Investigation of inflammation related gene polymorphism of the mannose-binding lectin 2 in schizophrenia and bipolar disorder

Objectives:To investigate the association between mannose-binding lectin 2 (MBL2) codon 54 polymorphism and clinical features of patients diagnosed with schizophrenia (SCZ) or bipolar disorder (BD).Methods:One hundred and eighteen patients with SCZ, 100 patients with BD, and 100 healthy volunteers were included in the case-control study. The patients consecutively admitted to the outpatient clinic in December 2017-May 2018 and were evaluated with some scales for clinical parameters. Polymerase chain reaction and RFLP were used to determine MBL2 polymorphism in DNA material.Results:The MBL2 gene polymorphism distributions in SCZ or BD patients were significantly different from the control group. The heterozygous genotype percentages were significantly higher in the control group than in the SCZ or BD patients (OR: 0.450; 95% Cl: 0.243-0.830; p=0.010; OR: 0.532; 95%Cl: 0.284-0.995; p=0.047, respectively), and there were statistically significant differences in the MBL2 polymorphism distributions between treatment-responsive SCZ or BD patients and treatment-resistant patients diagnosed with SCZ or BD. The heterozygous genotype percentages were also significantly higher in the treatment-responsive group than in the treatment-resistant group in SCZ or BD patients (OR: 7.857; 95% Cl: 1.006-61.363; p=0.023; OR: 8.782; 95% Cl: 1.114-69.197; p=0.016, respectively).Conclusion:The presence of a heterozygous MBL2 genotype seems to be favorable both in terms of the absence of SCZ and BD in the healthy population and treatment response for Turkish patients.

Schizophrenia (SCZ) and bipolar disorder (BD) are chronic psychiatric disorders that cause substantial disruptions in psychosocial capacity and occur in approximately 1% of the world population.¹ Genome-wide association studies (GWAS) of Psychiatric Genomics Consortium for SCZ recognized more than a hundred common single nucleotide polymorphisms (SNPs) with minor individual effects presenting susceptibility to the SCZ.² A similar mega-analysis for BD, although including a more moderate sample, identified common risk variants specific to BD.³ The long-lasting alterations in gene expression patterns after environmental exposures imply that epigenetic mechanisms might also play a critical role in chronic psychiatric disorders.⁴ Again, previous researches have constantly reported shared genetic etiology between SCZ and BD. Researches showing the genetic overlap between SCZ and BD have improved from studying family and twin inheritance to determine genetic correlation and performing polygenic risk score analysis from GWAS data in large case-control samples.⁵ Despite these researches with large sample size, the cause of both disorders is still relatively unknown; recent studies have shown that uncontrolled activity of microglia and excessive inflammatory responses caused by pro-inflammatory cytokines are among the factors that play a role in the development of SCZ and BD based on genetic susceptibility.^1,6 A relationship between SCZ and many autoimmune diseases and an increase in the prevalence of an autoimmune disease occurrence by about 45% have been found. Moreover, infections of embryonic and early childhood periods lead to delays in fetal brain development and excessive synaptic pruning during adolescence, are among the possible risk factors of psychosis.^7,8 Systemic inflammation and central inflammation are thought to be associated with episodes, remission, and prognosis of BD. Neuroendocrine irregularities, neurotransmitter abnormalities, and glial cell dysfunctions cause plastic alterations in the mood-regulating brain areas. The high rate of comorbid autoimmune diseases also supports this claim.⁹Mannose-binding lectin (MBL) has a vital function in the innate immune system by stimulating the complement system’s lectin pathway. Therefore, it is the only collectin that binds to microorganisms, serves as an opsonin, promotes phagocytosis, and stimulates macrophages. MBL2 gene, which consists of 4 exons in the q11.2-q21 region of the long arm of chromosome 10, encoded MBL. Mutation at codon 54 follows in a replacement of glycine to aspartic acid (allele B), and the normal MBL2 allele is defined by allele A.^10-12 In heterozygous mutants, serum MBL decreases almost 10-fold, whereas, in homozygous mutants, the level decreases to an undetectable level. MBL deficiency is the most common immune defect in humans, affecting approximately 5-7% of individuals.¹³ A decrease in serum MBL level can cause recurrent spontaneous miscarriage,¹⁴ premature birth,¹⁵ and exacerbation of chronic diseases such as ischemic heart disease,¹⁶ and severe infections such as sepsis and systemic inflammatory response syndrome (SIRS).¹⁷ Besides, previous studies suggested that MBL plays an essential role in the pathogenesis of autoimmune diseases.^12,18 We believe that this is the first case-control study comparing MBL2 genotype distributions in patients with SCZ or BD according to treatment resistance, clinical characteristics, and scale scores in detail.Aims of the studyWe aimed to examine whether MBL2 codon 54 polymorphism was involved in the etiopathogenesis and treatment response of SCZ and BD compared with healthy controls.     

