Inverse genetics tracing the differentiation pathway of human chondrocytes.

OBJECTIVE: Mammalian somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) via the forced expression of Yamanaka reprogramming factors. However, only a limited population of the cells that pass through a particular pathway can metamorphose into iPSCs, while the others do not. This study aimed to clarify the pathways that chondrocytes follow during the reprogramming process. DESIGN: The fate of human articular chondrocytes under reprogramming was investigated through a time-coursed single-cell transcriptomic analysis, which we termed an inverse genetic approach. The iPS interference technique was also employed to verify that chondrocytes inversely return to pluripotency following the proper differentiation pathway. RESULTS: We confirmed that human chondrocytes could be converted into cells with an iPSC phenotype. Moreover, it was clarified that a limited population that underwent the silencing of SOX9, a master gene for chondrogenesis, at a specific point during the proper transcriptome transition pathway, could eventually become iPSCs. Interestingly, the other cells, which failed to be reprogrammed, followed a distinct pathway toward cells with a surface zone chondrocyte phenotype. The critical involvement of cellular communication network factors (CCNs) in this process was indicated. The idea that chondrocytes, when reprogrammed into iPSCs, follow the differentiation pathway backward was supported by the successful iPS interference using SOX9. CONCLUSIONS: This inverse genetic strategy may be useful for seeking candidates for the master genes for the differentiation of various somatic cells. The utility of CCNs in articular cartilage regeneration is also supported.

Genome analyses revealed genetic admixture and selection signatures in Bos indicus.

The genomic diversity and relationship among seven diverse cattle breeds viz. Sahiwal, Tharparkar, Gir, Vechur, Ongole, Kangayam and Hariana were investigated in 132 random samples based on high density SNP array comprising > 777 K SNPs. A total of 1993 SNPs (0.25% of the total) having greater power (FST ≥ 0.20) to differentiate these cattle populations were identified, and utilized to partition genome of each animal into a predefined number of clusters. The structure of these cattle indicated shared ancestry of dairy breeds viz. Gir, Tharparkar and Sahiwal. Most of the animals (> 76%) of different populations under study except Vechur clustered into their own group of animals called breed. Vechur population retained highest rate of admixture, consistent with its crossing with other breeds. Ongole, Kangayam and Hariana shared comparatively less of their genome (≤ 15%) with other breeds. The study indicated that all seven breeds evolved from their independent ancestry but there was intermixing of these breeds in the recent past. The selection signatures identified between draft (Kangayam) and dairy breeds included several genes like FAM19A2, RAB31P, BEST3, DGKA, AHCY, PIGU and PFKP which are involved in immune response, metabolic pathway, transportation of glucose and sugars, signaling pathways, cellular processes, cell division and glycolysis regulation, respectively. Moreover, these genomic regions also harbour QTLs affecting milk performance traits. The signatures were also identified even between the dairy breeds. In comparison to large-sized cattle, there were significant differences in the number of QTLs affecting production (body weight, growth rate etc.) and morphological traits (height) in short-statured Vechur breed. The presence of HMGA2 gene in the selection signature on chromosome 5 may explain the variations in stature between these cattle.

Progress towards rabies control and elimination in Vietnam.

Rabies is a fatal viral disease that causes an estimated 59,000 human deaths each year. The majority of these deaths occur in developing countries in Asia. Canine rabies is endemic to Vietnam, which is, however, moving towards the disease's elimination. Many countries, such as Vietnam, have invested tremendous resources in controlling rabies, highlighting the goal of regional and global elimination of this neglected disease. In Vietnam, rabies is recognised as one of five high-priority, zoonotic diseases by the Ministry of Health and the Ministry of Agriculture and Rural Development. Investment by the government and by international partners for rabies prevention and control has played a substantial role in reducing human rabies deaths from 404 cases in 1992 to 74 cases in 2017. The catalyst for this effort was the Prime Minister's creation of the National Rabies Program in 1996, which led to increased support and resources for rabies prevention and control. Interventions carried out since then include the expansion of post-exposure prophylaxis centres throughout the country, the introduction or revision of key legislation and guidelines, and improved multisectoral One Health collaboration. In addition, support from international partners, such as the World Organisation for Animal Health (OIE), the World Health Organization (WHO), the Food and Agriculture Organization of the United Nations (FAO), and the Centers for Disease Control and Prevention (CDC), has helped to increase awareness, manage dog populations more effectively, and improve Vietnam's surveillance and diagnostic capabilities. To pursue the goal of eliminating dog-mediated rabies in Vietnam, political commitment is crucial. Resources must be made available to enforce the regulations and guidelines that will enable Vietnam to achieve greater canine rabies vaccination coverage. In this paper, the authors provide an overview of the animal and human health systems in Vietnam, as well as past, current and future directions of rabies prevention and control.

