Genetic and Stress-Induced Loss of NG2 Glia Triggers Emergence of Depressive-like Behaviors through Reduced Secretion of FGF2.
NG2-expressing glia (NG2 glia) are a uniformly distributed and mitotically active pool of cells in the central nervous system (CNS). In addition to serving as progenitors of myelinating oligodendrocytes, NG2 glia might also fulfill physiological roles in CNS homeostasis, although the mechanistic nature of such roles remains unclear. Here, we report that ablation of NG2 glia in the prefrontal cortex (PFC) of the adult brain causes deficits in excitatory glutamatergic neurotransmission and astrocytic extracellular glutamate uptake and induces depressive-like behaviors in mice. We show in parallel that chronic social stress causes NG2 glia density to decrease in areas critical to Major Depressive Disorder (MDD) pathophysiology at the time of symptom emergence in stress-susceptible mice. Finally, we demonstrate that loss of NG2 glial secretion of fibroblast growth factor 2 (FGF2) suffices to induce the same behavioral deficits. Our findings outline a pathway and role for NG2 glia in CNS homeostasis and mood disorders.


Prokaryotic membrane coat - like proteins: An update.
Membrane coat proteins are essential players in the eukaryotic endomembrane traffic system. Previous work identified proteins with the membrane-coat architecture in prokaryotes, specifically in the Planctomycetes, Verrucomicrobia and Chlamydiae (PVC) superphylum, bacteria that display the most developed prokaryotic endomembrane system. Hence, the membrane coat-like (MCL) proteins are predicted to play a central role in this system but their actual function is still unknown. In this work we strengthened previous structure predictions for these prokaryotic MCL proteins. We also detected new putative MCL proteins in the Planctomycete Gemmata obscuriglobus. Structural analysis of these revealed the presence of additional domains apart from the β-propeller and α-solenoid combination, characteristic of the membrane-coat architecture. Functions associated with these domains include some related to carbohydrate or membrane/lipid binding. Using homology-based methods, we found MCL proteins in other bacterial phyla, but the most abundant hits are still restricted to Planctomycetes and Verrucomicrobia. Detailed inspection of neighbouring genes of MCL in G. obscuriglobus supports the idea that the function of these proteins is related to membrane manipulation. No significant hits were found in Archaea, including Asgard archaea. More than 10 years after their original detection, PVC bacteria are still uniquely linked to eukaryotes through the structure of the MCL proteins sustaining their endomembrane system.


Standards of radium-226: from Marie Curie to the International Committee for Radionuclide Metrology.
In the early part of the 20th century, the pioneers of radioactivity research, led by Marie Curie, Ernest Rutherford and Stefan Meyer, formed a Commission internationale des étalons de radium. The Commission made arrangements for the preparation and intercomparisons of the international standards of radium, which were identified as the Paris standard and the Vienna standard. Otto Hönigschmid from Vienna prepared a first set of international secondary standards in 1912 and a second set in 1934. In both instances, these secondary standards were compared by gamma-ray measurements with the Paris and Vienna standards. The usage of these international standards of radium in the 20th century is described.


Integrated proteomics and genomics analysis of paradoxical eczema in psoriasis patients treated with biologics.
Few studies have explored the immunology and genetic risk of paradoxical eczema occurring as an adverse event of biologic therapy in patients with psoriasis. We sought to describe the systemic inflammatory signature of paradoxical eczema using proteomics and explore whether this is genetically mediated. This study used the Olink Target 96 Inflammation panel on 256 serum samples from 71 patients with psoriasis and paradoxical eczema, and 75 controls with psoriasis to identify differentially expressed proteins and enriched gene sets. Case samples from 1 or more time points (T1 prebiologic, T2 postbiologic, and T3 postparadoxical eczema) were matched 1:1 with control samples. Genes contributing to enriched gene sets were selected, and functional single nucleotide polymorphisms used to create polygenic risk scores in a genotyped cohort of 88 paradoxical eczema cases and 3124 psoriasis controls. STAMBP expression was lower in cases at T1 than in controls (log-fold change: -0.44; adjusted P = .022); no other proteins reached statistical significance at equivalent time points. Eleven gene sets including cytokine and chemokine pathways were enriched in cases at T2 and 10 at T3. Of the 39 proteins contributing to enriched gene sets, the majority are associated with the atopic dermatitis serum proteome. A polygenic risk score including 38 functional single nucleotide polymorphisms linked to enriched gene sets was associated with paradoxical eczema (adjusted P = .046). The paradoxical eczema systemic inflammatory proteome trends toward atopic dermatitis at a gene-set level and is detectable before onset of the phenotype. This signature could be genetically determined.


A quantitative structure-activity relationship study on a series of 10 para-substituted toluenes binding to cytochrome P4502B4 (CYP2B4), and their hydroxylation rates.
Molecular structural and molecular orbital calculations (AM1 method) are reported on a series of 10 para-substituted toluene derivatives and this structural information has been used to rationalize the differences between both rates of hydroxylation catalysed by cytochrome P4502B4 and binding to the same cytochrome P450, via the generation of quantitative structure-activity relationships (QSARs). It was found that the rate constant for hydroxylation can be described by a two-variable expression involving the dipole moment and volume of the solvent-accessible molecular surface (r = 0.98), whereas binding free energies are well characterized by combinations of molecular volume and various electronic frontier orbital parameters (r = 0.98 and 0.99). This study represents an advance on a previous evaluation by White and McCarthy (Arch Biochem Biophys 246: 19-32, 1986) who used empirical physico-chemical parameters to obtain similar results which were generally of lower statistical significance to those of the present work. The QSAR expressions suggest that both binding to P450 and metabolism for this series of compounds are dependent on the relative ability of the molecules to desolvate and occupy the heme binding site, together with electronic properties of the whole molecule and of the methyl group which undergoes hydroxylation.


[Anxiety and depression during chronic renal failure before end stage at the University hospital center Yalgado Ouedraogo of Ouagadougou (Burkina Faso)].
We wanted to know the prevalence of depression and anxiety, as well as the associated factors in patients with chronic renal failure in Burkina Faso. This was an analytical cross-sectional study conducted from February to May 2016. We included all adult patients with moderate or severe chronic renal failure. The diagnosis of anxiety and depression was made using the Hamilton scales. Identification of factors associated with both conditions required bi- and multivariate analyzes. The study involved 191 patients, with a mean age of 53.2±14.2 years and a sex ratio of 1.4. The prevalence of anxiety and depression was 42.4% and 66.5%, respectively. In 37.7% of cases, both anxiety and depression were noted. The mean age was 52.2±13.1 years for anxious patients and 53.5±13.3 years for the depressed. After multivariate analysis, female sex (odds ratio 2.2; adjusted P=0.014) was significantly associated with anxiety, and anxiety itself at depression (odds ratio 7.5; adjusted P<0.001). Anxiety and depression are very common during moderate or severe chronic renal failure in Burkina Faso. In view of their potentially serious consequences, there is a definite interest in their early detection by the nephrologist, especially in the female patient, and for early management.


Binocular vision findings in normally-sighted school aged children who used digital devices.
To determine the binocular vision status in normally-sighted school aged children who used digital devices. A cross-sectional study was conducted at B.P. Koirala Lions Center for Ophthalmic Studies, Kathmandu, Nepal for a duration of one year. One hundred and eighty school aged children (71 female and 109 male) aged 7 to 17 years were included in the study. All the children underwent detailed ophthalmic and binocular vision examinations. The duration of the use of digital devices by the children were asked to either the parents or guardians present at the time of the study. The study participants were divided into two groups: children who used digital devices for the last six months (users group) and those who hadn't used digital devices for the last six months (non users group). The users group was again divided into two subgroups: children who used digital devices for less than 3 hours per day and a day per week (low digital device users subgroup) and children who used digital devices for more than 3 hours per day and all days in a week (high digital device users subgroup). Accommodative amplitudes, accommodative facility, and positive fusional vergence for both near and distance were significantly reduced in the high digital device users group than in the low digital device users subgroup (p <0.01). Stereo acuity, near point of convergence, and negative fusional vergences for both near and distance were not statistically significantly different between the two subgroups. Prevalence of accommodative and vergence anomalies (except convergence insufficiency) was more in the high digital device users subgroup than in the low digital device users subgroup (p<0.01). Children who used digital devices for a significantly greater amount of time had significantly reduced amplitudes of accommodation, accommodative facility, and positive fusional vergence both at near and distance.


Shaping Block Copolymer Microparticles by Positively Charged Polymeric Nanoparticles.
Shape-transforming block copolymer (BCP) microparticles have attracted extensive attention due to their promising applications in nanotechnology, biomedicines, interfacial science, and other fields. As their performance is highly associated to their shape and structure, it is very important to realize the precise control of particle shape. In this report, a method is proposed to regulate the shape and structure of polystyrene-b-polydimethoxysiloxane (PS-b-PDMS) microparticles by using positively charged core-crosslinked nanoparticles (CNPs) as a cosurfactant, combining with cationic surfactant cetyltrimethylammonium bromide (CTAB). The electrostatic repulsive interactions between CNPs and CTAB dominate the shape of PS-b-PDMS particles. Upon introducing NaCl, the electrostatic repulsion is reduced, resulting in the reshape of PS-b-PDMS particles from striped Janus ellipsoids to onion-like microspheres at a critical concentration of NaCl (cNaCl ). Interestingly, it is found that the critical cNaCl first increases then reaches a plateau, with the increase in the crosslinking degree of the CNPs. The work provides a simple strategy to tailor the morphology of BCPs by manipulating the electrostatic interaction.


CS1, a potential new therapeutic antibody target for the treatment of multiple myeloma.
We generated a humanized antibody, HuLuc63, which specifically targets CS1 (CCND3 subset 1, CRACC, and SLAMF7), a cell surface glycoprotein not previously associated with multiple myeloma. To explore the therapeutic potential of HuLuc63 in multiple myeloma, we examined in detail the expression profile of CS1, the binding properties of HuLuc63 to normal and malignant cells, and the antimyeloma activity of HuLuc63 in preclinical models. CS1 was analyzed by gene expression profiling and immunohistochemistry of multiple myeloma samples and numerous normal tissues. HuLuc63-mediated antimyeloma activity was tested in vitro in antibody-dependent cellular cytotoxicity (ADCC) assays and in vivo using the human OPM2 xenograft model in mice. CS1 mRNA was expressed in >90% of 532 multiple myeloma cases, regardless of cytogenetic abnormalities. Anti-CS1 antibody staining of tissues showed strong staining of myeloma cells in all plasmacytomas and bone marrow biopsies. Flow cytometric analysis of patient samples using HuLuc63 showed specific staining of CD138+ myeloma cells, natural killer (NK), NK-like T cells, and CD8+ T cells, with no binding detected on hematopoietic CD34+ stem cells. HuLuc63 exhibited significant in vitro ADCC using primary myeloma cells as targets and both allogeneic and autologous NK cells as effectors. HuLuc63 exerted significant in vivo antitumor activity, which depended on efficient Fc-CD16 interaction as well as the presence of NK cells in the mice. These results suggest that HuLuc63 eliminates myeloma cells, at least in part, via NK-mediated ADCC and shows the therapeutic potential of targeting CS1 with HuLuc63 for the treatment of multiple myeloma.


