Low Rates of Lung Cancer Screening Referrals in Patients With Human Immunodeficiency Virus: A Correlational Study.

People living with HIV (PLWH) have an increased risk of lung cancer compared to the general population. In 2013, the United States Preventive Services Task Force (USPSTF) released their lung cancer screening (LCS) guidelines. However, the impact of these guidelines has not been well established in PLWH. The objective of this retrospective descriptive study is to evaluate the frequency of lung cancer screening referrals and factors associated with LCS referrals using the 2013 USPSTF screening guidelines in at-risk PLWH. We collected demographic and clinical information on PLWH from electronic medical records from July 2016 to July 2018. Descriptive statistics, chi-square tests, t-tests, Wilcoxon rank sum tests, and Fisher's exact tests were used for analysis. Only 14% of patients who met 2013 USPSTF screening guidelines were referred for screening. Patients who received a referral were more likely to have received tobacco cessation counseling. Patients who received and completed a referral were more likely to have hepatitis C infection. Quality improvement strategies are needed to improve rates of LCS in PLWH.

Spermatozoa Obtained From Alpaca vas deferens. Effects of Seminal Plasma Added at Post-thawing.

The viscous seminal plasma (SP) is currently a major impediment to the handling of ejaculate and the development of some biotechnologies in South American camelids. The vas deferens-collected spermatozoa of alpacas is a useful technique to avoid this problem. On the other hand, SP contains a large protein component that has been implicated in the function of spermatozoa within the female reproductive tract. In this sense, the low fertility achieved using transcervical insemination with frozen-thawed spermatozoa in alpacas could be improved by adding SP. This study aimed to evaluate the effect of the whole SP on some in vitro parameters of alpaca spermatozoa after the freezing-thawing-process and the fertility after artificial insemination. It would contribute to a better understanding of the interaction between thawed sperm cells and SP. Spermatozoa were obtained by surgically diverted vas deferens. The samples were diluted with a Tris-based extender, packaged in straws, and frozen. At thawing, each straw was divided into two post-thawing conditions: with the addition of 10% of PBS (control) or with 10% SP (treatment). The sperm cells were evaluated using dynamic parameters, sperm cell morphology, and morphometry. Fertility was assessed by an artificial insemination trial. All in vitro parameters were analyzed by ANOVA. A heterogeneity test was scheduled for the fertility trial. After the freezing-thawing process, motility and plasma membrane functionality was improved when SP was added. No differences were found for post-thaw viability between the control and treatment samples. The percentage of normal cells was higher with SP at post-thawing, and a decrease of the presence of bent tailed spermatozoa with a droplet in the SP group was observed. The length of the head spermatozoa was 3.4% higher in the samples with PBS compared to those in which SP was added. Females pregnant at day 25 post-insemination were 0/12 (with SP inside the straw) and 1/10 (without SP inside the straw). In conclusion, the presence of 10% SP at post-thawing improves sperm cells' motility, functionality, and morphology, indicating that it would be beneficial to improve the frozen-thawed alpaca's physiology spermatozoa. More fertility trials must be developed to increase this knowledge.

Nora Virus VP4b and ORF1 Circulate in Hemolymph of Infected D. melanogaster with Coordinate Expression of Vago and Vir-1.

Study of the novel RNA virus, Nora virus, which is a persistent, picorna-like virus that replicates in the gut of Drosophila melanogaster offers insight into human innate immunity and other picorna-like viruses. Nora virus infection leads to a locomotor abnormality and upregulation of two candidate target proteins, Vago and Virus-induced RNA 1 (Vir-1). These proteins are uncharacterized in response to Nora virus. We hypothesize that Nora virus is circulating in the hemolymph of Nora virus-infected D. melanogaster, allowing for migration beyond the primary site of replication in the gut. Analysis by qRT-PCR demonstrated biphasic viral load and corresponding vago and vir-1 transcription levels, suggesting transcription of vago and vir-1 occurs in response to viral infection. However, Vir-1 is also present in virus-free D. melanogaster suggesting basal expression or alternative functions. Presence of Nora virus RNA and the Viral Protein 4b (VP4b), in hemolymph of infected D. melanogaster supports the hypothesized circulation of Nora virus in the hemolymph. The study suggests that impaired locomotor function may be due to transport of Nora virus from the gut to the brain via the hemolymph.

Uso de la aplicación móvil de Salud Responde para la optimización de los recursos sanitarios / Use of the mobile application of Salud Responde for the optimisation of health resources

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Prediction of the increase in health services demand based on the analysis of reasons of calls received by a customer relationship management.

