A gene fusion approach to the study of pullulanase export and secretion in Escherichia coli.
A series of fusions between the gene for the Klebsiella pneumoniae secreted lipoprotein pullulanase (pulA) and the genes for cytoplasmic beta-galactosidase (lacZ) or periplasmic alkaline phosphatase (phoA) were created by transposon mutagenesis using mini-MudII1681 or TnphoA, respectively. The hybrid genes were expressed in Escherichia coli K-12 with or without the K. pneumoniae genes that promote pullulanase secretion in E. coli. We characterized seven different pulA-lacZ gene fusions encoding hybrid polypeptides containing from 14 to c. 1060 residues of pro-pullulanase. All but the smallest hybrid were fatty acylated and were toxic to producing cells, causing the accumulation of precursors of other exported proteins. Four different pulA-phoA gene fusions encoded hybrids with alkaline phosphatase activity. All four hybrids were fatty acylated, but were not toxic. Although the hybrids were apparently membrane-associated, they were not secreted into the medium either by E. coli carrying pullulanase secretion genes or by K. pneumoniae. Immunofluorescence tests indicated that the pullulanase secretion genes promoted the localization of one of these hybrids to the outer face of the E. coli outer membrane, which may have important implications for the design of live vaccine strains and of immobilized enzymes.


Ionic liquid mediated Cu-catalyzed cascade oxa-Michael-oxidation: efficient synthesis of flavones under mild reaction conditions.
Flavonoids are a class of natural products, found in a wide range of vascular plants and dietary components. Their low toxicity and extensive biological activities, including anti-cancer and anti-bacterial, have made them attractive candidates to serve as therapeutic agents for many diseases. Herein, we disclose a highly efficient synthetic method of CuI-catalyzed cascade oxa-Michael-oxidation, using chalcones as substrates, mediated by the ionic liquid [bmim][NTf2] at a low temperature. This efficient synthetic method has demonstrated high synthetic utility and can afford flavones in good to high yields (up to 98%).


Synthetic zinc tetrapyrroles complexing with pyridine as a single axial ligand.
Zinc chlorins were prepared from chlorophyll-a. Visible spectra in benzene showed that synthetic zinc chlorins complexed with pyridine as an axial ligand to form the monopyridine adducts. The equilibrium constants for the complexation were dependent upon the chlorin structure: substitution of electron-withdrawing groups at the peripheral position enhanced the coordinated ability of the central zinc. 1H NMR spectra in benzene-d6 also indicated that single pyridine coordinated to the central zinc. Comparison of the equilibrium constant in a zinc chlorin with those of the corresponding zinc bacteriochlorin (7,8-dihydrochlorin) and porphyrin (17,18-dedihydrochlorin) led to an increase in the saturation and flexibility of the tetrapyrrole pi-plane ligands making the central zinc more axial-ligated. All the zinc tetrapyrroles in benzene complexed with pyridine to form 5-coordinated (1:1) complexes, not 6-coordinated bisadducts. The observed equilibrium constants were consistent with the energy changes of the complexation calculated from molecular modeling.


Intraoperative fluoroscopy reduces the variability in femoral tunnel placement during single-bundle anterior cruciate ligament reconstruction.
To evaluate the effect of using intraoperative fluoroscopy on femoral and tibial tunnel positioning variability in single-bundle anterior cruciate ligament (ACL) reconstruction. A total of 80 consecutive patients with single-bundle ACL reconstruction between 2014 and 2016 were retrospectively reviewed. Among them, 40 underwent ACL reconstruction without fluoroscopy (non-fluoroscopy group) and 40 underwent fluoroscopy-assisted ACL reconstruction (fluoroscopy group). Femoral and tibial tunnel locations were evaluated using a standardized grid system with three-dimensional computed tomography images. Femoral and tibial tunnel location variability was compared between the groups. The operation time was longer in the fluoroscopy group than in the non-fluoroscopy group (61.3 ± 5.2 min vs. 55.5 ± 4.5 min, p < 0.001). In the fluoroscopy group, a guide pin was repositioned in 16 (40%) cases on the femoral side and 2 (5%) cases on the tibial side. No significant difference in the femoral tunnel location was observed between the fluoroscopy and non-fluoroscopy groups (anterior-posterior plane, 29.0% ± 3.2% vs. 30.0% ± 6.1%; proximal-distal plane, 30.8% ± 4.8% vs. 29.4% ± 8.3%; all parameters, n.s.); variability was significantly lower in the fluoroscopy group (p < 0.001 for both anterior-posterior and proximal-distal planes). No significant difference in the tibial tunnel location and variability was observed between the fluoroscopy and non-fluoroscopy groups (medial-lateral plane, 45.8% ± 2.0% vs. 46.6% ± 2.4%; anterior-posterior plane, 31.2% ± 4.0% vs. 31.0% ± 5.4%) (all parameters, n.s.). Tunnel positioning with fluoroscopic assistance is feasible and effective in achieving consistency in femoral tunnel placement despite a slightly longer operation time. Intraoperative fluoroscopy can be helpful in cases wherein identifying anatomical landmarks on arthroscopy was difficult or for surgeons with less experience who performed ACL reconstruction. IV.


Localized Sudeck's dystrophy and distal interphalangeal osteoarthritis of a finger: anatomicoradiologic study.
After an injury to the right ring finger, a 44-year-old woman experienced pain in the distal interphalangeal joint. A subcutaneous mucoid cyst was noted near the joint. The x-ray films revealed no fracture but a narrowing of the joint space and a well-defined radiolucent area in the ulnar condyle of the middle phalanx. The biopsy specimen of this area excluded infection or tumor and revealed active osteogenic remodelling. These elements permitted a diagnosis of distal interphalangeal osteoarthritis that was associated with highly localized Sudeck's dystrophy (also called " parcellar algodystrophy"). This unusual case suggests the possibility that this dystrophy might be favored by an "osteoarthritic terrain" and might also play a role in the evolution of the osteoarthritis.


Cross-regulation by TLR4 and T cell Ig mucin-3 determines severity of liver injury in a CCl4-induced mouse model.
Acute liver injury is a common pathological basis for a variety of acute liver diseases in the clinic, which can eventually lead to liver fibrosis and even liver failure. In this study, we found that T cell Ig and mucin domain protein 3 (Tim-3) and TLR4 receptors play important roles in CCl4-induced acute liver injury. Tim-3 is a negative regulator that is expressed by T cells and macrophages. Using antibodies against Tim-3 (anti-Tim-3 Ab), we studied the Tim-3 signal in an animal model of acute liver injury and found that a large number of inflammatory factors were upregulated. In vitro experimental data shown that anti-Tim-3 Ab treatment increased interferon-ɣ production by concanavalin A (ConA)-stimulated spleen T cells, and we found that the expression level of interleukin (IL)-6 was increased in a macrophage/spleen T cell coculture system, while administration of galectin-9 (Gal-9, a Tim-3 ligand) reduced the IL-6 production. This indicates the importance of the Tim-3/Gal-9 signalling pathway in maintaining hepatic homeostasis. The Tim-3 signalling pathway inhibits TLR4-mediated NF-κB activity, and an anti-Tim-3 Ab does not affect the liver injury in TLR4-deficient mice. Regulation between Tim-3 and TLR4 determines the severity of liver damage. The negative regulation of Tim-3 reflects the protective mechanisms of patients with impaired liver function, and these results provide important information about innate and adaptive responses in the regulation of liver damage. This finding is potentially important for the study of early liver injury.


The biometrical genetics of competitive parameters in Drosophila melanogaster.
Despite the importance of competition as an evolutionary determinant in natural populations there have been few studies of the genetical control of competitive ability. Here, we report the results of a biometrical analysis of four continuously varying traits which, between them, describe the competitive interactions in mixed cultures of Drosophila melanogaster. The analysis involved the parental, F1, F2 and backcross generations (including all reciprocals) derived from crosses between two highly inbred lines isolated from the Texas population of D. melanogaster. The competitive performance of each genotype in monoculture and in duoculture with a phenotypically distinct tester were assessed using a yield-density regression analysis. Appropriate genetic models were fitted using a variance weighted least squares procedure and the resulting genetic components of the generation means used to define the genetical architecture of competition. Of the four competitive parameters investigated here the e-value, which describes the competitive performance of the indicator genotype at a fixed reference density, was found to be determined by simple additive genetic effects with no evidence of significant dominance. Conversely, competitive performance in monoculture (intra-genotypic competition) did display a significant net dominance component and the observed values in the F1 and parental generations indicated some degree of heterosis. Of the two competitive parameters determining performance in duoculture (inter-genotypic sensitivity and inter-genotypic pressure) the former was found to have a complex genetic determination involving not only additive and dominance components of the progeny's own genotype but also dominance components of the F1 maternal genotypes. There were also additive-dominance and dominance-dominance non-allelic interactions. Heterosis was evident, determined both by the progeny's own genotype and by one of the F1 maternal genotypes.(ABSTRACT TRUNCATED AT 250 WORDS)


Linezolid vs. vancomycin in treatment of methicillin-resistant staphylococcus aureus infections: a meta-analysis.
This study aims to explore the treatment of methicillin-resistant staphylococcus aureus (MRSA) infection by using meta-analysis method. Pubmed/Medline, ScienceDirect, CNKI and Wanfang database were comprehensively searched to obtain the randomized controlled trials (RCTs) on linezolid and vancomycin in the treatment of MRSA infections. We extracted features and information of included studies and selected appropriate effect models based on the heterogeneity test results. The funnel plot was used to analyze publication bias. A total of seven RCTs including 5376 cases met the inclusion criteria. Meta-analysis showed that the clinical cure rate of linezolid group was higher than that of vancomycin group after treatment (OR = 1.85; 95% CI: 1.33-2.59, p<0.001) and follow-up (OR = 1.49; 95% CI: 1.17-1.91, p=0.001). In the microbiologically evaluable patients, end of therapy (EOT) MRSA clearance rate, and test of cure (TOC) MRSA clearance rate of linezolid were superior to those of vancomycin. Based on the combined analysis of randomized controlled trials, the efficacy of linezolid should be better than that of vancomycin in the treatment of infections caused by MRSA, but conclusions still need to be further validated by more well-designed RCTs of a large sample.


Demonstration of the Philadelphia translocation by fluorescence in situ hybridization (FISH) in paraffin sections and identification of aberrant cells by a combined FISH/immunophenotyping approach.
The Philadelphia translocation was demonstrated by two-colour fluorescence in situ hybridization (FISH) in decalcified paraffin sections of bone marrow from patients with chronic myelogenous leukaemia. FISH was combined with immunocytochemical detection of different membrane-bound or cytoplasmic antigens. With this new technique, the cells bearing the 9:22 translocation can be identified morphologically, as well as immunocytochemically, in tissue sections.


