Differential gene expression in an actinorhizal symbiosis: evidence for a nodule-specific cysteine proteinase.
Nodules formed on the roots of actinorhizal plants as a consequence of nitrogen-fixing symbioses with the actinomycete Frankia appear to result from modification of the developmental pathway that leads to lateral root formation. Presently no information exists about factors that control this developmental switch or, until now, about genes that are differentially expressed as a result of an altered developmental pathway. Differential screening of an Alnus glutinosa nodule cDNA library revealed altered levels of gene expression in nodules as compared with roots and allowed isolation of host plant nodule-specific cDNA sequences. The deduced amino acid sequence of one full-length cDNA, AgNOD-CP1, represents a nodule-specific cysteine proteinase similar to cysteine proteinases of the papain superfamily. Residues critical to catalysis, active site, and disulfide bridges are conserved. Suggested roles for this enzyme are as a defense response to Frankia invasion, as a component of tissue remodeling in root and nodule tissues, as a cell cycle component, or as an element of protein turnover. Complexity of hybridization patterns revealed by Southern blot analysis suggests that the gene for AgNOD-CP1 is a member of a multigene family. Northern hybridization results indicate that this gene may have been recruited for a role specific to this symbiosis, a phenomenon observed in the Rhizobium-legume symbioses, perhaps common to many microbe-plant interactions.


Human intrahepatic CD69 + CD8+ T cells have a tissue resident memory T cell phenotype with reduced cytolytic capacity.
Tissue resident memory T cells (TRM) have been identified in various tissues, however human liver TRM to date remain unidentified. TRM can be recognized by CD69 and/or CD103 expression and may play a role in the pathology of chronic hepatitis B (CHB) and hepatitis C virus infection (CHC). Liver and paired blood mononuclear cells from 17 patients (including 4 CHB and 6 CHC patients) were isolated and CD8+ T cells were comprehensively analysed by flowcytometry, immunohistochemistry and qPCR. The majority of intrahepatic CD8+ T cells expressed CD69, a marker used to identify TRM, of which a subset co-expressed CD103. CD69 + CD8+ T cells expressed low levels of S1PR1 and KLF2 and a large proportion (>90%) was CXCR6+, resembling liver TRM in mice and liver resident NK cells in human. Cytotoxic proteins were only expressed in a small fraction of liver CD69 + CD8+ T cells in patients without viral hepatitis, however, in livers from CHB patients more CD69 + CD8+ T cells were granzyme B+. In CHC patients, less intrahepatic CD69 + CD8+ T cells were Hobit+ as compared to CHB and control patients. Intrahepatic CD69 + CD8+ T cells likely TRM which have a reduced cytolytic potential. In patients with chronic viral hepatitis TRM have a distinct phenotype.


Obstetric Performance Following Post-Traumatic Recurrent Fundal Uterine Rupture: A Case Report.
A case of recurrent post-traumatic fundal uterine rupture followed by an uncomplicated alive birth, unusual obstetric performance following extensive myometrial damage, happened in Hawassa University comprehensive specialized hospital. The first incident of fundal rupture was 5 years earlier than the second, after she sustained a road traffic accident at the gestational age of 31 weeks. There was associated polytrauma. The second uterine rupture was at 33 weeks of gestation, following a fall-down accident on a flat surface while performing routine household activities. The third pregnancy was an uncomplicated elective cesarean delivery, and the tubes were not ligated as the woman strongly wishes to preserve her future fertility. A single facility experience with this rare clinical scenario of obstetric performance is reported to stimulate interest in additional research into the subsequent obstetric performance of patients with recurrent fundal uterine rupture and resultant extensive myometrial damage.


Radiographic disease patterns at the carpus.
Radiographic analysis of the wrist includes evaluation of general nonspecific alterations of the carpus, changes specific to one or several diseases, the location of the abnormalities, and the pattern of disease. Correlation with clinical history is extremely important. Some diseases, such as gout, are usually detectable clinically. Others, such as chondrocalcinosis or chronic infection, may have been unrecognized prior to the radiographic study. Special investigations are necessary in difficult cases.


The crystal structure of anhydrous beta-caffeine as determined from X-ray powder-diffraction data.
The crystal structure of the low-temperature form of anhydrous caffeine has been determined by using X-ray powder-diffraction data with a combined simulated-annealing/Rietveld method. Anhydrous caffeine crystallizes with five crystallographically independent molecules in a monoclinic C-centred unit cell with dimensions of a=43.0390(17), b=15.0676(6) and c=6.95314(14) A and a beta angle of 99.027(2) degrees.


Three trithiadiazepines and a trithiatriazepine.
The structures of 6-nitro-1,3λ(4)δ(2),5,2,4-trithiadiazepine [C2HN3O2S3, (1)], 6,7-dinitro-1,3λ(4)δ(2),5,2,4-trithiadiazepine [C2N4O4S3, (2)], 1,3λ(4)δ(2),5,2,4-trithiadiazepine-6,7-dicarbonitrile [C4N4S3, (3)] and 7-acetyl-1,3λ(4)δ(2),5,2,4,6-trithiatriazepine [C3H3N3OS3, (4)] presented here include the most precise determinations of these seven-membered 10 π-electron aromatic ring systems published to date. Both (2) and (3) are sited around crystallographic twofold axes with half a molecule per asymmetric unit. Comparison with other published derivatives of these rings reveals the effect of substituents on bonding, conformations and intermolecular interactions, including π-stacking. The deformation density analysis of (2) is consistent with the expected bonding electron density from other theoretical and experimental studies.


Imaging of nuclear Overhauser enhancement at 7 and 3 T.
Nuclear Overhauser enhancement (NOE) is a type of magnetization transfer using cross-relaxation. It originates from mobile macromolecules, which may have relevance to the evaluation of tumor features. We studied the value of NOE imaging at 7 and 3 T and suggest a utility for diagnosing human brain tumors. Two types of protein solution at different concentrations and pH values, and six normal Sprague Dawley (SD) rats, were used to detect NOE signal with a 7 T scanner. Then, six healthy volunteers and 11 patients with brain tumors (six gliomas and five meningiomas) were included at 3 T. Z-spectra were measured and NOE weighted (NOE*) images were acquired with a three-offset measurement. Wide spectral separation was shown at both 7 T and 3 T delineating the NOE peak in the Z-spectrum. The concentration dependence and pH independence of NOE were confirmed in phantom experiments, and NOE values were greater in white matter than in gray matter in vivo. At 3 T, data indicated that NOE* maps were slightly hypointense in gliomas and were not obviously different from meningiomas. Thus, NOE imaging may help distinguish benign from malignant tumors, and as such may contribute to diagnosing brain tumors.


Upfront special staining for Helicobacter pylori in gastric biopsy specimens is not indicated.
The practice of routine upfront use of special stains in biopsy specimens with minimal or no inflammation has not been evaluated. This study was conducted to determine the value of special stains for Helicobacter pylori in gastric biopsy specimens showing variable degrees of inflammation and to evaluate the practice of upfront ancillary staining of all mucosal biopsy specimens. Immunohistochemical or Diff-Quik stains were done on sections of 570 gastric biopsy specimens. The rates of positivity for H pylori were calculated in each category based on the degree of inflammation and classified as normal, minimal, mild, moderate, or severe. H pylori was not detected in 386 (67.7%) biopsy specimens that were classified as normal (6.0%) or with minimal inflammation (28.2%) or mild inactive gastritis (33.5%). The organism was identified by Diff-Quik or immunohistochemical stain in 76 (89.4%) of 85 with moderate active gastritis and 30 (93.8%) of 32 biopsy specimens showing severe active gastritis. Upfront staining of gastric biopsy specimens is not cost-effective since a significant proportion of the gastric biopsy specimens were normal or showed minimal inflammation; in none of these biopsy specimens was the organism found. Special stains should be performed only in selected biopsy specimens that reveal any degree of chronic active gastritis or moderate inactive gastritis.


Cryoprotection of day-4 mouse embryos by methanol.
Methanol was examined as a cryoprotective additive that permits the direct transfer of frozen--thawed Day-4 mouse embryos to foster mothers without dilution of the cryoprotectant. Methanol permeated the embryos rapidly, was not toxic and exerted a cryoprotective action. The highest level of survival (50%) of embryos in vitro was observed after equilibration in Medium PB1 containing 3.0 M-methanol, slow cooling (0.5 degrees C/min) to a temperature between -30 and -40 degrees C, rapid cooling (800 degrees C/min) and storage in liquid nitrogen (-196 degrees C), rapid warming (800 degrees C/min), and rapid dilution. A high rate of development in vivo to late-stage fetuses (up to 81%) was observed when cryopreserved embryos were transferred to pseudopregnant recipients immediately after thawing.


Weak signal detection based on the information fusion and chaotic oscillator.
Based on the chaotic oscillator, a method for weak signal detection using information fusion technology is proposed in this paper. On the one hand, various methods are employed to the amplitude detection of the same weak periodic signal, then the detection outcomes are fused by the adaptive weighted fusion method. On the other hand, during the detection course, information entropy, statistic distance, and Walsh transform are, respectively, used in the state recognition of chaotic oscillator from the viewpoint of time domain or frequency domain, then the recognition results are fused by the k/l fusion method. Numerical results show that the proposed approach detects signal more precisely, identifies state more accurately, and represents information more completely compared with traditional methods.


Case report. Magnetic resonance features of metastatic melanoma of the temporomandibular joint and mandible.
We report a case of histologically verified melanoma of the nose which presented 2 years after initial radiotherapy with left temporomandibular pain, dysfunction and dental sepsis. Conventional radiography revealed a partially dentate mandible with a destructive lesion involving the left condyle, an ill-defined lesion in the right retromolar region and chronic inflammatory apical root lesions. Since MRI of the nose was done at the initial presentation, it was postulated that MRI could be used to characterize the destructive jaw lesions. The MR features were similar to the original nasal lesion and accepted as proof of diagnosis of metastatic melanoma. A literature review reveals only 37 previous cases of metastasis to the temporomandibular joint with none of involvement by melanoma. The role of MRI in the diagnosis of this lesion is also described for the first time.


