Influence of implant restorative emergence angle and contour on peri-implant marginal bone loss: A systematic review and meta-analysis.

BACKGROUND: Implant restorative emergence angle and profile may have a negative impact on peri-implant marginal bone level and may increase the risk of developing peri-implantitis. However, the role of these prosthetic features on peri-implant health is still unclear. The aim of this systematic review and meta-analyses was to evaluate the long-term outcomes of implant restorations with an emergence angle of >30° in comparison to those with ≤30° in terms of changes in peri-implant marginal bone level, periodontal parameters, and prevalence rate of peri-implantitis. METHODS: Electronic databases were searched to identify observational studies that compared implant restorations with an emergence angle of >30° to those with ≤30°. The risk of bias was assessed using the Cochrane Collaboration's Risk of Bias tool. RESULTS: Four studies with 912 dental implants in 397 participants were included in the present review. Of these, 455 implants had restorations with an emergence angle of >30°, while the remaining implants had restorative emergence angle of ≤30°. The follow-up time varied between 3.8 and 10.9 years. Implant restorations with an emergence angle of ≤30° were associated with less changes in peri-implant marginal bone level compared to those with emergence angle of >30°. The difference, however, was not statistically significant (mean difference 0.80; 95% confidence interval (CI) -0.13 to 1.72; p = 0.09). In platform-matched implants, the difference between the two groups was statistically significant in favor of implant restorations with emergence angle of ≤30°. In terms of emergence profile, implant restorations with convex profile had significantly higher rate of peri-implantitis (57.8%) compared to implant restorations with concave or straight profile (21.3%) (risk ratio 2.32; 95% CI 1.12-4.82; p = 0.02). CONCLUSIONS: Within the limitation of this review, implant restorations with an emergence angles of >30° or ≤30° seem to have no significant influence on peri-implant marginal bone level. Platform-matched implants with an emergence angle of ≤30° may have positive effects on the peri-implant marginal bone level changes, but the evidence support is of low to moderate certainty.

Conservation of the Goitered gazelle (Gazella subgutturosa) under climate changes in Iraq.

Climate is a vital factor that shapes habitat suitability for many species across space and time. Gazella subgutturosa (Goitered gazelle) is a globally vulnerable mammal already extinct in some areas of Armenia and Georgia and is highly threatened in other areas of its distribution. In this study, new data were gathered for 33 locations in north-eastern Iraq, and then together with literature data, Species Distribution Models (SDMs) were used to explore the geographical distribution of the gazelle under current and future climate change scenarios. We studied the relationship between seven climate variables and 43 occurrence records to predict habitat suitability of the gazelle under the current climate, and also under four future climate scenarios (RCP2.6 and RCP8.5 for both 2050 and 2080). Annual precipitation and isothermality had the most influence on the distribution of Gazella subgutturosa. The most suitable habitat in both the current and future scenarios was located in north-eastern Iraq close to the Iranian border near the Zagros Mountains. There was no difference in habitat suitability for the gazelle inside Iraqi Protected Areas (PAs) compared to outside the PAs. Using the occurrence records and IUCN Red List national assessments, we found Iraqi Goitered gazelle populations to be classified as Endangered (EN). Our results suggest urgent conservation planning is needed to save this species, including the establishment of new PAs. These results contribute new baseline information, which was currently missing Goitered gazelle in about Iraq, to the IUCN SSC Antelope Specialist Group, which will hopefully aid with future global assessments and conservation.

Establishment of the First Comprehensive Adult and Pediatric Hematopoietic Stem Cell Transplant Unit in the United Arab Emirates: Rising to the Challenge.

Hematopoietic stem cell transplantation (HSCT) is increasingly indicated for various malignant and non-malignant diseases. In the United Arab Emirates (UAE), patients that could benefit from the procedure commonly need to seek medical care abroad in view of the lack of a comprehensive HSCT facility that could offer the full spectrum of interventions and monitoring protocols. This comes with considerable challenges related to coverage and logistics of travel. It also limits the continuity of clinical care, and presents inconvenience to patients who come from a different cultural background. In this article, we share our experiences and lessons learned during the establishment of the first comprehensive adult and pediatric HSCT unit in the UAE that is designed to cater for local citizens and residents, as well as neighboring countries facing similar availability challenges.

Development of new computational machine learning models for longitudinal dispersion coefficient determination: case study of natural streams, United States.

