Polyamine metabolism impacts T cell dysfunction in the oral mucosa of people living with HIV.

Metabolic changes in immune cells contribute to both physiological and pathophysiological outcomes of immune reactions. Here, by comparing protein expression, transcriptome, and salivary metabolome profiles of uninfected and HIV+ individuals, we found perturbations of polyamine metabolism in the oral mucosa of HIV+ patients. Mechanistic studies using an in vitro human tonsil organoid infection model revealed that HIV infection of T cells also resulted in increased polyamine synthesis, which was dependent on the activities of caspase-1, IL-1ß, and ornithine decarboxylase-1. HIV-1 also led to a heightened expression of polyamine synthesis intermediates including ornithine decarboxylase-1 as well as an elevated dysfunctional regulatory T cell (TregDys)/T helper 17 (Th17) cell ratios. Blockade of caspase-1 and polyamine synthesis intermediates reversed the TregDys phenotype showing the direct role of polyamine pathway in altering T cell functions during HIV-1 infection. Lastly, oral mucosal TregDys/Th17 ratios and CD4 hyperactivation positively correlated with salivary putrescine levels, which were found to be elevated in the saliva of HIV+ patients. Thus, by revealing the role of aberrantly increased polyamine synthesis during HIV infection, our study unveils a mechanism by which chronic viral infections could drive distinct T cell effector programs and Treg dysfunction.

A cattle graph genome incorporating global breed diversity.

Despite only 8% of cattle being found in Europe, European breeds dominate current genetic resources. This adversely impacts cattle research in other important global cattle breeds, especially those from Africa for which genomic resources are particularly limited, despite their disproportionate importance to the continent's economies. To mitigate this issue, we have generated assemblies of African breeds, which have been integrated with genomic data for 294 diverse cattle into a graph genome that incorporates global cattle diversity. We illustrate how this more representative reference assembly contains an extra 116.1 Mb (4.2%) of sequence absent from the current Hereford sequence and consequently inaccessible to current studies. We further demonstrate how using this graph genome increases read mapping rates, reduces allelic biases and improves the agreement of structural variant calling with independent optical mapping data. Consequently, we present an improved, more representative, reference assembly that will improve global cattle research.

Pain in the Prehospital Setting in Rwanda: Results of a Mixed-Methods Quality Improvement Project.

Introduction: Pain is a universal human experience tied to an individual's health but difficult to understand. It is especially important in health emergencies. We performed a two-step quality improvement project to assess pain management by the SAMU ambulance service in Kigali, Rwanda, examining how pain is assessed and treated by ambulance staff to facilitate development of standardized guidelines of pain management in the prehospital setting, which did not exist at the time of the study. Materials and Methods: Deidentified ambulance service records from December 2012 to May 2016 were analyzed descriptively for patient demographics, emergency conditions, pain assessment, and medications given. Then, anonymized, semistructured interviews of ambulance staff were conducted until thematic saturation was achieved. Data were analyzed using a grounded theory approach. Results: SAMU managed 11,161 patients over the study period, of which 6,168 (55%) were documented as reporting pain and 5,010 (45%) received pain medications. Men had greater odds of receiving pain medications compared to women (OR = 3.8, 95% CI (3.5, 4.1), p < 0.01). Twenty interviews were conducted with SAMU staff. They indicated that patients communicate pain in different ways. They reported using informal ways to measure pain or a standardized granular numeric scale. The SAMU team reviewed these results and developed plans to modify practices. Conclusions: We reviewed the existing quality of pain management in the prehospital setting in Kigali, Rwanda, assessed the SAMU staff's perceptions of pain, and facilitated standardization of prehospital pain management through context-specific guidelines.

The epidemiology and prehospital care of motorcycle crashes in a sub-Saharan African urban center.

OBJECTIVE: Road traffic crashes (RTCs) are common among motorcyclists in Kigali, Rwanda. The Service d'Aide Medicale Urgente (SAMU), a prehospital ambulance service, responds to many of these crashes. We aimed to describe motorcycle-related RTCs managed by SAMU. METHODS: SAMU clinical data including demographic information, injury characteristics, and management details were analyzed descriptively for all motorcycle crashes occurring between December 2012 and July 2016. RESULTS: Every patient included in this study was injured. These patients all called the ambulance for their injuries after a motorcycle crash. There were 2,912 motorcycle-related RTCs over the study period, representing 26% of all patients managed by SAMU. The incidence of motorcycle crashes in Kigali was 258 crashes per 100,000 people over the 3.5-year study period. The average age was 30 years and 80% were males. The most common injuries were to the lower extremities (n = 958, 33%), head (n = 878, 30%), or upper extremities (n = 453, 16%). Injuries often resulted in fractures of extremities (n = 740, 25%) and external hemorrhage anywhere in the body (unspecified region; n = 660, 23%), yet few were severe based on the Kampala Trauma Score (n = 23, 2%) and Glasgow Coma Scale (n = 42, 1.5%). The most common interventions were provision of diclofenac (n = 1,526, 52.5%), peripheral intravenous (IV) access (n = 1,217, 42%), and administration of IV fluids (n = 1,048, 36%). CONCLUSION: Motorcycle-related RTCs represent a large burden of disease for patients treated by SAMU in Kigali, Rwanda. Young men are most at risk of injury, which imposes a financial strain on society. Though injuries occurred frequently, critical trauma cases from motorcycle crashes were uncommon. This may be a result of several initiatives in Rwanda to improve road safety.

