Optimal design of trials to demonstrate the utility of?genomically‐guided therapy: Putting Precision Cancer?Medicine to the test

The new age of Precision Cancer Medicine, with specific biomarkers being used to direct targeted agents, generally concerns only a subset of patients within a certain histopathologically defined tumor type. This paradigm is challenged by the need to perform widespread molecular screening in certified laboratories, with results available to clinicians within reasonable timeframe. Tumor heterogeneity and clonal evolution must be considered in the decision making process. Adaptive and innovative clinical trial designs exploring predictive algorithms and reconsideration of traditional efficacy endpoints are required to rapidly translate scientific discoveries into patient care. Furthermore, international collaboration in cancer research and open discussions on the availability of investigational agents will likely redefine the drug development and approval process in the coming years.     

Participation of hypoxia-inducible factor-1α and lymphangiogenesis in metastatic and non-metastatic lower lip squamous cell carcinoma

This study evaluated the lymphatic density and HIF-1α immunoexpression in lower lip squamous cell carcinoma (LLSCC) and their correlation with clinicopathological (nodal metastasis, clinical stage, histological grade, recurrence and disease outcome) and survival parameters in 20 metastatic and 20 non-metastatic LLSCCs. Lymphatic density was established by counting microvessels (D2-40⁺) at the tumor core (intratumoral lymphatic density, ILD) and at the invasive front (peritumoral lymphatic density, PLD) and percentages of immunopositive cells for HIF-1α were established. No statistically significant differences in lymphatic densities in relation to clinicopathological parameters were observed (P > 0.05). All cases exhibited nuclear and cytoplasmic HIF-1α immunoexpression, with relatively high percentages of positivity, but this expression was not statistically different in relation to clinicopathological variables (P > 0.05). Positive correlations were observed between ILD and PLD (P = 0.002), and between nuclear HIF-1α immunoexpression at the tumor core and ILD (P = 0.001). The results suggest ILD and PLD are not directly related to the development of lymph node metastasis in LLSCC. The striking expression of HIF-1α suggests the involvement of this protein in the etiopathogenesis of LLSCCs, possibly stimulating lymphangiogenesis at the tumor core. However, this protein does not seem to exert a determining influence on the biological aggressiveness of these tumors.     

Influence of cortical bone anchorage on the primary stability of dental implants

Purpose

This retrospective chart review study assessed patient records to determine implant insertion torque (IT) and implant stability quotient (ISQ) values during implant placement to evaluate the correlation with cortical bone anchorage (mono- or bicortical).

Methods

Primary stability data (IT during implant placement surgery and ISQ values immediately after implant placement) and cone beam computed tomography of 33 patients (165 implants) were assessed. Patients were divided into the following groups: G1, implants with apical cortical bone contact; G2, implants with bicortical bone contact (apical and cervical regions); and G3, implants with cervical cortical bone contact.

Results

Sixty-eight implants were excluded due to cortical bone contact on regions other than implant apical or cervical. Ninety-seven implants were therefore assessed for this study. No implant failure was found after a mean 70.42-month follow-up time. Implants with bicortical anchorage (G2) showed higher IT (64.1 Ncm) during implant placement and higher ISQ values (76) (p?<?0.05). Monocortical implants (G1, apical, and G3, cervical) showed similar IT (G1 52.3 and G3 54.3) and ISQ values (G1 71.9 and G3 73) (p?>?0.05). No correlation (Pearson correlation coefficient) was found between the two stability measurement devices for the different cortical bone anchorages that were analyzed (G1 0.190, G2 0.039, and G3 ??0.027) (p?>?0.05).

Conclusions

Insertion torque values and implant stability quotients were influenced by cortical bone contact. No significant correlation was found between IT and ISQ values—higher insertion torque values do not necessarily lead to higher implant stability quotients.

     

Live and let die: Hydrogen peroxide production by the commensal flora and its role in maintaining a symbiotic microbiome

The majority of commensal oral streptococci are able to generate hydrogen peroxide (H₂O₂) during aerobic growth, which can diffuse through the cell membrane and inhibit competing species in close proximity. Competing H₂O₂ production is mainly dependent upon the pyruvate oxidase SpxB, and to a lesser extent the lactate oxidase LctO, both of which are important for energy generation in aerobic environments. Several studies point to a broad impact of H₂O₂ production in the oral environment, including a potential role in biofilm homeostasis, signaling, and interspecies interactions. Here, we summarize the current research regarding oral streptococcal H₂O₂ generation, resistance mechanisms, and the ecological impact of H₂O₂ production. We also discuss the potential therapeutic utility of H₂O₂ for the prevention/treatment of dysbiotic diseases as well as its potential role as a biomarker of oral health.     