Ultraviolet Mutagenesis Coupled with Next-Generation Sequencing as a Method for Functional Interrogation of Powdery Mildew Genomes.
Powdery mildews are obligate biotrophic fungal pathogens causing important diseases of plants worldwide. Very little is known about the requirements for their pathogenicity at the molecular level. This is largely due to the inability to culture these organisms in vitro or to modify them genetically. Here, we describe a mutagenesis procedure based on ultraviolet (UV) irradiation to accumulate mutations in the haploid genome of the barley powdery mildew pathogen Blumeria graminis f. sp. hordei. Exposure of B. graminis f. sp. hordei conidia to different durations of UV-C radiation (10 s to 12 min) resulted in a reduced number of macroscopically visible fungal colonies. B. graminis f. sp. hordei colony number was negatively correlated with exposure time and the total number of consecutive cycles of UV irradiation. Dark incubation following UV exposure further reduced fungal viability, implying that photoreactivation is an important component of DNA repair in B. graminis f. sp. hordei. After several rounds of UV mutagenesis, we selected two mutant isolates in addition to the parental B. graminis f. sp. hordei K1 isolate for whole-genome resequencing. By combining automated prediction of sequence variants and their manual validation, we identified unique UV-induced mutations in the genomes of the two isolates. Most of these mutations were in the up- or downstream regions of genes or in the intergenic space. Some of the variants detected in genes led to predicted missense mutations. As an additional insight, our bioinformatic analyses revealed a complex population structure within supposedly clonal B. graminis f. sp. hordei isolates.


Development of an immunogenic cell death prognostic signature for predicting clinical outcome and immune infiltration characterization in stomach adenocarcinoma.
Stomach adenocarcinoma (STAD) is a common gastric histological cancer type with a high mortality rate. Immunogenic cell death (ICD) plays a key factor during carcinogenesis progress, whereas the prognostic value and role of ICD-related genes (ICDRGs) in STAD remain unclear. The MSigDB database collecting ICDRGs were selected by univariate Cox regression analysis and LASSO algorithm to establish a novel risk model. The Kaplan-Meier survival analysis indicated a significant difference of OS rate of patients by risk score stratification. ESTIMATE, CIBERSORT, and single sample gene set enrichment analysis (ssGSEA) algorithms were conducted to estimate the immune infiltration landscape by risk stratification. Subgroup analysis and tumor mutation burden analysis were also analyzed to identify characteristics between groups. Differences in therapeutic responsiveness to chemotherapeutic drugs and targeted drugs were also analyzed between high-risk group and low-risk group. The impact of one ICDRG, GPX1, on the proliferation, migration and invasiveness of was confirmed by in vitro experiments in GC cells to test the reliability of bioinformatics results. This study gives evidence of the involvement of ICD process in STAD and provides a new perspective for further accurate assessment of prognosis and therapeutic efficacy in STAD patients. Stomach adenocarcinoma (STAD) is a common gastric histological cancer type with a high mortality rate. Immunogenic cell death (ICD) plays a key factor during carcinogenesis progress, whereas the prognostic value and role of ICD-related genes (ICDRGs) in STAD remains unclear. The MSigDB database collected ICDRGs were selected by univariate Cox regression analysis and LASSO algorithm to establish a novel risk model. The Kaplan-Meier survival analysis indicated a significant difference of OS rate of patients by risk score stratification. ESTIMATE, CIBERSORT, and single sample gene set enrichment analysis (ssGSEA) algorithms were conducted to estimate the immune infiltration landscape by risk stratification. Subgroup analysis and tumor mutation burden analysis were also analyzed to identify characteristics between groups. Differences in therapeutic responsiveness to chemotherapeutic drugs and targeted drugs were also analyzed between high-risk group and low-risk group. The impact of one ICDRG, GPX1, on the proliferation, migration and invasiveness of was confirmed by in vitro experiments in GC cells to test the reliability of bioinformatics results. This study gives evidence of the involvement of ICD process in STAD and provides a new perspective for further accurate assessment of prognosis and therapeutic efficacy in STAD patients.


Environmental factors contribute to the enhanced regeneration of frog sciatic sensory axons by a conditioning lesion.
The outgrowth of regenerating frog sciatic sensory axons after a crush lesion was measured from the distribution of axonally transported radioactive proteins. Five days after a single test crush the regeneration distance was 3.6 +/- 0.3 mm. If the nerve was subjected to a conditioning lesion 15 mm distal to and 5, 10 or 17 days prior to the test crush, there was an increased outgrowth distance (5.1 +/- 0.2 mm) 5 days after the test crush when the conditioning interval was 10 days. Prolongation of the time interval between the two lesions to 17 days did not significantly change the enhanced outgrowth. In contrast, if the conditioning and test lesions were applied at the same site, the regeneration distance 5 days after the test crush was already significantly increased after a conditioning interval of 5 days (5.9 +/- 0.5 mm). It was further enhanced after an interval of 10 days (7.8 +/- 0.5 mm) and yet further after 17 days (9.2 +/- 0.5 mm). When the conditioning and test lesions were superimposed, the regeneration occurred through a region of the nerve that was pre-degenerated due to the conditioning lesion. The positive correlation between the degree of degeneration and the outgrowth distance supports the theory that environmental factors contribute to the regenerating ability of peripheral nerves.


Is Hypothermia Helpful in Severe Subarachnoid Hemorrhage? An Exploratory Study on Macro Vascular Spasm, Delayed Cerebral Infarction and Functional Outcome after Prolonged Hypothermia.
Therapeutic hypothermia (TH) is an established treatment after cardiac arrest and growing evidence supports its use as neuroprotective treatment in stroke. Only few and heterogeneous studies exist on the effect of hypothermia in subarachnoid hemorrhage (SAH). A novel approach of early and prolonged TH and its influence on key complications in poor-grade SAH, vasospasm and delayed cerebral ischemia (DCI) was evaluated. This observational matched controlled study included 36 poor-grade (Hunt and Hess Scale >3 and World Federation of Neurosurgical Societies Scale >3) SAH patients. Twelve patients received early TH (<48 h after ictus), mild (35°C), prolonged (7 ± 1 days) and were matched to 24 patients from the prospective SAH database. Vasospasm was diagnosed by angiography, macrovascular spasm serially evaluated by Doppler sonography and DCI was defined as new infarction on follow-up CT. Functional outcome was assessed at 6 months by modified Rankin Scale (mRS) and categorized as favorable (mRS score 0-2) versus unfavorable (mRS score 3-6) outcome. Angiographic vasospasm was present in 71.0% of patients. TH neither influenced occurrence nor duration, but the degree of macrovascular spasm as well as peak spastic velocities were significantly reduced (p < 0.05). Frequency of DCI was 87.5% in non-TH vs. 50% in TH-treated patients, translating into a relative risk reduction of 43% and preventive risk ratio of 0.33 (95% CI 0.14-0.77, p = 0.036). Favorable functional outcome was twice as frequent in TH-treated patients 66.7 vs. 33.3% of non-TH (p = 0.06). Early and prolonged TH was associated with a reduced degree of macrovascular spasm and significantly decreased occurrence of DCI, possibly ameliorating functional outcome. TH may represent a promising neuroprotective therapy possibly targeting multiple pathways of DCI development, notably macrovascular spasm, which strongly warrants further evaluation of its clinical impact.


Dioscin Induces Apoptosis in Human Cervical Carcinoma HeLa and SiHa Cells through ROS-Mediated DNA Damage and the Mitochondrial Signaling Pathway.
Dioscin, a natural product, has activity against glioblastoma multiforme, lung cancer and colon cancer. In this study, the effects of dioscin against human cervical carcinoma HeLa and SiHa cells were further confirmed, and the possible mechanism(s) were investigated. A transmission electron microscopy (TEM) assay and DAPI staining were used to detect the cellular morphology. Flow cytometry was used to assay cell apoptosis, ROS and Ca(2+) levels. Single cell gel electrophoresis and immunofluorescence assays were used to test DNA damage and cytochrome C release. The results showed that dioscin significantly inhibited cell proliferation and caused DNA damage in HeLa and SiHa cells. The mechanistic investigation showed that dioscin caused the release of cytochrome C from mitochondria into the cytosol. In addition, dioscin significantly up-regulated the protein levels of Bak, Bax, Bid, p53, caspase-3, caspase-9, and down-regulated the protein levels of Bcl-2 and Bcl-xl. Our work thus demonstrated that dioscin notably induces apoptosis in HeLa and SiHa cells through adjusting ROS-mediated DNA damage and the mitochondrial signaling pathway.


The effect of excessive weight loss on skeletal muscle in man. A study of obese patients following gastroplasty.
Lean body mass, muscle biochemistry, enzymehistochemistry and muscle strength were analyzed before and after 10% and 18% body weight loss following gastroplasty in 16 obese patients. Subjective fatigue was also determined, using an arbitrary scale, before and after the operation. Lean body mass and alkali-soluble proteins (non-collagenic proteins) per DNA decreased significantly in the postoperative period. The proportions of type I and type II muscle fibers remained normal postoperatively. The muscle fiber area decreased significantly at 10% body weight loss, with a tendency towards restoration at 18% weight loss, despite continuing loss of lean body mass. Preoperatively the muscle strength, determined as maximum voluntary concentric and eccentric action of the knee extensor and flexor muscles, was not significantly different from that in sedentary, age-matched subjects, but was less than expected from the lean body mass, content of alkali-soluble proteins and muscle fiber size. Muscle strength was not significantly changed postoperatively. According to the fatigue scale, the patients' wellbeing was improved at 18% body weight loss compared with the preoperative status.


The effect of the number of possible words on word completion: a magnetoencephalographic study.
We examined the effect of the number of possible words in a word completion task on left superior temporal activity using magnetoencephalography. If this area is involved in access to phonological word representations, as assumed in dual-route models of reading, its activation for word fragments having many possible words (Many condition) would be greater than for fragments with one possible word (Single condition). Left superior temporal activity did not differ in strength between the conditions, while behavioral data suggested multiple accesses in the Many condition. Activation was shorter in the Many than in the Single condition, probably owing to bigram frequency difference. These results are inconsistent with the view that the left superior temporal area is related to lexical-route processing.


