The occurrence altitudes of middle atmospheric temperature inversions and mesopause over low-latitude Indian sector

We study the occurrence characteristics of mesospheric inversion layers (MILs) in the 60–105 km altitude region over the low-latitude Indian sector. We note that lower inversions in the mesospheric temperatures occur in the 70–75 km altitude regions while the upper inversions occur in 90–95 km altitude regions. The mesopause altitude is mostly noted to be ~ 98 km with the night-time mesopause (particularly in the year 2002) showing a small peak in the mesopause occurrence at ~ 75 km altitude. We note higher occurrence rate of MILs during high solar activity year compared to low solar activity year. It is also observed that night time MILs show a systematic seasonal variability, with higher occurrence of single and double temperature inversions during equinoxes

A Cryogenic Silicon Interferometer for Gravitational-wave Detection

The detection of gravitational waves from compact binary mergers by LIGO has opened the era of gravitational wave astronomy, revealing a previously hidden side of the cosmos. To maximize the reach of the existing LIGO observatory facilities, we have designed a new instrument that will have 5 times the range of Advanced LIGO, or greater than 100 times the event rate. Observations with this new instrument will make possible dramatic steps toward understanding the physics of the nearby universe, as well as observing the universe out to cosmological distances by the detection of binary black hole coalescences. This article presents the instrument design and a quantitative analysis of the anticipated noise floor

Human Immunodeficiency Virus Envelope Protein Gp120 Induces Proliferation but Not Apoptosis in Osteoblasts at Physiologic Concentrations

Patients with HIV infection have decreased numbers of osteoblasts, decreased bone mineral density and increased risk of fracture compared to uninfected patients; however, the molecular mechanisms behind these associations remain unclear. We questioned whether Gp120, a component of the envelope protein of HIV capable of inducing apoptosis in many cell types, is able to induce cell death in bone-forming osteoblasts. We show that treatment of immortalized osteoblast-like cells and primary human osteoblasts with exogenous Gp120 in vitro at physiologic concentrations does not result in apoptosis. Instead, in the osteoblast-like U2OS cell line, cells expressing CXCR4, a receptor for Gp120, had increased proliferation when treated with Gp120 compared to control (P<0.05), which was inhibited by pretreatment with a CXCR4 inhibitor and a G-protein inhibitor. This suggests that Gp120 is not an inducer of apoptosis in human osteoblasts and likely does not directly contribute to osteoporosis in infected patients by this mechanism

White Matter Hyperintensities in Vascular Contributions to Cognitive Impairment and Dementia (VCID): Knowledge Gaps and Opportunities

White matter hyperintensities (WMHs) are frequently seen on brain magnetic resonance imaging scans of older people. Usually interpreted clinically as a surrogate for cerebral small vessel disease, WMHs are associated with increased likelihood of cognitive impairment and dementia (including Alzheimer\u27s disease [AD]). WMHs are also seen in cognitively healthy people. In this collaboration of academic, clinical, and pharmaceutical industry perspectives, we identify outstanding questions about WMHs and their relation to cognition, dementia, and AD. What molecular and cellular changes underlie WMHs? What are the neuropathological correlates of WMHs? To what extent are demyelination and inflammation present? Is it helpful to subdivide into periventricular and subcortical WMHs? What do WMHs signify in people diagnosed with AD? What are the risk factors for developing WMHs? What preventive and therapeutic strategies target WMHs? Answering these questions will improve prevention and treatment of WMHs and dementia

The real risks of steroid injection for plantar fasciitis, with a review of conservative therapies

This article presents a review of conservative therapies for plantar fasciitis pain reduction with a discussion of steroid therapy risks. The therapies reviewed include orthoses, stretching, extracorporeal shockwave, BTX-A, and corticosteroid injection/iontophoresis. These modes were included based on the availability of double blinded randomized controlled trials. We noted the following findings. Orthoses, regardless of type, can improve pain levels. Plantar stretching shows limited short-term benefit (1 month), but can reflect significant long-term improvement (10 months). Extracorporeal shockwave therapy shows equivocal benefit with some studies showing significant improvement and others showing none. Although BTX-A injections were the least studied, significant pain improvement was demonstrated in the short and long term. Steroid injection/iontophoresis showed significant improvement in the short term (1 month). Steroid therapy, when coupled with plantar stretching, can provide efficacious pain relief; however, steroid injections should be combined with ultrasound monitoring to reduce complications

Frequency of LATE neuropathologic change across the spectrum of Alzheimer’s disease neuropathology: combined data from 13 community-based or population-based autopsy cohorts

Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) and Alzheimer’s disease neuropathologic change (ADNC) are each associated with substantial cognitive impairment in aging populations. However, the prevalence of LATE-NC across the full range of ADNC remains uncertain. To address this knowledge gap, neuropathologic, genetic, and clinical data were compiled from 13 high-quality community- and population-based longitudinal studies. Participants were recruited from United States (8 cohorts, including one focusing on Japanese–American men), United Kingdom (2 cohorts), Brazil, Austria, and Finland. The total number of participants included was 6196, and the average age of death was 88.1 years. Not all data were available on each individual and there were differences between the cohorts in study designs and the amount of missing data. Among those with known cognitive status before death (n = 5665), 43.0% were cognitively normal, 14.9% had MCI, and 42.4% had dementia—broadly consistent with epidemiologic data in this age group. Approximately 99% of participants (n = 6125) had available CERAD neuritic amyloid plaque score data. In this subsample, 39.4% had autopsy-confirmed LATE-NC of any stage. Among brains with “frequent” neuritic amyloid plaques, 54.9% had comorbid LATE-NC, whereas in brains with no detected neuritic amyloid plaques, 27.0% had LATE-NC. Data on LATE-NC stages were available for 3803 participants, of which 25% had LATE-NC stage > 1 (associated with cognitive impairment). In the subset of individuals with Thal Aβ phase = 0 (lacking detectable Aβ plaques), the brains with LATE-NC had relatively more severe primary age-related tauopathy (PART). A total of 3267 participants had available clinical data relevant to frontotemporal dementia (FTD), and none were given the clinical diagnosis of definite FTD nor the pathological diagnosis of frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP). In the 10 cohorts with detailed neurocognitive assessments proximal to death, cognition tended to be worse with LATE-NC across the full spectrum of ADNC severity. This study provided a credible estimate of the current prevalence of LATE-NC in advanced age. LATE-NC was seen in almost 40% of participants and often, but not always, coexisted with Alzheimer’s disease neuropathology

Entourage: the immune microenvironment following follicular lymphoma

In follicular lymphoma, nonmalignant immune cells are important. Follicular lymphoma depends on CD4+ cells, but CD8+ cells counteract it. We hypothesized that the presence of follicular lymphoma is associated with higher CD4+ than CD8+ cell numbers in the tumor microenvironment but not in the immune system. Using flow cytometry, pre-treatment and follow-up CD4/CD8 ratios were estimated in the bone marrow, blood and lymph nodes of untreated follicular lymphoma patients in two independent data sets (N1=121; N2=166). The ratios were analyzed for their relation with bone marrow lymphoma involvement. Bone marrows were also investigated with immunohistochemistry. In either data set, the bone marrow CD4/CD8 ratios were higher in bone marrows involved with lymphoma (P=0.043 and 0.0002, respectively). The mean CD4/CD8 ratio was 1.0 in uninvolved and 1.4 in involved bone marrows. Also higher in involved bone marrows were CD4/CD56 and CD3CD25/CD3 ratios. No blood or lymph node ratios differed between bone marrow-negative and -positive patients. Sequential samples showed increased bone marrow CD4/CD8 ratios in all cases of progression to bone marrow involvement. Immunohistochemistry showed CD4+, CD57+, programmed death-1+, forkhead box protein 3+ and CD21+ cells accumulated inside the lymphoma infiltrates, whereas CD8+, CD56+ and CD68+ cells were outside the infiltrates. This study provides evidence in vivo that the microenvironment changes upon follicular lymphoma involvement

The role of morphine in regulation of cancer cell growth

Morphine is considered the “gold standard” for relieving pain and is currently one of the most effective drugs available clinically for the management of severe pain associated with cancer. In addition to its use in the treatment of pain, morphine appears to be important in the regulation of neoplastic tissue. Although morphine acts directly on the central nervous system to relieve pain, its activities on peripheral tissues are responsible for many of the secondary complications. Therefore, understanding the impact, other than pain control, of morphine on cancer treatment is extremely important. The effect of morphine on tumor growth is still contradictory, as both growth-promoting and growth-inhibiting effects have been observed. Accumulating evidence suggests that morphine can affect proliferation and migration of tumor cells as well as angiogenesis. Various signaling pathways have been suggested to be involved in these extra-analgesic effects of morphine. Suppression of immune system by morphine is an additional complication. This review provides an update on the influence of morphine on the growth and migration potential of tumor cells

Follicular Dendritic Cell-Specific Prion Protein (PrPc) Expression Alone Is Sufficient to Sustain Prion Infection in the Spleen

Prion diseases are characterised by the accumulation of PrPSc, an abnormally folded isoform of the cellular prion protein (PrPC), in affected tissues. Following peripheral exposure high levels of prion-specific PrPSc accumulate first upon follicular dendritic cells (FDC) in lymphoid tissues before spreading to the CNS. Expression of PrPC is mandatory for cells to sustain prion infection and FDC appear to express high levels. However, whether FDC actively replicate prions or simply acquire them from other infected cells is uncertain. In the attempts to-date to establish the role of FDC in prion pathogenesis it was not possible to dissociate the Prnp expression of FDC from that of the nervous system and all other non-haematopoietic lineages. This is important as FDC may simply acquire prions after synthesis by other infected cells. To establish the role of FDC in prion pathogenesis transgenic mice were created in which PrPC expression was specifically “switched on” or “off” only on FDC. We show that PrPC-expression only on FDC is sufficient to sustain prion replication in the spleen. Furthermore, prion replication is blocked in the spleen when PrPC-expression is specifically ablated only on FDC. These data definitively demonstrate that FDC are the essential sites of prion replication in lymphoid tissues. The demonstration that Prnp-ablation only on FDC blocked splenic prion accumulation without apparent consequences for FDC status represents a novel opportunity to prevent neuroinvasion by modulation of PrPC expression on FDC

A Cryogenic Silicon Interferometer for Gravitational-wave Detection

The detection of gravitational waves from compact binary mergers by LIGO has opened the era of gravitational wave astronomy, revealing a previously hidden side of the cosmos. To maximize the reach of the existing LIGO observatory facilities, we have designed a new instrument able to detect gravitational waves at distances 5 times further away than possible with Advanced LIGO, or at greater than 100 times the event rate. Observations with this new instrument will make possible dramatic steps toward understanding the physics of the nearby Universe, as well as observing the Universe out to cosmological distances by the detection of binary black hole coalescences. This article presents the instrument design and a quantitative analysis of the anticipated noise floor