Partial changes in apoptotic pathways in hippocampus and hypothalamus of Cc2d1a heterozygous.

Alterations in the apoptosis pathway have been linked to changes in serotonin levels seen in autistic patients. Cc2d1a is a repressor of the HTR1A gene involved in the serotonin pathway. The hippocampus and hypothalamus of Cc2d1a ± mice were analyzed for the expression of apoptosis markers (caspase 3, 8 and 9). Gender differences were observed in the expression levels of the three caspases consistent with some altered activity in the open-field assay. The number of apoptotic cells was significantly increased. We concluded that apoptotic pathways are only partially affected in the pathogenesis of the Cc2d1a heterozygous mouse model. A) Apoptosis is suppressed because the cell does not receive a death signal, or the receptor cannot activate the caspase 8 pathway despite the death signal. B) Since Caspase 8 and Caspase 3 expression is downregulated in our mouse model, the mechanism of apoptosis is not activated.

Nerve growth factor and angiotensin converting enzyme 2 levels in children with neurodevelopmental disorders.

OBJECTIVE: Neurodevelopmental disorders (NDDs) are the most common psychiatric disorders in childhood, and there are many factors in their etiology. In recent years, many biomarkers have been studied to elucidate the etiology of these disorders. In this study, it was aimed to investigate the levels of nerve growth factor (NGF) and angiotensin converting enzyme 2 (ACE2) in attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and intellectual disability (ID). METHODS: The study included 74 children with NDDs (the number of patients in ADHD, ASD and ID groups were 24, 25 and 25 respectively) and 30 healthy controls (HCs). Serum NGF and ACE2 levels were studied with ELISA kits, also complete blood count (CBC), levels of fasting glucose and serum lipids were assessed. RESULTS: ACE2 levels were found to be lower in NDD group than HCs in girls. In boys with ASD, triglyceride levels were significantly higher than other groups. Also a positive correlation was found between ACE2 and NGF levels when all sample assessed together. CONCLUSIONS: This study is a premise for investigating ACE2 and NGF in NDDs. The role of these markers in ADHD, ASD, ID and other NDDs and their associations with gender should be assessed by studies in which both larger sample groups and more disorders.

Assessment of the canal anatomy of the premolar teeth in a selected Turkish population: a cone-beam computed tomography study.

BACKGROUND: Teeth may have additional roots and a different number of root canals. Overlooked root canals may cause endodontic failure. The aim of this study was to investigate the prevalence of root canals and the number of roots of premolars in a selected Turkish population. MATERIALS AND METHODS: A total of 2,570 teeth from 1,438 patients were evaluated. The cone-beam computed tomography scans of 1,055 maxillary and 1,515 mandibular premolars were examined. RESULTS: Type IV root canal morphology was observed most frequently in maxillary first premolars (77%), and the rates of single and double channel formations were very similar (51% and 49%, respectively). Of the second maxillary premolars, 57.4% had Type I morphology, and 89.9% of the teeth were single-rooted, while 68.6% had a single root canal. The most common formation was Type I (85%) among mandibular first premolars, and a single root was observed in 95.6% of these teeth. In addition, 87% of the mandibular first premolars had a single root canal. The second mandibular premolars mostly had Type I (95.4%) formation, and 99.3% of the teeth were single-rooted, while 96.9% had a single root canal. CONCLUSION: According to our findings, 51% of maxillary first premolars had a single root, 79.4% had two root canals, and 77% had Type IV (77%) formation. Maxillary second premolars mostly had Type I formation. In addition, a single root and single root canal formation were most common. Mandibular first premolars generally had a single root and single root canal formation, but 13% had two root canals, and 6.4% had Type V formation. More than 95% of mandibular second premolars had Type I formation.

The Characterization of Sex Differences in Hypoglycemia-Induced Activation of HPA Axis on the Transcriptomic Level.

