Design, Synthesis, and Applications of a Vanadium Complex: An Effective Catalyst for the Direct Conversion of Alcohols and Aldehydes to Esters.

A novel bench-stable V-catalyst [(L2)VIVO](ClO4) was synthesized and characterized by X-ray diffraction (XRD) analysis and FT-IR, UV-visible, and EPR spectroscopies, which confirmed its excellent catalytic activity. In application, aldehydes are rapidly converted into their corresponding esters without additives in a one-pot manner using a newly developed catalyst [(L2)VIVO](ClO4) and H2O2 as a green oxidant. The developed method is compatible with a broad range of densely substituted aldehydes and allows for the facile preparation of aliphatic, aromatic, and heterocyclic esters, including esters derived from CD3OD, methanol, ethanol, iso-propanol, n-butanol, sec-butyl alcohol, and propargylic alcohol. Gratifyingly, numerous alcohols also directly converted to their corresponding esters in a one-pot manner. We disclose herein the direct conversion of two different functionalities (alcohols and aldehydes) into esters (33 examples) with satisfactory yields, showing the potential of the developed catalyst toward varied oxidative organic transformations in a one-pot manner.

Development of clove oil based nanoencapsulated biopesticide employing mesoporous nanosilica synthesized from paddy straw via bioinspired sol-gel route.

Paddy straw (PS) burning is a concerning issue in South Asian countries, clamoring for exploring alternative management strategies. Being a rich source of silica, PS can be a potential nanosilica (SiNPs) source. The current study reports a pioneering approach for green synthesis of high-purity mesoporous SiNPs by sol-gel method using the aqueous extract of Sapindus mukorossi seed pericarp as a stabilizer. The mesoporous nature of SiNPs was harnessed as a carrier for the essential oil to develop the carrier-based formulation. SiNPs were characterized using XRD, EDX, FTIR, FE-SEM, TEM, AFM, DLS, water contact angle, and BET analysis. The synthesized SiNPs possessed a spheroid morphology with an average particle size of 20.34 ± 2.64 nm. XRD results confirmed its amorphous nature. The mesoporous nature of SiNPs was confirmed using BET analysis which showed a cumulative pore volume of 2.059 cm3/g and a high surface area of 746.32 m2/g. The SiNPs were further loaded with clove essential oil (CEO), and the encapsulation of CEO was assessed using UV-Vis, FTIR, and BET analysis. The in-vitro antifungal activity of CEO and CEO-loaded SiNPs (CEO-SiNPs) was evaluated using the agar plate assay. UV-Vis results depicted 62.64% encapsulation of CEO in SiNPs. The antifungal efficacy of CEO-SiNPs against F. oxysporum exhibited minimum inhibitory concentration (MIC), i.e., 125 mg/L, while the MIC of CEO was found to be 250 mg/L. The study delivers new insights into the holistic utilization of PS and propitious contribution toward the circular economy and Sustainable Development Goals (SDGs).

The in-vitro accuracy of fiducial marker-based versus markerless registration of an intraoral scan with a cone-beam computed tomography scan in the presence of restoration artifact.

OBJECTIVES: To determine the effect of restoration artifact ('metal artifact') on registration accuracy of an intraoral scan and cone-beam computed tomography (CBCT) scan, comparing fiducial marker-based registration with markerless registration. MATERIALS AND METHODS: A maxillary model was fitted with multiple configurations of zirconia crowns to simulate various states of oral rehabilitation. Intraoral scans and CBCT scans (half and full rotation) were acquired. Registration was performed using markerless (point-based registration with surface-based refinement) and fiducial marker-based registration. Each experimental condition was repeated 10 times (n = 320). The absolute deviation was measured at the canines and first molars, and the average and maximum values were analysed using multiple linear regression. RESULTS: R2 was 0.874 for average error and 0.858 for maximum error. For markerless registration, there were 0.041 mm (p < .001) and 0.045 mm (p < .001) increases in average and maximum error per crown, respectively. For fiducial marker-based registration, the effect of additional crowns was not statistically significant for average (p = .067) or maximum (p = .438) error. For a full arch of crowns, the regression model predicted average and maximum errors of 0.581 and 0.697 mm for the markerless technique, and 0.185 and 0.210 mm for the fiducial marker-based technique. Overall, the fiducial marker-based technique was more accurate for four or more crowns. The half rotation scan increased average error by 0.021 mm (p = .001) and maximum error by 0.029 mm (p < .001). CONCLUSIONS: Under the present study's experimental conditions, the fiducial marker-based technique should be considered if four or more full-coverage highly radiopaque restorations are present.

