Diagnosis and management of hyperparathyroidism.
The surgical experience with hyperparathyroidism at this institutition of 32 cases since January 1969, has been presented. The age range, sex ratio, associated disease and location of adenomas follows previously reported patterns. Analysis of various preoperative laboratory data confirm that no single test consistently can establish the diagnosis of hyperparathyroidism. At exploration, all glands should be identified and all adenomas removed. Subtotal parathyroidectomy consisting of excision of 3 3/4 glands should be performed for hyperplasia.


Continuous glycemia monitoring in perioperative period in patients undergoing total knee or hip arthroplasty: A protocol for a prospective observational study.
In every surgical subspecialty surgical site infection (SSI) or implant infections, although occur seldom, pose a threat to patients' health. Risk factors of such states is diabetes mellitus (DM), considered one of the most widespread health-related problems of the 21st century. Orthopedists perform big joint replacements that usually concern older adults and therefore often deal with patients suffering from comorbidities. DM is frequently one of them and can furthermore often remain underdiagnosed. The other risk for complication is a rapid beginning of the rehabilitation which starts on the day following the surgery. To eliminate the debilitating impact of DM and hypoglycemia on surgical patients, we aim to investigate the relationship between the glycemia values and the postoperative outcomes in certain periods of time in patients undergoing orthopedic surgeries. Participants meeting inclusion criteria will have inserted a glycemia measuring device (Dexcom G5, Inc., San Diego, CA) in the periods of time. First time it will take place 14 days prior to the surgery and right after the surgery for the second time for the period of another 14 days. All patients will undergo standard total knee arthroplasty or total hip arthroplasty procedures. Patients will be assessed preoperatively and 14 days, 1, 3, 6, 12, and 24 months postoperatively. The assessment of the joint condition will consist of: patient-reported outcomes (The Knee injury and Osteoarthritis Outcome Score, Harris Hip Score, the Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]); assessment of potential SSI and cardiovascular complications (the Finnish Diabetes Risk Score [FINDRISC], the Systematic Coronary Risk Evaluation [SCORE]) and the clinical examination. To investigate the influence of orthopedic surgery (anesthesia) on glycemia and the significance and safety of early patients mobilization after the big joints surgeries. To investigate changes of glycemia in patients with normal glycemia metabolism, potentially protecting them from hypoglycemia during hospital stay and increasing their awareness of potential development of DM in the future. Additionally, this study will correlate perioperative glycemic levels with risk of cardiovascular events in one year follow-up, and its influence on SSI and implant complications.


Behavioral tests for preclinical intervention assessment.
Select functional outcome tests commonly used for evaluating sensorimotor and cognitive capacity in rodents with focal intracerebral ischemic or hemorrhagic injury are described, along with upgrades and issues of concern for translational research. An emphasis is placed on careful quantitative and qualitative assessment of acute and long-term behavioral deficits, and on avoidance of frequent pitfalls. Methods for detecting different degrees of injury and treatment-related improvements are included. Determining the true potential of an intervention requires a set of behavioral analyses that can monitor compensatory learning. In a number of preclinical outcome tests, animals can develop remarkably effective "tricks" that are difficult to detect but frequently lead to dramatic improvements in performance, particularly with repeated practice. However, some interventions may facilitate learning without promoting brain repair, but these may not translate into a meaningful level of benefit in the clinic. Additionally, it is important to determine whether there are any preinjury functional asymmetries in order to accurately assess damage-related changes in behavior. This is illustrated by the fact that some animals have chronic endogenous asymmetries and that others, albeit infrequently, can sustain a spontaneous cerebral stroke, without any experimental induction, that can lead to chronic deficits as reflected by behavioral, imaging, and histological analyses. Finally, a useful new modification of the water maze that involves moving the platform from trial to trial within the target quadrant is reviewed, and its advantages over the standard version are discussed.


Thyroid function of steatitis-affected Mozambique tilapia Oreochromis mossambicus from a sub-tropical African reservoir.
Thyroid function and nutritional indicators were measured in obese, steatitis-affected Mozambique tilapia Oreochromis mossambicus from Loskop Reservoir (LR), South Africa. Plasma thyroid hormones (especially T3) and thyroid follicle histomorphology revealed high levels of activity in every aspect of the thyroid cascade measured in fish from LR compared to a reference population of steatitis-free fish. Concurrent measurements of nutritional state including plasma lipids, liver lipid content and hepatocyte size showed that fish from LR had significant energy stores indicative of abundant nutritional intake. There were distinct sex and seasonal differences, with the highest plasma lipids and T3 levels observed in steatitis-affected females during spring and summer. Positive correlations were observed between plasma lipids (especially cholesterol) and T3 concentrations in fish from both populations, indicating a link between lipid metabolism and thyroid function. There was no direct evidence of thyroid disruption, but this cannot be ruled out until further research determines the factors that underlie the homeostatic shift leading to elevated plasma and liver lipids and T3 levels in steatitis-affected tilapia.


[Psychologists working as members of the intensive care team could reduce the length of stay].
Both short and long term outcome of mechanically ventilated patients are dependent on the time spent on ventilator and on the intensive care unit. Health related quality of life of the survival of intensive care has been proved to be related with the physical and psychological effects of the intensive care itself. In our previous multicenter randomized trial we have demonstrated the effect of psychological support delivered at the time of intensive care. The aim of this post hoc analysis is to demonstrate the effect of the psychological support given by an ICU staff psychologist providing continuous care by the same therapist. 36 patients were included in the post hoc analysis, 17 in the control and 19 in the treatment group. The treatment group received daily psychological support based on positive suggestions delivered by the same therapist at least in 50% of the time. The control group received the same ICU care but without the involvement of the psychologist. There were no differences between the two groups in age, sex, SAPSII score and basic medical treatment. RESULTS showed a significant reduction in mechanical ventilation (3.6 days shorter, p < 0.014) and length of stay (4.2 days shorter, p < 0.022) of the treatment group compared to the control. These results suggest the value of a psychologist working as a full member of the ICU team and providing supplementary psychological support of patients.


Comparing depression-coping strategies of schizophrenic men and depressed and nondepressed college students.
Identified three significant functions by a discriminant analysis that compared depression coping strategies reported by schizophrenic men (N = 43) and depressed and nondepressed college men (N = 200) and women (N = 200). Function 1 was characterized by cigarette smoking and use of tranquilizers and little physical activity. This function appeared to follow a continuum of "pathology" with highest endorsement by schizophrenic men and lowest endorsement by nondepressed college men and women. Function 2 was identified as a sex-role dimension characterized by high levels of crying, self-confrontation, and creative activity reported by depressed and nondepressed college women and exceptionally low amounts of these behaviors reported by schizophrenic men. Function 3 was associated with self-blame, which appeared to be particularly characteristic of depressed college students. The effectiveness of depression coping strategies reported by schizophrenic men was assessed with a multiple regression analysis that used schizophrenic men's coping strategies to predict their depression scores. It was concluded that schizophrenic men can benefit most in reducing their depression from therapy that involves them socially in creative and physical activities.


Three new biflavonoids from the branches and leaves of Cephalotaxus oliveri and their antioxidant activity.
Three new biflavonoids, named oliveriflavones A-C (1-3), together with two known flavonoids (quercetin (4) and rutin (5)), were isolated from the endangered plant Cephalotaxus oliveri. The chemical structures of these compounds were elucidated by comprehensive spectroscopic methods including NMR, HRESIMS, IR, UV, and CD spectra. Compounds 1-5 were first isolated from the genus Cephalotaxus. All the compounds were tested for their antioxidant activity. Compounds 4 and 5 showed excellent activity with IC50 values of 0.03 ± 0.06 μM and 0.02 ± 0.10 μM, respectively.


Foamed lightweight materials made from mixed scrap metal waste powder and sewage sludge ash.
The porous properties and pozzolanic effects of sewage sludge ash (SSA) make it possible to produce lightweight materials. This study explored the effects of different metallic foaming agents, made from waste aluminium products, on the foaming behaviours and engineering characteristics, as well as the microstructure of sewage sludge ash foamed lightweight materials. The results indicated that aluminium powder and mixed scrap metal waste powder possessed similar chemical compositions. After proper pre-treatment, waste aluminium products proved to be ideal substitutes for metallic foaming agents. Increasing the amount of mixed scrap metal waste by 10-15% compared with aluminium powder would produce a similar foaming ratio and compressive strength. The reaction of the metallic foaming agents mainly produced pores larger than 10 microm, different from the hydration reaction of cement that produced pores smaller than 1 microm mostly. To meet the requirements of the lightweight materials characteristics and the compressive strength, the amount of SSA could be up to 60-80% of the total solids. An adequate amount of aluminium powder is 0.5-0.9% of the total solids. Increasing the fineness of the mixed scrap metal waste powder could effectively reduce the amount required and improve the foaming ratio.


Focal eosinophilic myositis--a rare cause of pseudotumor.
Idiopathic focal eosinophilic myositis is a rare benign pseudotumor of skeletal muscle of unknown cause, characterized by focal eosinophilic infiltration of striated muscle. It can mimic a soft tissue sarcoma clinically and on gross examination of the specimen. Microscopic examination establishes the diagnosis. It is important to recognize this pseudosarcomatous lesion so as to spare the patient from anxiety.


Shoulder rehabilitation: clinical application, evaluation, and rehabilitation protocols.
This chapter has discussed and illustrated a shoulder rehabilitation protocol based on restoration of the anatomy, biomechanics, physiology, and motor firing organization that is responsible for normal shoulder function. Many protocols exist in the literature, most of which appear to achieve good results. There are no outcomes data to suggest the most efficacious protocols. Adherence to the basic principles outlined in these chapters appears to allow the best framework for constructing a good program.


Using CRISPR/Cas9 Gene Editing to Investigate the Oncogenic Activity of Mutant Calreticulin in Cytokine Dependent Hematopoietic Cells.
Clustered regularly interspaced short palindromic repeats (CRISPR) is an adaptive immunity system in prokaryotes that has been repurposed by scientists to generate RNA-guided nucleases, such as CRISPR-associated (Cas) 9 for site-specific eukaryotic genome editing. Genome engineering by Cas9 is used to efficiently, easily and robustly modify endogenous genes in many biomedically-relevant mammalian cell lines and organisms. Here we show an example of how to utilize the CRISPR/Cas9 methodology to understand the biological function of specific genetic mutations. We model calreticulin (CALR) mutations in murine interleukin-3 (mIL-3) dependent pro-B (Ba/F3) cells by delivery of single guide RNAs (sgRNAs) targeting the endogenous Calr locus in the specific region where insertion and/or deletion (indel) CALR mutations occur in patients with myeloproliferative neoplasms (MPN), a type of blood cancer. The sgRNAs create double strand breaks (DSBs) in the targeted region that are repaired by non-homologous end joining (NHEJ) to give indels of various sizes. We then employ the standard Ba/F3 cellular transformation assay to understand the effect of physiological level expression of Calr mutations on hematopoietic cellular transformation. This approach can be applied to other genes to study their biological function in various mammalian cell lines.


