A morphologist's perspective on terminal growth and segmentation.
When approaching the study of terminal growth and segmentation, comparative morphology provides an important guide to formulate questions. There are often problems in unambiguously identifying the axis along which we wish to study terminal (often, actually, subterminal) growth, especially when the trunk axis is posteriorly prolonged in an appendage (as with the tail of vertebrates), or when the polarity of the "external animal" is other than the polarity of the "internal animal," as in polypoid bilaterians. We cannot ignore that the rear end of the main body axis is possibly defined very early in development in some groups, for example, arthropods, whereas in others, vertebrates, for example, it is defined much later. We cannot think of segmentation as always corresponding to the sequential posterior addition of new units, thus ignoring the widespread occurrence of double segmentation. A more subtle problem is represented by the overlapping of different processes, all of them contributing to elongating the body, such as segmentation, cell proliferation, cell rearrangement, and cell growth. Within a segmented trunk, cell proliferation and differentiation may go on in parallel from as many growth points as there are groups of regularly spaced cells. The main consequence, however, is not so much to expedite elongation as to reduce the disparity of metabolic conditions, gene expression patterns and "relative age" of different body districts, otherwise possibly troublesome within the limited space of the embryo.


A novel 'gene insertion/marker out' (GIMO) method for transgene expression and gene complementation in rodent malaria parasites.
Research on the biology of malaria parasites has greatly benefited from the application of reverse genetic technologies, in particular through the analysis of gene deletion mutants and studies on transgenic parasites that express heterologous or mutated proteins. However, transfection in Plasmodium is limited by the paucity of drug-selectable markers that hampers subsequent genetic modification of the same mutant. We report the development of a novel 'gene insertion/marker out' (GIMO) method for two rodent malaria parasites, which uses negative selection to rapidly generate transgenic mutants ready for subsequent modifications. We have created reference mother lines for both P. berghei ANKA and P. yoelii 17XNL that serve as recipient parasites for GIMO-transfection. Compared to existing protocols GIMO-transfection greatly simplifies and speeds up the generation of mutants expressing heterologous proteins, free of drug-resistance genes, and requires far fewer laboratory animals. In addition we demonstrate that GIMO-transfection is also a simple and fast method for genetic complementation of mutants with a gene deletion or mutation. The implementation of GIMO-transfection procedures should greatly enhance Plasmodium reverse-genetic research.


Pharmacokinetics, Pharmacodynamics, Safety and Immunogenicity of CMAB807, a New Denosumab Biosimilar, in Healthy Chinese Subjects.
Objective: Pharmacokinetics (PK), pharmacodynamics (PD), safety and immunogenicity studies were conducted to evaluate the bioequivalence of CMAB807, a biosimilar to denosumab (Prolia®), which is the only approved RANKL inhibitor for the treatment of osteoporosis. Methods: In this randomized, double-blind, single-dose phase I study, 132 healthy Chinese male subjects received a subcutaneous injection of 60 mg of CMAB807 or denosumab at a 1:1 ratio. The PK, PD, safety and immunogenicity results were assessed prior to and up to 126 days after administration. Results: The PK profiles of CMAB807 and denosumab were similar. The geometric mean ratios of the maximum concentration (Cmax), AUC0-t and AUCo-∞ were 102.41, 104.15 and 103.89%, respectively, and the 90% confidence interval was observed to be within 80.00-125.00%, which indicated the bioequivalence of CMAB807 and denosumab. The PD profiles of the two groups were also comparable. The production of the C-terminal cross-linking telopeptide of type I collagen (CTX1) was inhibited by up to 85% for 10 days, and this inhibition was sustained for up to 126 days in both the CMAB807 and denosumab groups. No subjects in the CMAB807 group, three subjects in the denosumab group before administration, and two subjects in the denosumab group after administration were positive for anti-drug antibody (ADA). Adverse events (AEs) were observed in 98.5% of subjects in both groups. The most common AE recorded was increased parathyroid hormone (PTH) levels, with incidences of 92.4 and 95.5% in the CMAB807 and denosumab groups, respectively. No clinically meaningful differences were observed in safety and immunogenicity between CMAB807 and denosumab. Conclusion: CMAB807 represents a new potential treatment option for patients with osteoporosis. Clinical Trial Registration: https://clinicaltrials.gov (Registration No. NCT03925051), http://www.chinadrugtrial/org.cn/index.html (Registration No. CTR20190800).


Ternary photovoltaic blends incorporating an all-conjugated donor-acceptor diblock copolymer.
We present a new fully conjugated diblock copolymer, P3HT-b-PFTBTT, containing donor and acceptor blocks with suitably positioned energy levels for use in a solar cell. This is the first block copolymer to be based on an existing high-performance polymer:polymer blend. We observe phase separation of the blocks and self-assembly behavior. In ternary blends with the respective homopolymers the diblock copolymer introduces lateral nanostructure without restricting P3HT crystallization in the charge transport direction, resulting in standing lamellae. By adding the diblock to the homopolymer blend as a compatibilizer, we prevent phase separation at elevated temperatures and benefit from a dramatic increase in P3HT ordering, allowing us to demonstrate polymer blend photovoltaics where the nanostructure is thermodynamically, rather than kinetically, controlled.


Molecular characterization of B-cell epitopes for the major fish allergen, parvalbumin, by shotgun proteomics, protein-based bioinformatics and IgE-reactive approaches.
Parvalbumins beta (β-PRVBs) are the main fish allergens. The only proven and effective treatment for this type of hypersensitivity is to consume a diet free of fish. We present the molecular characterization of B-cell epitopes by shotgun proteomics of different β-PRVBs combined with protein-based bioinformatics and IgE-reactive approaches. The final goal of this work is to identify potential peptide vaccine candidates for fish allergy. Purified β-PRVBs from the main fifteen different fish species that cause allergy were analyzed by shotgun proteomics. Identified β-PRVBs peptide sequences and ninety-eight β-PRVB protein sequences from UniProtKB were combined, aligned and analyzed to determine B-cell epitopes using the Kolaskar and Tongaonkar algorithm. The highest rated predicted B-cell peptide epitopes were evaluated by ELISA using the corresponding synthetic peptides and sera from healthy and fish allergic patients. A total of 35 peptides were identified as B-cell epitopes. The top B-cell peptide epitopes (LKLFLQV, ACAHLCK, FAVLVKQ and LFLQNFV) that may induce protective immune responses were selected as potential peptide vaccine candidates. The 3D model of these peptides were located in the surface of the protein. This study provides the global characterization of B-cell epitopes for all β-PRVBs sequences that will facilitate the design of new potential immunotherapies. SIGNIFICANCE: This work provides the global characterization of B-cell epitopes for all β-PRVBs sequences by Shotgun Proteomics combined with Protein-based Bioinformatics and IgE-reactive approaches. This study will increase our understanding of the molecular mechanisms whereby fish allergens elicit allergic reactions and will facilitate the design of new potential peptide vaccine candidates.


Bionomics and systematics of the oriental Anopheles sundaicus complex in relation to malaria transmission and vector control.
The taxonomic history, distribution, bionomics, systematics, and vector control strategies for the Anopheles sundaicus complex are reviewed in relation to malaria epidemiology. The lack of data on the bionomics, insecticide resistance, and vector capacity, as well as the general lack of surveillance and monitoring of potential vector populations, make the development of targeted control measures problematic. It will be necessary to elucidate, characterize and identify all members of the complex to determine their distributions, disease relationships, ecologic relationships, and resistance to insecticides. This knowledge is essential for epidemiologic studies, the design and implementation of appropriate vector control measures, and the development of strategies for monitoring and assessing the potential risk of malaria outbreaks due to members of the complex.


Antibiotic Resistance Genes in Phage Particles from Antarctic and Mediterranean Seawater Ecosystems.
Anthropogenic activities are a key factor in the development of antibiotic resistance in bacteria, a growing problem worldwide. Nevertheless, antibiotics and resistances were being generated by bacterial communities long before their discovery by humankind, and might occur in areas without human influence. Bacteriophages are known to play a relevant role in the dissemination of antibiotic resistance genes (ARGs) in aquatic environments. In this study, five ARGs (blaTEM, blaCTX-M-1, blaCTX-M-9, sul1 and tetW) were monitored in phage particles isolated from seawater of two different locations: (i) the Mediterranean coast, subjected to high anthropogenic pressure, and (ii) the Antarctic coast, where the anthropogenic impact is low. Although found in lower quantities, ARG-containing phage particles were more prevalent among the Antarctic than the Mediterranean seawater samples and Antarctic bacterial communities were confirmed as their source. In the Mediterranean area, ARG-containing phages from anthropogenic fecal pollution might allow ARG transmission through the food chain. ARGs were detected in phage particles isolated from fish (Mediterranean, Atlantic, farmed, and frozen), the most abundant being β-lactamases. Some of these particles were infectious in cultures of the fecal bacteria Escherichia coli. By serving as ARG reservoirs in marine environments, including those with low human activity, such as the Antarctic, phages could contribute to ARG transmission between bacterial communities.


Fixation of 4-part fractures of the proximal humerus: Can we identify radiological criteria that support locking plates or IM nailing? Comparative, retrospective study of 107 cases.
No objective criteria exist to help surgeons choose between IM nailing and plate fixation for 4-part fractures of the proximal humerus. The goal of this study was to identify radiological criteria that would make one technique a better choice than the other. This was a comparative, multicentre, retrospective study of 54 cases of antegrade nailing and 53 cases of plating performed between 1st January 2009 and 31 December 2011 for 4-part fractures of the proximal humerus. All patients had a minimum radiological and clinical follow-up of 18 months. The functional outcomes were evaluated using the weighted Constant score; a poor result was defined as a weighted Constant score<70%. The following radiological criteria were evaluated during the preoperative assessment and at the last follow-up: initial displacement and reduction of humeral head and tuberosities; morphology of the medial column (i.e. calcar comminution, posteromedial hinge, size of metaphyseal head extension); occurrence of avascular necrosis (AVN). After an average follow-up of 42 months, the weighted Constant scores and rate of poor outcomes were 77% and 48% in the nail group and 81% and 38% in the plate group, respectively (ns). The humeral head was reduced into an anatomical position, valgus or varus in 57%, 30% and 13% of cases in the nail group, and 58%, 29% and 13% in the plate group, respectively. The tuberosities healed in an anatomical position in 72% of nail cases and 70% of plate cases (ns). Only the presence of a medial hinge preoperatively had an effect on the functional outcomes in the nail and plate groups: the weighted Constant scores (P=0.05) and rate of poor outcomes (P=0.02) were 82% and 52% in the nail group and 97% and 9% in the plate group, respectively. The complication rates were comparable: the rates of AVN and articular screw penetration were 17% and 11% in the nail group, and 15% and 11% in the plate group, respectively. The surgical revision rate was 18.5% in the nail group and 30% in the plate group. If the medial hinge is preserved, we recommend locking plate fixation. In other cases, either technique can be used as long as the general rules of internal fixation are applied: reduction of the tuberosities, varus correction and stabilization of the calcar area. IV, retrospective study.


