A 3D finite element analysis of stress distribution on different thicknesses of mineral trioxide aggregate applied on various sizes of pulp perforation.

OBJECTIVES: The aim of this study was to evaluate the stress distribution on different thicknesses of mineral trioxide aggregate (MTA) placed on various widths of pulp perforations during the condensation of the composite resin material. MATERIALS AND METHODS: The mandibular molar tooth was modeled by COSMOSWorks program (SolidWorks, Waltham, MA). Three finite elemental analysis models representing 3 different dimensions of pulp perforations, 1, 2, and 3 mm in diameter, were created. The perforation area was assumed as filled with MTA with different thicknesses, 1, 2, and 3 mm for each pulp perforation width, creating a total of 9 different models. Then, a composite resin material was layered on MTA for each model. A 66.7 N load was applied and an engineering simulation program (ANSYS, Canonsburg, US) was used for the analysis. Results were presented considering von Mises stress criteria. RESULTS: As MTA thickness increased, the stress values recorded within the area between pulp and MTA decreased. Strain was decreased when the thickness of MTA increased. CONCLUSIONS: Stresses at MTA-pulp interface and strain on MTA decreased with the increase in MTA thickness. CLINICAL RELEVANCE: In clinical practice, when MTA is required for pulp capping, using a thick layer of the material seems to be a better option in order to reduce the stress under forces of hand condensation of overlying restorative materials.

Comparison of GnRH antagonist and agonist mini-dose long protocols in infertile cases undergoing controlled ovarian hyperstimulation.

AIM: The purpose of the present study was to determine if there is a difference between multi-dose gonadotropin releasing hormone (GnRH) antagonist protocol and long GnRH agonist protocol. MATERIALS AND METHODS: This retrospective study compared the data pertaining to patients chosen as per predetermined acceptance criteria, 113 of whom were administered multi-dose antagonist protocol for controlled ovarian hyperstimulation (COH) while 133 were administered long agonist protocol for COH at Suleymaniye Teaching Hospital of Obstetrics and Gynecology. RESULTS: While cancellation rate was found to be significantly higher in antagonist group (17.7% vs 11.28%), the number of follicles > 14 mm and > 16 mm, E2 level, and the number of retrieved oocytes on the day of hCG trigger were significantly lower in the same group. However, there was no difference between fertilization rates and embryonic development rates. The pregnancy rates per transfer and per cycle were found to be 40.9% and 31.7%, respectively; in the antagonist group they were lower, though not significantly, when compared to agonist group (44.1% and 39.1%, respectively). Ongoing pregnancy rates were found to be similar between the groups. CONCLUSION: GnRH antagonist treatment protocol has a level of efficacy similar to agonist treatment protocol in terms of pregnancy results for all groups.

An investigation of Candida species isolated from blood cultures during 17 years in a university hospital.

Candidemia is the most frequent manifestation observed with invasive candidiasis. The aim of this study was to analyse the trends of candidemia in a large tertiary-care hospital to determine the overall incidence during January 1996-December 2012, as well as to determine the susceptibility of 453 isolates according to the revised Clinical and Laboratory Standards Institute (CLSI) breakpoints. Candidemia episodes in adult and paediatric patients were retrospectively analysed from the laboratory data of Uludag University Healthcare and Research Hospital. The 17-year period studied was divided into three periods (1996-2001, 2002-2007 and 2008-2012) for better comparison, and candidemia incidence was determined by the ratio of total number of patients with candidemia per 1000 patients admitted to the hospital and per 10 000 patient days in these three periods. Redefined CLSI M27-A3 breakpoints were used for interpretation of antifungal susceptibility results. Candidemia incidence was determined as 2.2, 1.7 and 1.5 per 1000 admitted patients during 1996-2001, 2002-2007 and 2008-2012 respectively. A significantly decreased candidemia incidence was obtained in the third period. C. albicans (43.8%) was the most common candidemia agent, followed by C.parapsilosis (26.5%) in all three periods. According to the revised CLSI breakpoints, there was fluconazole resistance in C. albicans, C.parapsilosis, C.tropicalis and C.glabrata species (1.4%, 18.2%, 2.6% and 14.3% respectively). Almost all Candida species were found susceptible to voriconazole except one C.glabrata (7.1%) isolate. Candidemia is an important health problem. Local epidemiological data are determinative in the choice of appropriate antifungal treatment agents.

