Physiological variables for the objective detection of nerve block failure in dogs.

OBJECTIVE: To identify physiological variables for objectively detecting nociception indicative of intraoperative peripheral nerve block failure. STUDY DESIGN: A double-blinded randomized clinical study. ANIMALS: A sample of 14 male (40.8 ± 12 kg; mean ± standard deviation) and 16 female (34.3 ± 11.4 kg) client-owned dogs. METHODS: Dogs were randomly assigned to one of three groups for psoas compartment and proximal sciatic nerve blocks (0.2 mL kg-1 per site): guided bupivacaine (GBB), or saline (GSB) block or a blind bupivacaine block (BBB). Guided blocks were performed using an ultrasound-peripheral nerve locator combination. Premedication consisted of medetomidine 0.01 mg kg-1 and morphine 0.3 mg kg-1. General anaesthesia was induced with propofol and maintained with isoflurane in oxygen. Receiver operator characteristic curve analysis was used to compare actual values and change in values of physiological variables between GSB and GBB. The Youden index and associated criterion for each physiological variable were used to determine an objective measure for nociception. Fisher's exact t test, McNemar's test and Cohen's kappa statistical analysis were used to determine association, differences and inter-score reliability between the objective and subjective scoring for BBB. RESULTS: Cardiovascular variables had good discriminating ability to identify a nociceptive response (p < 0.01). The Youden indices for mean (MAP) and diastolic (DAP) arterial pressure were most reliable in detecting nociception. The highest sensitivity was that of ΔMAP (100%) with good agreement between the subjective and objective scores of Δheart rate or systolic arterial pressure (SAP). The use of ΔMAP, ΔSAP, ΔDAP had the best ability in indicating peripheral nerve block failure (p < 0.001). CONCLUSIONS AND CLINICAL RELEVANCE: Blood pressure values can detect a response to surgical stimulus in adequately anaesthetized dogs. The use of ΔMAP, ΔSAP or ΔDAP may be considered as objective measures to detect nerve block failure.

Accelerated Bayesian Inference for Molecular Simulations using Local Gaussian Process Surrogate Models.

While Bayesian inference is the gold standard for uncertainty quantification and propagation, its use within physical chemistry encounters formidable computational barriers. These bottlenecks are magnified for modeling data with many independent variables, such as X-ray/neutron scattering patterns and electromagnetic spectra. To address this challenge, we employ local Gaussian process (LGP) surrogate models to accelerate Bayesian optimization over these complex thermophysical properties. The time-complexity of the LGPs scales linearly in the number of independent variables, in stark contrast to the computationally expensive cubic scaling of conventional Gaussian processes. To illustrate the method, we trained a LGP surrogate model on the radial distribution function of liquid neon and observed a 1,760,000-fold speed-up compared to molecular dynamics simulation, beating a conventional GP by three orders-of-magnitude. We conclude that LGPs are robust and efficient surrogate models poised to expand the application of Bayesian inference in molecular simulations to a broad spectrum of experimental data.

Associations of brain morphology with cortical proteins of cognitive resilience.

In a recent proteome-wide study, we identified several candidate proteins for drug discovery whose cortical abundance was associated with cognitive resilience to late-life brain pathologies. This study examines the extent to which these proteins are associated with the brain structures of cognitive resilience in decedents from the Religious Orders Study and Memory and Aging Project. Six proteins were associated with brain morphometric characteristics related to higher resilience (i.e., larger anterior and medial temporal lobe volumes), and five were associated with morphometric characteristics related to lower resilience (i.e., enlarged ventricles). Two synaptic proteins, RPH3A and CPLX1, remained inversely associated with the lower resilience signature, after further controlling for 10 neuropathologic indices. These findings suggest preserved brain structure in periventricular regions as a potential mechanism by which RPH3A and CPLX1 are associated with cognitive resilience. Further work is needed to elucidate other mechanisms by which targeting these proteins can circumvent the effects of pathology on individuals at risk for cognitive decline.

