Plasma IL-6, TREM1, uPAR, and IL6/IL8 biomarkers increment further witnessing the chronic inflammation in type 2 diabetes.

OBJECTIVES: Type 2 diabetes (T2D) is known to be associated with chronic inflammation, but the inflammatory regulators/markers are not exactly defined and the link between them remains undetermined. The objective of this study is to identify these markers by testing traditional (IL6 & IL8) and non-traditional (TREM1 & uPAR) inflammatory markers. METHODS: Data and blood samples were obtained from 114 T2D and 74 non-diabetic Kuwaiti subjects attending health facilities in Kuwait. Chemical analyzers were used to measure glycemic and lipid profiles, while ELISA was used to measure plasma levels of insulin and several inflammatory markers. RESULTS: Showed that the IL-6 and TREM1 were significantly higher in T2D compared to non-diabetic controls, and the uPAR level was borderline higher in T2D but significantly correlated with IL-6 levels. Unexpectedly, IL8 was significantly below normal in T2D and IL6/IL8 ratio was significantly higher in T2D patients. Unlike other tested markers, uPAR was in addition strongly correlated with insulin levels and HOMA-IR index. CONCLUSIONS: Raised levels of IL6, TREMI, IL6/IL8 ratio, and the strong positive correlation of plasma levels of uPAR with IL-6, insulin, and HOMA-IR index, are reliable spectators of chronic inflammation in T2D patients. The reduced level of IL-8 in T2D was a peculiar observation that needs further explanation. Finally, the consequences and impact of the sustained rise of these inflammatory regulators in diabetic tissues need to be meticulously explored.

Diabetic sarcopenia: metabolic and molecular appraisal.

Myopathy is the missing slot from the routine clinical checkup for diabetic complications. Similarly, its pathophysiological, metabolic, and molecular bases are insufficiently explored. In this review, the above issues are highlighted with a focus on skeletal muscle atrophy (also described as diabetic sarcopenia), in contrast to the normal histological, physiological, and molecular features of the muscles. Literature search using published data from different online resources was used. Several diabetic myopathy etiological factors are discussed explicitly including; inflammation and immunological responses, with emphasis on TNFα and IL-6 overproduction, oxidative stress, neuropathy and vasculopathy, aging sarcopenia, antidiabetic drugs, and insulin resistance as a denominator. The pathophysiological hallmark of diabetic muscle atrophy is the decreased muscle proteins synthesis and increased degradation. The muscle protein degradation is conveyed by 4 systems; ubiquitin-proteasome, lysosomal autophagy, caspase-3, and calpain systems, and is mostly mediated via the IL6/STAT, TNF&IL6/NFκB, myostatin/Smad2/3, and FOXO1/3 signaling pathways, while the protein synthesis inhibition is mediated via suppression of the IGF1-PI3K-Akt-mTOR, and SC-Gαi2-pathways. Moreover, the satellite cells and multilineage muscle mesenchymal progenitor cells differentiation plays a major role on the fate of the affected muscle cells by taking an adipogenic, fibrogenic, or connective tissue lineage. As a conclusion, in this article, the pathological features of diabetic sarcopenia are reviewed at gross level, while at a molecular level the normal protein turnover, signal transduction, and pathways involved in muscle atrophy are described. Finally, an integrated network describing the molecular partakers in diabetic sarcopenia is presented.

Diabetes mellitus tendino-myopathy: epidemiology, clinical features, diagnosis and management of an overlooked diabetic complication.