Management of orthopedic oncology patients during coronavirus pandemic

The new measures implemented in hospitals also altered the operation of orthopedics and traumatology departments. The main purpose of this article is to discuss how orthopedic oncology clinics should be organized during the pandemic and to present the process management scheme for patients requiring orthopedic surgery, including trauma surgery, from diagnosis to treatment, together with our experiences. Instead of thinking about the global emergence of the epidemic, it is time to act decisively. At first glance, the coronavirus disease 2019 (COVID-19) pandemic and orthopedics may seem to be unrelated disciplines, but the provision of healthcare services to patients who require them proves that these two fields are parts of the same whole. Our experiences in treating neutropenic, lymphocytopenic, and chemotherapy patients seem to have proven beneficial during this process. We operated on 10 biopsy patients, 15 primary bone sarcomas, 9 soft tissue sarcomas, and 82 trauma patients within this time frame. Only three patients were suspected to have COVID-19 before admission. The early identification, strict isolation, and effective treatment of these patients prevented any nosocomial infections and disease-related comorbidities. This success is the result of the multidisciplinary cooperation of the Ministry of Health, our hospital, and our clinic.     

Traumatic growth and psychological resilience status of female victims of violence inpatients in a district psychiatric hospital

The aim of this study was to examine the traumatic mental growth and psychological resilience status of females who were receiving inpatient treatment at a district mental health hospital and had a history of being subjected to violence. One hundred-twenty female patients with a history of exposure to violence participated in the study. An introductory information form, the Traumatic Growth Inventory (TGI) and the Psychological Resilience Scale for Adults (PRSA) were used for data collection. This study found that all the participants were subjected to emotional violence, 65.8% to physical violence, 30.8% to sexual violence, and 94.2% to verbal violence at some point in their lives. Their TGI mean score (60.96?±?11.91) was above average, while their PRSA mean score (97.90?±?9.18) was below average. The participants' mean scores on the TGI and PRSA did not vary significantly by the type of violence (p?>?0.05) to which the women were exposed. Moreover, no statistically significant relationship was found between the TGI and the PRSA total scale and subscale mean scores (p?>?0.05). This study found that the posttraumatic growth of females who had a history of physical or emotional or sexual abuse was positive, and that their psychological resilience levels were inadequate.     

An Ixodes scapularis protein required for survival of Anaplasma phagocytophilum in tick salivary glands

Anaplasma phagocytophilum is the agent of human anaplasmosis, the second most common tick-borne illness in the United States. This pathogen, which is closely related to obligate intracellular organisms in the genera Rickettsia, Ehrlichia, and Anaplasma, persists in ticks and mammalian hosts; however, the mechanisms for survival in the arthropod are not known. We now show that A. phagocytophilum induces expression of the Ixodes scapularis salp16 gene in the arthropod salivary glands during vector engorgement. RNA interference-mediated silencing of salp16 gene expression interfered with the survival of A. phagocytophilum that entered ticks fed on A. phagocytophilum-infected mice. A. phagocytophilum migrated normally from A. phagocytophilum-infected mice to the gut of engorging salp16-deficient ticks, but up to 90% of the bacteria that entered the ticks were not able to successfully infect I. scapularis salivary glands. These data demonstrate the specific requirement of a pathogen for a tick salivary protein to persist within the arthropod and provide a paradigm for understanding how Rickettsia-like pathogens are maintained within vectors.     

Chronic migraine associated with the Chiari type 1 malformation

OBJECTIVE: Our objective was to assess the frequency and clinical characteristics of migraine in the patients with CM-1. METHODS: We analyzed migraine in 73 patients with CM-1. Migraine was classified according to the new International Headache Society criteria. We did not include patients who had intracranial, parenchymal, or cervical lesions other than CM-1 on brain and cervical magnetic resonance imaging. RESULTS: Of the 73 patients diagnosed as having CM-1, 11 (15.06%) had migraines; of them, 8 (10.95%) had chronic migraines, 2 (2.73%) had migraines with auras, and 1 (1.36%) had migraines without auras. The patients who had both migraines and CM-1 (group 1) were compared regarding clinical characteristics and demographic features to the control group having chronic migraines. The control group comprised subjects free of CM-1. Onset age of pain was earlier and the frequency of headache days per month, baseline pain intensity, exacerbation of pain intensity, nausea, vomiting, and pain aggravated by physical activity were significantly higher in group 1. CONCLUSIONS: Although we found the frequency of migraine to be similar to that in population-based studies, we detected a threefold increased frequency of chronic migraine in this special population. We believe that CM-1 may be a factor associated with chronic migraine.     

