Cytomegalovirus reactivation in ulcerative colitis patients: Early indicators.

Background: The association of. c: ytomegalovirus (CMV) infection with ulcerative colitis (UC) still remains a controversial topic for the clinicians. Aim: In this study, we aimed to elucidate the CMV infection related parameters in the exacerbation of UC. Material and Methods: In this study, 812 UC patients who have admitted to our institution between June 2008 and November 2020 were analyzed retrospectively. CMV infection was diagnosed by the detection of CMV DNA with polymerase chain reaction (PCR) in tissue biopsies with presence of clinical colitis symptoms. CMV negative UC patient group was defined as UC activation group with negative PCR results. Result: A total of 153 patients met the inclusion criteria during the study period, with a median age of 41.8 years. CMV PCR positivity had been detected in tissue biopsy in 43 (28.1%) UC patients. CMV-positive patients had a statistically significant higher frequency of steroid resistance, treatment with azathioprine, longer disease duration, longer remission, and hospitalization day. The mean C-reactive protein (CRP) level, platelet to lymphocyte ratio (PLR) were higher, and mean albumin level was lower in CMV positive patients, with statistically significance. Also, colectomy and anti-tumor necrosis factor-α (TNF-α) therapy were more frequent in CMV-reactivated group in long-term follow-up. In a multivariable model, steroid resistance, treatment with azathioprine, long disease duration, low albumin value was independently associated with colonic CMV infection. Conclusion: Steroid resistance, treatment with azathioprine, long disease duration, low albumin levels were significant risk factors for CMV colitis, among patients with UC activation.

Bilateral sagittal split ramus osteotomy using a conventional osteotome-hammer and a magnetic mallet device: an in vitro comparison.

OBJECTIVE: The conventional chisel osteotome technique (CCOT) and the magnetic mallet osteotome technique (MMOT) with a newly manufactured custom osteotome tip for the magnetic mallet device (MMD) were compared to determine whether magneto-dynamic osteotomies are as reliable for orthognathic surgery as the conventional method. MATERIALS AND METHODS: A custom osteotome tip compatible with a magnetic mallet device was manufactured. Thirty-two fresh 1-year-old sheep hemi-mandibles were chosen for osteotomy procedures to achieve the most human-like results. Sagittal split ramus osteotomies were performed, and lingual fracture pattern (LFP), basis split pattern (BSS), duration of sagittal split osteotomy, and alveolar inferior nerve injury were investigated macroscopically. RESULTS: Six of the defined fracture schemes were observed out of the 27 lingual split patterns. After LFP and BSS evaluation, the unfavorable fracture counts for MMOT and CCOT are 3 and 4, respectively. The macroscopic nerve damage assessment for both groups is 2 for MMOT and 1 for CCOT. Although the average durations are similar in both groups, the difference between MMOT samples is closer. None above showed a significant difference. CONCLUSIONS: MMOT was evaluated as a reliable alternative to CCOT in bilateral sagittal split ramus osteotomy based on the lingual and basis split patterns, duration, and nerve damage findings.

Evaluation of inter-maxillary fixation techniques for multi-piece Le Fort I osteotomies using finite element analysis.

OBJECTIVE: A strong postoperative occlusal relationship is essential for the long-term stability of the jaw relations post orthognathic surgery. In multi-piece Le Fort I osteotomy, obtaining a satisfactory inter-maxillary fixation (IMF) of the mobilized segments in the correct position and according to the preoperative plan is difficult. Herein, we aimed to evaluate three different IMF techniques (tooth-supported, bone-supported, or hybrid IMF) using finite element analysis (FEA) of the occlusal surfaces of four models: three multi-piece (lateral incisor-canine, central incisor-central incisor, and canine-first premolar) and a single one-piece Le Fort I osteotomy scenario. MATERIALS AND METHODS: Three different IMF techniques were applied separately to three different multi-piece models and a single one-piece Le Fort I model designed using related software. Simulation brought the lower and upper jaw models to the planned occlusion. Each model's occlusal force was applied to determine their distributions under 100 N, 300 N, and 800 N loads. Forces on the maxilla and mandible during fixation, the effect of these forces on the force distribution in the occlusion, and the accumulated stresses in these regions were determined with Algor Fempro and Rhinoceros software to determine the ideal fixation method. Data obtained were interpreted and evaluated according to the advantages and disadvantages of the actual surgical scenario. RESULTS: In all four models studied, the hybrid IMF technique was found to be the ideal IMF technique, followed by the teeth- and bone-supported IMF techniques. CONCLUSIONS: FEA allows the manipulation of single parameters, which clinical methods cannot obtain, thereby allowing each to be examined separately. Further clinical trials are required to validate these findings.