Tendino-myopathy, an unexplored niche, is a non-vascular unstated T2DM complication, which is largely disregarded in clinical practice, thus, we aim to explore it in this review. Literature search using published data from different online resources. Epidemiologically, reported prevalence varies around 10-90%, which is marked variable and unreliable. Clinically, diabetic tendino-myopathy is typified by restriction of movement, pain/tenderness, cramps and decreased functions. Moreover, myopathy is characterized by muscle atrophy, weakness and ischemia, and tendinopathy by deformities and reduced functions/precision. In tendonapthy, the three most affected regions are: the hand (cheiroarthropathy, Dupuytren's contracture, flexor tenosynovitis and carpel tunnel syndrome), shoulder (adhesive capsulitis, rotator cuff tendinopathy and tenosynovitis) and foot (Achilles tendinopathy with the risk of tear/rupture), in addition to diffuse idiopathic skeletal hyperostosis. Pathologically, it is characterized by decreased muscle fiber mass and increased fibrosis, with marked extracellular matrix remodeling and deposition of collagens. The tendon changes include decreased collagen fibril diameter, changed morphology, increased packing and disorganization, with overall thickening, and calcification. Diagnosis is basically clinical and radiological, while diagnostic biomarkers are awaited. Management is done by diabetes control, special nutrition and physiotherapy, while analgesics, steroids and surgery are used in tendinopathy. Several antisarcopenic drugs are in the pipeline. This review aims to bridge clinical practice with research and update routine diabetic checkup by inclusion of tendino-myopathies in the list with an emphasis on management.

Does four-week consecutive, dawn-to-sunset intermittent fasting during Ramadan affect cardiometabolic risk factors in healthy adults? A systematic review, meta-analysis, and meta-regression.

AIMS: This study aimed to evaluate the effects of Ramadan diurnal intermittent fasting (RDIF; 29-30 days) on cardiometabolic risk factors (CMRF) in healthy adults, and examine the effect of various cofactors on the outcomes using sub-group meta-regression. DATA SYNTHESIS: We conducted a systematic review and meta-analysis to measure the effect sizes of changes in CMRF in healthy adult Muslims observing RDIF. Ten scientific databases (EBSCOhost, CINAHL, Cochrane, EMBASE, PubMed/MEDLINE, Scopus, Google Scholar, ProQuest Medical, ScienceDirect, and Web of Science) were searched from the date of inception (1950) to the end of November 2020. The CMRF searched and analyzed were total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), diastolic blood pressure (DBP), and heart rate (HR). We identified 91 studies (4431 adults aged 18-85 years) conducted between 1982 and 2020 in 23 countries distributed over four continents. RDIF-induced effect sizes for CMRF were: TC (no. of studies K = 77, number of subjects N = 3705, Hedge's g = -0.092, 95% confidence interval (CI): -0.168, 0.016); TG (K = 74, N = 3591, Hedge's g = -0.127, 95% CI: -0.203, 0.051); HDL-C (K = 68, N = 3528, Hedge's g = 0.138, 95% CI: 0.051, 0.224); LDL-C (K = 65, N = 3354, Hedge's g = -0.115, 95% CI: -0.197, -0.034); VLDL-C (K = 13, N = 648, Hedge's g = -0.252, 95% CI: -0.431, 0.073), DBP (K = 32, N = 1716, Hedge's g = -0.255, 95% CI: -0.363, 0.147), and HR (K = 12, N = 674, Hedge's g = -0.082, 95% CI: -0.300, 0.136). Meta-regression revealed that the age of fasting people was a significant moderator of changes in both HDL-C (P = 0.02) and VLDL-C (P = 0.01). Male sex was the only significant moderator of changes in LDL-C (P = 0.055). Fasting time duration was the only significant moderator of HDL-C (P = 0.001) at the end of Ramadan. CONCLUSIONS: RDIF positively impacts CMRF, which may confer short-term transient protection against cardiovascular disease among healthy people.

Relationship between VEGFA polymorphisms and serum VEGF protein levels and recurrent spontaneous miscarriage.