Regulatory T cells in multiple sclerosis and myasthenia gravis.

Multiple sclerosis (MS) is a chronic debilitating disease of the central nervous system primarily mediated by T lymphocytes with specificity to neuronal antigens in genetically susceptible individuals. On the other hand, myasthenia gravis (MG) primarily involves destruction of the neuromuscular junction by antibodies specific to the acetylcholine receptor. Both autoimmune diseases are thought to result from loss of self-tolerance, which allows for the development and function of autoreactive lymphocytes. Although the mechanisms underlying compromised self-tolerance in these and other autoimmune diseases have not been fully elucidated, one possibility is numerical, functional, and/or migratory deficits in T regulatory cells (Tregs). Tregs are thought to play a critical role in the maintenance of peripheral immune tolerance. It is believed that Tregs function by suppressing the effector CD4+ T cell subsets that mediate autoimmune responses. Dysregulation of suppressive and migratory markers on Tregs have been linked to the pathogenesis of both MS and MG. For example, genetic abnormalities have been found in Treg suppressive markers CTLA-4 and CD25, while others have shown a decreased expression of FoxP3 and IL-10. Furthermore, elevated levels of pro-inflammatory cytokines such as IL-6, IL-17, and IFN-γ secreted by T effectors have been noted in MS and MG patients. This review provides several strategies of treatment which have been shown to be effective or are proposed as potential therapies to restore the function of various Treg subsets including Tr1, iTr35, nTregs, and iTregs. Strategies focusing on enhancing the Treg function find importance in cytokines TGF-ß, IDO, interleukins 10, 27, and 35, and ligands Jagged-1 and OX40L. Likewise, strategies which affect Treg migration involve chemokines CCL17 and CXCL11. In pre-clinical animal models of experimental autoimmune encephalomyelitis (EAE) and experimental autoimmune myasthenia gravis (EAMG), several strategies have been shown to ameliorate the disease and thus appear promising for treating patients with MS or MG.

Cattle trypanosomosis: the diversity of trypanosomes and implications for disease epidemiology and control.

Trypanosomosis is one of the most significant infectious threats to cattle in sub-Saharan Africa, and one form has also spread to Asia and South America. The disease is caused by a complex of trypanosome species, and the species and strain of parasite can have a profound influence upon the epidemiology of the host-parasite-vector relationships, the severity and course of infection, and, consequently, the implementation and development of control methods. This review will summarise our current knowledge of the relationship between trypanosome species/genotype and the phenotype of disease in cattle, and the implications that this has for ongoing efforts to develop diagnostics, drugs and vaccines for the control of cattle trypanosomosis.

Guided interventions in musculoskeletal ultrasound: what's the evidence?

Increasing histological and radiological understanding of the processes involved in soft-tissue injury is leading to novel targeted treatments. A number of reviews have recommended that these treatments should be performed with image guidance. This review describes current ultrasound-guided interventions and injections, together with the level of evidence for these. Discussion of guided interventions will include; percutaneous lavage (barbotage), brisement, dry needling, electrocoagulation, and of guided injections; corticosteroids, autologous substances (blood and platelet rich plasma), sclerosants, and prolotherapy (hyperosmolar dextrose). Representative imaging illustrating some of these techniques is included for correlation with the methods described. As these procedures are often performed in sportspeople, it is essential that the radiologist is aware of prohibited substances and methods outlined in an annual publication from the World Anti-Doping Association (WADA). Finally, future directions, including the use of autologous substances, mesenchymal and stem cells will be discussed.

Toward construct validity for a novel sensorized instrument-based minimally invasive surgery simulation system.