Activation of the hypothalamic-pituitary-adrenal (HPA) axis using an insulin tolerance test (ITT) is a medical diagnostic procedure that is frequently used in humans to assess the HPA and growth-hormone (GH) axes. Whether sex differences exist in the response to ITT stress is unknown. Thus, investigations into the analysis of transcripts during activation of the HPA axis in response to hypoglycemia have revealed the underlying influences of sex in signaling pathways that stimulate the HPA axis. We assessed four time points of ITT application in Balb/c mice. After insulin injection, expression levels of 192 microRNAs and 41 mRNAs associated with the HPA, GH and hypothalamic-pituitary-gonadal (HPG) axes were determined by real-time RT-PCR in the hypothalamus, pituitary and adrenal tissues, as well as blood samples (Raw data accession: https://drive.google.com/drive/folders/10qI00NAtjxOepcNKxSJnQbJeBFa6zgHK?usp=sharing ). Although the ITT is commonly used as a gold standard for evaluating the HPA axis, we found completely different responses between males and females with respect to activation of the HPA axis. While activation of several transcripts in the hypothalamus and pituitary was observed after performing the ITT in males within 10 min, females responded via the pituitary and adrenal immediately and durably over 40 min. Additionally, we found that microRNA alterations precede mRNA responses in the HPA axis. Furthermore, robust changes in the levels of several transcripts including Avpr1b and Avpr2 observed at all time points strongly suggest that transcriptional control of these genes occurs mostly via differential signaling in pituitary and blood between males and females. Male and female HPA axis responses to ITT involve a number of sophisticated regulatory signaling pathways of miRNAs and mRNAs. Our results highlight the first robust markers in several layers of HPA, HPG and GH axis involved in ITT/hypoglycemia stress-induced dynamics.

A view of response and resistance to atomoxetine treatment in children with ADHD: effects of CYP2C19 polymorphisms and BDNF levels.

OBJECTIVE: Although several genes have previously been studied about the treatment of Attention Deficit Hyperactivity Disorder (ADHD), the number of studies investigating the effects of genes on atomoxetine (ATX) treatment is very limited. In this study, we aimed to investigate the effect of CYP2C19 polymorphisms, which have a role in ATX biotransformation, on the treatment response and also to assess whether there is a relationship between BDNF and treatment response in children and adolescents with ADHD. METHODS: One hundred children with ADHD and 100 healthy controls (HCs) were included in this study. The treatment response was assessed 2 months after the start of the ATX treatment. DNA samples from peripheral venous blood were replicated using PCR and analyzed using the ILLUMINA next-generation sequencing method. The resulting fastqs were analyzed using Basespace's Variant Interpreter Program. Plasma BDNF levels were evaluated with ELISA kits. RESULTS: Treatment response was found to be lower in both heterozygous and homozygous carriers of the c.681G > A (CYP2C19*2) polymorphism. When the BDNF level was compared, it was found to be significantly higher in the ADHD group compared to HCs. Also, BDNF has a stronger predictive value for assessing resistance to ATX treatment. CONCLUSIONS: To our knowledge, this is the first study to assess the effects of CYP2C19 polymorphisms and BDNF levels together on ATX treatment in children. Further studies with an extensive population are needed to better understand the effects of CYP2C19 polymorphisms on treatment and side effects, as well as the effects of BDNF levels.

Novel alterations of CC2D1A as a candidate gene in a Turkish sample of patients with autism spectrum disorder.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with large genetic background, but identification of pathogenic variants has proceeded slowly because hundreds of loci are involved in this complex disorder. CC2D1A gene firstly associated with the intellectual disability (ID) in a family with a large deletion. We aimed to contribute to the literature by sequencing this gene and by this way we report novel CC2D1A variations in patients with ASD. METHODS: Forty families who have a child with a diagnosis of ASD were enrolled to the study. DNA samples were obtained from each family member. Bidirectional CC2D1A gene sequencing was performed with CEQ Cycle Sequencing Kit, and the products were analyzed on the Beckman CEQ 8000. All of the genetic analysis was conducted in Erciyes University Genome and Stem Cell Center (GENKOK). RESULTS: According to the sequencing results, we defined new alterations in this gene with two SNPs in exon 15 and 19 (rs747172992 and rs1364074600) in our patients. We found a pathogenic variant in one patient. This variant was located in the acceptor region. Six of the variants were missense mutations. Additionally, six different benign variants were detected in 30 patients; however, they were not associated with ASD. Two patients carried multiple rare variants. CONCLUSION: In vitro and in vivo functional analysis with this gene will help to understand its contribution to ASD pathogenesis. Future studies may help to elucidate the underlying biological mechanisms of these variants leading to the autism phenotype.

