Adult-onset combined oxidative phosphorylation deficiency type 14 manifests as epileptic status: a new phenotype and literature review.

BACKGROUND: Combined oxidative phosphorylation deficiency (COXPD) is a severe disorder with early onset and autosomal recessive inheritance, and has been divided into 51 types (COXPD1-COXPD51). COXPD14 is caused by a mutation in the FARS2 gene, which encodes mitochondrial phenylalanyl-tRNA synthetase (mt-PheRS), an enzyme that transfers phenylalanine to its cognate tRNA in mitochondria. Since the first case was reported in 2012, an increasing number of FARS2 variations have been subsequently identified, which present three main phenotypic manifestations: early onset epileptic encephalopathy, hereditary spastic paraplegia, and juvenile-onset epilepsy. To our knowledge, no adult cases have been reported in the literature. METHODS: We report in detail a case of genetically confirmed COXPD14 and review the relevant literature. RESULTS: Approximately 58 subjects with disease-causing variants of FARS2 have been reported, including 31 cases of early onset epileptic encephalopathy, 16 cases of hereditary spastic paraplegia, 3 cases of juvenile-onset epilepsy, and 8 cases of unknown phenotype. We report a case of autosomal recessive COXPD14 in an adult with status epilepticus as the only manifestation with a good prognosis, which is different from that in neonatal or infant patients reported in the literature. c.467C > T (p.T156M) has been previously reported, while c.119_120del (p.E40Vfs*87) is novel, and, both mutations are pathogenic. CONCLUSIONS: This case of autosomal recessive COXPD14 in an adult only presented as status epilepticus, which is different from the patients reported previously. Our study expands the mutation spectrum of FARS2, and we tended to define the phenotypes based on the clinical manifestation rather than the age of onset.

Geographical distribution of nitrate pollution and its risk assessment using GIS and Monte Carlo simulation in drinking water in urban areas of Fars province-Iran during 2017-2021.

Pollution of water resources with nitrate is currently one of the major challenges at the global level. In order to make macro-policy decisions in water safety plans, it is necessary to carry out nitrate risk assessment in underground water, which has not been done in Fars province for all urban areas. In the current study, 9494 drinking water samples were collected in four seasons in 32 urban areas of Fars province in Iran, between 2017 and 2021 to investigate the non-carcinogenic health risk assessment. Geographical distribution maps of hazard quotient were drawn using geographical information system software. The results showed that the maximum amount of nitrate in water samples in 4% of the samples in 2021, 2.5% of the samples in 2020 and 3% of the samples in 2019 were more than the standard declared by World Health Organization guidelines (50 mg/L). In these cases, the maximum amount of nitrate was reported between 82 and 123 mg/L. The HQ values for infants did not exceed 1 in any year, but for children (44% ± 10.8), teenagers (10.8% ± 8.4), and adults (3.2% ± 1.7) exceeded 1 in cities, years, and seasons, indicating that three age groups in the studied area are at noticeably significant non-carcinogenic risk. The results of the Monte Carlo simulation showed that the average value of non-carcinogenic risk was less than 1 for all age groups. Moreover, the maximum HQ values (95%) were higher than 1 for both children and teenager, indicating a significant non-carcinogenic risk for the two age groups.

Clinical and molecular characterization of novel FARS2 variants causing neonatal mitochondrial disease.

FARS2 encodes the mitochondrial phenylalanyl-tRNA synthetase (mtPheRS), which is essential for charging mitochondrial (mt-) tRNAPhe with phenylalanine for use in intramitochondrial translation. Many biallelic, pathogenic FARS2 variants have been described previously, which are mostly associated with two distinct clinical phenotypes; an early onset epileptic mitochondrial encephalomyopathy or a later onset spastic paraplegia. In this study, we report on a patient who presented at 3 weeks of age with tachypnoea and poor feeding, which progressed to severe metabolic decompensation with lactic acidosis and seizure activity followed by death at 9 weeks of age. Rapid trio whole exome sequencing identified compound heterozygous FARS2 variants including a pathogenic exon 2 deletion on one allele and a rare missense variant (c.593G > T, p.(Arg198Leu)) on the other allele, necessitating further work to aid variant classification. Assessment of patient fibroblasts demonstrated severely decreased steady-state levels of mtPheRS, but no obvious defect in any components of the oxidative phosphorylation system. To investigate the potential pathogenicity of the missense variant, we determined its high-resolution crystal structure, demonstrating a local structural destabilization in the catalytic domain. Moreover, the R198L mutation reduced the thermal stability and impaired the enzymatic activity of mtPheRS due to a lower binding affinity for tRNAPhe and a slower turnover rate. Together these data confirm the pathogenicity of this FARS2 variant in causing early-onset mitochondrial epilepsy.

