Levels of Interleukin‐(IL)‐12p40 are Markedly Increased in Brucellosis Among Patients with Specific IL‐12B Genotypes

Brucellosis remains a major zoonosis worldwide. Brucella antigens induce the production of T‐helper 1 (Th1) cytokines such as interleukin‐12 (IL‐12) in humans. We aimed to investigate the association of two single nucleotide polymorphisms (SNPs) in the gene encoding the IL‐12p40 cytokine (IL‐12B) with brucellosis and to examine the functionality of these SNPs through measuring serum levels of IL‐12p40. We genotyped IL‐12B gene rs3212227, A>C; rs6887695 G>C polymorphisms in a case‐control study on a total of 281 subjects including 153 patients with active brucellosis and 128 healthy controls, using RFLP and serum IL‐12p40 levels, were assessed by ELISA. The rs3212227 minor allele (C) and homozygote genotype (CC) were more frequent in controls compared with patients with brucellosis (P = 0.006, OR = 0.608, 95%CI = 0.429–0.861 for the C allele; P = 0.024, OR = 0.443, 95% CI: 0.218–0.900 for the CC genotype). Comparison of IL‐12B genotypes and serum levels of the IL‐12p40 revealed that rs3212227 AA genotype, with higher frequency in patients than in controls, was associated with increased levels of the cytokine (P = 0.0001). Furthermore, the distribution of haplotype and genotype combinations in our study suggested that rs3212227C/rs6887695C haplotype or CC/GC or CC/CC genotype combinations may protect controls against Brucella infection by contributing to a functional downregulation of the serum IL‐12p40 production in vivo, as shown by ELISA (P < 0.05). Overall, our study demonstrated that rs3212227 A variant was associated with higher levels of serum IL‐12p40 and could possibly contribute to an inherited predisposition to brucellosis.     

Serum copper and magnesium status in cats with nutritional secondary hyperparathyroidism

Nutritional secondary hyperparathyroidism (NSH) is a common disease in kittens in Iran. It occurs due to malnutrition with clinical signs of anorexia, lameness and irregularity in the vertebral column and long bones. In humans, hypomagnesaemia has been found to be associated with hyperparathyroidism. An association of copper deficiency with hypocalcaemia and the radiographic features of rickets and hyperparathyroidism have also been described in human infants. In humans, urinary excretion of copper and zinc is greater than normal in patients with untreated primary hyperparathyroidism. This survey was performed based on clinical, radiographic and laboratory findings to measure serum copper and magnesium in kittens suffering from NSH. A total of 27 kittens were diagnosed with NSH based on history, clinical examinations and radiographic findings. In addition, 10 healthy kittens were studied as controls. According to the radiographic findings, affected kittens were classified as having mild, moderate and severe NSH. They were also classified, based on age, into four groups (2–3, 3–4, 4–5 and 5–6 months). Total serum calcium, phosphorus, copper and magnesium were measured as biochemical parameters. Serum copper and magnesium were significantly lower in severe, moderate and mild cases with dietary osteoporosis in comparison to controls (p?<?0.05). NSH was most prevalent in cats between 2 and 3 months. No significant difference was found between males and females. Our data suggest that hypomagnesaemia and copper deficiency are associated with NSH in cats. Much still remains to be learnt about the exact role of magnesium and copper in cats suffering of NSH.     