What Do You Meme, Professor? An Experiment Using "Memes" in Pharmacy Education.
Memes are social or cultural constructs and ideas dispersed from person to person. The modern definition of memes applies to images, photographs, or videos shared on digital platforms juxtaposed with text that utilizes the emotion, meaning, or joke behind the original "meme" to communicate the author's message. Younger generations of learners are more prone to utilize digital and social media to distribute and consume information and use of these platforms has increased in modern classrooms. However, there are few examples of using memes for educational purposes, including student-generated content, and no known examples in pharmacy education. This commentary introduces the concept of a meme and describes an attempt to incorporate a student-generated meme assignment in a pharmacy course. Experiences and lessons learned are discussed as words of caution in incorporating and evaluating memes or other informal communication tools for educational purposes.


Consequences of teen dating violence: understanding intervening variables in ecological context.
Increasing attention has been given to the problem of teen dating violence with more research needed on mediating and moderating factors in the relationship between victimization and negative consequences. This article explores mental health and educational consequences of physical and sexual abuse by peers in a convenience sample of adolescents. Dating violence was associated with higher levels of depression, suicidal thoughts, and poorer educational outcomes. The use of alcohol and depression complicated the relationship between victimization and outcomes. Sex differences in patterns of perceived social support as a moderator were also examined with more significant effects for girls.


Use of isotopic analysis of vertebrae in reconstructing ontogenetic feeding ecology in white sharks.
We conducted stable 13C and 15N analysis on white shark vertebrae and demonstrated that incremental analysis of isotopes along the radius of a vertebral centrum produces a chronological record of dietary information, allowing for reconstruction of an individual's trophic history. Isotopic data showed significant enrichments in 15N with increasing sampling distance from the centrum center, indicating a correlation between body size and trophic level. Additionally, isotopic values verified two distinct ontogenetic trophic shifts in the white shark: one following parturition, marking a dietary switch from yolk to fish; and one at a total length of >341 cm, representing a known diet shift from fish to marine mammals. Retrospective trophic-level reconstruction using vertebral tissue will have broad applications in future studies on the ecology of threatened, endangered, or extinct species to determine life-long feeding patterns, which would be impossible through other methods.


Allelic composition of carotenoid metabolic genes in 13 founders influences carotenoid composition in juice sac tissues of fruits among Japanese citrus breeding population.
To enrich carotenoids, especially β-cryptoxanthin, in juice sac tissues of fruits via molecular breeding in citrus, allele mining was utilized to dissect allelic variation of carotenoid metabolic genes and identify an optimum allele on the target loci characterized by expression quantitative trait (eQTL) analysis. SNPs of target carotenoid metabolic genes in 13 founders of the Japanese citrus breeding population were explored using the SureSelect target enrichment method. An independent allele was determined based on the presence or absence of reliable SNPs, using trio analysis to confirm inheritability between parent and offspring. Among the 13 founders, there were 7 PSY alleles, 7 HYb alleles, 11 ZEP alleles, 5 NCED alleles, and 4 alleles for the eQTL that control the transcription levels of PDS and ZDS among the ancestral species, indicating that some founders acquired those alleles from them. The carotenoid composition data of 263 breeding pedigrees in juice sac tissues revealed that the phenotypic variance of carotenoid composition was similar to that in the 13 founders, whereas the mean of total carotenoid content increased. This increase in total carotenoid content correlated with the increase in either or both β-cryptoxanthin and violaxanthin in juice sac tissues. Bayesian statistical analysis between allelic composition of target genes and carotenoid composition in 263 breeding pedigrees indicated that PSY-a and ZEP-e alleles at PSY and ZEP loci had strong positive effects on increasing the total carotenoid content, including β-cryptoxanthin and violaxanthin, in juice sac tissues. Moreover, the pyramiding of these alleles also increased the β-cryptoxanthin content. Interestingly, the offset interaction between the alleles with increasing and decreasing effects on carotenoid content and the epistatic interaction among carotenoid metabolic genes were observed and these interactions complexed carotenoid profiles in breeding population. These results revealed that allele composition would highly influence the carotenoid composition in citrus fruits. The allelic genotype information for the examined carotenoid metabolic genes in major citrus varieties and the trio-tagged SNPs to discriminate the optimum alleles (PSY-a and ZEP-e) from the rest would promise citrus breeders carotenoid enrichment in fruit via molecular breeding.


An Uncommon Aflibercept Side Effect: Full Thickness Macular Hole Formation After Intravitreal Injections in Patients With Pre-existing Vitreomacular Traction.
Aflibercept is an intravitreally injected anti-vascular endothelial growth factor, commonly used in patients with several retinal pathologies, including neovascular age-related macular degeneration. We report a case series of three patients under treatment with an aflibercept regime for neovascular age-related macular degeneration, who were referred to vitreoretinal service between 2015-2016. In all cases, pre-existing vitreomacular traction was detected with an optical coherence tomography scan. All of them developed full-thickness macular hole after aflibercept intravitreal injections. The combined cataract and macular hole surgery was successful, with improvement in visual acuity. We suggest that dynamic alterations of the size of the pigment epithelium detachment resulting from intravitreal injections might intensify the pre-existing pathological adhesion of the vitreous-retinal interface and subsequently cause the formation of a full-thickness macular hole. Therefore, all practitioners treating patients with aflibercept intravitreal injections and pre-existing vitreomacular traction should be aware of the possible macular hole formation.


Behavior problems and mental health contacts in adopted, foster, and nonadopted children.
The implications of adoption for the emotional and behavioral adjustment of children have been an issue in child welfare for many years. Past research has suggested that adopted children are over-represented in mental health settings. In addition, some studies have suggested that adopted and nonadopted children differ on measures of social, emotional, behavioral, and cognitive functioning. The current study used data from a large, representative sample in the United States to examine whether adopted children are more likely to have had mental health contacts or emotional or behavioral problems than nonadopted children. Age of placement in the adoptive home was examined as a variable contributing to the adjustment of adopted children. Results suggest that adopted and foster children are more likely to have mental health contacts than nonadopted children. Results are mixed regarding whether adopted and foster children have more behavior problems than nonadopted children. However, significant differences between adopted, foster, and nonadopted children disappeared when a small group of influential cases were removed. This suggests that the differences seen between the groups reflect a small number of cases and are not representative of the groups of adoptees and foster children as a whole. The vast majority of adopted children showed patterns of behavior problems similar to those of nonadopted children. These results are discussed in relation to the past literature and areas for future research.


Reduced Self-Awareness Following a Combined Polar and Paramedian Bilateral Thalamic Infarction. A Possible Relationship With SARS-CoV-2 Risk of Contagion?
Reduced self-awareness is a well-known phenomenon investigated in patients with vascular disease; however, its impact on neuropsychological functions remains to be clarified. Importantly, selective vascular lesions provide an opportunity to investigate the key neuropsychological features of reduced self-awareness in neurocognitive disorders. Because of its rarity, we present an unusual case of a woman affected by a combined polar and paramedian bilateral thalamic infarction. The patient underwent an extensive neuropsychological evaluation to assess cognitive, behavioral, and functional domains, with a focus on executive functions. She was assessed clinically in the acute phase and after 6 months from the stroke, both clinically and by magnetic resonance imaging. The patient developed a cognitive impairment, characterised by prevalent executive dysfunction associated with reduced self-awareness and mood changes, in terms of apathy and depression. Such condition persisted after 6 months. In May 2020, the patient underwent the serology test in chemiluminescence to detect IgG antibodies against SARS-CoV-2. The result of the quantitative test highlighted a high probability of previous contact with the virus. We suggest that reduced self-awareness related to executive dysfunction and behavioral changes may be due to combined polar and paramedian bilateral thalamic lesion. Metacognitive-executive dysfunction affecting the instrumental abilities of everyday life might make people less able to take appropriate precautions, facilitating the risk of SARS-CoV-2 contagion.


Women's experiences and perceptions of women-centered care and respectful care during facility-based childbirth: A meta-synthesis.
The World Health Organization has recommended intrapartum care for a positive childbirth experience through respectful care based on women-centered care. This study aimed to explore women's experiences of facility-based childbirth to gain insights into their perceptions of women-centered care, including humanized childbirth and respectful maternity care during intrapartum care. Used the Joanna Briggs Institute method as the framework for this meta-synthesis, we searched the PubMed, EMBASE, CINAHL, PsycINFO, and LILCAS databases, and included qualitative studies and interviews of women's experiences and perceptions of women-centered care during facility-based childbirth published from 1990 to 2020 in English. Study quality was assessed using the Critical Appraisal Skills Programme checklist. NVivo software was used for data extraction and synthesis. There were 22 studies from 19 countries that met the established inclusion criteria. Five categories of experiences of facility-based childbirth and perceptions of women-centered care from the synthesized voices of women were generated: (i) value of women through childbirth; (ii) overwhelmed by unpleasant childbearing experiences; (iii) a sense of being respected and valued; (iv) a sense of being disrespected and abused; and (v) inadequate systems and resources. Our meta-synthesis indicated that respectful and helpful interaction between women and healthcare providers produced positive perceptions among women. This study emphasizes the importance of respectful interactions and intrapersonal experiences. Strong systems and positive environments lead to positive interactions between women and healthcare providers. Future studies need to consider cultural and economic differences in women-centered care and respectful care for childbirth in different contexts.


