Rapid biosynthesis of glycoprotein therapeutics and vaccines from freeze-dried bacterial cell lysates.
The advent of distributed biomanufacturing platforms promises to increase agility in biologic production and expand access by reducing reliance on refrigerated supply chains. However, such platforms are not capable of robustly producing glycoproteins, which represent the majority of biologics approved or in development. To address this limitation, we developed cell-free technologies that enable rapid, modular production of glycoprotein therapeutics and vaccines from freeze-dried Escherichia coli cell lysates. Here, we describe a protocol for generation of cell-free lysates and freeze-dried reactions for on-demand synthesis of desired glycoproteins. The protocol includes construction and culture of the bacterial chassis strain, cell-free lysate production, assembly of freeze-dried reactions, cell-free glycoprotein synthesis, and glycoprotein characterization, all of which can be completed in one week or less. We anticipate that cell-free technologies, along with this comprehensive user manual, will help accelerate development and distribution of glycoprotein therapeutics and vaccines.


Initiation patterns of monomorphic ventricular tachycardia in acute myocardial infarction: analysis of rhythm strips.
Monomorphic ventricular tachycardias (MVT) frequently occur in the acute phase of myocardial infarction (MI). In the past, some studies aimed to investigate the initiation pattern of ventricular tachycardias, although not in acute MI patients. The aim of the present study was to analyse the initiation pattern of MVT in acute MI using rhythm strips. This study utilized data on 255 rhythm strips defined as MVT, from 173 patients with acute ST-segment elevation MI. Monomorphic ventricular tachycardias that were not preceded by ventricular ectopic beats were defined as sudden onset MVT. Monomorphic ventricular tachycardias which were preceded by a single or multiple ectopic beats, including a short-long-short sequence, were defined as non-sudden onset MVT. Non-sudden onset episodes were more common than sudden onset episodes (172 episodes, 67.4% versus 83 episodes, 32.5%). The morphology of the ventricular ectopic beat initiating tachycardia was similar to the first beat of MVT in 127 episodes (73.8%), but not in the remaining 45 episodes (26.1%). In the non-sudden onset group, 117 episodes (68%) initiated with a single ectopic beat, while 55 episodes (32%) initiated with multiple complexes. The left ventricular ejection fraction of the patients with non-sudden onset MVT was lower (50 +/- 6 versus 56 +/- 5, P < 0.05). Monomorphic ventricular tachycardias with no sudden onset also had shorter coupling intervals (CI) (P < 0.001) and shorter prematurity index (PI) (P < 0.001) than MVT with sudden onset. Similarly, the ventricular tachycardia cycle length was shorter in the group of MVT subjects with non-sudden onset as compared with sudden onset (P < 0.05). In contrast, tachycardias with sudden onset were associated with a shorter preceding RR interval (P < 0.01). Analysis of rhythm strips demonstrated that MVT is most often preceded by ventricular ectopic beats in the acute phase of MI.


Effect of heated humidified high-flow nasal cannula (HFNC) oxygen therapy in dyspnea patients with advanced cancer, a randomized controlled clinical trial.
Heated humidified high-flow nasal cannula (HFNC) oxygen therapy is one of the most important oxygen therapy methods, which are commonly applied to relieve dyspnea in advanced cancer patients. Our study aims to observe the efficacy and safety of HFNC oxygen therapy on dyspnea patients with advanced cancer and explore the clinical application. Sixty subjects with advanced cancer requiring oxygen therapy from a grade 3, class A hospital in China were recruited and randomized (1:1) to traditional nasal catheter oxygen therapy or HFNC. Primary outcomes were dyspnea, oral dryness, and sleep condition, which were recorded after 72-h treatment. Secondary outcomes were heart rate (HR), respiration rate (RR), SpO2, PaO2, and PaCO2, which were recorded after 2, 6, 24, and 72 h treatment. Seventy-two hours after treatment, there were significant improvements in all primary outcomes (P < 0.001). PaO2 and RR were statistically changed 2 h after HFNC treatment (P < 0.001). PaCO2 and HR were statistically changed 24 h after HFNC treatment (P < 0.001). HFNC oxygen therapy has good effect, high safety, and is easy to be accepted by dyspnea patients with advanced cancer. It can be used as the first choice of oxygen therapy for these patients and has broad clinical prospects. This work was retrospectively registered in the Chinese Clinical Trials Registry (ChiCTR2100049582) on August 4, 2021.


Hydronephrosis and pelvic organ prolapse.
To determine the prevalence of hydronephrosis in a cohort of women who had undergone surgery for pelvic organ prolapse (POP). This observational, retrospective survey was conducted from January 2000 to December 2007 on 257 consecutive candidates for vaginal or abdominal surgical repair of POP (grade >2). In all patients, a standard clinical and instrumental urogynecologic workup was followed by POP repair. Follow-up visits were scheduled at 3, 6, and 9 months postoperatively and then annually. Preoperative hydronephrosis was found in 13 patients (5%) with a mean age of 69.2 +/- 6.6 years. It was moderate in 5 and severe in 8; bilateral in 8 (3.1%), monolateral in 5 (1.9%); and POP-related in 9 cases. Surgical POP repair resolved the prolapse all patients and cured the ureterohydronephrosis in 7, with moderate ectasia of the upper urinary tract persisting in 2. The renal function at diagnosis was normal in 12 of 13 patients with hydronephrosis (mean 113 +/- 15 micromol/L); 1 patient had a high serum creatinine concentration (220 micromol/L). No patient developed renal failure during a mean follow-up of 43.5 months. The prevalence of hydronephrosis was low in patients with POP who were candidates for surgery. POP repair usually resolves prolapse-related hydronephrosis and prevents serious long-term complications.


Synthesis, Characterization and Applications of Spinel Cobaltite Nanomaterials.
Recently, spinel structures (AB2O4) Nanoparticles (NPs) having binary and ternary mixtures of metal oxides have been established as promising redox catalysts. Due to the presence of two mixed valence metal cations, transport of electrons takes place easily between multiple transition-metal cations with relatively low energy of activation. Among these, spinel cobaltite (MCo2O4) is very attractive due to its low cost, non-toxicity, higher stability, higher electronic conductivity and electrochemical property. To date, MCo2O4 has been used in the fabrication of supercapacitors, electrodes for oxygen evolution reaction, and electrochemical sensors for glucose. A variety of MMCo2O4materials have been synthesized, characterized, and utilized in the fabrication of super capacitors, electrodes for oxygen evolution reaction, and electrochemical sensors for glucose. The progress in the field of the spinel MCo2O4 materials opens the door to novel and efficient applications in the nanoscience and nanotechnology, and elctrochemistry.


Distinct horizontal patterns in the spatial organization of superficial zone chondrocytes of human joints.
A better understanding of the unique cellular and functional properties of the superficial zone of articular cartilage may aid current strategies in tissue engineering which attempts a layered design for the repair of cartilage lesions to avert or postpone the onset of osteoarthritis. However, data pertaining to the cellular organization of non-degenerated superficial zone of articular cartilage is not available for most human joints. The present study analyzed the arrangement of chondrocytes of non-degenerated human joints (shoulder, elbow, knee, and ankle) by using fluorescence microscopy of the superficial zone in a top-down view. The resulting horizontal chondrocyte arrangements were tested for randomness, homogeneity or a significant grouping via point pattern analysis and were correlated with the joint type in which they occurred. The present study demonstrated that human superficial chondrocytes occurred in four distinct patterns of strings, clusters, pairs or single chondrocytes. Those patterns represented a significant grouping (p < 0.0001) with horizontal alignment. Each articular joint surface was dominated by only one of these four patterns (p < 0.001). Specific patterns correlated with specific diarthrodial joint types (p < 0.001). Further studies need to establish whether these organizational patterns are a consequence of their surrounding environment or whether they are linked to a functional purpose.


Characteristics of muscle fibers in rats with limb movements during sleep after spinal cord injury.
Previous studies have demonstrated that spinal cord injury (SCI) results in changes in sleep patterns through increased arousals and limb movements during sleep. Dramatic changes in muscle myosin heavy-chain isoforms have also been reported. The aim of this study was to investigate the characteristics of muscle fibers after SCI in rats with limb movements during sleep. Forty male Wistar rats were divided into four groups: SHAM, SCI 3, 7 and 15 days. Animals were subjected to electrode insertion surgery, 24-hour baseline sleep recording, SCI, and subsequent sleep recording for 3, 7, or 15 consecutive days. In addition, the gastrocnemius muscle and spinal cord were collected for histopathological/histochemical analyses. Our results indicate a rapid and progressive decrease in the cross-sectional area of type I fibers in the gastrocnemius muscle (35.76-24.74 μm(2)) after SCI. Additionally, we found SCI-induced changes in sleep patterns. Following SCI, we also observed limb movements in sleeping rats, as well as significant negative moderate correlations between type I fibers and limb movement. Our study strengthened the hypothesis by correlation between changes in types of muscle fiber (decline in type I fibers) and an increase in limb movements during sleep after SCI.


Tetraploid acute promyelocytic leukemia with double t(15;17) and PML/RARA rearrangements detected by fluorescence in situ hybridization analysis.
Acute promyelocytic leukemia (APL) is characterized by a serious hemorrhagic syndrome, unique morphologic findings, and its response to retinoids. Tetraploidy is a very rare chromosomal abnormality in acute myelocytic leukemia. This report presents a unique case of APL with a tetraploid clone characterized by two t(15;17) without other chromosomal changes, as well as PML/RARA rearrangements confirmed fluorescence in situ hybridization. The morphology of the blast cells was that of the classic M3 subtype, but the mean blast size exceeded that of control APL cases with diploidy. A chromosomal study revealed a 92,XXXX,t(15;17)(q22;q21)x2 karyotype in all 20 metaphase spreads. Despite all-trans-retinoic acid (ATRA) treatment and chemotherapy, leukemic cells persisted in the blood, and the patient died of an intracranial hemorrhage on the 16th day after admission.


PGE1 nebulisation during caesarean section for Eisenmenger's syndrome: a case report.
Eisenmenger's syndrome in pregnancy can lead to death in 50% to 65% of parturients. Expensive invasive monitoring and medication have improved management and outcomes. Cheaper alternatives for the management of high-risk patients who present with no prenatal care are still not available. We describe the obstetric anaesthesia management of a 34-year-old, 34-weeks pregnant woman who presented with a recent diagnosis of severe Eisenmenger's syndrome. A combined spinal epidural anaesthesia was used together with invasive cardiac monitoring as well as PGE1 nebulisation after delivery of the baby. This helped achieve a reduction of shunt, improvement of hypoxia and reduction of pulmonary pressures. We found this to be a cheaper and safe alternative in the management of such patients who present with no adequate prior management.


