An NCI-sponsored, randomized clinical trial tested whether patients with relapsed ovarian cancer might benefit from surgical debulking of tumors followed by chemotherapy, as compared with ...chemotherapy alone. No significant outcome differences were noted between the patients who underwent surgery and those treated with chemotherapy alone.
Arrays of electrodes for recording and stimulating the brain are used throughout clinical medicine and basic neuroscience research, yet are unable to sample large areas of the brain while maintaining ...high spatial resolution because of the need to individually wire each passive sensor at the electrode-tissue interface. To overcome this constraint, we developed new devices that integrate ultrathin and flexible silicon nanomembrane transistors into the electrode array, enabling new dense arrays of thousands of amplified and multiplexed sensors that are connected using fewer wires. We used this system to record spatial properties of cat brain activity in vivo, including sleep spindles, single-trial visual evoked responses and electrographic seizures. We found that seizures may manifest as recurrent spiral waves that propagate in the neocortex. The developments reported here herald a new generation of diagnostic and therapeutic brain-machine interface devices.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Blast exposure is associated with traumatic brain injury (TBI), neuropsychiatric symptoms, and long-term cognitive disability. We examined a case series of postmortem brains from U.S. military ...veterans exposed to blast and/or concussive injury. We found evidence of chronic traumatic encephalopathy (CTE), a tau protein-linked neurodegenerative disease, that was similar to the CTE neuropathology observed in young amateur American football players and a professional wrestler with histories of concussive injuries. We developed a blast neurotrauma mouse model that recapitulated CTE-linked neuropathology in wild-type C57BL/6 mice 2 weeks after exposure to a single blast. Blast-exposed mice demonstrated phosphorylated tauopathy, myelinated axonopathy, microvasculopathy, chronic neuroinflammation, and neurodegeneration in the absence of macroscopic tissue damage or hemorrhage. Blast exposure induced persistent hippocampal-dependent learning and memory deficits that persisted for at least 1 month and correlated with impaired axonal conduction and defective activity-dependent long-term potentiation of synaptic transmission. Intracerebral pressure recordings demonstrated that shock waves traversed the mouse brain with minimal change and without thoracic contributions. Kinematic analysis revealed blast-induced head oscillation at accelerations sufficient to cause brain injury. Head immobilization during blast exposure prevented blast-induced learning and memory deficits. The contribution of blast wind to injurious head acceleration may be a primary injury mechanism leading to blast-related TBI and CTE. These results identify common pathogenic determinants leading to CTE in blast-exposed military veterans and head-injured athletes and additionally provide mechanistic evidence linking blast exposure to persistent impairments in neurophysiological function, learning, and memory.
To improve skin cancer screening among survivors of childhood cancer treated with radiotherapy where skin cancers make up 58% of all subsequent neoplasms. Less than 30% of survivors currently ...complete recommended skin cancer screening.
This randomized controlled comparative effectiveness trial evaluated patient and provider activation (PAE + MD)
patient and provider activation with teledermoscopy (PAE + MD + TD) compared with patient activation alone (PAE), which included print materials, text messaging, and a website on skin cancer risk factors and screening behaviors. Seven hundred twenty-eight participants from the Childhood Cancer Survivor Study (median age at baseline 44 years), age > 18 years, treated with radiotherapy as children, and without previous history of skin cancer were randomly assigned (1:1:1). Primary outcomes included receiving a physician skin examination at 12 months and conducting a skin self-examination at 18 months after intervention.
Rates of physician skin examinations increased significantly from baseline to 12 months in all three intervention groups: PAE, 24%-39%, relative risk RR, 1.65, 95% CI, 1.32 to 2.08; PAE + MD, 24% to 39%, RR, 1.56, 95% CI, 1.25 to 1.97; PAE + MD + TD, 24% to 46%, RR, 1.89, 95% CI, 1.51 to 2.37. The increase in rates did not differ between groups (
= .49). Similarly, rates of skin self-examinations increased significantly from baseline to 18 months in all three groups: PAE, 29% to 50%, RR, 1.75, 95% CI, 1.42 to 2.16; PAE + MD, 31% to 58%, RR, 1.85, 95% CI, 1.52 to 2.26; PAE + MD + TD, 29% to 58%, RR, 1.95, 95% CI, 1.59 to 2.40, but the increase in rates did not differ between groups (
= .43).