La rage est une maladie virale à l'issue mortelle faisant chaque année un nombre estimé de 59 000 victimes humaines. La plupart de ces décès surviennent dans les pays en développement d'Asie. Au Vietnam, la rage canine est endémique mais le pays poursuit activement l'objectif d'éliminer la rage de son territoire. À l'instar du Vietnam, plusieurs pays ont investi des ressources colossales pour contrôler la rage, renforçant ainsi la dimension régionale et mondiale de l'objectif d'élimination de cette maladie négligée. Au Vietnam, la rage figure parmi les cinq zoonoses hautement prioritaires prises en compte par le ministère de la Santé et le ministère de l'Agriculture et du développement rural. Les investissements consacrés à la prévention et au contrôle de la rage par le gouvernement et ses partenaires internationaux ont joué un rôle déterminant dans la réduction du nombre de décès humains dus à la rage, qui est passé de 404 cas en 1992 à 74 cas en 2017. L'élément catalyseur de cet effort a été la création en 1996 du Programme national de lutte contre la rage par le premier ministre de l'époque, ce qui a permis de renforcer les ressources et le soutien dédiés à la prévention et à la lutte contre la rage. Depuis lors, les interventions ont porté sur la création de centres de prophylaxie post-exposition sur tout le territoire, l'introduction ou la révision de la législation et des lignes directrices applicables et l'amélioration de la collaboration Une seule santé. En outre, le soutien de partenaires internationaux tels que l'Organisation mondiale de la santé animale (OIE), l'Organisation mondiale de la santé (OMS), l'Organisation des Nations Unies pour l'alimentation et l'agriculture (FAO) et les Centres pour le contrôle et la prévention des maladies (CDC, États-Unis d'Amérique) a abouti à une meilleure sensibilisation, à une gestion plus efficace des populations de chiens et à un renforcement des capacités de surveillance et de diagnostic au Vietnam. Un engagement politique fort est indispensable pour réussir à éliminer totalement la rage transmise par les chiens au Vietnam. Des ressources doivent être rendues disponibles afin de mettre en oeuvre la réglementation et les lignes directrices pertinentes et d'augmenter ainsi la couverture vaccinale de la population canine du pays. Les auteurs décrivent les systèmes de santé animale et publique du Vietnam ainsi que les orientations passées, actuelles et futures de la prévention et du contrôle de la rage dans le pays.

La rabia es una enfermedad vírica fatal, que según las estimaciones mata a 59 000 personas al año, mayoritariamente en países en desarrollo asiáticos. La rabia canina es endémica en el Vietnam, país que no obstante avanza ahora hacia la eliminación de la enfermedad. Como el Vietnam, muchos países han invertido cantidades colosales de recursos en la lucha antirrábica, subrayando con ello su compromiso con el objetivo de eliminar esta enfermedad desatendida a escala regional y mundial. El Ministerio de Salud y el Ministerio de Agricultura y Desarrollo Rural del Vietnam tienen catalogada la rabia como una de las cinco enfermedades zoonóticas que revisten máxima prioridad. Las inversiones en prevención y control de la rabia realizadas por el gobierno y por asociados internacionales han ayudado sensiblemente a reducir el número de personas muertas por la rabia, que ha pasado de 404 casos en 1992 a 74 en 2017. El catalizador de este esfuerzo fue la creación en 1996, por iniciativa del Primer Ministro, del Programa Nacional contra la Rabia, que se tradujo en un aumento del apoyo y los recursos destinados a prevenir y combatir la enfermedad. Entre otras intervenciones, desde entonces se ha multiplicado en todo el país el número de centros donde se dispensa profilaxis tras la exposición, se han promulgado o revisado leyes, decretos y directrices fundamentales y se ha mejorado la colaboración multisectorial en clave de Una sola salud. Además, el respaldo de asociados internacionales como la Organización Mundial de Sanidad Animal (OIE), la Organización Mundial de la Salud (OMS), la Organización de las Naciones Unidas para la Alimentación y la Agricultura (FAO) o los Centros para el Control y la Prevención de Enfermedades (CDC) de los Estados Unidos ha ayudado a generar una mayor conciencia del problema, a gestionar más eficazmente las poblaciones de perros y a dotar al país de mejores medios de vigilancia y diagnóstico. Para hacer realidad el objetivo de eliminar del Vietnam la rabia transmitida por perros, la voluntad política es un factor clave, pues hay que poner sobre la mesa los recursos necesarios para aplicar los reglamentos y normas que permitirán al país ampliar la cobertura de vacunación canina antirrábica. Tras trazar una panorámica de los sistemas sanitario y zoosanitario del Vietnam, los autores describen el rumbo pasado, presente y futuro de las labores de prevención y control de la rabia en el país.