Currently, customer relationship management (CRM) tools are very important in our society because they provide a comunication channel to the healthcare system for patients. Salud Responde is a CRM that provides many health services for the entire population of Andalusia, in southern Spain. The number and frequenzy of phone calls received change along the year. They depend on many factors, such as weekdays, seasons, vaccination campaigns, environmental factors, pandemic periods, etc. All these are the main reasons number of health calls changes along the year. This variability makes that the current management of resources for offering emergency services based on historical data is inefficient. The factors, which influence the phone calls along the year, are different from one period to another. Therefore, it is clear to demand an improved in the current management system. In this context, the main goal for this research is to develop an expert system able to identify and analyze, using different data mining algorithms, the most relevant factors to predict the variability of health service demand. Thus, here, it is proposed a methodology in which using reasons calls received in the CRM as input data, it is possible to predict in advance the healthcare resources demand.

The Legacy of 1987 Boreali v. Axelrod: Board of Health Rule-Making Under Siege.

We explore how a 1987 New York State court decision-Boreali v. Axelrod-affected public health rule-making nationally and, with considerable impact, locally in New York City (NYC).We discuss the history of the origin of the NYC Board of Health (BOH), and establish that legislatures can be challenging venues in which to enact public health-related laws. We describe how, as the NYC Department of Health and Mental Hygiene began to tackle modern public health problems (e.g., chronic diseases caused by food and tobacco), the regulatory power of its BOH was challenged.In an era when industry funds political causes and candidates, the weakening of the independence of rule-making boards of health, such as the NYC BOH, might result in illness and death.

Analysis of immune-related genes during Nora virus infection of Drosophila melanogaster using next generation sequencing.

Drosophila melanogaster depends upon the innate immune system to regulate and combat viral infection. This is a complex, yet widely conserved process that involves a number of immune pathways and gene interactions. In addition, expression of genes involved in immunity are differentially regulated as the organism ages. This is particularly true for viruses that demonstrate chronic infection, as is seen with Nora virus. Nora virus is a persistent non-pathogenic virus that replicates in a horizontal manner in D. melanogaster. The genes involved in the regulation of the immune response to Nora virus infection are largely unknown. In addition, the temporal response of immune response genes as a result of infection has not been examined. In this study, D. melanogaster either infected with Nora virus or left uninfected were aged for 2, 10, 20 and 30 days. The RNA from these samples was analyzed by next generation sequencing (NGS) and the resulting immune-related genes evaluated by utilizing both the PANTHER and DAVID databases, as well as comparison to lists of immune related genes and FlyBase. The data demonstrate that Nora virus infected D. melanogaster exhibit an increase in immune related gene expression over time. In addition, at day 30, the data demonstrate that a persistent immune response may occur leading to an upregulation of specific immune response genes. These results demonstrate the utility of NGS in determining the potential immune system genes involved in Nora virus replication, chronic infection and involvement of antiviral pathways.

Selective liposome targeting of folate receptor positive immune cells in inflammatory diseases.

Activated macrophages play a key role in the development and maintenance of inflammatory diseases such as atherosclerosis, lupus, psoriasis, rheumatoid arthritis, ulcerative colitis, and many others. These activated macrophages, but not resting or quiescent macrophages highly up-regulate folate receptor beta (FR-ß). This differential expression of FR-ß provides a mechanism to selectively deliver imaging and therapeutic agents utilizing folate as a targeting molecule. In an effort to determine whether inflammatory diseases can be targeted utilizing a folate-linked nanosize carrier, a PEG-coated liposome was prepared that incorporated a folate conjugated PEG that also could transport imaging or therapeutic cargo. We demonstrate that these folate-liposomes specifically bind to folate receptor positive cells and accumulate at sites of inflammation in mouse models of colitis and atherosclerosis. These two animal models show that folate-targeted liposomes could be successfully utilized to deliver fluorescent molecules and an anti-inflammatory drug (betamethasone) for diagnostic and therapeutic applications.

Folate-conjugated liposomes target and deliver therapeutics to immune cells in a rat model of rheumatoid arthritis.

AIM: We endeavored to create a folate-targeted liposome (Fol-liposome) that could selectively target areas of inflammation. MATERIALS & METHODS: Fol-liposomes were prepared with encapsulated DiD fluorophore or betamethasone (BM) to image and treat an adjuvant-induced rat model of rheumatoid arthritis. RESULTS: Fol-liposomes selectively accumulated in arthritic rat paws to a greater extent than nontargeted liposomes. When these Fol-liposomes were used to encapsulate BM and administered to arthritic rats, animals exhibited less paw swelling, lower arthritis scores, a reduction in bone erosion, less splenomegaly and better maintenance of body weight when compared with nontreated or nontargeted BM-containing liposome groups. CONCLUSION: Fol-liposomes can selectively deliver imaging and therapeutic agents to sites of inflammation in a rat model of rheumatoid arthritis.