TLR-9 promoter polymorphisms (T-1237C and T-1486C) are not associated with systemic lupus erythematosus: a case control study and meta-analysis.
Toll like receptors (TLRs) are essential molecules implicated in both innate and adaptive immune response. Polymorphisms in TLR gene have been associated with various infectious diseases and autoimmune disorders. Role of TLR9 has been elegantly demonstrated in both human systemic lupus erythematosus (SLE) and mice model of lupus. In the present study we investigated association of TLR-9 promoter polymorphisms (T-1237C and T-1486C) with susceptibility/resistance to SLE in an Eastern Indian state which is endemic to parasitic diseases. 210 Female SLE patients who fulfilled the American College of Rheumatology criteria were enrolled along with matched healthy controls from Odisha, India. TLR-9 polymorphisms (T-1237C and T-1486C) were typed by polymerase chain reaction followed by restriction fragment length polymorphism. For meta-analysis, relevant literatures were searched from PubMed database and comprehensive meta-analysis V2 software was employed for analysis. Allele and genotype frequency of TLR-9 promoter polymorphisms (T-1237C and T-1486C) were comparable among SLE patients and controls. Further, meta-analysis of earlier reports and present study did not reveal a significant association of TLR-9 (T-1237C and T-1486C) polymorphisms with SLE. Data from the present study suggest that TLR-9 promoter polymorphisms are not associated with susceptibility to SLE in an area endemic to parasitic diseases.


Iodine-123 IMP SPECT before and after bypass surgery in a patient with occlusion of left anterior and middle cerebral arteries with basal abnormal telangiectasis (unilateral Moyamoya disease).
A case of left anterior and middle cerebral arterial occlusion with angiographic features similar to Moyamoya disease was reported. IMP SPECT of the patient revealed the success of bypass surgery clearly. The patient complained of transient right hemiparesis with aphasia 4 times. The cerebral arteriography disclosed occlusions of left anterior and middle cerebral arteries at their proximal portions. Right internal carotid and its branches were normal. I-123 IMP SPECT study showed hypoperfusion in left temporal lobe, basal ganglia with incomplete reperfusion on the delayed (4 hours after injection) SPECT images. After the superficial temporal-middle cerebral artery anastomosis, I-123 IMP SPECT showed improvement of the brain blood flow. I-123 IMP SPECT was very useful in detecting the ischemic areas and evaluating the revascularizing surgery in this case.


Detection and identification of NAP-2 as a biomarker in hepatitis B-related hepatocellular carcinoma by proteomic approach.
A lack of sensitive and specific biomarkers is a major reason for the high rate of Primary hepatocellular carcinoma (HCC)-related mortality. The aim of this study was to investigate potential proteomic biomarkers specific for HCC. 81 patients with hepatitis B-related HCC and 33 healthy controls were randomly divided into a training set (33 HCC, 33 controls) and a testing set (48 HCC, 33 controls). Serum proteomic profiles were measured using Surface-enhanced laser desorption/ionization-time-of-flight mass spectroscopy (SELDI-TOF-MS).) A classification tree was established by Biomarker Pattern Software (BPS). Candidate SELDI peaks were isolated by tricine-SDS-PAGE, identified by HPLC-MS/MS and validated by immunohistochemistry (IHC) in liver tissues. A total of 6 proteomic peaks (3157.33 m/z, 4177.02 m/z, 4284.79 m/z, 4300.80 m/z, 7789.87 m/z, and 7984.14 m/z) were chosen by BPS to establish a classification tree with the highest discriminatory power in the training set. The sensitivity and specificity of this classification tree were 95.92%, and 100% respectively in the testing set. A candidate marker of about 7984 m/z was isolated and identified as neutrophil-activating peptide 2 (NAP-2). IHC staining showed that NAP-2 signals were positive in HCC tissues but negative in adjacent tissues. The NAP-2 may be a specific proteomic biomarker of hepatitis B-related HCC.


Longitudinal study of the microleakage of two root-end filling materials using a fluid conductive system.
A comparison of the microleakage of mineral trioxide aggregate (MTA) and a high copper admix amalgam (Valiant PhD) in root-end preparations was made using a fluid conductive device. Thirty-three bilaterally matched pairs of extracted, single-rooted teeth were prepared and obturated using lateral compaction of gutta-percha. The root-ends were resected and 3-mm-deep class I cavity preparations were made. The root-end preparations were filled with either amalgam or MTA. Guttapercha coronal to the root-end fillings was removed leaving only the amalgam or MTA present as a barrier to fluid movement. In the fluid-conductive device, the root canals were filled with a phosphate-buffered saline solution at a pressure of 10 psi. The flow of fluid was measured and compared at 1, 2, 3, 4, 8, 12, 16, 20, and 24 wk. The results showed amalgam to have significantly higher microleakage after 4 wk and higher variability compared with the MTA group.


Long-Term Maternal and Child Outcomes Following Postnatal SSRI Treatment.
Although selective serotonin reuptake inhibitors (SSRIs) are recommended for postnatal depression treatment, there is a lack of evidence regarding long-term maternal and child outcomes following postnatal SSRI treatment. To examine whether postnatal SSRI treatment moderated postnatal depression-associated maternal and child outcomes across early childhood years. This cohort study used longitudinal data from the Norwegian Mother, Father and Child Cohort Study. Participating women were recruited in weeks 17 to 18 of pregnancy from 1999 to 2008 and were prospectively followed up after childbirth. Data analysis was performed between December 2021 to October 2022. Postnatal depression diagnosis (a binary indicator of eligibility for treatment) was defined as a score of 7 or greater on the 6-item version of the Edinburgh Postnatal Depression Scale. The Hopkins Symptom Checklist was used as a continuous indicator of and postnatal depressive symptomology at postpartum month 6. Postnatal SSRI treatment was identified using self-reported data at postpartum month 6. Maternal outcomes included self-reported depression symptomology and relationship satisfaction from childbirth to postpartum year 5. Child outcomes included maternal-report internalizing and externalizing problems, attention-deficit/hyperactivity disorder symptoms, and motor and language development at ages 1.5, 3, and 5 years. A propensity score adjustment method was used to control for prenatal factors associated with postnatal SSRI exposure probability. Among a total of 61 081 mother-child dyads, 8671 (14.2%) (mean [SD] age, 29.93 [4.76] years) met the criteria for postnatal depression diagnosis, 177 (2.0%) (mean [SD] age, 30.20 [5.01] years) of whom received postnatal SSRI treatment. More severe postnatal depression symptomology was associated with a range of adverse maternal and child outcomes. Focusing analyses only on the postnatal depression dyads indicated that postnatal SSRI treatment attenuated negative associations between postnatal depression and maternal relationship satisfaction at postpartum month 6 (moderation β, 0.13; 95% CI, 0.07-0.19), years 1.5 (moderation β, 0.11; 95% CI, 0.05-0.18) and 3 (moderation β, 0.12; 95% CI, 0.04-0.19), and for child ADHD at age 5 years (moderation β, -0.15; 95% CI, -0.24 to -0.05). Postnatal SSRI treatment mitigated the negative associations between postnatal depression and maternal depression, partner relationship satisfaction, child externalizing problems, and attention-deficit/hyperactivity disorder up to 5 years after childbirth. The results of this large prospective cohort study suggest that postnatal SSRI treatment was associated with a reduced risk of postnatal depression-associated maternal mental health problems and child externalizing behaviors across early childhood years. These findings suggest that postnatal SSRI treatment may bring benefits in the long term to women with postnatal depression and their offspring. This study potentially provides valuable information for clinicians and women with postnatal depression to make informed treatment decisions.


Oncogenic ras protein induces meiotic maturation of amphibian oocytes in the presence of protein synthesis inhibitors.
Microinjection of the activated ras oncogenic protein can induce the meiotic maturation of Xenopus laevis oocytes, a process that can also be triggered by progesterone or high concentrations of insulin. Cycloheximide and puromycin, well-known inhibitors of protein synthesis, block the maturation process induced by progesterone and insulin but do not affect the maturation caused by H-raslys12 protein microinjection. Theophylline, an inhibitor of cAMP phosphodiesterase that also affects oocyte protein synthesis, does cause a partial inhibition of ras protein-induced maturation. These findings indicate that ras protein acts on the oocyte maturation process at a point that is downstream of the protein synthesis requirement, a characteristic shared with the maturation promoting factor, an activity that appears in oocytes and mitotic cells at the onset of cell division.


Factors causing and reversing vasoconstriction in unventilated lung.
Vasoconstriction occuring a unventilated or hypoxic lung was studied in dogs and cats to elucidate mechanisms which both cause and reverse it. Lungs were perfused in vivo at constant pressure or constant blood flow; alternatively blood flow and pressure were measured with minimal operative interference. Stimulus-response curves of lung vessels to hypoxia showed a large response within the physiological range of P02 values. Vasoconstriction in unventilated lung caused by bronchial occlusion sometimes matched that caused by an equal degree of ventilation hypoxia but was sometimes greater. Responses to both stimuli varied widely between animals and in one animal at different times. This could be due to variable availability of a transmitter or variable presence of vasodilator substances. Both histamine and beta-adrenoreceptor stimulants caused pulmonary vasodilatation in unventilated lung. Histamine caused pulmonary vasoconstriction and vasodilatation in different circumstances which could be blocked respectively by H1 and H2 antihistamine drugs. Potent alpha- and beta-adrenoreceptor action on pulmonary vessels was demonstrated in both species. Alpha-adrenoreceptor blocking drugs caused dilatation and beta-adrenoreceptor blocking drugs caused vasoconstriction. The possible role of histamine and catecholamines in causing or reversing hypoxic vasoconstriction or in maintaining pulmonary vascular tone is discussed.


Ocular complications of smallpox vaccination.
To describe the ocular complications of smallpox vaccination and to discuss potential therapeutic options. Review of pertinent medical literature and recent treatment recommendations of the Centers for Disease Control and Prevention. After immunization against smallpox, vaccinia infection of the eyelid, conjunctiva, or ocular surface can result from accidental autoinoculation from a vaccination site before scab formation or from contact with a recently vaccinated individual. While uncommon, corneal involvement can lead to stromal opacification and scarring. Clinical findings of ocular and periocular vaccinia must be differentiated from those produced by other pathogens such as molluscum contagiosum, herpes simplex, varicella zoster, and acanthamoeba infections. Clinical diagnosis can be confirmed by electron microscopy to identify the presence of orthopoxvirus, as well as by virologic culture, polymerase chain reaction, and/or restriction endonuclease analysis of viral isolates. While the majority of ocular complications of smallpox vaccination in immunocompetent patients are self-limiting, selective cases may require treatment with trifluridine drops, topical corticosteroids and vaccinia immune globulin (VIG). Vaccinia virus does not appear to be sensitive to acyclovir. Specific treatment recommendations are outlined for the spectrum of ocular manifestations.


