Terminal patients in Belgian nursing homes: a cost analysis.
Policy makers and health care payers are concerned about the costs of treating terminal patients. This study was done to measure the costs of treating terminal patients during the final month of life in a sample of Belgian nursing homes from the health care payer perspective. Also, this study compares the costs of palliative care with those of usual care. This multicenter, retrospective cohort study enrolled terminal patients from a representative sample of nursing homes. Health care costs included fixed nursing home costs, medical fees, pharmacy charges, other charges, and eventual hospitalization costs. Data sources consisted of accountancy and invoice data. The analysis calculated costs per patient during the final month of life at 2007/2008 prices. Nineteen nursing homes participated in the study, generating a total of 181 patients. Total mean nursing home costs amounted to 3,243 € per patient during the final month of life. Total mean nursing home costs per patient of 3,822 € for patients receiving usual care were higher than costs of 2,456 € for patients receiving palliative care (p = 0.068). Higher costs of usual care were driven by higher hospitalization costs (p < 0.001). This study suggests that palliative care models in nursing homes need to be supported because such care models appear to be less expensive than usual care and because such care models are likely to better reflect the needs of terminal patients.


Cryptosporidiosis among children suffering from diarrhea in Benha, Egypt.
213 infant and child attending Pediatric clinic of Benha University Hospital suffering from diarrhea; were studied for the presence of cryptosporidial infection. Modified Ziehl Neelsen method was used for staining of smears and for confirmation of positive cases safranin-methylene blue method was also used Cryptosporidial oocysts were seen in the faeces of seven patients (3.2%). The results were discussed.


Regional analysis of inflammation and contractile function in reperfused acute myocardial infarction by in vivo 19F cardiovascular magnetic resonance in pigs.
Inflammatory cell infiltration is central to healing after acute myocardial infarction (AMI). The relation of regional inflammation to edema, infarct size (IS), microvascular obstruction (MVO), intramyocardial hemorrhage (IMH), and regional and global LV function is not clear. Here we noninvasively characterized regional inflammation and contractile function in reperfused AMI in pigs using fluorine (19F) cardiovascular magnetic resonance (CMR). Adult anesthetized pigs underwent left anterior descending coronary artery instrumentation with either 90 min occlusion (n = 17) or without occlusion (sham, n = 5). After 3 days, in surviving animals a perfluorooctyl bromide nanoemulsion was infused intravenously to label monocytes/macrophages. At day 6, in vivo 1H-CMR was performed with cine, T2 and T2* weighted imaging, T2 and T1 mapping, perfusion and late gadolinium enhancement followed by 19F-CMR. Pigs were sacrificed for subsequent ex vivo scans and histology. Edema extent was 35 ± 8% and IS was 22 ± 6% of LV mass. Six of ten surviving AMI animals displayed both MVO and IMH (3.3 ± 1.6% and 1.9 ± 0.8% of LV mass). The 19F signal, reflecting the presence and density of monocytes/macrophages, was consistently smaller than edema volume or IS and not apparent in remote areas. The 19F signal-to-noise ratio (SNR) > 8 in the infarct border zone was associated with impaired remote systolic wall thickening. A whole heart value of 19F integral (19F SNR × milliliter) > 200 was related to initial LV remodeling independently of edema, IS, MVO, and IMH. Thus, 19F-CMR quantitatively characterizes regional inflammation after AMI and its relation to edema, IS, MVO, IMH and regional and global LV function and remodeling.


Progression to type 1 diabetes and autoantibody positivity in relation to HLA-risk genotypes in children participating in the ABIS study.
Autoantibodies against beta-cell antigens together with human leukocyte antigen (HLA)-risk genotypes are used as predictive markers for type 1 diabetes (T1D). In this study, we have investigated the role of HLA-risk and -protective genotypes for development of beta-cell autoantibodies and progression to T1D in healthy children. T1D-related HLA genotypes and autoantibodies against glutamic acid decarboxylase [glutamic acid decarboxylase antibodies (GADA)] and islet antigen-2 (IA-2A) were studied at 1, 2.5 and 5 yr of age in unselected healthy children and children with T1D participating in the All Babies In Southeast Sweden (ABIS) study. GADA or IA-2A positivity at 5 yr of age was associated with DR4-DQ8 haplotype and DR3-DQ2/DR4-DQ8 genotype. By the age of 6-7 yr, we identified 32 children with T1D among the 17 055 participants in the ABIS study. Eight of 2329 (0.3%) non-diabetic children had permanent autoantibodies, and 143 of 2329 (6%) children had transient autoantibodies. HLA-risk genotypes associated with T1D, whereas protective genotypes were seldom found in children with T1D. Children with permanent autoantibodies had more often risk-associated DR4-DQ8 haplotype than autoantibody-negative children. No associations with HLA-risk or -protective genotypes were found for transient autoantibodies. The strong relation between HLA-risk alleles and T1D once again confirmed that HLA-risk genotypes play an important role for development of T1D. However, HLA genotypes seem not to explain induction of autoantibodies, especially transient autoantibodies, in the general population, emphasizing the role of environmental factors in the initiation of autoimmunity. It seems that HLA-risk genotypes are responsible for maturation of the permanent autoantibody response.


Lesser-curve ischaemic necrosis mimicking a gastric ulcer--a complication of highly selective vagotomy. A case report.
Ischaemic necrosis of the lesser curve of the stomach is thought to be a specific but rare complication of highly selective vagotomy. While it commonly presents as a free perforation, it may also present as sloughing of the mucosa only, a gastric fistula or a sealed perforation of the lesser curve mimicking a chronic gastric ulcer. We describe a case in which ischaemic necrosis of the lesser curve presented as a chronic gastric ulcer from a sealed perforation.


Chemo-mechanical dentine caries removal with Carisolv using a rotating brush.
The aim of this study was to assess the efficacy of removing dentine caries using carbide burs, Carisolv with hand instruments and Carisolv in combination with a new mechanical excavation method using a rotating brush. 36 extracted permanent teeth, with dentine caries, were assigned into 3 groups according to caries removal technique. Caries removal was monitored by checking the properties of the dentine with a dental explorer. After embedding and sectioning (400 microm), remaining caries was assessed by using a caries detector. In microscope images (7x) of the samples, the mean stain depth of the remaining carious tissue per tooth was calculated by AnalySIS computer software. Four to 8 applications (mean time = 10.9 min) of Carisolv were necessary for caries removal with the new method using rotating brushes. The mean thickness of residual dentine caries by this procedure (226 microm, +/- 136) was higher than the one using Carisolv with hand instruments (57 microm, +/- 39) or carbide burs (32 microm, +/- 20). Even in areas with good access to the lesion, an unacceptable amount of residual caries was observed. Thus, it seems that Carisolv using rotating brushes does not reach the degree of caries removal reached by additional mechanical abrasion of Carisolv using hand instruments or conventional rotating carbide burs.


Failure of cholestyramine to prevent bile salt injury to mouse gastric mucosa.
Bile salts have been implicated in the pathogenesis of gastritis and gastric ulcer. Because the bile salt binding agent cholestyramine has been suggested as a possible therapy for gastric ulcer, we studied the effects of cholestyramine, in the form of Questran, on bile salt-induced injury to mouse gastric mucosa. Solutions of taurocholate or of glycochenodeoxycholate, with or without added Questran, were instilled into the stomachs of fasted mice at pH 1, 3, 5, and 7. Taurocholate damaged the mucosa only at pH 1, whereas glycochenodeoxycholate caused injury at pH 1 and 3. Questran failed to prevent mucosal damage by either bile salt. The ineffectiveness of cholestyramine to prevent injury may be due to the nonionized fraction of bile salts at pH's below their pKa's which will not be sequestered by the anion exchange resin. This phenomenon may help explain the insignificant effect of Qestran treatment in promoting healing of gastric ulcers in a previous clinical trial.


Endothelial protein kinase C isoform identity and differential activity of PKCzeta in an athero-susceptible region of porcine aorta.
Endothelial protein kinase C (PKC) signaling was investigated in different regions of normal porcine aorta. The locations map to differential atherosclerotic susceptibility and correlate with sites of disturbed (DF) or undisturbed (UF) local flow profiles. Endothelial lysates were isolated from the inner curvature of the aortic arch (DF; athero-susceptible) and a nearby UF region of the descending thoracic aorta (UF; athero-protected), and in some experiments a distant athero-protected UF site, the common carotid artery. Total endothelial PKC activity in the DF regions was 145% to 240% of that in both UF locations (P<0.05), whereas the UF regions were not significantly different from each other. PKC protein isoforms alpha, beta, epsilon, iota, lambda, and zeta were expressed in similar proportions in both aortic regions, suggesting that differences of kinase activity were not directly attributable to expression levels. Inhibition of members of the "conventional" and "novel" PKC families had no differential effect on regional kinase activity. However, inhibition of PKCzeta, a member of the "atypical" PKC family, reduced the DF lysate kinase activity to that of UF levels (NS P=0.35). Differential phosphorylation of PKCzeta Thr410 and Thr560, along with increased levels of PKCzeta degradation products in UF endothelial lysates, suggested posttranslational modification of PKCzeta as the basis for site-specific differences in vivo. Steady-state regional heterogeneity of an important family of regulatory proteins in intact arterial endothelium in vivo may link localized athero-susceptibility and the associated hemodynamic environment.


Antiviral activity of caspase inhibitors: effect on picornaviral 2A proteinase.
Peptide-based fluoromethyl ketones have been considered for many years to be highly specific caspase inhibitors distinctly blocking the progress of apoptosis in a variety of systems. Here we demonstrate that these compounds can significantly reduce rhinovirus multiplication in cell culture. In their methylated forms they block eIF4GI cleavage in vivo and in vitro and inhibit the activity of picornaviral 2A proteinases.


The battle against Thalassemia in Pakistan: Way to move forward.
Thalassemia, one of the most common genetic hemoglobinopathy, is yet still an economy-depriving disorder, prevalent throughout the world. Specifically in Pakistan, numerous factors have led to the ever-increasing numbers of the affected masses. Amidst its battle with other diseases, it is worthy to highlight that the country did not overlook this disorder and hence, significant work has been done to change the thalassemia status of the country. From the establishment of reforms to private philanthropic organizations, Pakistan is actively fighting against the disorder. However, some more practical working and well-devised planning can help the country, attain a thalassemic-free status.