The influence of metal artifact reduction on the trueness of registration of a cone-beam computed tomography scan with an intraoral scan in the presence of severe restoration artifact.

PURPOSE: When planning guided implant surgery, highly radiopaque materials such as metals or zirconia produce streaking artifacts ('metal artifact') on cone-beam computed tomography scans, which can impair registration of the intraoral scan. This study aimed to determine the effect of metal artifact reduction on the trueness of registration in the presence of multiple full-coverage zirconia crowns. MATERIALS AND METHODS: A 3D-printed maxillary study model was restored with 12 full-coverage zirconia crowns and scanned with an intraoral scanner. Cone-beam computed tomography scans of the study model were acquired, with and without activation of the metal artifact reduction algorithm. Registration of the optical scans was performed using initial point-based registration with surface-based refinement, and the deviation was measured at four pre-defined dental landmarks. Welch's t-test was used to compare the registration error for the metal artifact reduction group with the control group. RESULTS: The average registration error was 0.519 mm (95% CI 0.507 to 0.531) with metal artifact reduction deactivated, compared to 0.478 mm (95% CI 0.460 to 0.496) without metal artifact reduction. Therefore, activation of the metal artifact reduction algorithm was associated with a 0.041 mm (95% CI 0.020 to 0.061, p < 0.001) increase in average registration error. CONCLUSIONS: The use of the metal artifact reduction algorithm slightly reduced trueness in this in vitro study. Clinicians are advised not to rely on a metal artifact reduction (MAR) algorithm for registration of a cone-beam computed tomography scan with an intraoral scan when planning guided implant surgery in the presence of restoration artifacts.

Platelet Rich Plasma (PRP) Growth Factor Concentration Varies in Men With Erectile Dysfunction.

BACKGROUND: Platelet Rich Plasma (PRP) is a novel therapy rich in growth factors and cytokines used to target the underlying causes of erectile dysfunction (ED). It is not known, however, if the composition of growth factors in PRP varies between men. AIM: To evaluate PRP growth factor variability among men with ED. METHODS: Whole blood was collected from 8 participants with at least a 6-month history of ED. Seven men with Peyronie's disease and 1 healthy male (without sexual dysfunction) were used as the control group. PRP was extracted from whole blood using the Arthrex Angel system. A Human Growth Factor Antibody Array for 41 proteins was performed using 3 participants and the healthy control. Using all 16 samples, quantitative detection of factors from the array that were decreased by 1.5-fold were validated with western blot. OUTCOMES: From the growth factor array, 2 growth factors-granulocyte-macrophage colony stimulating factor and transforming growth factor-ß were identified as having a 1.5-fold decrease between the participants and the control. Vascular endothelial growth factor (VEGF) was selected because androgens can upregulate VEGF production. Other than a weak negative correlation between VEGF expression and age, we found no correlation between growth factor expression for granulocyte-macrophage colony stimulating factor or transforming growth factor-ß and age, body mass index, or comorbidities. CLINICAL TRANSLATION: PRP growth factor concentration appears to vary among men with ED. PRP treatment for ED may need to be personalized for patients, depending on individual growth factor concentration. STRENGTHS AND LIMITATIONS: This study demonstrates the variability in PRP growth factors among men with ED. This is an important finding in the investigation of PRP as a restorative treatment option for men with ED. Our study, however, was limited by a small sample size. CONCLUSION: PRP growth factors vary among men with ED. Khodamoradi K, Dullea A, Golan R, et al. Platelet Rich Plasma (PRP) Growth Factor Concentration Varies in Men With Erectile Dysfunction. J Sex Med 2022;19:1488-1493.

Heterogeneity in Genomic Risk Assessment from Tissue Based Prognostic Signatures Used in the Biopsy Setting and the Impact of Magnetic Resonance Imaging Targeted Biopsy.