[Neonatal cyanosis due to fetal hemoglobin M-Osaka].
The case of a newborn with isolated neonatal cyanosis on day 1 is reported. The basic investigations were sufficient to reach the diagnosis. A rare abnormal fetal hemoglobin was isolated. The prognosis of this disease is excellent and self-resolving.


Tunable rare-earth metal-organic frameworks for ultra-high selenite capture.
Linkers and clusters with various conformations present challenges for the design and prediction of highly porous and stable rare-earth metal-organic frameworks (RE-MOFs) for trapping toxic ions in aqueous solutions. Herein, we designed and synthesized a series of RE-MOFs based on a malleable ligand to explore the effects of ligands, clusters, and configurations on structural stability. The results showed that the nonanuclear high-connected UPC-183 exhibited better stability than the hexanuclear low-connected RE-MOF (UPC-181/182 series). Due to the syngenetic effect of chemi- and physisorption, the adsorption capacity of UPC-183-Eu for selenite (SeO32-) is as high as 308.39 mg/g, recorded one of the highest ever reported for MOFs. Furthermore, we accurately analyzed the adsorption site of UPC-183-Eu for SeO32- through single-crystal structure and theoretical simulation. The ultra-high selenite adsorption capacity and removal efficiency endow UPC-183-Eu an excellent porous adsorbent for removing pollutants.


Hypogonadism does not mediate urinary calcium loss in pituitary-grafted rats.
Rats rendered chronically hyperprolactinemic by implantation of extra anterior pituitary glands (AP) under the kidney capsule have excess urinary calcium excretion. Although serum testosterone levels are normal in male AP-grafted rats, more subtle androgen deficiency might contribute to the increased calcium loss. Female AP-grafted rats lose the normal estrous cycle, which might also alter calcium homeostasis. The urinary calcium and calcium/sodium excretion ratio in gonadectomized AP-grafted rats of both sexes were compared with that of otherwise intact AP-grafted rats and muscle-grafted control rats. AP-grafted rats had increased urinary calcium excretion and calcium/sodium excretion ratio, regardless of gonadal status. Treatment of castrated male AP-grafted animals with testosterone or dihydrotestosterone did not have a significant effect on urinary calcium loss, nor did estrogen replacement of ovariectomized female AP-grafted rats. These studies indicate that the hypercalciuria of the AP-grafted rat is not mediated via an anti-gonadal effect of the prolactin-secreting pituitary graft.


Potential Effect of Bacopa monnieri on Nitrobenzene Induced Liver Damage in Rats.
The study was designed to evaluate the hepatoprotective activity of ethanolic extract of Bacopa monnieri in acute experimental liver injury induced by Nitrobenzene in rats. The extract at the dose of 200 mg/kg body weight was administered orally once every day for 10 days. The increased serum marker enzymes, Aspartate transaminase, Alanine transaminase and alkaline phosphatase were restored towards normalization significantly by the extract. Significant increase in SOD, CAT and GPx was observed in extract treated liver injured experimental rats. Histopathological examination of the liver tissues supported the hepatoprotection. It is concluded that the ethanolic extract of Bacopa monieri plant possess good hepatoprotective activity.


Immunolocalization of laminin in normal rat liver and biosynthesis of laminin by hepatic lipocytes in primary culture.
Laminin, a glycoprotein with a molecular weight of approximately 850,000 daltons, is a major constituent of most epithelial basement membranes. Its presence in the extracellular matrix of normal liver, however, is debated. Using two affinity-purified antibodies directed against laminin, we have localized the glycoprotein within normal rat liver and identified its cellular source. Immunofluorescent staining of rat liver sections revealed laminin in a continuous distribution around hepatic sinusoids, adjacent to hepatocytes and sinusoidal lining cells. To determine the cellular origin of laminin, three perisinusoidal cell populations (hepatocytes, sinusoidal endothelial cells, and lipocytes) were purified from enzymatically dispersed rat liver and were established in primary culture. By immunofluorescence, laminin was associated almost exclusively with lipocytes. Synthesis of laminin was demonstrated by immunoprecipitation of the protein from lipocyte culture medium pulse-labeled with radioactive methionine. These results show that in adult liver, laminin is present in the perisinusoidal matrix and is produced by hepatic lipocytes. Lipocytes, which have the capacity to produce collagen as well as laminin, may be the principal source of extracellular matrix proteins in the perisinusoidal space, and may contribute to subendothelial fibrosis resulting from liver injury.


Headache characteristics among patients with epilepsy and the association with temporal encephaloceles.
Our aim was to determine if headaches characteristic of possible Idiopathic Intracranial Hypertension (IIH) and in general were more prevalent in patients with versus without temporal encephaloceles (TEs) among patients with epilepsy. Electronic medical records were reviewed retrospectively. Among 474 patients with epilepsy, 103 patients (21.7%) had at least one TE diagnosed on initial MRI or on retrospective review by a board-certified neuroradiologist, while 371 patients had no TE present. The patients were grouped into one of four categories depending on their headache characteristics (IIH-like, peri-ictal, other, or no headaches). Analysis of the categories was performed using a Chi Square test. Patients with TEs were more likely to experience headaches of any type than no headaches and more likely to experience IIH-like headaches than to have other headaches or no headaches compared to patients without TEs. Interestingly, patients with TEs were also more likely to experience peri-ictal headaches compared to patients without TEs. However, patients with TEs were no more likely or unlikely to have other (non-IIH or peri-ictal) headaches vs no reported headaches and were not more or less likely to have elevated opening pressure. On retrospective review, patients with TEs and epilepsy were more likely to exhibit headache features characteristic of IIH or to have peri-ictal headaches compared to epilepsy patients without TEs. These findings underscore the need for careful and thorough history of associated headaches in patients with epilepsy so that those patients at risk for TEs can undergo careful inspection of MRI to evaluate for their presence, which may represent a focus for seizures.


Brain connectivity dynamics in cisgender and transmen people with gender incongruence before gender affirmative hormone treatment.
Large-scale brain network interactions have been described between trans- and cis-gender binary identities. However, a temporal perspective of the brain's spontaneous fluctuations is missing. We investigated the functional connectivity dynamics in transmen with gender incongruence and its relationship with interoceptive awareness. We describe four states in native and meta-state spaces: (i) one state highly prevalent with sparse overall connections; (ii) a second with strong couplings mainly involving components of the salience, default, and executive control networks. Two states with global sparse connectivity but positive couplings (iii) within the sensorimotor network, and (iv) between salience network regions. Transmen had more dynamical fluidity than cismen, while cismen presented less meta-state fluidity and range dynamism than transmen and ciswomen. A positive association between attention regulation and fluidity and meta-state range dynamism was found in transmen. There exist gender differences in the temporal brain dynamism, characterized by distinct interrelations of the salience network as catalyst interacting with other networks. We offer a functional explanation from the neurodevelopmental cortical hypothesis of a gendered-self.


[Induction of complete remission with adriamycin and cis-platinum in invasive thymoma].
Complete clinical remission was achieved in a very large lymphocytic thymoma with infiltration of both lungs and almost complete atelectasis of the left lung as well as superior vena cava syndrome using adriamycin (80 mg/m2, day 1) and cis-platinum (120 mg/m2, day 1). A dramatic reduction of tumour size was noticed already after the first cycle of chemotherapy. Remission still persists nine months after commencement of treatment.


Development of a signal-enhanced LFIA based on tyramine-induced AuNPs aggregation for sensitive detection of danofloxacin.
A signal-enhanced LFIA based on tyramine (TYR)-induced AuNPs aggregation has been developed for the sensitive detection of danofloxacin (DAN). In the model, the hydroxyl radical produced by HRP catalyzing H2O2 can trigger the TYR-AuNPs to aggregate on the T or C line for enhancing the detection signal. The linear range of TYR-AuNPs LFIA was 0.25-5 ng mL-1 with the limit of detection (LOD) of 0.032 ng mL-1, and the LOD was 8-fold lower than that of the traditional AuNPs LFIA (0.26 ng mL-1). The TYR-AuNPs LFIA could be used with the naked eyes to qualitatively detect DAN with a cut-off limit of 2.5 ng mL-1, which was 4-fold lower than that of the traditional AuNPs LFIA (10 ng mL-1). The recoveries of TYR-AuNPs LFIA were 86.04-105.14% and 92.41-110.19%, with the coefficient of variation of 1.71-2.05% and 4.42-5.89% in chicken and pork, respectively.


Oligoclonal and polyclonal synthesis of IgG in the central nervous system: an isoelectric focusing study.
The IgG pattern in isoelectric focusing (IEF) has been studied in 90 paired samples of cerebrospinal fluid (CSF) and sera obtained from patients in which intrathecal synthesis of IgG without barrier damage was detectable by Reiber's graph and formula (1980, J. Neurol. 224, 89). Thirty patients were affected by multiple sclerosis (MS), 30 by other inflammatory nervous diseases (OID), and 30 by noninflammatory nervous diseases (NID). At IEF two distinct pathological patterns of CSF IgG were detected: oligoclonal bands (OB), prevailing in the MS group (83% of cases), and a "polyclonal"--i.e., diffuse, uniform--increase of CSF IgG, prevailing in the NID (90%). The OID group was intermediate, 57% of cases with OB and 43% with polyclonal CSF IgG patterns. Overall, only 45 of 90 patients synthesizing IgG in the CNS had CSF OB. This suggests that the CNS immune response can imply either the synthesis of IgG of restricted heterogeneity (i.e., OB) or a polyclonal IgG synthesis, giving in IEF a serum-like pattern to the CSF.


Molecular crowding effects on structure and stability of DNA.
Living cells contain a variety of biomolecules including nucleic acids, proteins, polysaccharides, and metabolites as well as other soluble and insoluble components. These biomolecules occupy a significant fraction (20-40%) of the cellular volume. The total concentration of biomolecules reaches 400gL(-1), leading to a crowded intracellular environment referred to as molecular crowding. Therefore, an understanding of the effects of molecular crowding conditions on biomolecules is important to broad research fields such as biochemical, medical, and pharmaceutical sciences. In this review, we describe molecular conditions in the cytoplasm and nucleus, which are totally different from in vitro conditions, and then show the biochemical and biophysical consequences of molecular crowding. Finally, we discuss the effect of molecular crowding on the structure, stability, and function of nucleic acids and the significance of molecular crowding in biotechnology and nanotechnology.


