Comprehensive functional evaluation of head and neck squamous cell carcinoma with BH3-profiling demonstrates apoptotic competency and therapeutic efficacy of BH3-mimetics.

Evasion of apoptosis promotes tumor survival and contributes to resistance to cancer therapeutics in head and neck squamous cell carcinoma (HNSCC). Our recent work has demonstrated that HNSCC's highly express pro-survival anti-apoptotic proteins Bcl-xL and Mcl-1. Nevertheless, the mechanism of HNSCC to evade apoptosis is still not well understood. We used BH3 profiling, a functional assay which measures mitochondrial depolarization in response to the introduction of BH3 peptides, to evaluate apoptosis competency and dependency upon BCL-2 family anti-apoptotic proteins in a panel of immortalized and patient-derived HNSCC lines. We assessed response to BH3 mimetics including ABT-263 (navitoclax), an inhibitor of Bcl-2/Bcl-xL/Bcl-w, and S63845, an inhibitor of Mcl-1, both as single agents and in combination. We demonstrate that apoptosis signaling appears to be intact in the majority of HNSCC cells, and they are co-dependent upon Bcl-xL and Mcl-1 for survival. We found the combination to be highly synergistic in 2D culture and in 3D organoid models of HHNSCC. Given our findings that co-dependency on Bcl-xL and Mcl-1 is common, and co-inhibition of these molecules is synergistic for growth suppression in HNSCC cells, these results elucidate the therapeutic potential of BCL-xL and MCL-1 inhibition in HNSCC.

Characterization of a Diverse Set of Conditionally Reprogrammed Head and Neck Cancer Cell Cultures.

OBJECTIVE: To establish and characterize a diverse library of head and neck squamous cell cancer (HNSCC) cultures using conditional reprogramming (CR). METHODS: Patients enrolled on an IRB-approved protocol to generate tumor cell cultures using CR methods. Tumor and blood samples were collected and clinical information was recorded. Successful CR cultures were validated against banked reference tumors with short tandem repeat genotyping. Cell morphology was archived with photodocumentation. Clinical and demographic factors were evaluated for associations with successful establishment of CR culture. Human papilloma virus (HPV) genotyping, clonogenic survival, MTT assays, spheroid growth, and whole exome sequencing were carried out in selected cultures. RESULTS: Forty four patients were enrolled, with 31 (70%) successful CR cultures, 32% derived from patients who identified as Black and 61% as Hispanic. All major head and neck disease sites were represented, including 15 (48%) oral cavity and 8 (26%) p16-positive oropharynx cancers. Hispanic ethnicity and first primary tumors (vs. second primary or recurrent tumors) were significantly associated with successful CR culture. HPV expression was conserved in CR cultures, including CR-024, which carried a novel HPV-69 serotype. CR cultures were used to test cisplatin responses using MTT assays. Previous work has also demonstrated these models can be used to assess response to radiation and can be engrafted in mouse models. Whole exome sequencing demonstrated that CR cultures preserved tumor mutation burden and driver mutations. CONCLUSION: CR culture is highly successful in propagating HNSCC cells. This study included a high proportion of patients from underrepresented minority groups. LEVEL OF EVIDENCE: Not Applicable Laryngoscope, 134:2748-2756, 2024.

Organ-specific heterogeneity in tumor-infiltrating immune cells and cancer antigen expression in primary and autologous metastatic lung adenocarcinoma.