Serological survey for congenital toxoplasmosis among 4,136 pregnant women.
A prospective seroepidemiological survey for latent congenital toxoplasmosis was carried out among 4,136 women and 3,787 of their offspring in and around Montreal. The indirect immunofluorescent antibody test was used to titrate specific IgG and IgM antibodies and results were standardized in international units. The prevalence of antibodies was 40-8% for the mothers and 36-4% for the babies. Mean annual seroconversion rate was 0-95%. Thus, 30 women would have been expected to acquire toxoplasmosis during pregnancy: two cases only were observed and the reasons for it are discussed. Four cases of congenital toxoplasmosis were diagnosed serologically (0-1%), none of them showed any signs of illness. Preventive treatment was administered to 12 of 52 pregnant women suspected of a recently acquired infection.


Single-stage muscle flap reconstruction of major scrotal defects: report of two cases.
Major scrotal defect with exposed testes and/or spermatic cords are a challenge for the reconstructive surgeon. The bacterial flora of the perineum, difficulty of immobilisation and the contour of the testes make testicular cover a difficult task [Br. J. Plast. Surg. 41 (1988) 190]. Traditional approaches have used simple skin grafts or if not feasible, multi-staged procedures with initial burying of the testes under delayed medial thigh flaps. Better techniques then evolved to permit early single-staged coverage using flaps rather than skin grafts in these usually contaminated and unsuitable wounds to improve the cosmetic outcome of the reconstruction and reduce patient discomfort and hospital stay. Muscle flaps represent an excellent reconstruction option in the contaminated perineum especially in patients with impaired ability to deal with infection such as diabetic or toxic patients. We present two cases of reconstruction of the scrotum using simple, reliable single-stage muscle flap techniques with good aesthetic results and review the literature.


The value of micro-ELISA test in the diagnosis of Fasciola hepatica infection.
In sero-diagnosis of parasitic infection, it is essential to inspect cross-reactivity between the target parasite and other parasites in order to assess diagnostic performance. The aim of this study was to determine the cut-off value of antibody titer for diagnosis of F. hepatica (FH) infection by using the micro-ELISA and diagnostic performance of this test. The study population consisted of the following groups: FH group (n=42), Echinococcus granulosus (EG) group (n=27) and control group (n=33). The micro-ELISA test for detection of anti-F. hepatica antibody was performed in all groups. The test was positive in all patients with FH, in 3 out of 27 (11%) patients with EG and in none of the control group. Mean antibody titer was significantly higher in the FH group compared to the EG group (23.8 ± 0.9 DU vs. 5.7 ± 1.2 DU; p < 0.001) and compared to the control group (23.8 ± 0.9 DU vs. 2.4 ± 0.2 DU; p < 0.001). When we used 11,5 DU as a cut-off value for sero-diagnosis of FH, the positive predictive value was 93.3%, negative predictive value was 100%, sensitivity was 100%, and specificity was 95%. Cross-reactions are an important issue in serological diagnosis of parasitic infections. The micro-ELISA test for FH antibody can not definitely discriminate fascioliasis from hydatid disease.


Heterogeneity between triple negative breast cancer cells due to differential activation of Wnt and PI3K/AKT pathways.
The lack of a successful treatment for triple-negative breast cancer demands the study of the heterogeneity of cells that constitute these tumors. With this aim, two clones from triple negative breast MDA-MB-231 cancer cells were isolated: One with fibroblast-like appearance (F) and another with semi-epithelial (SE) morphology. Cells of the F clone have a higher migration and tumorigenesis capacity than SE cells, suggesting that these cells are in a more advanced stage of epithelial to mesenchymal transformation. In agreement, F cells have a diminished expression of the tight junction proteins claudins 1 and 4, and an increased content of β-catenin. The latter is due to an augmented activity of the canonical Wnt route and of the EGFR/PI3K/mTORC2/AKT pathway favoring the cytoplasmic accumulation of β-catenin and its transcriptional activity. In addition, F cells display increased phosphorylation of β-catenin at Tyr654 by Src. These changes favor in F cells, the over-expression of Snail that promotes EMT. Finally, we observe that both F and SE cells display markers of cancer stem cells, which are more abundant in the F clone.


Acute salivary gland enlargement following instrumentation of the upper airway.
A case of sudden enlargement of the submandibular and parotid salivary glands following endotracheal intubation is described. The literature concerning this condition is reviewed, and the possible causes are discussed.


Mechanisms of seed harvest by heteromyid rodents: soil texture effects on harvest rate and seed size selection.
Several lines of evidence show that soil texture plays an important role in the distribution of desert-dwelling heteromyid rodents. This is not surprising, since texture influences the energetic cost of digging burrows and of scratching at the soil surface to harvest buried seeds. Texture also may influence the efficiency with which seeds can be separated from the soil particles with which they are mixed. To explore mechanisms of "particle separation" by foraging heteromyids we measured seed harvest rates and size selection in the laboratory for a variety of seed sizes and soil textures. Harvest rate declined with increasing soil coarseness, and the preference for seeds of intermediate size that was apparent in fine soil disappeared when seeds were mixed with soil slightly coarser than the preferred seed size. In addition, there was evidence that particle separation efficiency is sensitive to the relative sizes of seeds and soil. A discontinity in the function relating harvest rate to soil texture occurred at finer soil textures for small seeds than for large seeds, suggesting that harvest techniques change once soil particle diameter equals or exceeds that of seeds. These results are consistent with the hypothesis that heteromyids use a combination of gravity-and rake-sorting mechanisms for particle separation.


Novel approach for the simultaneous detection of DNA from different fish species based on a nuclear target: quantification potential.
The development of DNA-based methods for the identification and quantification of fish in food and feed samples is frequently focused on a specific fish species and/or on the detection of mitochondrial DNA of fish origin. However, a quantitative method for the most common fish species used by the food and feed industry is needed for official control purposes, and such a method should rely on the use of a single-copy nuclear DNA target owing to its more stable copy number in different tissues. In this article, we report on the development of a real-time PCR method based on the use of a nuclear gene as a target for the simultaneous detection of fish DNA from different species and on the evaluation of its quantification potential. The method was tested in 22 different fish species, including those most commonly used by the food and feed industry, and in negative control samples, which included 15 animal species and nine feed ingredients. The results show that the method reported here complies with the requirements concerning specificity and with the criteria required for real-time PCR methods with high sensitivity.


Microcystins and anatoxin-a in Arctic biocrust cyanobacterial communities.
In the polar regions cyanobacteria are an important element of plant communities and represent the dominant group of primary producers. They commonly form thick highly diverse biological soil crusts that provide microhabitats for other organisms. Cyanobacteria are also producers of toxic secondary metabolites. In the present study we demonstrated that biocrust-forming cyanobacteria inhabiting the Kaffiøyra Plain, the north-west coast of Spitsbergen, are able to synthesize toxins, especially microcystins (MCs, from 0.123 to 11.058 μg MC-LR per g dry weight, DW) and anatoxin-a (ANTX-a, from 0.322 to 0.633 μg ANTX-a per g DW). To the best of our knowledge, this is the first report on the presence of ANTX-a in the entire polar region. The occurrence of cyanotoxins can exert a long-term impact on organisms co-existing in biocrust communities and can have far-reaching consequences for the entire polar ecosystem.


Experimental liver cirrhosis does not influence reproductive performance of female rats and development of hepatic biotransformation in their offspring.
Experimental hepatic cirrhosis was produced in virgin female Wistar rats by thioacetamide (TAA) administration with the drinking water from the 4th up to the 6th month of life. Mating occurred 31 +/- 3 d after cessation of TAA treatment. At the time the body mass of cirrhotic rats was not different from that of untreated controls. Body mass gain during pregnancy, length of gestation, litter size and body mass of the newborns were not influenced by experimental cirrhosis. Lactation seems to be slightly decreased in TAA-dams in the first 5 postnatal days, reflected by lower growth rates of TAA- and control-pups nursed by TAA- in comparison to control-dams. Somatic development (body mass) and hepatic biotransformation (ethylmorphine N-demethylation and ethoxycoumarin O-deethylation) were not different in the TAA- and control-offspring up to adulthood. Liver mass was enhanced in TAA-offspring at birth, but not any longer in 10-d-old and older rats.


Use of right lighting levels essential.
Hospital lighting must conform to a wide range of international standards. The purchaser of lights, ranging from bedside lamps to operating theatre units, is responsible for ensuring that a hospital's luminaires comply with relevant legislation. James Verrinder reports.


Pride or prejudice: does Phoenix flatter radiation therapy?
To compare disease-free survival (DFS) rates using a >0.4 ng/mL biochemical failure definition with the Phoenix (nadir+2 ng/mL) failure definition by analyzing a consecutive cohort of 1006 patients treated with low-dose-rate prostate brachytherapy (LDR-PB) monotherapy. Data for first 1006 consecutive LDR-PB implants (1998-2003) were extracted from a prospective database. Patients had low- (58%) or intermediate (42%)-risk disease. Three months neoadjuvant and 3 months concomitant androgen deprivation therapy were used in 65% of cases. The Phoenix definition was modified to "unfail" patients who had a benign prostate-specific antigen (PSA) bounce. The median followup is 7.5 years. The median PSA at latest followup for disease-free patients was 0.04 ng/mL. The Phoenix definition yielded 5- and 10-year Kaplan-Meier DFS estimates of 96.5 ± 1.2% and 93.7 ± 2.0%, respectively. Applying the >0.4 ng/mL threshold reduced these estimates to 94.4 ± 1.6% and 88.8 ± 3.0% (log rank, p = 0.015). Compared with Phoenix, applying a >0.4 ng/mL failure definition increased biochemical failure by ∼2% at 5 years and ∼5% at 10 years. These data show that Phoenix did not greatly exaggerate DFS estimates compared with a surgical-type threshold. However, this observation is a consequence of the exceptionally low residual PSA values characteristic of LDR-PB and cannot be generalized to other forms of radiation therapy.