STUDY QUESTION: Is recurrent spontaneous miscarriage (RSM) associated with changes in vascular endothelial growth factor (VEGF) serum levels, and with polymorphisms in the VEGFA gene? SUMMARY ANSWER: Reduced serum VEGF levels, and VEGFA -460T/C (rs833061), 398G/A (rs833068), -583T/C (rs3025020) variants, were associated with RSM. WHAT IS KNOWN ALREADY: Reduced expression of VEGF has been linked with spontaneous miscarriage, likely due to defective fetal and placental angiogenesis. Since VEGF production is in part inherited, VEGFA polymorphisms associated with altered VEGF secretion have been investigated for their association with RSM, often with variable conclusions. STUDY DESIGN, SIZE, DURATION: A retrospective case-control study, which was conducted between January 2011 and April 15, 2012. PARTICIPANTS/MATERIALS, SETTING, METHODS: Subjects comprised 296 women with RSM (mean age: 31.6 ± 5.4 year), and 305 age-matched (mean age: 31.6 ± 4.9 year) control Arab women, who had attended outpatient obstetrics and gynecology clinics in two teaching hospitals in Bahrain. VEGFA -2578C/A (rs699947), -460T/C (rs833061), -1154G/A (rs15703060), -634G/C (rs2010963), 398G/A (rs833068), 497G/A (rs833070), -583T/C (rs3025020) and 936C/T (rs3025039) genotyping was done by real-time PCR, with defined clusters; VEGF serum levels were measured by ELISA. MAIN RESULTS AND THE ROLE OF CHANCE: Higher minor allele frequency (MAF) and genotype distribution of -460T/C [corrected P (Pc) = 0.003], 398G/A (Pc = 0.016) and -583T/C (Pc < 0.001) single nucleotide polymorphisms (SNPs) were seen in RSM cases than control women. Increased RSM risk was seen with homozygous -460T/C and 398G/A SNPs and with heterozygous -583T/C, which had a stronger effect when homozygous. Serum VEGF levels were significantly reduced in RSM cases compared with control women (P = 0.016), and correlated with -460T/C, 398G/A and -583T/C genotypes. Haploview analysis revealed heterogeneity in linkage disequilibrium between VEGFA variants, and two blocks were identified: Block 1 comprising -2578C/A, -460T/C and -1154G/A, while Block 2 contained -634G/C, 398G/A, 497G/A, -583T/C and 936C/T. Both negatively and positively RSM-associated 3-locus (Block 1) and 5-locus (Block 2) VEGFA haplotypes were identified, after controlling for a number of covariates. LIMITATIONS, REASONS FOR CAUTION: The study was retrospective and can only demonstrate association and not a cause-effect relationship. Furthermore, it was limited to Bahraini Arabs,thereby necessitating parallel studies on other ethnic groups. WIDER IMPLICATIONS OF THE FINDINGS: Reduced VEGF secretion, and specific VEGFA variants may contribute to the pathogenesis of RSM. However, the association of VEGFA SNPs with RSM appears to be independent of their association with altered VEGF serum levels. The differential association of VEGFA variants with RSM is in line with previous findings on the contribution of ethnicity/racial background to genetic association studies.

Protein Z variants associated with protein Z plasma levels and with risk of idiopathic recurrent miscarriage.

Protein Z (PZ) deficiency due to anti-PZ autoantibodies and/or mutations in PZgene was linked with adverse pregnancy outcomes, including idiopathic recurrent miscarriage (IRM). We investigated the association of rs3024718, rs3024719, rs3024731, rs3024778, rs3024772, and rs3024735 (G79A) PZ variants and changes in PZ levels in 287 women with IRM, and 308 control women. Of the 6 single nucleotide polymorphisms (SNPs) analyzed, higher minor allele frequency of rs3024735 (G79A) and rs3024731 were seen in IRM cases than in control women. Significantly higher frequencies of rs3024735/G79A G/A and A/A (P< .001), rs3024719 G/A (P= .009), and rs3024731 A/A (P = .012), but not rs3024718 (P= .12), rs3024778 (P = .76), or rs3024772 (P= .27) genotype carriers were seen between IRM cases versus control women, respectively, and was linked with reduced PZ levels. Six-locus (rs3024718/rs3024719/rs3024778/rs3024731/rs3024735/rs3024772) PZhaplotypes analysis demonstrated increased frequency of GAGAAG and AGGTAG and reduced frequency of AGGTGC haplotypes in IRM cases, thereby conferring disease susceptibility and protective nature to these haplotypes, respectively. These results demonstrate that specific PZSNPs and haplotypes are significantly associated with IRM.

The relation of vascular endothelial growth factor (VEGF) gene polymorphisms on VEGF levels and the risk of vasoocclusive crisis in sickle cell disease.