Multi-Omics Analysis Elucidates The Immune And Intratumor Microbes Characteristics Of Ubiquitination Subtypes In Lung Adenocarcinoma.
Ubiquitination modification is closely related to cancer and participates in the regulation of tumor microenvironment. However, the role of ubiquitination modification in the immune response and prognosis of lung adenocarcinoma has not been elucidated. This study aims to establish a disease classification associated with ubiquitination and reveal the landscape of intratumor microbes in patients with lung adenocarcinoma for the first time. A total of 1314 patients with lung adenocarcinoma in the GEO and TCGA databases were included in our study. We constructed a ubiquitination scoring model using WGCNA and constructed ubiquitination subtypes using unsupervised clustering, analyzed the clinical characteristics, immune characteristics, and intratumor microbes characteristics, and screened out the relevant gene signatures, which were verified by RT-qPCR in human cancer cells. The results showed that the high ubiquitination subtype had poor prognosis, low degree of immune infiltration, high index of tumor stemness, and poor effect of immunotherapy. The subtypes with lower ubiquitination scores have better prognosis, higher tumor microenvironment score and better immunotherapy effect. The C2 subtype has high level of immune infiltration, lower intratumor microbes diversity and abundance, and good prognosis. The C3 subtype has low level of immune infiltration, higher intratumor microbes diversity and abundance, and poor prognosis. The C1 subtype has characteristics between C2 and C3. In summary, this paper constructs a scoring system and several subtypes based on ubiquitination genes, and analyzed the characteristics, which can help provide new methods for clinical treatment.


Simultaneous radioimmunoassay for specific antibodies to members of the human herpesvirus group.
A method of described for the simultaneous radioimmunoassay (RIA) for antibody to members of the human herpesvirus group. The RIA is compared with some of the conventional serologic techniques used to quantitate antibody to these viruses (Epstein-Barr virus, cytomegalovirus, herpesvirus type 1 and varicella-zoster virus). Color-coded beads, each coated with the antigens of a different herpesvirus, were similtaneously placed in a well which contained a human serum to be assayed for antibody to each of these 4 viruses. The results of this test were compared with the results obtained when the serum was assayed for antibody to the 4 viruses in 4 separate tests. We conclude that the antigen-antibody reactions do not significantly interfere with each other when a serum is assayed for antibody to the 4 viruses simultaneously. A comparison of the RIA with conventional serologic techniques shows excellent correlation in the antibody titers obtained. Features of the solid-phase RIA allow significant savings of time, reagents and space, and thus make it feasible for the small laboratory to screen large numbers of sera for antibody to a variety of antigens.


Quantifying radiation therapy response using apparent diffusion coefficient (ADC) parametric mapping of pediatric diffuse intrinsic pontine glioma: a report from the pediatric brain tumor consortium.
Baseline diffusion or apparent diffusion coefficient (ADC) characteristics have been shown to predict outcome related to DIPG, but the predictive value of post-radiation ADC is less well understood. ADC parametric mapping (FDM) was used to measure radiation-related changes in ADC and compared these metrics to baseline ADC in predicting progression-free survival and overall survival using a large multi-center cohort of DIPG patients (Pediatric Brain Tumor Consortium-PBTC). MR studies at baseline and post-RT in 95 DIPG patients were obtained and serial quantitative ADC parametric maps were generated from diffusion-weighted imaging based on T2/FLAIR and enhancement regions of interest (ROIs). Metrics assessed included total voxels with: increase in ADC (iADC); decrease in ADC (dADC), no change in ADC (nADC), fraction of voxels with increased ADC (fiADC), fraction of voxels with decreased ADC (fdADC), and the ratio of fiADC and fdADC (fDM Ratio). A total of 72 patients were included in the final analysis. Tumors with higher fiADC between baseline and the first RT time point showed a trend toward shorter PFS with a hazard ratio of 6.44 (CI 0.79, 52.79, p = 0.083). In contrast, tumors with higher log mean ADC at baseline had longer PFS, with a hazard ratio of 0.27 (CI 0.09, 0.82, p = 0.022). There was no significant association between fDM derived metrics and overall survival. Baseline ADC values are a stronger predictor of outcome compared to radiation related ADC changes in pediatric DIPG. We show the feasibility of employing parametric mapping techniques in multi-center studies to quantitate spatially heterogeneous treatment response in pediatric tumors, including DIPG.


Further evidence for ClockΔ19 mice as a model for bipolar disorder mania using cross-species tests of exploration and sensorimotor gating.
Bipolar disorder (BD) is a pervasive neuropsychiatric disorder characterized by episodes of mania and depression. The switch between mania and depression may reflect seasonal changes and certainly can be affected by alterations in sleep and circadian control. The circadian locomotor output cycles kaput (CLOCK) protein is a key component of the cellular circadian clock. Mutation of the Clock gene encoding this protein in ClockΔ19 mutant mice leads to behavioral abnormalities reminiscent of BD mania. To date, however, these mice have not been assessed in behavioral paradigms that have cross-species translational validity. In the present studies of ClockΔ19 and wildtype (WT) littermate mice, we quantified exploratory behavior and sensorimotor gating, which are abnormal in BD manic patients. We also examined the saccharin preference of these mice and their circadian control in different photoperiods. ClockΔ19 mice exhibited behavioral alterations that are consistent with BD manic patients tested in comparable tasks, including hyperactivity, increased specific exploration, and reduced sensorimotor gating. Moreover, compared to WT mice, ClockΔ19 mice exhibited a greater preference for sweetened solutions and greater sensitivity to altered photoperiod. In contrast with BD manic patients however, ClockΔ19 mice exhibited more circumscribed movements during exploration. Future studies will extend the characterization of these mice in measures with cross-species translational relevance to human testing.


Clinical decision support recommending ventilator settings during noninvasive ventilation.
NIV therapy is used to provide positive pressure ventilation for patients. There are protocols describing what ventilator settings to use to initialize NIV; however, the guidelines for titrating ventilator settings are less specific. We developed an advisory system to recommend NIV ventilator setting titration and recorded respiratory therapist agreement rates at the bedside. We developed an algorithm (NIV advisor) to recommend when to change the non-invasive ventilator settings of IPAP, EPAP, and FiO2 based on patient respiratory parameters. The algorithm utilized a multi-target approach; oxygenation, ventilation, and patient effort. The NIV advisor recommended ventilator settings to move the patient's respiratory parameters in a preferred target range. We implemented a pilot study evaluating the usability of the NIV advisor on 10 patients receiving critical care with non-invasive ventilation (NIV). Respiratory therapists were asked their agreement on recommendations from the NIV advisor at the patient's bedside. Bedside respiratory therapists agreed with 91% of the ventilator setting recommendations from the NIV advisor. The POB and VT values were the respiratory parameters that were most often out of the preferred target range. The IPAP ventilator setting was the setting most often considered in need of changing by the NIV advisor. The respiratory therapists agreed with the majority of the recommendations from the NIV advisor. We consider the IPAP recommendations informative in providing the respiratory therapist assistance in targeting preferred POB and Vt values, as these values were frequently out of the target ranges. This pilot implementation was unable to produce the results required to determine the value of the EPAP recommendations. The FiO2 recommendations from the NIV advisor were treated as ancillary information behind the IPAP recommendations.


Genome Sequences of Klebsiella variicola Isolates from Dairy Animals with Bovine Mastitis from Newfoundland, Canada.
Klebsiella variicola was recently reported as an emerging and/or previously misidentified species associated with opportunistic infections in humans. Here, we report the draft genome sequences of K. variicola isolates from two animals with clinical mastitis from a dairy farm in Newfoundland, Canada.


Does childbirth alter the reflex pelvic floor response to coughing?
To determine the prevalence of and to quantify the effect of reflex pelvic floor activation on coughing in nulliparous pregnant women, and to assess peripartal changes and any association with stress urinary incontinence. Between April 2008 and March 2010, 131 nulliparous pregnant women were recruited from an antenatal clinic. All participants were interviewed and underwent four-dimensional translabial ultrasound examination at antepartum (35.8 (mean) weeks' gestation) and postpartum (4.6 (mean) months) visits. Four-dimensional ultrasound volume datasets of the pelvic floor during coughs were obtained at a minimum frame rate of 16 Hz, using a 10° volume acquisition angle. To quantify a reflex levator contraction we measured the midsagittal hiatal diameter at multiple time points. Levator integrity was determined using tomographic ultrasound imaging. From 131 women recruited, 47 datasets were technically suboptimal, leaving 84. There was a visible pelvic floor reflex in 82 (98%) cases. At the postpartum visit this was reduced to 63/84, i.e. 75% (P < 0.001). The magnitude of a reflex contraction was markedly reduced postpartum, from 4.8 mm to 2.0 mm (P < 0.001), and this effect was associated with delivery mode (P = 0.042). There was a trend towards an association between lower reflex contraction magnitude and stress incontinence (0.87 ± 3.18 mm vs. 2.36 ± 3.5 mm; P = 0.08) at the postpartum follow-up visit. Pelvic floor reflexes are altered by childbirth. This alteration may be associated with vaginal delivery. Reflex magnitude may be associated with postpartum stress urinary incontinence. The clinical significance of this finding is uncertain.


Utilization and yield of drug screening in the emergency department.
Emergency qualitative tests for drugs are commonly ordered during evaluation of cases of suspected drug overdose. We prospectively compared the utilization and yield of drug screens based on urine and of identical tests of gastric contents under actual clinical conditions in a busy metropolitan emergency department. During the 4.5-month study period, physicians ordered drug screening in 405 of 582 (70%) study cases. Screens of both types of body fluid were ordered in only 95 cases (16%), suggesting study physicians regarded these tests to be functionally equivalent. Drug screens of gastric fluid were favored in cases involving acute ingestion and in medically complicated cases requiring gastric lavage. Urine drug screens were favored in clinically stable cases with primarily thought or behavior disorders. In the 95 cases for which both drug screens were ordered, gastric screens in 18 cases detected 20 drugs not detected by urine drug screening. Urine screening, on the other hand, identified 74 drugs not found on gastric screening in 48 cases. Gastric drug screening also performed poorly in comparison to quantitative serum drug levels. Seventeen false-positive urine or gastric screens were noted as well. Despite significant technical limitations, physicians frequently order drug screens in our emergency department. Qualitative drug screening of gastric fluid may prove useful in cases involving acute ingestion, but samples of urine and serum must also be submitted for analysis if optimal test performance is to be achieved.


