Impact of colonoscopy on health-related quality of life: findings from the RECEDE study.

BACKGROUND: Colonoscopy is a valuable diagnostic tool but the procedure and the preparation for it cause anxiety and discomfort that impacts on patients' health-related quality of life (HRQoL). The 'disutility' of undergoing an invasive colonoscopy needs to be considered and accounted for in comprehensive cost-utility analyses that compare different diagnostic strategies, yet there is little empirical evidence that can be used in such studies. To fill this gap, we collected and analysed data on the effect of a colonoscopy examination on patients' HRQoL that can be used in economic evaluations. METHODS: Patients scheduled to undergo a colonoscopy at a large NHS hospital were asked to complete the EuroQol EQ-5D-5 L instrument: (i) before the procedure, at the time of consent (T1), (ii) while undergoing bowel preparation (T2) and (iii) within 24 h after the procedure (T3). Complete responses were translated into preference-based HRQoL (utility) values using a UK-specific value set and were analysed using descriptive and inferential statistical analyses. RESULTS: Two-hundred and seventy-one patients with gastrointestinal symptoms referred for a colonoscopy provided complete EQ-5D-5 L questionnaires at all three assessment points. At T1, the mean EQ-5D-5 L value was 0.76 (95%CI: 0.734-0.786). This value dropped to 0.727 at T2 (95%CI: 0.7-0.754, before increasing again to 0.794 (95%CI: 0.768-0.819) at T3. Both changes were statistically significant (p-value < 0.001). CONCLUSIONS: Preference-based HRQoL (utility) values reported by patients undergoing a colonoscopy dropped during bowel preparation and rose again shortly after the colonoscopy. This pattern was largely consistent across patients with different characteristics, symptoms and diagnoses.

Nematicidal Property of Clindamycin and 5-hydroxy-2-methyl Furfural (HMF) from the Banana Endophyte Bacillus velezensis (YEBBR6) Against Banana Burrowing Nematode Radopholus similis.

Radopholus similis is a burrowing nematode which causes banana toppling disease and is of major economic threat for the banana production. Bacterial endophyte Bacillus velezensis (YEBBR6) produce biomolecules like 5-hydroxy-2-methyl furfural (HMF) and clindamycin in during interaction with Fusarium oxysporum f.sp. cubense. Molecular modelling and docking studies were performed on Radopholus similis protein targets such as calreticulin, cathepsin S-like cysteine proteinase, ß-1,4 -endoglucanase, reticulocalbin, venom allergen-like protein and serine carboxypeptidase to understand the mode of action of HMF and clindamycin against Radopholus similis. Structurally validated protein targets of R. similis were docked with biomolecules through AutoDock Vina module in PyRx 0.8 software to predict the binding energy of ligand and target protein. Among the chosen six targets, docking analysis revealed that clindamycin had the maximum binding affinity for ß-1,4-endoglucanase (- 7.2 kcal/mol), reticulocalbin (- 7.5 kcal/mol) and serine carboxypeptidase (- 6.9 kcal/mol) in comparison with HMF and the nematicide, carbofuran 3G. Besides, clindamycin also had the maximum binding energy for the target sites calreticulin and venom allergen-like protein compared to the small molecule HMF. Novel molecule, clindamycin produced by B. velezensis served as a potential inhibitor of the target sites associated in interrupting the functions of ß-1,4-endoglucanase, reticulocalbin, serine carboxypeptidase, calreticulin, cathepsin S-like cysteine proteinase, and venom allergen-like proteins. Besides, increased binding affinity of clindamycin with the protein target sites facilitated to explore it as a novel nematicidal molecule for the management of banana burrowing nematode R. similis. Thus, present investigation confirmed that, the small molecules clindamycin can be explored for nematicidal activity. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-022-01011-2.

Antiviral activity of basidiomycetous fungi against Groundnut bud necrosis virus in tomato.