Granger causality vs. dynamic Bayesian network inference: a comparative study.
In computational biology, one often faces the problem of deriving the causal relationship among different elements such as genes, proteins, metabolites, neurons and so on, based upon multi-dimensional temporal data. Currently, there are two common approaches used to explore the network structure among elements. One is the Granger causality approach, and the other is the dynamic Bayesian network inference approach. Both have at least a few thousand publications reported in the literature. A key issue is to choose which approach is used to tackle the data, in particular when they give rise to contradictory results. In this paper, we provide an answer by focusing on a systematic and computationally intensive comparison between the two approaches on both synthesized and experimental data. For synthesized data, a critical point of the data length is found: the dynamic Bayesian network outperforms the Granger causality approach when the data length is short, and vice versa. We then test our results in experimental data of short length which is a common scenario in current biological experiments: it is again confirmed that the dynamic Bayesian network works better. When the data size is short, the dynamic Bayesian network inference performs better than the Granger causality approach; otherwise the Granger causality approach is better.


Transcriptional regulation of stilbene synthases in grapevine germplasm differentially susceptible to downy mildew.
To limit the impact of the downy mildew disease of grapevine and reduce the need to recur to chemical treatments, an effective strategy might be recovering adaptive resistance traits in both cultivated and wild V. vinifera germplasm. Considering that stilbenes represent the most important class of phytoalexins in the Vitaceae, the constitutive expression and transcriptional activation of all the functional members of the stilbene synthase gene family were analysed in a group of nine grapevine genotypes following artificial infection with the oomycete Plasmopara viticola, the causal agent of the disease. In addition, in the same genotypes we analyzed the expression of genes encoding for two transcription factors involved in the transcriptional regulation of the stilbene synthase genes, namely VvMYB14 and VvMYB15, and of genes encoding for chalcone synthases. Downy mildew incidence and severity ranged from nihil to high in the grapevine genotypes considered, being low to moderate in a subgroup of V. vinifera genotypes. The constitutive expression of the stilbene synthase genes as well as the extent of their transcriptional activation following P. viticola inoculation appeared to be inversely related to the proneness to develop disease symptoms upon infection. In a specular manner, following P. viticola inoculation all the chalcone synthase genes were up-regulated in the susceptible grapevine genotypes and down-regulated in the resistant ones. The infection brought by P. viticola appeared to elicit a co-ordinated and sequential transcriptional activation of distinct stilbene synthase genes subsets, each of which may be regulated by a distinct and specific MYB transcription factor. The present results suggest that the induction of stilbene biosynthesis may contribute to the basal immunity against the downy mildew of grapevine, thus representing an adaptive resistance trait to recover, in both cultivated and wild V. vinifera germplasm. During the early stages of P. viticola infection, an antagonistic interaction between flavonol and stilbene biosynthesis might occur, whose outcome might determine the subsequent extent of disease symptoms. Further studies are needed to decipher the possible regulatory mechanisms involved in the antagonistic crosstalk between these two metabolic pathways in resistant and susceptible genotypes in response to P. viticola.


Proactive schema based link lifetime estimation and connectivity ratio.
The radio link between a pair of wireless nodes is affected by a set of random factors such as transmission range, node mobility, and environment conditions. The properties of such radio links are continually experienced when nodes status balances between being reachable and being unreachable; thereby on completion of each experience the statistical distribution of link lifetime is updated. This aspect is emphasized in mobile ad hoc network especially when it is deployed in some fields that require intelligent processing of data information such as aerospace domain.


Electrochemical Signatures of Interface-Dominated Behavior in the Testing of Calcium Foil Anodes.
Fundamental research and practical assembly of rechargeable calcium (Ca) batteries will benefit from an ability to use Ca foil anodes. Given that Ca electrochemistry is considered a surface-film-controlled process, understanding the interface's role is paramount. This study examines electrochemical signatures of several Ca interfaces in a benchmark electrolyte, Ca(BH4)2/tetrahydrofuran (THF). Preparation methodologies of Ca foils are presented, along with Ca plating/stripping through either pre-existing, native calcium hydride (CaH2), or pre-formed calcium fluoride (CaF2) interfaces. In contrast to earlier work examining Ca foil in other electrolytes, Ca foils are accessible for reversible electrochemistry in Ca(BH4)2/THF. However, the first cyclic voltammetry (CV) cycle reflects persistent, history-dependent behavior from prior handling, which manifests as characteristic interface-derived features. This behavior diminishes as Ca is cycled, though formation of a native interface can return the CV to interface-dominated behavior. CaF2 modification enhances such interface-dominance; however, continued cycling suppresses such features, collectively indicating the dynamic nature of certain Ca interfaces. Cell configuration is also found to significantly influence electrochemistry. With appropriate preparation of Ca foils, the signature of interface-dominated behavior is still present during the first cycle in coin cells, but higher current density compared to three-electrode cells along with moderate cycle life are readily achievable.


Public acceptability of non-pharmaceutical interventions to control a pandemic in the UK: a discrete choice experiment.
To understand how individuals trade off between features of non-pharmaceutical interventions (eg, lockdowns) to control a pandemic across the four nations of the UK. A survey that included a discrete choice experiment. The survey design was informed using policy documents, social media analysis and input from remote think-aloud interviews with members of the public (n=23). A nationwide survey across the four nations of the UK using an online panel between 29 October and 12 December 2020. Individuals who are over 18 years old. A total of 4120 adults completed the survey (1112 in England, 848 in Northern Ireland, 1143 in Scotland and 1098 in Wales). Adult's preferences for, and trade-offs between, type of lockdown restrictions, length of lockdown, postponement of routine healthcare, excess deaths, impact on the ability to buy things and unemployment. The majority of adults are willing to accept higher excess deaths if this means lockdowns that are less strict, shorter and do not postpone routine healthcare. On average, respondents in England were willing to accept a higher increase in excess deaths to have less strict lockdown restrictions introduced compared with Scotland, Northern Ireland and Wales, respectively. In all four countries, one out of five respondents were willing to reduce excess deaths at all costs. The majority of the UK population is willing to accept the increase in excess deaths associated with introducing less strict lockdown restrictions. The acceptability of different restriction scenarios varies according to the features of the lockdown and across countries. Governments can use information about trade-off preferences to inform the introduction of different lockdown restriction levels and design compensation policies that maximise societal welfare.


C3b/iC3b deposition on Streptococcus pneumoniae is not affected by HIV infection.
Streptococcus pneumoniae is a common cause of infection in both HIV positive patients and those with complement deficiencies. We hypothesised that HIV positive individuals might exhibit reduced opsonisation of pneumococcus with complement due to reduced levels of S. pneumoniae specific IgG. We discovered no difference in C3 deposition on S. pneumoniae between HIV positive or negative individuals, and furthermore C3 deposition remained unchanged as HIV progressed towards AIDS. We found no correlation between C3 deposition on S. pneumoniae and CD4 cell count in HIV infected individuals. Hence we have demonstrated no failure of complement immunity in HIV positive patients.


Two types of spheroid bodies in the nigral neurons in Parkinson's disease.
Dendritic spheroid bodies (SBs) and Lewy bodies (LBs) were identified in comparable numbers in the substantia nigra pars compacta (SBC) of nine parkinsonian cases and one case of striatonigral degeneration but were not found in cases of Huntington's disease or neurologically normal controls. The immunohistochemical profile of the SBs in dystrophic dendrites of nigrostriatal dopaminergic neurons was remarkably similar to that of the LBs found within dendrites or free of the SNC neuropil. Both types of inclusions stained positively with antibodies to tyrosine hydroxylase, ubiquitin and microtubule-associated protein-2 (MAP2), and negatively for Tau-2, although they had different ultrastructural appearances. A few intracellular LBs were stained by antibodies to neurofilament proteins (NFs) 68, 160, and 200 kD, but dendritic SBs and extracellular LBs were not so stained. These data indicate that dendritic SBs and extracellular LBs may have a common molecular pathogenetic origin in Parkinson's disease. On the other hand, the SBs seen in the pars reticulata (SNR) and in the distal nigrostriatal axons even in control cases were generally stained by antibodies to NFs and ubiquitin but not to MAP2. This latter staining pattern in similar to that shown by SBs in the anterior horn in ALS and in the cerebellum of neurologically normal brains and is believed typical of axonal as opposed to dendritic SBs.


[Effects of different anesthesia methods on perioperative hemodynamics and ECG in old CHD patients].
To explore an optimal anesthesia method with less impact on hemodynamics and electrocardiogram (ECG) of old patients with coronary artery disease (CHD) during abdominal operation. The 133 CHD patients waiting for abdominal operation were randomly divided into continuous epidural anesthesia (EA) group, general anesthesia group (GA) and combined spinal-epidural anesthesia (CSEA) group. Continuous monitoring was carried out during operation and mean arterial pressure (MAP), heart rate (HR), oxygen saturation (SaO2), abnormal ECG were measured respectively at different time for comparison and the differences of the above hemodynamic parameters and abnormal ECG features were compared among the 3 groups. At the 15 min and 30 min point after anesthesia, SaO2 in GA group was significantly increased compared to that in the EA group (P < 0.05). At 15 min, 30 min and 60 min point after anesthesia, MAP in CSEA group was significantly increased compared to that in the EA group (P < 0.05). At 30 min point after anesthesia, HR in CSEA group was increased significantly compared to the EA group (P < 0.05). At 15 min and 30 min point after anesthesia, SaO2 in the CSEA group was increased significantly compare to the EA group (P < 0.05). Compared with preanesthesia (T0) in EA group, MAP, HR and SaO2 decreased significantly at 15, 30 and 60 min after anesthesia (P < 0.05). The fluctuation of the three parameters in GA and CSEA groups were relatively small (P > 0.05). As well as the comparison of abnormal ECG among the 3 groups was concerned, the incidence of ST-T changes in GA and CSEA groups were significantly lower than that in EA group at the time of 15 min, 30 min and 60 min after anesthesia and at the time of surgery termination (P < 0.05, P < 0.01). The incidence of arrhythmia in GA and CSEA groups were significantly lower than that in EA group at the time of 15 min, 30 min and 60 min after anesthesia (P < 0.05, P < 0.01). Compared with T0 in the same group, the incidences of ST-T changes and arrhythmia in GA or CSEA group at the time of 15, 30 and 60 min after anesthesia and at the time of surgery termination were significantly lower than that before anesthesia (P < 0.05, P < 0.01). GA and CSEA have less impact on hemodynamics and have smaller incidence of abnormal ECG of old CHD patients with abdominal operation.