Uso de customer relationship management para mejorar la atención sanitaria de la ciudadanía. Servicio Salud Andalucía 24 horas. Salud Responde / Use of customer relationship management to improve healthcare for citizens. The 24h Andalusian Health Service: Healthline

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[Use of customer relationship management to improve healthcare for citizens. The 24h Andalusian Health Service: Healthline]. / Uso de customer relationship management para mejorar la atención sanitaria de la ciudadanía. Servicio Salud Andalucía 24 horas. Salud Responde.

Salud Responde (in English: Healthline) is a Health Service and Information Centre of the taxpayer-funded Andalusian Health System (AHS) that offers a Telephone Health Advisory Service called SA24h, among other services. The main objective of SA24h is to inform and advise citizens on health issues and the available health resources of the AHS. SA24h has a Customer Relationship Management information technology tool that organises information at various levels of specialization. Depending on the difficulty of the query, the citizen is attended by professionals with distinct profiles, providing a consensual response within the professionals working within Salud Responde or within other healthcare levels of the AHS. SA24h provided responses to 757,168 patient queries from late 2008 to the end of 01/12/2015. A total of 9.38% of the consultations were resolved by the non-health professionals working at Salud Responde. The remaining 84.07% were resolved by health staff. A total of 6.5% of users were referred to accident and emergency facilities while 88.77% did not need to attend their general practitioner within the next 24hours, thus avoiding unnecessary visits to health care facilities.

Relación de la concentración de homocisteína con factores de riesgo cardiovascular en pacientes con lupus eritematoso sistémico / Relationship of homocysteine with cardiovascular risk factors in patients with systemic lupus erythematosus

The cardiovascular complications are a leading cause of death in systemic lupus erythematosus (SLE), there is an association between hyperhomocysteinemia and the risk of cardiovascular disease. The objective was to establish the relationship between hcys with classic cardiovascular risk factors in patients with SLE and apparently healthy individuals (control group, CTR). SLE patients (female n = 19 and female n = 1) and the CTR group (female n = 14 and female n = 6) were determined: blood pressure, body mass index (BMI), waist / hip (ICC), blood glucose, lipid profile (cholesterol, HDL-c, LDL-c, VLDL-c and triglycerides) and hcys. Both groups had blood pressure, ICC (0.81 ± 0.06 vs 0.85 ± 0.07) and BMI (26.05 ± 5.33 vs 25.35 ± 3.66 kg/m2 kg/m2) , BG (LES, 76.7 ± 19.81 mg / dL vs 75.8 ± 11.70 mg / dL), cholesterol (170.3 ± 58.1 vs 167.40 ± 39.4 mg / dL), triglycerides (104.9 ± 55.4 vs 115.1 ± 63.6 mg / dL, P = 0.593), HDL-c (41.45 ± 6.54 mg / dL vs 42.35 ± 9.4 mg / dL ), LDL-c (107.9 ± 55.1 vs 101.7 ± 34.3 mg / dL), VLDL-c (20.9 ± 11.02 vs 23.3 ± 12.7 mg / dL) and Hcys (LES, 12.73 ± 4.91 mmol / L vs 16.08 ± 8.61 CTR mol / L) were within the reference values without statistically significant differences (P> 0.05). A correlation between Hcys, total cholesterol and LDL in SLE was found. It can be concluded that changes in total cholesterol and LDL is a direct consequence of Hcys.

La enfermedad arterial coronaria es una de las primeras causas de morbi-mortalidad a nivel mundial por lo que se convierte en un problema de salud pública. Esta es producida por diferentes factores de riesgos modificables y no modificables los cuales desencadenan en el individuo la aparición de la enfermedad, siendo el trabajador de la salud un individuo cuya actividad, exposición y estrés laboral es especial y determina su estado de salud, pudiendo desencadenar condiciones para afectar su área cardiovascular, se decide evaluar el riesgo de enfermedad arterial coronaria a corto plazo en una muestra de 99 profesionales que laboraban en la dirección municipal de salud del Municipio Bolívar estado Aragua,Venezuela, a los cuales se les realizó perfil lipídico (colesterol total, HDL colesterol, LDL colesterol, VLDL colesterol y triglicéridos, colesterol no HDL), glicemia y proteína C reactiva ultrasensible. La prevalencia de los factores de riesgo cardiovascular encontrados en estos individuos se categorizó según la escala de Framingham en: bajo riesgo (< 1 9%) resultó el 98,55% de las mujeres y 96,67% de los hombres, el riesgo moderado (10-19%) estuvo representado por 1,45% en mujeres y 3,33% en hombres de los trabajadores. Así mismo, el perfil lipídico, el IMC, los hábitos tabáquicos y alcohólicos fueron las variables más resaltantes de este estudio, siendo todos modificables con cambios de estilo de vida en estos trabajadores.