Effect of Dietary Supplementation with Coarse or Extruded Oat Hulls on Growth Performance, Blood Biochemical Parameters, Ceca Microbiota and Short Chain Fatty Acids in Broiler Chickens.
The purpose of this study was to determine the effect of dietary supplementation with coarse or extruded oat hulls on growth performance, blood biochemistry, cecal microbiota, and short chain fatty acids (SCFA) in broiler chickens. Chickens were randomly allotted to four dietary treatments consisting of a corn-wheat-soybean meal-based diet (Basal), Basal + Bacitracin methylenedisalicylate (BMD), Basal +3% coarse OH (COH), and basal +3% extruded OH (EOH). Feed intake (FI), body weight gain (BWG), and feed conversion ratio (FCR) were recorded weekly. On day 36, eight chickens/treatment were euthanized, blood samples were collected, and organ weights were determined. Cecal digesta samples were collected for the determination of SCFA concentration and microbial DNA sequence. Data were subjected to ANOVA using the mixed procedure of SAS. Alpha diversity was estimated with the Shannon index, and the significance of diversity differences was tested with ANOVA. Birds fed COH and EOH had reduced (p < 0.05) BWG, but there was no effect of treatment on FCR. There was a significant increase (p = 0.0050) in relative gizzard empty weight among birds that were fed COH, compared to the other treatments. Dietary treatments had no effect on blood biochemical parameters and SCFA concentration. Cecal microbial composition of chickens was mostly comprised of Firmicutes and Tenericutes. Seven OTUs that were differentially abundant among treatments were identified. In conclusion, supplementation of broiler chickens' diets with 3% COH or EOH did not affect the FCR, blood biochemical parameters and SCFA concentration, but modified few cecal microbiota at the species level. Dietary supplementation with COH but not EOH significantly increased the relative gizzard weight.


Addition of insulin glargine or NPH insulin to metformin monotherapy in poorly controlled type 2 diabetic patients decreases IGF-I bioactivity similarly.
The aim of this study was to compare IGF-I bioactivity 36 weeks after the addition of insulin glargine (A21Gly,B31Arg,B32Arg human insulin) or NPH insulin to metformin therapy in type 2 diabetic patients who had poor glucose control under metformin monotherapy. In the Lantus plus Metformin (LANMET) study, 110 poorly controlled insulin-naive type 2 diabetic patients were randomised to receive metformin with either insulin glargine (G+MET) or NPH insulin (NPH+MET). In the present study, IGF-I bioactivity was measured, retrospectively, in 104 out of the 110 initially included LANMET participants before and after 36 weeks of insulin therapy. IGF-I bioactivity was measured using an IGF-I kinase receptor activation assay. After 36 weeks of insulin therapy, insulin doses were comparable between the G+MET (68 ± 5.7 U/day) and NPH+MET (71 ± 6.2 U/day) groups (p = 0.68). Before insulin therapy, circulating IGF-I bioactivity was similar between the G+MET (134 ± 9 pmol/l) and NPH+MET (135 ± 10 pmol/l) groups (p = 0.83). After 36 weeks, IGF-I bioactivity had decreased significantly (p = 0.001) and did not differ between the G+MET (116 ± 9 pmol/l) and NPH+MET (117 ± 10 pmol/l) groups (p = 0.91). At baseline and after insulin therapy, total IGF-I concentrations were comparable in both groups (baseline: G+MET 13.3 ± 1.0 vs NPH+MET 13.3 ± 1.0 nmol/l, p = 0.97; and 36 weeks: 13.4 ± 1.0 vs 13.1 ± 0.9 nmol/l, p = 0.71). Total IGF-I concentration did not change during insulin therapy (13.3 ± 0.7 vs 13.3 ± 0.7 nmol/l, baseline vs 36 weeks, p = 0.86). Addition of insulin glargine or NPH insulin to metformin monotherapy in poorly controlled type 2 diabetic patients decreases serum IGF-I bioactivity in a similar manner.


Angiolymphoid hyperplasia with eosinophilia: removal with carbon dioxide laser in a patient on chronic oral anticoagulants.
A patient with angiolymphoid hyperplasia with eosinophilia of the arm is described. In spite of anticoagulant therapy, successful surgical removal of the lesion was carried out with carbon dioxide laser excision and vaporization.


Single photon emission computed tomography in motor neuron disease with dementia.
Single photon emission computed tomography with [123 I] isopropylamphetamine was carried out on a patient with motor neuron disease with dementia. [123 I] uptake was decreased in the frontal lobes. This would reflect the histopathological findings such as neuronal loss and gliosis in the frontal lobes.


Synthesis and concentration dependent antibacterial activities of CuO nanoflakes.
We report, synthesis and antibacterial activities of CuO nanoflakes. CuO nanoparticles are prepared at room temperature through sol-gel method. X-ray diffraction studies show the particles are monoclinic (crystalline) in nature. Scanning electron microscopy (SEM) images clearly show that the prepared particles are flake like in structure. Fourier transform infrared (FTIR) spectra exhibits three different bands that correspond to the Au and Bu modes. Antibacterial studies were performed on Shigella flexneri, Staphylococcus aureus, Staphylococcus epidermidis, Salmonella typhimurium, Bacillus subtilis, Escherichia coli, Vibrio cholera, Pseudomonas aeruginosa and Aeromonas liquefaciens bacterial strains. Among these bacterial strains, S. flexneri and B. subtilis are most sensitive to copper oxide nanoparticles than the positive control (Penicillin G) and S. typhimurium strain shows the less sensitive. Results show that sensitivity is highly dependent on the concentrations of CuO nanoflakes.


Microenvironmental Interaction Between Hypoxia and Endothelial Cells Controls the Migration Ability of Placenta-Derived Mesenchymal Stem Cells via α4 Integrin and Rho Signaling.
Mesenchymal stem cells (MSCs) are a powerful source for cell therapy in degenerative diseases. The migration ability of MSCs is an important factor that enhances the therapeutic effect of the cells when they are transplanted into target tissues or organs. Hypoxia and the endothelial barrier, which are representative migration microenvironmental factors, are known to be regulated by the integrin-mediated pathway in several cancers. However, their regulatory mechanisms in MSCs remain unclear. Here, the objectives of the study were to compare the expression of markers related to integrin-mediated signaling in placenta-derived MSCs (PDMSCs) dependent on hypoxia and co-cultured with human umbilical vein endothelial cells (HUVECs) and to evaluate their correlations between migration ability and microenvironmetal factors including hypoxia and endothelial cells. The migration abilities of PDMSCs exposed to hypoxic conditions were significantly increased compared with normal fibroblasts (WI-38) and control (P < 0.05). Interestingly, decreased integrin α4 in PDMSCs under hypoxia induce to increase migration abilities of PDMSCs. Also, Rho family-related markers were significantly increased in PDMSCs under hypoxic conditions compared with normoxia (P < 0.05). Furthermore, the migration ability of PDMSCs was decreased by Rho kinase inhibitor treatment (Y-27632) and co-culturing with HUVECs in an ex vivo system. ROCK activity was increased by inhibiting integrin α4 with HUVECs and hypoxia compared with the absence of HUVECs and under normoxia. The findings suggest microenvironment event by hypoxia and the interaction with endothelial cells may be useful as a regulator of MSC migration and provide insight into the migratory mechanism of MSCs in stem cell-based therapy.


CoPhosK: A method for comprehensive kinase substrate annotation using co-phosphorylation analysis.
We present CoPhosK to predict kinase-substrate associations for phosphopeptide substrates detected by mass spectrometry (MS). The tool utilizes a Naïve Bayes framework with priors of known kinase-substrate associations (KSAs) to generate its predictions. Through the mining of MS data for the collective dynamic signatures of the kinases' substrates revealed by correlation analysis of phosphopeptide intensity data, the tool infers KSAs in the data for the considerable body of substrates lacking such annotations. We benchmarked the tool against existing approaches for predicting KSAs that rely on static information (e.g. sequences, structures and interactions) using publically available MS data, including breast, colon, and ovarian cancer models. The benchmarking reveals that co-phosphorylation analysis can significantly improve prediction performance when static information is available (about 35% of sites) while providing reliable predictions for the remainder, thus tripling the KSAs available from the experimental MS data providing to a comprehensive and reliable characterization of the landscape of kinase-substrate interactions well beyond current limitations.


Dictyostelium rDNA consists of non-chromosomal palindromic dimers containing 5S and 36S coding regions.
Restriction enzyme mapping of snap-back DNA has been used to show that the ribosomal DNA (rRNA genes and spacers) from Dictyostelium discoideum exists as 88 kb (kb=1,000 base pairs) linear palindromic dimers. Analysis of the mobility of total cell DNA in 0.15% agarose gels indicates that the majority of the rDNA is not covalently attached to chromosomal DNA.


[Prognostic significance of the Lauren classification of patients with stomach carcinoma. A statistical analysis of long-term results following gastrectomy].
To evaluate the prognostic difference between the 2 major histological types of Lauren classification in gastric cancer, data on patients who underwent the same surgical procedure -- total gastrectomy -- were studied. 124 consecutive total gastrectomy cases treated from 1979 to 1986 were classified according to Lauren retrospectively into 2 groups, comprising 63 patients (50.8%) with intestinal type carcinoma and 61 in another group of diffuse (n = 44, 35.5%) or mixed type (n = 17, 13.7%) carcinoma. In regard to extent of total gastrectomy the two groups were comparable (splenectomy 50 times and compartment II lymphadenectomy 43 times in the intestinal type group, vs 49 and 39 times in the diffuse or mixed type group). The proportion of males (42 men, 21 women) and older patients (mean: 62 years) was greater in the intestinal type group than in the group of diffuse or mixed type carcinoma (34 men, 27 women, mean: 57 years). According to TNM stage no significant difference was observed in local tumor infiltration (pT stage), lymph node metastases (pN) and distal metastases (pM) between the two groups at the time of surgery. The stages of disease (UICC 1987) were similar in the two groups: Stage I: intestinal type 25.4% (16/63), diffuse or mixed type 23% (14/61), stage II: 19% (12/63) vs 14.7% (9/61), stage III: 14.3% (9/63) vs 19.7% (12/61), stage IV: 41.3% (26/63) vs 42.6% (26/61). The hospital mortality was 9.5% (6/63) in the intestinal-type group and 8.5% (5/61) in the group of diffuse or mixed carcinoma (no significant difference).(ABSTRACT TRUNCATED AT 250 WORDS)


A Task-Technology-Identity Fit Model of Smartwatch Utilisation and User Satisfaction: A Hybrid SEM-Neural Network Approach.
Smartwatches are wearable devices intended to be smartphone companions that capture health data and ease access to notifications. They have also become personalisable standing as a fashion statement. This combination resulted in staggering adoption rates recently leading to question whether smartwatch users' choice and use satisfaction emerge from utility features or from its fashion characteristics. This paper proposes and validates a fit theory to investigate the antecedents of adopters' satisfaction. Besides evaluating fit with identity, the model assesses both perceived and actual task-technology fit of smartwatches. A questionnaire-based quantitative approach is used to collect data from about 300 smartwatch users in Qatar. To test the proposed model, data is analysed using structural equation modeling (SEM) and artificial neural networks (ANN). Furthermore, ANN sensitivity analysis ranks the importance of the fit factors affecting users' choice during pre- and post-adoption stages. Both task-technology and technology-identity fit factors are quasi-equally important in explaining 62% of satisfaction variance. ANN analysis revealed that post-adoption satisfaction is primarily attributed to smartwatches' ability to fit with users' identity and secondarily to its perceived fit with tasks. Nevertheless, pre-adoption choice of smartwatches is mainly guided by their functionality. This paper is the first to propose and validate an integrated task-technology-identity fit model to explain smartwatch utilization and users' satisfaction. The originality also lies in assessing actual task-technology fit and as perceived by users. Employing two modes of analysis revealed extra insights too.