Implantation associated divergence in neutrophil glucocorticoid and cysteine-X-cysteine receptor genes in cattle.

The differential roles of Interferon-tau (IFNT) and Progesterone (P4) in triggering pro- and anti-inflammatory responses during peri-implantation period were assessed in cows. An ex vivo study was done by isolating neutrophils from the animals post artificial insemination (AI) at defined intervals and analyzing the expression changes of Glucocorticoid receptor-α (GRα) and Interleukin-8 receptor (CXCR1) genes. An in vitro study was also done isolating neutrophils from prepubertal heifers subjecting them to IFNT and Progesterone P4 supplementation separately. We observed that from day 14 post Artificial Insemination, there is a significant up-regulation of neutrophil GRα and CXCR1 in pregnant and non-pregnant cows respectively. The in vitro study showed that IFNT significantly up-regulates GRα whereas P4 significantly up-regulates CXCR1. The total leukocyte count and neutrophil count were also significantly higher in non-pregnant cows. We conclude that IFNT efficiently mediates neutrophil immunosuppression during peri-implantation period in cows by interacting with Interleukin 8 receptor and can also exert ligand independent actions on GRα.

Exploring the concentration-dependent actions of interferon-τ on bovine neutrophils to understand the process of implantation.

Interferon-τ (IFNT) is a major cytokine produced by the ruminant trophoectoderm during the peri-implantation period exerting immunomodulatory actions on various cells including neutrophils. The current in vitro study was undertaken to analyze the concentration-dependent effects of IFNT on neutrophil gene dynamics to understand its possible role in implantation process. The neutrophils were isolated from the blood of heifers and were cultured subjecting them to different IFNT concentrations (1, 5, or 10 ng/mL). The gene-expression patterns of different interferon-stimulated genes, l-selectin, CD31, CD11b, and progesterone-induced blocking factor (PIBF) were analyzed by quantitative real-time PCR. It was observed that at lower concentrations of IFNT, the IFI16, l-selectin, ISG15, and PIBF were upregulated, whereas at higher concentrations the same were down regulated. At all the experimental concentrations, IFI44, OAS1, MX genes were significantly upregulated and CD31, CD11b were significantly downregulated. At lower concentrations of IFNT, the neutrophil activity with respect to chemoattraction is stimulated, whereas at higher concentrations the same is reduced. Hence, it can be concluded that IFNT exerts concentration-dependent actions on neutrophil gene-expression dynamics indicating a fine modulation of its activity depending upon the temporal variation in its destined functions ultimately leading to successful implantation.

Interferon-tau stimulated gene expression: A proxy to predict embryonic mortality in dairy cows.