Although skin cancer screening rates increased more than 1.5-fold in each of the intervention groups, there were no differences between groups. Any of these interventions, if implemented, could improve skin cancer prevention behaviors among childhood cancer survivors.
As many people with intellectual disabilities (ID) live longer, the need for access to quality palliative care (PC) rises. People with ID realize significant barriers and inequities in accessing ...health care and PC. The need for integrated disability and PC services with extensive collaboration is great. The following tips are for PC clinicians caring for people with ID, their families, caregivers, and the community. While patient-centered care is difficult to distill into "tips," this article, written by an interdisciplinary team of PC and ID specialists, offers resources and references to improve the care provided to people with ID and serious illnesses.
Because rates of skin cancer are greater among adult survivors of childhood cancer who received radiation therapy than among the general population, the National Cancer Institute recommends skin ...self-examinations and annual physician examination. There has been no comprehensive assessment of survivors’ adherence to the skin cancer screening guidelines associated with skin self-examination (SSE) and physician whole-body skin examination (PSE). We conducted a cross-sectional survey of radiation-treated, adult 5-year survivors of childhood cancer, diagnosed between 1970 and 1986, in the Childhood Cancer Survivor Study cohort. Multivariate multinomial logit regression investigated the association between demographic, cancer diagnosis, patient activation, cancer treatment characteristics, and skin cancer screening practice. Among 728 survivors, 13.1% reported performing SSE in the prior 2 months plus receiving PSE in the prior 12 months, and 16.4% and 11.0% reported performing only an SSE or a PSE, respectively; 59.5% of survivors reported having had neither. Participants at the highest patient activation score were most likely to report SSE plus PSE compared with neither (adjusted relative risk ratio = 4.16, 95% confidence interval = 1.34–12.85). Most adult survivors of childhood cancer who had radiation therapy do not practice strategies that promote early detection of skin cancer. Interventions designed to activate survivors to increase their participation in screening are needed.
To determine polysomnographic parameter differences in children living at higher altitude to children living near sea level.
Prospective study of non-snoring, normal children recruited from various ...communities around Denver, CO. In-lab, overnight polysomnograms were performed at a tertiary care children's hospital. All children required residence for greater than one year at an elevation around 1,600 meters.
45 children (62% female), aged 3-5 years, 88.9% non-Hispanic white with average BMI percentile for age of 47.8% ± 30.7%.
Standard sleep indices were obtained and compared to previously published normative values in a similar population living near sea level (SLG). In the altitude group (AG), the apnea-hypopnea index was 1.8 ± 1.2 and the central apnea-hypopnea index was 1.7 ± 1.1, as compared to 0.9 ± 0.8 and 0.8 ± 0.7, respectively, (P ≤ 0.005) in SLG. Mean end-tidal CO2 level in AG was 42.3 ± 3.0 mm Hg and 40.6 ± 4.6 mm Hg in SLG (P = 0.049). The ≥ 4% desaturation index was 3.9 ± 2.0 in AG compared to 0.3 ± 0.4 in SLG (P < 0.001). Mean periodic limb movement in series index was 10.1 ± 12.3 in AG and 3.6 ± 5.4 in SLG (P = 0.001).
Comparison of altitude and sea level sleep studies in healthy children reveals significant differences in central apnea, apneahypopnea, desaturation, and periodic limb movement in series indices. Clinical providers should be aware of these differences when interpreting sleep studies and incorporate altitude-adjusted normative values in therapeutic-decision making algorithms.
