The effectiveness of proprioceptive and neuromuscular training compared to bracing in reducing the recurrence rate of ankle sprains in athletes: A systematic review and meta-analysis.

BACKGROUND: Ankle sprains are common musculoskeletal injuries in which the ligaments of the ankle partially or completely tear due to sudden stretching. OBJECTIVES: To critically appraise, evaluate and establish the best available evidence to determine the effectiveness of proprioceptive and neuromuscular training (PNT) compared to bracing in reducing the recurrence rate of ankle sprains in athletes. METHODOLOGY: The following seven databases were searched in June 2017: PubMed, Cochrane Library, PEDro, ScienceDirect, Scopus, SPORTDiscus, EBSCO Host: CINAHL. The main search terms used were "ankle sprains", "proprioceptive training", "neuromuscular training" and "bracing". The quality of the trials were critically appraised according to the PEDro scale. The RevMan 5© software was used to pool results. RESULTS: Three studies met the inclusion criteria and the quality according to the PEDro scale ranged from 4/10-7/10. The pooled data showed no difference between PNT and bracing in reducing the recurrence rate of ankle sprains in athletes at 12 months after initiation of the study. CONCLUSION: This systematic review of the overall effect suggested that current evidence (Level II) does not favour the use of PNT over bracing in reducing the recurrence rate of ankle sprains. Physiotherapists are advised to use either PNT or bracing according to the patients preference and their own expertise.

Multiple dynamic representations in the motor cortex during sensorimotor learning.

The mechanisms linking sensation and action during learning are poorly understood. Layer 2/3 neurons in the motor cortex might participate in sensorimotor integration and learning; they receive input from sensory cortex and excite deep layer neurons, which control movement. Here we imaged activity in the same set of layer 2/3 neurons in the motor cortex over weeks, while mice learned to detect objects with their whiskers and report detection with licking. Spatially intermingled neurons represented sensory (touch) and motor behaviours (whisker movements and licking). With learning, the population-level representation of task-related licking strengthened. In trained mice, population-level representations were redundant and stable, despite dynamism of single-neuron representations. The activity of a subpopulation of neurons was consistent with touch driving licking behaviour. Our results suggest that ensembles of motor cortex neurons couple sensory input to multiple, related motor programs during learning.

Immunogenetic Management Software: a new tool for visualization and analysis of complex immunogenetic datasets.

Here we describe the Immunogenetic Management Software (IMS) system, a novel web-based application that permits multiplexed analysis of complex immunogenetic traits that are necessary for the accurate planning and execution of experiments involving large animal models, including nonhuman primates. IMS is capable of housing complex pedigree relationships, microsatellite-based MHC typing data, as well as MHC pyrosequencing expression analysis of class I alleles. It includes a novel, automated MHC haplotype naming algorithm and has accomplished an innovative visualization protocol that allows users to view multiple familial and MHC haplotype relationships through a single, interactive graphical interface. Detailed DNA and RNA-based data can also be queried and analyzed in a highly accessible fashion, and flexible search capabilities allow experimental choices to be made based on multiple, individualized and expandable immunogenetic factors. This web application is implemented in Java, MySQL, Tomcat, and Apache, with supported browsers including Internet Explorer and Firefox on Windows and Safari on Mac OS. The software is freely available for distribution to noncommercial users by contacting Leslie.kean@emory.edu. A demonstration site for the software is available at http://typing.emory.edu/typing_demo , user name: imsdemo7@gmail.com and password: imsdemo.

Phenotype, distribution and alloreactive properties of memory T cells from cynomolgus monkeys.