Efficacy and safety of zanubrutinib plus R-CHOP in treatment of non-GCB DLBCL with extranodal involvement.
Treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) shows poor response rates in non-germinal center B cell-like (non-GCB) diffuse large B-cell lymphoma (DLBCL) patients with multiple extranodal involvement. This study aims to evaluate anti-tumor activity and safety of zanubrutinib with R-CHOP (ZR-CHOP) in treatment naïve non-GCB DLBCL with extranodal involvement. In this single-arm, phase 2, prospective, single-center study, patients with newly diagnosed non-GCB DLBCL with extranodal involvement enrolled between October 2020 to March 2022 received ZR-CHOP for 6 cycles followed by 2 cycles of maintenance treatment with rituximab and zanubrutinib. The primary endpoint included progression-free survival (PFS) in the intent-to-treat (ITT) population whereas the secondary endpoints included overall response rate (ORR), complete response (CR), and duration of response. Further, next-generation sequencing (NGS) was used for detection of different oncogenic mutations closely related to DLBCL pathogenesis. From October 2020 to March 2022, 26 patients were enrolled, and 23 of them were evaluated for efficacy after receiving 3 cycles of ZR-CHOP treatment. 1-year PFS and OS were 80.8% and 88.5% respectively while expected PFS and OS for 2-years are 74.0% and 88.5% respectively with median follow-up of 16.7 months and ORR was 91.3% (CR: 82.61%; PR: 8.70%). Oncogenic mutations closely related to DLBCL pathogenesis were assessed in 20 patients using NGS. B-cell receptor and NF-κB pathway gene mutations were detected in 10 patients, which occurred in MYD88 (7/19), CD79B (4/19), CARD11 (5/19), and TNFAIP3 (2/19). Hematological adverse events (AEs) ≥ grade 3 included neutropenia (50%), thrombocytopenia (23.1%), and anemia (7.7%) whereas non-hematological AEs ≥ grade 3 included pulmonary infection (19.2%). ZR-CHOP is safe and effective for treating treatment naïve non-GCB DLBCL patients with extranodal involvement. Clinicaltrials.gov, NCT04835870.


The effect of rosiglitazone on bone mass and fragility is reversible and can be attenuated with alendronate.
Rosiglitazone (RSG) is an antidiabetic drug that has been associated with increased peripheral fractures, primarily in postmenopausal women. In this report, we investigated the underlying mechanisms of RSG-associated bone loss in ovariectomized (OVX) rats and determined whether changes in bone parameters associated with RSG administration are reversible on treatment cessation or preventable by coadministration with an antiresorptive agent. Nine-month-old Sprague-Dawley rats underwent OVX or sham operation. Sham-operated rats received oral vehicle only; OVX animals were randomized to receive vehicle, RSG, alendronate (ALN), or RSG plus ALN for 12 weeks. All treatment started the day after ovariectomy. After the 12-week treatment period, the OVX and RSG groups also underwent an 8-week treatment-free recovery period. Bone densitometry measurements, bone turnover markers, biomechanical testing, and histomorphometric analysis were conducted. Microcomputed tomography was also used to investigate changes in microarchitecture. RSG significantly increased deoxypyridinoline levels compared with OVX. Significant exacerbation of OVX-induced loss of bone mass, strength, and microarchitectural deterioration was observed in RSG-treated OVX animals compared with OVX controls. These effects were observed predominantly at sites rich in trabecular bone, with less pronounced effects in cortical bone. Coadministration of RSG and ALN prevented the bone loss associated with RSG treatment. Following cessation of RSG treatment, effects on bone mass and strength showed evidence of reversal. Thus, treatment of OVX rats with RSG results in loss of bone mass and strength, primarily at sites rich in trabecular bone, mainly due to increased bone resorption. These effects can be prevented by concomitant treatment with ALN and may be reversed following discontinuation of RSG.


Etiology of neutrophilic granulocytic hypoplasia in a case of large granular lymphocytic leukemia with paraproteinemia.
The association between large granular lymphocytic leukemia (LGLL) and neutropenia is poorly understood. We attempted to assess whether neutropenia in LGLL with paraproteinemia has a different etiology than LGLL without paraproteinemia. We found neither direct serum inhibition of granulocyte/monocyte-colony forming units in vitro nor increased immunoglobulin binding to granulocytic neutrophils, neutrophil precursors, or granulocyte/monocyte-colony stimulating factor. Clonogenic assay experiments suggested that suppression of the patient's granulocyte/monocyte-colony forming units by the neoplastic T-cells and decreased granulocyte/monocyte-colony stimulating factor production contributed to the pathogenesis of neutropenia in this particular case.


Multicomponent self-assembly with a shape-persistent N-heterotriangulene macrocycle on Au(111).
Multicomponent network formation by using a shape-persistent macrocycle (MC6) at the interface between an organic liquid and Au(111) surface is demonstrated. MC6 serves as a versatile building block that can be coadsorbed with a variety of organic molecules based on different types of noncovalent interactions at the liquid-solid interface. Scanning tunneling microscopy (STM) reveals the formation of crystalline bicomponent networks upon codeposition of MC6 with aromatic molecules, such as fullerene (C60) and coronene. Tetracyanoquinodimethane, on the other hand, was found to induce disorder into the MC6 networks by adsorbing on the rim of the macrocycle. Immobilization of MC6 itself was studied in two different noncovalently assembled host networks. MC6 assumed a rather passive role as a guest and simply occupied the host cavities in one network, whereas it induced a structural transition in the other. Finally, the central cavity of MC6 was used to capture C60 in a complex three-component system. Precise immobilization of organic molecules at discrete locations within multicomponent networks, as demonstrated here, constitutes an important step towards bottom-up fabrication of functional surface-based nanostructures.


Comparison of bulbar and mucosal olfactory ensheathing cells using FACS and simultaneous antigenic bivariate cell cycle analysis.
Transplantation of olfactory ensheathing cells (OECs) is a promising route for CNS repair. There have, however, been major discrepancies between the results from different groups. Part of this can be attributed to variations in cell sources and culture protocols. Accurate estimation of the proportions of OECs and their associated fibroblasts (ONFs) and their evolution with time in culture is an essential baseline for establishing the reparative properties of transplants. In this study, we compare the evolution of cultures from the superficial layers of the olfactory bulb with tissue from the olfactory mucosa, both whole and split into lamina propria and epithelial layer. We used FACS based on p75 and Thy1 to provide a robust and objective numerical estimate of the numbers of OECs and ONFs, respectively in the cultures. A novel four color simultaneous antigenic bivariate cell cycle analysis shows that proliferation of OECs is time-limited, and is unable to prevent an overall loss of OECs with time. Overall, the numbers of OECs in the cultures were inversely correlated with the deposition of fibronectin (FN). Further, culture of the cells purified by flow cytometry shows that, whereas the Thy1 population is terminally differentiated, the p75 population from the mucosal samples generates subpopulations with different antigenic phenotypes, including the reappearance of a subpopulation of p75 cells expressing FN. Culturing epithelial samples at high density reveals an unexpected transient stem cell-like population of rapidly proliferating p75 positive cells.


Thermal annealing promoted room temperature phosphorescence: motion models and internal mechanism.
Thermal annealing has been proven to be an efficient method to optimize the device performance of organic and polymeric opto-electronic materials. However, no detailed information of aggregate structures was obtained for a deeper understanding of what happens during thermal annealing. Herein, through modulation of molecular configurations by tunable linkage positions, and the amplified amplitudes of molecular motions by incorporation of additional methylene units, accurate changes of aggregated structures upon thermal annealing have been achieved, accompanying with the 'turn-on' room temperature phosphorescence (RTP) response by about 4800- and 177-fold increase of lifetimes. The stretching and swing motion models have been proposed, which afforded an efficient way to investigate the science of dynamic aggregation in depth.


Synthesis and characterization of porous silicon as hydroxyapatite host matrix of biomedical applications.
In this work, porous-silicon samples were prepared by electrochemical etching on p-type (B-doped) Silicon (Si) wafers. Hydrofluoric acid (HF)-ethanol (C2H5OH) [HF:Et] and Hydrofluoric acid (HF)-dimethylformamide (DMF-C3H7NO) [HF:DMF] solution concentrations were varied between [1:2]-[1:3] and [1:7]-[1:9], respectively. Effects of synthesis parameters, like current density, solution concentrations, reaction time, on morphological properties were studied by scanning electron microscopy (SEM) and atomic force microscopy (AFM) measurements. Pore sizes varying from 20 nm to micrometers were obtained for long reaction times and [HF:Et] [1:2] concentrations; while pore sizes in the same order were observed for [HF:DMF] [1:7], but for shorter reaction time. Greater surface uniformity and pore distribution was obtained for a current density of around 8 mA/cm2 using solutions with DMF. A correlation between reflectance measurements and pore size is presented. The porous-silicon samples were used as substrate for hydroxyapatite growth by sol-gel method. X-ray diffraction (XRD) and SEM were used to characterize the layers grown. It was found that the layer topography obtained on PS samples was characterized by the evidence of Hydroxyapatite in the inter-pore regions and over the surface.


Group milleri streptococci: significant pathogens in solid organ recipients.
Group milleri streptococci (GMS) comprise a heterogeneous group of streptococci including the species intermedius, constellatus and anginosus. They may cause chronic intra-abdominal and intrathoracic abscesses, which are difficult to treat. This is a retrospective analysis including 45 transplant recipients in whom GMS were isolated. The epidemiology, clinical significance and the impact on the outcome in all transplant patients with infections caused by GMS during a 4-year period (2001-2004) was evaluated. The 45 solid organ recipients (88 isolates) included 34 liver-, four kidney/pancreas-, one kidney-, two small bowel-, three combined liver/kidney- and one combined kidney/small bowel transplant recipient. In 42 cases GMS caused intra-abdominal infection, in two cases pleural empyema and in one case soft tissue infection. Only a single isolate of GMS was cultured from blood. In 54 of the 88 specimens (61%), which grew GMS, other pathogens were also isolated. GMS frequently caused recurrent cholangitis (n = 17) associated with anastomotic and nonanastomotic biliary strictures. These cases were managed by repeated stenting or surgical intervention and prolonged antibiotic therapy. No patient died directly related to GMS infection and all except one case responded to combined surgical/antibiotic treatment. One pancreas graft was lost because of erosion haemorrhage associated with an abscess. GMS were susceptible to penicillin G, carbapenems and clindamycin, whereas cephalosporins and quinolones showed intermediate activity or resistance in some cases, and GMS in general were found resistant to aminoglycosides. GMS may cause serious infections in transplant recipients which are difficult to treat. Their prevalence in transplant surgical site infections thus far may have been underestimated.


