Unraveling the High Open Circuit Voltage and High Performance of Integrated Perovskite/Organic Bulk-Heterojunction Solar Cells.
We have demonstrated high-performance integrated perovskite/bulk-heterojunction (BHJ) solar cells due to the low carrier recombination velocity, high open circuit voltage (VOC), and increased light absorption ability in near-infrared (NIR) region of integrated devices. In particular, we find that the VOC of the integrated devices is dominated by (or pinned to) the perovskite cells, not the organic photovoltaic cells. A Quasi-Fermi Level Pinning Model was proposed to understand the working mechanism and the origin of the VOC of the integrated perovskite/BHJ solar cell, which following that of the perovskite solar cell and is much higher than that of the low bandgap polymer based organic BHJ solar cell. Evidence for the model was enhanced by examining the charge carrier behavior and photovoltaic behavior of the integrated devices under illumination of monochromatic light-emitting diodes at different characteristic wavelength. This finding shall pave an interesting possibility for integrated photovoltaic devices to harvest low energy photons in NIR region and further improve the current density without sacrificing VOC, thus providing new opportunities and significant implications for future industry applications of this kind of integrated solar cells.


The effects of human recombinant granulocyte-colony stimulating factor treatment during in vitro maturation of porcine oocyte on subsequent embryonic development.
Granulocyte colony-stimulating factor (G-CSF) is required for proliferation, differentiation, and survival of cells. It is also a biomarker of human oocyte developmental competence for embryo implantation. In humans, the G-CSF concentration peaks during the ovulatory phase of the ovarian cycle. In this study, the expressions of G-CSF and its receptor were analyzed by polymerase chain reaction in granulosa cells (GCs), CL, cumulus cells (CCs), and oocytes. Cumulus-oocyte complexes were aspirated from antral follicles of 1 to 3 mm (small follicles) and 4 to 6 mm (medium follicles). Cumulus-oocyte complexes from two kinds of follicles were matured in protein-free maturation medium supplemented with various concentrations of G-CSF (0, 10, and 100 ng/mL). By real-time polymerase chain reaction, the expressions of G-CSF and its receptor were detected in GCs, CL, CCs, and oocytes. Interestingly, the G-CSF transcript levels were significantly lower in oocytes than in the other cell types, whereas the G-CSF receptor transcript levels in oocytes were similar to those in GCs. After 44 hours of IVM, no differences in the rate of nuclear maturation were detected; however, the intracellular reactive oxygen species levels in oocytes from both groups of follicles matured with 10 ng/mL of human recombinant G-CSF (hrG-CSF) groups were significantly lower (P < 0.05). After parthenogenetic activation, the cleavage rates were significantly (P < 0.05) higher in 100 ng/mL hrG-CSF-treated small (63.3%) follicles than in 0, 10 ng/mL hrG-CSF-treated small (38.6% and 49.0%, respectively) follicles and 0 ng/mL hrG-CSF-treated medium (52.1%) follicles, and the cleavage rates were significantly (P < 0.05) higher in 10 ng/mL hrG-CSF-treated medium (76.3%) follicles than in all other groups. The blastocyst formation rates were significantly (P < 0.05) higher in 100 ng/mL hrG-CSF-treated small (31.2%) follicles than in 0 and 10 ng/mL hrG-CSF small (10.4% and 15.6%, respectively) follicles, and the 10 ng/mL hrG-CSF medium (45.7%) follicle was significantly (P < 0.05) higher than in all other groups. The total cell number in blastocysts from the 10 ng/mL hrG-CSF medium (106.5) follicles was significantly (P < 0.05) increased compared to 0, 10, 100 ng/mL hrG-CSF small (55.0, 73.7 and 59.5, respectively) follicles and 0, 100 ng/mL hrG-CSF-treated medium (82.5 and 93.5, respectively) follicles. After IVF, the blastocysts stage was significantly (P < 0.05) increased in 10 ng/mL hrG-CSF-treated medium (36.4%) follicles. Fertilization efficiency was significantly high in 100 ng/mL of small (29.1%) and 10 ng/mL of medium (44.0%) follicles. We also examined the Bcl2 and ERK2 transcript levels and found that they were significantly higher in the small and medium follicle treatment groups. In conclusion, these results indicate that hrG-CSF improve the viability of porcine embryos.


Median nerve injury caused by missed foreign body. Case report.
A 56-year-old woman sustained a delayed median nerve division after a penetrating injury of the right wrist by a piece of wood had gone unnoticed. There was no neurological damage at the time of the injury. The foreign body spread the median nerve apart, which subsequently reduced the sensitivity in the index finger. Removal of the wood resulted in complete recovery.


Modes of salmonid MHC class I and II evolution differ from the primate paradigm.
Rainbow trout (Oncorhynchus mykiss) and brown trout (Salmo trutta) represent two salmonid genera separated for 15--20 million years. cDNA sequences were determined for the classical MHC class I heavy chain gene UBA and the MHC class II beta-chain gene DAB from 15 rainbow and 10 brown trout. Both genes are highly polymorphic in both species and diploid in expression. The MHC class I alleles comprise several highly divergent lineages that are represented in both species and predate genera separation. The class II alleles are less divergent, highly species specific, and probably arose after genera separation. The striking difference in salmonid MHC class I and class II evolution contrasts with the situation in primates, where lineages of class II alleles have been sustained over longer periods of time relative to class I lineages. The difference may arise because salmonid MHC class I and II genes are not linked, whereas in mammals they are closely linked. A prevalent mechanism for evolving new MHC class I alleles in salmonids is recombination in intron II that shuffles alpha 1 and alpha 2 domains into different combinations.


The continuing role of material factors in child maltreatment and placement.
This article constitutes a 20-year update to a previous publication (Pelton, 1994), which showed that there is overwhelming evidence that poverty and low income are strongly related to child abuse and neglect. Subsequent evidence shows that the relationship continues to be strong. In addition, there is further evidence since the 1994 publication that this relation is not substantially due to class bias. Yet it is suggested that class bias does exist within the system. There is also further evidence that decreases in child maltreatment follow increases in material supports, and that job loss bears a complex relationship to child maltreatment. Findings pertaining to racial bias within the child welfare system continue to be mixed, but leave no doubt that racial disproportionalities within the system are overwhelmingly related to racial disproportionalities in the poverty population. There is continuing evidence that children placed in foster care are predominantly from impoverished families, and that changes in the level of material supports are related to risk of placement. It is suggested that the fact that there are nearly one million children in out-of-home placement (foster care and child-welfare involved adoption, combined) is indicative of the continuing dysfunction of the child welfare system, and that the differential response paradigm has not altered this dysfunction. A proposal for a fundamental restructuring of the child welfare system is recommended and restated here. Prospects for such change are briefly discussed. Also, to reduce poverty, a previously proposed universal social dividend and taxation system is briefly discussed and recommended.


Randomized Phase II Study of Nivolumab With or Without Ipilimumab Combined With Stereotactic Body Radiotherapy for Refractory Metastatic Pancreatic Cancer (CheckPAC).
To evaluate the clinical benefit of nivolumab with or without ipilimumab in combination with stereotactic body radiotherapy (SBRT) in patients with refractory metastatic pancreatic cancer (mPC). Between November 2016 and December 2019, patients with refractory mPC were randomly assigned 1:1 to SBRT of 15 Gy with nivolumab or nivolumab/ipilimumab stratified by performance status (ClinicalTrials.gov identifier: NCT02866383). The primary end point was the clinical benefit rate (CBR), defined as the percentage of patients with complete or partial response (PR) or stable disease, according to RECIST 1.1. Simon's 2-stage phase II optimal design was used independently for both arms, with CBR determining expansion to the second stage. Secondary end points included safety, response rate, duration of response, progression-free survival, and overall survival. Exploratory analyses included biomarkers related to the benefits. Eighty-four patients (41 SBRT/nivolumab and 43 SBRT/nivolumab/ipilimumab) received at least one dose of study treatment. CBR was 17.1% (8.0 to 30.6) for patients receiving SBRT/nivolumab and 37.2% (24.0 to 52.1) for SBRT/nivolumab/ipilimumab. PR was observed in one patient receiving SBRT/nivolumab and lasted for 4.6 months. Six patients receiving SBRT/nivolumab/ipilimumab achieved a PR with a median duration of response of 5.4 months (4.2 to not reached). Grade 3 or higher treatment-related adverse events occurred in 10 (24.4%) and 13 (30.2%) patients in the SBRT/nivolumab and SBRT/nivolumab/ipilimumab groups, respectively. Programmed cell death ligand-1 expression by tumor proportion score or combined positivity score of ≥ 1% was not associated with clinical benefits. On-treatment decreased serum interleukin-6, interleukin-8, and C-reactive protein levels were associated with better overall survival. Clinically meaningful antitumor activity and favorable safety profiles were demonstrated after treatment with SBRT/nivolumab/ipilimumab in patients with refractory mPC. However, the contribution from SBRT is unknown. Further studies are warranted.


The Internet and Loneliness.
The internet and related media play key roles in education, work, and leisure. It could be argued that people have better interpersonal interactions because of social media, which could reduce loneliness. But documented internet use patterns suggest that the internet increases loneliness. Studies conducted prior to and during the COVID-19 pandemic demonstrate an association between what's called "internet addiction" and loneliness, although findings vary with participant demographics and frequency and types of internet use. There is a need to conduct longitudinal research to determine the direction of causality and whether what we define as "balanced" internet behavior positively affects well-being.


Enhanced expression of the mouse L-histidine decarboxylase gene with a combination of dexamethasone and 12-O-tetradecanoylphorbol-13-acetate.
We previously reported that the induction of L-histidine decarboxylase (HDC) in mouse mastocytoma cells was synergistically potentiated with a combination of dexamethasone and 12-O-tetradecanoylphorbol-13-acetate (TPA) [Biochim. Biophys. Acta, 1133, 172-178 (1992)]. To clarify the molecular mechanism of this synergistic action on HDC expression, we have isolated genomic DNA clone (MGH5), including 5'-flanking region of the mouse HDC gene. The transcription start site and the nucleotide sequences of the promoter regions were determined. We found that this clone contains a TATA-like box and a GC-box in the promoter region, and several putative binding sites for regulatory proteins in the 5'-flanking region. With mastocytoma cells transiently transfected with 5' deletion constructs of HDC-CAT fusion gene, it was found that the sequence from -267 to -43 is essential for the regulatory elements(s) involved in the increased transcription of the HDC gene with dexamethasone and TPA.