Predictive risk-score model to select patients with intrahepatic cholangiocarcinoma for adjuvant chemotherapy.
The aim of this study was to develop a predictive model to identify individuals most likely to derive overall survival (OS) benefit from adjuvant chemotherapy (AC) after hepatic resection of intrahepatic cholangiocarcinoma (ICC). Patients who underwent hepatic resection of ICC between 1990 and 2020 were identified from a multi-institutional database. Factors associated with worse OS were identified and incorporated into an online predictive model to identify patients most likely to benefit from AC. Among 726 patients, 189 (26.0%) individuals received AC. Factors associated with OS on multivariable analysis included CA19-9 (Hazard Ratio [HR]1.17, 95%CI 1.04-1.31), tumor burden score (HR1.09, 95%CI 1.04-1.15), T-category (T2/3/4, HR1.73, 95%CI 1.73-2.64), nodal disease (N1, HR3.80, 95%CI 2.02-7.15), tumor grade (HR1.88, 95%CI 1.00-3.55), and morphological subtype (HR2.19, 95%CI 1.08-4.46). A weighted predictive score was devised and made available online (https://yutaka-endo.shinyapps.io/ICCrisk_model_for_AC/). Receipt of AC was associated with a survival benefit among patients at high/medium-risk (high: no AC, 0% vs. AC, 20.6%; medium: no AC, 36.4% vs. 40.8%; both p < 0.05) but not low-risk (low: no AC, 65.1% vs. AC, 65.1%; p = 0.73) tumors. An online predictive model based on tumor characteristics may help identify which patients may benefit the most from AC following resection of ICC.


Survey of blood centre readiness regarding removal of DEHP from blood bag sets: The BEST Collaborative Study.
Di(2-ethylhexyl) phthalate (DEHP) must be removed from blood bag sets in Europe by 27 May 2025. DEHP is known to interact with the red blood cell (RBC) membrane, resulting in reduced haemolysis and thus prolonging shelf-life. Current non-DEHP alternatives result in increased haemolysis requiring reconsideration of the RBC shelf-life. Although the immediate impact of eliminating DEHP is to the European community, the non-DEHP movement could affect blood bag set availability globally. The purpose of this survey is to understand blood centre readiness regarding the transition to non-DEHP blood collection and storage systems. A 24-question on-line survey was completed by members of the Biomedical Excellence for Safer Transfusion Collaborative research network. Responses were obtained from 16 blood collection or processing institutions. A majority of respondents (12/16) indicated that both shelf-life and haemolysis were equally important in selecting non-DEHP blood bag sets. Six respondents would accept a lower RBC product shelf-life compared to current practice. Respondents were not clear on the best non-DEHP vinyl material or RBC storage solution. Three European blood centres indicated they have developed non-DEHP transition plans. One challenge identified regarding the transition to non-DEHP is the extensive validation testing that will be required. Blood centres in Europe are concerned with meeting the sunset date for DEHP, considering that limited non-DEHP blood bag and RBC storage solutions are currently available. Banning DEHP in Europe, which may have global ramifications, represents a major challenge not yet fully understood by the transfusion medicine community.


NFYC-37 promotes tumor growth by activating the mevalonate pathway in bladder cancer.
Dysregulation of transcription is a hallmark of cancer, including bladder cancer (BLCA). CRISPR-Cas9 screening using a lentivirus library with single guide RNAs (sgRNAs) targeting human transcription factors and chromatin modifiers is used to reveal genes critical for the proliferation and survival of BLCA cells. As a result, the nuclear transcription factor Y subunit gamma (NFYC)-37, but not NFYC-50, is observed to promote cell proliferation and tumor growth in BLCA. Mechanistically, NFYC-37 interacts with CBP and SREBP2 to activate mevalonate pathway transcription, promoting cholesterol biosynthesis. However, NFYC-50 recruits more of the arginine methyltransferase CARM1 than NFYC-37 to methylate CBP, which prevents the CBP-SREBP2 interaction and subsequently inhibits the mevalonate pathway. Importantly, statins targeting the mevalonate pathway can suppress NFYC-37-induced cell proliferation and tumor growth, indicating the need for conducting a clinical trial with statins for treating patients with BLCA and high NFYC-37 levels, as most patients with BLCA have high NFYC-37 levels.


Heterotopic tracheal transplantation with omentum wrapping in the abdominal position preserves functional and structural integrity of a human tracheal allograft.
Transplantation of a human trachea has been reported only twice in the literature with limited documentation of the functional and structural properties of the allograft. A 57-year-old patient with chronic obstructive pulmonary disease with low segment tracheal stenosis was accepted for lung transplantation and 2-stage tracheal allotransplantation. Standard bilateral sequential lung transplantation was performed with the transfer of the donor trachea into the recipient's abdomen, which was wrapped in the greater omentum and sutured into the abdominal wall, similar to a stoma. The patient received immunosuppression consisting of cyclosporine A, mycophenolate mofetil, and cortisone. Sixty days later, the tracheal allograft presented with macroscopically normal appearance with maintained elasticity and rigidity. The patient underwent a cricotracheal resection 6 months after lung transplantation. However, reconstruction with direct end-to-end anastomosis was achievable. The tracheal allograft, therefore not needed for reconstruction, was harvested and underwent complete investigations. Cross-section of the graft revealed a mechanically stable and macroscopically intact trachea. Hematoxylin-eosin staining demonstrated vital cartilage covered by respiratory epithelium. Angiography, followed by corrosion studies and electromicroscopy, demonstrated excellent vascularization of the tracheal wall. The patient is alive 31 months posttransplantation and remains in bronchiolitis obliterans syndrome stage 0. Human trachea wrapped in omentum maintains its functional and structural integrity and may be used for 2-stage allotransplantation.


Interaction of the (2√3 × 3)rect. Adsorption-Site Basis and Alkyl-Chain Close Packing in Alkanethiol Self-Assembled Monolayers on Au(111): A Molecular Dynamics Study of Alkyl-Chain Conformation.
We show that the adsorption site basis of the (2√3 × 3)rect. phase of n-alkanethiol self-assembled monolayers plays a key role in determining the molecular conformation of the close-packed alkyl chains. Ten proposed reconstructed Au-S interfaces are used to explore the minimized energy alkyl-chain packing of n-decanethiol molecules using molecular dynamics with the all-atom description. In this comparative study, all models have the same alkyl-chain surface density of four molecules per unit cell; thus, differences are due to the headgroup spacing within the 4-molecule basis as opposed to the average surface density. We demonstrate for the first time the 4-molecule-basis twist structure driven by the packing of alkanethiol molecules in a large simulation box (100 molecules, 25 unit cells) using molecular dynamics. Our results validate the prediction put forward by Mar and Klein that to achieve the 4-molecule-basis twist symmetry observed by the experiment, the headgroups must deviate from the high-symmetry (√3 × √3)R30° sites. The key structural parameters: tilt, twist, and end-group height, as well as their spatial order, are compared with experimental results, which we show is a highly sensitive approach that can be used to vet proposed Au-S interfacial models.


Household perception and infestation dynamics of bedbugs among residential communities and its potential distribution in Africa.
Bedbugs have experienced an extraordinary upsurge in the recent past across the world. This cross-sectional study aimed to explore the community perception of the pest outbreaks, the population dynamics, and dispersal patterns under different habitat systems. A survey was conducted within communities in nine counties in Kenya, where geographical coordinates of the sites of bedbug presence were recorded and maximum entropy distribution modelling (MaxEnt) was used to map and predict the potentially suitable habitat, while system thinking and system dynamics approach with Vensim PLE 8.0.9 software was applied to implement bedbug infestation dynamics. Our results indicated that majority of the respondents had ample knowledge on bedbugs and were concerned about the physico-psychologic and socio-economic health effects. Spatial distribution analysis showed regions in Kenya with optimal to suitable for bedbug occurrence in the whole country, and similar results were found at continental level across Africa. Furthermore, infestation dynamics results showed a rapid mobility of bedbug from one house to another. In terms of management strategies, the models showed that the combination of chemical with other control methods was considerably much more effective compared to the use of chemical approach only, appointing integrated pest management strategy as a better intervention approach in controlling the pest.


Taxonomy 2.0: Sequencing of old type specimens supports the description of two new species of the Lasiocampa decolorata group from Morocco (Lepidoptera, Lasiocampidae).
The type of Lasiocampa decolorata (KLUG, 1830), collected in 1820, was successfully barcoded to generate a 658bp COI-fragment after 194 years. The resulting molecular data allowed the description of two closely related species from Morocco: Lasiocampa hannae SPEIDEL, MOOSER & WITT sp. n. from the Anti Atlas and Lasiocampa editae SPEIDEL, MOOSER & WITT sp. n. from the High Atlas.


Abatacept Use Is Associated with Steroid Dose Reduction and Improvement in Fatigue and CD4-Dysregulation in CVID Patients with Interstitial Lung Disease.
Interstitial lung disease (ILD) represents a severe clinical manifestation of systemic immune dysregulation in patients with common variable immunodeficiency (CVID). Its treatment often requires systemic immunosuppression beyond corticosteroids. To assess the safety and efficacy of abatacept in patients with CVID and ILD. Ten patients with confirmed diagnosis of CVID and ILD were included in a single-center, prospective, open-label, nonrandomized trial. Abatacept was administered subcutaneously at a dose of 125 mg/wk for 12 months. Abatacept was a safe treatment for ILD in CVID except for 1 case of bronchopulmonary aspergillosis. One additional patient terminated the trial prematurely because of recurrent bronchitis. Five of 8 patients treated per protocol benefited from the treatment according to American Thoracic Society/European Respiratory Society criteria. The primary end point of the study was met because single breath diffusing capacity of the lung for carbon monoxide was stable (62.5%) or improved (37.5%) in all patients treated per protocol. Although nodules (71%) and ground-glass opacities (57%) improved in most patients, other computed tomography pathologies were less responsive. Quality of life improved in 87.5% and fatigue in 57% of patients. Abatacept treatment was associated with significant improvement in CD4 T-cell dysregulation, signified by a decrease in serum soluble IL-2 receptor levels and of proliferating Ki67+ CD4 T cells, and a recovery of total lymphocytes, CD4+ T cells, and naive CD4 T cells. Abatacept may represent a treatment option for CVID-associated ILD. This pilot study demonstrated a good safety profile, steroid-sparing effect, positive immune modulation, and overall positive treatment response especially in quality of life. Larger controlled studies are needed to confirm these findings.