BACKGROUND: Tumor immune microenvironment (TIME) and cancer antigen expression, key factors for the development of immunotherapies, are usually based on the data from primary tumors due to availability of tissue for analysis; data from metastatic sites and their concordance with primary tumor are lacking. Although of the same origin from primary tumor, organ-specific differences in the TIME in metastases may contribute to discordant responses to immune checkpoint inhibitor agents. In immunologically 'cold' tumors, cancer antigen-targeted chimeric antigen receptor (CAR) T-cell therapy can promote tumor-infiltrating lymphocytes; however, data on distribution and intensity of cancer antigen expression in primary tumor and matched metastases are unavailable. METHODS: We performed a retrospective review of a prospectively maintained database of patients who had undergone curative resection of pathological stage I-III primary lung adenocarcinoma from January 1995 to December 2012 followed by metastatic recurrence and resection of metastatic tumor (n=87). We investigated the relationship between the primary tumor and metastasis TIME (ie, tumor-infiltrating lymphocytes, tumor-associated macrophages, and programmed death-ligand 1 (PD-L1)) and cancer antigen expression (ie, mesothelin, CA125, and CEACAM6) using multiplex immunofluorescence. RESULTS: Brain metastases (n=36) were observed to have fewer tumor-infiltrating lymphocytes and greater PD-L1-negative tumor-associated macrophages compared with the primary tumor (p<0.0001); this relatively inhibitory TIME was not observed in other metastatic sites. In one in three patients, expression of PD-L1 is discordant between primary and metastases. Effector-to-suppressor (E:S) cell ratio, median effector cells (CD20+ and CD3+) to suppressor cells (CD68/CD163+) ratio, in metastases was not significantly different between patients with varying E:S ratios in primary tumors. Cancer antigen distribution was comparable between primary and metastases; among patients with mesothelin, cancer antigen 125, or carcinoembryonic antigen adhesion molecule 6 expression in the primary tumor, the majority (51%-75%) had antigen expression in the metastases; however, antigen-expression intensity was heterogenous. CONCLUSIONS: In patients with lung adenocarcinoma, brain metastases, but not other sites of metastases, exhibited a relatively immune-suppressive TIME; this should be considered in the context of differential response to immunotherapy in brain metastases. Among patients with cancer antigen expression in the primary tumor, the majority had antigen expression in metastases; these data can inform the selection of antigen-targeted CARs to treat patients with metastatic lung adenocarcinoma.

CDK4/6 Inhibition Induces Senescence and Enhances Radiation Response by Disabling DNA Damage Repair in Oral Cavity Squamous Cell Carcinoma.

PURPOSE: HPV(-) OCSCC resists radiation treatment. The CDKN2A gene, encoding p16INK4A, is commonly disrupted in OCSCC. p16 inhibits CDK4/CDK6, leading to cell cycle arrest, but the biological sequelae of CDK4/6 inhibition in OCSCC remains understudied. This study examines whether inhibition of CDK4/6 enhances radiation response in OCSCC. METHODS: MTT assays were performed in OCSCC cell lines HN5 and CAL27 following treatment with palbociclib. Clonogenic survival and synergy were analyzed after radiation (RT-2 or 4Gy), palbociclib (P) (0.5 µM or 1 µM), or concurrent combination treatment (P+RT). DNA damage/repair and senescence were examined. CDK4/6 were targeted via siRNA to corroborate P+RT effects. Three-dimensional immortalized spheroids and organoids derived from patient tumors (conditionally reprogrammed OCSCC CR-06 and CR-18) were established to further examine and validate responses to P+RT. RESULTS: P+RT demonstrated reduced viability and synergy, increased ß-gal expression (~95%), and ~two-fold higher γH2AX. Rad51 and Ku80 were reduced after P+RT, indicating impairment of both HR and NHEJ. siCDK4/6 increased senescence with radiation. Spheroids showed reduced proliferation and size with P+RT. CR-06 and CR-18 further demonstrated three-fold reduced proliferation and organoids size with P+RT. CONCLUSION: Targeting CDK4/6 can lead to improved efficacy when combined with radiation in OCSCC by inducing senescence and inhibiting DNA damage repair.

Statistical Analysis of the Pouring Method's Influence on the Distribution of Metallic Macrofibres into Vibrated Concrete.

The use of fibre-reinforced concrete (FRC) in structural applications is increasing significantly as a result of (1) the acceptance of this composite into design guidelines and (2) the improvement in terms of sustainability performance that has been reported for cases where FRC has been used. In this context, fibre orientation and distribution are factors that govern the post-cracking response of the FRC. Researchers have already dealt with the analysis of both variables from an experimental and numerical perspective, and design-oriented recommendations were included in existing design guidelines (i.e., fib Model Code 2020). Nonetheless, there are still technical aspects to be answered within a research framework before the influence of these variables on the mechanical response of FRC could be covered with sufficient reliability. In this regard, this research is aimed at shedding light on the influence of the mould geometry and concrete pouring/vibration procedures on the fibre orientation and distribution variables as well as on the post-cracking performance of the FRC. An extensive experimental programme aimed at characterising these variables using novel testing techniques (i.e., an inductive non-destructive approach for quantifying fibre amount and orientation and the BCN test for assessing the pre- and post-cracking responses of the FRC) was carried out for this purpose. A relationship has been found between the shape of the formwork and the direction of pouring, along with the direction and distribution of the fibres, both of which proved to have an influence on the residual tensile strength of the concrete. However, it has been confirmed that the first crack resistance depends on the concrete matrix, with the addition of fibres having no relevant influence on that mechanical parameter. The results and conclusions derived from this experimental programme can be extended to FRCs and boundary conditions similar to those established herein.