Analysis of select esthetic nasal parameters in virtually planned orthognathic patients.

PURPOSE: Bony changes after orthognathic surgery are always followed by changes of the overlying soft tissues. Therefore, morphologic changes of the nose may be expected after procedures involving the maxilla. The purpose of this study was to evaluate the changes in the nasal region due to orthognathic surgery using computed tomography (CT) images of virtually planned patients. METHODS: 35 patients who underwent Le Fort I osteotomy, with or without bilateral sagittal split osteotomy, were included. 3D measurements on preoperative and postoperative images were performed and analyzed. RESULTS: The results revealed that aesthetically acceptable results can be achieved by orthognathic surgery alone. CONCLUSIONS: According to the results of this study, it can be concluded that it is best to reserve decisions on rhinoplasty to the post-orthognathic period.

Genome-wide association study in a rat model of temperament identifies multiple loci for exploratory locomotion and anxiety-like traits.

Common genetic factors likely contribute to multiple psychiatric diseases including mood and substance use disorders. Certain stable, heritable traits reflecting temperament, termed externalizing or internalizing, play a large role in modulating vulnerability to these disorders. To model these heritable tendencies, we selectively bred rats for high and low exploration in a novel environment [bred High Responders (bHR) vs. Low Responders (bLR)]. To identify genes underlying the response to selection, we phenotyped and genotyped 538 rats from an F2 cross between bHR and bLR. Several behavioral traits show high heritability, including the selection trait: exploratory locomotion (EL) in a novel environment. There were significant phenotypic and genetic correlations between tests that capture facets of EL and anxiety. There were also correlations with Pavlovian conditioned approach (PavCA) behavior despite the lower heritability of that trait. Ten significant and conditionally independent loci for six behavioral traits were identified. Five of the six traits reflect different facets of EL that were captured by three behavioral tests. Distance traveled measures from the open field and the elevated plus maze map onto different loci, thus may represent different aspects of novelty-induced locomotor activity. The sixth behavioral trait, number of fecal boli, is the only anxiety-related trait mapping to a significant locus on chromosome 18 within which the Pik3c3 gene is located. There were no significant loci for PavCA. We identified a missense variant in the Plekhf1 gene on the chromosome 1:95 Mb QTL and Fancf and Gas2 as potential candidate genes that may drive the chromosome 1:107 Mb QTL for EL traits. The identification of a locomotor activity-related QTL on chromosome 7 encompassing the Pkhd1l1 and Trhr genes is consistent with our previous finding of these genes being differentially expressed in the hippocampus of bHR vs. bLR rats. The strong heritability coupled with identification of several loci associated with exploratory locomotion and emotionality provide compelling support for this selectively bred rat model in discovering relatively large effect causal variants tied to elements of internalizing and externalizing behaviors inherent to psychiatric and substance use disorders.

High-throughput splicing assays identify missense and silent splice-disruptive POU1F1 variants underlying pituitary hormone deficiency.

Pituitary hormone deficiency occurs in ∼1:4,000 live births. Approximately 3% of the cases are due to mutations in the alpha isoform of POU1F1, a pituitary-specific transcriptional activator. We found four separate heterozygous missense variants in unrelated individuals with hypopituitarism that were predicted to affect a minor isoform, POU1F1 beta, which can act as a transcriptional repressor. These variants retain repressor activity, but they shift splicing to favor the expression of the beta isoform, resulting in dominant-negative loss of function. Using a high-throughput splicing reporter assay, we tested 1,070 single-nucleotide variants in POU1F1. We identified 96 splice-disruptive variants, including 14 synonymous variants. In separate cohorts, we found two additional synonymous variants nominated by this screen that co-segregate with hypopituitarism. This study underlines the importance of evaluating the impact of variants on splicing and provides a catalog for interpretation of variants of unknown significance in POU1F1.

Modified high-level Le Fort I advancement without malar augmentation: assessment of effect on midfacial aesthetics.

