A study of hospitalized COVID-19 patients with AKI in a setting of multiracial developing country.

BACKGROUND: The commonest indication for hospitalization in COVID-19 patients is hypoxemia or severe respiratory symptoms. However, COVID-19 disease may result in extrapulmonary complications including kidney-related pathology. The reported incidence of renal involvement related to COVID infection varies based on geographical location. OBJECTIVE: This study aimed to assess the incidence rate of AKI in hospitalized COVID-19 patients and identify risk factors and prognostic predictors. METHOD: In this retrospective study, we recruited hospitalized COVID-19 patients from January 2021 until June 2021 at the University Malaya Medical Center. The inclusion criteria were hospitalized for ≥ 48 h with confirmed COVID-19 infection and at least 18 years old. Patient demographic and clinical data were collected from electronic medical records. The staging of AKI was based on criteria as per KDIGO guidelines. RESULTS: One thousand five hundred twenty-nine COVID patients fulfilled the inclusion criteria with a male-to-female ratio of 759 (49.6%) to 770 (50.3%). The median age was 55 (IQR: 36-66). 500 patients (32.7%) had diabetes, 621 (40.6%) had hypertension, and 5.6% (n = 85) had pre-existing chronic kidney disease (CKD). The incidence rate of AKI was 21.1% (n = 323). The percentage of COVID patients in different AKI stages of 1,2 and 3 were 16.3%, 2.1%, and 2.7%, respectively. Fifteen hospitalized patients (0.98%) required renal replacement therapy. 58.8% (n = 190) of AKI group had complete recovery of kidney function. Demographic factors included age (p < 0.001), diabetes (p < 0.001), hypertension (p < 0.012), CKD (p < 0.001), and vaccination status (p = 0.042) were associated with an increased risk of developing AKI. We found that the AKI cohort had statistically significant lower platelet counts and higher ferritin levels than the non-AKI cohort. AKI is a risk predictor of prolonged hospitalization (p < 0.001) and higher mortality rates (P < 0.001). CONCLUSION: AKI is a common clinical complication among hospitalized COVID-19 patients. The etiology of AKI is multifactorial and may have an adverse impact on patient morbidity and mortality.

Disseminated Melioidosis with Spinal Intraosseous Abscess.

Melioidosis is endemic in the State of Sabah, Malaysia. We report a case of a 34-year-old man with one-week history of fever and cough, three days history of diarrhoea and vomiting, which was associated with a loss of appetite and loss of weight for one-month. Clinically, he had hepatosplenomegaly and crepitation over his right lower zone of lung. Chest radiograph showed right lower lobe consolidation. Ultrasound abdomen showed liver and splenic abscesses. Ultrasound guided drainage of splenic abscess yielded Burkholderia pseudomallei. Magnetic resonance imaging (MRI) lumbosacral confirmed right sacral intraosseous abscess after he developed back pain a week later. He received 6 weeks of intravenous antibiotics and oral co-trimoxazole, followed by 6 months oral co-trimoxazole and had full recovery.

Mechanically exfoliated In2Se3 as a saturable absorber for mode-locking a thulium-doped fluoride fiber laser operating in S-band.

The rise of 2D materials since the discovery of graphene has been exponential. Their mechanical, electrical and optical properties are exceptional, similar to their 3D counterparts. In this paper, an α-In2Se3 crystal is mechanically exfoliated and transferred directly onto a fiber ferrule to serve as a saturable absorber (SA). A thulium-doped fluoride fiber is used as a gain medium to generate mode-locked pulses together with the In2Se3-based SA. The SA has a modulation depth of 14.6% and a saturation intensity of 0.4 kW/cm2. The passively generated mode-locked pulses have a repetition rate of 6.93 MHz and a pulse width of 5.79 ps. The mode-locked pulses also have a signal-to-noise ratio of 65.4 dB and a time-bandwidth product of 0.36. The pulse energy and peak power are 0.179 nJ and 27.2 W, respectively.

Necrotising pneumonia: A pneumonia that may need surgical intervention.

