Mutation spectrum of retinoblastoma patients in Vietnam.

BACKGROUND: Retinoblastoma (RB), an intraocular malignancy commonly diagnosed in children, is mostly caused by inactivating mutations of both alleles of the RB1 gene. Early genetic screening for RB1 gene mutations would greatly improve treatment outcomes and patient management. METHODS: In this study, both somatic and germline mutations were detected in blood and tumour samples of 42 RB patients using direct sequencing and multiplex ligation-dependent probe amplification. RESULTS: In total, 34 different mutations were found in 36 patients, including 1 SNP, 4 large deletions, 5 splicing sites, 1 missense, 7 frameshifts and 17 nonsense mutations. There were five novel mutations and one unreported which have not been found in large databases such as Leiden Open Variation Database (LOVD) and ClinVar. CONCLUSION: A higher rate of RB patients carrying heterozygous germline mutation and highly prevalent with pathogenic truncated mutation, hence, early detection of RB is essential for vision salvation and genetic counselling.

Cancer Associated Macrophage-like Cells Are Prognostic for Highly Aggressive Prostate Cancer in Both the Non-Metastatic and Metastatic Settings.

Despite advancements in the early-stage detection and expansion of treatments for prostate cancer (PCa), patient mortality rates remain high in patients with aggressive disease and the overtreatment of indolent disease remains a major issue. Prostate-specific antigen (PSA), a standard PCa blood biomarker, is limited in its ability to differentiate disease subtypes resulting in the overtreatment of non-aggressive indolent disease. Here we assess engorged cancer-associated macrophage-like cells (CAMLs), a ≥50 µm, cancer-specific, polynucleated circulating cell type found in the blood of patients with PCa as a potential companion biomarker to PSA for patient risk stratification. We found that rising PSA is positively correlated with increasing CAML size (r = 0.307, p = 0.004) and number of CAMLs in circulation (r = 0.399, p < 0.001). Over a 2-year period, the presence of a single engorged CAML was associated with 20.9 times increased likelihood of progression (p = 0.016) in non-metastatic PCa, and 2.4 times likelihood of progression (p = 0.031) with 5.4 times likelihood of death (p < 0.001) in metastatic PCa. These preliminary data suggest that CAML cell monitoring, in combination with PSA, may aid in differentiating non-aggressive from aggressive PCas by adding biological information that complements traditional clinical biomarkers, thereby helping guide treatment strategies.

Viral Encephalitis after Hematopoietic Cell Transplantation: A Systematic Review.

Viral encephalitis is a rare but serious complication after hematopoietic cell transplantation (HCT). The nonspecific early signs and symptoms and rapid progression can make it difficult to diagnose and treat in a timely fashion. To better inform clinical decision making in post-HCT viral encephalitis, a systematic review of prior studies of viral encephalitis was performed, with the goal of characterizing the frequency of various infectious etiologies and their clinical course, including treatments and outcomes. A systematic review of studies of viral encephalitis was performed. Studies were included if they described a cohort of HCT recipients who were tested for at least 1 pathogen. Of 1613 unique articles initially identified, 68 met the inclusion criteria, with a total of 72,423 patients studied. A total of 778 cases of encephalitis were reported (1.1%). Human herpesvirus 6 (HHV-6) (n = 596), Epstein-Barr virus (n = 76), and cytomegalovirus (n = 33) were the most commonly reported causes of encephalitis, and HHV-6 encephalitis tended to occur the earliest, accounting for most cases prior to day +100 post-transplantation. Of 29,671 patients with available transplantation data, encephalitis was diagnosed in 282 of 4707 (6.0%) cord blood transplantation (CBT) recipients, in 372 of 24,664 (1.5%) non-CBT allogeneic HCT recipients, and in 5 of 300 (1.7%) autologous HCT recipients. Of the 282 CBT encephalitis cases, 270 (95.7%) were caused by HHV-6. Overall, 288 (37.0%) of the 778 patients with encephalitis died, and 75 deaths were attributable to encephalitis, with the time between diagnosis and death ranging from 3 to 192 days. Viral encephalitis occurs in approximately 1% of HCT recipients, and HHV-6 is the most common cause. Mortality following encephalitis in HCT recipients is high, indicating an urgent need for advancement in preventive and therapeutic strategies.

Merosin-deficient congenital muscular dystrophy type 1a: detection of LAMA2 variants in Vietnamese patients.