Natural streams longitudinal dispersion coefficient (Kx) is an essential indicator for pollutants transport and its determination is very important. Kx is influenced by several parameters, including river hydraulic geometry, sediment properties, and other morphological characteristics, and thus its calculation is a highly complex engineering problem. In this research, three relatively explored machine learning (ML) models, including Random Forest (RF), Gradient Boosting Decision Tree (GTB), and XGboost-Grid, were proposed for the Kx determination. The modeling scheme on building the prediction matrix was adopted from the well-established literature. Several input combinations were tested for better predictability performance for the Kx. The modeling performance was tested based on the data division for the training and testing (70-30% and 80-20%). Based on the attained modeling results, XGboost-Grid reported the best prediction results over the training and testing phase compared to RF and GTB models. The development of the newly established machine learning model revealed an excellent computed-aided technology for the Kx simulation.

Risk interrelationship among multiple primary tumors: A case report and review of literature.

RATIONALE: Along with advanced management in oncology, great progress has been recently achieved in the studies of multiple primary tumors. Several reports have studied the coexistence between lymphoma and either renal cell carcinoma (RCC) or Warthin tumor. However, the level of coexistence between these cases remains unclear due to the absence of a distinct link between them. PATIENT CONCERNS: We present a unique case of multiple primary tumors (lymphoma, RCC, and Warthin tumor) in an 80-year-old man and a review of the literature on the coexistence of RCC with lymphoma and lymphoma with Warthin tumor. DIAGNOSIS: With a history of RCC, the patient had a freely movable lump under his left ear, and the pathological report indicated Hodgkin lymphoma and Warthin tumor. INTERVENTION: RCC and Warthin tumor of the patient were surgically treated, followed by 2 cycles (14 days per cycle) of Epirubicin 40 mg day 1, Bleomycin 8 mg day 1, Vincristine 2 mg day 1, and Dacarbazine 500 mg day 1. The chemotherapy protocol was then changed to Epirubicin 40 mg day 1, Vincristine 2 mg day 1, and Dacarbazine 500 mg day 1 for 7 cycles. OUTCOMES: After the last day of chemotherapy, the patient showed a complete response. LESSONS: To the best of our knowledge, this paper is the first to report a case of multiple primary tumors with a complete response. For their early detection, favorable prognosis, and correlation identification, we suggest a transitive relation between these coexisting tumors. Therefore, similar studies should be conducted.

A constitutively-active IKK-complex at the axon initial segment.

BACKGROUND: Previous studies provided evidence for an accumulation of IκB-kinase (IKK) α/ß at the axon initial segment (AIS), a neuronal compartment defined by ankyrin-G expression. Here we explored whether the presence of the IKK-complex at the AIS was associated with the activation of IKK signaling at this site. METHODS AND RESULTS: Proximity-ligation assays (PLAs) using pan-IKKα/ß, phospho-IKKα/ß-specific as well as ankyrin-G specific antibodies validated their binding to proximal epitopes in the AIS, while antibodies to other phosphorylated signaling proteins showed no preference for the AIS. Small-hairpin mediated silencing of IKKß significantly reduced anti-phospho-IKKα/ß-immunoreactivities in the AIS. ank3 gene-deficient cerebellar Purkinje cells also exhibited no phosphorylated IKKα/ß at the proximal region of their axons. Transient ankyrin-G overexpression in PC12 cells augmented NF-κB transactivation in an ankyrin-G death-domain dependent manner. Finally, small molecule inhibitors of IKK-activity, including Aspirin, inhibited the accumulation of activated IKK proteins in the AIS. CONCLUSION: Our data suggest the existence of a constitutively-active IKK signaling complex in the AIS.

Viral etiology of respiratory infections in children in southwestern Saudi Arabia using multiplex reverse-transcriptase polymerase chain reaction.

OBJECTIVES: To investigate 15 respiratory viruses in children with acute respiratory tract infections (ARTIs) using multiplex reverse-transcriptase polymerase chain reaction (RT-PCR), and to analyze the clinical and epidemiological features of these viruses. METHODS: In a cross-sectional study, 135 children, ≤5 years of age who presented with ARTIs in Najran Maternity and Children Hospital, Najran, Saudi Arabia between October 2012 and July 2013 were included. The clinical and sociodemographic data, and the laboratory results were recorded using a standardized questionnaire. Two nasopharyngeal swabs were collected from each child: one for bacteriological examination, and the second for viral detection using multiplex RT-PCR. RESULTS: A single viral pathogen was detected in 76 patients, viral coinfections in 9, and mixed viral and bacterial pathogens in 15. Respiratory syncytial virus was isolated in 33 patients, human rhinovirus (hRV) in 22, adenovirus (AdV) in 19, human metapneumovirus in 13, influenza virus in 10, parainfluenza virus in 7, human corona virus (hCoV) in 4, and human bocavirus in one. CONCLUSION: Respiratory syncytial virus, hRV, and AdV were the most frequent viruses, accounting for more than two-thirds of the cases. Other viruses, such as MPV, hCoV NL63, and hCoV OC43, may play a role in pediatric ARTIs. Of significance is the potential use of multiplex RT-PCR to provide epidemiological and virological data for early detection of the emergence of novel respiratory viruses in the era of the Middle East respiratory syndrome coronavirus. 

