The effect of biosimilar administration on clinical outcomes in patients with adalimumab-controlled psoriasis.

Background: Adalimumab is an anti-tumour necrosis factor administered for the management of severe psoriasis. Previously limited to Humira, new biosimilar medications have now emerged including Amgevita. To date, there have been no comparison studies of adalimumab biosimilar use on different types of psoriasis. Objective: To investigate the implications of biosimilar medications and patient specific factors on clinical outcomes, including Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) scores. Methods: A clinical notes review was performed for all dermatology patients with adalimumab-controlled psoriasis at our centre. Demographic profile, psoriasis subtype and changes in clinical patterns as demonstrated by PASI and DLQI were extracted and analysed. Results: Of 91 records identified, 70 patients met the inclusion criteria. 21 patients (30%) demonstrated significant increase in PASI and DLQI scores with Amgevita. Scores improved to baseline once Humira was restarted. Findings reveal no difference in pre-adalimumab disease severity or mean age between the groups. Patients responding only to Humira had a greater proportion of females, and were likelier to have psoriatic arthritis (odds ratio [OR]: 10.63; p < 0.0002) and nail involvement (OR: 6.13, p < 0.02), compared with patients well controlled with Amgevita. Conclusions: This audit of a single dermatology centre suggests switching to a biosimilar adalimumab may exacerbate symptoms of psoriasis. Future studies should investigate whether findings are restricted to our study population, and consider the influence of other factors, such as disease subtypes and medication formulations.

The Effect of Doxycycline on Achilles Tendon Repair in a Rat Model.

INTRODUCTION: Doxycycline is a commonly used antibiotic that is also a potent inhibitor of matrix metalloproteinase (MMPs). The use of doxycycline in repairing tendon lesions has been previously investigated and conflicting findings have been reported on its effectiveness. In this study, we sought to evaluate the effects of exposure to doxycycline on Achilles tendon repair. MATERIALS AND METHODS: Twenty healthy rats of the same breed and gender were randomly assigned to two groups of sham, and Doxycycline group therapy. The rats underwent a surgical intervention in which a 2mm incision was performed on the lateral sides of the right Achilles tendons. The treatment group received oral gavage administrations of 50mg/kg/day of doxycycline for 30 days. After this duration, tissue samples were taken from the site of the injuries, which were then histologically evaluated for alignment of the collagen fibres, inflammation reaction, cellular density, and fibroblastic activity. RESULTS: The histological assessment of the tissue samples, revealed significant changes in the repaired tissues of the treatment group in comparison to the sham group; namely more irregularity in the alignment of the collagen fibres, increased cellular density, and increased fibroblastic activity. However, only the alignment of the collagen fibres reached the statistical significance. CONCLUSION: The results of this study indicate that exposure to doxycycline may result in the improvement of repair of the Achilles tendon injuries, especially collagen filament integrity.

Atmospheric coherence time measurement by four-aperture DIMM defocus velocity technique.

In this work, we estimate the atmospheric Fried parameter $ {r_0} $r0, average wind speed $ \bar v $v¯, and subsequently, atmospheric coherence time $ {\tau _0} $τ0 by experimental measurement via a four-aperture differential image motion monitor (DIMM) instrument at the Iranian National Observatory (INO) site. The experimental approach is based on the four-aperture DIMM defocus velocity theory, which uses the angle-of-arrival fluctuation measurement of starlight propagation through atmospheric turbulence in the form of a four-spot configuration provided by the four-aperture DIMM telescope. Here, we measure the defocus variance $ \sigma _{{C_4}}^2 $σC42 and its velocity variance $ \sigma _{\partial {C_4}/\partial t}^2 $σ∂C4/∂t2 and use the preceding theory to estimate the atmospheric turbulence parameters. We have implemented the data sampling at the INO site at an altitude of 3600 m above sea level with a 12-inch Meade Cassegrain telescope consisting of a four-aperture mask at its entrance pupil and a fast CCD camera recording short-exposure images with frame rates in the range of 480 fps to 620 fps from the Capella star. The experimental recorded data sets are analyzed and the results compared to those of our simulation and other methods and demonstrate good agreement.

Survival rate of colon and rectum cancer in Iran: A systematic review and meta-analysis.