Tomato is an important vegetable crop which is severely affected by Groundnut bud necrosis virus (GBNV). Until now effective antiviral agents have not been reported for the management of necrosis disease caused by GBNV. Therefore, a study was undertaken to manage the necrosis disease caused by GBNV using culture filtrate of basidiomycetous fungi viz., Coprinopsiscinerea, Ganoderma lucidum and Lentinula edodes. In vitro studies were conducted in the indicator host cowpea and primary host tomato in glasshouse under insect proof condition; co-inoculation spraying of culture filtrate of Ganoderma lucidum at 0.1% concentration reduced the lesion numbers and inhibited the virus population build-up when compared to inoculated control in the indicator host cowpea upto 77.83%. DAC-ELISA test was performed to quantify the virus titre, indicated reduced virus titre in co- inoculation spray of culture filtrate of G. lucidum treated cowpea with OD value 0.17 ± 0.01 at 405 nm and in tomato plants 0.14 ± 0.01 respectively. The viral copy numbers were quantified by qPCR. About 2.0 × 101 viral copy numbers were observed in tomato plants treated with G. lucidum (co-inoculation) which was lesser than untreated inoculated control plants (2.4 × 108). In order to identify the antiviral properties of G. lucidum, GCMS analysis was carried out and we found the triterpenoid compound Squalene. This is the first study to analyse and confirm the antiviral activity of G. lucidum against a plant virus.

The modern implementation of patient blood management (PBM) in Malaysia: the use of intravenous iron in severe anaemia with iron deficiency - A Case Report.

Anaemia is a common condition in Malaysia, and is mostly due to iron deficiency. In many cases, allogeneic blood transfusion (ABT) is administered unnecessarily to treat anaemia. Patient blood management (PBM) is a concept whereby a patient becomes his or her "own blood bank", instead of receiving ABT. The concept encompasses three pillars namely optimising erythropoiesis, minimising blood loss and harnessing human physiological reserve. We present a safe and fruitful outcome of managing severe anaemia without utilising any ABT, made possible with the PBM approach including administration of intravenous iron.

A low-power, high-speed, 9-channel germanium-silicon electro-absorption modulator array integrated with digital CMOS driver and wavelength multiplexer.

We demonstrate the first germanium-silicon C-band electro-absorption based waveguide modulator array and echelle-grating-based silicon wavelength multiplexer integrated with a digital CMOS driver circuit. A 9-channel, 10Gbps SiGe electro-absorption wavelength-multiplexed modulator array consumed a power of 5.8mW per channel while being modulated at 10.25Gbps by 40nm CMOS drivers delivering peak-to-peak voltage swings of 2V, achieving a modulation energy-efficiency of ~570fJ/bit including drivers. Performance up to 25Gbps on a single-channel SiGe modulator and CMOS driver is also reported.

Neutron scattering and neural-network quantum molecular dynamics investigation of the vibrations of ammonia along the solid-to-liquid transition.

Vibrational spectroscopy allows us to understand complex physical and chemical interactions of molecular crystals and liquids such as ammonia, which has recently emerged as a strong hydrogen fuel candidate to support a sustainable society. We report inelastic neutron scattering measurement of vibrational properties of ammonia along the solid-to-liquid phase transition with high enough resolution for direct comparisons to ab-initio simulations. Theoretical analysis reveals the essential role of nuclear quantum effects (NQEs) for correctly describing the intermolecular spectrum as well as high energy intramolecular N-H stretching modes. This is achieved by training neural network models using ab-initio path-integral molecular dynamics (PIMD) simulations, thereby encompassing large spatiotemporal trajectories required to resolve low energy dynamics while retaining NQEs. Our results not only establish the role of NQEs in ammonia but also provide general computational frameworks to study complex molecular systems with NQEs.

Colorectal cancer diagnostic biomarkers: Beyond faecal haemoglobin.

Colorectal cancer (CRC) is the third most common cancer worldwide, and the second commonest cause of cancer deaths worldwide. One of the most important prognostic factors, and thus a potential target for improving cancer care, is the stage of cancer at diagnosis. Earlier stage diagnosis is associated with better prognosis and longer survival times after treatment. At the same time, the use of targeted therapies and immunotherapy is improving CRC outcomes. Diagnostic biomarkers are key to both early detection and prediction of treatment responses. Currently faecal immunochemical testing for haemoglobin is perhaps the most widespread CRC diagnostic biomarker. However other biomarkers are approved for clinical use and others are in the validation stage of research prior to clinical use. This review focuses on these the evidence behind these biomarkers, their current and potential future use.