[Difficulties at work and work motivation of ulcerative colitis suffers].
Because ulcerative colitis (UC) repeats remission and relapse, it is necessary to keep the condition at the relapse time in mind when considering support to provide UC suffers with at the workplace. The aim of this survey was to clarify the difficulties at work and work motivation that UC suffers feel at present and experience at the worsening time, and the factors for maintaining work motivation. We carried out an anonymous questionnaire survey of patients with present or past work experience. The difficulties at work (17 items) and work motivation (4 items) in the past week and at the time when the symptoms were most intensive during work were investigated using a newly designed questionnaire. We regarded the time in the past week as the present, and the time when the symptoms were most intensive during work as the worsening time. There were 70 respondents (response rate 32.0%). Their mean age was 43.8 years, and their mean age at onset was 33.8 years. All subjects, except 2 subjects after surgery, took medicine. Fifty-three (75.7%) of the subjects were in remission at the present, and most of them (91.4%) managed their physical condition well. Difficulties at work that many subjects worried about at the present were relevant to work conditions, such as "Others at workplace do not understand having an intractable and relapsing disease" (41.4%) or "Feel delayed or lack of chance of promotion or career advancement due to the disease" (38.6%). At the worsening time, the management of physical condition went wrong, and the frequency of hospital visits was increased, but few subjects consulted with superiors or colleagues at workplace. Difficulties at work that many subjects underwent at the worsening time were relevant to symptoms, such as "Feel physically tired" (80.0%) or "Decline foods or alcoholic beverages offered at business parties" (72.9%). Those who maintained work motivation even at the worsening time received no work-related consideration and had an adviser in the workplace to talk to about the disease. These results suggest that to provide UC suffers with support at the workplace, it is important to create a working atmosphere in which UC suffers can easily notify superiors and colleagues of their disease or can consult a doctor regularly, and for the superiors and colleagues to become advisors in the workplace to talk to about disease and work.


A brief history of topographical anatomy.
This brief history of topographical anatomy begins with Egyptian medical papyri and the works known collectively as the Greco-Arabian canon, the time line then moves on to the excitement of discovery that characterised the Renaissance, the increasing regulatory and legislative frameworks introduced in the 18th and 19th centuries, and ends with a consideration of the impact of technology that epitomises the period from the late 19th century to the present day. This paper is based on a lecture I gave at the Winter Meeting of the Anatomical Society in Cambridge in December 2015, when I was awarded the Anatomical Society Medal.


Synapse maintenance and restoration in the retina by NGL2.
Synaptic cell adhesion molecules (CAMs) promote synapse formation in the developing nervous system. To what extent they maintain and can restore connections in the mature nervous system is unknown. Furthermore, how synaptic CAMs affect the growth of synapse-bearing neurites is unclear. Here, we use adeno-associated viruses (AAVs) to delete, re-, and overexpress the synaptic CAM NGL2 in individual retinal horizontal cells. When we removed NGL2 from horizontal cells, their axons overgrew and formed fewer synapses, irrespective of whether Ngl2 was deleted during development or in mature circuits. When we re-expressed NGL2 in knockout mice, horizontal cell axon territories and synapse numbers were restored, even if AAVs were injected after phenotypes had developed. Finally, overexpression of NGL2 in wild-type horizontal cells elevated synapse numbers above normal levels. Thus, NGL2 promotes the formation, maintenance, and restoration of synapses in the developing and mature retina, and restricts axon growth throughout life.


Prognostic significance of programmed cell death-1-positive cells in follicular lymphoma patients may alter in the rituximab era.
Programmed cell death-1 (PD-1) is involved in one of the inhibitory pathways of the B7-cluster of differentiation (CD) 28 family; this pathway is known to be involved in the attenuation of T-cell responses and promotion of T-cell tolerance. PD-1 is known to negatively regulate T-cell receptor-mediated proliferation and cytokine production, lead to alternation in the tumor microenvironment. Although several studies have shown that high levels of PD-1-positive cells in follicular lymphoma (FL) patients influence their prognosis, those studies included patients treated without rituximab, and the prognostic impact of PD-1 positivity in the rituximab era (R-era) has not yet been elucidated. We retrospectively studied 82 patients with FL uniformly treated with standard R-CHOP therapy at six institutions between 2001 and 2009 (median follow-up for survivors: 55 months). We also collected and examined biopsy specimens for diagnosis with respect to PD-1 positivity. The PD-1 positivity was significantly higher in male patients and patients with high beta-2 microglobulin (B2M ≥ 3.0) (P = 0.03 and 0.003, respectively). Three-year progression free survival (PFS) and overall survival (OS) were 60% and 86%, respectively. By univariate analysis, elevated LDH (P = 0.07) worsened PFS. Male gender (P = 0.03), high FLIPI score (P = 0.05), and high B2M levels (P = 0.08) worsened OS. Multivariate analysis detected no significant prognostic factors, including PD-1 positivity. However, in male subgroup, high levels of PD-1-positive cells were found to be a prognostic factor for PFS. Addition of rituximab might have altered the prognostic impact of PD-1-positive cells.


An approach to addressing subpopulation considerations in systematic reviews: the experience of reviewers supporting the U.S. Preventive Services Task Force.
Guideline developers and other users of systematic reviews need information about whether a medical or preventive intervention is likely to benefit or harm some patients more (or less) than the average in order to make clinical practice recommendations tailored to these populations. However, guidance is lacking on how to include patient subpopulation considerations into the systematic reviews upon which guidelines are often based. In this article, we describe methods developed to consistently consider the evidence for relevant subpopulations in systematic reviews conducted to support primary care clinical preventive service recommendations made by the U.S. Preventive Services Task Force (USPSTF). Our approach is grounded in our experience conducting systematic reviews for the USPSTF and informed by a review of existing guidance on subgroup analysis and subpopulation issues. We developed and refined our approach based on feedback from the Subpopulation Workgroup of the USPSTF and pilot testing on reviews being conducted for the USPSTF. This paper provides processes and tools for incorporating evidence-based identification of important sources of potential heterogeneity of intervention effects into all phases of systematic reviews. Key components of our proposed approach include targeted literature searches and key informant interviews to identify the most important subpopulations a priori during topic scoping, a framework for assessing the credibility of subgroup analyses reported in studies, and structured investigation of sources of heterogeneity of intervention effects. Further testing and evaluation are necessary to refine this proposed approach and demonstrate its utility to the producers and users of systematic reviews beyond the context of the USPSTF. Gaps in the evidence on important subpopulations identified by routinely applying this process in systematic reviews will also inform future research needs.


Advances in urothelial bladder cancer immunotherapy, dawn of a new age of treatment.
Urothelial bladder cancer displays a high number of somatic mutations that render these tumors more responsive to immunotherapy. Several immunotherapeutic agents were examined in patients with advanced stage urothelial bladder cancer and recently atezolizumab - an (PDL-1) immune checkpoint inhibitor antibody - was approved for the treatment of patients with metastatic disease progressing after platinum combination therapy. Despite the great success, there are still some unanswered questions and ongoing trials that are in progress to define the role of combination therapy and sequencing strategies. The objective of our manuscript is to summarize the most recent data on immunotherapy in advanced urothelial cancer. Current challenges and future perspectives of immunotherapy as a monotherapy or in combination strategies will also be analyzed.


Extended monitoring of resistance to Bacillus thuringiensis Cry1Ab maize in Diatraea saccharalis (Lepidoptera: Crambidae).
The sugarcane borer, Diatraea saccharalis (F.), is a major target of transgenic maize expressing Bacillus thuringiensis (Bt) proteins in South America and the mid-Southern region of the United States. During 2007-2009, a total of 986 feral individuals of D. saccharalis were collected from maize fields in six locations of Louisiana and Mississippi and examined for resistance to Cry1Ab maize using F 1/F 2 screens. Major resistance alleles to Cry1Ab maize in the populations sampled from non-Bt maize plants during 2007 and 2008 in Louisiana and 2009 in Mississippi were rare. From a total of 487 individuals collected from three locations in Louisiana in 2007 and 2008, only one individual was identified with major resistance alleles. In addition, no major resistance alleles were detected in 242 individuals collected from three locations in Mississippi in 2009. The frequency of major resistance alleles was estimated to be 0.002 with a 95% CI of 0.00025-0.0057 for the Louisiana populations and < 0.0061, with 95% probability, for the Mississippi populations. The resistance frequency estimated for the Louisiana populations in 2007 and 2008 was not significantly different from those reported previously for populations sampled in 2004-2006. However, among 200 individuals sampled from non-Bt maize plants in 2009 in Louisiana, six individuals were identified to possess major resistance alleles. The estimated major resistance allele frequency for the populations sampled from non-Bt maize plants in 2009 in Louisiana was 0.0176 with a 95% CI of 0.0072 to 0.0328, which was significantly greater than those estimated for the populations collected in 2004-2008. Similarly, the frequency of minor resistance alleles to Cry1Ab maize for the Louisiana populations collected in 2009 was also significantly greater than those estimated for the populations sampled before. In addition, two out of 57 feral individuals collected from Bt maize plants in Louisiana in 2009 were identified to carry major resistance alleles to Cry1Ab maize. Since 2010, transgenic maize expressing pyramided Bt genes has been planted in the US mid-Southern region and by 2011, pyramided Bt maize has replaced Cry1Ab maize as the dominant Bt maize for managing lepidopteran pests including D. saccharalis. The timely switching from single-gene Cry1Ab maize to the pyramided Bt maize should prevent further increases in Cry1Ab resistance allele frequency and thus ensure the continued success of Bt maize for managing D. saccharalis in the region.


Data driven high resolution modeling and spatial analyses of the COVID-19 pandemic in Germany.
The SARS-CoV-2 virus has spread around the world with over 100 million infections to date, and currently many countries are fighting the second wave of infections. With neither sufficient vaccination capacity nor effective medication, non-pharmaceutical interventions (NPIs) remain the measure of choice. However, NPIs place a great burden on society, the mental health of individuals, and economics. Therefore the cost/benefit ratio must be carefully balanced and a target-oriented small-scale implementation of these NPIs could help achieve this balance. To this end, we introduce a modified SEIRD-class compartment model and parametrize it locally for all 412 districts of Germany. The NPIs are modeled at district level by time varying contact rates. This high spatial resolution makes it possible to apply geostatistical methods to analyse the spatial patterns of the pandemic in Germany and to compare the results of different spatial resolutions. We find that the modified SEIRD model can successfully be fitted to the COVID-19 cases in German districts, states, and also nationwide. We propose the correlation length as a further measure, besides the weekly incidence rates, to describe the current situation of the epidemic.


