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1.
Malar J ; 23(1): 165, 2024 May 25.
Article in English | MEDLINE | ID: mdl-38796456

ABSTRACT

BACKGROUND: Mexico has experienced a significant reduction in malaria cases over the past two decades. Certification of localities as malaria-free areas (MFAs) has been proposed as a steppingstone before elimination is achieved throughout the country. The Mexican state of Quintana Roo is a candidate for MFA certification. Monitoring the status of insecticide susceptibility of major vectors is crucial for MFA certification. This study describes the susceptibility status of Anopheles albimanus, main malaria vector, from historically important malaria foci in Quintana Roo, using both phenotypic and genotypic approaches. METHODS: Adult mosquito collections were carried out at three localities: Palmar (Municipality of Othon P. Blanco), Buenavista (Bacalar) and Puerto Morelos (Puerto Morelos). Outdoor human-landing catches were performed by pairs of trained staff from 18:00 to 22:00 during 3-night periods at each locality during the rainy season of 2022. Wild-caught female mosquitoes were exposed to diagnostic doses of deltamethrin, permethrin, malathion, pirimiphos-methyl or bendiocarb using CDC bottle bioassays. Mortality was registered at the diagnostic time and recovery was assessed 24 h after exposure. Molecular analyses targeting the Voltage-Gated Sodium Channel (vgsc) gene and acetylcholinesterase (ace-1) gene were used to screen for target site polymorphisms. An SNP analysis was carried out to identify mutations at position 995 in the vgsc gene and at position 280 in the ace-1 gene. RESULTS: A total of 2828 anophelines were collected. The main species identified were Anopheles albimanus (82%) and Anopheles vestitipennis (16%). Mortalities in the CDC bottle bioassay ranged from 99% to 100% for all the insecticides and mosquito species. Sequence analysis was performed on 35 An. albimanus across the three localities; of those, 25 were analysed for vgsc and 10 for ace-1 mutations. All individuals showed wild type alleles. CONCLUSION: The results demonstrated that An. albimanus populations from historical malaria foci in Quintana Roo are susceptible to the main insecticides used by the Ministry of Health.


Subject(s)
Anopheles , Insecticide Resistance , Insecticides , Mosquito Vectors , Animals , Anopheles/genetics , Anopheles/drug effects , Insecticides/pharmacology , Insecticide Resistance/genetics , Mexico , Female , Mosquito Vectors/genetics , Mosquito Vectors/drug effects , Malaria/transmission
2.
Soft Matter ; 20(30): 5983-6001, 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39023447

ABSTRACT

The present study examines the impact of slip in Carbopol solutions during the restart flow in pipelines utilizing in situ visualization techniques. Rheological tests were conducted using smooth and hatched parallel plate geometries to obtain the rheological characteristics of the solutions. The behavior of the solutions in the creep tests is compared with those in the experimental unit. Three flow regimes were identified through rheological and experimental setup tests: non-flow, slip, and yielded. The slip regime allowed the establishment of a slip static yield stress value, indicating significant deformation states, and a restart pressure decrease of about 61% when compared to the static yield stress. The flow dynamics under the wall slip effect is captured by velocity profiles, velocity contour maps and velocity gradient. Transient correlations of the scaling law type were determined, with wall slip in proportion to the velocity gradient and wall shear stress. Additionally, the concentration of viscoplastic material in the solution increased the scaling law index. This research seeks to provide valuable findings by quantifying the effects of apparent wall slip through in situ measurements. Such insights are crucial for designing and managing pipeline transport systems that handle yield stress fluids, applicable across various industries including cosmetics, food processing, and the production of waxy oils.

3.
Med Vet Entomol ; 37(4): 845-858, 2023 12.
Article in English | MEDLINE | ID: mdl-37649415

ABSTRACT

Sand flies have expanded their areas of distribution, thereby increasing the risk of pathogen transmission in non-endemic areas. To establish efficient prevention and control strategies for the transmission of vector-borne pathogens, it is important to understand seasonal dynamics of their vectors. In Mexico, there are several areas where the contact between sand flies, hosts and reservoirs favours the transmission of the pathogen. We compared sand fly communities in a forest management area and a conserved area in Noh-Bec, Quintana Roo, Mexico. The analysis included species diversity, activity peaks and molecular detection of pathogens. Sand flies were collected from November to December 2021 and April to May 2022, during 84 night-traps. The conserved area showed higher numbers and greater species heterogeneity of sand flies as compared with the other sites. The ß-diversity analysis revealed that sites disturbed by logging (S1, S2, S3) had greater similarity (90%) in their sand fly species composition than a conserved area (S4) (similarity = 36%). Although none of the specimens were infected with Leishmania, we detected Wolbachia (19.4%) in all four sites, as well as Bartonella (3.25%) only in the disturbed sites. Further studies on the dynamics of sand fly populations and their association with pathogens are necessary.