Subtelomeric rearrangements in patients with idiopathic intellectual disabilitiy/ multiple congenital anomalies and recurrent miscarriages: seven years' experience.

Cryptic subtelomeric anomalies are a significant cause of idiopathic intellectual disability and/or multiple congenital anomalies (ID/MCA) and multiple miscarriages (MM). Effective preselection of patients is essential as the cost of subtelomeric testing is high and it is labor-intensive. Therefore, the aim of this study is to evaluate the frequency of subtelomeric anomalies by using commercial FISH probes in 151 patients of ID/MCA and 32 couples with MM who were referred to a genetic center during 7-year period and to determine whether performing subtelomeric testing is feasible for these groups of patients. We assessed the clinical information of all referrals including family history, physical examination, facial dysmorphism, congenital malformations and scored the ID/MCA patients according to the criteria suggested previously. The etiology was not elucidated and all patients had normal karyotypes. Subtelomeric deletions were found in 10 patients in ID/MCA group (6.62%). These were deletions of 14qter (2 patients), 18qter (2 patients), 18pter (2 patients), 15qter, 7pter, 8pter and 4qter. The clinical information of all patients having deletions has been summarized and confined with the current literature. No anomaly was detected in the MM group. In conclusion, the prevalence of subtelomeric anomalies in ID/MCA group in this study is consistent with the literature and subtelomeric FISH analysis is feasible in determining their etiology when a checklist is used. Besides, assessment of the genetic basis of ID/MCA had lead the prevention of the recurrence of such conditions in selected families as well as elucidating novel genetic causes of ID.

Evaluation of the effect of bun/albumin ratio on in-hospital mortality in hypertensive COVID-19 patients.

OBJECTIVE: The impact of COVID-19 infection still continues all over the world and is an important cause of mortality. The mortality rate due to infection varies between 1-5%. The mortality rate is higher in those with cardiovascular risk factors, especially in cases with hypertension. Some studies have shown that blood urea nitrogen (BUN) and albumin levels are associated with worse prognosis in patients with COVID-19. In our study, we aimed to investigate whether the BUN/albumin (BAR) ratio has an effect on in-hospital mortality in hypertensive COVID-19 patients. PATIENTS AND METHODS: A total of 800 hypertensive COVID-19 patients, (618 of whom were alive and 182 died) were included in our study. Patients with a history of heart failure, malignancy, acute coronary syndrome, and myocarditis were excluded. RESULTS: The median age of the study population was 69 (60-77 IQR) years, and 305 (38%) of these patients were men. There was no statistically significant difference between the patients who died during follow-up and cases that remained alive in terms of comorbidities except chronic obstructive pulmonary disease (COPD) which was significantly lower in surviving group (p=0.014). Multivariable logistic regression analysis revealed that age [OR: 1.04, CI (1.01-1.06); p=0.002], male gender [OR: 1.85, CI (1.13-3.02); p=0.010], lymphocyte count [OR: 0.63, CI (0.40-0.98); p=0.038], SaO2 [OR: 0.82, CI (0.79-0.85); p<0.001] and BAR level [OR: 1.09, CI (1.04-1.16); p=0.001] were independent predictors of in-hospital mortality. ROC analysis yielded that BAR is a better predictor of in-hospital mortality compared to albumin and BUN alone. CONCLUSIONS: BUN, albumin, and BAR levels were found to be reliable predictors of in-hospital mortality in COVID-19 patients, and BAR was also found to be a more reliable predictor than BUN and albumin levels. Hypertension is one of the major risk factors for morbidity and mortality in COVID-19 and, BAR presents additional prognostic data in hypertensive COVID-19 patients that may direct physicians for treatment intensification.

Approach to patients with chylothorax complicating pulmonary resection.