The embryonic mortality in cows is a growing concern for an ever-expanding dairy industry. The current study was an attempt to shorten the open period of dairy cows having suffered embryonic loss by diagnosing them at an earlier stage. The blood samples were collected from the Karan Fries (KF) cows on days 0 (day of AI/estrus), 4, 8, 12, 14, 16, 18, 21, 24, 28, 35 and 42 post insemination. The experimental animals were then categorized into pregnant (P), conception failure/early embryonic mortality (EEM) and late embryonic mortality cows (LEM), based on progesterone assay, ultrasonography and per-rectal palpation. There were 6 animals in each group. The plasma progesterone was higher in pregnant than EEM and LEM cows. Plasma Interferon-tau concentration was significantly (p < 0.05) lower in LEM than pregnant cows where it could be detected from day 14-21 but was non-detectable in EEM cows. The mRNA expression of ISG15, OAS1, MX1 and MX2 in blood neutrophils was significantly (p < 0.05) higher from day 8-42 as against day 0 in pregnant cows. The highest expression was observed around day 18-21 in pregnant cows. The ISG15, OAS1, MX1 and MX2 mRNA expression was significantly (p < 0.05) higher from day 4-42 as compared to day 0 in LEM cows, whereas in EEM cows the expression stayed close to that of day 0 (1.00 ±â€¯0.00). The mRNA expression of ISG15, OAS1, MX1 and MX2 started to decline from day 24 onwards. The degree of expression of Interferon-tau stimulated genes was higher in pregnant and LEM cows than EEM cows. The study reveals that the Interferon tau stimulated gene expression in neutrophils can act as peripheral biomarkers for detecting the embryonic mortality in dairy cows.

Factors affecting radiotherapy prescribing patterns in the post-mastectomy setting.

Background: Radiation therapy (rt) after mastectomy for breast cancer can improve survival outcomes, but has been associated with inferior cosmesis after breast reconstruction. In the literature, rt dose and fractionation schedules are inconsistently reported. We sought to determine the pattern of rt prescribing practices in a provincial rt program for patients treated with mastectomy and reconstruction. Methods: Women diagnosed with stages 0-iii breast cancer between January 2012 and December 2013 and treated with curative-intent rt were identified from a clinicopathology database. Patient demographic, tumour, and treatment information were extracted. Of the identified patients, those undergoing mastectomy were the focus of the present analysis. Results: Of 4016 patients identified, 1143 (28%) underwent mastectomy. The patients treated with mastectomy had a median age of 57 years, and 37% of them underwent reconstruction. Treatment with more than 16 fractions of rt was associated with autologous reconstruction [odds ratio (or): 37.2; 95% confidence interval (ci): 11.2 to 123.7; p < 0.001], implant reconstruction (or: 93.3; 95% ci: 45.3 to 192.2; p < 0.001), and treating centre. Hypofractionated treatment was associated with older age (or: 0.94; 95% ci: 0.92 to 0.96; p < 0.001), and living more than 400 km from a treatment centre (or: 0.37; 95% ci: 0.16 to 0.86; p = 0.02). Conclusions: Prescribing practices in breast cancer patients undergoing mastectomy are influenced by reconstruction intent, age, nodal status, and distance from the treatment centre. Those factors should be considered when making treatment decisions.

Assessing post-radiotherapy handover notes from a family physician perspective.

BACKGROUND: Across our province, post-radiotherapy (rt) handover notes are sent to family physicians (fps) after rt. Based on previous fp feedback, we created a revised post-radiotherapy handover note with more information requested by fps. The purpose of this study was to determine whether the revised handover note improved the note as a communication aid. METHODS: Potential common and rare treatment side effects, oncologist contact information, and treatment intent were added to the revised handover note. Both versions were sent alongside a questionnaire to fps. Paired t-tests were carried out to compare satisfaction differences. RESULTS: There was a response rate of 37% for the questionnaires. Significantly greater clarity in the following categories was observed: responsibility for patient follow-up (mean score improvement of 1.2 on a 7-point Likert scale, p < 0.001), follow-up schedule (1.1, p < 0.001) as well as how and when to contact the oncologist (1.4, p = 0.001). Family physicians were also more content with how the institute transitioned care back to them (1.5, p = 0.012). Overall, fps were generally satisfied with the content of the revised post-rt handover note and noted improvement over the previous version. The frequency of investigations and institute supports initiated such as counselling services were suggested further additions. CONCLUSIONS: The inclusion of potential treatment side effects, oncologist contact information, treatment intent and a well-laid out follow-up schedule were essential information needed by fps for an effective post-rt completion note. With these additions, the revised post-rt handover note showed significant improvement.

Biomechanics of coupled motion in the cervical spine during simulated whiplash in patients with pre-existing cervical or lumbar spinal fusion: A Finite Element Study.