Background: Merosin-deficient congenital muscular dystrophy type 1A (MDC1A), also known as laminin-α2 chain-deficient congenital muscular dystrophy (LAMA2-MD), is an autosomal recessive disease caused by biallelic variants in the LAMA2 gene. In MDC1A, laminin- α2 chain expression is absent or significantly reduced, leading to some early-onset clinical symptoms including severe hypotonia, muscle weakness, skeletal deformity, non-ambulation, and respiratory insufficiency. Methods: Six patients from five unrelated Vietnamese families presenting with congenital muscular dystrophy were investigated. Targeted sequencing was performed in the five probands. Sanger sequencing was carried out in their families. Multiplex ligation-dependent probe amplification was performed in one family to examine an exon deletion. Results: Seven variants of the LAMA2 (NM_000426) gene were identified and classified as pathogenic/likely pathogenic variants using American College of Medical Genetics and Genomics criteria. Two of these variants were not reported in the literature, including c.7156-5_7157delinsT and c.8974_8975insTGAT. Sanger sequencing indicated their parents as carriers. The mothers of family 4 and family 5 were pregnant and a prenatal testing was performed. The results showed that the fetus of the family 4 only carries c.4717 + 5G>A in the heterozygous form, while the fetus of the family 5 carries compound heterozygous variants, including a deletion of exon 3 and c.4644C>A. Conclusion: Our findings not only identified the underlying genetic etiology for the patients, but also provided genetic counseling for the parents whenever they have an offspring.

Epstein-Barr Virus and Human Herpesvirus-6 Reactivation in Acute COVID-19 Patients.

Beyond their pulmonary disease, many COVID-19 patients experience a complex constellation of characteristics, including hyperinflammatory responses, autoimmune disorders, and coagulopathies. However, the pathogenesis of these aspects of COVID-19 is obscure. More than 90% of people are latently infected with the lymphotropic herpesviruses Epstein-Barr Virus (EBV) and/or Human Herpesvirus-6 (HHV-6). Some of the inflammatory features of COVID-19 resemble clinical syndromes seen during EBV and HHV-6 infection, and these latent viruses can be reactivated by inflammatory mediators. We hypothesized that EBV and HHV-6 reactivation might be a common feature of early COVID-19, particularly in patients with more inflammation. We tested for EBV and HHV-6 reactivation in 67 patients acutely hospitalized with COVID-19 using previously validated quantitative PCR assays on the plasma. In our cohort, we found that 15/67 (22.4%) patients had detectable EBV and 3/67 (4.5%) had detectable HHV-6. This frequency of activation is somewhat more than the frequency reported for some healthy cohorts, such as blood donors and other healthy control cohorts. There was no association between EBV or HHV-6 and markers indicative of more inflammatory disease. We conclude that EBV and HHV-6 activation at about day 7 of hospitalization occurred in a modest fraction of our cohort of COVID-19 patients and was not associated with high levels of inflammation. In the modest fraction of patients, EBV and HHV-6 reactivation could contribute to some features of acute disease and pre-disposition to post-acute sequelae in a subset of patients.

Microglia in brain development and regeneration.

It has recently emerged that microglia, the tissue-resident macrophages of the central nervous system, play significant non-innate immune roles to support the development, maintenance, homeostasis and repair of the brain. Apart from being highly specialized brain phagocytes, microglia modulate the development and functions of neurons and glial cells through both direct and indirect interactions. Thus, recognizing the elements that influence the homeostasis and heterogeneity of microglia in normal brain development is crucial to understanding the mechanisms that lead to early disease pathogenesis of neurodevelopmental disorders. In this Review, we discuss recent studies that have elucidated the physiological development of microglia and summarize our knowledge of their non-innate immune functions in brain development and tissue repair.

Dysfunction of lipid storage droplet-2 suppresses endoreplication and induces JNK pathway-mediated apoptotic cell death in Drosophila salivary glands.