Posterior transformation, neurological abnormalities, and severe hematopoietic defects in mice with a targeted deletion of the bmi-1 proto-oncogene.
The bmi-1 proto-oncogene has been implicated in B-cell lymphomagenesis in E mu-myc transgenic mice. Distinct domains of the Bmi-1 protein are highly conserved within the Drosophila protein Posterior Sex Combs, a member of the Polycomb group involved in maintaining stable repression of homeotic genes during development. We have inactivated the bmi-1 gene in the germ line of mice by homologous recombination in ES cells. Null mutant mice display three phenotypic alterations: (1) a progressive decrease in the number of hematopoietic cells and an impaired proliferative response of these cells to mitogens; (2) neurological abnormalities manifested by an ataxic gait and sporadic seizures; and (3) posterior transformation, in most cases along the complete anteroposterior axis of the skeleton. The observations indicate that Mbi-1 plays an important role in morphogenesis during embryonic development and in hematopoiesis throughout pre- and postnatal life. Furthermore, these data provide the first evidence of functional conservation of a mammalian Polycomb group homolog.


TRIM/RBCC, a novel class of 'single protein RING finger' E3 ubiquitin ligases.
The TRIM/RBCC proteins are defined by the presence of the tripartite motif composed of a RING domain, one or two B-box motifs and a coiled-coil region. These proteins are involved in a plethora of cellular processes such as apoptosis, cell cycle regulation and viral response. Consistently, their alteration results in many diverse pathological conditions. The highly conserved modular structure of these proteins suggests that a common biochemical function may underlie their assorted cellular roles. Here, we review recent data indicating that some TRIM/RBCC proteins are implicated in ubiquitination and propose that this large protein family represents a novel class of 'single protein RING finger' ubiquitin E3 ligases.


Enhanced differentiation and delivery of mouse retinal progenitor cells using a micropatterned biodegradable thin-film polycaprolactone scaffold.
The deterioration of retinal tissue in advanced stages of retinitis pigmentosa and age-related macular degeneration and the lack of signaling cues for laminar regeneration are significant challenges highlighting the need for a tissue engineering approach to retinal repair. In this study, we fabricated a biodegradable thin-film polycaprolactone (PCL) scaffold with varying surface topographies using microfabrication techniques. Mouse retinal progenitor cells (mRPCs) cultured on PCL scaffolds exhibited enhanced potential to differentiate toward a photoreceptor fate in comparison to mRPCs cultured on control substrates, suggesting that PCL scaffolds are promising as substrates to guide differentiation of mRPCs toward a photoreceptor fate in vitro before transplantation. When cocultured with the retinal explants of rhodopsin null mice, mRPC/PCL constructs showed increased mRPC integration rates compared to directly applied dissociated mRPCs. Moreover, these mRPC/PCL constructs could be delivered into the subretinal space of rhodopsin null mice with minimal disturbance of the host retina. Whether cocultured with retinal explants or transplanted into the subretinal space, newly integrated mRPCs localized to the outer nuclear layer and expressed appropriate markers of photoreceptor fate. Thus, the PCL scaffold provides a platform to guide differentiation and organized delivery of mRPCs as a practical strategy to repair damaged retina.


Interfacial polarizations induced by incorporating traditional perovskites into reduced graphene oxide (RGO) for strong microwave response.
Incorporation of traditional perovskites into reduced graphene oxide (RGO) is an effective strategy to develop useful microwave absorbents. Taking advantage of the suitable impedance of La0.7Sr0.3MnO3 (LSMO), a novel and available microwave absorber was obtained. Here, we showed an outstanding and stable RGO material decorated with LSMO that can be used as an active component of microwave absorption devices. The as-prepared LSMO/RGO composites adopted the merits of RGO and LSMO and provided good properties, such as a controllable dissipation ability, optimized impedance matching, and broadened effective frequency bandwidth. For example, the minimum reflection loss (RL) value of LSMO/RGO composites with a 60% loading filler ratio reached -38.81 dB with a matching thickness of only 1.7 mm. Furthermore, the effective frequency bandwidth can be as wide as 5.64 GHz, with a thickness of 1.95 mm. Therefore, this work initiates a brand new avenue for artificial research of new materials for electromagnetic wave absorption.


Segmental duplications flank the multiple sclerosis locus on chromosome 17q.
Large chromosomal rearrangements, duplications, and inversions are relatively common in mammalian genomes. Here we report interesting features of DNA strands flanking a Multiple Sclerosis (MS) susceptibility locus on Chromosome 17q24. During the positional cloning process of this 3-Mb locus, several markers showed a radiation hybrid clone retention rate above the average (1.8-fold), suggestive for the existence of duplicated sequences in this region. FISH studies demonstrated multiple signals with three of the tested regional BACs, and 24 BACs out of 187 showed evidence for duplication in shotgun sequence comparisons of the 17q22-q24 region. Specifically, the MS haplotype region proved to be flanked by palindromic sequence stretches and by long segmental intrachromosomal duplications in which highly homologous DNA sequences (>96% identity) are present at both ends of the haplotype. Moreover, the 3-Mb DNA segment, flanked by the duplications, is inverted in the mouse genome when compared with the orientation in human and chimp. The segmental duplication architecture surrounding the MS locus raises the possibility that a nonallelic homologous recombination between duplications could affect the biological activity of the regional genes, perhaps even contributing to the genetic background of MS.


Hexaphosphapentaprismane: a new gateway to organophosphorus cage compound chemistry.
Several independent synthetic routes are described leading to the formation of a novel unsaturated tetracyclic phosphorus carbon cage compound tBu4C4P6 (1), which undergoes a light-induced valence isomerization to produce the first hexaphosphapentaprismane cage tBu4C4P6 (2). A second unsaturated isomer tBu4C4P6 (9) of 1 and the bis-[W(CO)5] complex 13 of 1 are stable towards similar isomerization reactions. Another starting material for the synthesis of the hexaphosphapentaprismane cage tBu4C4P6 (2) is the trimeric mercury complex [(tBu4C4P6)Hg]3 (11), which undergoes elimination of mercury to afford the title compound 2. Single-crystal X-ray structural determinations have been carried out on compounds 1, 2, 9, 11, and 13.


Composition of lymphocyte subpopulations in normal canine lymph nodes.
Flow cytometric immunophenotyping of lymph node aspirates has become a standard practice of canine lymphoma diagnostic workup. Ultimately, the combination of flow cytometry data, histopathology, and clinical signs allows consensus classification, and improves prognostic accuracy and therapeutic approaches. Although there is a growing body of information regarding lymphocyte population subsets in various types of lymphoma, only few studies provide information regarding the composition of the normal canine lymph node. The aim of this prospective study was to establish exploratory reference data for lymphocyte subpopulations in normal canine lymph nodes using an extended panel of antibodies. Popliteal lymph nodes excised from normal dogs were analyzed by cytology, multi-color flow cytometry using 11 different canine-specific and anti-human cross-reactive monoclonal antibodies, and polymerase chain reaction for antigen receptor rearrangement (PARR). Subpopulations from lymph nodes of 26 dogs were classified according to the following positive antibody reactions: CD11a(+) 92.2 ± 12.3%, CD3(+) 55.0 ± 14.1%, CD3-12(+) 57.3 ± 14%, CD5(+) 52.3 ± 12.7%, CD21(+) 33.9 ± 11.8%, CD79αcγ(+) 46.9 ± 14.8%, CD56(+) 4.9 ± 5.9%, and CD14(+) 5.5 ± 6.8%. There were 58.7 ± 9% CD4(+) and 21.3 ± 7.8% CD8(+) cells inside the gate of CD3(+) cells. Cytology revealed a mixed population of mostly lymphoid cells in all samples. The absence of a monoclonal or oligoclonal neoplastic population was confirmed by PARR. This study establishes for the first time flow cytometry data of lymphocyte populations in a larger group of normal canine lymph nodes, including populations positive for some new antibodies against CD3-12, CD5, CD11a, CD56, and CD79αcy.


Changes in Tumor Biology During Chemoradiation of Cervix Cancer Assessed by Multiparametric MRI and Hypoxia PET.
Imaging biomarkers assessed with magnetic resonance imaging (MRI) and/or positron emission tomography (PET) enable non-invasive tumor characterization in cervix cancer patients. We investigated the spatio-temporal stability of hypoxia, perfusion, and the cell density of tumors over time by repetitive imaging prior to, during, and after radio-chemotherapy. Thirteen patients were included in this prospective study. The imaging protocol included the following: [18F]fluoromisonidazole ([18F]FMISO)-PET/x-ray computed tomography (CT) and multiparametric (mp)-MRI at four time-points (TP): baseline (BL); and weeks 2 (TP1), 5 (TP2), and 19 after treatment start (follow-up FU). Complete datasets for six patients could be assessed for tumor volume, enhancement kinetics, diffusivity, and [18F]FMISO-avidity (P1-P6). In addition, two patients completed all PET/CT examinations (P7-P8) but not all MR scans; however, one of them had no hypoxia (P8). Descriptive statistics, correlations, and voxel-by-voxel analysis were performed. For various, independent reasons, five patients could not complete the study according to the protocol with all imaging sequences. Median tumor ADCs (in ×10-3 mm2/s) were 0.99 ± 0.10 at BL, 1.20 ± 0.12 at TP1, 1.33 ± 0.14 at TP2, and 1.38 ± 0.21 at FU. The median TBRpeak (tumor-to-background) was 2.7 ± 0.8 at BL, 1.6 ± 0.2 at TP1, 1.8 ± 0.3 at TP2, and 1.7 ± 0.3 at FU. The voxel-by-voxel analysis of the [18F]FMISO uptake at BL and TP1 showed no correlation. Between TP2 and TP1 and FU and TP2, weak correlations were found for two patients. Longitudinal mp-MR and PET imaging enables the in vivo tumor characterization over time. While perfusion and cell density decreased, there was a non-uniform change of hypoxia observed during radiotherapy. To assess the potential impact with regard to more personalized treatment approaches, hypoxia imaging-based dose painting for cervix cancer requires further research.


