Comparison of perioperative outcomes in obese and non-obese patients subjected to open lumbar spine surgery.

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.

Demographic and Clinical Characteristics of Patients With Cervical Spine Degeneration Reveal Frequent Cervicolumbar Tandem Spinal Stenosis in Mexico.

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.

What Can We Learn about the Bias of Microbiome Studies from Analyzing Data from Mock Communities?

It is known that data from both 16S and shotgun metagenomics studies are subject to biases that cause the observed relative abundances of taxa to differ from their true values. Model community analyses, in which the relative abundances of all taxa in the sample are known by construction, seem to offer the hope that these biases can be measured. However, it is unclear whether the bias we measure in a mock community analysis is the same as we measure in a sample in which taxa are spiked in at known relative abundance, or if the biases we measure in spike-in samples is the same as the bias we would measure in a real (e.g., biological) sample. Here, we consider these questions in the context of 16S rRNA measurements on three sets of samples: the commercially available Zymo cells model community; the Zymo model community mixed with Swedish Snus, a smokeless tobacco product that is virtually bacteria-free; and a set of commercially available smokeless tobacco products. Each set of samples was subject to four different extraction protocols. The goal of our analysis is to determine whether the patterns of bias observed in each set of samples are the same, i.e., can we learn about the bias in the commercially available smokeless tobacco products by studying the Zymo cells model community?

Associations between microbial communities and key chemical constituents in U.S. domestic moist snuff.

BACKGROUND: Smokeless tobacco (ST) products are widely used throughout the world and contribute to morbidity and mortality in users through an increased risk of cancers and oral diseases. Bacterial populations in ST contribute to taste, but their presence can also create carcinogenic, Tobacco-Specific N-nitrosamines (TSNAs). Previous studies of microbial communities in tobacco products lacked chemistry data (e.g. nicotine, TSNAs) to characterize the products and identify associations between carcinogen levels and taxonomic groups. This study uses statistical analysis to identify potential associations between microbial and chemical constituents in moist snuff products. METHODS: We quantitatively analyzed 38 smokeless tobacco products for TSNAs using liquid chromatography with tandem mass spectrometry (LC-MS/MS), and nicotine using gas chromatography with mass spectrometry (GC-MS). Moisture content determinations (by weight loss on drying), and pH measurements were also performed. We used 16S rRNA gene sequencing to characterize the microbial composition, and additionally measured total 16S bacterial counts using a quantitative PCR assay. RESULTS: Our findings link chemical constituents to their associated bacterial populations. We found core taxonomic groups often varied between manufacturers. When manufacturer and flavor were controlled for as confounding variables, the genus Lactobacillus was found to be positively associated with TSNAs. while the genera Enteractinococcus and Brevibacterium were negatively associated. Three genera (Corynebacterium, Brachybacterium, and Xanthomonas) were found to be negatively associated with nicotine concentrations. Associations were also investigated separately for products from each manufacturer. Products from one manufacturer had a positive association between TSNAs and bacteria in the genus Marinilactibacillus. Additionally, we found that TSNA levels in many products were lower compared with previously published chemical surveys. Finally, we observed consistent results when either relative or absolute abundance data were analyzed, while results from analyses of log-ratio-transformed abundances were divergent.

[Efforts towards the consolidation of public policies for the prevention of HPV-associated cancers in Puerto RicoEsforços realizados em Porto Rico para a consolidação de políticas públicas de prevenção de cânceres associados ao HPV]. / Esfuerzos realizados en Puerto Rico hacia la consolidación de políticas públicas para la prevención de cánceres asociados al VPH.

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.

Esfuerzos realizados en Puerto Rico hacia la consolidación de políticas públicas para la prevención de cánceres asociados al VPH / Efforts towards the consolidation of public policies for the prevention of HPV-associated cancers in Puerto Rico / Esforços realizados em Porto Rico para a consolidação de políticas públicas de prevenção de cânceres associados ao HPV