Determination of Fluorescent Whitening Agents in Cosmetics and Liquid Detergent by High-Performance Liquid Chromatography with Diode Array Detector in Tandem with Fluorescence Detector.
Five distyryl-type fluorescent whitening agents (FWA85, 210, 220, 351, and 353) were determined in cosmetics and liquid detergent by high-performance liquid chromatography with diode array detector in tandem with fluorescence detector. The samples were extracted with ultrasound in 33% acetonitrile for 10 minutes and the components were determined by ion-pair chromatography on an MG C18 column. The limits of detection were from 0.01 to 0.1 mg·kg-1 and the limits of quantification were from 0.04 to 0.4 mg·kg-1. The recovery was from 80.7 to 103.3%. A linear relationship was present from 0.10 to 100 µg·ml-1 of FWAs. The protocol was simple, sensitive, selective, and was successfully applied to analyze distyryl-type FWAs in cosmetics and liquid detergent. FWA351 and FWA85 were detected in several samples with the concentrations of 19.4-1,130 mg·kg-1.


First-principles study on the anisotropic transport of electrons and phonons in monolayer and bulk GaTe: a comparative study.
Recently, monoclinic-phase GaTe has attracted much attention due to its potential applications in nanoelectronics. Despite the experimental research, theoretical studies on the thermal and transport properties, which are necessary to provide information for future applications, are still absent. We have systematically investigated the electronic, phonon and electron transporting, and thermoelectric properties of monolayer and bulk GaTe using first-principles calculations plus the Boltzmann transport equation. At the valence band maximum and conduction band minimum, the effective mass shows large anisotropy as the band dispersions are along different k-paths. The group velocity of acoustic modes also shows large anisotropy owing to the in-plane low-symmetry. Our calculations reveal that the in-plane thermal conductivities, κa and κb, take 3.5 and 8.9 W m-1 K-1, respectively, for the bulk at 300 K, compared to κa = 5.5 and κb = 10.4 W m-1 K-1 of the monolayer. Due to the van der Waals interactions between interlayers, the out-of-plane thermal conductivity is very small, κc = 1.8 W m-1 K-1. The difference between the in-plane thermal conductivities of the bulk and the monolayer can be attributed to the strengthened Umklapp scattering, which is caused by the stiffening of the lowest-frequency optical mode in the bulk. The hole mobilities of the bulk is found to be about 12-35 cm2 V-1 s-1 at 300 K, in good agreement with the experimental results. The monolayer is found to have smaller mobility but larger anisotropy than those of the bulk. Interestingly, the out-of-plane conductivity is anomalously larger than the in-plane one for the bulk, which is attributed to the orbital overlaps between the interlayer Te atoms. Moreover, n-type GaTe is found to have much larger mobility and anisotropy than the p-type one, which is useful for future applications. Compared with the case of monolayer GaTe, thermoelectric performance can be enhanced by one order of magnitude for the bulk GaTe by exploiting the out-of-plane thermal and electrical conductivities.


[Research on bitter components from Coptis chinensis based on electronic tongue].
Isolated alkaloids from Coptis chinensis Franch. The compounds were identified as berberine, columbamine, groenlandicine, jatrorrhizine, magnoflorine, corydaldine and ferulic acid methylester. Then measured their bitter degree based on the electronic tongue and evaluated the antibacterial. The results based on the Electronic Tongue showed that berberine, columbamine, groenlandicine and jatrorrhizine have higher bitter degree than magnoflorine and corydaldine. And they also appeared better antibacterial activity on E. coli and S. aureus. The correlation coefficients between bitter degree and the two bacteria antibacterial activity were 0.983 and 0.911. So there was close relationship between the bitter degree and antibacterial activity of bitter components. Thus, it is confirmed further that bitter components are the material foundation of medicinal effectiveness of bitter herbs.


Spontaneous and on point: Do spontaneous mutations used for laboratory experiments cause pleiotropic effects that might confound bacterial infection and evolution assays?
Many selectable phenotypes in microbial systems, including antibiotic resistance, can be conferred by single point mutations. This is frequently exploited in research, where the selection and use of microbial mutants that are spontaneously resistant to antibiotics like rifampicin and streptomycin facilitate the recovery and/or quantification of a target microbe. Such mutations are commonly employed as genetic markers for in vitro and in vivo experiments, often with little consideration as to the ultimate system-level impact of these single nucleotide mutations on the physiology of the microbe. There is substantial literature on the pleiotropic effects of point mutations conferring antibiotic resistance; yet, it is unclear whether this work is considered by the research communities outside of the discipline. This review examines some of the known pleiotropic effects of point mutations that provide selectable resistance markers, and how these mutations may impact general physiology and growth in host and non-host environments.


Parenting practices and styles associated with adolescent sexual health in Dar es Salaam, Tanzania.
Parenting styles and practices are suggested to be important predictors of adolescent sexual health, mostly in Europe and North America. Limited research has been conducted on these processes in Sub-Saharan Africa, which has different patterns of adolescent sexual behavior and family traditions. This study qualitatively explored parenting practices and styles associated with adolescent sexual health in Tanzania, with 12 adolescents and 12 parents of adolescents. The themes we identified from the data included parental monitoring, preventive, and punitive behaviors. Parents were reported to use mostly punitive behaviors to correct or prohibit sexual behavior; parents also set clear rules about appropriate sexual behavior (e.g., modesty and abstinence). Parents were also reported to closely monitor their adolescent children's friendships and sexual behavior to minimize sexual behavior. However, some parents also engaged in positive preventive practices aimed at protecting their adolescent children.


The new woman as "tied-up dog": Amy E. Tanner's situated knowledges.
Amy E. Tanner pursued a series of ventures on the margins of the discipline of psychology from 1895 through the 1910s. As a midwesterner and a woman, she found herself denied opportunities at both research universities and elite women's colleges, spending the most visible phase of her career as G. Stanley Hall's assistant at Clark University. A narrative of Tanner's life furnishes more than a glimpse at the challenges faced by women scholars in the past. As an investigator engaged with the debate over the mental variability of the sexes, an active class passer in the name of social reform, and a spiritualist debunker, her broad interests illuminate how broadly the proper scope of the new psychology could be constituted. Throughout her writing, Tanner offered an embedded, situated account of knowledge production.


Comparative Effect of Different Polymerization Techniques on the Flexural and Surface Properties of Acrylic Denture Bases.
Polymerization techniques have been modified to improve physical and mechanical properties of polymethylmethacrylate (PMMA) denture base, as have the laboratory procedures that facilitate denture construction techniques. The purpose of the present study was to investigate the effect of autoclave polymerization on flexural strength, elastic modulus, surface roughness, and the hardness of PMMA denture base resins. Major Base and Vertex Implacryl heat-polymerized acrylic resins were used to fabricate 180 specimens. According to the polymerization technique, tested groups were divided into: group I (water-bath polymerization), group II (short autoclave polymerization cycle, 60°C for 30 minutes, then 130°C for 10 minutes), and group III (long autoclave polymerization cycle, 60°C for 30 minutes, then 130°C for 20 minutes). Each group was divided into two subgroups based on the materials used. Flexural strength and elastic modulus were determined by a three-point bending test. Surface roughness and hardness were evaluated with a profilometer and Vickers hardness (VH) test, respectively. One-way ANOVA and the Tukey-Kramer multiple-comparison test were used for results analysis, which were statistically significant at p ≤ 0.05. Autoclave polymerization showed a significant increase in flexural strength and hardness of the two resins (p < 0.05). The elastic modulus showed a significant increase in the major base resin, while a significant decrease was seen for Vertex Implacryl in all groups (p < 0.05); however, there was no significant difference in surface roughness between autoclave polymerization and water-bath polymerization (p > 0.05). Autoclave polymerization significantly increased the flexural properties and hardness of PMMA denture bases, while the surface roughness was within acceptable clinical limits. For a long autoclave polymerization cycle, it could be used as an alternative to water-bath polymerization.


EXPERIMENTAL STUDY OF BONE DENSITY IN PATIENTS WITH CONGENITAL PSEUDOARTHROSIS OF THE TIBIA BEFORE AND AFTER SURGERY.
The aim: Determine the changes in bone density that occur in the cortical layer of the tibia in patients with CPT after surgical treatment due to radiography data. Materials and methods: The study was performed on X-rays of the tibia of three patients with CPT, aged 5 to 7 years. X-rays were taken before surgery and 1 year after surgery. The optical density of the cortical layer of both tibia bones was determined, for which they were conditionally divided into 7 zones. Results: In all patients with CPT before treatment, there is significant decrease in the optical density of cortical bone tissue of the damaged tibia compared with contralateral. One year after surgery, there was an increase in the optical density of the cortical layer of both tibia of the studied patients. The increase in the density of the nonoperated tibia can be attributed to the active growth of patients. On the operated limb, the increase in the density of the cortical layer became statistically significant in all studied areas, which can be attributed not only to the growth of patients, but also to the possibility of active loading of the operated limb. Conclusions: In all patients with CPT before treatment, a statistically significant decrease in the density of cortical bone tissue of the damaged tibia was observed. As a result of the treatment there is an approximation of the bone density of the operated limb to the indicators of intact contralateral bone.


Postoperative Pain with Hand, Reciprocating, and Rotary Instrumentation Techniques after Root Canal Preparation in Primary Molars: A Randomized Clinical Trial.
The purpose of this randomized clinical trial was to evaluate the intensity and duration of postoperative pain after pulpectomy of primary teeth using three preparation techniques. A total of 60 patients were randomly allocated to three groups of 20 patients each, according to the root canal instrumentation techniques used. In group I, the teeth were prepared using manual NiTi K flex files till size 35. In group II, the teeth were prepared using NiTi K flex files till size 35 in reciprocating motion. In group III, the teeth were prepared using Kedo-S pediatric rotary files. After root canal preparation, the canals were obturated with endoflas paste and were restored permanently with composite filling material. The intensity and duration of postoperative pain were evaluated after 6, 12, 24, 48, and 72 hours, using a four-point pain-intensity scale. There was a statistically significant difference among the groups, wherein the postoperative pain was more in NiTi K flex files used in reciprocating motion followed by manual NiTi K flex files and Kedo-S pediatric rotary files. Postoperative pain was more with NiTi K flex files in reciprocating motion and was less with Kedo-S rotary files after root canal preparation in primary maxillary molars. Jeevanandan G, Ravindran V, Subramanian EMG, et al. Postoperative Pain with Hand, Reciprocating, and Rotary Instrumentation Techniques after Root Canal Preparation in Primary Molars: A Randomized Clinical Trial. Int J Clin Pediatr Dent 2020;13(1):21-26.


