Thermal sensitivity and seasonal change in the gut microbiome of a desert ant, Cephalotes rohweri.

Microorganisms within ectotherms must withstand the variable body temperatures of their hosts. Shifts in host body temperature resulting from climate change have the potential to shape ectotherm microbiome composition. Microbiome compositional changes occurring in response to temperature in nature have not been frequently examined, restricting our ability to predict microbe-mediated ectotherm responses to climate change. In a set of field-based observations, we characterized gut bacterial communities and thermal exposure across a population of desert arboreal ants (Cephalotes rohweri). In a paired growth chamber experiment, we exposed ant colonies to variable temperature regimes differing by 5°C for three months. We found that the abundance and composition of ant-associated bacteria were sensitive to elevated temperatures in both field and laboratory experiments. We observed a subset of taxa that responded similarly to temperature in the experimental and observational study, suggesting a role of seasonal temperature and local temperature differences amongst nests in shaping microbiomes within the ant population. Bacterial mutualists in the genus Cephaloticoccus (Opitutales: Opitutaceae) were especially sensitive to change in temperature-decreasing in abundance in naturally warm summer nests and warm growth chambers. We also report the discovery of a member of the Candidate Phlya Radiation (Phylum: Gracilibacteria), a suspected epibiont, found in low abundance within the guts of this ant species.

Analysis of genotype-by-environment interactions in a maize mapping population.

Genotype-by-environment interactions are a significant challenge for crop breeding as well as being important for understanding the genetic basis of environmental adaptation. In this study, we analyzed genotype-by-environment interactions in a maize multiparent advanced generation intercross population grown across 5 environments. We found that genotype-by-environment interactions contributed as much as genotypic effects to the variation in some agronomically important traits. To understand how genetic correlations between traits change across environments, we estimated the genetic variance-covariance matrix in each environment. Changes in genetic covariances between traits across environments were common, even among traits that show low genotype-by-environment variance. We also performed a genome-wide association study to identify markers associated with genotype-by-environment interactions but found only a small number of significantly associated markers, possibly due to the highly polygenic nature of genotype-by-environment interactions in this population.

Modeling allelic diversity of multiparent mapping populations affects detection of quantitative trait loci.

The search for quantitative trait loci that explain complex traits such as yield and drought tolerance has been ongoing in all crops. Methods such as biparental quantitative trait loci mapping and genome-wide association studies each have their own advantages and limitations. Multiparent advanced generation intercross populations contain more recombination events and genetic diversity than biparental mapping populations and are better able to estimate effect sizes of rare alleles than association mapping populations. Here, we discuss the results of using a multiparent advanced generation intercross population of doubled haploid maize lines created from 16 diverse founders to perform quantitative trait loci mapping. We compare 3 models that assume bi-allelic, founder, and ancestral haplotype allelic states for quantitative trait loci. The 3 methods have differing power to detect quantitative trait loci for a variety of agronomic traits. Although the founder approach finds the most quantitative trait loci, all methods are able to find unique quantitative trait loci, suggesting that each model has advantages for traits with different genetic architectures. A closer look at a well-characterized flowering time quantitative trait loci, qDTA8, which contains vgt1, highlights the strengths and weaknesses of each method and suggests a potential epistatic interaction. Overall, our results reinforce the importance of considering different approaches to analyzing genotypic datasets, and shows the limitations of binary SNP data for identifying multiallelic quantitative trait loci.

De novo assembly, annotation, and comparative analysis of 26 diverse maize genomes.

We report de novo genome assemblies, transcriptomes, annotations, and methylomes for the 26 inbreds that serve as the founders for the maize nested association mapping population. The number of pan-genes in these diverse genomes exceeds 103,000, with approximately a third found across all genotypes. The results demonstrate that the ancient tetraploid character of maize continues to degrade by fractionation to the present day. Excellent contiguity over repeat arrays and complete annotation of centromeres revealed additional variation in major cytological landmarks. We show that combining structural variation with single-nucleotide polymorphisms can improve the power of quantitative mapping studies. We also document variation at the level of DNA methylation and demonstrate that unmethylated regions are enriched for cis-regulatory elements that contribute to phenotypic variation.

Digest: Exposing the role of rare alleles in inbreeding depression in monkeyflower.