Subject(s)
Phlebotomus , Psychodidae , Animals , Mexico , Insect Vectors , Forests
4.
Rev Cardiovasc Med ; 23(6): 188, 2022 Jun.
Article in English | MEDLINE | ID: mdl-39077174

ABSTRACT

Age is associated with increased cardiovascular risk factors and cardiovascular disease, which constitutes the leading cause of morbidity and mortality in elderly population. In this text we thoroughly review current evidence regarding the impact on cardiovascular disease of the most important cardiovascular risk factors, especially prevalent and common in the elderly population. Diagnosis and treatment approaches are also addressed, also highlighting the importance of adequate primary and secondary prevention and management. Also, the relationship between cardiovascular disease and some comorbidities and geriatric conditions, such as frailty, particularly common in the elderly, is reviewed, together with some other issues, less often addressed but closely related to ageing, such as genetics, structural and electrical heart changes and oxidative stress. All such questions are of great importance in the comprehensive approach of risk factors and cardiovascular disease in the elderly.

5.
Article in Spanish | MEDLINE | ID: mdl-35350461

ABSTRACT

The purpose of this special report is to describe chronologically the events that contributed to the development and approval of legislation and subsequent implementation of a school vaccination mandate in order to prevent HPV and HPV-associated cancers in Puerto Rico (PR). Starting in 2010, PR initiated public-policy approvals aimed at improving cancer registries and HPV vaccine coverage through health insurance for adolescents aged 11 to 18 years. In 2014, scientific and community efforts succeeded in documenting the magnitude of morbidity caused by HPV and jointly developing HPV vaccine prevention and promotion strategies. In August 2018, PR became one of the first four territories of the United States of America to implement the HPV vaccine school entry requirement to decrease the incidence of HPV-associated cancers on the island. In 2019, it was enshrined in law that every immunization provider must submit immunization data to the Puerto Rico Immunization Registry. The case of PR demonstrates that public policy-making alongside collaboration between academic, scientific, and community coalitions can achieve population change and measurable outcomes aimed at HPV prevention. Countries with a similar public health problem could adopt efforts similar to those presented herein and align them with the World Health Organization goal of eradicating cervical cancer by 2030.


O propósito deste relatório especial é descrever cronologicamente os eventos que contribuíram para o desenvolvimento e a aprovação de legislação, e a implementação da exigência escolar de vacinação em Porto Rico (PR), a fim de prevenir o HPV e os cânceres associados a ele. A partir de 2010, PR iniciou as aprovações de políticas públicas com o objetivo de aprimorar o registro dos casos de câncer e a cobertura vacinal contra o HPV, por meio de planos de saúde, em adolescentes de 11 a 18 anos. Em 2014, esforços científicos e comunitários permitiram documentar a magnitude das doenças causadas pelo HPV e elaborar conjuntamente estratégias de prevenção e promoção da vacina contra o HPV. Em agosto de 2018, PR foi um dos primeiros quatro territórios dos Estados Unidos da América a implementar a vacina contra o HPV como exigência escolar, a fim de diminuir a incidência de cânceres associados ao HPV na ilha. Em 2019 ficou garantido por lei que todos os vacinadores devem enviar informações ao Registro de Imunização. O caso de PR demonstra que o desenvolvimento de políticas públicas, em conjunto com parcerias entre coalizões acadêmicas, científicas e comunitárias, alcança mudanças populacionais e resultados mensuráveis dirigidos à prevenção do HPV. Países com uma problemática de saúde pública similar poderiam adotar esforços semelhantes aos apresentados e alinhá-los ao objetivo da Organização Mundial da Saúde: a erradicação do câncer cervical até 2030.