Sex differences in symptoms of psychosis in a non-selected, general population sample.
Little is known about sex differences in psychosis beyond the borders of clinical disorder. A general population sample of 7,076 subjects was assessed using the Composite International Diagnostic Interview, in order to explore sex differences in the prevalence of any positive and negative symptoms of psychosis, and to examine to what degree any differences could be explained by differences in level of affective symptoms. Male sex was associated with higher prevalence of negative symptoms (OR = 1.6, 95% CI = 1.0, 2.5), independent of differences in affective symptoms and presence of DSM-III-R psychotic disorder. Women had higher rates of positive psychotic experiences (OR = 0.8, 95% CI = 0.7, 0.9), but this difference disappeared after adjustment for depressive symptoms (adjusted OR = 1.2, 95% CI = 0.9, 1.5). The sex differences in psychopathology that are seen in schizophrenia are expressed beyond the clinical phenotype, suggesting sex-dependent continuous and normal variation of several psychosis dimensions. The higher rates of positive psychotic experiences seen in women may be secondary to differences in the rate of affective symptoms.


A simple quantitative index of the P3 amylase isoenzyme in the diagnosis of acute pancreatitis.
Following a report (Legaz, M.E. and Kenny, M.A. (1976) Clin. Chem. 22, 57--62) that the amylase isoenzyme, P3, is elevated in acute pancreatitis but not in other conditions a new "P3 Index" is proposed. This reflects the ratio of the P3 isoenzyme to the major salivary isoenzyme, S1. The P3 Index eliminates the problems of peak overlap which prevent accurate detection or direct quantitation of P3. In acute pancreatitis a large increase in 3 produces a serum P3 Index of below 80%. Normal serum exhibits a P3 Index of above 80%. Most causes of hyperamylasaemia observed without acute pancreatitis also exhibited a P3 Index of above 80%. The P3 Index seems to be a useful aid to the diagnosis or exclusion of acute pancreatitis in patients exhibiting equivocal hyperamylasaemia.


New quinolone- and 1,8-naphthyridine-3-carboxamides as selective CB2 receptor agonists with anticancer and immuno-modulatory activity.
Several recent studies suggest that selective CB2 receptor agonists may represent a valid pharmacological approach in the treatment of various diseases due to the absence of relevant psychoactive side effect. In this study, we synthesized and tested a series of new quinoline-2(1H)-one- and 4-hydroxy-2-oxo-1,2-dihydro-1,8-naphthyridine derivatives characterized by a 4-methylcyclohexylamido substituent in position 3 of the heterocyclic nucleus with high CB2 receptor affinity and selectivity. Two compounds showing the best binding and selectivity profile behaved as a full agonist and a partial agonist at the CB2 receptor and induced a concentration-dependent decrease of cell viability on LNCaP, a prostatic cancer cell line expressing CB2 receptor. Moreover considering that the CB2 receptor is mainly expressed in cells and organs of the immune system, the same compounds were studied for their potential immune-modulatory and anti-inflammatory effects in activated lymphocytes isolated from healthy controls and multiple sclerosis (MS) patients.


Agility performance in healthy older adults is associated with handgrip strength and force development: results from a 1-year randomized controlled trial.
Handgrip strength is considered as important indicator for general fitness in older adults. However, it does not notably reflect adaptations from whole-body training but may reflect adaptions of multicomponent exercise training. These approaches seem to be more functional and related to relevant daily tasks. Effects of multicomponent agility training on handgrip strength are analysed. Healthy older adults (N = 79, 69.3 ± 4.4 years, 64% female) were randomly assigned to an intervention (IG) or control group (CG). IG took part in a twice weekly 60 min multicomponent agility training for 12 months. Adherence rate of the participants was 75 ± 10 %. Neither maximum handgrip strength (Fmax) differed between groups (IG: 318 ± 97 N, CG: 302 ± 92 N) nor did it change after the intervention (IG: 315 ± 90 N, CG: 301 ± 97 N). Mixed ANOVA for Fmax (F(1,49) = 0.018, p = 0.893) revealed no significant group × time interaction with an effect size of [Formula: see text]. Similar results were observed for rate of force development (RFD) (F(1,49) = 0.038, p = 0.847) with an effect size [Formula: see text] . RFD did not differ between groups in pre (IG: 876 ± 585 N/s, CG: 712 ± 303 N/s) and post (IG: 890 ± 424 N/s, CG: 702 ± 368 N/s) measurements. Correlation for ACE and Fmax (r(64) = - 0.367, p = 0.005) and for RFD (r(64) = - 0.487, p < 0.001) was found to be negative. A 1-year multicomponent agility training does not affect handgrip strength in healthy older adults. However, handgrip strength (Fmax and RFD) is associated with agility, thus both handgrip strength indicators and agility might serve as local and functional vitality surrogates.


Kinetochores and microtubules wed without a ring.
Proper chromosome segregation in mitosis requires tethering of spindle microtubules to the kinetochore. Using electron tomography of mammalian cells, McIntosh et al. (2008) now report the presence of fibrils that connect the inner kinetochore to the curved protofilaments at microtubule ends, suggesting a new model for force generation in chromosome movement.


Omicron BA.1 neutralizing antibody response following Delta breakthrough infection compared with booster vaccination of BNT162b2.
Longitudinal data are lacking to compare booster effects of Delta breakthrough infection versus third vaccine dose on neutralizing antibodies (NAb) against Omicron. Participants were the staff of a national research and medical institution in Tokyo who attended serological surveys on June 2021 (baseline) and December 2021 (follow-up); in between, the Delta-dominant epidemic occurred. Of 844 participants who were infection-naïve and had received two doses of BNT162b2 at baseline, we identified 11 breakthrough infections during follow-up. One control matched to each case was selected from boosted and unboosted individuals. We compared live-virus NAb against Wild-type, Delta, and Omicron BA.1 across groups. Breakthrough infection cases showed marked increases in NAb titers against Wild-type (4.1-fold) and Delta (5.5-fold), and 64% had detectable NAb against Omicron BA.1 at follow-up, although the NAb against Omicron after breakthrough infection was 6.7- and 5.2-fold lower than Wild-type and Delta, respectively. The increase was apparent only in symptomatic cases and as high as in the third vaccine recipients. Symptomatic Delta breakthrough infection increased NAb against Wild-type, Delta, and Omicron BA.1, similar to the third vaccine. Given the much lower NAb against Omicron BA.1, infection prevention measures must be continued irrespective of vaccine and infection history while the immune evasive variants are circulating.


Hydrogen peroxide- and cell-density-regulated expression of NADH-cytochrome b5 reductase in HeLa cells.
Environmental conditions regulate the expression of different antioxidant enzymes in cell culture. We have studied the effect of cell density and hydrogen peroxide on the expression of NADH-cytochrome b5 reductase in HeLa cells. Polypeptide levels of the NADH-cytochrome b5 reductase increased about three fold in confluent HeLa cells compared to sparse cells. Addition of H2O2 to HeLa cells altered expression levels of the NADH-cytochrome b5 reducatase in a concentration-dependent way, being sparse cells more sensitive to H2O2 addition than confluent cells. The presence of pyruvate, a H2O2 scavenger, produced a significant increment (200%) in the levels of NADH-cytochrome b5 reductase in sparse cells, but less increase (25%) in confluent cells, suggesting that generation of endogenous H2O2 could repress NADH-cytochrome b5 reductase expression, particularly in sparse cultures. Accordingly, confluent HeLa cells showed significantly lower levels of reactive oxygen species than cells in sparse cultures. Addition of tert-butylhydroquinone, a compound which generates reactive oxygen species through redox cycling, also reduced expression of the NADH-cytochrome b5 reductase. Increments in several antioxidant enzymes taking place during confluency could participate in the increase of NADH-cytochrome b5 reductase expression by reducing reactive oxygen species levels in cells. Overall, our results support that acute oxidative stress caused by H2O2 inhibits the expression levels of NADH-cytochrome b5 reductase, most likely due to inhibition of SP1 transcriptional activity. On the other hand, adaptation to H2O2 involved increased expression of the cytochrome b5 reductase, supporting the existence of additional regulatory mechanisms.


Exenatide.
Exenatide is an incretin mimetic. It improves glycaemic control via various glucoregulatory mechanisms, including glucose-dependent insulinotropism, suppression of inappropriately high glucagon levels, delayed gastric emptying and reduction of food intake. In three large, well designed, phase III trials in adults with type 2 diabetes mellitus and suboptimal glycaemic control despite treatment with metformin and/or a sulfonylurea, mean changes from baseline in glycosylated haemoglobin (HbA(1c)) significantly favoured subcutaneous exenatide 5 or 10microg twice daily over placebo after 30 weeks' treatment (primary endpoint). Relative to placebo, reductions from baseline in bodyweight were significantly greater with twice-daily exenatide 5microg (in two studies) or 10microg (in all three studies). Post hoc completer analyses revealed that the beneficial effects of exenatide on HbA(1c) and bodyweight were maintained for up to 82 weeks. Adjunctive therapy with subcutaneous exenatide 10microg twice daily improved glycaemic control to a similar extent as insulin glargine in patients with type 2 diabetes suboptimally controlled with metformin plus a sulfonylurea in a large, well designed, 26-week, phase III trial. Subcutaneous exenatide was generally well tolerated in patients with type 2 diabetes. The incidence of hypoglycaemia in patients receiving exenatide plus metformin was similar to that seen in placebo plus metformin recipients; however, in patients receiving a sulfonylurea (with or without metformin), the incidence of hypoglycaemia was numerically higher with exenatide than with placebo.


Electronic health record: design and implementation of a lab test request module.
The electronic health record (EHR) has become a fundamental tool in health care. The ordering and inclusion of lab tests and results is one of the most frequently requested services by EHR users. We have designed, developed and implemented in Andalusia, an autonomous community in the south of Spain (8.3 million inhabitants), a unified lab test request module for the Andalusian public health system EHR. After implementing the module in 27 laboratories, our objective is to assess its impact on healthcare activities and to ascertain whether its functional design addresses the needs and expectations of users. We surveyed laboratory and healthcare professionals to assess their opinion of the module's operation in daily practices and the effect it has had on pre- and post-analytical quality indicators (before and after lab test module implementation). All the laboratories surveyed noted that the implementation of the laboratory module in the EHR improved the analytical process, highlighting better safety in patient identification, less programming or container errors and shorter response times. Clinical professionals gave the module a rating of 7.8 out of 10, positively highlighting the speed at which results are delivered and their integration in the EHR. In terms of the model's drawbacks, laboratories have highlighted its rigidity in solving errors and clinical professionals have noted the requirement of adapting to a new nomenclature. It is also necessary to expand coding to all the tests available in clinical laboratories. The results of our survey indicate that the functional design of our analytical testing module is suitable for user needs, allowing to integrate information from multiple laboratories in a single region. Based on our experience, the key aspects for the success of this project have been: a design conceived for both laboratories and clinical professionals, the involvement of laboratories as a key element of the project, as well as sufficient time of local piloting before widespread implementation which is basic for the success of a computer application that affects so many potential users of the health care system.