The Transient Multidrug Resistance Phenotype of Salmonella enterica Swarming Cells Is Abolished by Sub-inhibitory Concentrations of Antimicrobial Compounds.
Swarming motility is the rapid and coordinated multicellular migration of bacteria across a moist surface. During swarming, bacterial cells exhibit increased resistance to multiple antibiotics, a phenomenon described as adaptive or transient resistance. In this study, we demonstrate that sub-inhibitory concentrations of cefotaxime, ciprofloxacin, trimethoprim, or chloramphenicol, but not that of amikacin, colistin, kanamycin or tetracycline, impair Salmonella enterica swarming. Chloramphenicol-treated S. enterica cells exhibited a clear decrease in their flagellar content, while treatment with other antibiotics that reduced swarming (cefotaxime, ciprofloxacin, and trimethoprim) inhibited polar chemoreceptor array assembly. Moreover, the increased resistance phenotype acquired by swarming cells was abolished by the presence of these antimicrobials. The same occurred in cells treated with these antimicrobial agents in combination with others that had no effect on swarming motility. Our results reveal the potential of inhibiting swarming ability to enhance the therapeutic effectiveness of antimicrobial agents.


Safety and efficacy of partial splenic embolization in telaprevir-based triple therapy for chronic hepatitis C.
Pegylated-interferon/ribavirin (peg-IFN/RBV) therapy with a protease inhibitor is the standard therapy for genotype 1b chronic hepatitis C. Despite improving treatment outcomes, patients with thrombocytopenia are often difficult to treat because interferon commonly exacerbates thrombocytopenia. In this study, partial splenic embolization (PSE) was performed in patients with hypersplenism-induced thrombocytopenia to determine the effectiveness of this method as a potential treatment. Patients were pretreated with PSE and then received triple combination therapy. The safety and efficacy of PSE was evaluated. Eighteen patients were analyzed, including 12 patients with the interleukin 28B (IL28B) major genotype and 12 patients with the inosine triphosphatase (ITPA) major genotype. The median embolization rate with PSE was 70% (range: 40-85%). PSE increased the patients' platelet counts from 71.5×10(3) /μL (53-99×10(3) /μL) to 121.5×10(3) /μL (70-194×10(3) /μL; p=0.0002). The patients' platelet counts fluctuated above 50×10(3) /μL during the treatment. Specifically, the increase in the platelet count was significantly associated with the ITPA major genotype compared with the minor genotype (p=0.0057 at 2 weeks, p=0.0031 at 3 weeks, and p=0.0148 at 4 weeks). Adherence to peg-IFN-α2b was sufficient (1.38 μg/kg/week). The rapid viral response rate was 72.2% (13/18), the end of treatment response rate was 88.9% (16/18), and the sustained virological response (SVR) rate was 66.7% (12/18). The SVR rate for patients with the IL28B major genotype was 83.3% (10/12). No adverse effect due to PSE pretreatment was found in any patients. Furthermore, no patient discontinued treatment due to thrombocytopenia. PSE, in conjunction with triple combination therapy, is a useful and safe method to treat genotype 1b chronic hepatitis C patients with hypersplenism-induced thrombocytopenia.


High prevalence of Schistosoma japonicum and Fasciola gigantica in bovines from Northern Samar, the Philippines.
The cause of zoonotic schistosomiasis in the Philippines is Schistosoma japonicum, which infects up to 46 mammalian hosts, including humans and bovines. In China, water buffaloes have been identified as major reservoir hosts for schistosomiasis japonica, contributing up to 75% of human transmission. In the Philippines, water buffaloes (carabao; Bubalus bubalis carabanesis) have, historically, been considered unimportant reservoirs. We therefore revisited the possible role of bovines in schistosome transmission in the Philippines, using the recently described formalin-ethyl acetate sedimentation (FEA-SD) technique and a qPCR assay to examine fecal samples from 153 bovines (both carabao and cattle) from six barangays in Northern Samar. A high prevalence of S. japonicum was found using qPCR and FEA-SD in both cattle (87.50% and 77.08%, respectively) and carabao (80.00% and 55.24%, respectively). The average daily egg output for each bovine was calculated at 195,000. High prevalence and infection intensity of F. gigantica was also found in the bovines by qPCR and FEA-SD (95.33% and 96.00%, respectively). The identification of bovines as major reservoir hosts for S. japonicum transmission suggests that bovine treatment and/or vaccination, as one becomes available, should be included in any future control program that aims to reduce the disease burden due to schistosomiasis in the Philippines.


Contribution of males to brood care can compensate for their food consumption from a shared resource.
The sharing of the same food source among parents and offspring can be a driver of the evolution of family life and parental care. However, if all family members desire the same meal, competitive situations can arise, especially if resource depletion is likely. When food is shared for reproduction and the raising of offspring, parents have to decide whether they should invest in self-maintenance or in their offspring and it is not entirely clear how these two strategies are balanced. In the burying beetle Nicrophorus vespilloides, parents care for their offspring either bi- or uniparentally at a vertebrate carcass as the sole food source. The question of whether biparental care in this species offers the offspring a better environment for development compared with uniparental care has been the subject of some debate. We tested the hypothesis that male contribution to biparental brood care has a beneficial effect on offspring fitness but that this effect can be masked because the male also feeds from the shared resource. We show that a mouse carcass prepared by two Nicrophorus beetles is lighter compared with a carcass prepared by a single female beetle at the start of larval hatching and provisioning. This difference in carcass mass can influence offspring fitness when food availability is limited, supporting our hypothesis. Our results provide new insights into the possible evolutionary pathway of biparental care in this species of burying beetles.


Characteristics of 73 patients, 1984-1993, treated by plasma exchange for Guillain-Barre syndrome.
Acute Guillain-Barre syndrome (GBS) is a demyelinating polyneuropathy which responds readily to plasma exchange (PEX). According to the North American Acute GBS PEX study there is a 50% or more reduction in the recovery time if PEX is initiated early in the course of the disease. Demyelinating antibodies are usually IgM. IgA antibodies require prolonged PEX. Patients with predominant IgG antibodies have chronic inflammatory demyelinating polyneuropathy (CIDP), which requires an even longer course of PEX, over weeks to months or years. We reviewed records of 73 patients with the initial diagnosis of GBS treated with PEX. Among these patients, 55 had classic GBS, three had the Miller-Fisher variant, two had CIDP, and 13 had demyelinating-like polyneuropathies associated with other conditions including malignancy, vaccine-related myelitis, steroid-induced myopathy, polymyositis, botulism, gram-negative sepsis, Sjogren's, and AIDS. Hughes grading system was used. Patients were graded 3 to 5, with grade 3 patients being unable to walk 5 m without support, grade 4 patients being bed or chair bound, and grade 5 patients being ventilator dependent. Of 60 unassociated (GBS) demyelinating cases receiving a mean of 6.5 PEX procedures, 13 (21%) were intubated early in the treatment, with four (6%) remaining ventilator dependent post-PEX. Of 51 non-intubated patients, 15 became ambulatory post-PEX. Patients with the Miller-Fisher variant showed improvement within 6 hours of PEX initiation. We did not investigate correlation of GBS with infection; however, we did observe a rise in CMV titer among 15% of the 58 patients with acute GBS. Considering our results we believe that intensive PEX on a daily basis for a few days is necessary for severely affected individuals. We advise five to nine procedures at consultation unless early, rapid recovery occurs.


Antidepressants and suicidal risk.
Only 5% of suicidal patients on the average use their prescribed antidepressant to commit suicide. Underprescription of antidepressants and failure of antidepressant therapy appear to be of greater practical importance than the toxicity of individual compounds. Prescribing less toxic agents, therefore, will not be of great advantage, especially if they are less efficacious. Several antidepressants including the selective serotonin reuptake inhibitors (SSRIs) may increase suicidal behavior by energizing depressed patients to act along preexisting suicidal thoughts or by inducing akathisia with associated self-destructive impulses. For acutely suicidal patients, the use of more sedating antidepressants is recommended. Clinical trials could not confirm a superiority of SSRIs over tricyclics in reducing the number of suicide attempts. There is evidence from large international data sources and a large multicenter controlled trial that lithium prophylaxis decreases the suicide risk and overall mortality in affective disorders. A suicide-preventing effect has not been demonstrated conclusively for antidepressants or non-lithium mood stabilizers.


Analysis of health service amenable and non-amenable mortality before and since China's expansion of health coverage in 2009.
To explore early impacts of China's health reforms in 2009 on mortality. Annual mortality counts were obtained from 161 counties across all 31 provinces of mainland China between 2006 and 2012. We examined time-series of health service amenable mortality counts, including separate analyses for deaths from stroke and ischaemic heart diseases (IHD). Non-amenable mortality counts, including separate models for oesophageal and pancreatic cancers, were also analysed as part of a negative-outcome strategy to provide stronger foundations for falsification. Deaths due to amenable causes were hypothesised to decrease, whereas non-amenable causes of mortality would remain uninfluenced. All analyses were conducted using multilevel negative binomial regression. Geographical variation was observed for each mortality indicator, especially for IHD, oesophageal and pancreatic cancers. Negative covariances in all models indicated slight degrees of convergence in these geographic variations over time (but not significantly for deaths from oesophageal and pancreatic cancers). Linear and square functions of time indicated a curvilinear inverted parabolic trend between 2006 and 2012 for stroke and IHD mortality. Reduction in health-service amenable mortality over time was observed, but also for health service non-amenable mortality, including deaths from oesophageal cancer. Pancreatic cancer was found to increase across the study period. In counties where residents had more years of education, mortality from stroke was lower and reducing faster over time. A similar spatiotemporal patterning was observed for deaths from oesophageal cancer, and health service amenable and non-amenable causes. Counties with higher mean education years had higher mortality from IHD and pancreatic cancer, but also larger reductions in mortality were evident in areas with greater years of education. Although there was no clear evidence of an early impact of China's health reform on mortality, this does not rule out potentially important contributions to reducing the burden of disease in the longer term.