BRCA1 regulates caveolin-1 expression and inhibits cell invasiveness.
BRCA1 is involved in multiple biological processes including DNA damage repair, cell growth, apoptosis, and transcriptional activation. Also, BRCA1 plays key roles in inhibiting cancer progression. Caveolin-1 is identified as a tumor suppressor and regulates the invasiveness of cells. However, the interactions between BRCA1 and caveolin-1 remain largely unknown. We have investigated the potential function of BRCA1 in regulation of caveolin-1 gene expression and its subcellular localization as well. The observations from RT-PCR, transfection, RNAi, and luciferase assays implied that BRCA1 could elevate caveolin-1 mRNA levels via transactivation of the caveolin-1 promoter region. Additionally, immunofluorescent approach showed that BRCA1 might inhibit the invasiveness and metastatic abilities of mammalian cells by inducing the redistribution of caveolin-1 from the cytoplasm to the cell membrane.


Life after near death: long-term outcomes of emergency department thoracotomy survivors.
Predictors of hospital survival after emergency department thoracotomy (EDT) are well established, but little is known of long-term outcomes after hospital survival. Our primary study objective was to analyze the long-term social, cognitive, functional, and psychological outcomes in EDT survivors. Review of our Level I trauma center registry (2000-2010) revealed that 37 of 448 patients survived hospitalization after EDT. Demographics and clinical characteristics were analyzed. After attempts to contact survivors, 21 patients or caretakers were invited to an outpatient study evaluation; 16 were unreachable (none of whom were present in the Social Security Death Index). Study evaluation included demographic and social data and an outpatient multidisciplinary assessment with validated scoring instruments (Mini-Mental Status Exam, Glasgow Outcome Scores, Timed Get-Up and Go Test, Functional Independence Measure Scoring, SF-36 Health Survey, and civilian posttraumatic stress disorder checklist). After extended hospitalization (43 ± 41 days), disposition varied (home, 62%; rehabilitation, 32%; skilled nursing facility, 6%), but readmission was common (33%) in the 37 EDT hospital survivors. Of the 21 contacted, 16 completed the study evaluation, 2 had died, 1 remained in a comatose state, and 2 were available by telephone only. While unemployment (75%), daily alcohol (50%), and drug use (38%) were common, of the 16 patients who underwent the comprehensive, multidisciplinary outpatient assessment after a median of 59 months following EDT, 75% had normal cognition and returned to normal activities, 81% were freely mobile and functional, and 75% had no evidence of posttraumatic stress disorder upon outpatient screening. Despite the common belief that EDT survivors often live with severe neurologic or functional impairment, we have found that most of our sampled EDT survivors had no evidence of long-term impairment. It is our hope that these results are considered by physicians making life or death decisions regarding the "futility" of EDT in our most severely injured patients.


Geometric distortion correction of high-resolution 3 T diffusion tensor brain images.
Diffusion-weighted images based on echo planar sequences suffer from distortions due to field inhomogeneities from susceptibility differences as well as from eddy currents arising from diffusion gradients. In this paper, a novel approach using nonlinear warping based on optic flow to correct distortions of baseline and diffusion weighted echo planar images (EPI) acquired at 3 T is presented. The distortion correction was estimated by warping the echo planar images to the anatomically correct T2-weighted fast spin echo images (T2-FSE). A global histogram intensity matching of the T2-FSE precedes the base line EPI image distortion correction. A local intensity-matching algorithm was used to transform labeled T2-FSE regions to match intensities of diffusion-weighted EPI images prior to distortion correction of these images. Evaluation was performed using three methods: (i) visual comparison of overlaid contours, (ii) a global mutual information index, and (iii) a local distance measure between homologous points. Visual assessment and the global index demonstrated a decrease in geometrical distortion and the distance measure showed that distortions are reduced to a subvoxel level. In conclusion, the warping algorithm is effective in reducing geometric distortions, enabling generation of anatomically correct diffusion tensor images at 3 T.


Tuberculosis in Kidney Transplant Recipients: A Nationwide Cohort in a Low Tuberculosis Incidence Country.
World Health Organization recommends tuberculosis (TB) preventive treatment for risk groups such as patients preparing for organ transplantation. Pretransplant screening or treatment of latent TB infection has not been routine practice in Finland. In this nationwide registry study, we assessed the risk of TB among kidney transplant recipients compared to the general population. TB cases were identified by data linkage of the national infectious disease and the national transplant registries between 1995 and 2019. Standardized incidence ratios were calculated with adjustment for age, sex, and annual TB dynamics. A total of 4101 kidney transplants in 3900 recipients with a follow-up of 37 652 patient-years were included. Eighteen TB cases were detected. Patients diagnosed with TB were older (median age 64 y, interquartile range 56-66) at transplantation than those without TB (median 51 y, interquartile range 41-60, P < 0.001). The standardized incidence ratio of TB was 6.9 among kidney transplant recipients compared to general population during the whole study period 1995-2019 but decreased from 12.5 in 1995-2007 to 3.2 in 2008-2019. The standardized incidence ratio was 44.2 during the first year after transplantation. Significant differences in 5-y graft losses were not detected between TB patients and those without TB. The standardized incidence ratio of TB in kidney transplant recipients has decreased over the years, but these patients remain at risk of TB, especially during the first posttransplant year. Cost-benefit analysis is required to address feasibility of latent TB infection screening among transplant candidates in countries with low incidence of TB.


Fabrication and characterisation of poly(sulfonated) and poly(sulfonic acid) dissolving microneedles for delivery of antibiotic and antifungal agents.
Skin and soft tissue infections (SSTIs) arise from microbial ingress into the skin. In this study, poly(2-acrylamido-2-methyl-1-propanesulfonic acid) (polyAMPS), which has been reported to exhibit antimicrobial properties was synthesised for the manufacture of microarray patches (MAPs). The free acid and sodium salt of polyAMPS with controlled molar masses and narrow dispersity were synthesised via reversible addition - fragmentation chain-transfer (RAFT) polymerisation reaction with a monomer conversion of over 99%, as determined by 1H NMR. The polymers were shown to be biocompatible when evaluated using a fibroblast dermal cell line while agar plating assay using cultures of C. albican demonstrated that the acid form of polyAMPS exhibited antimicrobial inhibition, which is potentiated in the presence of antimicrobial agents. The synthesised polymers were then used to fabricate dissolving MAPs, which were loaded with either ITRA or levofloxacin (LEV). The MAPs displayed acceptable mechanical resistance and punctured ex vivo skin to a depth of 600 µm. Skin deposition studies revealed that the MAPs were able to administer up to ∼ 1.9 mg of LEV (delivery efficiency: 94.7%) and ∼ 0.2 mg of ITRA (delivery efficiency: 45.9%), respectively. Collectively, the synthesis and development of this novel pharmaceutical system may offer a strategy to manage SSTIs.


Mechanisms of NO and N2O production by enriched nitrifying sludge in a sequencing batch reactor: Effects of hydroxylamine.
NO and N2O as important greenhouse gases andtheir production mechanisms during nitrification are not completely understood. This study aimed to analyze the effect of hydroxylamine (NH2OH) on NO and N2O produced by nitrifying bacteria from activated sludge in a sequencing batch reactor (SBR). Experimental results showed that when nitrite (NO2-) accumulated during aerobic ammonia (NH4+) oxidation, N2O was the main product. The total amount of NO and N2O produced by NH2OH oxidation was positively correlated with dissolved oxygen (DO) levels. The imbalance of NH4+ oxidation caused by NH2OH addition was more conducive to the generation of NO and N2O under high DO conditions. When NH2OH was added into the reactor with NO2- as the substrate, the production of NO and N2O under high DO levels was mainly related to NH2OH oxidation. Under low DO conditions, NO and N2O from the biotic/abiotic hybrid pathways were more significant in the reactor of the coexistence of NO2- and NH2OH, which could be mainly caused by the pathways of nitrifier denitrification and abiotic reaction. Besides, limited amount of NO and N2O was generated by heterotrophic denitrification pathway during autotrophic nitrification. The implications for the above results are important for understanding the production of NO and N2O under NH2OH stress in nitrifying sludge reactor.


Computing hospitalization rates in presence of repeated events: impact and countermeasures to avoid misinterpretation.
The admission rate, including both first and recurrent events, is a clear overall measure of hospital utilization, its variability accounting for individual propensity to disease recurrence. In this paper, we compared two variance estimators derived from the Poisson and negative binomial distribution of directly and indirectly age/gender-standardized hospitalization rates allowing for multiple events. The latter approach accommodates departures from the assumption of randomness of repeated events required by the Poisson distribution. We apply these methods to a retrospective cohort based on hospital discharge data in 2001 of Piedmont (north-western Italy) residents. Estimated standard errors under the negative binomial for both directly and indirectly standardized rates result in almost twice those under the Poisson distribution. Our analysis confirms that ignoring the typical non-random nature of repeated events underestimates the true variance of rates and can lead to biased optimistic interpretation of study results.


Obesity in children and adolescents with acquired brain injury.
To measure the prevalence of obesity and to assess associated clinical factors in children and adolescents with acquired brain injury (ABI). This cross-sectional study included 88 subjects aged between 2.4-17.7 years attending the Brain Injury Clinic at a tertiary paediatric hospital. Body mass index (BMI) and BMI z-scores were calculated. Obesity and overweight were defined using the International Obesity Taskforce cut-points. Associations were examined between BMI z-scores and the following: ABI severity, mobility level, duration from injury and presence of radiological injury. The prevalence of obesity in this population (obese = 15%) was higher than those in Australian children and adolescents (1995 National Nutrition Survey) while the prevalence of overweight (19.3%) was comparable. There was a linear trend for the participants to have a higher BMI z-score with increasing level of mobility (F = 6.91, df 1.70, p = 0.011). There is no data about obesity in children and adolescents with ABI. The study with limited statistical power suggests that obesity is prevalent in this population and increases with increasing level of mobility. Further studies are required to address the issue of obesity and related complications in this population.


Phylogenetic diversity of nitrogen-fixing bacteria in mangrove sediments assessed by PCR-denaturing gradient gel electrophoresis.
Culture-independent PCR-denaturing gradient gel electrophoresis (DGGE) was employed to assess the composition of diazotroph species from the sediments of three mangrove ecosystem sites in Sanya, Hainan Island, China. A strategy of removing humic acids prior to DNA extraction was conducted, then total community DNA was extracted using the soil DNA kit successfully for nifH PCR amplification, which simplified the current procedure and resulted in good DGGE profiles. The results revealed a novel nitrogen-fixing bacterial profile and fundamental diazotrophic biodiversity in mangrove sediments, as reflected by the numerous bands present DGGE patterns. Canonical correspondence analysis (CCA) revealed that the sediments organic carbon concentration and available soil potassium accounted for a significant amount of the variability in the nitrogen-fixing bacterial community composition. The predominant DGGE bands were sequenced, yielding 31 different nifH sequences, which were used in phylogenetic reconstructions. Most sequences were from Proteobacteria, e.g. alpha, gamma, beta, delta-subdivisions, and characterized by sequences of members of genera Azotobacter, Desulfuromonas, Sphingomonas, Geobacter, Pseudomonas, Bradyrhizobium and Derxia. These results significantly expand our knowledge of the nitrogen-fixing bacterial diversity of the mangrove environment.