Outcrossing is maintained in many hermaphroditic species despite theoretical work suggesting that alleles increasing selfing should invade outcrossing populations. Brown and Kelly (2019) identify reasons why this may not have occurred in an outcrossing population of monkeyflower, namely that inbreeding depression causes strong reductions in fitness, resulting in selection for the maintenance of outcrossing. They find that genetic load imposed by rare alleles is inversely correlated with fitness-associated traits, providing evidence that recessive, deleterious alleles contribute to inbreeding depression.

Low levels of the immunoregulator Semaphorin 4D (CD100) in sera of HIV patients.

INTRODUCTION: Semaphorin-4D (CD100), generated by CD4/CD8 T-cells and its receptor on B cells - CD72, play a role in immune regulation. Both have soluble forms - sCD100/sCD72. METHODS: sCD100 and sCD72 levels were determined by ELISA (MyBioSource, USA). RESULTS: 28 chronic HIV patients and 50 matched healthy volunteers participated in our study. Before treatment, CD4 T-cells counts were 267 ±â€¯216 cells/mcl and viral load (VL) was 586,675 ±â€¯1897,431 copies/ml. Two years following HAART, CD4 T-cells counts rose to 475 ±â€¯264 cells/mcl and VL dropped to 2050 ±â€¯10,539 copies/ml. CD8 T-cells counts were stable. sCD72 levels prior (4.13 ±â€¯2.03 ng/ml) and following HAART (3.53 ±â€¯2.01 ng/ml) were similar to control levels (4.51 ±â€¯2.66 ng/ml). sCD100 levels before (40.47 ±â€¯31.4 ng/ml) and following HAART (37.68 ±â€¯29.44 ng/ml) were significantly lower compared to controls (99.67 ±â€¯36.72 ng/ml) despite the significant increase in CD4 T-cells counts. CONCLUSIONS: The permanent low levels of the immunoregulator sCD100 suggest a role for CD100 in the immune dysfunction and T cells exhaustion of HIV.

Treatment of Radial Head Fractures and Need for Revision Procedures at 1 and 2 Years.

PURPOSE: Optimal treatment strategies for radial head fractures remain a subject of debate. We examined national practice patterns in the management of radial head fractures to determine rates of surgical treatment, type of surgery employed, and the incidence of reoperation. METHODS: Between 2007 and 2011, we identified patients with radial head fractures along with their associated injuries by International Classification of Diseases, Ninth Revision codes in a national database of orthopedic insurance records. For those who underwent surgery, the type of intervention was identified and each patient was observed to determine whether a subsequent procedure was needed by 1 and 2 years. Chi-square analysis was performed to make comparisons between groups. RESULTS: A total of 58,404 radial head fractures were identified between 2007 and 2011; of these, 2,981 underwent surgical treatment (5.1%). Rates of surgical intervention were significantly higher in the context of associated injuries. Among the 2,981 radial head fractures treated surgically, 57.1% underwent open reduction internal fixation (ORIF), 37.9% were treated with radial head arthroplasty, and 4.9% underwent radial head excision. When the surgically treated radial head fracture was associated with a coronoid fracture, elbow dislocation, or proximal ulna fracture, 64.2%, 54.3%, and 47.2% were treated with arthroplasty, respectively, compared with 32.6%, 41.9%, and 52.6% treated with ORIF, respectively. After initial surgical treatment, 12.7% and 14.4% of radial head fractures that underwent ORIF required a secondary surgery at 1 and 2 years, respectively, compared with 8.6% and 10.7% of radial head arthroplasties and 8.3% and 8.4% of resections. CONCLUSIONS: Rates of arthroplasty were significantly higher in the context of associated injury, particularly in the setting of a coronoid fracture or elbow dislocation. Fractures initially treated with ORIF had a higher rate of revision surgery at both 1 and 2 years after the index procedure compared with arthroplasty. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.

