Single-Cell Approach Reveals Intercellular Heterogeneity in Phage-Producing Capacities.

Bacteriophage burst size is the average number of phage virions released from infected bacterial cells, and its magnitude depends on the duration of an intracellular progeny accumulation phase. Burst size is often measured at the population level, not the single-cell level, and consequently, statistical moments are not commonly available. In this study, we estimated the bacteriophage lambda (λ) single-cell burst size mean and variance following different intracellular accumulation period durations by employing Escherichia coli lysogens bearing lysis-deficient λ prophages. Single lysogens can be isolated and chemically lysed at desired times following prophage induction to quantify progeny intracellular accumulation within individual cells. Our data showed that λ phage burst size initially increased exponentially with increased lysis time (i.e., period between induction and chemical lysis) and then saturated at longer lysis times. We also demonstrated that cell-to-cell variation, or "noise," in lysis timing did not contribute significantly to burst size noise. The burst size noise remained constant with increasing mean burst size. The most likely explanation for the experimentally observed constant burst size noise was that cell-to-cell differences in burst size originated from intercellular heterogeneity in cellular capacities to produce phages. The mean burst size measured at different lysis times was positively correlated to cell volume, which may determine the cellular phage production capacity. However, experiments controlling for cell size indicated that there are other factors in addition to cell size that determine this cellular capacity. IMPORTANCE Phages produce offspring by hijacking a cell's replicative machinery. Previously, it was noted that the variation in the number of phages produced by single infected cells far exceeded cell size variation. It was hypothesized that this variation is a consequence of variation in the timing of host cell lysis. Here, we show that cell-to-cell variation in lysis timing does not significantly contribute to the burst size variation. We suggest that the constant burst size variation across different host lysis times results from cell-to-cell differences in capacity to produce phages. We found that the mean burst size measured at different lysis times was positively correlated to cell volume, which may determine the cellular phage production capacity. However, experiments controlling for cell size indicated that there are other factors in addition to cell size that determine this cellular capacity.

Spontaneous Regression of Hepatocellular Carcinoma From Autoinfarction and Implications on Liver Transplantation.

Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide. Spontaneous regression of HCC due to autoinfarction is rare. This case series describes 2 cases of HCC autoinfarction that affected transplant candidacy: 1 patient previously ineligible because of tumor size and not meeting the Milan criteria became eligible after autoinfarction and tumor shrinkage while the second one was delisted in the view of improved symptoms of chronic liver disease and significant HCC regression. These cases provide an opportunity to review the pathogenesis of HCC autoinfarction and to remind practitioners of how this entity might alter decision-making around transplant eligibility.

Fatal Autochthonous Hepatitis E Induced Acute on Chronic Liver Failure Presenting with Multiorgan Failure in a Non-endemic Country: Brief Review of Intensive Care Unit Management.

Hepatitis E is usually a self-limiting disease that is considered rare in western countries. Outside of endemic regions, hepatitis E is seldom considered a cause of liver failure. We describe the first reported case of hepatitis E induced acute liver failure in the Caribbean island of Trinidad and the wider Caribbean; all traditionally considered non-endemic regions. The patient was a previously well young female who, upon investigation, was found to have radiographic signs suggesting underlying chronic liver disease. Subsequent testing yielded a positive hepatitis E immunoglobulin (Ig) M leading to the diagnose of hepatitis E induced acute on chronic liver failure. The patient's condition quickly deteriorated following the expected pattern of multiorgan failure associated with the disease. She died after a six-day intensive care unit (ICU) stay.

Challenges to Delivering Home Parenteral Nutrition in Adult Patients With Limited English Proficiency.

Failure to properly administer parenteral nutrition (PN) solutions can have deleterious effects on patients prescribed such therapies. The last few decades have seen diversification of the general population in the United States and elsewhere, with healthcare systems serving an increasing number of non-English-speaking patients and a more ethnically diverse population. Clinicians who provide care to this patient population encounter challenges in ensuring compliance and safe use of PN because of cultural and language barriers. Here we describe our experience of treating patients with limited English proficiency with respect to the barriers that prevent compliant and safe use of PN, especially in those discharged with home PN. We also describe the methods that we use to navigate these common issues to help clinicians provide the safest level of care to patients regardless of the patient's English proficiency.