Establishment of a diverse head and neck squamous cancer cell bank using conditional reprogramming culture methods.

Most laboratory models of head and neck squamous cell cancer (HNSCC) rely on established immortalized cell lines, which carry inherent bias due to selection and clonality. We established a robust panel of HNSCC tumor cultures using a "conditional reprogramming" (CR) method, which utilizes a rho kinase inhibitor (Y-27632) and co-culture with irradiated fibroblast (J2 strain) feeder cells to support indefinite tumor cell survival. Sixteen CR cultures were successfully generated from 19 consecutively enrolled ethnically and racially diverse patients with HNSCC at a tertiary care center in the Bronx, NY. Of the 16 CR cultures, 9/16 were derived from the oral cavity, 4/16 were derived from the oropharynx, and 3/16 were from laryngeal carcinomas. Short tandem repeat (STR) profiling was used to validate culture against patient tumor tissue DNA. All CR cultures expressed ΔNp63 and cytokeratin 5/6, which are markers of squamous identity. Human papillomavirus (HPV) testing was assessed utilizing clinical p16 staining on primary tumors, reverse transcription polymerase chain reaction (RT-PCR) of HPV16/18-specific viral oncogenes E6 and E7 in RNA extracted from tumor samples, and HPV DNA sequencing. Three of four oropharyngeal tumors were p16 and HPV-positive and maintained HPV in culture. CR cultures were able to establish three-dimensional spheroid and murine flank and orthotopic tongue models. CR methods can be readily applied to all HNSCC tumors regardless of patient characteristics, disease site, and molecular background, providing a translational research model that properly includes patient and tumor diversity.

Comprehensive Assessment of the Universal Healthcare System in Dentistry Japan: A Retrospective Observational Study.

Japan's universal healthcare insurance is facing economic challenges due to the advanced aging society, however, objective data of dental expenditure has never been introduced. This study aimed to identify the associated factors with dental expenditures using government-provided digitized insurance claims data and calculated the spending in the context of dental cost per person (DCPP). Seven associated factors analyzed were age, demographic, geographic, socioeconomic, regional wealth, the impact of the 8020-national campaign implementation (keep 20 teeth at age 80), and the effect of the home-visit dentistry for the elders. The average DCPP was high in older populations (75+) in all prefectures. The prefectures with the highest and lowest DCPP were significant compared to other states and retained their respective places in the cost hierarchy over the four years. The prefectures with more citizens participating in government assistance programs (GAP) had greater DCPPs. Dental costs were significantly related to geographic regions, age, per capita income, government assistance program prevalence, office complete denture frequency, and home visit care per patient. With a growing aging population, dental care costs will continue to increase, burdening its fiscal future. Associated factors identified should be considered to control the contentious increase of healthcare cost.

Effect of Steel Fibre Reinforcement on Flexural Fatigue Behaviour of Notched Structural Concrete.

One of the biggest challenges in facilitating the installation of concrete is the development of fibre-reinforced concrete. Although nowadays fibre reinforced concrete is relatively common, it is still necessary to deepen in the study on its behaviour, especially regarding its fatigue behaviour. This paper proposes a new methodology to analyse the bending fatigue behaviour of notched test specimens. From these tests, it was possible to verify that, despite carrying out the tests with load control, the presence of fibres extends the fatigue life of the concrete after cracking. This effect is of great importance since during the extra lifetime with the cracked concrete, the damage to the concrete will be evident and the corresponding maintenance measures can be carried out. Regarding the analysis of the results, in addition to obtaining a traditional S-N curve, two new criteria have been applied, namely energy and notch growth. From these two new approaches, it was possible to determine critical energy values that can be used as predictive indicators of the collapse of the element. Moreover, from the notch growth analysis, it was possible to determine crack growth rate as a function of the stress conditions for the concrete and the specific geometry. From the comparison among the results obtained from the different tests, a limit cracking index of 0.05 mm can be defined.