Pharmacokinetics of propentofylline and the quantitation of its metabolite hydroxypropentofylline in human volunteers.
Propentofylline (PPF, 3-methyl-1-(5-oxohexyl)-7-propylxanthine) has been reported to be effective for the treatment of both vascular dementia and dementia of the Alzheimer type. The pharmacological effects of PPF may be exerted via the stimulation of nerve growth factor, increased cerebral blood flow, and inhibition of adenosine uptake. The objectives of this experiment are to determine the kinetic behavior of PPF, to identify, and to quantify its metabolite in human. Blood samples were obtained from human volunteers following oral administration of 200 mg of PPF tablets. For the identification and quantification of the metabolite, 3-methyl-1-(5-hydroxyhexyl)-7-propylxanthine (PPFOH), PPFOH was synthesized and identified by gas chromatography/mass spectroscopy (GC/MS) and 1H-nuclear magnetic resonance spectroscopy. The molecular weight of synthesized metabolite is 308 dalton. The PPF and PPFOH in plasma were extracted with diethyl ether and identified by electron impact GC/MS. The plasma concentrations of PPF and PPFOH were determined by gas chromatography/nitrogen phosphorus detector in plasma and their pharmacokinetic parameters were determined. The mean half-life of PPF was 0.74 hr. The areas under the curve (AUCs) of PPF and PPFOH were 508 and 460 ng.hr/ml, respectively. Cmax of PPF was about 828.4 ng/ml and the peak concentration was achieved at about 2.2 hr (Tmax). These results indicate that PPF is rapidly disappeared from blood due to extensive metabolism into PPFOH.


Renal dysfunction following high-dose carboplatin treatment.
A case history is reported or renal failure during and after treatment with carboplatin for 3 days, total dose 750 mg/m2, in a conditioning regimen prior to autologous bone marrow transplantation. Pretreatment renal function was compromised after nephrectomy and chemotherapy with cisplatin. A decrease in glomerular filtration rate concurred with a decrease in excretion of platinum in the urine and an increase in urinary beta 2 microglobulin. Treatment with high-dose carboplatin in patients with impaired renal function and previous treatment with cisplatin may lead to further loss of renal function.


Canadian medical research strategy for the eighties. II. Promise or performance as the basis for the distribution of research funds?
It is widely accepted that public funds for medical research should be distributed to those who can best state what they propose to do with the funds. This should ensure ultimate public control over how the funds are spent, responsible budgeting on the part of the researcher and optimal progress in the understanding of disease. In this article it is argued that this "promise" system of distributing funds achieves none of these objectives. The primary basis for the distribution of funds should not lie in the imaginary world of future promise; which is difficult to evaluate and leads to a hyperpoliticization of the funding process. Instead, funds should be distributed on the basis of the real world of past research and budgetary performance. The "performance" approach lends itself well to a situation in which the majority of medical researchers have a long term commitment to a sustained career in medical research, a stable level of expenditure and a record of the effectiveness with which they have spent past funds.


In vitro ovicidal effect of p-coumaric acid from Acacia bilimekii aerial parts against Haemonchus contortus.
Acacia bilimekii is a plant with a high content of protein, fibre, and condensed tannins, making it an excellent feed for small ruminants with anthelmintic potential. This study aimed to evaluate the ovicidal activity of a hydroalcoholic extract (Ab-HA) and fractions from A. bilimekii aerial parts on Haemonchus contortus. The ovicidal activity of the Ab-HA extract and its fractions obtained by chromatographic fractionation were evaluated through the egg hatching inhibition (EHI) test. The results showed that the Ab-HA extract had 91% EHI at 20,000 µg/mL with a mean effective concentration (EC50) of 9260 µg/mL. After liquid-liquid fractionation of Ab-HA extract, the aqueous fraction (Ab-Aq) did not show ovicidal activity, whereas the organic fraction (Ab-EtOAc) showed a better EHI than the Ab-HA extract (98.9% at 2500 µg/mL). Then, the chemical fractionation of Ab-EtOAc allowed obtaining six bioactive fractions (AbR12-17) with an EHI greater than 90% at 1500 µg/mL. The best treatment was AbR15 (98.7% EHI at 750 µg/mL). Chemical analysis by HPLC-PDA of AbR15 indicated the presence of p-coumaric acid and the flavone luteolin as major compounds. Additionally, the commercial p-coumaric acid standard was evaluated in the EHI assay and showed an EHI of 97% at 62.5 µg/mL. Meanwhile, the confocal laser scanning microscopy analysis demonstrated a colocalization effect between p-coumaric acid and the H. contortus embryonated eggs. These results indicate that due to their major chemical compounds (including p-coumaric acid), the aerial parts of the plant A. bilimekii, could be considered as natural potential tool for controlling haemonchosis in small ruminants.


Going forward with genetics: recent technological advances and forward genetics in mice.
Forward genetic analysis is an unbiased approach for identifying genes essential to defined biological phenomena. When applied to mice, it is one of the most powerful methods to facilitate understanding of the genetic basis of human biology and disease. The speed at which disease-causing mutations can be identified in mutagenized mice has been markedly increased by recent advances in DNA sequencing technology. Creating and analyzing mutant phenotypes may therefore become rate-limiting in forward genetic experimentation. We review the forward genetic approach and its future in the context of recent technological advances, in particular massively parallel DNA sequencing, induced pluripotent stem cells, and haploid embryonic stem cells.


Knockdown of Ggps1 in chondrocyte expedites fracture healing by accelerating the progression of endochondral ossification in mice.
Bone fracture healing is achieved through the proliferation and differentiation of stem cells, while bone marrow stem cells (BMSCs) contribute to endochondral ossification. During fracture healing, mesenchymal progenitor cells first form a cartilaginous blastema that becomes vascularized to recruit precursor cells of osteoblasts through the bone morphogenetic protein 2 (Bmp2)/Smad-dependent Runx2 pathway. Statins deplete geranylgeranyl diphosphate (GGPP), which participates in the regulation of BMSCs differentiation, through the inhibition of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase, leading to impaired protein geranylgeranylation, which strongly impacts the bone synthesis induced by Bmp2. Accordingly, we would like to investigate the role of geranylgeranyl diphosphate synthase 1 (Ggps1) in bone fracture via endochondral ossification in mice. We used a Cre-loxP system, namely the tamoxifen-inducible Collagen 2-CreERT2 Ggps1 fl/fl, to eliminate specifically the Ggps1 activity in chondrocytes of 8-10-week-old mice. We found that the endochondral bone formation, calcification and vasculogenesis of the bony callus were accelerated in fractures in Ggps1-/-mice. Together, the results of this study confirm that the specific deletion of Ggps1, using the Collagen 2-CreERT2 mice, will accelerate the fracture healing process by activating the Bmp2/Smad-dependent Runx2 pathway. In addition, we managed to improve the fracture healing process by inhibiting the Ggps1 activity and its related products with statin drugs.


SO2 Poisoning of Cu-CHA deNO x Catalyst: The Most Vulnerable Cu Species Identified by X-ray Absorption Spectroscopy.
Cu-exchanged chabazite zeolites (Cu-CHA) are effective catalysts for the NH3-assisted selective catalytic reduction of NO (NH3-SCR) for the abatement of NO x emission from diesel vehicles. However, the presence of a small amount of SO2 in diesel exhaust gases leads to a severe reduction in the low-temperature activity of these catalysts. To shed light on the nature of such deactivation, we characterized a Cu-CHA catalyst under well-defined exposures to SO2 using in situ X-ray absorption spectroscopy. By varying the pretreatment procedure prior to the SO2 exposure, we have selectively prepared CuI and CuII species with different ligations, which are relevant for the NH3-SCR reaction. The highest reactivity toward SO2 was observed for CuII species coordinated to both NH3 and extraframework oxygen, in particular for [CuII 2(NH3)4O2]2+ complexes. Cu species without either ammonia or extraframework oxygen ligands were much less reactive, and the associated SO2 uptake was significantly lower. These results explain why SO2 mostly affects the low-temperature activity of Cu-CHA catalysts, since the dimeric complex [CuII 2(NH3)4O2]2+ is a crucial intermediate in the low-temperature NH3-SCR catalytic cycle.


The Cell-Cycle Arrest and Apoptotic Functions of p53 in Tumor Initiation and Progression.
P53 is a transcription factor highly inducible by many stress signals such as DNA damage, oncogene activation, and nutrient deprivation. Cell-cycle arrest and apoptosis are the most prominent outcomes of p53 activation. Many studies showed that p53 cell-cycle and apoptosis functions are important for preventing tumor development. p53 also regulates many cellular processes including metabolism, antioxidant response, and DNA repair. Emerging evidence suggests that these noncanonical p53 activities may also have potent antitumor effects within certain context. This review focuses on the cell-cycle arrest and apoptosis functions of p53, their roles in tumor suppression, and the regulation of cell fate decision after p53 activation.


Oligomerization of cytosine-containing nucleotide analogs in aqueous solution.
Bisphosphoimidazolides of 2'-deoxycytidine and of its acyclic analog C can be oligomerized in aqueous solution in the presence of Mn(II). Under certain conditions, a range of products extending to at least the 20mer can be obtained. These products are of interest as possible templates for oligomerization of the complementary monomers.


Anxiety stress and nociceptive responses in mice.
Nociception in laboratory animals appears to be influenced by physical or emotional stressors. Nevertheless, the reported data are not univocal. Discrepancies seem to be caused by some kind of stress model and/or by the timing of stressor application. The aim of the present work is to study the influence of chronic application of a well-controlled and defined anxiety stress paradigm (rotational stress) on the behavioral formalin pain responses in mice maintained in a low-stress environment. The results indicate that emotional chronic stress increases specific pain responses in the late inflammatory phase and, correspondingly, decreases self-grooming. Locomotor activity appears influenced by pain presence only. The hormonal and neural mechanisms that could be involved in the observed nonspecific and specific nociceptive responses to stress are discussed.


Detection of human adenoviruses in influenza-negative patients with respiratory tract infections in Nanning, China.
Human adenoviruses (HAdV) have been known to cause a range of diseases, including respiratory tract infections (RTIs). However, there is limited information available regarding the genotype diversity and epidemiology of HAdV associated with RTIs in Nanning. Between June 2019 and December 2021, throat swab, nasal swab, or nasopharyngeal swab samples were obtained from individuals hospitalized with respiratory tract infections (RTIs). Statistical software was used to analyze the epidemiological data. The highly conserved 132-bp gene region of the HAdV hexon was targeted for the detection of HAdV using a qPCR assay. An 875-bp hexon gene fragment was subjected to phylogenetic analysis. Significant variations were observed in the age and gender distribution of HAdV-positive patients (P = 0.004 and P = 0.025, respectively). The age distribution of HAdV-positive patients showed that 67.89% of those who tested positive were the age group of 0-6 years. Furthermore, the prevalence of HAdV detection was highest during spring and autumn, with a peak in February. Additionally, genotyping of the 36 HAdV-positive samples with 875-bp fragments identified the presence of circulating HAdV species B, C, and E in Nanning between 2019 and 2021. This study identified an association between HAdV prevalence and age as well as season. Among hospitalized patients with RTIs in Nanning, HAdV-B, HAdV-C, and HAdV-E were found to be co-circulating. The most commonly detected genotypes were HAdV-C1, HAdV-C6, and HAdV-E4.