6.
J Public Health Manag Pract ; 27(6): E228-E235, 2021.
Article in English | MEDLINE | ID: mdl-32810076

ABSTRACT

CONTEXT: In September 2017, Hurricanes Irma and Maria impacted Puerto Rico, causing significant disruption of immunization services and vaccine losses due to widespread infrastructure and electrical grid damage and resulting cold chain failures. OBJECTIVE: To describe posthurricane efforts undertaken to restore and strengthen immunization services provided by Puerto Rico's federally funded Vaccines for Children (VFC) Program, a network of clinics that provide vaccines to eligible children. DESIGN: Historical records were reviewed to characterize Puerto Rico's prehurricane immunization system. Site visits to assess VFC clinic posthurricane operational status were conducted by the Puerto Rico Department of Health, working with the Centers for Disease Control and Prevention and other partners. Infrastructure repair and acquisition of backup generators, temperature data loggers, and replacement vaccines were carried out to restore operations. RESULTS: Prior to the hurricanes, 224 VFC clinics throughout the island provided immunizations. An initial assessment 10 days after Hurricane Maria showed that only 11 (5%) of the clinics were operational. Reasons included ongoing power outages; difficulties in obtaining generator fuel; equipment or facility damage; and damaged vaccines. The VFC clinics were restored incrementally; 123 (55%) were operational by December 2017, 193 (86%) by May 2018, and 204 (91%) by May 2019. Long-term recovery activities are underway and focus on strengthening Puerto Rico's immunization system to withstand future disasters, including improving backup power systems. CONCLUSION: Through coordinated efforts of the Puerto Rico Department of Health, the Centers for Disease Control and Prevention, and other partners, the operational status of VFC clinics posthurricanes was assessed and operations restored. Emergency plans for vaccine storage and handling, which called for alternative vaccine storage locations and backup generators, were inadequate to address disasters of the magnitude of Hurricanes Irma and Maria; such plans need to consider the possibility of large-scale disasters that result in long-term power outages.


Subject(s)
Cyclonic Storms , Disasters , Child , Humans , Immunization , Immunization Programs , Puerto Rico
7.
Lancet Oncol ; 17(7): 976-983, 2016 Jul.
Article in English | MEDLINE | ID: mdl-27267608

ABSTRACT

BACKGROUND: Immunotherapy targeting the PD-1 axis has activity in several tumour types. We aimed to establish the activity and safety of the PD-1 inhibitor pembrolizumab in patients with untreated brain metastases from melanoma or non-small-cell lung cancer (NSCLC). METHODS: In this non-randomised, open-label, phase 2 trial, we enrolled patients aged 18 years or older with melanoma or NSCLC with untreated brain metastases from the Yale Cancer Center. Patients had at least one untreated or progressive brain metastasis between 5 and 20 mm in diameter without associated neurological symptoms or the need for corticosteroids. Patients with NSCLC had tumour tissue positive for PD-L1 expression; this was not required for patients with melanoma. Patients were given 10 mg/kg pembrolizumab every 2 weeks until progression. The primary endpoint was brain metastasis response assessed in all treated patients. The trial is ongoing and here we present an early analysis. The study is registered with ClinicalTrials.gov, number NCT02085070. FINDINGS: Between March 31, 2014, and May 31, 2015, we screened 52 patients with untreated or progressive brain metastases (18 with melanoma, 34 with NSCLC), and enrolled 36 (18 with melanoma, 18 with NSCLC). A brain metastasis response was achieved in four (22%; 95% CI 7-48) of 18 patients with melanoma and six (33%; 14-59) of 18 patients with NSCLC. Responses were durable, with all but one patient with NSCLC who responded showing an ongoing response at the time of data analysis on June 30, 2015. Treatment-related serious and grade 3-4 adverse events were grade 3 elevated aminotransferases (n=1 [6%]) in the melanoma cohort, and grade 3 colitis (n=1 [6%]), grade 3 pneumonitis (n=1 [6%]), grade 3 fatigue (n=1 [6%]), grade 4 hyperkalemia (n=1 [6%]), and grade 2 acute kidney injury (n=1 [6%]) in the NSCLC cohort. Clinically significant neurological adverse events included transient grade 3 cognitive dysfunction and grade 1-2 seizures (n=3 [17%]) in the melanoma cohort. INTERPRETATION: Pembrolizumab shows activity in brain metastases in patients with melanoma or NSCLC with an acceptable safety profile, which suggests that there might be a role for systemic immunotherapy in patients with untreated or progressive brain metastases. FUNDING: Merck and the Yale Cancer Center.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Agents/therapeutic use , Brain Neoplasms/drug therapy , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Melanoma/drug therapy , Adenocarcinoma/drug therapy , Adenocarcinoma/secondary , Aged , Brain Neoplasms/secondary , Carcinoma, Large Cell/drug therapy , Carcinoma, Large Cell/secondary , Carcinoma, Non-Small-Cell Lung/secondary , Female , Follow-Up Studies , Humans , Lung Neoplasms/pathology , Lymphatic Metastasis , Male , Melanoma/pathology , Middle Aged , Neoplasm Staging , Prognosis , Skin Neoplasms/drug therapy , Skin Neoplasms/pathology , Survival Rate
9.
Catheter Cardiovasc Interv ; 83(4): 642-6, 2014 Mar 01.
Article in English | MEDLINE | ID: mdl-24214580