Minimally invasive surgical training is complicated due to the constraints imposed by the surgical environment. Sensorized laparoscopic instruments capable of sensing force in five degrees of freedom and position in six degrees of freedom were evaluated. Novice and expert laparoscopists performed the complex minimally invasive surgical task of suturing using the novel instruments. Their force and position profiles were compared. The novel minimally invasive surgical instrument proved to be construct valid and capable of detecting differences between novices and experts in a laparoscopic suturing task with respect to force and position. Further evaluation is mandated for a better understanding of the ability to predict performance based on force and position as well as the potential for new metrics in minimally invasive surgical education.

Whole lung lavage for pulmonary alveolar proteinosis.

A 26-year-old male presented with complaints of dry cough of six months and progressive breathlessness of three months duration. He was coughing out milky white sputum for two months and had lost 12 kg weight in two months. He had an evening rise in temperature of one month duration. Clinically, the patient was in respiratory distress and the respiratory system examination revealed bilateral velcro crackles. High resolution computed tomography chest showed bilateral diffuse reticulonodular opacities and "Crazy Paving" pattern suggestive of alveolar proteinosis. Broncho alveolar lavage showed eosinophilic granular material, which was periodic acid-Schiff positive. Open lung biopsy was done to confirm the diagnosis and the histopathologic examination revealed eosinophilic secretions with granular appearance suggestive of pulmonary alveolar proteinosis. Subsequently, patient underwent bilateral sequential whole lung lavage under general anesthesia. Patient showed marked clinical and radiological improvement after sequential whole lung lavage.

The association between central venous pressure, pneumoperitoneum, and venous carbon dioxide embolism in laparoscopic hepatectomy.

BACKGROUND: Laparoscopic hepatectomy (LH) is increasingly used. However, the safety and outcomes of LH have yet to be elucidated. The risk of venous gas embolism is increased during liver parenchymal transection. This risk may be increased with positive pressure carbon dioxide (CO(2)) pneumoperitoneum (PP). This may be exacerbated further when low central venous pressure (CVP) anesthesia is used to minimize hemorrhage during liver resection. METHODS: To determine the risk of CO(2) venous embolism, hand-assisted laparoscopic left hepatic lobectomy was performed for 26 domestic pigs. They were divided into three groups involving, respectively, positive gradient (normal-pressure PP of 12-14 mmHg and low CVP of 5-7 mmHg), negative gradient (low-pressure PP of 7-8 mmHg and normal CVP of 10-12 mmHg), and neutral gradient (normal-pressure PP and normal CVP or low-pressure PP and low CVP). Transesophageal echocardiography (TEE) was used intraoperatively to assess the presence of emboli in the suprahepatic vena cava and the right side of the heart. The TEE was recorded and analyzed by blinded observers. Carbon dioxide embolism also was monitored using end-tidal CO(2) and compared with TEE. RESULTS: Carbon dioxide embolism was demonstrated in 19 of the 26 cases. The majority of gas emboli were small gas bubbles associated with dissection of the major hepatic veins. No statistically significant difference in the occurrence of gas emboli was observed between the groups. Of the 19 animals, 18 experienced no significant hemodynamic changes. One pig in the positive gradient group experienced hypotension in relation to gas embolism. The effects were only transient and did not preclude safe completion of the operation. CONCLUSIONS: Carbon dioxide embolism during LH occurs frequently. Clinically, this finding appears to be nominal, but care must be taken when dissection around large veins is performed, and awareness by the surgical and anesthesiology teams of potential venous air embolism is essential. Further evaluation of this phenomenon is required.

Manipulation of gold nanoparticles: influence of surface chemistry, temperature, and environment (vacuum versus ambient atmosphere).

We have manipulated raw and functionalized gold nanoparticles (with a mean diameter of 25 nm) on silicon substrates with dynamic atomic force microscopy (AFM). Under ambient conditions, the particles stick to silicon until a critical amplitude is reached by the oscillations of the probing tip. Beyond that threshold, the particles start to follow different directions, depending on their geometry and adhesion to the substrate. Higher and lower mobility were observed when the gold particles were coated with methyl- and hydroxyl-terminated thiol groups, respectively, which suggests that the adhesion of the particles to the substrate is strongly reduced by the presence of hydrophobic interfaces. Under ultrahigh vacuum conditions, where the water layer is absent, the particles did not move, even when operating the atomic force microscope in contact mode. We have also investigated the influence of the temperature (up to 150 degrees C) and of the geometrical arrangement of the particles on the manipulation process. Whereas thermal activation has an important effect in enhancing the mobility of the particles, we did not find differences when manipulating ordered versus random distributions of particles.

Removal of ocular artifacts from EEG using adaptive thresholding of wavelet coefficients.

