Targeting the LOX/hypoxia axis reverses many of the features that make pancreatic cancer deadly: inhibition of LOX abrogates metastasis and enhances drug efficacy

Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer‐related mortality. Despite significant advances made in the treatment of other cancers, current chemotherapies offer little survival benefit in this disease. Pancreaticoduodenectomy offers patients the possibility of a cure, but most will die of recurrent or metastatic disease. Hence, preventing metastatic disease in these patients would be of significant benefit. Using principal component analysis (PCA), we identified a LOX/hypoxia signature associated with poor patient survival in resectable patients. We found that LOX expression is upregulated in metastatic tumors from Pdx1‐Cre KrasG12D/+ Trp53R172H/+ (KPC) mice and that inhibition of LOX in these mice suppressed metastasis. Mechanistically, LOX inhibition suppressed both migration and invasion of KPC cells. LOX inhibition also synergized with gemcitabine to kill tumors and significantly prolonged tumor‐free survival in KPC mice with early‐stage tumors. This was associated with stromal alterations, including increased vasculature and decreased fibrillar collagen, and increased infiltration of macrophages and neutrophils into tumors. Therefore, LOX inhibition is able to reverse many of the features that make PDAC inherently refractory to conventional therapies and targeting LOX could improve outcome in surgically resectable disease

Hypertrophic Adenoid Is A Major Infection Site Of Human Bocavirus 1.

Human bocavirus 1 (HBoV1) is associated with respiratory infections worldwide, mainly in children. Similar to other parvoviruses, it is believed that HBoV1 can persist for long periods of time in humans, probably through maintaining concatemers of the virus single-stranded DNA genome in the nuclei of infected cells. Recently, HBoV-1 was detected in high rates in adenoid and palatine tonsils samples from patients with chronic adenotonsillar diseases, but nothing is known about the virus replication levels in those tissues. A 3-year prospective hospital-based study was conducted to detect and quantify HBoV1 DNA and mRNAs in samples of the adenoids (AD), palatine tonsils (PT), nasopharyngeal secretions (NPS), and peripheral blood (PB) from patients undergoing tonsillectomy for tonsillar hypertrophy or recurrent tonsillitis. HBoV1 was detected in 25.3% of the AD samples, while the rates of detection in the PT, NPS, and PB samples were 7.2%, 10.5%, and 1.7%, respectively. The viral loads were higher in AD samples, and 27.3% of the patients with HBoV had mRNA detectable in this tissue. High viral loads and detectable mRNA in the AD were associated with HBoV1 detection in the other sample sites. The adenoids are an important site of HBoV1 replication and persistence in children with tonsillar hypertrophy. The adenoids contain high HBoV1 loads and are frequently positive for HBoV mRNA, and this is associated with the detection of HBoV1 in secretions.523030-

Screen-printed back-to-back electroanalytical sensors: heavy metal ion sensing

Screen-printed back-to-back microband electroanalytical sensors are applied to the quantification of lead(II) ions for the first time. In this configuration the electrodes are positioned back-to-back with a common electrical connection to the two working electrodes with the counter and reference electrodes for each connected in the same manner as a normal "traditional" screen-printed sensor. Proof-of-concept is demonstrated for the electroanalytical sensing of lead(II) ions utilising square-wave anodic stripping voltammetry where an increase in the electroanalytical sensitivity is observed by a factor of 5 with the back-to-back microband configuration at a fixed lead(II) ion concentration of 5 μg L(-1) utilising a deposition potential and time of -1.2 V and 30 seconds respectively, compared to a conventional (single) microband electrode. The back-to-back microband configuration allows for the sensing of lead(II) ions with a linear range from 5 to 110 μg L(-1) with a limit of detection (based on 3σ) corresponding to 3.7 μg L(-1). The back-to-back microband configuration is demonstrated to quantify the levels of lead(II) ions within drinking water corresponding to a level of 2.8 (±0.3) μg L(-1). Independent validation was performed using ICP-OES with the levels of lead(II) ions found to correspond to 2.5 (±0.1) μg L(-1); the excellent agreement between the two methods validates the electroanalytical procedure for the quantification of lead(II) ions in drinking water. This back-to-back configuration exhibits an excellent validated analytical performance for the determination of lead(II) ions within drinking water at World Health Organisation levels (limited to 10 μg L(-1) within drinking water)

Dental Health and Mortality in People With End-Stage Kidney Disease Treated With Hemodialysis: A Multinational Cohort Study

