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.

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.

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.

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.

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.

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.

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.

Modulation of post-partum reproductive performance in dairy cows through supplementation of long- or short-chain fatty acids during transition period.

Thirty-six cross-bred cows were used to study the effect of long-chain (flaxseed) or short-chain (butyric acid) fatty acid supplementation on metabolic status, ovarian function and reproduction performance during transition period. Control cows received a routine feed of transition diet, while the cows in two treatment groups were supplemented with either 750-g crushed flaxseed or 250 g butyric acid per cow per day. Ovarian activity was monitored by transrectal ultrasonography on 10th, 20th and 30th days post-partum. Blood samples were collected by jugular venipuncture into heparinized polystyrene tubes; plasma was prepared and stored under -20 °C until analysis. Results indicated that cows in flaxseed group were in positive energy balance as indicated by lower NEFA and Beta hydroxy Butyrate and higher glucose concentrations. Uterine involution was completed well within 30 days post-partum in all the cows in flaxseed fed group compared to 76.9% in butyric acid supplemented and 61.5% in control groups. The size of dominant follicle and corpus luteum was significantly higher (p < 0.05) for flaxseed group compared to control group, which in turn resulted in higher concentrations of plasma progesterone. Cows fed on diets supplemented with flaxseed exhibited post-partum heat earlier and bred sooner (p < 0.05) than control cows. It has been noticed that supplementation of flaxseed and butyric acid enhanced involution of uterus, early resumption of cyclicity and thereby early breeding. However, in view of the encouraging results obtained for flaxseed supplemented group, its organic nature and easier availability at farmer's gate, we concluded that flaxseed can be safely included in transition diet to modulate reproductive performance of dairy cattle.

18-FDG-PET in assessing disease activity in Takayasu arteritis: a meta-analysis.

OBJECTIVES: To assess the diagnosis value of 18-FDG-PET in estimating disease activity in Takayasu arteritis. METHODS: A complete search of PubMed, EMBASE and The Cochrane Library was finished to July 25, 2012. Sensitivity and specificity as well as pooled estimates of positive and negative likelihood ratios (PLR and NLR) were calculated by Meta-Disc. We also calculated the area under the sROC curve (AUC) and the Q* index. RESULTS: The meta-analysis was finished with 6 study retrieved from the database search. The pooled sensitivity, and specificity with 95% confidence interval were 70.1% (95% CI, 58.6-80.0) and 77.2% (95% CI, 64.2-87.3). The PLR and NLR were 2.313 (95% CI 1.108-4.829) and 0.341 (95% CI 0.142-0.824). The AUC was 0.805(±0.084) and Q* index was 0.7402 (±0.0739). CONCLUSIONS: 18-FDG-PET had moderate diagnosis value in assessing TA activity. It may add additional value to the current diagnosis methods.

Effect of supplementation of vitamin E, copper and zinc on the in vitro phagocytic activity and lymphocyte proliferation index of peripartum Sahiwal (Bos indicus) cows.

To study the effect of vitamin E (VE), copper (Cu) and zinc (Zn) supplementation on the in vitro phagocytic activity (PA) and lymphocyte proliferation response (LPR) of blood neutrophils and lymphocytes, thirty Sahiwal pregnant cows (six in each group) in their late gestation at 30 days before the expected date of calving were selected from the NDRI experimental herd and supplemented with various micronutrients from 30 days before calving to 45 days after calving. Cows were supplemented individually with VE (1000 IU/cow/day), Cu (20 ppm/cow/day) and Zn (80 ppm/cow/day) and also with a combination of VE, Cu and Zn to study cumulative effect of all micronutrients. One group without any supplementation acted as a control. Blood neutrophils and lymphocytes were isolated and studied for their PA and LPR. Supplementation of micronutrients like VE, Cu, Zn and a combination of all these nutrients significantly (p < 0.01) increased the PA of experimental cows as compared to control (unsupplemented) cows during the pre-partum period. During post-partum, all the micronutrients (VE, Cu, Zn and their combination) showed a significant (p < 0.01) increase in the PA of experimental cows as compared to control cows. Of all the groups, significant (p < 0.01) and maximum PA was observed in the combination group followed by Zn-supplemented group during both the pre- and post-partum period. A significant (p < 0.01) increase in LPR of B lymphocytes was observed in combination-supplemented group during the pre-partum period and during both the pre- and post-partum period in the Cu-supplemented group.

Selection of suitable reference genes for quantitative gene expression studies in milk somatic cells of lactating cows (Bos indicus).

We assessed the suitability of 9 internal control genes (ICG) in milk somatic cells of lactating cows to find suitable reference genes for use in quantitative PCR (qPCR). Eighteen multiparous lactating Sahiwal cows were used, 6 in each of 3 lactation stages: early (25 ± 5 d in milk), mid (160 ± 15 d in milk), and late (275 ± 25 d in milk) lactation. Nine candidate reference genes [glyceraldehyde 3-phosphate dehydrogenase (GAPDH), protein phosphatase 1 regulatory subunit 11 (PPP1R11), ß-actin (ACTB), ß-2 microglobulin (B2M), 40S ribosomal protein S15a (RPS15A), ubiquitously expressed transcript (UXT), mitochondrial GTPase 1 (MTG1), 18S rRNA (RN18S1), and ubiquitin (UBC)] were evaluated. Three genes, ß-casein (CSN2), lactoferrin (LTF), and cathelicidin (CAMP) were chosen as target genes. Very high amplification was observed in 7 ICG and very low level amplification was observed in 2 ICG (UXT and MTG1). Thus, UXT and MTG1 were excluded from further analysis. The qPCR data were analyzed by 2 software packages, geNorm and NormFinder, to determine suitable reference genes, based on their stability and expression. Overall, PPP1R11, ACTB, UBC, and GAPDH were stably expressed among all candidate reference genes. Therefore, these genes could be used as ICG for normalization of qPCR data in milk somatic cells through lactation.