OBJECTIVE: The association of vascular endothelial growth factor (VEGFA) variants and VEGF secretion with sickle cell disease (SCD) vasoocclusive crisis (VOC) was investigated in 210 VOC patients and 114 pain-free control patients. METHODS: VEGFA -2578C/A (rs699947), -460T/C (rs833061), -1154G/A (rs15703060), -634G/C (rs2010963), 398G/A (rs833068), 497G/A (rs833070), -583T/C (rs3025020), and 936C/T (rs3025039) were carried out by real-time PCR. RESULTS: Higher frequency of rs2010963 C-allele, rs833068 A-allele, and rs3025020 C-allele and significant differences in rs2010963, rs833068, and rs3025020 genotype distribution were seen in VOC than steady-state patients. Increased VOC risk was seen with rs2010963 as heterozygous and more as homozygous, and in rs833068 and rs3025020 homozygous carriers. While there were no differences in VEGF levels between VOC and steady-state controls, there was a progressive decline in serum VEGF in rs2010963 and rs833068 heterozygous and homozygous genotypes, but an opposite trend was seen in VOC patients. Haploview analysis revealed high LD between rs699947, rs833061, rs1570360, rs2010963, rs833068, and rs833070, but weak or no LD between rs3025020 and rs3025039 and other SNPs. Six-locus (rs699947/rs833061/rs1570360/rs2010963/rs833068/rs833070) VEGFA haplotype analysis identified haplotype 111111 to be negatively (OR = 0.68) and haplotype 111222 to be positively (OR = 1.89) associated with VOC. rs2010963, rs833068, and rs3025020 were correlated with VOC type, while rs3025020 was correlated with hospitalization, VOC treatment, and duration. CONCLUSION: Specific VEGFA variants contribute to the pathogenesis of SCD VOC.

Anti-phosphatidylserine, anti-cardiolipin, anti-ß2 glycoprotein I and anti-prothrombin antibodies in recurrent miscarriage at 8-12 gestational weeks.

OBJECTIVE: To investigate the association of antibodies to ß2-glycoprotein I (anti-ß2GPI), cardiolipin (ACA), phosphatidylserine (anti-PS) and prothrombin (anti-PT) with recurrent spontaneous miscarriage (RSM). STUDY DESIGN: Case-control study involving 277 RSM cases and 288 controls: autoantibody levels were measured by ELISA. Differences between cases and controls were analyzed by nonparametric Mann-Whitney test, and logistic regression was used in analyzing the association of autoantibodies with RSM. RESULTS: Anti-PS IgG, ACA IgM and IgG, and anti-PT IgM were significantly associated with RSM risk, and differential antibody association was noted according to BMI and primary and secondary RSM. Higher prevalence of elevated anti-PS IgG was seen in cases, with the strongest risk above the 99th percentile. For ACA IgM, 28 cases (10.1%) and 5 controls (1.7%) were positive, with increasing OR for increasing cut-off points, which was significant at antibody titers >99th percentile. For ACA IgG, 101 cases (36.5%) and 13 controls (4.5%) were positive, with graded increase in OR for increasing cut-off points, which was significant at titers >90th percentile (maximal at titers >99th percentile). For anti-PT, 23 cases (12.0%) and 9 controls (6.1%) were positive, with increased OR at titers >90th percentile. Regression analyses confirmed the independent association of anti-PS IgG, ACA IgM and IgG with RSM, and significant RSM risk was associated with high anti-PS IgG (P<0.001) and ACA IgM (P<0.001) titers, and a dose-dependent increase in RSM risk was seen with progressively increased ACA IgG titers. No significant association existed between anti-PT IgM and RSM. CONCLUSION: Elevated ACA IgM and IgG, and anti-PS IgG antibodies are positively associated with RSM.

Protein Z polymorphisms associated with vaso-occlusive crisis in young sickle cell disease patients.