RESUMEN El propósito de este informe especial es describir cronológicamente los eventos que contribuyeron al desarrollo y aprobación de la legislación e implementación del requisito escolar de vacunación en Puerto Rico (PR), con el fin de prevenir el VPH y los cánceres asociados a este. A partir del 2010, PR inició las aprobaciones de políticas públicas con el objetivo de mejorar el registro de casos de los cánceres y la cobertura de la vacuna contra el VPH a través de los planes médicos en adolescentes de 11 a 18 años. En el 2014, los esfuerzos científicos y comunitarios lograron documentar la magnitud de las enfermedades causadas por el VPH, y desarrollar en conjunto, estrategias de prevención y promoción de la vacuna contra el VPH. En agosto de 2018, PR logró ser uno de los primeros cuatro territorios de los Estados Unidos de América en implementar la vacuna contra el VPH como requisito escolar con el fin de disminuir la incidencia de cánceres asociados al VPH en la isla. En el 2019 se garantizó por ley que todo proveedor de vacunación debe reportar al Registro de Inmunización. El caso de PR demuestra que el desarrollo de políticas públicas junto con colaboraciones entre coaliciones académicas, científicas y comunitarias, logran cambios poblacionales y resultados medibles dirigidos a la prevención de VPH. Países con una problemática de salud pública similar podrían adoptar esfuerzos similares a los presentados, y alinearlos al objetivo de la Organización Mundial de la Salud: erradicación del cáncer cervical para 2030.

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.

RESUMO 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.

Intervención educativa para la inclusión social de jóvenes de comunidades periurbanas / Educational intervention for the social inclusion of young people from peri-urban communities / Intervenção educativa para a inclusão social de jovens de comunidades periurbanas

El presente trabajo consiste en una investigación llevada a cabo en una comunidad periurbana marginada del municipio de Conkal, en el Estado de Yucatán, México. Objetivo: diseñar una estrategia integral de intervención educativa para contribuir a reducir la violencia escolar en estudiantes de una telesecundaria de Xcuyún, Yucatán. Metodología: investigación acción y diseño de una estrategia educativa integral con base en el método del marco lógico; se elaboraron dos talleres que fueron impartidos como un currículum adicional extraescolar, obteniendo participación de toda la comunidad estudiantil durante su implementación. Resultados y conclusión: la intervención fue satisfactoria, logrando un ligero incremento en el nivel de resiliencia, el cual pasó de medio a alto; complementariamente, las calificaciones en la prueba final sobre el uso de internet y dispositivos móviles, fueron aprobatorias, mostrándose un conocimiento incorporado a su bagaje cultural, para el uso inteligente y responsable de estas herramientas.

This work consists of an investigation carried out in a marginalized peri-urban community in the municipality of Conkal, in the State of Yucatan, Mexico. Objective: to design a comprehensive educational intervention strategy to contribute to reduce school violence in students of a telesecundaria of Xcuyún, Yucatán. Methodology: action research and design of a comprehensive educational strategy based on the logical framework method; two workshops were developed and taught as an additional extracurricular curriculum, obtaining the participation of the entire student community during its implementation. Results and conclusion: the intervention was satisfactory, achieving a slight increase in the level of resilience, which went from medium to high; additionally, the grades in the final test on the use of internet and mobile devices were passing, showing a knowledge incorporated to their cultural background, for the intelligent and responsible use of these tools.

Este trabalho consiste num projeto de investigação levado a cabo numa comunidade periurbana marginalizada no município de Conkal, no Estado de Yucatán, México. Objetivo: conceber uma estratégia de intervenção educativa abrangente para ajudar a reduzir a violência escolar entre os alunos de uma telesecundária em Xcuyún, Yucatán. Metodologia: investigação-ação e conceção de uma estratégia educativa abrangente baseada no método do quadro lógico; foram desenvolvidos dois workshops e ministrados como um currículo extracurricular adicional, obtendo a participação de toda a comunidade estudantil durante a sua implementação. Resultados e conclusão: a intervenção foi satisfatória, conseguindo um ligeiro aumento do nível de resiliência, que passou de médio a elevado; além disso, as notas no teste final sobre a utilização da Internet e dos dispositivos móveis foram positivas, demonstrando um conhecimento incorporado na sua formação cultural, para a utilização inteligente e responsável destas ferramentas.

Nerve preservation during partial sacrectomy by two-stage anterior and posterior approach: illustrative case.

