Capacidad pro-apoptótica in vitro de Valeriana rígida y Valeriana decusata sobre una línea celular de cáncer de mama / In vitro pro-apoptotic capacity of Valerian rigid and Valerian decussata in cancer cells

Resumen El cáncer representa un problema de salud pública a nivel mundial, con altas tasas de incidencia y mortalidad en países desarrollados y no desarrollados. En la actualidad se están evaluando alternativas terapéuticas de origen natural, con el propósito de establecer tratamientos más eficientes y menos invasivos. Dado que la apoptosis es el tipo de muerte programada que experimentan las células cancerosas por los tratamientos con los fármacos antineoplásicos,el objetivo de esta investigación, fue evaluar in vitro la capacidad pro-apoptótica y citotóxica de los extractos de valeriana, sobre una línea celular de cáncer de mama (MCF-7). En este estudio las células MCF7 se cultivaron y trataron con diferentes concentraciones de los extractos de la raíz, hojas y tallos de Valeriana rígida y Valeriana decussata. La viabilidad celular se evaluó mediante el ensayo MTT. Para la determinación de la expresión génica de las proteínas anti y pro-apoptóticas (Bax, Bcl-2 y p53), se usó el ensayo de la PCR cuantitativa de transcripción inversa. Las diferentes concentraciones de los extractos (10-8 a 10-1 mg/mL) disminuyeron la viabilidad (proliferación) celular en concentraciones dependientes. Estos extractos indujeron la expresión génica de las proteínas Bax y Bcl-2, pero no de p53. La expresión de Bax fue mayor que la de Bcl-2 e indujo un elevado índice Bax/Bcl-2 (condición proapoptotica). En conclusión, se determinó que los extractos de Valeriana decussata y Valeriana rígida poseen efecto reductor de la viabilidad (proliferación) de la línea celular de cáncer de mama MCF-7, probablemente mediado por la alteración de la relación de las proteínas Bax y Bcl-2 vinculadas a la apoptosis.

Abstract Cancer represents a worldwide public health problem, with high incidence and mortality rates in developed and undeveloped countries. Currently, therapeutic alternatives of natural origin are being evaluated with the purpose of establishing more efficient and less invasive treatments. Apoptosis is the type of programmed death cancer cells undergo during treatment with anti-neoplastic drugs. Therefore, the aim of this research was to evaluate in vitro the pro-apoptotic and cytotoxic capacity of valerian extracts on a breast cancer cell line (MCF-7). In this study, MCF7 cells were cultured and treated with different concentrations of the extracts of the root, leaves and stems of Valeriana rígida and Valeriana decussata. Cell viability was assessed by the MTT assay. Quantitative reverse transcription PCR assays were used for the determination of gene expression of anti- and proapoptotic proteins (Bax, Bcl-2, p53). Different concentrations of the extracts (10-8 to 10-1 mg/mL) decreased cell viability (proliferation) in a concentration-dependent manner. These extracts induced gene expression of Bax and Bcl-2 proteins but not of p53. The expression of Bax was higher than that of Bcl-2, causing an elevated Bax/Bcl-2 ratio (proapoptotic condition). In conclusion, it was determined that Valeriana decussata and Valeriana rígida extracts have a viability (proliferation) reducing effect on the MCF-7 breast cancer cell line, probably mediated by altering the ratio of Bax and Bcl-2 proteins linked to apoptosis.

Utilizing a "Crawl, Walk, Run" Training Model to Enhance Field Sanitation Capabilities for Peacekeeping Forces: A Recommendation for the Department of Defense Global Health Engagement Enterprise.

