Identifying exceptional malaria occurrences in the absence of historical data in South Sudan: a method validation.

BACKGROUND: Detecting unusual malaria events that may require an operational intervention is challenging, especially in endemic contexts with continuous transmission such as South Sudan. Médecins Sans Frontières (MSF) utilises the classic average plus standard deviation (AV+SD) method for malaria surveillance. This and other available approaches, however, rely on antecedent data, which are often missing. OBJECTIVE: To investigate whether a method using linear regression (LR) over only 8 weeks of retrospective data could be an alternative to AV+SD. DESIGN: In the absence of complete historical malaria data from South Sudan, data from weekly influenza reports from 19 Norwegian counties (2006-2015) were used as a testing data set to compare the performance of the LR and the AV+SD methods. The moving epidemic method was used as the gold standard. Subsequently, the LR method was applied in a case study on malaria occurrence in MSF facilities in South Sudan (2010-2016) to identify malaria events that required a MSF response. RESULTS: For the Norwegian influenza data, LR and AV+SD methods did not perform differently (P > 0.05). For the South Sudanese malaria data, the LR method identified historical periods when an operational response was mounted. CONCLUSION: The LR method seems a plausible alternative to the AV+SD method in situations where retrospective data are missing.

European all-cause excess and influenza-attributable mortality in the 2017/18 season: should the burden of influenza B be reconsidered?

OBJECTIVES: Weekly monitoring of European all-cause excess mortality, the EuroMOMO network, observed high excess mortality during the influenza B/Yamagata dominated 2017/18 winter season, especially among elderly. We describe all-cause excess and influenza-attributable mortality during the season 2017/18 in Europe. METHODS: Based on weekly reporting of mortality from 24 European countries or sub-national regions, representing 60% of the European population excluding the Russian and Turkish parts of Europe, we estimated age stratified all-cause excess morality using the EuroMOMO model. In addition, age stratified all-cause influenza-attributable mortality was estimated using the FluMOMO algorithm, incorporating influenza activity based on clinical and virological surveillance data, and adjusting for extreme temperatures. RESULTS: Excess mortality was mainly attributable to influenza activity from December 2017 to April 2018, but also due to exceptionally low temperatures in February-March 2018. The pattern and extent of mortality excess was similar to the previous A(H3N2) dominated seasons, 2014/15 and 2016/17. The 2017/18 overall all-cause influenza-attributable mortality was estimated to be 25.4 (95%CI 25.0-25.8) per 100,000 population; 118.2 (116.4-119.9) for persons aged 65. Extending to the European population this translates into over-all 152,000 deaths. CONCLUSIONS: The high mortality among elderly was unexpected in an influenza B dominated season, which commonly are considered to cause mild illness, mainly among children. Even though A(H3N2) also circulated in the 2017/18 season and may have contributed to the excess mortality among the elderly, the common perception of influenza B only having a modest impact on excess mortality in the older population may need to be reconsidered.

Gold and Hydroxyapatite Nano-Composite Scaffolds for Anterior Cruciate Ligament Reconstruction: In Vitro Characterization.

Current anterior cruciate ligament (ACL) graft replacement materials often fail due to the lack of biological integration. While many newly developed extracellular matrix based scaffolds show good biocompatibility they often do not entice cellular remodeling and the rebuilding of a functional ligament. We have proposed the conjugation of gold nanoparticles (AuNP) and hydroxyapatite nanoparticles (nano-HAp) to acellular tissue to enhance cell attachment and proliferation while maintaining an improved degradation resistance and open microstructure. We are the first to investigate the double conjugation of AuNP and nano-HAp onto decellularized tissue to improve the tissue remodeling response. Decellularized porcine diaphragm was crosslinked with two types of nano-HAp and amine-functionalized AuNP with 1-ethyl-3-(3-dimethlaminopropyl) carbodiimide (EDC) crosslinker. Scaffolds were characterized using electron microscopy, differential scanning calorimetry, and fibroblast assays. Results demonstrated that scaffolds with nano-HAp have increased thermal stability at low levels of crosslinking. The open microstructure of the scaffold was not compromised allowing for cell migration while still providing increased degradation resistance. The addition of < 200 nm nano-HAp decreased cell viability compared to scaffolds without nanoparticles, but the addition of AuNP to scaffolds showed enhanced cell viability in the presence of < 200 nm nano-HAp. The addition of < 40 nm nano-HAp showed an increase in cell viability compared to scaffolds crosslinked without nanoparticles. It is concluded that attaching AuNP and < 40nm nano-HAp to extracellular matrices may improve overall properties.