The generation of active fragments of complement receptor type 2 by trypsin digestion.
B lymphocytes and Raji cells express the complement receptor type 2 (CR2) of 145 kDa which recognises the C3d fragment of C3. When intact cells are treated with trypsin, CR2 is degraded. There is a parallel loss in C3d-mediated rosetting and in proteins which bind to C3d-Sepharose. Initially 97 and then 83 kDa fragments of CR2 are produced which retain C3d binding activity. These fragments are associated with the cell surface and mediate rosetting. Purified 125I-labelled CR2, solubilised in detergent, produces fragments of apparently identical size on treatment with trypsin. The 83 kDa fragment produced by trypsin treatment closely resembles the major C3d binding protein spontaneously released into Raji cell culture medium.


Reduction of Ischemia Reperfusion-Related Brain Hemorrhage by Stachybotrys Microspora Triprenyl Phenol-7 in Mice With Antioxidant Effects.
Stachybotrys microspora triprenyl phenol-7 (SMTP-7) has both thrombolytic and anti-inflammatory effects, but its neuroprotective effects on cerebral ischemia are still unclear. The present study assessed the antioxidative and neurovascular unit (NVU) protective effects of SMTP-7 using transient middle cerebral artery occlusion (tMCAO) mice. After 60 minutes tMCAO, 0.9% NaCl, tissue-type plasminogen activator (tPA), SMTP-7 or tPA + SMTP-7 was intravenously administrated through subclavian vein just before the reperfusion, and these mice were examined at 24 hours after reperfusion. We histologically assessed the hemorrhage and expressive changes of antioxidative markers in brains. SMTP-7 treatment showed a similar antithrombotic effect to tPA, but significantly decreased the hemorrhage volumes and the number of 4-HNE, 3-NT and 8-OHdG positive cells, meanwhile, ameliorated the decrease of collagen IV in the ischemic brains. However, tPA + SMTP-7 treatment did not decrease hemorrhage volumes nor showed NVU protective effect. The present study suggested that SMTP-7 provided therapeutic benefits for ischemic stroke through antioxidative and NVU protective effects unlike tPA alone or tPA + SMTP-7.


Z-Ala-Ile-OH, a dipeptide building block suitable for the formation of orthorhombic microtubes.
Self-assembling dipeptides have emerged in the last two decades as promising building blocks for the development of novel biomaterials. Among the various classes of dipeptides, aromatic dipeptides and especially diphenylalanine (Phe-Phe), which forms hexagonal nanotubes, have been the most extensively studied. However, aliphatic peptides or mixed aromatic-aliphatic dipeptides seem just as promising, exhibiting various structures ranging from amyloid fibrils to microtubes. Herein we report the single-crystal structure of an aliphatic dipeptide, alanine-isoleucine (Ala-Ile), C17H24N2O5, protected with a benzyloxycarbonyl (Z) group at the N-terminus. The protected dipeptide crystallizes in the orthorhombic space group P212121 and forms hollow microtubes with orthorhombic symmetry upon evaporation on glass surfaces, as shown by field emission scanning electron microscopy (FESEM). These findings provide an increased understanding of the correlation between the single-crystal structure of the peptide building block and its self-assembly mechanism, and expand the library of available building blocks for microtechnological applications.


Experimental morphological study of rapidly resolved implants used for the treatment of ventral hernias.
Experimental defect in the abdominal wall, created in 36 outbred albino rats, was closed with an implant (biocompatible connective-tissue element). The inflammatory aseptic reaction of tissues to the implant during the initial period of its healing was followed by replacement of the implant by solid connective tissue, strong and hermetic. This film can be recommended for fortification of aponeurosis sutures after resection of hernias.


Transport characteristics and morphology of the colon and coprodeum in two wild birds of different habitats, the rock ptarmigan (Lagopus mutus) and the common murre (Uria aalge).
Dietary salt intake in domestic fowl affects epithelial transport and morphology of the lower intestine (colon and coprodeum). This study investigated lower intestinal morphology and transport activity in two wild bird species with natural diets containing either low or high salt. Tissues from rock ptarmigan (Lagopus mutus) and common murres (Uria aalge) were sampled for histology and electrophysiological analyses. The ptarmigan exists on a low salt diet, while the murre lives on a high protein and high salt diet. The ptarmigan colon and coprodeum had villi/folds and crypts and the epithelium contained absorptive epithelial cells, mitochondria-rich cells and goblet cells. The colon had significant amiloride-inhibitable Isc, 5-15 μA/cm(2), with no glucose-stimulated Isc, and no significant phloridzin inhibition. The coprodeum also had high amiloride-inhibitable Isc. This transport pattern corresponded to that of chickens on low-salt diets. However, the ptarmigan colon also had a significant lysine/leucine-stimulated Isc of 3±1.0 μA/cm(2). The short U. aalge colon was similar to that of ptarmigans, but with no villi. It demonstrated a significant lysine/leucine-stimulated Isc (11±3.5 μA/cm(2)) with no amiloride-inhibitable Isc, similar to the high-salt chicken colon, but with no Na(+)-glucose cotransport. The murre coprodeum was inert to all substances and showed high resistance (1000 Ω·cm(2)), with a multilayered squamous epithelium. Despite some variations possibly associated with dietary protein intake, we conclude that natural high and low salt diets in different avian species are associated with different lower intestinal transport patterns, providing for post-renal adjustments in ion and water excretion.


Growth factor- and phorbol ester-induced changes in cell morphology analyzed by digital image processing.
We have developed the computer-aided image processing analysis to visualize and quantitate the cell motility and morphological changes in living cultured cells. The effect of growth factors on cell motility and morphology has been analyzed by this method. Insulin, insulin-like growth factor-I (IGF-I), and epidermal growth factor (EGF) elicited membrane rufflings in rat embryo fibroblast 3Y1 cells as well as in human epidermoid carcinoma KB cells. Insulin and IGF-I also induced ruffling membranes in Balb/c-3T3 cells. The quantitative analysis by the programmed trace mode of the AVEC system has shown that the motion of the membrane rufflings was observed within 2 min, reached the maximum level within 4-8 min, and rapidly decreased within 10-15 min after the addition of these growth factors. The analysis also revealed the temperature- and growth factor concentration-dependent changes in the motion of membrane rufflings elicited by these growth factors. 12-O-Tetradecanoylphorbol-13-acetate, one of the well-known tumor promoters, rapidly induced cell rounding in Balb/c-3T3 cells. This change of cell morphology could be also quantified by the trace mode analysis. The fluorescent phalloidin staining experiment indicated that these growth factor- or phorbol ester-induced morphological changes were accompanied by the reorganization of filamentous actin. Furthermore, we were able to visualize actin stress fibers in living EBTr cells by enhancing the video image and to follow the reduction of stress fibers induced by cytochalasin B without any fixation or fluorescent probes.


The effect of adult diet on the biology of butterflies : 1. The common imperial blue, Jalmenus evagoras.
This study examines the effect that sugars and amino acids in the adult diet of Jalmenus evagoras can have on female feeding behaviour, somatic maintenance, longevity, fecundity and egg weight. The presence of sugars in their adult food stimulated butterflies of this species to feed, and they appeared to compensate for low (1% wt/wt) sugar diets by feeding for longer periods. Butterflies were also more likely to feed on diets containing amino acids than on water controls. The availability of sugar allowed females to maintain or even increase their body weight and fat body size, but amino acids had no effect on these variables. Individuals on the medium (25% wt/wt) sugar diet attained the greatest longevity. Female fecundity was increased as much as threefold by the availability of sugar. However, amino acids in the diet had no effect on either longevity or fecundity. Egg weight was not affected by the concentration of sugars or amino acids in the adult diet, but was correlated with the weight of the female butterfly. These results demonstrate that the availability of carbohydrates in the adult diet could play an important role in the population dynamics of this species. However, the presence of amino acids had little effect on most of the variables measured, nor was there any interaction effect between sugars and amino acids.


Radionuclide impurities in [¹⁸F]F⁻ and [¹⁸F]FDG for positron emission tomography.
The paper describes radionuclide impurities (γ-emitters and (3)H) in proton irradiated (18)O enriched water from an Nb target vessel with Nb entrance window, their distribution in different synthesis steps and finally in the PET radiopharmaceuticals [(18)F]Fluoride and [(18)F]FDG.


Fat oxidation at rest and during exercise in male monozygotic twins.
We aimed to investigate if hereditary factors, leisure-time physical activity (LTPA) and metabolic health interact with resting fat oxidation (RFO) and peak fat oxidation (PFO) during ergometer cycling. We recruited 23 male monozygotic twin pairs (aged 32-37 years) and determined their RFO and PFO with indirect calorimetry for 21 and 19 twin pairs and for 43 and 41 twin individuals, respectively. Using physical activity interviews and the Baecke questionnaire, we identified 10 twin pairs as LTPA discordant for the past 3 years. Of the twin pairs, 8 pairs participated in both RFO and PFO measurements, and 2 pairs participated in either of the measurements. We quantified the participants' metabolic health with a 2-h oral glucose tolerance test. Fat oxidation within co-twins was correlated at rest [intraclass correlation coefficient (ICC) = 0.54, 95% confidence interval (CI) 0.15-0.78] and during exercise (ICC = 0.67, 95% CI 0.33-0.86). The LTPA-discordant pairs had no pairwise differences in RFO or PFO. In the twin individual-based analysis, PFO was positively correlated with the past 12-month LTPA (r = 0.26, p = 0.034) and the Baecke score (r = 0.40, p = 0.022) and negatively correlated with the area under the curve of insulin (r = - 0.42, p = 0.015) and glucose (r = - 0.31, p = 0.050) during the oral glucose tolerance test. Hereditary factors were more important than LTPA for determining fat oxidation at rest and during exercise. Additionally, PFO, but not RFO, was associated with better metabolic health.


[Growth and heat resistance of rats repeatedly exposed to heat during early ontogenesis].
The influence of a 10-fold heat training from the 1st to the 10th to the 20th, and from the 20th to the 30th days after birth on further growth and resistance of the animals to the high temperature was investigated. The growth and survival of rats was found to depend on the regimen of heat training. The animals aged 10 to 20 days proved to be most sensitive to the action of high temperature. Heat resistance of these rats turned out to be maximally increased at the period of primary sexual maturation, and the growth rate was retarded in comparison with the animals subjected to heat training at other age periods.