Relationship between interleukin-13 rs20541 single nucleotide polymorphisms and therapeutic efficacy in children with asthma.
To investigate the relationship between therapeutic efficacy in children with asthma and interleukin-13 (IL-13) rs20541 polymorphisms. Fifty children with moderate-to-severe asthma were assigned to the GG, GA, and AA groups according to the IL-13 gene locus rs20541 polymorphism. The patients received budesonide inhalation suspension 1 mg twice daily combined with fluticasone propionate 80 µg/inhalation. The improvement of clinical symptoms (gasping, coughing, and wheezing), improvement of lung function, and adverse reactions were observed. Lung function did not significantly differ among three groups before treatment. After treatment, the time to symptom relief was significantly shorter in the GG group than that in the other two groups. The forced expiratory volume in one second and percent predicted peak expiratory flow were also significantly better in the GG group than in the other two groups. Budesonide inhalation suspension combined with fluticasone propionate is an effective treatment regimen for moderate-to-severe asthma. Polymorphism of the IL-13 rs20541 locus may be correlated with therapeutic efficacy. Patients carrying the GG allele were more responsive than their counterparts with the GA or AA allele.


Mortality Associated with Severe Sepsis Among Age-Similar Women with and without Pregnancy-Associated Hospitalization in Texas: A Population-Based Study.
BACKGROUND The reported mortality among women with pregnancy-associated severe sepsis (PASS) has been considerably lower than among severely septic patients in the general population, with the difference being attributed to the younger age and lack of chronic illness among the women with PASS. However, no comparative studies were reported to date between patients with PASS and age-similar women with severe sepsis not associated with pregnancy (NPSS). MATERIAL AND METHODS We used the Texas Inpatient Public Use Data File to compare the crude and adjusted hospital mortality between women with severe sepsis, aged 20-34 years, with and without pregnancy-associated hospitalizations during 2001-2010, following exclusion of those with reported chronic comorbidities, as well as alcohol and drug abuse. RESULTS Crude hospital mortality among PASS vs. NPSS hospitalizations was lower for the whole cohort (6.7% vs. 14.1% [p<0.0001]) and those with ≥3 organ failures (17.6% vs. 33.2% [p=0.0100]). Adjusted PASS mortality (odds ratio [95% CI]) was 0.57 (0.38-0.86) [p=0.0070]. CONCLUSIONS Hospital mortality was unexpectedly markedly and consistently lower among women with severe sepsis associated with pregnancy, as compared with contemporaneous, age-similar women with severe sepsis not associated with pregnancy, without reported chronic comorbidities. Further studies are warranted to examine the sources of the observed differences and to corroborate our findings.


Physician reasons for nonpharmacologic treatment of hyperglycemia in older patients newly diagnosed with type 2 diabetes mellitus.
To identify reasons why primary care physicians (PCPs) do not treat older patients newly diagnosed with type 2 diabetes mellitus (T2DM) with antihyperglycemic agents following diagnosis. US PCPs were surveyed via the internet regarding their reasons for not treating patients aged >65 years diagnosed with T2DM and had not yet initiated antihyperglycemic therapy for ≥6 months after diagnosis. PCPs were requested to provide relevant clinical information for untreated older patients and select applicable reasons for not initiating treatment from a list of 35 possibilities, grouped into five categories. A total of 508 PCPs completed the online survey and provided complete clinical data for 770 patients. The reasons provided by the first-ranked physician for not initiating antihyperglycemic therapy were related to diet and exercise (57.5%); mild hyperglycemia (23.8%); patient's concerns (13.4%); concerns about antihyperglycemic agents (3.0%); and comorbidities and polypharmacy (2.3%). The "diet and exercise" category was the most common first-ranked non-treatment reason, regardless of recent hemoglobin A(1c) (HbA(1c)) stratum. Reasons within the "patient's concerns," "concerns related to antihyperglycemic agents," and "comorbidities and polypharmacy" categories tended to be selected more often as first-ranked reasons by physicians for patients with higher HbA(1c) values. Of the 158 patients whose physicians planned to initiate antihyperglycemic therapy within the next month, 54.4% already had a most recent HbA(1c) value above their physician-stated threshold for treatment initiation. In the PCPs studied, there was a tendency to select appropriate reasons for non-treatment with antihyperglycemic agents given their patients' glycemic status. However, there was inertia related to the initiation of pharmacological therapy in some older patients with newly diagnosed T2DM. Important factors included physicians' perceptions of "mild" hyperglycemia and the HbA(1c) threshold for using antihyperglycemic agents.


Calcium deposition in photocrosslinked poly(Pro-Hyp-Gly) hydrogels encapsulated rat bone marrow stromal cells.
Reproducing the features of the extracellular matrix is important for fabricating three-dimensional (3D) scaffolds for tissue regeneration. A collagen-like polypeptide, poly(Pro-Hyp-Gly), is a promising material for 3D scaffolds because of its excellent physical properties, biocompatibility, and biodegradability. In this paper, we present a novel photocrosslinked poly(Pro-Hyp-Gly) hydrogel as a 3D scaffold for simultaneous rat bone marrow stromal cell (rBMSC) encapsulation. The hydrogels were fabricated using visible-light photocrosslinking at various concentrations of methacrylated poly(Pro-Hyp-Gly) (20-50 mg/ml) and irradiation times (3 or 5 min). The results show that the rBMSCs encapsulated in the hydrogels survived 7 days of incubation. Calcium deposition on the encapsulated rBMSCs was assessed with scanning electron microscope observation, Alizarin Red S, and von Kossa staining. The most strongly stained area was observed in the hydrogel formed with 30 mg/ml of methacrylated poly(Pro-Hyp-Gly) with 5-min irradiation. These findings demonstrate that poly(Pro-Hyp-Gly) hydrogels support rBMSC viability and differentiation, as well as demonstrating the feasibility of using poly(Pro-Hyp-Gly) hydrogels as a cytocompatible, biodegradable 3D scaffold for tissue regeneration.


A gene encoding a membrane protein exists upstream of the amoA/amoB genes in ammonia oxidizing bacteria: a third member of the amo operon?
The gene cluster encoding ammonia monooxygenase (AMO) in the chemolithotrophic soil bacterium Nitrosospira sp. NpAV was found to contain a third open reading frame, termed amoC, upstream of the genes amoA and amoB that encode the subunits of AMO. The amoC gene and its flanking regions were isolated and sequenced from a 4.4 kb EcoRI fragment that contains one of three copies of the ammonia monooxygenase gene cluster. The presence of this gene upstream of the other two amoA gene copies in Nitrosospira NpAV as well as upstream of amoA genes in the genomes of other ammonia oxidizing nitrifiers (strains in the genera Nitrosomonas, Nitrosopira, Nitrosolobus and Nitrosovibrio) was confirmed using genomic DNA, oligodeoxyribonucleotide primers and the PCR. The amoC gene in Nitrosospira sp. NpAV encodes a 270 amino acid polypeptide of approximately 36 kDa. Topological analysis of the predicted primary structure revealed 6 membrane spanning domains. The amoC gene was expressed in recombinant Escherichia coli from its indigenous promoter.


Predictors of mode of birth and duration of labour following induction using prostaglandin vaginal gel.
Using data from a randomised controlled trial (RCT) comparing two policies of prostaglandin (PGE2) vaginal gel induction of labour (IOL) at term, this study aimed to determine: (i) demographic/clinical factors that predict IOL outcomes; and (ii) clinical characteristic(s) of women who would benefit from a policy of amniotomy once technically possible as opposed to giving more PGE2. Following an initial PGE2 dose, women were randomised to amniotomy or repeat-PGE2. Using RCT data, two multivariate models were developed, assessing the relationship between demographic/clinical characteristics and the outcomes of caesarean section (CS), and vaginal delivery within 24 h (VD < 24 h). Regression-equations were used to predict the likelihood of CS and VD < 24 h, varying independent predictors from the multivariate analyses. Of 245 term women undergoing IOL, 90 had a CS, 155 delivered vaginally and 79 had a VD < 24 h. Controlling for confounders, nulliparity [adjusted odds ratio (aOR) = 3.71 (1.55, 8.88)] and modified Bishop's score (MBS) at first review [aOR = 0.78 (0.66, 0.92)] were independently associated with CS. Nulliparity [aOR = 0.06 (0.02, 0.15)], MBS at first review [aOR = 1.66 (1.35, 2.05)], and a policy of early amniotomy [aOR = 2.28 (1.04, 5.00)] were associated with VD < 24 h. Modelling using regression equations, and varying both MBS at first review and parity, there was no scenario where repeat PGE2 was predicted to be superior to an earlier amniotomy. Following IOL using PGE2 vaginal gel at term, both parity and cervical favourability at first review are associated with CS and VD < 24 h. All combinations of parity and MBS at first review predicted fewer CS and greater likelihood of VD < 24 h with a policy of amniotomy once technically possible.


Hypercholesterolemia attenuates the anti-ischemic effect of preconditioning during coronary angioplasty.
Cardioprotection by preconditioning is limited in some animal models of hypercholesterolemia. We studied ischemic preconditioning induced by coronary angioplasty in hypercholesterolemic and normocholesterolemic patients by means of a beat-to-beat analysis of ST segments. Thirty coronary disease patients were classified into normocholesterolemic and hypercholesterolemic groups. Intracoronary ECG was recorded during three consecutive balloon inflations of 2-min duration with 5-min intervals. In normocholesterolemic patients, the ST segment was continuously elevated during the occlusions and rapidly normalized after balloon deflations. Repeated occlusions significantly attenuated ST-segment elevation from 1.28 +/- 0.67 to 0.88 +/- 0.51 mV (p < 0.001) and decreased the time to normalization of ST segment. In hypercholesterolemic patients, the ST segment was rapidly elevated in the first 30 s of the first occlusion, and normalization of the ST segment was longer on the first reperfusion. However, in these patients, repeated occlusions abolished the initial elevation of the ST segment but did not attenuate maximal ST-segment elevation (1.24 +/- 1.11 mV vs 1.21 +/- 1.09 mV) and failed to decrease the time to normalization of the ST segment. Hypercholesterolemia accelerates the evolution of myocardial ischemia, delays recovery on reperfusion, and deteriorates the anti-ischemic effect of preconditioning in humans.


Formation of ice nanotube with hydrophobic guests inside carbon nanotube.
A composite ice nanotube inside a carbon nanotube has been explored by molecular-dynamics and grand canonical Monte Carlo simulations. It is made from an octagonal ice nanotube whose hollow space contains hydrophobic guest molecules such as neon, argon, and methane. It is shown that the attractive interaction of the guest molecules stabilizes the ice nanotube. The guest occupancy of the hollow space is calculated by the same method as applied to clathrate hydrates.


