<Emphasis Type="Italic">T-</Emphasis>Scores and <Emphasis Type="Italic">Z</Emphasis>-Scores

Bone mineral density (BMD) can be measured by a variety of techniques at several skeletal sites. Once measured, the manufacturers’ software uses the BMD to calculate a T-score and/or Z-score. Both T-scores and Z-scores are derived by comparison to a reference population on a standard deviation scale. The recommended reference group for the T-score is a young gender-matched population at peak bone mass, while the Z-score should be derived from an age-matched reference population. T-scores and Z-scores are widely quoted in scientific publications on osteoporosis and BMD studies, and are the values used for DXA diagnostic criteria and current clinical guidelines for the management of osteoporosis. Errors in BMD measurement, differences in reference populations, and variations in calculation methods used, can all affect the actual T-score and Z-score value. Attempts to standardize these values have made considerable progress, but inconsistencies remain within and across BMD technologies. This can be a source of confusion for clinicians interpreting BMD results. A clear understanding of T-scores and Z-scores is essential for correct interpretation of BMD studies in clinical practice.     

<Emphasis Type="Italic">Anisakis</Emphasis> spp. burden in <Emphasis Type="Italic">Trachurus trachurus</Emphasis>

Anisakis is a parasite of marine mammals that uses a great number of fish species as intermediate or paratenic hosts. It is common in commercially important marine fishes and its presence is of great concern for both human health and economic reasons. Horse mackerels (Trachurus trachurus) originated from the Northern Aegean Sea were examined for the presence of Anisakis spp. larvae. The prevalence of Anisakis spp. was found 98.8 %. The number of parasites was significantly related to the host’s length but was not related to the fish gender. The month of sampling affected the size of the fishes and consequently the number of parasites. The length of larvae was not related to the host’s length. The present study resulted in the design of a prediction model for the number of existing parasites in the fish by measuring only its Fixed Length.     

Association of <Emphasis Type="Italic">Lewis</Emphasis> and <Emphasis Type="Italic">Secretor</Emphasis> gene polymorphisms and <Emphasis Type="Italic">Helicobacter pylori</Emphasis> seropositivity among Japanese-Brazilians

Background Secretor (Se) and Lewis (Le) genes are involved in the synthesis of Lewis b (Le^b) and type I antigens throughout the body, especially in the epithelial cells of gastric mucosa. Helicobacter pylori can attach to the gastric epithelial cells with the blood group antigen-binding adhesin, which binds to Le^b or H type I carbohydrate structures. In a previous study, a marked association between H. pylori seropositivity and polymorphism of the Se and Le genes was observed among Japanese outpatients of a gastroenterology clinic. The present work aims to investigate the associations between Se and Le gene polymorphisms and H. pylori infection among Japanese-Brazilians.Methods The subjects consisted of 942 healthy volunteer Japanese-Brazilians, who were tested for the presence of anti-H. pylori IgG antibodies and genotyped for Se and Le polymorphisms.Results The sex-age-adjusted odds ratios (aORs) for H. pylori seropositivity were 0.99 for the Sese genotype relative to the SeSe genotype (95% confidence interval [CI], 0.73–1.33), and 1.03 for sese relative to SeSe (95% CI, 0.71–1.48). On the other hand, the aOR for the subjects with the le allele (Lele or lele) relative to the LeLe genotype was 1.48 (95% CI, 1.07–1.79). When the Se and Le genotypes were analyzed in combination according to risk group, no statistically significant association was observed.Conclusions These results are inconsistent with previous work and may have been modulated by an external factor or some other unidentified factor. Japanese-Brazilians are genotypically the same as Japanese, but their lifestyle is adapted to that of Brazil. Further investigations are necessary to clarify this influence on susceptibility to H. pylori infection.     