The 'beauty arch', an aesthetic feature of the midface, is a double-S-shaped curve that extends downward from the lateral canthus. This retrospective study evaluated whether modified high Le Fort I advancement (combined with impaction or down-grafting) without malar augmentation can approximate a patient's 'ideal' beauty arch (IBA). Pre- and postoperative profile (natural head position) photographs for 36 patients with midfacial hypoplasia were aligned digitally. For each individual, standardized methods were used to identify landmarks and draw the preoperative real beauty arch (RBA), postoperative RBA, and IBA. Distances from a defined landmark to each arch were measured and means were compared. The mean advancement range was 4.2 ± 2.2 mm, and the mean pre- and postoperative RBA distances were significantly different (138.7 ± 24.1 vs 145.0 ± 25.8 pixels, respectively; P = 0.0001). In the impaction and down-grafting subgroups, there was no significant correlation between amount of maxillary movement and the difference between pre- and postoperative RBA distances (P > 0.05 for both). The postoperative RBA was satisfactorily close to the IBA in 35 cases (97.2%); one patient required later augmentation. The findings suggest that modified high Le Fort I advancement surgery without malar augmentation provides satisfactory malar projection for most patients with maxillary hypoplasia.

The origin of SARS-CoV-2 in Istanbul: Sequencing findings from the epicenter of the pandemic in Turkey.

OBJECTIVE: Turkey is one of the latest countries that COVID-19 disease was reported, with the first case on March 11, 2020, and since then, Istanbul became the epicenter of the pandemic in Turkey. Here, we reveal sequences of the virus isolated from three different patients with various clinical presentations. METHODS: Nasopharyngeal swab specimens of the patients were tested positive for the COVID-19 by qRT-PCR. Viral RNA extraction was performed from the same swab samples. Amplicon based libraries were prepared and sequenced using the Illumina NextSeq platform. Raw sequencing data were processed for variant calling and generating near-complete genome sequences. All three genomes were evaluated and compared with other worldwide isolates. RESULTS: The patients showed various clinics (an asymptomatic patient, patient with mild disease, and with severe pulmonary infiltration). Amplicon-based next-generation sequencing approach successfully applied to generate near-complete genomes with an average depth of 2.616. All three viral genomes carried the D614G variant (G clade according to GISAID classification) with implications for the origin of a spread first through China to Europe then to Istanbul. CONCLUSION: Here, we report the viral genomes circulating in Istanbul for the first time. Further sequencing of the virus isolates may enable us to understand variations in disease presentation and association with viral factors if there is any. In addition, the sequencing of more viral genomes will delineate the spread of disease and will guide and ease the necessary measures taken to stem the spread of the novel coronavirus.

A novel homozygous mutation with different clinical presentations in 2 IRAK-4-deficient siblings: first case with recurrent salmonellosis and non-hodgkin lymphoma

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Genetics of Combined Pituitary Hormone Deficiency: Roadmap into the Genome Era.

The genetic basis for combined pituitary hormone deficiency (CPHD) is complex, involving 30 genes in a variety of syndromic and nonsyndromic presentations. Molecular diagnosis of this disorder is valuable for predicting disease progression, avoiding unnecessary surgery, and family planning. We expect that the application of high throughput sequencing will uncover additional contributing genes and eventually become a valuable tool for molecular diagnosis. For example, in the last 3 years, six new genes have been implicated in CPHD using whole-exome sequencing. In this review, we present a historical perspective on gene discovery for CPHD and predict approaches that may facilitate future gene identification projects conducted by clinicians and basic scientists. Guidelines for systematic reporting of genetic variants and assigning causality are emerging. We apply these guidelines retrospectively to reports of the genetic basis of CPHD and summarize modes of inheritance and penetrance for each of the known genes. In recent years, there have been great improvements in databases of genetic information for diverse populations. Some issues remain that make molecular diagnosis challenging in some cases. These include the inherent genetic complexity of this disorder, technical challenges like uneven coverage, differing results from variant calling and interpretation pipelines, the number of tolerated genetic alterations, and imperfect methods for predicting pathogenicity. We discuss approaches for future research in the genetics of CPHD.

Intrusion of a Liquid Droplet into a Powder under Gravity.

Intrusion of a liquid droplet into a hexagonal close-packed array of spheres under gravity is investigated using analytical methods and volume-of-fluid simulations. Four regimes of ultimate fluid behavior are identified: (A) no liquid imbibition into the bed, (B) trapping of liquid high in the bed, (C) liquid descending to the bottom of the bed, and (D) liquid spreading around the surface of all particles. These regimes are mapped based on the contact angle and Bond number of the system. Many aspects of the dynamics and ultimate liquid behavior are captured using a simplified model of a mass of liquid moving under gravity in a vertical capillary of undulating cross-sectional area. This simplified model is used to form momentum transport equations with four forms of nondimensional time, which are shown to collapse the simulation data with different fluid parameters in different regimes.

