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.     

Laparoscopic versus open resection of colorectal liver metastasis

Background

Findings have shown laparoscopic liver resection (LLR) to be feasible and safe, but the data in the literature regarding oncologic outcomes are scant. This study aimed to compare the perioperative and short-term oncologic outcomes between LLR and open resection of colorectal liver metastasis (CLM).

Methods

Between January 2006 and April 2012, 40 patients underwent LLR of CLM. These patients were compared with a consecutive matched group of 40 patients who underwent open resection within the same period. Data were obtained from a prospective institutional review board (IRB)-approved database. Statistical analysis was performed using t test, Chi-square, and Kaplan–Meier survival.

Results

The groups were similar in terms of age, gender, tumor size, number of tumors, and type of resections performed. The operative time was similar in the two groups, but the estimated blood loss was less in the LLR group than in the open resection group. The length of stay was shorter in the LLR group (3.7 vs 6.5 days; p < 0.001). The 2-year overall survival rate was 89 % for LLR and 81 % for open resection. The median disease-free survival time was 23 months in each group.

Conclusions

The findings suggest that LLR is associated with less blood loss and a shorter hospital stay than open resection for CLM. According to our short-term results, LLR is equivalent to open resection in terms of oncologic outcomes.     

Novel transient receptor potential vanilloid 1 receptor antagonists for the treatment of pain: structure-activity relationships for ureas with quinoline, isoquinoline, quinazoline, phthalazine, quinoxaline, and cinnoline moieties

Novel transient receptor potential vanilloid 1 (TRPV1) receptor antagonists with various bicyclic heteroaromatic pharmacophores were synthesized, and their in vitro activity in blocking capsaicin activation of TRPV1 was assessed. On the basis of the contribution of these pharmacophores to the in vitro potency, they were ranked in the order of 5-isoquinoline > 8-quinoline = 8-quinazoline > 8-isoquinoline > or = cinnoline approximately phthalazine approximately quinoxaline approximately 5-quinoline. The 5-isoquinoline-containing compound 14a (hTRPV1 IC50 = 4 nM) exhibited 46% oral bioavailability and in vivo activity in animal models of visceral and inflammatory pain. Pharmacokinetic and pharmacological properties of 14a are substantial improvements over the profile of the high-throughput screening hit 1 (hTRPV1 IC50 = 22 nM), which was not efficacious in animal pain models and was not orally bioavailable.     

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.