Association between e-cigarette use and food insecurity among low-income adults.
Previous research quantifying the relationship between tobacco use and food insecurity has focused on cigarette smoking. E-cigarette use has become popular in recent years. Drawing on large, population-based survey data, this study augments the previous research, considering the association of e-cigarette use with food insecurity among low-income adults. We analysed data from the California Health Interview Survey in 2014-2019. The study sample consisted of 25 948 respondents aged 18-64 who lived in low-income (<200% of the Federal Poverty Level) households. Multivariable logistic regression models were estimated to examine the associations of e-cigarette use as well as dual use of e-cigarettes and cigarettes with food insecurity. Of California low-income adults, 6.4% identified as current e-cigarette users (3.0% dual users of e-cigarettes and cigarettes, and 3.4% sole e-cigarette users) and 43.0% reported food insecurity. After controlling for confounding factors, food insecurity was significantly more likely to be reported among current e-cigarette users (adjusted OR (AOR)=1.67; 95% CI 1.25 to 2.23) compared with never e-cigarette users, and among dual users (AOR=2.21; 95% CI 1.63 to 3.00), current sole e-cigarette users (AOR=1.66; 95% CI 1.15 to 2.40), and current sole cigarette smokers (AOR=1.46; 95% CI 1.22 to 1.76) compared with never tobacco users. The odds of food insecurity among dual users were significantly greater than sole cigarette smokers but not statistically different from sole e-cigarette users. Using e-cigarette is an associated risk factor for food insecurity among low-income adults. Dual use of e-cigarettes and cigarettes has a significantly greater risk of food insecurity compared with smoking cigarettes alone.


Long-term preservation of whole blood samples for flow cytometry analysis in normal and HIV-infected individuals from Africa.
A whole blood method requiring less than 4 ml of heparinized blood was developed to assess the practicality of preparing whole blood samples that could be easily stored, transported and readily used to determine the lymphocyte phenotypes and proliferation responses of individuals from remote areas who are infected with the human immunodeficiency virus. Minor modifications in standard whole blood procedure for lymphocyte phenotyping have significantly increased the stability of light scatter and fluorescence intensity of the cells for subsequent flow cytometry (FC) analysis. These changes include removal of lysis solution prior to fixation, fixation of monoclonal antibody-stained cells in 1% paraformaldehyde for 30 minutes and storage of fixed samples in medium containing 1% bovine serum albumin. Lymphocyte subsets and their functional subsets could reliably be determined on samples stored for up to 4 weeks. Further, blood samples could be kept at room temperature for up to 96 hours or at ambient temperature during transportation from Africa before staining for FC without affecting their quantitation. While samples could be processed for FC analysis under field-laboratory conditions, proliferation assays could only be performed on samples that were transported within 48 hours of their collection. The whole blood method saves time and expense and decreases the volumes of blood required to perform phenotypic analysis and functional assays on specimens collected in remote areas.


SiPep: a system for the prediction of tissue-specific minor histocompatibility antigens.
Approximately 50 years ago it was found that inbred strains of mice were able to reject tumours and skin grafts from major histocompatibility complex (MHC) identical donors. They proposed that additional transplantation antigens must exist outside the MHC. These were described as minor histocompatibility antigens (mHAgs). Since then, related studies in humans have identified 16 human mHAgs. The aim of this work is to increase the number of known mHAgs by prediction of candidate minor histocompatibility loci by identifying coding single nucleotide polymorphisms (SNPs) where the amino acid variation lies within an MHC-binding peptide and alters the ability of that peptide to bind. We have developed an algorithm called SiPep which uses peptide sequences derived from the flanking regions of known non-synonymous SNPs, various MHC-binding and proteolytic cleavage evaluation methods and protein expression data to predict mHAgs. We have processed 45094 SNPs using the SiPep algorithm and have stored the results in a database called SNPBinder. The facilities to process submitted proteins through the SiPep algorithm as well as the SNPBinder database are available to the public. A set of peptides that are predicted as possible mHAgs by the SiPep algorithm have been tested using refolding assays and gel filtration and the results are presented in this paper. The SiPep tools and SNPBinder database are available free of charge via the internet. An HTML interface providing search facilities can be found at the following address: http://www.sipep.org/.


A tangential radiographic projection for investigation of the equine temporomandibular joint.
To (1) describe a tangential radiographic projection of the equine temporomandibular joint (TMJ) and (2) optimize the radiographic angle and determine its use in standing sedated horses. Descriptive study. Cadaveric equine skulls (n=11); 8 horses with a history of quidding or headshaking. Tangential radiographic projections were taken of a TMJ of a cadaveric skull before and after intra-articular injection of radiographic contrast. Additional tangential radiographic projections were taken after TMJ dissection and placement of a wire along the articular surface of the mandibular condyle. Subsequently, 3 tangential radiographs were taken of both TMJs of 10 skulls at 75 degrees , 70 degrees , and 65 degrees to the dorsal plane (Rt/Le15Cd70D-Le/RtRVO). Each of the 3 images for each TMJ was ranked by 4 observers who were unaware of the projection angle. Interobserver variation was calculated using a Friedman analysis of variance and significance of the most prevalent angle with a 1-sample repeated measures test. Tangential radiographic projections of both TMJs were then taken of 8 standing sedated horses. Tangential radiographic projections allowed the lateral half of the TMJ to be viewed without superimposition of other structures and the anatomic orientation was determined. A 70 degrees projection to the dorsal plane was ranked as significantly better than other views (P<.001). There was no significant interobserver variation and the technique was safely performed in standing sedated horses with excellent image quality obtained. Tangential radiography of the TMJ may complement and add to information obtained from clinical examination and ultrasonography before referral for more advanced imaging techniques.


Ki-67, oestrogen receptor, and progesterone receptor proteins in the human rete ovarii and in endometriosis.
To examine proliferative activity using the Ki-67 protein, oestrogen receptor protein, and progesterone receptor protein expression in the rete ovarii, and to make comparisons with their expression in endometriosis. Immunohistochemistry was used to study the rete ovarii in 24 cases and endometriosis in seven cases, using antibodies to Ki-67 protein (growth fraction (GF) quantified using a point score method) and oestrogen receptor and progesterone receptor (quantified using the H score method). There was no evidence of a significant difference in the Ki-67 protein, oestrogen receptor, and progesterone receptor in the rete ovarii in different phases of the menstrual cycle (proliferative phase: GF = 1.052, oestrogen receptor H score = 13.4, progesterone receptor H score = 15.32; secretory phase: GF = 0.736, oestrogen receptor H score = 7.5, progesterone receptor H score = 1.84). The expression of all three proteins was greater in the foci of endometriosis (GF = 6.99, oestrogen receptor H score = 152.02, progesterone receptor H score = 127.36) than in the rete ovarii (p < 0.0005-0.0008, Mann-Whitney U test). There is a low rate of cellular proliferation in the rete ovarii and this structure shows less responsiveness to hormone stimulation than foci of endometriosis. These differences may provide a useful tool to distinguish the rete ovarii from endometriosis in cases of diagnostic difficulty.


The Interoceptive Sensitivity and Attention Questionnaire: Evaluating Aspects of Self-Reported Interoception in Patients With Persistent Somatic Symptoms, Stress-Related Syndromes, and Healthy Controls.
This study aimed to validate the Interoceptive Sensitivity and Attention Questionnaire (ISAQ), a 17-item self-report measure assessing sensitivity and attention to interoceptive signals. In study 1, exploratory and confirmatory factor analysis was performed in a student convenience sample (n = 1868). In study 2, ISAQ data of a healthy sample (n = 144) and various patient groups experiencing stress-related syndromes (overstrain, n = 63; burnout, n = 37; panic disorder [PD]. n = 60) and/or persistent somatic symptoms in daily life (irritable bowel syndrome, n = 38; fibromyalgia and/or chronic fatigue syndrome, n = 151; medically unexplained dyspnea [MUD], n = 29) were compared. Three subscales were revealed: (F1) sensitivity to neutral bodily sensations, (F2) attention to unpleasant bodily sensations, and (F3) difficulty disengaging from unpleasant bodily sensations. Overall, patients with fibromyalgia and/or chronic fatigue syndrome and patients with MUD scored significantly higher on F1 (p = .009 and p = .027, respectively) and F2 (p = .002 and p < .001, respectively) than healthy controls. Patients with PD had higher scores on subscales F2 (p < .001) and F3 (p < .001) compared with healthy controls, as well as higher scores on F2 compared with all other patient groups (pPD versus MUD = .008; all other p values < .001). Interoceptive sensibility-the self-reported aspect of interoception-is not a homogeneous or unitary construct. The subscales of the ISAQ differentiate healthy controls from patients with persistent somatic and/or stress-related complaints in daily life and distinguish different patient groups. The ISAQ can be used as a concise, reliable, and clinically relevant research tool to further disentangle adaptive and maladaptive aspects of interoceptive ability.


Phenotypic and growth characterization of human mesenchymal stem cells cultured from permanent and deciduous teeth.
A step-by-step approach to harvesting stem cells from the pulp of permanent and deciduous teeth, the problems faced during culture, and the differences in the growth properties and morphology of cells obtained from both the sources has been discussed as a precursor to the use of these cells in therapy. To isolate, culture, and study the morphology and growth characteristics of mesenchymal stem cells from the dental pulp of permanent teeth (dental pulp stem cells; DPSC) and exfoliated deciduous teeth (stem cells from human exfoliated deciduous; SHED). Cell culture study carried out at the Department of Oral and Maxillofacial Pathology, Ragas Dental College and Hospital, Chennai. Fifteen permanent teeth and thirteen deciduous teeth from ten subjects were used. The growth characteristics and phenotype of cultured DPSCs and SHED were studied from the fourth passage on 24-well plates. Data analysis was done using SPSS ® version 10.05. Linear regression analysis was performed to derive the slope from growth curves and Mann-Whitney U test was performed to compare the fibroblastoid: epithelioid cell ratio between permanent and deciduous tooth pulp groups. Protocol for the culture of DPSC and SHED was standardized. DPSC and SHED populations were morphologically distinct. The cells from permanent tooth pulp showed a higher proportion of spindle-shaped fibroblastoid cells, whereas deciduous pulp culture showed a higher proportion of epithelioid cells. The seeding efficiency of DPSC - 88.9% (14 th permanent tooth pulp) and 91.7% (15 th permanent tooth pulp) was higher as compared to SHED - 84.25% (10 th deciduous tooth pulp). Permanent and deciduous teeth are both viable sources of stem cells. The permanent teeth were easier to culture because of a lower chance of contamination with oral microflora. The growth characteristics of the cells obtained from both these sources were similar. However, there was a difference in the ratio of fibroblastoid cells to epithelioid cells between the cultures obtained from the permanent and deciduous teeth.