Molecular characterization of Aeromonas hydrophila isolates from diseased fishes in district Kasur, Punjab, Pakistan / Caracterização molecular de isolados de Aeromonas hydrophila de peixes doentes no distrito de Kasur, Punjab, Paquistão

Abstract Pakistan is an agricultural country and fisheries play a very important role in the economic development of the country. Different diseases are prevalent in Pakistani fish but information related to the causative agents is not well-known. Keeping in view the significance of bacterial pathogens as the causative agents of multiple fish diseases, the present study was conducted for identification, characterization and analysis of virulence genes of Aeromonas spp. isolated from diseased fishes. A total of fifty fish samples having multiple clinical indications were collected from different fish farms of district Kasur, Punjab Pakistan. For isolation of Aeromonas spp. samples were enriched and inoculated on Aeromonas isolation medium. Isolates were identified and characterized by different biochemical tests, Analytical Profile Index (API) 20E kit and Polymerase Chain Reaction (PCR) assays. All isolates were screened for three putative virulence genes including aerolysin (aer), haemolysin (hyl) and heat labile cytotonic enterotoxin (alt). Seven isolates of Aeromonas (A.) hydrophila were retrieved and identified based on API 20E. These isolates were further confirmed as A. hydrophila on the basis of PCR assays. Three isolates were detected positive for the presence of virulence genes (alt and hyl). Whereas aerolysin (aer) gene was not present in any of A. hydrophila isolates. The present study confirmed A. hydrophila as the causative agent of epizootic ulcerative syndrome and motile Aeromonas septicemia in fish farms of district Kasur, Punjab Pakistan. Moreover, detection of two virulence genes (alt and hyl) in A. hydrophila isolates is a threat for fish consumers of study area.

Resumo O Paquistão é um país agrícola, onde a pesca desempenha um papel muito importante para o desenvolvimento econômico. Diferentes doenças são prevalentes em peixes do Paquistão, mas as informações relacionadas aos agentes causadores não são bem conhecidas. Tendo em vista a importância dos patógenos bacterianos como agentes causadores de múltiplas doenças em peixes, o presente estudo foi conduzido para identificação, caracterização e análise de genes de virulência de isolados de Aeromonas spp. de peixes doentes. Foram coletadas 50 amostras de peixes com múltiplas indicações clínicas em diferentes fazendas do distrito de Kasur, Punjab, Paquistão. Para isolar Aeromonas spp., as amostras foram enriquecidas e inoculadas em meio de isolamento. Os isolados foram identificados e caracterizados por diferentes testes bioquímicos, kit Analytical Profile Index (API) 20E, e ensaios de reação em cadeia da polimerase (PCR). Todos os isolados foram selecionados para três genes de virulência putativos, incluindo aerolisina (aer), hemolisina (hyl) e enterotoxina citotônica termolábil (alt). Sete isolados de Aeromonas hydrophila foram recuperados e identificados com base no API 20E. Esses isolados foram posteriormente confirmados como A. hydrophila de acordo com ensaios de PCR. Três isolados indicaram a presença de genes de virulência (alt e hyl), enquanto o gene aerolisina (aer) não esteve presente em nenhum dos isolados de A. hydrophila. O presente estudo confirmou A. hydrophila como o agente causador da síndrome ulcerativa epizoótica e septicemia móvel por Aeromonas em fazendas de peixes, no distrito de Kasur, Punjab, Paquistão. Além disso, a detecção de dois genes de virulência (alt e hyl) em isolados de A. hydrophila é uma ameaça para os consumidores de peixes da área de estudo.

Molecular characterization of Aeromonas hydrophila isolates from diseased fishes in district Kasur, Punjab, Pakistan