Association between cognitive health and masticatory conditions: a descriptive study of the national database of the universal healthcare system in Japan.

Cognitive health is subject to decline with increasing numbers of lost teeth which impacts mastication. This study is a descriptive data analysis of the association between masticatory and cognitive conditions using a large database. We obtained the dental and medical records from Japan's universal healthcare system (UHCS) from the national database in 2017. The data from 94% of the Japanese population aged 65 and over is included. It is inclusive of diagnostic codes for various types of cognitive impairment, as well as dental treatment records from 2012 to 2017. The cognitive impairment group was compared to those without a diagnosis of cognitive impairment. Crude odds ratio between loss of mastication with natural teeth (exposure) and cognitive impairments (outcome) were compared. Patients who have lost masticatory function are likely to have cognitive impairment with an odds ratio of 1.89 (p<0.0001) for early elderly (aged 65-75) and 1.33 (p<0.0001) for advanced elderly (over 75). Patients who are edentulous and function with complete dentures are likely to have cognitive impairment with an odds ratio of 2.38 (p<0.0001) and 1.38 (p<0.0001), respectively. The data shows a convincing and significant result of an association between cognitive health and oral health, related to masticatory conditions.

Palbociclib Renders Human Papilloma Virus-Negative Head and Neck Squamous Cell Carcinoma Vulnerable to the Senolytic Agent Navitoclax.

We demonstrate that inhibition of cyclin-dependent kinases 4/6 (CDK4/6) leads to senescence in human papillomavirus (HPV)-negative (-) head and neck squamous cell carcinoma (HNSCC), but not in HPV-positive (+) HNSCC. The BCL-2 family inhibitor, navitoclax, has been shown to eliminate senescent cells effectively. We evaluated the efficacy of combining palbociclib and navitoclax in HPV- HNSCC. Three HPV- HNSCC cell lines (CAL27, HN31, and PCI15B) and three HPV+ HNSCC cell lines (UPCI-SCC-090, UPCI-SCC-154, and UM-SCC-47) were treated with palbociclib. Treatment drove reduced expression of phosphorylated Rb (p-Rb) and phenotypic evidence of senescence in all HPV- cell lines, whereas HPV+ cell lines did not display a consistent response by Rb or p-Rb and did not exhibit morphologic changes of senescence in response to palbociclib. In addition, treatment of HPV- cells with palbociclib increased both ß-galactosidase protein expression and BCL-xL protein expression compared with untreated controls in HPV- cells. Co-expression of ß-galactosidase and BCL-xL occurred consistently, indicating elevated BCL-xL expression in senescent cells. Combining palbociclib with navitoclax led to decreased HPV- HNSCC cell survival and led to increased apoptosis levels in HPV- cell lines compared with each agent given alone. IMPLICATIONS: This work exploits a key genomic hallmark of HPV- HNSCC (CDKN2A disruption) using palbociclib to induce BCL-xL-dependent senescence, which subsequently causes the cancer cells to be vulnerable to the senolytic agent, navitoclax.

Relación entre el tipo de alimentación de los lactantes y la edad de gateo: AMI Pediátrico: Ciudad Bolívar, Estado Bolívar / Relationship between the type of feeding of infants and the age of crawling: Pediatric AMI: Bolivar City, Bolivar State