The Forgotten Variable of Shear Stress in Mitral Annular Calcification: Whole Blood Viscosity

Objective

The aim of this research was to assess the relationship between mitral annular calcification (MAC) and whole blood viscosity (WBV).

Subjects and Methods

A total of 184 patients with MAC and 133 patients without MAC were enrolled in the study. The WBV was calculated with a confirmed formulation using the hematocrit and total plasma protein at a low shear rate (LSR) and high shear rate (HSR). Early diastolic mitral annular velocity (Ea) and late diastolic mitral annular velocity (Aa) were measured using pulse Doppler tissue echocardiography. Pearson''s correlation analysis was performed to assess the relationship between WBV and mitral annular motion velocities. The effects of different variables on the occurrence of MAC were assessed in univariate and multivariate logistic regression analysis.

Results

In patients with MAC, WBV values were significantly higher at HSR (18.04 ± 0.84 vs. 17.25 ± 0.96 208 s^-1, p < 0.001) and at LSR (78.0 ± 14.2 vs. 61.9 ± 17.1 0.5 s^-1, p < 0.001). The WBV at HSR and LSR were significantly correlated with Ea (r = −0.477, p < 0.001; r = −0.385, p < 0.001, respectively) and Aa (r = −0.544, p < 0.001; r = −0.323, p < 0.001, respectively). Multivariate analysis showed that WBV of both shear rates was an independent predictor of MAC. Using the ROC curve, a cut-off value of 70.1 for WBV at LSR had a sensitivity of 83.7% and a specificity of 73.7% (AUC 0.785, p < 0.001) and a WBV cut-off value of 17.5 at HSR had a sensitivity of 79.6% and a specificity of 71.4% (AUC 0.761, p < 0.001) for the prediction of MAC.

Conclusion

Patients with MAC had significantly higher WBV, which independently predicted the presence of MAC. WBV had an inverse correlation with mitral annular motion velocities, indicating that a higher WBV may lead to greater limitation in annular motion and, thus, more calcification.Key Words: Mitral valve calcification, Shear stress, Blood viscosity     

The utility of cytokeratins 7 and 20 (CK7/20) immunohistochemistry in the distinction of short-segment Barrett esophagus from gastric intestinal metaplasia: Is it reliable?

BACKGROUND: The purpose of the present correlative immunohistochemical study was to assess the utility of cytokeratin (CK7 and CK20) expression in the diagnosis of short-segment Barrett esophagus, particularly its efficacy in differentiating Barrett mucosa from intestinal metaplasia of the gastric cardia and corpus. METHODS: Two groups of endoscopic biopsy specimens were examined, including 20 endoscopic biopsy specimens of short-segment Barrett esophagus (Group A) and equal number exhibiting Helicobacter pylori associated intestinal metaplasia of the gastric cardia and corpus (Group B). All were investigated by immunohistochemistry using the standard ABC method for CK7 and CK20 expression. Fisher's exact test was used for statistical analysis of Barrett CK7/20 and gastric CK7/20 patterns between the groups. RESULTS: The anticipated pattern of reactivity in Barrett mucosa (CK7: strong diffuse positivity in superficial and deep glands; CK20: positivity in surface epithelium and superficial glands) was seen in 2 cases of Group A specimens. The expected gastric pattern (CK7: patchy immunostaining with variable involvement of deep glands; CK20: patchy immunostaining of superficial and deep glands in incomplete intestinal metaplasia / absence of CK7 immunoreactivity with strong CK20 staining in superficial and deep glands in complete intestinal metaplasia) was seen in 8 cases of Group B specimens. The respective sensitivity and false-negativity values of CK7/20 staining for Barrett pattern in Group A were 10% and 90%, respectively. These values for gastric pattern in Group B were 40% and 60%, respectively. The specificity and false-positivity values of both patterns were same (100% and 0%, respectively). There was no statistically significant difference for Barrett pattern between the two groups (P = 0.487), while the observation of gastric pattern was significantly higher in Group B than in Group A (P = 0.02). CONCLUSIONS: We concluded that these hypothesized and recently applied diagnostic criteria involving CK7 and CK20 immunoreactivity are not reliable in distinguishing short-segment Barrett esophagus from intestinal metaplasia as seen in gastric cardia and corpus.