The lipid storage droplet-2 (LSD-2) protein of Drosophila is a homolog of mammalian perilipin 2, which is essential for promoting lipid accumulation and lipid droplet formation. The function of LSD-2 as a regulator of lipolysis has also been demonstrated. However, other LSD-2 functions remain unclear. To investigate the role of LSD-2, we performed tissue-specific depletion in the salivary glands of Drosophila using a combination of the Gal4-upstream activating sequence system and RNA interference. LSD-2 depletion inhibited the entry of salivary gland cells into the endoreplication cycle and delayed this process by enhancing CycE expression, disrupting the development of this organ. The deficiency of LSD-2 expression enhanced reactive oxygen species production in the salivary gland and promoted JNK-dependent apoptosis by suppressing dMyc expression. This phenomenon did not result from lipolysis. Therefore, LSD-2 is vital for endoreplication cell cycle and cell death programs.

Multiplex SuperSelective PCR Assays for the Detection and Quantitation of Rare Somatic Mutations in Liquid Biopsies.

SuperSelective primers, by virtue of their unique design, enable the simultaneous identification and quantitation of inherited reference genes and rare somatic mutations in routine multiplex PCR assays, while virtually eliminating signals from abundant wild-type sequences closely related to the target mutations. These assays are sensitive, specific, rapid, and low cost, and can be performed in widely available spectrofluorometric thermal cyclers. Herein, we provide examples of SuperSelective PCR assays that target eight different somatic EGFR mutations, irrespective of whether they occur in the same codon, occur at separate sites within the same exon, or involve deletions. In addition, we provide examples of SuperSelective PCR assays that detect specific EGFR mutations in circulating tumor DNA present in the plasma of liquid biopsies obtained from patients with non-small-cell lung cancer. The results suggest that multiplex SuperSelective PCR assays may enable the choice, and subsequent modification, of effective targeted therapies for the treatment of an individual's cancer, utilizing frequent noninvasive liquid biopsies.

Prognostic Implications of High-Sensitivity Troponin T Levels Among Patients Attending Emergency Departments and Evaluated for an Acute Coronary Syndrome.

BACKGROUND: With increasing age, patients with suspected acute coronary syndromes (ACS) and elevated high-sensitivity troponin T (HsTnT) levels, type-1 myocardial infarction (MI) is diagnosed less often, though associations among these factors, gender, and prognosis is unclear. METHODS: Patients presenting to the emergency department (ED) with potential ACS who underwent HsTnT testing were prospectively identified and followed. Diagnoses were adjudicated according to the Fourth Universal Definition of MI as follows: type-1 MI, type-2 MI, acute myocardial injury, chronic myocardial injury, and other diagnoses. Age in years was categorized: younger (<65); elderly (65-79), and very elderly (≥80). RESULTS: Among 2738 patients with HsTnT measurements, 1611 were suitable for adjudication (42% ages 65 years and younger). Type-2 MI and chronic myocardial injury diagnoses were more common in those ages 65 years and older, whereas younger patients had more type-1 MI diagnoses. Late mortality rates at median 41 months (interquartile range [IQR] 10-57) were 44% (223 out of 506) in those ages 80 years and older, 22% (92 out of 423) in patients 65-79 years, and 7% (46 out of 682) in those 65 years and younger, irrespective of adjudicated diagnoses, log rank P ≤ .001. On multivariable analyses, the adjusted mortality hazard ratios for increasing HsTnT levels irrespective of diagnoses were attenuated in those age 80 years and older compared to younger patients. CONCLUSIONS: Patients ages 65 years and older constituted ~60% of ED attendances of patients with suspected ACS, and more had type 2 MI and chronic myocardial injury diagnoses compared to younger patients. The relative mortality impact of HsTnT levels was lower among elderly patients irrespective of adjudicated diagnoses.

Human Herpesvirus 6 Infection in Pediatric Liver Transplantation: Single-Center Study of Incidence, Outcomes, and Management.

