Knowing risk factors for household transmission of Ebola virus is important to guide preventive measures during Ebola outbreaks.
We enrolled all confirmed persons with Ebola who were the first case ...in a household, December 2014-April 2015, in Freetown, Sierra Leone, and their household contacts. Cases and contacts were interviewed, contacts followed prospectively through the 21-day incubation period, and secondary cases confirmed by laboratory testing.
We enrolled 150 index Ebola cases and 838 contacts; 83 (9.9%) contacts developed Ebola during 21-day follow-up. In multivariable analysis, risk factors for transmission included index case death in the household, Ebola symptoms but no reported fever, age <20 years, more days with wet symptoms; and providing care to the index case (P < .01 for each). Protective factors included avoiding the index case after illness onset and a piped household drinking water source (P < .01 for each).
To reduce Ebola transmission, communities should rapidly identify and follow-up all household contacts; isolate those with Ebola symptoms, including those without reported fever; and consider closer monitoring of contacts who provided care to cases. Households could consider efforts to minimize risk by designating one care provider for ill persons with all others avoiding the suspected case.
Background Small intestinal bacterial overgrowth (SIBO) is expected in postgastrectomy patients; however, its role has not been clarified. This study was to estimate the prevalence of SIBO and ...investigate the clinical role of SIBO in postgastrectomy patients.
Methods This prospective study involved 76 patients who underwent gastrectomy for early gastric cancer with no evidence of recurrence. An H2–CH4 breath test with oral glucose challenge test was performed to diagnose SIBO and dumping syndrome. Sigstad dumping questionnaires, serum glucose, hematocrit and pulse rate were simultaneously monitored for every 30 min for 3 hours.
Key Results There were significant differences in SIBO between the postgastrectomy patients and controls (77.6%vs 6.7%, P < 0.01). Abdominal fullness or borborygmus during oral glucose load were more common in SIBO‐positive than in negative patients (50.8%vs 17.6%, P = 0.03), and were the independent factors for predicting SIBO in postgastrectomy patients (P = 0.02). The prevalences of dumping syndrome and hypoglycemia after oral glucose were 35 (46.1%) and 19 (25.0%), and were not different between both groups. However, the plasma glucose was significantly lower in SIBO‐positive than in SIBO‐negative patients at 120 and 150 min after oral glucose load (P < 0.05). No significant differences were observed in pulse rate and hematocrit in both groups.
Conclusions & Inferences SIBO is common among postgastrectomy patients. It appears to be associated with postprandial intestinal symptoms and might aggravate late hypoglycemia. SIBO could be a new therapeutic target for managing intestinal symptoms in postgastrectomy patients.
Objectives
This study investigated the relationship between oral hygiene conditions, activities of daily living (ADL) and cognitive ability in older Korean patients in long‐term care facilities.
...Methods
Ninety older persons (65+) were randomly sampled from a possible 112 residents in a single facility. They participated in a 2‐month‐long survey. The Korean Modified Barthel Index was used to measure the ADL, and cognitive ability was measured using the Mini‐Mental State Examination, Korean version. Oral hygiene status was measured using the Simplified Oral Hygiene Index and the Tongue Coating Index (TCI).
Results
Older participants with complete dependence manifested significantly poorer oral hygiene (P < 0.05). Scores on the TCI were significantly higher in participants who were dentulous with partial dependence (P < 0.05). A multiple regression analysis showed that dependence and being dentulous significantly predicted poorer oral hygiene (P < 0.05).
Conclusions
This study suggests that older participants with complete dependence had poor oral hygiene on tooth surfaces, while participants with partial dependence had poor tongue hygiene. In addition, dentulous older participants had poorer tongue hygiene than edentulous ones. This indicates the need to assess tooth status and provide oral care services via ADL in long‐term care facilities.