Abstract Pakistan is an agricultural country and fisheries play a very important role in the economic development of the country. Different diseases are prevalent in Pakistani fish but information related to the causative agents is not well-known. Keeping in view the significance of bacterial pathogens as the causative agents of multiple fish diseases, the present study was conducted for identification, characterization and analysis of virulence genes of Aeromonas spp. isolated from diseased fishes. A total of fifty fish samples having multiple clinical indications were collected from different fish farms of district Kasur, Punjab Pakistan. For isolation of Aeromonas spp. samples were enriched and inoculated on Aeromonas isolation medium. Isolates were identified and characterized by different biochemical tests, Analytical Profile Index (API) 20E kit and Polymerase Chain Reaction (PCR) assays. All isolates were screened for three putative virulence genes including aerolysin (aer), haemolysin (hyl) and heat labile cytotonic enterotoxin (alt). Seven isolates of Aeromonas (A.) hydrophila were retrieved and identified based on API 20E. These isolates were further confirmed as A. hydrophila on the basis of PCR assays. Three isolates were detected positive for the presence of virulence genes (alt and hyl). Whereas aerolysin (aer) gene was not present in any of A. hydrophila isolates. The present study confirmed A. hydrophila as the causative agent of epizootic ulcerative syndrome and motile Aeromonas septicemia in fish farms of district Kasur, Punjab Pakistan. Moreover, detection of two virulence genes (alt and hyl) in A. hydrophila isolates is a threat for fish consumers of study area.

Resumo O Paquistão é um país agrícola, onde a pesca desempenha um papel muito importante para o desenvolvimento econômico. Diferentes doenças são prevalentes em peixes do Paquistão, mas as informações relacionadas aos agentes causadores não são bem conhecidas. Tendo em vista a importância dos patógenos bacterianos como agentes causadores de múltiplas doenças em peixes, o presente estudo foi conduzido para identificação, caracterização e análise de genes de virulência de isolados de Aeromonas spp. de peixes doentes. Foram coletadas 50 amostras de peixes com múltiplas indicações clínicas em diferentes fazendas do distrito de Kasur, Punjab, Paquistão. Para isolar Aeromonas spp., as amostras foram enriquecidas e inoculadas em meio de isolamento. Os isolados foram identificados e caracterizados por diferentes testes bioquímicos, kit Analytical Profile Index (API) 20E, e ensaios de reação em cadeia da polimerase (PCR). Todos os isolados foram selecionados para três genes de virulência putativos, incluindo aerolisina (aer), hemolisina (hyl) e enterotoxina citotônica termolábil (alt). Sete isolados de Aeromonas hydrophila foram recuperados e identificados com base no API 20E. Esses isolados foram posteriormente confirmados como A. hydrophila de acordo com ensaios de PCR. Três isolados indicaram a presença de genes de virulência (alt e hyl), enquanto o gene aerolisina (aer) não esteve presente em nenhum dos isolados de A. hydrophila. O presente estudo confirmou A. hydrophila como o agente causador da síndrome ulcerativa epizoótica e septicemia móvel por Aeromonas em fazendas de peixes, no distrito de Kasur, Punjab, Paquistão. Além disso, a detecção de dois genes de virulência (alt e hyl) em isolados de A. hydrophila é uma ameaça para os consumidores de peixes da área de estudo.

Quality of Care for Prostate Cancer in Kashmir, India: A Real-World Study.

Purpose Despite the importance of quality care for patients with prostate cancer, significant gaps exist in healthcare delivery, including diagnosis and treatment. Our objective was to assess the quality of care (QoC) using retrospective data from prostate care patients in our center. Methods We performed a retrospective study of prostate cancer patients registered at a dedicated cancer care center in the Kashmir region from 2012 to 2020. A set of 15 quality indicators representing crucial facets of diagnosis, pathology, and treatment was identified from a comprehensive list developed and validated by other researchers. Results The final analysis of all indicators was conducted on 46 patients with a median age of 70 years (52-92 years). In the majority of patients, the diagnosis (89.1%) was made through a prostatic biopsy, while only five patients were diagnosed solely based on the prostate-specific antigen. Transrectal ultrasound (TRUS) or transurethral resection (TURP)-guided biopsy was documented in 84.8% of patients, with Gleason grading documented in 87.5% of patients. However, the number of positive cores was mentioned for only 25.7% of patients. Radical prostatectomy was the primary treatment for most patients with localized prostate cancer (58.3%). The majority of patients with metastatic prostate cancer were treated with orchidectomy (55%), owing to easy access and the lower cost of surgical castration. Conclusion The study demonstrated a lack of compliance with many QoC indicators at the diagnostic and therapeutic levels. However, large-scale, population-based studies are needed to establish the compliance of prostate cancer QoC in Kashmir. The quality indicator assessment can guide the necessary actions required to improve QoC for prostate cancer patients.