Prevalence and risk factors associated with Q fever infection in slaughterhouse workers in Fars province, Iran.

OBJECTIVE: Q fever is a main occupational zoonotic disease. Slaughterhouse is one of the most remarkable ways of transmitting the infection from livestock to humans. This study aimed to survey the prevalence of Q fever in slaughterhouse workers in Fars province, Iran, for the first time. METHODS: Ninety serum samples were collected from slaughterhouse workers and tested to detect Immunoglobulin G (IgG) against Coxiella burnetii using ELISA and indirect immunofluorescence assay (IFA). PCR was also applied to identify C. burnetii DNA in the blood samples. RESULTS: Q fever seroprevalence was found at 26.7% in ELISA, showing recent infection. This result indicates that Q fever seroprevalence is relatively high in the Fars region. IFA showed a high seroprevalence of total IgG antibodies at 1:64 titer (73.3%) and relatively high IgG at 1:256 titer (40%) against C. burnetii. 2.2% of the workers were recognized as having probable acute Q fever. The IgG II prevalence at 1:64 and 1:256 titers was, respectively, 63.3% and 24.4% positive. The IgG I prevalence at 1:64 and 1:256 titers was also found 33.3% and 22.2% positive, respectively. Molecular prevalence of Q fever was also 8.9%. A significant relationship was found between IgG I seropositivity and longer work experience and employing other livestock-related jobs (animal husbandry and butchery) (P < 0.05). CONCLUSIONS: As such, the high seroprevalence of Q fever among abattoir workers highlights the importance of further comprehensive epidemiological studies, occupational screening programs, and preventive measures for Q fever in high-risk groups. This also warns animal health care organizations about the risk of Q fever infection in livestock in this region.

Lung cancer registry and monitoring: Feasibility study and application (fars lung cancer registry project).

Background: Lung cancer (LC) is the second most common and deadliest cancer in the world. Despite the control of the progressive course of LC in developed countries, studies indicate an increase in the incidence of the disease in developing countries. We designed a stepwise approach-based surveillance system for registering LC in our region (fars lung cancer registry "FaLCaRe" Project). Materials and Methods: A questionnaire was designed and agreed upon by the steering committee using the Delphi method. Variables in nine fields were divided into three groups based on their importance: core, expanded core, and optional. The web-based data bank software was designed. The informative site about LC and team services was designed and launched for professional and community (www.falcare.org) educational purposes. Results: 545 variables in nine fields were designed (20 core variables). Primary data of 39 LC patients (24 men and 15 women) with a mean age of 62 years were analyzed. Twenty-six patients had a history of smoking. Moreover, 39% and 26% of patients had a history of hookah smoking and opium use, respectively. Adenocarcinoma was the most prevalent pathologic findings in cases. More than 80% of patients were diagnosed in stages 3 and 4 of cancer. Conclusion: FaLCaRe Project with the capabilities seen in it can be used as a model for national LC registration. With continuous valid data registry about LC, it is possible to make decisions at the national level for control and management its consequences while drawing the natural history of the LC.

FARS1-related disorders caused by bi-allelic mutations in cytosolic phenylalanyl-tRNA synthetase genes: Look beyond the lungs!