INTRODUCTION: DoD Global Health Engagement (GHE) planners can follow a number of models to effectively plan and execute successful GHE activities. One recommendation that could provide a significant return on investment for the DoD GHE enterprise is to utilize a "Crawl, Walk, Run" training model to build or enhance a specific medical capability for a Partner Nation (PN). Through the African Peacekeeping Rapid Response Partnership (APRRP) program, U.S. military medical subject matter experts serving as instructors for a Field Sanitation Course (FSC) delivered to the Senegalese Armed Forces (SAF), gained first-hand experience of the positive outcomes that resulted from incorporating this training model into the DoD GHE process. MATERIALS AND METHODS: The SAF completed three APRRP-led, in-person FSC iterations: May 2019 (crawl phase), September 2019 (walk phase), and February 2020 (run phase). Approximately 1 year after the completion of the in-person FSCs, in the midst of the COVID-19 pandemic, USU's CGHE offered a Field Sanitation Virtual Engagement to augment the FSC, emphasize specific field sanitation topics, and discuss lessons learned with the SAF on the deployment of their Level 2 Hospital. RESULTS: Before deploying their Level 2 Hospital during the COVID-19 pandemic, the SAF conducted a base camp assessment and found multiple ways to apply the knowledge and skills learned through the APRRP FSC to address issues related to waste management, pest control, and personal protective measures to protect against COVID-19. The SAF's progress in strengthening and institutionalizing their field sanitation capabilities can be seen by their execution of their own variation of the FSC-in preparation for their deployment, the SAF conducted three of their own FSCs, which closely resembled the APRRP-administered course. CONCLUSIONS: The "Crawl, Walk, Run" training model demonstrates an excellent teaching method that develops PN instructors so they can train more personnel in the long-term, thus building both capacity and capability. This gives the PN the opportunity to sustainably institutionalize a course, allowing them to continue training it in perpetuity. Implementing this training model flexibly to adapt to the differing needs of each PN and each line of effort would increase the success of DoD GHE activities when training PNs. It would also ensure the PN has the capability to sustainably institutionalize a course and can independently train future cohorts through internal iterations of the course.

Arracacia xanthorrhiza Bancr compounds decrease β-actin, hypoxia-inducible factor-1 and nitric oxide production in HeLa cells / Los componentes de la Arracacia xanthorrhiza Bancr disminuyen las producciones de la actina β, del factor-1 inducible por la hipoxia y del óxido nítrico en células Hela

Abstract The treatment of cancer patients with anti-cancer drugs is often accompanied by the presence of undesirable side effects. The use of natural plant derivatives alone, or in conjunction with existing anti-neoplastic drugs, has been suggested to obtain better results and decrease these side effects. Nitric oxide (NO•), the hypoxia-inducible factor-1 (HIF-1), and decreased concentration of actin play important roles in cancer progression. The beneficial effects of polyphenols in various organ disorders including cancer has been reported. The aim of this study was to determine the effect of Arracacia xanthorrhiza Bancr extracts, white (WAXB) and red (RAXB) variants (compounds rich in polyphenols) on the concentrations of β-actin, NO• and HIF-1 in Hela cells cultures, to uncover possible anti-neoplastic effects. Extracts from the plant leaves were added to Hela cell cultures at a concentration of 10-3 mg/mL, and after 24 hours of culture, the concentrations of β-actin, NO• and HIF-1 were determined by immunohistochemical, biochemical and western blot assays. Both extracts reduced the concentrations of β-actin, NO• and HIF-1 (p<0.001), similar to the methotrexate effect. These results suggest an antineoplastic effect of the studied plant extracts and highlight the possibility of their use in the treatment of neoplasms.