Abundantly available biomass wastes from agriculture can serve as effective environmental remediation materials. In this study, activated biochar was fabricated from macadamia nutshell (MCN) through ...carbonization and chemical modification. The resultant biochars were used as adsorbents to remove toxic metal ions such as Cu2+ and Zn2+ from aqueous solutions. The results showed that the activated MCN biochar has a high adsorption capacity for toxic metal ions. When MCN biochar was activated with K2CO3, the adsorption efficiencies for Cu2+ and Zn2+ were 84.02% and 53.42%, respectively. With H3PO4 activation, the Cu2+- and Zn2+-adsorption performances were 95.92% and 67.41%, respectively. H2O2-modified MCN biochar had reasonable Cu2+- and Zn2+-adsorption efficiencies of 79.33% and 64.52%, respectively. The effects of pH, adsorbent concentration and adsorption time on the removal performances of Cu2+ and Zn2+ in aqueous solution were evaluated. The results exhibited that the activated MCN biochar showed quick adsorption ability with an optimal pH of 4 and 4.5 for both Cu2+ and Zn2+, respectively.
Abstract Resistance to available therapeutic agents has been a common problem thwarting progress in treatment of castrate-resistant and metastatic prostate cancer (PCa). Overexpression of the Bcl-2 ...family members, including Mcl-1, in PCa cells is known to inhibit intracellular mitochondrial-dependent apoptosis. Here we report the development of a novel transgenic mouse model that spontaneously develops prostatic intraepithelial neoplasia and adenocarcinoma by the inducible, conditional knockout of transforming growth factor β receptor type II in stromal fibroblastic cells (Tgfbr2ColTKO ). The Tgfbr2ColTKO prostate epithelia demonstrated down-regulation of luminal and basal differentiation markers, as well as Pten expression and up-regulation of Mcl-1. However, unlike in men, Tgfbr2ColTKO prostates exhibited no regression acutely after castration. The administration of Sabutoclax (BI-97C1), a pan-active Bcl-2 protein family antagonist mediated apoptosis in castrate-resistant PCa cells of Tgfbr2ColTKO mice and human subcutaneous, orthotopic, and intratibial xenograft PCa models. Interestingly, Sabutoclax had little apoptotic effect on benign prostate tissue in Tgfbr2ColTKO and wild-type mice. Sabutoclax was able to block c-Met activation, a critical axis in PCa metastatic progression. Further, Sabutoclax synergistically sensitized PC-3 cells to the cytotoxic effects of docetaxel (Taxotere). Together, these data suggest that Sabutoclax inhibits castrate-resistant PCa alone at the primary and bone metastatic site as well as support sensitivity to docetaxel treatment.
PurposeIntegrating uses and gratifications theory with social exchange theory, this study examines the antecedents of online brand community commitment and engagement and their impact on offline ...purchase intention.Design/methodology/approachPurposive sampling was used to administer an online survey to 205 members of a Facebook brand community of a global retailer.FindingsThe results verified the significant influence of online self-congruity on commitment and engagement and confirmed the full mediating role of engagement between commitment and offline purchase intention.Research limitations/implicationsThe study focused on a global chain retailer's peer-initiated online brand community as the focal data collection site.Practical implicationsThe findings provide several managerial implications that can help retailers understand consumer behaviors in peer-initiated online brand communities.Originality/valueThe study offers insights into the dynamics between individual and group characteristics in online brand communities.
Cognitive impairments in schizophrenia are associated with lower gamma oscillation power in the prefrontal cortex (PFC). Gamma power depends in part on excitatory drive to fast-spiking parvalbumin ...interneurons (PVIs). Excitatory drive to cortical neurons varies in strength, which could affect how these neurons regulate network oscillations. The authors investigated whether variability in excitatory synaptic strength across PVIs could contribute to lower prefrontal gamma power in schizophrenia.
In postmortem PFC from 20 matched pairs of comparison and schizophrenia subjects, levels of vesicular glutamate transporter 1 (VGlut1) and postsynaptic density 95 (PSD95) proteins were quantified to assess variability in excitatory synaptic strength across PVIs. A computational model network was then used to simulate how variability in excitatory synaptic strength across fast-spiking (a defining feature of PVIs) interneurons (FSIs) regulates gamma power.
The variability of VGlut1 and PSD95 levels at excitatory inputs across PVIs was larger in schizophrenia relative to comparison subjects. This alteration was not influenced by schizophrenia-associated comorbid factors, was not present in monkeys chronically exposed to antipsychotic medications, and was not present in calretinin interneurons. In the model network, variability in excitatory synaptic strength across FSIs regulated gamma power by affecting network synchrony. Finally, greater synaptic variability interacted synergistically with other synaptic alterations in schizophrenia (i.e., fewer excitatory inputs to FSIs and lower inhibitory strength from FSIs) to robustly reduce gamma power.