Notch family members follow stringent requirements for intracellular domain dimerization at sequence-paired sites.
Notch signaling is essential for multicellular life, regulating core functions such as cellular identity, differentiation, and fate. These processes require highly sensitive systems to avoid going awry, and one such regulatory mechanism is through Notch intracellular domain dimerization. Select Notch target genes contain sequence-paired sites (SPS); motifs in which two Notch transcriptional activation complexes can bind and interact through Notch's ankyrin domain, resulting in enhanced transcriptional activation. This mechanism has been mostly studied through Notch1, and to date, the abilities of the other Notch family members have been left unexplored. Through the utilization of minimalized, SPS-driven luciferase assays, we were able to test the functional capacity of Notch dimers. Here we show that the Notch 2 and 3 NICDs also exhibit dimerization-induced signaling, following the same stringent requirements as seen with Notch1. Furthermore, our data suggested that Notch4 may also exhibit dimerization-induced signaling, although the amino acids required for Notch4 NICD dimerization appear to be different than those required for Notch 1, 2, and 3 NICD dimerization. Interestingly, we identified a mechanical difference between canonical and cryptic SPSs, leading to differences in their dimerization-induced regulation. Finally, we profiled the Notch family members' SPS gap distance preferences and found that they all prefer a 16-nucleotide gap, with little room for variation. In summary, this work highlights the potent and highly specific nature of Notch dimerization and refines the scope of this regulatory function.


In vitro biological response of human osteoblasts in 3D chitosan sponges with controlled degree of deacetylation and molecular weight.
We have studied the effect of chitosan sponges, produced from chitosan batches with distinct degree of deacetylation (DDA) and molecular weight (Mw), on the adhesion, growth and differentiation of primary human osteoblasts with an aim to offer a suitable tool for guided bone regeneration. All the chitosan sponges revealed similar microstructure, irrespective of the DDA (58, 73, 82, 88, and 91 %) and Mw (749, 547, 263, 215, and 170 kDa, respectively). Cell spreading was higher on sponges having a higher DDA. Higher DDA induced a more pronounced increase in alkaline phosphatase activity, osteopontin (OPN), vascular endothelial growth factor-A (VEGF), interleukin-6 (IL-6), and reduction in monocyte chemoattractant protein-1 (MCP-1), sclerostin (SOST) and dickkopf related protein-1 as compared to lower DDA. Lower DDA induced the increased secretion of osteoprotegerin and SOST as compared to higher DDA. The combination of higher DDA and Mw induced an increased secretion of VEGF and IL-6, however reduced the secretion of OPN as compared to chitosan with similar DDA but with lower Mw. In summary, the variations in cellular responses to the different chitosan sponges indicate a potential for individual tailoring of desired responses in guided bone regeneration.


A kinetic approach on hexavalent chromium removal with metallic iron.
This paper examines the mechanism of Cr(VI) removal with Fe(0), and the possible effect of various experimental parameters, from a kinetic perspective. The experimental data was analyzed using five different kinetic models: three for chemical reactions and two for adsorption processes. It was found that the process fitted well to the zero-order kinetic model for all investigated systems, excepting experiments conducted at 6 °C and those with nano-Fe(0), when the process followed the Ho's pseudo second-order model. Therefore, even though, under acidic conditions, chemical reduction can be generally considered as the main mechanism of Cr(VI) removal with Fe(0), under some experimental conditions (e.g. when working with nano-Fe(0) or at low temperatures), adsorption seems to be the dominant removal path. The enhanced Cr(VI) removal noticed in co-presence of SO42- and Cl- anions reiterates the significance of the secondary reductant Fe(II) within the process of Cr(VI) removal with Fe(0).


Predictive factors for early mortality after percutaneous endoscopic and radiologically-inserted gastrostomy.
Gastrostomy insertion is of benefit to selected patients, but 30-day mortality is as high as 54% in some patient groups. The current study examines risk factors associated with 30-day mortality in a cohort of patients who underwent percutaneous endoscopic gastrostomy (PEG) or radiologically-inserted gastrostomy (RIG) in a district general hospital over a 2.5 year period. A retrospective review of case notes was performed for all patients who underwent a PEG (n=53) or RIG (n=40) insertion in the period January 2009-July 2011. PEG/RIG re-insertions were excluded. Demographic, clinical, and biochemical data were analysed. Multivariate regression analysis was used to identify risk factors for early mortality after gastrostomy insertion. The indications for gastrostomy insertion were similar in the PEG and RIG groups and included mainly dysphagic stroke, chronic neuromuscular disease and head and neck cancer. The patients in the RIG group were older and had a higher incidence of cardiovascular co-morbidities. The overall 30-day mortality was 11% in the PEG and 40% in the RIG group. The multivariate regression analysis suggested that cardiovascular co-morbidities and RIG insertion were independent risk factors for early mortality. The main cause of death 30 days after gastrostomy insertion was pneumonia, which was significantly more common in the RIG group. Our data suggest that PEG should be the procedure of choice when considering gastrostomy insertion and RIG should be reserved as a second-line approach for cases in which PEG is technically difficult or contraindicated.


Impact of COVID-19 lockdown in children with neurological disorders in Italy.
The costs and benefits of full lockdown measures are debated. Neurologically impaired children are a vulnerable population with specific needs in terms of protection against infection and access to health services. We investigated the effects of lockdown on the health of children with neurological disorders and on their access to care during lockdown. Data from 514 children (282 males - 232 females) were collected through physician-administered interviews to investigate: the occurrence of viral-like physical symptoms, the correlation between the risk of developing such symptoms and several demographic and clinical variables, the occurrence of any worsening of the children's neurological conditions during lockdown, and their access to care services during this period. 49.1% experienced at least one symptom during the study period, but no child developed severe complications. The prevalence of symptoms was significantly lower during lockdown than during the previous two months. The underlying neurological condition worsened in 11.5% of the patients. Children who regularly left the home during lockdown were greater risk of exhibiting symptoms. During lockdown, 67.7% had a specialist appointment cancelled, 52.6% contacted their paediatrician, and 30.9% contacted their child neuropsychiatrist. Among patients who usually receive rehabilitation, 49.5% continued remotely. Lockdown protected children from infections. Telemedicine and telerehabilitation constituted a valid alternative for the care and treatment of these children, but they should not become a widespread and definitive model of care. COVID-19 and other emergency response plans must take into account the specific needs of children with disabilities.


Immunotherapy: State-of-the-art review of therapies and theratypes.
Through its disease-modifying potential, immunotherapy is the keystone to curing allergic diseases. Allergen immunotherapy, applied for more than a century, is currently supported by novel modalities such as mAb-based therapies or small molecules targeting the key nodes of the allergic inflammation network. In this review, a summary of the most significant advances in immunotherapy is presented, addressing not only novel approaches to stratifying patients but also major controlled clinical trials and real-world evidence that strengthen the role of immunotherapy in the treatment of allergies.


Design of SiOx/TiO2@C hierarchical structure for efficient lithium storage.
The large volume expansion effect and unstable solid electrolyte interface films of SiOx-based anode materials have hindered their commercial development. It has been shown that composite doping is a general strategy to solve critical problems. In this study, TiO2-doped core-shell SiOx/TiO2@C composites were created using the sol-gel method. On the one hand, the uniformly dispersed TiO2nanoparticles can alleviate the volume expansion of the SiOxactive material during the lithiation process. On the other hand, they can react with Li+to form LixTiO2, thereby increasing the ion diffusion rate in the composite material. The outer carbon shell acts as a protective layer that not only alleviates the volume expansion of the composite, but also improve the electron migration rate of the composite. The prepared SiOx/TiO2@C composite has a reversible capacity of 828.2 mA h g-1(0.2 A g-1100 cycles). After 500 cycles, it still maintains a reversible capacity of 500 mA h g-1even at a high current density of 2 A g-1. These findings suggest that SiOx/TiO2@C composites have a bright future in applications.


CDC staging based on absolute CD4 count and CD4 percentage in an HIV-1-infected Indian population: treatment implications.
CD4+ T-cell levels are an important criterion for categorizing HIV-related clinical conditions according to the CDC classification system and are therefore important in the management of HIV by initiating antiretroviral therapy and prophylaxis for opportunistic infections due to HIV among HIV-infected individuals. However, it has been observed that the CD4 counts are affected by the geographical location, race, ethnic origin, age, gender and changes in total and differential leucocyte counts. In the light of this knowledge, we classified 600 HIV seropositive antiretroviral treatment (ART)-naïve Indian individuals belonging to different CDC groups A, B and C on the basis of CDC criteria of both CD4% and CD4 counts and receiver operating characteristic (ROC) curves were generated. Importantly, CDC staging on the basis of CD4% indicated significant clinical implications, requiring an early implementation of effective antiretroviral treatment regimen in HIV-infected individuals deprived of treatment when classified on the basis of CD4 counts.


A cognitive model of response omissions in distraction paradigms.
The effects of distraction on responses manifest in three ways: prolonged reaction times, and increased error and response omission rates. However, the latter effect is often ignored or assumed to be due to a separate cognitive process. We investigated omissions occurring in two paradigms that manipulated distraction. One required simple stimulus detection of younger participants, the second required choice responses and was completed by both younger and older participants. We fit data from these paradigms with a model that identifies three causes of omissions: two are related to the process of accumulating the evidence on which a response is based: intrinsic omissions (due to between-trial variation in accumulation rates making it impossible to ever reach the evidence threshold) and design omissions (due to response windows that cause slow responses not to be recorded; a third, contaminant omissions, allows for a cause unrelated to the response process. In both data sets systematic differences in omission rates across conditions were accounted for by task-related omissions. Intrinsic omissions played a lesser role than design omissions, even though the presence of design omissions was not evident in descriptive analyses of the data. The model provided an accurate account of all aspects of the detection data and the choice-response data, but slightly underestimated overall omissions in the choice paradigm, particularly in older participants, suggesting that further investigation of contaminant omission effects is needed.


The production of aflatoxin B1 or G 1 by Aspergillus parasiticus at various combinations of temperature and water activity is related to the ratio of aflS to aflR expression.
The influence of varying combinations of water activity (aw) and temperature on growth, aflatoxin biosynthesis and aflR/aflS expression of Aspergillus parasiticus was analysed in the ranges 17-42°C and 0.90-0.99 aw. Optimum growth was at 35°C. At each temperature studied, growth increased from 0.90 to 0.99 aw. Temperatures of 17 and 42°C only supported marginal growth. The external conditions had a differential effect on aflatoxin B1 or G1 biosynthesis. The temperature optima of aflatoxin B1 and G1 were not at the temperature which supported optimal growth (35°C) but either below (aflatoxin G1, 20-30°C) or above (aflatoxin B1, 37°C). Interestingly, the expression of the two regulatory genes aflR and aflS showed an expression profile which corresponded to the biosynthesis profile of either B1 (aflR) or G1 (aflS). The ratios of the expression data between aflS:aflR were calculated. High ratios at a range between 17 and 30°C corresponded with the production profile of aflatoxin G1 biosynthesis. A low ratio was observed at >30°C, which was related to aflatoxin B1 biosynthesis. The results revealed that the temperature was the key parameter for aflatoxin B1, whereas it was water activity for G1 biosynthesis. These differences in regulation may be attributed to variable conditions of the ecological niche in which these species occur.


