Nasal versus oronasal continuous positive airway pressure masks for obstructive sleep apnea: a pilot investigation of pressure requirement, residual disease, and leak.
This single-blinded, randomized, controlled pilot study aimed to investigate whether there is a difference between nasal and oronasal masks in therapeutic continuous positive airway pressure (CPAP) requirement, residual disease, or leak when treating obstructive sleep apnea (OSA) and if differences were related to measures of upper airway size. Patients with severe OSA currently using CPAP at ≥4 h/night with a nasal mask were examined (including Mallampati scale, incisal relationship, and mandibular protrusion) and then randomized to receive auto-positive airway pressure (PAP) or fixed CPAP at a manually titrated pressure for 1 week each at home, with immediate crossover. Within each week, a nasal mask and two oronasal masks were to be used for two or three nights each in random order. Data were downloaded from the device. Twelve patients completed the trial (mean ± SD AHI 59.8 ± 28.6 events/h; CPAP 11.1 ± 3.2 cmH(2)O; BMI 37.7 ± 5.0 kg/m(2)). During auto-PAP, the median 95th percentile pressure delivered with all masks was within 0.5 cmH(2)O (p > 0.05). During CPAP, median residual AHI was 0.61 (IQR = 1.18) for the nasal mask, 1.70 (IQR = 4.04) for oronasal mask 1, and 2.48 (IQR = 3.74) for oronasal mask 2 (p = 0.03). The 95th percentile leak was lowest with the nasal mask during both CPAP and auto-PAP (both p < 0.01). Differences in pressure or residual disease were not related to measures of upper airway shape or body habitus. In obese OSA patients changing from a nasal to oronasal mask increased leak and residual AHI but did not affect the therapeutic pressure requirement. The findings of the current study highlight mask leak as the major difficulty in the use of oronasal masks.


Transplantation of RPE in age-related macular degeneration: observations in disciform lesions and dry RPE atrophy.
A study was carried out to investigate whether human RPE allografts are tolerated or rejected in the subretinal space and to determine the feasibility of RPE transplantation in subjects with age-related macular degeneration (AMD). Patches of human fetal RPE (13-20 weeks of gestational age) were transplanted into the subretinal space of five patients after surgical removal of subfoveal fibrovascular membranes, and to four subjects with dry geographic atrophy. Suspensions of RPE cells were transplanted to four other patients with nonexudative AMD. Results were evaluated with clinical ophthalmological examination, SLO microperimetry and fluorescein angiography over 8-20 months. In disciform lesions, RPE transplants developed macular edema and fluorescein leakage concomitant with gradual reduction of visual acuity, implying host-graft rejection, over 1-6 months. In geographic atrophy, three of four transplants showed little change in shape and size after 12 months (one transplant was slowly rejected). In non-exudative AMD, RPE suspension transplants showed no evidence of rejection and were associated with the disappearance of drusen; visual acuity remained stable and SLO microperimetry confirmed retinal function over the transplanted area. Human RPE allografts are not invariably rejected in the subretinal space without immunosuppression. The rejection rate is lower in nonexudative than in neovascular AMD. An intact blood-retinal barrier is likely to protect against rejection. It is technically feasible to transplant human RPE into the submacular space without adversely affecting visual function in nonexudative AMD over relatively long periods of time.


Cortisol responses to serial MRI scans in healthy adults and in depression.
Magnetic resonance imaging (MRI) scans are a novel environment for most participants. The hypothalamic-pituitary-adrenal (HPA) axis modulates neurohormonal responses to novel and stressful experiences. We sought to examine the neurohormonal responses to MRI scans with the measurement of salivary cortisol. We examined: (1) acute effects of MRI scans by acquiring cortisol measurements immediately preceding and following the scan in comparison with basal cortisol levels, and (2) effects of novelty by measuring cortisol during repeated MRI scans in the same subjects. We examined these effects in two groups of subjects: healthy individuals (n=27, mean age 41.6 years) and patients with depression (n=24, mean age 40.0 years). Both groups showed elevated cortisol levels immediately preceding the MRI scan, particularly for the initial MRI scan, which normalised after the follow up MRI scans as compared with mean basal cortisol levels. There were no significant differences in the acute or mean basal cortisol levels between the groups. In summary, the MRI experience is stressful, particularly for the initial scan, but the stress response is reduced with subsequent scans.


Temporal Trends in Antimicrobial Resistance of Fecal Escherichia coli from Deer.
The changing epidemiologic role of wildlife as reservoirs of antimicrobial-resistant bacteria (ARB) is poorly understood. In this study, we characterize the phenotypic resistance of commensal Escherichia coli from fecal samples of 879 individual white-tailed (Odocoileus virginianus; WTD) over a ten-year period and analyze resistance patterns. Our results show commensal E. coli from WTD had significant linear increases in reduced susceptibility to 5 of 12 antimicrobials, including broad-spectrum cephalosporins and fluoroquinolones, from 2006 to 2016. In addition, the relative frequency distribution of minimal inhibitory concentrations of two additional antimicrobials shifted towards higher values from across the study period. The prevalence of multidrug-resistant commensal E. coli increased over the study period with a prevalence of 0%, 2.2%, and 3.7% in 2006, 2012, and 2016, respectively. WTD may be persistently and increasingly exposed to antibiotics or their residues, ARB, and/or antimicrobial resistance genes via contaminated environments like surface water receiving treated wastewater effluent.


Nitric oxide affects IL-6 expression in human peripheral blood mononuclear cells involving cGMP-dependent modulation of NF-κB activity.
Interleukin 6 (IL-6) and nitric oxide (NO) are important mediators of the inflammatory response. We report that in human peripheral blood mononuclear cells (PBMCs), NO exerts a biphasic effect on the expression of IL-6. Using sodium nitroprusside (SNP) and S-nitrosoglutathione (GSNO) as NO-donating compounds, we observed that both mRNA and protein levels of IL-6 increased at lower (≤10μM) and decreased at higher (>100μM) concentrations of NO donors. Changes in the expression of IL-6 correlated with changes in the activity of NF-κB, which increased at lower and decreased at higher concentrations of both NO donors as shown by the electrophoretic mobility shift assay (EMSA). The effects of NO on NF-κB activity were cGMP-dependent because they were reversed in the presence of ODQ, the inhibitor of soluble guanylyl cyclase (sGC), and KT5823, the inhibitor of cGMP-dependent protein kinase (PKG). Moreover, the membrane permeable analog of cGMP (8-Br-cGMP) mimicked the effect of the NO donors. These observations show that NO, depending on its concentration, may act in human PBMCs as a stimulator of IL-6 expression involving the sGC/cGMP/PKG pathway.


Bioavailability and pharmacokinetics of beta-methyldigoxin after multiple oral and intravenous doses.
To obtain true half lives, glycoside elimination from six healthy subjects was studied for 14 days after multiple intravenous doses or oral administration of a daily maintenance dose of beta-methyldigoxin 0.3 mg. After oral or intravenous administration of beta-methyldigoxin ceased, the plasma concentrations declined from the 14th to the 16th days with a half life of 1.7 days. From the 16th to the 20th day a change from a shorter to a longer half life of 2.8 and 2.9 days was observed. Similar half lives were found in urine: after the last dose the initial slope from the 14th to the 16th day had a half life of 1.8 days, and the terminal slope had one of 3.2 days. The results indicate release of the glycoside from slowly equilibrating tissues.


Emerging recombination of the C2 sub-genotype of HFMD-associated CV-A4 is persistently and extensively circulating in China.
Sporadic outbreaks caused by coxsackievirus A4 (CV-A4) have been reported worldwide. To further elucidate the detailed genetic characteristics and evolutionary recombination events of CV-A4, virus samples from nationwide hand, foot and mouth disease (HFMD) surveillance, encompassing 27 out of the 31 provinces in China, were investigated. Comprehensive and systematic phylogenetic analyses were performed by using 29 complete genomes, 142 complete CV-A4 VP1 sequences. Four genotypes (A, B, C and D) and five sub-genotypes (C1-C5) were re-identified based on the complete VP1 sequences. C2 is the predominant sub-genotype of CV-A4 associated with HFMD and has evolved into 3 clusters. Cluster 1 is a major cluster that has been persistently and extensively circulating in China since 2006 and has been associated with all severe cases. All the sequences showed high homology with the CV-A4 prototype in the P1 region, while higher identities with CV-A5, CV-14 and CV-16 in the P2 and P3 regions. Recombination analysis revealed that C2 had two specific genetic recombination patterns with other EV-A prototypes in the 5'-UTR and 3D region compared with C5. These recombination patterns might be associated with the increased transmissibility of C2 viruses, which were obtained due to their persistent and extensive circulation in populations.


N,O-Nucleoside Analogues: Metabolic and Apoptotic Activity.
Two new families of N,O-nucleoside analogues containing the anthracene moiety introduced through the nitrosocarbonyl ene reaction with allylic alcohols were prepared. The core structure is an isoxazolidine heterocycle that introduces either atom either a phenyl ring or dimethyl moiety at the C3 carbon. Different heterobases were inserted at the position 5 of the heterocyclic ring. One of the synthesized compounds demonstrated a good capacity to induce cell death and an appreciable nuclear fragmentation was evidenced in treated cells.


Nodal Recurrence is a Primary Driver of Early Relapse for Patients with Sentinel Lymph Node-Positive Melanoma in the Modern Therapeutic Era.
Management of patients with sentinel lymph node (SLN)-positive melanoma has changed dramatically over the last few years such that completion lymph node dissection (CLND) has become uncommon, and many patients receive adjuvant immunotherapy or targeted therapy. This study seeks to characterize patterns and predictors of early recurrence in this setting. All patients with primary cutaneous melanoma undergoing sentinel lymph node biopsy (SLNB) between 3/2016 and 12/2019 were identified. The subset with a positive SLN who did not undergo CLND were examined for further analysis of outcomes and predictors of recurrence. Overall, 215 patients with SLN-positive melanoma who did not have CLND were identified. Adjuvant systemic therapy was administered to 102 (47%), with 93% of this subset receiving immunotherapy (n = 95). Median follow-up from SLNB was 20 months (IQR 12-28.5 months), and 57 patients (27%) recurred during this time. The SLN basin was the most common site of recurrence (n = 38, 67% of recurrence), with isolated nodal recurrence being the most common first site of recurrent disease (n = 22, 39% of recurrence). On multivariable analysis, lymphovascular invasion (LVI) of the primary tumor, two or more involved nodes, and > 1 mm nodal deposit were independently associated with higher rates of nodal relapse. Nodal recurrence is a primary driver of early disease relapse for patients with SLN-positive melanoma who do not undergo CLND in the era of effective adjuvant systemic therapy. LVI, ≥ 2 nodes, or > 1 mm nodal disease identifies patients at particularly high risk of nodal relapse.