BACKGROUND: Preserving the neurological function of sacral nerves during total or partial sacrectomy is challenging. OBSERVATIONS: The authors describe a case of an osseous desmoplastic fibroma of the sacrum in a 51-year-old woman. The patient attended the authors' institution with loss of muscle strength and sensitivity impairment in both legs, gait instability, bowel constipation, urinary incontinence, and weight loss. Preoperative magnetic resonance imaging and positron emission tomography/computed tomography showed intrapelvic and posterior extension of the tumor but sparing of S1 and the sacroiliac and lumbosacral joints. After a multidisciplinary discussion of the case, a staged anterior-posterior approach to the sacrum was chosen. The abdominal approach allowed full mobilization of the uterus, ovaries, bladder, and colon and protection of iliac vessels. After tumor resection, a synthetic surgical mesh was placed over the sacrum to minimize soft tissue defects. Then, the posterior stage allowed the authors to perform a bicortical osteotomy, achieving wide tumor excision with minimal nerve root injury. Spinopelvic fixation was not necessary, because both sacroiliac and lumbosacral joints remained intact. A few days after the surgery, the patient restarted ambulation and recovered sphincter control. LESSONS: Multidisciplinary planning and a staged abdominal and posterior approach for partial sacrectomy were fundamental to preserve neurological function in this case.

Chronic subclinical spondylotic myelopathy exacerbated by COVID-19: A case report.

INTRODUCTION: Besides typical respiratory symptoms, the coronavirus disease 2019, also known as COVID-19, is characterized by a wide range of neurological symptoms that result from the injury of the brain and peripheral nerves. Only a few reports have described the involvement of the spinal cord among COVID-19 patients. Furthermore, little is known about the risk of individuals with chronic degenerative conditions of the spine for acute neurological complications of COVID-19. CASE PRESENTATION: Here, we describe the case of a 73-year-old man with a subclinical cervical multifocal spondylotic myelopathy that manifested neurological symptoms of spinal cord injury only some days after getting infected with SARS-CoV-2. The patient did not show any data associated with respiratory involvement and improved clinically after decompressive spinal surgery and administration of steroids. CONCLUSIONS: This is the first reported case of an acute exacerbation of a chronic degenerative condition of the spine caused by COVID-19.

Restoring the Duality between Principal Components of a Distance Matrix and Linear Combinations of Predictors, with Application to Studies of the Microbiome.

Appreciation of the importance of the microbiome is increasing, as sequencing technology has made it possible to ascertain the microbial content of a variety of samples. Studies that sequence the 16S rRNA gene, ubiquitous in and nearly exclusive to bacteria, have proliferated in the medical literature. After sequences are binned into operational taxonomic units (OTUs) or species, data from these studies are summarized in a data matrix with the observed counts from each OTU for each sample. Analysis often reduces these data further to a matrix of pairwise distances or dissimilarities; plotting the first two or three principal components (PCs) of this distance matrix often reveals meaningful groupings in the data. However, once the distance matrix is calculated, it is no longer clear which OTUs or species are important to the observed clustering; further, the PCs are hard to interpret and cannot be calculated for subsequent observations. We show how to construct approximate decompositions of the data matrix that pair PCs with linear combinations of OTU or species frequencies, and show how these decompositions can be used to construct biplots, select important OTUs and partition the variability in the data matrix into contributions corresponding to PCs of an arbitrary distance or dissimilarity matrix. To illustrate our approach, we conduct an analysis of the bacteria found in 45 smokeless tobacco samples.

CXCL12 retargeting of an adenovirus vector to cancer cells using a bispecific adapter.

Ad vectors are promising delivery vehicles for cancer therapeutic interventions. However, their application is limited by promiscuous tissue tropism and hepatotoxicity. This limitation can be avoided by altering the native tropism of Ads so that they can be redirected to the target cells through alternate cellular receptors. The CXCR4 chemokine receptor belongs to a large superfamily of G-protein-coupled receptors and is known to be upregulated in a wide variety of cancers, including breast cancer and melanoma. These receptors have been associated with cancer cell survival, progression, and metastasis. In the current study, an Ad to cancer cells overexpressing CXCR4 by using a bispecific adapter, sCAR-CXCL12, was retargeted. The sCAR-CXCL12 adapter contained the soluble ectodomain form of the native Ad5 receptor (sCAR), which was fused to a mature human chemokine ligand, CXCL12, through a short peptide linker. A dramatic increase in the infectivity of cancer cells using a targeted Ad vector compared with an untargeted vector was observed. Furthermore, sCAR-CXCL12 attenuated Ad infection of liver ex vivo and in vivo and enhanced Ad vector infection of xenograft tumors implanted in immunodeficient SCID-bg mice. Thus, the sCAR-CXCL12 adapter could be used to retarget Ad vectors to chemokine receptor-positive tumors.

Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial.

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.

Characterization of Bacterial Communities in Selected Smokeless Tobacco Products Using 16S rDNA Analysis.