State-Feedback Set Stabilization of Boolean Networks With State-Dependent Random Impulses.
In this article, we are devoted to addressing the state-feedback set stabilization of Boolean control networks with state-dependent random impulses by utilizing a hybrid index model. By comparison with the previous impulsive Boolean networks, this model can be used to describe the instantaneousness of various impulsive behaviors more clearly. In order to avoid the occurrence of Zeno phenomenon, we first introduce the basic concept of forward completeness and further establish the judging criterion. After that, an algorithm is presented to derive the largest control invariant subset of a given subset. Based on this, we derive a necessary and sufficient criterion for finite-time feedback set stabilizability. Similarly, the result is also obtained for the asymptotic case, and the asymptotic set stabilizers are designed by dividing the whole state space into several layers. Moreover, we also investigate the relationships between different stabilizabilities. Last, two illustrative examples are presented to demonstrate the efficiency of the theoretical results.


Isopentyl-Sulfide-Impregnated Nano-MnO₂ for the Selective Sorption of Pd(II) from the Leaching Liquor of Ores.
Conventional separation methods are not suitable for recovering palladium present in low concentrations in ore leaching solutions. In this study, a novel isopentyl sulfide (S201)-impregnated α-MnO₂ nanorod adsorbent (BISIN) was prepared, characterized, and applied for the selective adsorption and separation of palladium from the leaching liquor of ores. Batch studies were carried out, and the main adsorption parameters were systematically investigated, in addition to the relevant thermodynamic parameters, isotherms, and kinetic models. The thermodynamic parameters reflected the endothermic and spontaneous nature of the adsorption. Moreover, the experimental results indicated that the Langmuir isotherm model fits the palladium adsorption data well and the adsorption was well described by the pseudo-second-order kinetic model. The main adsorption mechanisms of palladium were elucidated at the molecular level by X-ray crystal structure analysis. Thiourea was found to be an excellent desorption agent, and the palladium-thiourea complex was also confirmed by X-ray crystal structure analysis. The results indicated that almost all of the Pd(II) (>99.0%) is adsorbed on BISIN, whereas less than 2% of the adsorbed Pt(IV), Fe3+, Cu2+, Ni2+, and Co2+ is observed under the optimum conditions. The proposed method can be used for the efficient adsorption and separation of palladium from the leaching liquor of ores.


Feasibility of using ring-mounted Halcyon Linac for single-isocenter/two-lesion lung stereotactic body radiation therapy.
To demonstrate the plan quality and delivery efficiency of volumetric-modulated arc therapy (VMAT) with the Halcyon Linac ring delivery system (RDS) in the treatment of single-isocenter/two-lesion lung stereotactic body radiation therapy (SBRT). Sixteen previously treated non-coplanar VMAT single-isocenter/two-lesion lung SBRT plans delivered with SBRT-dedicated C-arm TrueBeam Linac were selected. Prescribed dose was 50 Gy to each lesion over five fractions with treatment delivery every other day and AcurosXB algorithm as the final dose calculation algorithm. TrueBeam single-isocenter plans were reoptimized for Halcyon Linac with coplanar geometry. Both TrueBeam and Halcyon plans were normalized for identical combined target coverage and evaluated. Conformity indices (CIs), heterogeneity index (HI), gradient index (GI), gradient distance (GD), and D2cm were compared. The normal lung V5Gy, V10Gy, V20Gy, mean lung dose (MLD), and dose to organs at risk (OAR) were evaluated. Treatment delivery parameters, including beam-on time, were recorded. Halcyon plans were statistically similar to clinically delivered TrueBeam plans. No statistical differences in target conformity, dose heterogeneity, or intermediate-dose spillage were observed (all, p > 0.05). Halcyon plans, on average, demonstrated statistically insignificant reduced maximum dose to most adjacent OAR and normal lung. However, Halcyon yielded statistically significant lower maximal dose to the ribs (p = 0.041) and heart (p = 0.026), dose to 1 cc of ribs (p = 0.035) and dose to 5 cc of esophagus (p = 0.043). Plan complexity slightly increased as seen in the average increase of total monitor units, modulation factor, and beam-on time by 480, 0.48, and 2.78 min, respectively. However, the estimated overall treatment time was reduced by 2.22 min, on average. Mean dose delivery accuracy of clinical TrueBeam plans and the corresponding Halcyon plans was 98.9 ± 0.85% (range: 98.1%-100%) and 98.45 ± 0.99% (range: 97.9%-100%), respectively, demonstrating similar treatment delivery accuracy. SBRT treatment of synchronous lung lesions via single-isocenter VMAT on Halcyon RDS is feasible and dosimetrically equivalent to clinically delivered TrueBeam plans. Halcyon provides excellent plan quality and shorter overall treatment time that may improve patient compliance, reduce intrafraction movement, improve clinic efficiency, and potentially offering lung SBRT treatments for underserved patients on a Halcyon only clinic.


Surveillance as a safe and effective option for treatment of stage I seminoma.
Introdubction: Stage I seminoma has a very good prognosis, yet approximately 15% have subclinical metastatic disease and will relapse after orchidectomy alone. Several management approaches have been investigated. We aimed to evaluate the clinical outcomes of real-world patients with stage I seminoma, analysing prognostic factors influencing treatment choice and oncological outcomes. Retrospective, single institution study, with 55 patients diagnosed with clinical stage I seminoma between 2007 and 2020. Selected patients were analysed regarding three management approaches - surveillance, adjuvant radiotherapy and adjuvant carboplatin AUC7. Overall survival and progression-free survival outcomes were analysed. Predictors of treatment choice were determined, and predictors of recurrence were analysed in patients on active surveillance. The median follow-up time was 91 months (13-165). Overall survival at 10 years was 98.2%. Stage I seminoma patients had a 1-, 3- and 10-year progression free survival of 98%, 94% and 89%, respectively. Three-year progression free survival was 92.0% for those on active surveillance (IC95%, 91.5-92.5%), 95.2% for carboplatin (IC95%, 94.8-95.6%) and 100% for those on adjuvant radiotherapy (p > 0.05). All relapses on active surveillance protocols occurred during the first 24 months. Overall, 43% of patients who underwent adjuvant treatment reported adverse effects of therapy, with higher incidence on radiotherapy group (63%). Stage I seminoma have excellent prognosis, high cure rates, and low treatment-associated morbidity. Active surveillance is a safe modality when applied to selected patients. Adjuvant radiotherapy and adjuvant chemotherapy with carboplatin show similar results, with fewer adverse effects on chemotherapy arm.


Development of a high resolution x-ray inspection system using a carbon nanotube based miniature x-ray tube.
A new concept for a non-destructive testing device using a novel carbon nanotube (CNT) based miniature x-ray tube is proposed. The device can be used for small-scale internal inspection of objects. To investigate the effectiveness of the proposed concept, the device was fabricated and its performance was systematically analyzed. The non-destructive testing device consists of a CNT based miniature x-ray tube, a scintillator, an optical lens, and a detector. The size of the focal spot needed to identify objects as small as 5 µm was calculated through simulation. An electron optics simulation software, E-GUN, was used to optimize the geometries of both the focusing cup and the x-ray target to achieve the desired focal spot size of the x-ray tube. The CNT based miniature x-ray tube was fabricated using the brazing process, and an NdFeB focusing lens was used to further reduce the focal spot size. XR images were obtained using the fabricated device and the spatial resolutions of the images were evaluated using the modulation transfer function (MTF). The fields of view (FOVs) per probe are 7.1 mm2 and 1.8 mm2 when using a 5× optical lens and a 10× optical lens, respectively. The FOV can be increased by increasing the number of probes incorporated into the device. MTF10 values were determined to be 105 lp/mm and 230 lp/mm when using the 5× optical lens and 10× optical lens, respectively. By using an optical lens to enlarge the XR images, the effect of focal spot was minimized and clear XR images were obtained.


[A case of metastatic breast carcinoma of the cervical muscles].
A 57-year-old woman was referred to another hospital with bilateral breast masses. Incisional biopsy findings indicated bilateral breast invasive lobular carcinoma, with positive estrogen receptor(ER)status and negative human epidermal growth factor receptor 2(HER2)status. Close inspection did not show the presence of distant metastasis, but lymphadenopathy was noted in the left supraclavicular region, and bilateral TxN3M0, Stage IIIC breast cancer was diagnosed. We performed a simple, double mastectomy, and endocrine therapy was initiated. Treatment with anastrozole followed by tamoxifen resulted in a temporary response. Because of progression after both treatments, chemotherapy was initiated. Complete response was observed in the left supraclavicular lymph node metastases after 4 courses of docetaxel and cyclophosphamide. Two years after treatment was discontinued, metastatic breast carcinoma in the stomach was diagnosed. Immediately after fulvestrant administration, the patient complained of neck stiffness. Several examinations revealed thickening of the cervical muscles with an abnormal signal. Core needle biopsy of the cervical muscle lesion revealed the presence of metastatic adenocarcinoma, with negative ER status and negative HER2 status. Chemotherapy with capecitabine was initiated, and this resulted in stable disease.


Crown lengthening: a surgical flap approach.
In many instances it is not possible to place a restoration margin without encroaching on the periodontal attachment apparatus. A surgical crown-lengthening procedure can provide a good solution to this common clinical problem. This article discusses indication and contraindication for surgical crown-lengthening procedures and presents an appropriate surgical technique.


Ulososides and urabosides--triterpenoid saponins from the Caribbean marine sponge Ectyoplasia ferox.
Three new triterpene glycosides, named ulososide F (1), urabosides A (2) and B (3), together with the previously reported ulososide A (4), were isolated from the Caribbean marine sponge Ectyoplasia ferox. Their structures were elucidated using extensive interpretation of 1D and 2D-NMR data, as well as HRESIMS. The aglycon of all compounds is a rare 30-norlonastane and the sugar residues were identified after acid hydrolysis and GC analyses. Cytotoxicities of the isolated compounds were evaluated against Jurkat and CHO cell lines by a MTT in vitro assay as well as a hemolysis assay. Unexpectedly, all these saponin derivatives showed very low activity in our bioassays.


How adaptive laboratory evolution can boost yeast tolerance to lignocellulosic hydrolyses.
The yeast Saccharomyces cerevisiae is an excellent candidate for establishing cell factories to convert lignocellulosic biomass into chemicals and fuels. To enable this technology, yeast robustness must be improved to withstand the fermentation inhibitors (e.g., weak organic acids, phenols, and furan aldehydes) resulting from biomass pretreatment and hydrolysis. Here, we discuss how evolution experiments performed in the lab, a method commonly known as adaptive laboratory evolution (ALE), may contribute to lifting yeast tolerance against the inhibitors of lignocellulosic hydrolysates (LCHs). The key is that, through the combination of whole-genome sequencing and reverse engineering, ALE provides a robust platform for discovering and testing adaptive alleles, allowing to explore the genetic underpinnings of yeast responses to LCHs. We review the insights gained from past evolution experiments with S. cerevisiae in LCH inhibitors and propose experimental designs to optimise the discovery of genetic variants adaptive to biomass toxicity. The knowledge gathered through ALE projects is envisaged as a roadmap to engineer superior yeast strains for biomass-based bioprocesses.