Aminoacyl-tRNA synthetases (ARSs) catalyze the first step of protein biosynthesis (canonical function) and have additional (non-canonical) functions outside of translation. Bi-allelic pathogenic variants in genes encoding ARSs are associated with various recessive mitochondrial and multisystem disorders. We describe here a multisystem clinical phenotype based on bi-allelic mutations in the two genes (FARSA, FARSB) encoding distinct subunits for tetrameric cytosolic phenylalanyl-tRNA synthetase (FARS1). Interstitial lung disease with cholesterol pneumonitis on histology emerged as an early characteristic feature and significantly determined disease burden. Additional clinical characteristics of the patients included neurological findings, liver dysfunction, and connective tissue, muscular and vascular abnormalities. Structural modeling of newly identified missense mutations in the alpha subunit of FARS1, FARSA, showed exclusive mapping to the enzyme's conserved catalytic domain. Patient-derived mutant cells displayed compromised aminoacylation activity in two cases, while remaining unaffected in another. Collectively, these findings expand current knowledge about the human ARS disease spectrum and support a loss of canonical and non-canonical function in FARS1-associated recessive disease.

Seroprevalence of anti-hepatitis E antibodies and antigens among HIV-infected patients in Fars Province, southern Iran.

OBJECTIVE: HIV-infected patients have immunological and clinical features that might affect the pathogenesis, as well as the outcome of the HIV/HEV co-infection. The current study aimed to determine the seroprevalence of anti-HEV antibodies and HEV antigens among HIV-infected patients in Fars Province, Southwest Iran. METHODS: Blood samples (5 mL) were collected from 251 HIV-confirmed patients. Respective data, including patients' demographic information, were obtained for each patient. The presence of HEV antigens and anti-HEV antibodies (IgG) were assessed by commercial ELISA kits, based on the manufacturers' instructions. RESULTS: Out of 251 cases, 158 (62.9%) were male and 91 (36.3%) were female. Patients' age varied from 14 to 83 (mean: 40 ± 9.7) years. Out of 251 HIV positive cases, 26 (10.4%) were positive for anti-HEV IgG antibodies and 6 (2.4%) were positive for HEV-antigens. Also, 2 (0.8%) of the patients were positive for both anti-HEV IgG antibodies and antigens. Statistical analysis revealed no significant association between sex and seropositivity to either HEV antigen or antibodies. Moreover, no significant association was seen between age and seropositivity to HEV antigen or antibody (P = 0.622 and 0.945, respectively). CONCLUSION: Our results showed a relatively low prevalence of HEV-antibodies in HIV-infected patients, indicating that HIV positive patients may not be at greater risk of HEV infection than the general population. Moreover, HEV-antigen was detected in a few cases of HIV-infected individuals which indicate an acute or chronic HEV infection in these patients.

Ex vivo anti-microbial efficacy of various formaldehyde releasers against antibiotic resistant and antibiotic sensitive microorganisms involved in infectious keratitis.

BACKGROUND: Corneal infections with antibiotic-resistant microorganisms are an increasingly difficult management challenge and chemically or photochemically cross-linking the cornea for therapy presents a unique approach to managing such infections since both direct microbial pathogens killing and matrix stabilization can occur simultaneously. The present study was undertaken in order to compare the anti-microbial efficacy, in vitro, of 5 candidate cross-linking solutions against 5 different microbial pathogens with relevance to infectious keratitis. METHODS: In vitro bactericidal efficacy studies were carried out using 5 different FARs [diazolidinyl urea (DAU), 1,3-bis(hydroxymethyl)-5,5-dimethylimidazolidine-2,4-dione (DMDM), sodium hydroxymethylglycinate (SMG), 2-(hydroxymethyl)-2-nitro-1,3-propanediol (NT = nitrotriol), 2-nitro-1-propanol (NP)] against 5 different microbial pathogens including two antibiotic-resistant species [methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), Pseudomonas aeruginosa (PA), and Candida albicans (CA)]. Standard in vitro antimicrobial testing methods were used. RESULTS: The results for MSSA were similar to those for MRSA. DAU, DMDM, and SMG all showed effectiveness with greater effects generally observed with longer incubation times and higher concentrations. Against MRSA, 40 mM SMG at 120 min showed a > 95% kill rate, p < 0.02. Against VRE, 40 mM DAU for 120 min showed a > 94% kill rate, p < 0.001. All FARs showed bactericidal effect against Pseudomonas aeruginosa, making PA the most susceptible of the strains tested. Candida showed relative resistance to these compounds, requiring high concentrations (100 mM) to achieve kill rates greater than 50%. CONCLUSION: Our results show that each FAR compound has different effects against different cultures. Our antimicrobial armamentarium could potentially be broadened by DAU, DMDM, SMG and other FARs for antibiotic-resistant keratitis. Further testing in live animal models are indicated.