The measurement of urinary Δ¹-piperideine-6-carboxylate, the alter ego of α-aminoadipic semialdehyde, in Antiquitin deficiency.
The assessment of urinary α-aminoadipic semialdehyde (α-AASA) has become the diagnostic laboratory test for pyridoxine dependent seizures (PDS). α-AASA is in spontaneous equilibrium with its cyclic form Δ(1)-piperideine-6-carboxylate (P6C); a molecule with a heterocyclic ring structure. Ongoing diagnostic screening and monitoring revealed that in some individuals with milder ALDH7A1 variants, and patients co-treated with a lysine restricted diet, α-AASA was only modestly increased. This prompted us to investigate the diagnostic power and added value of the assessment of urinary P6C compared to α-AASA. Urine samples were diluted to a creatinine content of 0.1 mmol/L, followed by the addition of 0.01 nmol [(2)H(9)]pipecolic acid as internal standard (IS) and 5 μL was injected onto a Waters C(18) T3 HPLC column. Chromatography was performed using water/methanol 97/3 (v/v) including 0.03 % formic acid by volume with a flow rate of 150 μL/min and detection was accomplished in the multiple reaction monitoring mode: P6C m/z 128.1 > 82.1; [(2)H(9)]pipecolic acid m/z 139.1 > 93.1. Due to the dualistic nature of α-AASA/P6C, and the lack of a proper internal standard, the method is semi quantitative. The intra-assay CVs (n = 10) for two urine samples of proven PDS patients with only modest P6C increases were 4.7% and 8.1%, whereas their inter-assay CVs (n = 10) were 16 and 18% respectively. In all 40 urine samples from 35 individuals with proven PDS, we detected increased levels of P6C. Therefore, we conclude that the diagnostic power of the assessments of urinary P6C and α-AASA is comparable.


Studies on the mechanism of selective retention of porphyrins and metalloporphyrins by cancer cells.
Comparative studies of the toxicity, stability, and retention of the water-soluble porphyrin, tetraphenylporphyrin sulfonate (TPPS), and its complex with Mn(III), have been made with the human breast cancer cell line MCF-7 wild type, and an adriamycin-resistant line derived from it, termed AdrR. Based on growth inhibition, we determined the maximum non-toxic concentration of MnTPPS tolerated by these cells. The integrity of MnTPPS in vitro was investigated by fluorescence microscopy, and we found that there is very little dissociation of MnTPPS within these cells within 4 days. We report novel proton magnetic resonance relaxation measurements of the bulk water of cells in a gel matrix undergoing perfusion. A slightly greater net uptake of MnTPPS in the wild-type cells was observed compared to AdrR; however, there was no significant difference in retention of MnTPPS. These results indicate that over a period of several hours the mechanism of selective retention of these compounds in tumour cells is not due to specific interaction with heme-binding protein, of which there is enhanced expression in the resistant cells. The fact that the net rate of washout of MnTPPS is approximately the same as the net rate of uptake also appears to eliminate compartmentalization or enzymatic modification of MnTPPS within these cells.


Phosphatidylcholine-cholesterol interactions: bilayers of heteroacid lipids containing linoleate lose calorimetric transitions at low cholesterol concentration.
Model membranes composed of cholesterol plus one of two phosphatidylcholines (PC), each containing a saturated and a dienoic acyl chain, have been studied by differential scanning calorimetry. The gel to liquid-crystalline phase transition temperature of 1-palmitoyl-2-linoleoyl PC was -19.5 degrees C and that of 1-stearoyl-2-linoleoyl PC was -13.7 degrees C. The addition of cholesterol to the phosphatidylcholines in aqueous dispersion resulted in the progressive removal of the phase transition as observed by differential scanning calorimetry. Per mole of sterol in the membrane, cholesterol was more effective at reducing the enthalpy change of the phase transitions of these bilayers containing dienoic phosphatidylcholines than it is in eliminating the transition of membranes made with other phospholipids that contain more saturated chains. No transitions in membranes made with palmitoyl-linoleoyl PC or stearoyl-linoleoyl PC could be detected calorimetrically when 17 mol% cholesterol was present.


Corrigendum: Cognitive Reserve and Anxiety Interactions Play a Fundamental Role in the Response to the Stress.
[This corrects the article DOI: 10.3389/fpsyg.2021.673596.].


Effect of glycosylation on the mechanism of renaturation of invertase from yeast.
N-Glycosylation occurs cotranslationally as soon as the growing polypeptide chain enters the endoplasmic reticulum, before the final native-like folded state is reached. We examined the role of the carbohydrate chains in the mechanism of protein folding. The in vitro folding and association of yeast invertase are used as an experimental system. External invertase contains approximately 50% carbohydrate, whereas cytoplasmic invertase is not glycosylated. The functional native state of both proteins is a homodimer. At pH greater than or equal to 6.5 and at protein concentrations below 3 micrograms/ml, the kinetics of reactivation and the final yields are similar for the two invertases. For both proteins, reactivation is a sequential reaction with a lag phase at the beginning. The nonglycosylated protein tends to aggregate during reactivation at low pH and at protein concentrations above 3 micrograms/ml. After separation of inactive material, the renatured protein is indistinguishable from the original native state by a number of physicochemical and functional criteria. The results suggest that the carbohydrate moiety does not affect the mechanism of folding and association of invertase. However, glycosylation improves the solubility of unfolded or partially folded invertase molecules and hence leads to a suppression of irreversible aggregation. Such a protective effect may also be important for the in vivo maturation of nascent glycosylated protein chains.


MR imaging of the basal ganglia in chronic liver disease: correlation of T1-weighted and magnetisation transfer contrast measurements with liver dysfunction and neuropsychiatric status.
Conventional T1-weighted spin echo (T1WSE) and T1-weighted magnetization transfer (MT) images were obtained in 26 patients with biopsy-proven cirrhosis (nine Child's grade A, 10 Child's grade B and seven Child's grade C). Four subjects showed no evidence of neuropsychiatric impairment on clinical, psychometric and electrophysiological testing, seven showed evidence of subclinical hepatic encephalopathy and 15 were classified as having overt hepatic encephalopathy. Signal intensities of basal ganglia nuclei (head of caudate, putamen, globus pallidus and thalamus) and adjacent brain parenchyma were measured and contrast calculated. On T1WSE imaging, contrast measurements of the globus pallidus were significantly greater in patients with neuropsychiatric dysfunction than in those who were unimpaired (p < 0.05). This was not observed in the other basal ganglia nuclei. Patients with subclinical and overt hepatic encephalopathy could not be distinguished on the basis of contrast measurements of the globus pallidus or of any other nucleus. T1WSE contrast measurements of the globus pallidus were increased with elevations in blood ammonia levels (p < 0.05) and with the severity of liver dysfunction, when graded according to the Pugh's score (p < 0.05) Those patients with the worst liver injury (Child's grade C) had significantly greater T1WSE pallidal contrast measurements (p < 0.05) than those patients with minimal liver injury (Child's grade A). The patients with intermediate liver damage (Child's grade B) could not be distinguished from the other two groups. While MT imaging highlighted the basal ganglia and showed a correlation between globus pallidus contrast and blood ammonia levels (p < 0.05), no other relationship between MT contrast measurements and either the degree of hepatic encephalopathy or the severity of liver dysfunction was found.


Overexpression of c-maf is a frequent oncogenic event in multiple myeloma that promotes proliferation and pathological interactions with bone marrow stroma.
The oncogene c-maf is translocated in approximately 5%-10% of multiple myelomas. Unexpectedly, we observed c-maf expression in myeloma cell lines lacking c-maf translocations and in 50% of multiple myeloma bone marrow samples. By gene expression profiling, we identified three c-maf target genes: cyclin D2, integrin beta7, and CCR1. c-maf transactivated the cyclin D2 promoter and enhanced myeloma proliferation, whereas dominant inhibition of c-maf blocked tumor formation in immunodeficient mice. c-maf-driven expression of integrin beta7 enhanced myeloma adhesion to bone marrow stroma and increased production of VEGF. We propose that c-maf transforms plasma cells by stimulating cell cycle progression and by altering bone marrow stromal interactions. The frequent overexpression of c-maf in myeloma makes it an attractive target for therapeutic intervention.


p-Toluenesulfonic acid combined with hydrogen peroxide-assisted pretreatment improves the production of fermentable sugars from walnut (Juglans regia L.) shells.
This study presents p-toluenesulfonic acid (p-TsOH) pretreatment combined with subsequent hydrogen-peroxide pretreatment for the fractionation of all lignocellulosic components from walnut shells (WNS). The main focus of this study is the production of fermentable sugars. During p-TsOH pretreatment (55% p-TsOH, 1:10 solid-to-liquid ratio, 90 °C, 120 min), 50.2% of lignin and 88.3% of xylan were dissolved. Subsequently, the p-TsOH pretreated WNS without washing (to reduce water consumption) was further pretreated with 40% (v/v) H2O2 and 74.6% of lignin was removed at 60 °C for 120 min. Compared with the glucose yield of 10.2% from p-TsOH pretreated WNS, the glucose yield from the p-TsOH/H2O2 pretreated WNS could be significantly improved to 94.4%. Structural characterization analysis showed increases in porosity, biomass disruption, and cellulose crystallinity during p-TsOH/H2O2 pretreatment. Mass balance demonstrated that 1000 g of WNS produced 295.1 g of fermentable sugars (263.6 g glucose and 31.5 g xylose).


Intraparenchymal pulmonary lymph node: case report and literature review.
A case of a 44-year-old woman with a solitary pulmonary coin lesion is presented. Histologic study of this nodule revealed a normal intraparenchymal pulmonary lymph node. A review of the literature discusses the incidence and characteristics of this entity.


Sacrococcygeal teratoma in Northeastern Nigeria: 18-years experience.
Although sacrococcygeal teratomas are rare, there have been several reports from various parts of Nigeria, outside the Northeast region. This report reviews the experience with this tumour from the northeastern part of Nigeria. A retrospective study of 21 children with histologically confirmed sacrococcygeal teratoma managed in 18 years. Over the 18-year-period, 21 histologically confirmed cases of sacrococcygeal teratoma were seen-80% were girls. Thirteen (60.9%) presented during the neonatal period. Eighteen patients presented with benign sacrococcygeal teratoma while three patients and a recurrence from an initial benign tumour had malignant sacrococcygeal teratoma. All malignant tumours had a significant presacral component. There were associated congenital malformations in 3 (14.3%) of the patients. All the benign tumours were resectable. Using the American Academy of Pediatrics (Altman's) classification, 13 patients were type I, 5 patients type II, 3 patients type Ill and none was for type IV. The commonest post-operative complication was wound infection in six patients. Others were wound dehiscence in three and post-operative diarrhoea in two patients. Three deaths were recorded in this series. The size of mass greater than 5 cm did not correlate with the incidence of post-operative complications (P=0.367). The post-operative follow-up was very poor; but there was a recurrence in a girl, two-years after the initial surgery. Our study revealed that most of our patients with sacrococcygeal teratoma present early to hospital with benign lesions and the immediate post-operative results were excellent. However, the follow-up was poor as such long-term post-operative results are difficult to study. It is to be recommended that sacrococcygeal teratoma presenting early to hospital should have prompt surgical intervention.