Comparison of MRI, [18F]FDG PET/CT, and 99mTc-UBI 29-41 scintigraphy for postoperative spondylodiscitis-a prospective multicenter study.
Postoperative infection still constitutes an important complication of spine surgery, and the optimal imaging modality for diagnosing postoperative spine infection has not yet been established. The aim of this prospective multicenter study was to assess the diagnostic performance of three imaging modalities in patients with suspected postoperative spine infection: MRI, [18F]FDG PET/CT, and SPECT/CT with 99mTc-UBI 29-41. Patients had to undergo at least 2 out of the 3 imaging modalities investigated. Sixty-three patients enrolled fulfilled such criteria and were included in the final analysis: 15 patients underwent all 3 imaging modalities, while 48 patients underwent at least 2 imaging modalities (MRI + PET/CT, MRI + SPECT/CT, or PET/CT + SPECT/CT). Final diagnosis of postoperative spinal infection was based either on biopsy or on follow-up for at least 6 months. The MRI, PET/CT, and SPECT/CT scans were read blindly by experts at designated core laboratories. Spine surgery included metallic implants in 46/63 patients (73%); postoperative spine infection was diagnosed in 30/63 patients (48%). Significant discriminants between infection and no infection included fever (P = 0.041), discharge at the wound site (P < 0.0001), and elevated CRP (P = 0.042). There was no difference in the frequency of infection between patients who underwent surgery involving spinal implants versus those who did not. The diagnostic performances of MRI and [18F]FDG PET/CT analyzed as independent groups were equivalent, with values of the area under the ROC curve equal to 0.78 (95% CI: 0.64-0.92) and 0.80 (95% CI: 0.64-0.98), respectively. SPECT/CT with 99mTc-UBI 29-41 yielded either unacceptably low sensitivity (44%) or unacceptably low specificity (41%) when adopting more or less stringent interpretation criteria. The best diagnostic performance was observed when combining the results of MRI with those of [18F]FDG PET/CT, with an area under the ROC curve equal to 0.938 (95% CI: 0.80-1.00). [18F]FDG PET/CT and MRI both possess equally satisfactory diagnostic performance in patients with suspected postoperative spine infection, the best diagnostic performance being obtained by combining MRI with [18F]FDG PET/CT. The diagnostic performance of SPECT/CT with 99mTc-UBI 29-41 was suboptimal in the postoperative clinical setting explored with the present study.


Fovea center detection based on the retina anatomy and mathematical morphology.
In this work, we present a new fovea center detection method for color eye fundus images. This method is based on known anatomical constraints on the relative locations of retina structures, and mathematical morphology. The detection of this anatomical feature is a prerequisite for the computer aided diagnosis of several retinal diseases, such as Diabetic Macular Edema. The proposed method is adaptive to local illumination changes, and it is robust to local disturbances introduced by pathologies in digital color eye fundus images (e.g. exudates). Our experimental results using the DRIVE image database indicate that our method is able to detect the fovea center in 37 out of 37 images (i.e. with a success rate of 100%). Using the DIARETDB1 database, our method was able to detect the fovea center in 92.13% of all tested cases (i.e. in 82 out of 89 images). These results indicate that our approach potentially can achieve a better performance than comparable methods proposed in the literature.


Stereotactic Arrhythmia Radioablation (STAR): Assessment of cardiac and respiratory heart motion in ventricular tachycardia patients - A STOPSTORM.eu consortium review.
To identify the optimal STereotactic Arrhythmia Radioablation (STAR) strategy for individual patients, cardiorespiratory motion of the target volume in combination with different treatment methodologies needs to be evaluated. However, an authoritative overview of the amount of cardiorespiratory motion in ventricular tachycardia (VT) patients is missing. In this STOPSTORM consortium study, we performed a literature review to gain insight into cardiorespiratory motion of target volumes for STAR. Motion data and target volumes were extracted and summarized. Out of the 232 studies screened, 56 provided data on cardiorespiratory motion, of which 8 provided motion amplitudes in VT patients (n = 94) and 10 described (cardiac/cardiorespiratory) internal target volumes (ITVs) obtained in VT patients (n = 59). Average cardiac motion of target volumes was < 5 mm in all directions, with maximum values of 8.0, 5.2 and 6.5 mm in Superior-Inferior (SI), Left-Right (LR), Anterior-Posterior (AP) direction, respectively. Cardiorespiratory motion of cardiac (sub)structures showed average motion between 5-8 mm in the SI direction, whereas, LR and AP motions were comparable to the cardiac motion of the target volumes. Cardiorespiratory ITVs were on average 120-284% of the gross target volume. Healthy subjects showed average cardiorespiratory motion of 10-17 mm in SI and 2.4-7 mm in the AP direction. This review suggests that despite growing numbers of patients being treated, detailed data on cardiorespiratory motion for STAR is still limited. Moreover, data comparison between studies is difficult due to inconsistency in parameters reported. Cardiorespiratory motion is highly patient-specific even under motion-compensation techniques. Therefore, individual motion management strategies during imaging, planning, and treatment for STAR are highly recommended.


Inhibition by bestatin of a mouse ascites tumor dipeptidase. Reversal by certain substrates.
Bestatin, [(2S,3R)-3-amino-2-hydroxy-4-phenyl-butanoyl]-L-leucine, a known inhibitor of aminopeptidases, is shown to be a potent linear competitive inhibitor (KI,2.7 nM) of a dipeptidase purified from Ehrlich-Lettré hyperdiploid mouse ascites tumor cells. This inhibition can be classified as "slow binding" but not as "tight binding." Substrate protects the enzyme from bestatin inhibition when enzyme and inhibitor are in approximately equimolar concentrations. Addition of substrate (6 mM) partially (by about 20%) reverses dipeptidase inhibition by bestatin, but the time required for maximum recovery depends on the nature of the substrate. Substrates with lower Km (0.28-1.4 mM) values that exhibit substantial substrate inhibition require longer times (23-65 min) than those with higher Km values that show little substrate inhibition. Substrates with Km values higher than 1.5 mM do not reverse inhibition. The inhibition of the tumor dipeptidase by bestatin has been compared with inhibition by a variety of inhibitors of other Zn-metallo-proteolytic enzymes. These inhibitors were far less potent (KI, 0.063-10 mM), indicating a difference between the tumor dipeptidase and other enzymes of that class. Our results are discussed in terms of a postulated model of the bestatin molecule in the active site of the tumor dipeptidase, an enzyme which has not been studied by x-ray crystallographic means. The phenyl group of bestatin is placed in a hydrophobic pocket that is external but adjacent to the active site of the tumor dipeptidase. The shape of this pocket, as it appears from our results plus modeling, is such that only certain R groups of substrate can fit. The existence of such a pocket might explain the differential effect of substrates in the reversal of bestatin inhibition of the dipeptidase and also might explain substrate inhibition by misalignment of R groups into this pocket.


[Recurrence of capsular pseudoexfoliation on intraocular implant].
We here report the case of a 79-year old patient who underwent cataract by phacoemulsification associated with preoperative left and right eyes pseudo-capsular exfoliation in 2000. He had pseudo-exfoliative glaucoma with recurrence on the implant.


Effect of induction of SOS response on expression of pBR322 genes and on plasmid copy number.
Several lines of evidence are presented that indicate that the level of tetracycline resistance of Esherichia coli strains harboring plasmid pBR322 varies according to whether the SOS system of the host bacteria has been induced. These include use of strains in which the SOS system is expressed constitutively (lexA def.), is thermoinducible (recA441) or noninducible (lexA ind-), or is highly repressed (multiple copies of lexA+). Similar induction was observed with the product of another plasmid gene, beta-lactamase. The amounts of extractable plasmid DNA were also increased by SOS induction, and we propose that the SOS-induced increases in levels of tetracycline resistance and beta-lactamase activity are due to an increased plasmid copy number.


Repeated inspiratory occlusions acutely impair myocardial function in rats.
Repeated episodes of hypoxia and sympathetic activation during obstructive sleep apnoea are implicated in the initiation and progression of cardiovascular diseases, but the acute effects are unknown. We hypothesized that repeated inspiratory occlusions cause acute myocardial dysfunction and injury. In 22 spontaneously breathing pentobarbital-anaesthetized rats, inspiration was occluded for 30 s every 2 min for 3 h. After approximately 1.5 h, mean arterial pressure started to fall; heart rate between occlusions was stable throughout, consistent with only transient increases in sympathetic activity during each occlusion. Three hours of occlusions resulted in ventricular diastolic dysfunction (reduced peak rate of change of ventricular pressure and slower relaxation). Post-occlusions, the left ventricular contractile response to dobutamine was blunted. After 1 h of recovery, left ventricular pressure generation had returned to values no different from those in sham animals in 5 of 9 of the animals. Cardiac myofibrils from rats subjected to occlusions had depressed calcium-activated myosin ATPase activity, indicating myofilament contractile dysfunction that was not due to breakdown of contractile proteins. Haematoxylin and eosin-stained cross-sections revealed multifocal areas of necrosis within the septum and both ventricles. Repeated inspiratory occlusions, analogous to moderately severe obstructive sleep apnoea, acutely cause global cardiac dysfunction with multifocal myocardial infarcts.


Quantitative determination of saturated oligogalacturonic acids in enzymatic digests of polygalacturonic acid, pectin and carrot pomace by on-line LC-ESI-MS.
A method for the quantitative determination of oligogalacturonic acids (OGAs) by on-line high-performance liquid chromatographic (HPLC) separation and mass spectrometric detection via an electrospray interface (ESI-MS) without additional desalting steps was developed. Saturated OGAs up to a degree of polymerization (dp) of 3 were quantified by comparison with reference compounds. The calibration plots showed high linearity (R(2)>0.99), and the detection limits for dp 1, 2, and 3 were 11, 28, and 6 ng per injection, respectively. Non- and partially methyl-esterified OGAs with a dp of 3 and 4 were calculated semi-quantitatively as dp 3. The analytical system was used for the quantification of OGAs of digests obtained by incubation of polygalacturonic acid, pectin, and carrot pomace with commercial enzyme preparations. Furthermore, methyl-esterified OGAs up to a dp of 12 containing up to 4 methyl esters were detected in a pectin digest.