PURPOSE: Genomic prognostic signatures are used on prostate biopsy tissue for cancer risk assessment, but tumor heterogeneity and multifocality may be an issue. We evaluated the variability in genomic risk assessment from different biopsy cores within the prostate using 3 prognostic signatures (Decipher, CCP, GPS). MATERIALS AND METHODS: Men in this study came from 2 prospective prostate cancer trials of patients undergoing multiparametric magnetic resonance imaging and magnetic resonance imaging targeted biopsy with genomic profiling of positive biopsy cores. We explored the relationship among tumor grade, magnetic resonance imaging risk and genomic risk for each signature. We evaluated the variability in genomic risk assessment between different biopsy cores and assessed how often magnetic resonance imaging targeted biopsy or the current standard of care (profiling the core with the highest grade) resulted in the highest genomic risk level. RESULTS: In all, 224 positive biopsy cores from 78 men with prostate cancer were profiled. For each signature, higher biopsy grade (p <0.001) and magnetic resonance imaging risk level (p <0.001) were associated with higher genomic scores. Genomic scores from different biopsy cores varied with risk categories changing by 21% to 62% depending on which core or signature was used. Magnetic resonance imaging targeted biopsy and profiling the core with the highest grade resulted in the highest genomic risk level in 72% to 84% and 75% to 87% of cases, respectively, depending on the signature used. CONCLUSIONS: There is variation in genomic risk assessment from different biopsy cores regardless of the signature used. Magnetic resonance imaging directed biopsy or profiling the highest grade core resulted in the highest genomic risk level in most cases.

Current Treatment Modalities Targeting Tumor Microenvironment in Castration-Resistant Prostate Cancer.

Prostate cancer (PCa) is responsible for significant cancer-related morbidity and mortality following local treatment failure in men. The initial stages of PCa are typically managed with a combination of surgical resection and/or androgen deprivation therapy (ADT). Unfortunately, a significant proportion of PCa continues to progress despite being at castrate levels of testosterone (<50 ng/dl), at which point it is coined castration-resistant prostate cancer (CRPC). In recent years, many novel therapeutics and drug combinations have been created for CRPC patients. These include immune checkpoint inhibitors, chemokine receptor antagonists, steroidogenic enzyme inhibition, and novel tyrosine kinase inhibitors as well as combinations of drugs. The selection of the most appropriate therapy depends on several factors like stage of the disease, age of the patient, metastasis, functional status, and response towards previous therapies. Here, we review the current state of the literature regarding treatment modalities, focusing on the treatment recommendations per the American Urological Association (AUA), recent clinical trials, and their limitations. An accurate and reliable overview of the strengths and limitations of PCa therapeutics could also allow personalized therapeutic interventions against PCa.

Alterations of tumor microenvironment by nitric oxide impedes castration-resistant prostate cancer growth.

Immune targeted therapy of nitric oxide (NO) synthases are being considered as a potential frontline therapeutic to treat patients diagnosed with locally advanced and metastatic prostate cancer. However, the role of NO in castration-resistant prostate cancer (CRPC) is controversial because NO can increase in nitrosative stress while simultaneously possessing antiinflammatory properties. Accordingly, we tested the hypothesis that increased NO will lead to tumor suppression of CRPC through tumor microenvironment. S-nitrosoglutathione (GSNO), an NO donor, decreased the tumor burden in murine model of CRPC by targeting tumors in a cell nonautonomous manner. GSNO inhibited both the abundance of antiinflammatory (M2) macrophages and expression of pERK, indicating that tumor-associated macrophages activity is influenced by NO. Additionally, GSNO decreased IL-34, indicating suppression of tumor-associated macrophage differentiation. Cytokine profiling of CRPC tumor grafts exposed to GSNO revealed a significant decrease in expression of G-CSF and M-CSF compared with grafts not exposed to GSNO. We verified the durability of NO on CRPC tumor suppression by using secondary xenograft murine models. This study validates the significance of NO on inhibition of CRPC tumors through tumor microenvironment (TME). These findings may facilitate the development of previously unidentified NO-based therapy for CRPC.

The role of leptin and obesity on male infertility.