Colorectal cancer is one of the deadliest cancers worldwide. Effective screening, surveillance and prevention can decrease its incidence, mortality and burden. This meta-analysis aims to provide a pooled estimation of 5-year survival rate for colorectal cancer based on topography codes and treatment in Iranian population. A systematic search for literature was done in international and national databases up to July 2018. Twenty-seven studies from 4929 articles met the eligible criteria. The overall pooled 5-year survival rates of colorectal cancer, colon, rectal and sigmoid were 56% (95% CI: 49, 63), 53% (95% CI: 41, 65), 52% (95% CI: 41, 62) and 38% (95% CI: 22, 55), respectively. In addition, 5-year survival rate of colorectal cancer after surgery was 64% (95%CI: 50, 78). Subgroup analysis by type of data source showed significantly higher rate of survival in oncology center (29%) than hospital-based (p=0.005). As a conclusion, low survival rate of colorectal cancer in Iran necessitates effective screening and surveillance strategies to find precancerous polyps and detect early-stage cases with lower stage risk of cancer.

Use of a 4-aperture DIMM instrument for atmospheric coherence time estimation: an analytical development.

We report on an analytic method to estimate the Fried parameter r0, average wind speed v¯, and subsequently the atmospheric coherence time τ0 via a 4-aperture differential image motion monitor (DIMM) instrument. The theory developed here shows that the velocity of defocus aberration is statistically related to atmospheric turbulence parameters which are measured by means of angle of arrival (AA) fluctuations. Then, using the variance of the defocus velocity of four spots and the derived analytic relation, the atmospheric coherence time can be estimated. In parallel to the analytic work, some sequences of a star image with 700 Hz acquisition frequency are considered to simulate the atmospheric defocus and its variations by the 4-aperture DIMM instrument for the first 10 km near the ground in both one- and three-layer atmospheric models. The estimations from the analytic method are found to be in good agreement with the simulation data obtained for starlight propagating through different atmospheric conditions.

Brucellosis as a neglected disease in a neglected population: a seroepidemiological study of migratory nomads in the Fars province of Iran.

This study assessed the seroprevalence of brucellosis and its risk factors in migratory nomads in the Fars province of Iran. Active brucellosis was defined as the combination of clinical symptoms, including fever, chills, night sweats, headache, low back pain, arthralgia, or myalgia, and positive laboratory testing, including either a serum agglutination test (SAT) ⩾1:80 with a 2-mercaptoethanol (2-ME) test ⩾1:40, or a SAT <1:80 combined with a positive Coombs Wright test (CWT) at a titre of at least threefold higher than SAT titre results. For the 536 participants, the female (316, 59%) to male (220, 41%) ratio was 1·4 and the participants' mean age was 32·4 ± 18·9 (range 1-96) years. Of all participants, 325 (60·6%) showed clinical symptoms; in symptomatic participants, the Rose Bengal plate test was positive in 33 (6·1%) cases, the SAT was positive in 18 (3·3%) cases, and the 2-ME test was positive in 30 (5·5%) cases. Positive SAT and 2-ME results were seen in 18 (3·3%) cases, but a negative SAT and a positive CWT were found in 36 (6·7%) cases. As a result, active brucellosis was detected in 54 cases, indicating a prevalence of 10% (95% confidence interval 8-12). In conclusion, we determined that brucellosis is a prevalent yet neglected disease in this nomadic population. Brucellosis control is not possible as long as these high-risk populations remain neglected.

Comment on "Modeling the electrical conduction in DNA nanowires: Charge transfer and lattice fluctuation theories".

In a recent paper [S. Behnia and S. Fathizadeh, Phys. Rev. E 91, 022719 (2015)10.1103/PhysRevE.91.022719] an analytical approach is proposed for the investigation of the conductivity properties of DNA. The authors use mean Lyapunov exponent methods as the backbone of their approach and try to interpret properties of the system based on its behavior. Their interpretation regarding the change in nature of the mean Lyapunov exponent at the denaturation temperatures and discussions of stability and instability based on the mean Lyapunov exponent method are questioned. Moreover there is misunderstanding between mean Lyapunov exponent and Lyapunov exponent.

All-optical switching between optical bistability and multistability in a defect dielectric medium doped with a multiple quantum well nanostructure.

In this paper, optical bistability (OB) and multistability (OM) properties of a defect dielectric slab are studied. A GsAs multiple quantum well nanostructure (MQW) with 17.5 nm GaAs wells and 15 nm Al(0.3) Ga(0.7) barriers is used in the dielectric medium as a defect layer. Therefore, properties of the refractive index of the slab can be changed in the presence of MQWs. It is observed that switching from OB to OM can be obtained by controlling some external parameters. We find that the exciton spin relaxation and thickness of the slab have essential roles in adjusting the OB and OM properties of the probe light through the slab. Moreover, transmission, reflection, and absorption properties of the propagating pulse through the slab are also discussed. We show that the subluminal and superluminal light transmission or reflection can be obtained via amplification of the probe pulse through the medium. We hope that our proposed model may be suitable for the development of nanoscale devices in all-optical quantum information technology.