Assessment of pain in people living with dementia at the end of life: a systematic review.
People with dementia may not receive the same quality of palliative care as those with other life-limiting conditions, particularly at end of life (EoL). To understand the best way to examine pain in people with dementia. A systematic review of tools to assess pain in patients with dementia near the end of life; PubMed, Medline, Embase, EBSCO Host, CINAHL Plus, Web of Science, Psycinfo, PsycArticles and Scopus were searched. A total of 15 articles were identified, which were qualitatively synthesised. There are a range of pain assessment tools that are appropriate for use in people with dementia, but all 15 studies used a formal tool. A more robust approach is needed to improve the quality of research for measurement and management of pain in this population.


Evaluation of a clinical decision support tool for osteoporosis disease management: protocol for an interrupted time series design.
Osteoporosis affects over 200 million people worldwide at a high cost to healthcare systems. Although guidelines on assessing and managing osteoporosis are available, many patients are not receiving appropriate diagnostic testing or treatment. Findings from a systematic review of osteoporosis interventions, a series of mixed-methods studies, and advice from experts in osteoporosis and human-factors engineering were used collectively to develop a multicomponent tool (targeted to family physicians and patients at risk for osteoporosis) that may support clinical decision making in osteoporosis disease management at the point of care. A three-phased approach will be used to evaluate the osteoporosis tool. In phase 1, the tool will be implemented in three family practices. It will involve ensuring optimal functioning of the tool while minimizing disruption to usual practice. In phase 2, the tool will be pilot tested in a quasi-experimental interrupted time series (ITS) design to determine if it can improve osteoporosis disease management at the point of care. Phase 3 will involve conducting a qualitative postintervention follow-up study to better understand participants' experiences and perceived utility of the tool and readiness to adopt the tool at the point of care. The osteoporosis tool has the potential to make several contributions to the development and evaluation of complex, chronic disease interventions, such as the inclusion of an implementation strategy prior to conducting an evaluation study. Anticipated benefits of the tool may be to increase awareness for patients about osteoporosis and its associated risks and provide an opportunity to discuss a management plan with their physician, which may all facilitate patient self-management.


Photocatalytic degradation of methylene blue with spent FCC catalyst loaded with ferric oxide and titanium dioxide.
The spent fluid catalytic cracking (FCC) catalyst has been loaded with ferric oxide (Fe2O3) and titanium dioxide (TiO2). Fe-Ti/SF composite (loaded with 5 wt% TiO2 and 5 wt% Fe2O3), Fe/SF composite (loaded with10 wt% Fe2O3) and Ti/SF composite (loaded with 10 wt% TiO2) have been fabricated via a modified-impregnation method. The band gaps of the Fe-Ti/SF, Fe/SF and Ti/SF composites (evaluated by the energy versus [F(R∞)hv]n) are 2.23, 1.98 and 3.0 eV, respectively. Electrochemical impedance spectroscopy shows that the Fe-Ti/SF has lower electron transfer resistance, it has the small charge transfer resistance and fast charge transfer rate. The interparticle electrons transfer between the Fe2O3 and TiO2, which can improve the separation of the photo-electrons and holes. The holes transfer from valence band of TiO2 to the valence band of Fe2O3, which can provide more active sites around the adsorbed molecules. The methylene blue degradation efficiencies (with the Fe-Ti/SF, Fe/SF and Ti/SF composites) are ~ 94.2%, ~ 22.3% and ~ 54.0% in 120 min, respectively. This work reveals that the spent FCC catalyst as supporter can be loaded with Fe2O3 and TiO2. This composite is highly suitable for degradation of methylene blue, which can provide a potential method to dispose the spent FCC catalyst in industry.


Sensitive and isotope selective (14NO/15NO) online detection of nitric oxide by faraday-laser magnetic resonance spectroscopy.
The monitoring of trace amounts of nitric oxide (NO) is of great interest for biomedical applications. High-resolution infrared spectroscopy, like laser magnetic resonance spectroscopy (LMRS), is a versatile technique for the quantitative and isotope-selective analysis of low concentrations of NO. The ability to distinguish between different NO isotopomeres is of special interest for pharmaceutical and biomedical applications when tracer investigations are performed. With LMRS using Faraday modulation, a sensitivity of 1-2 ppbV for 15NO can be achieved. With further improvements and development of the sensor, we expect a sub-ppbV sensitivity.


Protective effects of Qing-Re-Huo-Xue formula on bleomycin-induced pulmonary fibrosis through the p53/IGFBP3 pathway.
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing lung disease with high mortality. Inflammation and epithelial mesenchymal transformation (EMT) may play an important role in the occurrence and development of IPF. Qing-Re-Huo-Xue formula (QRHXF) has been used clinically by our team for half a century and has obvious therapeutic effects on lung disease. Nevertheless, the role and mechanism of QRHXF in the treatment of IPF have never been studied. A mouse pulmonary fibrosis model was established by intratracheal injection of BLM. The effects of QRHXF on the treatment of pulmonary fibrosis were studied by pulmonary function testing, imaging examination, pathological staining, transmission electron microscopy (TEM) observation and mRNA expression. Tandem mass tag (TMT)-based quantitative proteomics was carried out to analyse the lung protein expression profiles between the control (CTL), bleomycin (BLM) and QRHXF (BLM + QRHXF) groups. Immunohistochemistry and qRT-PCR were used to verify the possible existence of drug target proteins and signalling pathways. The results of pulmonary function, lung pathology and imaging examinations showed that QRHXF could significantly alleviate BLM-induced pulmonary fibrosis in vivo. Additionally, inflammatory cell infiltration and EMT were markedly reduced in BLM-induced PF mice administered QRHXF. Proteomics detected a total of 35 proteins, of which 17 were upregulated and 18 were downregulated. A total of 19 differentially expressed proteins (DEPs) overlapped between the BLM versus CTL groups and the BLM + QRHXF versus BLM groups. The expression of p53 and IGFBP3 was reversed in the QRHXF intervention group, which was verified by immunohistochemistry and qRT-PCR. QRHXF attenuated BLM-induced pulmonary fibrosis, and regulation of the p53/IGFBP3 pathway might be associated with its efficacy, which holds promise as a novel treatment strategy for pulmonary fibrosis patients.


Pain assessment and management in cognitively impaired nursing home residents: association of certified nursing assistant pain report, Minimum Data Set pain report, and analgesic medication use.
The primary purpose of this preliminary study was to investigate the associations between certified nursing assistant (CNA) report of pain, Minimum Data Set (MDS) report of pain, and analgesic medication use in cognitively impaired nursing home residents. Correlational study. Three nursing homes in the greater Birmingham, Alabama area. Fifty-seven cognitively impaired nursing home residents with a mean Mini-Mental State Examination (MMSE) score of 11.1. Pain was assessed using a three-item proxy pain questionnaire (PPQ), developed by the researchers and administered to the residents' primary CNA. MDS and analgesic medication data corresponding with the time of PPQ data collection were gathered from medical records. Cognitive status was measured with the MMSE. The PPQ elicited substantially higher estimates of pain prevalence than the MDS (48% versus 20%), and the PPQ and the MDS were not well correlated (pain frequency: r=.19, P=.18; pain intensity: r=.22, P=.11). The PPQ was also more strongly associated with analgesic medication use than the MDS. Cognitive status was significantly associated with pain report on the PPQ but not on the MDS. Test-retest reliability coefficients for the three items of the PPQ were excellent, ranging from.84 to.87 (P </=.01). The CNA-generated PPQ was a more sensitive measure of pain than the MDS for this sample. Although the MDS represents an important step toward systematic and standardized assessment of pain, more emphasis should be placed on multimodal assessment, including CNAs' perceptions and observations about pain experienced by cognitively impaired nursing home residents.


Does endovenous laser ablation induce endothelial damage at the saphenofemoral junction?
One of the possible complications of endovenous laser ablation (EVLA) is thrombus progression into the common femoral vein or popliteal vein with the potential risk of pulmonary embolism or stroke. We set out to investigate the effect of laser energy applied under standardized treatment conditions on biomarkers of platelet and endothelial activation and on the hemostatic system. Twenty patients with incompetence of the great saphenous vein were included in this prospective study. Blood samples of the iliofemoral and anticubital veins were collected before, during, and after EVLA. Plasma levels of soluble (s) P-selectin, soluble thrombomodulin (sTM), prothrombin fragment F1+2 (F1+2), and d-dimer were measured. (s) P-selectin and sTM were analyzed as surrogate markers of endothelial and platelet activation. F1+2 and d-dimer were monitored to quantify the degree of surgical trauma. Whereas there was no immediate rise of (s) P-selectin and sTM plasma concentrations in iliofemoral or anticubital blood, plasma levels of F1+2 and d-dimer increased significantly after EVLA. Pulsed mode laser ablation with an 810-nm fiber does not induce measurable platelet and endothelium activation in the iliofemoral or systemic blood. Furthermore, the immediate surgical trauma associated with EVLA appears to be modest. The authors have indicated no significant interest with commercial supporters.


Everyday functioning of male adolescents who later died by suicide: Results of a pilot case-control study using mixed-method analysis.
Previous research has shown a link between difficulties in everyday functioning and suicidality in adolescence. The majority of research in this field focuses on suicidal ideation and attempts, rather than on completed suicide. The main goal of this study is to better characterize everyday functioning among young men who later completed suicide. Based on previous literature, we hypothesized that the functioning of adolescents who died by suicide would be poor, compared to controls. The current study is a record-driven study, which examined summaries of screening interviews performed by the Israeli Defense Forces (IDF) of 20 male adolescents who later completed suicide, compared with 20 matched living controls. The current study is a pilot stage of a larger project. The study used unique data, collected as part of the IDF pre-induction process, in the months or years before the tragic outcome. The data were extracted by two psychologists, blinded to the participants׳ suicide or non-suicide outcome, using mixed-method technique, combining qualitative and quantitative analysis. The main findings indicated that, in comparison with controls, male adolescents who later died by suicide were described as having more interpersonal difficulties, were more likely to be involved in violent behavior, had more difficulties in dealing with problems in everyday functioning and had an avoidant conflict resolution style. Functional difficulties are apparent in a wide range of behavioral domains in adolescents who later complete suicide. These findings indicate a need for interventions that might assist young persons, and it is possible that such assistance might reduce the likelihood of suicide. However, because suicide is a rare outcome and these behavioral traits are common in adolescence, the presence of such traits might not be useful in identifying people at risk of suicide.