Global Asthma Network survey suggests more national asthma strategies could reduce burden of asthma

BACKGROUND: Several countries or regions within countries have an effective national asthma strategy resulting in a reduction of the large burden of asthma to individuals and society. There has been no systematic appraisal of the extent of national asthma strategies in the world. METHODS: The Global Asthma Network (GAN) undertook an email survey of 276 Principal Investigators of GAN centres in 120 countries, in 2013-2014. One of the questions was: "Has a national asthma strategy been developed in your country for the next five years? For children? For adults?". RESULTS: Investigators in 112 (93.3%) countries answered this question. Of these, 26 (23.2%) reported having a national asthma strategy for children and 24 (21.4%) for adults; 22 (19.6%) countries had a strategy for both children and adults; 28 (25%) had a strategy for at least one age group. In countries with a high prevalence of current wheeze, strategies were significantly more common than in low prevalence countries (11/13 (85%) and 7/31 (22.6%) respectively, p < 0.001). Interpretation. In 25% countries a national asthma strategy was reported. A large reduction in the global burden of asthma could be potentially achieved if more countries had an effective asthma strategy

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Global Asthma Network survey suggests more national asthma strategies could reduce burden of asthma.

BACKGROUND: Several countries or regions within countries have an effective national asthma strategy resulting in a reduction of the large burden of asthma to individuals and society. There has been no systematic appraisal of the extent of national asthma strategies in the world. METHODS: The Global Asthma Network (GAN) undertook an email survey of 276 Principal Investigators of GAN centres in 120 countries, in 2013-2014. One of the questions was: "Has a national asthma strategy been developed in your country for the next five years? For children? For adults?". RESULTS: Investigators in 112 (93.3%) countries answered this question. Of these, 26 (23.2%) reported having a national asthma strategy for children and 24 (21.4%) for adults; 22 (19.6%) countries had a strategy for both children and adults; 28 (25%) had a strategy for at least one age group. In countries with a high prevalence of current wheeze, strategies were significantly more common than in low prevalence countries (11/13 (85%) and 7/31 (22.6%) respectively, p<0.001). INTERPRETATION: In 25% countries a national asthma strategy was reported. A large reduction in the global burden of asthma could be potentially achieved if more countries had an effective asthma strategy.

Kinematic analysis of diseased and adjacent segments in degenerative lumbar spondylolisthesis.

BACKGROUND CONTEXT: Degenerative spondylolisthesis is a common pathologic condition that leads to lumbar instability and significant clinical symptoms. The effect of this pathology on adjacent lumbar motion segments, however, has not yet been studied. PURPOSE: To characterize the motion characteristics of lumbar degenerative spondylolisthesis at both the diseased and adjacent levels in patients with low-grade, single-level lumbar degenerative spondylolisthesis using kinetic magnetic resonance imaging (kMRI). STUDY DESIGN: Retrospective study of patient kMRIs. PATIENT SAMPLE: One-hundred twelve patient MRIs with low-grade, single-level lumbar spondylolisthesis were included. OUTCOME MEASURES: Angular and translational motion. METHODS: This study compared 112 patients diagnosed with low-grade (Grade 1 or 2), single-level lumbar degenerative spondylolisthesis at L3-L4, L4-L5, or L5-S1 with 296 control patients without spondylolisthesis. Angular and translational motion were measured using patient kMRIs. The level of slip was graded according to the Meyerding classification system, and disc degeneration was classified according to the Pfirrmann system. Instability was defined as translational motion greater than 4 mm. RESULTS: Lumbar hypomobility was often present regardless of the level of degenerative spondylolisthesis. A slip at L3-L4 resulted in the largest decrease in lumbar range of motion. Instability at the diseased level was most common at L3-L4 (36%), followed by L5-S1 (31%) and L4-L5 (30%). Instability at the adjacent segments was most frequent at L4-L5 (49%), followed by L5-S1 (34%) and L3-L4 (23%). Patients with stable spondylolisthesis generally had decreased angular motion at all lumbar levels. Translational motion at the diseased level was consistently increased. Disc degeneration was significantly greater at the level of slip for the L3-L4 and L4-L5 spondylolisthesis groups and equal to the control group in the L5-S1 group. There was no significant difference in disc degeneration at adjacent segments in L3-L4 and L4-L5 degenerative spondylolisthesis patients, but there was a significant decrease with an L5-S1 slip. CONCLUSIONS: There were a similar percentage of patients in each degenerative spondylolisthesis group with lumbar instability. Angular motion decreased at the diseased level with L3-L4 and L5-S1 spondylolisthesis, but increased with L4-L5 spondylolisthesis. Translational motion, however, increased at the diseased level in all three groups. There was compensatory hypermobility at adjacent levels in patients with unstable spondylolisthesis at L3-L4 and L4-L5, but not at L5-S1.