Variants in TNF and NOS3 (eNOS) genes associated with sepsis in adult patients.

BACKGROUND: Sepsis is a life-threatening condition caused by a dysregulated host response to infections and is a leading cause of death in hospitalized patients. The present study aimed to elucidate the possible association between sepsis and the tumor necrosis factor (TNF) gene -308G/A (rs1800629) polymorphism, as well as endothelial nitric oxide synthase (eNOS, NOS3) gene -786T/C (rs2070744), 4a/4b (27 bp-VNTR in intron 4, rs61722009) and 894G/T (Glu298Asp, rs1799983) polymorphisms. METHODS: In total, 188 septic adult cases and 188 healthy controls were enrolled. Genomic DNAs from the controls and patients were analyzed by polymerase chain reaction and restriction fragment length polymorphism methods. RESULTS: There were significant associations between the G/G genotype and G allele of the TNF -308G/A (rs1800629) polymorphism in the sepsis group (p < 0.001). The presence of the T/C genotype (p = 0.002) and C allele (p = 0.001) of the -786T/C (rs2070744) was markedly associated with an increased risk of sepsis. However, no significant associations were found with 4a/4b (27 bp-VNTR in intron 4, rs61722009) and 894G/T (Glu298Asp, rs1799983) polymorphisms. Higher 4bGC and lower 4bTT haplotype frequencies were associated with sepsis. CONCLUSIONS: Our results strongly suggest that TNF gene (-308G/A, rs1800629) and NOS3 gene -786T/C (rs2070744) polymorphisms may modify individual susceptibility to sepsis in the Turkish population.

Serum vitamin D, vitamin D binding protein levels and leukocyte vitamin D receptor gene expression in patients with ischaemic stroke.

OBJECTIVE: To investigate the possible contributions of serum 25 hydroxyvitamin D and vitamin D binding protein levels along with leukocyte vitamin D receptor gene expression in patients with ischaemic stroke. METHODS: The randomised controlled single-blind study was conducted at the Mayo Hospital, Lahore, Pakistan, from September 2015 to September 2017, and comprised patients aged 40-75 years with Arbeitsgemeinschaft für Osteosynthesefragen type A2 and A3 per trochanteric fracture. The patients randomised into two equal groups. In Group A, patients were treated by closed reduction and internal fixation with dynamic hip screw, while those in Group B were treated by closed reduction and internal fixation by proximal femoral nail. Follow-up was done at 2nd, 6th and 12th weeks, and at 6th, 9th and 12th month post-operatively. Variables evaluated were frequency of union, surgical time, approximate amount of blood loss and complications. The functional assessment was done by using Harris hip score. SPSS 20 was used for data analysis. RESULTS: Of the 90 subjects, 51 (56.6%) were cases with a mean age of 65.2±14.3 years, and 39 (43.3%) were controls with a mean age of 61.1±16.7 years. There was no difference between the groups with respect to vitamin D deficiency, serum vitamin D binding protein levels and leukocyte vitamin D receptor gene expressions (p>0.05). A negative correlation was found between 25-hydroxyvitamin D levels and the severity of ischaemic stroke (p=0.0342). CONCLUSION: There was a correlation between serum 25-hydroxyvitamin D levels and severity of ischaemic stroke as assessed by the National Institutes of Health Stroke Scale.