Risk factors for osteoporosis in chronic schizophrenia on long-term treatment with antipsychotics: a cross-sectional study.
Little is known about the laboratory variable risks with bone mineral density (BMD) in patients with schizophrenia. This study was designed to fully investigate the related risk factors for decreased BMD in schizophrenia, as well as evaluate the gender difference of BMD. The BMD of the forearm of 211 patients (males/females = 140/71) who met the diagnostic criteria for DSM-5 schizophrenia was measured by dual-energy X-ray absorptiometry. Basic demographic information, clinical assessments, and laboratory variables (regarding nutrition, hormones, metabolism, and inflammatory markers) were comprehensively collected. Among 211 subjects, seventy-four (35%) patients had low BMD. Males had a significantly lower BMD T-score than females (P = 0.002). Multiple regression analyses showed that the independent risks with low BMD were lower folate, glycosylated hemoglobin levels, higher age, serum ferritin, and follicle-stimulating hormone (FSH) levels. In female patients, the BMD was mainly associated with age and serum hormones (FSH and testosterone), while the BMD of male patients was primarily related to age, microelements (serum ferritin and 25-OH-VD), and parathyroid hormone. Our study found several meaningful correlations between osteoporosis and schizophrenia, especially regarding laboratory measures, which may provide new clues to identifying or preventing osteoporosis in clinical patients.


Delivering monoclonal antibodies via inhalation: a systematic review of clinical trials in asthma and COPD.
Advances in understanding the pathophysiology of asthma and chronic obstructive pulmonary disease (COPD) led to investigation of biologic drugs targeting specific inflammatory pathways. No biologics are licensed for COPD while all the approved monoclonal antibodies (mAbs) for severe asthma treatment are systemically administered. Systemic administration is associated with low target tissue exposure and risk of systemic adverse events. Thus, delivering mAbs via inhalation may be an attractive approach for asthma and COPD treatment due to direct targeting of the airways. This systematic review of randomized control trials (RCTs) evaluated the potential role of delivering mAbs via inhalation in asthma and COPD treatment. Five RCTs were deemed eligible for a qualitative analysis. Compared to systemic administration, delivering mAbs via inhalation is associated with rapid onset of action, greater efficacy at lower doses, minimal systemic exposure, and lower risk of adverse events. Although some of the inhaled mAbs included in this study showed a certain level of efficacy and safety in asthmatic patients, delivering mAbs via inhalation is still challenging and controversial. Further adequately powered and well-designed RCTs are needed to assess the potential role of inhaled mAbs in the treatment of asthma and COPD.


Proteomic profiling and genome-wide mapping of O-GlcNAc chromatin-associated proteins reveal an O-GlcNAc-regulated genotoxic stress response.
O-GlcNAc modification plays critical roles in regulating the stress response program and cellular homeostasis. However, systematic and multi-omics studies on the O-GlcNAc regulated mechanism have been limited. Here, comprehensive data are obtained by a chemical reporter-based method to survey O-GlcNAc function in human breast cancer cells stimulated with the genotoxic agent adriamycin. We identify 875 genotoxic stress-induced O-GlcNAc chromatin-associated proteins (OCPs), including 88 O-GlcNAc chromatin-associated transcription factors and cofactors (OCTFs), subsequently map their genomic loci, and construct a comprehensive transcriptional reprogramming network. Notably, genotoxicity-induced O-GlcNAc enhances the genome-wide interactions of OCPs with chromatin. The dynamic binding switch of hundreds of OCPs from enhancers to promoters is identified as a crucial feature in the specific transcriptional activation of genes involved in the adaptation of cancer cells to genotoxic stress. The OCTF nuclear factor erythroid 2-related factor-1 (NRF1) is found to be a key response regulator in O-GlcNAc-modulated cellular homeostasis. These results provide a valuable clue suggesting that OCPs act as stress sensors by regulating the expression of various genes to protect cancer cells from genotoxic stress.


Rosiglitazone treatment increases subcutaneous adipose tissue glucose uptake in parallel with perfusion in patients with type 2 diabetes: a double-blind, randomized study with metformin.
We have shown that rosiglitazone increases whole-body and adipose tissue insulin sensitivity in humans. The aim of this study was to further examine whether possible changes in adipose perfusion could explain increased adipose tissue glucose uptake (GU). Thirty-seven patients with newly diagnosed type 2 diabetes were included. Patients were randomized into treatment with rosiglitazone, metformin, or placebo for 26 wk in a double-blinded trial. Femoral adipose flow and GU were measured with [15O]H2O, [18F]fluorodeoxyglucose and positron emission tomography during euglycemic hyperinsulinemia. Adipose masses were measured using magnetic resonance imaging. Metformin and rosiglitazone treatment improved glycemic control, but only rosiglitazone increased whole-body insulin sensitivity. Rosiglitazone treatment increased flow by 72% (P < 0.01) and GU by 23% (P < 0.05) and thereby decreased adipose tissue glucose extraction by 18% (P < 0.05); no changes were observed in the metformin or placebo-treated groups. When the adipose masses were taken into account, rosiglitazone treatment increased flow by 73% (P < 0.01) and GU by 24% (P < 0.05). During hyperinsulinemia, flow correlated with GU (r = 0.63; P < 0.01). In conclusion, s.c. GU is associated with flow in patients with type 2 diabetes. Rosiglitazone treatment enhances GU and flow but decreases glucose extraction, suggesting that perfusion may contribute to adipose tissue insulin sensitization by rosiglitazone.


Comparison of electrodiagnostic criteria for demyelination in patients with chronic inflammatory demyelinating polyneuropathy (CIDP).
This study compared sensitivity, specificity, positive and negative likelihood ratios (LR) of four previously published sets of electrodiagnostic criteria for demyelination in 64 patients whose history and physical examination indicated that chronic inflammatory demyelinating polyneuropathy was a possible diagnosis. Sensitivity of the sets of criteria ranged from 56-70 % and specificity from 85-98 %. Positive LRs ranged from 4.67-28 and negative LR's from 0.35-0.45. The results showed that one set of electrodiagnostic criteria was considerably more helpful than the other three in establishing the diagnosis CIDP. If, however, the test results of the sets were not consistent with demyelination, the effect of the negative test results on the probability of the diagnosis CIDP was similar for all four sets.


Testing the effect of specific orders to provide oral liquid nutritional supplements to nursing home residents: a quality improvement project.
To improve nursing home (NH) staff delivery of oral liquid nutritional supplements between meals to residents with a history of weight loss. Pre-Post intervention study. Two skilled nursing homes. Eighteen long term care residents. At baseline all participants had a non-specific physician's order to receive a nutritional supplement. The intervention consisted of specifying the physician's order as follows: "Give 4 oz high protein supplement at 10 am, 2 pm, and 7 pm". Research staff conducted direct observations for two days during and between meals for a total of 4 days, or 12 possible observation periods per participant before and one week following the intervention. Research staff documented NH staff delivery of snacks (including high protein supplements) and amount consumed (fluid ounces) for the high protein supplements using a standardized protocol during each observation period. Before the specific order was written participants were offered any type of snack an average of 1.82 times per day and a high protein supplement 0.59 times per day. After the specific order was written participants were offered any type of snack an average of 1.59 times per day and a high protein supplement 0.91 times per day. There were no statistically significant differences in the average number of times snacks or supplements were offered before and after the specific order was written. The proportion of snacks offered that were high protein supplements did increase after the specific order was written (p<0.001). When a high protein supplement was provided, most residents consumed 100% of it. Oral liquid nutritional supplements were not provided consistent with orders in NH practice. The specificity of the order related to type of supplement and time of delivery did not influence when and how often supplements are provided to residents but it did influence the type of nutritional supplement offered.


Effect of tortilla-preparation process on aflatoxins B1 and B2 in corn.
Naturally contaminated corn containing 450 and 54 ppb aflatoxins Bi and B2, respectively was treated with Ca(OH)2 for making tortillas. The cleaned corn and tortillas were analyzed for aflatoxins B1 and B2 by high performance liquid chromatography (HPLC) and confirmed by thin layer chromatography (TLC). The average concentrations of aflatoxins B1 and B2 in the final products (tortillas) were only 40% and 28% lower than that in starting materials (corn kernels), respectively. Aflatoxins G1 and G2 were not detected in either corn or tortilla samples.


[Angioscopic observation of the ruptured plaque cap in a patient with acute myocardial infarction with particular reference to the mechanism of plaque rupture].
A 45-year-old man was admitted with the diagnosis of acute inferior myocardial infarction. After successful thrombolytic therapy, coronary angiography showed TIMI grade 3 flow with the filling defect and haziness on the infarct-related coronary segment. Repeat coronary angiography and coronary angioscopy were performed on the 28th hospital day. Coronary angiography showed 50% stenosis of the luminal diameter of the right coronary artery. Coronary angioscopy showed a white plaque with ruptured cap which occupied one third of the circumferential coronary artery. The torn ends of the cap were longitudinal, and projected into the lumen during the cardiac cycle. Plaque rupture and thrombus formation are important in the pathogenesis of acute coronary syndromes, although the mechanism of plaque rupture is still controversial. The present angioscopic findings seem to support the concept that circumferential tension or mechanical stretch from part of the coronary artery causes the longitudinal fissure at the weakened site of the plaque cap.


Salmonella Bacteriophage Diversity According to Most Prevalent Salmonella Serovars in Layer and Broiler Poultry Farms from Eastern Spain.
The exploration of novel nonantibiotic interventions in the field, such as the use of bacteriophages, is necessary to avoid the presence of Salmonella. Bacteriophages are a group of viruses widely distributed in nature, strictly associated with the prokaryotic cell. Researchers have demonstrated the success of phage therapy in reducing Salmonella counts in poultry products. However, the impact that phage concentration in the environment may have against certain Salmonella serovars is not well understood. Therefore, the aim of this study was to assess Salmonella phage prevalence in commercial poultry farms in terms of the production type: layers or broilers. The most prevalent Salmonella serovars isolated in poultry production were used for phage isolation. Salmonella specific phages were isolated from 141 layer and broiler farms located in the Valencia region during 2019. Analysis of the samples revealed that 100% presented Salmonella phages, the most prevalent being against serovar S. Enteritidis (93%), followed by S. Virchow (59%), S. Typhimurium (55%), S. Infantis (52%) and S. Ohio (51%). These results indicate that poultry farms could represent an important source of Salmonella phages. Nevertheless, further studies are needed to assess the epidemiology of phages against other serovars present in other countries and their diversity from the point of view of molecular studies.