Folate receptor-ß in activated macrophages: ligand binding and receptor recycling kinetics.

Activated macrophages overexpress a receptor for the vitamin folic acid termed the folate receptor ß (FR-ß). Because conjugation of folate to low molecular weight drugs, genes, liposomes, nanoparticles, and imaging agents has minor effects on FR binding, the vitamin can be exploited to target both therapeutic and imaging agents to activated macrophages without promoting their uptake by other healthy cells. In this paper, we characterize the binding, internalization, and recycling kinetics of FR-ß on activated macrophages in inflamed tissues of rats with adjuvant-induced arthritis. Our results demonstrate that saturation of macrophage FR is achieved at injection doses of ∼150-300 nmol/kg, with more rapidly perfused tissues saturating at lower doses than inflamed appendages. After binding, FR-ß internalizes and recycles back to the cell surface every ∼10-20 min, providing empty receptors for additional folate conjugate uptake. Because the half-life of low molecular weight folate conjugates in the vasculature is usually <1 h, these data suggest that targeting of folate conjugates to activated macrophages in vivo can be maximized by frequent dosing at conjugate concentrations that barely saturate FR (∼150 nmol/kg), thereby minimizing nonspecific binding to receptor-negative tissues and maximizing the probability that unoccupied cell surface receptors will be exposed to folate-drug conjugate.

EMAC volunteers: liability and workers' compensation.

The Emergency Management Assistance Compact (EMAC) provides a mechanism for states to assist each other during natural disasters and other emergencies. Congress ratified EMAC in 1996, and all 50 states and 3 territories have adopted it. EMAC allows a state affected by a disaster to request personnel and materiel from another state. For personnel requests, EMAC provides that the requesting state cover the tort liability and the responding state cover the workers' compensation liability. This article discusses the limitations of EMAC in deploying volunteers and how the Uniform Emergency Volunteer Health Practitioners Act and other provisions address those limitations.

Farmacovigilancia y medicina interna / Pharmacovigilance and internal medicine

En Medicina Interna es indispensable conocer y reportar las Reacciones Adversas a los Medicamentos (RAM). Se presentan cuatro (4) situaciones de este tipo, provenientes del Servicio de Medicina Interna del Hospital General del Oeste, Caracas, Venezuela. Caso 1: paciente con SIDA y toxoplasmosis cerebral, en tratamiento con antiretrovirales, trimetoprim-sulfa y pirimetamina. Consulta a la emergencia por presentar lesiones cutáneas. Caso 2: paciente de 24 años, síndrome de Down, con comunicación interventricular corregida, hipotiroidismo controlado y Hepatitis C en tratamientocon ribavirina – tegainterferon, con abscesoinguinal. Se encuentra pancitopenia severa y progresiva. Caso 3: Mujer de 70 años en preoperatori de facotomía en quien se diagnóstica trombosis venosa profunda poplítea izquierda. Se prescribe enoxaparina – warfarina y se aprecia un hematoma del recto anterior del abdomen. Se identifica el uso previo y simultáneo de productos herbarios. Caso 4: paciente que ingiere un producto sin registro sanitario y prohibido por las autoridades regulatorias del país; contiene compuestos no declarados: diclofenac sódico y esteroides. La farmacovigilancia es indispensable en un servicio de medicina interna.

Pharmacovigilanceis essential in the practice of Internal Medicine. Four situations from an Internal Medicine Department of the Hospital General del Oeste, Caracas, Venezuela, are analyzed. Case 1: patient with AIDS and cerebral toxoplasmosis, trated with antiretroviral drugs, trimetoprim-sulfimetoxasol and pyrimethamine. This patient consultedbecause of with cutaneous. Case 2: 24 year-old patient with Down syndrome, corrected congenital cardiac disease, treated hypothyroidism and hepatitis C treated with ribavirin - tegainterferon had an inguinal abscess. A severe and progressive pancytopenia is found and It analyzed the high suspicion causality of RAM. Case 3: A 70 year-old woman, was examined for a preoperative evaluation and a left popliteal deep vein thrombosis is found. Enoxaparin - warfarin were prescribed and in the next 24 hours a hematoma of abdominal rectus was found. The oriented anamnesis identifies the use of herbal products. Drug interaction is discussed. Case 4: regulatory authorities prohibit an unregistered health product that has not reported compounds: diclofenac and steroids. Pharmacovigilance is essential in a department of internal medicine.