Emphysematous Gastritis Associated with Sarcina ventriculi.

Emphysematous gastritis is a rare and lethal gastrointestinal emergency if not promptly identified and managed. In rare cases, emphysematous gastritis is associated with Sarcina ventriculi infection, usually in patients with delayed gastric emptying. Here we report a lethal case of S. ventriculi-associated emphysematous gastritis in the absence of delayed gastric emptying in which the diagnosis was confirmed postmortem. This case provides an opportunity to review the clinical presentation, pathophysiology, and management of emphysematous gastritis so that the condition can be promptly diagnosed and managed to prevent significant morbidity and mortality.

Transport in Floquet-Bloch Bands.

We report Floquet band engineering of long-range transport and direct imaging of Floquet-Bloch bands in an amplitude-modulated optical lattice. In one variety of Floquet-Bloch bands we observe tunable rapid long-range high-fidelity transport of a Bose condensate across thousands of lattice sites. Quenching into an opposite-parity Floquet-hybridized band allows Wannier-Stark localization to be controllably turned on and off using modulation. A central result of this work is the use of transport dynamics to demonstrate direct imaging of a Floquet-Bloch band structure. These results demonstrate that transport in dynamical Floquet-Bloch bands can be mapped to transport in quasistatic effective bands, opening a path to cold atom quantum emulation of ultrafast multiband electronic dynamics.

Does the benefit from treating to lower blood pressure targets vary with age? A systematic review and meta-analysis.

BACKGROUND: Recommendations differ regarding how blood pressure targets should vary with age. Crucial to this controversy is whether treatment benefit varies with age. METHODS: Systematic searches were conducted for trials randomizing treatment in intensive arms to the recommended SBP targets: 120-140 mmHg. Head-to-head meta-analyses and meta-regression were conducted. RESULTS: Sixteen trials met criteria. Relative to higher targets, lower targets reduced cardiovascular events, but treatment benefit differed significantly among trials due to patient age. Treatment significantly benefited older patients (mean age 77, SD = 72-81), relative risk (RR) = 0.77 (0.61,0.97), P = 0.025, but not younger patients (mean age 61, SD = 53-70), RR = 0.90 (0.78,1.03), P = 0.121, even though the latter had much greater statistical power. The (RR in 80 year olds)/(RR in 55 year olds) = 0.68 (0.47,0.97), P = 0.036. Though statistically nonsignificant, corresponding trends for more specific outcomes favored older patients: Coronary artery disease 0.80, stroke 0.85, heart failure 0.54, and total mortality 0.76. For adverse effects this trend was 0.86 (0.33,2.26). The number needed to treat to lower targets to prevent one cardiovascular event over 10 years in eight populations declined with age by 94%+. CONCLUSION: In these novel results, for both RR and absolute risk, treating to SBPs of 120-140 mmHg versus higher targets benefited older patients more than younger patients without an age-related increase in the RR for adverse effects. Nonetheless, because all clinical trials excluded the most frail older patients, clinicians must consider individual patient characteristics such as frailty, autonomy, and cognitive ability when choosing blood pressure targets.

Diagnostic yield of capsule endoscopy for small bowel arteriovenous malformations in patients with hereditary hemorrhagic telangiectasia: a systematic review and meta-analysis.

Background and study aims Small bowel arteriovenous malformations (AVMs) pose a bleeding risk and have traditionally been diagnosed by invasive enteroscopic procedures in patients with hereditary hemorrhagic telangiectasia (HHT). Capsule endoscopy (CE) is emerging as a safe and non-invasive alternative for small intestinal evaluation, but its diagnostic yield and utility in diagnosing small bowel AVMs in HHT patients are understudied. The aim of this study was to meta-analyze the utility of CE for diagnosing AVMs in HHT patients. Methods A meta-analysis and systematic review of the literature on CE in HHT patients identified in the PubMed, EMBASE, Scopus, and Cochrane databases from inception to March 2018 were conducted. Summary effects were estimated using a random effects model. Results After applying exclusion criteria, five studies (n = 124 patients) were eligible for meta-analysis. The pooled diagnostic yield for visualization of small bowel AVMs by CE was 77.0 % (95 % CI 65.8 - 85.4 %, P  < 0.001). Conclusions CE has a good diagnostic yield for small bowel AVMs in HHT. It can be regarded as a sufficient, noninvasive diagnostic modality for identifying small bowel AVMs in HHT patients.