An ethnobotanical study of antimalarial plants in Togo Maritime Region.
Malaria continues to be of great concern in Togo, as it accounts for high mortality rates, principally in children. Although plant-based medicines are the only means in major malarious regions of the country, still very little is known about the medicinal plants and medical practices of the indigenous people. The present study aimed to document the indigenous medicinal plant utilization for the management of malaria and related symptoms in Togo Maritime Region. Fifty Traditional Healers (TH) were selected with the help leaders of Togolese Traditional Healers Associations and information on their knowledge on the use of plants for malaria therapeutic purposes was gathered using a semi-structured interviews. After enquiries, 52 plant species belonging to 49 genera and 29 families were recorded. The most represented families were Rubiaceae and Rutaceae with four species each. Traditional healers agreed more in the treatment of malaria (ICF=0.70), fever (ICF=0.33) and anemia (ICF=0.20). For the treatment of malaria, 38.46% (20/52) of the species cited in the study were of high fidelity level (FL=100%). The leaves (58.22%), leafy stem (33.78%) and fruits (8.52%) were the most used parts in concoctions. The main mode of preparation was decoction (69%) and the administration was essentially by oral route (79%) and body-bath (14%). The issue of the study showed that Togo Maritime Region TH have a good knowledge of antimalarial plants. However the study must be extend to the whole country to lead to innovative strategies in malaria control. Such results could be a starting point for in vitro antimalarial screenings.


Relationship of urotensin I induced vasodilatory action in rat thoracic aorta to Ca2+ regulation.
The relaxant effects of the synthetic fish neuropeptide urotensin I were examined in helical strips of rat aorta. In K+-depolarized aorta strips, urotensin I and verapamil competitively inhibited Ca2+-induced contractions. Urotensin I relaxed, in a concentration-dependent manner, the contraction produced by the Ca2+ ionophore A23187, whereas verapamil had no effect on this contraction, even at a concentration of 10(-5) M. In the absence and presence of extracellular Ca2+, urotensin I inhibited both components of the contractions elicited by norepinephrine or urotensin II, another fish neuropeptide. Verapamil reduced only the norepinephrine or urotensin II induced contraction in the presence of extracellular Ca2+, with little or no change in the contraction in Ca2+-free buffer. The urotensin I induced relaxation response in aortic strips contracted by 40 mM KCl was enhanced by pretreatment with papaverine or forskolin. Pretreatment with dibutyryl cAMP did not significantly alter the action of urotensin I. The presence or absence of endothelial cells did not change the response to urotensin I. These results suggest that urotensin I antagonizes the action and (or) mobilization of extracellular and intracellular Ca2+.


Effect of coexistent carpal tunnel abnormality on sensory conduction findings in polyneuropathy.
To investigate the change of pattern of sensory conduction findings in polyneuropathy with coexistent carpal tunnel abnormality (CTAbN). We reviewed sensory conduction findings of 46 patients with acute inflammatory demyelinating polyradiculoneuropathy (AIDP) and 66 with diabetic polyneuropathy (DP). Both groups were categorized into those with and without CTAbN according to transcarpal median sensory conduction velocities. In AIDP, median sensory nerve action potential (SNAP) amplitudes were reduced, whereas sural SNAP amplitudes remained unchanged. Median SNAP amplitude was lowest, and sural/median SNAP amplitude ratio was highest in AIDP with coexistent CTAbN. In DP, both median and sural SNAP amplitudes were reduced. Their sural/median SNAP amplitude ratios remained unchanged. Incidence of abnormal median-normal sural pattern was higher in AIDP than in DP. Nevertheless, these incidences did not alter with coexistent CTAbN. The ulnar SNAP amplitude and sural/ulnar SNAP amplitude ratio were not significantly different between those with and without CTAbN in both AIDP and DP groups. Coexistent CTAbN caused further increase of sural/median SNAP amplitude ratio only in AIDP.


Chronological changes in the morphological features of early gastric cancer, especially recent changes in macroscopic findings.
At the National Cancer Center, 1,300 patients with early gastric cancer were operated on during a period of 21 years, from 1962 to the end of May 1983, and the chronological sequence of the pathological features was analyzed by dividing the 21 years into five periods (I approximately V). The number of elderly patients, especially those above the age of 70 years increased with time, reaching about 20% of all patients in the later period. As to the CMA classification, lesions in A region (antral region) tended to increase, reaching 32.8% in the last period. Lesions on the anterior and posterior wall increased, reaching 20.2% and 30.5%, respectively. Lesions on the greater curvature side were almost unchanged in frequency. The depressed type of carcinoma tended to increase in frequency in the later period, accounting for 75.3% of the total. The depressed type lesions, especially those consisting mainly of IIc element, were therefore subdivided into deep IIc and shallow IIc. In the later period, shallow IIc or not readily detected indistinct IIc increased markedly, reaching 83.3% in Period V. In the initial period, 40% of the lesions were larger than 5 cm. In the later period, lesions larger than 5 cm decreased to 10%, and more than 40% were 2 cm or smaller. Histologically, differentiated and undifferentiated types were found at almost the same frequency. In the later period, the differentiated type became more frequent, reaching as much as 58.2%. Ulcerative lesions (presence of ulcers or ulcer scars in the cancerous lesions) comprised more than 90% of depressed type early gastric cancer, but gradually decreased to 71.9% in the later period. From these findings, early gastric cancer may be said to be changing. Factors contributing to such changes were studied with reference to the progress and multiplication of diagnostic techniques, changes in age composition of the population and changes in environmental factors.


Increased mean platelet volume in chronic hepatitis B patients with inactive disease.
Hepatitis B virus (HBV) infection is a major public health problem worldwide, responsible for considerable morbidity and mortality from chronic liver disease. Conflicting findings on the possible association between HBV surface antigen (HBsAg) positivity, indicating inactive HBsAg carrier status, and atherosclerosis have been reported. Platelet activation and aggregation are central processes in the pathophysiology of atherosclerosis. Mean platelet volume, a determinant of platelet activation, is a newly emerging risk factor for atherothrombosis. Elevated MPV levels have been identified as an independent risk factor for myocardial infarction in patients with coronary heart disease, and for death or recurrent vascular events after myocardial infarction. Moreover, increased platelet size has been reported in patients with vascular risk factors such as diabetes mellitus, in patients with acute ischemic stroke, and essential hypertension. According to our knowledge, there has been no previous study of MPV in inactive HBsAg carriers. Therefore, we have investigated the possible association between HBsAg positivity and MPV. We selected 260 inactive HBsAg carriers, and 80 healthy control subjects matched for age, sex, and body mass index. The MPV level was significantly higher in the inactive HBsAg carrier group than in the control group (8.8+/-1.2 fl vs 8.1+/-0.9 fl, P=.001). Our results suggest that inactive HBsAg carriers tend to have relatively increased platelet activation and an atherothrombotic risk.


A biologically plausible learning rule for the Infomax on recurrent neural networks.
A fundamental issue in neuroscience is to understand how neuronal circuits in the cerebral cortex play their functional roles through their characteristic firing activity. Several characteristics of spontaneous and sensory-evoked cortical activity have been reproduced by Infomax learning of neural networks in computational studies. There are, however, still few models of the underlying learning mechanisms that allow cortical circuits to maximize information and produce the characteristics of spontaneous and sensory-evoked cortical activity. In the present article, we derive a biologically plausible learning rule for the maximization of information retained through time in dynamics of simple recurrent neural networks. Applying the derived learning rule in a numerical simulation, we reproduce the characteristics of spontaneous and sensory-evoked cortical activity: cell-assembly-like repeats of precise firing sequences, neuronal avalanches, spontaneous replays of learned firing sequences and orientation selectivity observed in the primary visual cortex. We further discuss the similarity between the derived learning rule and the spike timing-dependent plasticity of cortical neurons.


Cattle and sheep develop preference for drinking water containing grape seed tannin.
Ingestion of small amounts of some types of condensed tannins (CTs) by ruminant livestock can provide nutritional, environmental and economic benefits. However, practical methods are needed to make these tannins more available to ruminant livestock. Results from previous trials with crude quebracho and black wattle tannin indicated that cattle and/or sheep would not preferentially drink water containing these tannins. Therefore, we conducted preference trials to determine if cattle and sheep would learn to prefer water containing purified grape seed tannin (GST) that provided up to 2% of their daily dry matter (DM) intake. After gradual exposure to increasing amounts of this tannin in water during a pre-trial period, five adult ewes and five yearling heifers fed lucerne (Medicago sativa) pellets (19% CP) were offered water and several concentrations of GST solutions for either 15 (sheep trial) or 20 days (cattle trial). We measured intake of all liquids daily. Concentrations of blood urea were also measured for heifers when they drank only tannin solutions or water. Both sheep and cattle developed preferences for water with GST in it over water alone (P < 0.01) although this preference appeared earlier in the trial for sheep than for cattle. For the sheep, mean daily intake of water alone and all tannin solutions (in total) was 0.6 and 6.1 l, respectively. For the cattle, mean daily intake of water and all tannin solutions in total was 21.8 and 20.6 l, respectively, in the first half of the trial and 10.8 and 26.1 l, respectively, in the second half of the trial. Compared with the other tannin solutions, both sheep and cattle drank more of the solution with the highest tannin concentration (2% of daily DM intake as GST) than of water on more trial days (P < 0.05). Ingestion of water with the highest concentration of GST reduced blood plasma urea concentration in the cattle by 9% to 14% (P ≤ 0.10) compared with ingestion of water alone. Results from the trials suggest that providing grape seed and perhaps other CTs via drinking water may be a practical way to introduce CTs into sheep and cattle diets.