Short-term correlation properties of R-R interval dynamics at different exercise intensity levels.
Methods based on non-linear heart rate (HR) dynamics have been suggested to probe features in HR behaviour that are not easily detected by the traditional HR variability indices. This study tested the hypothesis that analysis of correlation properties of R-R intervals provides useful information on HR fluctuation during exercise. High- (HF) and low-frequency (LF) spectral components and a short-term scaling exponent (alpha1) of HR variability, were analysed for nine healthy subjects at rest, during incremental and steady-state exercise, during atropine infusion and during incremental exercise after atropine administration. During the incremental exercise test alpha1 increased from rest to an intensity level of approximately 40% of VO2max (from 1.07+/-0.24 to 1.50+/-0.25, P<0.001) and thereafter decreased linearly until the end of exercise (from 1.50+/-0.25 to 0.38 +/- 0.10, P<0.001). Atropine infusion increased the scaling exponent alpha1 value from 0.91+/-0.23 to 1.37+/-0.31 (P<0.001). During exercise after atropine infusion, a linear reduction was observed in the scaling exponent alpha1 from 1.37+/-0.23 to 0.25+/-0.08 (P<0.001). Analogous changes in alpha1 were seen during long-term steady-state exercise compared to incremental exercise. Conventional HR variability indices did not show any significant changes during exercise at high exercise intensity levels. alpha1 correlated with the LF/HF ratio at rest (r=0.90, P<0.001), but the correlation was weaker after atropine (r=0.71, P<0.05) and during exercise (e.g. r=0.33, P=NS at the level of 40% of VO2max). In conclusion, incremental exercise test until exhaustion results in bidirectional changes in correlation properties of R-R interval dynamics. These changes can be explained by the intensity of vagal and sympathetic input to the sinus node during the different intensity levels of exercise. Changes in alpha1 values can be detected also in high intensity levels, when the conventional measures of HR variability can not be applied.


Preschool children perceived by mothers as irregular eaters: physical and psychosocial predictors from a birth cohort study.
Parents often report their children display irregular eating patterns. Our aim is to describe the stability of maternal-perceived irregular eating of their offspring from 6 months to 2-4 years of age and to investigate factors that are associated with maternal perceived irregular eating of their 2-4 year old offspring. A longitudinal mother-child linked analysis was carried out using 5 year follow-up data from a population-based prospective birth cohort of 5122 mothers who were participants in the Mater-University Study of Pregnancy, Brisbane. Measures included responses to standardized questionnaires, pediatrician review and standardized measures such as the Peabody Picture Vocabulary Test-Revised and the Child Behavior Checklist. 20.2% and 7.6% of mothers respectively stated their 2-4 year old was sometimes or often an irregular eater. Continuity of feeding difficulties from age 6 months was prominent: 48% of 6 month olds with a feeding problem were 'sometimes' or 'often' irregular eaters at age 2-4 years. From a multivariable analysis, both child-intrinsic factors (chronic physical morbidity, sleeplessness and anxiety-depressive symptoms) and factors that impinge upon the child (poor maternal health and maternal depression and anxiety) independently contributed to irregular eating status at age 2-4 years. We conclude that approximately one third of mothers had some concern with their child's irregular eating, 7.6% of mothers were often concerned. Irregular eating children were usually physically well, more likely to have persisting feeding problems, sleeplessness, behavioral problems and lived with mothers with perceived poor physical and mental health. Intervention strategies should be family orientated and include child, mother and mother-child psychosocial approaches.


Ambient-Temperature Waterborne Polymer/rGO Nanocomposite Films: Effect of rGO Distribution on Electrical Conductivity.
Electrically conductive polymer/rGO (reduced graphene oxide) films based on styrene and n-butyl acrylate are prepared by a variety of aqueous latex based routes involving ambient temperature film formation. Techniques based on miniemulsion polymerization using GO as surfactant and "physical mixing" approaches (i.e., mixing an aqueous polymer latex with an aqueous GO dispersion) are employed, followed by heat treatment of the films to convert GO to rGO. The distribution of GO sheets and the electrical conductivity depend strongly on the preparation method, with electrical conductivities in the range 9 × 10-4 to 3.4 × 102 S/m. Higher electrical conductivities are obtained using physical mixing compared to miniemulsion polymerization, which is attributed to the former providing a higher level of self-alignment of rGO into larger linear domains. The present results illustrate how the distribution of GO sheets within these hybrid materials can to some extent be controlled by judicious choice of preparation method, thereby providing an attractive means of nanoengineering for specific potential applications.


Anticonvulsant properties of ropizine in epileptic and nonepileptic beagle dogs.
Studies were conducted on a colony of purebred beagle dogs. Animals with spontaneous seizures were classed as epileptic beagles (EB). Those without spontaneous seizures were termed nonepileptic beagles (NEB). The median convulsant current for maximal electroshock seizure (MES) threshold was 175(194-158)mA for EB and 390 (417-364) mA for NEB. Similarly the median convulsant dose of pentylenetetrazol (PTZ) was 7.9 (10.1-6.2) mg/kg for EB and 20.2 (24.2-17.6) mg/kg for NEB. Following pretreatment with graded doses of ropizine (SC 13504), the median protective dose against MES was 6.0(9.2-3.9) mg/kg in EB and 3.2(4.8-2.1) mg/kg in NEB. Based on the incidence of ataxia, EB had a median toxic dose (TD50) of 14.0(16.5-11.9) mg/kg, while in NEB it was 18.0(23.6-13.7)mg/kg. The TD50 doses were unable to protect against a convulsive dose of PTZ. It is concluded first that ropizine may have anti-grand mal activity but apparently lacks an anti-petit mal action. Secondly, EB are more sensitive than NEB to the convulsive effects of electric current and PTZ, yet less responsive to the anticonvulsant actions of ropizine.


Complete mitochondrial genome of Schizopygopsis chengi chengi (Cyprinidae, Schizothoracinae, Schizopygopsis).
The complete mitochondrial DNA sequence of Schizopygopsis chengi chengi collected from the Dadu River was determined in this study. The complete mitochondrial genome of S. chengi chengi was a circular molecule of 16 688 bp in size, and all genes showed the typical gene arrangement conforming to the vertebrate consensus. Twelve protein-coding genes (except ND6) of S. chengi chengi and other 22 Schizothoracinae species from two genera were used for phylogenetic analysis by Bayesian inference and maximum likelihood methods. The topology confirmed the close genetic relationship between S. chengi chengi and S. chengi baoxinggensis.


[Possibilities, problems and present status of hip sonography of infant hips].
The author reports on hip-joint examinations in 16 000 infants, using sonography (age: 1 day up to 12-15 months). Particular attention is given to the classification of disturbances of maturation of the hip joint described. The use of angles and the possibility of making mistakes during measurement are demonstrated. The ultrasonographic traces are compared with X-rays to demonstrate the accuracy of ultrasonic investigation of infant hip joints. Determination of hip-joint maturity using the "sonometer" is described.


In vitro decondensation of human sperm chromatin.
The swelling of human sperm head and the decondensation of the sperm chromatin were investigated using a microscopic observation and the increased binding of AMD as the probes. Incubation of the human spermatozoa with 1 mM DTT produced sperm head swelling within 30 min. Addition of soybean trypsin inhibitor or PMSF blocked the swelling induced by 1 mM DTT. The DTT induced a large increase in the binding of AMD to the spermatozoa, to the sperm head and to the triton X-100 treated spermatozoa. This increase in AMD binding was completely abolished by the presence of PMSF. These results suggested the participation of a sulfhydryl reducing agent and a proteolytic enzyme in the sperm head swelling and the chromatin decondensation. The simplicity of probing the chromatin decondensation with AMD binding offers a means to study kinetic and quantitative aspects of the process.


Arterial Hypertension, Aldosterone, and Atrial Fibrillation.
Atrial fibrillation is the most common sustained arrhythmia, with a prevalence of 1-2% in the general population and over 15% in people older than 80 years. Due to aging of the population it imposes an increasing burden on the healthcare system because of the need for life-long pharmacological treatment and the associated increased risk of heart failure and hospitalization. Hence, identification of the factors that predispose to atrial fibrillation it is of utmost relevance. Several conditions exist that are characterized by inappropriately high levels of aldosterone, mostly primary aldosteronism and the severe or drug-resistant forms of arterial hypertension. In these forms, aldosterone can cause prominent target organ damage, mostly in the heart, vasculature, and kidney. This review examines the experimental data and clinical evidences that support a link between hyperaldosteronism and atrial fibrillation, and how this knowledge should lead to a change in our management of the hypertensive patients presenting with atrial fibrillation.


Pixel classification based color image segmentation using quaternion exponent moments.
Image segmentation remains an important, but hard-to-solve, problem since it appears to be application dependent with usually no a priori information available regarding the image structure. In recent years, many image segmentation algorithms have been developed, but they are often very complex and some undesired results occur frequently. In this paper, we propose a pixel classification based color image segmentation using quaternion exponent moments. Firstly, the pixel-level image feature is extracted based on quaternion exponent moments (QEMs), which can capture effectively the image pixel content by considering the correlation between different color channels. Then, the pixel-level image feature is used as input of twin support vector machines (TSVM) classifier, and the TSVM model is trained by selecting the training samples with Arimoto entropy thresholding. Finally, the color image is segmented with the trained TSVM model. The proposed scheme has the following advantages: (1) the effective QEMs is introduced to describe color image pixel content, which considers the correlation between different color channels, (2) the excellent TSVM classifier is utilized, which has lower computation time and higher classification accuracy. Experimental results show that our proposed method has very promising segmentation performance compared with the state-of-the-art segmentation approaches recently proposed in the literature.


Hydroxyapatite-armored poly(ε-caprolactone) microspheres and hydroxyapatite microcapsules fabricated via a Pickering emulsion route.
Hydroxyapatite (HAp) nanoparticle-armored poly(ε-caprolactone) (PCL) microspheres were fabricated via a "Pickering-type" emulsion solvent evaporation method in the absence of any molecular surfactants. It was clarified that the interaction between carbonyl/carboxylic acid groups of PCL and the HAp nanoparticles at an oil-water interface played a crucial role in the preparation of the stable Pickering-type emulsions and the HAp nanoparticle-armored microspheres. The HAp nanoparticle-armored PCL microspheres were characterized in terms of size, size distribution, morphology, and chemical compositions using scanning electron microscopy, laser diffraction, energy dispersive X-ray microanalysis, and thermogravimetric analysis. The presence of HAp nanoparticles at the surface of the microspheres was confirmed by scanning electron microscopy and energy dispersive X-ray microanalysis. Pyrolysis of the PCL cores led to the formation of the corresponding HAp hollow microcapsules.