INTRODUCCIÓN: Cuando se evalúa el desarrollo neurocognitivo de bebes alimentados exclusivamente con leche humana en relación a sucedáneos, se encuentra que el desarrollo neuroconductual de los niños alimentados exclusivamente al pecho es superior. OBJETIVO: determinar la relación existente entre el tipo de alimentación de los lactantes y la edad de gateo, en la unidad de atención médica inmediata de pacientes pediátricos del Hospital Julio Criollo Rivas. Octubre 2018 ­ febrero 2019. Ciudad Bolívar, Estado Bolívar. METODOLOGÍA: fue un estudio de campo, de corte transversal, analítico, comparativo de casos y controles no experimental, conformado por el 30% de los lactantes menores aparentemente sanos entre 5 meses y un año de edad, que consumen lactancia materna exclusiva y lactancia artificial, atendidos en la unidad de atención médica inmediata del hospital "Julio Criollo Rivas" de Ciudad Bolívar, estado Bolívar. RESULTADOS: Durante el período de estudio, fueron evaluados 200 pacientes y se obtuvo que, de 43 pacientes que recibieron lactancia materna exclusiva hasta los 6 meses, el 51,16% (n=22) adquirieron la habilidad de gateo a los 7 meses, y de 157 pacientes que tuvieron ablactación precoz sólo el 32,48% (n=51) adquirieron la habilidad de gateo a los 7 meses. CONCLUSIONES: existe influencia de la lactancia materna en la adquisición de la habilidad de gateo, observándose adquisición precoz de la misma en el grupo que recibió lactancia materna exclusiva hasta los 6 meses de edad.

INTRODUCTION: When evaluating the neurocognitive development of babies exclusively fed with human milk in relation to substitutes, it is found that the neurobehavioral development of children fed exclusively to the breast is superior. OBJECTIVE: to determine the relationship between the type of feeding of the infants and the age of crawling, in the unit of immediate medical attention of pediatric patients of the Hospital Julio Criollo Rivas. October 2018 - February 2019. Ciudad Bolívar, Bolívar State. METHODOLOGY: was a field study, cross-sectional, analytical, non-experimental comparative cases and controls, consisting of 30% of apparently healthy younger infants between 5 months and 1 year of age, who consume exclusive breastfeeding and artificial lactation, attended in the immediate medical care unit of the "Julio Criollo Rivas" hospital in Ciudad Bolívar, Bolívar state. RESULTS: it was obtained that of 43 patients who received breastfeeding exclusive until 6 months, 51.16% (n = 22), acquired the ability to crawl at 7 months, and of 157 patients who had early ablation only 32.48% (n = 51) acquired the ability to I crawl at 7 months. CONCLUSIONS: there is an influence of breastfeeding in the acquisition of the ability to crawl, observing precocious acquisition of it in the group that received exclusive breastfeeding until 6 months of age.

Apoptosis signaling molecules as treatment targets in head and neck squamous cell carcinoma.

OBJECTIVES: To evaluate BCL-2 family signaling molecules in head and neck squamous cell carcinoma (HNSCC) and examine the ability of therapeutic agents with variable mechanisms of action to induce apoptosis in HNSCC cells. METHODS: messenger ribonculeic acid (mRNA) expression of BAK, BAX, B-cell lymphoma (Bcl-2), BCL2 Like 1 (BCL2L1), and MCL1 were measured in The Cancer Genome Atlas (TCGA) head and neck cancer dataset, as well as in a dataset from a cohort at Montefiore Medical Center (MMC). Protein expression was similarly evaluated in a panel of HNSCC cell lines (HN30, HN31, HN5, MDA686LN, UMSCC47). Cell viability and Annexin V assays were used to assess the efficacy and apoptotic potential of a variety of agents (ABT-263 [navitoclax], A-1210477, and bortezomib. RESULTS: Expression of BAK, BAX, BCL2L1, and MCL1 were each significantly higher than expression of BCL2 in the TCGA and MMC datasets. Protein expression demonstrated the same pattern of expression when examined in HNSCC cell lines. Treatment with combined ABT-263 (navitoclax)/A-1210477 or with bortezomib demonstrated apoptosis responses that approached or exceeded treatment with staurospaurine control. CONCLUSION: HNSCC cells rely on inhibition of apoptosis via BCL-xL and MCL-1 overexpression, and induction of apoptosis remains a potential therapeutic option as long as strategies overcome redundant anti-apoptotic signals. LEVEL OF EVIDENCE: NA Laryngoscope, 130:2643-2649, 2020.