Global burden of asthma among children.

About 334 million people worldwide suffer from asthma, and this figure may be an underestimation. It is the most common chronic disease in children. Asthma is among the top 20 chronic conditions for global ranking of disability-adjusted life years in children; in the mid-childhood ages 5-14 years it is among the top 10 causes. Death rates from asthma in children globally range from 0.0 to 0.7 per 100 000. There are striking global variations in the prevalence of asthma symptoms (wheeze in the past 12 months) in children, with up to 13-fold differences between countries. Although asthma symptoms are more common in many high-income countries (HICs), some low- and middle-income countries (LMICs) also have high levels of asthma symptom prevalence. The highest prevalence of symptoms of severe asthma among children with wheeze in the past 12 months is found in LMICs and not HICs. From the 1990s to the 2000s, asthma symptoms became more common in some high-prevalence centres in HICs; in many cases, the prevalence stayed the same or even decreased. At the same time, many LMICs with large populations showed increases in prevalence, suggesting that the overall world burden is increasing, and that therefore global disparities in asthma prevalence are decreasing. The costs of asthma, where they have been estimated, are relatively high. The global burden of asthma in children, including costs, needs ongoing monitoring using standardised methods.

Demographic analysis of open and arthroscopic distal clavicle excision in a private insurance database.

PURPOSE: The purpose of this study was to evaluate and quantify the demographic characteristics of patients undergoing open and arthroscopic distal clavicle excision (DCE) in the United States while also describing changes in practice patterns over time. METHODS: Patients who underwent DCE from 2004 to 2009 were identified by Current Procedural Terminology (CPT) codes in a national database of orthopaedic insurance records. The year of procedure, age, sex, geographic region, and concomitant rotator cuff repair or subacromial decompression (SAD) were recorded for each patient. Results were reported as the incidence of procedures identified per 10,000 patients searched in the database. RESULTS: Between 2004 and 2009, 73,231 DCEs were performed; 74% were arthroscopic and 26% were open. The incidence of arthroscopic DCE increased from 37.8 in 2004 to 58.5 in 2009 (P < .001), whereas the incidence of open DCE decreased from 21.1 in 2004 to 14.1 in 2009 (P < .001). Sixty-one percent of DCEs were performed in men (P < .001). Women were more likely to undergo an arthroscopic procedure (P < .001). Arthroscopic DCE was most common in patients aged 50 to 59 years (P < .001). Open DCE was most common in patients aged 60 to 69 years (P < .001). Open rotator cuff repair and SAD were concomitantly performed in 38% and 23% of open DCEs, respectively. Arthroscopic rotator cuff repair and SAD were concomitantly performed in 33% and 95% arthroscopic DCEs, respectively. CONCLUSIONS: This analysis of DCE using a private insurance database shows that arthroscopic DCEs progressively increased, whereas open DCEs concomitantly decreased between 2004 and 2009. The majority of DCEs were performed in men between the ages of 50 and 59 years. Both arthroscopic and open DCEs are frequently performed in conjunction with rotator cuff repair or SAD. LEVEL OF EVIDENCE: Level IV, cross-sectional study.

Lumbar clinical adjacent segment pathology: predilection for proximal levels.

STUDY DESIGN: Retrospective case series. OBJECTIVE: To evaluate reoperations for lumbar adjacent segment pathology (ASP) during a 10-year period. SUMMARY OF BACKGROUND DATA: ASP after lumbar arthrodesis is an important clinical problem. There remains controversy, however, on the distribution of the most commonly affected levels. METHODS: Thirty-one patients undergoing revision operation for ASP in the lumbar spine were included in this study. Patients' charts were evaluated for demographic data including age at index and revision operations, time to revision operation, and index and revision levels fused. RESULTS: L4-L5 was the most commonly instrumented level in both single-level (n = 12), and multilevel (n = 13) index fusions. The mean length of time from the index operation to revision surgery was 81 months (range, 11-570 mo). Kaplan-Meier analysis predicted a disease-free survival rate of 32.3% at 5 years and of 12.9% at 10 years after the index operation. L3-L4 was the most commonly affected level by ASP with 75% (16/20) requiring reoperation. L2-L3 was the next most commonly affected level at 52% (14/27). The L5-S1 disk was relatively protected from ASP, with only 4/17 (24%) disks at risk developing ASP. A subgroup analysis of patients undergoing revision after a single-level L4-L5 arthrodesis revealed ASP at L3-L4 in 83% (10/12) of patients, compared with only 3/12 (25%) at L5-S1 (P < 0.05). Of all cases of ASP, the proximal segments were involved 90% of the time. CONCLUSION: ASP most commonly affects proximal levels in the lumbar spine. In this cohort of patients undergoing revision fusion for ASP, 90% of affected levels were rostral to the index level(s). In patients undergoing L4-L5 single-level arthrodesis, L3-L4 is at high risk, whereas L5-S1 is somewhat protected. Surgeons should pay particular attention to proximal levels when planning a lumbar arthrodesis, however, motion segments distal to fusion may not be as protected as previously thought. LEVEL OF EVIDENCE: 4.