<Emphasis Type="Italic">hSNF5</Emphasis><Emphasis Type="Italic">/INI1</Emphasis> mutation analysis in acute myeloid leukemia

Previous studies indicated that region 11.2 of the long arm of chromosome 22 (22q11.2) might be a locus encoding a tumor suppressor gene, since its deletion is a recurrent genetic characteristic of aggressive pediatric cancer. This region is found in the human immunodeficiency virus integrase interactor 1 (hSNF5/INI1) gene. To investigate whether the hSNF5/INI1 gene is involved in leukemogenesis, mutation analysis of the hSNF5/INI1 gene was performed in the present study using 5 hematopoietic cell lines, acute myeloid leukemia (AML) specimen and normal control. We found two single nucleotide polymorphisms at the hSNF5/INI1 gene in exon 4 and exon 9. The results of this study suggest that the hSNF5/INI1 gene does not play an important role in the leukemogenesis of AML.     

<Emphasis Type="SmallCaps">L</Emphasis>-Carnitine inhibits protein glycation <Emphasis Type="Italic">in vitro</Emphasis> and <Emphasis Type="Italic">in vivo</Emphasis>: evidence for a role in diabetic management

Glycation-initiated changes in tissue proteins are suggested to play an important role in the development of diabetes-related pathological changes. The purpose of this study was to examine the anti-glycating effect of L-carnitine (CA) in vivo in the high-fructose diet-fed rat and to determine the potential of CA to inhibit in vitro glycation. Additionally the glucose-disposal efficiency of CA in the rat diaphragm was investigated. High-fructose diet (60 g/100 g diet)-fed rats were treated with CA (300 mg/kg/day i.p.) for 60 days. The effect of CA on glucose, fructose and fructosamine in plasma, methyl glyoxal and glycated haemoglobin in whole blood and skin and tail tendon collagen glycation were determined. The inhibitory effect of CA on the glycation of bovine serum albumin in vitro was compared with that of aminoguanidine (AG), a known antiglycation agent. Glucose utilisation induced by insulin in the control rat diaphragm was monitored in the presence and absence of CA. High-fructose feeding induced hyperglycaemia and glycation of haemoglobin and skin and tail tendon collagen. In CA-administered fructose-fed rats glycation was significantly reduced. In vitro glycation and accumulation of advanced glycation end products were mitigated by CA. CA was more effective than AG in inhibiting glycation in vitro. CA also enhanced the utilisation of glucose in the rat diaphragm. The findings of the study reveal that CA not only has antiglycation effect but also enhances glucose disposal in the rat diaphragm. These findings provide evidence for the therapeutic utility of CA in diabetes and associated complications.     

Epigenetic factors Polycomb (<Emphasis Type="Italic">Pc</Emphasis>) and Suppressor of zeste (<Emphasis Type="Italic">Su</Emphasis>(<Emphasis Type="Italic">z</Emphasis>)2) negatively regulate longevity in <Emphasis Type="Italic">Drosophila melanogaster</Emphasis>

The process of aging is a hallmark of the natural life span of all organisms and individuals within a population show variability in the measures of age related performance. Longevity and the rate of aging are influenced by several factors such as genetics, nutrition, stress, and environment. Many studies have focused on the genes that impact aging and there is increasing evidence that epigenetic factors regulate these genes to control life span. Polycomb (PcG) and trithorax (trxG) protein complexes maintain the expression profiles of developmentally important genes and regulate many cellular processes. Here, we report that mutations of PcG and trxG members affect the process of aging in Drosophila melanogaster, with perturbations mostly associated with retardation in aging. We find that mutations in polycomb repressive complex (PRC1) components Pc and Su(z)2 increase fly survival. Using an inducible UAS-GAL4 system, we show that this effect is tissue-specific; knockdown in fat body, but not in muscle or brain tissues, enhances life span. We hypothesize that these two proteins influence life span via pathways independent of their PRC1 functions, with distinct effects on response to oxidative stress. Our observations highlight the role of global epigenetic regulators in determining life span.     