Pneumonia is primarily a disease that is usually managed medically with antibiotics. However, in rare cases it may progress to necrotising pneumonia, which is an uncommon but severe complication of bacterial pneumonia. This case illustrates a typical case of necrotising pneumonia complicated with parenchymal and pleural complication such as empyema, pneumothorax with possible bronchopleural fistula. Early consultation with thoracic surgeon can be life-saving.

Oscillatory behavior of vortex-lattice melting transition line in mesoscopic Bi_{2}Sr_{2}CaCu_{2}O_{8+y} superconductors.

The vortex-lattice melting transition of a limited number of vortices confined in mesoscopic square superconductors was studied by c-axis resistance measurements using stacks of intrinsic Josephson junctions in Bi_{2}Sr_{2}CaCu_{2}O_{8+y}. In contrast to the melting transition in bulk crystals, we have first found a clear oscillatory behavior in the field dependence of the melting temperature in small samples of 5-10 µm square. The periods of the oscillations roughly obey the regularity of the matching conditions of square vortex lattices surrounded by a square boundary and the melting temperatures are enhanced around the vortex number of i^{2} (where i is an integer). The results suggest that a confinement effect by the square boundary stabilizes square lattice structures which are realized around i^{2} vortex number even in competition with the favorable Abrikosov triangular lattice in the bulk.

Annotated computed tomography coronary angiogram images and associated data of normal and diseased arteries.

Computed Tomography Coronary Angiography (CTCA) is a non-invasive method to evaluate coronary artery anatomy and disease. CTCA is ideal for geometry reconstruction to create virtual models of coronary arteries. To our knowledge there is no public dataset that includes centrelines and segmentation of the full coronary tree. We provide anonymized CTCA images, voxel-wise annotations and associated data in the form of centrelines, calcification scores and meshes of the coronary lumen in 20 normal and 20 diseased cases. Images were obtained along with patient information with informed, written consent as part of the Coronary Atlas. Cases were classified as normal (zero calcium score with no signs of stenosis) or diseased (confirmed coronary artery disease). Manual voxel-wise segmentations by three experts were combined using majority voting to generate the final annotations. Provided data can be used for a variety of research purposes, such as 3D printing patient-specific models, development and validation of segmentation algorithms, education and training of medical personnel and in-silico analyses such as testing of medical devices.

Utilisation of emergency medical service among Singapore patients presenting with ST-segment elevation myocardial infarction: prevalence and impact on ischaemic time.

BACKGROUND: Previous studies in Western countries found that the emergency medical service (EMS) was under-used in patients with myocardial infarction. AIM: We sought to determine the prevalence of immediate EMS utilisation among Singapore patients presenting with ST-segment elevation myocardial infarction (STEMI), and correlated the use of the EMS with the symptom-to-balloon and door-to-balloon times. METHODS: We studied 252 patients admitted with STEMI to our institution from August 2008 to September 2009. Information regarding demographic characteristics, whether EMS was used, reperfusion procedural details and mortality rates were collected prospectively. RESULTS: Among the recruited patients, 89 (35.3%) used the EMS (EMS group) and 163 (64.7%) did not use the EMS (non-EMS group). In the latter group, 98 (60.1%) arrived at our institution through their own transport, 56 (34.4%) first consulted general practitioners, and 9 (5.5%) initially consulted another hospital without acute medical services. Among the 245 (out of 252, 97.2%) patients who received percutaneous coronary intervention (PCI), the EMS group was more likely to undergo primary PCI (P= 0.003) while the non-EMS group was more likely to undergo non-urgent PCI (P= 0.002). In patients who underwent primary PCI, the EMS group had a shorter symptom-to-balloon time (average difference 81.6 min, P= 0.002). The door-to-balloon time was similar for both groups. CONCLUSION: Despite the availability of a centralised EMS, 64.7% of patients with STEMI did not contact EMS at presentation. These patients were less likely to receive primary PCI and had a significantly longer symptom-to-balloon time.

1.3 µm dissipative soliton resonance generation in Bismuth doped fiber laser.