Human COL7A1-corrected induced pluripotent stem cells for the treatment of recessive dystrophic epidermolysis bullosa.

Patients with recessive dystrophic epidermolysis bullosa (RDEB) lack functional type VII collagen owing to mutations in the gene COL7A1 and suffer severe blistering and chronic wounds that ultimately lead to infection and development of lethal squamous cell carcinoma. The discovery of induced pluripotent stem cells (iPSCs) and the ability to edit the genome bring the possibility to provide definitive genetic therapy through corrected autologous tissues. We generated patient-derived COL7A1-corrected epithelial keratinocyte sheets for autologous grafting. We demonstrate the utility of sequential reprogramming and adenovirus-associated viral genome editing to generate corrected iPSC banks. iPSC-derived keratinocytes were produced with minimal heterogeneity, and these cells secreted wild-type type VII collagen, resulting in stratified epidermis in vitro in organotypic cultures and in vivo in mice. Sequencing of corrected cell lines before tissue formation revealed heterogeneity of cancer-predisposing mutations, allowing us to select COL7A1-corrected banks with minimal mutational burden for downstream epidermis production. Our results provide a clinical platform to use iPSCs in the treatment of debilitating genodermatoses, such as RDEB.

Correlation of ultrasonographic parameters with serum creatinine in chronic kidney disease.

OBJECTIVE: The purpose of our study is to correlate renal echogenicity with serum creatinine in order to determine the significance of renal echogenicity when it comes to identifying the progression of chronic kidney disease (CKD) and for the sonographic grading of CKD. MATERIALS AND METHODS: Sixty patients above 30 years of age who had been diagnosed with CKD according to the guidelines of the National Kidney Foundation were included in the study. Patients on kidney replacement therapy or with fatty liver findings on ultrasonography were excluded. Ultrasounds of kidneys were performed by two radiologists who were blind to the patients' serum creatinine levels. Renal cortical echogenicity was compared with serum creatinine. Statistical analysis was performed using one-way ANOVA followed by Scheffe's test. The relationship between serum creatinine and sonographic features was assessed by correlation coefficient analysis. A P value less than 0.05 was considered statistically significant. RESULTS: Mean serum creatinine was 2.80 mg/dl for Grade 1 (range: 0.9-9.2 mg/dl), 3.69 mg/dl for Grade 2 (range: 1.2-10.3 mg/dl), 3.86 mg/dl for Grade 3 (range: 1.1-6.5 mg/dl), and 7.90 mg/dl for Grade 4 (range: 3.1-11.4 mg/dl). The grades being determined by cortical echogenicity on imaging A statistically significant, positive correlation was observed between serum creatinine and grading based on cortical echogenicity (P = 0.004). CONCLUSION: Renal echogenicity and its grading correlates better with serum creatinine in CKD than other sonographic parameters such as longitudinal size, parenchymal thickness, and cortical thickness. Hence, renal echogenicity is a better parameter than serum creatinine for estimating renal function in CKD, and has the added advantage of irreversibility.

Synthesis, anti-inflammatory, analgesic, and antibacterial activities of some triazole, triazolothiadiazole, and triazolothiadiazine derivatives.

This study is concerned with the synthesis of new 1,2,4-triazoles, 1,3,4-thiadiazoles, and 1,3,4-thiadiazines derivatives. Derivatives 3a-i were obtained by condensation of 4-amino-3-(4-pyridine)-5-mercapto-1,2,4-triazole 1 with the appropriate aldehyde. Compounds 4a-i were synthesized in a one pot reaction involving compounds 3a-i, formaldehyde, and morpholine. Condensation of compound 1 with the appropriate acids or 4-substituted phenacyl bromide gave compounds 6a-d and 8a-f respectively. The chemical structures of the newly synthesized derivatives were elucidated using different spectral and elemental methods of analysis. All compounds were evaluated for their anti-inflammatory activity and the most potent derivatives were tested for their analgesic activity using indomethacin as a reference drug. In addition, ulcerogenicity and LD(50) for the most active compounds were evaluated. Moreover, the antibacterial activities of the newly synthesized derivatives were investigated.

Role of vacuolar ATPase in the trafficking of renal type IIa sodium-phosphate cotransporter.