ABSTRACT

OBJECTIVE: To evaluate the impact of learning on outcome with use of two different left atrial appendage (LAA) occlusion devices. BACKGROUND: Two self-expanding devices, the Watchman and the Amplatzer Cardiac Plug (ACP), have been used for LAA occlusion in the last few years. It has been demonstrated that complications associated with implantation decrease in frequency with operator experience. However, the role of operator experience has not been compared across the two device types. METHODS: The study comprises 31 consecutive patients who underwent LAA occlusion. We compare the first 10 patients in whom an ACP was implanted with the subsequent eleven patients who underwent ACP implantation and with 10 cases where a Watcthman device was implanted. The composite safety end point comprised procedure-related events and excessive bleeding events. We also performed 3 months echocardiographic and clinical follow-up. RESULTS: There were not significant differences in the basal clinical and echocardiographical characteristics across the three groups. Cardiac complications only occurred in the ACP initial experience group (9% vs. 0% vs. 0% P = 0.04). Echocardiographic and clinical follow-up at 3 months was completed in all patients. No significant residual leak was detected. One patient in the ACP initial experience group developed a thrombus on the device. One patient in ACP late experience presented an ischemic stroke. CONCLUSIONS: Complications associated with LAA occlusion cluster early in the peri-procedural period and significantly decrease in frequency with operator experience. Initial experience gained with one of device may improve outcome with use of alternative LAA occlusion devices.


Subject(s)
Atrial Appendage , Atrial Fibrillation/therapy , Cardiac Catheterization/instrumentation , Clinical Competence , Learning Curve , Aged , Aged, 80 and over , Atrial Appendage/diagnostic imaging , Atrial Fibrillation/diagnosis , Atrial Fibrillation/physiopathology , Cardiac Catheterization/adverse effects , Equipment Design , Female , Humans , Male , Time Factors , Treatment Outcome , Ultrasonography
10.
J Oral Maxillofac Surg ; 72(5): 892-901, 2014 May.
Article in English | MEDLINE | ID: mdl-24583086

ABSTRACT

PURPOSE: Maxillary sinus grafting is a predictable and reliable procedure that has been routinely performed for more than 30 years. The complication rate is low, but some cases may require additional surgery, and the outcome of oral rehabilitation may be affected. The purpose of the present study was to evaluate the early and late complications after sinus lift procedures performed in the authors' center, with special attention to risk factors and their connection to the principles of prevention and treatment. MATERIALS AND METHODS: A retrospective analysis of 127 patients was performed. During an 8-year period, patients underwent preprosthetic surgery with implants and a maxillary sinus lift procedure because of maxillary atrophy. In total, 202 sinus lift procedures were performed and 364 implants were placed (117 simultaneously and 247 delayed). Clinical data, local or systemic disease, risk factors, type of surgery, intraoperative and postoperative complications, and the evolution of the implant zone were recorded. RESULTS: The most common intraoperative complication was damage to the Schneiderian membrane (25.7%), which did not show any connection to postoperative complications. Thirty patients (14.9%) developed postoperative complications, including wound infection, abscess, or dehiscence with drainage (9 cases), maxillary sinusitis of the operated area (6 cases), partial exposure of the simultaneous onlay graft (6 cases), and loss of the graft (2 cases). CONCLUSION: Sinus lift surgery is a proven and reliable technique because of the low observed rate of postoperative complications and the success rate of implants placed into the grafted area. To minimize risk, care must be taken with all technical details and risk factors that can lead to fatality.


Subject(s)
Intraoperative Complications , Postoperative Complications , Sinus Floor Augmentation/adverse effects , Abscess/etiology , Adult , Aged , Autografts/transplantation , Bone Substitutes/therapeutic use , Bone Transplantation/methods , Dental Implantation, Endosseous/methods , Dental Implants/adverse effects , Diabetes Complications , Female , Follow-Up Studies , Graft Survival , Humans , Intraoperative Complications/prevention & control , Male , Maxilla/surgery , Maxillary Sinusitis/etiology , Middle Aged , Nasal Mucosa/injuries , Periodontal Atrophy/surgery , Postoperative Complications/prevention & control , Retrospective Studies , Risk Factors , Smoking , Surgical Wound Dehiscence , Surgical Wound Infection/etiology , Young Adult
11.
P R Health Sci J ; 33(3): 122-8, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25244881

ABSTRACT

OBJECTIVE: The Asthma Control Test (ACT) questionnaire has been widely used and validated in various ethnic groups, showing an adequate correlation with physician assessment of asthma control. We sought to evaluate the relationship between ACT-defined asthma control and peak flow measures in subjects living in Puerto Rico. METHODS: A retrospective evaluation of data collected by a mobile asthma clinic in 2 cities in Puerto Rico was conducted. The participants completed an asthma and rhinitis survey. Self-reported asthmatics answered the age-appropriate Spanish version of the ACT. Peak flows (PEF) were measured. Subjects were skin-tested against the common local aeroallergens. The study was approved by the University of Puerto Rico's IRB. RESULTS: We evaluated data from 70 subjects aged 4 to 68. Of them, 82.85% were 12 years old or older, 64.3% reported having a history of asthma, 57.14% reported that they still suffered from asthma, 81.4% reported that they suffered from rhinitis, and 78.57% were sensitized to at least 1 antigen. The mean ACT score of current asthmatics was 18.97, while that of past asthmatics was 23.83 (p = 6.6e-6). The variability of PEF increased as the ACT score increased. Age had no impact on asthma control (p > 0.25), while the effect of PEF on the control of asthma was tied to gender. Rhinitis was also associated with poor asthma control as defined by the ACT score. No other covariate was found to be statistically significant (p < 0.05). CONCLUSION: Our study supports the use of the ACT to evaluate asthma control in asthmatics living in Puerto Rico. Research into factors associated with poor asthma control, and the importance of rhinitis with regard to such control, is needed.