Handgrip Strength Asymmetry Is Associated With Limitations in Individual Basic Self-Care Tasks.
This investigation sought to determine the associations between handgrip strength (HGS) asymmetries and limitations in individual activities of daily living (ADL). The analytic sample included 18,468 participants from the 2006 to 2016 waves of the Health and Retirement Study. Those with HGS >10% stronger on either hand had any HGS asymmetry. Individuals with HGS >10% stronger on their dominant or non-dominant hand had dominant or non-dominant HGS asymmetry, respectively. ADL abilities were self-reported. Those with any HGS asymmetry had 1.21 (95% confidence interval [CI] = [1.01-1.46]) greater odds for a toileting limitation and 1.25 (CI = [1.03-1.52]) greater odds for a transferring limitation. Individuals with dominant HGS asymmetry had 1.24 (CI = [1.01-1.53]) greater odds for a transferring limitation. Those with non-dominant HGS asymmetry had 1.39 (CI = [1.01-1.93]) and 1.44 (CI = [1.05-1.96]) greater odds for a bathing and toileting limitation, respectively. HGS asymmetries could help to identify future limitations in specific ADLs.


Mithplatins: Mithramycin SA-Pt(II) Complex Conjugates for the Treatment of Platinum-Resistant Ovarian Cancers.
DNA coordinating platinum (Pt) containing compounds cisplatin and carboplatin have been used for the treatment of ovarian cancer therapy for four decades. However, recurrent Pt-resistant cancers are a major cause of mortality. To combat Pt-resistant ovarian cancers, we designed and synthesized a conjugate of an anticancer drug mithramycin with a reactive Pt(II) bearing moiety, which we termed mithplatin. The conjugates displayed both the Mg2+ -dependent noncovalent DNA binding characteristic of mithramycin and the covalent crosslinking to DNA of the Pt. The conjugate was three times as potent as cisplatin against ovarian cancer cells. The DNA lesions caused by the conjugate led to the generation of DNA double-strand breaks, as also observed with cisplatin. Nevertheless, the conjugate was highly active against both Pt-sensitive and Pt-resistant ovarian cancer cells. This study paves the way to developing mithplatins to combat Pt-resistant ovarian cancers.


Enzyme association with lipidic Langmuir-Blodgett films: interests and applications in nanobioscience.
This review presents the recent advances in the achievement of organized proteo-lipidic nanostructures based on Langmuir-Blodgett technology and their potential applications in the nanobioscience area. By using the self-assembled properties of amphiphilic biomolecules at the air-water interface, the Langmuir-Blodgett (LB) technique offers the possibility to prepare ultrathin layers suitable for biomolecule immobilization at the molecular level. This review will provide a general overview of the enzyme association with preformed Langmuir-Blodgett films in connection with their potential applications in biosensing device developments, and then introduce the design of a new functionalised biomimetic nanostructure with oriented recognition site. The potential applications of such an organized proteo-lipidic nanostructure for biocatalysis investigations of an immobilised enzyme in a biomimetic situation and for the development of bioelectronic devices are finally discussed.


Priming GPCR signaling through the synergistic effect of two G proteins.
Although individual G-protein-coupled receptors (GPCRs) are known to activate one or more G proteins, the GPCR-G-protein interaction is viewed as a bimolecular event involving the formation of a ternary ligand-GPCR-G-protein complex. Here, we present evidence that individual GPCR-G-protein interactions can reinforce each other to enhance signaling through canonical downstream second messengers, a phenomenon we term "GPCR priming." Specifically, we find that the presence of noncognate Gq protein enhances cAMP stimulated by two Gs-coupled receptors, β2-adrenergic receptor (β2-AR) and D1 dopamine receptor (D1-R). Reciprocally, Gs enhances IP1 through vasopressin receptor (V1A-R) but not α1 adrenergic receptor (α1-AR), suggesting that GPCR priming is a receptor-specific phenomenon. The C terminus of either the Gαs or Gαq subunit is sufficient to enhance Gα subunit activation and cAMP levels. Interaction of Gαs or Gαq C termini with the GPCR increases signaling potency, suggesting an altered GPCR conformation as the underlying basis for GPCR priming. We propose three parallel mechanisms involving (i) sequential G-protein interactions at the cognate site, (ii) G-protein interactions at distinct allosteric and cognate sites on the GPCR, and (iii) asymmetric GPCR dimers. GPCR priming suggests another layer of regulation in the classic GPCR ternary-complex model, with broad implications for the multiplicity inherent in signaling networks.


[Analysis of the mechanism of perception of temperature stimuli by the ampullae of Lorenzini of Black Sea skates].
The single nerve fibre responses of the Lorenzini ampulla to thermal stimulation were studied in the Black Sea skates, Trygon pastinaca, and Raja clavata. Cooling of sea water applied to the ampulla capsule or to the skin overlying the sensory organ increased firing rate wheras warming led to transient decrease in frequency. The thermal sensitivity or receptors was found to depend on threshold to electric current. Static discharge rate of the receptors has positive or negative temperature coefficient according to the temperature range. Cooling of sea water increased the latency of response to electric stimuli. Biological significance of the thermal sensitivity of the Lorenzini ampulla is discussed.


The effect of the benzodiazepine antagonist, flumazenil, on psychometric performance in acute ethanol intoxication in man.
The effect on cognitive and psychomotor performance of the benzodiazepine (BZD) antagonist, flumazenil, in antagonising the central effect, of ethanol in man has been investigated. Eight healthy adult male volunteers, aged 23 to 32 years, participated in the study. Following a loading infusion, stable blood ethanol levels with a mean value of 1.6 g x l-1 were produced by a maintenance infusion. When stable blood levels of ethanol were reached, 5.0 mg flumazenil/placebo was administered intravenously, and after 15 and 75 min a test battery evaluating psychomotor and cognitive functions was applied. The test battery was sensitive to the test model, but no significant improvement in the test scores could be demonstrated following the administration of flumazenil. It is concluded that flumazenil has no influence on psychomotor functions in acute ethanol intoxication.


Serum thyroglobulin as a preclinical tumour marker in subgroups of thyroid cancer.
Serum samples from a biological serum bank taken several years before the diagnosis of cancer, were analysed for S-Tg and S-TSH in 43 patients with thyroid cancer and compared to 128 healthy controls matched for age, sex, geographical region and time of blood sampling. The main finding was the difference in S-Tg between cases and controls, the highest values being found in sera from cases. Relative risk of thyroid cancer increases with increasing S-Tg levels (the global test giving P less than 0.0005). Extremely high levels were found in 4 cases with follicular and 3 with anaplastic cancers. No such statistically significant difference was found in S-TSH concentration. Possible explanations for the elevated S-Tg observed several years before clinically evident malignant tumour are discussed.


Emergency MRI utilization trends at a tertiary care academic medical center: baseline data.
This study evaluates utilization trends of emergency department (ED)-ordered magnetic resonance imaging (MRI) examinations in an adult academic medical center over a 5-year period (2001-2005). MRI examinations from the ED-ordering location were identified by searching the radiology information system (RIS). Overall MRI volume and ED patient encounters were also assessed during the same period. Each examination was assessed by type of examination, examination completion time, and primary and secondary clinical indications by reviewing the RIS and medical record. During the study period, 1,900 ED-ordered MRI examinations were performed on 1,020 patients. During the same period, 62,823 total MRI examinations were performed, and the total ED patient volume was 420,840. ED-ordered MRI volume increased 391% over the study period (125 to 614 examinations/year), whereas total MRI volume increased only 38.9% and ED patient volume in our institution actually decreased by -9%. MRI examinations of the brain, magnetic resonance angiography of the head and neck, and spinal MRI were the most commonly ordered tests. Clinical indications were analyzed. Peak times of ED-ordered examination completion were between 4:00 PM and 11:00 PM. A total of 15.5% of examinations required overtime or callback of MRI technologists for completion. Multiple reasons are suggested that may increase utilization (perceived need for diagnostic certainty, as well as medico-legal and patient-driven factors). Whether this increase in MRI utilization resulted in improved patient outcomes is unclear and should be studied further. Implications for radiologist coverage and resident training are discussed.


Laparoscopic and endoscopic management of perforated duodenal ulcers.
Acid peptic perforation of the duodenum remains a surgical challenge. Plication alone may be satisfactory management if the ulcer diathesis is medically controlled. Laparoscopic management for plication has been safely applied in a variety of populations. This study assessed a combination of endoscopy and laparoscopy to manage early duodenal perforation. Forty-two patients with early (less than 12 hours) perforation were managed by laparoscopic plication and lavage. Endoscopy identified the site of perforation and guided repair in 35 of 42. All patients were followed with Helicobacter pylori treatment and examined by endoscopy at 3 months. Forty case control patients who had open procedures for duodenal perforation were evaluated for comparison. Endoscopic/laparoscopic management was completely effective and compared favorably with open procedures with regard to surgical time and complications. Endoscopic snaring of omentum and pulling into the defect proved to be an effective adjunct for plication. Endoscopic/laparoscopic repair of perforated duodenal ulcers is a safe and effective surgical tactic if followed by treatment for Helicobacter pylori.


Chilling injury in human kidney tubule cells after subzero storage is not mitigated by antifreeze protein addition.
By preventing freezing, antifreeze proteins (AFPs) can permit cells and organs to be stored at subzero temperatures. As metabolic rates decrease with decreasing temperature, subzero static cold storage (SZ-SCS) could provide more time for tissue matching and potentially lead to fewer discarded organs. Human kidneys are generally stored for under 24 h and the tubule epithelium is known to be particularly sensitive to static cold storage (SCS). Here, telomerase-immortalized proximal-tubule epithelial cells from humans, which closely resemble their progenitors, were used as a proxy to assess the potential benefit of SZ-SCS for kidneys. The effects of hyperactive AFPs from a beetle and Cryostasis Storage Solution were compared to University of Wisconsin Solution at standard SCS temperatures (4 °C) and at -6 °C for up to six days. Although the AFPs helped guard against freezing, lower storage temperatures under these conditions were not beneficial. Compared to cells at 4 °C, those stored at -6 °C showed decreased viability as well as increased lactate dehydrogenase release and apoptosis. This suggests that this kidney cell type might be prone to chilling injury and that the addition of AFPs to enable SZ-SCS may not be effective for increasing storage times.