Syphilis and HIV co-infection in an Israeli HIV clinic: incidence and outcome.

The re-emergence of syphilis among HIV-infected patients has been reported in recent years. We evaluated co-infection among heterosexual immigrants in an Israeli AIDS center. The records of 1060 HIV-infected patients were evaluated for positive syphilis serology between the years 2000 and 2005, and all seropositive patients were further evaluated. We found 150 HIV/syphilis co-infected patients (57% men, 93% of African origin), of who 135 were found to have late latent syphilis. Lumbar puncture (LP) was performed in 51 patients, 16 (31%) had abnormal cerebrospinal fluid (CSF) compatible with neurosyphilis. Abnormal CSF correlated with the absence of previous anti-syphilis treatment, but not with CD4 count, viral load or Venereal Disease Research Laboratory titres. Penicillin was recommended to all patients according to their disease stages and 81 patients completed 12 months post-treatment follow-up. Twenty-one of 81 (26%) treatments were successful, 33 (41%) showed 'serofast reaction' and 27 (33%) failed therapy. In conclusion, a high incidence of syphilis with CSF reactivity suggestive of neurosyphilis was observed in heterosexual Ethiopian HIV-infected patients. Thus, repeated serological screening and CSF evaluation seems to be indicated in these patients. Penicillin therapy resulted in 'serofast reaction' or treatment failure for most patients. More, intensive treatment might be needed for HIV/syphilis in co-infected patients, especially those with severe immune-deficiency and prolonged syphilis infection.

Inhibition of RhoA signaling with increased Bves in trabecular meshwork cells.

PURPOSE: Blood vessel epicardial substance (Bves) is a novel adhesion molecule that regulates tight junction (TJ) formation. TJs also modulate RhoA signaling, which has been implicated in outflow regulation. Given that Bves has been reported in multiple ocular tissues, the authors hypothesize that Bves plays a role in the regulation of RhoA signaling in trabecular meshwork (TM) cells. METHODS: Human TM cell lines NTM-5 and NTM-5 transfected to overexpress Bves (NTM-w) were evaluated for TJ formation, and levels of occludin, cingulin, and ZO-1 protein were compared. Assays of TJ function were carried out using diffusion of sodium fluorescein and transcellular electrical resistance (TER). Levels of activated RhoA were measured using FRET probes, and phosphorylation of myosin light chain (MLC-p), a downstream target of RhoA, was assessed by Western blot analysis. RESULTS: Overexpression of Bves led to increased TJ formation in NTM-5 cells. Increased TJ formation was confirmed by increased occludin, cingulin, and ZO-1 protein. Functionally, NTM-w cells showed decreased permeability and increased TER compared with NTM-5 cells, consistent with increased TJ formation. NTM-w cells also exhibited decreased levels of active RhoA and lower levels of MLC-p than did NTM-5 cells. These findings support a TJ role in RhoA signaling. CONCLUSIONS: Increased Bves in TM cells leads to increased TJ formation with decreased RhoA activation and decreased MLC-p. This is the first report of a regulatory pathway upstream of RhoA in TM cells. In TM tissue, RhoA has been implicated in outflow regulation; thus, Bves may be a key regulatory molecule in aqueous outflow.

Prevention of human immunodeficiency virus mother-to-child transmission in Israel.