Individualized Homeopathic Medicines in the Treatment of Knee Osteoarthritis: Double-Blind, Randomized, Placebo-Controlled Feasibility Trial.

INTRODUCTION: This study aimed at examining the feasibility issues of comparing individualized homeopathic medicines (IHMs) with identical-looking placebos for treating knee osteoarthritis (OA). METHODS: Forty eligible patients participated in this double-blind, randomized (1:1), placebo-controlled feasibility trial in the outpatient clinics of a homeopathic hospital in West Bengal, India. Either IHMs or identical-looking placebos were administered, along with mutually agreed-upon concomitant care guidelines. The Knee Injury and Osteoarthritis Outcome Score (KOOS) was the primary outcome measure, and derived Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores from KOOS, EQ-5D-5L questionnaire, and Visual Analog Scale (VAS) were the secondary outcomes; all measured at baseline and after 2 months. Group differences and effect sizes (Cohen's d) were estimated using an intention-to-treat approach. p-Values less than 0.05 (two-tailed) were considered statistically significant. RESULTS: Enrolment/screening and trial retention rates were 43% and 85% respectively. Recruitment was difficult owing to the coronavirus disease 2019 (COVID-19) lockdown. Group differences were statistically significant, favoring IHMs against placebos in all the KOOS sub-scales: symptoms (p < 0.001), pain (p = 0.002), activities of daily living (p < 0.001), sports or recreation (p = 0.016), and quality of life (p = 0.002). Derived WOMAC scores from KOOS favored IHMs against placebos: stiffness (p < 0.001) and pain (p < 0.001). The EQ-5D-5L questionnaire score (p < 0.001) and EQ-5D-5L VAS scores (p < 0.001) also yielded significant results, favoring IHMs over placebos. All the effect sizes ranged from moderate to large. Sulphur was the most frequently prescribed homeopathic medication. Neither group reported any harm or serious adverse events. CONCLUSION: Although recruitment was sub-optimal due to prevailing COVID-19 conditions during the trial, the action of IHMs was found to be superior to that of placebos in the treatment of knee OA. Larger and more definitive studies, with independent replications, are required to substantiate the findings. TRIAL REGISTRATION: CTRI/2021/02/031453.

Random forest analysis reveals taxa predictive of Prunus replant disease in peach root microbiomes.

Successive plantings of Prunus species produce suboptimal growth and yield in many California soils due to a poorly understood soilborne disease complex, Prunus replant disease (PRD). We explored the hypothesis that PRD is mediated by microbial taxa in roots of Nemaguard peach, a rootstock for almond and other stone fruits. In a greenhouse bioassay, portions of 10 replant soils were treated with fumigation or pasteurization or left untreated as a control before being planted with peach seedlings. Ten weeks after planting, seedlings were considered PRD-affected if their top fresh weights in the control were significantly reduced, compared to the weights in pasteurization and fumigation treatments; plants with equivalent top weights in all treatments were considered to be non-affected. The roots were washed from the soil, frozen, extracted for total DNA, and used for metabarcoding of rRNA gene amplicons from bacteria, fungi, and oomycetes. High-throughput amplicon sequencing revealed that root microbial community shifts resulted from preplant treatments, and specific taxa were associated with PRD induction among controls. Random forest (RF) analysis discriminated effectively between PRD-affected and non-affected root communities. Among the 30 RF top-ranked amplicon sequence variant (ASV) predictors, 26 were bacteria, two were oomycetes, and two were fungi. Among them, only Streptomyces scabiei, Steroidobacter denitrificans, Streptomyces bobili, and Pythium mamillatum had root abundances ≥5% that were either associated positively (former two ASVs) or negatively (latter two) with PRD. Thus, our findings were consistent with microbial mediation of PRD in roots and suggested taxa that may be involved in the mediation.