OBJECTIVES: Loss of motion following spine segment fusion results in increased strain in the adjacent motion segments. However, to date, studies on the biomechanics of the cervical spine have not assessed the role of coupled motions in the lumbar spine. Accordingly, we investigated the biomechanics of the cervical spine following cervical fusion and lumbar fusion during simulated whiplash using a whole-human finite element (FE) model to simulate coupled motions of the spine. METHODS: A previously validated FE model of the human body in the driver-occupant position was used to investigate cervical hyperextension injury. The cervical spine was subjected to simulated whiplash exposure in accordance with Euro NCAP (the European New Car Assessment Programme) testing using the whole human FE model. The coupled motions between the cervical spine and lumbar spine were assessed by evaluating the biomechanical effects of simulated cervical fusion and lumbar fusion. RESULTS: Peak anterior longitudinal ligament (ALL) strain ranged from 0.106 to 0.382 in a normal spine, and from 0.116 to 0.399 in a fused cervical spine. Strain increased from cranial to caudal levels. The mean strain increase in the motion segment immediately adjacent to the site of fusion from C2-C3 through C5-C6 was 26.1% and 50.8% following single- and two-level cervical fusion, respectively (p = 0.03, unpaired two-way t-test). Peak cervical strains following various lumbar-fusion procedures were 1.0% less than those seen in a healthy spine (p = 0.61, two-way ANOVA). CONCLUSION: Cervical arthrodesis increases peak ALL strain in the adjacent motion segments. C3-4 experiences greater changes in strain than C6-7. Lumbar fusion did not have a significant effect on cervical spine strain.Cite this article: H. Huang, R. W. Nightingale, A. B. C. Dang. Biomechanics of coupled motion in the cervical spine during simulated whiplash in patients with pre-existing cervical or lumbar spinal fusion: A Finite Element Study. Bone Joint Res 2018;7:28-35. DOI: 10.1302/2046-3758.71.BJR-2017-0100.R1.

Lipopolysaccharide suppresses IgE-mast cell-mediated reactions.

BACKGROUND: Clinical and experimental analyses have identified a central role for IgE/FcεRI/mast cells in promoting IgE-mediated anaphylaxis. Recent data from human studies suggest that bacterial infections can alter susceptibility to anaphylaxis. OBJECTIVE: We examined the effect of LPS exposure on the induction of IgE-mast cell (MC) mediated reactions in mice. METHODS: C57BL/6 WT, tlr4-/- and IL10-/- mice were exposed to LPS, and serum cytokines (TNF and IL-10) were measured. Mice were subsequently treated with anti-IgE, and the symptoms of passive IgE-mediated anaphylaxis, MC activation, Ca2+ -mobilization and the expression of FcεRI on peritoneal MCs were quantitated. RESULTS: We show that LPS exposure of C57BL/6 WT mice constraints IgE-MC-mediated reactions. LPS-induced suppression of IgE-MC-mediated responses was TLR-4-dependent and associated with increased systemic IL-10 levels, decreased surface expression of FcεRI on MCs and loss of sensitivity to IgE activation. Notably, LPS-induced desensitization of MCs was short term with MC sensitivity to IgE reconstituted within 48 hours, which was associated with recapitulation of FcεRI expression on the MCs. Mechanistic analyses revealed a requirement for IL-10 in LPS-mediated decrease in MC FcεRI surface expression. CONCLUSIONS & CLINICAL RELEVANCE: Collectively, these studies suggest that LPS-induced IL-10 promotes the down-regulation of MC surface FcεRI expression and leads to desensitization of mice to IgE-mediated reactions. These studies indicate that targeting of the LPS-TLR-4-IL-10 pathway may be used as a therapeutic approach to prevent adverse IgE-mediated reactions.

Intraoperative serum lactate is not a predictor of survival after glioblastoma surgery.