We investigated the association of protein Z (PZ) promoter (rs3024718, rs3024719, and rs3024731) and intron (rs3024735; G79A) SNPs with sickle cell disease (SCD) vaso-occlusive crisis (VOC). Study subjects included 239 SCD patients with VOC and 138 pain-free SCD control patients. PZ genotyping was done by allelic discrimination (real-time PCR) assays. The minor allele frequency of rs3024718 (P=0.03), rs3024719 (P=0.02), rs3024731 (P<0.001), and rs3024735 (P<0.001) were higher in VOC patients than control SCD patients. Significant differences in the distribution of rs3024731 (P=0.028) and rs3024735 (P=0.045) genotypes were seen between VOC and steady-state SCD patients. This association remained significant after adjusting for gender, HbS, and HbF. Four-locus (rs3024718/rs3024719/rs3024731/rs3024735) PZ haplotypes analysis demonstrated increased frequency of GAAA (P=0.024), AGAA (P=0.011), and GGTG (P=0.002), and reduced frequency of AGTG haplotype (P=0.001) in VOC than in steady-state control patients, thereby conferring disease susceptibility and protective nature to these haplotypes, respectively. Of these, only AGTG (P(c)=0.001) and GGTG (P(c)=0.018) remained significant after applying the Bonferroni correction. In conclusion, specific PZ variants and haplotypes are significantly associated with SCD VOC.

Replication study of common variants in CDKAL1 and CDKN2A/2B genes associated with type 2 diabetes in Lebanese Arab population.

We investigated the association of CDKAL1 (rs7754840 and rs7756992) and CDKN2A/2B (rs10811661) variants with T2DM. Higher MAF of rs7754840 and rs7756992 were seen in patients, and both were associated with T2DM under additive, dominant, and recessive models. CDKAL1 rs7754840 and rs7756992, but not CDKN2A/2B rs10811661, are associated with T2DM in Lebanese.

Contribution of VEGF polymorphisms to variation in VEGF serum levels in a healthy population.

OBJECTIVE: Vascular endothelial growth factor (VEGF) is a pro-angiogenic factor. Variability in VEGF expression, induced by specific VEGFA variants, are involved in angiogenesis-related disorders. This study examined the genotype distribution and functional role (VEGF expression) of rs699947, rs833061, rs1570360, rs2010963, rs833068, rs833070, rs3025020, and rs3025039 VEGFA variants and their haplotypes in 519 healthy Bahraini individuals of both genders. METHODS AND RESULTS: The distribution of the eight VEGFA polymorphisms screened was in Hardy-Weinberg equilibrium. The minor allele frequencies of rs699947 (0.42), rs833061 (0.32), rs1570360 (0.31), rs2010963 (0.33), rs833068 (0.37), rs833070 (0.42), rs3025020 (0.33), and rs3025039 (0.13) were generally compared to those established for Caucasians. Of the variants tested, rs3025020 was associated with increased VEGF serum levels (p=0.019), while rs3025039 was associated with decreased levels (p=0.038). Linkage analysis identified two VEGFA blocks, the first, spanning 16 kb, was not associated with altered VEGF levels, while the second, spanning 3 kb containing rs3025020 and rs3025039, was linked with higher VEGF expression, of which the (-583)T/(+936)T haplotype (p=0.008) was linked with higher VEGF levels compared to the (-583)C/(+936)C (all wild-type) haplotype. CONCLUSION: These results support the association of rs30250202 and rs3025039, and specific VEGF haplotypes, with altered VEGF serum levels, although the exact functional mechanisms remain to be elucidated.

Analysis of interleukin-18 promoter polymorphisms and changes in interleukin-18 serum levels underscores the involvement of interleukin-18 in recurrent spontaneous miscarriage.