1 US Geological Survey, National Wildlife Health Center, Honolulu Field Station, PO Box 50167, Honolulu, HI 96850, USA
2 NOAA-National Marine Fisheries Service, Pacific Islands Fisheries Science ...Center, 2570 Dole Street, Honolulu, HI 96822, USA
3 Hawaii Institute of Marine Biology, School of Ocean and Earth Science and Technology, University of Hawaii at Manoa, PO Box 1346, Kaneohe, HI 96744, USA
4 College of Veterinary Medicine, Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853-6401, USA
Correspondence Thierry M. Work thierry_work{at}usgs.gov
Fibropapillomatosis (FP) of green turtles has a global distribution and causes debilitating tumours of the skin and internal organs in several species of marine turtles. FP is associated with a presently non-cultivable alphaherpesvirus Chelonid fibropapilloma-associated herpesvirus (CFPHV). Our aims were to employ quantitative PCR targeted to pol DNA of CFPHV to determine (i) if DNA sequesters by tumour size and/or cell type, (ii) whether subculturing of cells is a viable strategy for isolating CFPHV and (iii) whether CFPHV can be induced to a lytic growth cycle in vitro using chemical modulators of replication (CMRs), temperature variation or co-cultivation. Additional objectives included determining whether non-tumour and tumour cells behave differently in vitro and confirming the phenotype of cultured cells using cell-type-specific antigens. CFPHV pol DNA was preferentially concentrated in dermal fibroblasts of skin tumours and the amount of viral DNA per cell was independent of tumour size. Copy number of CFPHV pol DNA per cell rapidly decreased with cell doubling of tumour-derived fibroblasts in culture. Attempts to induce viral replication in known CFPHV-DNA-positive cells using temperature or CMR failed. No significant differences were seen in in vitro morphology or growth characteristics of fibroblasts from tumour cells and paired normal skin, nor from CFPHV pol -DNA-positive intestinal tumour cells. Tumour cells were confirmed as fibroblasts or keratinocytes by positive staining with anti-vimentin and anti-pancytokeratin antibodies, respectively. CFPHV continues to be refractory to in vitro cultivation.
Present address: Tufts University, Cummings School of Veterinary Medicine, 200 Westboro Road, North Grafton, MA 01536, USA.
To understand the interplay between host cytotoxic T-lymphocyte (CTL) responses and the mechanisms by which HIV-1 evades them, we studied viral evolutionary patterns associated with host CTL ...responses in six linked transmission pairs. HIV-1 sequences corresponding to full-length p17 and p24 gag were generated by 454 pyrosequencing for all pairs near the time of transmission, and seroconverting partners were followed for a median of 847 days postinfection. T-cell responses were screened by gamma interferon/interleukin-2 (IFN-γ/IL-2) FluoroSpot using autologous peptide sets reflecting any Gag variant present in at least 5% of sequence reads in the individual's viral population. While we found little evidence for the occurrence of CTL reversions, CTL escape processes were found to be highly dynamic, with multiple epitope variants emerging simultaneously. We found a correlation between epitope entropy and the number of epitope variants per response (r = 0.43; P = 0.05). In cases in which multiple escape mutations developed within a targeted epitope, a variant with no fitness cost became fixed in the viral population. When multiple mutations within an epitope achieved fitness-balanced escape, these escape mutants were each maintained in the viral population. Additional mutations found to confer escape but undetected in viral populations incurred high fitness costs, suggesting that functional constraints limit the available sites tolerable to escape mutations. These results further our understanding of the impact of CTL escape and reversion from the founder virus in HIV infection and contribute to the identification of immunogenic Gag regions most vulnerable to a targeted T-cell attack.
Rapid diversification of the viral population is a hallmark of HIV-1 infection, and understanding the selective forces driving the emergence of viral variants can provide critical insight into the interplay between host immune responses and viral evolution. We used deep sequencing to comprehensively follow viral evolution over time in six linked HIV transmission pairs. We then mapped T-cell responses to explore if mutations arose due to adaption to the host and found that escape processes were often highly dynamic, with multiple mutations arising within targeted epitopes. When we explored the impact of these mutations on replicative capacity, we found that dynamic escape processes only resolve with the selection of mutations that conferred escape with no fitness cost to the virus. These results provide further understanding of the complicated viral-host interactions that occur during early HIV-1 infection and may help inform the design of future vaccine immunogens.
(Abstracted from N Engl J Med 2019;381:1929–1939)The National Comprehensive Cancer Network recommends secondary cytoreduction for ovarian cancer patients with recurrent disease who have received no ...treatment for a period of 6 months following a complete response from prior chemotherapy. Retrospective reviews and meta-analyses have shown the most benefit from this operation in those with platinum-sensitive disease and those with little or no postoperative residual disease.
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