Polymer translocation through a gradient channel.
The translocation of polymer through a channel with a gradient interaction between the polymer and the channel is studied. The interaction is expressed by E = E0 + kx, where E0 is the initial potential energy at the entrance, x is the position of the monomer inside the channel, and k is the energy gradient. The mean first passage time τ is calculated by using Fokker-Planck equation for two cases (1) N > L and (2) N < L under the assumption that the diffusion rate D is a constant, here N is the polymer length and L is the length of channel. Results show that there is a minimum of τ at k = k(c) for both cases, and the value kc is dependent on E0 and driving force f. At large f, the scaling relation τ ∼ N is observed for long polymer chains. But the scaling relation is dependent on the energy gradient k for an unforced driving translocation.


Electrophysiologic characterization of an organic anion transporter cloned from winter flounder kidney (fROAT).
The two-electrode voltage clamp technique was used to demonstrate translocation of p-aminohippurate (PAH) and related compounds such as loop diuretics in Xenopus laevis oocytes expressing the renal organic anion transporter from winter flounder kidney (fROAT). In fROAT-expressing oocytes, PAH (0.1 mM) induced a depolarization of 4.2 +/- 0.4 mV and at a holding potential of -60 mV an inward current of -22.6 +/- 3.5 nA. PAH-induced current and the current calculated from [3H]-PAH uptake were of similar magnitude. Depolarization, inward current, and current-to-uptake relation indicated exchange of the monovalent PAH with a divalent anion, possibly alpha-ketoglutarate (alpha-KG), causing net efflux of one negative charge. The kinetic analysis of PAH-induced currents revealed that translocation is dependent on membrane potential, saturable with an apparent Km of 58 +/- 8 microM, and sensitive to probenecid and furosemide. In contrast to probenecid and furosemide, the loop diuretics bumetanide, ethacrynic acid, and tienilic acid and the nephrotoxic mycotoxin ochratoxin A elicited inward currents indicating translocation through fROAT. Substrate-dependent currents provide a tool to elucidate the structure/function relationship of the renal organic anion transporter.


Cerebellar projections to the somatic pretectum in the cat.
Neurons in the somatic pretectum receive input from the dorsal column nuclei (DCN) and project to a comparable "somatic" portion of the dorsal accessory nucleus of the inferior olive (DAO). This somatic DAO is reciprocally connected with the anterior interpositus nucleus of the cerebellum. One question that arises is whether this circuitry is further controlled by an output specifically from the anterior interpositus nucleus to the somatic pretectum. Wheatgerm agglutinin conjugated to horseradish peroxidase was injected into various parts of the cat pretectum. Injection sites were interpreted as including the somatic pretectum if neurons in the DCN were retrogradely labeled and if anterograde terminal labeling occurred in somatic DAO. The locations of retrogradely labeled neurons within the deep cerebellar nuclei were then compared in cases in which the injection sites included or excluded the somatic pretectum. In all cases in which the injection site included the somatic pretectum, retrogradely labeled neurons were observed in the anterior interpositus nucleus as well as in the lateral cerebellar nuclei. In some of these cases, neurons in the posterior interpositus and medial nuclei were also labeled. In contrast, in cases in which the pretectal injection site was located outside or at the border of the somatic pretectum, retrogradely labeled neurons were observed only in the lateral, posterior interpositus, and medial nuclei. Thus, the somatic pretectum appears to receive input primarily from neurons in the anterior interpositus nucleus, along with some input from neurons in the lateral nucleus. These results provide additional evidence for a pathway through the DCN in which sequentially processed somatic information has access to and is modulated by cerebellar circuitry. The existence of such a pathway supports the conclusion that neurons in the DCN convey somatic information important not only for cutaneous, kinesthestic, and other bodily sensations, but also for the control of movement.


Developing job-related preplacement medical examinations.
Federal regulations prohibiting discrimination in hiring require that employment selection procedures to evaluate applicants be based on job-related criteria. The preplacement physical examination used in employment, particularly in the placement of handicapped persons, must also be conducted in a job-related manner. This paper discusses the development and use of the physical examination in selecting and placing applicants for jobs in the workplace with special reference to handicapped persons and disabled veterans. It presents and justifies a method of performing these examinations in a manner consistent with humanistic and business goals as well as the goals of federal regulatory agencies prohibiting employment discrimination.


Vaccination against hydatid disease.
Hydatid disease is a parasitic infection that causes widespread human morbidity and mortality. Livestock animals, particularly sheep, are involved in the parasite's lifecycle. A defined antigen vaccine has been developed which can prevent hydatid infection in sheep. The vaccine has been shown to be highly effective in animal trials, with almost complete immunity persisting for more than a year after vaccination. Use of the vaccine in livestock may decrease transmission of the parasite and, indirectly, reduce the incidence of infections in humans. In some regions animal vaccination or other hydatid control measures are unlikely to be applicable. In these areas, direct vaccination of humans against hydatid infection may be the only practical option for disease prevention. The extraordinary effectiveness of the hydatid vaccine in the parasite's natural animal hosts singles this vaccine out as having perhaps the greatest potential for development of the first effective human vaccine against a parasitic disease.


Injury risk of nonpowder guns.
Nonpowder guns (ball-bearing [BB] guns, pellet guns, air rifles, paintball guns) continue to cause serious injuries to children and adolescents. The muzzle velocity of these guns can range from approximately 150 ft/second to 1200 ft/second (the muzzle velocities of traditional firearm pistols are 750 ft/second to 1450 ft/second). Both low- and high-velocity nonpowder guns are associated with serious injuries, and fatalities can result from high-velocity guns. A persisting problem is the lack of medical recognition of the severity of injuries that can result from these guns, including penetration of the eye, skin, internal organs, and bone. Nationally, in 2000, there were an estimated 21840 (coefficient of variation: 0.0821) injuries related to nonpowder guns, with approximately 4% resulting in hospitalization. Between 1990 and 2000, the US Consumer Product Safety Commission reported 39 nonpowder gun-related deaths, of which 32 were children younger than 15 years. The introduction of high-powered air rifles in the 1970s has been associated with approximately 4 deaths per year. The advent of war games and the use of paintball guns have resulted in a number of reports of injuries, especially to the eye. Injuries associated with nonpowder guns should receive prompt medical management similar to the management of firearm-related injuries, and nonpowder guns should never be characterized as toys.


Hindlimb torsional alignment changes in growing rabbits after patellar dislocation.
Torsional malalignment has been considered as a risk factor for patellar dislocation. But the influence of patellar dislocation for torsional alignment development remains unknown. The present study aims to investigate whether the torsional alteration of the hindlimb occurs after patellar dislocation in growing rabbits. In the present study, 30 one-month-old rabbits were included. The experimental group consisted of 30 left knees of rabbits which underwent patellar lateral dislocation. The control group consisted of 30 right knees of the rabbits which no surgical procedure was performed. The Computed Tomography (CT) scan was performed after the surgery and at the point the rabbits were skeletal mature (5 months post-surgery). The angles of femoral version and tibial torsion were measured using a three-dimensional method and analyzed between the experimental group and the control group. After the surgery, the femoral version and tibial torsion in the experimental and control group were not significantly different. However, 5 months after surgery, the angle of femoral version in the experimental group (-5.50 ± 6.13°) was significantly different from that in the control group (-10.90 ± 4.74°) (P < 0.05). But the angle of tibial torsion in the experimental group (7.17 ± 7.25°) and control group (4.47 ± 6.34°) were not significantly different (P = 0.144). From this study, patellar dislocation can lead to alteration of femoral version in growing rabbits. So patellar dislocation may affect on lower extremity alignment. These findings may develop pathology and etiology of patellar dislocation.


Electrocardiographic and histopathological characterizations of diabetic cardiomyopathy in rats.
Diabetes is a clinical condition that is associated with insulin deficiency and hyperglycemia. Cardiomyopathy, retinopathy, neuropathy, and nephropathy are well known complications of the elevated blood glucose. Diabetic cardiomyopathy is a clinical disorder that is associated with systolic and diastolic dysfunction along with cardiac fibrosis, inflammation, and elevated oxidative stress. In this study, diabetes was induced by intraperitoneal injection of streptozotocin (STZ) 50 mg/kg. We determined the plasma levels of cardiac troponin-T (cTnT) and creatinine kinase MB (CK-MB) by ELISA. Diabetic rats showed abnormal cardiac architecture and increased collagen production. Significant elevation in ST-segment, prolonged QRS, and QT-intervals and increased ventricular rate were detected. Additionally, diabetic rats showed a prolongation in P wave duration and atrial tachyarrhythmia was observed. Plasma levels of cTnT and CK-MB were elevated. In conclusion, these electrocardiographic changes (elevated ST-segment, prolonged QT interval, and QRS complex, and increased heart rate) along with histopathological changes and increased collagen formation could be markers for the development of diabetic cardiomyopathy in rats.


A modified protocol for isolation and purity evaluation of a staphylococcal acidic polysaccharide by chromatography and capillary electrophoresis.
The extracellular slime of Staphylococcus epidermidis contains, amongst various macromolecules, an acidic polysaccharide (PS) of a molecular mass of 20 kDa with significant antigenic and biological properties. The isolation procedure used so far includes multiple fractionations in anion-exchange chromatographic columns before its final purification by gel filtration chromatography. This protocol is laborious, time-consuming and includes the risk of unnecessary loss of PS quantities. Because of the significance of this PS, a modified protocol resulting in an easier and quicker isolation procedure was developed. Furthermore, identification, purity, charge density and molecular integrity of the isolated polysaccharide were evaluated by a reverse-polarity capillary electrophoresis method.


