Continuous turnover of neurons in the olfactory bulb is implicated in several key aspects of olfaction. There is a dramatic decline postnatally in the number of migratory neuroblasts en route to the ...olfactory bulb in humans, and it has been unclear to what extent the small number of neuroblasts at later stages contributes new neurons to the olfactory bulb. We have assessed the age of olfactory bulb neurons in humans by measuring the levels of nuclear bomb test-derived 14C in genomic DNA. We report that 14C concentrations correspond to the atmospheric levels at the time of birth of the individuals, establishing that there is very limited, if any, postnatal neurogenesis in the human olfactory bulb. This identifies a fundamental difference in the plasticity of the human brain compared to other mammals.
► Carbon dating establishes cell turnover dynamics in the human olfactory bulb ► The yearly exchange rate of nonneuronal cells is 2.0%–3.4% ► Olfactory bulb neurons are as old as the individual ► <1% of olfactory bulb neurons are exchanged over 100 years in humans
Bergmann et al. measure the cellular integration of 14C in olfactory bulb neurons from humans exposed to nuclear bomb tests. Results show that olfactory bulb neurons in humans are as old as the individual and argue that adult olfactory bulb neurogenesis is minimal in humans.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
When people with stroke recover gait speed, they report improved function and reduced disability. However, the minimal amount of change in gait speed that is clinically meaningful and associated with ...an important difference in function for people poststroke has not been determined.
The purpose of this study was to determine the minimal clinically important difference (MCID) for comfortable gait speed (CGS) associated with an improvement in the modified Rankin Scale (mRS) score for people between 20 to 60 days poststroke.
This was a prospective, longitudinal, cohort study.
The participants in this study were 283 people with first-time stroke prospectively enrolled in the ongoing Locomotor Experience Applied Post Stroke (LEAPS) multi-site randomized clinical trial. Comfortable gait speed was measured and mRS scores were obtained at 20 and 60 days poststroke. Improvement of >or=1 on the mRS was used to detect meaningful change in disability level.
Mean (SD) CGS was 0.18 (0.16) m/s at 20 days and 0.39 (0.22) m/s at 60 days poststroke. Among all participants, 47.3% experienced an improvement in disability level >or=1. The MCID was estimated as an improvement in CGS of 0.16 m/s anchored to the mRS.
Because the mRS is not a gait-specific measure of disability, the estimated MCID for CGS was only 73.9% sensitive and 57.0% specific for detecting improvement in mRS scores.
We estimate that the MCID for gait speed among patients with subacute stroke and severe gait speed impairments is 0.16 m/s. Patients with subacute stroke who increase gait speed >or=0.16 m/s are more likely to experience a meaningful improvement in disability level than those who do not. Clinicians can use this reference value to develop goals and interpret progress in patients with subacute stroke.
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DOBA, FSPLJ, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
The myelination of axons by oligodendrocytes has been suggested to be modulated by experience, which could mediate neural plasticity by optimizing the performance of the circuitry. We have assessed ...the dynamics of oligodendrocyte generation and myelination in the human brain. The number of oligodendrocytes in the corpus callosum is established in childhood and remains stable after that. Analysis of the integration of nuclear bomb test-derived (14)C revealed that myelin is exchanged at a high rate, whereas the oligodendrocyte population in white matter is remarkably stable in humans, with an annual exchange of 1/300 oligodendrocytes. We conclude that oligodendrocyte turnover contributes minimally to myelin modulation in human white matter and that this instead may be carried out by mature oligodendrocytes, which may facilitate rapid neural plasticity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Vibrio cholerae is a globally important pathogen that is endemic in many areas of the world and causes 3-5 million reported cases of cholera every year. Historically, there have been seven ...acknowledged cholera pandemics; recent outbreaks in Zimbabwe and Haiti are included in the seventh and ongoing pandemic. Only isolates in serogroup O1 (consisting of two biotypes known as 'classical' and 'El Tor') and the derivative O139 can cause epidemic cholera. It is believed that the first six cholera pandemics were caused by the classical