Mediastinal lymph node dissection, an important part of surgery for non-small cell lung cancer, is associated with a risk of chylothorax. Although mortality has significantly decreased in recent years, it still worries thoracic surgeons. In this report we reviewed our experience on chylothorax with 26 cases and assessed the outcomes after conservative and surgical approaches. Between January 2000 and June 2010, twenty-six patients developed chylothorax after pulmonary resection performed for non-small cell lung cancer. Initially, all cases were treated conservatively with cessation of oral intake and the application of talc poudrage. If the conservative method failed, a surgical approach was used, which consisted either of suturing the leak or of mass ligation. The mean age of patients was 56 ± 9.05 years, and 3 were female. Chylothorax was more common on the right side, in lobectomy cases, in cases with adenocarcinoma, and in patients with advanced stage lung cancer, but the difference did not reach statistical significance. Conservative treatment was successful in 19 of 26 (73 %) patients, four of whom had undergone pneumonectomy. Seven out of 26 cases (27%) required thoracotomy to control the chylous leak. Though thoracotomy was required mostly for the right side (6 right vs. 1 left, p = 0.15), and in patients who had had pneumonectomy as their first operation (4 patients vs. 3, p = 0.18), this did not reach statistical significance. No patient died as a result of surgical intervention. In conclusion, chylothorax is not rare after pulmonary resection performed for lung cancer. But it is not as dangerous as it used to be. Talc pleurodesis has increased the success of conservative management and minimized the need for surgical intervention. In cases of high output leak the surgeon should not hesitate to perform surgery. VATS can be performed instead of open surgery in suitable cases.

Electronic microarrays in DNA computing.

DNA Computing is a rapidly-developing interdisciplinary area which could benefit from more experimental results to solve practical problems with the current biological tools. In this study, we have integrated microelectronics and molecular biology techniques for the storage of information and basic arithmetic operations via DNA. Using 16 different complementary sequences of DNA, we stored 4 bits of information on an electronic microarray and read the data via the fluorescent signal strength coming from the microarray pads. We also showed the possibility of addition and subtraction of quantities of fluorescently tagged DNA determined via their fluorescent signal strength. We conclude that the hybrid technology we employed, based on a matured Si-CMOS platform, has the potential to strengthen the pursuit of DNA Computation as well as finding its own niche applications.

Electronic microarrays in DNA computing.

DNA Computing is a rapidly-developing interdisciplinary area which could benefit from more experimental results to solve practical problems with the current biological tools. In this study, we have integrated microelectronics and molecular biology techniques for the storage of information and basic arithmetic operations via DNA. Using 16 different complementary sequences of DNA, we stored 4 bits of information on an electronic microarray and read the data via the fluorescent signal strength coming from the microarray pads. We also showed the possibility of addition and subtraction of quantities of fluorescently tagged DNA determined via their fluorescent signal strength. We conclude that the hybrid technology we employed, based on a matured Si-CMOS platform, has the potential to strengthen the pursuit of DNA computation as well as finding its own niche applications.

Process research and development for a tetrazole-based growth hormone secretagogue (GHS) pharmaceutical development candidate.

BMS-317180 (1) is a potent, orally active agonist of the human growth hormone secretagogue (GHS) receptor. This manuscript details the process research and development efforts that enabled the synthesis of the phosphate salt of 1 on a multi-kilogram scale. Key considerations in the development of this process focused on safe execution and the requirement for telescoped synthetic transformations (i.e., without isolation of intermediate products) to contend with a lack of suitably crystalline products.

Characteristics and prognosis of resected T3 non-small cell lung cancer.

AIM: The aim this study is to determine the characteristics, survival, and factors affecting the survival of resected T3 non-small cell lung cancer. METHODS: The records of 97 cases were retrospectively reviewed with T3 non-small cell lung cancer patients that were operated between 1996-2001. Complete resection was achieved in 71 (73.2%) patient. The distribution of N status was 47.4%, 28.9%, and 23.7% for N0, N1 and N2 respectively. The evaluated prognostic factors in univariate and multivariate analyses were, histologic type, type of resection, N status, subgroups of pT3, resection margins and effect of adjuvant therapy. RESULTS: Overall 5-year survival rate was 24.3%. Median survival and 5-year survival of the patients whose tumors resected completely was 33 months and 31.5%, whereas 18 months and 7.3% for the patients resected incompletely (P=0.03). Median survival being not significantly different among the three subgroups: 25, 23, and 32 months (P=0.7) in the bronchial pT3, mediastinal pT3, and peripheral pT3 subgroups, respectively. Histology (P=0.57), type of surgical resection (lobectomy versus pneumonectomy) (P=0.25), and use of adjuvant therapy (P=0.054) did not influence the survival significantly. However N status influenced the survival significantly (P=0.01). According to the multivariate analyses, two factors were selected as prognostic indicators: N2 status (P=0.03) and incomplete resection (P=0.03). CONCLUSION: Three pT3 subgroups did not show survival differences. Complete resection and N2 status are the two most influencing factors in survival of the patients. Adjuvant therapy effected the survival and the quality of life reversely.