Paying for pharmaceutical registration in developing countries.
Fees charged by drug regulatory authorities (DRAs) may be used as a policy instrument to speed up regulatory approval, to encourage retention of quality staff and to stimulate introduction of generics versus new chemical entities. Often, the cost recovery function of these registration fees is not related to the true cost of the pharmaceutical regulatory process. In this paper, we scaled new drug registration fees of various DRAs to indices of economic development - the GNP per capita and the total government health expenditure per capita. Based on our analyses of 34 countries, most DRA registration fees for new drug applications for developing/non-OECD countries are less than the current GNP/capita of that country or are about US dollars 5000 for each US dollars 1000 spent per capita on healthcare. At present, each US dollars 1000 new drug registration fee for the developing/non-OECD countries analyzed corresponds to a total pharmaceutical market share of about US dollars 85 million. Our analyses further suggest little relationship between DRA registration fees and drug approval times in developing countries. The situation is complex, however, as policy tradeoffs are important to consider. Differential registration fees, presumably designed to encourage locally produced versus imported products, may violate international trade regulations. Moreover, certain DRA registration fees may provide perverse incentives for the pharmaceutical industry. Developing countries should require that DRA registration fees be based on accurate accounting of the cost of services provided. At present levels, these fees could be increased without disincentive to the pharmaceutical industry. For new drug registration fees, our analyses suggest that developing countries could charge between 1-5 times their GNP per capita or between US dollars 17000 and US dollars 80000 for each US dollars 1000 spent per capita on healthcare.


Enzyme activity analysis of CYP2C18 with exon 5 skipped.
To study the enzyme activity of CYP2C18 variant with exon 5 skipped. A full length CYP2C18 cDNA X1 and an exon 5 skipped variant CYP2C18 X2 were separately subcloned into mammalian expression vector pREP9 to transfect HepG2 cells. The expression of CYP2C18 mRNA in transgenic cells and human liver tissues were determined by RT-PCR. The enzyme activity of CYP2C18 to oxidate tolbutamide in postmitochondrial supernate (S9) fraction was determined by HPLC. The cytotoxicity of ifosfamide to transgenic cells was evaluated by MTT test. HepG2-CYP2C18 X1 cells showed strong expression of the full length CYP2C18 mRNA. On the other hand, HepG2-CYP2C18 X2 cells had only infinitesimal expression of the exon-skipped CYP2C18 as well as the full length CYP2C18, while non-transfected HepG2 cell only demonstrated an infinitesimal expression of the full length CYP2C18. The expression of CYP2C18 exons 2 to 7 was also analyzed by RT-PCR in 7 extratumoral liver tissues. Among them, 3 samples expressed only wild type mRNA, whereas 4 samples expressed both wild type and alternative splicing products. The tolbutamide hydroxylase activity of CYP2C18 was tested, and it was shown that HepG2-2C18 X1 cells had higher enzyme activity than those of HepG2-2C18 X2 and HepG2 cells. The relative survival of HepG2-CYP2C18 X1 cells was lower than that of HepG2 cells with 1, 2, and 4 mmol/L ifosfamide treatments. In contrast, the relative survival of HepG2-CYP2C18 X2 cell was the same as that of HepG2 cell in 0.5 and 1 mmol/L of ifosfamide, but lower than that of HepG2 cell in 2 and 4 mmol/L of ifosfamide. CYP2C18 X1 could metabolize tolbutamide and ifosfamide efficiently. The exon 5-skipped CYP2C18 X2 could not metabolize tolbutamide, and could not metabolize ifosfamide effectively at low concentrations.


Future directions for nursing education.
Critical reflection on the introduction to baccalaureate education as the entry-to-practice requirement in Canada is timely. Efforts to chart future directions for nursing education must take into account long-standing issues from the past.


Pharmacokinetics of 99mTc-labeled oligonucleotides.
Oligonucleotides labeled with gamma-emitting radionuclides are likely to find eventual applications as radiopharmaceuticals. Accordingly, methods of radiolabeling single-stranded DNA by chelation with the gamma-emitting radionuclide 111In and, more importantly, with 99mTc, have been developed. As an emerging technology, the results of only two pharmacokinetic investigations with 99mTc-labeled DNA have been reported thus far, both from this laboratory. This review focuses on the pharmacokinetic properties in mice of 99mTc when radiolabeled by one method (SHNH) to a 22-base native phosphodiester and phosphorothioate DNA. The labeled phosphodiester DNA displayed an affinity for proteins through its 99mTc-SHNH chelate. The affinity for proteins of the labeled phosphorothioate DNA was even greater and was attributed in this case to both the chelate and to the modified, and lipophilic, DNA backbone. As a consequence of this binding, and the recognized increased stability of the phosphorothioate DNA towards nucleases, probably explained the long-term retention of label in organs such as liver, spleen and kidney. In conclusion, under the conditions of these investigations, the labeled phosphodiester and phosphorothioate DNAs studied were both judged to be unsuitable for most applications as radiopharmaceuticals.


A giant pseudoaneurysm becoming apparent after cardiac resynchronisation therapy.
A 57-year-old male patient with coronary artery disease developed a pseudoaneurysm after an inferior infarct in 1997. He underwent coronary bypass surgery and resection of the pseudoaneurysm located at the inferior wall. Unfortunately, the pseudoaneurysm recurred due to dehiscence of the patch, necessitating a second surgical intervention. After six years he developed progressive heart failure due to severe left ventricular dysfunction. He was referred to our institution for cardiac resynchronisation therapy (CRT) because of drug refractory heart failure which was associated with a left bundle branch block, ejection fraction of 12%, and a NYHA class IV status. After successful implantation of a biventricular pacemaker, a remarkable clinical recovery was observed. Left ventricular function improved and echocardiography now demonstrated that the pseudoaneurysm at the inferior wall had recurred for the third time. This diagnosis could not be established by preoperative echocardiography.


A large decoy set of protein-protein complexes produced by flexible docking.
Computational methods are needed to help characterize the structure and function of protein-protein complexes. To develop and improve such methods, standard test problems are essential. One important test is to identify experimental structures from among large sets of decoys. Here, a flexible docking procedure was used to produce such a large ensemble of decoy complexes. In addition to their use for structure prediction, they can serve as a proxy for the nonspecific, protein-protein complexes that occur transiently in the cell, which are hard to characterize experimentally, yet biochemically important. For 202 homodimers and 41 heterodimers with known X-ray structures, we produced an average of 1217 decoys each. The structures were characterized in detail. The decoys have rather large protein-protein interfaces, with at least 45 residue-residue contacts for every 100 contacts found in the experimental complex. They have limited intramonomer deformation and limited intermonomer steric conflicts. The decoys thoroughly sample each monomer's surface, with all the surface amino acids being part of at least one decoy interface. The decoys with the lowest intramonomer deformation were analyzed separately, as proxies for nonspecific protein-protein complexes. Their interfaces are less hydrophobic than the experimental ones, with an amino acid composition similar to the overall surface composition. They have a poorer shape complementarity and a weaker association energy, but are no more fragmented than the experimental interfaces, with 2.1 distinct patches of interacting residues on average, compared to 2.6 for the experimental interfaces. The decoys should be useful for testing and parameterizing docking methods and scoring functions; they are freely available as PDB files at http://biology.polytechnique.fr/decoys.


[Development and optimization of the methods for determining activity of plasminogen activator inhibitor-1 in plasma].
The activity and content of plasminogen activator inhibitor-1 (PAI-1) are important indicators of pathological processes, because its content in plasma increases at acute myocardium infarction, tumor, diabetes mellitus, etc. The present work is dedicated to the development and optimization of the methods of PAI-1 activity definition, which can be used in clinical practice. We have proposed the modification of the method COATEST PAI with the usage of chromogenic substrate S2251. According to our modification, the cyanogen bromide fragments of human fibrinogen have been changed into bovine desAB-fibrin. We have also developed the method with the usage of fibrin films. In this method fibrin is used as a stimulator of activation reaction and as a substrate at the same time. Using fibrin, the native substrate of plasmin, we provide high specificity of the reaction and exclude the cross-reaction with other plasma enzymes.


Calibrating animal-borne proximity loggers.
Growing interest in the structure and dynamics of animal social networks has stimulated efforts to develop automated tracking technologies that can reliably record encounters in free-ranging subjects. A particularly promising approach is the use of animal-attached 'proximity loggers', which collect data on the incidence, duration and proximity of spatial associations through inter-logger radio communication. While proximity logging is based on a straightforward physical principle - the attenuation of propagating radio waves with distance - calibrating systems for field deployment is challenging, since most study species roam across complex, heterogeneous environments.In this study, we calibrated a recently developed digital proximity-logging system ('Encounternet') for deployment on a wild population of New Caledonian crows Corvus moneduloides. Our principal objective was to establish a quantitative model that enables robust post hoc estimation of logger-to-logger (and, hence, crow-to-crow) distances from logger-recorded signal-strength values. To achieve an accurate description of the radio communication between crow-borne loggers, we conducted a calibration exercise that combines theoretical analyses, field experiments, statistical modelling, behavioural observations, and computer simulations.We show that, using signal-strength information only, it is possible to assign crow encounters reliably to predefined distance classes, enabling powerful analyses of social dynamics. For example, raw data sets from field-deployed loggers can be filtered at the analysis stage to include predominantly encounters where crows would have come to within a few metres of each other, and could therefore have socially learned new behaviours through direct observation. One of the main challenges for improving data classification further is the fact that crows - like most other study species - associate across a wide variety of habitats and behavioural contexts, with different signal-attenuation properties.Our study demonstrates that well-calibrated proximity-logging systems can be used to chart social associations of free-ranging animals over a range of biologically meaningful distances. At the same time, however, it highlights that considerable efforts are required to conduct study-specific system calibrations that adequately account for the biological and technological complexities of field deployments. Although we report results from a particular case study, the basic rationale of our multi-step calibration exercise applies to many other tracking systems and study species.


New Insights on Degumming and Bleaching Process Parameters on The Formation of 3-Monochloropropane-1,2-Diol Esters and Glycidyl Esters in Refined, Bleached, Deodorized Palm Oil.
This paper examines the interactions of degumming and bleaching processes as well as their influences on the formation of 3-monochloropropane-1,2-diol esters (3-MCPDE) and glycidyl esters in refined, bleached and deodorized palm oil by using D-optimal design. Water degumming effectively reduced the 3-MCPDE content up to 50%. Acid activated bleaching earth had a greater effect on 3-MCPDE reduction compared to natural bleaching earth and acid activated bleaching earth with neutral pH, indicating that performance and adsorption capacities of bleaching earth are the predominant factors in the removal of esters, rather than its acidity profile. The combination of high dosage phosphoric acid during degumming with the use of acid activated bleaching earth eliminated almost all glycidyl esters during refining. Besides, the effects of crude palm oil quality was assessed and it was found that the quality of crude palm oil determines the level of formation of 3-MCPDE and glycidyl esters in palm oil during the high temperature deodorization step of physical refining process. Poor quality crude palm oil has strong impact towards 3-MCPDE and glycidyl esters formation due to the intrinsic components present within. The findings are useful to palm oil refining industry in choosing raw materials as an input during the refining process.