A new species of Phylloicus Müller 1880 (Trichoptera: Calamoceratidae) from Espírito Santo State, southeastern Brazil.
The worldwide caddisfly family Calamoceratidae comprises about 175 extant species in eight genera (Holzenthal et al. 2007). Among these, two are exclusively recorded from the Neotropics: Banyallarga Navás with 18 described species (Prather 2004) and Phylloicus Müller with 57 described species (Prather 2003, Dumas & Nessimian 2010, Santos & Nessimian 2010, Quinteiro et al. 2011), both genera recently reviewed by Prather (2003, 2004).


Neuroprotective effects of Polygonum multiflorum on nigrostriatal dopaminergic degeneration induced by paraquat and maneb in mice.
The neuroprotective effects of Polygonum multiflorum extract (PME) and its two fractions, ethanol-soluble PME (PME-I) and -insoluble PME (PME-II), on the degeneration of nigrostriatal dopaminergic neurons induced by a combination of paraquat and maneb (PQMB) were investigated in male C57BL/6 mice. The mice were treated twice a week for 6 weeks with intraperitoneal injections of PQMB. This combination caused a reduction of spontaneous locomotor activity, motor incoordination, and declines of dopamine level in the striatum and tyrosine hydroxylase-positive neurons in the substantia nigra. Administration of PME and PME-I once daily for 47 days during 6 weeks of PQMB treatment and last 8 days after PQMB significantly attenuated the impairment of behavioral performance and the decrease in striatal dopamine level and substantia nigral tyrosine hydroxylase-positive neurons in the PQMB-treated animals, whereas the administration of PME-II had no effect on these behavioral, neurochemical and histological indices. The present findings suggest that PME has a beneficial influence on parkinsonism induced by PQMB and that the effects of PME are attributable to some substance(s) included in the ethanol-soluble fraction of PME (PME-I).


Carcinoembryonic antigen (CEA) and gastrointestinal cancer associated antigen CA 19-9 in bronchioloalveolar carcinomas and pulmonary adenocarcinomas.
The concentrations of carcinoembryonic antigen (CEA) and the gastrointestinal cancer associated antigen CA 19-9 were studied by radioimmunoassay in serum samples from patients with malignant and benign pulmonary tumours. Elevated levels of either markers were found in 14% of patients with malignant tumours and in none of the cases with benign lesions. Following removal of the tumour, a decline in high CA 19-9 levels was found. The advanced tumours produced the highest serum CA 19-9 concentrations but elevated values were also found in small bronchioloalveolar carcinomas and pulmonary adenocarcinomas. Immunohistochemical staining for CEA and CA 19-9 was performed on routine histopathological specimens. About half of the cases of bronchioloalveolar carcinomas and pulmonary adenocarcinomas were CA 19-9 positive and about 90% were CEA positive. No correlation between intensity of tissue expression and serum levels of CA 19-9 could be demonstrated. However, the bronchioloalveolar carcinomas and pulmonary adenocarcinomas which produced high serum levels of CA 19-9 also stained positively.


The role of the pineal gland in the photoperiodic control of reproduction in different hamster species.
The pineal gland is known to play a central role in the photoperiodic control of reproduction in seasonal breeders. The present review, based on experimental data obtained in four different species of hamster, the Syrian or golden, the Djungarian or Siberian, the Turkish and the European, attempts to evaluate the role of the pineal in this phenomenon, the message which is conveyed from this gland as well as the mechanism of action of this message. Melatonin one of the 5-methoxyindoles rhythmically synthesized in the pineal gland, appears to be the pineal hormone conveying the photoperiodic message. The importance of the duration of the nocturnal peak of circulating melatonin is now well established, but our knowledge on the sites of action and on the mechanisms of action of melatonin is still rather poor. The presently available data suggest that melatonin can act at different levels, either on specific receptors, on receptors of other transmitters, on various molecular processes after diffusion in the cell or indirectly via effects on other endocrine hormones, e.g. gonadal steroids.


Successive order scattering transport approximation for laser light propagation in whole blood medium.
An analytical solution method of the radiative transport equation, describing light scattering distribution in whole blood, is derived by applying successive order scattering approximation and transport approximation. By separating coherent components of scattered fluxes, the transport equation can be represented in terms of each order scattering flux, and the equations for each order scattering flux have a simplified integration term of scattering contribution that usually makes the solution complicated or even impossible. Also, actual phase function can be used for calculation of angular dependent scattering distribution that is approximated by the sum of the zeroth- and first-order Legendre polynomial in diffusion theory, or the sum of isotropic and coherent components in transport approximation. The method is then used to calculate reflectance from a half-space blood medium. It is found that first-order scattering flux alone produces a good agreement with experimental data and higher-order scattering fluxes are negligible in whole blood.


A comparison between Chevron and Mitchell osteotomies for hallux valgus.
A retrospective study of 15 Mitchell and 15 Chevron osteotomies was undertaken in order to compare the efficacy of these two procedures in the correction of hallux valgus. Patient satisfaction, clinical findings, and roentgenographic measurements were all carefully evaluated after follow-up periods of 21 +/- 5 months for the Chevron and 34 +/- 8 months for the Mitchell procedures. Differences observed were a better correction of the angle between the first and second metatarsals by the Mitchell osteotomy (2.3 vs 5.5 degrees) and a tendency to loose the correction in the immediate postoperative period for the Chevron osteotomy. However, no clinical superiority could be demonstrated, nor did patient satisfaction differ in the two techniques. The authors conclude that these procedures give essentially equivalent results. Although the outcome was generally considered satisfactory by the patient, nearly 40% of both groups had metatarsalgia in the lateral rays, which stresses the importance of carefully considering load distribution across the foot in planning any corrective surgery.


Accuracy of parasitological and immunological tests for the screening of human schistosomiasis in immigrants and refugees from African countries: An approach with Latent Class Analysis.
Schistosomiasis is a neglected infection affecting millions of people, mostly living in sub-Saharan Africa. Morbidity and mortality due to chronic infection are relevant, although schistosomiasis is often clinically silent. Different diagnostic tests have been implemented in order to improve screening and diagnosis, that traditionally rely on parasitological tests with low sensitivity. Aim of this study was to evaluate the accuracy of different tests for the screening of schistosomiasis in African migrants, in a non endemic setting. A retrospective study was conducted on 373 patients screened at the Centre for Tropical Diseases (CTD) in Negrar, Verona, Italy. Biological samples were tested with: stool/urine microscopy, Circulating Cathodic Antigen (CCA) dipstick test, ELISA, Western blot, immune-chromatographic test (ICT). Test accuracy and predictive values of the immunological tests were assessed primarily on the basis of the results of microscopy (primary reference standard): ICT and WB resulted the test with highest sensitivity (94% and 92%, respectively), with a high NPV (98%). CCA showed the highest specificity (93%), but low sensitivity (48%). The analysis was conducted also using a composite reference standard, CRS (patients classified as infected in case of positive microscopy and/or at least 2 concordant positive immunological tests) and Latent Class Analysis (LCA). The latter two models demonstrated excellent agreement (Cohen's kappa: 0.92) for the classification of the results. In fact, they both confirmed ICT as the test with the highest sensitivity (96%) and NPV (97%), moreover PPV was reasonably good (78% and 72% according to CRS and LCA, respectively). ELISA resulted the most specific immunological test (over 99%). The ICT appears to be a suitable screening test, even when used alone. The rapid test ICT was the most sensitive test, with the potential of being used as a single screening test for African migrants.


In vitro anticancer activity and cytotoxicity screening of phytochemical extracts from selected traditional Chinese medicinal plants.
The purpose of this study was to evaluate the anticancer activity of 10 selected traditional Chinese medicinal plants on 4 cancer cell lines, namely MCF-7 (breast carcinoma), BALL-1 (acute lymphoblastic leukemia), Huh-7 (hepatocellular carcinoma), HeLa (cervical carcinoma) and their cytotoxicity on a normal cell line, namely MCF-10A (non-tumorigenic mammary epithelial line), about which there were few reports previously. Six phytochemical extracts, namely petroleum ether extract (PEE), chloroform extract (CE), ethyl acetate extract (EAE), n-butanol extract (BE), the remainder after extraction (RE) and water extract (WE) from each plant were prepared. These 60 extracts were screened for their cytotoxicity on the aforementioned cell lines using MTT assay. All plant species showed certain anticancer activity against at least one of the 4 cancer cell lines and obvious selective cytotoxicities were observed. Compared with Huh-7 and HeLa cells, MCF-7 and BALL-1 cells were more sensitive to the treatments of the phytochemical extracts. The PEE, CE and EAE of Brassica campestris, the PE and CE of Hibiscus syriacus, as well as the BE of Pittosporum tobira exhibited strong anticancer activity but weak cytotoxicity on the normal cell line. Our results provided new evidence for anticancer activities of these plants which could be useful for developing new anticancer therapies.


Natalizumab: a new therapy for acute ischemic stroke?
Natalizumab, a well-characterized treatment for multiple sclerosis, is a humanized antibody against alpha-4 integrin (CD49d) that mitigates the transmigration of leukocytes across the endothelium. Although numerous experimental studies have evaluated the efficacy of anti-CD49d antibody treatment for ischemic stroke, discrepancies in their results have raised concerns about the benefits of this approach. This article reviews the main experimental studies on the blockage of CD49d and identifies the potential underlying causes for their inconclusive results. Despite these divergences and the difficulties in translation of experimental studies, a phase II clinical trial has recently been conducted to evaluate the efficacy of natalizumab in stroke patients (ACTION trial). Preliminary results of the trial are also discussed here, together with a general overview of the emerged importance of the neuroprotective strategies based on the mitigation of post-stroke neuroinflammation. Expert commentary: Despite natalizumab showing positive effects on functional outcome similar to what was found in experimental models, a better understanding of how this happens without reducing the infarct volume requires further research. Therefore, new clinical trials are needed to confirm its neuroprotectant role in ischemic stroke.