The importance of monitoring intramyocardial temperature during hypothermic myocardial protection.
In 50 patients undergoing cardiac operation, hypothermic cardioplegic solution was infused into the root of the aorta immediately after aortic cross-clamping. Cardiac standstill was achieved within 1 to 3 minutes. However, monitoring of intramyocardial temperature with a needle thermistor revealed that such core cooling is unpredictable (the intramyocardial temperature achieved ranged from 7 degrees to 33 degrees C), unstable (this temperature can rise at more than 0.5 degrees C per minute), and uneven (a difference of up to 17 degrees C was observed between the intramyocardial temperature of the anterior and posterior left ventricular sites). The area supplied by the stenotic coronary artery was least protected. Monitoring of intramyocardial temperature enables one to know when supplementary cooling is indicated. We conclude that widespread differences in this temperature during cardiac operation make monitoring advisable for optimal myocardial protection.


Detection of microbial biofilms inside the lumen of ureteral stents: two case reports.
We report large biofilm structures that covered almost the entirety of the lumen and surface of double-J stents in two postrenal transplant patients, with no development of urinary tract infection. Biofilm bacteria of one patient were integrated by coccus in a net structure, whereas overlapping cells of bacilli were present in the other patient. To the best of our knowledge, this is the first time that high-quality images of the architecture of noncrystalline biofilms have been found inside double-J stents from long-term stenting in renal transplant recipients. Two renal transplant recipients, a 34-year-old male and a 39-year-old female of Mexican-Mestizo origin, who underwent a first renal transplant and lost it due to allograft failure, had a second transplant. Two months after the surgical procedure, double-J stents were removed and analyzed using scanning electron microscopy (SEM). None of the patients had an antecedent of UTI, and none developed UTI after urinary device removal. There were no reports of injuries, encrustation, or discomfort caused by these devices. The bacterial biofilm inside the J stent from long-term stenting in renal transplant recipients was mainly concentrated on unique bacteria. Biofilm structures from the outside and inside of stents do not have crystalline phases. Internal biofilms may represent a high number of bacteria in the double-J stent, in the absence of crystals.


Single-cell genome sequencing of protozoan parasites.
Despite considerable genetic variation within hosts, most parasite genome sequencing studies focus on bulk samples composed of millions of cells. Analysis of bulk samples is biased toward the dominant genotype, concealing cell-to-cell variation and rare variants. To tackle this, single-cell sequencing approaches have been developed and tailored to specific host-parasite systems. These are allowing the genetic diversity and kinship in complex parasite populations to be deciphered and for de novo genetic variation to be captured. Here, we outline the methodologies being used for single-cell sequencing of parasitic protozoans, such as Plasmodium and Leishmania spp., and how these tools are being applied to understand parasite biology.


Mouse strain- and age-dependent effects of binge methamphetamine on dopaminergic signaling.
We have shown that a single "binge" dose of methamphetamine (Meth) in mice has long-lasting effects on open-field behavior dependent on mouse strain and age. Here we further investigated the impact of genotype and age on tyrosine hydroxylase (TH) loss and dopamine (DA) metabolism due to a high binge dose of Meth (4 × 5 mg/kg × 2 h × 2 days). Administration of high dose Meth or saline (Sal) to adolescent (PND 40) and adult (PND 80) C57BL/6 (B6), DBA/2 (DBA), and 129S6SvEv/Tac (129) mice was followed by a 1mg/kg Meth or Sal (control) challenge 40 days later. Striatal and prefrontal cortex tissues were collected 1h following the challenge. Meth-pretreated adolescent B6 and DBA mice exhibited losses in striatal DA concentrations; DBA adolescents also showed losses in striatal 3,4-dihydroxyphenylacetic acid (DOPAC) and increased DA turnover. Pre-exposed B6 and 129 adults demonstrated significant decreases in striatal DA, DOPAC, and increased DA turnover; DBA adults showed significant losses in striatal DA and increased DA turnover. 129 and DBA adults exhibited increases and decreases, respectively, in prefrontal cortex DA. Adult pretreated B6 mice produced significant losses in striatal TH. The results again show age and genotype dependent differences in Meth-induced DA alterations.


Brivaracetam Retention Rate and Seizure Outcomes in Patients with Drug-Resistant Focal Epilepsy Included in the Medical Need Program in Belgium: A Real-World, Multicenter, Chart Review.
New treatments are needed for patients with drug-resistant epilepsy to improve seizure control without decreasing quality of life. In Belgium, a Medical Need Program (MNP) was initiated to make a new antiepileptic drug (brivaracetam; high-affinity synaptic vesicle protein 2A ligand) available as adjunctive therapy to treat focal seizures in patients failing treatment with three or more different antiepileptic drugs. This is a real-world chart review of the majority of patients (71%) enrolled in the MNP. Retention and seizure outcomes of brivaracetam adjunctive treatment were evaluated in 175 patients aged ≥ 16 years enrolled in the MNP between June 2016 and May 2017 at six centers; 95.4% were previously/concomitantly treated with levetiracetam. Safety events data were also collected. In this highly drug-resistant population, 85.8%, 73.9%, and 64.9% of patients remained on brivaracetam, while seizure frequency decreased from baseline in 32.0%, 37.1%, and 37.3% of patients after 3, 6, and 9 months' treatment, respectively. Patients achieving 3-month seizure freedom increased from 3.2% after 3 months' treatment to 10.2% and 10.7% after 6 and 9 months' treatment, respectively. Six-month seizure freedom was achieved by 5.7% of patients at any time. Qualitative evaluation of seizures by physicians demonstrated 44.2%, 38.8%, and 43.2% of patients improved and 42.8%, 50.9%, and 50.6% remained unchanged during 3, 6, and 9 months' follow-up, respectively. No safety signals were identified. Retention was high during 9 months of brivaracetam treatment in drug-resistant patients, including those previously/concomitantly treated with levetiracetam; 3-month seizure freedom increased from 3.2% after 3 months to 10.7% after 9 months of treatment.


Over-expression of Kv1.5 in rat cardiomyocytes extremely shortens the duration of the action potential and causes rapid excitation.
Genetically abnormal action potential duration (APD) can be a cause of arrhythmias that include long and short QT interval syndrome. The aim of this study was to evaluate the arrhythmogenic effect of short QT syndrome induced by the over-expression of Kv1.5 in rat. From Sprague-Dawley rats on fetal days 18-19, cardiomyocytes were excised and cultured with and without transfection with the Kv-1.5 gene using an adenovirus vector. The expression of Kv1.5 was proven by immunohistochemistry and Western blot analysis. In the culture dish and in the whole cells, the electrical activities were recorded using the whole-cell patch-clamp technique and the effects of 4-AP and verapamil were tested. After transfection with Kv1.5 for 12h, immunohistochemical staining and Western blot analysis were positive for Kv1.5 while they were negative in the control transfected with only Lac-Z. In the culture dish, the myocytes showed spontaneous beating at 115beats/min (bpm) just prior to the transfection with Kv1.5 and increased to 367bpm at 24h. The control myocytes showed stable beating rates during culturing. 4-AP at 200microM slowed down the rate and verapamil abolished the beating. In the whole cells, the maximal resting membrane potential was slightly depolarized and APD was extremely abbreviated both at 50% and 90% of repolarization compared with those of the control. Rapid spontaneous activities were found in a single myocyte with Kv1.5 transfection and 4-AP slowed down the frequency of the activities with a reversal of the shortened APD. The over-expression of Kv1.5 induced short APD and triggered activities in rat cardiomyocytes. This model can be used to study the arrhythmogenic substrate of short QT syndrome.


Infective endocarditis following human-to-human enterococcal transmission: a complication of intravenous narcotic abuse.
Two heroin addicts, husband and wife, who shared injection paraphernalia extensively, developed enterococcal endocarditis within six weeks of one another. The etiologic organisms were of the same subspecies and had identical antibiotic susceptibilities and biochemical profiles. The clinical, epidemiologic, and bacteriologic data strongly suggest human-to-human transmission of the pathogen.


Baculovirus infection influences host protein expression in two established insect cell lines.
We identified host proteins that changed in response to host cell susceptibility to baculovirus infection. We used three baculovirus-host cell systems utilizing two cell lines derived from pupal ovaries, Hz-AM1 (from Helicoverpa zea) and Hv-AM1 (from Heliothis virescens). Hv-AM1 cells are permissive to Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and semi-permissive to H. zea single nucleopolyhedrovirus (HzSNPV). Hz-AM1 cells are non-permissive to AcMNPV. We challenged each cell line with baculovirus infection and after 24h determined protein identities by MALDI TOF/TOF mass spectrometry. For Hv-AM1 cells, 21 proteins were identified, and for Hz-AM1 cells, 19 proteins were newly identified (with 8 others having been previously identified). In the permissive relationship, 18 of the proteins changed in expression by 70% or more in AcMNPV infected Hv-AM1 cells as compared with non-infected controls; 12 were significantly decreased and 6 cellular proteins were significantly increased. We also identified 3 virus-specific proteins. In the semi-permissive infections, eight proteins decreased by 2-fold or more. Non-permissive interactions did not lead to substantial changes in host cell protein expression. We hypothesize that some of these proteins act in determining host cell specificity for baculoviruses.


[Cutaneo-visceral disseminated flat angioma, glaucoma, hypospadias and testicular ectopy].
A case of associated disease in a child is described. It consisted of a disseminated capillary naevus with a vascular malformation in the gastrointestinal tract, bilateral congenital glaucoma, hypospadias, and bilateral ectopic testicles.


Effect of handling of plasma samples on histamine radio-enzyme assay.
1. Freeze-thawing of plasma samples increased the histamine level at physiological histamine concentrations as analyzed by radio-enzyme assay, but not by high performance liquid chromatography. 2. Heating of plasma samples decreased the histamine levels. 3. Enzymatic or non-enzymatic formation of histamine during handling of plasma samples was not detected. 4. Some albumin preparations contain histamine.