<Emphasis Type="Italic">N</Emphasis>-acetyl-cysteine accelerates transfer of diabetes into non-obese diabetic<Emphasis Type="Italic"> scid</Emphasis> mice

Aims/hypothesis Type 1 diabetes mellitus is caused by autoimmune pancreatic beta cell destruction, and the destructive process involves several molecular mechanisms including oxygen-reactive species. A cysteine derivative, N-acetyl-cysteine, is widely used as an antioxidant, but the role of N-acetyl-cysteine in the protection of pancreatic beta cells in Type 1 diabetes remains unclear. The aim of this study was to clarify the effect of N-acetyl-cysteine on beta cells using an adoptive transfer system in a murine model of Type 1 diabetes.Methods Splenocytes from diabetic female non-obese diabetic mice were transferred into female non-obese diabetic scid/scid recipients to induce diabetes. Just after transfer, N-acetyl-cysteine was administered to non-obese diabetic scid recipients. Two weeks after transfer, the pancreas of the recipients was examined histologically, and cytokine mRNA expression in the pancreas was analysed. In vitro, CD4-positive splenocytes from diabetic donor mice were stimulated with anti-CD3 and anti-CD28 antibodies with or without N-acetyl-cysteine.Results Treatment with N-acetyl-cysteine significantly accelerated the transfer of diabetes into non-obese diabetic scid recipients. Treatment with N-acetyl-cysteine accelerated the infiltration of mononuclear cells accompanied by CD8-positive cells into the intra-islet region of the recipients pancreas, and enhanced interferon-gamma mRNA expression in the pancreas. In vitro, treatment with N-acetyl-cysteine enhanced interferon-gamma and interleukin-2 production by CD4-positive splenocytes of the diabetic donor mice.Conclusions/interpretation N-acetyl-cysteine accelerates the transfer of diabetes into non-obese diabetic scid mice and this effect is accompanied by the promotion of local infiltration and T-helper cell type 1 responses.     

<Emphasis Type="Italic">Aspergillus</Emphasis> and <Emphasis Type="Italic">Penicillium</Emphasis> allergens: Focus on proteases

Penicillium and Aspergillus species are prevalent airborne fungi. It is imperative to identify and characterize their major allergens. Alkaline and/or vacuolar serine proteases are major allergens of several prevalent Penicillium and Aspergillus species. They are also major immunoglobulin (Ig) E-reacting components of the most prevalent airborne yeast, Rhodotorula mucilaginosa, and the most prevalent Cladosporium species, C. cladosporioides. IgE cross-reactivity has been detected among these major pan-fungal serine protease allergens. In addition, the alkaline serine protease of P. chrysogenum (Pen ch 13) induces histamine release from basophils of asthmatic patients, degrades the tight junction protein occludin, and stimulates release of proinflammatory mediators from human bronchial epithelial cells. In addition to induction of IgE and inflammatory airway responses, the alkaline serine protease allergen of A. fumigatus (Asp f 13) has synergistic effects on Asp f 2-induced immune response in mice. Studies of these serine protease major allergens elucidate the diverse allergic disease mechanisms and facilitate the development of better therapeutic strategies.     

<Emphasis Type="Italic">Mycoplasma genitalium</Emphasis>

Mycoplasma genitalium was initially isolated from men with nongonococcal urethritis in 1980. Subsequent studies to assess the association of M. genitalium with human disease were inhibited however because on repeated attempts the organism proved extremely difficult to culture. Fortunately, the development and use of specific polymerase chain reaction assays allowed progress in this arena and provided evidence of the association between M. genitalium and urethritis, cervicitis, and endometritis. A serologic association has also been noted between M. genitalium antibody and salpingitis and tubal factor infertility. In addition, sexual transmission of M. genitalium in heterosexual partners has also been demonstrated. Currently, studies are underway to further assess these associations and provide additional information about the significance of this organism with regards to sexual transmission, infertility in women, and its association with other genital tract disease processes. Recent studies have suggested that M. genitalium-associated infections are best treated with azithromycin.     