Genome-wide studies of von Willebrand factor propeptide identify loci contributing to variation in propeptide levels and von Willebrand factor clearance.

UNLABELLED: Essentials Variants at ABO, von Willebrand Factor (VWF) and 2q12 contribute to the variation in plasma in VWF. We performed a genome-wide association study of plasma VWF propeptide in 3,238 individuals. ABO, VWF and 2q12 loci had weak or no association or linkage with plasma VWFpp levels. VWF associated variants at ABO, VWF and 2q12 loci primarily affect VWF clearance rates. SUMMARY: Background Previous studies identified common variants at the ABO and VWF loci and unknown variants in a chromosome 2q12 linkage interval that contributed to the variation in plasma von Willebrand factor (VWF) levels. Whereas the association with ABO haplotypes can be explained by differential VWF clearance, little is known about the mechanisms underlying the association with VWF single-nucleotide polymorphisms (SNPs) or with variants in the chromosome 2 linkage interval. VWF propeptide (VWFpp) and mature VWF are encoded by the VWF gene and secreted at the same rate, but have different plasma half-lives. Therefore, comparison of VWFpp and VWF association signals can be used to assess whether the variants are primarily affecting synthesis/secretion or clearance. Methods We measured plasma VWFpp levels and performed genome-wide linkage and association studies in 3238 young and healthy individuals for whom VWF levels had been analyzed previously. Results and conclusions Common variants in an intergenic region on chromosome 7q11 were associated with VWFpp levels. We found that ABO serotype-specific SNPs were associated with VWFpp levels in the same direction as for VWF, but with a much lower effect size. Neither the association at VWF nor the linkage on chromosome 2 previously reported for VWF was observed for VWFpp. Taken together, these results suggest that the major genetic factors affecting plasma VWF levels, i.e. variants at ABO, VWF and a locus on chromosome 2, operate primarily through their effects on VWF clearance.

The use of HbA1c as an aid in the diagnosis of gestational diabetes mellitus.

The ability of HbA1c was evaluated in the diagnosis of gestational diabetes mellitus (GDM) and for the implications of its use in clinical practice. A total of 339 pregnant women with an estimated gestational age of 24-28 weeks were evaluated for GDM using an oral glucose tolerance test (OGTT) based on International Association of Diabetes and Pregnancy Study Group (IADPSG) criteria. A ROC curve was drawn to determine the sensitivity and specificity of HbA1c in detecting GDM. An HbA1c cut-off value of ≥ 5.2% had sensitivity of 64.15% and specificity of 67.48% in diagnosing GDM, and a positive predictive value of 26.77%. Using two cut-offs in the 'rule-in and rule-out' algorithm, 94.4% of the GDM cases would have been detected but 33% (43 of the 130) women would had been misclassified. HbA1c is not suitable to use alone for the diagnosis of GDM and is not useful in decreasing the need for OGT testing.

The value of transvaginal sonography in detecting endometrial pathologies in postmenopausal women with or without bleeding.

AIM: The aim of this study was to estimate the incidence of endometrial pathologies and compare the findings in postmenopausal women with or without bleeding who had endometrial thickness ≥5 mm. METHODS: Between January 2010 and December 2012 medical records of postmenopausal patients who underwent endometrial biopsy were reviewed retrospectively. 91 patients who presented with postmenopausal bleeding (Group A) with an endometrial thickness equal to or greater than 5 mm and 44 patients with an incidental finding of increased endometrial thickness (≥5 mm) on ultrasound without bleeding (Group B) were included in the study. RESULTS: The mean endometrial thickness of patients in group A (9.3±4.6) was significantly lower than women in group B (11±4.6). Seven (7.7%) cases of endometrial hyperplasia and 6 (6.6%) cases of endometrial carcinoma were detected in women with bleeding, 2 (4.5%) cases of endometrial hyperplasia and no cases of endometrial carcinoma were diagnosed in group B women. The prevalence of endometrial carcinoma associated with endometrial thickness in group A women whereas we cannot see this relation in group B women. The mean endometrial thickness was highest in women with the histopathologic diagnosis of polyps in this group. CONCLUSION: In postmenopausal women with bleeding, the risk of endometrial carcinoma increases with increasing endometrial thickness; however, the use of endometrial thickness as a screening test for endometrial carcinoma may not be effective in women without bleeding. 6.5 mm cut-off seems to be acceptable thickness for polyp detection in postmenopausal women with bleeding.

Genome-wide association study and meta-analysis of intraocular pressure.