Leptin Administration Enhances Islet Transplant Performance in Diabetic Mice

Islet transplantation is an effective method to obtain long-term glycemic control for patients with type 1 diabetes, yet its widespread use is limited by an inadequate supply of donor islets. The hormone leptin has profound glucose-lowering and insulin-sensitizing action in type 1 diabetic rodent models. We hypothesized that leptin administration could reduce the dose of transplanted islets required to achieve metabolic control in a mouse model of type 1 diabetes. We first performed a leptin dose-response study in C57Bl/6 mice with streptozotocin (STZ)-induced diabetes to determine a leptin dose insufficient to reverse hyperglycemia. Subsequently, we compared the ability of suboptimal islet transplants of 50 or 125 syngeneic islets to achieve glycemic control in STZ-induced diabetic C57Bl/6 mice treated with or without this dose of leptin. The dose-response study revealed that leptin reverses STZ-induced diabetes in a dose-dependent manner. Supraphysiological leptin levels were necessary to restore euglycemia but simultaneously increased risk of hypoglycemia, and also lost efficacy after 12 days of administration. In contrast, 1 µg/day leptin only modestly reduced blood glucose but maintained efficacy throughout the study duration. We then administered 1 µg/day leptin to diabetic mice that underwent transplantation of 50 or 125 islets. Although these islet doses were insufficient to ameliorate hyperglycemia alone, coadministration of leptin with islet transplantation robustly improved control of glucose and lipid metabolism, without increasing circulating insulin levels. This study reveals that low-dose leptin administration can reduce the number of transplanted islets required to achieve metabolic control in STZ-induced diabetic mice.The current state-of-the-art for achieving long-term glycemic control in type 1 diabetic patients is transplantation of cadaveric donor islets. Whereas frequent episodes of hyperglycemia and hypoglycemia occur with insulin therapy, islet transplantation can effectively eliminate these excursions and maintain glycemia within a target range of 3.3 to 7.8 mmol/L (1). Unfortunately, islet transplantation is not widely available because of limited donor islet supply. Most transplant recipients require islets from at least two cadaveric donors to achieve target glycemia (1,2), and the decline of graft function within 5 years of transplantation necessitates that most patients resume insulin therapy (2). Thus, a strategy to reduce the number of islets needed to achieve insulin independence is essential for widespread application of islet transplantation from cadaveric donor islets.The hormone leptin has a well-recognized role in glucose homeostasis (3). Recent studies have demonstrated that high-dose leptin administration reverses hyperglycemia and dyslipidemia in type 1 diabetic rodent models (4–8). However, leptin is unlikely to replace insulin as a therapy for type 1 diabetes because it offers little, if any, advantage over insulin injections with regard to metabolic control and quality of life. Alternatively, glycemic control and insulin requirements for type 1 diabetic patients may be improved by leptin and insulin cotherapy. In diabetic mice, leptin administration reduced the insulin dose needed to ameliorate hyperglycemia (9), and combined leptin and insulin administration achieved better glycemic control than insulin alone (6).Because islet transplantation provides superior metabolic control over insulin injections, we investigated whether leptin as an adjunct to islet transplantation could provide tighter glycemic control with fewer transplanted islets. Such an effect could increase the availability and efficacy of islet transplantation as a treatment. To test this, we examined whether leptin administration could reduce the number of transplanted islets needed to reverse streptozotocin (STZ)-induced diabetes in mice (STZ-diabetic mice). Because high-dose leptin alone can restore normoglycemia in STZ-diabetic rodents (4–8), which thereby can enhance islet graft function (10,11), we first performed a dose-response study in STZ-diabetic mice to identify a leptin dose that was insufficient to reverse hyperglycemia. Subsequently, we administered this dose of leptin to diabetic mice transplanted with 50 or 125 syngeneic islets (17 and 42% of an optimal dose of 300 islets, respectively) to determine whether leptin cotherapy could enhance the ability of these suboptimal islet doses to achieve metabolic control.     

Evaluation of clinical outcomes of cementless total hip arthroplasty in patients under 30 years of age

Background

Historically, performing a successful hip joint replacement in patients aged fewer than 30 years has been an orthopedic challenge. The newer generation of prostheses and surgical techniques has the potential to increase the longevity of implants. The purpose of this study was to evaluate the outcomes of cementless hip arthroplasty in patients aged fewer than 30 years.