Cardiovascular Concerns in <Emphasis Type="Italic">BRCA1</Emphasis> and <Emphasis Type="Italic">BRCA2</Emphasis> Mutation Carriers

Purpose of review

BRCA1 and BRCA2 mutation carriers can be at increased cardiovascular risk. The goal of this review is to provide information about factors associated with increased cardiovascular risk, methods to prevent cardiovascular toxicities, and recommended screening guidelines.

Recent findings

BRCA1/2 mutation carriers who are diagnosed with cancer are often exposed to chemotherapy, chest radiotherapy, and/or HER2 directed therapies, all of which can be cardiotoxic. In addition, BRCA1/2 carriers often undergo prophylactic salpingoopherectomies, which may also increase cardiovascular risks.

Summary

Understanding the potential for increased cardiovascular risk in individuals with a BRCA1 or BRCA2 mutation, as well as gold standard practices for prevention, detection, and treatment of cardiac concerns in this population, is important.

     

Increase of <Emphasis Type="Italic">Drosophila melanogaster</Emphasis> lifespan due to <Emphasis Type="Italic">D</Emphasis>-<Emphasis Type="Italic">GADD45</Emphasis> overexpression in the nervous system

The GADD45 protein family plays an important role in stress signaling and participates in the integration of cellular response to environmental and physiological factors. GADD45 proteins are involved in cell cycle control, DNA repair, apoptosis, cell survival and aging, and inflammatory response by complicated protein–protein interactions. In Drosophila melanogaster a single D-GADD45 ortholog (GG1086) has been described. Our data show that overexpression of the D-GADD45 gene in the nervous system leads to a significantly increase of Drosophila lifespan without a decrease in fecundity and locomotor activity. The lifespan extension effect is more pronounced in males than in females, which agrees with the sex-dependent expression of this gene. The longevity of D. melanogaster with D-GADD45 overexpression is apparently due to more efficient recognition and repair of DNA damage, as the DNA comet assay showed that the spontaneous DNA damage in the larva neuroblasts is reduced with statistical significance.     

An update on the geohelminths: <Emphasis Type="Italic">Ascaris lumbricoides</Emphasis>, hookworms, <Emphasis Type="Italic">Trichuris trichiura</Emphasis>, and <Emphasis Type="Italic">Strongyloides stercoralis</Emphasis>

Geohelminths remain prevalent throughout the developing world where levels of sanitation, personal hygiene, and maternal education are low. The five species of nematodes responsible for the bulk of disease are Ascaris lumbricoides, the hookworms Ancylostoma duodenale and Necator americanus, Trichuris trichiura, and Strongyloides stercoralis. Geohelminths are acquired through ingestion of fecally contaminated food or water or through contact with infected soil. In developing countries, infection with more than one nematode species and high worm burdens are common. The morbidity is substantial, particularly among children, and deaths occur. Geohelminthic infections are encountered in industrialized countries among immigrants and long-term travelers who have lived in endemic regions where sanitation is poor, and occasionally following autochthonous transmission.     

Colistin resistant <Emphasis Type="Italic">Escherichia coli</Emphasis> carrying <Emphasis Type="Italic">mcr</Emphasis>-<Emphasis Type="Italic">1</Emphasis> in urban sludge samples: Dhaka,Bangladesh

Of 48 bacteria belonging to the family Enterobacteriaceae tested from urban sludge samples, one Escherichia coli isolate was resistant to colistin and possessed the resistance marker gene mcr-1 found for the first time from Bangladesh. The colistin resistant E. coli was multidrug resistant showing resistance to 11 different antibiotics tested.     