DNA microarray analysis of Staphylococcus aureus causing bloodstream infection: bacterial genes associated with mortality?

Providing evidence for microbial genetic determinants' impact on outcome in Staphylococcus aureus bloodstream infections (SABSI) is challenging due to the complex and dynamic microbe-host interaction. Our recent population-based prospective study reported an association between the S. aureus clonal complex (CC) 30 genotype and mortality in SABSI patients. This follow-up investigation aimed to examine the genetic profiles of the SABSI isolates and test the hypothesis that specific genetic characteristics in S. aureus are associated with mortality. SABSI isolates (n = 305) and S. aureus CC30 isolates from asymptomatic nasal carriers (n = 38) were characterised by DNA microarray analysis and spa typing. Fisher's exact test, least absolute shrinkage and selection operator (LASSO) and elastic net regressions were performed to discern within four groups defined by patient outcome and characteristics. No specific S. aureus genetic determinants were found to be associated with mortality in SABSI patients. By applying LASSO and elastic net regressions, we found evidence suggesting that agrIII and cna were positively and setC (=selX) and seh were negatively associated with S. aureus CC30 versus non-CC30 isolates. The genes chp and sak, encoding immune evasion molecules, were found in higher frequencies in CC30 SABSI isolates compared to CC30 carrier isolates, indicating a higher virulence potential. In conclusion, no specific S. aureus genes were found to be associated with mortality by DNA microarray analysis and state-of-the-art statistical analyses. The next natural step is to test the hypothesis in larger samples with higher resolution methods, like whole genome sequencing.

Role of brain aldosterone and mineralocorticoid receptors in aldosterone-salt hypertension in rats.

Central blockade of mineralocorticoid receptors (MRs) or angiotensin II type 1 receptors (AT1Rs) attenuates aldosterone (aldo)-salt induced hypertension. We examined the role of the subfornical organ (SFO), aldo synthesized locally in the brain, and MR and AT1R specifically in the paraventricular nucleus (PVN) in aldo-salt hypertension. Wistar rats were treated with subcutaneous aldo (1 µg/h) plus saline as drinking fluid, and gene expression was assessed by real-time qPCR. Other sets of rats received chronic intra-cerebroventricular (icv) infusion of aldo synthase (AS) inhibitor FAD286, MR blocker eplerenone or vehicle, electrolytic or sham lesions of the SFO, or intra-PVN infusion of AAV-MR-siRNA or AAV-AT1aR-siRNA. Infusion of aldo had no effect on 11ßHSD2, MR and AT1R mRNA in different nuclei but increased CYP11B2 mRNA in the SFO, and serum and glucocorticoid-kinase 1 (Sgk1) and epithelial sodium channel (ENaC) γ subunit mRNA in the SFO and supraoptic nucleus (SON). MR-siRNA decreased both MR and AT1R mRNA in the PVN by ∼ 60%, but AT1aR-siRNA only decreased AT1R mRNA. SFO lesion, blockade of brain AS or MR, or knockdown of MR or AT1R in the PVN similarly attenuated aldosterone-induced saline intake by ∼ 50% and hypertension by ∼ 70%. These results suggest that an increase in circulating aldosterone may via MR and AT1R in the SFO increase local aldosterone production in hypothalamic nuclei such as the SON and PVN, and via MR enhance AT1R signaling in the PVN. This central aldosterone-MR-AT1R neuro-modulatory pathway appears to play a major role in the progressive hypertension.

Treatment of canine nasopharyngeal stenosis using balloon-expandable metallic stents: long-term follow-up of four cases.

Four dogs were diagnosed with nasopharyngeal stenosis using endoscopy and magnetic resonance imaging. Treatment using balloon-expandable metallic stent, placed under fluoroscopic and endoscopic guidance, resulted in immediate resolution of clinical signs. All dogs were clinically normal 40 to 62 months following stent placement.