A role of the endothelial nitric oxide system in acute renal colic caused by ureteral stone.

BACKGROUND AND AIMS: Endothelial nitric oxide synthase gene polymorphisms play a role in some pathophysiological processes. In this study, the possible effects of endothelial nitric oxide synthase gene polymorphisms on ureteral stone disease in patients who were admitted to the emergency department with severe pain due to renal colic are examined. MATERIALS AND METHODS: The study groups were designed as controls and patients. The control group was formed from the healthy volunteers who applied to the blood center next to the emergency service. The patient group comprised patients who were diagnosed with ureteral stone disease with severe pain. All of the genetic studies were based on extracted peripheral blood samples using the necessary procedures from the Genome and Stem Cell Center at Erciyes University (GENKOK). The data were analyzed with SPSS (IBM, ver 20, United Sate). RESULTS: The study group comprised 62 females and 138 males, and the control group comprised 64 females and 136 males. All of the stones that caused renal colic were found to be localized in the ureters and the ureterovesical junction. The genotypes of the intron 4 polymorphism were found to be as follows: 4a/4a in 10 people, 4b/4a in 115, and 4b/4b in 275 people. The GG genotype of the eNOS-G894T polymorphism was found in 108 patients in the study group and in117 of the healthy individuals. There was no statistically significant difference between the two groups regarding these data. CONCLUSION: Although this study is the first in the literature to examine the relationship between renal colic and endothelial nitric oxide synthase gene polymorphisms, our study demonstrated that no relation was found.

Anatomical landmarks of mandibular interforaminal region related to dental implant placement with 3D CBCT: comparison between edentulous and dental mandibles.

BACKGROUND: Anterior mandibular (interforaminal) region is important in implant applications as it serves a basis for neurovascular bedding and holds the prosthesis for patients. Treatment planning for dental implant patients is often complicated by the unknown extent of the anterior loop of the neurovascular bundle. Anatomical structures including mandibular incisive canal (MIC) and lingual foramen (LF) should also be examined as part of the detailed analysis for their neurovascular structures. This study aimed to detect the positions of LF and MIC as well as the prolongation of interforaminal region in Anatolian population to supply the reference data of the surgical safe zone in chin for the clinicians. MATERIALS AND METHODS: Mandibles of 70 adult specimens (35 edentulous + 35 dentate) were retrieved from the Department of Anatomy, Ege University. Images of the dry mandibles were obtained using a cone beam computed tomography unit applying a standardized exposure protocol. Afterwards, mandibles were sawn into vertical sections according to the respective tomographic cross-sections. Images were evaluated for the absence/presence of the MIC, its dimensions and antero-posterior length for both edentulous and dentate groups. In addition; the presence, number, location, labial canal and LF diameter and height of the LF were determined for both groups. RESULTS: The MIC was observed in 80 and 68.6% of the dentate and edentulous groups, consecutively (p > 0.05). The MIC continued towards the incisor region in a slightly downward direction. The LF was observed in all dentate mandibles (100%), while it was present in 94.3% of the edentulous mandibles (p > 0.05). For the dentate group, 62.9% of the specimens had two foramens and 20% had three foramens in the mandibular midline. Mean length of the MIC in dentate groups and edentulous groups was measured as 2.55 ± 0.809 and 3.08 ± 1.745 mm, respectively. Well-defined MIC mean diameter in dentate groups and edentulous groups were measured as 2.44 ± 0.702 and 2.35 ± 0.652 mm, respectively. Significant difference was found between dentate and edentulous group in most of the parameters except for the LF and the diameter of the MIC (p > 0.05). The correlation between observers' measurements ranged between 0.742 and 0.993 for all anatomical landmarks and mandible groups. CONCLUSION: The MIC and LF are associated with neurovascular bundle variations in number, location and size. Therefore, clinicians should determine each of these anatomical structures on a case-by-case basis to recognize their presence and to take measures for the possible implications of various treatment options. These guidelines included leaving a 2 mm safety zone between an implant and the coronal aspect of the neurovascular bundle. To avoid neurovascular injury during surgery in the interforaminal area, guidelines were developed with respect to validating the presence of an anterior loop of the neurovascular bundle.