PURPOSE OF REVIEW: Several studies suggest a strong association between leptin, obesity, and infertility with respect to the hypothalamic-pituitary-gonadal (HPG) axis, androgen regulation, and sperm production, but the direct mechanistic association between these is still largely unexplored. This review focuses on understanding the association between leptin, obesity, and male infertility. RECENT FINDINGS: Obesity is linked to fertility dysfunction in both genders. Obesity in men may affect their fertility by impaired spermatogenesis, reduced testosterone levels, erectile dysfunction, and poor libido by putatively targeting the HPG and hypothalamic-pituitary-adrenal axes. Leptin plays key roles in many metabolic functions, including reproduction. High concentrations of leptin have been found in infertile men with disorders affecting the testicular parenchyma, including nonobstructive azoospermia, oligozoospermia, and oligo-astheno-teratozoospermia. Additionally, serum leptin levels have negative associations with serum testosterone levels and sperm parameters and positive associations with serum follicle-stimulating hormone and luteinizing hormone levels and abnormal sperm morphology. SUMMARY: Excessive leptin production may be a significant contributor to the development of androgen insufficiency and reduced reproductive function in obese men. Understanding the relation between leptin, obesity, and reproduction may shed light on future targeted treatments for male infertility.

Effect of Distortions on the Geometric and Electronic Structures of One-Electron Oxidized Vanadium(IV), Copper(II), and Cobalt(II)/(III) Salen Complexes.

The ligands N,N'-bis(3-tert-butyl-5-methoxysalicylidene)-1,2-ethanediamine and N,N'-bis(3-tert-butyl-5-methoxysalicylidene)-1,3-propanediamine were chelated to V(IV)═O (1, 2), Cu(II) (3, 4), Co(II) (5), and Co(III) (6). The X-ray crystal structures of 1-6 were solved. The vanadium center in 1-2 resides in square pyramidal geometry, with an axially bound oxo ligand, whereas the metal ion displays a tetrahedrally distorted square planar geometry in 3-5. The extent of distortion is correlated to the length of the diamine spacer: The longer the linker, the larger the tetrahedral distortions. Complex 6 is octahedral with a bidentate acetate molecule that completes the coordination sphere. All the complexes were characterized by UV-vis and EPR spectroscopies, as well as DFT calculations and electrochemistry. Complexes 1-6 exhibit a reversible one-electron oxidation wave in the range -0.11-0.26 V vs Fc+/Fc. The cations 1+ and 2+ were structurally characterized, showing an octahedral V(V) ion with one oxo and one water molecule coordinated in axial positions. Their vis-NIR spectra are dominated by a band at 727 and 815 nm, respectively, which is assigned to a phenolate-to-vanadium(V) charge transfer (CT) transition. The crystal structures of 3+ and 4+ are congruent with Cu(II)-radical species, wherein the metal center remains four-coordinated. Both feature a Class II (Robin-Day classification scale) IVCT transition at around 1200 nm (ε > 1 mM cm-1), indicative of partial localization of the radical. The structure of 5+ displays a square pyramidal cobalt ion, where the fifth (axial) coordination is occupied by a water molecule. It displays a NIR feature at 1244 nm and is described as intermediate between high spin Co(III) and Co(II) radical. In the presence of acetate the dimer [(5)2(µ-OAc)]+ forms, which was structurally characterized and shows a blue shift and lowering in intensity of the NIR absorption band in comparison to 5+. Complex 6+ is a genuine Co(III) radical complex, wherein the phenoxyl moiety is localized on one side of the molecule.

Tumor Microenvironment and Nitric Oxide: Concepts and Mechanisms.