Gastric Hematoma Secondary to Heterotopic Pancreas of the Stomach: Unexpected Cause of Upper Gastrointestinal Bleeding.

Upper gastrointestinal bleeding remains a common cause of hospitalizations and common causes include peptic ulcer disease, esophageal and gastric varices, and malignancies. Infrequently, rare and unexpected causes are encountered. Initial management is generally the same regardless of the cause that is focused on hemodynamic stabilization followed by endoscopy to assess and treat the cause of bleeding. We report a case of a 19-year-old female who presented with upper gastrointestinal bleeding and endoscopy showed a submucosal hematoma secondary to gastric ectopic pancreas or heterotopic pancreas. She was also treated for Helicobacter pylori infection. She was managed medically and was discharged without further recurrence of bleeding.

Integration of Topological Insulator Josephson Junctions in Superconducting Qubit Circuits.

The integration of semiconductor Josephson junctions (JJs) in superconducting quantum circuits provides a versatile platform for hybrid qubits and offers a powerful way to probe exotic quasiparticle excitations. Recent proposals for using circuit quantum electrodynamics (cQED) to detect topological superconductivity motivate the integration of novel topological materials in such circuits. Here, we report on the realization of superconducting transmon qubits implemented with (Bi0.06Sb0.94)2Te3 topological insulator (TI) JJs using ultrahigh vacuum fabrication techniques. Microwave losses on our substrates, which host monolithically integrated hardmasks used for the selective area growth of TI nanostructures, imply microsecond limits to relaxation times and, thus, their compatibility with strong-coupling cQED. We use the cavity-qubit interaction to show that the Josephson energy of TI-based transmons scales with their JJ dimensions and demonstrate qubit control as well as temporal quantum coherence. Our results pave the way for advanced investigations of topological materials in both novel Josephson and topological qubits.

Molecular characterization of Aeromonas hydrophila isolates from diseased fishes in district Kasur, Punjab, Pakistan.

Pakistan is an agricultural country and fisheries play a very important role in the economic development of the country. Different diseases are prevalent in Pakistani fish but information related to the causative agents is not well-known. Keeping in view the significance of bacterial pathogens as the causative agents of multiple fish diseases, the present study was conducted for identification, characterization and analysis of virulence genes of Aeromonas spp. isolated from diseased fishes. A total of fifty fish samples having multiple clinical indications were collected from different fish farms of district Kasur, Punjab Pakistan. For isolation of Aeromonas spp. samples were enriched and inoculated on Aeromonas isolation medium. Isolates were identified and characterized by different biochemical tests, Analytical Profile Index (API) 20E kit and Polymerase Chain Reaction (PCR) assays. All isolates were screened for three putative virulence genes including aerolysin (aer), haemolysin (hyl) and heat labile cytotonic enterotoxin (alt). Seven isolates of Aeromonas (A.) hydrophila were retrieved and identified based on API 20E. These isolates were further confirmed as A. hydrophila on the basis of PCR assays. Three isolates were detected positive for the presence of virulence genes (alt and hyl). Whereas aerolysin (aer) gene was not present in any of A. hydrophila isolates. The present study confirmed A. hydrophila as the causative agent of epizootic ulcerative syndrome and motile Aeromonas septicemia in fish farms of district Kasur, Punjab Pakistan. Moreover, detection of two virulence genes (alt and hyl) in A. hydrophila isolates is a threat for fish consumers of study area.

Developing sulfur-doped titanium oxide nanoparticles loaded chitosan/cellulose-based proangiogenic dressings for chronic ulcer and burn wounds healing.