A folate receptor-α-specific ligand that targets cancer tissue and not sites of inflammation.

UNLABELLED: Folic acid has been frequently exploited to target attached drugs to cells that overexpress a folate receptor (FR). Unfortunately, folic acid and folate-linked drugs bind equally well to both major isoforms of the FR-that is, FR-α, which is primarily expressed on malignant cells, and FR-ß, which is upregulated on activated monocytes and macrophages. Because both major isoforms of FR can be expressed simultaneously in the same organism, folic acid cannot enable selective targeting of therapeutic and imaging agents to either tumor masses or sites of inflammation. In an effort to develop a targeting ligand that can selectively deliver attached imaging and therapeutic agents to tumor cells, we constructed a reduced and alkylated form of folic acid, N(5), N(10)-dimethyl tetrahydrofolate (DMTHF) that exhibits selectivity for FR-α. METHODS: DMTHF-(99m)Tc was injected into mice bearing FR-α-expressing tumor xenografts and imaged by γ-scintigraphy. The selectivity for FR-α over FR-ß in vivo was examined by γ-scintigraphic images of animal models of various inflammatory diseases such as apolipoprotein E-deficient mice with atherosclerosis, DBA/1 LacJ mice with induced arthritis, C57BL/6J mice with muscle injury, and BALB/C mice with both FR-α tumor and ulcerative colitis, by administration of equal doses of DMTHF-(99m)Tc and EC20-(99m)Tc. The uptake of radiochelates in various organs was quantified by biodistribution studies. DMTHF-near-infrared dye conjugate and DMTHF-Oregon green dye conjugates were synthesized and evaluated for FR-α selectivity over FR-ß in rat peritoneal macrophages and human peripheral blood monocytes, respectively, by flow cytometry. Fluorescence-guided imaging was also performed using folate and DMTHF dye conjugates. RESULTS: The new targeting ligand was found to bind malignant cells in mice with solid tumor xenografts but not peripheral blood monocytes or inflammatory macrophages in animal models of atherosclerosis, rheumatoid arthritis, muscle injury, or ulcerative colitis. Results from optical and radioimaging studies and biodistribution experiments confirm the differential specificity of this new ligand for malignant masses. CONCLUSION: The new targeting ligand DMTHF enables selective noninvasive imaging and therapy of tumor tissues in the presence of inflammation.

Imaging sites of infection using a 99mTc-labeled folate conjugate targeted to folate receptor positive macrophages.

EC20, a folate-targeted (99m)Tc based radioimaging agent with a high folate receptor (FR) binding affinity, has been used for both the diagnosis and the staging of FR positive malignancies (currently in phase III trials) and also for the localization of inflamed lesions characterized by the accumulation of FR+ macrophages. Because recent evidence has suggested that FR+ macrophages might accumulate at sites of infectious disease, this study evaluated whether EC20 might prove similarly useful for imaging bacterial infection foci. Using gamma scintigraphic imaging, it was demonstrated that EC20 accumulated at sites of Staphylococcus aureus infection with a significant difference (P < 0.0001, n = 12) in enrichment noted between infected and noninfected limbs. Confirmation that the elevated uptake of EC20 in infected limbs was FR-mediated was supported by suppression of EC20 accumulation in the presence of a 200-fold excess of free folic acid (P < 0.0001, n = 12). This study establishes for the first time the use of EC20 to image and localize sites of infectious disease.

Synthesis and activity of folate conjugated didemnin B for potential treatment of inflammatory diseases.

A folate receptor targeted didemnin B conjugate was synthesized using a hydrophilic peptide spacer linked to folate via a releasable disulfide carbonate linker. Cell cytotoxicity and TNF-α inhibition in RAW264.7 macrophage-like cells exhibited IC(50)s of 13 and 5 nM, respectively. Folate didemnin B was found to be ∼50-100 fold more potent than didemnin B itself. More importantly, activity of the prodrug was blocked by excess folic acid, demonstrating receptor-mediated cellular uptake of the conjugate.