Muscle Derived Stem Cells Stimulate Muscle Myofiber Repair and Counteract Fat Infiltration in a Diabetic Mouse Model of Critical Limb Ischemia.

BACKGROUND: Critical Limb Ischemia (CLI) affects patients with Type 2 Diabetes (T2D) and obesity, with high risk of amputation and post-surgical mortality, and no effective medical treatment. Stem cell therapy, mainly with bone marrow mesenchymal, adipose derived, endothelial, hematopoietic, and umbilical cord stem cells, is promising in CLI mouse and rat models and is in clinical trials. Their general focus is on angiogenic repair, with no reports on the alleviation of necrosis, lipofibrosis, and myofiber regeneration in the ischemic muscle, or the use of Muscle Derived Stem Cells (MDSC) alone or in combination with pharmacological adjuvants, in the context of CLI in T2D. METHODS: Using a T2D mouse model of CLI induced by severe unilateral femoral artery ligation, we tested: a) the repair efficacy of MDSC implanted into the ischemic muscle and the effects of concurrent intraperitoneal administration of a nitric oxide generator, molsidomine; and b) whether MDSC may partially counteract their own repair effects by stimulating the expression of myostatin, the main lipofibrotic agent in the muscle and inhibitor of muscle mass. RESULTS: MDSC: a) reduced mortality, and b) in the ischemic muscle, increased stem cell number and myofiber central nuclei, reduced fat infiltration, myofibroblast number, and myofiber apoptosis, and increased smooth muscle and endothelial cells, as well as neurotrophic factors. The content of myosin heavy chain 2 (MHC-2) myofibers was not restored and collagen was increased, in association with myostatin overexpression. Supplementation of MDSC with molsidomine failed to stimulate the beneficial effects of MDSC, except for some reduction in myostatin overexpression. Molsidomine given alone was rather ineffective, except for inhibiting apoptosis and myostatin overexpression. CONCLUSIONS: MDSC improved CLI muscle repair, but molsidomine did not stimulate this process. The combination of MDSC with anti-myostatin approaches should be explored to restore myofiber MHC composition.

Perfluoroalkyl substances measured in breast milk and child neuropsychological development in a Norwegian birth cohort study.

Perfluoroalkyl substances (PFASs) are chemicals with potential neurotoxic effects although the current evidence is still limited. This study investigated the association between perinatal exposure to perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) and neuropsychological development assessed at 6, 12 and 24 months. We measured PFOS and PFOA in breast milk samples collected one month after delivery by mothers of children participating in the HUMIS study (Norway). Cognitive and psychomotor development was measured at 6 and at 24 months using the Ages and Stages Questionnaire (ASQ-II). Behavioral development was assessed using the infant-toddler symptom checklist (ITSC) at 12 and at 24 months. Weighted logistic regression and weighted negative binomial regression models were applied to analyze the associations between PFASs and ASQ-II and ITSC, respectively. The median concentration of PFOS was 110 ng/L, while the median for PFOA was 40 ng/L. We did not detect an increased risk of having an abnormal score in ASQ-II at 6 months or 24 months. Moreover, no consistent increase in behavioral problems assessed at 12 and 24 months by ITSC questionnaire was detected. We observed no association between perinatal PFOS and PFOA exposure and early neuropsychological development. Further longitudinal studies are needed to confirm the effects of these compounds on neuropsychological development in older children.

Use of silicone tracheal stoma stents for temporary tracheostomy in dogs with upper airway obstruction.

OBJECTIVES: To report the use of silicone tracheal stoma stents for temporary tracheostomy in dogs with upper airway obstruction. METHODS: Retrospective review of medical records for dogs in which silicone tracheal stoma stents were placed. RESULTS: Eighteen dogs had a silicone tracheal stoma stent placed for maintenance of a tracheostomy stoma for periods ranging from three hours to eight months. No intra-operative or immediate postoperative complications were recorded. In 11 dogs the stent was removed by simple traction after a period ranging from 36 hours to 6 weeks, and the tracheal stoma was left to heal by second intention. Five of the 18 dogs were determined as being tracheostomy dependent and underwent conversion to permanent tracheostomy after a period ranging from five days to eight months following stent placement. One dog was euthanased after three months, with the stent still in place, because of poor respiratory function, and one dog died of unrelated reasons. In 6 of 10 dogs (60%) where the stent was in place for five days or more, granulation tissue formation caused dislodgement of the stent. CLINICAL SIGNIFICANCE: Silicone tracheal stoma stents may be used as an alternative to conventional tracheostomy tubes in selected dogs with upper airway obstruction. Long-term use of the stent beyond five days is not recommended because of granulation tissue formation. The long-term consequences of partial tracheal ring resection are unknown.