Mortality and morbidity in patients with X-linked agammaglobulinaemia.

BACKGROUND: X-linked agammaglobulinaemia (XLA) is a genetic disorder characterised by a defect in the generation of mature B cells, lack of antibodies production, and susceptibility to recurrent bacterial infections. Understanding of the risk factors responsible for morbidity and mortality in these patients can help in a better management of this disorder. However, there is a lack of specific studies in the literature regarding the morbidity and mortality of XLA patients. This study is designed to evaluate morbidities and mortality and survival rates in Iranian patients with XLA diagnosis during the past 20 years. METHODS: We have registered the clinical data of the XLA patients and followed them up until 2010. At the time of diagnosis, a four-page questionnaire including complete medical information was filled out for all patients. Follow-up information was gathered either by reviewing the patients' hospital records or regularly visiting the patients. RESULTS: Among 41 patients, 26.8% died during the follow up period. All of the complications before the initiation of treatment such as pneumonia, otitis media and diarrhoea were reduced after immunoglobulin replacement, except sinusitis and conjunctivitis. There were significant associations between some immunological and clinical characteristics such as lymphocyte subsets, consanguinity marriage and mortality. CONCLUSION: Despite recent advances in the treatment of XLA, these patients still suffer from severe complications. Associations between poor prognosis and clinical and some immunological characteristics of the patients may help physicians to select poor prognoses patients at higher risk of mortality to develop prevention strategies for them.

Pulmonary tuberculosis in migratory nomadic populations: the missing link in Iran's National Tuberculosis Programme.

OBJECTIVE: To detect pulmonary tuberculosis (PTB) in migratory nomadic populations in Fars Province, southern Iran. DESIGN: Cross-sectional study. RESULTS: In this study, 5506 (82.8%) of a total nomad population of 6650 from 1337 tents were screened for PTB. The mean age was 27.4 ± 18.2 years (range 1-109). Based on clinical symptoms, 141/5506 (2.6%) were identified as TB suspects. One male and three female adult new smear-positive PTB cases were detected, giving an incidence rate of 0.7/1000 population compared to 0.08/1000 in the general population of the region, and 28.4/1000 TB suspects. The median time to onset of symptoms in detected cases was 82.5 days. Tribal stigma against female TB patients was one of the main barriers to appropriate health-seeking behaviour. CONCLUSIONS: The incidence of smear-positive PTB among migratory nomads is approximately nine-fold higher than in the general population. Active screening of TB in migratory nomads should be integrated into Iran's national TB control programme. The issue of destigmatisation, particularly among female TB patients, should also be addressed.

Multifractal analysis of thermal denaturation based on the Peyrard-Bishop-Dauxois model.

The theory of DNA dynamics is exceedingly complex and not easily explained. In the past two decades, by adapting methods of statistical physics, the dynamics of DNA in contact with a thermal bath is widely studied. In this paper, the thermal denaturation of DNA in the framework of the Peyrard-Bishop-Dauxois (PBD) model through the Rényi dimension is investigated. As a result, the Rényi dimension spectrum of the melting transition process reveals the multifractal nature of the dynamics of the Peyrard-Bishop-Dauxois model. Also, it can be concluded that the Rényi dimension (D(q)) at negative values of q is the characteristic signature of pre-melting and thermal denaturation of DNA. Furthermore, this approach is in excellent agreement with previous experimental studies.

Effects of methyl-beta-cyclodextrin and cholesterol on cryosurvival of spermatozoa from C57BL/6 mouse.

MBCD and Cholesterol-Loaded-Cyclodextrin (CLC) were examined for their abilities to increase the cryosurvival of C57BL/6 mouse sperm, the main strain of genetically engineered mice. The intactness of acrosome and motility of frozen/thawed spermatozoa were used to monitor cryosurvival. In this experimental study, male mice were randomly divided in 6 groups: control 1, experimental 1, experimental 2, control 2, experimental 3 and experimental 4. In experimental groups 1 and 2 spermatozoa were exposed to 0.75 and 1 mM MBCD and in experimental groups 3 and 4 were exposed to two different concentrations of CLC (1 and 2 mg mL(-1)) over a period of 1 h and were subsequently cryopreserved. Spermatozoa in control 1 group were frozen without any exposure to CLC or MBCD and in control 2 (vehicle), sperms were incubated with 4 mM MBCD. The post-thaw sperms were evaluated for their motility and acrosomal status. The values of the intact acrosome and motility increased significantly with concentration of CLC compared to controls and MBCD experimental groups (p<0.05). These results indicate that cryosurvival of C57BL/6 mouse spermatozoa is enhanced by exposure to MBCD which loaded with cholesterol (CLC) before freezing and MBCD alone can not protect sperm from freeze-thaw damage efficiently compare to CLC.