Modulation of age- and cancer-associated DNA methylation change in the healthy colon by aspirin and lifestyle.
Aberrant DNA methylation in gene promoters is associated with aging and cancer, but the circumstances determining methylation change are unknown. We investigated the impact of lifestyle modulators of colorectal cancer (CRC) risk on the stability of gene promoter methylation in the colonic mucosa. We measured genome-wide promoter CpG methylation in normal colon biopsies (n = 1092) from a female screening cohort, investigated the interaction of lifestyle factors with age-dependent increase in methylation with log-linear multivariable regression, and related their modifying effect to hypermethylation in CRC. All statistical tests were two-sided. Of 20025 promoter-associated CpGs analyzed, 1713 showed statistically significant age-dependent methylation gains. Fewer CpGs acquired methylation in users of aspirin (≥ 2 years) and hormonal replacement therapy (HRT age ≥ 50 years) compared with nonusers (43 vs 1355; 1 vs1377, respectively), whereas more CpGs were affected in smokers (≥ 20 years) and individuals with a body mass index (BMI) of 25 kg/m(2) and greater compared with control groups (180 vs 39; 554 vs 144, respectively). Fifty percent of the CpGs showing age-dependent methylation were found hypermethylated in CRC (odds ratio [OR] = 20; 95% confidence interval [CI] = 18 to 23; P < 2 × 10(-16)). These loci gained methylation with a higher median rate compared with age-only methylated sites (P = 2 × 10(-76)) and were enriched for polycomb regions (OR = 3.67). Importantly, aspirin (P < .001) and HRT use (P < .001) reduced the methylation rate at these cancer-related genes, whereas smoking (P < .001) and high BMI (P = .004) increased it. Lifestyle, including aspirin use, modulates age-associated DNA methylation change in the colonic epithelium and thereby impacts the evolution of cancer methylomes.


Enhancing mean estimators in median ranked set sampling with dual auxiliary information.
When measuring the research variable is complicated, expensive, or problematic, median ranked set sampling (MRSS) is often utilized since it is straightforward to rank the components using a low-cost sorting criterion. Using this sampling scheme, many authors considered the problem of population mean estimation with a single auxiliary variable in order to obtain more precised estimators than the traditional ratio type regression estimators. In this article, we extend their ideas based on regression approach using two auxiliary variables and introduce a new regression-type estimator along with its theoretical expression of minimum mean square error (MSE). The suggested estimator's applicability is demonstrated using both simulated and real-world data sets.


Novel functions of a retroposed gene.
Retroposed protein-coding genes are commonly considered to be nonfunctional duplicates. However, they often gain transcriptional capability and have important roles. Amici et al. recently identified novel functions of a retroposed gene. HAPSTR2, a retrocopy of HAPSTR1, encodes a protein that stabilizes the HAPSTR1 protein and functionally buffers its loss.


Biotechnological applications of versatile plant lipid transfer proteins (LTPs).
Plant AMPs are usually cysteine-rich, and can be classified in several classes, including lipid transfer proteins (LTPs). LTPs are small plant cationic peptides, and can be classified in two subclasses, LTP1 (9-10 kDa) and LTP2 (7 kDa). They have been identified and isolated from various plant species and can be involved in a number of processes, including responses against several phytopathogens. LTP1 presents 4 parallel α- helices and a 310-helix fragment. These structures form a tunnel with large and small entrances. LTP2 presents 3 parallel α- helices, which form a cavity with triangular structure. Both LTP subclasses present a hydrophobic cavity, which makes interaction with different lipids and general hydrophobic molecules possible. Several studies report a broad spectrum of activity of plant LTPs, including antibacterial, antifungal, antiviral, antitumoral, and insecticidal activity. Thus, these molecules can be employed in human and animal health as an alternative to the conventional treatment of disease, well as providing the source of novel drugs. However, employing peptides in human health can present challenges, such as the toxicity of peptides, the difference between the results found in in vitro assays and in pre-clinical or clinical tests and their low efficiency against Gram-negative bacteria. In this context, plant LTPs can be an interesting alternative means by which to bypass such challenges. This review addresses the versatility of plant LTPs, their broad spectrum of activities and their potential applications in human and animal health and in agricultural production, and examines challenges in their biotechnological application.


The β-casein in camels: molecular characterization of the CSN2 gene, promoter analysis and genetic variability.
The β-casein is the most abundant protein in camel milk and its encoding gene (CSN2) is considered in other species a 'major' gene for the presence of alleles associated to different level of expression. In the present paper, we report for the first time the characterization of the nucleotide sequence of the whole β-casein-encoding gene (CSN2) plus 2,141 bp at the 5'-flanking region in Camelus dromedarius. The promoter region and the complete cDNA are also provided for the first time in Camelus bactrianus. The gene is spread over 7.8 kb and consists of 9 exons varying in length from 24 bp (exon 5) to 519 bp (exon 7), and 8 introns from 95 bp (intron 5) to 1,950 bp (intron 1). The composite response element (CoRE) region was identified in the promoter, whereas the presence of mature microRNA sequences improves the knowledge on the factors putatively involved in the gene regulation. A total of 46 polymorphic sites have been detected. The transition g.2126A>G falls within the TATA-box of dromedary CSN2 promoter with a putative influence on the transcription factor binding activity. The frequency of the G allele is 0.35 in a population of 180 she-camels belonging to 4 different ecotypes. In the same population, a conservative SNP (g.4175C>A) was found at the codon 7 of the signal peptide, whereas a comparative analysis with a cDNA sequence available in the database evidenced a missense SNP (g.4180T(Leu)>G(Arg)) at exon 2. Four SNPs were found in the bactrian camel. The SNP c.666G>A is responsible for the amino acid change Met(201)→Ile and it represents the first missense allele at the β-casein in camels. Finally, five interspersed repeated elements were identified at intronic level, whereas the presence of putative bio-functional peptides belonging to ACE-inhibitor and anti-oxidative families confirms the potential protective role of the camel milk for the human nutrition.


[Has surgery of the vitreous evolved?].
Three ports pars plana vitrectomy has been described 50 years ago. From indications to salvage the peripheral retina function, it has progressively shifted towards functional indications in macular pathologies, trying initially to stabilize and now to improve visual acuity. This has been achieved by improvement, not only of surgical material but also of microscopes, intraoperative rools such as perfluorocarbone liquids and more recently the use of vital dyes.


Randomized controlled trial of a self-management intervention in persons with spinal cord injury: design of the HABITS (Healthy Active Behavioural Intervention in SCI) study.
To evaluate the effectiveness of a 16-week self-management intervention on physical activity level and self-management skills (self-efficacy, proactive coping and problem solving skills) in persons with chronic SCI. Multicenter randomized controlled trial (RCT). Eighty persons with a SCI for at least 10 years and aged 18 to 65 will randomly be assigned to the intervention (self-management) or the control group (information provision). During the 16-week self-management intervention (one home-visit, five group and five individual sessions) active lifestyle will be stimulated and self-management skills will be taught. Data will be collected at baseline (T0), 16 (T1) and 42 (T2) weeks after baseline. Primary outcome measure is level of daily physical activity (self-report/objectively measured). Secondary outcome measures are self-managements skills, stage of behaviour change and attitude. This is the first RCT on self-management in people with chronic spinal cord injury. This trial will provide knowledge on the effects of a self-management intervention on physical active lifestyle in persons with a long-term SCI.


Use of US Blood Donors for National Serosurveillance of Severe Acute Respiratory Syndrome Coronavirus 2 Antibodies: Basis for an Expanded National Donor Serosurveillance Program.
The Recipient Epidemiology and Donor Evaluation Study-IV-Pediatric (REDS-IV-P) Epidemiology, Surveillance and Preparedness of the Novel SARS-CoV-2 Epidemic (RESPONSE) seroprevalence study conducted monthly cross-sectional testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in blood donors in 6 US metropolitan regions to estimate the extent of SARS-CoV-2 infections over time. During March-August 2020, approximately ≥1000 serum specimens were collected monthly from each region and tested for SARS-CoV-2 antibodies using a well-validated algorithm. Regional seroprevalence estimates were weighted based on demographic differences compared with the general population. Seroprevalence was compared with reported coronavirus disease 2019 (COVID-19) case rates over time. For all regions, seroprevalence was <1.0% in March 2020. New York, New York, experienced the biggest increase (peak seroprevalence, 15.8% in May). All other regions experienced modest increases in seroprevalence (1%-2% in May-June to 2%-4% in July-August). Seroprevalence was higher in younger, non-Hispanic black, and Hispanic donors. Temporal increases in donor seroprevalence correlated with reported case rates in each region. In August, 1.3-5.6 estimated cumulative infections (based on seroprevalence data) per COVID-19 case were reported to the Centers for Disease Control and Prevention. Increases in seroprevalence were found in all regions, with the largest increase in New York. Seroprevalence was higher in non-Hispanic black and Hispanic than in non-Hispanic white blood donors. SARS-CoV-2 antibody testing of blood donor samples can be used to estimate the seroprevalence in the general population by region and demographic group. The methods derived from the RESPONSE seroprevalence study served as the basis for expanding SARS-CoV-2 seroprevalence surveillance to all 50 states and Puerto Rico.


The range fraction: an applied method to characterize regional groundwater responses to climate inputs.
An important component of ongoing water-resource investigations in the eastern Great Basin, USA, has been to ascertain the impact of future predicted climate change on groundwater availability. As a first step in that analysis, it was hypothesized that potentiometric fluctuations at certain wells would reflect annual-scale precipitation variation. Potentiometric behavior at a well depends on local hydrologic conditions, well construction, and human activities, in addition to natural recharge and regional water levels. Moreover, measurement data are limited for many wells. After preliminarily screening, a large body of well and climate station data, short-term potentiometric responses to annual-scale climate inputs, were identified at 18 wells using a simple visualization methodology developed during the study. For water levels displaying multi-annual trends, the signals were measured as deviations from a linear trendline. Groundwater responses lagged precipitation signals by less than 1 year to as much as 3 years, with most wells showing at most a 1- to 2-year delay. Response amplitude was variable and strongly depended on the hydrologic setting of each well.


Effect of combination of peripheral oxytocin and naltrexone at subthreshold doses on food intake, body weight and feeding-related brain gene expression in male rats.
In a recent case report involving a male with hypothalamic obesity, concurrent administration of oxytocin (OT) and an opioid receptor antagonist, naltrexone (NTX), synergistically affected energy balance. Here, by using laboratory rats, we examined whether the reported synergy between OT and NTX in the context of food intake extends beyond that one unique case. We found that intravenous OT+NTX combination, at doses subthreshold for each of the drugs individually, decreased episodic consumption of a 10% sucrose solution in non-deprived animals. Daily administration of OT and NTX just before a scheduled, 2-hour, high-fat high-sugar (HFHS) meal over 24 days, decreased cumulative HFHS diet intake, but without a change in body weight due to compensatory standard chow intake during the remainder of the day. The NTX-OT treatment affected expression of several feeding-related genes in the hypothalamus, brain stem and nucleus accumbens, brain regions essential for the regulation of energy- and reward-driven consumption. We conclude that OT and NTX act synergistically to decrease food consumption in rats and that this transient effect is accompanied by changes in brain processes relevant to feeding.