Mutant adenosine deaminase 2 in a polyarteritis nodosa vasculopathy.

BACKGROUND: Polyarteritis nodosa is a systemic necrotizing vasculitis with a pathogenesis that is poorly understood. We identified six families with multiple cases of systemic and cutaneous polyarteritis nodosa, consistent with autosomal recessive inheritance. In most cases, onset of the disease occurred during childhood. METHODS: We carried out exome sequencing in persons from multiply affected families of Georgian Jewish or German ancestry. We performed targeted sequencing in additional family members and in unrelated affected persons, 3 of Georgian Jewish ancestry and 14 of Turkish ancestry. Mutations were assessed by testing their effect on enzymatic activity in serum specimens from patients, analysis of protein structure, expression in mammalian cells, and biophysical analysis of purified protein. RESULTS: In all the families, vasculitis was caused by recessive mutations in CECR1, the gene encoding adenosine deaminase 2 (ADA2). All the Georgian Jewish patients were homozygous for a mutation encoding a Gly47Arg substitution, the German patients were compound heterozygous for Arg169Gln and Pro251Leu mutations, and one Turkish patient was compound heterozygous for Gly47Val and Trp264Ser mutations. In the endogamous Georgian Jewish population, the Gly47Arg carrier frequency was 0.102, which is consistent with the high prevalence of disease. The other mutations either were found in only one family member or patient or were extremely rare. ADA2 activity was significantly reduced in serum specimens from patients. Expression in human embryonic kidney 293T cells revealed low amounts of mutant secreted protein. CONCLUSIONS: Recessive loss-of-function mutations of ADA2, a growth factor that is the major extracellular adenosine deaminase, can cause polyarteritis nodosa vasculopathy with highly varied clinical expression. (Funded by the Shaare Zedek Medical Center and others.).

Serum micro-rna profiles in patients with autosomal dominant polycystic kidney disease according to hypertension and renal function.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a common hereditary disorder with unclear disease mechanism. Currently, overt hypertension and increased renal volume are the best predictors of renal function. In this study, we assessed the usefulness of selected circulating microRNAs (miRs) to predict disease progress in a cohort with ADPKD. METHODS: Eighty ADPKD patients (44.6 ± 12.7 years, 40% female, 65% hypertensive) and 50 healthy subjects (HS; 45.4 ± 12.7, 44% female) were enrolled in the study. Serum levels of 384 miRs were determined by Biomark Real Time PCR. Groups were compared using the limma method with multiple-testing correction as proposed by Smyth (corrected p < 0.01 considered significant). RESULTS: Comparing ADPKD to HS, we found significant differences in blood levels of 18 miRs (3 more and 15 less abundant). Of these, miR-3907, miR-92a-3p, miR-25-3p and miR-21-5p all rose while miR-1587 and miR-3911 decreased as renal function declined in both cross-sectional and longitudinal analysis. Using ROC analysis, an increased baseline miR-3907 in the circulation predicted a > 10% loss of GFR over the following 12 months (cut-off >2.2 AU, sensitivity 83%, specificity 78%, area 0.872 [95% CI: 0.790-0.953, p < 0.001]). Adjusting for age and starting CKD stage using multiple binary logistic regression analysis did not abrogate the predictive value. CONCLUSION: Increased copy numbers of miR-3907 in the circulation may predict ADPKD progression and suggest pathophysiological pathways worthy of further study.

Thiopental versus ketofol in paediatric sedation for magnetic resonance imaging: A randomized trial.