Noninvasive monitoring of serial changes in pulmonary vascular resistance and acute vasodilator testing using cardiac magnetic resonance.
The study sought to evaluate the ability of cardiac magnetic resonance (CMR) to monitor acute and long-term changes in pulmonary vascular resistance (PVR) noninvasively. PVR monitoring during the follow-up of patients with pulmonary hypertension (PH) and the response to vasodilator testing require invasive right heart catheterization. An experimental study in pigs was designed to evaluate the ability of CMR to monitor: 1) an acute increase in PVR generated by acute pulmonary embolization (n = 10); 2) serial changes in PVR in chronic PH (n = 22); and 3) changes in PVR during vasodilator testing in chronic PH (n = 10). CMR studies were performed with simultaneous hemodynamic assessment using a CMR-compatible Swan-Ganz catheter. Average flow velocity in the main pulmonary artery (PA) was quantified with phase contrast imaging. Pearson correlation and mixed model analysis were used to correlate changes in PVR with changes in CMR-quantified PA velocity. Additionally, PVR was estimated from CMR data (PA velocity and right ventricular ejection fraction) using a formula previously validated. Changes in PA velocity strongly and inversely correlated with acute increases in PVR induced by pulmonary embolization (r = -0.92), serial PVR fluctuations in chronic PH (r = -0.89), and acute reductions during vasodilator testing (r = -0.89, p ≤ 0.01 for all). CMR-estimated PVR showed adequate agreement with invasive PVR (mean bias -1.1 Wood units,; 95% confidence interval: -5.9 to 3.7) and changes in both indices correlated strongly (r = 0.86, p < 0.01). CMR allows for noninvasive monitoring of acute and chronic changes in PVR in PH. This capability may be valuable in the evaluation and follow-up of patients with PH.


The preterm rat: a model for studies of acute and chronic neonatal lung disease.
A preterm rat model has been developed for studies of acute and chronic neonatal lung disease. Premature delivery 24 h before the normal time of delivery is associated with immature pulmonary phospholipid and antioxidant enzyme profiles. The premature lung is more fragile and ruptures at a lower lung vol (172 +/- 8 microL) than the full-term fetal lung (259 +/- 14 microL). Only 7% of premature lungs will float in liquid, after inflation to 85% of the rupture vol, compared with 87% of term fetal lungs. This lung immaturity was reflected in a survival rate of only 6% by 36 h after delivery if the preterm pups were placed in air, which increased to 47% when they were placed in greater than 95% oxygen. Though greater than 95% oxygen enhanced survival of preterm pups during the 1st wk of life, these survivors had a 50% mortality during the 2nd wk of exposure to greater than 95% oxygen. The preterm pup will tolerate intraperitoneal injection of antioxidant enzymes entrapped in liposomes and has a better retention of these liposomes in the lung compared with the term pup. We conclude that the preterm rat is a suitable model for studies of acute and chronic neonatal lung disease.


Emotional effects of hypospadias surgery on Turkish boys.
The aim of this study is to investigate in Turkish boys the emotional effects of hypospadias repair before and after the optimal age for repair. Forty hypospadias patients treated in our department were included in this study. Group 1 consisted of 13 patients operated on at less than 30 months of age. Group 2 consisted of 27 patients operated on at over 30 months of age. Age at time of study, severity of hypospadias, age at repair and number of operations were evaluated for both groups retrospectively. Socio-economic and socio-demographic characteristics of these patients including place of residence, educational level of their parents and parental occupations were determined. The Turkish versions of the Children's Depression Inventory and the State-Trait Anxiety Inventory for Children A-State scale were used to evaluate the emotional effects of hypospadias surgery. For statistical analysis, the Mann-Whitney U test, Student's t test and Chi-squared test were used. There was a significant difference in the age at repair between Groups 1 and 2. No significant differences existed in severity of hypospadias and number of operations between the two groups. All 40 patients had the same socio-economic and socio-demographic characteristics. Group 1 did not significantly differ from Group 2 in regard to the educational level of their parents and parental occupations. Age at repair, which was the only difference between the two groups, did not affect the level of depression and anxiety-state symptoms. There is a close relationship between emotional effect of hypospadias surgery and age at repair. Possibility of depression and anxiety, which were dominating emotional symptoms among boys operated on for hypospadias, was found not to be high after the recommended age. It is concluded that, as hypospadias surgery creates a circumcised penis, the degree of emotional trauma is lower in Turkish boys than in other nationalities.


Fact or fiction: the "5 mm Rule" in greater tuberosity fractures of the proximal humerus.
The purposes of this study were 1) to assess the outcome of nonoperative management of GT fractures with > 5 mm of displacement and 2) to assess whether there is a correlation between degree of displacement and outcome. This study was a retrospective review of consecutive low-energy GT fractures from 2011 to 2020. Radiographs from all visits were reviewed. The direction of maximal displacement was assessed. Subjects were stratified based on the amount of maximal displacement: Group 1: 0-5 mm, Group 2: 5-10 mm, Group 3: > 10 mm. Range of motion (ROM) at the time of final follow-up was assessed. The presence of persistent shoulder pain after healing was noted, as well as whether supplemental subacromial corticosteroid injection was provided as part of long-term treatment. A cohort of 93 fractures comprised the study group. Mean age was 62 years. Mean follow-up was 20 months. All fractures went on to union. Mean displacement was 6.2 mm. There were 43 patients in Group 1, 43 in Group 2, and 7 in Group 3. Maximal displacement was most commonly inferolateral or lateral, accounting for a combined 77% of all patients. There was no difference in final ROM between displacement groups, with at least 155 degrees of forward elevation and 45 degrees of ER in all three groups. There was no difference between Group 1 and Groups 2/3 in frequency of persistent pain or likelihood of receiving a steroid injection. Our findings do not support a discrete 5 mm displacement threshold for surgical repair of isolated greater tuberosity fractures.


Transfollicular elimination of sebaceous glands in a patient with disseminate and recurrent infundibulofolliculitis.
Disseminate and recurrent infundibulofolliculitis (DRIF) is a rare form of folliculitis characterized by multiple papules widely distributed on the trunk and extremities. We present a 37-year-old man with confirmed DRIF complicated by transfollicular elimination of the sebaceous unit, an additional finding of DRIF that has rarely been reported.


Aminopyridazine derivatives and TXA2-PGI2 balance.
Experiments carried out under the conditions adopted showed the strong affinity of aminopyridazine derivatives for the eicosanoids TXA2 and PGI2. But this affinity depended on the chemical structure of the molecule: a small change in the radical grafted onto the pyridazine ring could completely modify the pharmacological activity of the molecule. Consequently it should be possible to control the properties of pyridazine derivatives according to pharmacological needs. Thus: --pyridazin-3-one derivatives were mainly active on TXA2 biosynthesis: 2-aminoalkyl 5-arylidene 6-methyl (4H) pyridazin-3-ones inhibited the TXA2-synthesizing activity of cardiac tissue whereas 3-amino 4,6-diaryl pyridazin-3-ones were specific inhibitors of the TXA2 synthetase in vitro, but these effects were weak. --pyridazine derivatives were devoid of any effect on the TXA2-synthesizing activity of cardiac tissue: they acted on either TXA2 synthetase or PGI2 synthetase according to the radicals grafted onto the pyridazine ring. --none of the compounds under study was active on the PGI2-synthesizing activity of cardiac tissue.


HLA-associated susceptibility to childhood B-cell precursor ALL: definition and role of HLA-DPB1 supertypes.
Childhood B-cell precursor (BCP) ALL is thought to be caused by a delayed immune response to an unidentified postnatal infection. An association between BCP ALL and HLA class II (DR, DQ, DP) alleles could provide further clues to the identity of the infection, since HLA molecules exhibit allotype-restricted binding of infection-derived antigenic peptides. We clustered >30 HLA-DPB1 alleles into six predicted peptide-binding supertypes (DP1, 2, 3, 4, 6, and 8), based on amino acid di-morphisms at positions 11 (G/L), 69 (E/K), and 84 (G/D) of the DPbeta(1) domain. We found that the DPbeta11-69-84 supertype GEG (DP2), was 70% more frequent in BCP ALL (n=687; P<10(-4)), and 98% more frequent in cases diagnosed between 3 and 6 years (P<10(-4)), but not <3 or >6 years, than in controls. Only one of 21 possible DPB1 supergenotypes, GEG/GKG (DP2/DP4) was significantly more frequent in BCP ALL (P=0.00004) than controls. These results suggest that susceptibility to BCP ALL is associated with the DP2 supertype, which is predicted to bind peptides with positively charged, nonpolar aromatic residues at the P4 position, and hydrophobic residues at the P1 and P6 positions. Studies of peptide binding by DP2 alleles could help to identify infection(s) carrying these peptides.


Assessing the effectiveness of oxathiapiprolin toward Phytophthora agathidicida, the causal agent of kauri dieback disease.
Phytophthora species cause disease and devastation of plants in ecological and horticultural settings worldwide. A recently identified species, Phytophthoraagathidicida, infects and ultimately kills the treasured kauri trees (Agathis australis) that are endemic to New Zealand. Currently, there are few options for managing kauri dieback disease. In this study, we sought to assess the efficacy of the oomycide oxathiapiprolin against several life cycle stages of two geographically distinct P. agathidicida isolates. The effective concentration to inhibit 50% of mycelial growth (EC50) was determined to be ∼0.1 ng/ml, indicating that P. agathidicida mycelia are more sensitive to oxathiapiprolin than those from most other Phytophthora species that have been studied. Oxathiapiprolin was also highly effective at inhibiting the germination of zoospores (EC50 = 2-9 ng/ml for the two isolates) and oospores (complete inhibition at 100 ng/ml). In addition, oxathiapiprolin delayed the onset of detached kauri leaf infection in a dose-dependent manner. Collectively, the results presented here highlight the significant potential of oxathiapiprolin as a tool to aid in the control of kauri dieback disease.


Towards improving compound selection in structure-based virtual screening.
Structure-based virtual screening is now an established technology for supporting hit finding and lead optimisation in drug discovery. Recent validation studies have highlighted the poor performance of currently used scoring functions in estimating binding affinity and hence in ranking large datasets of docked ligands. Progress in the analysis of large datasets can be made through the use of appropriate data mining techniques and the derivation of a broader range of descriptors relevant to receptor-ligand binding. In addition, simple scoring functions can be supplemented by simulation-based scoring protocols. Developments in workflow design allow the automation of repetitive tasks, and also encourage the routine use of simulation-based methods and the rapid prototyping of novel modelling and analysis procedures.


Mycotechnology: the role of fungi in biotechnology.
Fungi have been important in both ancient and modern biotechnological processes. Processes and products that utilize fungi include baking, brewing, and the production of antibiotics, alcohols, enzymes, organic acids, and numerous pharmaceuticals. The advent of recombinant DNA technology and large scale genomics analysis has placed yeasts and filamentous fungi in the forefront of contemporary commercial applications. The term 'mycotechnology' is introduced here to describe the enormous impact of fungi on biotechnology.