<Emphasis Type="Italic">Fas/FasL,Bcl2</Emphasis> and <Emphasis Type="Italic">Caspase</Emphasis>-<Emphasis Type="Italic">8</Emphasis> gene polymorphisms in Chinese patients with rheumatoid arthritis

Apoptosis signals are necessary for maintaining homeostasis and an adequate immune response. Dysregulation of apoptosis-related genes in the immune system has an important impact on autoimmune diseases such as rheumatoid arthritis (RA). Thus, we investigated the association between Fas rs2234767 G/A, FasL rs763110 C/T, Bcl2 rs12454712 T/C, Bcl2 rs17757541 C/G, and Caspase-8 rs1035142 G/T polymorphisms and RA susceptibility in a Chinese population. These five single-nucleotide polymorphisms (SNPs) were studied in a Chinese population consisting of 615 patients with RA and 839 controls. Genotyping was performed using a custom-by-design 48-Plex SNP scan TM kit. Furthermore, we undertook a meta-analysis between FasL rs763110 C/T and RA. This study indicated that Fas rs2234767 and Bcl2 rs17757541 polymorphisms were risk factors for RA. No association was observed between FasL rs763110 C/T, Bcl2 rs12454712 T/C, and Caspase-8 rs1035142 G/T polymorphisms and RA in this study. The results of this meta-analysis suggested no significant association between FasL rs763110 C/T and RA. However, stratification analysis of this meta-analysis indicated that FasL rs763110 C/T increased the risk of Caucasian RA patients. In conclusion, this study demonstrated that Fas rs2234767 G/A and Bcl2 rs17757541 T/C polymorphisms might be associated with an increased risk of RA. This meta-analysis revealed that FasL rs763110 C/T was associated with an increased risk of Caucasian RA patients.     

Coexistent Rearrangements of c-<Emphasis Type="Italic">MYC</Emphasis>,<Emphasis Type="Italic">BCL2</Emphasis>, and<Emphasis Type="Italic">BCL6</Emphasis> Genes in a Diffuse Large B-Cell Lymphoma

We present a patient with stage III de novo diffuse large B-cell lymphoma. The lymphoma cells showed mature B-cell immunophenotype but lacked surface immunoglobulin (Ig) expression. Long-distance and long-distance inverse polymerase chain reaction assays to detect the oncogene/Ig gene rearrangement revealed that the cells carried 3 independent fusion genes, namely, c-MYC/Ig heavy chain gene (IgH), BCL2/IgH, and Ig lambda light chain gene/BCL6. Thus, the lymphoma cells concurrently carried t(8;14)(q24;q32), t(14;18)(q32;q21), and t(3;22)(q27;q11), which developed in association with class switching, V/D/J recombination, and somatic hypermutation, respectively. The lymphoma responded to chemoradiotherapy, and the patient has been well for 2 years, suggesting that multiple oncogene rearrangements may not necessarily be associated with poor clinical outcome.     

Novel mutations in <Emphasis Type="Italic">WWOX</Emphasis>, <Emphasis Type="Italic">RARS2</Emphasis>, and <Emphasis Type="Italic">C10orf2</Emphasis> genes in consanguineous Arab families with intellectual disability

Intellectual disability is a heterogeneous disease with many genes and mutations influencing the phenotype. Consanguineous families constitute a rich resource for the identification of rare variants causing autosomal recessive disease, due to the effects of inbreeding. Here, we examine three consanguineous Arab families, recruited in a quest to identify novel genes/mutations. All the families had multiple offspring with non-specific intellectual disability. We identified homozygosity (autozygosity) intervals in those families through SNP genotyping and whole exome sequencing, with variants filtered using Ingenuity Variant Analysis (IVA) software. The families showed heterogeneity and novel mutations in three different genes known to be associated with intellectual disability. These mutations were not found in 514 ethnically matched control chromosomes. p.G410C in WWOX, p.H530Y in RARS2, and p.I69F in C10orf2 are novel changes that affect protein function and could give new insights into the development and function of the central nervous system.