Serum levels of anti-hepatitis B surface antibodies among vaccinated children aged 1 to 12 years in a rural community in Fars Province, southern Iran.

The present study aimed to find out the levels of anti-HBsAb among vaccinated children in a rural community in Fars Province, Southern Iran. Blood samples were taken from 550 children, aged 1-12 years (mean 6.4 ± 3.5), in 2017 from three villages in the area. A structured questionnaire was used to get the sociodemographic data of the subjects along with determinants concerning the Hepatitis B. Sera samples were examined for anti-HBsAb, using an ELISA commercial kit. Anti-HBsAb were detected in 468 (85.1%) of the subjects. Of the seropositive subjects, 37 (45.1%) were female and 45 (54.9%) were male. In the age group of 0-5 years, 88.7% of the subjects were seropositive. This rate was 84.3% and 78.1% in the age group of 6-10 years old and older than 10 years, respectively. There was a significant association (p < .05) between the anti-HBsAb and age. Findings of the current study revealed that children living in a rural community in southern Iran have appropriate protection against HBV even more than 10 years after being vaccinated. The decline in seropositivity rate of anti-HBsAb with age may further point out the need for a booster dose of HBV vaccine.

A patient with juvenile-onset refractory status epilepticus caused by two novel compound heterozygous mutations in FARS2 gene.

FARS2 encodes mitochondrial phenylalanyl transfer ribonucleic acid (RNA) synthetase and is implicated in autosomal recessive combined oxidative phosphorylation deficiency 14. The clinical manifestation can be divided into early onset epileptic phenotype and spastic paraplegia phenotype. The purpose of this study was to report a case of juvenile manifesting refractory epilepsy caused by two novel compound heterozygous mutations in the FARS2 gene. Microscopic and histochemical examination as well as next-generation sequencing and reconstruction of the three-dimensional structure of FARS2 protein were performed. A 17-year-old man with no developmental delays suffered from generalized tonic-clonic convulsion since 12 years of age and developed refractory status epilepticus 5 years later. No specific etiology was found following brain imaging, muscle biopsy and metabolic studies. DNA sequencing identified two novel compound heterozygous mutations in FARS2, (p.V197M and p.F402S), derived from each parents, respectively. These mutations affected the structure or thermodynamic stability of the protein. This is a case report of juvenile-onset refractory epilepsy caused by two novel compound heterozygous mutations in the FARS2 gene. This case confirms and expands the clinicalphenotype and the genotypic spectrum of the FARS2 gene.

Analysis and identification of the hidden relationships between effective factors in the mortality rate caused by road accidents: A case study of Fars Province, Iran.