OBJECTIVE: To evaluate the association of interleukin-18 (IL-18) promoter single-nucleotide polymorphisms rs1946519 (-656C/A), rs187238 (-137G/C), rs360718 (-119A/C), and rs360717 (-105G/A) and changes in IL-18 serum levels with recurrent spontaneous miscarriage (RSM). DESIGN: Case-control study. SETTING: Outpatient obstetrics and gynecology clinics. PATIENT(S): Women with confirmed RSM (n = 282), and 283 age- and ethnically matched controls. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): IL-18 genotyping was accomplished by allelic discrimination assays; serum IL-18 levels were measured by ELISA. RESULT(S): The minor allele frequencies of rs360717 and rs1946519, but not rs360718 or rs187238, were higher in patients with RSM. Significant differences in the distribution of the rs360717 and rs1946519 genotypes were noted between patients and controls, and both rs360717 and rs1946519 IL-18 single-nucleotide polymorphisms showed significant association with RSM under additive, dominant, and recessive models. Lower serum IL-18 levels were seen between patients and controls and were more pronounced in rs360717 and rs1946519 heterozygous and homozygous genotypes. Four-locus (rs1946519/rs187238/rs360718/rs360717) IL-18 haplotype analysis identified that the AGAA (Pc<.001), CGAA (Pc<.001), and ACAG (Pc=.018) haplotypes were associated with a reduction in IL-18 secretion and with increased RSM risk, after adjustments for body mass index, menarche, and gravida. CONCLUSION(S): These results demonstrated that reduced IL-18 levels and rs360717 and rs1946519 IL-18 variants are significantly associated with RSM.

Genetic variations in the interleukin-21 gene and the risk of recurrent idiopathic spontaneous miscarriage.

OBJECTIVES: Insofar as recurrent spontaneous miscarriage (RSM) is linked with dysregulated immunity and inflammatory changes, and given the pro-inflammatory role of interleukin-21 (IL-21), we examined the association between IL-21 polymorphisms and RSM. METHODS AND RESULTS: IL-21 rs2055979, rs13143866, rs9992580, and rs4833837 were genotyped in 235 cases of RSM and 235 controls. Regression analysis was employed in assessing the contribution of IL-21 variants to the overall RSM risk. Higher minor allele and genotype frequencies of rs2055979 and rs13143866, but not rs9992580 or rs4833837, were seen in RSM patients than in the controls. IL-21 haplotype [rs9992580/rs4833837/rs2055979/rs13143866] analysis revealed a lower frequency of the TGCG haplotype, and a higher frequency of the GGCG and GAAA haplotypes in patients, thus conferring protection from or a susceptibility to RSM by these haplotypes respectively. Regression analysis confirmed the association of TGCG [OR (95%CI)=0.09 (0.05-0.16)], and GGCG [OR (95%CI)=2.52 (1.34-4.54)] and GAAA [OR (95%CI)=4.02 (2.20-7.70)] haplotypes, after adjusting for age and BMI. CONCLUSIONS: Our findings indicate that IL-21 is a novel susceptibility gene for RSM.

Effect of the functional VEGFA-583C/T variant on vascular endothelial growth factor levels and the risk of recurrent spontaneous miscarriage.

The association of vascular endothelial growth factor (VEGF) -583C/T variant with recurrent miscarriage (RSM) was investigated in 173 RSM cases and 248 control women. Increased minor allele and genotype frequencies of -583C/T, and reduced serum VEGF concentrations were associated with increased risk of RSM.

Anti-annexin V IgM and IgG autoantibodies and the risk of idiopathic recurrent spontaneous miscarriage.

Anti-annexin V antibodies have been identified as risk factors for recurrent spontaneous miscarriage (RSM) in some, but not all previous studies. We investigated the association between anti-annexin IgM and IgG in RSM cases and control women. Blood samples from 244 women with idiopathic RSM, and 283 multi-parous control women were tested for anti-annexin V antibodies by ELISA. A significant elevation in anti-annexin V IgM and IgG was seen in the RSM cases. An increased prevalence of elevated anti-annexin V IgM and to a lesser extent anti-annexin V IgG was seen in RSM patients. Receiver operating characteristic analysis indicated that the area under the curve for anti-annexin V IgM was 0.916, and for anti-annexin V IgG was 0.725. A systematic shift in anti-annexin V IgM and IgG distributions toward higher values occurred in RSM women, which was confirmed by percentile analysis. For each of the anti-annexin V isotypes, the adjusted odds ratio increased as the percentile value increased; the strongest risk was for anti-annexin V IgM, in which the 99th percentile (P99) was associated with a 165-fold higher risk than P50, and for anti-annexin V IgG where P99 was associated with a 38-fold higher risk than P50. In addition, a higher prevalence of elevated anti-annexin V IgM and anti-annexin V IgG was seen in RSM cases than in control women. We conclude that anti-annexin V IgM and IgG antibody positivity are independent risk factors for RSM.