In this work, a Figure-9 (F9) bismuth-doped fiber laser (BiDFL) operating in the dissipative soliton resonance (DSR) regime is presented. The 1338 nm laser used a BiDF as the active gain medium, while a nonlinear amplifying loop mirror (NALM) in an F9 configuration was employed to obtain high energy mode-locked pulses. The wave breaking-free rectangular pulse widened significantly in the time domain with the increase of the pump power while maintaining an almost constant peak power of 0.6 W. At the maximum pump power, the mode-locked laser delivered a rectangular-shaped pulse with a duration of 48 ns, repetition rate of 362 kHz and a radio-frequency signal-to-noise ratio of more than 60 dB. The maximum output power was recorded at around 11 mW with a corresponding pulse energy of 30 nJ. This is, to the best of the author's knowledge, the highest mode-locked pulse energy obtained at 1.3 µm as well as the demonstration of an NALM BiDFL in a F9 configuration.

Imaging the vortex-lattice melting process in the presence of disorder

General arguments suggest that first-order phase transitions become less sharp in the presence of weak disorder, while extensive disorder can transform them into second-order transitions; but the atomic level details of this process are not clear. The vortex lattice in superconductors provides a unique system in which to study the first-order transition on an inter-particle scale, as well as over a wide range of particle densities. Here we use a differential magneto-optical technique to obtain direct experimental visualization of the melting process in a disordered superconductor. The images reveal complex behaviour in nucleation, pattern formation, and solid-liquid interface coarsening and pinning. Although the local melting is found to be first-order, a global rounding of the transition is observed; this results from a disorder-induced broad distribution of local melting temperatures, at scales down to the mesoscopic level. We also resolve local hysteretic supercooling of microscopic liquid domains, a non-equilibrium process that occurs only at selected sites where the disorder-modified melting temperature has a local maximum. By revealing the nucleation process, we are able to experimentally evaluate the solid-liquid surface tension, which we find to be extremely small.

A DNA microarray-based genetic screen for nonhomologous end-joining mutants in Saccharomyces cerevisiae.

We describe a microarray-based screen performed by imposing different genetic selections on thousands of yeast mutants in parallel, representing most genes in the yeast genome. The presence or absence of mutants was detected by oligonucleotide arrays that hybridize to 20-nucleotide "barcodes." We used this method to screen for components of the nonhomologous end-joining (NHEJ) pathway. Known components of the pathway were identified, as well as a gene not previously known to be involved in NHEJ, NEJ1. Nej1 protein interacts with the amino terminus of LIF1/XRCC4, a recently recognized "guardian of the genome" against cancer.

Human L1 retrotransposition: cis preference versus trans complementation.

Long interspersed nuclear elements (LINEs or L1s) comprise approximately 17% of human DNA; however, only about 60 of the approximately 400,000 L1s are mobile. Using a retrotransposition assay in cultured human cells, we demonstrate that L1-encoded proteins predominantly mobilize the RNA that encodes them. At much lower levels, L1-encoded proteins can act in trans to promote retrotransposition of mutant L1s and other cellular mRNAs, creating processed pseudogenes. Mutant L1 RNAs are mobilized at 0.2 to 0.9% of the retrotransposition frequency of wild-type L1s, whereas cellular RNAs are mobilized at much lower frequencies (ca. 0.01 to 0.05% of wild-type levels). Thus, we conclude that L1-encoded proteins demonstrate a profound cis preference for their encoding RNA. This mechanism could enable L1 to remain retrotransposition competent in the presence of the overwhelming number of nonfunctional L1s present in human DNA.

Nanostructure characterisation of flow-formed Cr-Mo-V steel using transmission Kikuchi diffraction technique.

Nowadays flow-forming has become a desired near net shape manufacturing method as it provides excellent mechanical properties with improved surface finish and significant manufacturing cost reduction. However, the material is subjected to excessive plastic deformation during flow-forming process, generating a very fine and complex microstructure. In addition, the intense dislocation density and residual stress that is generated in the component during processing makes the microstructure characterisation using conventional micro-analytical tools challenging. Thus, the microstructure/property relationship study in such a material is rather difficult. In the present study a flow-formed Cr-Mo-V steel nanostructure and crystallographic texture were characterised by means of Transmission Kikuchi Diffraction (TKD). Here, TKD is shown to be a powerful technique in revealing very fine martensite laths within an austenite matrix. Moreover, fine precipitates in the order of 20-70 nm on the martensite lath boundaries were clearly imaged and characterised. This greatly assisted in understanding the preferable site formation of the carbides in such a complex microstructure. The results showed that the actual TKD spatial resolution was in the range of 5-10 nm using 25 kV for flow-formed Cr-Mo-V steel.