Mutagenic and chromosome-breaking effects of azide in barley and human leukocytes.
Azide (10-3 M, solution buffered at pH 3) is more effective in inducing mutations in embryonic shoots of seeds germinated between 8 and 16 h than in non-germinated seeds and in seeds germinated between 0 and 8 h and 16 to 28 h. This peak of chlorophyll-deficient seedling mutation frequency coincides with maximum frequencies of seeding lethals and DNA replication in the cells of the embryonic shoot. The mutation data suggest azide may only act on replicating DNA. Azide induced no chromosome-aberration frequencies significantly above controls in (1) embryonic shoots of barley seeds germinated for 8--12 h, (2) microspores of barley and (3) human leukocytes. It appears to be a point-mutation mutagen.


Delaying surgery after neoadjuvant chemoradiotherapy for rectal cancer may reduce postoperative morbidity without compromising prognosis.
This retrospective study investigated whether the interval between neoadjuvant chemoradiotherapy and surgery for rectal cancer influences postoperative morbidity or prognosis. Data from 189 patients receiving neoadjuvant 5-fluorouracil-based chemoradiotherapy were examined. Associations between interval length and clinicopathological characteristics were analysed. The median interval was 73 (range 6-215) days. Operations performed were abdominoperineal resection (60.3 per cent), anterior resection (37.6 per cent) and Hartmann's procedure (2.1 per cent). Forty-six patients (24.3 per cent) received postoperative chemotherapy. Interval was not significantly associated with pathological tumour (P = 0.648) or node (P = 0.964) category after chemoradiotherapy, or pathological complete response (P = 0.499). Logistic regression showed that shorter intervals (by 1 week) independently predicted anastomotic leakage (odds ratio (OR) 0.97 (95 per cent confidence interval (c.i.) 0.94 to 1.00)) and perineal wound complications (OR 0.97 (0.95 to 0.99)). Interval was not related to local recurrence (hazard ratio (HR) 1.01 (95 per cent c.i. 1.00 to 1.02)), metastasis (HR 1.00 (0.99 to 1.01)) or death (HR 1.00 (0.99 to 1.01)). Only circumferential resection margin and nodal involvement were independent predictors of survival. Delaying surgery beyond 8 weeks after neoadjuvant chemoradiotherapy may reduce postoperative morbidity, without compromising prognosis.


The identification of a species-specific antigen from Necator americanus.
A 17 kD protein of Necator americanus was isolated by SDS-PAGE and used to raise monospecific antisera in rabbits. ELISA and Western blotting against a range of parasite extracts demonstrated the species specificity of this protein. It is expressed at all stages of the life-cycle, appears to be accumulated through the larval stages to adulthood, and can be localized in the oesophageal glands and cuticle of the adult parasite. The possible nature and diagnostic potential of this protein is discussed.


If it is not cough, it must be dysgeusia: differing adverse effects of angiotensin-converting enzyme inhibitors in the same individual.
Presented is an unusual case of a 66-year-old-resident of a long-term care facility, who manifested severe dysgeusia and impaired quality of life attributed to the angiotensin-converting enzyme (ACE) inhibitor enalapril; not realized at the time was the fact that he had an adverse reaction-cough-just weeks earlier from another ACE inhibitor in the same class, quinapril, thus illustrating different adverse effects to two antihypertensives in the same class. Cough and dysgeusia are symptoms that may be easily overlooked as side effects of medications. As polypharmacy is common in nursing home settings, health care providers need to be vigilant about adverse drug reactions which are common, but preventable and often reversible.


Health information technology:Fallacies and Sober realities - Redux A homage to Bentzi Karsh and Robert Wears.
Since the publication of "Health Information Technology: Fallacies and Sober Realities" in 2010, health information technology (HIT) has become nearly ubiquitous in US healthcare facilities. Yet, HIT has yet to achieve its putative benefits of higher quality, safer, and lower cost care. There has been variable but largely marginal progress at addressing the 12 HIT fallacies delineated in the original paper. Here, we revisit several of the original fallacies and add five new ones. These fallacies must be understood and addressed by all stakeholders for HIT to be a positive force in achieving the high value healthcare system the nation deserves. Foundational cognitive and human factors engineering research and development continue to be essential to HIT development, deployment, and use.


Transvestites' women revisited: a nonpatient sample.
Data obtained from seven female partners of nonpatient transvestites are presented. None were receiving psychiatric treatment. The group was self-assembled and affiliated with a cross-dressing social organization. The sample was divided into Acceptors and Rejectors based on the degree of acceptance of their mate's cross-dressing activities. Mean relationship duration was 9.9 years. None were traumatized by accidental discovery of their mate's transvestism. Childhood loss of parent(s), substance abuse, and divorce were rare. None had had homosexual experiences. Four of seven transvestite mates were reported by their partners to have gender dysphoric symptoms at some point in their lives. All of the couples' children (two male, three female) knew of their father's transvestism by direct observation at young ages; sons from two different families were noted to cross-dress spontaneously.


Breeding biology aspects of spotted flapshell Turtle, Lissemys punctata (Lacepede 1788), in Bangladesh.
This study was conducted to determine the breeding season, gonadal development, egg laying period, clutch size and other biological aspects of spotted flapshell turtle, Lissemys punctata, of Bangladesh between January 1997 and December 2001. The egg laying period of L. punctata, was found between August and March. The nesting sites were elevated fallow lands in secluded areas. The female turtle laid all the mature eggs at a time for each clutch at night. A gravid female turtle laid three clutches of eggs in each year and the mean clutch size was 13.0 ± 1.9 eggs and mean weight of each egg was 10.3 ± 1.3 g. The eggs are spherical in shape and whitish in color. The mean incubation period was 173 ± 34 days (range 119-225 days). The incubation period of first clutch was the longest than the second and third clutches. Hatching success was found 41%. Maximum hatching was observed in June. The present investigation was made to explore the possibility to raise turtle farming in captive condition. The findings would, hopefully, help to rear the species and to assess the commercial potentiality of turtle farming in captive condition, that is, in the eco-climatic condition of Bangladesh.


Contractile responses elicited by hydrogen peroxide in aorta from normotensive and hypertensive rats. Endothelial modulation and mechanism involved.
The present study analyses the influence of hypertension and endothelium on the effect induced by hydrogen peroxide (H2O2) on basal tone in aortic segments from normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) of 6-month-old, as well as the possible mechanisms involved. Single (1 mM) or cumulative (100 nM-10 mM) concentrations of H2O2 produced a transient contraction or a concentration-dependent increase of basal tone, respectively, in segments from WKY and SHR. In both cases, the contractions were higher in intact segments from hypertensive than from normotensive rats, and increased by endothelium removal in both strains. Catalase (1000 u ml(-1), a H2O2 scavenger) abolished the contraction elicited by 1 mM H2O2 in both strains. Superoxide dismutase (SOD, 150 u ml(-1)) and dimethylsulphoxide (DMSO, 7 mM), scavengers of superoxide anions and hydroxyl radicals, respectively, did not alter H2O2-induced contractions in intact segments from both strains. However, L-NG-nitroarginine methyl ester (L-NAME, 100 microM, a nitric oxide synthase inhibitor) increased the response to H2O2 in normotensive rats, although the increase was less than that produced by endothelium removal. Incubation of segments with 1 mM H2O2 for 15 min and subsequent washout reduced the contractile responses induced by 75 mM KCl in intact segments from SHR and in endothelium-denuded segments from both strains; this effect being prevented by catalase (1000 u ml(-1)). Indomethacin (10 microM, a cyclo-oxygenase inhibitor) and SQ 29,548 (10 microM, a prostaglandin H2/thromboxane A2 receptor antagonist) practically abolished the contractions elicited by H2O2 in normotensive and hypertensive rats. We conclude that: (1) the oxidant stress induced by H2O2 produces contractions mediated by generation of a product of the cyclo-oxygenase pathway, prostaglandin H2 or more probably thromboxane A2, in normotensive and hypertensive rats; (2) oxygen-derived free radicals are not involved in the effect of H2O2; (3) in normotensive rats, endothelium protects against H2O2-mediated injury to contractile machinery, determined by the impairment of KCl-induced contractions; and (4) endothelial nitric oxide has a protective role on the contractile effect induced by H2O2, that is lost in hypertension.


Electrocardiographic signs of coronary heart disease in a "low risk" population in rural Crete.
Ischemic heart disease (IHD) has been shown to be very uncommon in the population of Crete. Therefore, we established a research project in a rural part of Crete to survey the cardiovascular risk profile and follow the incidence of cardiovascular disease over time. This study investigated the prevalence of ECG abnormalities in the population of five villages and compared the prevalence of hypertension, obesity, diabetes, and hypercholesterolemia in those with and without ECG signs of IHD. A cross-sectional study was conducted in a group from 15 to 79 years of age (n = 1218); overall attendance was 926 (76%). Studies included case history, clinical status, laboratory variables, and 12-lead ECG. Technically acceptable ECGs were read and coded blindly for 895 subjects (97%). Minnesota codes suggesting "Probable IHD" were recorded in 3.3% of the women and 3.5% of the men from 45 to 79 years of age. Hypertension was more common in subjects with than in those without "Probable IHD." This also tended to be the case for diabetes. Cholesterol and body mass index were relatively high in both groups. The present prevalence of "Probable IHD" in Cretans appears to be very similar to that observed in other population surveys. Also, the contemporary cardiovascular risk factor profile in the population was quite unfavorable, with a relatively high prevalence of smoking, dyslipidemia, hypertension, and diabetes. The prevalence of "Probable IHD" was lowest in the village where the health center was situated (1% vs 4.5%), and this difference was also reflected in differences among the villages of some important risk factors for IHD as well as in the way patients with hypertension and other diseases were cared for. Thus, it seems IHD is becoming more prevalent in the "low risk" population of Crete. This may very well be a result of a more unfavorable lifestyle and a higher rate of risk factors than before.


Current understanding of organically bound tritium (OBT) in the environment.
It has become increasingly recognized that organically bound tritium (OBT) is the more significant tritium fraction with respect to understanding tritium behaviour in the environment. There are many different terms associated with OBT; such as total OBT, exchangeable OBT, non-exchangeable OBT, soluble OBT, insoluble OBT, tritiated organics, and buried tritium, etc. A simple classification is required to clarify understanding within the tritium research community. Unlike for tritiated water (HTO), the environmental quantification and behaviour of OBT are not well known. Tritiated water cannot bio-accumulate in the environment. However, it is not clear whether or not this is the case for OBT. Even though OBT can be detected in terrestrial biological materials, aquatic biological materials and soil samples, its behaviour is still in question. In order to evaluate the radiation dose from OBT accurately, further study will be required to understand OBT measurements and determine OBT fate in the environment. The relationship between OBT speciation and the OBT/HTO ratio in environmental samples will be useful in this regard, providing information on the previous tritium exposure conditions in the environment and the current tritium dynamics.