Power-efficient III-V/silicon external cavity DBR lasers.

We report the design and characterization of external-cavity DBR lasers built with a III-V-semiconductor reflective-SOA with spot-size converter edge-coupled to SOI waveguides containing Bragg grating mirrors. The un-cooled lasers have wall-plug-efficiencies of up to 9.5% at powers of 6 mW. The lasers are suitable for making power efficient, hybrid WDM transmitters in a CMOS-compatible SOI optical platform.

Wide bandwidth, low loss 1 by 4 wavelength division multiplexer on silicon for optical interconnects.

We demonstrate an add/drop filter based on coupled vertical gratings on silicon. Tailoring of the channel bandwidth and wavelength is experimentally demonstrated. The concept is extended to implement a 1 by 4 wavelength division multiplexer with 6 nm channel separation, 3 nm bandwidth, a flat top response with < 0.8 dB ripple within the 3 dB passband, 1 dB insertion loss and 16 dB crosstalk suppression. The device is ultracompact, having a footprint < 2 X 10(-9)/2.

Molecular modelling of coat protein of the Groundnut bud necrosis tospovirus and its binding with Squalene as an antiviral agent: In vitro and in silico docking investigations.

Bud blight disease caused by groundnut bud necrosis virus (GBNV) is a serious constraint in the cultivation of agricultural crops such as legumes, tomato, chilies, potato, cotton etc. Owing to the significant damage caused by GBNV, an attempt was made to identify suitable organic antiviral agents through molecular modelling of the nucleocapsid Coat Protein of GBNV; molecular docking and molecular dynamics that disclosed the interaction of the ligands viz., Squalene and Ganoderic acid-A with coat protein of GBNV. Invitro inhibitory effect of Squalene and Ganoderic acid-A was examined in comparison with different concentrations, against GBNV in cowpea plants under glasshouse condition. The different concentrations of Squalene (50, 100, 150, 250 and 500 ppm) tested in vitro resulted in reduction of lesion numbers (1.69 cm2) as well as reduced virus titre in co-inoculation spray. The present study suggests the antiviral activity of Squalene by effectively fitting into binding site of coat protein of GBNV with favourable hydrophilic as well as strong hydrophobic interactions thereby challenging and blocking the binding of viral replication RNA with coat protein and propagation. The present organic antiviral molecules will be helpful in development of suitable eco-friendly formulations to mitigate GBNV infection disease in plants.

Mining the Genome of Bacillus velezensis VB7 (CP047587) for MAMP Genes and Non-Ribosomal Peptide Synthetase Gene Clusters Conferring Antiviral and Antifungal Activity.

Chemical pesticides have an immense role in curbing the infection of plant viruses and soil-borne pathogens of high valued crops. However, the usage of chemical pesticides also contributes to the development of resistance among pathogens. Hence, attempts were made in this study to identify a suitable bacterial antagonist for managing viral and fungal pathogens infecting crop plants. Based on our earlier investigations, we identified Bacillus amyloliquefaciens VB7 as a potential antagonist for managing Sclerotinia sclerotiorum infecting carnation, tobacco streak virus infecting cotton and groundnut bud necrosis infecting tomato. Considering the multifaceted action of B. amyloliquefaciens VB7, attempts were made for whole-genome sequencing to assess the antiviral activity against tomato spotted wilt virus infecting chrysanthemum and antifungal action against Fusarium oxysporum f. sp. cubense (Foc). Genome annotation of the isolate B. amyloliquefaciens VB7 was confirmed as B. velezensis VB7 with accession number CP047587. Genome analysis revealed the presence of 9,231,928 reads with an average read length of 149 bp. Assembled genome had 1 contig, with a total length of 3,021,183 bp and an average G+C content of 46.79%. The protein-coding sequences (CDS) in the genome was 3090, transfer RNA (tRNA) genes were 85 with 29 ribosomal RNA (rRNA) genes and 21 repeat regions. The genome of B. velezensis VB7 had 506 hypothetical proteins and 2584 proteins with functional assignments. VB7 genome had the presence of flagellin protein FlaA with 987 nucleotides and translation elongation factor TU (Ef-Tu) with 1191 nucleotides. The identified ORFs were 3911 with 47.22% GC content. Non ribosomal pepide synthetase cluster (NRPS) gene clusters in the genome of VB7, coded for the anti-microbial peptides surfactin, butirosin A/butirosin B, fengycin, difficidin, bacillibactin, bacilysin, and mersacidin the Ripp lanthipeptide. Antiviral action of VB7 was confirmed by suppression of local lesion formation of TSWV in the local lesion host cowpea (Co-7). Moreover, combined application of B. velezensis VB7 with phyto-antiviral principles M. Jalapa and H. cupanioides increased shoot length, shoot diameter, number of flower buds per plant, flower diameter, and fresh weight of chrysanthemum. Further, screening for antifungal action of VB7 expressed antifungal action against Foc in vitro by producing VOC/NVOC compounds, including hexadecanoic acid, linoelaidic acid, octadecanoic acid, clindamycin, formic acid, succinamide, furanone, 4H-pyran, nonanol and oleic acid, contributing to the total suppression of Foc apart from the presence of NRPS gene clusters. Thus, our study confirmed the scope for exploring B. velezensis VB7 on a commercial scale to manage tomato spotted wilt virus, groundnut bud necrosis virus, tobacco streak virus, S. sclerotiorum, and Foc causing panama wilt of banana.