The cancer tissue exists not as a single entity, but as a combination of different cellular phenotypes which, taken together, dramatically contribute to the entirety of their ecosystem, collectively termed as the tumor microenvironment (TME). The TME is composed of both immune and nonimmune cell types, stromal components, and vasculature-all of which cooperate to promote cancer progression. Not all immune cells, however, are immune-suppressive; some of them can promote the immune microenvironment to fight the invading and uncontrollably dividing cell populations at the initial stages of tumor growth. Yet, many of these processes and cellular phenotypes fall short, and the immune ecosystem more often than not ends up stabilizing in favor of the "resistant" resident cells that begin clonal expansion and may progress to metastatic forms. Stromal components, making up the extracellular matrix and basement membrane, are also not the most innocuous: CAFs embedded throughout secrete proteases that allow the onset of one of the most invasive processes-angiogenesis-through destruction of the ECM and the basement membrane. Vasculature formation, because of angiogenesis, is the largest invader of the TME and the reason metastasis happens. Vasculature is so sporadic and omnipresent in the TME that most drug therapies are mainly focused on stopping this uncontrollable process. As the tumor continues to grow, different processes are constantly supplying it with the ingredients favorable for tumor progression and eventual metastasis. For example, angiogenesis promotes blood vessel formation that will allow the bona fide escape of tumor cells to take place. Another process like hypoxia will present itself in several forms throughout the tumor (mild or acute, cycling or permanent), starting mechanisms such as epithelial to mesenchymal transitions (EMT) of resident cells and inadvertently placing the cells in such a stressful condition that production of ROS and DNA damage is unavoidable. DNA damage can induce mutagenicity while allowing resistant cells to survive. This is where drugs and treatments can subsequently suffer in effectiveness. Finally, another molecule has just surfaced as being a very important player in the TME: nitric oxide. Often overlooked and equated with ROS and initially assigned in the category of pathogenic molecules, nitric oxide can definitely do some damage by causing metabolic reprogramming and promotion of immunosuppressive phenotypes at low concentrations. However, its actions seem to be extremely dose-dependent, and this issue has become a hot target of current treatment goals. Shockingly, nitric oxide, although omnipresent in the TME, can have a positive effect on targeting the TME broadly. Thus, while the TME is a myriad of cellular phenotypes and a combination of different tumor-promoting processes, each process is interconnected into one whole: the tumor microenvironment.

Artificial Intelligence in Reproductive Urology.

PURPOSE OF REVIEW: The promise of artificial intelligence (AI) in medicine has been widely theorized over the past couple of decades. It has only been with technological advances over the past few years that physicians and computer scientists have started discovering its true clinical potential. Reproductive urology is a sub-discipline that AI could be of great contribution, as current predictive models and subjectivity within the field have several limitations. We review the literature to summarize recent AI applications in reproductive urology. RECENT FINDINGS: Early AI applications in reproductive urology focused on predicting semen parameters based on questionnaires that identify potential environmental factors and/or lifestyle habits impacting male fertility. AI has shown success in predicting the patient subpopulation most likely to need a genetic workup for azoospermia. With recent advances in image processing, automated sperm detection is a reality. Semen analyses, once a laboratory-only diagnostic test, have moved into health consumer homes with the advent of AI. AI's prospects in medicine are considerable and there is strong potential for AI within reproductive urology. Research in identifying the factors that can affect reproductive success either naturally or with assisted reproduction is of paramount importance to move the field forward.

S-Nitrosoglutathione Reductase (GSNOR) Deficiency Results in Secondary Hypogonadism.