Materials and methods

In this cross-sectional study, 41 patients (46 hips) were studied with a mean age of 24, 4 (from 17 to 30 years) of whom underwent cementless metal–polyethylene hip arthroplasty from 2004 to 2007. The Harris hip score (HHS) was used to assess the functional consequences. Patients were followed up in terms of early complications (thrombophlebitis of the lower limbs, dislocation, hematoma and infection) and late complications (aseptic loosening, dislocation and reoperation) at weeks 3 and 6, at 3 and 6 months, 1 year after surgery and annually thereafter.

Results

Patients were followed for an average of 5 years and 2 months (from 51 to 82 months). One early complication (symptomatic thrombophlebitis) and one late dislocation (2.2 %) were observed. There were no cases of aseptic loosening or osteolysis at the end of follow-up. The preoperative HHS was 59.6 (from 41 to 76), which rose to 82 and 83.5 after the 1-year and final follow-up, respectively, which was a significant increase.

Conclusions

Hip arthroplasty using a new generation of cementless proximal porous prosthesis with resistant polyethylene to cover the joint surfaces in patients aged fewer than 30 years is satisfactory and is accompanied by low complications.     

Changes in the macroscopic morphology of hip muscles in low back pain

Low back pain is a major health issue affecting the lumbopelvic muscles. Morphological changes in hip muscles, such as alterations in the muscle cross-sectional area and muscle volume, may occur in patients with low back pain. This systematic review was conducted to investigate whether patients with low back pain have macroscopic changes in their hip muscle morphology compared with asymptomatic, healthy individuals, based on current evidence. The electronic databases of PubMed/Medline, Ovid, Scopus, Embase^®, and Google Scholar were searched from the inception to August 31, 2018. We only included full texts of original studies regarding macroscopic morphological alterations, including atrophy and fat infiltration, in hip muscles of patients with low back pain compared with asymptomatic controls. The quality of the included studies was determined using an assessment tool based on the Newcastle–Ottawa Scale. The scale was modified for the purposes of this study. Sixteen comparative observational studies were found eligible to be included in this review. Eleven were classified as high quality and four as moderate quality. The morphological changes in the psoas major, gluteus maximus, gluteus medius, gluteus minimus, and piriformis muscles were assessed in the primary studies. All selected studies were considered B level of evidence studies. The strength of conclusions for the psoas major, gluteal, and piriformis muscles was moderate. The results revealed that there is substantial controversy about the morphological changes in hip muscles in patients with low back pain; however, the majority of high-quality studies concluded that atrophy of hip muscles is evident in patients with low back pain. The psoas major muscle was the most commonly investigated hip muscle for morphological changes. Major methodological limitations of the included studies were identified and discussed. The present systematic review does not include a formal meta-analysis because of very significant differences in the primary studies in terms of study populations and methodologies. Finally, in clinical practice, it is recommended that physical therapists develop exercise programs to improve hip muscle function in patients with low back pain.     

Fertility and infertility implications in rheumatoid arthritis; state of the art

Background

A bulk of investigations imply that women with rheumatoid arthritis (RA) deliver fewer children in comparison to healthy women.

Purpose

This review article attempts to clarify the involvement of infertility-related issues in both RA men and women. Moreover, the effect of RA disease on the fertility quality and quantity will be discussed.

Results

Declined fertility rate in RA women seems to stem from modified inflammatory settings, advanced maternal age, limited sexual activity, and adverse effects of drugs on ovarian function. Women with RA may have smaller families and seem to be slower to conceive relative to their peer women. The chance of gestation in RA women may drop due to suppressed sexual function through pain and fatigue. In addition, treatment of RA women with non-steroidal anti-inflammatory drugs (NSAIDs) may prevent ovulation and therefore hinder the conception.

Conclusions

A complex interaction between RA disease and fertility related issues is present. Despite an increase rate of infertility in RA females or males, the mechanisms involved in this outcome is still unknown. Plausible causes of the decreased fertility rate in RA patients might be due to inflammatory cytokines, suppressed sexual activity, drug treatments, mother age, personal choice, or a combination of these elements.