Subject(s)
Asthma/diagnosis , Asthma/physiopathology , Peak Expiratory Flow Rate , Adolescent , Adult , Aged , Asthma/prevention & control , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Puerto Rico , Retrospective Studies , Young Adult
12.
Cir Cir ; 92(1): 59-68, 2024.
Article in English | MEDLINE | ID: mdl-38537236

ABSTRACT

OBJECTIVE: Obesity is a global epidemic affecting developing countries. The relationship between obesity and perioperative outcomes during elective lumbar spine surgery remains controversial, especially in those without morbid disease. MATERIALS AND METHODS: We retrospectively revised the medical records of patients with lumbar spine degeneration subjected to elective surgery. The data retrieved included demographic and clinical characteristics, body mass index (BMI), obesity status (BMI ≥ 30), surgical interventions, estimated blood loss (EBL), operative time, length of stay (LOS), and post-operative complications. Perioperative outcomes were compared between Grade I-II obese and non-obese individuals. RESULTS: We enrolled 53 patients, 18 with Grade I-II obesity. Their median age was 51, with no differences in gender, comorbidities, laboratory parameters, and surgical procedures received between groups. No clinically relevant differences were found between grade I-II obese and non-obese participants in EBL (300 mL vs. 250 mL, p = 0.069), operative time (3.2 h vs. 3.0 h, p = 0.037), and LOS (6 days vs. 5 days, p = 0.3). Furthermore, BMI was not associated with the incidence of significant bleeding and long stay but showed a modest correlation with operative time. CONCLUSION: Grade I-II obesity does not increase surgical complexity nor perioperative complications during open lumbar spine surgery.


OBJETIVO: La obesidad es una epidemia mundial que afecta a países subdesarrollados. Su relación con los resultados de la cirugía de columna lumbar electiva sigue siendo controvertida, especialmente en obesos sin enfermedad mórbida. MÉTODOS: Se revisaron los expedientes de pacientes con degeneración de la columna lumbar sometidos a cirugía. Los datos recuperados incluyeron características demográficas y clínicas, índice de masa corporal (IMC), estado de obesidad (IMC > 30), intervenciones quirúrgicas, sangrado estimado, tiempo operatorio, tiempo de estancia y complicaciones. Los resultados se compararon entre individuos obesos grado I-II y controles. RESULTADOS: Se incluyeron 53 pacientes, 18 con obesidad de grado I-II. La edad media fue de 51 años, sin diferencias en el sexo, las comorbilidades, los parámetros de laboratorio y los procedimientos quirúrgicos recibidos entre grupos. No se encontraron diferencias relevantes entre los participantes obesos y los no obesos en sangrado (300 vs. 250 mL, p = 0.069), tiempo operatorio (3.2 vs. 3.0 horas, p = 0.037) y estancia (6 vs. 5 días, p = 0.3). El IMC no se asoció con hemorragia y larga estancia, pero mostró una correlación modesta con el tiempo operatorio. CONCLUSIONES: La obesidad grado I-II no predispone a complicaciones durante la cirugía de columna lumbar.


Subject(s)
Lumbar Vertebrae , Spinal Fusion , Humans , Middle Aged , Lumbar Vertebrae/surgery , Retrospective Studies , Spinal Fusion/methods , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Minimally Invasive Surgical Procedures/adverse effects , Obesity/complications , Obesity/epidemiology , Treatment Outcome
13.
Hum Vaccin Immunother ; 20(1): 2323264, 2024 Dec 31.
Article in English | MEDLINE | ID: mdl-38599678