biotype, but El Tor has subsequently spread globally and replaced the classical biotype in the current pandemic. Detailed molecular epidemiological mapping of cholera has been compromised by a reliance on sub-genomic regions such as mobile elements to infer relationships, making El Tor isolates associated with the seventh pandemic seem superficially diverse. To understand the underlying phylogeny of the lineage responsible for the current pandemic, we identified high-resolution markers (single nucleotide polymorphisms; SNPs) in 154 whole-genome sequences of globally and temporally representative V. cholerae isolates. Using this phylogeny, we show here that the seventh pandemic has spread from the Bay of Bengal in at least three independent but overlapping waves with a common ancestor in the 1950s, and identify several transcontinental transmission events. Additionally, we show how the acquisition of the SXT family of antibiotic resistance elements has shaped pandemic spread, and show that this family was first acquired at least ten years before its discovery in V. cholerae.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Recent evidence suggests that the effects of meditation practice on affective processing and resilience have the potential to induce neuroplastic changes within the amygdala. Notably, literature ...speculates that meditation training may reduce amygdala activity during negative affective processing. Nonetheless, studies have thus far not verified this speculation. In this longitudinal study, participants (N = 21, 9 men) were trained in awareness-based compassion meditation (ABCM) or matched relaxation training. The effects of meditation training on amygdala activity were examined during passive viewing of affective and neutral stimuli in a non-meditative state. We found that the ABCM group exhibited significantly reduced anxiety and right amygdala activity during negative emotion processing than the relaxation group. Furthermore, ABCM participants who performed more compassion practice had stronger right amygdala activity reduction during negative emotion processing. The lower right amygdala activity after ABCM training may be associated with a general reduction in reactivity and distress. As all participants performed the emotion processing task in a non-meditative state, it appears likely that the changes in right amygdala activity are carried over from the meditation practice into the non-meditative state. These findings suggest that the distress-reducing effects of meditation practice on affective processing may transfer to ordinary states, which have important implications on stress management.
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BFBNIB, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Objective To assess the acceptability of pre-pandemic influenza vaccination among healthcare workers in public hospitals in Hong Kong and the effect of escalation in the World Health Organization’s ...alert level for an influenza pandemic.Design Repeated cross sectional studies using self administered, anonymous questionnairesSetting Surveys at 31 hospital departments of internal medicine, paediatrics, and emergency medicine under the Hong Kong Hospital Authority from January to March 2009 and in May 2009Participants 2255 healthcare workers completed the questionnaires in the two studies. They were doctors, nurses, or allied health professionals working in the public hospital system.Main outcome measures Stated willingness to accept pre-pandemic influenza vaccination (influenza A subtypes H5N1 or H1N1) and its associating factors.Results The overall willingness to accept pre-pandemic H5N1 vaccine was only 28.4% in the first survey, conducted at WHO influenza pandemic alert phase 3. No significant changes in the level of willingness to accept pre-pandemic H5N1 vaccine were observed despite the escalation to alert phase 5. The willingness to accept pre-pandemic H1N1 vaccine was 47.9% among healthcare workers when the WHO alert level was at phase 5. The most common reasons for an intention to accept were “wish to be protected” and “following health authority’s advice.” The major barriers identified were fear of side effects and doubts about efficacy. More than half of the respondents thought nurses should be the first priority group to receive the vaccines. The strongest positive associating factors were history of seasonal influenza vaccination and perceived risk of contracting the infection. Conclusions The willingness to accept pre-pandemic influenza vaccination was low, and no significant effect was observed with the change in WHO alert level. Further studies are required to elucidate the root cause of the low intention to accept pre-pandemic vaccination.