The study findings suggest that greater variability in excitatory synaptic strength across PVIs, in combination with other modest synaptic alterations in these neurons, can markedly lower PFC gamma power in schizophrenia.
Background and purpose:
Aortic complications account for the major mortality in Marfan syndrome (MFS), a connective tissue disorder caused by mutations in FBN1 encoding fibrillin‐1. We hypothesized ...that MFS impaired endothelial function and nitric oxide (NO) production in the aorta.
Experimental approach:
Mice (at 3, 6, 9 and 12 months of age) heterozygous for the Fbn1 allele encoding a cysteine substitution (Fbn1
C1039G/+, Marfan mice, n=75), the most common class of mutation in MFS, were compared with age‐matched control littermates (n=75). Thoracic and abdominal aortas from the two groups were studied.
Key results:
Isometric force measurements revealed that relaxation to ACh (but not to sodium nitroprusside) was diminished in the phenylephrine‐precontracted Marfan thoracic aorta at 6 months of age (pEC50=6.12±0.22; maximal response, Emax=52.7±6.8%; control: pEC50=7.34±0.19; Emax=84.8±2.2%). At one year, both inhibition of NO production with Nω‐nitro‐L‐arginine methyl ester, or denudation of endothelium increased the phenylephrine‐stimulated contraction in the control thoracic aorta by 35%, but had no effect in the Marfan aorta, indicating a loss of basal NO production in the Marfan vessel. From 6 months, a reduced phosphorylation of endothelial NOS (eNOS)Ser1177 and AktThr308 detected by Western blotting was observed in the Marfan thoracic aorta, which was accompanied by decreased levels of cGMP. Expressions of Akt and eNOS in the abdominal aorta were not different between the two groups.
Conclusions and Implications:
MFS impairs endothelial function and signaling of NO production in the thoracic aorta, suggesting the importance of NO in the age‐related progression of thoracic aortic manifestations.
British Journal of Pharmacology (2007) 150, 1075–1083. doi:10.1038/sj.bjp.0707181
Trastuzumab emtansine is the current standard treatment for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer whose disease progresses after treatment ...with a combination of anti-HER2 antibodies and a taxane.
We conducted a phase 3, multicenter, open-label, randomized trial to compare the efficacy and safety of trastuzumab deruxtecan (a HER2 antibody-drug conjugate) with those of trastuzumab emtansine in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane. The primary end point was progression-free survival (as determined by blinded independent central review); secondary end points included overall survival, objective response, and safety.
Among 524 randomly assigned patients, the percentage of those who were alive without disease progression at 12 months was 75.8% (95% confidence interval CI, 69.8 to 80.7) with trastuzumab deruxtecan and 34.1% (95% CI, 27.7 to 40.5) with trastuzumab emtansine (hazard ratio for progression or death from any cause, 0.28; 95% CI, 0.22 to 0.37; P<0.001). The percentage of patients who were alive at 12 months was 94.1% (95% CI, 90.3 to 96.4) with trastuzumab deruxtecan and 85.9% (95% CI, 80.9 to 89.7) with trastuzumab emtansine (hazard ratio for death, 0.55; 95% CI, 0.36 to 0.86; prespecified significance boundary not reached). An overall response (a complete or partial response) occurred in 79.7% (95% CI, 74.3 to 84.4) of the patients who received trastuzumab deruxtecan and in 34.2% (95% CI, 28.5 to 40.3) of those who received trastuzumab emtansine. The incidence of drug-related adverse events of any grade was 98.1% with trastuzumab deruxtecan and 86.6% with trastuzumab emtansine, and the incidence of drug-related adverse events of grade 3 or 4 was 45.1% and 39.8%, respectively. Adjudicated drug-related interstitial lung disease or pneumonitis occurred in 10.5% of the patients in the trastuzumab deruxtecan group and in 1.9% of those in the trastuzumab emtansine group; none of these events were of grade 4 or 5.
Among patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane, the risk of disease progression or death was lower among those who received trastuzumab deruxtecan than among those who received trastuzumab emtansine. Treatment with trastuzumab deruxtecan was associated with interstitial lung disease and pneumonitis. (Funded by Daiichi Sankyo and AstraZeneca; DESTINY-Breast03 ClinicalTrials.gov number, NCT03529110.).
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