Iron chelation abrogates excessive formation of hydroxyl radicals and lipid peroxidation products in monocytes of patients with Eales' disease: direct evidence using electron spin resonance spectroscopy.
Eales' disease (ED) is an idiopathic retinal vasculitis condition, which affects the retina of young adult males. Retinal changes include perivasculitis, non-perfusion and neovascularization. Disruption of blood-retinal barrier (BRB) is the common feature in intra-ocular inflammatory diseases. Disruption of BRB results in vascular hyper permeability and infiltration of circulating leukocytes into the retinal parenchyma. Monocyte (MC) activation results in oxidant thrust and subsequent tissue damage. This has been reported in various intra-ocular inflammatory diseases such as uveitis and Behcet's disease. However, there are no such reports available in ED. Hence in the present study we have investigated the role of MC activation and hydroxyl radicals (OH) production and its possible involvement in promoting the development of retinal vasculitis in patients with ED. Twelve patients with ED and twelve healthy volunteers were recruited for the study. MC was separated from their peripheral blood. MC from patients with ED and control subjects was stimulated with phorbol-12-myristate-acetate (PMA) and OH generated was analyzed using an electron spin resonance spectrometer (ESR). Superoxide dismutase (SOD), thiobarbituric acid reactive substances (TBARS), and iron content was determined in MC to assess the oxidant thrust and antioxidant defense. OH generation was elevated in MC from patients with ED, which coincided with diminished SOD activity and elevated levels of iron and TBARS, when compared with healthy control subjects. OH generation was abrogated when MC from ED were co-incubated with PMA and iron chelators such as diethylenetriaminepentacetic acid (DTPA) and desferrioxamine. Iron chelation also inhibited TBARS accumulation restored SOD activity in MC of patients with ED. For the first time we have demonstrated the production of OH generation in MC of patients with ED using ESR. Further we have shown the beneficial effect of iron chelation in mitigating free radical mediated changes in cellular metabolism. Based on our findings, we provide further evidence for the role of oxidant thrust in promoting retinal tissue damage in patients with ED.


Discovery and characterization of cadherin domains in Saccharophagus degradans 2-40.
Saccharophagus degradans strain 2-40 is a prominent member of newly discovered group of marine and estuarine bacteria that recycle complex polysaccharides. The S. degradans 2-40 genome codes for 15 extraordinary long polypeptides, ranging from 274 to 1,600 kDa. Five of these contain at least 52 cadherin (CA) and cadherin-like (CADG) domains, the types of which were reported to bind calcium ions and mediate protein/protein interactions in metazoan systems. In order to evaluate adhesive features of these domains, recombinant CA doublet domains (two neighboring domains) from CabC (Sde_3323) and recombinant CADG doublet domains from CabD (Sde_0798) were examined qualitatively and quantitatively for homophilic and heterophilic interactions. In addition, CA and CADG doublet domains were tested for adhesion to the surface of S. degradans 2-40. Results showed obvious homophilic and heterophilic, calcium ion-dependent interactions between CA and CADG doublet domains. Likewise, CA and CADG doublet domains adhered to the S. degradans 2-40 surface of cells that were grown on xylan from birch wood or pectin, respectively, as a sole carbon source. This research shows for the first time that bacterial cadherin homophilic and heterophilic interactions may be similar in their nature to cadherin domains from metazoan lineages. We hypothesize that S. degradans 2-40 cadherin and cadherin-like multiple domains contribute to protein-protein interactions that may mediate cell-cell contact in the marine environment.


Long-term outcomes of the 'primary extension technique' in the prevention of Steal syndrome.
To report our 13 years of experience with the 'primary extension technique' for the prevention of dialysis-associated steal syndrome. All diabetic patients undergoing upper arm autogenous elbow fistula formation using the primary extension technique between September 2001 and September 2014 at a single centre were included. At follow-up all patients were evaluated for patency, adequacy of needling and the presence or absence of steal symptoms. In primary extension technique, the fistula is formed by anastomosing the median cubital vein with the proximal radial or ulnar artery just below the brachial artery bifurcation. In total, 64 operations of the primary extension technique were included in this study. All patients were diabetic. Primary failure was 5%, follow-up 23-84 months. Nine patients (14%) developed cephalic vein thrombosis. In these cases, the basilic vein was successfully transposed to the existing fistula. In eight patients (12.5%), the cephalic vein required superficialisation. In three patients, the flow was preferentially into the basilic vein with poor maturation of cephalic vein. Of these three patients, there was a small proximal cephalic vein in one patient and stenosis in the other two patients. One patient who developed dialysis-associated steal syndrome is included in the results as they were listed for primary extension technique fistula formation but in fact did not have their fistula formed using primary extension technique. Instead, the anastomosis was formed proximal to the bifurcation of the brachial artery. Symptoms improved with revision of the fistula. Our 13-year experience demonstrates that the primary extension technique is a safe and effective procedure for fistula formation. Patency rates are comparable to brachio-cephalic and brachio-basilic fistulas and primary extension technique is effective in the prevention of dialysis-associated steal syndrome.


Prevalence of liver injury in patients with coronavirus disease 2019 (COVID-19) : a systematic review and meta-analysis.
The coronavirus disease 2019 (COVID-19) represents a public health emergency of international concern, causing thousands of deaths worldwide. We performed a systematic review with meta-analysis in order to investigate the prevalence of COVID-19-induced liver injury. We searched MEDLINE, Scopus, Web of Science and the Cochrane Library, for studies reporting laboratory data about COVID-19 patients, with last update on 25th March 2020. The primary outcome was the pooled prevalence of COVID- 19-induced liver damage, mainly represented by increase in serum transaminases and bilirubin. The secondary outcome was the description of abnormalities in serum albumin and prothrombin time (PT). We focused on laboratory data only on hospital admission, and adopted random-effects model for meta-analysis. Eleven studies were eligible for meta-analysis. Out of 793 included patients, the pooled prevalence of COVID-19-related liver damage was 22.17% (95% CI 17.64 to 27.07), mostly indicated by hypertransaminasemia. Serum bilirubin was increased in 5.53% (95% CI 3.60 to 7.85) of cases. Abnormal serum albumin was observed in 78.92% (95% CI 39.82 to 99.56), and increased PT value in 19.98% (95% CI 2.49 to 78.23), but these results derived from significantly heterogeneous studies. COVID-19-induced liver injury must not be ignored, as it is observed in one fifth of infected patients. Prospective studies evaluating liver function during the course of COVID-19 are needed to provide a complete overview of hepatic involvement during this viral infection.


Tsetse Bloodmeal Analyses Incriminate the Common Warthog Phacochoerus africanus as an Important Cryptic Host of Animal Trypanosomes in Smallholder Cattle Farming Communities in Shimba Hills, Kenya.
Trypanosomes are endemic and retard cattle health in Shimba Hills, Kenya. Wildlife in the area act as reservoirs of the parasites. However, wild animal species that harbor and expose cattle to tsetse-borne trypanosomes are not well known in Shimba Hills. Using xeno-monitoring surveillance to investigate wild animal reservoirs and sources of trypanosomes in Shimba Hills, we screened 696 trypanosome-infected and uninfected tsetse flies for vertebrate DNA using multiple-gene PCR-High Resolution Melting analysis and amplicon sequencing. Results revealed that tsetse flies fed on 13 mammalian species, preferentially Phacochoerus africanus (warthogs) (17.39%, 95% CI: 14.56-20.21) and Bos taurus (cattle) (11.35%, 95% CI: 8.99-13.71). Some tsetse flies showed positive cases of bloodmeals from multiple hosts (3.45%, 95% CI: 2.09-4.81), including warthog and cattle (0.57%, 95% CI: 0.01-1.14). Importantly, tsetse flies that took bloodmeals from warthog had significant risk of infections with Trypanosoma vivax (5.79%, 95% CI: 1.57-10.00), T. congolense (7.44%, 95% CI: 2.70-12.18), and T. brucei sl (2.48%, 95% CI: -0.33-5.29). These findings implicate warthogs as important reservoirs of tsetse-borne trypanosomes affecting cattle in Shimba Hills and provide valuable epidemiological insights to underpin the parasites targeted management in Nagana vector control programs in the area.


Endothelin-a receptor in rat skeletal muscle microvasculature.
Although the effect of endothelin-1 (ET-1) on vascular tone has been studied extensively at the arterial/arteriolar level, little is known about the direct effect of ET-1 at the level of the capillary. Using intravital microscopy, we determined capillary red blood cell velocity and arteriolar diameter responses to ET-1, ET(A)-receptor blocker BQ-123, and ET(B)-receptor blocker BQ-788 applied locally on capillaries in rat extensor digitorum longus (EDL) muscle. Using immunohistochemistry, we examined capillaries in this muscle and microvascular endothelial cells isolated from this muscle for immunoreactivity with ET(A)-receptor antibody. ET-1 (10(-9) to 10(-5) M in micropipette) caused quick reductions (i.e., within several seconds), whereas BQ-123 (10(-8) to 10(-4) M) and BQ-788 (10(-6) and 10(-4) M) caused quick increases, in both velocity and diameter. Capillaries and endothelial cells showed ET(A)-receptor immunoreactivity. We conclude that the microvasculature of the rat EDL muscle is sensitive to ET-1 and its receptor blockers and that the ET(A) receptor may be present in the capillary wall of this muscle, including the endothelium.


[The decision to extract in orthodontics].
Serial extractions of premolars are submitted, in the present state of the contemporary orthodontics, in opposition to the non-extraction treatments (maxillary expansion, molar distancing...). The choice depends on many parameters including the severity and the nature of the malocclusion, the age and the morphological type of the patient and also the "orthodontic philosophy" relating to the techniques used by each orthodontist. The indications and contraindications of these teeth removals are explained showing the benefits and the disadvantages in different cases. "Orthodontics extractions" of other teeth (2nd bicuspid, 1st and 2nd molar, incisor) are also discussed.


Measurement of volume changes in mouse spermatozoa using an electronic sizing analyzer and a flow cytometer: validation and application to an infertile mouse model.
The importance of sperm volume has recently been highlighted in a knockout mouse model in which infertility was caused by defects in volume reguiation, which led to sperm transport failure in the female tract. Inhibition of volume regulation by human sperm, resulting in failure of penetration of cervical mucus in vitro, has also been reported. The present work aims to establish a sensitive and convenient method for monitoring changes in sperm volume for functional studies. Mature murine sperm obtained from the cauda epididymidis were analyzed by flow cytometry for their forward and side (90 degrees C) scatter of a 488-nm excitation wavelength laser, and the data were compared with volumes measured by electronic sizing using a Coulter counter. Changes in cell volume were induced by releasing or diluting sperm into culture media of various osmolalities (208-520 mmol/kg). Forward scatter signal (FSS) intensity correlated well with volume measurement obtained by a Coulter counter (R =.83; P <.001), confirming that FSS reflects Coulter counter findings as for somatic cells. Sperm swelling was also induced by the presence of quinine, a wide-spectrum channel blocker, in a medium of 330 mmol/kg, which is similar to the osmolality of uterine fluid. The effect of quinine on sperm volume was more obvious when analyzed by flow cytometry than by electronic sizing. This effect was even more marked after dead sperm identified by fluorescent dye were eliminated from analysis using flow cytometry. Swelling was characterized by an increase in forward scatter and side scatter, generating a subpopulation of sperm that correlated well (R =.79; P <.0001) with the population of sperm exhibiting an angulation of the tail, which is a morphological manifestation of swollen murine sperm. Flow cytometric analysis revealed that infertile sperm released from the cauda epididymidis of c-ros knockout mice were significantly larger than those of fertile sperm from heterozygous mice. This finding directly substantiates the suggestion that infertile sperm are defective in their volume regulation. Laser scatter analysis of viable murine sperm by flow cytometry offers a convenient and sensitive method for the study of sperm volume regulation.