Carfilzomib as a potential inhibitor of NADH-dependent enoyl-acyl carrier protein reductases of Klebsiella pneumoniae and Mycobacterium tuberculosis as a drug target enzyme: insights from molecular docking and molecular dynamics.
Multiple antibiotic-resistant strains of Klebsiella pneumoniae can cause life-threatening infections. Bacterial enoyl-acyl carrier protein (ACP) reductases (ENRs) are considered critical targets for developing antibiotics. Our current study aims to identify inhibitors of K. pneumoniae ENRs (FabI and FabV). Due to the unavailability of experimental structures, protein models of FabI and FabV were predicted and validated in this study. Virtual screening of the 1930 FDA-approved drug database was conducted against the active site of the FabI protein with the help of the LEA3D server, and carfilzomib was chosen among the screened drugs for further docking studies. Carfilzomib, a proteasome inhibitor used in the treatment of multiple myeloma, was among the best-suited compounds obtained from the virtual screening and was found to be bactericidal in the in vitro experiment. Carfilzomib was docked against the active sites of the FabI and FabV proteins, and the ENR of Mycobacterium tuberculosis, InhA. Carfilzomib showed a high binding affinity with all three proteins. Molecular dynamics (MD) simulations were conducted following the docking studies. MD simulations revealed that carfilzomib binds strongly to the active sites of the above mentioned ENRs. Our study found that carfilzomib is a potential inhibitor of the ENRs of K. pneumoniae and M. tuberculosis. This is a possible mechanism of its bactericidal property against M. tuberculosis observed in vitro in addition to its predicted actions on zinc-dependent metalloprotease-1 and peptide deformylase, two other drug target enzymes of M. tuberculosis. Our study suggests that this drug could be used as a lead compound to develop antibiotics that can selectively act against ENRs of bacteria, without interfering with the activities of human proteasome. Communicated by Ramaswamy H. Sarma.


Antiepileptic drug discontinuation by people with epilepsy in the general population.
Rate, reasons, and predictors of antiepileptic drug (AED) discontinuation were investigated in a well-defined cohort of people with epilepsy to verify efficacy and tolerability of treatment up to 20 years from treatment initiation. The history of AED usage in children and adults with epilepsy registered with 123 family physicians in an area of Northern Italy between 2000 and 2008 was recorded. Cumulative probabilities of AED withdrawal for specific reasons were estimated using cumulative incidence functions. The probabilities of withdrawing for terminal remission, and of achieving sustained remission while still on treatment, were also evaluated. The roles of sex, age at diagnosis, seizure types, duration at diagnosis, and syndrome were assessed with hazard ratios and 95% confidence intervals. Seven hundred thirty-one of 747 individuals were treated with one or more AEDs during the disease course. The three commonest drugs were valproate, carbamazepine, and phenobarbital. Reported reasons for AED withdrawal were, in decreasing order, terminal remission, ineffectiveness, and adverse events. The probability of withdrawing the first AED for terminal remission was 1.0% at 1 year and increased to 20.0% at 20 years. Corresponding rates were 2.9% and 12.6% for ineffectiveness and 0.5% and 3.3% for adverse events. Reasons for withdrawal varied with individuals' age, sex, disease characteristics, and drugs. The initial AED given was retained in the majority of cases. Terminal remission, lack of efficacy, and adverse effects were, in decreasing order, the commonest reasons for AED discontinuation. Withdrawal could be predicted by age at diagnosis, sex, and clinical characteristics and varies among drugs.


Heavy rare earth elements affect early life stages in Paracentrotus lividus and Arbacia lixula sea urchins.
Heavy rare earth elements (HREEs) have been scarcely studied for their toxicity, in spite of their applications in several technologies. Thus HREEs require timely investigations for their adverse health effects. Paracentrotus lividus and Arbacia lixula embryos and sperm were exposed to trichloride salts of five HREEs (Dy, Ho, Er, Yb and Lu) and to Ce(III) as a light REE (LREE) reference to evaluate: 1) developmental defects (% DD) in HREE-exposed larvae or in the offspring of HREE-exposed sperm; 2) mitotic anomalies; 3) fertilization success; and 4) reactive oxygen species (ROS) formation, and nitric oxide (NO) and malondialdehyde (MDA) levels. Nominal HREE concentrations were confirmed by inductively coupled plasma mass spectrometry (ICP-MS). HREEs induced concentration-related DD increases in P. lividus and A. lixula larvae, ranging from no significant DD increase at 10-7M HREEs up to ≅100% DD at 10-5M HREE. Larvae exposed to 10-5M Ce(III) resulted in less severe DD rates compared to HREEs. Decreased mitotic activity and increased aberration rates were found in HREE-exposed P. lividus embryos. Significant increases in ROS formation and NO levels were found both in HREE-exposed and in Ce(III) embryos, whereas only Ce(III), but not HREEs resulted in significant increase in MDA levels. Sperm exposure to HREEs (10-5-10-4M) resulted in a concentration-related decrease in fertilization success along with increase in offspring damage. These effects were significantly enhanced for Dy(III), Ho(III), Er(III) and Yb(III), compared to Lu(III) and to Ce(III). HREE-associated toxicity affected embryogenesis, fertilization, cytogenetic and redox endpoints showing different toxicities of tested HREEs.


Dual-task walking improvement with enhanced kinesthetic awareness in Parkinson's disease with mild gait impairment: EEG connectivity and clinical implication.
Due to basal ganglia dysfunction, short step length is a common gait impairment in Parkinson's disease (PD), especially in a dual-task walking. Here, we use electroencephalography (EEG) functional connectivity to investigate neural mechanisms of a stride awareness strategy that could improve dual-task walking in PD. Eighteen individuals with PD who had mild gait impairment walked at self-paced speed while keeping two interlocking rings from touching each other. During the dual-task walking trial, the participants received or did not receive awareness instruction to take big steps. Gait parameters, ring-touching time, and EEG connectivity in the alpha and beta bands were analyzed. With stride awareness, individuals with PD exhibited greater gait velocity and step length, along with a significantly lower mean EEG connectivity strength in the beta band. The awareness-related changes in the EEG connectivity strength of the beta band positively correlated with the awareness-related changes in gait velocity, cadence, and step length, but negatively correlated with the awareness-related change in step-length variability. The smaller reduction in beta connectivity strength was associated with greater improvement in locomotion control with stride awareness. This study is the first to reveal that a stride awareness strategy modulates the beta band oscillatory network and is related to walking efficacy in individuals with PD in a dual-task condition.


Association of alcohol consumption with prevalence of fatty liver after adjustment for dietary patterns: Cross-sectional analysis of Japanese middle-aged adults.
Moderate alcohol intake is associated with reduced prevalence or incidence of fatty liver. However, whether or not the association is independent of dietary patterns remains unclear. We aimed to evaluate the cross-sectional association of alcohol intake with fatty liver after accounting for dietary patterns and obesity. We assessed 4579 adults aged 30-79 years who participated in routine clinical examinations in St. Luke's International Hospital, Japan (January to March, 2015). We assessed their habitual diet using diet-history questionnaire, estimated alcohol intake, and derived dietary pattern variables using factor analysis. Fatty liver was ascertained using ultrasonography. Linear and U-shaped associations of alcohol intake with fatty liver were evaluated using Poisson regression, and a post hoc analysis was conducted after detecting potential outliers for alcohol intake and excluding them using sex-specific statistics (median plus 2 × interquartile range). Fatty liver was ascertained in 1120 participants (24.5%). Whereas no significant association of alcohol intake with fatty liver was observed when potential outliers of alcohol intake were included (p = 0.25), a significant U-shaped association was observed after excluding the outliers with and without adjustment for dietary patterns (p = 0.003 and 0.02, respectively). The lowest prevalence was estimated when alcohol consumption was approximately 7% of energy, with a prevalence ratio of 0.72 (95% confidence interval = 0.59-0.86) compared to non-drinkers. The association became imprecise and attenuated toward the null after further adjustment for body mass index (p = 0.06). Alcohol intake showed a U-shaped association with fatty liver prevalence. This association was independent of underlying dietary patterns, while it was sensitive to excessive alcohol intake and obesity status, providing clinical implications for the prevention of fatty liver.


Tacrolimus and quality of life after kidney transplantation--a multicenter study.
Kidney transplantation is currently the treatment of choice for end-stage renal disease. Although new immunosuppressive drugs have been introduced into clinical practice, the effect of such medication on quality of life (QoL) in transplant recipients is still unclear. The present study analyzes the impact of tacrolimus-based immunosuppression on QoL in a representative sample of adult kidney transplant recipients from Rio Grande do Sul, a Brazilian southern state. This was a cross-sectional multicenter study which used the SF-36 Health Survey for measuring QoL. The effect of tacrolimus on QoL was adjusted for possible confounders using multiple linear regression. A total of 272 patients (from 11 different centers) were evaluated, 48 of them were treated with tacrolimus. Transplant patients in use of tacrolimus presented significant higher scores in the physical component summary of SF-36 than non-users (49.1+/-8.3 vs. 46.1+/-8.7; p=0.03), and such difference was noted in the physical functioning and general health subscales (81.5+/-17.1 and 74.7+/-21.8; 74.6+/-22.3 and 67.1+/-22.3 for users and non-users of tacrolimus, respectively, p<0.05). The effect of tacrolimus remained significant after adjustment for age, gender, skin color and time since transplantation (coeff.: 2.83; 95% CI: 0.05-5.6, p=0.045). The association between tacrolimus-based immunosuppression and better perception of physical functioning and general health for renal transplant patients represents a significant finding as it may influence therapeutical decisions and contribute to maximize kidney transplantation benefits.


Optometry and the military.
This article comments on several of the major issues facing military optometry which were aired earlier this year at the AOA Federal Service Optometry Seminar. Among these issues, all of which influence recruitment and retention of optometry officers, are constructive credit, bonus and incentive pay, promotion policies, and optimum scope of care. Dr. Turner emphasizes that solutions to these problem areas depend not only upon AOA actions but also personal efforts and professionalism of military OD's.