Mediastinectomy for management of chronic pyogranulomatous pleural disease in dogs.

The medical records of 12 dogs with chronic pyogranulomatous pleural disease unresponsive to medical management were reviewed retrospectively. Resection of the mediastinal pleura (mediastinectomy) was performed through a median sternotomy to remove all diseased and surgically accessible mediastinal pleural tissue. Dogs were re-examined two weeks postoperatively, and long-term outcome was evaluated by contacting owners by phone. Twelve dogs underwent mediastinectomy; additional surgeries included subtotal pericardiectomy (8), lung lobectomy (4) and partial diaphragmatic resection (2). Histology of resected tissue consistently revealed neutrophilic, pyogranulomatous cellulitis/serositis. Foreign material was evident in the mediastinal tissue of five dogs and microorganisms were recovered from three dogs. Two dogs developed pneumothorax immediately postoperatively; one dog developed haemothorax one month postoperatively and was euthanased. Median follow-up time was eight months (range: 6-43 months); eleven dogs were alive and considered to be symptom-free by their owners. Mediastinectomy resulted in complete resolution of symptoms in most dogs (92 per cent) and was associated with a low incidence of major complications. The results of this study indicated that mediastinectomy results in favourable outcome for dogs with chronic pleural pyogranulomatous pleural disease unresponsive to medical management.

Evaluating the effect of ration composition on income over feed cost and milk yield.

Feed is generally the greatest expense for milk production. With volatility in feed and milk markets, income over feed cost (IOFC) is a more advantageous measure of profit than simply feed cost per cow. The objective of this study was to evaluate the effects of ration cost and ingredient composition on IOFC and milk yield. The Pennsylvania State Extension Dairy Team IOFC tool (http://extension.psu.edu/animals/dairy/business-management/financial-tools/income-over-feed-cost/introduction-to-iofc) was used to collect data from 95 Pennsylvania lactating dairy cow herds from 2009 to 2012 and to determine the IOFC per cow per day. The data collected included average milk yield, milk income, purchased feed cost, ration ingredients, ingredient cost per ton, and amount of each ingredient fed. Feed costs for home-raised feeds for each ration were based on market values rather than on-farm cost. Actual costs were used for purchased feed for each ration. Mean lactating herd size was 170 ± 10.5 and daily milk yield per cow was 31.7 ± 0.19 kg. The mean IOFC was $7.71 ± $1.01 cost per cow, ranging from -$0.33 in March 2009 to $16.60 in September 2011. Data were analyzed using a one-way ANOVA in SPSS (IBM Corp., Armonk, NY). Values were grouped by quartiles and analyzed with all years combined as well as by individual year. Purchased feed cost per cow per day averaged $3.16 ± $1.07 for 2009 to 2012. For 2009 to 2012 combined, milk yield and IOFC did not differ with purchased feed cost. Intermediate levels (quartiles 2 and 3) of forage cost per cow per day between $1.45 and $1.97 per cow per day resulted in the greatest average IOFC of $8.19 and the greatest average milk yield of 32.3 kg. Total feed costs in the fourth quartile ($6.27 or more per cow per day) resulted in the highest IOFC. Thus, minimizing feed cost per cow per day did not maximize IOFC. In 2010, the IOFC was highest at $8.09 for dairies that fed 1 or more commodity by-products. Results of the study indicated that intermediate levels of forage cost and higher levels of total feed cost per cow per day resulted in both higher milk yield and higher IOFC. This suggests that optimal ration formulation rather than least cost strategies may be key to increasing milk yield and IOFC, and that profit margin may be affected more by quality of the feed rather than the cost.

Prevalence and causes of vision loss in Southeast Asia and Oceania: 1990-2010.

