the transthiolation reaction between GSH and hydroxyethyldisulphide. The thiol-transfer reaction is composed of two steps, the formation of GSSG occurring through the generation of an intermediate mixed disulphide between GSH and the target disulphide. Unlike glutaredoxin, which is only able to catalyse the second step of the transthiolation process, glutathioneS-transferase catalyses both steps of the reaction. Data are presented showing that bovine lens glutathione S-transferase and rat liver glutaredoxin, which was used as a thioltransferase enzyme model, can operate in synergy to catalyse the GSH-dependent reduction of hydroxyethyldisulphide.
Assuntos
Glutationa Transferase/metabolismo , Cristalino/enzimologia , Oxirredutases/metabolismo , Proteína Dissulfeto Redutase (Glutationa) , Proteínas/metabolismo , Animais , Bovinos , Cromatografia DEAE-Celulose , Cromatografia em Gel , Cromatografia por Troca Iônica , Glutarredoxinas , Glutationa Transferase/isolamento & purificação , Isoenzimas/isolamento & purificação , Isoenzimas/metabolismo , Cinética , Fígado/metabolismo , Masculino , Proteínas/isolamento & purificação , Ratos , Ratos Sprague-DawleyRESUMO
To enhance knowledge in the area of in vitro testing of antibiotics and to understand the limitations of available methods for susceptibility testing, we conducted a MEDLINE literature search in the English language to accumulate relevant articles. Headings searched included microbial sensitivity tests; Kirby-Bauer; laboratory tests; antiinfective agents; antibiotics, combined; microbiological techniques; blood bactericidal assay; and pharmacology, clinical. The management of patients with serious life-threatening infections can be complicated by recent changes in organism nomenclature, newly marketed antibiotics, and new isolation and sensitivity testing methods. With the addition of formulary constraints, many problems and controversies arise regarding interpretation of antibiotic sensitivity results. Comprehensive care for infected patients requires assessment of current antibiotic therapy and options for alternative therapy. By applying pharmacodynamic and pharmacokinetic knowledge to known limits of in vitro testing results, the clinician is able to select the most efficient antibiotic or antibiotic combination.
Assuntos
Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana , Técnicas In VitroRESUMO
An examination is made of external humeral epicondylalgia and its surgical treatment by Hohmann's operation (tenomyotomy of the epicondyloids). 52 clinical cases operated by this technique in the various Hospitals in the Milan area during the period from 1966 to 1976 are reviewed. The Authors conclude by asserting the superiority of Hohmann's operation as compared with other surgical techniques, since ogods results are accompanied by simplicity and low risk.