PURPOSE: An analysis and identification of the hidden relationships between effective factors in the mortality rate caused by road accidents in Fars Province of Iran to prevent and reduce traffic accidents in the future. METHODS: This cross-sectional study was conducted to integrate all the pervious researches performed on mortality rate of road traffic accidents in Fars Province from March 21, 2013 to March 20, 2017. In order to reveal the relationships between the factors affecting mortality rates of road traffic accidents, the data regarding road traffic accidents extracted from resources such as Legal Medicine Organization, Traffic Police, Accident & Emergency Department, as well as Department of Roads and Urban Development of Fars Province, then cleaned and the applicable attributes embedded in the data all aggregated for further analysis. It should be noted that the data not related to Fars Province were deleted, the data analyzed, converted and the aggregation between various attributes identified. The aggregation between these different attributes as well as the FP-growth algorithm and two indexes of support and confidence calculated and interesting and effective rules extracted. In the end, several accident-provoking factors, the degree of consecutive and interdependence of each one in road accidents identified and introduced. The statistical analysis was conducted by using Rapid Miner software. RESULTS: Of the 6216 people dead due to road traffic accidents, 4865 (79.02%) were male and 1292 (20.98%) were female, 59 of them have no clear gender. The largest portion of people died of road traffic accidents belonged to married and self-employed men who collided with motorcycles in autumn. Moreover, young individuals (aged 19-40 years) with secondary educational level who died of accidents in summer at 12:00 a.m. and then 5:00 p.m. in outer city main roads of Kazerun-Shiraz, then Darab-Shiraz, Fasa-Darab and in within-city main streets had the highest mortality rates. Among women, the middle-aged group (aged 41-65 years) followed by young-aged group (aged 19-40 years) with elementary educational level and then illiterate accounted for the highest mortality rate of road traffic accidents. The automobiles involved in accidents included Pride, Peugeot 405, Peykan pickup, Samand, Peugeot Pars, other vehicles and motorcycles. CONCLUSION: The high mortality rate of illiterate and low-literate in various age groups indicates that educational level plays a crucial role as a factor in road accidents, requiring related organizations such as Traffic Police and Ministry of Education to take necessary measures and policies.

FARS2 deficiency; new cases, review of clinical, biochemical, and molecular spectra, and variants interpretation based on structural, functional, and evolutionary significance.

An increasing number of mitochondrial diseases are found to be caused by pathogenic variants in nuclear encoded mitochondrial aminoacyl-tRNA synthetases. FARS2 encodes mitochondrial phenylalanyl-tRNA synthetase (mtPheRS) which transfers phenylalanine to its cognate tRNA in mitochondria. Since the first case was reported in 2012, a total of 21 subjects with FARS2 deficiency have been reported to date with a spectrum of disease severity that falls between two phenotypes; early onset epileptic encephalopathy and a less severe phenotype characterized by spastic paraplegia. In this report, we present an additional 15 individuals from 12 families who are mostly Arabs homozygous for the pathogenic variant Y144C, which is associated with the more severe early onset phenotype. The total number of unique pathogenic FARS2 variants known to date is 21 including three different partial gene deletions reported in four individuals. Except for the large deletions, all variants but two (one in-frame deletion of one amino acid and one splice-site variant) are missense. All large deletions and the single splice-site variant are in trans with a missense variant. This suggests that complete loss of function may be incompatible with life. In this report, we also review structural, functional, and evolutionary significance of select FARS2 pathogenic variants reported here.

Forecasting zoonotic cutaneous leishmaniasis using meteorological factors in eastern Fars province, Iran: a SARIMA analysis.

OBJECTIVES: To predict the occurrence of zoonotic cutaneous leishmaniasis (ZCL) and evaluate the effect of climatic variables on disease incidence in the east of Fars province, Iran using the Seasonal Autoregressive Integrated Moving Average (SARIMA) model. METHODS: The Box-Jenkins approach was applied to fit the SARIMA model for ZCL incidence from 2004 to 2015. Then the model was used to predict the number of ZCL cases for the year 2016. Finally, we assessed the relation of meteorological variables (rainfall, rainy days, temperature, hours of sunshine and relative humidity) with ZCL incidence. RESULTS: SARIMA(2,0,0) (2,1,0)12 was the preferred model for predicting ZCL incidence in the east of Fars province (validation Root Mean Square Error, RMSE = 0.27). It showed that ZCL incidence in a given month can be estimated by the number of cases occurring 1 and 2 months, as well as 12 and 24 months earlier. The predictive power of SARIMA models was improved by the inclusion of rainfall at a lag of 2 months (ß = -0.02), rainy days at a lag of 2 months (ß = -0.09) and relative humidity at a lag of 8 months (ß = 0.13) as external regressors (P-values < 0.05). The latter was the best climatic variable for predicting ZCL cases (validation RMSE = 0.26). CONCLUSIONS: Time series models can be useful tools to predict the trend of ZCL in Fars province, Iran; thus, they can be used in the planning of public health programmes. Introducing meteorological variables into the models may improve their precision.

New insights into the phenotype of FARS2 deficiency.