The high frequency of memory T cells present in primates is thought to represent a major barrier to tolerance induction in transplantation. Therefore, it is crucial to characterize these memory T cells and determine their functional properties. High numbers of memory T cells were detected in peripheral blood and all lymphoid tissues except lymph nodes, which were essentially the site of naïve T cells. The majority of CD8(+) memory T cells were effector memory cells located in the blood and bone marrow while most CD4(+) memory T cells were central memory cells present in the spleen. Next, memory T cells from over 100 monkeys were tested for their response to alloantigens by ELISPOT. Memory alloreactivity mediated via direct but not indirect allorecognition was detected in all animals. The frequency of allospecific memory T cells varied dramatically depending upon the nature of the responder/stimulator monkey combination tested. MHC gene matching was generally associated with a low-memory alloreactivity. Nevertheless, low anamnestic alloresponses were also found in a significant number of fully MHC-mismatched monkey combinations. These results show that selected donor/recipient combinations displaying a low memory alloresponsiveness can be found. These combinations may be more favorable for transplant tolerance induction.

Resources for genetic management and genomics research on non-human primates at the National Primate Research Centers (NPRCs).

The National Primate Research Centers (NPRCs) established Working Groups (WGs) for developing resources and mechanisms to facilitate collaborations among non-human primate (NHP) researchers. Here we report the progress of the Genome Banking and the Genetics and Genomics WGs in developing resources to advance the exchange, analysis and comparison of NHP genetic and genomic data across the NPRCs. The Genome Banking WG has established a National NHP DNA bank comprising 1250 DNA samples from unrelated animals and family trios from the 10 NHP species housed within the NPRC system. The Genetics and Genomics WG is developing SNP arrays that will provide a uniform, highly informative, efficient and low-cost method for rhesus and long-tailed macaque genotyping across the eight NPRCs. This WG is also establishing a Biomedical Informatics Research Network-based portal for shared bioinformatics resources including vital statistics, genotype and population data and information on the National NHP DNA bank.

Simultaneous positive and purifying selection on overlapping reading frames of the tat and vpr genes of simian immunodeficiency virus.

Tat-specific cytotoxic T cells have previously been shown to exert positive Darwinian selection favoring amino acid replacements of an epitope of simian immunodeficiency virus (SIV). The region of the tat gene encoding this epitope falls within a region of overlap between the tat and vpr reading frames, and nonsynonymous nucleotide substitutions in the tat reading frame were found to occur disproportionately in such a way as to cause synonymous changes in the vpr reading frame. Comparison of published complete SIV genomes showed Tat to be the least conserved at the amino acid level of nine proteins encoded by the virus, while Vpr was one of the most conserved. Numerous parallel amino acid changes occurred within the Tat epitope independently in different monkeys, and purifying selection on the vpr reading frame, by limiting acceptable nonsynonymous substitutions in the tat reading frame, evidently has enhanced the probability of parallel evolution.

CD8(+) lymphocytes from simian immunodeficiency virus-infected rhesus macaques recognize 14 different epitopes bound by the major histocompatibility complex class I molecule mamu-A*01: implications for vaccine design and testing.

It is becoming increasingly clear that any human immunodeficiency virus (HIV) vaccine should induce a strong CD8(+) response. Additional desirable elements are multispecificity and a focus on conserved epitopes. The use of multiple conserved epitopes arranged in an artificial gene (or EpiGene) is a potential means to achieve these goals. To test this concept in a relevant disease model we sought to identify multiple simian immunodeficiency virus (SIV)-derived CD8(+) epitopes bound by a single nonhuman primate major histocompatibility complex (MHC) class I molecule. We had previously identified the peptide binding motif of Mamu-A*01(2), a common rhesus macaque MHC class I molecule that presents the immunodominant SIV gag-derived cytotoxic T lymphocyte (CTL) epitope Gag_CM9 (CTPYDINQM). Herein, we scanned SIV proteins for the presence of Mamu-A*01 motifs. The binding capacity of 221 motif-positive peptides was determined using purified Mamu-A*01 molecules. Thirty-seven peptides bound with apparent K(d) values of 500 nM or lower, with 21 peptides binding better than the Gag_CM9 peptide. Peripheral blood mononuclear cells from SIV-infected Mamu-A*01(+) macaques recognized 14 of these peptides in ELISPOT, CTL, or tetramer analyses. This study reveals an unprecedented complexity and diversity of anti-SIV CTL responses. Furthermore, it represents an important step toward the design of a multiepitope vaccine for SIV and HIV.

Tat-specific cytotoxic T lymphocytes select for SIV escape variants during resolution of primary viraemia.

Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections are characterized by early peaks of viraemia that decline as strong cellular immune responses develop. Although it has been shown that virus-specific CD8-positive cytotoxic T lymphocytes (CTLs) exert selective pressure during HIV and SIV infection, the data have been controversial. Here we show that Tat-specific CD8-positive T-lymphocyte responses select for new viral escape variants during the acute phase of infection. We sequenced the entire virus immediately after the acute phase, and found that amino-acid replacements accumulated primarily in Tat CTL epitopes. This implies that Tat-specific CTLs may be significantly involved in controlling wild-type virus replication, and suggests that responses against viral proteins that are expressed early during the viral life cycle might be attractive targets for HIV vaccine development.

Definition of five new simian immunodeficiency virus cytotoxic T-lymphocyte epitopes and their restricting major histocompatibility complex class I molecules: evidence for an influence on disease progression.

Simian immunodeficiency virus (SIV) infection of the rhesus macaque is currently the best animal model for AIDS vaccine development. One limitation of this model, however, has been the small number of cytotoxic T-lymphocyte (CTL) epitopes and restricting major histocompatibility complex (MHC) class I molecules available for investigating virus-specific CTL responses. To identify new MHC class I-restricted CTL epitopes, we infected five members of a family of MHC-defined rhesus macaques intravenously with SIV. Five new CTL epitopes bound by four different MHC class I molecules were defined. These included two Env epitopes bound by Mamu-A*11 and -B*03 and three Nef epitopes bound by Mamu-B*03, -B*04, and -B*17. All four restricting MHC class I molecules were encoded on only two haplotypes (b or c). Interestingly, resistance to disease progression within this family appeared to be associated with the inheritance of one or both of these MHC class I haplotypes. Two individuals that inherited haplotypes b and c separately survived for 299 and 511 days, respectively, while another individual that inherited both haplotypes survived for 889 days. In contrast, two MHC class I-identical individuals that did not inherit either haplotype rapidly progressed to disease (survived <80 days). Since all five offspring were identical at their Mamu-DRB loci, MHC class II differences are unlikely to account for their patterns of disease progression. These results double the number of SIV CTL epitopes defined in rhesus macaques and provide evidence that allelic differences at the MHC class I loci may influence rates of disease progression among AIDS virus-infected individuals.

Virus-specific cytotoxic T-lymphocyte responses select for amino-acid variation in simian immunodeficiency virus Env and Nef.

Cytotoxic T-lymphocyte (CTL) responses to human immunodeficiency virus arise early after infection, but ultimately fail to prevent progression to AIDS. Human immunodeficiency virus may evade the CTL response by accumulating amino-acid replacements within CTL epitopes. We studied 10 CTL epitopes during the course of simian immunodeficiency virus disease progression in three related macaques. All 10 of these CTL epitopes accumulated amino-acid replacements and showed evidence of positive selection by the time the macaques died. Many of the amino-acid replacements in these epitopes reduced or eliminated major histocompatibility complex class I binding and/or CTL recognition. These findings strongly support the CTL 'escape' hypothesis.

Major histocompatibility complex class I genes in primates: co-evolution with pathogens.

The major histocompatibility complex (MHC) is the most polymorphic genetic system known, playing a central role in the cellular immune response to pathogens. The relationship between the MHC of humans and non-human primates has increased our understanding of MHC evolution and how polymorphism of this gene family may have been generated. We will review MHC class I evolution in great apes and Old World and New World primates and discuss new data from the simian immunodeficiency virus/rhesus monkey animal model that demonstrate the role of MHC class I alleles in selecting for new populations of viruses. This suggests that certain pathogens co-evolve with the MHC class I molecules they encounter in a population.

Predicting the severity of motor vehicle accident injuries using models of ordered multiple choice.