Evaluation of methods to estimate glomerular filtration rate versus actual drug clearance in patients with chronic spinal cord injury.

STUDY DESIGN: A retrospective chart review. OBJECTIVES: To evaluate different methods of estimating renal function compared with patient-specific vancomycin and aminoglycoside (AG) clearance (CL(DRUG)) in patients with spinal cord injury (SCI), and to develop a new equation to more accurately estimate glomerular filtration rate (GFR) in SCI patients in order to optimize dosing for vancomycin and AG. SETTING: Veterans Affairs medical center in California, United States of America, tertiary care facility with the largest inpatient SCI center in the VA system. METHODS: Retrospective data collection from patient records. Pharmacokinetic analysis was performed to obtain actual CL(DRUG,) which is compared with different methods of estimating GFR.A total of 310 patients were initially assessed; however, only 141 patients met the inclusion criteria, had a diagnosis of chronic SCI, and received vancomycin or AG with at least one drug level at steady state from January to December of 2008. RESULTS: All four equations evaluated to estimate GFR significantly overestimated CL(DRUG): the Modification of Diet in Renal Disease equation by 141%, Cockcroft-Gault equation by 83%, Chronic Kidney Disease Epidemiology Collaboration equation by 82% and 24-h endogenous creatinine clearance by 71% (P<0.001). The modified Cockcroft-Gault equation (CL(M)) showed improvement, however, still overestimated CL(DRUG) by 39% (P<0.001). Thus, a new equation for SCI (CL(SCI)) was developed which underestimated CL(DRUG) by <5% (P=0.16). CONCLUSION: Compared with different methods of estimating GFR, CL(SCI)=2.3 × x (0.7) (x equals CL(M) in ml min(-1)) more accurately estimates CL(DRUG) in chronic SCI patients.

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.

In vitro phagocytic activity of milk neutrophils during lactation cycle in Murrah buffaloes of different parity.

Milk samples were collected from 34 lactating Murrah buffaloes on days 0, 5, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240, 270 and day 300 after calving. Milk somatic cell counts (SCC) were highest in multiparous buffaloes. Milk SCC were significantly lower in buffaloes of third and fourth parity during early lactation and than increased significantly (p < 0.01) by the end of lactation. Milk neutrophils were significantly lower in all the buffaloes during early lactation, but increased significantly (p < 0.01) afterwards. Milk lymphocytes were significantly higher during early lactation, but decreased significantly (p < 0.01) by the end of lactation. Phagocytic activity (PA) was highest in day 1 colostrum and then decreased significantly (p < 0.01) by the fourth milking in buffaloes of second, third and fourth parity. Phagocytic index (PI) was also highest in colostrums of primiparous buffaloes. Irrespective of parity, maximum PA and PI was observed during mid lactation. In terms of in vitro phagocytic activity, early lactation is the most critical period followed by late and mid lactation.

Changes in colostrum of Murrah buffaloes after calving.

Colostrum samples were collected from 8 Murrah buffaloes on days 1, 2, 3, 4 and 5 after calving. Levels of IgG averaged 54.0 mg/ml at calving, then decreased significantly (P < 0.01). IgA and IgM on day 1 were 3.22 mg/ml and 5.22 mg/ml, respectively; both decreased during the first five days after calving. Values of IgA and IgM were higher than those reported in cows. SCC values, which were high at calving (500,000 per ml), reduced significantly (P < 0.01) on day 2, then decreased slightly until day 5 (180,000 per ml). At calving, macrophages were the most prominent cells in buffalo colostrum, followed by lymphocytes and neutrophils. Phagocytic activity was 23% at calving and reduced significantly (P < 0.01) to 14% on day 5. Phagocytic index was highest in the first colostrum, and then decreased non-significantly.

Nicolau syndrome following intramuscular benzathine penicillin.

Nicolau syndrome (NS) is a rare complication of an intramuscular injection characterized by severe pain, skin discoloration, and varying levels of tissue necrosis. The case outcomes vary from atrophic ulcers and severe pain to sepsis and limb amputation. We describe a case of a seven-year-old boy with diagnosis of NS after intramuscular benzathine penicillin injection to the ventrolateral aspect of the left thigh. Characteristic violaceous discoloration of skin and immediate injection site pain identified it as a case of NS. The case was complicated by rapid progression of compartment syndrome of the lower limb, proceeding to acute renal failure and death. Associated compartment syndrome can be postulated as a poor prognostic factor for NS.

Staphylococcal toxic shock syndrome.

A 28 year old male presented with fever, tachycardia, generalized lymphadenopathy and diffuse rash over the body. He failed to respond to intravenous antibiotics and developed cardiogenic shock, multiple organ failure and died within six hours after hospitalization. Staphylococcus aureus colonies were revealed on blood culture.

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.

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.