Lymphocytes bearing the gamma delta T-cell receptor in normal human intestine and celiac disease.
Monoclonal antibodies to T-cell receptors were used to investigate the prevalence of the two distinct T-cell subpopulations (TCR alpha beta+ and TCR gamma delta+ cells) in the intestinal mucosa of children with celiac disease (gluten-sensitive enteropathy) as compared with normal intestinal mucosa. TCR gamma delta+ cells were rarely identified in the epithelium of human fetal or normal postnatal intestine and few were present in the lamina propria, whereas the number of distribution of TCR alpha beta+ cells closely resembled that of CD3+ cells. Compared with normal intestine, a significant increase in the number of CD3+, CD8+, TCR alpha beta+, and TCR gamma delta+ intraepithelial lymphocytes was present in celiac disease. Although the mucosal TCR gamma delta+ cells were less numerous than TCR alpha beta+ cells in celiac disease, there was a marked increase in the number of TCR gamma delta+ cells as compared with controls. The ligand recognized by the gamma delta T-cell receptor and the function of these cells have not been determined; however, these findings suggest a possible role for TCR gamma delta+ lymphocytes in mucosal immune responses and tissue injury as seen in celiac disease.


In vitro assessment of platelet storage lesion in leucoreduced random donor platelet concentrates.
Currently platelet concentrates (PC) are collected using different synthetic materials and different centrifugation/leucocyte-removal processes. Upon exposure to artificial surfaces and high centrifugation forces, blood cells can undergo various levels of stress-induced, cellular activation/fragmentation and release reactions which may not only influence the extent of the platelet storage lesion but may also contribute to poor clinical effectiveness of the PC and transfusion reactions. An array of assays, used for quality control of PC, was performed in two different groups of PC prepared from random donor plasma on days 1, 3 and 5 of storage. The group 1 PC were not leucoreduced while the group 2 PC underwent prestorage leucoreduction using a PL50E filter. As current recommendations for the evaluation of PC include the measurement of platelet activation, in this study CD62P on platelet membrane was measured. Furthermore, in vitro studies indicate that sHLA antigens may modulate immune competent cell function so, the presence of sHLA-1 in blood components is considered a marker of immunological reactivity and this, too, was measured. The levels of CD62P and sHLA-1 were significantly lower in leucoreduced PC than in non-leucoreduced ones. However, the overall rate of increase of sHLA-1 during storage was faster in the leucoreduced group of PC. No significant differences were detected regarding other assays of quality. Based on our findings, leucoreduced PC differ from non-leucoreduced ones in terms of some specific markers such as CD62P as a marker of platelet activation and sHLA-1 as a marker of immunological reactivity. Pre-storage leucofiltration, followed by storage in currently used plastic bags is a safe procedure for PC for up to 5 days. The available leucoreduction technologies are not, however, sufficiently robust to completely abrogate transfusions reactions, and improvements are required to reach the goal of optimised yield and minimal transfusion reactions with platelet therapy.


Premature infants in car seats: effect of sleep state on breathing.
Previous studies have shown that premature infants may be at risk for hypoxemia and bradycardia when placed in standard car seats. However, the relationship of such breathing abnormalities to sleep state have not been studied. The purpose of the present study was to investigate the effect of car seat positioning on respiratory patterns in preterm infants during sleep and to evaluate their relationship to sleep state. Complete polysomnography, including sleep and breathing parameters, was performed on twenty-eight premature infants. Each infant was randomly assigned to the car seat or prone (crib) position for the first recording period. Following the recording of at least two sleep cycles, the position was reversed. The percentage of active and quiet sleep was calculated and breathing parameters were measured. In the car seat, the infants spent significantly more time in active sleep and less time in quiet sleep than in the prone position, of the respiratory parameters, periodic breathing (PB) was significantly higher in the car seat. The presence of at least one abnormal breathing events (bradycardia, desaturation, PB apnoea) was also significantly higher in the car seat. An analysis of variance (ANOVA) of PB revealed significant sleep-state effect (active vs. quiet sleep), but no significant condition or interaction effects, indicating that PB was more frequent in active sleep regardless of the sleeping condition. It is concluded that increased active sleep in the car seat condition, rather than the positioning of the infant in the seat per se, may account for the increase in periodic breathing and possibly other breathing abnormalities reported in car seats.


Case Report: Endocapillary Glomerulopathy Associated With Large Granular T Lymphocyte Leukemia.
Large granular T lymphocyte leukemia (T-LGLL) is a rare indolent lymphocyte leukemia. The clonal proliferation of T cells, which is related to STAT3 gene mutation and abnormal Fas-mediated apoptosis pathway after cell activation, plays a major role in disease progression. Some studies have found that the exogenous and continuous stimulation of endogenous antigens, such as virus infection, is related to the pathogenesis of T-LGLL. The renal pathological manifestations of T-LGLL have rarely been described. In this study, we report a case of T-LGLL with kidney involvement as proteinuria, acute kidney injury, with the appearance of circulating T-LGL infiltrating intra-glomerular capillaries, and endocapillary glomerulopathy. We also summarize reported cases of renal injury associated with LGLL.


Sex-specific effects of NLRP6/AVR and ADM loci on susceptibility to essential hypertension in a Sardinian population.
Coronary artery disease, heart failure, fatal arrhythmias, stroke, and renal disease are the most common causes of mortality for humans, and essential hypertension remains a major risk factor. Elucidation of susceptibility loci for essential hypertension has been difficult because of its complex, multifactorial nature involving genetic, environmental, and sex- and age-dependent nature. We investigated whether the 11p15.5 region syntenic to rat chromosome 1 region containing multiple blood pressure quantitative trait loci (QTL) detected in Dahl rat intercrosses harbors polymorphisms that contribute to susceptibility/resistance to essential hypertension in a Sardinian population. Initial testing performed using microsatellite markers spanning 18 Mb of 11p15.5 detected a strong association between D11S1318 (at 2.1 Mb, P = 0.004) and D11S1346 (at 10.6 Mb, P = 0.00000004), suggesting that loci in close proximity to these markers may contribute to susceptibility in our Sardinian cohort. NLR family, pyrin domain containing 6/angiotensin-vasopressin receptor (NLRP6/AVR), and adrenomedullin (ADM) are in close proximity to D11S1318 and D11S1346, respectively; thus we tested single nucleotide polymorphisms (SNPs) within NLRP6/AVR and ADM for their association with hypertension in our Sardinian cohort. Upon sex stratification, we detected one NLRP6/AVR SNP associated with decreased susceptibility to hypertension in males (rs7948797G, P = 0.029; OR = 0.73 [0.57-0.94]). For ADM, sex-specific analysis showed a significant association between rs4444073C, with increased susceptibility to essential hypertension only in the male population (P = 0.006; OR = 1.44 [1.13-1.84]). Our results revealed an association between NLRP6/AVR and ADM loci with male essential hypertension, suggesting the existence of sex-specific NLRP6/AVR and ADM variants affecting male susceptibility to essential hypertension.


Chronic heat stress and prenatal development in sheep: II. Placental cellularity and metabolism.
Aspects of placental protein and energy metabolism were examined in pregnant ewes subjected to either thermoneutral (TN, 18 to 20 degrees C, 30% humidity, n = 7) or hot (H, 30 to 40 degrees C, 40% humidity, n = 5) temperatures through mid and late gestation. Fetal and placental weights and total content of protein, RNA, and DNA were reduced (P less than .001) in H ewes. Placental protein and RNA concentrations (mg/g) were not different, and DNA concentrations were slightly greater (P less than .1), in H vs TN ewes. Thus, heat seemed to greatly reduce total cell number and placentome size and only slightly decrease cell size. Ratios of RNA to DNA indicated a reduced capacity for protein synthesis in H placenta. However, in vitro fractional rates of protein synthesis in tissue slices from the fetal and maternal placenta and from the myoendometrium were not different between TN and H ewes. The H ewes had greater placental protein concentrations of hydroxyproline and glycine, perhaps suggesting a greater collagen content. In vitro oxygen consumption of fetal placenta, but not of maternal placenta or myoendometrium, was lower in H than in TN ewes. This lower oxygen consumption was partially due to a lower Na+,K+ ATPase-dependent oxygen consumption.


[Modulation of suppressor activity by thymosin].
Modulation of suppressor cell activity by thymosin was evaluated in vivo in a murine tumor system, and in vitro on human lymphocytes. We showed that splenocytes from tumor bearing mice were able to enhance tumor growth in a syngeneic system. This enhancement was T dependent and disappeared by Thymosin treatment. A decrease of Tumor size associated with injection of bone marrow cells treated by thymosin was observed. In the human system we showed that ConA stimulated lymphocytes were able to suppress the response of normal lymphocytes to PHA, PWM and ConA, and in MLC. This effect was significantly blocked in presence of thymosin fraction 5.


Impaired Skeletal Muscle Development and Regeneration in Transglutaminase 2 Knockout Mice.
Skeletal muscle regeneration is triggered by local inflammation and is accompanied by phagocytosis of dead cells at the injury site. Efferocytosis regulates the inflammatory program in macrophages by initiating the conversion of their inflammatory phenotype into the healing one. While pro-inflammatory cytokines induce satellite cell proliferation and differentiation into myoblasts, growth factors, such as GDF3, released by healing macrophages drive myoblast fusion and myotube growth. Therefore, improper efferocytosis may lead to impaired muscle regeneration. Transglutaminase 2 (TG2) is a versatile enzyme participating in efferocytosis. Here, we show that TG2 ablation did not alter the skeletal muscle weights or sizes but led to the generation of small size myofibers and to decreased grip force in TG2 null mice. Following cardiotoxin-induced injury, the size of regenerating fibers was smaller, and the myoblast fusion was delayed in the tibialis anterior muscle of TG2 null mice. Loss of TG2 did not affect the efferocytic capacity of muscle macrophages but delayed their conversion to Ly6C-CD206+, GDF3 expressing cells. Finally, TG2 promoted myoblast fusion in differentiating C2C12 myoblasts. These results indicate that TG2 expressed by both macrophages and myoblasts contributes to proper myoblast fusion, and its ablation leads to impaired muscle development and regeneration in mice.