Anti-tumor effect of syngeneic spleen cells treated with immune RNA and tumor antigen.
The anti-tumor effect of syngeneic spleen cells, xenogeneic immune RNA (l-RNA) and tumor antigen (TA) was studied in a chemically induced (N-methyl-N-nitro-sourethane) colon carcinoma model in BALB/c mice. When the mice were treated, sequentially, with these three elements by local injection under the tumor, complete tumor regression was observed in 25% of the animals. Complete tumor regression was observed in 17% of animals treated by injection of spleen cells pre-incubated with l-RNA in vitro followed by an injection of TA. When spleen cells were treated first with l-RNA and then with mitomycin-C, therapeutic benefit was obtained and the survival rate of mice treated with these spleen cells and TA was significantly higher than that of the control group (no treatment). The anti-tumor effect of this treatment was abrogated completely when spleen cells were treated with mitomycin-C prior to l-RNA incubation. When spleen cells were incubated with TA in vitro or after incubation with l-RNA and then injected into tumor-bearing mice, no anti-tumor effect was noted. These data suggest that DNA synthesis and/or lymphocyte proliferation is essential for the action of l-rna in sensitizing lymphocytes but not essential in the interaction of l-RNA-sensitized lymphocytes with TA. In addition it appeared that, under the conditions used, the participation of host factors was essential in the latter interaction, since treatment of l-RNA-sensitized lymphocytes with TA in vitro was ineffective.


Specific ion binding to carboxylic surface groups and the pH dependence of the Hofmeister series.
Ion binding to acidic groups is a central mechanism for ion-specificity of macromolecules and surfaces. Depending on pH, acidic groups are either protonated or deprotonated and thus change not only charge but also chemical structure with crucial implications for their interaction with ions. In a two-step modeling approach, we first determine single-ion surface interaction potentials for a few selected halide and alkali ions at uncharged carboxyl (COOH) and charged carboxylate (COO(-)) surface groups from atomistic MD simulations with explicit water. Care is taken to subtract the bare Coulomb contribution due to the net charge of the carboxylate group and thereby to extract the nonelectrostatic ion-surface potential. Even at this stage, pronounced ion-specific effects are observed and the ion surface affinity strongly depends on whether the carboxyl group is protonated or not. In the second step, the ion surface interaction potentials are used in a Poisson-Boltzmann model to calculate the surface charge and the potential distribution in the solution depending on salt type, salt concentration, and solution pH in a self-consistent manner. Hofmeister phase diagrams are derived on the basis of the long-ranged forces between two carboxyl-functionalized surfaces. For cations we predict direct, reversed, and altered Hofmeister series as a function of the pH, qualitatively similar to recent experimental results for silica surfaces. The Hofmeister series reversal for cations is rationalized by a reversal of the single-cation affinity to the carboxyl group depending on its protonation state: the deprotonated carboxylate (COO(-)) surface group interacts most favorably with small cations such as Li(+) and Na(+), whereas the protonated carboxyl (COOH) surface group interacts most favorably with large cations such as Cs(+) and thus acts similarly to a hydrophobic surface group. Our results provide a general mechanism for the pH-dependent reversal of the Hofmeister series due to the different specific ion binding to protonated and deprotonated surface groups.


Reproducibility of electrocardiographic findings in patients with suspected reflex neurally-mediated syncope.
The reproducibility of electrocardiographic (ECG) recordings in syncopal recurrences and the diagnostic role of nonsyncopal arrhythmias are not well known. The objective of this study was to analyse the reproducibility of the ECG findings recorded with implantable loop recorders in 41 patients with suspected neurally-mediated syncope who were included in the International Study on Syncope of Uncertain Origin-2 study and that had > or =2 events recorded by implantable loop recorders. In these patients, the electrocardiogram obtained with the first documented syncope (index syncope) was compared with other recorded events. Twenty-two patients had > or =2 syncopes, and their electrocardiograms were reproducible in 21 (95%): 15 with sinus rhythm, 5 with asystole, and 1 with ventricular tachycardia; 1 had asystole at first syncope and sinus rhythm at recurrent syncope. In 32 patients with nonsyncopal episodes, an arrhythmia was documented in 9, and all of them had the same arrhythmia during the index syncope (100% reproducibility); conversely, when sinus rhythm was documented (23 patients) during nonsyncopal episodes, an arrhythmia was still documented in 6 during the index syncope (70% reproducibility; p = 0.0004). In conclusion, the ECG findings during the first syncope are highly reproducible in subsequent syncopes. The presence of an arrhythmia during nonsyncopal episodes is also highly predictive of the mechanism of syncope, but the presence of sinus rhythm does not rule out the possibility of arrhythmia during syncope. Therefore the finding of an arrhythmia during a nonsyncopal episode allows the etiologic diagnosis of syncope, and eventually to anticipate treatment, without waiting for syncope.


Association between serum free IGF-I and IGFBP-3 levels in type-I diabetes patients affected with associated autoimmune diseases or diabetic complications.
Patients with type 1 diabetes (T1DM) present lower serum free IGF and IGFBP-3 values than healthy people. T1DM patients often present with associated autoimmune diseases such as thyroiditis or coeliac disease, and over time they frequently develop proliferative retinopathy, neuropathy or nephropathy in different combinations. The aim of this study was to evaluate the effect of two associated autoimmune diseases or three diabetic complications on the serum free IGF-I or IGFBP-3 levels in T1DM patients, who also have a family history of T1DM. Design. 246 T1DM patients were enrolled, and then subdivided into groups according to diabetic complications or associated autoimmune diseases. Demographic and clinical data were recorded. Serum free IGF-I and IGFBP-3 levels were determined by IRMA. IGF-I and IGFBP-3 generally present correlated serum values as confirmed in this study. Those patients with autoimmune thyroiditis and coeliac disease presented with significantly lower serum values of IGFBP-3, whereas free IGF-I was significantly lower in patients with the different diabetic complications. Retinopathy presented a slightly significant reduction in serum free IGF-I, while neuropathy and nephropathy showed a more pronounced fall. The number of complications was related to progressively decreasing free IGF-I levels. T1DM family history was associated with lower serum free IGF-I concentrations. These findings were confirmed after correction for age, glycosylated haemoglobin levels, insulin treatment protocol, body mass index, serum creatinine and sex. Despite a direct correlation between serum free IGF-I and IGFBP-3, the correlation between the two molecules in patients with associated autoimmune diseases was lost, possibly due to different mechanisms of metabolic regulation.


GENETIC STRUCTURE AND EVOLUTION OF A FIRE ANT HYBRID ZONE.
Two introduced fire ants, Solenopsis invicta and S. richteri, hybridize over an extensive area in the United States spanning central Mississippi, Alabama, and western Georgia. We studied a portion of this hybrid zone in northwestern Mississippi in detail by sampling ants at many sites along two transects extending across the zone and examining gene frequency and size distributions at a large number of genetic and morphological markers. The distributional patterns at these markers are most consistent with the mosaic hybrid zone model, whereby the distribution of various fire ant genotypes is determined initially by the historical patterns of colonization of newly available habitats. However, these distributional patterns probably do not reflect the equilibrium state of interactions because of the very recent secondary contact of the species (< 60 yr) and the dynamic nature of available nesting habitats in this area. Our data suggest that, with prolonged contact and interaction, differential fitness of various hybrid genotypes due to intrinsic and extrinsic selective factors is important in structuring the hybrid zone. For instance, consistent differential introgression of morphological and genetic markers, combined with previous evidence of differences in developmental stability among genotypes, suggest reduced fitness of hybrids relative to parentals due to intrinsic selection (as may be caused by breakup of parental gene complexes). Furthermore, marked reductions in the occurrence of parental-like hybrids in areas where the similar parental species is common suggest reduced fitness of these parental-like hybrids in competition with the parentals (i.e., extrinsic selection). Because the relative roles of such deterministic as well as stochastic forces apparently vary both spatially and temporally, the eventual distribution of the various fire ant genotypes and the fate of the hybrid zone in the United States is difficult to predict.


Stiffness distribution in insect cuticle: a continuous or a discontinuous profile?
Insect cuticle is a biological composite with a high degree of complexity in terms of both architecture and material composition. Given the complex morphology of many insect body parts, finite-element (FE) models play an important role in the analysis and interpretation of biomechanical measurements, taken by either macroscopic or nanoscopic techniques. Many previous studies show that the interpretation of nanoindentation measurements of this layered composite material is very challenging. To develop accurate FE models, it is of particular interest to understand more about the variations in the stiffness through the thickness of the cuticle. Considering the difficulties of making direct measurements, in this study, we use the FE method to analyse previously published data and address this issue numerically. For this purpose, sets of continuous or discontinuous stiffness profiles through the thickness of the cuticle were mathematically described. The obtained profiles were assigned to models developed based on the cuticle of three insect species with different geometries and layer configurations. The models were then used to simulate the mechanical behaviour of insect cuticles subjected to nanoindentation experiments. Our results show that FE models with discontinuous exponential stiffness gradients along their thickness were able to predict the stress and deformation states in insect cuticle very well. Our results further suggest that, for more accurate measurements and interpretation of nanoindentation test data, the ratio of the indentation depth to cuticle thickness should be limited to 7% rather than the traditional '10% rule'. The results of this study thus might be useful to provide a deeper insight into the biomechanical consequences of the distinct material distribution in insect cuticle and also to form a basis for more realistic modelling of this complex natural composite.


[Experimental studies on the poly-hydroxybutyrate membrane modified by gamma-radiation and mixed with calcium sulfate].
The objective of this study was to learn the property of poly-hydroxybutyrate membrane (PHBm) modified by gamma-radiation and mixture of calcium sulfate, and to explore the possibility of using modified PHBm for guided tissue regeneration (GTR). The PHB was treated by 5 KGy gamma-radiation and mixed with 1/10 calcium sulfate. The modified PHB membrane was prepared by solvent-casting techniques. The mechanical properties and molecular weight of the modified PHBm were tested. Degradability of the modified PHBm was analyzed in vitro in a buffer solution of KH2PO4-Na2HPO4. Biodegradability and biocompatibility of the modified PHBm were inspected 1, 2, 3 and 6 months after the embedding of the modified PHBm into dogs. The morphology was analyzed by scanning electron microscopy (SEM) and molecular weight was tested to evaluate the biodegradability of PHBm. Biocompatibility of the modified PHBm was observed through tissue response by light microscopy. The extension strength and the extension strain at fracture of the modified PHBm were 23.8 MPa and 1.0% respectively. The morphologic observation of the modified PHBm at different terms showed that the modified PHBm was biodegraded gradually in vitro and in vivo. The capsule surrounding the modified PHBm was mainly composed of fibrocytes and few lymphocytes. The longer the time elapsed, the thinner the capsule enveloping the modified PHBm grew. The modified PHBm possesses satisfactory mechanical properties and biocompatibility, and it is biodegradable in vitro and in vivo. The modified PHB membrane could be applied as GTR membrane.