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BFBNIB, CMK, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Intestinal epithelial cells (IEC) interact with a high density of Gram-positive bacteria and are active participants in mucosal immune responses. Recognition of Gram-positive organisms by Toll-like ...receptor (TLR)2 induces proinflammatory gene expression by diverse cells. We hypothesized that IEC are unresponsive to Gram-positive pathogen-associated molecular patterns and sought to characterize the functional responses of IEC to TLR2-specific ligands. Human colonic epithelial cells isolated by laser capture microscopy and IEC lines (Caco-2, T84, HT-29) were analyzed for expression of TLR2, TLR6, TLR1, and Toll inhibitory protein (Tollip) mRNA by RT-PCR and quantitative real-time PCR. Response to Gram-positive bacterial ligands was measured by NF-kappa B reporter gene activation and IL-8 secretion. TLR2 protein expression was analyzed by immunofluorescence and flow cytometry. Colonic epithelial cells and lamina propria cells from both uninflamed and inflamed tissue demonstrate low expression of TLR2 mRNA compared with THP-1 monocytes. IECs were unresponsive to TLR2 ligands including the staphylococcal-derived Ags phenol soluble modulin, peptidoglycan, and lipotechoic acid and the mycobacterial-derived Ag soluble tuberculosis factor. Transgenic expression of TLR2 and TLR6 restored responsiveness to phenol soluble modulin and peptidoglycan in IEC. In addition to low levels of TLR2 protein expression, IEC also express high levels of the inhibitory molecule Tollip. We conclude that IEC are broadly unresponsive to TLR2 ligands secondary to deficient expression of TLR2 and TLR6. The relative absence of TLR2 protein expression by IEC and high level of Tollip expression may be important in preventing chronic proinflammatory cytokine secretion in response to commensal Gram-positive bacteria in the gut.
This study was conducted to evaluate sexual function in adult survivors of childhood cancers and investigate possible relationships between sexual function and quality of life, as measured by general ...well-being, self-esteem, body image, and depressive symptoms.
This cross-sectional survey was performed in our centre from 14 August 2015 to 8 September 2017. Adult patients who had a history of childhood cancers, and who were disease-free for >3 years, were approached for the study during clinical follow-up. Clinical information was collected from medical records. Self-administered questionnaires regarding quality of life and sexual functioning were given to the patients and resulting data were analysed.
Two hundred patients agreed to participate in the study. The overall response rate was 64.8%. Ninety-one (45.5%) patients were women, and the mean age was 25.4 ± 5.57 years. The overall sexual functioning score was 28.3 ± 20.09. Forty-eight (24.0%) patients reported at least one sexual problem. Among patients who reported no sexual problems, more had haematological cancers (P=0.009), fewer underwent surgery (P=0.004), fewer underwent surgery with external effects (P=0.032), and fewer were regular social drinkers (P=0.013); additionally, they had a higher mean Rosenberg self-esteem scale score (P=0.010), lower mean body image scale score (P=0.008), and lower mean Patient Health Questionnaire score (P=0.001).
Aspects of life beyond disease condition and physical function should be considered in adult survivors of childhood cancers. Appropriate referral and intervention should be initiated for these patients when necessary.
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FFLJ, NUK, ODKLJ, UL, UM, UPUK
To determine the influence of histopathological diagnosis on the outcome of "radioresistant" brain metastases treated with stereotactic radiosurgery (SRS).
Patients (n = 189) with "radioresistant" ...brain metastases (n = 264) were consecutively treated with SRS between August 1991 and July 2002. The primary site of brain metastases was melanoma (n = 103), renal cell carcinoma (n = 77), and sarcoma (n = 9). The median age of the patients was 52 years, and the median Karnofsky Performance Scale score was 80. Initial brain metastasis presentation was single in 112 patients (59%). The median SRS dose was 18 Gy (range, 10-24 Gy). The median tumor volume was 1.6 cm3 (range, 0.06-27.5 cm3). The median follow-up of all patients was 7.4 months (range, 0.16-52 mo).
The actuarial freedom from progression after 1 year was 64% for renal cell carcinoma patients, 47% for melanoma patients, and 0% for sarcoma patients (P < 0.001). The median survival time for all patients from time of SRS was 7.5 months. The rate of 1-year survival was 40% for renal cell carcinoma patients, 25% for melanoma patients, and 22% for sarcoma patients (P = 0.0354). The incidence of neurological death was lower among patients diagnosed with renal cell carcinoma (31%) than among patients with melanoma (66%) or sarcoma (60%) (P = 0.001).
Survival after SRS is significantly worse for patients with melanoma and sarcoma brain metastases compared with patients with renal cell carcinoma. Our data show that progressive brain metastases seem to cause most of the cancer-related deaths among patients with SRS-treated melanoma and sarcoma brain metastases. Future investigations using chemotherapy or novel agents to enhance the effectiveness of SRS to melanoma and sarcoma brain metastases seem warranted.
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