The effect of combined resistance exercise training and vitamin D3 supplementation on musculoskeletal health and function in older adults: a systematic review and meta-analysis.
In older adults, there is a blunted responsiveness to resistance training and reduced muscle hypertrophy compared with younger adults. There is evidence that both exercise training and vitamin D supplementation may benefit musculoskeletal health in older adults, and it is plausible that in combination their effects may be additive. The aim of this systematic review was to evaluate the effectiveness of combined resistance exercise training and vitamin D3 supplementation on musculoskeletal health in older adults. A comprehensive search of electronic databases, including Science Direct, Medline, PubMed, Google Scholar and Cochrane Central Register of Controlled Trials (Cochrane CENTRAL accessed by Wiley Science) was conducted. Eligible studies were randomised controlled trials including men and women (aged ≥65 years or mean age ≥65 years); enlisting resistance exercise training and vitamin D3 supplementation; including outcomes of muscle strength, function, muscle power, body composition, serum vitamin D/calcium status or quality of life comparing results with a control group. The review was informed by a preregistered protocol (http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42015020157). Seven studies including a total of 792 participants were identified. Studies were categorised into two groups; group 1 compared vitamin D3 supplementation and exercise training versus exercise alone (describing the additive effect of vitamin D3 supplementation when combined with resistance exercise training) and group 2 compared vitamin D3 supplementation and exercise training versus vitamin D3 supplementation alone (describing the additive effect of resistance exercise training when combined with vitamin D3 supplementation).Meta-analyses for group 1 found muscle strength of the lower limb to be significantly improved within the intervention group (0.98, 95% CI 0.73 to 1.24, p<0.001); all other outcomes showed small but non-significant positive effects for the intervention group. The short physical performance battery (SPPB), timed up and go (TUG), muscle strength of the lower limb and femoral neck bone mineral density showed significantly greater improvements in the intervention group for group 2 comparisons. This review provides tentative support for the additive effect of resistance exercise and vitamin D3 supplementation for the improvement of muscle strength in older adults. For other functional variables, such as SPPB and TUG, no additional benefit beyond exercise was shown. Further evidence is required to draw firm conclusions or make explicit recommendations regarding combined exercise and vitamin D3 supplementation.


[Radiation assisted diagnosis and complex treatment of penile carcinoma].
Recurrence-free survival rate after conservative treatment of penile carcinoma was as high as 81%. The best results were obtained with use of combined radiotherapy (monotherapy and telegamma therapy concurrent with penile resection or circumcision) (91.6 and 75%, respectively). Organ-saving treatment was most effective in T1-T2 penile carcinoma while MRI yielded the most reliable diagnostic evidence on depth of primary tumor invasion and regional lymph node involvement.


Isoquinoline synthesis by heterocyclization of tosylmethyl isocyanide derivatives: total synthesis of mansouramycin B.
A new method for the synthesis of isoquinolines through a catalytic acid-mediated cyclization of α-benzyl TosMIC derivatives has been developed. This methodology has been successfully applied to the total synthesis of mansouramycin B. This is the first total synthesis of this compound to be reported in the literature.


Knowledge, attitudes, and practices of Sudanese residents towards COVID-19.
Coronavirus disease 2019 (COVID-19) is a severe acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Sufficient knowledge, positive attitudes, and correct practices are crucial for the prevention of COVID-19. This study aimed at assessing the knowledge, attitudes and practices of a sample of Sudanese residents towards COVID-19. A cross-sectional community-based survey was conducted on 812 participants, including both sexes and aged 18 years and above, with the exclusion of health care workers. Considerable care was taken to include people with different education levels. Among the survey respondents (n=812), 45.8% were women, 40.4% held a bachelor's degree, 5.7% were uneducated, and 51.1% were aged 18-25 years. The overall correct rate of the knowledge questionnaire was 78.2%; 66.9% agreed that religious gatherings and events should be cancelled to prevent the spread of COVID-19; 34.1% of respondents wore medical masks; and 57.9% avoided shaking hands in recent days. This study showed that sampled Sudanese residents have incomplete knowledge and poor practices towards COVID-19. However, we found that women and people aged 18-25 years were more knowledgeable and had more positive attitudes towards COVID-19. We hope that concerned authorities will establish awareness programmes to improve the ability to combat this disease.


Identification of optimal strategies for state transition of complex biological networks.
Complex biological networks typically contain numerous parameters, and determining feasible strategies for state transition by parameter perturbation is not a trivial task. In the present study, based on dynamical and structural analyses of the biological network, we optimized strategies for controlling variables in a two-node gene regulatory network and a T-cell large granular lymphocyte signaling network associated with blood cancer by using an efficient dynamic optimization method. Optimization revealed the critical value for each decision variable to steer the system from an undesired state into a desired attractor. In addition, the minimum time for the state transition was determined by defining and solving a time-optimal control problem. Moreover, time-dependent variable profiles for state transitions were achieved rather than constant values commonly adopted in previous studies. Furthermore, the optimization method allows multiple controls to be simultaneously adjusted to drive the system out of an undesired attractor. Optimization improved the results of the parameter perturbation method, thus providing a valuable guidance for experimental design.


Passive stiffness of rat cardiac myocytes.
Intact single cells were isolated from adult rat hearts by enzymatic digestion and suspended in 0.25 mM Ca++ Tyrode's solution. Quiescent, clearly striated rodlike cells were selected for study of the elastic properties of the cells at various stages of membrane and myofilament extraction. Selected cells were placed in a relaxing solution (pCa + 9, 10 mn EGTA) and then each end gently pulled into the tip of a closely fitting suction micropipette for attachment to a force transducer and length perturbation driver. This procedure was performed in low Ca++ to prevent Ca++ loading of the cell during attachment and at room temperature to prevent chemical skinning of the cell. Stiffness was measured by applying a 5-Hz sinusoidal length perturbation (5 percent L0) to one end of the cell while measuring the induced tension change at the other. The ratio of sinusoidal tension change to applied length change (stiffness) was determined for each cell over a length range of about 1-1.3 L0 before removal of the contractile filaments and up to 3.0 L0 after treatment with 0.6 M KI. The stiffness-length relation was measured first in relaxing solution and then in 0.25 mM Ca++ Tyrode's. If spontaneous contractions or contracture occurred the cell was rejected. If the cell remained quiescent and relaxed it was treated again with relaxing solution and 1 percent Triton X-100 to remove the membranes. The stiffness-length relation was again measured and then the cell was superfused with 0.47 M KCl/10 mM pyrophosphate solution to remove the myosin filaments.(ABSTRACT TRUNCATED AT 250 WORDS)


Positioning the library at the epicenter of the networked biomedical enterprise.
The changing economic environment in which our biomedical enterprises operate presents unparalleled opportunities to the profession of medical librarianship. Evidence-based medicine, patient empowerment, asynchronous learning networks, and research colaboratories each involve a new type of shared information, or access to information in new ways or by different people. These tasks are ones with which librarianship is directly involved. Librarians are therefore placed perfectly to provide new products and services. To position the library at the epicenter of the networked biomedical enterprise we must meet three challenges: We must align the library's business strategy with that of the larger enterprise. We must provide services in ways that will scale-up to enable new business strategies. We must measure the effectiveness of services in ways that document their role in supporting the enterprise.


Invasive rodent eradication on islands.
Invasive mammals are the greatest threat to island biodiversity and invasive rodents are likely responsible for the greatest number of extinctions and ecosystem changes. Techniques for eradicating rodents from islands were developed over 2 decades ago. Since that time there has been a significant development and application of this conservation tool. We reviewed the literature on invasive rodent eradications to assess its current state and identify actions to make it more effective. Worldwide, 332 successful rodent eradications have been undertaken; we identified 35 failed eradications and 20 campaigns of unknown result. Invasive rodents have been eradicated from 284 islands (47,628 ha). With the exception of two small islands, rodenticides were used in all eradication campaigns. Brodifacoum was used in 71% of campaigns and 91% of the total area treated. The most frequent rodenticide distribution methods (from most to least) are bait stations, hand broadcasting, and aerial broadcasting. Nevertheless, campaigns using aerial broadcast made up 76% of the total area treated. Mortality of native vertebrates due to nontarget poisoning has been documented, but affected species quickly recover to pre-eradication population levels or higher. A variety of methods have been developed to mitigate nontarget impacts, and applied research can further aid in minimizing impacts. Land managers should routinely remove invasive rodents from islands <100 ha that lack vertebrates susceptible to nontarget poisoning. For larger islands and those that require nontarget mitigation, expert consultation and greater planning effort are needed. With the exception of house mice (Mus musculus), island size may no longer be the limiting factor for rodent eradications; rather, social acceptance and funding may be the main challenges. To be successful, large-scale rodent campaigns should be integrated with programs to improve the livelihoods of residents, island biosecurity, and reinvasion response programs.


[Comparative study on the predictive factors of anxiety among Quebec university students during the pandemic (COVID-19)].
Objective In this study, we present the results of a comparative research carried out on three cohorts of university students in the context of a pandemic. Several research indicate that the anxiety level of populations has increased significantly. Method In this article, we present the results of a comparative study of three cohorts study conducted on 1674 Quebec students. Participants were recruited at three separate time points, in the summer of 2020 (cohort 1; N = 398), in the fall of 2020 (cohort 2; N = 621) and in the winter of 2021 (cohort 3; N = 655). Anxiety was measured using Beck's anxiety inventory and several sociodemographic variables were tested. Results Results from cohort 1 indicate that being younger and having a mental health diagnosis may be vulnerability factors for anxiety. For cohort 2, the interaction of gender x diagnosis x program of study had a significant effect. Age and family income were predictive of significant anxiety in cohort 3. Limitations and perspectives of the study are explored. Conclusion The study recommends that the results be considered in developing preventive and intervention programs in the post-pandemic period.


Randomized trial of cefepime monotherapy or cefepime in combination with amikacin as empirical therapy for febrile neutropenia.
A multicenter open randomized trial was conducted to compare cefepime monotherapy with cefepime/amikacin combination (dual) therapy in treating febrile neutropenic patients with hematologic disorders. Among the 189 evaluable patients, 5.8% had microbiologically and 10.6% had clinically documented infections. Excellent response was seen in 32.6% and 45.7% of monotherapy and dual therapy recipients, respectively, at day 3 (P=.065). At day 3, patients with neutrophil counts of <500/ mu L receiving dual therapy had a better response than did those receiving monotherapy (45% vs. 27.6%; P=.024). The same was true for patients with leukemia. Adverse events were minimal, and early death was observed in 7 patients in the dual therapy group and 5 patients in the monotherapy group. Overall, cefepime monotherapy is as effective as dual therapy for the initial treatment of febrile neutropenic patients. Further study is warranted for patients with severe neutropenia and leukemia who may benefit from dual therapy.


Torsional stiffness in healing fractures: influence of ossification: an experimental study in rats.
Different fracture fixation techniques and fracture environment influence bone formation in healing fractures. However, the influence on the development of biomechanical properties has not been clear described. We evaluated the influence of fracture fixation stability and fracture environment on mechanical properties in healing femoral fractures in rats. Animals were treated surgically with external fixation: 1 group (27 rats) with 0-mm fracture gap size with bone ends touching, corresponding to an axial stiffness of 265 (SD 34) N/mm, and a second group (27 rats) with 2-mm fracture gap size corresponding to an axial stiffness of 30 (SD 2.1) N/mm. From each group, 6-7 animals were killed at 2, 4, 6 and 12 weeks. Torsional test revealed a delay in torsional stiffness in fractures in group 2 compared to group 1. In group 2, the torsional stiffness of the contralateral femora was found to be greater at 12 weeks than the torsional stiffness in group 1. We found that during fracture healing, the development of torsional stiffness corresponds to the magnitude of endochondral ossification and late response of bone formation. A significantly increased torsional stiffness in the non-fractured leg of rats with delayed fracture healing was also found, possibly indicating a response to loading conditions or a systemic stimulation of bone mass.