Does head and cervical posture correlate to malocclusion? A systematic review and meta-analysis.
The association of head and cervical posture with malocclusion has been studied for many years. Despite extensively encouraging researches, no conclusive evidence has been reached for clinical application. To identify the question "Does head and cervical posture correlate to malocclusion?", a systematic review and meta-analysis based on the available studies were carried out (PROSPERO registration number: CRD42022319742). A search of PubMed, Embase, Cochrane Library, and the grey literature was performed without language restrictions. The study screening, data extraction, risk-of-bias evaluation and methodological quality assessment were performed by two independent investigators. When a disagreement arose, a third author was consulted. 6 original cross-sectional studies involving 505 participants were included, which were of moderate methodological quality. NL/VER in Class Ⅱ group and NL/CVT in Class Ⅲ group showed significant differences compared to Class Ⅰ group, but no significant differences were observed in most of the variables like NSL/VER, OPT/CVT, OPT/HOR, CVT/HOR, NSL/OPT, NSL/CVT, NL/OPT in Class Ⅱ and Ⅲ groups. The results suggested that the current research evidence is not sound enough to prove the association of head and cervical posture with sagittal malocclusion. Better controlled design and a larger sample size are required for clarifying this question in future study.


Quality of life and clinical symptom improvement support prostatic artery embolization for patients with acute urinary retention caused by benign prostatic hyperplasia.
To show that prostatic artery embolization (PAE) improves quality of life (QoL) and lower urinary tract symptoms in patients with acute urinary retention caused by benign prostatic hyperplasia (BPH). This was a single-center prospective study of PAE in 11 patients with BPH managed with indwelling urinary catheters. International Prostate Symptom Score (IPSS), ultrasound, magnetic resonance (MR) imaging, QoL, and urodynamic tests were used to assess outcomes. Prostate size ranged from 30 to 90 g, and embolizations were performed with 300-500-μm Embosphere microspheres. The rate of technical success (ie, bilateral PAE) was 75%, and the rate of clinical success (ie, catheter removal and symptom improvement) was 91% (10 of 11 patients). Postembolization syndrome manifested as mild pain in the perineum, retropubic area, and/or urethra. Ten of 11 patients urinated spontaneously after Foley catheter removal 4-25 days after PAE (mean, 12.1 d). No major complications were observed. Follow-up ranged from 19 to 48 months. In an asymptomatic patient, a discrete area of hypoperfusion suggesting small ischemia of the bladder was observed on 30-day MR imaging follow-up, but the bladder was normal on 90-day MR imaging. After 1 year, mean prostate volume reduction was greater than 30%, symptoms were mild (mean IPSS, 2.8 ± 2.1; P = .04), no erectile dysfunction was observed, and QoL improved significantly (mean, 0.4 ± 0.5; P = .001) using the paired t test. Patients with severe symptoms and acute urinary retention caused by BPH can be treated safely by PAE, which improves clinical symptoms and QoL.


4-Methylpyrazole: a controlled study of safety in healthy human subjects after single, ascending doses.
4-Methylpyrazole (4-MP), an inhibitor of alcohol dehydrogenase, is a possible future drug for the treatment of methanol and ethylene glycol intoxications and the severe ethanol-disulfiram reaction. Therefore a placebo-controlled, double-blind, single-dose, randomized, sequential, ascending-dose "Phase I study" was performed in healthy volunteers in order to determine the tolerance of 4-MP at dose levels of 10 (n = 4), 20 (n = 4), 50 (n = 4), and 100 mg/kg (n = 3). Along with each dose group, there were two placebos except with the 100 mg/kg group where there was only one placebo. In the 10 and 20 mg/kg group there were no side-effects in any subject. At the 50 mg/kg level, three out of four subjects experienced slight to moderate nausea and dizziness from 0 to 2.5 h after dosing. In the 100 mg/kg group all three subjects reported side-effects like nausea, dizziness, and vertigo, that were short-lived in two subjects, but lasted up to 30 h in one subject. The study was stopped after evaluation of the latter subject, so fewer subjects were completed in this last group. Despite these subjective side-effects, there were no significant changes in objective clinical parameters like pulse, blood pressure, body temperature, or blood and urine chemistries. We conclude that at a single dose of 4-MP (10-20 mg/kg) producing plasma levels within a probable therapeutic range, no side-effects were attributed to 4-MP.


The haemodynamic effects of umbilical cord milking in term infants: a randomised controlled trial.
Umbilical cord milking (UCM) is a method that allows for postnatal placental transfusion. The benefits of UCM have been demonstrated in some studies, but knowledge about its haemodynamic effects in term infants is limited. The aim of this study was to evaluate the haemodynamic effects of UCM in term infants. In this prospective, randomised controlled study, 149 healthy term infants with a birth week of ≥37 weeks were randomly assigned to either the UCM or immediate cord clamping (ICC) group. Blinded echocardiographic evaluations were performed in all the neonates in the first 2-6 h. Superior vena cava (SVC) flow measurements were higher in the UCM group compared to the ICC group (132.47 ± 37.0 vs. 126.62 ± 34.3 mL/kg/min), but this difference was not statistically significant. Left atrial diameter (12.23 ± 1.99 vs. 11.43 ± 1.78 mm) and left atrium-to-aorta diastolic diameter ratio (1.62 ± 0.24 vs. 1.51 ± 0.22) were significantly higher in the UCM group. There were no significant differences in other echocardiographic parameters between the two groups. We found no significant difference in the SVC flow measurements in term infants who underwent UCM versus those who underwent ICC. This lack of significant difference in SVC flow may be explained by the mature cerebral autoregulation mechanism in term neonates.


Industrialization of Biology.
The advancement of synthetic biology over the past decade has contributed substantially to the growing bioeconomy. A recent report by the National Academies highlighted several areas of advancement that will be needed for further expansion of industrial biotechnology, including new focuses on design, feedstocks, processing, organism development, and tools for testing and measurement; more particularly, a focus on expanded chassis and end-to-end design in an effort to move beyond the use of E. coli and S. cerivisiea to organisms better suited to fermentation and production; second, continued efforts in systems biology and high-throughput screening with a focus on more rapid techniques that will provide the needed information for moving to larger scale; and finally, work to accelerate the building of a holacratic community with collaboration and engagement between the relevant government agencies, industry, academia, and the public.


Administration of breast milk cell fractions to neonates with birthweight equal to or less than 1800 g: a randomized controlled trial.
Most premature and very low birthweight infants cannot tolerate breast milk feeding in the first few days of life and are deprived of its benefits. This study evaluates the clinical outcomes of administering breast milk cell fractions to neonates with a birthweight of ≤1800 g. We conducted a randomized controlled trial on 156 infants in the neonatal intensive care unit of Mahdieh Maternity Hospital in Tehran, Iran, from May 2019 to April 2020. All neonates with a birthweight ≤1800 g were enrolled and divided into intervention and control groups using stratified block randomization. Neonates in the intervention group received the extracted breast milk cell fractions (BMCFs) of their own mother's milk after being centrifuged in the first 6 to 12 h after birth. The control group received routine care, and breastfeeding was started as soon as tolerated in both groups. Study outcomes were necrotizing enterocolitis (NEC), death, and in-hospital complications. We divided participants into two groups: 75 neonates in the intervention group and 81 neonates in the control group. The mean birthweight of neonates was 1390.1 ± 314.4 g, and 19 (12.2%) neonates deceased during their in-hospital stay. The incidence of NEC was similar in both groups. After adjustment for possible confounders in the multivariable model, receiving BMCFs were independently associated with lower in-hospital mortality (5 [26.3%] vs. 70 (51.1%]; odds ratio (OR): 0.24; 95% confidence interval [CI] 0.07, 0.86). Also, in a subgroup analysis of neonates with birthweight less than 1500 g, in-hospital mortality was significantly lower in the intervention group (4 [9.5%] vs. 13 [30.2%]; OR: 0.24; 95% CI 0.07, 0.82). There were no differences in major complications such as bronchopulmonary dysplasia and retinopathy of prematurity between the two groups. No adverse effects occurred. Our research demonstrated a significantly lower mortality rate in neonates (with a birthweight of ≤1800 g) who received breast milk cell fractions on the first day of life. Since this is a novel method with minimal intervention, we are looking forward to developing and evaluating this method in larger studies. IIranian Registry of Clinical Trials. Registered 25 May 2019, IRCT20190228042868N1 .


Phagocytosis of formol treated red blood cells.
Formol treated red blood cells have been established to be phagocytized by human leukocytes in the presence of compatible AB0 standard test sera in case such red blood cells are stored continuously in water or in case they are incubated in saliva in advance for one hour at least at 37 degrees C. If formol treated red blood cells are continuously stored in 0.9% NaCl solution or if they are lyophilized in addition they will not be engulfed by human leukocytes in presence of compatible standard test sera of the AB0 system. The additional treatment with papain of formol treated red blood cells will cause a moderate phagocytosis.


Effect of simulated microgravity and its associated mechanism on pulmonary circulation in rats.
To study the effect of Simulated Microgravity and its Associated Mechanism on Pulmonary Circulation in Rats). Rat tail-suspension model was used to simulate the physiological effects of microgravity and changes in pulmonary blood vessel morphology, pulmonary arterial and venous blood pressure, pulmonary vascular resistance, pulmonary vasomotoricity, as well as the regulation of pulmonary circulation by cytokines produced and released by the lung of rats were measured. The walls of pulmonary blood vessels of rats were thickened, and the pulmonary artery was reconstructed with increased pulmonary vascular resistance. The pulmonary blood vessels of rats became more prone to dilation as contractions increased. Rat epithelial Adrenomedulin gene transcription and protein expression were upregulated. The level of basic fibroblast growth Factor of rat was also elevated. Findings from the present study on rats revealed that the microgravity can affect pulmonary blood vessel structure, pulmonary arterial pressure, and pulmonary blood vessel self-regulation and cytokine production.