Identification of novel HLA-A*0201-restricted epitopes from anterior gradient-2 as a tumor-associated antigen against colorectal cancer.
Anterior gradient-2 (AGR2) promotes tumor growth, cell migration and cellular transformation and its enhanced expression is almost completely restricted to malignant tissues, thus making AGR2 an interesting target for the development of immunotherapeutic strategies. We investigated whether the AGR2 molecule comprises human leukocyte antigen (HLA)-A*0201-binding epitopes recognized by human cytotoxic T lymphocytes (CTLs), which could be targeted in dendritic cell (DC)-based cancer immunotherapy against colorectal cancer (CRC). We reviewed the sequence of AGR2 for peptides that could potentially bind to HLA-A*0201 with the aid of a computer-based program. Five candidate peptides with different binding scores were synthesized and tested. These peptides were then assessed for their immunogenicity to elicit specific immune responses mediated by CTLs in vitro by means of enzyme-linked immunospot assays and CTL assays. AGR2 was highly expressed in several CRC cell lines, including DK01, DLD1, KM12C, HCT-8 and HT-29. DCs pulsed with AGR2-P2 (aa 11-19; LLVALSYTL) or AGR2-P4 (aa 127-135; RIMFVDPSL) generated potent CTLs that could lyse T2 cells pulsed with AGR2-P2 or AGR2-P4 and HLA-A0201(+) AGR2-positive CRC cell lines in a strong dose-dependent and HLA-A*0201-restricted manner. In conclusion, these novel epitopes derived from AGR2 protein may be attractive candidates for DC-based immunotherapy for CRC.


Engineering strategies for enhancing the performance of electrochemical paper-based analytical devices.
Applications of electrochemical detection methods in microfluidic paper-based analytical devices (μPADs) has revolutionized the area of point-of-care (POC) testing towards highly sensitive and selective quantification of various (bio)chemical analytes in a miniaturized, low-coat, rapid, and user-friendly manner. Shortly after the initiation, these relatively new modulations of μPADs, named as electrochemical paper-based analytical devices (ePADs), gained widespread popularity within the POC research community thanks to the inherent advantages of both electrochemical sensing and usage of paper as a suitable substrate for POC testing platforms. Even though general aspects of ePADs such as applications and fabrication techniques, have already been reviewed multiple times in the literature, herein, we intend to provide a critical engineering insight into the area of ePADs by focusing particularly on the practical strategies utilized to enhance their analytical performance (i.e. sensitivity), while maintaining the desired simplicity and efficiency intact. Basically, the discussed strategies are driven by considering the parameters potentially affecting the generated electrochemical signal in the ePADs. Some of these parameters include the type of filter paper, electrode fabrication methods, electrode materials, fluid flow patterns, etc. Besides, the limitations and challenges associated with the development of ePADs are discussed, and further insights and directions for future research in this field are proposed.


[Academic satisfaction in residents of the north zone, Mexico City].
Resident academic satisfaction has been linked to academic performance and quality of care. To analyze the perception of academic satisfaction in medical residents of the North Decentralized Administrative Operation Body 2 of the Instituto Mexicano del Seguro Social (IMSS), north of Mexico City. Cross-sectional analytical study. A total of 346 resident physicians of different specialties and academic degrees were found, enrolled in the residence halls in the northern zone of the IMSS, Mexico City from January to February 2022. The dependent variable was the level of academic satisfaction. Descriptive and inferential statistics and p ≤ 0.05 were produced for statistical significance. The level of high satisfaction was 80.6% and the level of poor or low satisfaction was 1.7%. The dimension most affected in the negative bases was that of "Perception of teaching" in which 13% of the doctors surveyed refer to the need for some retraining of teachers. The best qualified dimension was "Perception of the role of autonomies" where 35.3% have an excellent perception of their personal work. The highest degree of satisfaction decreased during the second year. There is a high degree of satisfaction among resident doctors, however it is necessary to work to improve satisfaction in the remaining 20%.


Susceptibility to lethal cerebral malaria is regulated by epistatic interaction between chromosome 4 (Berr6) and chromosome 1 (Berr7) loci in mice.
In humans, cerebral malaria is a rare but often lethal complication of infection with Plasmodium parasites, the occurrence of which is influenced by complex genetic factors of the host. We used a mouse model of experimental cerebral malaria (ECM) with Plasmodium berghei ANKA to study genetic factors regulating appearance of neurological symptoms and associated lethality. In a genome-wide screen of N-ethyl-N-nitrosourea-mutagenized mice derived from C57BL/6J (B6) and 129S1/SvImJ (129) mouse strains, we detected a strong interaction between the genetic backgrounds of these strains, which modulates ECM resistance. We have mapped a major gene locus to central chromosome 4 (log of the odds (LOD) 6.7; 79.6-97.3 Mb), which we designate Berr8. [corrected]. B6 alleles at Berr6 are associated with resistance, and are inherited in a co-dominant fashion. In mice heterozygous for Berr6 B6/129 alleles, resistance to ECM is strongly modulated by a second locus, Berr7, that maps to the proximal portion of chromosome 1 (LOD 4.03; 41.4 Mb). 129 alleles at Berr7 are associated with ECM resistance in a dosage-dependent fashion. Results are discussed in view of the possible role of this two-locus system in susceptibility to unrelated inflammatory conditions in mice and humans.


HIV-1 DNA for the measurement of the HIV reservoir is predictive of disease progression in seroconverters whatever the mode of result expression is.
HIV-1 DNA levels, reported as copies/10(6) peripheral blood mononuclear cells (PBMC), are very predictive of disease progression in seroconverters, independently of CD4(+)T cell count and HIV-RNA. Previously, HIV-DNA levels have sometimes been reported by other means: copies/10(6) CD4(+)T cells, reflecting the proportion of infected cells; or copies/mL whole blood, reflecting the global blood reservoir size. We investigated if the predictive value over the natural course of the disease depends on how the results are reported. Results reported as HIV-DNA copies/10(6) PBMC were converted to copies/10(6) CD4(+)T cells or to copies/mL whole blood for 422 seroconverters included in the French SEROCO cohort (ANRS). The three methods for reporting HIV-DNA levels yielded different ranges, but these values were highly correlated. The level of HIV-DNA during the seroconversion period was strongly associated with disease progression in all three reporting methods. This reinforces the value of HIV-DNA quantification in physiopathological and therapeutical studies, particularly in an era of research aimed at diminishing the HIV reservoir. Even if blood represents a small part of this reservoir, HIV-DNA in blood is a simple marker that provides an informative picture of the global reservoir and is strongly predictive of disease progression.


The impact of cardiomotor rehabilitation on endothelial function in elderly patients with chronic heart failure.
To explore the effects of cardiac exercise rehabilitation on peripheral blood endothelial progenitor cells (EPC) in elderly patients with chronic heart failure. 80 elderly patients with chronic heart failure were selected from March 2017 to March 2019 and randomly divided into two groups (N = 40). The control group was treated routinely and walked freely for 30-60 min every day. The patients in the exercise rehabilitation group developed a cardiac exercise rehabilitation plan. Then, cardiac function and peripheral blood B-natriuretic peptide (BNP) levels in the two groups were compared. The cell viability, proliferation, apoptosis, and invasion ability of EPCs were detected. The levels of the PI3K/AKT pathway and eNOS and VEGF were compared. There were no significant differences in all indexes between the two groups before treatment (P > 0.05), and both improved significantly after treatment (P < 0.05). After treatment, LVEF and LVFS in the exercise rehabilitation group were significantly higher than those in the control group (P < 0.05), and LVEDD and LVESD were significantly lower than those in the control group (P < 0.05). The BNP level in the exercise rehabilitation group was significantly lower than that in the control group (P < 0.05). The cell viability, proliferation, invasion ability of EPC, and the levels of PI3K, AKT, eNOS, and VEGF mRNA and protein in the exercise rehabilitation group were significantly higher than those in the control group. Apoptosis rate was significantly lower than those in the control group (P < 0.05). Visceral exercise rehabilitation can improve cardiac ejection and myocardial function in elderly patients with chronic heart failure, and can promote the vitality, proliferation, and invasion of peripheral blood EPC, and promote the expression of eNOS and VEGF by upregulating the PI3K/AKT pathway to promote angiogenesis and endothelial function.


Presumed isolated inflammation of the superior oblique muscle in idiopathic orbital myositis.
To describe isolated involvement of the superior oblique muscle in association with idiopathic orbital myositis. A case report with review of the literature. A 57-year-old man with acquired strabismus participated. Oral steroid therapy was administered. Clinical and radiographic features before and after treatment were measured. Computed tomographic scanning showed isolated enlargement of the superior oblique muscle consistent with orbital myositis. Clinical and radiographic abnormalities quickly improved after oral steroid therapy. Orbital pseudotumor may present as a myositis isolated to the superior oblique muscle. This extremely rare condition has been reported in only three patients, each of whom lacked early diagnosis or treatment. Early recognition may improve chances for a successful clinical outcome.


BmRobo2/3 is required for axon guidance in the silkworm Bombyx mori.
Axon guidance is critical for proper wiring of the nervous system. During the neural development, the axon guidance molecules play a key role and direct axons to choose the correct way to reach the target. Robo, as the receptor of axon guidance molecule Slit, is evolutionarily conserved from planarians to humans. However, the function of Robo in the silkworm, Bombyx mori, remained unknown. In this study, we cloned robo2/3 from B. mori (Bmrobo2/3), a homologue of robo2/3 in Tribolium castaneum. Moreover, BmRobo2/3 was localized in the neuropil, and RNAi-mediated knockdown of Bmrobo2/3 resulted in the longitudinal connectives forming closer to the midline. These data demonstrate that BmRobo2/3 is required for axon guidance in the silkworm.


Cat allergen exposure in a naturalistic exposure chamber: A prospective observational study in cat-allergic subjects.
To determine the proportion and reproducibility of cat-allergic mild asthmatics with early asthmatic response (EAR) during cat allergen exposure in a naturalistic exposure chamber (NEC). This was a prospective, observational study in 30 cat-allergic mild asthmatics who received two 180-min cat-allergen (Felis domesticus allergen 1 [Fel d 1]) challenges 27 days apart in an NEC. An EAR (≥20% reduction from baseline in forced expiratory volume in 1 s [FEV1]) was observed in 67% and 52% of subjects at first and second NEC exposure, respectively, with similar median time to EAR; 44% of subjects had an EAR on days 1 and 28. Late asthmatic response (≥15% reduction in FEV1 within 24 h of NEC exit) was observed in 33% of subjects following either exposure. Average FEV1 and total nasal symptom score during NEC exposure were highly correlated within subjects between NEC exposures (r = 0.91, p < 0.0001; r = 0.73, p < 0.001), but total ocular symptom score was not. Time to EAR, but not average FEV1, was significantly associated with NEC Fel d 1 concentration, which was variable. There were no serious adverse events; 12/30 subjects experienced 20 adverse events (including asthma, 10%; headache, 10%). The NEC model demonstrates that average FEV1 change is highly reproducible and has a low correlation with cat allergen levels. However, time to EAR and incidence of EAR are less reproducible and are highly correlated with NEC allergen levels. Average FEV1, rather than incidence of EAR or time to EAR, could be considered as an endpoint for interventional trials testing cat-specific anti-allergy therapies using an NEC.