Mechanisms by which calcium ions regulate the steroidogenic actions of luteinizing hormone in isolated ovarian cells in vitro.
Incubation of swine granulosa cells in chemically defined medium selectively deficient in calcium ions markedly impaired progesterone production in response to submaximal and maximally stimulating concentrations of LH. Accumulation of progesterone in response to LH was reduced significantly in both cells and medium, without a discernible shift in the time-course of progestin production. The reduction in progesterone accumulation could not be accounted by increased formation of the catabolite 20 alpha-hydroxypregn-4-en-3-one. In addition, progesterone secretion basally or in response to exogenously supplied pregnenolone was not altered in calcium-deficient incubations. Administration of verapamil or diltiazem, organic inhibitors of net transmembrane calcium uptake, also suppressed LH-stimulated progesterone production. Conversely, micromolar concentrations of the divalent cation ionophore A23187 significantly enhanced the stimulatory effects of LH. The mechanisms of calcium action were examined further in relation to the cAMP effector system. Calcium deprivation significantly suppressed the dose-dependent accumulation of cAMP in granulosa cells treated with LH but had no effect on basal levels. Omission of calcium ions from the extracellular medium also markedly impaired production of progesterone in response to 8-bromo-cAMP, cholera toxin, or 3-isobutyl-l-methylxanthine. The present studies suggest that calcium ions significantly modulate LH-stimulated progesterone biosynthesis in isolated ovarian cells in vitro. Specific regulatory actions of calcium ions in granulosa cells may be exerted at several levels, including LH-stimulated cAMP accumulation and at intracellular loci distal to the actual generation of cAMP.


Critical role of the endocannabinoid system in the regulation of food intake and energy metabolism, with phylogenetic, developmental, and pathophysiological implications.
The endocannabinoid system (ECS) consists of two receptors (CB(1) and CB(2)), several endogenous ligands (primarily anandamide and 2-AG), and over a dozen ligand-metabolizing enzymes. The ECS has deep phylogenetic roots and regulates many aspects of embryological development and homeostasis, including neuroprotection and neural plasticity, immunity and inflammation, apoptosis and carcinogenesis, pain and emotional memory, and the focus of this review: hunger, feeding, and metabolism. The ECS controls energy balance and lipid metabolism centrally (in the hypothalamus and mesolimbic pathways) and peripherally (in adipocytes and pancreatic islet cells), acting through numerous anorexigenic and orexigenic pathways (e.g., ghrelin, leptin, orexin, adiponectin, endogenous opioids, and corticotropin-releasing hormone). Obesity leads to excessive endocannabinoid production by adipocytes, which drives CB(1) in a feed-forward dysfunction. Phylogenetic research suggests the genes for endocannabinoid enzymes, especially DAGLalpha and NAPE-PLD, may harbor mildly deleterious alleles that express disease-related phenotypes. Several CB(1) inverse agonists have been developed for the treatment of obesity, including rimonabant, taranabant, and surinabant. These drugs are efficacious at reducing food intake as well as abdominal adiposity and cardiometabolic risk factors. However, given the myriad beneficial roles of the ECS, it should be no surprise that systemic CB(1) blockade induces various adverse effects. Alternatives to systemic blockade include CB(1) partial agonists, pleiotropic drugs, peripherally restricted antagonists, allosteric antagonists, and endocannabinoid ligand modulation. The ECS offers several discrete targets for the management of obesity and its associated cardiometabolic sequelae.


Fine structure of the haplosporidan Kernstab, a persistent, intranuclear mitotic apparatus.
The fine structure of the haplosporidan mitotic apparatus is described from observations of plasmodial nuclei of Minchinia nelsoni, M. costalis, Minchinia sp., and Urosporidium crescens. The apparatus, which is the Kernstab of light-microscope studies, consists of a bundle of microtubules terminating in a spindle pole body (SPB) at each end of the bundle. A few microtubules extend from SPB to SPB, but most either extend from an SPB and terminate in the nucleoplasm or lie in the nucleoplasm, free of either SPB. The bundle lengthens during mitosis, increasing the SPB-to-SPB distance by a factor of 2 to 3 as compared to interphase nuclei. SPBs are not in contact with the nuclear envelope, being found always in the nucleoplasm which is delimited by the nuclear envelope throughout mitosis. The mitotic apparatus is persistent through interphase, at least in a form which is not significantly different from that found in mitotic nuclei.


Medical school forensic psychiatry units in health care delivery facilities rather than criminal justice institutions: an alternative model.
We have presented a model for developing forensic psychiatric treatment and teaching services of a medical school Department of Psychiatry, but where these services are the basic comprehensive health care delivery system for the entire community. These offer consultative and treatment services for adult and family court clinic, psychiatric forensic services, of forensic psychiatry open bed and medium security-type bed, as well as day hospital and outpatient services. All of these are sited in the normal health care delivery system of the university teaching hospitals and its patient treatment, teaching, and research facilities. Consultative services are offered on request to the criminal justice system, but the basic health care delivery system is controlled administratively by the ordinary university teaching hospital authorities and exists as a one of a kind unit at the Royal Ottawa Hospital. The Royal Ottawa Hospital is a private nonprofit hospital, with its own Board of Trustees, and is affiliated with the medical school, as part of a major university network. We believe it important to present this model for an overall forensic psychiatric service, in contradistinction to the more commonly established forensic psychiatric facilities in state mental hospitals, in a special facility for the criminally insane, or in a criminal justice system institution such as a penitentiary. We believe that our model for forensic psychiatric facilities has great advantages for the patient. Here the patient is treated in a specialized facility (as all psychiatric patients with specialized problems should be); but one which is a specialized forensic facility, within the range of specialized psychiatric facilities that are needed by an urban community.(ABSTRACT TRUNCATED AT 250 WORDS)


Genetic Characteristics and Phylogeny of 969-bp S Gene Sequence of SARS-CoV-2 from Hawai'i Reveals the Worldwide Emerging P681H Mutation.
The COVID-19 pandemic has ravaged the world, caused over 1.8 million deaths in its first year, and severely affected the global economy. Hawai'i has not been spared from the transmission of SARS-CoV-2 in the local population, including high infection rates in racial and ethnic minorities. Early in the pandemic, we described in this journal various technologies used for the detection of SARS-CoV-2. Herein we characterize a 969-bp SARS-CoV-2 segment of the S gene downstream of the receptor-binding domain. At the John A. Burns School of Medicine Biocontainment Facility, RNA was extracted from an oropharyngeal swab and a nasal swab from 2 patients from Hawai'i who were infected with SARS-CoV-2 in August 2020. Following PCR, the 2 viral strains were sequenced using Sanger sequencing, and phylogenetic trees were generated using MEGAX. Phylogenetic tree results indicate that the virus has been introduced to Hawai'i from multiple sources. Further, we decoded 13 single nucleotide polymorphisms across 13 unique SARS-CoV-2 genomes within this region of the S gene, with 1 non-synonymous mutation (P681H) found in the 2 Hawai'i strains. The P681H mutation has unique and emerging characteristics with a significant exponential increase in worldwide frequency when compared to the plateauing of the now universal D614G mutation. The P681H mutation is also characteristic of the new SARS-CoV-2 variants from the United Kingdom and Nigeria. Additionally, several mutations resulting in cysteine residues were detected, potentially resulting in disruption of the disulfide bridges in and around the receptor-binding domain. Targeted sequence characterization is warranted to determine the origin of multiple introductions of SARS-CoV-2 circulating in Hawai'i.


Maternal perceptions of family-provider relationships and well-being in families of children with Down syndrome.
The purpose of this study was twofold: (a) to describe parental perceptions of family-provider relationships, and (b) to explore links between parental perceptions of family-provider relationships and well-being in families with children who have Down syndrome. Mailed questionnaires were used to collect data from 94 families that include a child with Down syndrome. Data from 89 mothers are the focus of this report. The results indicate that when mothers of children with Down syndrome believe that their family's relationship with health care providers is positive and family-centered, they feel more satisfied with the care that their child is receiving and they are more likely to seek help from health care providers. In addition, when a discrepancy exists between what mothers want the family-provider relationship to be and what they believe the relationship is, mothers feel less satisfied with the care that their child is receiving. Finally, higher levels of individual and family well-being are reported by mothers who (a) want, and believe they have, positive family-centered relationships with providers, and (b) feel more satisfied with care received. Results of this study contribute to a better understanding of the role that health care providers play in individual and family adaptation to chronic conditions.


The Joint Effects of Spatial Cueing and Transcranial Direct Current Stimulation on Visual Acuity.
The present study examined the mutual influence of cortical neuroenhancement and allocation of spatial attention on perception. Specifically, it explored the effects of transcranial Direct Current Stimulation (tDCS) on visual acuity measured with a Landolt gap task and attentional precues. The exogenous cues were used to draw attention either to the location of the target or away from it, generating significant performance benefits and costs. Anodal tDCS applied to posterior occipital area for 15 min improved performance during stimulation, reflecting heightened visual acuity. Reaction times were lower, and accuracy was higher in the tDCS group, compared to a sham control group. Additionally, in post-stimulation trials tDCS significantly interacted with the effect of precuing. Reaction times were lower in valid cued trials (benefit) and higher in invalid trials (cost) compared to neutrally cued trials, the effect which was pronounced stronger in tDCS group than in sham control group. The increase of cost and benefit effects in the tDCS group was of a similar magnitude, suggesting that anodal tDCS influenced the overall process of attention orienting. The observed interaction between the stimulation of the visual cortex and precueing indicates a magnification of attention modulation.


The significance of pancreatic islet cell antibody and abnormal glucose tolerance during pregnancy.
Five out of 50 pregnant subjects with impaired glucose tolerance (a 2 hr venous plasma glucose concentration over 6.6 mmol/1) had cytoplasmic islet cell antibody (ICAb cyto) in their sera. Three of these 5 developed unequivocal insulin-dependent diabetes in the first year following pregnancy, while none of the others did so. When taken in conjunction with the presence of islet cell antibody, the severity of impairment of glucose tolerance during pregnancy (but not obesity) was an additional indicator of the likelihood of developing insulin-dependent diabetes during the first postpartum year.