Self-supported nickel nanoparticles on germanophosphate glasses: synthesis and applications in catalysis

The development of supported catalysts based on simple procedures without waste products and time-consuming steps is highly desirable. In this paper, self-supported nickel-based nanoparticles were obtained at the surface of the germanophosphate glasses by bottom-up process and evaluated as potential catalysts for the benzyl alcohol oxidation and bis(indolyl)methanes synthesis. A classical melt-quenching technique was used for preparing the nickel-doped germanophosphate glasses, followed by annealing under a hydrogen atmosphere at 400 °C for two different times. The approach enabled the synthesis of self-supported nanoparticles as a homogeneous film, covering the glass surface. The physical and chemical properties of synthesized glasses were characterized by UV-vis and Raman spectroscopies and thermal analysis. Scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS) were performed to monitor the growth process, morphology and chemical bonding structure of the nanoparticles surface.

The development of supported catalysts based on simple procedures without waste products and time-consuming steps is highly desirable.     

Current concepts in MRI of rectus femoris musculotendinous (myotendinous) and myofascial injuries in elite athletes

Rectus femoris injuries are extremely common in athletes, particularly in soccer players, rugby player, and sprinters. Magnetic resonance imaging (MRI) plays a key role in diagnosis, prognosis, and rehabilitation of these injuries. The current article discusses current concepts in the diagnosis and treatment of rectus femoris injuries in elite athletes, including a discussion of the less well known myofascial injuries and key prognostic factors as seen at MR imaging.     

The role of vision in Parkinson's disease locomotion control: free walking task

The current study addressed the role of visual information in the control of locomotion in people with Parkinson's disease. Twelve healthy individuals and 12 mild to moderate Parkinson's disease patients were examined while walking at self-selected velocities, under three visual sampling conditions: dynamic (normal lighting), static (static visual samples) and voluntary visual sampling. Subjects wore liquid crystal glasses for visual manipulation. Outcome measures included spatial-temporal parameters, braking and propulsive impulses, number of samples and total duration of voluntary visual samples. Interaction between groups and visual conditions was not observed for kinematic parameters or braking and propulsive impulses. There were no significant differences between groups for voluntary visual sampling variables. These findings suggest that the visual control of locomotion in Parkinson's disease patients was similar to that observed in controls. Furthermore, Parkinson's disease patients were not more dependent on visual information than healthy individuals for the locomotion control.     

Nocturia × disturbed sleep: a review

In this article, we provide a concise review of the literature on nocturia and its interference with sleep and, consequently, on quality of life. There are few studies addressing the possible influences of nocturia on sleep disruption. Nocturia is a potential contributor to sleep disorders because affected individuals experience nonrestorative sleep due to frequent interruptions. We also attempted to determine whether individuals with nocturia wake to urinate or, alternately, urinate because they are awake. This review attempts to outline this specific association by examining the possible interactions with other medical conditions and the pathophysiology and prevalence. Most studies have observed a higher prevalence among women; however, the impact on quality of life is higher in men. Nocturia is not necessarily associated with natural aging. The exploration of these topics provides information to clarify the implications of nocturia on sleep, sleep disruption, and other related consequences. Additional evidence is still required to address the question of whether nocturia leads to disordered sleep or whether disordered sleep leads to nocturia.     

Credentialing for transvaginal mesh placement—a case for “added qualification” in competency

Introduction and hypothesis

A process of added qualification of transvaginal mesh (TVM) placement is desirable.

Methods

Through a physician-led partnership of specialty societies, centers of excellence, and industry, a core curriculum encompassing mesh/graft biology, technical skills, and safety can be coupled with current educational endeavors instructing surgeons in the use of TVM. A posttest process can verify a knowledge-based competency in mesh/graft safety. An auditing process after implementation would be optimal.

Results

We recommend implementation of a five-step process in order to accomplish these goals.

Conclusions

It is hoped through these efforts, the ultimate goal of patient safety may be reached.