ß-Catenin and NF-κB co-activation triggered by TLR3 stimulation facilitates stem cell-like phenotypes in breast cancer.

Cancer stem cells (CSCs) are responsible for tumor initiation and progression. Toll-like receptors (TLRs) are highly expressed in cancer cells and associated with poor prognosis. However, a linkage between CSCs and TLRs is unclear, and potential intervention strategies to prevent TLR stimulation-induced CSC formation and underlying mechanisms are lacking. Here, we demonstrate that stimulation of toll-like receptor 3 (TLR3) promotes breast cancer cells toward a CSC phenotype in vitro and in vivo. Importantly, conventional NF-κB signaling pathway is not exclusively responsible for TLR3 activation-enriched CSCs. Intriguingly, simultaneous activation of both ß-catenin and NF-κB signaling pathways, but neither alone, is required for the enhanced CSC phenotypes. We have further identified a small molecule cardamonin that can concurrently inhibit ß-catenin and NF-κB signals. Cardamonin is capable of effectively abolishing TLR3 activation-enhanced CSC phenotypes in vitro and successfully controlling TLR3 stimulation-induced tumor growth in human breast cancer xenografts. These findings may provide a foundation for developing new strategies to prevent the induction of CSCs during cancer therapies.

Low muscle mass and sarcopenia: common and predictive of osteopenia in inflammatory bowel disease.

BACKGROUND: Body composition is poorly studied in inflammatory bowel disease (IBD). Sarcopenia describes a loss of muscle mass and strength. AIM: To assess the prevalence of low lean mass (LM), sarcopenia and associated morbidity in an adult IBD cohort. METHODS: Cross-sectional data were gathered on pre-menopausal 18- to 50-year-old patients with IBD. Whole-body dual-energy X-ray absorptiometry, anthropometric assessment and grip strength were performed. Low LM was defined as ≥1 s.d. below the population mean for appendicular skeletal muscle index [ASMI (kg)/height (m)²], and sarcopenia as both ASMI and grip strength ≥1 s.d. below population mean. Multivariate regression analyses were performed. RESULTS: Of 137 participants (median age 31 years, BMI 24.8 kg/m(2) ), 56% were male and 69% had Crohn's disease (CD). Low LM and sarcopenia were observed in 21% and 12% of patients, respectively, and osteopenia/osteoporosis in 38% of patients (mean lumbar spine t-score -0.3 ± s.d. 1.1). Grip strength predicted low LM and sarcopenia better than did body mass index (BMI) (OR 4.8 vs. OR 0.7 for low-LM, P < 0.05 both). Normal BMI was falsely reassuring in 72% and 76% of patients with low ASMI and sarcopenia, respectively. Low LM and sarcopenia (OR = 3.6, P = 0.03; OR = 6.3, P = 0.02; respectively), but not BMI nor fat mass, predicted osteopenia/osteoporosis. CONCLUSIONS: Low lean mass and sarcopenia are common in patients with IBD, and important to recognise as they predict osteopenia/osteoporosis. Grip strength testing should be incorporated into routine clinical practice to detect low lean mass deficits, which may go unrecognised using BMI alone.

New primer strategy improves precision of differential display.

To increase the reproducibility and to reduce the false positives in the initial mRNA differential display, modified long composite primers were developed based on both mRNA differential display and RNA arbitrarily primed PCR fingerprinting methods. Ten-base nucleotides were added at the 5' ends of the primers used in the initial mRNA differential display. These included a restriction site to aid cloning. PCR began with one low-stringency cycle (40 degrees C for annealing) followed by 35 high-stringency cycles (60 degrees C for annealing). The modified method significantly improved the reproducibility and sensitivity of the mRNA differential display while still keeping the characteristics of the original method.

Methylxanthine and non-xanthine phosphodiesterase inhibitors. Their effects on adenosine uptake and the low Km cyclic AMP phosphodiesterase in intact rat adipocyte.