BACKGROUND: To assess prevalence and causes of vision impairment in Southeast Asia and Oceania in 1990 and 2010. METHODS: Based on a systematic review of medical literature, prevalence of moderate and severe vision impairment (MSVI; presenting visual acuity <6/18 but ≥3/60 in the better eye) and blindness (presenting visual acuity <3/60) was estimated for 1990 and 2010. RESULTS: In Oceania, the age-standardised prevalence of blindness and MSVI did not decrease significantly (1.3% to 0.8% and 6.6% to 5.1%) respectively, but in Southeast Asia, blindness decreased significantly from 1.4% to 0.8%, a 43% decrease. There were significantly more women blind (2.18 million) compared with men (1.28 million) in the Southeast Asian population in 2010, but no significant gender differences in MSVI in either subregion. Cataract was the most frequent cause of blindness in Southeast Asia and Oceania in 1990 and 2010. Uncorrected refractive error, followed by cataract, macular degeneration, glaucoma and diabetic retinopathy were the most common causes for MSVI in 1990 and 2010. With the increasing size of the older population, there have been relatively small increases in the number of blind (2%), and with MSVI (14%) in Southeast Asia, whereas increases have been greater in Oceania of 14% for blindness and of 31% for MSVI. CONCLUSIONS: The prevalence of blindness has reduced significantly from 1990 to 2010, with moderate but non-significant lowering of MSVI. Cataract and uncorrected refractive error are the main causes of vision impairment and blindness; cataract continues as the main cause of blindness, but at lower proportions.

Successful management of an arytenoid chondrosarcoma in a dog.

An eight-year-old Doberman pinscher was presented with a four-week history of inspiratory stridor, dysphonia, inappetence and weight loss. Inspiratory stridor was apparent and became more pronounced during gentle compression of the larynx. Previous investigations, including laryngoscopy, had revealed the presence of a left-sided arytenoid mass. Histological examination of pinch biopsies was not diagnostic. The mass was removed by resection of the arytenoid cartilage through a ventral laryngotomy allowing salvage of the cuneiform process. Histological examination of the laryngeal mass was consistent with a chondrosarcoma, grade I, infiltrating the arytenoid cartilage. Re-examination at 12 months showed complete resolution of the clinical signs and no signs of metastatic disease. To the authors' knowledge this is the first report of successful surgical intervention for laryngeal chondrosarcoma. This case demonstrates that resection via a ventral laryngotomy may be a viable and curative therapeutic option for some sarcomas of the larynx.

Successful treatment of bilateral Paecilomyces pyelonephritis in a German shepherd dog.

A six-year-old female entire German shepherd dog was investigated for polyuria, polydipsia and lethargy. Investigations revealed a mild azotaemia and abdominal ultrasound revealed marked bilateral dilation of the renal pelves with echogenic material and proximal left hydroureter. Urine cytological examination and aspirates from the right renal pelvis revealed mats of fungal hyphae consistent with fungal bezoar formation. Fungal cultures revealed a profuse growth of Paecilomyces variotii. Initial treatment with oral itraconazole was unsuccessful, leading to bilateral nephrotomies to remove the fungal material. Postoperatively the Paecilomyces infection persisted despite continued itraconazole therapy. Treatment was commenced with amphotericin B, leading to resolution of the dog's clinical signs. To the authors' knowledge this is the first report of canine Paecilomyces pyelonephritis, without disseminated systemic disease, which documents its successful treatment.

WHO guidelines for the programmatic management of drug-resistant tuberculosis: 2011 update.

The production of guidelines for the management of drug-resistant tuberculosis (TB) fits the mandate of the World Health Organization (WHO) to support countries in the reinforcement of patient care. WHO commissioned external reviews to summarise evidence on priority questions regarding case-finding, treatment regimens for multidrug-resistant TB (MDR-TB), monitoring the response to MDR-TB treatment, and models of care. A multidisciplinary expert panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to develop recommendations. The recommendations support the wider use of rapid drug susceptibility testing for isoniazid and rifampicin or rifampicin alone using molecular techniques. Monitoring by sputum culture is important for early detection of failure during treatment. Regimens lasting ≥ 20 months and containing pyrazinamide, a fluoroquinolone, a second-line injectable drug, ethionamide (or prothionamide), and either cycloserine or p-aminosalicylic acid are recommended. The guidelines promote the early use of antiretroviral agents for TB patients with HIV on second-line drug regimens. Systems that primarily employ ambulatory models of care are recommended over others based mainly on hospitalisation. Scientific and medical associations should promote the recommendations among practitioners and public health decision makers involved in MDR-TB care. Controlled trials are needed to improve the quality of existing evidence, particularly on the optimal composition and duration of MDR-TB treatment regimens.