Protein PEGylation for cancer therapy: bench to bedside.

PEGylation is a biochemical modification process of bioactive molecules with polyethylene glycol (PEG), which lends several desirable properties to proteins/peptides, antibodies, and vesicles considered to be used for therapy or genetic modification of cells. However, PEGylation of proteins is a complex process and can be carried out using more than one strategy that depends on the nature of the protein and the desired application. Proteins of interest are covalently conjugated or non-covalently complexed with inert PEG strings. Purification of PEGylated protein is another critical step, which is mainly carried out based on electrostatic interactions or molecular sizes using chromatography. Several PEGylated drugs are being used for diseases like anemia, kidney disease, multiple sclerosis, hemophilia and cancers. With the advancement and increased specificity of the PEGylation process, the world of drug therapy, and specifically cancer therapy could benefit by utilizing this technique to create more stable and non-immunogenic therapies. In this article we describe the structure and functions of PEGylation and how this chemistry helps in drug discovery. Moreover, special emphasis has been given to CCN-family proteins that can be targeted or used as therapy to prevent or block cancer progression through PEGylation technology.

Synchronous MALT lymphoma of the colon and stomach and regression after eradication of Strongyloides stercoralis and Helicobacter pylori.

Mucosa-associated lymphoid tissue (MALT) is vital for host immunological surveillance against pathogens. MALT lymphoma, also known as extranodal marginal zone B cell lymphoma, is a non-Hodgkin's lymphoma subtype that predominantly arises in the gastrointestinal tract. Chronic Helicobacter pylori (H. pylori) infection is a common cause of gastric MALT lymphoma, although other infections are reported in association with extragastric MALT lymphomas. To our knowledge, here we report the first case of synchronous MALT lymphomas of the colon and stomach in the presence of Strongyloides stercoralis and H. pylori infections that resolved after eradication of both organisms.

Observation and Uses of Position-Space Bloch Oscillations in an Ultracold Gas.

We report the observation and characterization of position-space Bloch oscillations using cold atoms in a tilted optical lattice. While momentum-space Bloch oscillations are a common feature of optical lattice experiments, the real-space center-of-mass dynamics are typically unresolvable. In a regime of rapid tunneling and low force, we observe real-space Bloch oscillation amplitudes of hundreds of lattice sites, in both ground and excited bands. We demonstrate two unique capabilities enabled by tracking of Bloch dynamics in position space: measurement of the full position-momentum phase-space evolution during a Bloch cycle, and direct imaging of the lattice band structure. These techniques, along with the ability to exert long-distance coherent control of quantum gases without modulation, may open up new possibilities for quantum control and metrology.

Corrigendum to "Miliary Tuberculosis Presenting with ARDS and Shock: A Case Report and Challenges in Current Management and Diagnosis".

[This corrects the article DOI: 10.1155/2017/9287021.].

Quantum simulation of ultrafast dynamics using trapped ultracold atoms.

Ultrafast electronic dynamics are typically studied using pulsed lasers. Here we demonstrate a complementary experimental approach: quantum simulation of ultrafast dynamics using trapped ultracold atoms. Counter-intuitively, this technique emulates some of the fastest processes in atomic physics with some of the slowest, leading to a temporal magnification factor of up to 12 orders of magnitude. In these experiments, time-varying forces on neutral atoms in the ground state of a tunable optical trap emulate the electric fields of a pulsed laser acting on bound charged particles. We demonstrate the correspondence with ultrafast science by a sequence of experiments: nonlinear spectroscopy of a many-body bound state, control of the excitation spectrum by potential shaping, observation of sub-cycle unbinding dynamics during strong few-cycle pulses, and direct measurement of carrier-envelope phase dependence of the response to an ultrafast-equivalent pulse. These results establish cold-atom quantum simulation as a complementary tool for studying ultrafast dynamics.

A Case-Control Study of the Association between Vitamin D Levels and Gastric Incomplete Intestinal Metaplasia.