BACKGROUND: Cancer cells can produce lactate in high concentrations. Two previous studies examined the clinical relevance of serum lactate as a biomarker in patients with brain tumors. Patients with high-grade tumors have higher serum concentrations of lactate than those with low-grade tumors. We hypothesized that serum lactic could be used of biomarker to predictor of survival in patients with glioblastoma (GB). METHODS: This was a retrospective study. Demographic, lactate concentrations and imaging data from 275 adult patients with primary GB was included in the analysis. The progression free survival (PFS) and overall survival (OS) rates were compared in patients who had above and below the median concentrations of lactate. We also investigated the correlation between lactate concentrations and tumor volume. Multivariate analyses were conducted to test the association lactate, tumor volume and demographic variables with PFS and OS. RESULTS: The median serum concentration of lactate was 2.3mmol/L. A weak correlation was found between lactate concentrations and tumor volume. Kaplan-Meier curves demonstrated similar survival in patients with higher or lower than 2.3mmol/L of lactate. The multivariate analysis indicated that the intraoperative levels of lactate were not independently associated with changes in survival. On another hand, a preoperative T1 volume was an independent predictor PFS (HR 95%CI: 1.41, 1.02-1.82, p=0.006) and OS (HR 95%CI: 1.47, 1.11-1.96, p=0.006). CONCLUSION: This retrospective study suggests that the serum concentrations of lactate cannot be used as a biomarker to predict survival after GB surgery. To date, there are no clinically available serum biomarkers to determine prognosis in patients with high-grade gliomas. These tumors may produce high levels of lactic acid. We hypothesized that serum lactic could be used of biomarker to predictor of survival in patients with glioblastoma (GB). In this study, we collected perioperative and survival data from 275 adult patients with primary high-grade gliomas to determine whether intraoperative serum acid lactic concentrations can serve as a marker of prognosis. The median serum concentration of lactate was 2.3mmol/L. Our analysis indicated the intraoperative levels of lactate were not independently associated with changes in survival. This retrospective study suggests that the serum concentrations of lactate cannot be used as a biomarker to predict survival after GB surgery.

OM-85 is an immunomodulator of interferon-ß production and inflammasome activity.

The inflammasome-IL-1 axis and type I interferons (IFNs) have been shown to exert protective effects upon respiratory tract infections. Conversely, IL-1 has also been implicated in inflammatory airway pathologies such as asthma and chronic obstructive pulmonary disease (COPD). OM-85 is a bacterial extract with proved efficacy against COPD and recurrent respiratory tract infections, a cause of co-morbidity in asthmatic patients. We therefore asked whether OM-85 affects the above-mentioned innate immune pathways. Here we show that OM-85 induced interferon-ß through the Toll-like receptor adaptors Trif and MyD88 in bone marrow-derived dendritic cells. Moreover, it exerted a dual role on IL-1 production; on the one hand, it upregulated proIL-1ß and proIL-1α levels in a MyD88-dependent manner without activating the inflammasome. On the other hand, it repressed IL-1ß secretion induced by alum, a well-known NLRP3 activator. In vivo, OM-85 diminished the recruitment of inflammatory cells in response to peritoneal alum challenge. Our findings therefore suggest that OM-85 favors a protective primed state, while dampening inflammasome activation in specific conditions. Taken together, these data bring new insights into the mechanisms of OM-85 action on innate immune pathways and suggest potential explanations for its efficacy in the treatment of virus-induced airway diseases.

Emerging Major Histocompatibility Complex Class I-Related Functions of NLRC5.

Recent evidence demonstrates a key role for the nucleotide-binding oligomerization domain-like receptor (NLR) family member NLRC5 (NLR family, CARD domain containing protein 5) in the transcriptional regulation of major histocompatibility complex (MHC) class I and related genes. Detailed information on NLRC5 target genes in various cell types and conditions is emerging. Thanks to its analogy to CIITA (class II major MHC transactivator), a NLR family member known for over 20 years to be the master regulator of MHC class II gene transcription, also the molecular mechanisms underlying NLRC5 function are being rapidly unraveled. MHC class I molecules are crucial in regulating innate and adaptive cytotoxic responses. Whereas CD8+ T cells detect antigens presented on MHC class I molecules by infected or transformed cells, natural killer (NK) lymphocytes eliminate target cells with downregulated MHC class I expression. Data uncovering the relevance of NLRC5 in homeostasis and activity of these two lymphocyte subsets have been recently reported. Given the importance of CD8+ T and NK cells in controlling infection and cancer, it is not surprising that NLRC5 is also starting to emerge as a central player in these diseases. This chapter summarizes and discusses novel insights into the molecular mechanisms underlying NLRC5 activity and its relevance to pathological conditions. A thorough understanding of both aspects is essential to evaluate the clinical significance and therapeutic potential of NLRC5.

Effect of feed supplement and additives on stress mitigation in Karan Fries heifers.