Rapid Improvements in Physical Activity and Sedentary Behavior in Patients With Acute Myocardial Infarction Immediately Following Hospital Discharge.
Background Little is known about changes in physical activity (PA) and sedentary behavior (SB) patterns in the acute phase of a myocardial infarction (MI). We objectively assessed PA and SB during hospitalization and the first week after discharge. Methods and Results Consecutively admitted patients hospitalized with an MI were approached to participate in this prospective cohort study. SB, light-intensity PA, and moderate-vigorous intensity PA were objectively assessed for 24 h/d during hospitalization and up to 7 days after discharge in 165 patients. Changes in PA and SB from the hospital to home phase were evaluated using mixed-model analyses, and outcomes were stratified for predefined subgroups based on patient characteristics. Patients (78% men) were aged 65±10 years and diagnosed with ST-segment-elevation MI (50%) or non-ST-segment-elevation MI (50%). Sedentary time was high during hospitalization (12.6 [95% CI, 11.8-13.7] h/d) but substantially decreased following transition to the home environment (-1.8 [95% CI, -2.4 to -1.3] h/d). Furthermore, the number of prolonged sedentary bouts (≥60 minutes) decreased between hospital and home (-1.6 [95% CI, -2.0 to -1.2] bouts/day). Light-intensity PA (1.1 [95% CI, 0.8-1.6] h/d) and moderate-vigorous intensity PA (0.2 [95% CI, 0.1-0.3] h/d) were low during hospitalization but significantly increased following transition to the home environment (light-intensity PA: 1.8 [95% CI, 1.4-2.3] h/d; moderate-vigorous intensity PA: 0.4 [95% CI, 0.3-0.5] h/d; both P<0.001). Improvements in PA and SB were similar across groups, except for patients who underwent coronary artery bypass grafting and who did not improve their PA patterns after discharge. Conclusions Patients with MI demonstrate high levels of SB and low PA volumes during hospitalization, which immediately improved following discharge at the patient's home environment. Registration URL: trialsearch.who.int/; Unique identifier: NTR7646.


Metabolic syndrome by the new IDF criteria in Hong Kong Chinese adolescents and its prediction by using body mass index.
The International Diabetes Federation (IDF) has recently proposed a new set of criteria to define metabolic syndrome (MES) in children and adolescents. We estimated the rate of MES by these new IDF criteria and investigated the use of body mass index (BMI) in predicting MES in Chinese adolescents. This is a cross-sectional, population-based study of 1616 Chinese adolescents. sensitivity, specificity and likelihood ratio were calculated to assess the accuracy in using BMI to predict the presence of MES. In the study population, 48.6% were boys. The median age was 14.0 and 15.0 years for boys and girls respectively and the overall prevalence of MES was 1.2% (boys 1.5%; girls 0.8%). Using BMI > or =25 kg/m(2), the sensitivity, specificity and likelihood ratio to predict MES were 100%, 85.0% and 6.7% respectively. The corresponding figures were 52.6%, 97.1% and 18.1%, respectively, using BMI > or =30 kg/m(2). Metabolic syndrome was found in 1.2% of Chinese adolescents in Hong Kong. BMI is a useful clinical tool to predict clustering of cardiometabolic risk factors in adolescents.


Enhanced transfection of primary cortical cultures using arginine-grafted PAMAM dendrimer, PAMAM-Arg.
PAMAM-Arg is a cationic arginine-grafted polyamidoamine (PAMAM) dendrimer. In the previous study, we reported that PAMAM-Arg facilitates transfection in a range of mammalian cell types. In the present study, we investigated the transfection efficiency of PAMAM-Arg in primary cortical cultures, which are known to be extremely vulnerable to exogenous gene transfection. PAMAM-Arg/DNA complexes showed particularly high transfection efficiencies and low cytotoxicity in primary cortical cells, as compared to other gene carriers such as, native PAMAM, polyethylenimine (BPEI), and Lipofectamine. Efficient transfection was not limited to neurons but extended to all three glial cells, astrocytes, microglia, and oligodendrocytes, present in these primary cortical cultures. The potential use of PAMAM-Arg was demonstrated by efficient gene knock-down by transfecting HMGB1 shRNA-expressing plasmid. The numbers of green fluorescent protein (GFP)-positive and HMGB1-negative cells indicated that PAMAM-Arg/shRNA-expressing plasmid complex suppressed target gene expression in over 40% of cells, which is the highest level achieved to date in primary cortical culture by any gene carrier. Here, we present evidence of the successful delivery and expression of both a reporter gene and of a shRNA-expressing plasmid in primary cortical cells, which demonstrates the potential of PAMAM-Arg for mediating gene delivery to primary neuronal cells.


The epidemiology of patellar luxation in dogs attending primary-care veterinary practices in England.
Canine patellar luxation is one of the most common orthopaedic disorders of dogs and is a potential welfare concern because it can lead to lameness, osteoarthritis and pain. However, there are limited epidemiological data on the disorder relating to the general population of dogs in England. This study aimed to investigate the VetCompass Programme database of dogs attending primary-care veterinary practices in England to report on the prevalence, risk factors and clinical management of diagnosed patellar luxation cases. The study included all dogs with at least one electronic patient record in the VetCompass database from September 1(st), 2009 to August 31(st), 2014. Candidate patellar luxation cases were identified using free-text word searching of the clinical notes and VeNom diagnosis term fields. Univariable and multivariable binary logistic regression modelling was used for risk factor analysis. The overall dataset comprised 210,824 dogs attending 119 clinics in England. The prevalence of patellar luxation diagnosis in dogs was 1.30 % (95 % confidence interval (CI) 1.21-1.39). Of the 751 incident cases, 293 (39.0 %) received medical management, 99 (13.2 %) received surgical intervention and 28 (3.7 %) were referred for further management. Multivariable modelling documented 11 breeds with increased odds of patellar luxation compared with crossbred dogs, including the Pomeranian (odds ratio [OR]: 6.5, 95 % CI 4.0-10.7, P < 0.001), Chihuahua (OR: 5.9, 95 % CI 4.4-7.9, P < 0.001), Yorkshire Terrier (OR: 5.5, 95 % CI 4.3-7.1, P < 0.001) and French Bulldog (OR: 5.4, 95 % CI 3.1-9.3, P < 0.001). Dogs with bodyweight below their mean for breed and sex had a 1.4 times odds of diagnosis (95 % CI 1.2-1.6, P < 0.001). Dogs aged ≥ 12.0 years showed 0.4 times the odds (95 % CI 0.3-0.5, P < 0.001) compared with dogs aged < 3.0 years. Females had 1.3 times the odds (95 % CI 1.1-1.5, P < 0.001), neutered dogs had 2.4 times the odds (95 % CI 1.8-3.2, P < 0.001) and insured dogs had 1.9 times the odds (95 % CI 1.6-2.3, P < 0.001). Patellar luxation warrants inclusion as a welfare priority in dogs and control strategies that include this disorder should be considered as worthwhile breeding goals, especially in predisposed breeds.


Chlorhexidine varnish may be useful adjunct to routine periodontal therapy?
PubMed, Embase and the Cochrane Library were searched for relevant studies. Only controlled human trials of chlorhexidine varnish using clinical outcomes were included: other chlorhexidine preparations (mouth rinses/ gels) were excluded, as were studies with concomitant preventive measures, eg, fluoride varnishes. Details of data extraction methods are not provided and a qualitative summary is presented. Ten studies were identified. Comparisons were difficult because of considerable variation in the study parameters, such as varnishes with different chlorhexidine concentrations, different ages of participants, number of applications and clinical indices employed. Eight of the 10 studies found improvements in clinical parameters. The application of chlorhexidine varnish seems to have beneficial effects in people who have chronic gingivitis, improving their plaque accumulation and bleeding levels and reducing their gingival index. It is possible to maintain this beneficial effect for prolonged periods of time, although this requires re-applications of the varnish.


Adipocyte-derived stem cells for the face.
This review gives a basic overview of the current state of fat transplantation in view of adipose-derived stem cells. Current technologies regarding facial rejuvenation are presented, with a brief review of the procedures.


Gonadotropin stimulation for in vitro fertilization and embryo transfer in insulin-dependent diabetics: follicular response, oocyte quality, embryo development, and follicular environment.
Two IDD patients were stimulated with gonadotropins for IVF and ET. Both patients had high E2 response and greater than or equal to 5 preovulatory oocytes retrieved, normal fertilization and cleavage rates, and transfer; neither conceived. Follicular fluid showed levels of E2, P, A, hCG, and PRL similar to non-IDD. Epidermal growth factor could not be detected in FF. Insulin-dependent diabetes patients can undergo gonadotropin stimulation for IVF with customary responses. Their follicular milieu resembles that of non-IDD patients except for a lack of EGF.


Updates in Neonatal Extracorporeal Membrane Oxygenation and the Artificial Placenta.
Extracorporeal life support, initially performed in neonates, is now commonly used for both pediatric and adult patients requiring pulmonary and/or cardiac support. Data suggests the clinical feasibility of Extracorporeal Membrane Oxygenation for premature infants (29-33 weeks estimated gestational age [EGA]). For extremely premature infants less than 28 weeks EGA, an artificial placenta has been developed to recreate the fetal environment. This approach is investigational but clinical translation is promising. In this article, we discuss the current state and advances in neonatal and "preemie Extracorporeal Membrane Oxygenation" and the development of an artificial placenta and its potential use in extremely premature infants.


Hereditary increased muscle mechanical irritability and progressive contracture with stretch-induced electromyographic activity.
A son and mother are reported with autosomal dominantly transmitted painless, increased mechanical irritability in the limb and trunk muscles and progressive finger contracture. Immediately after a tap, muscle swelling appeared. With light tapping, wavelike muscle surface movements appeared. Progressive contractures developed first in the proximal interphalangeal finger joints and subsequently involving the lower arm muscles. The contractures disappeared in the local curare test. No spontaneous activity was recorded on concentric needle recording. Serial repetitive activity was recorded with fine wire electrode recording, induced by muscle stretch, performed by percussion hammer blows or by prolonged finger grasp. A slight, irritative peripheral nervous lesion could be the cause. The chronic sensorimotor polyneuropathy may be also a part of the syndrome.


COVID-19-associated Mucormycosis: A clinico-epidemiological study.
There was an unprecedented increase in COVID-19-associated-Mucormycosis (CAM) cases during the second pandemic wave in India. This observational study was done to know the epidemiological profile of CAM cases andincluded all patients admitted with mucormycosis between May 2021 and July 2021. Out of the enrolled 208 CAM cases (either SARS-CoV-2 RT-PCR or serology positive), 204, three and one had rhino-orbital-cerebral, pulmonary and gastrointestinal mucormycosis, respectively. 95.7 % of the patients had diabetes, out of which 42.3 % were recently diagnosed. Mean HbA1c was 10.16 ± 2.56 %. 82.5 % of the patients were unvaccinated. During their COVID-19 illness, 86.5 % were prescribed antibiotics, 84.6 % zinc preparations, 76.4 % ivermectin, and 64.9 % steroids, while only 39.5 % required oxygen therapy. The frequency of blood groups A, B, O and AB in our CAM patients was 29.5 %, 18.9 %, 38.9 % &12.6 %, respectively. At three months follow up, 60 (28.8 %) patients died, four (1.9 %) stopped antifungal treatment, and 144(69.23 %) were on antifungal treatment. 55 % (n = 33) of deaths occurred within 15 days of admission. Mortality was significantly associated with higher age, RT-PCR positive for SARS-CoV-2, raised serum creatinine and alkaline phosphatase during treatment. At 6 months follow-up, eight more patients died, three due to chronic kidney disease, four patients who had stopped treatment and one patient who was on a ventilator due to COVID-19 associated pneumonia and the rest 140(67.3 %) survived. Uncontrolled hyperglycemia, SARS-CoV-2 infection, rampant use of antibiotics, zinc supplementation and steroids were some of the risk factors for mucormycosis. Despite the overwhelming number of patients with an uncommon disease like mucormycosis, the six months mortality was much lower than expected.