Psychological disturbances encountered by the healthcare professionals, military professionals and general public in Sri Lanka during COVID-19 pandemic: a cross-sectional study.
The COVID-19 pandemic is a serious global health concern, posing a greater risk of psychological vulnerabilities for frontline healthcare workers (HCWs), military professionals and the general public around the globe. These psychological issues appear to be long lasting and heighten the risk of mental health disorders. Therefore, this study aimed to identify psychological problems encountered by HCWs, military professionals, and the general public in Sri Lanka during the COVID-19 pandemic. A descriptive cross-sectional study was undertaken with 367 participants, including frontline HCWs (n = 128), military professionals (n = 102), and the general public (n = 137). Depression and anxiety were assessed using the Peradeniya Depression Scale (PDS) and the Generalized Anxiety Disorder scale (GAD-7), respectively. Mean (± SD) age of the participants was 35.0 (± 10.6) years. A reasonable proportion of participants experienced depressive symptoms (39.25%, n = 144) and severe anxiety (12.8%, n = 47). Military professionals showed depressive symptoms (73.50%, n = 75) and severe anxiety (32.4%, n = 33) predominantly. Multivariate binary logistic regression revealed that only the level of education and professional engagement affected depressive symptoms and severe anxiety (p < 0.01). Having a high level of education was a protective factor for depressive symptoms (Adjusted OR = 0.34) compared to lower-level education, while being a HCW (Adjusted OR = 4.40) and military professional (Adjusted OR = 5.43) were identified as risk factors for depressive symptoms compared to the general public. Similarly, having a high level of education was a protective factor for severe anxiety (Adjusted OR = 0.29) compared to lower-level education, while being a HCW (Adjusted OR = 3.90) and military professional (Adjusted OR = 4.52) were identified as risk factors for severe anxiety compared to the general public. The current study revealed a greater level of anxiety and depressive symptoms among frontline HCWs and military professionals in Sri Lanka during the pandemic of COVID-19 compared to the general public. Therefore, providing psychological first aid for them to better deal with mental problems and an emergency preparedness plan to deal with sudden outbreaks of infectious situations are important.


Ultrasonic liposuction in the treatment of gynecomastia.
Ultrasound-assisted liposuction is a technique that is widely used all over the body for minimal access lipectomy. Recently, it has been reported to be especially suitable for the treatment of gynecomastia. To date, however, there is only one published study that specifically addresses ultrasound-assisted liposuction as a treatment modality for gynecomastia. A review was undertaken of all the gynecomastia patients treated with ultrasound-assisted liposuction by a single surgeon over a 3-year period. Thirteen consecutive patients (aged 16 to 57 years) with bilateral, diffuse, soft to moderately firm gynecomastia were studied. There were no early postoperative complications of hematoma, seroma, infection, or thermal injury. Similarly, there were no treatment-induced asymmetries, contour deformities, or irregularities. One patient requested "touch-up" ultrasound-assisted liposuction for "residual" breast tissue several months after an initial satisfactory correction of chest contour. None of the patients required initial open-excision or skin-reduction procedures. Patients were asked to rate their cosmetic results in four categories on linear analogue scales with a maximal score of 10. The average scores were 9.1 for overall satisfaction, 9.2 for scars, 9.2 for shape, and 8.9 for improved self confidence. Ultrasound-assisted liposuction is an effective treatment modality in patients with homogenous soft to moderately firm gynecomastia, giving good cosmetic results and a high level of patient satisfaction.


The effects of certain H(1)-antagonists on visual evoked potential in rats.
The present study was undertaken to clarify the effects of certain H(1)-antagonists on visual evoked potential (VEP) in rats. Pyrilamine (5 and 10 mg/kg), diphenhydramine (5 and 10 mg/kg) and chlorpheniramine (10 and 20 mg/kg) caused a significant reduction in the amplitude of late VEP components (P(3)-N(3), N(3)-P(4)), although these drugs showed no significant changes in early VEP components (P(1)-N(1), N(1)-P(2)). Cyproheptadine caused a slight enhancement of late components of VEP at a dose of 20 mg/kg. On the other hand, epinastine caused no significant effect on late VEP components even at a dose of 20 mg/kg. The reduction in the late VEP components induced by pyrilamine and diphenhydramine was significantly antagonised by pre-treatment of histidine (200 and 500 mg/kg), but not by physostigmine even at a dose of 0.01 mg/kg. The effect induced by cyproheptadine was significantly potentiated by histidine (500 mg/kg), and significantly reduced by DOI (2 mg/kg). These results indicate that an inhibition of the late VEP components induced by H(1)-antagonist pyrilamine, diphenhydramine and chlorpheniramine may be due to an inhibition of specific sensory system relating the histaminergic mechanisms. In addition, slight enhancement of these components induced by cyproheptadine may be attributable to its anti-serotonergic effects.


Road Narrow-Inspired Strain Concentration to Wide-Range-Tunable Gauge Factor of Ionic Hydrogel Strain Sensor.
The application of stretchable strain sensors in human movement recognition, health monitoring, and soft robotics has attracted wide attention. Compared with traditional electronic conductors, stretchable ionic hydrogels are more attractive to organization-like soft electronic devices yet suffer poor sensitivity due to limited ion conduction modulation caused by their intrinsic soft chain network. This paper proposes a strategy to modulate ion transport behavior by geometry-induced strain concentration to adjust and improve the sensitivity of ionic hydrogel-based strain sensors (IHSS). Inspired by the phenomenon of vehicles slowing down and changing lanes when the road narrows, the strain redistribution of ionic hydrogel is optimized by structural and mechanical parameters to produce a strain-induced resistance boost. As a result, the gauge factor of the IHSS is continuously tunable from 1.31 to 9.21 in the strain range of 0-100%, which breaks through the theoretical limit of homogeneous strain-distributed ionic hydrogels and ensures a linear electromechanical response simultaneously. Overall, this study offers a universal route to modulate the ion transport behavior of ionic hydrogels mechanically, resulting in a tunable sensitivity for IHSS to better serve different application scenarios, such as health monitoring and human-machine interface.


Roles of GRK and PDE4 activities in the regulation of beta2 adrenergic signaling.
An important focus in cell biology is understanding how different feedback mechanisms regulate G protein-coupled receptor systems. Toward this end we investigated the regulation of endogenous beta(2) adrenergic receptors (beta2ARs) and phosphodiesterases (PDEs) by measuring cAMP signals in single HEK-293 cells. We monitored cAMP signals using genetically encoded cyclic nucleotide-gated (CNG) channels. This high resolution approach allowed us to make several observations. (a) Exposure of cells to 1 muM isoproterenol triggered transient increases in cAMP levels near the plasma membrane. Pretreatment of cells with 10 muM rolipram, a PDE4 inhibitor, prevented the decline in the isoproterenol-induced cAMP signals. (b) 1 muM isoproterenol triggered a sustained, twofold increase in phosphodiesterase type 4 (PDE4) activity. (c) The decline in isoproterenol-dependent cAMP levels was not significantly altered by including 20 nM PKI, a PKA inhibitor, or 3 muM 59-74E, a GRK inhibitor, in the pipette solution; however, the decline in the cAMP levels was prevented when both PKI and 59-74E were included in the pipette solution. (d) After an initial 5-min stimulation with isoproterenol and a 5-min washout, little or no recovery of the signal was observed during a second 5-min stimulation with isoproterenol. (e) The amplitude of the signal in response to the second isoproterenol stimulation was not altered when PKI was included in the pipette solution, but was significantly increased when 59-74E was included. Taken together, these data indicate that either GRK-mediated desensitization of beta2ARs or PKA-mediated stimulation of PDE4 activity is sufficient to cause declines in cAMP signals. In addition, the data indicate that GRK-mediated desensitization is primarily responsible for a sustained suppression of beta2AR signaling. To better understand the interplay between receptor desensitization and PDE4 activity in controlling cAMP signals, we developed a mathematical model of this system. Simulations of cAMP signals using this model are consistent with the experimental data and demonstrate the importance of receptor levels, receptor desensitization, basal adenylyl cyclase activity, and regulation of PDE activity in controlling cAMP signals, and hence, on the overall sensitivity of the system.


Neuromuscular issues in cavovarus foot.
Differential muscle weakness can cause a cavus foot deformity. Presenting complaints in the hindfoot may include ankle instability, secondary arthritis, or peroneal tendonitis. Presenting complaints in the forefoot may include stress fractures, callus formation over the lateral border of the foot, claw toes, first ray overload, and metatarsalgia. More general presenting complaints can include a drop-foot gait, decreased walking tolerance, and difficulty with shoe or orthotic fitting. To surgically correct the foot shape, soft tissue contractures need to be released, bone deformity corrected, and muscles balanced to optimize their strength and prevent recurrence of the deformity. This article reviews the diagnosis and management of the cavovarus foot secondary to longstanding muscle imbalance.


Identification of fibroblast growth factor receptor 3 mutations in urine sediment DNA samples complements cytology in bladder tumor detection.
Mutations in fibroblast growth factor 3 receptor (FGFR3) are frequent events in low-grade bladder tumors. To assess the potential utility of the detection of FGFR3 mutations in a screening modality, the authors analyzed urine sediment DNA samples from 192 patients in a retrospective study. Urine sediment DNA samples from 192 patients were prepared. Seventy-two patients had undergone transurethral resection (TURBT group) of mainly Ta lesions and 120 patients had undergone cystectomy (cystectomy group). The majority of patients in the cystectomy group had more advanced tumors compared with patients in the TURBT group. DNA preparations were screened for FGFR3 mutations in exons 7, 10, and 15 using single-strand conformation polymorphism (SSCP) and DNA sequencing. Using SSCP, 67% of patients in the TURBT group and 28% in the cystectomy group displayed FGFR3 mutations. Comparative analysis of cytology results and FGFR3 mutational analysis were performed in 122 cases. Within the TURBT group, FGFR3 mutation analysis outperformed cytology. FGFR3 mutation analysis identified change in 68% of urine sediment DNA samples whereas cytology recorded the presence of tumor cells in 32% of the DNA samples. In the cystectomy group, cytology outperformed FGFR3 mutation analysis. Cytology recorded tumor detection in 90% of patients, while SSCP identified mutational change in 24%. Combining FGFR3 mutation results with cytology in both groups correctly identified tumor presence in 105 of 122 (86%) of patients. The greater sensitivity of FGFR3 mutation detection over cytology in identifying the presence of low-grade, superficial bladder tumors represents a potential new tool to complement standard cytology in screening patients for bladder tumors and recurrent disease.