Mutations in FARS2 are known to cause dysfunction of mitochondrial translation due to deficient aminoacylation of the mitochondrial phenylalanine tRNA. Here, we report three novel mutations in FARS2 found in two patients in a compound heterozygous state. The missense mutation c.1082C>T (p.Pro361Leu) was detected in both patients. The mutations c.461C>T (p.Ala154Val) and c.521_523delTGG (p.Val174del) were each detected in one patient. We report abnormal in vitro aminoacylation assays as a functional validation of the molecular genetic findings. Based on the phenotypic data of previously reported subjects and the two subjects reported here, we conclude that FARS2 deficiency can be associated with two phenotypes: (i) an epileptic phenotype, and (ii) a spastic paraplegia phenotype.

Marijuana and the Risk of Fatal Car Crashes: What Can We Learn from FARS and NRS Data?

Lab studies have shown that marijuana can severely impair driving skills. Epidemiological studies, however, have been inconclusive regarding the contribution of marijuana use to crash risk. In the United States, case-control studies based on the merging of comparable crash Fatality Analysis Reporting System (FARS) and non-crash National Roadside Survey (NRS) data have been applied to assess the contribution of drugs to crash risk, but these studies have yielded confusing, even contradictory results. We hypothesize that such a divergence of results emanates from limitations in the databases used in these studies, in particular that of the FARS. The goal of this effort is to examine this hypothesis, and in doing so, illuminate the pros and cons of using these databases for drugged-driving research efforts. We took advantage of two relatively recent cannabis crash risk studies that, despite using similar databases (the FARS and the NRS) and following similar overall approaches, yielded opposite results (Li, Brady, & Chen, 2013; Romano, Torres-Saavedra, Voas, & Lacey, 2014). By identifying methodological similarities and differences between these efforts, we assessed how the limitations of the FARS and NRS databases contributed to contradictory and biased results. Because of its limitations, we suggest that the FARS database should neither be used to examine trends in drug use nor to obtain precise risk estimates. However, under certain conditions (e.g., based on data from jurisdictions that routinely test for drugs, with as little variation in testing procedures as possible), the FARS database could be used to assess the contribution of drugs to fatal crash risk relative to other sources of risk such as alcohol.

A Newly Identified Missense Mutation in FARS2 Causes Autosomal-Recessive Spastic Paraplegia.

Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by spasticity of the lower limbs due to pyramidal tract dysfunction. Here, we report that a missense homozygous mutation c.424G>T (p.D142Y) in the FARS2 gene, which encodes a mitochondrial phenylalanyl tRNA synthetase (mtPheRS), causes HSP in a Chinese consanguineous family by using combination of homozygous mapping and whole-exome sequencing. Immunohistochemical experiments were performed showing that the FARS2 protein was highly expressed in the Purkinje cells of rat cerebellum. The aminoacylation activity of mtPheRS was severely disrupted by the p.D142Y substitution in vitro not only in the first aminoacylation step but also in the last transfer step. Taken together, our results indicate that a missense mutation in FARS2 contributes to HSP, which has the clinical significance of the regulation of tRNA synthetases in human neurodegenerative diseases.

Clinical findings in a patient with FARS2 mutations and early-infantile-encephalopathy with epilepsy.

The FARS2 gene encodes the mitochondrial phenylalanyl-tRNA synthetase and is implicated in autosomal recessive combined oxidative phosphorylation deficiency 14, a clinical condition characterized by infantile onset epilepsy and encephalopathy. Mutations in FARS2 have been reported in only few patients, but a detailed description of seizures, electroencephalographic patterns, magnetic resonance imaging findings, and long-term follow-up is still needed. We provide a clinical report of a child with FARS2-related disease manifesting drug-resistant infantile spasms associated with focal seizures. By comparative genomic hybridization analysis we identified a heterozygous microdeletion in the short arm of chromosome 6, inherited from the mother, that encompasses the first coding exon of FARS2. By sequencing of the FARS2 gene we identified a variant c.1156C>G; p.(R386G), inherited from the father. By using standard spectrophotometric techniques in skin fibroblasts, we found a combined abnormality of complexes I and IV of the mitochondrial respiratory chain. The main clinical features of the patient included axial hypotonia, mild distal hypertonia, and psychomotor delay. The magnetic resonance imaging showed microcephaly, frontal cerebral atrophy, and signal changes of dentate nuclei. At the age of 3 years and 6 months, the patient was still under treatment with vigabatrin and he has been seizure free for the last 23 months. © 2016 Wiley Periodicals, Inc.