This paper presents statistical evidence showing how variations in the attributes of road users can lead to variations in the probabilities of sustaining different levels of injury in motor vehicle accidents. Data from New South Wales, Australia, is used to estimate two models of multiple choice which are reasonably commonplace in the econometrics literature: the ordered logit model and the ordered probit model. Our estimated parameters are significantly different from zero at small levels of significance and have signs which are consistent with our prior beliefs. As a benchmark for comparison, we consider the risks faced by a 33-year-old male driver of a 10-year-old motor vehicle who is involved in a head-on collision while travelling at 42 kilometres per hour. We estimate that this benchmark victim will remain uninjured with a probability of almost zero, will require treatment from a medical officer with a probability of approximately 0.7, will be admitted to hospital with a probability of approximately 0.3, and will be killed with a probability of almost zero. We find that increases in the age of the victim and vehicle speed lead to slight increases in the probabilities of serious injury and death. Other factors which have a similar or greater effect on the probabilities of different types of injury include seating position, blood alcohol level, vehicle type, vehicle make and type of collision.

Amebiasis complicating carcinomas: a diagnostic dilemma.

Two black African women and one black American man had carcinomas of cervix, perineum, and sigmoid colon, respectively. In each of these patients, trophozoites of Entamoeba histolytica had invaded the surface of the tumor, and in some areas had invaded more deeply into the stroma between the tumor cells. Although it is well known that cutaneous amebiasis of anus, penis, vulva, and cervix can mimic squamous cell carcinoma, it may be, perhaps, less well known that carcinomas at these sites may be colonized by trophozoites of E. histolytica. In patients with amebiasis but without an associated carcinoma, a correct diagnosis of amebiasis spares the patient unnecessary and sometimes mutilating surgery. But a diagnosis of amebiasis, when there is an unrecognized underlying carcinoma, delays effective treatment of the carcinoma. A smear that establishes a diagnosis of cutaneous amebiasis, therefore, should be followed by biopsy to exclude or confirm an underlying carcinoma.

Enterobiasis: a histopathological study of 259 patients.

Enterobius worms or their eggs, or both, are present in preserved tissue sections or tissue specimens of 259 patients whose medical records are on file at the Armed Forces Institute of Pathology, Washington D.C., U.S.A. The most common site of infection (86.5%) was found to be the lumen of the appendix, where the worms provoke no reaction. Of the 259 patients 11 (4.2%) had worms and/or eggs in granulomas of the abdominal and pelvic peritoneum, and an equal number had granulomas on the peritoneum of the salphinx or on the surface of the ovary. There were also ectopic worms and/or eggs in granulomas on the peritoneum of the small and large intestines (2.7%). These Enterobius granulomas form around degenerating adult worms, around discrete eggs, around clusters of eggs, and, we believe, also around the tracks of migrating worms. Three patients (1.2%) had worms in perianal abscesses. A necrotic granuloma, removed from the lung of one patient, surrounded a degenerating adult worm. This suggests that the worm, carried to the lung as an embolus, impacted in a pulmonary arteriole. A stool specimen of one patient contains eggs of Enterobius, and that of another patient contains an adult Enterobius. This is the largest recorded histopathological study of enterobiasis in man.

Malassezia furfur--disseminated infection in premature infants.

Three infants, born prematurely, died after clinical illnesses of 67, 65, and 60 days from infection by Malassezia furfur. Each infant had been nourished with lipid emulsions delivered through deep-line catheters. The infections, all discovered at autopsy, were characterized by massive involvement of lungs. Two of the three had endocardial vegetations containing M. furfur; all three had lesions in liver, kidney, and spleen, and two had lesions in adrenal, pancreas, and colon. In addition, one of the infants had acute meningoencephalitis caused by M. furfur. In some of the distant organs, yeast cells of M. furfur were growing in the lumina of small vessels, filling the lumina, but causing no vasculitis or infarction. In addition to these benign collections of yeasts within vessels, there were acute inflammatory lesions as well. These were consolidation, vasculitis, granulomatous inflammation, septic thrombosis, and septic infarction of lung and foci of necrosis and inflammation in kidney and liver. Two previously reported autopsies described neonates with lesions in lung and heart. The authors' three cases for which autopsies were performed had lesions in lung and heart too but, in addition, had dissemination with acute lesions in kidney and liver. Finally, one patient had a severe meningoencephalitis caused by M. furfur.