Relación entre el tipo de lactancia y la frecuencia de infecciones respiratorias en niños menores de 2 años. Hospital Ruiz y Páez. Ciudad Bolívar-estado Bolívar / Relationship between the type of breastfeeding and the frequency of respiratory infections in children under 2 years of age. Ruiz y Páez Hospital, Bolívar city-Bolívar state

Las infecciones respiratorias agudas y la nutrición tienen un doble vínculo, porque ante una mala alimentación y desnutrición el niño tiene más probabilidades de contraer dichas infecciones respiratorias. Si no se presta la adecuada atención a la alimentación de los niños, las infecciones respiratorias producen déficit en el crecimiento y desarrollo del niño, pérdida de peso y desnutrición en un niño originalmente bien nutrido. Por tal motivo, se realizó una investigación para estudiar la relación entre el tipo de lactancia y la incidencia de infecciones respiratorias en niños menores de 2 años en la unidad de emergencia Pediátrica del Hospital Ruiz y Páez en los meses de febrero a abril del año 2020, fue un estudio de campo, analítico, de corte transversal, comparativo de casos y controles no experimentales, conformada por el 30% de los niños menores de 2 años con diagnóstico de infección respiratoria atendidos en dicha institución. Las Infecciones respiratorias entre los niños que consumen lactancia exclusiva y lactancia artificial, se registraron 16 casos de laringotraqueobronquitis donde 5 correspondían a pacientes con lactancia exclusiva y 11 a lactancia artificial, seguido de 15 casos de neumonía donde 7 casos pertenecían al grupo de lactancia exclusiva y 8 a lactancia artificial, por otro lado se diagnosticaron 14 casos de bronquiolitis donde 5 casos pertenecían al grupo de lactancia materna y 9 casos a lactancia artificial, por último se registraron 2 casos de tuberculosis en los pacientes con lactancia artificial.

Acute respiratory infections and nutrition have a double link, because in the face of poor diet and malnutrition the child is more likely to contract these respiratory infections. If proper attention is not paid to children's nutrition, respiratory infections lead to deficits in the child's growth and development, weight loss, and malnutrition in an originally well-nourished child. For this reason, an investigation was carried out to study the relationship between the type of lactation and the incidence of respiratory infections in children under 2 years of age in the Pediatric emergency unit of the Ruiz y Páez Hospital in the months of February to April of the year 2020. , was a cross-sectional, analytical, cross-sectional, comparative study of cases and non-experimental controls, made up of 30% of children under 2 years of age with a diagnosis of respiratory infection treated at said institution. Respiratory infections among children consuming exclusive breastfeeding and artificial breastfeeding, 16 cases of laryngotracheobronchitis were registered where 5 corresponded to patients with exclusive breastfeeding and 11 to artificial lactation, followed by 15 cases of pneumonia where 7 cases belonged to the exclusive breastfeeding group and 8 to artificial lactation, on the other hand, 14 cases of bronchiolitis were diagnosed where 5 cases belonged to the breastfeeding group and 9 cases to artificial lactation, lastly, 2 cases of tuberculosis were registered in patients with artificial lactation.

Optimal targeting of BCL-family proteins in head and neck squamous cell carcinoma requires inhibition of both BCL-xL and MCL-1.

Mechanisms of treatment resistance in head and neck squamous cell carcinoma (HNSCC) are not well characterized. In this study, HNSCC tumors from a cohort of prospectively enrolled subjects on an ongoing tissue banking study were divided into those that persisted or recurred locoregionally (n=23) and those that responded without recurrence (n=35). Gene expression was evaluated using llumina HumanHT-12-v3 Expression BeadChip microarrays. Sparse Partial Least Squares - Discriminant Analysis (sPLS-DA) identified 135 genes discriminating treatment-resistant from treatment-sensitive tumors. BCL-xL was identified among 23% of canonical pathways derived from this set of genes using Ingenuity Pathway analysis. The BCL-xL protein was expressed in 8 HNSCC cell lines examined. Cells were treated with the BCL-xL inhibitor, ABT-263 (navitoclax): the average half maximal inhibitory concentration (IC50) was 8.9µM (range 6.6µM - 13.9µM). Combining ABT-263 did not significantly increase responses to 2 Gy radiation or cisplatin in the majority of cell lines. MCL-1, a potential mediator of resistance to ABT-263, was expressed in all cell lines and HNSCC patient tumors, in addition to BCL-xL. Treatment with the MCL-1 inhibitor, A-1210477, in HNSCC cell lines showed an average IC50 of 10.7µM (range, 8.8µM to 12.7µM). Adding A-1210477 to ABT-263 (navitoclax) treatment resulted in an average 7-fold reduction in the required lethal dose of ABT-263 (navitoclax) when measured across all 8 cell lines. Synergistic activity was confirmed in PCI15B, Detroit 562, MDA686LN, and HN30 based on Bliss Independence analysis. This study demonstrates that targeting both BCL-xL and MCL-1 is required to optimally inhibit BCL-family pro-survival molecules in HNSCC, and co-inhibition is synergistic in HNSCC cancer cells.