BACKGROUND: Excess reactive oxygen species and reactive nitrogen species are implicated in male infertility and impaired spermatogenesis. AIM: To investigate the effect of excess reactive nitrogen species and nitrosative stress on testicular function and the hypothalamic-pituitary-gonadal axis using the S-nitrosoglutathione reductase-null (Gsnor-/-) mouse model. METHODS: Testis size, pup number, and epididymal sperm concentration and motility of Gsnor-/- mice were compared with those of age-matched wild-type (WT) mice. Reproductive hormones testosterone (T), luteinizing hormone (LH), and follicle-stimulating hormone were compared in Gsnor-/- and WT mice. Immunofluorescence for Gsnor-/- and WT testis was performed for 3ß-hydroxysteroid dehydrogenase and luteinizing hormone receptor (LHR) and compared. Human chorionic gonadotropin and gonadotropin-releasing hormone stimulation tests were performed to assess and compare testicular and pituitary functions of Gsnor-/- and WT mice. OUTCOMES: Evaluation of fertility and reproductive hormones in Gsnor-/- vs WT mice. Response of Gsnor-/- and WT mice to human chorionic gonadotropin and gonadotropin-releasing hormone to evaluate LH and T production. RESULTS: Gsnor-/- mice had smaller litters (4.2 vs 8.0 pups per litter; P < .01), smaller testes (0.08 vs 0.09 g; P < .01), and decreased epididymal sperm concentration (69 vs 98 × 106; P < .05) and motility (39% vs 65%; P < .05) compared with WT mice. Serum T (44.8 vs 292.2 ng/dL; P < .05) and LH (0.03 vs 0.74 ng/mL; P = .04) were lower in Gsnor-/- than in WT mice despite similar follicle-stimulating hormone levels (63.98 vs 77.93 ng/mL; P = .20). Immunofluorescence of Gsnor-/- and WT testes showed similar staining of 3ß-hydroxysteroid dehydrogenase and LHR. Human chorionic gonadotropin stimulation of Gsnor-/- mice increased serum T (>1,680 vs >1,680 ng/dL) and gonadotropin-releasing hormone stimulation increased serum LH (6.3 vs 8.9 ng/mL; P = .20) similar to WT mice. CLINICAL TRANSLATION: These findings provide novel insight to a possible mechanism of secondary hypogonadism from increased reactive nitrogen species and excess nitrosative stress. STRENGTHS AND LIMITATIONS: Limitations of this study are its small samples and variability in hormone levels. CONCLUSION: Deficiency of S-nitrosoglutathione reductase results in secondary hypogonadism, suggesting that excess nitrosative stress can affect LH production from the pituitary gland. Masterson TA, Arora H, Kulandavelu S, et al. S-Nitrosoglutathione Reductase (GSNOR) Deficiency Results in Secondary Hypogonadism. J Sex Med 2018;15:654-661.

Immediate and early implant placement in single-tooth gaps in the anterior maxilla: A prospective study on ridge dimensional, clinical, and aesthetic changes.

OBJECTIVES: This prospective study evaluated the impact of timing of placement (immediate and early) on the horizontal ridge dimensional changes, clinical, and aesthetic outcomes of implants placed in single-tooth gaps in the anterior maxilla. MATERIALS AND METHODS: Implants were placed in single-tooth gaps in the anterior maxilla of 30 patients, either immediately after extraction (Group A, n = 15) or after a healing period of 4-8 weeks (Group B, n = 15). In both groups, implant placement was followed by a 3- to 4-month period of non-submerged healing, after which definitive crowns were placed. Study models were obtained before extraction (T0), at implant placement (T1), at the insertion of a definitive crown (T2), and 1-year thereafter (T3). Horizontal ridge dimensional changes were measured by superimposing the optical scans of the study models from different time-points. Radiographs and photographs were used to evaluate changes in marginal bone levels and soft tissue recession. Aesthetic evaluation was carried out using the Pink and White Esthetic Score (PES and WES) indices. Patient-reported outcomes were measured using a subjective questionnaire. RESULTS: A 100% implant survival rate was observed in both groups after a 1-year follow-up. Analysis showed a labial horizontal tissue dimensional change of 0.61 mm and 0.72 mm from T0 to T3 in Groups A and B, respectively. Acceptable PES values were observed in both groups (Group A: 9.40; Group B: 9.27) after the 1-year follow-up period. No incidence of advanced mucosal recession was observed between definitive crown insertion and 1-year follow-up in both groups. No significant changes were observed for all other measured variables at different time-points. CONCLUSIONS: Immediate and early placed implants in single-tooth gaps in the anterior maxilla showed similar ridge dimensional changes as well as acceptable clinical, aesthetic, and patient-centred outcomes in the short-term (1-year follow-up).

Clinical and aesthetic outcomes of immediately placed single-tooth implants with immediate vs. delayed restoration in the anterior maxilla: A retrospective cohort study.