The effect of maneb, zineb, and ethylenethiourea on the humoral activity of the pituitary-thyroid axis in rat.
Ethylenebisdithiocarbamates (EBDCs) maneb and zineb are widely used fungicides the final metabolite of which is ethylenethiourea (ETU). EBDCs distort the humoral activity of the thyroid gland, and ETU is especially active in this respect. Male Wistar rats were exposed either to exogenous (100 ng i.p.) or endogenous (+4 degrees C) TRH stimulation. ETU (100-500 mg/kg i.p.) caused no changes in serum TSH levels whereas zineb (70-500 mg/kg i.p.) significantly decreased the bursts induced by cold or exogenous TRH. Maneb (20-200 mg/kg i.p.) significantly decreased the cold-induced TSH response while it had no effect on the TRH-stimulated TSH secretion. None of the agents caused significant changes in serum T3 or T4 levels. It seems that maneb, and zineb, but not ETU, inhibit rat TSH secretion through an action on the endogenous TRH at the hypothalamic or pituitary level. The mechanism behind this action may be the inhibition of dopamine-beta-hydroxylase.


Impact of white matter hyperintensity volume progression on rate of cognitive and motor decline.
White matter hyperintensity (WMH) change on brain MRI is observed with increased frequency in the elderly and has been independently associated with neurologic decline. The degree to which the location and rate of volume increase in WMH affects other structural brain changes along with cognitive and motor performance over time may determine subsequent degrees of risk for dementia and other syndromes of aging. One hundred four cognitively intact men and women followed longitudinally for up to 13 years underwent at least three MRIs with corresponding annual cognitive and neurologic assessments. Brain volume, ventricular CSF (vCSF), and total periventricular (PV) and subcortical WMH volumes were measured. Progression of MRI volumes was examined in relation to rates of cognitive, motor, and cerebral volume change based on slopes of outcomes. Higher initial total and PV WMH volume was associated with total WMH, PV WMH, and vCSF progression, and with increased time and number of steps to walk 30 feet. Progression of PV WMH volume was associated with increased time to walk 30 feet. Progression of subcortical WMH volume was associated with decreased performance on logical memory testing and increased rate of vCSF volume change. Increased total and periventricular (PV) white matter hyperintensity (WMH) burden and progression of PV WMH burden are associated with decreased gait performance over time, while progression of subcortical WMH volume is associated with memory decline in cognitively intact elderly. Greater progression of WMH burden is associated with an increased risk of memory and gait dysfunction, and thus should not be considered a benign process.


Economic evaluation of a workplace intervention for sick-listed employees with distress.
To evaluate the cost effectiveness, cost utility and cost benefit of a workplace intervention compared with usual care for sick-listed employees with distress. An economic evaluation was conducted alongside a randomised controlled trial. Employees with distress and who were sick-listed for 2-8 weeks were randomised to a workplace intervention (n=73) or to usual care (n=72). The workplace intervention is a stepwise process involving the sick-listed employee and their supervisor, aimed at formulating a consensus-based plan for return to work (RTW). The effect outcomes were lasting RTW and quality-adjusted life years (QALYs). Healthcare utilisation was measured over 12 months. Cost effectiveness analyses (CEA) and cost utility analyses (CUA) were conducted from the societal perspective and cost benefit analyses (CBA) from the employer perspective. Bootstrapping techniques were used to estimate cost and effect differences, related CIs, and cost effectiveness and cost utility ratios. Cost effectiveness planes were presented and subgroup analyses were performed. CEA and CUA revealed no statistically significant differences in lasting RTW, QALYs or costs. The CBA indicated a statistically significant higher cost of occupational health services in the workplace intervention group. The workplace intervention was not cost effective according to the CEA, CUA and CBA. Widespread implementation of the workplace intervention for sick-listed employees with distress is not recommended because there was no economic benefit compared with usual care. Future trials should confirm if the workplace intervention is cost effective for the subgroup employees who intended to return to work despite symptoms. This trial has been registered at the Dutch National Trial Register ISRCTN92307123.


Laws of large numbers and langevin approximations for stochastic neural field equations.
In this study, we consider limit theorems for microscopic stochastic models of neural fields. We show that the Wilson-Cowan equation can be obtained as the limit in uniform convergence on compacts in probability for a sequence of microscopic models when the number of neuron populations distributed in space and the number of neurons per population tend to infinity. This result also allows to obtain limits for qualitatively different stochastic convergence concepts, e.g., convergence in the mean. Further, we present a central limit theorem for the martingale part of the microscopic models which, suitably re-scaled, converges to a centred Gaussian process with independent increments. These two results provide the basis for presenting the neural field Langevin equation, a stochastic differential equation taking values in a Hilbert space, which is the infinite-dimensional analogue of the chemical Langevin equation in the present setting. On a technical level, we apply recently developed law of large numbers and central limit theorems for piecewise deterministic processes taking values in Hilbert spaces to a master equation formulation of stochastic neuronal network models. These theorems are valid for processes taking values in Hilbert spaces, and by this are able to incorporate spatial structures of the underlying model.Mathematics Subject Classification (2000): 60F05, 60J25, 60J75, 92C20.


Interfacing With Alpha Motor Neurons in Spinal Cord Injury Patients Receiving Trans-spinal Electrical Stimulation.
Trans-spinal direct current stimulation (tsDCS) provides a non-invasive, clinically viable approach to potentially restore physiological neuromuscular function after neurological impairment, e.g., spinal cord injury (SCI). Use of tsDCS has been hampered by the inability of delivering stimulation patterns based on the activity of neural targets responsible to motor function, i.e., α-motor neurons (α-MNs). State of the art modeling and experimental techniques do not provide information about how individual α-MNs respond to electrical fields. This is a major element hindering the development of neuro-modulative technologies highly tailored to an individual patient. For the first time, we propose the use of a signal-based approach to infer tsDCS effects on large α-MNs pools in four incomplete SCI individuals. We employ leg muscles spatial sampling and deconvolution of high-density fiber electrical activity to decode accurate α-MNs discharges across multiple lumbosacral segments during isometric plantar flexion sub-maximal contractions. This is done before, immediately after and 30 min after sub-threshold cathodal stimulation. We deliver sham tsDCS as a control measure. First, we propose a new algorithm for removing compromised information from decomposed α-MNs spike trains, thereby enabling robust decomposition and frequency-domain analysis. Second, we propose the analysis of α-MNs spike trains coherence (i.e., frequency-domain) as an indicator of spinal response to tsDCS. Results showed that α-MNs spike trains coherence analysis sensibly varied across stimulation phases. Coherence analyses results suggested that the common synaptic input to α-MNs pools decreased immediately after cathodal tsDCS with a persistent effect after 30 min. Our proposed non-invasive decoding of individual α-MNs behavior may open up new avenues for the design of real-time closed-loop control applications including both transcutaneous and epidural spinal electrical stimulation where stimulation parameters are adjusted on-the-fly.


B7-H3 and B7-H4 are independent predictors of a poor prognosis in patients with pancreatic cancer.
B7-H3 and B7-H4 belong to the peripheral membrane protein B7 family and are hypothesized to regulate immunity. These proteins are expressed in human pancreatic cancer (PC), but their prognostic significance is poorly understood. The present study examined the association between B7-H3 and B7-H4 expression and the overall survival time in patients with PC that underwent surgery at the Second Affiliated Hospital to Zhengzhou University between April 2000 and January 2009. Immunohistochemical analysis demonstrated that B7-H3 and B7-H4 were expressed in 35 (88%) and 30 (75%) tumor tissue samples, respectively, which were obtained from 40 patients with PC. Statistical analysis revealed that B7-H3 expression was associated with an early tumor-node-metastasis stage (stage I and II; P<0.01), and B7-H4 expression was associated with tumors located in the body and tail of the pancreas (P<0.01) and lymph node metastasis (P=0.02). In addition, using Spearman's rank correlation coefficient, the present study demonstrated a positive correlation between B7-H3 expression and B7-H4 expression (r=0.37; P=0.02) in tumor samples. B7-H4 expression (P=0.01), tumors located in the pancreatic body and tail (P<0.01), lymph node metastasis (P=0.02) and combined B7-H3 and B7-H4 expression (P<0.01) were indicators of a poor overall survival time. However, solitary B7-H4 expression (P=0.03) and combined B7-H3 and B7-H4 expression (P=0.04) remained significant prognostic factors following adjustment for other prognostic factors in a multivariate Cox's proportional hazards regression model. Therefore, the present results indicate that solitary B7-H4 expression and a combination of B7-H3 and B7-H4 expression are independent predictors of a poor prognosis in patients with PC.


Veterinary bacteriology in Denmark from the 1880s to 2022.
This paper gives an account of the history of veterinary bacteriology including clinical veterinary bacteriology as well as the area of veterinary public health in Denmark from the 1880s to 2022. We describe key persons, including B. Bang, C.O. Jensen, K.A. Jensen and others who made important contributions to the development of these areas of microbiological expertise, and we discuss how challenges ranging from bovine tuberculosis to bacterial antimicrobial resistance have been met. Further, we describe progress in research on important bacterial pathogens both with regard to animal clinical aspects and zoonotic food-related aspects. Finally, we describe current issues in relation to One Health and research organization.


Do patients in hospitals benefit from single rooms? A literature review.
In the context of growing attention for 'healing environments' and 'evidence based design' an increasing number of hospitals have decided to provide single-bedded rooms. However it remains unclear to what extent these policy decisions are based on scientific evidence. The aim of this study is to review the literature on benefits of single patient rooms for patients. The following outcome measures were used: privacy and dignity, patient satisfaction with care, noise and quality of sleep, hospital infection rates, recovery rates, and patient safety issues. We selected 25 studies for review. Randomized controlled trials on this subject were scarce, but other empirical studies have been found. We found that single rooms have a moderate effect on patient satisfaction with care, noise and quality of sleep, and the experience of privacy and dignity. Conflicting results have been found on hospital infection rates. Some studies did not show significant differences, while others concluded that single rooms decrease the risk of hospital infections. Evidence on recovery rates and patient safety was lacking. Too few sound studies were found to evaluate the effects of single patient rooms thoroughly. Future research should build the body of knowledge on single-bedded rooms in order to explore their impact on well-being and healing on both patients and staff. Also consequences of single rooms to management of care should be explored. Research should support policy making by exploring, indicating and initiating improvements in patient housing and quality of care.