Background Dental disease is more extensive in adults with chronic kidney disease, but whether dental health and behaviors are associated with survival in the setting of hemodialysis is unknown. Study Design Prospective multinational cohort. Setting & Participants 4,205 adults treated with long-term hemodialysis, 2010 to 2012 (Oral Diseases in Hemodialysis [ORAL-D] Study). Predictors Dental health as assessed by a standardized dental examination using World Health Organization guidelines and personal oral care, including edentulousness; decayed, missing, and filled teeth index; teeth brushing and flossing; and dental health consultation. Outcomes All-cause and cardiovascular mortality at 12 months after dental assessment. Measurements Multivariable-adjusted Cox proportional hazards regression models fitted with shared frailty to account for clustering of mortality risk within countries. Results During a mean follow-up of 22.1 months, 942 deaths occurred, including 477 cardiovascular deaths. Edentulousness (adjusted HR, 1.29; 95% CI, 1.10-1.51) and decayed, missing, or filled teeth score ≥ 14 (adjusted HR, 1.70; 95% CI, 1.33-2.17) were associated with early all-cause mortality, while dental flossing, using mouthwash, brushing teeth daily, spending at least 2 minutes on oral hygiene daily, changing a toothbrush at least every 3 months, and visiting a dentist within the past 6 months (adjusted HRs of 0.52 [95% CI, 0.32-0.85], 0.79 [95% CI, 0.64-0.97], 0.76 [95% CI, 0.58-0.99], 0.84 [95% CI, 0.71-0.99], 0.79 [95% CI, 0.65-0.95], and 0.79 [95% CI, 0.65-0.96], respectively) were associated with better survival. Results for cardiovascular mortality were similar. Limitations Convenience sample of clinics. Conclusions In adults treated with hemodialysis, poorer dental health was associated with early death, whereas preventive dental health practices were associated with longer survival

A prescrição de medicamentos em um município do Norte do Paraná Drug prescription in a city of the north of Paraná

INTRODUÇÃO: No setor saúde, os medicamentos representam um instrumento essencial para a capacidade resolutiva dos serviços prestados. Neste processo, dá-se grande importância à política de medicamentos, que regulamenta um dos maiores gastos nos serviços públicos de saúde, em especial os medicamentos essenciais, que são aqueles considerados indispensáveis para atender a maior parte da população assistida pelo Sistema Único de Saúde, e que são distribuídos gratuitamente. OBJETIVO: Identificar os indicadores de prescrição do município de Ibiporã, PR. METODOLOGIA: Para tal, foram recolhidas 3.119 prescrições médicas de Clínica Geral, Pediatria e Ginecologia do município. A partir destas receitas, foram calculados os indicadores de prescrição propostos pela Organização Mundial da Saúde (OMS) e os medicamentos prescritos foram classificados obedecendo à classificação da Anatomical Therapeutic Chemical, também da OMS. RESULTADOS: No município de Ibiporã, PR, são prescritos, em média, dois medicamentos por receita médica. Do total de medicamentos prescritos, 70,2% são prescritos por seus nomes genéricos. Em 22,0% das prescrições foi encontrada a indicação de antibióticos. Houve prescrição de injetáveis em 7,0% das receitas médicas. Em relação à lista municipal de medicamentos, 58,4% dos medicamentos fazem parte desta lista. CONSIDERAÇÕES FINAIS: Tais resultados sugerem dificuldades na implantação de uma política de medicamentos essenciais. Neste contexto, estes indicadores podem contribuir para a formulação de políticas voltadas para a reorientação dos serviços farmacêuticos, promovendo a melhoria do acesso e o uso racional dos medicamentos.<br>INTRODUCTION: Drugs represent an essential tool in the decision-making process of services provided by the healthcare industry. In this process, we can attribute great importance to drug policies, which regulate one of the highest expenses in public health services, especially essential medicines. The latter are considered indispensable to attend most of the population assisted by the National Health System and are distributed free of charge. OBJECTIVE: To identify prescription indicators in the City of Ibipora, PR. METHODOLOGY: 3,119 medical prescriptions in General Practice, Pediatrics and Gynecology were analyzed. Prescription indicators proposed by the World Health Organization (WHO) were calculated based on these prescriptions, and the drugs prescribed were classified according to the WHO's Anatomical Therapeutical Chemical classification. RESULTS: On average, two drugs were prescribed per medical prescription in the city of Ibipora, PR. Of the total medicines prescribed, 70.2% were prescribed by their generic names. Antibiotics were prescribed in 22.0% of prescriptions. Injectable drugs were prescribed in 7.0% of medical prescriptions; 58.4% of medicines prescribed were listed in the municipal list of drugs. FINAL CONSIDERATIONS: These results suggest difficulties in introducing policies for essential drugs. In this context, the present indicators can contribute to the creation of policies to redirect pharmaceutical services, thus promoting improved access, and a more rational use of drugs