The analysis of association between <Emphasis Type="Italic">SNCA</Emphasis>, <Emphasis Type="Italic">HUSEYO</Emphasis> and <Emphasis Type="Italic">CSMD1</Emphasis> gene variants and Parkinson’s disease in Iranian population

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder. Both genetic and environmental factors are involved in the etiology of the disease. Many studies have revealed the susceptibility genes and variations for PD which need further confirmation. Here we evaluated the association of variations in SNCA, HUSEYO and CSMD1 genes with PD. A case–control study was conducted with 489 PD patients and 489 healthy controls. DNA was extracted from peripheral blood of all subjects and rs356220 and rs11931074 in SNCA, rs2338971 in HUSEYO and rs12681349 in CSMD1 were genotyped using PCR–RFLP method. The genotypes and allele frequencies were significantly different between case and control groups for rs356220, rs11931074 and rs2338971 but not for rs12681349. We provided further evidence that rs356220 is associated with increased risk of PD supporting previous studies in Caucasian-based and Japanese populations. The association of rs11931074 with decreased risk of PD was also significant. This study revealed the first evidence of the association of rs2338971 with increased risk of PD in the Iranian population. Nevertheless, these findings need further validation via more replication studies.     

Single leg landing kinematics in volleyball athletes: A comparison between athletes with and without active extension low back pain

PurposeThe purpose of this study was to compare kinematics of the lower extremity and lumbar spine during a single leg landing task between female volleyball athletes with and without persistent low back pain (LBP).MethodsIn this cross sectional study, 36 volunteer female volleyball athletes with (n = 18) and without (n = 18) LBP were recruited. Two specifically trained physical therapists selected only athletes with a specific movement-based subgroup of LBP for inclusion. Three dimensional kinematic and ground reaction force data were recorded for each athlete across three single leg landing trials by utilizing a Vicon 6-camera motion capture system and one in-floor embedded Kistler force plate, respectively. Independent t-tests compared data between the two groups.ResultsLumbar lordosis when standing (p = 0.046) as well as on initial contact (p = 0.025) and at the time which the maximal vertical ground reaction force occurred (p = 0.020) were significantly greater in the LBP group. There were no other significant differences.ConclusionsThe tendency for this specific subgroup of athletes to consistently adopt more extended lumbar postures in both static and dynamic tasks may be worth considering by those involved in coaching, performance optimizing and injury prevention.     

Acid‐sensing ion channel 1a drives AMPA receptor plasticity following ischaemia and acidosis in hippocampal CA1 neurons

Key points

• The hippocampal CA1 region is highly vulnerable to ischaemic stroke. Two forms of AMPA receptor (AMPAR) plasticity – an anoxic form of long‐term potentiation and a delayed increase in Ca²⁺‐permeable (CP) AMPARs – contribute to this susceptibility by increasing excitotoxicity.
• In CA1, the acid‐sensing ion channel 1a (ASIC1a) is known to facilitate LTP and contribute to ischaemic acidotoxicity.
• We have examined the role of ASIC1a in AMPAR ischaemic plasticity in organotypic hippocampal slice cultures exposed to oxygen glucose deprivation (a model of ischaemic stroke), and in hippocampal pyramidal neuron cultures exposed to acidosis.
• We find that ASIC1a activation promotes both forms of AMPAR plasticity and that neuroprotection, by inhibiting ASIC1a, circumvents any further benefit of blocking CP‐AMPARs.
• Our observations establish a new interaction between acidotoxicity and excitotoxicity, and provide insight into the role of ASIC1a and CP‐AMPARs in neurodegeneration. Specifically, we propose that ASIC1a activation drives certain post‐ischaemic forms of CP‐AMPAR plasticity.

Abstract

The CA1 region of the hippocampus is particularly vulnerable to ischaemic damage. While NMDA receptors play a major role in excitotoxicity, it is thought to be exacerbated in this region by two forms of post‐ischaemic AMPA receptor (AMPAR) plasticity – namely, anoxic long‐term potentiation (a‐LTP), and a delayed increase in the prevalence of Ca²⁺‐permeable GluA2‐lacking AMPARs (CP‐AMPARs). The acid‐sensing ion channel 1a (ASIC1a), which is expressed in CA1 pyramidal neurons, is also known to contribute to post‐ischaemic neuronal death and to physiologically induced LTP. This raises the question does ASIC1a activation drive the post‐ischaemic forms of AMPAR plasticity in CA1 pyramidal neurons? We have tested this by examining organotypic hippocampal slice cultures (OHSCs) exposed to oxygen glucose deprivation (OGD), and dissociated cultures of hippocampal pyramidal neurons (HPNs) exposed to low pH (acidosis). We find that both a‐LTP and the delayed increase in the prevalence of CP‐AMPARs are dependent on ASIC1a activation during ischaemia. Indeed, acidosis alone is sufficient to induce the increase in CP‐AMPARs. We also find that inhibition of ASIC1a channels circumvents any potential neuroprotective benefit arising from block of CP‐AMPARs. By demonstrating that ASIC1a activation contributes to post‐ischaemic AMPAR plasticity, our results identify a functional interaction between acidotoxicity and excitotoxicity in hippocampal CA1 cells, and provide insight into the role of ASIC1a and CP‐AMPARs as potential drug targets for neuroprotection. We thus propose that ASIC1a activation can drive certain forms of CP‐AMPAR plasticity, and that inhibiting ASIC1a affords neuroprotection.