Rib metastases from a non-tonsillar squamous cell carcinoma in a dog.

Metastatic spread to the ribs in a 15-year-old, male, neutered, Irish setter is reported occurring secondary to an oral squamous cell carcinoma (SCC). The dog presented with a history of a rapidly growing SCC of the right upper incisive region, which was confirmed by histopathology as a SCC. Thoracic radiographs showed bony lesions associated with the body of the right third rib, and the fifth and seventh costal cartilages. A rostral partial maxillectomy was performed as palliative treatment for the oral mass and a core biopsy of the lesion on the third rib was performed. The rib lesion was identified histopathologically as a metastatic SCC. A review of the literature of oropharyngeal SCC and the metastatic potential of non-tonsillar SCC is presented, in particular metastatic bone disease. This case report suggests possible implications of metastatic bone disease for treatment and prognosis for future cases of non-tonsillar SCC.

TGFß signaling in head and neck squamous cell carcinoma.

Transforming growth factor beta (TGFß) is a key regulator of epithelial cell proliferation, immune function and angiogenesis. Because TGFß signaling maintains epithelial homeostasis, dysregulated TGFß signaling is common in many malignancies, including head and neck squamous cell carcinoma (HNSCC). Defective TGFß signaling in epithelial cells causes hyperproliferation, reduced apoptosis and increased genomic instability, and the compensatory increase in TGFß production by tumor epithelial cells with TGFß signaling defects further promotes tumor growth and metastases by increasing angiogenesis and inflammation in tumor stromal cells. Here, we review the mouse models that we used to study TGFß signaling in HNSCC.

Role of fluorescence in situ hybridization in sequencing the tomato genome.

The tomato (Solanum lycopersicum L.) genome is being sequenced by a consortium of laboratories in 10 countries. Seventy-seven percent of the tomato genome (DNA) is located in repeat-rich, gene-poor, pericentric heterochromatin, while 23% of the genome is located in repeat-poor, gene-rich, distal euchromatin. It is estimated that approximately 90% of tomato's nuclear genes can be characterized by limiting the sequencing effort to euchromatin while avoiding the problems involved in sequencing the repetitive DNA in heterochromatin. Sequencing is being performed on tomato nuclear DNA cloned into bacterial artificial chromosome (BAC) vectors. Fluorescence in situ hybridization (FISH) is used to help direct the sequencing effort by cytologically demonstrating the location of selected BACs on tomato chromosomes. While mitotic metaphase chromosomes are too short and compact for this purpose, long pachytene chromosomes are ideal. BACs localized in euchromatin can be used confidently as anchors for the assembly of BAC contigs that extend through the euchromatic length of each chromosome arm. Another important role for FISH is identification of BACs near telomeres and near borders with pericentric heterochromatin to indicate that sequencing should not extend much further. This role of FISH is enhanced by our ability to estimate base pair distances between localized BACs and these chromosomal features. Finally, it is noteworthy that when BAC-FISH is combined with chromosomal in situ suppression (CISS) hybridization to block repeats and localize single/low copy sequences, the great majority of BACs localize to single sites. This observation is consistent with tomato being an ancient diploid.

Treatment of idiopathic chylothorax in 14 dogs by ligation of the thoracic duct and partial pericardiectomy.

The outcome and complications associated with thoracic duct ligation combined with partial pericardiectomy in 14 dogs with idiopathic chylothorax were investigated retrospectively. Nine of the dogs were treated in the uk and five in Italy. All of them were reassessed clinically four weeks after surgery and the respiratory function and any pleural fluid accumulation were evaluated; they were followed up by telephone contact for at least six months. Eleven of the dogs were clinically normal and had no radiographic signs of pleural effusion when reassessed after four weeks. Two showed radiographic signs of a minor accumulation of pleural fluid but were clinically normal; when reassessed after three months they showed similar radiographic signs and clinical findings; but after four months there was no evidence of pleural effusion. One dog had a major complication that required a second surgical intervention.