Development of biomaterials supporting angiogenesis are highly desired in medical applications. In current work, chitosan and cellulose were cross-linked by using triethyl orthoformate and loaded with sulfur-doped titanium oxide nanoparticles. A readily available and inexpensive titanium oxide was added as a potential proangiogenic agent based on our group findings and other reports on metal oxide nanoparticles activity to stimulate angiogenesis. A simple freeze gelation method led to the development of flexible, foldable, and porous membranes. To investigate the chemical characteristics of the synthesized membranes, Fourier-transform infrared spectroscopy was used. Scanning electron microscopy equipped with energy-dispersive X-ray microanalysis was employed for surface morphological investigations. The cross-linked membranes showed higher degree of swelling capacity compared to the same material with titania-loaded nanoparticles in vitro. The synthesized materials showed higher degree of degradation in H2 O2 as compared to phosphate-buffered saline and lysozyme. Chorioallantoic membrane assay was done to investigate the angiogenic potential. Titanium oxide nanoparticles loaded membranes (CLHTS-5 wt%) exhibited the best degree of angiogenesis in comparison to the other tested materials. In CLHTS-5 wt% experimental group, a good level of attachment and ingrowth of several blood vessels was observed. Interestingly, the same tested group (CLHTS-5 wt%) had shown the increasing trend of cellular metabolic rate of the seeded cells from Day 0 to Day 7 in vitro. These findings were further confirmed by the decline in lactate dehydrogenase enzyme release which was monitored until 72 h, indicating the promising ability of this biomaterial in wound healing applications.

Characterization of soils conducive and non-conducive to Prunus replant disease.

Successive orchard plantings of almond and other Prunus species exhibit reduced growth and yield in many California soils. This phenomenon, known as Prunus replant disease (PRD), can be prevented by preplant soil fumigation or anaerobic soil disinfestation, but its etiology is poorly understood and its incidence and severity are hard to predict. We report here on relationships among physicochemical variables, microbial community structure, and PRD induction in 25 diverse replant soils from California. In a greenhouse bioassay, soil was considered to be "PRD-inducing" when growth of peach seedlings in it was significantly increased by preplant fumigation and pasteurization, compared to an untreated control. PRD was induced in 18 of the 25 soils, and PRD severity correlated positively with soil exchangeable-K, pH, %clay, total %N, and electrical conductivity. The structure of bacterial, fungal, and oomycete communities differed significantly between the PRD-inducing and non-inducing soils, based on PERMANOVA of Bray Curtis dissimilarities. Bacterial class MB-A2-108 of phylum Actinobacteria had high relative abundances among PRD-inducing soils, while Bacteroidia were relatively abundant among non-inducing soils. Among fungi, many ASVs classified only to kingdom level were relatively abundant among PRD-inducing soils whereas ASVs of Trichoderma were relatively abundant among non-inducing soils. Random forest classification effectively discriminated between PRD-inducing and non-inducing soils, revealing many bacterial ASVs with high explanatory values. Random forest regression effectively accounted for PRD severity, with soil exchangeable-K and pH having high predictive value. Our work revealed several biotic and abiotic variables worthy of further examination in PRD etiology.

Reappearance of first Shapiro step in narrow topological Josephson junctions.

In Josephson junctions, a supercurrent across a nonsuperconducting weak link is carried by electron-hole bound states. Because of the helical spin texture of nondegenerate topological surface states, gapless bound states are established in junctions with topological weak link. These have a characteristic 4π-periodic current phase relation (CΦR) that leads to twice the conventional Shapiro step separation voltage in radio frequency-dependent measurements. In this context, we identify an attenuated first Shapiro step in (Bi0.06Sb0.94)2Te3 (BST) Josephson junctions with AlO x capping layer. We further investigate junctions on narrow, selectively deposited BST nanoribbons, where surface charges are confined to the perimeter of the nanoribbon. Within these junctions, previously identified signatures of gapless bound states are absent. Because of confinement, transverse momentum sub-bands are quantized and a topological gap opening is observed. Surface states within these quantized sub-bands are spin degenerate, which evokes bound states of conventional 2π-periodic CΦR within the BST nanoribbon weak link.

Preoperative resource utilization prior to minimally invasive repair of pectus excavatum.