Aspectos clínico-epidemiológicos del aborto en un hospital de Upata. Estado Bolívar-Venezuela / Clinical and epidemiological aspects of abortion in a hospital of Upata. State Bolivar Venezuela

Resumen Introducción. El aborto se ha convertido en un problema de salud pública. Una las causas que podría estar influyendo para su aumento es la falta de información sobre el control prenatal, por lo anterior, este es un tema que no escapa de la realidad y de la práctica médica. Objetivo. Caracterizar clínica y epidemiológicamente el aborto. Materiales y Métodos. Estudio observacional, descriptivo, retrospectivo, realizado en el Hospital "Gervasio Vera Custodio" Upata-Estado Bolívar, Venezuela, durante el periodo comprendido de enero a diciembre de 2013. Se recolecto datos de 207 historias clínicas de mujeres con diagnóstico de aborto. En el análisis estadístico se aplicó la prueba chi2 de Pearson. Resultados. Se encontró que la edad prevalente de aborto fue de 21 a 30 años con 42%. La edad gestacional más frecuente de las pacientes fue de 1 a 8 semanas con 50%. De estas 93,5% no cumplieron control prenatal. El tipo de aborto más frecuente fue espontáneo con 98,5%. Se realizó legrado uterino a 97%, de las cuales, 8,5% presentaron complicaciones. Se encontraron diferencias estadísticamente significativas al relacionar la edad materna con la edad gestacional. Conclusiones. Existió alta prevalencia de aborto espontáneo en el grupo de 21 a 30 años de edad, presentados entre las semanas 1 a 8 de gestación. La técnica más segura fue el legrado uterino. Finalmente, se encontró bajo cumplimiento del control prenatal.

Abstract Introduction. The abortion has become a public health problem may be due to the lack of information about prenatal care, so that this is an issue which does not escape reality and everyday medical practice. Objective. Characterize the abortion clinic and epidemiologically. Materials and Methods. An observational, descriptive, retrospective study at the Hospital "Gervasio Vera Custodio" Upata-Ciudad Bolivar, Venezuela was performed from January to December 2013. Data from 207 women with diagnosed a diagnosis of abortion were collected from medical records. Pearson chi-square test was applied for the statistical analysis. Results. It was found that abortion was prevalent among 21-30 years old with a 42%. The most common gestational age of abortion was 1 to 8 weeks in the 50% and 93.5% of them did not meet prenatal care. The most frequent abortion was spontaneous in 98.5% ot the patients. Curettage was performed in 97%, of which 8.5% had complications. Statistically significant differences were found to maternal age related to gestational age. Conclusion. There was high prevalence of abortion in the group of 21-30 years of age with 1 to 8 weeks of gestation. The safest practice was the uterine curettage. Finally, the mayority of the cases had no prenatal care.

Thoracic aortic aneurysm in a pre-Columbian (210 BC) inhabitant of Northern Chile: Implications for the origins of syphilis.

The aim of this work is to report a probable first case of a thoracic aortic aneurysm in the remains of a pre-Columbian individual from South America and to explore the relationship of this case to the only other paleopathological case previously described. We also consider the implications of both cases for the origins of syphilis. This study is based on the macroscopical analysis of human remains recovered during excavation of the Chiu Chiu 273 prehistoric cemetery, in the Antofagasta Region of Northern Chile. Ceramic sherds from the grave have a thermoluminescence date of 2160±100 A.P. or 210 B.C. The skeletal remains of an adult individual display resorptive lesions in both the sternum and the first two thoracic vertebrae, which are suggestive of a thoracic aortic aneurysm. The lesions observed in the case described are clearly compatible with the development of an aneurysm of the thoracic aorta (ascending portion and arch). We suggest that this aneurysm has a syphilitic etiology, considering the vascular segments compromised, the type of lesions observed, and the prevalent etiology of this kind of cardiovascular pathology in pre-penicillin times. Since the only two cases of thoracic aortic aneurysms reported to date have been found in the Americas and are clearly pre-Columbian, it can be suggested that venereal syphilis was present in the Americas in times before European contact.