AIM: The objective of this study was to evaluate the effects of protected fat plus yeast, niacin, zinc, and chromium dietary supplementation on the reduction of heat stress in Karan Fries (KF) heifers during hot humid months. MATERIALS AND METHODS: The basal ration for both the control and treatment groups was the same, containing maize as green fodder and concentrate mixture. However, the treatment group was supplemented with protected fat (2.5% of dry matter intake [DMI]), yeast (10 g/animal/day), niacin (6 g/animal/day), zinc (40 mg/kg DMI), and chromium (1.5 mg/kg DMI). RESULT: The overall mean value of afternoon rectal temperature for control and treatment group was 103.17±0.09 and 102.72±0.10°F, respectively, and was significantly (p<0.01) lower in the treatment group. The overall mean value of afternoon respiration rate for control and treatment group was 76.35±0.56 and 73.13±0.58 breaths/min, respectively, and was also significantly (p<0.01) lower in the treatment group. The overall mean value of afternoon pulse rate for control and treatment group was 97.09±0.63 and 94.67±0.67 beats/minute, respectively, and was also significantly (p<0.01) lower in the treatment group. Finally, the mean cortisol concentration for control and treatment group was 3.94±0.05 ng/ml and 3.70±0.06 ng/ml, respectively, and was significantly (p<0.01) lower in the treatment group. CONCLUSION: The present study shows that supplementation with the above feed additives could serve as a heat stress abatement strategy in growing KF heifers during extreme conditions in summer months.

The use of isoflurane and desflurane as inhalational agents for glioblastoma surgery. A survival analysis.

BACKGROUND: Several studies have examined the impact of anesthetics on cancer recurrence. Isoflurane but not desflurane has protumoral effects. We hypothesize the use of isoflurane but not desflurane during surgery for primary GBM is an independent predictor of disease progression and mortality. METHODS: 378 adult patients were included in the study. The progression free survival (PFS) and overall survival (OS) rates at 1 and 5years were compared in patients who had either desflurane or isoflurane alone or in combination with propofol infusion. Multivariate analyses were conducted to test the association between preoperative, intraoperative and postoperative hyperglycemia with PFS and OS. RESULTS: Kaplan-Meier curves demonstrated similar survival in patients who had either desflurane or isoflurane. The use of a propofol infusion during surgery did not affect survival. Univariate analysis demonstrated that age, body mass index and the adjusted Charlson comorbidity score were associated with reduced survival. The multivariate analysis confirmed that age and BMI but not the type volatile anesthetic use were independent prognostic factors for PFS (HR, 95%CI: 1.07, 0.85-1.37, 9=0.531) and OS (HR, 95%CI: 1.13, 0.86-1.48, p=0.531). CONCLUSION: The use of isoflurane or desflurane during GBM surgery is not associated with reduced PFS or OS.

Preoperative statin use is not associated with improvement in survival after glioblastoma surgery.

Cohort studies have suggested that the use of statins is associated with decreased risk of glioma formation and mortality. Here, a cohort of patients with glioblastoma multiforme (GBM) was analyzed to further investigate associations between preoperative use of statins and recurrence, and progression free and overall survival. Patients who had surgery for GBM (N=284) were followed up for a median of 18.1months. Seventy-eight patients were taking statins preoperatively while the rest were not. Cox proportional hazards models adjusted for several covariates of interest were applied before and after propensity score matching. Compared with statin users, those not taking the lipid-lowering drugs had similar progression free survival before (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.70-1.26; p=0.68) and after propensity score matching (HR 0.95, 95% CI 0.67-1.35; p=0.68). Mortality was similar between both groups of patients before (HR 0.94, 95% CI 0.70-1.22; p= 0.73) and after propensity score matching (HR 1.13, 95% CI 0.78-1.64; p=0.49). Age and dexamethasone use were independent prognostic factors of survival. Contrary to previously published evidence, this study could not find an association between preoperative statin use and longer survival in GBM patients. Due to the small number of patients and retrospective nature of the study, further work is needed to understand the role of perioperative statins in GBM patients.

Molecular characterisation of wild-type G1P[8] and G3P[8] rotaviruses isolated in Vietnam 2008 during a vaccine trial.