Discovery of Potent and Orally Bioavailable Dihydropyrazole GPR40 Agonists.

G protein-coupled receptor 40 (GPR40) has become an attractive target for the treatment of diabetes since it was shown clinically to promote glucose-stimulated insulin secretion. Herein, we report our efforts to develop highly selective and potent GPR40 agonists with a dual mechanism of action, promoting both glucose-dependent insulin and incretin secretion. Employing strategies to increase polarity and the ratio of sp3/sp2 character of the chemotype, we identified BMS-986118 (compound 4), which showed potent and selective GPR40 agonist activity in vitro. In vivo, compound 4 demonstrated insulinotropic efficacy and GLP-1 secretory effects resulting in improved glucose control in acute animal models.

Indole diterpenoid synthetic studies. The total synthesis of (+)-nodulisporic acid F.

[structure: see text] A stereocontrolled total synthesis of (+)-nodulisporic acid F, the simplest member of a family of novel ectoparasiticidal agents, has been achieved. Highlights of the effective modular synthetic strategy include anionic union of a tricyclic lactone with o-toluidine via our 2-substituted indole synthetic protocol, an optimized C-ring construction protocol, and a late-stage installation of the alpha,beta-unsaturated carboxylic acid side chain via the B-alkyl Suzuki-Miyaura cross-coupling tactic.

Indole diterpenoid synthetic studies. Construction of the heptacyclic core of (-)-nodulisporic acid D.

[structure: see text] Construction of the heptacyclic core of (-)-nodulisporic acid D, a representative member of a recently discovered class of architecturally complex, ectoparasiticidal indole alkaloids, has been achieved. The modular synthetic strategy comprises an expedient, stereocontrolled synthesis of a tricyclic western hemisphere, in conjunction with union of an eastern hemisphere, exploiting the 2-substituted indole synthetic protocol introduced and developed in our laboratory.

A new modular indole synthesis. Construction of the highly strained CDEF parent tetracycle of nodulisporic acids A and B.

[reaction: see text] Construction of the highly strained CDEF parent tetracycle, a structural motif found only in the potent ectoparasiticidal agents (+)-nodulisporic acids A and B and related congeners, has been achieved via a new modular indole synthesis, exploiting a sequential Stille cross-coupling/Buchwald-Hartwig union/cyclization tactic. The new indole synthesis holds the promise of rapid assembly of diverse, highly substituted indoles possessing uncommon substitution patterns.

The effects of psychiatric treatment on depression, anxiety, quality of life, and sexual dysfunction in patients with inflammatory bowel disease.

OBJECTIVE: Depression and anxiety are common disorders in inflammatory bowel disease (IBD). Our aim is to prospectively determine the effect of psychiatric treatment on scores for depression, anxiety, quality of life (QoL), and sexual dysfunction in an outpatient population diagnosed with IBD and also anxiety and/or depression disorder. PATIENTS AND METHODS: Patients who scored higher than the cutoff point on the Hospital Anxiety Depression Scale were referred for further structured psychiatric evaluation and determination of the need for psychiatric drug treatment. Patients who underwent drug therapy completed Short Form-36 (SF-36) and the Arizona Sexual Experience Scale at baseline and after 6 months of follow-up. RESULTS: Major depressive disorder and generalized anxiety disorder were the most common diagnoses. After 6 months, 47 patients had completely adhered to drug treatment (group A), whereas 20 were nonadherent (group B). In group A, all domains of SF-36, Arizona Sexual Experience Scale, depression/anxiety scores, and Crohn's disease activity index were statistically improved after treatment when compared with the baseline. In group B, the three domains of SF-36, platelet count, and mean corpuscular volume were worse between baseline and at 6 months. CONCLUSION: In IBD patients having any psychiatric disorder, 6 months of antidepressant drug treatment is associated with an improvement in depression, anxiety, QoL, and sexual functioning scores, as well as an improvement in Crohn's disease activity index. On the other hand, insufficient psychiatric treatment seems to be related to a poor QoL.