Molecular detection of Crimean-Congo haemorrhagic fever virus in ticks collected from infested livestock populations in a New Endemic Area, South of Iran.

OBJECTIVE: Crimean-Congo haemorrhagic fever (CCHF) is a viral zoonotic disease with potentially fatal systemic effects on man. We aimed to determine the presence of CCHF virus among collected ticks from domestic livestock from October 2012 to September 2013. METHODS: A total of 1245 hard and soft ticks were collected from naturally infested ruminants in Marvdasht County, Fars Province, south of Iran. Nine tick species and one unidentified species in four disparate genera were detected. A total of 200 ticks were randomly selected and analysed by reverse transcription-polymerase chain reaction (RT-PCR) for the presence of CCHF virus genome. RESULTS: The viral genome was detected in 4.5% (9 samples) of the studied tick population. The infected ticks belonged to the species of Hyalomma marginatum' Hyalomma anatolicum and Rhipicephalus sanguineus. The viruses detected in these three tick species were clustered in the same lineage as Matin and SR3 strains in Pakistan and some other Iranian strains. These results indicate that the ticks were wildly infected with a genetically closely related CCHF virus in the region. CONCLUSION: Regular controls and monitoring of livestock to reduce the dispersion of ticks and providing information to those involved in high-risk occupations are urgently required.

Study of the pattern of mortality caused by Traffic Accidents (TAs) in The South of Iran.

OBJECTIVE: To investigate the pattern of mortality caused by road traffic accidents and its associated factors. METHODS: The retrospective cross-sectional study was conducted in the Fars province of Iran and comprised data of all people having died in road traffic accidents from March 21, 2011, to March 19, 2012. Using census method, all files related to deaths in road accidents were reviewed at the Legal Medicine Centre. Data was analysed using SPSS20. RESULTS: Of the 1668 people dead, 1291(77.4%) were male and 377(22.6 %) were female. The highest rate related to the age group 21-30 with 454(27%) killed. As for education level, the highest rate of mortality was 410(24.5%) for illiterate people and the least was 9(0.5%) for those having Masters degree or higher. In terms of time of year, the highest rate of mortality was 167(10%) between August 23and September 22, while the least was 82(5%) between July 23and August22. Head trauma was reported as the most important cause of death in 1191(71.4%) cases. CONCLUSIONS: Despite some minor differences, all provinces in Iran have the same patterns of death related to road traffic accidents.

Mutations in FARS2 and non-fatal mitochondrial dysfunction in two siblings.

Recently, mutations in FARS2, which encodes for mitochondrial phenylalanyl-tRNA synthetase, have been implicated in autosomal recessive combined oxidative phosphorylation deficiency 14. Associated clinical features in three previously reported patients with confirmed FARS2 mutations include infantile onset epilepsy, and a fatal Alpers-like encephalopathy. Herein, we report on two siblings with global developmental delay, dysarthria and tremor and compound heterozygous FARS2 abnormalities. They have a heterozygous missense mutation, c.1255C>T which predicts p.Arg419Cys in exon 7 of FARS2, inherited from their father and uncovered on exome sequencing, and an interstitial deletion of chromosome 6p25.1 inherited from their mother and uncovered on SNP array. This interstitial deletion includes all of exon 6 and parts of introns 5 and 6 of FARS2. Biochemical studies were also consistent with a mitochondrial disorder. While these siblings had considerable developmental difficulties, they are making consistent developmental progress and appear to be considerably less severely affected than the other patients reported in the literature with FARS2 associated mitochondrial disease. Thus, this study expands the phenotypic spectrum of FARS2 related disease and emphasizes intragenic deletion in the list of causative mutations.