Cloning and characterization of cDNAs encoding for long-chain saturated acyl-ACP thioesterases from the developing seeds of Brassica juncea.
Four types of cDNAs corresponding to the fatty acyl-acyl carrier protein (ACP) thioesterase (Fat) enzyme were isolated from the developing seeds of Brassica juncea, a widely cultivated species amongst the oil-seed crops. The mature polypeptides deduced from the cDNAs showed sequence identity with the FatB class of plant thioesterases. Southern hybridization revealed the presence of at least four copies of BjFatB gene in the genome of this amphidiploid species. Western blot and RT-PCR analyses showed that the BjFatB class thioesterase is expressed poorly in flowers and leaves, but significantly in seeds at the mid-maturation stage. The enzymatic activities of different BjFatB isoforms were established upon heterologous expression of the four BjFatB CDSs in Escherichia coli K27fadD88, a mutant strain of fatty acid beta-oxidation pathway. The substrate specificity of each BjFatB isoform was determined in vivo by fatty acid profile analyses of the culture supernatant and membrane lipid of the recombinant K27fadD88 and E. coli DH10B (fadD(+)) clones, respectively. The BjFatB1 and BjFatB3 were predominantly active on C18:0-ACP substrate, whereas BjFatB2 and BjFatB4 were specific towards C18:0-ACP as well as C16:0-ACP. These novel FatB genes may find potential application in metabolic engineering of crop plants through their over-expression in seed tissues to generate stearate-rich vegetable fats/oils of commercial importance.


[The new S3 guideline "Prevention of cervical carcinoma" : What is important for pathology?]
Of the numerous aspects involved in the diagnosis, treatment, and follow-up of cervical uterine precursor lesions, epidemiology, virology, cytology, human papillomavirus (HPV) testing, and diagnostic algorithms for equivocal and HPV-positive findings are important for pathologists. Cytology will continue to be used as a preventive medical check-up in young women, while HPV-based screening is suggested for older women. HPV screening has yielded a significant reduction in cancer precursors and invasive cervical carcinoma in numerous studies. In contrast to the sensitivity, the specificity of the HPV test is inferior to that of cytology and the morphological biomarker p16/Ki-67, so that they are suitable as methods in the triage of HPV-positive findings. Cytological abnormalities and mildly dysplastic changes could be further clarified by an HPV test or the p16/Ki-67 test. The HPV test should also be used in the follow-up of patients after conization.


Self-rectifying resistive memory in passive crossbar arrays.
Conventional computing architectures are poor suited to the unique workload demands of deep learning, which has led to a surge in interest in memory-centric computing. Herein, a trilayer (Hf0.8Si0.2O2/Al2O3/Hf0.5Si0.5O2)-based self-rectifying resistive memory cell (SRMC) that exhibits (i) large selectivity (ca. 104), (ii) two-bit operation, (iii) low read power (4 and 0.8 nW for low and high resistance states, respectively), (iv) read latency (<10 μs), (v) excellent non-volatility (data retention >104 s at 85 °C), and (vi) complementary metal-oxide-semiconductor compatibility (maximum supply voltage ≤5 V) is introduced, which outperforms previously reported SRMCs. These characteristics render the SRMC highly suitable for the main memory for memory-centric computing which can improve deep learning acceleration. Furthermore, the low programming power (ca. 18 nW), latency (100 μs), and endurance (>106) highlight the energy-efficiency and highly reliable random-access memory of our SRMC. The feasible operation of individual SRMCs in passive crossbar arrays of different sizes (30 × 30, 160 × 160, and 320 × 320) is attributed to the large asymmetry and nonlinearity in the current-voltage behavior of the proposed SRMC, verifying its potential for application in large-scale and high-density non-volatile memory for memory-centric computing.


Culturing of primary hepatocytes as entrapped aggregates in a packed bed bioreactor: a potential bioartificial liver.
Conventional culture systems for hepatocytes generally involve cells cultured as flat, monolayer cells, with limited cell-cell contact, in a static pool of medium, unlike the liver in vivo where the parenchymal cells are cuboidal, with extensive cell-cell contact, and are continuously perfused with blood. We report here a novel bioreactor system for the culturing of primary hepatocytes with cuboidal cell shape, extensive cell-cell contact, and perfusing medium. The hepatocytes were inoculated into the bioreactor and allowed to recirculate at a rate optimal for them to collide and form aggregates. These newly-formed aggregates were subsequently entrapped in a packed bed of glass beads. The bioreactor was perfused with oxygenated nutrient medium, with controlled oxygen tension, pH, and medium perfusion rate. The hepatocytes were viable for up to the longest time point studied of 15 days in culture based on urea synthesis, albumin synthesis and cell morphology. Light microscopy studies of hepatocytes cultured for 15 days in the bioreactor showed interconnecting three-dimensional structures resembling the hepatic cell plate in the liver organ. Electron microscopy studies on the same cells revealed ultrastructure similar to the hepatocytes in vivo, including the presence of plentiful mitochondria, rough and smooth endoplasmic reticulum, glycogen granules, peroxisomes, and desmosomes. We believe that our hepatocyte bioreactor is a major improvement over conventional culture systems, with important industrial applications including toxicology, drug metabolism, and protein/peptide synthesis. The hepatocyte bioreactor concept may also be used as the basis for the development of a bioartificial liver to provide extracorporeal hepatic support to patients with hepatic failure.


The Use of Islamic Patterned Art Therapy: Healing of Psychological Problems Among University Students.
This study was designed to adopt art therapy from an Islamic perspective by adding/including shapes and designs of Islamic origin. This was basically color therapy and was designed to find its effectiveness in reducing depression, anxiety. Stress and enhancing psychological well-being of university students with high and low-religious levels from Islamabad and Rawalpindi. This study was carried out in two phases. The first phase was to develop Islamic adult coloring book with Islamic patterns and calligraphy. The second phase was the main study, and it was an experimental study which included screening out a sample, consisting of mild to moderate levels of depression, anxiety and stress and high and low-religiosity levels. A sample of 60 university students received Islamic patterned art therapy. On the basis of religiosity, two groups were formed as either a high-religious group or a low-religious group with individuals in both groups completing fourteen sessions. Pre- and post-test assessments were undertaken via the psychometric tools DASS-21, psychological well-being scale and religiosity scale. Statistics from the independent sample t-test and paired sample t-test and repeated measures ANOVA for within group and between group comparisons, revealed that there was a significant difference from pre-test to post-test assessments of depression anxiety and stress and psychological well-being, whereas there were nonsignificant gender differences on the bases of high and low-religiosity levels. Therefore, it could be concluded that Islamic patterned art therapy was found effective in reducing depression anxiety stress and increasing psychological well-being of university students.


Plasmodium chabaudi: in vivo effects of Ca2+ antagonists on chloroquine-resistant and chloroquine-sensitive parasites.
The effects of Ca2+ antagonists, verapamil, nicardipine, and diltiazem, on susceptibility to chloroquine were examined in mice infected with chloroquine-sensitive and chloroquine-resistant lines of Plasmodium chabaudi. In mice that received no chloroquine, daily injections of 50 mg/kg of verapamil, nicardipine, or diltiazem did not affect the growth of both sensitive and resistant parasites. When mice were injected daily with verapamil plus 2 to 3 mg/kg chloroquine, the chloroquine-sensitive parasite became more susceptible to chloroquine than the parasite in mice given chloroquine alone. On the other hand, in mice infected with chloroquine-resistant parasites, verapamil severely suppressed the growth of the parasite when accompanied by daily injections of 2 to 3 mg/kg of chloroquine, at which doses resistant parasites grew steadily in the absence of verapamil, indicating reversal of chloroquine resistance. This reversal was dose-dependent between 5 and 50 mg/kg of verapamil. Daily injections of nicardipine or diltiazem at 50 mg/kg also reversed resistance to chloroquine in resistant parasites. These results indicate that Ca2+ antagonists increase the susceptibility to chloroquine in a sensitive line of P. chabaudi and reverse chloroquine resistance in a resistant line.


Design and synthesis of 5,6-fused heterocyclic amides as Raf kinase inhibitors.
Two scaffolds based on 5,6-fused heterocyclic backbones were designed and synthesized as Raf kinase inhibitors. The scaffolds were assessed for in vitro pan-Raf inhibition, activity in cell proliferation and target modulation assays, and pharmacokinetic parameters.


Brazilian hospitals' performance: an assessment of the unified health system (SUS).
This paper assesses the economic efficiency of Brazilian general hospitals that provide inpatient care for the Unified Health System (SUS). We combined data envelopment analysis (DEA) and spatial analysis to identify predominant clusters, measure hospital inefficiency and analyze the spatial pattern of inefficiency throughout the country. Our findings pointed to a high level of hospital inefficiency, mostly associated with small size and distributed across all Brazilian states. Many of these hospitals could increase production and reduce inputs to achieve higher efficiency standards. These findings suggest room for optimization, but inequalities in access and the matching of demand and supply must be carefully considered in any attempt to reorganize the hospital system in Brazil.


Cardiolipin affects the supramolecular organization of ATP synthase in mitochondria.
F(1)F(0) ATP synthase forms dimers that tend to assemble into large supramolecular structures. We show that the presence of cardiolipin is critical for the degree of oligomerization and the degree of order in these ATP synthase assemblies. This conclusion was drawn from the statistical analysis of cryoelectron tomograms of cristae vesicles isolated from Drosophila flight-muscle mitochondria, which are very rich in ATP synthase. Our study included a wild-type control, a cardiolipin synthase mutant with nearly complete loss of cardiolipin, and a tafazzin mutant with reduced cardiolipin levels. In the wild-type, the high-curvature edge of crista vesicles was densely populated with ATP synthase molecules that were typically organized in one or two rows of dimers. In both mutants, the density of ATP synthase was reduced at the high-curvature zone despite unchanged expression levels. Compared to the wild-type, dimer rows were less extended in the mutants and there was more scatter in the orientation of dimers. These data suggest that cardiolipin promotes the ribbonlike assembly of ATP synthase dimers and thus affects lateral organization and morphology of the crista membrane.