Resumen El tratamiento de pacientes con cáncer utilizando drogas-antineoplásicas presenta problemas relacionados con efectos colaterales indeseables. Se ha sugerido el uso de derivados de plantas naturales solas, o en combinación con drogas antineoplásicas existentes para obtener mejores resultados y disminuir los efectos colaterales. Así mismo, se ha reportado que el óxido nítrico (NO•), el factor-1 inducible por hipoxia (HIF-1) y la disminución de la expresión de la actina tienen un papel en la progresión del cáncer. También se ha reportado los efectos beneficiosos de lo polifenoles en varios desordenes orgánicos, incluyendo el cáncer. El objetivo de este estudio fue determinar los efectos de los extractos procedentes de la Arracacia xanthorrhiza Bancr blanca (AXBB) y la variedad roja (AXBR) (compuestos ricos en polifenoles) en las concentraciones de la actina-beta, el NO• y el HIF-1 en cultivo de células Hela, para destacar sus posibles efectos antineoplásicos. A los cultivos de células Hela se les agregaron los extractos de las hojas de AXBB o AXBR (10-3 mg/mL, concentración final) y después de 24 horas de cultivo se determinaron las concentraciones de la actina-beta, el NO• y el HIF-1 por métodos inmunohistoquímicos, bioquímicos y western blot. Ambos extractos disminuyeron las concentraciones de la actina-beta, el NO• y el HIF-1 (p<0,001) de una manera similar al efecto del metotrexato. Estos resultados sugieren un efecto antineoplásico de estos extractos y destacan la posibilidad de ser usados para el tratamiento de las neoplasias.

Conducting Virtual Global Health Engagement (GHE) activities in the Midst of the Global COVID-19 Pandemic: Considerations for the Department of Defense GHE Enterprise.

The global COVID-19 pandemic resulted in restriction of non-essential travel across the globe, as seen in the Office of the Under Secretary of Defense Memorandum, "Force Health Protection Guidance (Supplement 4): DoD Guidance for Personnel Traveling During the Novel Coronavirus Outbreak" (11 March 2020). This resulted in the suspension of most, if not all, Department of Defense (DoD) security cooperation (SC) programs, including DoD Global Health Engagement (GHE) activities.1 One such program is the African Peacekeeping Rapid Response Partnership (APRRP), which relies heavily on face-to-face interactions with select African Partner Nations (PNs), and which was significantly impacted by the inability to conduct in-person training with key partners. In light of these restrictions and suspended activities, the Uniformed Services University of the Health Sciences' (USU's) Center for Global Health Engagement (CGHE), in support of the US Africa Command (USAFRICOM) Office of the Command Surgeon, explored virtual means to execute DoD GHE activities to continue engaging its APRRP PNs, pending return to in-country activities.

Coiling Versus Microsurgical Clipping in the Treatment of Unruptured Middle Cerebral Artery Aneurysms: A Meta-Analysis.

BACKGROUND: Open microsurgical clipping of unruptured intracranial aneurysms has long been the gold standard, yet advancements in endovascular coiling techniques have begun to challenge the status quo. OBJECTIVE: To compare endovascular coiling with microsurgical clipping among adults with unruptured middle cerebral artery aneurysms (MCAA) by conducting a meta-analysis. METHODS: A systematic search was conducted from January 2011 to October 2015 to update a previous meta-analysis. All studies that reported unruptured MCAA in adults treated by microsurgical clipping or endovascular coiling were included and cumulatively analyzed. RESULTS: Thirty-seven studies including 3352 patients were included. Using the random-effects model, pooled analysis of 11 studies of microsurgical clipping (626 aneurysms) revealed complete aneurysmal obliteration in 94.2% of cases (95% confidence interval [CI] 87.6%-97.4%). The analysis of 18 studies of endovascular coiling (759 aneurysms) revealed complete obliteration in 53.2% of cases (95% CI: 45.0%-61.1%). Among clipping studies, 22 assessed neurological outcomes (2404 aneurysms), with favorable outcomes in 97.9% (95% CI: 96.8%-98.6%). Among coiling studies, 22 examined neurological outcomes (826 aneurysms), with favorable outcomes in 95.1% (95% CI: 93.1%-96.5%). Results using the fixed-effect models were not materially different. CONCLUSION: This updated meta-analysis demonstrates that surgical clipping for unruptured MCAA remains highly safe and efficacious. Endovascular treatment for unruptured MCAAs continues to improve in efficacy and safety; yet, it results in lower rates of occlusion.