ABSTRACT

Dengvaxia is the first dengue vaccine recommended in the United States (U.S.). It is recommended for children aged 9-16 y with laboratory-confirmed previous dengue infection and living in areas where dengue is endemic. We conducted focus groups with parents and in-depth interviews with key informants (i.e. practicing pediatricians, physicians from immunization clinics, university researchers, and school officials) in Puerto Rico (P.R.) to examine acceptability, barriers, and motivators to vaccinate with Dengvaxia. We also carried out informal meetings and semi-structured interviews to evaluate key messages and educational materials with pediatricians and parents. Barriers to vaccination included lack of information, distrust toward new vaccines, vaccine side effects and risks, and high cost of/lack of insurance coverage for laboratory tests and vaccines. Motivators included clear information about the vaccine, a desire to prevent future dengue infections, the experience of a previous dengue infection or awareness of dengue fatality, vaccine and laboratory tests covered by health insurance, availability of rapid test results and vaccine appointments. School officials and parents agreed parents would pay a deductible of $5-20 for Dengvaxia. For vaccine information dissemination, parents preferred an educational campaign through traditional media and social media, and one-on-one counseling of parents by healthcare providers. Education about this vaccine to healthcare providers will help them answer parents' questions. Dengvaxia acceptability in P.R. will increase by addressing motivators and barriers to vaccination and by disseminating vaccine information in plain language through spokespersons from health institutions in P.R.


Subject(s)
Dengue Vaccines , Dengue , Vaccines , Child , Humans , Dengue/prevention & control , Dengue Vaccines/adverse effects , Parents , Puerto Rico/epidemiology , United States , Vaccination/methods , Adolescent
14.
Lab Invest ; 93(3): 268-78, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23358109

ABSTRACT

Metastatic involvement of the skeleton is a frequent consequence of advanced prostate cancer. These skeletal metastases cause a number of debilitating complications and are refractory to current treatments. New therapeutic options are being explored, including conditionally replicating adenoviruses (CRAds). CRAds are engineered to selectively replicate in and destroy tumor cells and can be 'armed' with exogenous transgenes for enhanced potency. We hypothesized that a CRAd armed with osteoprotegerin (OPG), an inhibitor of osteoclastogenesis, would inhibit the progression of prostate cancer bone metastases by directly lysing tumor cells and by reducing osteoclast activity. Although prostate cancer bone metastases are predominantly osteoblastic in nature, increased osteoclast activity is critical for the growth of these lesions. Ad5-Δ24-sOPG-Fc-RGD is a CRAd that carries a fusion of the ligand-binding domains of OPG and the Fc region of human IgG1 in place of the viral E3B genes. To circumvent low tumor cell expression of the native adenoviral receptor, an arginine-glycine-aspartic acid (RGD) peptide insertion within the viral fiber knob allows infection of cells expressing α(v) integrins. A 24-base pair deletion (Δ24) within viral E1A limits replication to cells with aberrant retinoblastoma cell cycle regulator/tumor suppressor expression. We have confirmed that Ad5-Δ24-sOPG-Fc-RGD replicates within and destroys prostate cancer cells and, in both murine and human coculture models, that infection of prostate cancer cells inhibits osteoclastogenesis in vitro. In a murine model, progression of advanced prostate cancer bone metastases was inhibited by treatment with Ad5-Δ24-sOPG-Fc-RGD but not by an unarmed control CRAd.


Subject(s)
Bone Neoplasms/secondary , Bone Neoplasms/therapy , Oncolytic Virotherapy/methods , Osteoprotegerin/pharmacology , Prostatic Neoplasms/pathology , Adenoviridae/genetics , Analysis of Variance , Animals , Cell Line, Tumor , Humans , Immunoglobulin G/genetics , Luciferases , Male , Mice , Oligopeptides/genetics , Oligopeptides/metabolism , Osteoclasts/drug effects , Osteoprotegerin/genetics , Osteoprotegerin/metabolism , Real-Time Polymerase Chain Reaction , X-Ray Microtomography
15.
Mol Ther ; 20(12): 2222-33, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22948673

ABSTRACT

Targeting the tumor stroma in addition to the malignant cell compartment is of paramount importance to achieve complete tumor regression. In this work, we modified a previously designed tumor stroma-targeted conditionally replicative adenovirus (CRAd) based on the SPARC promoter by introducing a mutated E1A unable to bind pRB and pseudotyped with a chimeric Ad5/3 fiber (Ad F512v1), and assessed its replication/lytic capacity in ovary cancer in vitro and in vivo. AdF512v1 was able to replicate in fresh samples obtained from patients: (i) with primary human ovary cancer; (ii) that underwent neoadjuvant treatment; (iii) with metastatic disease. In addition, we show that four intraperitoneal (i.p.) injections of 5 × 10(10) v.p. eliminated 50% of xenografted human ovary tumors disseminated in nude mice. Moreover, AdF512v1 replication in tumor models was enhanced 15-40-fold when the tumor contained a mix of malignant and SPARC-expressing stromal cells (fibroblasts and endothelial cells). Contrary to the wild-type virus, AdF512v1 was unable to replicate in normal human ovary samples while the wild-type virus can replicate. This study provides evidence on the lytic capacity of this CRAd and highlights the importance of targeting the stromal tissue in addition to the malignant cell compartment to achieve tumor regression.