Functional differentiation within latissimus dorsi.
"Functional differentiation" within skeletal muscle refers to the ability of the Central Nervous System (CNS) to control, with a degree of independence, individual subunits of a muscle during a particular muscle contraction. Essentially, the concept of functional differentiation within skeletal muscle suggests an ability of the CNS to selectively activate those segments of a muscle which have the most appropriate line of action for the task as a means of ensuring the muscles efficient utilisation. The present study was undertaken to determine whether functional differentiation was present within the radiate muscle, Latissimus Dorsi, during a series of isometric muscle contractions. Six surface electrode pairs were placed along the origin of the muscle and electromyographic (EMG) potentials were recorded during isometric contractions in various planes and levels of contraction intensity. The EMG waveforms were integrated (IEMG) and then normalised. The normalised EMG waveforms (nIEMG) were then statistically compared to determine if muscle fibres within the detection area of each electrode pair had varied their contribution to the total activity of the muscle, from one isometric contraction to another. Alterations in the contribution of each site were taken to be indicative of functional differentiation. The results of this study indicated that functional differentiation did occur within Latissimus Dorsi. In essence, the most caudal fibres were utilised preferentially when subjects performed adduction from an abducted position of the shoulder joint. Conversely, activity was distributed over the entire muscle when subjects attempted adduction from the anatomical position. A similar situation was observed when subjects performed horizontal extension from either a flexed or abducted position.(ABSTRACT TRUNCATED AT 250 WORDS)


Highly lethal H5N1 influenza virus in asia: Genesis and options for control.
Extract: Unprecedented animal epidemics of avian influenza viruses of the H5N1 subtype have been reported in Asia in 2004. These outbreaks resulted in the destruction of hundreds of millions of poultry. Of the 44 persons in Asia infected with H5N1 viruses, 32 died (20 in Vietnam and 12 in Thailand). It is impossible to predict whether H5 subtype viruses will acquire the ability to spread among humans and cause a new pandemic. The highly pathogenic Z genotype of H5N1 is now endemic in southeastern Asia and will continue to threaten veterinary and human public health. Influenza A viruses belong to the Orthomyxoviridae family and can be divided into 15 hemagglutinin (HA) and 9 neuraminidase (NA) subtypes on the basis of antigenic and sequence differences in these surface glycoproteins (proteins with sugar groups attached). In wild aquatic birds, influenza's natural hosts, the viruses cause no disease. Periodically, influenza viruses are transmitted to other hosts and cause transient infections and occasional deaths. Less frequently, influenza viruses are transmitted to other species and become adapted to the new hosts. Thus permanent lineages of influenza A viruses are established in humans, swine, horses, and domestic poultry.


Cell type-/inducer-specific bidirectional regulation by thalidomide and phenylphthalimides of tumor necrosis factor-alpha production and its enantio-dependence.
Regulation by thalidomide and phenylphthalimide analogs (FPP-33 and PPS-33) of TNF-alpha production is specific to cell type and to inducer, i.e., (i) the compounds enhance TPA-induced TNF-alpha production by human leukemia HL-60 cells, while they inhibit TPA-induced TNF-alpha production by another human leukemia cell line, THP-1, and (ii) the compounds inhibit TNF-alpha production by both HL-60 and THP-1 cells when the cells are stimulated with okadaic acid (OA). The structure-activity relationships of these compounds are similar in the four assay systems (TPA/HL-60, TPA/THP-1, OA/HL-60, and OA/THP-1). However, optically active analogs, (S)- and (R)-alpha-methylthalidomides, show distinct bidirectional regulatory effects on TNF-alpha production, i.e., only the (S)-form shows TNF-alpha production-enhancing activity in the TPA/HL-60 assay system, while the (R)-form shows much more potent TNF-alpha production-inhibiting activity than the (S)-form in the other assay systems.


Dosimetric comparison of automatically propagated prostate contours with manually drawn contours in MRI-guided radiotherapy: A step towards a contouring free workflow?
The prostate demonstrates inter- and intra- fractional changes and thus adaptive radiotherapy would be required to ensure optimal coverage. Daily adaptive radiotherapy for MRI-guided radiotherapy can be both time and resource intensive when structure delineation is completed manually. Contours can be auto-generated on the MR-Linac via a deformable image registration (DIR) based mapping process from the reference image. This study evaluates the performance of automatically generated target structure contours against manually delineated contours by radiation oncologists for prostate radiotherapy on the Elekta Unity MR-Linac. Plans were generated from prostate contours propagated by DIR and rigid image registration (RIR) for forty fractions from ten patients. A two-dose level SIB (simultaneous integrated boost) IMRT plan is used to treat localised prostate cancer; 6000 cGy to the prostate and 4860 cGy to the seminal vesicles. The dose coverage of the PTV 6000 and PTV 4860 created from the manually drawn target structures was evaluated with each plan. If the dose objectives were met, the plan was considered successful in covering the gold standard (clinician-delineated) volume. The mandatory PTV 6000 dose objective (D98% > 5580 cGy) was met in 81 % of DIR plans and 45 % of RIR plans. The SV were mapped by DIR only and for all the plans, the PTV 4860 dose objective met the optimal target (D98% > 4617 cGy). The plans created by RIR led to under-coverage of the clinician-delineated prostate, predominantly at the apex or the bladder-prostate interface. Plans created from DIR propagation of prostate contours outperform those created from RIR propagation. In approximately 1 in 5 DIR plans, dosimetric coverage of the gold standard PTV was not clinically acceptable. Thus, at our institution, we use a combination of DIR propagation of contours alongside manual editing of contours where deemed necessary for online treatments.


Polygenic score for sleep duration. Association with cognition.
Age-related changes in sleep include a reduction in total sleep time and a greater incidence of sleep disorders, and are also an integral part of neurodegenerations. In the present study, we aimed to: a) identify common genetic variants that may influence self-reported sleep duration, and b) examine the association between the identified genetic variants and performance in different cognitive domains. A sample of 197 cognitively healthy participants, aged 20-80 years, mostly non-Hispanic Whites (69%), were selected from the Reference Abilities Neural Network and the Cognitive Reserve study. Each participant underwent an evaluation of sleep function and assessment of neuropsychological performance on global cognition and four different domains (memory, speed of processing, fluid reasoning, language). Published GWAS summary statistics from a Polygenic Score (PS) for sleep duration in a large European ancestry cohort (N = 30,251) were used to derive a PS in our study sample. Multivariate linear models were used to test the associations between the PS and sleep duration and cognitive performance. Age, sex, and education were used as covariates. Secondary analyses were conducted in three age-groups (young, middle, old). Higher PS was linked to longer sleep duration and was also associated with better performance in global cognition, fluid reasoning, speed of processing, and language, but not memory. Results especially for fluid reasoning, language, and global cognition were driven mostly by the young group. Our study replicated the previously reported association between sleep-PS and longer sleep duration. We additionally found a significant association between the sleep-PS and cognitive function. Our results suggest that common genetic variants may influence the link between sleep duration and cognitive health.


Enlarged amniotic cavity: a new sonographic sign of early embryonic death.
In the process of evaluating sonograms to determine the status of early gestations, it was noted that enlargement of the amniotic cavity appeared to correlate with embryonic death. This study tested that hypothesis by comparing the size of the amniotic cavity with the crown-rump length (CRL) and the size of the chorionic cavity in 25 normal gestations and 10 cases of embryonic death. Measurements included diameter of the amniotic cavity (Da), diameter of the chorionic cavity (Dc), and CRL. Normal first-trimester embryos have distinct rates of growth for both chorionic and amniotic cavities. Least-squares linear regression of CRL on Da for normal embryos reveals Da = 1.1 x CRL - 0.07 (r = .988, n = 25, p less than 10(-8)), indicating that Da and CRL are almost equal. An abnormal embryo, especially at 5-6 weeks' gestation, will have an abnormally large amniotic cavity for its CRL and the size of its chorionic cavity. The CRL-Da difference of 0.11 +/- 0.20 cm in normal embryos differed significantly from that difference of 0.86 +/- 0.38 cm in abnormal embryos (p less than 10(-8)); however, the chorionic cavity was still appropriate in size for the CRL. These results suggest that an amniotic cavity that is enlarged relative to the CRL and the size of the chorionic cavity is evidence of embryonic death.


Importance of the anatomic features of the lacrimal artery for orbital approaches.
Knowledge of variations in the possible patterns of origin, course, and distribution of the lacrimal artery are necessary for the diagnosis and important for the treatment of orbital disorders. The vascularization of 38 lacrimal glands was studied by orbital dissection subsequent to injection of the arterial bed with red-dyed latex. The origin, calibration, and branches of the lacrimal artery and its topographic relations were investigated. In all subjects, arteria lacrimalis originated from ophthalmic artery. On the right, the lacrimal artery sprang from the angle of the ophthalmic artery in 63.15% of the cases, from the curve of the ophthalmic artery in 26.31%, and from the first part the ophthalmic artery in 5.26%. The outer diameter of the lacrimal artery was measured as 1.02 +/- 0.17 mm on the right and 1.03 +/- 0.16 mm on the left. In 68.42 of the cases on the right and in 52.63 of the cases on the left, the lacrimal artery was present, and the lacrimal nerve was seen in a superolateral position with respect to the origin of the artery. Variability of the glandular branch in its course toward lacrimal gland was observed. Recurrent meningeal branch was seen in six cases on the right and in five on the left. On the right, of the six cases, two passed through meningoorbital foramen, and four passed through superior orbital fissure and entered middle cranial fossa. On the left, of the five cases, two passed through meningoorbital foramen, and three passed through superior orbital fissure and entered middle cranial fossa. In this case, the lacrimal gland is the site of an intraorbital anastomosis between internal and external carotid systems. This article confirms the well-known variability of the lacrimal arterial branches and their relation to the lacrimal gland. These variations have been discussed and described with respect to the embryonic development. A better understanding of the vascular anatomy of the lacrimal gland should allow modification of surgical techniques to reduce bleeding during biopsy or excision of the lacrimal gland.