Competitive insulin autoantibody assay. Prospective evaluation of subjects at high risk for development of type I diabetes mellitus.
A quantitative fluid-phase radioassay for autoantibodies reacting with insulin (competitive insulin autoantibody assay, CIAA) was developed. The assay's features include 1) use of a physiologic amount of 125I-labeled insulin, 2) parallel incubations with supraphysiologic cold insulin (competitive), and 3) an incubation time of 7 days and a single-step multiple-wash polyethylene glycol separation. Mean +/- SE CIAA levels in 50 controls were 8 +/- 1.4 nU/ml (range -16-33.3). In 36 cytoplasmic islet cell antibody (ICA)-positive nondiabetic first-degree relatives of type I (insulin-dependent) patients less than 30 yr of age, CIAA levels exceeded the normal range in 20 (55.6%) of 36 (mean 86.8 +/- 17.1 nU/ml). In 26 ICA-positive relatives greater than 30 yr of age, only 5 (19.2%) of 26 exceeded the normal range (mean 26.1 +/- 9.4 nU/ml); P less than .001 compared with younger ICA-positive relatives). Six ICA-negative HLA-identical siblings of type I diabetic patients had normal CIAA levels (mean 3.6 +/- 5.8 nU/ml), and only 2 of 13 ICA-negative identical twins discordant for diabetes (mean 15.4 +/- 6.6 nU/ml) exceeded the normal range. Nine (50%) of 18 ICA-positive schoolchildren exceeded the normal range (mean 105.3 +/- 36.7 nU/ml). Genetically susceptible subjects negative for CIAA (with only 3 exceptions) remained negative for CIAA on multiple determinations (3 conversions observed), and CIAA levels of positive subjects were relatively stable. Linear regression of the first CIAA level versus last (interval between sampling 1 mo to 10 yr) in genetically susceptible individuals showed a highly significant correlation (r = .95, P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)


Elevated temperature (heat stress) in vitro reduces androstenedione and estradiol and increases progesterone secretion by follicular cells from bovine dominant follicles.
Dairy cattle are susceptible to heat stress-induced reductions in fertility; however, direct effects of hyperthermia on specific reproductive functions are difficult to determine in vivo. The objective of this experiment was to examine the effect of elevated temperature in vitro on follicular steroidogenesis, to gain insight into specific follicular responses associated with heat stress. Dominant follicles were obtained from Holstein heifers on day 6 post-estrus (luteal phase; n = 4) or day 8, 36 h after an injection with 25 mg PGF(2alpha) to induce regression of the corpus luteum (follicular phase; n = 4). Pieces of follicle wall were isolated from dominant follicles and cultured for 96 h with 0, 2 or 100 ng/ml LH or FSH at 37, 39 or 41 degrees C. Concentrations of androstenedione, estradiol and progesterone were determined in culture media collected every 24h. During the last 48 h of culture, basal secretion of androstenedione and estradiol by pieces of follicle wall was lower at 41 degrees C than at 37 or 39 degrees C (P < 0.05). In contrast, cumulative secretion of progesterone by pieces of follicle wall in medium alone was higher at 41 degrees C than at 37 or 39 degrees C (P < 0.05). Pieces of follicle wall responded to treatment with both low (2 ng/ml) and high (100 ng/ml) doses of gonadotropins at all temperatures. However, gonadotropin-induced secretion of androstenedione and estradiol was generally lower, whereas gonadotropin-induced secretion of progesterone was higher at 41 degrees C and sometimes at 39 than at 37 degrees C. The changes in basal steroidogenesis and in responses to gonadotropins suggest that follicular cells begin to luteinize at elevated temperatures in vitro. Premature luteinization of follicular cells in vivo has been associated with reduced fertility in cattle with persistent follicles, suggesting that the premature differentiation of follicular cells observed in the current study may be responsible, in part, for the reduced fertility of dairy cattle under heat-stressed conditions.


Nepeta menthoides Boiss. & Buhse freeze-dried aqueous extract versus sertraline in the treatment of major depression: A double blind randomized controlled trial.
Depression is the most common psychiatric disorder in the world. The conventional medications for depression, however, often have significant side effects. These adverse effects of conventional therapies, have motivated researchers to study alternative options including complementary and traditional treatments for solving the problem. To compare the efficacy of Nepeta menthoides Boiss. & Buhse freeze-dried aqueous extract with sertraline in the treatment of major depression. From April to September of 2015, 72 patients from two psychiatry clinics of Shiraz University of Medical Sciences who met the criteria for major depression based on the structured clinical interview as defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th edition, participated in a two-armed double-blind randomized controlled trial. Subjects were randomly assigned to receive Nepeta menthoides or sertraline for four weeks. Patients were evaluated in terms of the Beck Depression Inventory-II (BDI-II) total score and common side effects of medications at the base line, the second and fourth weeks, and two weeks following the intervention (i.e. in the sixth week). The mean changes in the Beck Depression Inventory scores in Nepeta menthoides group were significantly higher in terms of the BDI-II scores diminution as compared to that of the control (p≤0.001). Two weeks follow up after intervention showed a lower recurrence rate in the Nepeta menthoides group (p≤0.001). Nepeta menthoides may have potential benefits in the control of mood in patients suffering from major depression. Sustention of antidepressant effect and delay in the recurrence of depression could be considered worthwhile using this herb.


Hypoxic-ischemic brain injury activates early hippocampal stem/progenitor cells to replace vulnerable neuroblasts.
Although the phenomenon of ongoing neurogenesis in the hippocampus is well described, it remains unclear what relevance this has in terms of brain self-repair following injury. In a highly regulated developmental program, new neurons are added to the inner granular cell layer of the dentate gyrus (DG) where slowly dividing radial glial-like type 1 neural stem/progenitors (NSPs) give rise to rapidly proliferating type 2 neural progenitors which undergo selection and maturation into functional neurons. The induction of these early hippocampal progenitors after injury may represent an endogenous mechanism for brain recovery and remodeling. To determine what role early hippocampal progenitors play in remodeling following injury, we utilized a model of hypoxic-ischemic injury on young transgenic mice that express green fluorescent protein (GFP) specifically in neural progenitors. We demonstrate that this injury selectively activates programmed cell death in committed but immature neuroblasts, which is followed by proliferation of both early type 1 and later type 2 progenitors. This subsequently leads to newly generated neurons becoming stably incorporated into the DG.


Susceptibility of immortalized porcine kidney macrophages to porcine reproductive and respiratory syndrome virus-2 infection.
Porcine reproductive and respiratory syndrome virus (PRRSV) displays restricted tropism to porcine alveolar macrophages in nature. Meanwhile, non-porcine cell lines derived from African green monkey kidney cell lines are permissive to PRRSV, resulting in their widespread use in PRRSV research. Furthermore, genetically modified cell lines expressing receptors targeted by PRRSV have been established. We previously established porcine immortalized kidney-derived macrophages (IPKMs) that maintained typical macrophage function. In the present study, we demonstrated the advantages of IPKMs for PRRSV research. IPKMs expressed receptors for PRRSV such as CD163 and CD169. The efficiency of virus isolation from field biological samples was higher for IPKMs than for MARC-145 cells. Five different clusters of North American type PRRSV were propagated in IPKMs. Four field strains continuously produced progeny viruses during 10 continuous passages. The efficiency of virus isolation from field biological samples and continuous progeny virus production in the sequential passages using IPKMs indicated that these cells are good vessels for PRRSV research.


How do people perceive different advice for rotator cuff disease? A content analysis of qualitative data collected in a randomised experiment.
To explore how people perceive different advice for rotator cuff disease in terms of words/feelings evoked by the advice and treatment needs. We performed a content analysis of qualitative data collected in a randomised experiment. 2028 people with shoulder pain read a vignette describing someone with rotator cuff disease and were randomised to: bursitis label plus guideline-based advice, bursitis label plus treatment recommendation, rotator cuff tear label plus guideline-based advice and rotator cuff tear label plus treatment recommendation. Guideline-based advice included encouragement to stay active and positive prognostic information. Treatment recommendation emphasised that treatment is needed for recovery. Participants answered questions about: (1) words/feelings evoked by the advice; (2) treatments they feel are needed. Two researchers developed coding frameworks to analyse responses. 1981 (97% of 2039 randomised) responses for each question were analysed. Guideline-based advice (vs treatment recommendation) more often elicited words/feelings of reassurance, having a minor issue, trust in expertise and feeling dismissed, and treatment needs of rest, activity modification, medication, wait and see, exercise and normal movements. Treatment recommendation (vs guideline-based advice) more often elicited words/feelings of needing treatment/investigation, psychological distress and having a serious issue, and treatment needs of injections, surgery, investigations, and to see a doctor. Words/feelings evoked by advice for rotator cuff disease and perceived treatment needs may explain why guideline-based advice reduces perceived need for unnecessary care compared to a treatment recommendation.


Are surgical masks manufactured from sterilisation wrap safe?
Due to regional shortages some health services have proposed using surgical masks manufactured from sterilisation wrap. However, there has been little assessment of the safety of this practice. Therefore, we developed our own prototypes and evaluated whether they met regulatory standards. Surgical mask prototypes were manufactured from two thickness grades of commercial sterilisation wrap. Safety was assessed in the context of regulatory standards. As it was not previously reported, we developed and performed differential pressure and synthetic blood penetration resistance experiments in accordance with official methodology. Bacterial filtration efficiency was comparable between sterilisation wrap and commercial surgical masks. Both prototypes met regulatory standards for synthetic blood resistance, whilst only our thinner mask fulfilled acceptable differential pressure ('breathability') thresholds. Acceptable barrier and breathability properties can be achieved with surgical masks produced from sterilisation wrap. Therefore, this may be a reasonable method to supplement stock if required. Unless there are shortages mandating alternatives, health-care workers should always use approved personal protective equipment.