Interplay between proteasome function and inflammatory responses in e-cig vapor condensate-challenged lung epithelial cells.
Exposure to cigarettes and other nicotine-based products results in persistent inflammation in the lung. In recent years, electronic cigarettes (e-cigs) have become extremely popular among adults and youth alike. E-cigarette vapor-induced oxidative stress promotes protein breakdown, DNA damage and cell death, culminating in a variety of respiratory diseases. The proteasome, a multi-catalytic protease, superintends protein degradation within the cell. When cells are stimulated with inflammatory cytokines such as IFN-γ and TNF-α, the constitutive catalytic proteasome subunits are replaced by the inducible subunits-low-molecular mass polypeptide (LMP)2 (β1i), multi-catalytic endopeptidase complex-like (MECL)1 (β2i), and LMP7 (β5i), which are required for the production of certain MHC class I-restricted T-cell epitopes. In this study, we used human alveolar epithelial cells (A549) and exposed them to filtered air or (1%) tobacco-flavored (TF) electronic cigarette vapor condensate (ECVC) ± nicotine (6 mg/ml) (TF-ECVC ± N) for 24 h. We observed an increase in the levels of IFN-γ, TNF-α, and inducible proteasome subunits (LMP7/PSMB8, LMP2/PSMB9, MECL1/PSMB10), and a reduced expression of constitutive proteasome subunits (β1/PSMB6 and β2/PSMB7) in challenged A549 cells. Interestingly, knockdown of the inducible proteasome subunit LMP7 reversed ECVC-induced expression of NADPH oxidase and immunoproteasome subunits in A549 cells. In addition, pre-exposure to an LMP7 inhibitor (ONX-0914) abrogated the mRNA expression of several NOX subunits and rescued the excessive production/release of inflammatory cytokines/chemokines (IL-6, IL-8, CCL2, and CCL5) in ECVC-challenged cells. Our findings suggest an important role of LMP7 in regulating the expression of inflammatory mediators during ECVC exposure. Overall, our results provide evidence for proteasome-dependent ROS-mediated inflammation in ECVC-challenged cells.


Effects of pain severity and CT imaging on analgesia prescription in acute appendicitis.
Previously, analgesics were avoided in suspected appendicitis to avoid masking the diagnosis. We determined use of analgesia in patients with appendicitis to determine recent trends over time and explore predictors of use of analgesia. A retrospective review of the National Hospital Ambulatory Medical Care Survey 2006-2010 was conducted including emergency department (ED) patients with acute appendicitis (ICD-9-CM 540.xx). The association between demographic and clinical information with ED visit prescription of analgesics/opioids was determined using univariate (χ(2)) and multivariate (logistic regression) analyses. There were an estimated 763000 ED patient visits for acute appendicitis from 2006 to 2010. Mean age was 32, 74% were under age 19, 69% were male. Sixty-four percent of patients received any analgesia in the ED and 58% received an opioid; use of analgesics did not change over time. Of all patients, 68% had computed tomographic (CT) imaging. There was a positive trend in analgesic use with increasing pain (27% for no pain to 71% for severe pain, P = .08); a similar trend was seen for opioids but was not significant (P = .12). Analgesic use was lower for elderly (age >65) patients (odds ratio [OR] 0.09, 95% confidence interval [CI] 0.01-0.56) and private insurance (OR 0.14, 95% CI 0.05-0.43), and higher for patients with CT scans (OR 3.73, 95% CI 1.61-8.66). Pain severity was not associated with administration of analgesics after controlling for other factors. Use of analgesia and opioids analgesia has remained stable over time. Factors associated with prescription of any analgesia and opioids were older age and payment source. Use of CT was associated with prescription of analgesics.


Nitrous oxide (N2O) emissions from a pilot-scale oxidation ditch under different COD/N ratios, aeration rates and two shock-load conditions.
Nitrous oxide (N2O) generated from wastewater treatment plants (WWTPs) has drawn attention due to its high emission load and significant greenhouse effect. In the present study, N2O emissions from a pilot-scale Carrousel oxidation ditch under various chemical oxygen demand (COD) to nitrogen ratio (COD/N) and aeration rates were systematically investigated. The highest N2O emission factor was 0.142 ± 0.013%, at COD/N of 5 and aeration rate of 1.8 m3 h-1, which was much lower than the majority of previous studies. The results could be attributed to the high internal recycle ratio of the oxidation ditch process which lightened the burden of influent load to the system. The profiles of N2O emissions and dissolved N2O concentration along the channels showed a distinct spatial variation that N2O emissions primarily occurred in the aeration zones due to the air stripping effect. However, both the aeration and anoxic zones contributed to N2O generation due to autotrophic nitrification (AN), which was considered to be the main N2O generation process. In addition, two simulated shock-load conditions, ammonia overload shock and aeration failure shock, were carried out to explore the response of the biological nitrogen removal (BNR) system. The results indicated that both shock-loads lead to excessive N2O emissions, especially at higher aeration rates, which could be explained by the improved N2O generation by AN process during the shock-load period. This study offered new insights into the role of operational parameters to N2O emission and the alternative approach for N2O mitigation during both the steady-state operation and shock-load conditions in the oxidation ditch process.


An update on asthma management.
Asthma remains a major cause of morbidity in the Australian community, despite enhanced strategies and interventions for achieving optimal outcomes. Although there is some evidence of over use of high doses of inhaled corticosteroids (ICS), there is also evidence for under use of ICS, despite long-term data demonstrating clear benefits of low doses. The present paper briefly discusses some of the issues that are pertinent to the development of sensitization and atopic disease, but focuses mainly on the current understanding of best clinical practice for adults with asthma and the optimal approach to management. A clear definition of asthma control and a systematic approach to down-titration to minimize ICS doses is crucial to achieving better outcomes. Patient self-management education and optimal therapy are the keys to achieving better outcomes, although uncertainty remains about recommendations for mild asthma, despite new data.


Structure and expression of MHC class Ib genes of the central M region in rat and mouse: M4, M5, and M6.
The M region at the telomeric end of the murine major histocompatibility complex (MHC) contains class I genes that are highly conserved in rat and mouse. We have sequenced a cosmid clone of the LEW rat strain (RT1 haplotype) containing three class I genes, RT1.M6-1, RT1.M4, and RT1.M5. The sequences of allelic genes of the BN strain (RT1n haplotype) were obtained either from cDNAs or genomic clones. For the coding parts of the genes few differences were found between the two RT1 haplotypes. In LEW, however, only RT1.M5 and RT1.M6 have open reading frames; whereas in BN all three genes were intact. In line with the findings in BN, transcription was found for all three rat genes in several tissues from strain Sprague Dawley. Protein expression in transfectants could be demonstrated for RT1.M6-1 using the monoclonal antibody OX18. By sequencing of transcripts obtained by RT-PCR, a second, transcribed M6 gene, RT1.M6-2, was discovered, which maps next to RT1.M6-1 outside of the region covered by the cosmid. In addition, alternatively spliced forms for RT1.M5 and RT1.M6 were detected. Of the orthologous mouse genes, H2-M4, H2-M5, and H2-M6, only H2-M5 has an open reading frame. Other important differences between the corresponding parts of the M region of the two species are insertion of long LINE repeats, duplication of RT1.M6, and the inversion of RT1.M5 in the rat. This demonstrates substantial evolutionary dynamics in this region despite conservation of the class I gene sequences themselves.


Periprosthetic humeral fracture after Copeland resurfacing and the role of revision arthroplasty: A report of three cases.
Follow-up series of the Copeland resurfacing hemiarthroplasty have reported few postoperative fractures around the prosthesis. We report three cases of periprosthetic fracture around a Copeland resurfacing arthroplasty. Due to prosthetic loosening and tuberosity comminution, all cases were managed with revision shoulder arthroplasty. All patients had good functional outcome and range of movement on early follow-up.


Substance p: localization in the central nervous system and in some primary sensory neurons.
Antibodies to substance P with a high titer have been produced and used in immunohistochemical studies on the peripheral and central nervous system of the rat and the cat. Evidence was obtained for the localization of substance P in a certain population of primary sensory neurons, probably small nerve cells with unmyelinated processes. Substance P or a peptide similar to it was also observed in cell bodies in the medial habenula and in probable nerve terminals in many brain areas. The results give morphological support for a transmitter (or modulator) role of substance P in the nervous system.


Measurements of right ventricular volumes in man from single plane cineangiograms. A comparison to the biplane approach.
An area-length expression for RV volume determination from single plane cineangiograms has been developed and verified against the biplane volumes with the aid of the RV human casts. A close correlation was found to exist between the two methods (r = 0.93). Ten patients with normal hearts were subsequently studied. Biplane and single plane RV cineangiogrpahic analyses yielded virtually identical results. The single plane expression was equally valid in the end-systolic and the end-diastolic volume analysis.


Immobilization of β-1,3-xylanase on pitch-based hyper-crosslinked polymers loaded with Ni2+ for algal biomass manipulation.
β-1,3-xylanase plays an important role in the conversion of algal biomass into renewable chemical commodities and functional xylooligosaccharides. Efficient immobilization of the target enzymes that could integrate the separation, purification, and immobilization in one-step may have great potentials. The cheap and easily obtained pitch was adopted as the raw material to prepare the hyper-cross-linked polymers with the specific surface areas of 560 m2/g and the Ni2+ loading about 80 mg/g. As a carrier, it could immobilize and purify the β-1,3-xylanases directly from the crude cell debris with the activity recovery of (80.66 ± 0.87) %. The half-life of the immobilized β-1,3-xylanases was 50 min at 50 °C, which was significantly longer than the free ones with only 14 min. The immobilized β-1,3-xylanases could retain 65 % of the activity after stored at 30 ℃ for 80 h, they could also retain 87 % of the original activity after 15 cycles of reuse. In terms of potential applications in the manipulation of algae Caulerpa lentillifera, the immobilized β-1,3-xylanases could release 30 % more reducing sugar in 85 h. The method proposed here is promising for algal biomass manipulation because of its low cost, stable storage, convenient recycling and excellent reusability.