The bacterial communities present in smokeless tobacco (ST) products have not previously reported. In this study, we used Next Generation Sequencing to study the bacteria present in U.S.-made dry snuff, moist snuff and Sudanese toombak. Sample diversity and taxonomic abundances were investigated in these products. A total of 33 bacterial families from four phyla, Actinobacteria, Firmicutes, Proteobacteria and Bacteroidetes, were identified. U.S.-produced dry snuff products contained a diverse distribution of all four phyla. Moist snuff products were dominated by Firmicutes. Toombak samples contained mainly Actinobacteria and Firmicutes (Aerococcaceae, Enterococcaceae, and Staphylococcaceae). The program PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) was used to impute the prevalence of genes encoding selected bacterial toxins, antibiotic resistance genes and other pro-inflammatory molecules. PICRUSt also predicted the presence of specific nitrate reductase genes, whose products can contribute to the formation of carcinogenic nitrosamines. Characterization of microbial community abundances and their associated genomes gives us an indication of the presence or absence of pathways of interest and can be used as a foundation for further investigation into the unique microbiological and chemical environments of smokeless tobacco products.

Complication rate in 200 consecutive sinus lift procedures: guidelines for prevention and treatment.

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.

Value of positron emission tomography scan in stage III cutaneous melanoma: a systematic review and meta-analysis.

PURPOSE: The objective of this study was to review the collective experience and utility of FDG-PET scans (FDG-PET) in the detection of systemic metastases in patients with stage III melanoma. METHODS: A systematic search for relevant studies published between 1990 and 2012 was performed. We included English language studies that evaluated melanoma patients with stage III disease, with at least 10 patients per study, and collected statistical data to assess FDG-PET utility in the detection of distant metastases. The SIGN tool was used to evaluate methodological quality and a meta-analysis was performed using Stata statistical software to quantify the clinical utility of FDG-PET. RESULTS: The systematic search yielded 9 studies eligible for inclusion in quantitative analyses with a total of 623 patients. The overall sensitivity of FDG-PET in detecting systemic metastases was 89.42% (95% CI: 65.07-97.46), and specificity was 88.78% (95% CI: 77.04-94.91). The pooled positive likelihood ratio was 7.97 (95% CI: 3.58-17.71) and the negative likelihood ratio was 0.12 (95% CI: 0.03-0.47). The area under the summary receiver operating curve (SROC) was 0.94 (95% CI: 0.92-0.96) and the diagnostic odds ratio (DOR) was 66.84 (95% CI: 10.66-418.89). A change in stage and/or management was noted in 22% (126/573) of patients when FDG-PET was utilized. CONCLUSIONS: Our findings indicate that FDG-PET may be useful in detecting distant metastases in patients with stage III melanoma. For this highly selected group of patients, FDG-PET has a high sensitivity, specificity and performance, frequently leading to a change in treatment plan.

The primate vaginal microbiome: comparative context and implications for human health and disease.

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.

Expression of osteoprotegerin from a replicating adenovirus inhibits the progression of prostate cancer bone metastases in a murine model.

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.

A tumor-stroma targeted oncolytic adenovirus replicated in human ovary cancer samples and inhibited growth of disseminated solid tumors in mice.

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.

A simplified method for the generation of human osteoclasts in vitro.

Osteoclasts are large, multinucleated cells responsible for the resorption of mineralized bone matrix. These cells are critical players in the bone turnover involved in bone homeostasis. Osteoclast activity is connected to the establishment and expansion of skeletal metastases from a number of primary neoplasms. Thus, the formation and activation of osteoclasts is an area of research with many potential avenues for clinical translation. Past studies of osteoclast biology have utilized primary murine cells cultured in vitro. Recently, techniques have been described that involve the generation of osteoclasts from human precursor cells. However, these protocols are often time-consuming and insufficient for generating large numbers of osteoclasts. We therefore developed a simplified protocol by which human osteoclasts may be easily and reliably generated in large numbers in vitro. In this study, osteoclasts were differentiated from bone marrow cells that had been aliquotted and frozen. Cells were generated by culture with recombinant macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL). Both human and murine RANKL were shown to efficiently generate osteoclasts, although higher concentrations of murine RANKL were required. Formation of osteoclasts was demonstrated qualitatively by tartrate-resistant acid phosphatase (TRAP) staining. These cells were fully functional, as confirmed by their ability to form resorption pits on cortical bone slices. Functional human osteoclasts can be difficult to generate in vitro by current protocols. We have demonstrated a simplified system for the generation of human osteoclasts in vitro that allows for large numbers of osteoclasts to be obtained from a single donor.