BACKGROUND: Preoperative testing to assess the physiologic impact of pectus excavatum is sometimes ordered to meet third-party payor preauthorization requirements. This study describes the utility of physiologic testing prior to minimally invasive repair of pectus excavatum (MIRPE). METHODS: We retrospectively reviewed patients that underwent MIRPE from 1/2012-7/2016 at two academic children's hospitals. Data collected included demographics, insurance, Haller Index (HI), pulmonary function tests (PFTs) and echocardiograms (ECHO) obtained, and preauthorization denials. RESULTS: A total of 360 patients (mean age 15.7 ± 2.0 years; mean HI 4.5 ± 1.5) underwent MIRPE (Hospital 1: 189, Hospital 2: 171). Commercial insurers covered 84% of patients. Hospital 1 obtained more frequent preoperative testing (PFTs: 73% vs 6%, p < 0.0001). Overall, 72% of PFTs were normal with abnormal studies limited to mild findings. Similarly, 85% of ECHOs were normal. Third-party payors more frequently denied preauthorization for MIRPE at Hospital 2 (11% vs. 5%, p = 0.03). CONCLUSIONS: More frequent preoperative testing may decrease initial preauthorization denials for MIRPE; however, this increased utilization of resources may not be necessary as the majority of test results are normal.

Successful treatment of refractory secondary immune thrombocytopenia (antiphospholipid antibody syndrome-associated) with the combination of rituximab and romiplostim at the cost of severe bone pain: A case report and review of literature.

INTRODUCTION: Immune thrombocytopenia is an autoimmune disorder associated with increased thrombocyte destruction and impaired production in the bone marrow. Proposed mechanisms include an antibody or autoreactive T-cell-associated autoimmunity and thrombopoietin deficiency among others. Clinical manifestations are predominantly mucocutaneous hemorrhages including petechiae, purpura, mucosal bleeding in the urinary or the gastrointestinal tracts, menorrhagia, and epistaxis. The purpose of the treatment is to prevent bleeding rather than normalizing the platelet counts. First-line treatments include corticosteroids ± intravenous immunoglobulin and Anti-D which mainly decrease antibody-mediated platelet destruction and increase the number of peripheral Tregs. Second-line and subsequent therapies include splenectomy, chimeric anti-CD20 antibody (rituximab), which eliminates B cells and act as an immunomodulatory agent, and Thrombopoietin receptor agonists (romiplostim), which promote platelet production. CASE REPORT: We describe a 40-year-old male patient diagnosed with immune thrombocytopenia that was refractory to first-line corticosteroid and intravenous immunoglobulin and second-line romiplostim monotherapy treatments.Management and outcome: The patient was given the romiplostim and rituximab combination which not only successfully treated thrombocytopenia but also resulted in grade 3 bone pains and the patient's subsequent refusal to continue therapy. DISCUSSION: Common adverse effects of rituximab are infusion reactions and prolonged immunosuppression; those of romiplostim include thrombosis, headaches, arthralgia-myalgia, and gastrointestinal symptoms. This case shows that romiplostim has not caused any discernible side effects when given alone, while combination with rituximab resulted in severe bone and joint pains. We hypothesize that this combination regimen shows a synergistic effect both in terms of efficacy and adverse-effect probability and/or severity.

Left atrio-oesophageal fistula after atrial fibrillation ablation.

We report a case of a 68-year-old woman who presented with atypical chest pain and fluctuating neurological symptoms 4 weeks after cryoballoon ablation procedure for atrial fibrillation. Brain imaging showed multiple embolic infarcts, while the chest imaging revealed an abnormal connection between the posterior wall of the left atrium and the oesophagus. Based on her clinical presentation and the imaging findings, a diagnosis of left atrio-oesophageal fistula (AOF) was established. AOF carries a high mortality rate unless an urgent surgical repair is performed. Oesophageal instrumentation for an echocardiogram or endoscopy should be avoided as it can result in massive air embolus, causing stroke or death.

Blood acid-base, haematological and haemostatic effects of hydroxyethyl starch (130/0.4) compared to succinylated gelatin colloid infusions in normovolaemic dogs.