BACKGROUND/AIMS: Total body phosphate homeostasis is regulated by expression of type IIa sodium phosphate cotransporter (NpT2a) in the apical membrane (BBM) of renal proximal tubule cells. NpT2a expression is regulated by dietary phosphate and PTH but the mechanisms for trafficking of the protein are unknown. Based on 2D gel electrophoresis and mass spectroscopy data that changes in dietary phosphate stimulated changes in BBM expression of vacuolar H(+)-ATPase, we hypothesized that vacuolar H(+)-ATPase plays a significant role in regulation of NpT2a in opossum kidney (OK) cells, a model for renal proximal tubule transport. METHODS: Role of vacuolar H(+)-ATPase was studied in opossum kidney (OK) cells by examining the effect of inhibition of vacuolar H(+)-ATPase on Pi uptake and NpT2a expression. RESULTS: Pretreatment of OK cells with bafilomycin A(1) and concanamycin A, inhibitors of vacuolar H(+)-ATPases, blocked high phosphate- and PTH-induced degradation of NpT2a, but had no effect on high phosphate or PTH induced inhibition of sodium-dependent phosphate transport. Exposure of the cells to bafilomycin A(1) significantly decreased phosphate transport and apical membrane expression of NpT2a. Treatment with brefeldin A, an inhibitor of Golgi transport, decreased phosphate transport and apical membrane expression of NpT2a while treatment of cells with both brefeldin A and bafilomycin A(1) had no additive effect. CONCLUSION: We conclude that vacuolar H(+)-ATPase plays a significant role in exocytosis of NpT2a into the apical membrane and in degradation of NpT2a but has no role in endocytosis.

Case report: malignant teratoma of the uterine corpus.

BACKGROUND: Teratomas are the commonest germ cell tumours and are most frequently found in the testes and ovary. Extragonadal teratomas are rare and mainly occur in midline structures. Uterine teratomas are extremely rare with only a few previous case reports, usually involving mature teratomas of the uterine cervix. CASE PRESENTATION: We report an 82-year-old lady presenting with post-menopausal bleeding. Initial investigations revealed a benign teratoma of the uterus which was removed. Her symptoms persisted and a recurrent, now malignant, teratoma of the uterine corpus was resected at hysterectomy. Six months after surgery she relapsed with para-aortic lymphadenopathy and was treated with a taxane, etoposide and cisplatin-containing chemotherapy regimen followed by retroperitoneal lymph node dissection. CONCLUSION: In this report we discuss the aetiology, diagnosis and management of uterine teratomas, and review previous case studies.

PTH-mediated regulation of Na+-K+-ATPase requires Src kinase-dependent ERK phosphorylation.

Parathyroid hormone (PTH) inhibits Na+-K+-ATPase activity by serine phosphorylation of the alpha1-subunit through ERK-dependent phosphorylation and translocation of protein kinase Calpha (PKCalpha). On the basis of previous studies, we postulated that PTH regulates sodium pump activity through Src kinase, PLC, and calcium-dependent ERK phosphorylation. In the present work utilizing opossum kidney cells, a model of renal proximal tubule, PTH-stimulated ERK phosphorylation and membrane translocation of PKCalpha were prevented by inhibition of Src kinase, PLC, and calcium entry. Pharmacological inhibition of PLA2 did not prevent PTH-stimulated ERK phosphorylation but completely prevented PKCalpha translocation. Silencing the expression of cytosolic or calcium-independent PLA2 also prevented PTH-mediated phosphorylation of Na+-K+-ATPase alpha1-subunit and PKCalpha without blocking ERK phosphorylation. Inhibition of Na+-K+-ATPase activity by the PLA2 metabolites arachidonic acid and 20-hydroxyeicosatetraenoic acid was prevented by specific inhibition of PKCalpha but not by U0126, a MEK-1 inhibitor. Transient transfection of constitutively active MEK-1 cDNA induced phosphorylation of Na+-K+-ATPase alpha1-subunit and PKCalpha, which was prevented by PLA2 inhibition. We conclude that PTH stimulates Na+-K+-ATPase phosphorylation and decreases the activity of Na+-K+-ATPase by a sequential activation of a signaling pathway involving Src kinase, PLC, ERK, PLA2, and PKCalpha.

Nanostructure, effective properties, and deformation pattern of the cochlear outer hair cell cytoskeleton.

We consider the mechanical properties of the outer hair cell cytoskeleton. The cytoskeleton is represented as a set of microdomains of different sizes and orientations composed of actin filaments and spectrin crosslinks. An intermediate material between domains is also introduced. The domain characteristics are randomly generated and the histograms of the cytoskeleton stiffness moduli are obtained. We solve an inverse problem and estimate the stiffness of the crosslink and connective molecule in the intermediate material. We discovered a pattern of highly inhomogeneous deformation of the cytoskeleton where the circumferential strain is primarily determined by the deformation of the intermediate material.