OBJECTIVE: To evaluate the impact of the timing of restoration on clinical and aesthetic outcomes following immediate implant placement in the maxillary aesthetic zone. MATERIAL AND METHODS: Forty patients (16 males, 24 females) with a mean age of 50.55 ± 12.79 years (range 19-74) who had a single maxillary anterior tooth replaced by an immediate implant were included in this study. Twenty patients had their implant restored immediately with a provisional restoration (Group A), while the other 20 patients had a delayed restoration placed after 3-4 months of non-submerged healing (Group B). Clinical parameters and hard-tissue changes were evaluated after a mean follow-up period of 3 years. Aesthetic evaluation was carried out using the Pink Esthetic Score (PES) and the White Esthetic Score (WES). RESULTS: No significant differences were observed in the bone level changes between the two groups: 0.05 ± 0.65 mm mesially and 0.06 ± 0.52 mm distally for the immediate group and 0.30 ± 0.54 mm mesially and 0.21 ± 0.60 mm distally for the delayed group, respectively. The median PES scores were 11.5 for Group A and 10 for Group B. Mean PES and WES scores did not differ significantly between Groups A and B: PES (11.1 vs. 10.3; p = .16) and WES (8.4 vs. 7.8; p = .16). In terms of individual PES variables, the distal papillae were significantly better in Group A as compared to Group B (p = .006). CONCLUSIONS: Within the limits of this study, timing of restoration seemed to positively affect the aesthetic outcomes of immediately placed implants as evidenced by higher median PES values for the immediate restoration group when compared to the delayed restoration group. Restoration timing had no impact on the individual PES variables, except for the distal papillary height which was superior in the immediate restoration group.

Evaluation of the influence of implant placement timing on the esthetic outcomes of single tooth implant treatment in the anterior maxilla: A retrospective study.

OBJECTIVES: The purpose of this retrospective study was to investigate the influence of implant placement timing on the esthetic outcomes for single implants in the anterior maxilla. MATERIALS AND METHODS: One hundred and ten patients (48 males; 62 females) who received a single-tooth implant after extraction either immediately (Type 1); after 4-8 weeks (Type 2); after 8-16 weeks (Type 3); or more than 16 weeks (Type 4) were evaluated in terms of esthetic outcomes after a mean post-placement interval of 26.3 months (range 12-116). Esthetic outcomes were measured using the Pink and White Esthetic Score (PES; WES). Stepwise regression analysis was performed to analyze the effect of timing of placement, as well as patient demographics and other clinical parameters on the esthetic outcomes. RESULTS: No statistically significantly differences in PES were found between the various treatment modalities with Type 1 implants (n = 33) scoring 10.58 ± 1.65 (median: 11), followed by 10.36 ± 2.09 (median: 10.5), 9.68 ± 2.43 (median: 10), and 9.63 ± 2.21 (median: 10) for Type 2 (n = 14), Type 3 (n = 19), and Type 4 (n = 44), respectively. For immediate implants, a trend towards better esthetic outcomes was observed when implant placement was done flaplessly in cases with intact buccal bone (Type 1A, median PES 11) as compared to cases with partial/complete missing buccal plates where a flap was raised (Type 1B, median PES 10). Overall, the only parameter that influenced esthetic outcomes (as measured by PES) was gender, with females having significantly superior results. The median WES was 8 and 96% of the crowns were deemed esthetically acceptable, with crowns placed by specialist prosthodontists yielding higher scores than those placed by general practitioners. CONCLUSIONS: Single tooth implants in the anterior maxilla showed satisfactory outcomes when measured with objective esthetic criteria. Timing of implant placement did not significantly influence the esthetic outcomes, although a trend towards better outcomes was seen with immediate implant placement as observed by higher median PES values. CLINICAL SIGNIFICANCE: Single tooth implant placement in the anterior maxilla is a predictable treatment modality for achieving acceptable esthetic outcomes regardless of the timing of placement.

Recurrent Prosthetic Pulmonary Valve Endocarditis in Repaired Tetralogy of Fallot.

25 year old male who was a known case of repaired Tetralogy of Fallot with history of early prosthetic pulmonary valve fungal endocarditis in 2012 presented in 2016 with history of prolonged fever. On subsequent work up, he was diagnosed to have recurrent fungal prosthetic pulmonary valve endocarditis.

Prokineticin receptor 1 is required for mesenchymal-epithelial transition in kidney development.

