Five-year Long-term Outcomes of Stereotactic Body Radiation Therapy for Operable Versus Medically Inoperable Stage I Non–small-cell Lung Cancer: Analysis by Operability,Fractionation Regimen,Tumor Size,and Tumor Location

Background

Stereotactic body radiation therapy (SBRT) is standard for medically inoperable stage I non–small-cell lung cancer (NSCLC) and is emerging as a surgical alternative in operable patients. However, limited long-term outcomes data exist, particularly according to operability. We hypothesized long-term local control (LC) and cancer-specific survival (CSS) would not differ by fractionation schedule, tumor size or location, or operability status, but overall survival (OS) would be higher for operable patients.

Spike‐associated networks and intracranial electrographic findings

Aims. Functional connectivity is providing new insights into the network nature of epilepsy with growing clinical applications. Our objective was to validate a novel magnetoencephalography‐based method to non‐invasively measure the epileptic network. Methods. We retrospectively identified pediatric and adult patients with refractory focal epilepsy who underwent pre‐surgical magnetoencephalography with subsequent intracranial electrographic monitoring. Magnetoencephalography tracings were visually reviewed, and interictal epileptiform discharges (“spikes”) were individually marked. We then evaluated differences in whole‐brain connectivity during brief epochs preceding the spikes and during the spikes using the Network‐Based Statistic to test differences at the network level. Results. In six patients with statistically‐significant network differences, we observed substantial overlap between the spike‐associated networks and electrographically active areas identified during intracranial monitoring (the spike‐associated network was 78% and 83% sensitive for intracranial electroencephalography‐defined regions in the irritative and seizure onset zones, respectively). Conclusion. These findings support the neurobiological validity of the spike‐associated network method. Assessment of spike‐associated networks has the potential to improve surgical planning in epilepsy surgery patients by identifying components of the epileptic network prior to implantation.     

Longitudinal Positron Emission Tomography of Dopamine Synthesis in Subjects with GBA1 Mutations

Mutations in GBA1, the gene mutated in Gaucher disease, are a common genetic risk factor for Parkinson disease, although the penetrance is low. We performed [¹⁸F]-fluorodopa positron emission tomography studies of 57 homozygous and heterozygous GBA1 mutation carriers (15 with parkinsonism) and 98 controls looking for early indications of dopamine loss using voxelwise analyses to identify group differences in striatal [¹⁸F]-fluorodopa uptake (K_i). Forty-eight subjects were followed longitudinally. Cross-sectional and longitudinal comparisons of K_i and K_i change found significant effects of Parkinson disease. However, at baseline and over time, striatal [¹⁸F]-fluorodopa uptake in mutation carriers without parkinsonism did not significantly differ from controls. ANN NEUROL 2020;87:652–657     

Life on the Western Front of Israel Stressful Living Conditions and Adolescent Cannabis Use

Negative implications of exposure to violence on health and well-being of youth have been observed and studied worldwide and especially in Israel. Youth in the Western Negev of the country have been exposed to missile and terror attacks for more than a decade. However, implications of such prolonged exposure have not been fully studied. This study is aimed at the implications of exposure to such conditions on youth in the town of Ofakim in the Negev. A focus group was conducted with youth following the Israeli Defense Forces’ “Protective Edge” response to continued attacks from Gaza (July–August 2014). Focus group participants reported high stress levels during the operation that resulted in an increase of substance use including alcohol, tobacco, cannabis, and synthetic cannabis-like substances (e.g., “Nice Guy,” “Spice,” and “Black Mamba”) and changes in eating and sleeping behavior. The Ofakim resilience center served as a shelter for participants providing for them with physical and emotional comfort. Staying in the “shelter” used for protection against missile attack promoted youth resilience. Exposure to violence has a significant impact on the health and well-being of young people and others. A secure receptive facility that provides trust and support can serve as an important moderator of the negative impact of emergency conditions. From the results reported in this article, further research is needed to fully assess the long-term effects of stress conditions including the use of cannabis and synthetic cannabis-like substances among youth and other residents in the Western Negev.