OBJECTIVE: To compare the efficiency of intravenous thiopental against intravenous ketamine-propofol combination in paediatric sedation for magnetic resonance imaging. METHODS: This prospective study was conducted at Ondokuz Mayis University Hospital, Samsun, Turkey, from July 1, 2014, to January 1, 2015, and comprised children aged 1 month to 12 years undergoing elective magnetic resonance imaging who were randomly assigned to two equal groups. Group I received thiopental 3 mg/kg intravenously followed by an additional dose of thiopental 1 mg/kg to achieve a Ramsay sedation score of 4. Group II received ketofol, a 1:1 mixture of ketamine 10 mg/mL and propofol 10 mg/mL, in a single syringe intravenously at a dose of 0.5 mg/kg at 1 minute intervals and titrated to reach a Ramsay sedation score of 4. The groups were compared for total drug dose, time to sedation, recovery time, total sedation time, and adverse effects. Data was analysed using SPSS 22. RESULTS: There were 120 children in the study; 60(50%) in each group. The time to sedation was significantly longer with ketofol than thiopental (p<0.01). The mean recovery time was significantly shorter with thiopental than with ketofol (p<0.01). Total sedation time was significantly longer with ketofol than thiopental (p<0.01). Overall, 17(28.3%) ketofol patients had adverse events, whereas no thiopental patients had adverse events (p<0.0001). CONCLUSIONS: Thiopental had a comparable effectiveness with shorter anaesthesia inductions and recovery times than ketofol. Intravenous thiopental can be an effective and safe alternative drug in sedating children undergoing magnetic resonance imaging.

Genetic expressions of thrombophilic factors in patients with Sheehan's syndrome.

PURPOSE: The aim of this study was to evaluate the roles of factors associated with coagulation in the etiology and pathogenesis of Sheehan's syndrome (SS) which is a frequent cause of hypopituitarism in underdeveloped and developing regions of the world. METHODS: Mean prothrombin time (PT), activated partial thromboplastin time (APTT) and expression levels of genes, which included methylenetetrahydrofolate reductase (MTHFR), angiotensin I converting enzyme (ACE), coagulation factor V (FV), FVII, FVIII and FIX in 44 patients with SS were compared with 43 healthy subjects. RESULTS: The mean expression level of the ACE gene was significantly lower, while that of the FV gene was significantly higher in the patients with SS. No significant difference was found between the patients with SS and the healthy subjects in the comparisons of the remaining gene expression values, as well as in the PT and APTT values. CONCLUSION: An increased expression of the FV gene may be a contributing factor for the development of SS in some patients. Further studies are required to clarify the roles of coagulation disorders in the development of SS.

The roles of CC2D1A and HTR1A gene expressions in autism spectrum disorders.

Classical autism belongs to a group of heterogeneous disorders known as autism spectrum disorders (ASD). Autism is defined as a neurodevelopmental disorder, characterized by repetitive stereotypic behaviors or restricted interests, social withdrawal, and communication deficits. Numerous susceptibility genes and chromosomal abnormalities have been reported in association with autism but the etiology of this disorder is unknown in many cases. CC2D1A gene has been linked to mental retardation (MR) in a family with a large deletion before. Intellectual disability (ID) is a common feature of autistic cases. Therefore we aimed to investigate the expressions of CC2D1A and HTR1A genes with the diagnosis of autism in Turkey. Forty-four autistic patients (35 boys, 9 girls) and 27 controls were enrolled and obtained whole blood samples to isolate RNA samples from each participant. CC2D1A and HTR1A gene expressions were assessed by quantitative Real-Time PCR (qRT-PCR) in Genome and Stem Cell Center, Erciyes University. Both expressions of CC2D1A and HTR1A genes studied on ASD cases and controls were significantly different (p < 0.001). The expression of HTR1A was undetectable in the ASD samples. Comparison of ID and CC2D1A gene expression was also found statistically significant (p = 0.028). CC2D1A gene expression may be used as a candidate gene for ASD cases with ID. Further studies are needed to investigate the potential roles of these CC2D1A and HTR1A genes in their related pathways in ASD.