The objective of the study was to investigate the HIV-mother-to-child transmission (MTCT) rate in Israel. This was a retrospective study of HIV-infected pregnant women, mainly immigrants from Ethiopia, in six Israeli AIDS centres, in 2000-2005. Medical records of mothers and newborns were evaluated for HIV status, treatment and MTCT rates. Three hundred pregnancies of 241 HIV-infected women, resulting in 304 live births, were studied. In 86/241(36%) women, HIV diagnosis was made during the current pregnancy or shortly after labour. Thirty others were diagnosed during previous pregnancies. Highly active antiretroviral therapy (HAART) was prescribed in 76% of pregnancies. The mean viral load before labour was 23,000 +/- 100,000 copies/mL with a mean CD4 of 406 +/- 223 (range 4-1277) cells/mm(3). Caesarian sections were preformed in 175/300 pregnancies (103/175 with viral load <1000 copies/mL). During labour, azidothymidine (AZT) was given to 80% and nevirapine to 8% of the women. Eighty-eight percent of the neonates received AZT for six weeks. The overall HIV-MTCT rate was 3.6%. MTCT correlated significantly with delayed HIV diagnosis, low CD4, lack of HAART during pregnancy and lack of perinatal treatment. HIV treatment of mothers and their newborns throughout pregnancy, labour and perinatal period are crucial for effective prevention of MTCT, emphasizing the need for early HIV screening, diagnosis and treatment.

Prevalence of asthma symptoms in Latin America: the International Study of Asthma and Allergies in Childhood (ISAAC).

The prevalence of respiratory symptoms indicative of asthma in children from Latin America has been largely ignored. As part of the International Study of Asthma and Allergies in Childhood (ISAAC), 17 centers in 9 different Latin American countries participated in the study, and data from 52,549 written questionnaires (WQ) in children aged 13-14 years and from 36,264 WQ in 6-7 year olds are described here. In children aged 13-14 years, the prevalence of asthma ever ranged from 5.5-28%, and the prevalence of wheezing in the last 12 months from 6.6-27%. In children aged 6-7 years, the prevalence of asthma ever ranged from 4.1-26.9%, and the prevalence of wheezing in the last 12 months ranged from 8.6-32.1%. The lower prevalence in centers with higher levels of atmospheric pollution suggests that chronic inhalation of polluted air in children does not contribute to asthma. Furthermore, the high figures for asthma in a region with a high level of gastrointestinal parasite infestation, and a high burden of acute respiratory infections occurring early in life, suggest that these factors, considered as protective in other regions, do not have the same effect in this region. The present study indicates that the prevalence of asthma and related symptoms in Latin America is as high and variable as described in industrialized or developed regions of the world.

Worldwide variations in the prevalence of symptoms of atopic eczema in the International Study of Asthma and Allergies in Childhood.

BACKGROUND: Little is known about the prevalence of atopic eczema outside Northern Europe. OBJECTIVES: We sought to describe the magnitude and variation in the prevalence of atopic eczema symptoms throughout the world. METHODS: A cross-sectional questionnaire survey was conducted on random samples of schoolchildren aged 6 to 7 years and 13 to 14 years from centers in 56 countries throughout the world. Those children with a positive response to being questioned about the presence of an itchy relapsing skin rash in the last 12 months that had affected their skin creases were considered to have atopic eczema. Children whose atopic eczema symptoms resulted in sleep disturbance for 1 or more nights per week were considered to have severe atopic eczema. RESULTS: Complete data was available for 256,410 children aged 6 to 7 years in 90 centers and 458,623 children aged 13 to 14 years in 153 centers. The prevalence range for symptoms of atopic eczema was from less than 2% in Iran to over 16% in Japan and Sweden in the 6 to 7 year age range and less than 1% in Albania to over 17% in Nigeria for the 13 to 14 year age range. Higher prevalences of atopic eczema symptoms were reported in Australasia and Northern Europe, and lower prevalences were reported in Eastern and Central Europe and Asia. Similar patterns were seen for symptoms of severe atopic eczema. CONCLUSIONS: Atopic eczema is a common health problem for children and adolescents throughout the world. Symptoms of atopic eczema exhibit wide variations in prevalence both within and between countries inhabited by similar ethnic groups, suggesting that environmental factors may be critical in determining disease expression. Studies that include objective skin examinations are required to confirm these findings.