Anti-annexin V IgG and IgM antibodies in sickle cell disease patients with vaso-occlusive crisis.

Vaso-occlusive crisis (VOC) is a significant cause of morbidity and mortality in sickle cell anemia (SCA) patients; however, its mechanisms are poorly understood. In view of their prothrombotic nature, we hypothesized that SCA-associated VOC may be due to the presence of anti-annexin V antibodies. Anti-annexin V antibodies were measured with ELISA in 177 VOC and 81 steady-state SCA patients. Anti-annexin V IgM and IgG concentrations were significantly higher in VOC patients than in steady-state patients and were associated with elevated VOC risk. After categorizing anti-annexin V antibodies, the adjusted odds ratio increased as the percentile value increased. Monovariate logistic regression analysis demonstrated a positive dose-effect relationship for anti-annexin V IgM with VOC, with increased VOC risk seen with increased antibody titers. Multivariate logistic regression analyses confirmed the association of anti-annexin V IgM, more so than IgG, as an independent VOC risk factor. Anti-annexin V IgG antibodies correlated positively with VOC type and negatively with HbF and age of VOC onset, while anti-annexin V IgM correlated positively with VOC type, duration, frequency, site, pain severity, hospitalization, and medication, and negatively with age of VOC onset and HbS levels. High levels of anti-annexin V IgM antibodies constitute a risk factor for VOC in SCA patients.

High Frequency of anti-protein Z IgM and IgG autoantibodies in women with idiopathic recurrent spontaneous miscarriage.

PROBLEM: Protein Z (PZ) system is an anticoagulant pathway involved in the physiologic regulation of coagulation, and PZ deficiency reportedly enhances prothrombophilic mechanisms, including those implicated with idiopathic recurrent miscarriage (RSM). We investigate plasma anti-PZ IgM and IgG levels in RSM women and in multiparous control women. METHODS: Anti-PZ IgM and IgG levels were measured in 265 RSM women and 283 age-matched control women by ELISA. RESULTS: Elevated anti-PZ IgG (P < 0.001) and IgM (p < 0.001) titers were seen in patients. The areas under the curves for ROC curve for anti-PZ IgM (0.898 ± 0.044) and IgG (0.898 ± 0.042) demonstrated no variation in diagnostic capacity. Multivariate analysis confirmed the association of elevated anti-PZ IgM [adjusted odds ratio, aOR (95% CI) = 6.46 (2.44-17.11)] and IgG [aOR (95% CI) = 7.44 (2.54-21.79)] as independent predictors of RSM after adjusting for confounding covariates and demonstrated a clear gradation of increasing RSM risk associated with increased antibody titers. CONCLUSION: The presence of anti-PZ IgM and IgG antibodies are risk factors for RSM.

The prevalence of absence of the palmaris longus muscle in the Bahraini population.

Absence of the palmaris longus muscle has been well documented in several populations at a prevalence rate ranging between 2.2 and 63.9% which varies according to race, sex, and side of the body. There is little documentation of the prevalence of absence of this muscle from populations in the Arabian Gulf region. We examined 1,043 subjects, 3-85 years old, from the Kingdom of Bahrain for the presence or absence of the palmaris longus muscle using the conventional test for the presence of this muscle. Statistical analyses investigated the association of muscle absence with sex, hand dominance, and laterality. The palmaris longus muscle was absent in 36.8% of subjects. Bilateral absence (19%) was more common than unilateral absence (17.9%) with preponderance in female subjects. The muscle was absent more often on the left side than the right (P = 0.003). In the right upper limbs the muscle was absent in female subjects more than male subjects (P = 0.031). This study reaffirms that there is population variation in the frequency of absence of the palmaris longus muscle. The tendon of the palmaris longus bifurcated at the wrist in 7.1% of subjects, with male subjects showing this feature more frequently than female subjects in the right hand (P = 0.037) and the left hand (P = 0.030). This has not been reported before. The clinical significance of our findings is discussed.