Infrared spectra of CF(2)=CHD and CF(2)=CD(2): scaled quantum-chemical force fields and an equilibrium structure for 1,1-difluoroethylene.
Infrared (IR) spectra in the gas phase are reported for CF(2)=CHD and CF(2)=CD(2) in the region 350-4000 cm(-1). Ab initio calculations of an harmonic force-field and anharmonicity constants have been made with an MP2/aug-cc-pVTZ model. These enable a number of Fermi resonances in each species to be analyzed and a complete set of "observed" harmonic frequencies to be derived. The latter are combined with similar data for CF(2)=CH(2) in a scaling of the model harmonic force field to both anharmonic and harmonic frequencies. Inspection of the scale factors reveals minor defects of the model, evident in the out-of-plane wagging modes and in the CF stretch/CF stretch interaction force constant. Fermi resonance treatments involved in all isotopomers studied are compatible with the overall force-field refinement results. The treatment leaves a small anomaly in the (13)C shift on nu(1). Improved microwave spectra are reported for five isotopic species, and a semiexperimental equilibrium structure for F(2)C=CH(2) is determined and compared favorably with the structure obtained from new high-level ab initio calculations. Centrifugal distortion constants are predicted for the five isotopic species, and those for F(2)C=CH(2) are compared with values fit to microwave spectra.


Expression in yeast and purification of functional recombinant human poly(ADP-ribose)polymerase (PARP). Comparative pharmacological profile with that of the rat enzyme.
Human poly(ADP-ribose)polymerase (PARP) was expressed in the yeast line JEL1 under the control of a GAL promoter. Proteins were extracted and human recombinant PARP purified to apparent homogeneity. The pharmacological profile of this human enzyme was characterised in terms of the effects of known inhibitors of PARP belonging to various chemical families and this was compared with that of the rat enzyme purified from rat testes, using the same purification protocol. The rat and the human enzymes appeared very similar in terms of their sensitivities to those selected inhibitors.


Preoptic and hypothalamic regulation of multi-tiered, chronologically arranged female rat sexual behavior.
As in many mammalian behaviors, sexual behavior exhibits structure. Each modular components of the structure, that are linked together over time, occur in probabilistic manner. Endocrine milieu, in particular sex hormones, define the probability to synchronize the behavior with the production of gametes. Developmental experience and environmental cues affect the hormonal milieu of the brain. This is especially true in female mammals, in which ova mature with certain intervals along with ovarian secretion of sex hormones. Estrogens secreted by mature ovarian follicles support both affiliative and executive components of female sexual behavior. In the absence of the ovarian steroids, females avoid males when possible, or antagonize and reject males when put together. Female sexual behavior is intimately linked with the estrous cycle in many species such that females are only receptive for a brief period at the estrus stage surrounding ovulation. Thus, in the rat, females strongly influence the outcome of mating encounter with a male. Affiliative or solicitatory behavior shown by females in estrus leads to the female adapting the lordosis posture, which is characterized by hindleg postural rigidity and lordotic dorsiflexion of the spine, in response to touch-pressure somatosensory stimuli on the skin of the flanks, rump-tail base, perineum region given by male partner. The posture facilitates intromission and consequently fertilization. Although dependence on estrogens is the most important feature of female rat sexual behavior, cervical probing combined with palpation of the hindquarter skin acts as a supranormal stimulus to elicit lordosis. Thus, lordosis behavior is a hub of multi-tiered, chronologically arranged set of behaviors and estrogen appear to alter excitability of neural network for lordosis.


Alternative therapies: Part II. Congestive heart failure and hypercholesterolemia.
Natural supplements are widely used by the American public but, while claims of their therapeutic effects abound, medical research does not always support their effectiveness. Clinical trials using Q10 for the management of congestive heart failure have had conflicting results; hawthorn is prescribed in Germany for the treatment of this condition, but no trials have been conducted in the United States. Although initial research about the use of garlic in the management of hypercholesterolemia was encouraging, follow-up studies have failed to verify these results. Substituting soy protein for high-fat animal protein diets, however, does have a beneficial effect on serum lipid levels. So far, cholestin (a natural product containing several statins) has proved to be a cost-saving lipid-lowering medication, and fenugreek may offer modest improvement as well. Gugulipid is also promising but requires further research.


[In vitro efficacy of Ingavirin against the pandemic influenza virus A(H1N1/09)v].
Ingavirin was shown to be efficient in inhibition of the influenza virus strains A/California/04/2009 (H1N1)v, A/California/07/2009 (H1N1)v, A/Moscow/225/2009 (H1N1)v and A/Moscow/226/2009 (H1N1)v, as well as the strains A/Chicken/Kurgan/05/2005 (H5N1) and A/Aichi/2/68 (H3N2) in the MDCK cell culture. The hemagglutinin and cytopathic activity of the influenza virus strains decreased at entering Ingavirin in vitro.


Clinical Quality Indicators for Monitoring Hospitalizations Among Older People with Dementia Accessing Aged Care Services.
There is a need for clinical quality indicators (CQIs) that can be applied to dementia quality registries to monitor care outcomes for people with Alzheimer's disease and other forms of dementia. To develop tertiary and primary care-based dementia CQIs for application to clinical registries for individuals with dementia accessing aged care services and determine 1) annual trends in CQI incidence between 2011-2012 and 2015-2016, 2) associated factors, and 3) geographic and facility variation in CQI incidence. This retrospective repeated cross-sectional study included non-Indigenous individuals aged 65-105 years who lived with dementia between July 2008-June 2016, were assessed for government-funded aged care services, and resided in New South Wales or Victoria (n = 180,675). Poisson or negative binomial regression models estimated trends in annual CQI incidence and associated factors. Funnel plots examined CQI variation. Between 2011-2012 and 2015-2016, CQI incidence increased for falls (11.0% to 13.9%, adjusted incidence rate ratio (aIRR) 1.05 (95% CI 1.01-1.06)) and delirium (4.7% to 6.7%, aIRR 1.09 (95% CI 1.07-1.10)), decreased for unplanned hospitalizations (28.7% to 27.9%, aIRR 0.99 (95% CI 0.98-0.99)) and remained steady for fracture (6.2% to 6.5%, aIRR 1.01 (95% CI 0.99-1.01)) and pressure injuries (0.5% to 0.4%, aIRR 0.99 (95% CI 0.96-1.02)). Being male, older, having more comorbidities and living in a major city were associated with higher CQI incidence. Considerable geographical and facility variation was observed for unplanned hospitalizations and delirium CQIs. The CQI results highlighted considerable morbidity. The CQIs tested should be considered for application in clinical quality registries to monitor dementia care quality.


A functional link between heme oxygenase and cyclo-oxygenase activities in cortical rat astrocytes.
Recent evidence shows that the activation of heme oxygenase (HO) within the CNS is associated with increased prostanoid production. In this study, we investigated whether changes in HO activity induced by pharmacological manipulation are associated with parallel variations in cyclo-oxygenase (COX) activity and prostaglandin production in an in vitro paradigm of CNS cells, i.e. primary cultures of rat cortical astrocytes. Pharmacological tools commonly used to induce changes in HO activity, namely the HO enhancers hemin and CoCl(2) as well as the HO inhibitor Sn-mesoporphyrin-9 (SnMP9), were tested in our model, and the variations in COX activity associated with the above treatments were monitored by measuring a COX end product, prostaglandin E2 (PGE2), released into the incubation medium. We found that the increase in HO activity induced by hemin and/or CoCl(2) was not consistently associated with increases in prostaglandin production, whereas HO inhibition by SnMP9 was normally followed by a decrease in PGE2 release. The above effect was observed after both acute (30 min) and prolonged (24 hr) incubations, suggesting that baseline HO activity contributes to the maintenance of normal PG production in this model. Experiments with the stable HO end products biliverdin and bilirubin suggest that these products may play a role in mediating HO-induced COX activation.


The effect of primary care availability on antibiotic consumption in Hungary: a population based panel study using unfilled general practices.
We analyse the effect of primary care availability on antibiotic consumption and on the quality of antibiotic prescribing behaviour. Retrospective panel design, secondary analysis of settlement-level administrative panel data (n=2320 settlements, T=72 months). We analyse antibiotic consumption of the population of villages in Hungary, over years 2010 to 2015. We exploit the geographical and time variation in unfilled (mainly single-handed) general practices as a source of exogenous variation in the availability of primary care. We control for socioeconomic characteristics and settlement fixed effects in a panel regression framework. Antibiotic expenditures and days of therapy (DOT); consumption of narrow-spectrum and broad-spectrum antibiotics; consumption of Access, Watch and Reserve antibiotics according to the AWaRe categorisation; number of visits to the general practitioner (GP). If the general practice of a village becomes unfilled, the number of GP visits decreases on average by 9.3% (95% CI 5.6% to 12.9%), antibiotics DOT decrease on average by 3.2% (95% CI 1.0% to 5.4%) and expenditures on antibiotics decrease on average by 2.5% (95% CI 0.3% to 4.7%). The negative effect on antibiotic consumption is stronger in settlements where secondary care is less available, and where antibiotics were previously overprescribed. The quality of prescribing behaviour measured by the relative changes in the narrow-spectrum vs broad-spectrum as well as the Access versus Watch and Reserve antibiotics deteriorates significantly as a consequence of worse primary care availability. Limited availability of primary care reduces the consumption of antibiotics and at the same time impairs the quality of prescriptions through a decrease of the number of doctor-patient encounters.


Tackling the neurological manifestations in Wilson's disease - currently available treatment options.
Wilson's disease (WD) is a potentially treatable, inherited disorder resulting from impaired copper metabolism. Pathological copper accumulation causes a range of symptoms, most commonly hepatic and a wide spectrum of neurological symptoms including tremor, dystonia, chorea, parkinsonism, dysphagia, dysarthria, gait and posture disturbances. To reduce copper overload, anti-copper drugs are used that improve liver function and neurological symptoms in up to 85% of patients. However, in some WD patients, treatment introduction leads to neurological deterioration, and in others, neurological symptoms persist with no improvement or improvement only after several years of treatment, severely affecting the patient's quality of life. This review appraises the evidence on various pharmacological and non-pharmacological therapies, neurosurgical procedures and liver transplantation for the management of neurological WD symptoms. The authors also discuss the neurological symptoms of WD, causes of deterioration and present symptomatic treatment options. Based on case and series reports, current recommendations and expert opinion, WD treatment is focused mainly on drugs leading to negative copper body metabolism (chelators or zinc salts) and copper-restricted diet. Treatment of WD neurological symptoms should follow general recommendations of symptomatic treatment. Patients should be always considered individually, especially in the case of severe, disabling neurological symptoms.