Antibacterial prophylaxis for gram-positive and gram-negative infections in cranial surgery: A meta-analysis.

BACKGROUND: Perioperative antibiotic prophylaxis against gram positive and gram negative infections is considered standard of care in the perioperative management of patients undergoing cranial surgery. The antibiotic regimen which best reduces the risk of surgical site infections (SSIs) remains controversial. OBJECTIVES: A systematic literature review and meta-analysis were conducted to examine the effect of various prophylactic antibiotics on infection incidence among patients undergoing cranial surgeries. METHODS: A comprehensive search was conducted on Pubmed, EMBASE and Cochrane databases through October 2014 for studies that evaluated the efficacy of antibiotic prophylaxis among patients undergoing cranial surgeries. Pooled effect estimates using both fixed- and random-effect models were calculated. RESULTS: Eight articles were included in the meta-analysis, with a combined total of 1655 cranial procedures. Among these, 74 cases of SSIs were reported after patients received a single antibiotic or a combination of 2 or more antibiotics (pooled incidence of SSIs=6.00%; 95% CI=4.80%, 7.50%; fixed-effects model; I2=73.7%; P-heterogeneity<0.01). Incidence of SSI was 1.00% (95% CI=0.40%, 2.60%) for non-MRSA gram-positive bacterial infections; 2.70% (95% CI=0.90%, 8.00%) for gram-negative bacterial infections; 6.00% (95% CI=4.50%, 7.80%) for gram negative, and non-MRSA gram-positive bacterial infections; and 11.3% (95% CI=7.20%, 17.4%) for gram negative and MRSA gram-positive bacterial infections. Subgroup analysis revealed an effect modification by drug class (P=0.05) and infection type (P-interaction=0.01). More specifically, lincosamides (2.70%; n=1 group), glycopeptides (2.80%; n=1), third generation cephalosporins (5.30%; n=2), antibiotics combination (4.90%; n=4), and penicillin-family antibiotics (5.90%, n=1) offered better coverage against infections than first generation cephalosporins (22.0%; n=2). A meta-regression analysis on study length was not significant (P=0.13). Random-effect models were not materially different form fixed-effects. No evidence of publication bias was found. CONCLUSION: Lincosamides, glycopeptides, third generation cephalosporins, other combinations of prophylactic antibiotics, or penicillin-family antibiotics alone offer better coverage against SSIs than first generation cephalosporin among cranial surgery patients.

Defensive Medicine in U.S. Spine Neurosurgery.

STUDY DESIGN: Observational cross-sectional survey. OBJECTIVE: To compare defensive practices of U.S. spine and nonspine neurosurgeons in the context of state medical liability risk. SUMMARY OF BACKGROUND DATA: Defensive medicine is a commonly reported and costly phenomenon in neurosurgery. Although state liability risk is thought to contribute greatly to defensive practice, variation within neurosurgical specialties has not been well explored. METHODS: A validated, online survey was sent via email to 3344 members of the American Board of Neurological Surgeons. The instrument contained eight question domains: surgeon characteristics, patient characteristics, practice type, insurance type, surgeon liability profile, basic surgeon reimbursement, surgeon perceptions of medical legal environment, and the practice of defensive medicine. RESULTS: The overall response rate was 30.6% (n = 1026), including 499 neurosurgeons performing mainly spine procedures (48.6%). Spine neurosurgeons had a similar average practice duration as nonspine neurosurgeons (16.6 vs 16.9 years, P = 0.64) and comparable lifetime case volume (4767 vs 4,703, P = 0.71). The average annual malpractice premium for spine neurosurgeons was similar to nonspine neurosurgeons ($104,480.52 vs $101,721.76, P = 0.60). On average, spine neurosurgeons had a significantly higher rate of ordering labs, medications, referrals, procedures, and imaging solely for liability concerns compared with nonspine neurosurgeons (89.2% vs 84.6%, P = 0.031). Multivariate analysis revealed that spine neurosurgeons were roughly 3 times more likely to practice defensively compared with nonspine neurosurgeons (odds ratio, OR = 2.9, P = 0.001) when controlling for high-risk procedures (OR = 7.8, P < 0.001), annual malpractice premium (OR = 3.3, P = 0.01), percentage of patients publicly insured (OR = 1.1, P = 0.80), malpractice claims in the last 3 years (OR = 1.13, P = 0.71), and state medical-legal environment (OR = 1.3, P = 0.37). CONCLUSION: State-based medical legal environment is not a significant driver of increased defensive medicine associated with neurosurgical spine procedures. LEVEL OF EVIDENCE: 3.