Metabolic Pathways for Degradation of Aromatic Hydrocarbons by Bacteria.
The aim of this review was to build an updated collection of information focused on the mechanisms and elements involved in metabolic pathways of aromatic hydrocarbons by bacteria. Enzymes as an expression of the genetic load and the type of electron acceptor available, as an environmental factor, were highlighted. In general, the review showed that both aerobic routes and anaerobic routes for the degradation of aromatic hydrocarbons are divided into two pathways. The first, named the upper pathways, entails the route from the original compound to central intermediate compounds still containing the aromatic ring but with the benzene nucleus chemically destabilized. The second, named the lower pathway, begins with ring de-aromatization and subsequent cleavage, resulting in metabolites that can be used by bacteria in the production of biomass. Under anaerobic conditions the five mechanisms of activation of the benzene ring described show the diversity of chemical reactions that can take place. Obtaining carbon and energy from an aromatic hydrocarbon molecule is a process that exhibits the high complexity level of the metabolic apparatus of anaerobic microorganisms. The ability of these bacteria to express enzymes that catalyze reactions, known only in non-biological conditions, using final electron acceptors with a low redox potential, is a most interesting topic. The discovery of phylogenetic and functional characteristics of cultivable and noncultivable hydrocarbon degrading bacteria has been made possible by improvements in molecular research techniques such as SIP (stable isotope probing) tracing the incorporation of (13)C, (15)N and (18)O into nucleic acids and proteins. Since many metabolic pathways in which enzyme and metabolite participants are still unknown, much new research is required. Therefore, it will surely allow enhancing the known and future applications in practice.


Ki 67 is a major, but not the sole determinant of Oncotype Dx recurrence score.
Immunohistological assessment of Ki 67 expression is less expensive than Oncotype Dx, which is currently used to identify patients with lymph node-negative breast cancer, who will benefit from adjuvant chemotherapy. The relationship of immunohistologically measured Ki 67 to Oncotype DX recurrence score (RS) was examined in 53 cases of T1-2 N0 M0 (oestrogen receptor-positive, HER2/neu negative) breast cancer. There was a strong linear correlation between Ki 67 value and the Oncotype Dx RS. All patients in the low Ki 67 group (Ki 67 of ≤ 10%) had Oncotype Dx RSs of low or intermediate risk. The vast majority of patients (93.8%) in the high-Ki 67 group (Ki 67 ≥ 25%) had oncotype RSs of high or intermediate risk. Ki 67 proliferation value is a major, but not the sole determinant of Oncotype Dx score.


A case of alveolar rhabdomyosarcoma with a chromosomal translocation, t(2;13)(q37;q14).
We report on an alveolar rhabdomyosarcoma occurring in a 17-year-old girl. Histologically, the tumour exhibited a proliferation of small, round cells and formed alveolar structures. Immunohistochemical studies of the tumour cells showed desmin and creatine kinase MM positivity. In electron-microscopic studies, the tumour cells showed an abundance of glycogen granules, and myofilaments were recognized in the cytoplasm. Chromosome analysis revealed a translocation, t(2;13)(q37;q14), which is though to be common in this subtype of rhabdomyosarcoma. Conventional ultrastructural and immunohistochemical investigations and chromosome analysis thus appear to be a highly promising combination of methods for improved pathological diagnosis of alveolar rhabdomyosarcoma.


[Multifocal (chaotic) atrial tachycardia in a newborn infant].
Description of multifocal (chaotic) atrial tachycardia in a newborn, which reverted to sinus rhythm after treatment with digitoxin.


First aid management of paediatric burn and scald injuries in Southern Malawi: A mixed methods study.
In sub-Saharan Africa, burn and scald injuries occur more commonly in children aged less than five years, than in any other age group, and carry a high lifetime morbidity. The optimal first aid at the time of injury includes the use of cool running water, which can reduce pain, scarring, and skin grafting. Data on the types of first aid used in Malawi is lacking, as is an in-depth understanding of the underlying factors which may influence this health behaviour. This study sought to: (a) document the types of first aid after paediatric burn and scald injuries in Southern Malawi; and (b) explore factors affecting the choice of first aid used. We conducted a sequential explanatory mixed methods study. Quantitative analysis of a prospectively collected database of all patients aged less than 17 years admitted to the only burn unit in Southern Malawi was followed by thematic analysis of semi-structured interviews with 15 adults who had witnessed a paediatric burn or scald injury. 1326 patients aged less than 17 years were admitted to the Queen Elizabeth Central Hospital between July 2009 and December 2016. Median age was 3.0 years (IQR 1.9-5.0) and male to female ratio 1:0.9. The commonest cause of injury was hot liquid (45%), followed by open fire (31%) and porridge (12%). First aid was applied in 829 patients (69%), the commonest applications used were water (31%) and egg (21%). There was a statistically significant association between the type of first aid and secondary education of the father (p = 0.009) or mother (p = 0.036); however, the type of first aid used was more likely to be egg rather than water. Analysis of qualitative interviews identified four main themes: perceived roles and responsibilities within the community, drivers of individual behaviours, availability, and trust. Participants reported using eggs as a first aid treatment, as these were readily available and were seen to reduce the occurrence of blisters and prevent peeling of the skin. By comparison, there was a strong underlying fear of using water on burn injuries due to its association with peeling of the skin. Intergenerational learning appeared to play a strong role in influencing what is used at the time of injury, and mothers were the key source of this information. This study provides the largest description of first aid use in sub-Saharan Africa, strengthening the evidence that remedies aside from water are commonly used and that higher parental education levels do not translate to increased use of water, but rather use of alternative treatments. Our qualitative findings allow improved understanding of how first aid for paediatric burns is perceived in rural Malawi communities, providing insight as to why certain first aid choices are made and the possible barriers and facilitators to the adoption of water as a first aid treatment.


Gender differences in autobiographical narratives: he shoots and scores; she evaluates and interprets.
Research on autobiographical narratives consistently demonstrates that whereas women's narratives emphasize evaluative information, men's narratives are factually oriented. These narrative differences might reflect gender differences in either the autobiographical knowledge base or the way information from the knowledge base is selected when a narrative is constructed. The present experiment evaluated these two (potentially complementary) hypotheses by assessing memory soon after an event and after a period of 6 weeks, using both open-ended (narrative) and factually oriented (questionnaire) measures. Consistent with past literature, women told longer, richer, more evaluative narratives than did men. However, men recalled more factual information both initially and after 6 weeks and also constructed narratives that were more factually oriented. These data suggest that men and women value factual information differently and that these differences influence both the contents of the autobiographical knowledge base and the way that information in the knowledge base is used to construct personal narratives.


Construction of the Vero cell culture system that can produce infectious HCV particles.
The hepatitis C virus is a major cause of chronic liver disease worldwide. Lack of culture system supporting virus production has been one of the major impediments in HCV research and vaccine development. Here, we use a HCV (1b) full-length cDNA clone that replicates and produces integrated and infectious virus particles in cultured Vero cells. Evidence shows that the replication of virus particles is robust, producing over 10(8) copies of positive RNA per milliliter of the culture cells within 48 h. Sucrose density gradient centrifugation of the cell lysate reveals that the HCV virions have a density of about 1.17 g/ml and a spherical morphology with an average diameter of about 55 nm. Secreted virus is infectious for Huh7 cells and can be neutralized by CD81- and E2-specific antibodies. This system establishes a powerful framework for studying the virus life cycle and developing vaccine research.


Infection of the enteric nervous system by Borna disease virus (BDV) upregulates expression of Calbindin D-28k.
Borna disease virus (BDV) is a neurotropic agent infecting distinct neuronal subpopulations in the central nervous system of various mammalian species possibly including humans. Horses, a major natural host for BDV, show gastrointestinal dysfunctions besides characteristic neurological symptoms. Therefore, we hypothesized that enteric neurons may be targets of BDV replication. The presence of BDV-specific antigen in subpopulations of the ENS was investigated. Four-week-old Lewis rats were infected intracerebrally and sacrificed 4-14 weeks post infection (p.i.). BDV-immunoreactive neurons were found in submucous and myenteric neurons of the proximal colon. Fourteen weeks p.i., the proportion of BDV-positive neurons was 44+/-17 and 24+/-7% in the submucous and myenteric plexus, respectively. The majority of BDV-positive myenteric neurons showed immunoreactivity for choline acetyltransferase. Expression of Calbindin D-28k (CALB) was found in 96% of submucous and 67% of myenteric BDV-immunoreactive neurons. Additionally, the number of CALB-immunoreactive neurons was significantly higher in the myenteric plexus of infected rats compared to controls. These data indicate that BDV infects specific subpopulations of enteric neurons. Therefore, the ENS might serve as a site for BDV replication and as an immunoprivileged reservoir for BDV. In addition, upregulation of CALB in neurons of the myenteric plexus is probably induced during BDV-infection.


UV-induced degradation of securin is mediated by SKP1-CUL1-beta TrCP E3 ubiquitin ligase.
Securin is a chaperone protein with bifunctional properties. It binds to separase to inhibit premature sister chromatid separation until the onset of anaphase, and it also takes part in cell-cycle arrest after UV irradiation. At metaphase-to-anaphase transition, securin is targeted for proteasomal destruction by the anaphase-promoting complex or cyclosome (APC/C), allowing activation of separase. However, although securin is reported to undergo proteasome-dependent degradation after UV irradiation, the ubiquitin ligase responsible for securin ubiquitylation has not been well characterized. In this study, we show that UV radiation induced a marked reduction of securin in both the nucleus and cytoplasm. Moreover, we show that GSK-3beta inhibitors prevent securin degradation, and that CUL1 and betaTrCP are involved in this depletion. We also confirmed that SKP1-CUL1-betaTrCP (SCF(betaTrCP)) ubiquitylates securin in vivo, and identified a conserved and unconventional betaTrCP recognition motif (DDAYPE) in the securin primary amino acid sequence of humans, nonhuman primates and rodents. Furthermore, downregulation of betaTrCP caused an accumulation of securin in non-irradiated cells. We conclude that SCF(betaTrCP) is the E3 ubiquitin ligase responsible for securin degradation after UV irradiation, and that it is involved in securin turnover in nonstressed cells.