Rotavirus vaccines work better in developed countries than in developing countries, leading to the question of whether the circulating strains are different in these two settings. In 2008, a clinical trial of the pentavalent rotavirus vaccine was performed in Nha Trang, Vietnam, in which the efficacy was reported to be 64 %. Although samples were collected independently from the clinical trial, we examined faecal specimens from children hospitalised for rotavirus diarrhoea and found that G3P[8] and G1P[8] were co-dominant at the time of the clinical trial. The aim of this study was to explore whether they were divergent from the strains circulating in the developed countries where the vaccine efficacy is high. Two G3P[8] and two G1P[8] strains that were regarded as representatives based on their electropherotypes were selected for full-genome sequencing. The genotype constellation was G1/G3-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1. All but the VP4 genes, one of which belonged to the emerging P[8]b genotype (OP354-like VP4), clustered into one or more lineages/alleles with the strains circulating in developed countries, with ≥97.5 % nucleotide sequence identity. Additionally, 10 G1 and 12 G3 VP7 sequences as well as 31 VP4 sequences were determined. No amino acid differences were observed between the Vietnamese strains and strains in the developed countries that were likely to have affected the neutralisation specificity of their VP7 and VP4. In conclusion, apart from prevalent P[8]b VP4, virtually no differences were observed between the predominant strains circulating in Vietnam at the time of the clinical trial and the strains in the developed countries; hence, the lower vaccine efficacy was more likely to be due to factors other than strain divergence.

High-sensitivity C-reactive protein predicts adverse cardiovascular events in patients with Takayasu arteritis with coronary artery involvement.

The study aimed to assess the association of high-sensitivity C-reactive protein (hsCRP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) to major adverse cardiovascular events (MACE) in Takayasu arteritis (TA) patients with coronary artery disease (CAD). Data on 60 TA patients with CAD and 60 age- and severity-matched patients with CAD hospitalized in Fuwai Hospital from 2005 to August 2014 were assessed. The clinical features, laboratory data, coronary angiographic findings, treatment, and follow-up outcomes were summarized retrospectively. MACE were defined as death from cardiac causes, myocardial infarction, nonfatal target vessel revascularization, or rehospitalization due to unstable or progressive angina. CAD patients had more atherogenic lipid and lipoprotein profiles such as lower levels of high-density lipoprotein cholesterol (HDL-C) (1.0 ± 0.2 vs. 1.3 ± 0.3 mmol/L, p = 0.01) and higher levels of low-density lipoprotein cholesterol (LDL-C) (2.5 ± 0.9 vs. 2.2 ± 1.1 mmol/L, p = 0.04) in contrast with TA-CAD patients. During a mean follow-up period of 3.2 years, 31 patients with Takayasu coronary arteritis reached the endpoint. Multivariate Cox proportional hazards model demonstrated that log(hsCRP) (HR = 5.3, 95 % CI = 1.1-27.8, p = 0.04) was a significant and independent predictor of MACE in patients with Takayasu coronary arteritis. Elevated baseline levels of hsCRP predict cardiovascular events, independent of other prognostic markers in TA-related CAD patients.

Alterations in cortisol concentrations and expression of certain genes associated with neutrophil functions in cows developing retention of fetal membranes.

Elevated cortisol concentrations have been reported to impair the functions and alter the life span of neutrophils in cows. The present study assessed the cortisol concentrations and expression of few genes related to longevity (Fas, Caspase 3, Bcl2) and margination (CD 62L, CD 18/11b) of neutrophils in relation to retention of fetal membranes (RFM) in dairy cows. Cortisol concentrations were significantly higher on the day of calving and day 2 postpartum in RFM cows than normal cows. Expression of CD 62L was significantly lower on the day of calving and day 2 postpartum in RFM cows than normal cows. While expression of Fas and GR was significantly lower on the day of calving, expression of Bcl2 was lower on day 7±2 pre-partum in RFM cows compared to normal cows. No significant difference was observed in the expression of CD 18/11b and Caspase 3 between RFM and normal cows. Cortisol concentration was negatively correlated with expression of GR, Fas, CD 62L, CD18/CD11b and Caspase 3, while positively correlated with immature neutrophil percentage and expression of Bcl2. It may be inferred that cortisol concentrations and expression of certain genes associated with lifespan and margination of neutrophils were altered in cows developing RFM compared to those expelled the fetal membranes normally.