Predictors and Rates of Delayed Symptomatic Hyponatremia after Transsphenoidal Surgery: A Systematic Review [corrected].

BACKGROUND: Delayed symptomatic hyponatremia (DSH) is a known complication of transsphenoidal surgery that can lead to prolonged hospital stay, readmission, and in rare cases, death. Many potential predictors for development of DSH have been investigated. A better understanding of DSH risk can lead to better patient outcomes. We performed a systematic review to determine the rates and predictors of DSH after both endoscopic transsphenoidal surgery and microscopic transsphenoidal surgery. METHODS: A systematic search of the literature was conducted using MEDLINE/PUBMED, EMBASE, and Cochrane databases. Inclusion criteria were 1) case series with at least 10 cases reported, 2) adult patients who underwent eTSS or mTSS for pituitary tumors, and 3) reported occurrence of DSH (defined as serum sodium level <135 mEq/L with associated symptoms) after postoperative day 3. Data were analyzed using CMA V.3 Statistical Software (2014). RESULTS: Ten case series satisfied the inclusion criteria for a total of 2947 patients. Various factors including age, gender, cerebrospinal fluid leak, and tumor size were investigated as potential predictors of DSH. DSH event rates for both mTSS and eTSS fell between around 4 and 12 percent and included a variety of proposed predictors. CONCLUSIONS: Age, gender, tumor size, rate of decline of blood sodium, and Cushing disease are potential predictors of DSH. By identifying patients at high risk for DSH, preventative efforts can be implemented in the perioperative setting to reduce the incidence of potentially catastrophic hyponatremia following transsphenoidal surgery.

Geographic uniformity of the Lyme disease spirochete (Borrelia burgdorferi) and its shared history with tick vector (Ixodes scapularis) in the Northeastern United States.

Over 80% of reported cases of Lyme disease in the United States occur in coastal regions of northeastern and mid-Atlantic states. The genetic structure of the Lyme disease spirochete (Borrelia burgdorferi) and its main tick vector (Ixodes scapularis) was studied concurrently and comparatively by sampling natural populations of I. scapularis ticks along the East Coast from 1996 to 1998. Borrelia is genetically highly diverse at the outer surface protein ospC. Since Borrelia is highly clonal, the ospC alleles can be used to define clones. A newly designed reverse line blotting (RLB) assay shows that up to 10 Borrelia clones can infect a single tick. The clone frequencies in Borrelia populations are the same across the Northeast. On the other hand, I. scapularis populations show strong regional divergence (among northeastern, mid-Atlantic, and southern states) as well as local differentiation. The high genetic diversity within Borrelia populations and the disparity in the genetic structure between Borrelia and its tick vector are likely consequences of strong balancing selection on local Borrelia clones. Demographically, both Borrelia and I. scapularis populations in the Northeast show the characteristics of a species that has recently expanded from a population bottleneck. Major geological and ecological events, such as the last glacial maximum (18,000 years ago) and the modern-day expansion of tick habitats, are likely causes of the observed "founder effects" for the two organisms in the Northeast. We therefore conclude that the genetic structure of B. burgdorferi has been intimately shaped by the natural history of its main vector, the northern lineage of I. scapularis ticks.