Two-dimensional speckle tracking echocardiography is useful in early detection of left ventricular impairment in patients with Crohn's disease.

OBJECTIVE: Crohn's disease (CD) is a chronic inflammatory bowel disease that can affect the entire gastrointestinal tract. Cardiac involvement is considered very rare. Pericarditis, myocarditis, endocarditis, cardiomyopathy and complete heart block are some of the cardiac extraintestinal manifestations of CD. The aim of this study was to explore the left ventricular (LV) functions with two-dimensional (2D) speckle tracking echocardiography (STE) in patients with CD with normal cardiac functions. PATIENTS AND METHODS: We enrolled 50 consecutive patients with CD and 50 age and sex matched healthy controls. All patients underwent a transthoracic echocardiogram with evaluation of LV functions with 2D STE. RESULTS: Baseline characteristics were similar between patients with CD (24 male, mean age: 41.0 ± 13.9 years) and controls (24 male, mean age: 40.1 ± 7.3 years). Although conventional echocardiographic parameters were similar between two groups, global longitudinal strain was significantly lower in patients with CD compared to controls (19.6 ± 3.3 versus 21.2 ± 2.9, p = 0.014). Correlation analysis revealed that Crohn's Disease Activity Index is inversely correlated with LV global longitudinal strain (r = -0.703, p < 0.001) in patients with CD. We also evaluated inflammatory parameters such as CRP, erythrocyte sedimentation rate, and complete blood counts in patients with CD. Correlation analysis revealed that only platelet value is weakly correlated with Crohn's Disease Activity Index (r = 0.311, p = 0.083). CONCLUSIONS: Crohn's disease is associated with impairment in LV global longitudinal myocardial function. Crohn's Disease Activity Index is also strongly correlated with LV global longitudinal strain. 2D-STE may be an useful method for early detection of LV impairment in patients with CD.

Marsupialization of the pancreas for infected pancreatic necrosis.

Infected pancreatic necrosis is a devastating and lethal complication of acute pancreatitis. Late death is usually a result of sepsis. W.A. Altemeier and J.W. Alexander established in 1963 that open drainage of the necrotic pancreas is mandatory for survival (Arch Surg 1963;87:96-105). In 1981, E.D. Davidson and E.L. Bradley III concluded that "marsupialization" is the most effective method of open drainage (Surgery 1981;89:252-6). At our institution, we have a series of 10 patients who have undergone marsupialization for treatment of infected pancreatic necrosis. Our mortality rate was 30 per cent. One death resulted from sepsis after an infected necrotic pancreas was found with a colonic anastomotic leak at emergency exploratory celiotomy. Of note, further debridement was not performed. A second death occurred in a female with idiopathic pancreatitis and leukocytopenia, and we are uncertain whether that played a role in the failure of surgical intervention. The third death was in a young alcoholic with hyperlipidemia and severe pancreatitis who was septic 8 days before surgery. The patient died on postoperative day 1. Of the survivors, some were old, many were septic, and all but one returned for further debridement. Our series supports open debridement of infected pancreatic necrosis as a life-saving maneuver and marsupialization as an effective means of open drainage.

Axillary hibernoma: an unusual soft tissue tumor.

Hibernomas are rare soft tissue tumors of brown fat differentiation. A case of a large axillary hibernoma, along with a review of its pathology, is presented. This tumor matches the largest hibernoma in the literature and is the largest in an axillary site.

Nutritional immunity: a prospective study of thirty-three patients with acute appendicitis.

During a recent 12-month period, serum iron levels, total iron binding capacities (TIBC), and latent iron binding capacities (LIBC) were studied preoperatively and 72 hrs postoperatively in 33 consecutive patients with pathologically confirmed acute appendicitis. Preoperative serum iron levels were significantly reduced in these patients (mean serum iron 32 micrograms/dl; P less than .0001) compared to established normal values (mean 100 micrograms/dl). LICBs were correspondingly elevated whereas TIBCs and mean hemoglobin values remained within the normal range. The reduced availability of serum iron in response to an acute infectious challenge such as appendicitis supports earlier experimental studies by others which suggest that nutritional immunity participates in host resistance to infection. In this study, the degree of serum iron suppression was directly related to the severity of disease (P less than .01).