Influence of the type of dietary fat on developmental growth of the mammary gland in immature and mature female BALB/c mice.

The purpose of this study was to determine whether or not the type of dietary fat can affect mammary gland growth processes in the immature and mature female BALB/c mouse. Groups of immature and mature mice were fed one of the following purified semisynthetic diets containing different types of fat, i.e., five vegetable oil diets (5% corn oil, 20% corn oil, 20% olive oil, 20% linseed oil, 19% coconut oil-1% corn oil); two animal fat diets (20% lard, 19% beef tallow-1% corn oil); and one fish oil diet (19% Menhaden oil-1% corn oil). In addition, fish-corn oil diets (20%) containing three different levels of corn oil (15%, 10%, 4.5%) and fish oil (5%, 10%, 15.5%) were also examined in these studies. Immature mice were fed these diets from 21 to 45 days of age, ovariectomized at 35 days of age, given injections daily of 17 beta-estradiol (1 microgram) and progesterone (1 mg) on Days 42 to 44, and sacrificed on Day 45. Mammary ductal expansion through the mammary fat-pad (mm, nipple to farthest end bud) was determined on the inguinal (No. 4) mammary glands. Mature mice were fed these diets from 28 to 128 days of age. Half of these mice were sacrificed between 118 and 128 days of age during the stage of estrus of the estrous cycle. The remaining half were given injections daily of 17 beta-estradiol (1 microgram) and progesterone (1 mg) from 118 to 127 days of age and sacrificed on Day 128. Mammary developmental growth was assessed on inguinal mammary glands by ascription of development scores, determination of epithelial area (mm2), and determination of total DNA levels. In both immature mice and mammotrophic hormone-treated mature mice fed the fish oil diet (19% Menhaden oil-1% corn oil, 15.5% Menhaden oil-4.5% corn oil), significantly (P less than 0.05) reduced developmental growth of the mammary gland was observed when compared to mice fed the 19 to 20% vegetable oil or animal fat diets. No significant difference in mammary gland developmental growth was observed among the groups of mice fed the 19 to 20% vegetable oil or animal fat diets. In immature mice and mammotrophic hormone-treated mature mice, significantly (P less than 0.05) reduced mammary gland developmental growth was observed in mice fed the 5% corn oil diet compared with mice fed the 20% corn oil diet. In mature mice not treated with exogenous mammotrophic hormones, no significant effect of diet on mammae development was observed.(ABSTRACT TRUNCATED AT 400 WORDS)

Infections caused by Penicillium marneffei in China and Southeast Asia: review of eighteen published cases and report of four more Chinese cases.

One accidental and 17 natural human infections caused by Penicillium marneffei have been reported in the literature. The accidental infection, in Paris, followed inoculation of a culture from a Vietnamese bamboo rat into the finger of a mycologist. All patients with natural infections had lived or traveled in the Far East. Nine of these patients were Chinese, all from Guangxi Zhuang Autonomous Region. The four additional infections from Guangxi reported herein bring the total to 21 natural infections. P. marneffei is a primary pathogen of humans, causing two clinical types of disease: focal infection and fatal, progressive, disseminated infection. There are three histopathologic reactions: (1) granulomatous; (2) suppurative; and (3) anergic and necrotizing. The first two reactions are seen in patients with "normal" immunity and the third in patients with compromised immunity. P. marneffei is unique among species of Penicillium because of its thermal dimorphism, its recognized ecologic niche (restricted to the Far East), and its propensity to infect the lungs and the reticuloendothelial system and to proliferate within histiocytes.

Nodules in the conjunctiva, bung-eye, and bulge-eye in Africa caused by Mansonella perstans.

Eight patients from Uganda, Sudan, Nigeria, and Zaire presented with swelling of the eyelids, proptosis, or conjunctival granulomas. In 5 patients the cause was Mansonella perstans; in 1, it was a Wuchereria bancrofti-like worm; and in 2, an unidentifiable worm. The morphologic features and histopathologic changes in the conjunctiva and periorbital fat are described and illustrated.