Single Lung Transplantation With Concomitant Cardiac Surgery in a Patient With Cystic Fibrosis: A Case Report.
Cystic fibrosis is a congenital, progressive disease affecting many organs. It frequently leads to severe respiratory failure, which can be treated by means of a double lung transplantation. Single lung transplantation is justified only in certain cases. This is a case report describing a 20-year-old female patient who became the recipient of a single lung transplant as a result of cystic fibrosis. The transplant was performed during cardiothoracic surgery, which included an intervention in the right atrium. At the age of 14, the patient underwent left pneumonectomy. In addition, the patient had a percutaneous endoscopic gastrostomy placed and a vascular port implanted. During preoperative evaluation, she presented with clinical symptoms of chronic respiratory failure. The patient was approved for lung transplantation at the age of 16. After 2 years on the national lung transplant waiting list, in 2018, the patient underwent right lung transplantation and removal of numerous thrombi in the right atrium during 1 procedure. This surgery was accomplished with the use of extracorporeal circulation, which is an extracorporeal membrane oxygenator combined with cardiopulmonary bypass. The patient was discharged 3 weeks after the procedure in good general condition. Presently, her pulmonary function is excellent and she presents with normal respiratory capacity. Patients with cystic fibrosis often require double lung transplantation. Under normal circumstances, performing only a single lung transplantation would be considered medical malpractice. However, in certain cases, a single lung transplant is a life-saving procedure.


Study on crack evolutional behavior of rocks in triaxial compression based on colony growth dynamics model.
The crack propagation behavior of rock during compression involves complex mechanisms. Describing the growth behavior of a large number of cracks with conventional mechanical models is a major challenge. Therefore, in this work, we propose a new method to describe crack growth behavior by considering crack bodies as free voxels that can expand and coalesce within a rock sample according to certain rules. Specifically, we first propose a crack growth model that quantitatively describes the crack growth ratio and crack growth rate, which are integrally related to the loading rate, internal friction angle, cohesion, initial porosity, and confining stress. Second, to avoid the complex analytical process of the traditional mechanical model in solving the propagation directions of multiple cracks, we introduce a method for determining the crack growth directions of shearing failure based on the colony growth assumption. This method defines the crack propagation direction as a synthetic vector of the inertial direction, the attractive direction, the Coulomb direction, and the edge direction. Moreover, a new mathematical description method of fracture energy and plastic energy is proposed to calculate the crack growth at each time step. The simulation results show that our crack growth model for shearing failure agrees well with the experimental results and explains the fracture behavior and transformation law of cracks to some extent.


News & Notes: Effect of Surfactants on Cellulase Production by Nectria catalinensis
The effect of different nonionic surfactants (Tween 80, Tween 20, Triton X-100) and polyethylene glycol (PEG 6000) was tested on cellulolytic enzyme system production. Tween 80 gave the highest yield of endoglucanase, exoglucanase, and cellobiase at the 20th day of growth, presumably by causing increased permeability of cell membranes and/or by promoting the release of cell-bound enzymes. Maximal yield of endoglucanase was achieved with 1.7 mM Tween 80, whereas exoglucanase and cellobiase were at 0.85 mM. In the same way, this compound increased fungal growth. On the other hand, Tween 20 and Triton X-100 inhibited growth and cellulolytic enzyme production. High yields of endoglucanase and exoglucanase were achieved with PEG 6000 in comparison with the control, presumably by increasing enzyme stability.


8-OH-DPAT in the median raphe nucleus decreases while in the medial septal area it may increase anxiety in female rats.
The experiment evaluated the effects of 8-OH-DPAT on the activity of virgin female rats (diestrus) in the elevated plus maze. The 5-HT1A receptor agonist was infused into the median raphe nucleus (N = 60) and medial septal area (N = 68) 10 min before the test. Five groups for each brain area were analyzed: intact, saline (0.2 microl) and 8-OH-DPAT (0.2; 0.5 and 2.0 microg rat(-1)). The following measures were recorded: number of entries onto open and enclosed arms and time spent on the open and enclosed arms. In addition, the frequency of stretch-attend and head-dipping were also evaluated. The results showed that in the median raphe nucleus only the highest dose of 8-OH-DPAT (2.0 microg) increased the percentage of time spent on the open arms. On the other hand, in medial septal area 8-OH-DPAT in the dose of 0.5 microg decreased the percentage of time spent on the open arms, while the doses of 0.2 and 2.0 microg had no significant impact on anxiety. Data suggest that 8-OH-DPAT acting on 5-HT1A somatodendritic autoreceptors decreases anxiety. However, at a specific dosage and acting on postsynaptic receptors of the medial septal area, 8-OH-DPAT can increase anxiety.


[The french school of public health (FSPH): III. Disease prevention and screening].
The ongoing epidemiological transition is characterized by the increasing predominance of degenerative diseases. New responses from the health system are thus needed, reorganizing curative services as well as preventive strategies. The latter have to target risk factors for degenerative disease in order to improve primary prevention. And for all other diseases with unknown or non-modifiable risk factors, screening (or secondary prevention) is an option to be considered as a public health response. Early diagnosis and early treatment can improve the prognosis of patients screened in defined conditions. Although medical screening is generally well accepted by health professionals, screening is rather sophisticated and encounters substantial difficulties when implemented in the real world. This article briefly presents the main theoretical and practical drawbacks of early diagnosis. Screening will substantially improve health if the knowledge and skills of healthcare professionals are substantially increased.


[Meniscus and cartilaginous lesions. Influence of the delay between ACL injury and ligament reconstruction in 40-year-old patients].
Anterior cruciate ligament (ACL) reconstruction is increasingly proposed for patients aged over 40 years. We report a retrospective analysis of a consecutive series of middle-aged patients who underwent ACL reconstruction surgery in order to analyze the development of meniscal and cartilage lesions and ascertain short-term outcome. Thirty-five patients aged over 40 years (mean 46.1 years) underwent hamstring ACL reconstruction, 19 for persistent instability after functional treatment and 16 after a recent tear in patients who wanted to resume their sports activities. Mean follow-up was 25 months. The IKDC 1993 score was noted as was the Arpege score for sports activity and Telos at 15 and 25kg. At the last follow-up, the IKDC score was A or B in 85% of patients. Among the first intention ligamentoplasties, 94% were scored A or B at last follow-up and all had a single leg jump test greater than 76%. Among patients operated on after failure of functional treatment, 79% were scored A or B (p>0.05) and 32% had a single leg jump test less than 75% (p<0.05). Intraoperative discovery of meniscal or cartilage damage was statistically less significant in first intention patients than after failure of functional treatment. Somewhat less than half of the active and motivated patients aged over 40 years who underwent a first intention operation were unable to resume their sports activities at the same level. However, patients who underwent ACL repair after failure of functional treatment unexpectedly recovered sports activities after an interruption of several months or even years. Age is not a barrier to ACL reconstruction. The time from injury to surgery is a prognostic factor predictive of meniscal and osteochondral damage. Early repair of the ACL preserves the knee's meniscal and cartilaginous stock. For active motivated patients aged over 40 years, who undergo a first-intention procedure, resumption of sports activities at the same level cannot be guaranteed after ACL. However, for patients who undergo surgery after failure of functional treatment, ACL reconstruction not only eliminates the troublesome laxity but also enables resumption of sports activities even after several months or years of interruption.


Subjective and objective indicators of neighbourhood safety and physical activity among UK adolescents.
The health benefits of regular physical activity in adolescence are well-documented and many health-related behaviours are established in adolescence. The neighbourhood environment is a key setting for physical activity for adolescents and feeling unsafe in their neighbourhood may be a potential barrier to physical activity. This study aimed to examine associations between neighbourhood safety and physical activity using objective and subjective measures for both. Participants (n = 10,913) came from the Millennium Cohort Study, a nationally representative UK longitudinal birth cohort. Linear regression and Zero Inflated Poisson models were used to examine associations between subjective and objective indicators of safety (self-reported safety, Index of Multiple Deprivation crime, Reported Crime Incidence) and physical activity (self-reported weekly and device-measured physical activity). Adolescents who feel unsafe in their neighbourhood, or who live in areas with high IMD crime or violent crime rates report 0.29 (95% CI -0.49, -0.09) 0.32 (95% CI -0.47, -0.16) and 0.20 (95% CI -0.39, -0.20) fewer days of physical activity, respectively. No associations were found between Reported Crime Incidence and either objective or subjective measures of physical activity. This study demonstrates varying associations between subjective safety and objective crime with physical activity levels in adolescence, highlighting the complexities around subjective and objective measurements and their associations with health outcomes.


Midmembranous vocal fold lamina propria proteoglycans across selected species.
We examined the proteoglycan (PG) and associated sulfated glycosaminoglycan (GAG) content of the midmembranous vocal fold lamina propria (LP) of humans, dogs, pigs, and ferrets. The LP PG levels were assessed indirectly by quantifying the associated sulfated GAGs, and immunohistochemical analyses of specific PGs and/or GAGs (PGs/GAGs) were conducted. Sulfated GAGs constituted approximately (average +/- SEM) 14.7 +/- 2.1 microg per milligram of tissue total protein in the human LP--similar to levels in canine, porcine, and ferret LPs (p > .05). Immunohistochemical analysis identified versican, chondroitin 4- and 6-sulfate, and heparan sulfate in the LP extracellular matrix--PGs/GAGs previously believed to be localized only intracellularly and in the basement membrane. Observations of PG/GAG staining patterns resulted in identification of microstructurally based subdivisions of canine, porcine, and ferret LPs. The sulfated GAG concentration in human LP was similar to that of dermis. In contrast to the interspecies similarity in LP sulfated GAG levels, immunohistochemical analysis indicated notable interspecies differences in specific PG/GAG distributions. Moreover, spatial variations in the presence of several PGs/GAGs were observed--variations that may be integral in maintaining normal LP physiology. Finally, the noted canine, porcine, and ferret LP subdivisions may yield insight into the adaptation of LP microstructure to the phonatory needs of each species.


A giant intrathoracic osteolipoma: A case report and review of the literature.
Lipomas are ubiquitous and can occur anywhere in the body. Intrathoracic lipomata are rare benign lesions. However, a complete removal giant intrathoracic osteolipoma is achieved with only 18 cases previous cases described in medical literature from 1960 to 2008. A 66-year-old female presented to our hospital suffered from mild chest pain and mild shortness of breath for more than 10 days. A subsequent chest X-ray and CT scans revealed a large homogeneous, low-attenuation fat density mass containing an oval calcification area in the center of the mass. Following surgical resection was performed successfully to remove the entire mass, which weighed a total of 1568g and measured 26cm×19cm×12cm in size. The histological analysis confirmed a giant intrathoracic osteolipoma without evidence of malignancy. Intrathoracic lipomas are rare, slow-growing benign tumors without any symptom, which originate from the adipose tissue in submesothelial layers of the pleura parietalis, diaphragm, mediastinal and extrapericardial. They may extend into the chest cavity and fully encapsulate in most cases. Chest X-ray and CT and MRI scans are the most helpful tests in the diagnosis of intrathoracic lipomas. Complete enbloc removal of lipoma whenever possible, is the only definitive treatment option and the only way to prevent future recurrences. This case is the largest intrathoracic osteolipoma documented in the modern literature. Complete enbloc removal of lipoma whenever possible, is the only definitive treatment option.