Abbreviations

a‐LTP

anoxic LTP

AMPAR

AMPA receptor

ASIC1a

acid‐sensing ion channel 1a

CP‐AMPAR

calcium‐permeable AMPAR

HPN

hippocampal pyramidal neuron

I–V

current–voltage

KO

knockout

LTP

long‐term potentiation

NASPM

1‐naphthyl acetyl spermine

NFATc

nuclear factor of activated T cells

NMDAR

NMDA receptor

OGD

oxygen glucose deprivation

OHSC

organotypic hippocampal slice culture

PcTx1

psalmotoxin 1

PI

propidium iodide

RI

rectification index

TBS

theta‐burst stimulation

WT

wild type

     

Diagnostic accuracy of emergency physician performed graded compression ultrasound study in acute appendicitis: a prospective study

Purpose

Accurate early diagnosis of appendicitis can decrease its complications and minimize the mortality, morbidity and costs. This prospective study evaluates the accuracy of bedside emergency physician performed ultrasound study diagnosis in acute appendicitis.

Methods

Patients who were suspicious to have appendicitis based on their clinical findings were included and underwent emergency physician performed ultrasound study. Then they were followed up until the recognition of final diagnosis based on pathology report or identification of an alternative diagnosis. Ultrasound studies were done by post-graduate year three emergency medicine residents or emergency medicine attending physicians who were attended in a 4 h didactic and practical course and with 7.5 MHz linear probe both in longitudinal and axial axes.

Results

Ninety-seven patients were included and analyzed. 27 (27.8 %) of patients had appendicitis according to the results of emergency physicians performed ultrasound studies. 19 (70.37 %) of them had appendicitis according to their pathologic reports too. Forty-three (44.3 %) of patients had appendicitis according to pathology reports. Only 19 (44.18 %) of them were diagnosed by emergency physicians. Emergency physician performed ultrasound study had a sensitivity of 44.18 %, specificity of 85.18 %, positive predictive value of 70.37 %, negative predictive value of 65.71 % and overall accuracy of 67.01 % in diagnosing appendicitis in patients clinically suspicious to have acute appendicitis.

Conclusion

Emergency physician performed bedside ultrasound has an acceptable overall accuracy but its sensitivity is low thus it can help emergency physicians to diagnose the acute appendicitis when used in conjunction with other clinical and para-clinical evaluations but not per se.     

A systematic review of changes in women’s physical activity before and during pregnancy and the postnatal period

Objectives: To determine the magnitude and type of naturally occuring physical activity changes in women around the time of pregnancy. Background: This systematic review synthesises the results of studies examining naturally occurring physical activity in women before they become pregnant and the magnitude and type of changes during pregnancy and the postnatal period. Methods: Electronic databases were searched for relevant articles and PRISMA guidelines for selection of articles were used. Only studies examining naturally occurring, non-intervention changes in regular activity levels were included. The quality assessment was based on protocols of the Cochrane Database of Systematic Reviews. Of the initial 720 titles, 24 studies met the inclusion criteria and were included in the final review. Results: Compared to pre-pregnancy, the magnitude of physical activity decreased over the course of pregnancy and postnatally and the types of activities tended to be of lesser intensity than pre-pregnancy. The quality of the research was varied; methodological limitations included using subjective methods of assessment of physical activity (9/24), failing to report reliabilities or validity of measures used (8/24), no information on parity (13/24) or level of fitness prior to pregnancy (11/24). Conclusion: The evidence suggests a marked decrease in the amount and type of moderate to strenuous physical activity during the transition to motherhood, which does not always increase again postpartum. Patient education targeting specific physical activities at regular intervals during and after pregnancy to improve long-term maternal health is necessary.     