Epigenetic changes in the CDKN2A locus are associated with differential expression of P16INK4A and P14ARF in HPV-positive oropharyngeal squamous cell carcinoma.

Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) is recognized as a distinct disease entity associated with improved survival. DNA hypermethylation profiles differ significantly by HPV status suggesting that a specific subset of methylated CpG loci could give mechanistic insight into HPV-driven OPSCC. We analyzed genome-wide DNA methylation of primary tumor samples and adjacent normal mucosa from 46 OPSCC patients undergoing treatment at Montefiore Medical Center, Bronx, NY using the Illumina HumanMethylation27 beadchip. For each matched tissue set, we measured differentially methylated CpG loci using a change in methylation level (M value). From these analyses, we identified a 22 CpG loci panel for HPV+ OPSCC that included four CDKN2A loci downstream of the p16(INK4A) and p14(ARF) transcription start sites. This panel was significantly associated with overall HPV detection (P < 0.05; ROC area under the curve = 0.96, 95% CI: 0.91-1.0) similar to the subset of four CDKN2A-specific CpG loci (0.90, 95% CI: 0.82-0.99) with equivalence to the full 22 CpG panel. DNA hypermethylation correlated with a significant increase in alternative open reading frame (ARF) expression in HPV+ OPSCC primary tumors, but not to the other transcript variant encoded by the CDKN2A locus. Overall, this study provides evidence of epigenetic changes to the downstream region of the CDKN2A locus in HPV+ oropharyngeal cancer that are associated with changes in expression of the coded protein products.

Telemedicine in acute-phase injury management: a review of practice and advancements.

OBJECTIVES: To offer a systematic review of the body of literature in the emerging field of telemedicine in the management of acute-phase injuries. MATERIALS AND METHODS: We conducted a literature review. RESULTS: Telemedicine has only recently been applied to the specialties of trauma, emergency care, and surgery. The potential benefits of telemedicine include a decrease in travel expenses, enhanced continuity of care, and increased access to specialized consultants in medically underserved and rural areas. CONCLUSIONS: There still exist barriers to the use of teletechnologies in medicine that limit their wider adoption. Poor infrastructure, limited equipment availability, and insufficient access to training and education for medical personnel have prevented wider use.

Forebrain striatal-specific expression of mutant huntingtin protein in vivo induces cell-autonomous age-dependent alterations in sensitivity to excitotoxicity and mitochondrial function.

HD (Huntington's disease) is characterized by dysfunction and death of striatal MSNs (medium-sized spiny neurons). Excitotoxicity, transcriptional dysregulation and mitochondrial abnormalities are among the mechanisms that are proposed to play roles in HD pathogenesis. To determine the extent of cell-autonomous effects of mhtt (mutant huntingtin) protein on vulnerability to excitotoxic insult in MSNs in vivo, we measured the number of degenerating neurons in response to intrastriatal injection of QA (quinolinic acid) in presymptomatic and symptomatic transgenic (D9-N171-98Q, also known as DE5) mice that express mhtt in MSNs but not in cortex. After QA, the number of degenerating neurons in presymptomatic DE5 mice was not significantly different from the number in WT (wild-type) controls, suggesting the early, increased vulnerability to excitotoxicity demonstrated in other HD mouse models has a largely non-cell-autonomous component. Conversely, symptomatic DE5 mice showed significantly fewer degenerating neurons relative to WT, implying the resistance to excitotoxicity observed at later ages has a primarily cell-autonomous origin. Interestingly, mitochondrial complex II respiration was enhanced in striatum of symptomatic mice, whereas it was reduced in presymptomatic mice, both relative to their age-matched controls. Consistent with the QA data, MSNs from symptomatic mice showed decreased NMDA (N-methyl-d-aspartate) currents compared with age-matched controls, suggesting that in addition to aging, cell-autonomous mechanisms mitigate susceptibility to excitotoxicity in the symptomatic stage. Also, symptomatic DE5 mice did not display some of the electrophysiological alterations present in other HD models, suggesting that blocking the expression of mhtt in cortical neurons may restore corticostriatal function in HD.