Elevated intraocular pressure (IOP) is a major risk factor for glaucoma and is influenced by genetic and environmental factors. Recent genome-wide association studies (GWAS) reported associations with IOP at TMCO1 and GAS7, and with primary open-angle glaucoma (POAG) at CDKN2B-AS1, CAV1/CAV2, and SIX1/SIX6. To identify novel genetic variants and replicate the published findings, we performed GWAS and meta-analysis of IOP in >6,000 subjects of European ancestry collected in three datasets: the NEI Glaucoma Human genetics collaBORation, GLAUcoma Genes and ENvironment study, and a subset of the Age-related Macular Degeneration-Michigan, Mayo, AREDS and Pennsylvania study. While no signal achieved genome-wide significance in individual datasets, a meta-analysis identified significant associations with IOP at TMCO1 (rs7518099-G, p = 8.0 × 10(-8)). Focused analyses of five loci previously reported for IOP and/or POAG, i.e., TMCO1, CDKN2B-AS1, GAS7, CAV1/CAV2, and SIX1/SIX6, revealed associations with IOP that were largely consistent across our three datasets, and replicated the previously reported associations in both effect size and direction. These results confirm the involvement of common variants in multiple genomic regions in regulating IOP and/or glaucoma risk.

Xiphoid syndrome: an uncommon occupational disorder.

We report a case of a 45-year-old man, complaining of swelling and pain in his epigastric region for the last 3 years. According to his medical history, he had undergone various investigations and treatments for gastro-oesophageal reflux, without relief. He had had a history of chronic repeated microtraumas to his sternum during 9 years of working as a carpenter, as a result of placing wood against his anterior chest wall and pushing the former into a plank cutting machine. On examination, a tender swelling was palpable as an immobile, hard mass showing minimal protrusion under the skin on the xiphoid process. He was diagnosed as having xiphoid syndrome. We prescribed anti-inflammatory medication and advised him to avoid pressure on his anterior chest wall, especially on the sternum, while cutting wood. At follow-up, the symptoms were relieved. Xiphoid syndrome may be seen in people performing hard physical work who incur sustained pressure or friction on their anterior chest wall. The case emphasizes the importance of the occupational history as well as clinical and radiological investigation of unusual conditions as mentioned above.

Granular cell tumor of the breast.

Granular cell tumor is a rare benign soft-tissue neoplasm, usually appearing in the tongue, the oral cavity and subcutaneous tissue. Examples of granular cell tumor of breast are encountered in 30-50-year-old women. Herein, we report ultrasonographic and mammographic imaging findings of a 59 years old woman presented with a painless palpable mass, which was diagnosed as granular cell tumor on histopathological analysis.

Efficacy of a modified sequential therapy including bismuth subcitrate as first-line therapy to eradicate Helicobacter pylori in a Turkish population.

BACKGROUND: Eradication rates of Helicobacter pylori with standard triple therapy are not satisfactory. Sequential therapy is an alternative method to overcome this problem. OBJECTIVES: The aim of this study was to assess efficacy of a modified sequential therapy with the addition of a bismuth preparation, as first-line treatment in the eradication of H. pylori infection. MATERIALS AND METHODS: One hundred and forty-two H. pylori-positive patients were included in the study. Patients were given a 14-day sequential therapy program consisting of pantoprazole, 40 mg (b.i.d. for 14 days); colloidal bismuth subcitrate, 300 mg 4 (two tablets before breakfast and dinner, for 14 days); amoxicillin, 1 g (b.i.d.for the first 7 days); tetracycline, 500 mg (q.i.d. for the second 7 days); and metronidazole, 500 mg (t.i.d. for the second 7 days). Eradication was tested by urea breath test (UBT) 6 weeks after completion of treatment. RESULTS: Of the 142 patients included, 131 completed the study. "Per-protocol" and "intention-to-treat" analyses revealed high eradication rates in this group (92.0-95% CI, 87.2-96.8%, and 81.0-95% CI, 74.5-87.4%, respectively). There was no relation to sex and age with this modified sequential therapy. Compliance was satisfactory (11 patients - four women and seven men were unavailable for follow-up), and side effects were minimal (six patients had to stop treatment - metronidazole-related facial swelling and numbness on the face and hands in two patients; tetracycline-related fever and epigastric pain and nausea and vomiting in two patients; and amoxicillin-related diarrhea and vaginal discharge in two patients). These side effects were reversible and resolved after the cessation of the related medication. CONCLUSIONS: This 14-day modified sequential treatment, including bismuth, achieves a significantly high eradication rates in patients with H. pylori infection, with five satisfactory patient compliance and minor side effects.