Inference of Ancestry in Forensic Analysis I: Autosomal Ancestry-Informative Marker Sets.
An expanding choice of ancestry-informative marker single nucleotide polymorphisms (AIM-SNPs) is becoming available for the forensic user in the form of sensitive SNaPshot-based tests or in alternative single-base extension genotyping systems (e.g., Sequenom iPLEX) that can be adapted for analysis with SNaPshot. In addition, alternative ancestry-informative variation: Indels and STRs can be analyzed using direct PCR-to-CE techniques that offer the possibility to detect mixed profiles. We review the current forensically viable AIM panels, their optimized PCR multiplexes, and the population differentiation power they offer. We also describe how improved population divergence balance can be achieved with the enlarged multiplex scales of next-generation sequencing approaches to enable analysis of admixed individuals without biased estimation of co-ancestry proportions.


Comparative protective effect of hawthorn berry hydroalcoholic extract, atorvastatin, and mesalamine on experimentally induced colitis in rats.
The protective effect of hydroalcoholic extract of hawthorn berries (HBE) on acetic acid (AA)-induced colitis in rats was investigated. Forty-two Wistar rats were divided into seven groups, including control and test groups (n=6). The control animals received saline, and the test animals were treated with saline (sham group), mesalamine (50 mg/kg; M group), atorvastatin (20 mg/kg; A group), HBE (100 mg/kg; H group), mesalamine and HBE (HM group), or atorvastatin plus HBE (HA group), 3 days before and a week after colitis induction. Colitis was induced by administration of 1 mL AA (4%) via a polyethylene catheter intrarectally. High-performance liquid chromatography analyses showed that HBE contained 0.13% and 0.5% oleanolic acid and ursolic acid, respectively. Elevated myeloperoxidase activity and lipid peroxidation were attenuated in the HA group. The H and HM groups showed marked reductions in colitis-induced decreases in total thiol molecules and body weight. The histopathological studies revealed that HBE decreased colitis-induced edema and infiltration of neutrophils. Our data suggest the anti-inflammatory and antioxidant effects of HBE and atorvastatin protect against AA-induced colitis. The anti-inflammatory effect of HBE may be attributable to its ability to decrease myeloperoxidase activity as a biomarker of neutrophil infiltration.


Vaginal endoscopic oophorectomy with vaginal hysterectomy: a simple minimal access surgery technique.
The main advantage of laparoscopic assisted vaginal hysterectomy (LAVH) is ease of access to the ovaries; despite this, LAVH is infrequently performed due to the inherent difficulty of the technique. Lower morbidity, shorter length of surgery, reduced hospital stay and more rapid recovery are the main advantages of vaginal hysterectomy, but one of its limitations is the accessibility of the ovaries. Three methods of vaginal endoscopic oophorectomy following vaginal hysterectomy are described in this paper. Endoscopic vaginal oophorectomy was successfully performed during 82 cases of vaginal hysterectomy and the results show that the technique is simple, safe and easy to learn, and an alternative to laparotomy and LAVH in the absence of pelvic adhesions.


DPPA5A suppresses the mutagenic TLS and MMEJ pathways by modulating the cryptic splicing of Rev1 and Polq in mouse embryonic stem cells.
Genetic alterations are often acquired during prolonged propagation of pluripotent stem cells (PSCs). This ruins the stem cell quality and hampers their full applications. Understanding how PSCs maintain genomic integrity would provide the clues to overcome the hurdle. It has been known that embryonic stem cells (ESCs) utilize high-fidelity pathways to ensure genomic stability, but the underlying mechanisms remain largely elusive. Here, we show that many DNA damage response and repair genes display differential alternative splicing in mouse ESCs compared to differentiated cells. Particularly, Rev1 and Polq, two key genes for mutagenic translesion DNA synthesis (TLS) and microhomology-mediated end joining (MMEJ) repair pathways, respectively, display a significantly higher rate of cryptic exon (CE) inclusion in ESCs. The frequent CE inclusion disrupts the normal protein expressions of REV1 and POLθ, thereby suppressing the mutagenic TLS and MMEJ. Further, we identify an ESC-specific RNA binding protein DPPA5A which stimulates the CE inclusion in Rev1 and Polq. Depletion of DPPA5A in mouse ESCs decreased the CE inclusion of Rev1 and Polq, induced the protein expression, and stimulated the TLS and MMEJ activity. Enforced expression of DPPA5A in NIH3T3 cells displayed reverse effects. Mechanistically, we found that DPPA5A directly regulated CE splicing of Rev1. DPPA5A associates with U2 small nuclear ribonucleoprotein of the spliceosome and binds to the GA-rich motif in the CE of Rev1 to promote CE inclusion. Thus, our study uncovers a mechanism to suppress mutagenic TLS and MMEJ pathways in ESCs.


Grape seed extracts inhibit dentin matrix degradation by MMP-3.
Since Matrix metalloproteinases (MMPs) have been suggested to contribute to dentin caries progression, the hypothesis that MMP inhibition would affect the progression of dentin caries is clinically relevant. Grape seed extracts (GSE) have been previously reported to be natural inhibitors of MMPs. To evaluate the capacity of a GSE mouthrinse to prevent the degradation of demineralized dentin matrix by MMP-3 (stromelysin-1). Standardized blocks of dentin obtained from sound permanent teeth extracted for orthodontic reasons were demineralized with Ethylenediaminetetraacetic acid (EDTA) and pretreated either with (A) GSE (0.2% w/v), (B) amine fluoride (AmF) (20% w/v), (C) a mouthrinse which contains both, (D) placebo, (E) sodium fluoride (0.15 mg.ml(-1)), (F) PBS, (G) Chlorhexidine digluconate (CHX), or (H) zinc chloride (ZnCl2). The dentin blocks were then incubated with activated recombinant MMP-3. The supernatants were analyzed by Western Blot for several dentin matrix proteins known to be MMP-3 substrate. In parallel, scanning electron microscopy (SEM) was performed on resin replica of the dentin blocks. Western blot analysis of the supernatants revealed that MMP-3 released from the dentin matrix small proteoglycans (decorin and biglycan) and dentin sialoprotein (DSP) in the AmF, sodium fluoride, PBS and placebo pretreated groups, but not in the GSE and mouthrinse pretreated groups. SEM examination of resin replica showed that the mouthrinse and its active components not only had an anti-MMP action but also modified the dentin surface accessibility. This study shows that GSE either alone or combined with AmF as in the evaluated mouthrinse limits dentin matrix degradation. This association may be promising to prevent the progression of caries within dentin. However, the procedure should be adapted to clinically relevant durations.


Tert-butylhydroquinone protects PC12 cells against ferrous sulfate-induced oxidative and inflammatory injury via the Nrf2/ARE pathway.
Increasing evidence had proved the critical role of iron in the pathogenesis of numerous neurodegenerative diseases because of its capacity to promote the formation of reactive oxygen species (ROS). Tert-butylhydroquinone (tBHQ) was a metabolite of butylated hydroxyanisole, a widely used food antioxidant. This study was aimed to investigate the protective effects of tBHQ on a cellular model of neurodegenerative disease, which was established in PC12 cells by exposure to ferrous sulfate (FS), and elucidate the potential protective mechanisms. The results showed that FS exposure increased lactate dehydrogenase (LDH) release and cell apoptosis in PC12 cells, accompanied by significant increases in the bax/bcl-2 ratio, cytochrome c release, and caspase-3 cleavage. It also enhanced the ROS production, malondialdehyde (MDA) content (lipid peroxidation), γ-H2A.X formation (DNA damage), and promoted nuclear factor kappa B (NF-κB) activation and expressions of cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). tBHQ pretreatment alleviated FS-induced LDH release, cell apoptosis, oxidative stress and inflammatory response by promoting Nrf2 nuclear translocation and the protein levels of Nrf2 downstream target genes heme oxygenase-1 (Hmox-1), nicotinamide adenine dinucleotide phosphate (NADPH): quinone oxidoreductase-1 (Nqo1) and glutathione peroxidase-1 (Gpx1). tBHQ alleviated the FS-induced LDH release in control siRNA-treated PC12 cells, but failed to alleviate FS-induced LDH release in Nrf2 siRNA-treated cells. These findings suggested that pretreatment with tBHQ protected PC12 cells from FS-induced oxidative and inflammatory injury via the Nrf2/ARE pathway. tBHQ was promising as a potential therapeutic agent for neurodegenerative diseases induced by iron toxicity and should be encouraged for further research.


Staining of paraganglionic cells with lead hematoxylin.
Lead hematoxylin staining in most paraganglionic cells is too faint to be observed in the light microscope (LM). Paraganglionic cells which appear stained (LM) are also known to contain more and larger specific granules (as seen in the electron microscope, EM) than those paraganglionic cells remaining unstained (LM). However, also specific granules in lead hematoxylin-negative paraganglionic cells (LM) bind lead ions (EM), which behaviour is the basis of lead hematoxylin staining. It is concluded that lead hematoxylin stains matrix material of specific granules but the amount of granule material mostly is too small to yield colour intensities to be observed in the LM.


