The effect of scoliosis support orthosis bracing on adult spinal deformity patients: evaluation of gait and dynamic balance.

Non-operative treatment is regarded as the first-line therapy for patients with adult spinal deformity (ASD) without neurologic deficits or significant impairment. While there is high-level evidence supporting the use of rigid bracing in adolescent idiopathic scoliosis, there is a paucity of literature pertaining to the use of scoliosis support orthosis (SSO) in ASD patients. To investigate the impact of an SSO on pain, gait parameters, and functional balance measures in symptomatic ASD patients. Thirty ASD patients (26 Females, Age: 72.7, Cobb Angle: 47.1°) were evaluated on 3 different occasions: first day of bracing: baseline (Pre), and 45-min post fitting (Post45m), and after 8-weeks of bracing for 4 hours a day (Post8w). Each patient performed a 6-minute walk (over-ground gait), a dynamic balance test, and completed VAS, ODI, and SRS22r. Significant short- and long-term improvements using SSO were found in the 6-minute walk (Pre: 278.6; Post45m: 322.2; Post8w: 338.8 m, p<0.001), walking speed (Pre: 0.88; Post45m: 0.97; Post8w: 0.97 m/s, p<0.001), head total sway distance during the balance test (Pre: 81.33; Post45m: 68.63; Post8w: 60.72 cm, p=0.048), low-back pain (VAS: Pre: 5.5; Post45m: 3.5; Post8w: 3.3, p<0.001), and for the ODI (Pre: 41.9; Post45m: 32.9; Post8w: 30.1, p=0.005).This study demonstrated clinically significant improvements in PROMs, spatiotemporal gait measures, and functional balance measures after continuous use of a SSO. These improvements were observed immediately following brace-fitting and maintained at an 8-week follow-up. Given these results, it is reasonable to consider a SSO for conservative management of patients with mild symptoms of pain and deformity, and who have not yet progressed to meet surgical indications.

Prevalence of fibromyalgia and co-morbid bipolar disorder: A systematic review and meta-analysis.

BACKGROUND: Fibromyalgia (FM) is a chronic disorder with high morbidity and significant health service utilization costs. Few studies have reported on the phenotypic overlap of FM and bipolar disorder (BD). The aim of this review is to qualitatively and quantitatively summarize the results and clinical implications of the extant literature on the co-occurrence of FM and BD. METHODS: A systematic search of PubMed/Medline, Cochrane, PsycINFO, CINAHL and Embase was conducted to search for relevant articles. Articles were included if incidence and/or prevalence of BD was determined in the FM sample. Results of prevalence were pooled from all studies. Pooled odds ratio (OR) was calculated based on case-control studies using standard meta-analytic methods. RESULTS: A total of nine studies were included. The pooled rate of BD comorbidity in samples of FM patients was 21% (n=678); however, results varied greatly as a function of study methodology. Case-controlled studies revealed a pooled OR of 7.55 of BD co-morbidity in samples of FM patients [95% Confidence Interval (CI)=3.9-14.62, FM n=268, controls n=413] with low heterogeneity (I(2)=0%). LIMITATIONS: The current study was limited by the low number of available studies and heterogeneity of study methods and results. CONCLUSIONS: These data strongly suggest an association between BD and FM. Future studies employing a validated diagnostic screen are needed in order to more accurately determine the prevalence of BD in FM. An adequate psychiatric assessment is recommended in FM patients with suspected symptoms consistent with BD prior to administration of antidepressants in the treatment of FM.

Outbreak of gastroenteritis caused by Yersinia pestis in Afghanistan.

Plague, which is most often caused by the bite of Yersinia pestis-infected fleas, is a rapidly progressing, serious disease that can be fatal without prompt antibiotic treatment. In late December 2007, an outbreak of acute gastroenteritis occurred in Nimroz Province of southern Afghanistan. Of the 83 probable cases of illness, 17 died (case fatality 20·5%). Being a case was associated with consumption or handling of camel meat (adjusted odds ratio 4·4, 95% confidence interval 2·2-8·8, P<0·001). Molecular testing of patient clinical samples and of tissue from the camel using PCR/electrospray ionization-mass spectrometry revealed DNA signatures consistent with Yersinia pestis. Confirmatory testing using real-time PCR and immunological seroconversion of one of the patients confirmed that the outbreak was caused by plague, with a rare gastrointestinal presentation. The study highlights the challenges of identifying infectious agents in low-resource settings; it is the first reported occurrence of plague in Afghanistan.

Occult acetabular fractures in elderly patients: a report of three cases.

Three elderly patients with acetabular fractures not evident on the initial plain radiographs are presented. All had a fall and were unable to bear weight. Cross-sectional imaging and repeated plain radiography confirmed fractures of the acetabulum. Occult acetabular fractures may occur in elderly patients after a fall and present with persistent discomfort and difficulty walking. When there is reason to suspect such a fracture, further diagnostic studies, including a Judet view radiograph, bone scan, computed tomographic scan or magnetic resonance image should be performed.

Clinical and genetic analysis of CMT1B in a Nigerian family.