Subject(s)
Adenovirus E1A Proteins/genetics , Oncolytic Virotherapy/methods , Ovarian Neoplasms/therapy , Animals , Cell Line, Tumor , Female , Humans , Mice , Ovarian Neoplasms/genetics , Stromal Cells/metabolism , Xenograft Model Antitumor Assays
16.
Am J Phys Anthropol ; 152 Suppl 57: 119-34, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24166771

ABSTRACT

The primate body hosts trillions of microbes. Interactions between primate hosts and these microbes profoundly affect primate physiology, reproduction, health, survival, and ultimately, evolution. It is increasingly clear that primate health cannot be understood fully without knowledge of host-microbial interactions. Our goals here are to review what is known about microbiomes of the female reproductive tract and to explore several factors that influence variation within individuals, as well as within and between primate species. Much of our knowledge of microbial variation derives from studies of humans, and from microbes located in nonreproductive regions (e.g., the gut). We review work suggesting that the vaginal microbiota affects female health, fecundity, and pregnancy outcomes, demonstrating the selective potential for these agents. We explore the factors that correlate with microbial variation within species. Initial colonization by microbes depends on the manner of birth; most microbial variation is structured by estrogen levels that change with age (i.e., at puberty and menopause) and through the menstrual cycle. Microbial communities vary by location within the vagina and can depend on the sampling methods used (e.g., swab, lavage, or pap smear). Interindividual differences also exist, and while this variation is not completely understood, evidence points more to differences in estrogen levels, rather than differences in external physical environment. When comparing across species, reproductive-age humans show distinct microbial communities, generally dominated by Lactobacillus, unlike other primates. We develop evolutionary hypotheses to explain the marked differences in microbial communities. While much remains to be done to test these hypotheses, we argue that the ample variation in primate mating and reproductive behavior offers excellent opportunities to evaluate host-microbe coevolution and adaptation.


Subject(s)
Microbiota , Primates/microbiology , Primates/physiology , Vagina/microbiology , Animals , Anthropology, Physical , Biological Evolution , Disease , Female , Humans
17.
Attach Hum Dev ; 15(1): 1-23, 2013.
Article in English | MEDLINE | ID: mdl-23216390

ABSTRACT

This multi-method multi-informant study assessed 105 Puerto Rican kindergartners' sense of self-worth in family relationships as coded from their responses to the Attachment Story Completion Task (ASCT). The ASCT scores were compared with responses to two other age-appropriate self-evaluation measures (the Cassidy Puppet Interview and the Pictorial Scales of Social Acceptance). Correlations of children's scores on the three self-measures with maternal ratings of the mother-child relationship and teacher ratings of the child's prosocial behavior with peers were then compared. ASCT self-worth and Puppet Interview scores were strongly correlated with each other and both were modestly related to the pictorial social acceptance scales. All three measures were significantly associated with maternal and teacher reports of child behavior, but the strongest correlations were obtained with the ASCT. Coding the ASCT in terms of self-worth appears to be a promising approach for evaluating young children's (vicariously expressed) self-worth in family relationships.


Subject(s)
Child Behavior , Mother-Child Relations , Object Attachment , Peer Group , Projective Techniques , Self Concept , Adult , Child , Child, Preschool , Female , Humans , Interpersonal Relations , Male , Personality Assessment , Psychometrics , Puerto Rico , Surveys and Questionnaires
18.
Attach Hum Dev ; 15(1): 25-49, 2013.
Article in English | MEDLINE | ID: mdl-23216391

ABSTRACT

Three related hypotheses derived from attachment theory were examined in this multi-informant and multi-method study of 71 postdivorce mothers and their preschool children (40 boys, 31 girls): (1) mother-child interactions observed at home will be related to attachment-related representations by children (Attachment Story Completion Task or ASCT) and mothers (Parent Attachment Interview or PAI); and (2) these variables will be inversely correlated with maternal depressive symptoms and positively with social support (from mother's parents and the child's father); and (3) mother-child observations and representations will predict teacher-rated peer behavior. Where appropriate, child gender, maternal income, and child receptive language were statistically controlled. More harmonious observed mother-child interactions were associated with children's sense of self-worth in family relationships (ASCT) and maternal accounts of sensitive-effective guidance (PAI). Observational and representational variables were inversely correlated with maternal depressive symptoms. Mothers' satisfaction with social support from their parents was indirectly linked to the family variables while social support from the child's father had no measurable effect on the mother-child variables. Mother-child variables and teacher ratings were uncorrelated but explained independent variance in ASCT self-worth scores.