Two replication fork remodeling pathways generate nuclease substrates for distinct fork protection factors.

Fork reversal is a common response to replication stress, but it generates a DNA end that is susceptible to degradation. Many fork protection factors block degradation, but how they work remains unclear. Here, we find that 53BP1 protects forks from DNA2-mediated degradation in a cell type-specific manner. Fork protection by 53BP1 reduces S-phase DNA damage and hypersensitivity to replication stress. Unlike BRCA2, FANCD2, and ABRO1 that protect reversed forks generated by SMARCAL1, ZRANB3, and HLTF, 53BP1 protects forks remodeled by FBH1. This property is shared by the fork protection factors FANCA, FANCC, FANCG, BOD1L, and VHL. RAD51 is required to generate the resection substrate in all cases. Unexpectedly, BRCA2 is also required for fork degradation in the FBH1 pathway or when RAD51 activity is partially compromised. We conclude that there are multiple fork protection mechanisms that operate downstream of at least two RAD51-dependent fork remodeling pathways.

Diagnosis of anomalous origin of left coronary artery from pulmonary artery in an adult by 64-slice CT angiography.

Anomalous origin of Left Coronary Artery from Pulmonary Artery (ALCAPA) presenting in adult age is a rare entity. We report an adult patient with exertional angina, who was diagnosed to have ALCAPA conclusively and non-invasively by 64-slice CT angiography.

Effect of Headspace and Trapped Volatile Organic Compounds (VOCs) of the Chinese Caterpillar Mushroom, Ophiocordyceps sinensis (Ascomycetes), against Soil-Borne Plant Pathogens.

Headspace volatile metabolites produced by Ophiocordyceps sinensis were tested against soil-borne plant pathogens (namely, Fusarium oxysporum f. sp. lycopersici, F. oxysporum f. sp. cubense, Thanatephorus cucumeris, Athelia rolfsii, and Macrophomina phaseolina). Diffusible volatile metabolites produced by O. sinensis inhibited 52% and 48% of the mycelial growth of F. oxysporum f. sp. lycopersici and F. oxysporum f. sp. cubense, respectively. In addition to inhibiting mycelial growth, the headspace volatile metabolites also induced several morphological changes in the culture characteristics and mycelia of the tested fungi. Stunted and depressed colony growth was observed for F. oxysporum f. sp. cubense and F. oxysporum f. sp. lycopersici. The headspace volatile compounds produced by O. sinensis were trapped in a glass cartridge (Porapak Q). The trapped compounds were eluted from the column by using hexane and then, by using gas chromatography-mass spectrometry, were identified as tetratetracontane, 1(2H)-naphthalenone, 3, 4-dihydro-3-methyl, 3-hexenoic acid, 1-methyl-3-ethyladamantane, and phenol, 3-ethyl.