Contemporary temperature-driven divergence in a Nordic freshwater fish under conditions commonly thought to hinder adaptation.
Evaluating the limits of adaptation to temperature is important given the IPCC-predicted rise in global temperatures. The rate and scope of evolutionary adaptation can be limited by low genetic diversity, gene flow, and costs associated with adaptive change. Freshwater organisms are physically confined to lakes and rivers, and must therefore deal directly with climate variation and change. In this study, we take advantage of a system characterised by low genetic variation, small population size, gene flow and between-trait trade-offs to study how such conditions affect the ability of a freshwater fish to adapt to climate change. We test for genetically-based differences in developmental traits indicating local adaptation, by conducting a common-garden experiment using embryos and larvae from replicate pairs of sympatric grayling demes that spawn and develop in natural cold and warm water, respectively. These demes have common ancestors from a colonization event 22 generations ago. Consequently, we explore if diversification may occur under severely constraining conditions. We found evidence for divergence in ontogenetic rates. The divergence pattern followed adaptation predictions as cold-deme individuals displayed higher growth rates and yolk conversion efficiency than warm-deme individuals at the same temperature. The cold-deme embryos had a higher rate of muscle mass development. Most of the growth- and development differences occurred prior to hatch. The divergence was probably not caused by genetic drift as there was a strong degree of parallelism in the divergence pattern and because phenotypic differentiation (Q(ST)) was larger than estimated genetic drift levels (microsatellite F(ST)) between demes from different temperature groups. We also document that these particular grayling populations cannot develop successfully at temperatures above 12°C, whereas other European populations can, and that increasing the muscle mass development rate comes at the cost of some skeletal trait development rates. This study shows that genetically based phenotypic divergence can prevail even under conditions of low genetic variation and ongoing gene flow. Furthermore, population-specific maximum development temperatures along with musculoskeletal developmental trade-offs may constrain adaptation.


[Role of the pathologist in the diagnosis of palpebral keratoacanthoma: case report and literature review].
We report the case of a keratoacanthoma of the lower lid in a 14-year-old girl posing diagnostic difficulty with differentiating the lesion from a verrucous squamous cell carcinoma on histologic examination of an incisional biopsy. It was only upon complete excision of the tumor that the diagnosis of keratoacanthoma could be made and that of malignancy ruled out. We discuss the clinical and histologic diagnostic criteria for keratoacanthoma and assert that wide biopsy is essential for adequate morphologic study to enable better therapeutic management.


Oxygenated pentacyclic triterpenoids from the stems and branches of Enkianthus chinensis.
Thirty new pentacyclic triterpenoids, including five oleanane-type (1-5), twenty-three ursane-type (9-23, 26-33) and two taraxerane-type (24 and 25), along with fourteen known triterpenoids, were isolated from the stems and branches of Enkianthus chinensis. Their structures were elucidated by extensive spectroscopic analyses, X-ray crystallographic data and electronic circular dichroism (ECD) techniques. Sixteen compounds (1-5, 9-13, 20, 22, 32, 34-36) bearing a gem-hydroxymethyl group at C-4 represent rare examples of pentacyclic triterpenoids. In the in vitro biological activity evaluation, compounds 8, 9, 12-14, 17, 24, and 44 exhibited potent hepatoprotective effects at 10 μM. Moreover, compound 25 showed latent activity against HSV-1 with an IC50 value of 6.4 μM.


Effects of engineered nano-titanium dioxide on pore surface properties and phosphorus adsorption of sediment: its environmental implications.
Understanding the environmental safety and human health implications of engineered nanoparticles (ENPs) is of worldwide importance. As an important ENPs, engineered nano-TiO(2) (Enano-TiO(2)) may have been substantially deposited in aquatic sediments because of its widely uses. Sediment pore surface properties would be thus significantly influenced due to the large surface area of Enano-TiO(2). In this study, Enano-TiO(2) was found to greatly impact on sediment pore surface properties. The attachment of Enano-TiO(2) particles to sediment surfaces enhanced markedly BET specific surface area and t-Plot external specific surface area, and thereby increased sediment phosphorus (P) adsorption maximum (S(max)). Contrarily, the fill of Enano-TiO(2) particles into the micropores of sediments could significantly reduce t-Plot micropore specific surface area, and cause slight decrease in sediment P binding energy (K). Clearly, P sorbed in sediment would be easily released because of the decreasing P binding energy of the sediment with elevated Enano-TiO(2). Enano-TiO(2) would thus cause aggravated endogenous pollution in water if such sediment was re-suspended on disturbance. The results obtained in this study contribute to our increasing knowledge of how to regulate physicochemical behavior of pollutants in sediments under the influences of Enano-TiO(2) and/or similar ENPs.


Challenges in medically assisted reproduction - Ethics, law and society: An invited scientific review by the European Board and College of Obstetrics and Gynaecology (EBCOG).
Τhe methods of medically assisted reproduction (MAR) are being widely applied all over the world ever since the birth of Louise Brown, the first child conceived after in vitro fertilization (IVF) of a human oocyte and subsequent transfer into the uterus of the ensuing embryo. The possible risks associated with the application of the different MAR methods have given rise to a debate concerning the necessity of a regulatory framework regarding the application of these methods especially in view of the crucial and ambiguous legal and ethical issues attached.


Examining the factors shaping consumer attitude towards the popular alcoholic beverages in Hungary.
The study of consumer attitudes is particularly important for products related to tradition. Pálinka is Hungary's national beverage; the homemade distillate is primarily legally different from pálinka and it cannot be marketed. The main goal of the research is to analyse the role of the three attitude components (cognitive, affective and conative), consumer ethnocentrism and drinking motives in shaping the consumer attitude towards the Hungarian pálinka and the homemade distillate and a popular, but not Hungarian beverage, whisky. Data were collected by questionnaires using a quota sampling method, resulting in a sample of 626 respondents. In this paper we demonstrate the importance of the affective component using structural equation modelling, and the way consumer ethnocentrism influences the favorable consumer attitude to homemade distillate through emotions. The study has revealed the opposite effect of consumer ethnocentrism in the case of whisky, and the lack of effect in the case of pálinka. The social alcohol drinking motivation also shapes the favorable consumer attitudes towards the homemade distillate and whisky. The consumer preference is also supported by using the Multiattribute Attitude Model and the conjoint-analysis. The scientific value of the study lies in using different methods for understanding the factors that can shape the consumer attitude towards national beverages. Improving the consumer attitude towards pálinka requires a comprehensive marketing strategy covering all three attitudinal components, and from a consumer ethnocentrism perspective, the positioning of pálinka as a national drink needs to be strengthened by the producers. The study has ignored the role of brand, tradition, packaging and nostalgia. Future research can examine the role of these factors in consumer attitude towards national alcoholic beverages. By inserting the conceptual model of this study into the Theory of Planned Behaviour model, the effects of the subjective norms and perceived behavioral control can also be analysed.


The combination of ultrasound and chlorogenic acid to inactivate Staphylococcus aureus under planktonic, biofilm, and food systems.
This study aimed to investigate the mechanism of different treatments, namely, ultrasound (US), chlorogenic acid (CA), and ultrasound combined with chlorogenic acid (US plus CA) on the inactivation of Staphylococcus aureus planktonic and biofilm cells. Results showed that the combined treatment of US and CA exhibited remarkable synergistic antibacterial and antibiofilm effects. Scanning electron microscopy images indicated that the combined treatment of US and CA caused the most serious damage to the cell morphology. Confocal laser scanning microscopy images revealed that the combined treatment led to sharp increase and severe damage to the permeability of the cell membrane, causing the release of ATP and nucleic acids and decreasing the exopolysaccharide contents in S. aureus biofilm. Finally, the combined treatment of US plus 1% CA for 60 min inactivated S. aureus cells by 1.13 lg CFU/g on mutton. Thus, the combined treatment of US and CA had synergistic effect against S. aureus under planktonic, biofilm, and food systems.


Development of a quality of care measurement system for children and adolescents. Methodological considerations and comparisons with a system for adult women.
To describe the development of a pediatric quality of care measurement system designed to cover multiple clinical topics that could be applied to enrollees in managed care organizations and to compare the development of this system with the concurrent development of a similar system for adult women. Indicators were developed for 21 pediatric (ages 0-18 years) clinical topics and 20 adult (ages 17-50 years) women's clinical topics. Indicators were classified by the strength of evidence supporting them. A modified Delphi method was used to obtain validity and feasibility ratings from a pediatric expert panel and an adult women's expert panel. Indicators were categorized by type of care (preventive, acute, or chronic), function (screening, diagnosis, treatment, or follow up), and modality (history, physical examination, laboratory/radiology study, medication, other intervention, or other contact). Of 557 pediatric and 391 adult women's proposed indicators, 453 (81%) and 340 (87%), respectively, were retained by the 2 expert panels. A lower percentage of final pediatric indicators than adult indicators were based on randomized, controlled trials and other rigorous studies (18% vs 40%, P < .001). The expert panels were more likely to retain indicators based on rigorous studies (93% retained) than on descriptive studies and expert opinion (81% retained, P < .001). A higher percentage of pediatric indicators than women's indicators were for preventive care (30% vs 11%, P < .001) and a lower percentage were for acute care (36% vs 49%, P < .001) or chronic care (34% vs 41%, P = .06). This study contributes to the field of pediatric quality of care assessment by providing many more indicators than have been available previously and by documenting the strength of evidence supporting these indicators. Formal consensus methods are essential for the development of pediatric quality measures because the evidence base for pediatric care is more limited than for adult care.


Interpreting per capita loads of organic matter and nutrients in municipal wastewater: A study on 168 Italian agglomerations.
The size of an agglomeration is expressed in population equivalent, referring to the maximum average weekly load during the year according to the European Directive 271/91. This quantity, multiplied by the daily biochemical oxygen demand (BOD) produced by one population equivalent (which is 60 g d-1 PE-1, by definition), yields the design biodegradable organic load of the wastewater treatment plant. The same agglomeration size is compared against the capacity of the wastewater treatment plant (WWTP) for plant conformity verification by the European Commission. However, field observations show remarkable fluctuations of the daily mass flows entering a WWTP, often considerably below or above the expected load calculated according to the Directive prescriptions. A wrong estimation of the real influent load adversely affects the plant design and operation, and may lead to a misleading verification of its conformity to the agglomeration. In this work, a statistical data analysis on 168 agglomerations was performed, aiming at verifying the consistency between the expected loads of BOD, chemical oxygen demand (COD), nitrogen and phosphorus and the mass flows measured at the treatment plant inlet. Only 30-40% of the total analysed cases were found having an actual load compatible with the expected one. In these cases, the average per capita daily loads of BOD, COD, nitrogen and phosphorus, calculated over 2-3 years data pools, resulted: 44.6 ± 5.9, 82.4 ± 11, 9.4 ± 1.1, and 1.08 ± 0.13 g d-1, respectively, while the daily BOD per capita production of 60 g represented a value in between the 70th and the 90th percentiles of the actual daily load distributions. For the remaining 60-70% of the total cases, variably-remarkable positive or negative discrepancies between the nominal pollutant loads generated by the agglomeration and those measured at the plant inlet could be detected and possible causes were pointed out.