Synthetic colloids are commonly administered to dogs to treat absolute or relative hypovolaemia. Voluven® (tetrastarch 130/0.4) and Gelofusine® (succinylated gelatin) are available to veterinarians in South Africa. In humans, use of these products has caused acid-base derangements, changes in haematology and impaired haemostasis. We aimed to investigate these effects in healthy normovolaemic dogs. Eight healthy adult beagle dogs underwent a cross-over study, receiving Voluven® or Gelofusine® (10 mL/kg/h for 120 min) once each with a 14-day washout between treatments. Dogs were premedicated with dexmedetomidine (10 µg/kg intramuscularly). Anaesthesia was induced with propofol and the dogs were maintained with isoflurane-in-oxygen. The anaesthetised dogs were connected to a multi-parameter monitor to monitor physiological parameters throughout. Catheters placed in a jugular vein and dorsal metatarsal artery allowed sampling of venous and arterial blood. Blood was collected immediately prior to commencement of colloid infusion, after 60 min infusion and at the end of infusion (120 min) to allow for arterial blood gas analysis, haematology and coagulation testing (activated partial thromboplastin time [aPTT], prothrombin time [PT] and thromboelastography [TEG]). There was no effect, between treatments or over time, on blood pH. The haemoglobin concentration, erythrocyte count and haematocrit decreased significantly over time (all p 0.01), with no differences between treatments, and remained within normal clinical ranges. There were no differences between treatments or over time for the TEG, aPTT and PT tests of haemostasis. At the dose studied, Voluven® and Gelofusine® had comparably negligible effects on blood acid-base balance and coagulation in normovolaemic dogs.

Helicobacter pylori: An Underrated Cause of Immune Thrombocytopenic Purpura. A Comprehensive Review.

Idiopathic thrombocytopenic purpura (ITP) is the autoimmune-mediated destruction of platelets. ITP is a diagnosis of exclusion after other identifiable etiologies have been ruled out. After the first report by Gasbarrini et al. (1998) showing rising platelet counts in ITP patients following Helicobacter pylori (HP) eradication therapy, there is growing evidence that highlights the role of HP in triggering ITP. However, the exact pathophysiology of HP-associated ITP is still unclear, but many theories have been implicated in this regard. According to various reports, the postulated mechanisms for the role of HP in cITP include molecular mimicry, increased plasmacytoid dendritic cell numbers, phagocytic perturbation, and variable host immune response to HP virulence factors. One famous theory suggested molecular mimicry between platelet surface antigen and bacterial virulence factor, i.e. cytotoxin-associated gene A (CagA). It is thought that a chronic inflammatory response following an HP infection induces the host autoantibodies' response against CagA, which cross-reacts with platelet surface glycoproteins; therefore, it may accelerate platelet destruction in the host reticuloendothelial system. However, further studies are mandated to better understand the causal link between ITP and HP and study the role of biogeography. Nowadays, it is recommended that every patient with ITP should undergo HP diagnostic testing and triple therapy should be administered in all those candidates who test positive for HP infection. In our review, there were a few pregnant female ITP patients who took HP eradication therapy mainly after 20 weeks of gestation without maternal or fetal worst outcomes. However, large-scale studies are advisable to study the adverse fetal outcomes following triple therapy use.

Selective area growth and stencil lithography for in situ fabricated quantum devices.

The interplay of Dirac physics and induced superconductivity at the interface of a 3D topological insulator (TI) with an s-wave superconductor (S) provides a new platform for topologically protected quantum computation based on elusive Majorana modes. To employ such S-TI hybrid devices in future topological quantum computation architectures, a process is required that allows for device fabrication under ultrahigh vacuum conditions. Here, we report on the selective area growth of (Bi,Sb)2Te3 TI thin films and stencil lithography of superconductive Nb for a full in situ fabrication of S-TI hybrid devices via molecular-beam epitaxy. A dielectric capping layer was deposited as a final step to protect the delicate surfaces of the S-TI hybrids at ambient conditions. Transport experiments in as-prepared Josephson junctions show highly transparent S-TI interfaces and a missing first Shapiro step, which indicates the presence of Majorana bound states. To move from single junctions towards complex circuitry for future topological quantum computation architectures, we monolithically integrated two aligned hardmasks to the substrate prior to growth. The presented process provides new possibilities to deliberately combine delicate quantum materials in situ at the nanoscale.