Aim: Low circulating vitamin D levels are associated with gastric adenocarcinoma, but whether vitamin D levels are associated with premalignant gastric mucosal changes is unknown. Here, we determined associations between vitamin D levels and gastric incomplete intestinal metaplasia, a known gastric adenocarcinoma risk factor. Methods: This was a retrospective, unmatched, case-control study comparing serum 25-hydroxyvitamin D levels among subjects with gastric incomplete intestinal metaplasia (cases; n = 103) and those without gastric incomplete intestinal metaplasia (controls; n = 216). The 25-hydroxyvitamin D levels were categorized as normal (30­100 ng/dL), vitamin D insufficiency (VDi; 20­29 ng/dL), and vitamin D deficiency (VDd; <20 ng/dL). Using multivariable logistic regression, odds ratios (ORs) were calculated and adjusted to age, gender, ethnicity, body mass index, history of hypertension or diabetes mellitus, and timing of vitamin D collection to assess associations between 25-hydroxyvitamin D levels and gastric incomplete intestinal metaplasia. Results: A majority of case subjects were male, Hispanic, and did not have hypertension or diabetes mellitus. The average serum 25-hydroxyvitamin D level was significantly lower in the intestinal metaplasia group than the control group (19.7 ng/dL vs. 34.7 ng/dL; p < 0.001). Hypovitaminosis D was more common in subjects with incomplete intestinal metaplasia in a multivariable regression model (OR 54.1, 95% CI 21.8­134.3; p < 0.001). VDd (OR 129.0, 95% CI 43.7­381.2; p < 0.001) and VDi (OR 31.0, 95% CI 11.9­80.3; p < 0.001) were more common in patients with incomplete intestinal metaplasia than healthy subjects, with VDd slightly more prevalent than VDi (OR 4.0, 95% CI 1.7­9.6; p < 0.001). Conclusions: Vitamin D deficiency and insufficiency are more common in patients with gastric incomplete intestinal metaplasia than healthy subjects and may play a role in the development of premalignant phenotypes related to gastric adenocarcinoma.

Antiphospholipid syndrome presenting as acute mesenteric venous thrombosis involving a variant inferior mesenteric vein and successful treatment with rivaroxaban.

Acute mesenteric venous thrombosis (MVT) is the rarest cause of acute mesenteric ischaemia, so thrombosis of a variant inferior mesenteric vein (IMV) is especially uncommon in the setting of antiphospholipid syndrome (APS). Here, we present such a case of seronegative APS initially manifesting as an anomalous IMV thrombosis in a 76-year-old woman. Although guidelines support anticoagulation with vitamin K antagonists in these patients, we anticoagulated with rivaroxaban (a direct oral anticoagulant (DOAC)) due to patient preference, which resulted in complete clinical and endoscopic resolution. IMV thrombosis is a rare form of MVT, only two case reports describe successful anticoagulation with DOACs in the setting of MVT and none report APS as an underlying aetiology. Therefore, this case provides the opportunity to review the pathophysiology of MVT, APS and their medical management including current trends in anticoagulation.

A rare case of thrombotic microangiopathy triggered by acute pancreatitis.

Thrombotic microangiopathy (TMA) occurring after acute pancreatitis is rarely described. Without prompt intervention, TMA can be, and often is, lethal, so prompt recognition is important. Here, we present a case of a 61-year-old woman with a history of alcohol misuse who presented with epigastric pain, nausea and vomiting after binge drinking. Elevated serum lipase and imaging were suggestive of acute-on-chronic pancreatitis. Although the patient's symptoms of acute pancreatitis subsided, her anaemia, thrombocytopenia and acute kidney injury worsened. A peripheral blood smear revealed schistocytes, prompting suspicion for TMA. Therapeutic plasma exchange (TPE) was promptly initiated and she completed 10 TPE sessions that improved her anaemia and serum creatinine and resolved the thrombocytopenia. Since TPE was effective and the ADAMTS13 assay revealed 55% activity in the absence of anti-ADAMTS13 IgG prior to initiation of therapy, a confident diagnosis of TMA caused by acute pancreatitis was made. There was no evidence of relapse 2 years later.