The effects of methylxanthines and non-xanthine phosphodiesterase-inhibitors on the low Km cyclic AMP phosphodiesterase of intact rat adipocytes were studied. Methylxanthines and papaverine stimulated rather than inhibited the enzyme when intact adipocytes were incubated in their presence. The effect of papaverine was not abolished by adenosine deaminase and was enhanced by adenosine. On the other hand, the effect of xanthine inhibitors and adenosine do not enhance each other. The difference in behaviour of these inhibitors could not be explained by their effects on adenosine uptake at the concentrations studied. Both agents inhibited adenosine uptake when measured after 15 sec and 10 min, with methylisobutylxanthine (MIX) having a greater inhibitory effect than papaverine only if uptake was measured after 15 sec. Effects similar to that of adenosine with the inhibitors on phosphodiesterase were obtained with insulin, which has been shown to act through a similar or related mechanism to that of adenosine. This was not the case with lipolytic agents whose effects were not potentiated by either MIX or papaverine. Under certain conditions the degree of stimulation of the enzyme was in fact decreased. Thus lipolytic and antilipolytic agents probably stimulated phosphodiesterase through distinct mechanisms.

Clinical significance of serum soluble interleukin-2 receptor in chronic myeloproliferative disorders.

Serum soluble interleukin-2 receptor (sIL-2R) levels were determined in patients with chronic myeloproliferative disorders (CMPD): 18 with chronic myelogenous leukemia in chronic phase (CML in CP), seven with CML in accelerated phase (AP) or blastic crisis (BC), six with polycythemia vera (PV), eight with essential thrombocythemia (ET), one with primary myelofibrosis (PMF), and 50 controls. The mean (+/-S.E.M.) levels were higher in CMPD than in controls (CML in AP or BC, 2693 +/- 694 U/ml, P < 0.0001; CML in CP, 792 +/- 63 U/ml, P < 0.0001; PV 553 +/- 89 U/ml, P < 0.05; ET, 449 +/- 56 U/ml; PMF, 628 U/ml vs. controls, 395 +/- 25 U/ml). Patients with CML in CP had significantly higher serum sIL-2R levels than patients with ET (P < 0.005), and levels were markedly elevated in AP and BC (P < 0.001). Serum sIL-2R levels were positively correlated with WBC count and lactic dehydrogenase in CMPD, and in CML in CP. Serum sIL-2R levels in CMPD were negatively correlated with RBC and platelet counts. Serum sIL-2R levels were significantly lower in patients with CML in CP who showed a cytogenetic response after interferon (IFN) therapy than in those who showed no response (P < 0.05). These findings suggest that a high serum sIL-2R level reflects the leukocyte growth in CMPD and is useful both for differentiating CML from other CMPD and for predicting the response to IFN therapy in CML.

Peroxisome proliferators increase the formation of BPDE-DNA adducts in isolated rat hepatocytes.

Peroxisome proliferators are known to modulate the activity of xenobiotic-metabolising enzymes, including glutathione S-transferase (GST) and cytochrome P-450 (CYP). In this study the effect of peroxisome proliferators silvex and di(2-ethylhexyl)phthalate (DEHP) on the formation of (+)-anti-benzo(a)pyrene -7,8-dihydrodiol-9,10-epoxide (BPDE)-DNA adducts from a proximate mutagen and carcinogen (-)-transbenzo(a)pyrene-7,8-dihydrodiol (BPDD) has been investigated. Rat CYP1A1 metabolises BPDD to mutagenic BPDE, which may form DNA adducts or, alternatively, be detoxified by hydrolysis or glutathione conjugation. In this experiment the formation of BPDE-DNA adducts was significantly increased in hepatocytes isolated from all silvex treated rats and two out of four DEHP treated rats (14 day treatment). The activity of CYP1A1 was increased whereas GST was reduced by the peroxisome proliferator silvex. These changes were more significant than those induced by DEHP. We have hypothesised that the formation of BPDE-DNA adducts was primarily due to the increased BPDD activation to BPDE versus reduced detoxication of BPDE. Other hepatic changes induced by the peroxisome proliferators, e.g. peroxisome proliferation per se and increased mitotic activity of the liver could have an effect on the outcome of BPDD exposure.