Matched-Pair Analysis: Large-Sized Defects in Surgery of Lower Limb Nonunions.
The treatment of large-sized bone defects remains a major challenge in trauma and orthopaedic surgery. Although there are many treatment options, there is still no clear guidance on surgical management, and the influence of defect size on radiological and clinical outcome remains unclear due to the small number of affected patients. The aim of the present study was to determine the influence of defect size on the outcome of atrophic and infected nonunions of the tibia or the femur based on the diamond concept in order to provide recommendations for treatment guidance. All medical records, surgical reports, laboratory data and radiological images of patients treated surgically for atrophic or infected nonunions of the lower limbs (femur or tibia) between 1 January 2010 and 31 December 2020 were examined. Patients with proximal, diaphyseal or distal nonunions of the femur or tibia who were surgically treated at our institution according to the "diamond concept" and attended our standardised follow-up program were included in a database. Surgical treatment was performed as a one- or two-step procedure, depending on the type of nonunion. Patients with a segmental bone defect ≥5 cm were matched with patients suffering a bone defect <5 cm based on five established criteria. According to our inclusion and exclusion criteria, 70 patients with a bone defect ≥5 cm were suitable for analysis. Two groups were formed by matching: the study group (bone defect ≥5 cm; n = 39) and control group (bone defect <5 cm; n = 39). The study was approved by the local ethics committee (S-262/2017). The mean defect size was 7.13 cm in the study and 2.09 cm in the control group. The chi-square test showed equal consolidation rates between the groups (SG: 53.8%; CG: 66.7%). However, the Kaplan-Meier curve and log-rank test showed a significant difference regarding the mean duration until consolidation was achieved, with an average of 15.95 months in the study and 9.24 months in the control group (α = 0.05, p = 0.001). Linear regression showed a significant increase in consolidation duration with increasing defect size (R2 = 0.121, p = 0.021). Logistic regression modelling showed a significant negative correlation between consolidation rate and revision performance, as well as an increasing number of revisions, prior surgeries and total number of surgeries performed on the limb. Clinical outcomes showed equal full weight bearing of the lower extremity after 5.54 months in the study vs. 4.86 months in the control group (p = 0.267). Surprisingly, defect size does not seem to have a significant effect on the consolidation rate and should not be seen as a risk factor. However, for the treatment of large-sized nonunions, the follow-up period should be prolonged up to 24 months, due to the extended time until consolidation will be achieved. This period should also pass before a premature revision with new bone augmentation is performed. In addition, it should be kept in mind that as the number of previous surgeries and revisions increases, the prospects for consolidation decrease and a change in therapeutic approach may be required.


In-hospital and short-term prognostic factors in acute pulmonary edema: clinical and morphological features.
There are extensive records which have included patients with acute heart failure (AHF), but specific studies about prognosis in acute pulmonary edema (PE) are scarce and have enrolled a small number of patients. The objectives of this study were to evaluate the predictive factors of short-term evolution in patients with PE. This was a prospective, two-center survey of 70 consecutive patients admitted for acute cardiogenic PE. The follow-up was performed one month after discharge. The composite endpoint was in-hospital death, and death of any cause or readmission for heart failure (HF) at one month after discharge. Heart and lung tissue analysis was performed postmortem to identify morphological features of PE. In-hospital mortality was 4.2%, another 14.2% died in the first month, and an additional 10% required rehospitalization for HF. The characteristics significantly associated with end-point occurrence were: history of kidney disease, anemia, diabetes mellitus, lack of prior angiotensin-converting enzyme inhibitor÷angiotensin-receptor blocker treatment, lower systolic blood pressure (BP) at admission, lower diastolic BP at admission, creatinine at admission and at discharge, an increase in creatinine during stay, glomerular filtration rate at admission, serum sodium at admission, decrease in serum sodium during hospitalization, N-terminal prohormone of brain natriuretic peptide (NT-proBNP) at discharge, right ventricle fractional area change, left atrium volume index. We created a multiple logistic regression model and identified five prognostic factors: age, diabetes, creatinine, diastolic BP, serum sodium. This model correctly classified 48 (96%) patients without worsening and 13 (65%) patients with worsening, providing an overall accuracy of 87.1%. Necropsy was performed on five patients and fragments of left ventricle myocardium and lung were harvested for histopathological and immunohistochemical studies. The myocardium exhibited fibrosis areas where the myocytes were completely or partially replaced by collagen fibers. Lung tissue analysis revealed some case-to-case differences, but the common finding was alveoli size larger than normal, with the lumen completely or almost completely covered by an eosinophilic liquid. The factors that best predicted the short-term outcome in PE were age, diabetes, diastolic BP, creatinine, serum sodium.


Ammonium piperidine-1-carbodithio-ate.
The title compound, NH(4) (+)·C(6)H(10)NS(2) (-), is composed of an ammonium cation and a piperidine-1-carbodithio-ate anion which exhibits positional disorder. The atoms of the ring have a structural disorder and they are divided into two sites, with occupancy factors of 0.584 and 0.426.. In the crystal, the cation and anion are linked by N-H⋯S hydrogen bonds to form an infinite two-dimensional network.


[High-risk needlestick injuries and virus transmission : A prospective observational study].
Needlestick injuries (NSI) of healthcare personnel (HCP) are work-related accidents with a risk of transmission of blood-borne human immunodeficiency virus (HIV), hepatitis B and C viruses (HBV, HCV). Along with preventive measures to avoid accidental NSI, preventing the risk and diagnosis of an infection from NSI are given a high priority. Thus, follow-up monitoring of NSI is of great interest. Evaluation of the follow-up monitoring after NSI with respect to early recognition of transmission of HIV, HCV and HBV as well as adherence and psychological burden of HCP. Clinical and serological investigations of the injured HCP including determining the individual risk of infection in the situation of NSI, analysis of accident protocols by the accident insurance consultant and use of a self-developed standardized questionnaire. No virus transmissions from NSI were found during the observation period (23 March 2014 until 31 October 2017). A total of 112 NSI with infectious index patients (HIV 35.7%, HCV 54.5%, HBV 2.7%, coinfection 7.1%) and 3 incidents from unknown index patients were analyzed. Of the index patients six received the first diagnosis of a blood-borne infection (2 HCV infections, 4 HIV infections) after NSI. In nearly all incidents (98.3%) the HCP took measures to disinfect and flush the injury and 85.1% of the HCP exposed to HIV or unknown infection risk undertook postexposure prophylaxis (HIV-PEP) within 2 h and another 12.8% within 10 h. Follow-up examination was attended by 97.4% of the HCP, three quarters of the HCP felt concerned following NSI and 12.2% were very concerned. Through adequate management and follow-up of NSI low transmission rates can be achieved after exposure to blood-borne viruses within the occupational environment.


[Studies on central and peripheral hemodynamics using radiocardiography and Xenon-133 muscle clearance in patients with essential hypertension].
Examination of 80 patients with essential hypertension revealed a significant correlation between the tonus of peripheral muscular arterioles on the one hand, and the stage and duration of hypertension and age of the patients, on the other hand. The correlation between arteriolar tonus and indicators of cardiac pump function was less marked. The results confirmed the close relationship between changes of peripheral blood bed and development of hypertension. The use of 133Xe half-period for measuring the peripheral arteriolar tonus proved a simple, but informative method adding an important indicator of peripheral haemodynamics to the results of haemodynamic examination.


Increased or decreased levels of Caenorhabditis elegans lon-3, a gene encoding a collagen, cause reciprocal changes in body length.
Body length in C. elegans is regulated by a member of the TGFbeta family, DBL-1. Loss-of-function mutations in dbl-1, or in genes encoding components of the signaling pathway it activates, cause worms to be shorter than wild type and slightly thinner (Sma). Overexpression of dbl-1 confers the Lon phenotype characterized by an increase in body length. We show here that loss-of-function mutations in dbl-1 and lon-1, respectively, cause a decrease or increase in the ploidy of nuclei in the hypodermal syncytial cell, hyp7. To learn more about the regulation of body length in C. elegans we carried out a genetic screen for new mutations causing a Lon phenotype. We report here the cloning and characterization of lon-3. lon-3 is shown to encode a putative cuticle collagen that is expressed in hypodermal cells. We show that, whereas putative null mutations in lon-3 (or reduction of lon-3 activity by RNAi) causes a Lon phenotype, increasing lon-3 gene copy number causes a marked reduction in body length. Morphometric analyses indicate that the lon-3 loss-of-function phenotype resembles that caused by overexpression of dbl-1. Furthermore, phenotypes caused by defects in dbl-1 or lon-3 expression are in both cases suppressed by a null mutation in sqt-1, a second cuticle collagen gene. However, whereas loss of dbl-1 activity causes a reduction in hypodermal endoreduplication, the reduction in body length associated with overexpression of lon-3 occurs in the absence of defects in hypodermal ploidy.


Assessment of BRAF V600E Status in Colorectal Carcinoma: Tissue-Specific Discordances between Immunohistochemistry and Sequencing.
Although sequencing provides the gold standard for identifying colorectal carcinoma with BRAF V600E mutation, immunohistochemistry (IHC) with the recently developed mouse monoclonal antibody VE1 for BRAF V600E protein has shown promise as a more widely available and rapid method. However, we identified anecdotal discordance between VE1 IHC and sequencing results and therefore analyzed VE1 staining by two different IHC methods (Leica Bond and Ventana BenchMark) in whole tissue sections from 480 colorectal carcinomas (323 BRAF wild-type, 142 BRAF V600E mutation, and 15 BRAF non-V600E mutation). We also compared the results with melanomas and papillary thyroid carcinomas (PTC). With the Bond method, among 142 BRAF V600E-mutated colorectal carcinomas, 77 (54%) had diffuse VE1 staining and 48 (33%) had heterogeneous staining, but 17 (12%) were negative. Among 323 BRAF wild-type colorectal carcinomas, 196 (61%) were negative, but 127 (39%) had staining, including 7 with diffuse staining. When positivity was defined as staining in ≥ 20% of tumor cells, VE1 IHC had sensitivity of 75% and specificity of 93% for BRAF V600E mutation. With the Ventana method, among 57 BRAF V600E-mutated colorectal carcinomas, 36 (63%) had diffuse VE1 staining, whereas 6 (11%) had no or weak (<20% of tumor cells) staining. Among 33 BRAF wild-type colorectal carcinomas, 16 (48%) had no or weak staining, whereas 15 (45%) had heterogeneous staining. In contrast with colorectal carcinoma, Bond and Ventana VE1 IHC in melanoma and PTC were highly concordant with sequencing results. We conclude that VE1 IHC produces suboptimal results in colorectal carcinoma and should not be used to guide patient management.


A deep learning-based recognition for dangerous objects imaged in X-ray security inspection device.
Several limitations in algorithms and datasets in the field of X-ray security inspection result in the low accuracy of X-ray image inspection. In the literature, there have been rare studies proposed and datasets prepared for the topic of dangerous objects segmentation. In this work, we contribute a purely manual segmentation for labeling the existing X-ray security inspection dataset namely, SIXRay, with the pixel-level semantic information of dangerous objects. We also propose a composition method for X-ray security inspection images to effectively augment the positive samples. This composition method can quickly obtain the positive sample images using affine transformation and HSV features of X-ray images. Furthermore, to improve the recognition accuracy, especially for adjacent and overlapping dangerous objects, we propose to combine the target detection algorithm (i.e., the softer-non maximum suppression, Softer-NMS) with Mask RCNN, which is named as the Softer-Mask RCNN. Compared with the original model (i.e., Mask RCNN), the Softer-Mask RCNN improves by 3.4% in accuracy (mAP), and 6.2% with adding synthetic data. The study result indicates that our proposed method in this work can effectively improve the recognition performance of dangerous objects depicting in the X-ray security inspection images.