     

HIV Neuropathogenesis in the Presence of a Disrupted Dopamine System

Antiretroviral therapy (ART) has transformed HIV into a chronic condition, lengthening and improving the lives of individuals living with this virus. Despite successful suppression of HIV replication, people living with HIV (PLWH) are susceptible to a growing number of comorbidities, including neuroHIV that results from infection of the central nervous system (CNS). Alterations in the dopaminergic system have long been associated with HIV infection of the CNS. Studies indicate that changes in dopamine concentrations not only alter neurotransmission, but also significantly impact the function of immune cells, contributing to neuroinflammation and neuronal dysfunction. Monocytes/macrophages, which are a major target for HIV in the CNS, are responsive to dopamine. Therefore, defining more precisely the mechanisms by which dopamine acts on these cells, and the changes in cellular function elicited by this neurotransmitter are necessary to develop therapeutic strategies to treat neuroHIV. This is especially important for vulnerable populations of PLWH with chemically altered dopamine concentrations, such as individuals with substance use disorder (SUD), or aging individuals using dopamine-altering medications. The specific neuropathologic and neurocognitive consequences of increased CNS dopamine remain unclear. This is due to the complex nature of HIV neuropathogenesis, and logistical and technical challenges that contribute to inconsistencies among cohort studies, animal models and in vitro studies, as well as lack of demographic data and access to human CNS samples and cells. This review summarizes current understanding of the impact of dopamine on HIV neuropathogenesis, and proposes new experimental approaches to examine the role of dopamine in CNS HIV infection.

HIV Neuropathogenesis in the Presence of a Disrupted Dopamine System. Both substance abuse disorders and the use of dopaminergic medications for age-related diseases are associated with changes in CNS dopamine concentrations and dopaminergic neurotransmission. These changes can lead to aberrant immune function, particularly in myeloid cells, which contributes to the neuroinflammation, neuropathology and dysfunctional neurotransmission observed in dopamine-rich regions in HIV+ individuals. These changes, which are seen despite the use antiretroviral therapy (ART), in turn lead to further dysregulation of the dopamine system. Thus, in individuals with elevated dopamine, the bi-directional interaction between aberrant dopaminergic neurotransmission and HIV infection creates a feedback loop contributing to HIV associated neurocognitive dysfunction and neuroHIV. However, the distinct contributions and interactions made by HIV infection, inflammatory mediators, ART, drugs of abuse, and age-related therapeutics are poorly understood. Defining more precisely the mechanisms by which these factors influence the development of neurological disease is critical to addressing the continued presence of neuroHIV in vulnerable populations, such as HIV-infected older adults or drug abusers. Due to the complexity of this system, understanding these effects will require a combination of novel experimental modalities in the context of ART. These will include more rigorous epidemiological studies, relevant animal models, and in vitro cellular and molecular mechanistic analysis.

     

Prosthesis-Patient Mismatch Increases Early and Late Mortality in Low Risk Aortic Valve Replacement

PPM was highly associated with long-term all-cause mortality. Small Aortic Valve Annulus MDT (SAVA-MDT) exploring options to prevent PPM, including the implantation of newer generation prosthetic valves, aortic root enlargement and TAVI, should be established.

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Delivery mode is associated with maternal mental health following childbirth

Childbirth is a life-transforming event often followed by a time of heightened psychological vulnerability in the mother. There is a growing recognition of the importance of obstetrics aspects in maternal well-being with the way of labor potentially influencing psychological adjustment following parturition or failure thereof. Empirical scrutiny on the association between mode of delivery and postpartum well-being remains limited. We studied 685 women who were on average 3 months following childbirth and collected information concerning mode of delivery and pre- and postpartum mental health. Analysis of variance revealed that women who had cesarean section or vaginal instrumental delivery had higher somatization, obsessive compulsive, depression, and anxiety symptom levels than those who had natural or vaginal delivery as well as overall general distress, controlling for premorbid mental health, maternal age, education, primiparity, and medical complication in newborn. Women who underwent unplanned cesarean also had higher levels of childbirth-related PTSD symptoms excluding those with vaginal instrumental. The risk for endorsing psychiatric symptoms reflecting clinically relevant cases increased by twofold following unplanned cesarean and was threefold for probable childbirth-related PTSD. Maternal well-being following childbirth is associated with the experienced mode of delivery. Increasing awareness in routine care of the implications of operative delivery and obstetric interventions in delivery on a woman’s mental health is needed. Screening at-risk women could improve the quality of care and prevent enduring symptoms. Research is warranted on the psychological and biological factors implicated in the mode of delivery and their role in postpartum adjustment.

     

Chlorhexidine. An adjunct to periodontal therapy

Chlorhexidine is an effective antimicrobial agent. Its application can enhance periodontal therapy. The pharmacology of chlorhexidine and suggestions for its use are outlined. In addition, its potential for inducing cancer and bacterial resistance are discussed.     

The complete-coverage restoration and the gingival sulcus

There is an interrelationship between complete coverage restorations and the gingiva. The terminal margin plays an important role in maintaining gingival health. Periodontal disease is minimal with restorations which do not invade the sulcus, but the caries attack rate, retention, or esthetic requirements may compel entry into the sulcus.The technique described in this report permits entry into the gingival sulcus without creating permanent injury. The preparation also provides adequate space for the gold collar without injury to the gingiva.