Identification of factors regulating renal development is important to understand the pathogenesis of congenital kidney diseases. Little is known about the molecular mechanism of renal development and functions triggered by the angiogenic hormone prokineticin-2 and its receptor, PKR1. Utilizing the Gata5 (G5)-Cre and Wilms tumor 1 (Wt1)(GFP)cre transgenic lines, we generated mutant mice with targeted PKR1 gene disruptions in nephron progenitors. These mutant mice exhibited partial embryonic and postnatal lethality. Kidney developmental defects in PKR(G5-/-) mice are manifested in the adult stage as renal atrophy with glomerular defects, nephropathy, and uremia. PKR1(Wt1-/-) embryos exhibit hypoplastic kidneys with premature glomeruli and necrotic nephrons as a result of impaired proliferation and increased apoptosis in Wt1(+) renal mesenchymal cells. PKR1 regulates renal mesenchymal-epithelial transition (MET) that is involved in formation of renal progenitors, regulating glomerulogenesis toward forming nephrons during kidney development. In the isolated embryonic Wt1(+) renal cells, overexpression or activation of PKR1 promotes MET defined by the transition from elongated cell to octagonal cell morphology, and alteration of the expression of MET markers via activating NFATc3 signaling. Together, these results establish PKR1 via NFATc3 as a crucial modifier of MET processing to the development of nephron. Our study should facilitate new therapeutic opportunities in human renal disorders.-Arora, H., Boulberdaa, M., Qureshi, R., Bitirim, V., Messadeq, N., Dolle, P., Nebigil, C. G. Prokineticin receptor 1 is required for mesenchymal-epithelial transition in kidney development.

Correlation between pre-operative buccal bone thickness and soft tissue changes around immediately placed and restored implants in the maxillary anterior region: A 2-year prospective study.

OBJECTIVES: This study evaluated the correlation between pre-operative buccal cortical bone thickness and peri-implant tissue response following immediate placement and restoration of implants in the maxillary aesthetic zone. MATERIAL AND METHODS: Eighteen patients (3 males, 15 females) with an age range of 19-57 years requiring the replacement of a single maxillary anterior tooth were included in this prospective study. Patients were selected on the basis of defined criteria: intact socket walls, absence of any acute infection in the sockets, absence of any gingival marginal pathology and attainment of a high primary stability (≥30 Ncm) at implant placement. Regardless of buccal bone thickness, all participating patients underwent the same treatment strategy that involved removal of the failed tooth, flapless surgery, immediate implant placement, grafting of the implant-socket gap and connection of a screw-retained provisional restoration. Buccal bone thickness was evaluated using pre-operative CBCT scans. Intra-oral photographs were taken before implant placement (baseline) and at 1- and 2-year follow-up to assess soft tissue changes around the implants. Aesthetic evaluation was carried out using the pink esthetic score (PES). RESULTS: All implants remained osseointegrated during the follow-up period of 2 years with mesial papilla, distal papilla, and mid-facial gingiva showing a mean recession of 0.06 ± 0.71 mm, 0.25 ± 0.78 mm, and 0.22 ± 0.83 mm, respectively. Pink esthetic score values improved from a median value of 9 (IQR 8.75-10.25) pre-operatively to 11 (IQR 9.75-12) at the end of 2 years. No significant correlation was found between buccal bone thickness (range 0.45-1.24 mm) and soft tissue or aesthetic changes. CONCLUSIONS: Within the limits of this study, no significant correlation could be found between pre-operative buccal bone width and the soft tissue and aesthetic outcome following immediate implant placement and restoration in the anterior maxilla. Therefore, favourable clinical and aesthetic outcomes could be achieved by applying a strict selection criteria and treatment protocol regardless of the initial thickness of the buccal bone.

Study of apoptosis-related interactions in colorectal cancer.

Abnormalities in apoptotic functions contribute to the pathogenesis of colorectal cancer. In this study, molecular interactions behind the apoptotic regulation have been explored. For this purpose, enrichment analysis was performed considering microRNAs (miRNAs) that putatively target TP53 and altered during colon cancer. This revealed gene associated with both TP53 and miRNAs. Further analysis showed that a significant molecular interaction between the shortlisted candidates (TP53, miR-143, KRAS, BCL2, and PLK1) exists. Mutation study was conducted to confirm the clinical relevance of candidates. It showed that the mutation extent does not significantly alter survival in patients thus making these candidates suitable as drug targets. Overall, we showed the importance of interactions between TP53, miR-143, KRAS, BCL2, and PLK1 with respect to colorectal cancer using bioinformatics approach.