Nutlin-3a Nanodisks Induce p53 Stabilization and Apoptosis in a Subset of Cultured Glioblastoma Cells.

Nanodisks (ND) are ternary complexes of phospholipid, one or more hydrophobic bioactive agents and an apolipoprotein scaffold. These nanoscale assemblies are organized as a disk-shaped lipid bilayer whose perimeter is stabilized by an apolipoprotein scaffold. Solubilization of hydrophobic bioactive agents is achieved by their integration into the ND lipid milieu. When the cis-imidazoline, nutlin-3a, was incubated with phosphatidylcholine and apolipoprotein A-I, it was conferred with aqueous solubility as judged by spectroscopic analysis. Nondenaturing polyacrylamide gel electrophoresis yielded evidence of a homogeneous population of ND particles ~9 nm in diameter. Gel filtration chromatography experiments revealed the association of nutlin-3a with ND is reversible. Biological activity of nutlin-3a ND was examined in three distinct glioblastoma cell lines, U87MG, SF763 and SF767. Incubation of U87MG cells with nutlin-3a ND induced concentration-dependent cell growth arrest and apoptosis. SF763 cells demonstrated modest cell growth arrest only at high concentrations of nutlin-3a ND and no apoptosis. SF767 cells were unaffected by nutlin-3a ND. Immunoblot analysis revealed nutlin-3a ND induced time-dependent stabilization of the master tumor suppressor, p53, and up regulation of the E3 ubiquitin ligase, murine double minute 2 in U87MG cells, but not the other glioma cell lines. The nanoscale size of the formulation particles, their facile assembly and nutlin-3a solubilization capability suggest ND represent a potentially useful vehicle for in vivo administration of this anti-tumor agent.

PAM-4 Signaling over VCSELs with 0.13microm CMOS Chip Technology.

We present results for VCSEL based links operating PAM-4 signaling using a commercial 0.13microm CMOS technology. We perform a complete link analysis of the Bit Error Rate, Q factor, random and deterministic jitter by measuring waterfall curves versus margins in time and amplitude. We demonstrate that VCSEL based PAM-4 can match or even improve performance over binary signaling under conditions of a bandwidth limited, 100meter multi-mode optical link at 5Gbps. We present the first sensitivity measurements for optical PAM-4 and compare it with binary signaling. Measured benefits are reconciled with information theory predictions.

Chromosome and interphase analysis of placental mosaicism in intrauterine growth retardation.

Confined placental mosaicism is found in a higher percentage of cases of unexplained intrauterine growth retardation (IUGR) than in those of normal pregnancies. To test this hypothesis of cytogenetically abnormal placental cells associated with IUGR, we identified patients in whose fetuses IUGR was suspected during the antepartum period by clinical and serial ultrasonography and Doppler examinations and confirmed by immediate neonatal physical examination. At birth placental biopsy samples and cord blood were collected and coded. Similar specimens were obtained from non-IUGR pregnancies during that period to avoid bias in evaluation of results. These specimens were processed for standard cytogenetic studies and fluorescent in situ hybridization (FISH) of interphase cells to detect any chromosomal mosaicism in a double-blind fashion. Results were obtained on 26 IUGR placentas. Of these placentas, 22 were cytogenetically normal on standard karyotype analysis and interphase fluorescent studies. Four placentas were shown to have some chromosomal aneuploidy: one with the same chromosome anomaly in multiple cells and the other with multiple single-cell aneuploidy. Of these placentas, cytogenetic and FISH studies showed one to have a monosomy 21 cell line, two placentas showed mosaicism on karyotyping, which was not confirmed by FISH, and one placenta had a suggested chromosomal instability. All placentas had normal anatomy regardless of the chromosome findings and no chromosome anomalies were seen in any of the infants. Non-IUGR placentas showed no chromosomal-confined mosaicism and all had normal findings on placental pathologic examination.

A scalable optoelectronic neural system using free-space optical interconnects.

The design of a scalable, fully connected 3-D optoelectronic neural system that uses free-space optical interconnects with silicon-VLSI-based hybrid optoelectronic circuits is proposed. The system design uses a hardware-efficient combination of pulsewidth-modulating optoelectronic neurons and pulse-amplitude-modulating electronic synapses. Low-area, high-linear-dynamic-range analog synapse and neuron circuits are proposed. SPICE circuit simulations and an experimental demonstration of the free-space optical interconnection system are included.