Recent prevalence and characteristics of patients with hepatitis delta virus in Hokkaido, Japan.
Although hepatitis delta virus (HDV) coinfection with hepatitis B virus (HBV) is a global health concern, the global prevalence of HDV infections remains unknown due to insufficient data in many countries. In Japan, HDV prevalence has not been updated for over 20 years. We aimed to investigate the recent prevalence of HDV infections in Japan. We screened 1264 consecutive patients with HBV infection at Hokkaido University Hospital between 2006 and 2022. Patients' serums were preserved and subsequently tested for HDV antibody (immunoglobulin-G). Available clinical information was collected and analyzed. We compared the changes in liver fibrosis using the Fibrosis-4 (FIB-4) index between propensity-matched patients with and without the evidence of anti-HDV antibodies and corrected for baseline FIB-4 index, nucleoside/nucleotide analog treatment, alcohol intake, sex, HIV coinfection, liver cirrhosis, and age. After excluding patients without properly stored serums and those lacking appropriate clinical information, 601 patients with HBV were included. Of these, 1.7% of patients had detectable anti-HDV antibodies. Patients with anti-HDV antibody serum positivity had a significantly higher prevalence of liver cirrhosis, significantly lower prothrombin time, and a higher prevalence of HIV coinfection than those who demonstrated serum anti-HDV antibody negativity. A propensity-matched longitudinal analysis revealed that liver fibrosis (FIB-4 index) progressed more rapidly in patients with positive results for anti-HDV antibody tests. The recent prevalence of HDV infections in Japanese patients with HBV was 1.7% (10/601). These patients experienced rapid liver fibrosis progression, highlighting the importance of routine HDV testing.


Asymptomatic hyperthyroidism in older adults: is it a distinct clinical and laboratory entity?
Hyperthyroidism is the result of increased serum free thyroid hormone levels and is associated with a well recognized set of clinical signs and symptoms. However, older patients who develop hyperthyroidism tend to have fewer hyperadrenergic signs and an increased incidence of weight loss, cardiac arrhythmias and, occasionally, apathetic mood. This article highlights the paucity of clinical signs and symptoms of hyperthyroidism in older people and reviews the potential biochemical changes in thyroid hormone physiology that may account for an altered clinical presentation in older people with hyperthyroidism. First, a brief vignette from our own clinical practice is described to highlight an unusual presentation of hyperthyroidism in an older woman. The subject is then reviewed on the basis of relevant articles identified through a MEDLINE search of the English literature, using the key words 'hyperthyroidism' and 'aging'. The available evidence indicates that the clinical syndrome of asymptomatic hyperthyroidism in older adults appears to be distinct from the more widely recognized syndromes of apathetic hyperthyroidism or thyroid hormone resistance. Age-related changes in thyroid hormone economy and reduced cellular uptake of thyroid hormone as well as changes in thyroid hormone regulation of gene expression may account for reduced manifestations of hyperthyroidism in older adults. Thus, in addition to the well known changes in thyroid gland anatomy and function with aging, there may be an age-related resistance to thyroid hormone action. Asymptomatic hyperthyroidism may well be a syndrome that is currently under-diagnosed.


Risk factors for foot-pad dermatitis in chicken and turkey broilers in France.
A prospective cohort study was conducted in the Brittany region to identify the risk factors related to foot-pad dermatitis (considered an indicator of animal well-being) in chicken and turkey broilers reared under commercial conditions. Factors related to the shed, equipment, litter management and stocking density were recorded; the dependent variable was the prevalence of lesions observed on the slaughterhouse chain. Lesions were scored from 0 (no lesion) to 3 (severe lesion). Our survey lasted from May 1999 to October 2000. Fifty flocks of chicken broilers (15 farms), 27 flocks of female turkey broilers (21 farms) and 41 flocks of male turkey broilers (27 farms) were surveyed. In chicken broilers, 10% of flocks were of high quality (80% of birds with score 0) and this was related to the use of concrete floors with a thin layer of wood shavings. In turkey broilers, 48% of female and 46% of male flocks were of bad quality (>10% of birds with score 3). A poor fan ventilation system (<150m(3)/h/kg) was a significant risk factor. Turkey flocks of high quality were not observed. Stocking density had no influence on the prevalence of foot-pad dermatitis. We concluded that it is possible under high commercial stocking densities to have flocks with a low prevalence of foot-pad dermatitis in chicken broilers, whereas it is not in turkey broilers. Hence in chicken broilers, implementing a monitoring system based on the observation of foot-pad dermatitis prevalence at slaughter appears to be more appropriate than to legislate stocking density. In turkey broilers, it would probably be necessary either to reduce the stocking density drastically or to investigate new systems of floor drainage.


Management of otitis media with effusion.
Timmy, a two-year-old, has received two antibiotic courses (ampicillin, cefaclor) for acute otitis media during the past year. Today, his mom visits your pharmacy and mentions that they have just returned from an appointment with the boy's doctor. Timmy was diagnosed with otitis media with effusion, which the doctor described as fluid in the ears unaccompanied by fever or any signs of pain or discomfort. She is puzzled that the doctor did not prescribe any antibiotics this time. Worried about her son's recurrent ear problems, she asks your advice. Your review of Timmy's history reveals that he is otherwise healthy except for the two previous episodes of acute otitis media. Further discussion with Timmy's mom also reveals that his father is a heavy smoker.


Response Surface Optimization for Investigating Antioxidant Potential of Camellia Sinensis and Withania Somnifera in Synergistic Manner.
The paper highlights the synergistic potential of the novel combination of Camellia sinensis (Kangra green tea) and Withania somnifera (Ashwagandha). One variable at a time approach was used to find antioxidant potential of C. sinensis and W. somnifera alone and in combination. Optimization of antioxidant potential was done by using different plant concentrations of C. sinensis and W. somnifera using a statistical approach of central composite design (CCD) of RSM (response surface methodology). Initial antioxidant activity during optimization of the solvent system was observed in methanol for C. sinensis with DPPH, superoxide radical scavenging assay and hydrogen peroxide scavenging assay (44.9 ± 0.62, 43.77 ± 0.10, 43.88 ± 0.10% scavenging) and for W. somnifera (40.22 ± 0.39, 43.29 ± 1.12, 41.88 ± 0.11% scavenging), respectively. Initially, IC50 has been calculated for C. sinensis (235.26 ± 0.012 μg/mL) and W. somnifera (256.39 ± 0.43 μg/mL) in methanol. Before statistical optimization, the maximum synergistic antioxidant potential of C. sinensis (200 μg/mL) and W. somnifera (150 μg/mL) with DPPH assay, superoxide radical scavenging and hydrogen peroxide scavenging assay was found to be 56.57 ± 0.62, 56.99 ± 0.42, 55.44 ± 0.53% scavenging, respectively. IC50 value has been calculated for C. sinensis + W. somnifera (IC50 = 215.47 ± 0.06 μg/mL). Optimization of plant concentration using CCD of RSM resulted in enhancement of antioxidant potential of C. sinensis (200.5 μg/mL) and W. somnifera (200.5 μg/mL) was found to be 78.01 ± 0.01% scavenging when compared to the initial antioxidant potential, i.e., 56.57 ± 0.62% scavenging shows a 1.37-fold increase from initial antioxidant potential. Research unveils that using various combination of C. sinensis and W. somnifera enhance the antioxidant potential in vitro. The online version contains supplementary material available at 10.1007/s40011-022-01423-6.


[Physico-chemical characteristics of the plasma membrane of the human placenta in placental insufficiency].
Lipid peroxidation, microviscosity, lipid fraction ratios and glycoprotein carbohydrate metabolism were investigated in syncytiotrophoblastic plasmatic membranes of patients with placental insufficiency. Changes are demonstrated in the above parameters, as compared to normal values, indicative of profound structural transformations of placental membranes. Hyperbaric oxygenation is shown to have a favorable effect on structure and properties of placental membranes.


Health Services for Gender-Based Violence: Médecins Sans Frontières Experience Caring for Survivors in Urban Papua New Guinea.
Levels of gender-based violence in Papua New Guinea (PNG) are high; health services for survivors are limited. Evidence from the few existing health services for survivors can inform improvements in care in this and similar settings. Médecins Sans Frontières supported health services for survivors in Lae, PNG from 2008-2013. Routine monitoring data from August 2010-April 2013 were used to describe patient and service characteristics. 5,892 individuals received care over 6,860 presentations, the majority self-referred or referred by friends and family. Presentations were attributed to intimate partner violence(62%), non-partner sexual violence(15%), other forms of violence(3%), and past (but not current) violence(21%). 97% were female; an estimated 4.9% (95%CI:4.8-5.0%) of females resident in the catchment area presented to the programme during the 2.8years analysed. Of presentations for non-partner sexual violence, 79% knew their abuser and 50% were children <16 years. 92% of presentations reporting current violence received medical treatment for injuries. The majority of patients who received multiple counselling sessions reported improved functioning and decreased severity of psycho-social complaints. Community awareness of the availability of free, best-practice, accessible, confidential medical and counselling services for sexual and gender-based violence in Lae, PNG resulted in many survivors presenting for care. High levels of ongoing intimate partner violence and child sexual abuse by known abusers indicates that alongside comprehensive medical care, access to effective services in non-health sectors such as policing, protection and legal services are needed if survivors are to escape the cycle of violence.


Design, synthesis, biological evaluation and molecular docking studies of novel benzofuran-pyrazole derivatives as anticancer agents.
This study deals with design and synthesis of novel benzofuran-pyrazole hybrids as anticancer agents. Eight compounds were chosen by National Cancer Institute (NCI), USA to evaluate their in vitro antiproliferative activity at 10(-5)M in full NCI 60 cell panel. The preliminary screening of the tested compounds showed promising broad-spectrum anticancer activity. Compound 4c was further assayed for five dose molar ranges in full NCI 60 cell panel and exhibited remarkable growth inhibitory activity pattern against Leukemia CCRF-CEM, MOLT-4, Lung Cancer HOP-92, Colon Cancer HCC-2998, CNS Cancer SNB-75, Melanoma SK-MEL-2, Ovarian Cancer IGROV1, Renal Cancer 786-0, RXF 393, Breast Cancer HS 578T and T-47D (GI50: 1.00-2.71μM). Moreover, enzyme assays were carried out to investigate the possible antiproliferative mechanism of action of compound 4c. The results revealed that compound 4c has good c-Src inhibitory activity at 10μM. In addition, molecular docking studies showed that 4c could bind to the ATP Src pocket sites. Fulfilling the Lipinskiís rule of five in addition to its ADME profile and the biological results, all strongly suggest that 4c is a promising Src kinase inhibitor.