Improving Biodegradation of Clofibric Acid by Trametes pubescens through the Design of Experimental Tools.
Clofibric acid (CLF) is the main pharmacologically active metabolite in composition of the pharmaceutical products used for controlling blood lipid content. This xenobiotic compound is highly persistent in the aquatic environment and passes unchanged or poorly transformed in wastewater treatment plants. A white-rot fungal strain of Trametes pubescens was previously selected, for its ability for clofibric acid biodegradation (up to 30%) during cultivation in submerged system under aerobic conditions at an initial CLF concentration of 15 mg L-1. Plackett-Burman design (PBD) and response surface methodology (RSM) were used for experimental planning, mathematical modelling and statistical analysis of data of the biotechnological process of CLF biotransformation by Trametes pubescens fungal strain. After optimization, the capacity of the selected Trametes pubescens strain to degrade CLF was increased by cultivation in a liquid medium containing 3 g·L-1 yeast extract, 15 g·L-1 peptone, 5 g·L-1 glucose and mineral salts, inoculated at 2% (v/v) vegetative inoculum and cultivated at pH 5.5, during 14 days at 25 °C and 135 rpm. In these optimized biotechnological conditions, the CLF biotransformation yield was 60%.


Assessing Listeria monocytogenes growth kinetics in rice pudding at different storage temperatures.
Rice pudding is a popular artisanal dairy dessert highly consumed in the main rice-producing countries, including Egypt. This study aimed to evaluate and model the growth of Listeria monocytogenes in rice pudding dessert stored at different temperatures (4-25 °C) over its shelf-life. Lab-scale rice pudding samples were prepared following a traditional Egyptian recipe and inoculated with a three-strain cocktail of L. monocytogenes (ca. 3 × 102 cfu/g). Inoculated rice pudding samples (pH = 6.67 ± 0.06 and aw = 0.99 ± 0.002) were stored at different isothermal conditions (4, 8, 12, 18, and 25 °C) and microbiologically analysed for up to 30 days for pathogen quantification by plate count methodology. Global regression analysis was used to fit the Baranyi model coupled with the Ratkowsky model to growth data, relating L. monocytogenes concentrations (N, log cfu/g) with storage temperature (°C) and times (d). Model validation was performed using published independent data. L. monocytogenes growth potential increased by increasing storage temperature. The estimated Ratkowsky model parameters were b = 0.0819 ± 0.0017 log cfu/d·°C and Tmin = -3.28 ± 0.20 °C. The indices RMSE = 0.39 and R2adj = 0.97 indicated a good agreement between the experimental data and the model predictions. The estimated maximum growth rate (μmax) values ranged between 0.355 and 5.363 log cfu/d from 4 to 25 °C. The model was successfully validated using published L. monocytogenes Scott A and California strains growth data in rice pudding samples stored at 5, 12 and 22 °C, as evidenced by the assessed statistical indices. The predictive model developed and validated in this study will aid in decision-making regarding the microbiological safety of rice pudding dessert with respect to L. monocytogenes growth, considering a wide range of storage temperatures.


Use of social media platforms by migrant and ethnic minority populations during the COVID-19 pandemic: a systematic review.
Migrants and ethnic minority groups have been disproportionately impacted by COVID-19 and have lower levels of vaccine uptake in some contexts. We aimed to determine the extent and nature of social media use in migrant and ethnic minority communities for COVID-19 information, and implications for preventative health measures including vaccination intent and uptake. A systematic review of published and grey literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched databases including Embase, Web of Science, PubMed NIH, CINAHL, facilitated through the WHO Global Research on COVID-19 database from 31 December 2019 to 9 June 2021. Research reporting the use of social media by migrants and/or ethnic minority groups in relation to COVID-19. We extracted data on key outcomes, study design, country, population under study and sample size. 1849 unique records were screened, and 21 data sources were included, including populations in the UK, USA, China, Jordan, Qatar and Turkey. We found evidence of consistent use of a range of social media platforms for COVID-19 information in some migrant and ethnic minority populations (including WeChat, Facebook, WhatsApp, Instagram, Twitter, YouTube), which may stem from difficulty in accessing COVID-19 information in their native languages or from trusted sources. Some evidence suggested circulating misinformation and social media use may be associated with lower participation in preventative health measures, including vaccine intent and uptake, findings which are likely relevant to multiple population groups. Social media platforms are an important source of information about COVID-19 for some migrant and ethnic minority populations. Urgent actions and further research are now needed to better understand effective approaches to tackling circulating misinformation, and to seize on opportunities to better use social media platforms to support public health communication and improve vaccine uptake. This study has been registered with PROSPERO (CRD42021259190).


Ubiquitous expression of human SCA2 gene under the regulation of the SCA2 self promoter cause specific Purkinje cell degeneration in transgenic mice.
The objective of this work was the generation of an animal model of the SCA2 disease for future studies on the benefits of therapeutic molecules and neuropathological mechanisms that underline this human disorder. The transgenic fragment was microinjected into pronuclei of B6D2F1 X OF1 mouse hybrid strain. For Northern blots, RNAs were hybridized with a human cDNA fragment from the SCA2 gene and a mouse beta-actin cDNA fragment. Monoclonal antibody directed to the N-terminal of the ataxin 2 protein with 22Q was used for Western blot analysis. A rotating rod apparatus was utilized to measure motor coordination of mice. Immunohistochemical detection of Purkinje neurons was performed with anti-calbindin 28K as primary antibody. Ubiquitous expression of the SCA2 transgene with 75 CAG repeats regulated by the SCA2 self promoter was obtained after generation of our transgenic mice. Analysis of transgenic mice revealed significant differences of motor coordination compared with the wild type littermates. Specific degeneration of Purkinje neurons and transgene over-expression in the brain, liver and skeletal muscle, rather than in lungs and kidneys was also observed, resembling the expression pattern of the ataxin 2 in humans.


Effect of stretch frequency on osteogenesis of periodontium during periodontal ligament distraction.
Periodontal ligament distraction (PDLD) can accelerate orthodontic tooth movement (OTM). However, the effect of stretch frequency on osseous formation during PDLD remains unclear. Here, we sought to identify the effect of PDLD frequency on the osteogenic remodelling of the periodontium. (i) In vitro, five human periodontal ligament stem cell (PDLSC) cultures were randomized to either static conditions or exposure to a cyclic stretch force involving 12% deformation at frequencies of 0.3, 0.5, 0.7 or 1.0 Hz for 12 h, and the osteogenic differentiation of PDLSCs was assessed using Western blotting. (ii) In vivo, 18 beagle dogs underwent orthodontic distalization of bilateral maxillary first premolars. In the test groups, PDLD was performed at a frequency of two or six times/day, while Ni-Ti coil springs were applied to mimic traditional OTM in the control group. The amount of OTM and histological staining was estimated after force loading for 5, 10 and 15 days. (i) In vitro, the expression of osteogenic-specific markers (runt-related transcription factor 2 [Runx2], type I collagen [COL-I] and osteocalcin [OCN]) increased with the frequency of tensile force, to a peak at 0.7 Hz. (ii) In vivo, both PDLD groups displayed a greater rate of OTM and a higher bone metabolism than the control group. The expression of COL-I and OCN was significantly reinforced in the six times/day-PDLD group in comparison to the two times/day-PDLD group. The cyclic stretch force enhances osteogenesis of the periodontium in a frequency-dependent manner.


ALD coated polypropylene hernia meshes for prevention of mesh-related post-surgery complications: an experimental study in animals.
In this work, thermal atomic layer deposition (ALD) was used to synthesize vanadium (V)-doped TiO2thin nanofilm on polypropylene (PP) hernia meshes. Multiple layers of (Al2O3+ TiVOx) nano-films were coated on the PP hernia mesh surface to provide a layer with a total thickness of 38 nm to improve its antibacterial properties, thereby, prevent mesh-related post-surgery complications. Highly conformal V-doped TiO2nanofilm were deposited on PP mesh at a temperature of 85 °C. Rats and rabbits have been used to evaluate the tissue reaction on coated PP hernia meshes and biomechanical testing of the healed tissue. Five rabbits and ten rats have been implanted with ALD coated and uncoated (control) PP meshes into the back of rats and abdominal wall of rabbits. Histology of the mesh-adjacent tissues and electron microscopy of the explanted mesh surface were performed to characterize host tissue response to the implanted PP meshes. The effect of V-doped TiO2coating on a living organism and fibroblast functions and bacterial activities were studied. The present results indicated that ALD coating improves adhesion properties and exhibited enhanced antibacterial activity compared to uncoated PP mesh. It was shown that V-doped TiO2coatings were highly effective in inhibitingS. aureusandE. coliadhesion and exhibited excellent antibacterial activity. We found that V-doping of TiO2, unlike bare TiO2, allows generated and further procured strong redox reactions which effectively kills bacteria under visible light. We have reported comparative analysis of the use of undoped (bare) TiO2and V-doped TiO2as a coating for PP meshes and their action in biological environment and preventing biofilms formation compared with uncoated PP meshes. The PP meshes coated with V-doped TiO2showed significantly lower shrinkage rates compared with an identical PP mesh without a coating. We have shown that ALD coatings provide non-adhesive and functional (antibacterial) properties.


Effective analgesia with low-dose ketamine and reduced dose hydromorphone in ED patients with severe pain.
We assessed the analgesic effect and feasibility of low-dose ketamine combined with a reduced dose of hydromorphone for emergency department (ED) patients with severe pain. This was a prospective observational study of adult patients with severe pain at an urban public hospital. We administered 0.5 mg of intravenous (IV) hydromorphone and 15 mg of IV ketamine, followed by optional 1 mg hydromorphone IV at 15 and 30 minutes. Pain intensity was assessed at 12 intervals over 120 minutes using a 10-point verbal numerical rating scale (NRS). Patients were monitored throughout for adverse events. Dissociative side effects were assessed using the side effects rating scale for dissociative anesthetics. Of 30 prospectively enrolled patients with severe pain (initial mean NRS, 9), 14 reported complete pain relief (NRS, 0) at 5 minutes; the mean reduction in NRS pain score was 6.0 (SD, 3.2). At 15 minutes, the mean reduction in NRS pain score was 5.0 (SD, 2.8). The summed pain intensity difference and percent summed pain intensity difference scores were 25 (95% confidence interval [CI], 21-30) and 58% (95% CI, 49-68) at 30 minutes and 41 (95% CI, 34-48) and 50% (95% CI, 42-58) at 60 minutes, respectively. Most patients (80%) reported only weak or modest side effects. Ninety percent of patients reported that they would have the medications again. No significant adverse events occurred. Low-dose ketamine combined with a reduced dose hydromorphone protocol produced rapid, profound pain relief without significant side effects in a diverse cohort of ED patients with acute pain.