Neutropenia in patients with primary antibody deficiency disorders

Neutropenia is characterized by decrease in the absolute number of circulating neutrophils and an increase susceptibility to infections. The current study was performed in order to explain the clinical and laboratory findings of patients with antibody deficiency disorders associated neutropenia. The patients' records of 19 neutropenic cases out of 207 patients with antibody deficiencies, who had been referred to Children's Medical Center and enrolled in Iranian primary immunodeficiency registry, were reviewed. Nineteen cases (14 male and 5 female), with a mean age of 10.7+/-5.7 years, were associated with neutropenia (9.2%). The disorders with associated neutropenia were Hyper IgM syndromes (3 of 8), Common variable immunodeficiency (13 of 109), and X-linked agammaglobulinemia (3 of 45). The median age for the onset of disease and diagnosis age were 15 months (1-134) and 3.8 years (6 months-13 years), respectively. The most common infections during the course of illness were pneumonia (13 cases), diarrhea (12 cases), oral candidiasis (9 cases), otitis media (6 cases), sinusitis (6 cases), cutaneous infections (5 cases), and abscess (5 cases). Other less frequent infections were: conjunctivitis, oral ulcers, meningitis, and osteomyelitis. Three neutropenic patients died because of recurrent infections. Neutropenia may occur in any of the primary immunodeficiency disorders. Persistent or severe infections always pose a supposition, which deserves further evaluation for detecting an underlying immune deficiency syndrome and neutropenia, since a delay in diagnosis may result in a serious organ damage or even death of the patient.     

Development of an Indirect ELISA Using Different Fragments of Recombinant Ncgra7 for Detection of Neospora caninum Infection in Cattle and Water Buffalo

Background:

Dense granules are immunodominant proteins for the standardization of immunodiagnostic procedures to detect neosporosis. In the presented study different fragment of a dense-granule protein was evaluated for serodiagnosis of Neospora caninum in cattle and water buffalo.

Methods:

NcGRA7, from N. caninum tachyzoites was amplified. PCR product and pMAL-c2X plasmid were digested with EcoR1 restriction enzyme and expressed in Escherichia coli to evaluate its competence for detection of anti- N. caninum antibodies with ELISA in comparison with commercial IDEXX ELISA. Furthermore, 230 sera of presumably healthy cattle and water buffaloes (108 cattle and 122 water buffaloes) were analyzed by both tests to determine the agreement of these two procedures.

Results:

Sensitivities and specificities of NcGRA7-based ELISA were 94.64% and 90.38% respectively using sera of cattle, but were 98.57% and 86.54% in the case of buffaloes respectively. A good correlation between the results of IDEXX ELISA and ELISA based on recombinant NcGRA7 for detecting N. caninum antibodies was appeared. Analyzing by Mc Nemar′s showed that NcGRA7-based ELISA has acceptable capability to differentiate the positive results in comparison with IDEXX ELISA.

Conclusion:

NcGRA7-based ELISA considering utilized new fragment of genomic DNA is a good tool for serodiagnosis of anti- N. caninum antibodies for screening and epidemiological purposes on cattle herd and water buffaloes as well.     

Outcome of lupus nephritis in Iranian children: prognostic significance of certain features

The objective of this study was to determine the clinical and histopathological features and outcome of children with lupus nephritis (LN). Of 84 children with systemic lupus erythematosus (SLE), we retrospectively studied 58 children (69%) under 15 years of age with biopsy-proven LN who had been followed between October 1989 and January 2005. The mean age at diagnosis or initial referral was 10.6 ± 2.25 years, and the mean follow-up was 5.3 ± 4.1 years. Class IV LN was observed in 34 (58.6%) patients. The 5-year patient and renal survival rates were 82.5 and 78.5%, respectively, in the total group, and 75 and 85.8%, respectively, in patients with Class IV LN. No independent predictor of unfavorable outcome, including renal histology, was detected by multivariate analysis. The mid-term patient and the renal survival rates of Iranian children with biopsy-proven LN are high. Within 5 years of follow-up, renal histology was not a predictor for survival.     

Fragile X syndrome screening of families with consanguineous and non-consanguineous parents in the Iranian population

Fragile X syndrome is the most common form of inherited mental retardation (MR). It is caused by the expansion of CGG triplet repeats in the fragile X mental retardation 1 (FMR1) gene. In mentally retarded males, the frequency of fragile X syndrome is approximately 2–3 percent, but little is known about its proportion in mentally retarded patients from countries where parental consanguinity is common.The objective of this study was to estimate the frequency of fragile X syndrome (FXS) in mentally retarded patients from Iran. We examined a total of 508 families with MR that had been referred to the Genetics Research Center (GRC) in Tehran of which 467 families had at least two mentally retarded children. In 384 families, the parents were related and in 124 they were not related of which most of them had putative or established X-linked inheritance pattern. Full FMR1 mutations were found in 32 of the 508 families studied (6.3%), in 19 out of 124 families with apparently unrelated parents (15.3%), and in 13 of the 384 consanguineous families (3.4%). Thus, in Iran, the relative frequency of FXS seems to be high, and in patients with unrelated parents is much higher. We also show that even in families with consanguineous parents, FXS has to be ruled out before assuming that familial MR is due to autosomal recessive gene defects. Molecular studies are in progress to explain the high proportion of FMR1 mutations in mentally retarded offspring of unrelated Iranian parents.