We report a Nigerian family with a late-onset autosomal dominant neuropathy consistent with Charcot-Marie-Tooth disease. Electrophysiological examination of the index patient confirmed a severe demyelinating neuropathy with secondary axonal features. Sequence analysis of the myelin protein zero (MPZ) gene identified a C-to-G transversion at nucleotide position 234, resulting in a serine-to-tryptophan mutation in codon 78 (S78W) of the translated protein. The presence of this novel missense mutation suggests a diagnosis of Charcot-Marie-Tooth disease type 1B. Our study confirms the worldwide distribution of this disorder and extends the genetic spectrum of mutations in the MPZ gene.

SHP1 protein-tyrosine phosphatase inhibits gp91PHOX and p67PHOX expression by inhibiting interaction of PU.1, IRF1, interferon consensus sequence-binding protein, and CREB-binding protein with homologous Cis elements in the CYBB and NCF2 genes.

The CYBB and NCF2 genes encode the phagocyte respiratory burst oxidase proteins, gp91PHOX and p67PHOX. Previously, we identified homologous CYBB and NCF2 cis elements that are necessary for lineage-specific transcription during late myeloid differentiation. We determined that these homologous cis elements are activated by PU.1, IRF1, interferon consensus sequence-binding protein (ICSBP), and the CREB-binding protein (CBP). Since expression of PU.1 and ICSBP is lineage-restricted, our investigations identified a mechanism of lineage-specific CYBB and NCF2 transcription. Since PU.1, IRF1, ICSBP, and CBP are expressed in undifferentiated myeloid cells, our investigations did not determine the mechanism of differentiation stage-specific CYBB and NCF2 transcription. In the current investigations, we determine that SHP1 protein-tyrosine phosphatase (SHP1-PTP) inhibits gp91PHOX and p67PHOX expression, in undifferentiated myeloid cell lines, by decreasing interaction of PU.1, IRF1, ICSBP, and CBP with the CYBB and NCF2 genes. We also determine that IRF1 and ICSBP are tyrosine-phosphorylated during interferon gamma differentiation of myeloid cell lines, and we identify IRF1 and ICSBP tyrosine residues that are necessary for CYBB and NCF2 transcription. Therefore, these investigations identify a novel mechanism by which SHP1-PTP antagonizes myeloid differentiation and determine that tyrosine phosphorylation of IRF1 and ICSPB mediates stage-specific transcriptional activation in differentiating myeloid cells.

Tyrosine phosphorylation of HoxA10 decreases DNA binding and transcriptional repression during interferon gamma -induced differentiation of myeloid leukemia cell lines.

The DNA binding affinity of HoxA10 is increased by partnering with Pbx proteins. A consensus sequence for Pbx1-HoxA10 DNA binding has been derived, but genuine target genes have not been identified. We noted that the derived Pbx-HoxA10 DNA-binding consensus is similar to a repressor element in the CYBB promoter. The CYBB gene, which encodes the respiratory burst oxidase component gp91(phox), is expressed only in myeloid cells that have differentiated beyond the promyelocyte stage. In these studies, we demonstrate that interferon gamma (IFN-gamma)-induced differentiation of myeloid cell lines abolishes in vitro Pbx-HoxA10 binding to either the derived consensus or the similar CYBB sequence. We also demonstrate that HoxA10, overexpressed in myeloid cell lines, represses reporter gene expression from artificial promoter constructs with Pbx-HoxA10 binding sites. We determine that HoxA10 has endogenous repression domains that are not functionally altered by IFN-gamma treatment. However, IFN-gamma-induced differentiation of myeloid cell lines leads to HoxA10 tyrosine phosphorylation, which decreases in vitro DNA binding to Pbx-HoxA10 binding sites. Therefore, these investigations identify the CYBB gene as a potential target for HoxA10 and define repression of genes expressed in mature myeloid cells as a novel role for HoxA10 during myeloid differentiation.

Recruitment of CREB-binding protein by PU.1, IFN-regulatory factor-1, and the IFN consensus sequence-binding protein is necessary for IFN-gamma-induced p67phox and gp91phox expression.

Activation of the phagocyte respiratory burst oxidase requires interaction between the oxidase components p47phox, p67phox, p22phox, and gp91phox. IFN-gamma induces transcription of the genes encoding p67phox (the NCF2 gene) and gp91phox (the CYBB gene) during monocyte differentiation, and also in mature monocytes. In these studies, we identify an NCF2 cis element, necessary for IFN-gamma-induced p67phox expression, and determine that this element is activated by cooperation between the transcription factors PU.1, IFN regulatory factor 1 (IRF1), and the IFN consensus-binding protein (ICSBP). Previously, we identified a CYBB cis element, necessary for IFN-gamma-induced gp91phox expression, and also activated by this transcription factor combination. In these investigations, we determine that recruitment of a coactivator protein, CBP (the CREBbinding protein), to the CYBB or NCF2 promoter is the molecular mechanism of transcriptional activation by PU.1, IRF1, and ICSBP. Also, we determine that the multiprotein interaction of CBP with PU. 1, IRF1, and ICSBP requires either the CYBB- or NCF2--binding site. Because IFN-gamma induces simultaneous expression of p67phox and gp91phox, these investigations identify a molecular event that coordinates oxidase gene transcription during the inflammatory response. Also, these investigations identify CBP recruitment by cooperation between PU.1, IRF1, and ICSBP as a novel molecular mechanism for IFN-gamma-induced activation of myeloid genes that are involved in the system of host defense.