Ribonucleic acid synthesis in rabbit erythroid cells.
Kinetic studies on the synthesis of RNA in mature bone-marrow erythroid cells from rabbits were made by measuring the incorporation of [2-3H]adenosine into the ATP pool and RNA over periods up to 8h. By use of equations to fit the pool specific radioactivity and an equation using the same type of pool to generate the rate of linear DNA synthesis, good agreement between the pool parameters is found, provided that the ATP pool is measured in whole cell extracts, and assuming that the dATP and ATP pools equilibrate rapidly. RNA-synthesis rates were measured by using curve fits to equations developed by using the pool specific-radioactivity curves. The rate of synthesis of poly(A)-containing RNA varied in three experiments from 90 to 220mol/min per cell, with half-life of nuclear processing of 12-22 min with a mean of 16 min. Ribosomal RNA is synthesized at a rate of 70-200 mol/min per cell with an average half-life of nuclear processing of 37 min for the 18S RNA and 214 min for the 28S RNA. When the stable rRNA components are subtracted from the nRNA synthesis, the rate of nRNA synthesis is between 2 and 6fg/min per cell with an average half-life of degradation of 27 min. The rate of synthesis of poly(A)-containing RNA is 1.5-3.5% of the RNA-synthesis rates. These rates are compared with the RNA-synthesis rates found in L cells and concentrations of globin mRNA found in various erythroid-cell preparations.


CutFEM forward modeling for EEG source analysis.
Source analysis of Electroencephalography (EEG) data requires the computation of the scalp potential induced by current sources in the brain. This so-called EEG forward problem is based on an accurate estimation of the volume conduction effects in the human head, represented by a partial differential equation which can be solved using the finite element method (FEM). FEM offers flexibility when modeling anisotropic tissue conductivities but requires a volumetric discretization, a mesh, of the head domain. Structured hexahedral meshes are easy to create in an automatic fashion, while tetrahedral meshes are better suited to model curved geometries. Tetrahedral meshes, thus, offer better accuracy but are more difficult to create. We introduce CutFEM for EEG forward simulations to integrate the strengths of hexahedra and tetrahedra. It belongs to the family of unfitted finite element methods, decoupling mesh and geometry representation. Following a description of the method, we will employ CutFEM in both controlled spherical scenarios and the reconstruction of somatosensory-evoked potentials. CutFEM outperforms competing FEM approaches with regard to numerical accuracy, memory consumption, and computational speed while being able to mesh arbitrarily touching compartments. CutFEM balances numerical accuracy, computational efficiency, and a smooth approximation of complex geometries that has previously not been available in FEM-based EEG forward modeling.


Unique purified hydrated-gelatin diet for feeding dietary fiber to Wistar rats.
A purified hydrated gelatin diet was developed for feeding dietary fibers to Wistar rats. A dry fiber mix was prepared that consisted of 54.91 dextrose, 13.80 casein, 2.97 AIN mineral mix, 1.28 AIN vitamin mix, 0.17 dl-methionine, 6.80 lard and 5.10 gelatin (g/100g total dry feed). Either cellulose, hemicellulose, lignin, or pectin (15 g/100 g total dry feed) was added to the hydrated dry fiber mix and blended until complete distribution and hydration of the fiber was achieved. After gelling, these hydrated diets were stable for up to 24 hours in environmental conditions commonly encountered in animal facilities. Gel weep was minimal thus permitting feed consumption to be monitored conveniently by weighing the residue in the feeders. In situ examination of stomach contents after feeding such hydrated diets to rats indicated that the gelatin gel was readily degraded and did not confound gel formation by fiber itself. Feed efficiency values (g gain/100 kcal digestible energy) for these diets following a 26-day feeding trial were as follows: no fiber, 6.21; cellulose, 6.38; hemicellulose, 6.23; lignin, 6.52; and pectin, 5.53.


Mechanical properties of an experimental resin based composite containing silver nanoparticles and bioactive glass.
To compare the elastic modulus, flexural strength, and hardness of an experimental resin based composite (RBC) with and without containing silver nanoparticles (AgNPs) and bioactive glass (BAG) with a commercially available RBC. This study was conducted, during the period August 2016-May 2018, at the Department of Dental Materials, Peshawar Dental College, Peshawar (Pakistan) and Department of Chemistry, University of Montreal, Canada. Test specimens made in the commercial RBC acted as Group-1 (G1). An experimental RBC containing 70 wt % filler content was synthesized. It was first used as such to prepare test specimens to act as the experimental control group (G2). This RBC was then modified by adding various amounts of BAG (5%, 10% and 15%) and a fixed amount of 0.009% AgNPs to use the so modified RBCs for preparing the test specimens to belong to three groups (G3, G4 & G5). The AgNPs had been synthesized in situ by reduction of salt during photo-polymerization. Flexural strength (FS), elastic modulus (EM) and Vickers hardness were determined using universal testing machine and hardness tester respectively. Data were analyzed using one-way ANOVA and Tukey post-hoc test. Except for G3 restorations showing significantly lower mean FS value, the FS for those in the other groups were not significantly different (p>0.05). Elastic modulus of the experimental RBC restorations was though higher than those of the others but the difference was statistically insignificant (p>0.05). Reduced Vickers hardness values were documented for the restorations in the G4 and G5 compared to those in the G3 but again the difference was insignificant (p>0.05). Flexural strength and hardness values of the test specimens in the experimental RBCs were significantly lower than those made in the commercial hybrid RBC (p<0.05). BAG and AgNPs addition to the experimental RBC in the mentioned concentration adversely affected the tested mechanical properties.


The localization of DHEA sulfotransferase in steroidogenic and steroid metabolizing tissues of the adult rhesus macaque monkey.
Dehydroepiandrosterone sulfate is a major secretory product of the human adrenal cortex during intrauterine development as well as during adulthood. There are few animal experimental models that share this characteristic pattern of adrenal cortical steroidogenesis, which probably accounts for the relative paucity of information about the control of development and function of the adrenal androgen secretory apparatus. Adrenal androgen production in the rhesus macaque shares many similarities with that of the human. We sought to determine the tissue distribution of the enzyme DHEA sulfotransferase (DST) in the rhesus. Tissues were harvested at the time of autopsy from 7 adult monkeys (5 M, 2 F) ranging from 8-15 yrs old, and were fixed in 4% paraformaldehyde, embedded in paraffin, and sectioned at 5 mu thickness. Tissue sections were immunostained for DST with an anti-human liver DST antibody. DST was not detected in the testis or ovary. In the liver, immunoreactive DST was detected only in hepatocytes and in the kidney, DST was found only in the epithelial cells lining the collecting tubules. In the adrenal, DST was present in the cells of the zona reticularis but was not found in the cells of the medulla, zona fasciculata or in the very prominent zona glomerulosa. DST was most prominent in cells that were closest to the reticularis-medullary border. In most adrenals evaluated, the immunopositive cells were scattered, rather than forming a continuous band of cells around the medulla. The tissue distribution of DST in the adult rhesus macaque is qualitatively similar that observed in the adult human. These data aresuggestive that the rhesus might be an excellent model for the exploration of factors that regulate adrenal androgen production during development, aging, and in response to illness and stress, all of which have been found to be associated with variations in DHEA and DHEA sulfate production in the human.


Tool guidance using a compact robotic assistant.
Surgical robots in popular clinical use are generally large machines, which limits their practical use to some extent. This study aims to investigate the potential of a small, table-mounted robot for tool guidance in minimally invasive surgery (MIS). In particular, its multipurpose use for guidance of various tools was investigated. A compact robot capable of manipulating MIS tools was designed and built. The robot can move in four degrees of freedom (DOF): three rotational and one translational. These DOF correspond to motion constrained by a trocar. The robot kinematics are based on a bevel-geared "spherical mechanism," which allows trocar-constrained motion using a small mechanical device. The robot was tested in a porcine model by manipulating scopes and robotic grasping tools using a joystick as directed by a surgeon. Holding a laparoscope, the robot provided superior stability as a camera assistant. It manipulated the scope for visualization of the liver, spleen, bowel, etc. during manual tissue manipulation. Its compactness allowed increased space around the operating table, and the robot was in fact manipulated by joystick from across the room. Maneuvering grasping tools, the robot similarly provided a stable and dexterous platform for tissue manipulation. The test results suggest that the use of robotics for surgery may be enhanced via compact devices to include more hybrid robotic-manual procedures. The robot motion is smoother and more repeatable than that of a human operator. Use of a foot joystick could also place camera control directly with the surgeon. Flexible endoscopes can also be used with the robot for highly dexterous visualization. Notably, changing tools with this system is a very straightforward process and can be achieved without re-registration of the robot's position/orientation. Therefore, combined with other simple robotic tools for grasping, cautery, etc., compact robotic systems based on this technology could replace the large systems in current use, potentially increasing the impact of robots on medical care. This represents an important step towards multifunctional compact surgical robots.


LRRK2 Targeting Strategies as Potential Treatment of Parkinson's Disease.
Parkinson's Disease (PD) affects millions of people worldwide with no cure to halt the progress of the disease. Leucine-rich repeat kinase 2 (LRRK2) is the most common genetic cause of PD and, as such, LRRK2 inhibitors are promising therapeutic agents. In the last decade, great progress in the LRRK2 field has been made. This review provides a comprehensive overview of the current state of the art, presenting recent developments and challenges in developing LRRK2 inhibitors, and discussing extensively the potential targeting strategies from the protein perspective. As currently there are three LRRK2-targeting agents in clinical trials, more developments are predicted in the upcoming years.


Impact of Mobility Device Use on Quality of Life in Children With Friedreich Ataxia.
To determine how mobility device use impacts quality of life in children with Friedreich ataxia. Data from 111 pediatric patients with genetically confirmed Friedreich ataxia were collected from a prospective natural history study utilizing standardized clinical evaluations, including health-related quality of life using the Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Module. Mobility device use was associated with worse mean PedsQL total, physical, emotional, social, and academic subscores, after adjusting for gender, age of disease onset, and Friedreich Ataxia Rating Scale score. The magnitude of the difference was greatest for the physical subscore (-19.5 points, 95% CI = -30.00, -8.99, P < .001) and least for the emotional subscore (-10.61 points, 95% CI = -20.21, -1.02, P = .03). Transition to or between mobility devices trended toward worse physical subscore (-16.20 points, 95% CI = -32.07, -0.33, P = .05). Mobility device use is associated with significant worsening of all domains of quality of life in children with Friedreich ataxia.