     

Synthesis and Solution Processing of Nylon‐5 Ferroelectric Thin Films: The Renaissance of Odd‐Nylons?

Among odd‐nylons, nylon‐5 exhibits the highest remanent polarization and is thus a desirable material for many applications of ferroelectric polymers. However, nylon‐5 has never been used as a ferroelectric material, because the synthesis of nylon‐5 and its processing into thin films are challenging. This work revisits the synthesis of nylon‐5 via anionic ring opening polymerization (AROP) and studies the effect of reaction time and scale‐up on (i) molecular weight (M_n), (ii) melting point (T_m), (iii) yield, and (iv) ferroelectric properties. For the first time, the molecular weight of nylon‐5 is characterized via size exclusion chromatography (SEC), nuclear magnetic resonance (NMR) spectroscopy, as well as matrix assisted laser desorption ionization time of flight mass spectroscopy (MALDI ToF‐MS), showing M_n values of up to 12 500 g mol^‐1. Extended reaction times and the synthesis on a larger scale increase the molecular weight and yield. Nylon‐5 thin films are fabricated from a TFA:acetone (60:40 mol%) solvent mixture. Nylon‐5 thin‐film capacitors are ferroelectric and show a remanent polarization as high as 12.5 ± 0.5 μC cm^‐2, which is stable in time. The high remanent polarization values, combined with the facile solution processing, render nylon‐5 a promising candidate for future microelectronic and multi‐ferroic applications.     

Promoter methylation of Bax and Bcl2 genes and their expression in patients with Behcet’s disease

BCL2 and BAX genes are a group of signalling inducer and inhibitor genes playing a key role in the process of cellular physiological death (apoptosis). These genes, through the JAK/STAT signalling pathway, affect different cytokines on cell function and subsequently lead to the pathophysiology of diseases, especially autoimmune diseases. In addition, altering the methylation of genes can affect their expression. Since the aetiology and pathology of Behcet's disease is not fully understood, the aim of this study was to determine the methylation pattern of BCL2 and BAX genes in patients with Behcet's disease and compare it with those of control group. This was a case–control study on 51 patients with Behcet and 61 control subjects. Blood samples were received from all subjects. Subsequently, the peripheral blood mononuclear cells (PBMCs) were isolated by Ficoll method and the methylation of the sites was investigated using quantitative methylation specific PCR (qMS‐PCR) technique after extraction of DNA by salting out method and its examination with Nano drop. The results of methylation and expression of Bax gene suggest that the methylation level in the patient group significantly increased compared to the healthy individuals (p‐value < .05). Furthermore, the results related to Bax gene expression revealed that the mean of gene expression in the patient group has decreased compared to the healthy group, and this decrease was statistically significant (p‐value < .05). The rate of expression and methylation of Bcl2 did not indicate any change in the two patient and healthy groups. Given the results of this study, it can be guessed that perhaps DNA methylation is involved in certain conditions of the disease and it may result in regulation of the expression of the involved genes such as Bax gene, in the pathogenesis of the disease.     

Evaluation of polycyclic aromatic hydrocarbons (PAHs) in fish: a review and meta-analysis

Abstract

Polycyclic aromatic hydrocarbons (PAHs) are a group of pollutants which occur in considerable amounts in the environment and food. In this study, a meta-analysis study was conducted on PAHs concentrations in fish in different parts of the world. The results showed that the PAHs were observed and quantified in fish in the most considered studies. The maximum and minimum concentration of PAHs was found in Cynoglossus Bilineatus fish of Persian Gulf (3970?ng/kg) and Cyprinus Carpio fish of Caspian Sea (0.004?ng/kg), respectively. These values are below the maximum value currently allowed by European Union regulations (12.0?μg/kg wet weight).