Crush injury to peripheral nerve. An electron microscope study employing horseradish peroxidase.
Electron microscope observations were made of rat peroneal nerve after crushing using intravenously injected horseradish peroxidase (HRP) as a tracer protein to indicate changes in vascular permeability. At 1/2 h and 2 d after the crush there was gross leakage of HRP from damaged capillaries at the site of injury but none from vessels above or below this. Ultrastructurally vessels at the site of crush showed broken and separated endothelial cells. Proximally and distally there was little abnormal in the vessel walls; vesicles containing HRP were absent and tight-junctions between cells remained intact. Twenty-one days after the crush, leakage of HRP was found both at the site of crush and along the distal segment. The only change in vessel walls was an obvious increase in vesicles filled with HRP. Tracer was also found both in perivascular locations and throughout the endoneurial space.


Waste-to-nutrition: a review of current and emerging conversion pathways.
Residual biomass is acknowledged as a key sustainable feedstock for the transition towards circular and low fossil carbon economies to supply whether energy, chemical, material and food products or services. The latter is receiving increasing attention, in particular in the perspective of decoupling nutrition from arable land demand. In order to provide a comprehensive overview of the technical possibilities to convert residual biomasses into edible ingredients, we reviewed over 950 scientific and industrial records documenting existing and emerging waste-to-nutrition pathways, involving over 150 different feedstocks here grouped under 10 umbrella categories: (i) wood-related residual biomass, (ii) primary crop residues, (iii) manure, (iv) food waste, (v) sludge and wastewater, (vi) green residual biomass, (vii) slaughterhouse by-products, (viii) agrifood co-products, (ix) C1 gases and (x) others. The review includes a detailed description of these pathways, as well as the processes they involve. As a result, we proposed four generic building blocks to systematize waste-to-nutrition conversion sequence patterns, namely enhancement, cracking, extraction and bioconversion. We further introduce a multidimensional representation of the biomasses suitability as potential as nutritional sources according to (i) their content in anti-nutritional compounds, (ii) their degree of structural complexity and (iii) their concentration of macro- and micronutrients. Finally, we suggest that the different pathways can be grouped into eight large families of approaches: (i) insect biorefinery, (ii) green biorefinery, (iii) lignocellulosic biorefinery, (iv) non-soluble protein recovery, (v) gas-intermediate biorefinery, (vi) liquid substrate alternative, (vii) solid-substrate fermentation and (viii) more-out-of-slaughterhouse by-products. The proposed framework aims to support future research in waste recovery and valorization within food systems, along with stimulating reflections on the improvement of resources' cascading use.


External sphincter-sparing anal fistulotomy (ESSAF): a simplified technique for the treatment of fistula-in-ano.
Fistula-in-ano due to cryptoglandular disease is a common condition. While a simple anal fistula can be treated successfully by a fistulotomy, the risk of potential damage to the anal sphincters and subsequent poor functional outcomes persist in a large portion of patients with complex fistulae. Several sphincter-preserving treatment procedures have been described for complex fistulae over the past 3 decades, with variable results and complication rates, and no procedure is proven to be superior to the others. We developed external sphincter-sparing anal fistulotomy (ESSAF), a reproducible simple modification of the ligation of intersphincteric fistula tract (LIFT) technique for the treatment of complex fistula-in-ano.. The aim of the present study was to describe the technique and our outcomes. This was a retrospective review of all patients who underwent ESSAF for a complex anal fistula at our institution from January 2014 to December 2019. The primary outcome measure of this study was the primary fistula healing rate. Secondary outcome measures included fecal and/or gas incontinence and postoperative complications. During the ESSAF procedure, the mucosa and skin overlying the fistula tract are incised to allow complete exposure of the sphincter complex. Then the internal sphincter muscle fibers overlying the tract are divided and the tract is meticulously curetted and debrided. Next, the internal opening of the tract traversing the external sphincter muscle is suture-ligated with absorbable sutures. Then, a minimal amount of mucosa is advanced and the incision is partially closed with absorbable sutures, while its external portion is left open for drainage. Fifty-nine patients [43 males, median age was 50 years (range 36-63 years)] underwent ESSAF for complex anal fistula during the study period. Mean follow-up was 12 ± 14.7 months. Of the 59 patients, 42 (71.2%) experienced fistula closure, with a median healing time of 8 weeks (IQR 4-16 weeks). None of the patients developed significant anal incontinence following the procedure. One patient (1.7%) suffered from soiling and another patient (1.7%) developed postoperative bleeding. There were no infectious complications. Of the 17 patients (28.8%) who failed to heal successfully, 9 (15.2%) did not heal primarily and 8 (16%) experienced recurrence after complete healing. Thirteen (76%) of these patients underwent reoperation with complete recovery after ESSAF (n = 4), fistulotomy (n = 8) or endorectal advancement flap (ERAF) (n = 1). Overall ESSAF initiated recovery in 93.2% of the patients. ESSAF is a feasible, safe, reproducible and effective sphincter-sparing procedure for the treatment of complex anal fistulae.


Increased expression of hepatocyte growth factor in cerebrospinal fluid and intracranial artery in moyamoya disease.
The etiology of moyamoya disease still remains unknown. This study was aimed to explore the role of hepatocyte growth factor (HGF), a strong inducer of angiogenesis, in development of moyamoya disease. We studied cerebrospinal fluid (CSF) from 39 patients with moyamoya disease (24 children and 15 adults), 6 control patients with cervical spondylosis, and 7 control patients with internal carotid artery occlusion. CSF level of HGF was determined by enzyme-linked immunosorbent assay technique. We also evaluated the distribution of HGF and its cellular receptor c-Met in the carotid fork obtained from 2 patients with moyamoya disease and 2 control patients. CSF level of HGF was 408.2+/-201.6 pg/mL and 443.2+/-193.5 pg/mL in patients with cervical spondylosis and internal carotid artery occlusion, respectively (mean+/-SD). On the other hand, CSF level of HGF was 820.3+/-319.0 pg/mL in patients with moyamoya disease, being significantly higher than those in 2 control groups (P<0.01). Both HGF and c-Met were widely distributed in the media and thickened intima of the carotid fork in patients with moyamoya disease but not in control patients. This study revealed that HGF is densely found in the carotid fork, and its CSF level is markedly elevated in moyamoya disease, suggesting that HGF may be a key protein for pathogenesis of moyamoya disease.


Interaction of Constitutive Nitric Oxide Synthases with Cyclooxygenases in Regulation of Bicarbonate Secretion in the Gastric Mucosa.
Neuronal NO synthase blocker 7-nitroindazole suppressed bicarbonate secretion in rat gastric mucosa induced by mild local irritation with 1 M NaCl (pH 2.0). Non-selective blocker of neuronal and endothelial synthases, Nω-nitro-L-arginine (L-NNA), did not affect HCO3- production, but inhibited secretion after pretreatment with omeprazole. Non-selective cyclooxygenase blocker indomethacin inhibited HCO3- production under conditions of normal synthase activity and in the presence of L-NNA, but was ineffective when co-administered with 7-nitroindazole. It was concluded that neuronal and endothelial synthases are involved in different mechanisms of regulation of HCO3- secretion in the gastric mucosa induced by mild irritation. Activation of neuronal synthase stimulated HCO3- production, which is mediated mainly through activation of cyclooxygenase. Theoretically, activation of endothelial synthase should suppress HCO3- production. The effect of endothelial synthase depends on acid secretion in the stomach and bicarbonate concentration in the submucosa, as it was demonstrated in experiments with intravenous NaHCO3 infusion.


Effects of promoter, intron and enhancer elements on transient gene expression in sugar-cane and carrot protoplasts.
Various chimaeric promoter regions coupled to the uidA beta-glucuronidase gene were evaluated for transient expression strength following electroporation into sugar-cane (monocot) and carrot (dicot) protoplasts. Multiple enhancer elements increased expression in sugar-cane, by up to 400-fold for the artificial Emu promoter relative to the CaMV 35S promoter. The relative expression strengths of promoters varied substantially between the species. Sugar-cane also differed in some respects from previously tested species in the family Poaceae. For example, in sugar-cane the nopaline synthase and CaMV 35S promoters were of equivalent strength, and insertion of Adh1 intron 1 into the 5' transcribed region decreased expression strength.


Evaluation of Changes in the Expression Profile of mRNA and Proteinencoding Adiponectin in Ishikawa Cell Line under the Influence of Cisplatin - Preliminary Report.
A reduced concentration of adiponectin is considered as an independent factor of the risk of inducing endometrial cancer. Cisplatin is a drug used in the therapy of this type of neoplasm. However, knowledge of the effects of cisplatin on the adiponectin level is still limited. The purpose of this study was to assess the impact of cisplatin depending on the concentration and time of exposition of the cells to the drug on the adiponectin level in the endometrial cancer cell line. Cells of endometrial cancer cell line Ishikawa were exposed for 12,24 and 48 hour periods to cisplatin with the following concentrations: 2.5μM, 5μM, 10μM. The changes in the expression profile of adiponectin were compared to the RtqPCR reaction and ELISA test. The STATISTICA 13.0 PL program was used for statistical analysis (p<0.05). In the culture without the drug, the concentration of adiponectin was statistically lower than in the cell culture incubated with the drug. Changes on the mRNA level seem to be more specific than on the protein level, although in both cases, the same trend in the expression changes was noted. The longer the time of exposition of the cells to the drug, the expression of mRNA, and the adiponectin protein increased. Changes in the expression profile were characterized statistically (p<0.05). Cisplatin, in a noticeable way, changes the expression profile of adiponectin. Molecular analysis indicated that in the case of endometrial cancer therapy should be implemented with a concentration of no less than 5 μM.