New look at myocardial infarction: toward a better aspirin.

The evidence for the formation of NO and of its oxidation products, as well as of prostacyclin and thromboxane by the infarcted heart muscle is reviewed. The importance of inflammatory cells, primarily macrophages of cardiac origin is documented. Because of its side effects on gastric mucosa and kidney by aspirin, several modifications of aspirin are currently being developed. These are based on eliminating their inflammatory effect by selective inhibition of COX-2, or by attaching an NO-delivering side chain to the aspirin molecule (NO-aspirin), or by combining two preparations, an NO donor with aspirin. NO-aspirins and the combination of an NO-donor with aspirin promise to be beneficial in the early stages of myocardial infarction. Unfortunately, the main beneficial effect of aspirin, that of inhibition of thrombus formation, is also the cause for its most dreaded complication, hemorrhagic stroke. None of the new aspirins is able to prevent this complication.

PU.1, interferon regulatory factor 1, and interferon consensus sequence-binding protein cooperate to increase gp91(phox) expression.

gp91(phox) is a subunit of the phagocyte respiratory burst oxidase catalytic unit. Transcription of CYBB, the gene encoding gp91(phox), is restricted to terminally differentiated phagocytic cells. An element in the proximal CYBB promoter binds a protein complex, referred to as hematopoiesis-associated factor (HAF1), that is necessary for interferon-gamma (IFNgamma)-induced gp91(phox) expression. In these investigations, we determined that HAF1 was a multiprotein complex, cross-immunoreactive with the transcription factors PU.1, interferon regulatory factor 1 (IRF-1), and interferon consensus sequence-binding protein (ICSBP). In electrophoretic mobility shift assay, the HAF1 complex was reconstituted by either in vitro translated PU.1 with IRF-1 or PU.1 with ICSBP, but not by IRF-1 with ICSBP. HAF1a, a slower mobility complex with the same binding site specificity as HAF1, was also investigated. Similar to the HAF1 complex, the HAF1a complex was cross-immunoreactive with PU. 1, IRF-1, and ICSBP. Unlike the HAF1 complex, reconstitution of the HAF1a complex required in vitro translated PU.1 with both IRF-1 and ICSBP. An artificial promoter construct containing the HAF1/HAF1a binding site was modestly activated in the myelomonocytic cell line U937 by co-transfection either with PU.1 and IRF-1 or with PU.1 and ICSBP, but it was strongly activated by co-transfection with PU.1, IRF-1, and ICSBP. This activation required serine 148-phosphorylated PU.1. These studies describe a novel mechanism for PU.1 transcriptional activation via interaction with both IRF-1 and ICSBP, a target gene for the interaction of IRF-1 with ICSBP, and a novel activation function for ICSBP as a component of a multiprotein complex.

Identification and characterization of TF1(phox), a DNA-binding protein that increases expression of gp91(phox) in PLB985 myeloid leukemia cells.

The CYBB gene encodes gp91(phox), the heavy chain of the phagocyte-specific NADPH oxidase. CYBB is transcriptionally inactive until the promyelocyte stage of myelopoiesis, and in mature phagocytes, expression of gp91(phox) is further increased by interferon-gamma (IFN-gamma) and other inflammatory mediators. The CYBB promoter region contains several lineage-specific cis-elements involved in the IFN-gamma response. We screened a leukocyte cDNA expression library for proteins able to bind to one of these cis-elements (-214 to -262 base pairs) and identified TF1(phox), a protein with sequence-specific binding to the CYBB promoter. Electrophoretic mobility shift assay with nuclear proteins from a variety of cell lines demonstrated binding of a protein to the CYBB promoter that was cross-immunoreactive with TF1(phox). DNA binding of this protein was increased by IFN-gamma treatment in the myeloid cell line PLB985, but not in the non-myeloid cell line HeLa. Overexpression of recombinant TF1(phox) in PLB985 cells increased endogenous gp91(phox) message abundance, but did not lead to cellular differentiation. Overexpression of TF1(phox) in myeloid leukemia cell lines increased reporter gene expression from artificial promoter constructs containing CYBB promoter sequence. These data suggested that TF1(phox) increased expression of gp91(phox).

Mars: microwave detection of carbon monoxide.

The 115-gigahertz microwave line of carbon monoxide has been detected in the spectrum of Mars. The measurement is sensitive to carbon monoxide between the surface and an altitude of approximately 50 kilometers in the martian atmosphere. This extends the altitude region to well above that previously sensed.

Venus: microwave detection of carbon monoxide.

The 115-gigahertz microwave line of carbon monoxide has been detected in the spectrum of Venus. The measurement proves that the carbon monoxide mixing ratio increases above an altitude of 85 kilometers in the Venus stratosphere and provides quantitative information on carbon monoxide in the altitude region from 80 to 110 kilometers. This altitude region is well above that which has been previously sensed.