Herpes simplex virus - induced interferon production and activation of natural killer cells in SM/J mice. Relation to antiviral resistance.
We have studied the susceptibility of SM/J mice to intraperitoneal (i.p.) infection with herpes simplex virus type 1 (HSV) and have searched for correlations of susceptibility with the activation of Natural Killer (NK) cells and with local induction of interferon. SM/J were exceedingly susceptible to virus infection as they could be killed by less than 10 plaque forming units (PFU). The NK cell system of these mice, as measured by the activity of spleen cells against YAC-1 lymphoma cells, was hyperreactive, which is in agreement with previous findings of others. The peritoneal exudate cells (PEC) of uninfected mice had no activity. However, 18 h after i.p. injection of HSV NK cell activity was detected in the PEC population, which was at least as high as that in C57BL/6 mice that are resistant to HSV infection. Thus it appears as if the NK cell system does not play a major role in antiviral resistance in our experimental system. In contrast, from our previous work it would rather appear that the magnitude of the early local interferon response is important for resistance. The current data obtained in SM/J mice are in accordance with this, in that these highly susceptible mice are deficient in their early interferon response. Homozygous beige mice were found to be as resistant to infection with HSV as C57BL/6 mice. While the NK cell activity in their PEC population after injection of HSV was low, the titers of locally induced interferon were as high as those in the controls.


Polymer dots as a novel probe for fluorescence sensing of dopamine and imaging in single living cell using droplet microfluidic platform.
We report here simple synthetic method for preparing polymer dots (Pdots) via hydrothermal treatment of organic dye (neutral red), urea and trisodium citrate. The prepared Pdots with enhanced quantum yield (quantum yield: 30.2%) was used as a selective and sensitive probe for fluorescent sensing of dopamine (DA) with high selectivity and sensitivity. The as-synthesized Pdots exhibited strong fluorescence intensity at 435 nm, which DA can trigger remarkable fluorescence quenching of such luminescent Pdots on the basis of inner filter effect (IFE) and static quenching effect (SQE). A wide linearity range (0.001 μM-900 μM) for DA detection was obtained with lower DL (3 S/N) of 0.28 nM, and no interference from other molecules such as ascorbic acid, urine acid, glutathione, glucose, epinephrine, arginine, cysteine, proline, creatinine, serine; alanine, L-therionine, Hg2+, Mg2+, K+, Ca2+ and Na+. The designed sensor was successfully applied in the imaging of DA in single living PC12 cells using droplet microfluidic approach, indicating its acceptable practicability of the proposed assay for DA detection with ultrahigh sensitivity in biological samples.


Sodium persulfate-assisted mechanochemical degradation of tetrabromobisphenol A: Efficacy, products and pathway.
In recent years, activated persulfate (PS) oxidation has been developed as a new advanced oxidation process for the degradation of organic pollutants. On the other hand, the mechanochemical method has exhibited a unique advantage in dealing with chemical wastes. The degradation of tetrabromobisphenol A (TBBPA), a widely used brominated flame retardant (BFR), in wastes has attracted considerable attention. In this study, the efficacy of a CaO-mechanochemical (CaO-MC) treatment system assisted by the addition of PS for the degradation of TBBPA was investigated. Under the optimum reaction conditions with a mole ratio of PS:CaO = 1:4 and less than 12.5% of TBBPA by mass, the degradation and debromination of TBBPA were completed within 2 h, while the mineralization was completed within 4 h. Characterization of the milled sample by XRD revealed that CaSO4 crystallization occurred. The TG results illustrate that there was little organic matter left after 4 h of milling. Raman and FT-IR spectra exhibited the TBBPA destruction process and disappearance of the organic groups. Through analysis by LC/MS/MS, seventeen intermediates were identified. The mechanism of TBBPA degradation by the PS-assisted CaO-MC treatment system was explained from two aspects, the course of crystallization and the degradation of TBBPA by activated PS, and two parallel initiation pathways were proposed.


Possible role of the 11-cis-retinyl conformation in controlling the dual decay processes of excited rhodopsin.
In this work, we examine how the reported dual decay processes of rhodopsin and binding site stereospecificity can be accounted for by the recently available crystal structure of rhodopsin. Arguments are presented for possible presence of two rhodopsin "rotamers" that fit within the binding cavity. Directed pathways of decay could account for the observed excited decay processes. We summarize evidence for the possible existence of two different ground-state configurations that give rise to two different excited species.


Drug-Polymer Miscibility and the Overlap Concentration (C*) as Measured by Rheology: Variation of Polymer Structure.
Amorphous solid dispersions (ASDs), wherein a drug is molecularly dispersed in a polymer, can improve physical stability and oral bioavailability of poorly soluble drugs. Risk of drug crystallization is usually averted using high polymer concentrations. However, we demonstrated recently that the overlap concentration, C*, of polymer in drug melt is the minimum polymer concentration required to maintain drug in the amorphous state following rapid quench. This conclusion was confirmed for several drugs mixed with poly(vinylpyrrolidone) (PVP). Here we assess the solid-state stability of ASDs formulated with a variety of polymers and drugs and at various polymer concentrations (C) and molecular weights (MWs). We further test the hypothesis that degree of drug crystallization decreases with increasing C/C* and vanishes when C>C*, where C* depends on polymer MW and strength of drug-polymer interaction. We test our hypothesis with ASDs consisting of ketoconazole admixed with polyacrylic acid, polymethacrylic acid and poly (methacrylic acid-co-ethyl acrylate); and felodipine admixed with PVP and poly (vinylpyrrolidone-co-vinyl acetate). Values of C* for polymers in molten drug are rheologically determined. Crystallization behavior is assessed by measuring enthalpy of fusion, ΔHf and by X-ray diffraction. We confirm that ΔHf/ΔHf, C = 0 = f(C/C∗), and essentially no crystallization occurs when C>C*. Our findings will aid researchers in designing or selecting appropriate polymers to inhibit crystallization of poorly soluble drugs. This research also suggests that C* as determined by rheology can be used to compare drug-polymer interactions for similar molecular weight polymers.


Nicotine-upregulated miR-30a arrests cell cycle in G1 phase by directly targeting CCNE2 in human periodontal ligament cells.
The consumption of nicotine via smoking tobacco has been reported to stimulate the occurrence and progression of periodontitis. Many studies have demonstrated that nicotine prevents the regeneration of periodontal tissues primarily by inhibiting the proliferation of human periodontal ligament (PDL) cells. However, the mechanisms underlying this process are still unclear. Therefore, we investigated whether nicotine-upregulated miR-30a inhibited the proliferation of human PDL cells by downregulating cyclin E2 (CCNE2), in vitro. Quantitative real-time PCR analysis revealed that nicotine upregulated the expression of miR-30a in human PDL cells. In addition, nicotine inhibited the proliferation of human PDL cells by inducing cell cycle arrest. To support this hypothesis, we showed that nicotine downregulated the expression of CCNE2 in human PDL cells, whereas inhibition of miR-30a restored CCNE2 expression that had been downregulated by nicotine. Furthermore, using luciferase reporter assays, we found that miR-30a directly interacts with the CCNE2 3'UTR. In conclusion, these findings indicate that nicotine-upregulated miR-30a inhibits the proliferation of human PDL cells by downregulating the expression of CCNE2.


A cell-based evaluation of a non-essential amino acid formulation as a non-bioactive control for activation and stimulation of muscle protein synthesis using ex vivo human serum.
The purpose of this study was to compare the effect of treating skeletal muscle cells with media conditioned by postprandial ex vivo human serum fed with either isonitrogenous Non-Essential Amino Acid (NEAA) or a whey protein hydrolysate (WPH) on stimulating Muscle Protein Synthesis (MPS) in C2C12 skeletal muscle cells. Blood was taken from six young healthy males following overnight fast (fasted) and 60 min postprandial (fed) ingestion of either WPH or NEAA (0.33 g.kg-1 Body Mass). C2C12 myotubes were treated with media conditioned by ex vivo human serum (20%) for 4 h. Activation of MPS signalling (phosphorylation of mTOR, P70S6K and 4E-BP1) were determined in vitro by Western Blot and subsequent MPS were determined in vitro by Western Blot and surface sensing of translation technique (SUnSET) techniques, respectively. Media conditioned by NEAA fed serum had no effect on protein signalling or MPS compared to fasted, whereas media conditioned by WPH fed serum significantly increased mTOR (Ser2448), P70S6K and 4E-BP1 phosphorylation (p<0.01, p<0.05) compared to fasted serum. Furthermore, the effect of media conditioned by WPH fed serum on protein signalling and MPS was significantly increased (p<0.01, p<0.05) compared to NEAA fed serum. In summary, media conditioned by NEAA fed serum did not result in activation of MPS. Therefore, these in vitro findings suggest the use of isonitrogenous NEAA acts as an effective control for comparing bioactivity of different proteins on activation of MPS.


Murine monoclonal antibody MB-2D10 recognizes Rh-related glycoproteins in the human red cell membrane.
The human red cell membrane components reacting with monoclonal antibody MB-2D10 were examined by immunoblotting. The antibody bound to a diffusely staining band extending from Mr 30,000 up to the high-molecular-weight region of the gel in normal membranes and in Rhnull U + membranes, but not in Rhnull U - membranes. Treatment of normal red cells with an endoglycosidase F-containing preparation destroyed the epitope recognized by MB-2D10. The reactivity of the antibody with purified preparations of Rh-related glycoproteins D30 polypeptide, D50 polypeptide, R6A32 polypeptide, and R6A45 polypeptide was also examined. Only the purified R6A45 and D50 components reacted with MB-2D10. These results show that MB-2D10 recognizes a carbohydrate-dependent epitope on the R6A45 and D50 group of Rh-related polypeptides. The results also suggest the possibility that the U antigen arises from interaction between glycophorin B and the Rh-related components D50 and R6A45.


"Airborne" suture tying technique: Simple steps to make it easy.
A multitude of microsurgical suture techniques have been described. Although accurate apposition and eversion of the vessel ends is paramount for the patency of anastomosis, rapidity is usually of secondary importance. However, in situations in which either multiple anastomoses are required or timely revascularization is crucial, speed becomes a determinant factor for eventual success. "Airborne" suture tying is aimed at decreasing operative time by streamlining the microvascular anastomosis. Over the years, several considerations have emerged as key points for achieving mastery of this helpful maneuver. Herein, we simplify the technique by breaking the maneuver into 2 components: the "charioteer" loop and the "lasso" loop. Relevant literature, indications, and benefits are discussed followed by step-by-step descriptions. Both back table and in vivo video demonstrations are presented online.