Angiotensin-converting enzyme 2-at the heart of the COVID-19 pandemic.
ACE2 is the indispensable entry receptor for SARS-CoV and SARS-CoV-2. Because of the COVID-19 pandemic, it has become one of the most therapeutically targeted human molecules in biomedicine. ACE2 serves two fundamental physiological roles: as an enzyme, it alters peptide cascade balance; as a chaperone, it controls intestinal amino acid uptake. ACE2's tissue distribution, affected by co-morbidities and sex, explains the broad tropism of coronaviruses and the clinical manifestations of SARS and COVID-19. ACE2-based therapeutics provide a universal strategy to prevent and treat SARS-CoV-2 infections, applicable to all SARS-CoV-2 variants and other emerging zoonotic coronaviruses exploiting ACE2 as their cellular receptor.


The influence of coronary collateral flow on the assessment of myocardial perfusion by videodensitometry.
Coronary collateral flow often mitigates the effects of coronary artery obstruction and has a significant impact on the prognosis of patients with coronary artery disease. In the presence of variable degrees of coronary collateral flow, digital radiographic assessment of myocardial blood flow has not been quantitatively validated. A distal coronary arterial collateral path was created into the left anterior descending coronary artery (LAD) bed in 8 anesthetized pigs. Both LAD and collateral paths were pump-perfused and corresponding flows measured. A number of commonly used digital indices and parametric images of myocardial perfusion were then extracted from the sequence of images filmed before and during the injection of contrast. Data were acquired at 5 levels of total flow (LAD flow + collateral flow): 100, 85, 70, 55 and 40% of maximally vasodilated, baseline flow. At each level of total flow, data were acquired at 4 levels of collateral flow ratios (collateral flow/total flow): 0, 10, 25 and 50%. Regional percent segment shortening, reflecting myocardial blood flow, decreased as total flow fell, and remained unaltered when coronary collateral ratio alone was altered without change in total flow. On the other hand, linear regression between total flow and digital indices at 10, 25 and 50% coronary collateral flow ratios, compared with 0%, showed a successive and significant downward displacement, documenting an underestimation of flow by all digital indices in the presence of collateral flow. In the absence of a collateral pathway and during maximal coronary vasodilation with adenosine, digital radiographic indices of myocardial perfusion, based upon indicator dilution theory, show a relatively good correlation with regional transmural myocardial blood flow. However, due to underestimation of total transmural blood flow, these indices have limited utility when myocardial perfusion is provided in part by a collateral pathway. The effect is probably related to an alteration in the regional vascular volume into which iodinated contrast is injected.


[Antibiotic strategies in trauma surgery : Treatment of implant-associated infections].
Implant-associated infections represent a serious complication following fracture management. Due to biofilm formation, an optimized treatment strategy is required to treat these infections. Interdisciplinary cooperation between trauma surgeon, infectious diseases specialist and microbiologist enables the deployment of a concerted surgical and antibiotic treatment concept, which significantly influences treatment success. Fracture healing and chronic osteomyelitis prevention are the primary treatment goals. In general, the eradication of infection is possible with surgical debridement, change or removal of the implant and adequate antibiotic therapy. In some cases, suppressive therapy until consolidation of fracture and later removal of the implant is an option.


Chylothorax associated with substernal goiter treated with transcervical thyroidectomy.
Substernal goiters are frequently associated with compressive symptoms. Compression of the trachea and esophagus are common, whereas thoracic duct compression is a rare occurrence. We report a rare case of a 72-year-old woman with thoracic duct compression by a large substernal goiter that presented with shortness of breath. After undergoing thoracentesis multiple times, the patient was treated with thyroidectomy. Transcervical thyroidectomy was performed without sternotomy. This led to resolution of her symptoms. Confirmation of chylothorax resolution was obtained with postoperative computed tomography of the chest. Chylothorax is a rare sequela of substernal goiters. It can be managed with thyroidectomy. Sternotomy was avoided in this case.


Potential adverse effects on animal health and performance caused by the addition of mineral adsorbents to feeds to reduce mycotoxin exposure.
The contamination of feed with mycotoxins is a continuing feed quality and safety issue, leading to significant losses in livestock production and potential human health risks. Consequently, various methods have been developed to reduce the occurrence of mycotoxins in feed; however, feed supplementation with clay minerals or mineral adsorbents is the most prominent approach widely practiced by farmers and the feed industry. Due to a negatively charged and high surface area, pore volume, swelling ability, and high cation exchange capacity, mineral adsorbents including bentonite, zeolite, montmorillonite, and hydrated sodium calcium aluminosilicate can bind or adsorb mycotoxins to their interlayer spaces, external surface, and edges. Several studies have shown these substances to be partly or fully effective in counteracting toxic effects of mycotoxins in farm animals fed contaminated diets and thus are extensively used in livestock production to reduce the risk of mycotoxin exposure. Nevertheless, a considerable number of studies have indicated that these agents may also cause undesirable effects in farm animals. The current work aims to review published reports regarding adverse effects that may arise in farm animals (with a focus on pig and poultry) and potential interaction with veterinary substances and nutrients in feeds, when mineral adsorbents are utilized as a technological feed additive. Furthermore, results of in vitro toxicity studies of both natural and modified mineral adsorbents on different cell lines are reported. Supplementation of mycotoxin-contaminated feed with mineral adsorbents must be carefully considered by farmers and feed industry.


Quantitative two-dimensional echocardiographic assessment of left ventricular shape in ischemic heart disease.
Since data on systematic noninvasive quantitative assessment of left ventricular (LV) shape in ischemic heart disease are very scanty, we used new size-independent LV shape descriptors to study the correlation between LV shape and LV ejection fraction in 46 men with a 70% or more stenosis of one or more coronary arteries on angiography. Angiocardiographic LV ejection fraction was over 55% [mean: 69 (+/- 6 SD)%] in 20 patients (group I), and under 55% [mean: 43 (+/- 9 SD)%] in 26 patients (group II). Our LV shape descriptors showed statistically significant differences between group I and group II patients, indicating a more spherical LV shape in group II (p values less than 0.005). Within the whole patient group (N = 46), and also within the subgroup of patients with regional LV hypokinesis or akinesis (N = 26), correlation between LV shape alteration (toward the spherical) and LV ejection fraction was not strong; it was better in the subgroup (N = 10) with regional LV wall dyskinesis. There was poor correlation between angiocardiographic LV chamber volume and alteration (toward spherical) in LV shape. Thus, we have documented quantitatively that patients with ischemic heart disease and low LV ejection fraction tend to have a more spherical LV shape than patients with a normal ejection fraction. Quantification of LV shape based on simple, easily made two-dimensional echocardiographic measurements may help in noninvasive identification of patients with deteriorating LV function, especially when a change toward the spherical is detected in serial echocardiograms.


What makes a respondent-driven sampling "seed" productive? Example of finding at-risk Massachusetts men who have sex with men.
Several recent studies have sought to elaborate upon the applicability and validity of respondent-driven sampling (RDS) to find hard-to-reach samples in general and men who have sex with men (MSM) in particular. Few published studies have elucidated the characteristics associated with initial RDS participants ("seeds") who successfully recruited others into a study. A total of 74 original seeds were analyzed from four Massachusetts studies conducted between 2006 and 2008 that used RDS to reach high-risk MSM. Seeds were considered "generative" if they recruited two or more subsequent participants and "non-generative" if they recruited zero or one participant. Overall, 34% of seeds were generative. In separate multivariable logistic regression models controlling for age, race, health insurance, HIV status, and the study for which the seed was enrolled, unprotected anal sex in the past 12 months [adjusted odds ratio (AOR) = 6.68; 95% confidence interval (95% CI) = 1.27-35.12; p = 0.03], cocaine use during sex at least monthly during the past 12 months (AOR = 8.81; 95% CI = 1.68-46.27; p = 0.01), and meeting sex partners at social gatherings (AOR = 7.42; 95% CI = 1.58-34.76; p = 0.01) and public cruising areas (AOR = 4.92; 95% CI = 1.27-19.01; p = 0.02) were each significantly associated with increased odds of being a generative seed. These findings have methodological and practical implications for the recruitment of MSM via RDS. Finding ways to identify RDS seeds that are consistently generative may facilitate collecting a sample that is closer to reflecting the MSM who live in all of the communities in a given location or study sample.


Diabetes mellitus and disturbances in brain connectivity: a bidirectional relationship?
Diabetes mellitus (DM) is associated with deficits across multiple cognitive domains. The observed impairments in cognitive function are hypothesized to be subserved by alterations in brain structure and function. Several lines of evidence indicate that alterations in glial integrity and function, as well as abnormal synchrony within brain circuits and associated networks, are observed in adults with DM. Microangiopathy and alterations in insulin homeostasis appear to be principal effector systems, although a unitary explanation subsuming the complex etiopathology of white matter in DM is unavailable. A contemporary model of disease pathophysiology for several mental disorders, including but not limited to mood disorders, posits abnormalities in the synchronization of cellular systems in circuits. The observation that similar abnormalities occur in diabetic populations provides the basis for hypothesizing the convergence of pathoetiological factors. Herein, we propose that abnormal structure, function and chemical composition as well as synchrony within and between circuits is an accompaniment of DM and is shared in common with several mental disorders.


Removal of disinfection by-product precursors in drinking water treatment processes: Is fluorescence parallel factor analysis a promising indicator?
This work investigated the removal efficiency of disinfection by-product (DBP) precursors by different drinking water treatment processes and evaluated the feasibility of using fluorescence components removal as an indicator. A four-component (including tryptophan-like, protein-bound, tyrosine-like, and humic-like components) parallel factor analysis model was developed basing on 288 fluorescence excitation-emission matrices. Among all treatment processes, coagulation-sedimentation process showed the best performance, with mean removal ratios of 30% in total fluorescence intensity and 31% in total formation potential (FP) of DBPs, respectively. It preferentially removed humic-like component C4 (43%). Advanced treatment processes were less effective in comparison. Ozone and biological activated carbon (BAC) combined process reduced 20% of total fluorescence intensity, while ultrafiltration process reduced < 3%. Ozonation and BAC filtration preferentially removed free amino acids (i.e., C1 and C3) and protein-bound (i.e., C2) components, with mean removal ratios of 12% and 17%, respectively. Significant correlations (p < 0.01, double-tailed) were observed between four fluorescence components removal and FPs reduction of three trihalomethanes, dichloroacetonitrile (DCAN), and 1,1-dichloropropanone (1,1-DCP). Specifically, the correlation coefficients for three trihalomethanes and 1,1-DCP followed the order of C4 > C1 > C2 > C3, while the order for DCAN was C2 > C4 > C1 > C3.