Application of multiplex PCR with histopathologic features for detection of familial breast cancer in formalin-fixed, paraffin-embedded histologic specimens.

Breast cancer is the most common malignancy among females in the world. Age and familial history are the major risk factors for the development of this disease in Iran. Mutations of BRCA1 and BRCA2 genes are associated with a greatly increased risk for development of familial breast cancer. Frequency of BRCA mutations was identified in familial breast cancers (FBC) and non-familial breast cancers (NFBC) by molecular genetics, morphological and Immunohistochemical methods. Thirty forth formalin-fixed, paraffin-embedded breast tissue tumors were analyzed from 16 patients with FBC and 18 patients with NFBC. Three 5382insC mutations detected by multiplex PCR in 16 familial breast cancers. Immunohistochemical method was used to detect estrogen receptor (ER) and progesterona receptor (PR) and TP53. Comparison of ER, PR and TP53 exhibited high difference (P < 0.0001) in familial breast cancers and non-familial breast cancers. Our results demonstrated that 5382insC mutation, ER, PR, TP53, mitotic activity, polymorphism, necrosis and tubules can serve as the major risk factors for the development of FBC.

The neuroprotective effects of progesterone on experimental diabetic neuropathy in rats.

This study was conducted to investigate the neuroprotective effects of progesterone (PROG) on electrophysiological and histomorphometrical alternation in STZ-induced diabetic neuropathy starting from 4 weeks after the diabetic induction. Thirty adult male Sprague-Dawley rats were randomly divided into 3 groups (with 10 rats in each), control (nondiabetic), untreated diabetic and diabetic PROG-treated. Diabetes was induced in adult male rats by a single dose injection of streptozotocin (STZ, 55 mg kg(-1), i.p.). In the PROG-treated group, 4 weeks after induce of diabetes; rats were treated with PROG (8 mg kg(-1), i.p., every two days) for 6 weeks. Diabetic rats showed a significant reduction in motor nerve conduction velocity (MNCV), mean myelinated fibers (MFs) diameter, axon diameter and myelin sheath thickness in the sciatic nerve after 6 weeks. In the untreated diabetic group endoneurial edema was observed in sciatic nerve and the numbers of MFs with infolding into the axoplasm, irregularity of fibers, myelin sheath with unclear boundaries and alteration in myelin compaction were also increased. Long-term treatment with PROG increased MNCV significantly and prevented all these abnormalities in treated diabetic rats. Our findings indicated that PROG as a therapeutic approach can protect neurophysiologic and histomorphologic alterations induced by peripheral diabetic neuropathy.

Investigation on mtDNA deletions and twinkle gene mutation (G1423C) in Iranian patients with chronic progressive external opthalmoplagia.

BACKGROUND: Chronic progressive external ophthalmoplagia (CPEO) is a phenotypic mitochondrial disorder that affects external ocular and skeletal muscles and is associated with a single or multiple mitochondrial DNA (mtDNA) deletions and also nuclear gene mutations. There are also some reports about the relationship between CPEO and the nuclear Twinkle gene which encodes a kind of mitochondrial protein called Twinkle. AIMS: To study the mtDNA deletions and Twinkle gene G1423C point mutation in Iranian patients with CPEO. MATERIALS AND METHODS: We collected 23 muscle samples from patients with CPEO, 9 women (mean age 34.3 years) and 14 men (36.7 years). Multiplex polymerase chain reaction (PCR) method was used to find the presence of single or multiple deletions in mtDNA. Single stranded conformational polymorphism (SSCP) and restriction fragment length polymorphism (PCR-RFLP) methods were carried out to investigate point mutation (G1423C) in the Twinkle gene in all DNA samples. RESULTS: Different sizes of mtDNA deletions were detected in 16 patients (69.6%). Each of the 5.5, 7, 7.5 and 9 kb deletions existed only in 1 patient. Common deletion (4977bp) and 8 kb deletion were detected in 5 and 3 patients respectively. Multiple deletions were also present in 4 patients. Out of 23 patients included in our study, two cases (8.7%) had Twinkle gene mutation (G1423C) and 5 patients (21.7%) did not show any deletions in mtDNA or the Twinkle gene mutation. CONCLUSION: Our study provides evidence that the investigation of mtDNA and Twinkle gene mutations in CPEO may help with early diagnosis and prevention of the disease. Patients who did not show deletions in the mtDNA or G1423C mutation in the Twinkle gene may have other mtDNA, Twinkle or nuclear gene mutations.