Effects of P6 acustimulation with the ReliefBand on postoperative nausea and vomiting in patients undergoing gynecological laparoscopy.

We investigated the effects of P6 acustimulation on the incidence of postoperative nausea and vomiting (PONV), antiemetic requirements, and side effects in patients undergoing gynecological laparoscopy with a high risk of PONV. Sixty-two patients were divided into 2 groups randomly: a ReliefBand group (RB group) and a sham ReliefBand group (S group). The P6 acustimulation device (ReliefBand Medical Technologies LLC, Chicago, Illinois) was wrapped around the wrists of the patients 15 to 30 minutes before the operation and activated before the induction of anesthesia. The patients' hemodynamic parameters, nausea scale (verbal rating scale), pain scale (visual analogue scale), PONV score, rescue antiemetics, analgesic requirements, adverse effects, and satisfaction scores in the first 24 hours were recorded. The verbal rating scale scores in the early postoperative period and 6 hours postoperatively were significantly higher in the RB group than in the S group. The PONV scores at 15 minutes and at 6 and 12 hours postoperatively were significantly higher in the S group than in the RB group. The verbal rating scale scores of the patients with higher Apfel risk scores (3 or 4 points) in the early postoperative period and 6 hours postoperatively were significantly lower in the RB group than in the S group. The PONV scores of the patients with high Apfel risk scores at 15 minutes and at 6 and 12 hours postoperatively were significantly lower in the RB group than in the S group. The number of patients and doses of antiemetics required were significantly lower in the RB group than in the S group. Patient satisfaction scores were significantly higher in the RB group than in the S group. Acustimulation with the P6 ReliefBand decreased the severity of nausea, PONV scores, and antiemetic requirements in the early postoperative period of gynecological laparoscopy patients.

Comparison of placebo and intrauterine lidocaine with/or without rectal diclofenac sodium suppositories used in office endometrial biopsy.

OBJECTIVE: To compare the effects of intrauterine lidocaine, intrauterine lidocaine plus rectal diclofenac, and a placebo on analgesia and to determine the satisfaction of patients and surgeons in cases of endometrial biopsy. METHODS: The double-blind, randomised, placebo-controlled study was conducted in the Department of Obstetrics and Gynaecology of the Ondokuz Mayis University, Samsun,Turkey, from April 2013 to January 2014, and comprised patients scheduled for in-office endometrial biopsy.They were divided into three groups: Group P, 5ml of 0.9% saline intrauterine; Group L, 5ml of 2% lidocaine intrauterine; and Group LD, 5ml of 2% lidocaine intrauterine ± 10min before the procedure plus 50mg of rectal diclofenac sodium. Haemodynamic changes and visual analogue scale scores were recorded during the preoperative period, when the cervix was grasped with a tenaculum, immediately after intrauterine instillation, during uterine curettage and at postoperative 10 min. The patient and the surgeon were questioned about their satisfaction 15 min after the procedure. SPSS 21 was used for statistical analysis. RESULTS: The 90 patients in the study were divided into three equal groups of 30(33.33%) each. There were no statistically significant inter-group differences in age, bodyweight, parity, number of postmenopausal patients, haemodynamic parameters and American Society of Anesthesiologists scores (p>0.05 in all categories). In Group P, the visual analogue scale score estimated when the cervix was grasped with the tenaculum was lower when compared with Group L and Group LD (p=0.029 and p=0.007, respectively). At other measurement time points, the scores did not differ between the groups. The groups did not differ with respect to patient and surgeon satisfaction and complication rates (p>0.05). CONCLUSION: Intrauterine lidocaine or intrauterine lidocaine plus rectal diclofenac application had no effect on visual analogue scale scores, patient satisfaction and vasovagal reaction.

The effects of music, white noise, and ambient noise on sedation and anxiety in patients under spinal anesthesia during surgery.