Morbidity and mortality of diabetes with surgery.

The prevalence of Type 2 diabetes mellitus (T2DM) has increased; as a result the number of patients with T2DM undergoing surgical procedures has also increased. This population is at high risk of macrovascular (cardiovascular disease, peripheral vascular disease) or microvascular (retinopathy, nephropathy or neuropathy) complications, both increasing their perioperative morbidity and mortality. Diabetes patients are more at risk of poor wound healing, respiratory infection, myocardial infarction, admission to intensive care, and increased hospital length of stay. This leads to increased inpatient costs. The outcome of perioperative glycaemia management remains a significant clinical problem without a universally accepted solution. The majority of evidence on morbidity and mortality of T2DM patients undergoing surgery comes from the setting of cardiac surgery; there was less evidence on noncardiac surgery and bariatric surgery. Bariatric surgery is increasingly performed in patients with severe obesity complicated by T2DM, but is distinguished from general surgery as it immediately improves the glucose homeostasis postoperatively. The improvements in glycaemia are thought to be independent of weight loss and this requires different postoperative management. Patients usually have to follow specific preoperative diets which lead to improvement in glycaemia immediately before surgery. Here we review the available data on the mortality and morbidity of patients with T2DM who underwent elective surgery (cardiac, non-cardiac and bariatric surgery) and the current knowledge of the impact that preoperative, intraoperative and postoperative glycaemic management has on operative outcomes.

La prevalencia de la diabetes mellitus tipo 2 (DM2) ha incrementado en los últimos años, y como resultado, el número de pacientes con DM2 sometidos a procedimientos quirúrgicos también ha aumentado. Esta población posee un alto riesgo de complicaciones macrovasculares (enfermedad cardiovascular, enfermedad vascular periférica) o microvasculares (retinopatía, nefropatía o neuropatía), ambos incrementan tanto la mortalidad como la morbilidad perioperatoria de estos pacientes. Los pacientes con diabetes tienen un mayor riesgo de una mala cicatrización de las heridas, infección respiratoria, infarto de miocardio, ingreso en la UCI y mayor duración de la estancia hospitalaria. Todo esto incrementa los costes de tratamiento de este tipo de pacientes. El control de la glucemia perioperatoria sigue siendo un importante problema clínico sin una solución universalmente aceptada. La mayoría de los conocimientos sobre la morbilidad y mortalidad de los pacientes con DM2 sometidos a cirugía proviene de la de la cirugía cardíaca, y algunos, aunque menos, de la cirugía no cardiaca y cirugía bariátrica. La cirugía bariátrica se realiza cada vez más en pacientes con obesidad mórbida complicado con diabetes tipo 2, y se diferencia de la cirugía general en que inmediatamente mejora la homeostasis de la glucosa tras la operación. Las mejoras en el control de la glucemia parecen ser independientes de la pérdida de peso y esto requiere un manejo postoperatorio diferente. Los pacientes por lo general tienen que seguir dietas específicas preoperatorias que conducen a la mejora de la glucemia inmediatamente antes de la cirugía. En este artículos revisamos los datos disponibles sobre la mortalidad y la morbilidad de los pacientes con diabetes tipo 2 sometidos a cirugía (cirugía cardíaca, no cardíaco y bariátrica) y el conocimiento actual de los efectos preoperatorios, intraoperatorios y postoperatorios que el control de la glucemia tiene sobre los resultados operatorios.

Dual-scale topology optoelectronic processor.

The dual-scale topology optoelectronic processor (D-STOP) is a parallel optoelectronic architecture for matrix algebraic processing. The architecture can be used for matrix-vector multiplication and two types of vector outer product. The computations are performed electronically, which allows multiplication and summation concepts in linear algebra to be generalized to various nonlinear or symbolic operations. This generalization permits the application of D-STOP to many computational problems. The architecture uses a minimum number of optical transmitters, which thereby reduces fabrication requirements while maintaining area-efficient electronics. The necessary optical interconnections are space invariant, minimizing space-bandwidth requirements.