Identification of a new human mtDNA polymorphism (A14290G) in the NADH dehydrogenase subunit 6 gene.

Leber's hereditary optic neuropathy (LHON) is a maternally inherited form of retinal ganglion cell degeneration leading to optic atrophy in young adults. Several mutations in different genes can cause LHON (heterogeneity). The ND6 gene is one of the mitochondrial genes that encodes subunit 6 of complex I of the respiratory chain. This gene is a hot spot gene. Fourteen Persian LHON patients were analyzed with single-strand conformational polymorphism and DNA sequencing techniques. None of these patients had four primary mutations, G3460A, G11788A, T14484C, and G14459A, related to this disease. We identified twelve nucleotide substitutions, G13702C, T13879C, T14110C, C14167T, G14199T, A14233G, G14272C, A14290G, G14365C, G14368C, T14766C, and T14798C. Eleven of twelve nucleotide substitutions had already been reported as polymorphism. One of the nucleotide substitutions (A14290G) has not been reported. The A14290G nucleotide substitution does not change its amino acid (glutamic acid). We looked for base conservation using DNA star software (MEGALIGN program) as a criterion for pathogenic or nonpathogenic nucleotide substitution in A14290G. The results of ND6 gene alignment in humans and in other species (mouse, cow, elegans worm, and Neurospora crassa mold) revealed that the 14290th base was not conserved. Fifty normal controls were also investigated for this polymorphism in the Iranian population and two had A14290G polymorphism (4%). This study provides evidence that the mtDNA A14290G allele is a new nonpathogenic polymorphism. We suggest follow-up studies regarding this polymorphism in different populations.

Identification of a new human mtDNA polymorphism (A14290G) in the NADH dehydrogenase subunit 6 gene

Leber's hereditary optic neuropathy (LHON) is a maternally inherited form of retinal ganglion cell degeneration leading to optic atrophy in young adults. Several mutations in different genes can cause LHON (heterogeneity). The ND6 gene is one of the mitochondrial genes that encodes subunit 6 of complex I of the respiratory chain. This gene is a hot spot gene. Fourteen Persian LHON patients were analyzed with single-strand conformational polymorphism and DNA sequencing techniques. None of these patients had four primary mutations, G3460A, G11788A, T14484C, and G14459A, related to this disease. We identified twelve nucleotide substitutions, G13702C, T13879C, T14110C, C14167T, G14199T, A14233G, G14272C, A14290G, G14365C, G14368C, T14766C, and T14798C. Eleven of twelve nucleotide substitutions had already been reported as polymorphism. One of the nucleotide substitutions (A14290G) has not been reported. The A14290G nucleotide substitution does not change its amino acid (glutamic acid). We looked for base conservation using DNA star software (MEGALIGN program) as a criterion for pathogenic or nonpathogenic nucleotide substitution in A14290G. The results of ND6 gene alignment in humans and in other species (mouse, cow, elegans worm, and Neurospora crassa mold) revealed that the 14290th base was not conserved. Fifty normal controls were also investigated for this polymorphism in the Iranian population and two had A14290G polymorphism (4 percent). This study provides evidence that the mtDNA A14290G allele is a new nonpathogenic polymorphism. We suggest follow-up studies regarding this polymorphism in different populations.

Study of platelet-associated immunoglobulins of IgG, IgM, IgA, and IgE classes and platelet kinetics in 33 patients with idiopathic thrombocytopenic purpura.

The role of platelet-associated immunoglobulins (PAIg) of four different immunoglobulin classes--IgM, IgG, IgA, and IgE--and their relation to platelet count and platelet kinetics was studied in 33 patients with idiopathic thrombocytopenic purpura (ITP). During the course of 1 year, repeated determinations of PAIg were made. The results indicate that PAIgG, PAIgM, and PAIgA are present in all ITP patients, and that autoantibodies of all three Ig classes show highly significant correlations to the platelet counts (p < 0.0001). Double logarithmic negative correlations have been found between PAIgG and platelet count (r = -0.71), PAIgM and platelet count (r = -0.84), and PAIgA and platelet count (r = -0.79). Statistical analyses using partial correlation and multiple regression methods showed that PAIgM is predominantly related to the platelet count, whereas PAIgG and PAIgA are only of secondary importance. Accordingly, a relation of PAIgM (and PAIgA) to increased liver destruction of platelets was found in kinetic studies using 111indium-labeled platelets. Taken together, these results suggest a predominant role of PAIgM in the pathogenesis of ITP.