PURPOSE: To compare effects of music, white noise, and ambient (background) noise on patient anxiety and sedation. DESIGN: Open, parallel, and randomized controlled trial. METHODS: Seventy-five patients aged 18 to 60 years who were scheduled for surgical procedures under spinal anesthesia were randomly assigned to ambient noise (Group O), white noise (Group B), or music groups (Group M). We evaluated patients' anxiety and sedation levels via the Observer's Assessment of Alertness/Sedation (OAA/S) scale and the State-Trait Anxiety Inventory (STAI) questionnaire. FINDING: At 5 minutes before surgery, the STAI-State Anxiety Inventory (SA) value was significantly lower in Group M than the other groups. At 30-minute recovery, Group M showed significantly lower STAI-SA values than the other groups. Patient satisfaction was highest in Group M. OAA/S values were not significantly different between groups during any period (P > .05). CONCLUSIONS: We suggest that patient-selected music reduces perioperative anxiety and contributes to patient satisfaction during the perioperative period.

Robot-related injuries in the workplace: An analysis of OSHA Severe Injury Reports.

Industrial robots are increasingly commonplace, but research on prototypical accidents and injuries has been sparse, hindering evidence-based safety strategies. Using Severe Injury Reports (SIRs) from the U.S. Occupational Safety and Health Administration (OSHA), we identified 77 robot-related accidents from 2015-2022. Of these, 54 involved stationary robots, resulting in 66 injuries, mainly finger amputations and fractures to the head and torso. Mobile robots caused 23 accidents, leading to 27 injuries, mainly fractures to the legs and feet. A two-stage deductive-inductive thematic analysis was performed using text data from the final narratives in the reports to discover patterns in tasks, precipitating mechanisms, and contributing factors. Findings highlight the need for guards and collision avoidance systems that detect individual extremities. Post-contact strategies should focus on mitigating finger amputations. More structured and detailed narratives in the SIRs are needed.

Autism-Related Cc2d1a Heterozygous Mice: Increased Levels of miRNAs Retained in DNA/RNA Hybrid Profiles (R-Loop).

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with a highly variable expression of phenotypes (restricted interest or activity and repetitive behavior in communication and social interactions), genes (mutation), markers (alteration of transcription) and pathways. Loss of function of the CC2D1A gene appears to primarily affect the brain, leading to a range of behavioral problems in humans. In our study published in 2020, we found that the expressions of miR-19a-3p, miR-361-5p, miR-150-5p, miR-3613-3p, miR-126-3p and miR-499a-5p were downregulated in the serum samples of autistic patients, their families and mouse models (Cc2d1a +/- and valproic acid treated males). Here, acquired non-Mendelian hereditary character in a genetically defined mouse model of autism (Cc2d1a +/-) correlates with the transcriptional alteration of five miRNAs. We seek to test the hypothesis that miRNA levels vary by changes in RNA/DNA structure during development, thereby creating transcription alteration and cell memory. Behavioral tests were conducted on the offspring of Cc2d1a (+/-) mutant and control mice, such as novel object, social interaction, marble burying and tail suspension behavior. Two RNA fractions were isolated from mouse hippocampal tissues and sperm cells via standard TRIzol extraction: free RNA and the fraction of RNA bound to DNA in the form of a DNA/RNA hybrid (R-loop). The expression levels of miR-19a-3p, miR-361-5p, miR-150-5p, miR-126-3p and miR-499a-5p were investigated by quantitative real-time RT-PCR. We report differences in the distribution of five miRNAs in the hippocampus between male and female mice, particularly in colonies of Cc2d1a (+/-) mice. Furthermore, the number of miRNAs engaged in the DNA/RNA hybrid fraction is generally higher in the mutant pedigree than in the control group. On the other hand, in sperm, both fractions are at lower levels than in controls. R-loops contribute to the physiology and pathology of organisms including human disease. Here, we report a variation in five miRNA levels between gender and tissue. Our results suggest that the transcription levels of these five miRNAs are directly regulated by their RNA.