Subject(s)
Divorce , Interpersonal Relations , Mother-Child Relations , Object Attachment , Peer Group , Self Concept , Adult , Child, Preschool , Depression , Female , Humans , Male , Midwestern United States , Projective Techniques , Social Support , Surveys and Questionnaires
19.
Int J Spine Surg ; 17(5): 670-677, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37460237

ABSTRACT

BACKGROUND: Limited literature exists regarding the differences in demographics, causes, comorbidities, presentation, and structural changes associated with cervical spine degeneration in patients from distinct geographic regions. The authors aimed to evaluate the demographic and clinical characteristics of patients with cervical spine degeneration admitted to a single center in Mexico. METHODS: This study enrolled patients with degenerative disease of the cervical spine. Clinical data were retrieved from medical records and retrospectively characterized. RESULTS: A total of 50 patients with cervical spine degeneration were included in the analysis. Of these, 26% were men with a median age of 54 years. Hypertension, depression, anxiety, obesity, and alcohol consumption were presented in about a quarter of the participants. In addition, we observed hypertriglyceridemia and hypercholesterolemia in 72% and 46% of participants, respectively. The median duration of symptoms was 11 months, including radicular arm/neck pain (80%), tingling (80%), reduced muscle strength (48%), and gait disturbances (48%). Forty percent of patients had 2 cervical segments radiologically involved, mainly at C5-C6, with changes such as disc herniation (88%), foraminal stenosis with nerve root compression (67%), reduced spinal canal-to-vertebral body ratio (38%), and ligamentum flavum hypertrophy (24%). Also, 22% of patients showed degenerative cervical myelopathy. Strikingly, 48% of enrolled individuals showed cervicolumbar tandem spinal stenosis, mainly in L4-L5 and L5-S1, who were generally older, had a longer duration of symptoms, and had a higher comorbidity burden, including hyperglycemia, hypertension, and depression. CONCLUSIONS: The demographic and clinical characteristics of degenerative cervical spine disease in Mexico differ with respect to other geographical regions by a younger age of diagnosis, a high frequency of cardiovascular, metabolic, and mental health comorbidities, and an increased prevalence of concomitant lumbar spinal stenosis. CLINICAL RELEVANCE: Our findings reveal a considerably high burden of cervicolumbar tandem spinal stenosis as a distinctive feature of Mexican patients with cervical spine degeneration.

20.
Cir Cir ; 2023 Aug 08.
Article in Spanish | MEDLINE | ID: mdl-37553009

ABSTRACT

Background: The Disability of the Arm, Shoulder and Hand (DASH) questionnaire assesses the impact of upper extremity disorders on quality of life. However, its use in the Mexican population has not been formally validated. Objective: To conduct a cultural adaptation and validation of the DASH questionnaire to evaluate the perspective of patients with neurogenic disorders of the upper extremity regarding the impact on their quality of life. Method: We performed an adaptation of the Spanish version of the DASH questionnaire to the Mexican vocabulary and applied it to 478 volunteers. Ceiling effect, floor effect, item-total correlation, descriptive statistics of items and total score, internal consistency, precision, cross-sectional and longitudinal validity were estimated by comparing healthy controls and affected individuals with different disability levels. Results: Our DASH questionnaire version was equivalent to those previously approved and showed homogeneity of the items with respect to the total value of the questionnaire (Cronbach's alpha > 0.96). In addition, it showed an accuracy of 7.25 points and the crosssectional and longitudinal validity was documented with significant differences between groups and subgroups with distinct disability levels. Conclusions: The DASH questionnaire can be used with a high level of confidence in the Mexican population.


Antecedentes: El cuestionario de discapacidad de brazo, hombro y mano (DASH, Disabilities of the Arm, Shoulder and Hand) mide el impacto de patologías del miembro superior en la calidad de vida. Sin embargo, su uso en la población mexicana no ha sido formalmente validado. Objetivo: Realizar la adaptación cultural y validación del cuestionario DASH para conocer la perspectiva de pacientes con trastornos neurogénicos del miembro superior respecto al impacto en su calidad de vida. Método: Se realizó una adaptación al vocabulario mexicano de la versión española del cuestionario DASH y se aplicó en 478 voluntarios. Se estimaron el efecto techo, el efecto suelo, la correlación ítem-total, las medidas de tendencia central de ítems y el puntaje total, la consistencia interna, la precisión y la validez transversal y longitudinal mediante la comparación de individuos sanos y enfermos con diferente nivel de discapacidad. Resultados: Nuestra versión del cuestionario DASH resultó equivalente a las previamente aprobadas y mostró homogeneidad de los ítems respecto al valor total del cuestionario (alfa de Cronbach > 0.96). Además, tuvo una precisión de 7.25 puntos y se documentó la validez transversal y longitudinal con diferencias significativas entre grupos y subgrupos con diferente nivel de discapacidad. Conclusiones: El cuestionario DASH puede ser empleado con un nivel de confianza alto en la población mexicana.

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