Electroencephalogram (EEG) gives researchers a non-invasive way to record cerebral activity. It is a valuable tool that helps clinicians to diagnose various neurological disorders and brain diseases. Blinking or moving the eyes produces large electrical potential around the eyes known as electrooculogram. It is a non-cortical activity which spreads across the scalp and contaminates the EEG recordings. These contaminating potentials are called ocular artifacts (OAs). Rejecting contaminated trials causes substantial data loss, and restricting eye movements/blinks limits the possible experimental designs and may affect the cognitive processes under investigation. In this paper, a nonlinear time-scale adaptive denoising system based on a wavelet shrinkage scheme has been used for removing OAs from EEG. The time-scale adaptive algorithm is based on Stein's unbiased risk estimate (SURE) and a soft-like thresholding function which searches for optimal thresholds using a gradient based adaptive algorithm is used. Denoising EEG with the proposed algorithm yields better results in terms of ocular artifact reduction and retention of background EEG activity compared to non-adaptive thresholding methods and the JADE algorithm.

Stapled versus conventional surgery for hemorrhoids.

BACKGROUND: Hemorrhoids are one of the most common anorectal disorders. The Milligan­Morgan open hemorrhoidectomy is the most widely practiced surgical technique used for the management of hemorrhoids and is considered the current "gold standard". Circular stapled hemorrhoidopexy was first described by Longo in 1998 as alternative to conventional excisional hemorrhoidectomy. Early, small randomized­controlled trials comparing stapled hemorrhoidopexy with traditional excisional surgery have shown it to be less painful and that it is associated with quicker recovery. The reports also suggest a better patient acceptance and a higher compliance with day­case procedures potentially making it more economical. A previous Cochrane Review of stapled hemorrhoidopexy and conventional excisional surgery has shown that the stapled technique is associated with a higher risk of recurrent hemorrhoids and some symptoms in long term follow­up. Since this initial review, several more randomized controlled trials have been published that may shed more light on the differences between the novel stapled approach and conventional excisional techniques. OBJECTIVES: This review compares the use of circular stapling devices and conventional excisional techniques in the surgical treatment of hemorrhoids. Its goal is to ascertain whether there is any difference in the outcomes of the two techniques in patients with symptomatic hemorrhoids. SEARCH STRATEGY: We searched all the major electronic databases (MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) from 1998 to December 2009. SELECTION CRITERIA: All randomized controlled trials comparing stapled hemorrhoidopexy to conventional excisional hemorrhoidal surgeries with a minimum follow­up period of 6 months were included. DATA COLLECTION AND ANALYSIS: Data were collected on a data sheet. When appropriate, an Odds Ratio was generated using a random effects model. MAIN RESULTS: Patients with SH were significantly more likely to have recurrent hemorrhoids in long term follow up at all time points than those with CH (12 trials, 955 patients, OR 3.22, CI 1.59­6.51, p=0.001). There were 37 recurrences out of 479 patients in the stapled group versus only 9 out of 476 patients in the conventional group. Similarly, in trials where there was follow up of one year or more, SH was associated with a greater proportion of patients with hemorrhoid recurrence (5 trials, 417 patients, OR 3.60, CI 1.24­10.49, p=0.02). Furthermore, a significantly higher proportion of patients with SH complained of the symptom of prolapse at all time points (13 studies, 1191 patients, OR 2.65, CI 1.45­4.85, p=0.002). In studies with follow up of greater than one year, the same significant outcome was found (7 studies, 668 patients, OR 3.14, CI 1.20­8.22, p=0.02). Patients undergoing SH were more likely to require an additional operative procedure compared to those who underwent CH (8 papers, 553 patients, OR 2.75, CI 1.31­5.77, p=0.008). When all symptoms were considered, patients undergoing CH surgery were more likely to be asymptomatic (12 trials, 1097 patients, OR 0.59, CI 0.40­0.88). Non significant trends in favor of SH were seen in pain, pruritis ani, and fecal urgency. All other clinical parameters showed trends favoring CH.

Neural classification of lung sounds using wavelet coefficients.

Electronic auscultation is an efficient technique to evaluate the condition of respiratory system using lung sounds. As lung sound signals are non-stationary, the conventional method of frequency analysis is not highly successful in diagnostic classification. This paper deals with a novel method of analysis of lung sound signals using wavelet transform, and classification using artificial neural network (ANN). Lung sound signals were decomposed into the frequency subbands using wavelet transform and a set of statistical features was extracted from the subbands to represent the distribution of wavelet coefficients. An ANN based system, trained using the resilient back propagation algorithm, was implemented to classify the lung sounds to one of the six categories: normal, wheeze, crackle, squawk, stridor, or rhonchus.