BACKGROUND: Distinctions between HHV-6 primary infection in seronegative patients and HHV-6 reactivation in seropositive patients remains largely undescribed in pediatric liver transplant (LT) recipients. METHODS: We implemented pretransplant serology testing of HHV-6 in a large pediatric hospital and retrospectively assessed the incidence, manifestations and outcomes of HHV-6 infections over a 3-year period. RESULTS: Among 101 pediatric LT recipients, 96 had pretransplant HHV-6 serologies; 34 (35.4%) were seronegative and 62 (64.6%) seropositive. Posttransplantation, 8/25 (32%) seronegative patients had HHV-6 DNAemia (primary infection) compared to 2/48 (4%) seropositive patients (p=0.002). Compared to seropositive patients, seronegative patients with HHV-6 DNAemia were younger, and had symptoms of fever and/or elevated aminotransferases in association with higher viral loads, in the first month post-transplant. More than 90% of seronegative patients and 77.8% of seropositive patients had HHV-6 detected by PCR in liver biopsy obtained for concerns of allograft rejection, but most had no detectable concomitant DNAemia. Active replication of virus in the liver was confirmed by in situ hybridization in select cases. While HHV-6 infection occurred among patients on prophylaxis doses of antivirals for CMV, HHV-6 DNAemia and presenting symptoms resolved on treatment doses. CONCLUSIONS: HHV-6 DNA-emia occurred more frequently in seronegative pediatric LT recipients, usually in the early posttransplant period, and was subsequently detected in allograft biopsies. HHV-6 cannot be ruled out as a cause of hepatitis in the absence of allograft tissue testing and specialized virological assays, as HHV-6 may disrupt local allograft immune homeostasis while evading traditional screening methods using blood or plasma. The assessment of pre-transplant HHV-6 serological status may be important for risk stratification and post-transplant management of pediatric LT recipients.

Retrospective case analysis of antiviral therapies for HHV-6 encephalitis after hematopoietic stem cell transplantation.

Human herpesvirus 6 (HHV-6) is one of the most common causes of encephalitis in allogeneic hematopoietic stem cell transplant (HCT) recipients and is associated with significant morbidity and mortality. There are no FDA-approved treatments specifically for HHV-6 encephalitis; HHV-6 disease is typically treated with CMV antivirals. A review of antiviral medications used to treat HHV-6 encephalitis was conducted by aggregating data from case reports found on PubMed. Articles were included if they examined at least one HCT patient diagnosed with HHV-6 encephalitis and described their treatment course and outcome. Key data were abstracted from 123 cases described in 52 studies. The proportion of patients with encephalitis who died or developed sequelae was 63.6% among ganciclovir monotherapy recipients (n = 44), 55.3% among foscarnet monotherapy recipients (n = 47), and 37.5% among recipients of combination therapy with foscarnet and ganciclovir (n = 32). Logistic regression revealed that recipients of foscarnet (OR 4.286, 95% CI 1.235-14.877, P = .022) and ganciclovir (OR 5.625, 95% CI 1.584-19.975, P = .008) monotherapies were more likely to develop sequelae compared to recipients of combination therapy, respectively. In multivariate analyses, non-cord blood transplant was identified as an independent risk factor for developing sequelae after receiving ganciclovir monotherapy (OR 5.999, 95% CI 1.274-28.254, P = .023). There was no difference in mortality between patients who received combination therapy and those who received monotherapy. In conclusion, combination therapy with foscarnet and ganciclovir may reduce sequelae, but not mortality, secondary to HHV-6 encephalitis.

Effects of Launaea sarmentosa Extract on Lipopolysaccharide-Induced Inflammation via Suppression of NF-κB/MAPK Signaling and Nrf2 Activation.

Launaea sarmentosa has been extensively used as a nutrient herb in traditional Vietnamese remedies for the treatment of various diseases, especially inflammatory diseases. However, no detailed research has been conducted examining the molecular mechanisms involved in the suppression of inflammatory response. Here, we studied the effects of L. sarmentosa methanol extract on lipopolysaccharide (LPS)-induced inflammation using RAW 264.7 macrophages. The extract demonstrated potent antioxidant activity owing to the presence of polyphenolic and flavonoid components. Pretreatment with the extract inhibited LPS-mediated secretion of nitric oxide, reactive oxygen species, and tumor necrosis factor-α as well as the expression of inflammatory cytokines. Furthermore, the activation of the nuclear factor-kappa B pathway and phosphoinositide-3-kinase/protein kinase B pathways was blocked by the extract by inhibiting Akt phosphorylation. Additionally, the mitogen-activated protein kinase pathway was suppressed, and endoplasmic reticulum stress was attenuated. Furthermore, the extract promoted the activity of nuclear factor erythroid-2-related factor 2 resulting in the up-regulation of heme oxygenase-1 pathway, leading to the suppression of oxidative stress and inflammatory response. Taken together, the results indicate that L. sarmentosa exhibits anti-inflammatory effects, and hence, can be further developed as a novel drug for the treatment of diseases associated with excessive inflammation.

Comparison of Late Cardiac Death and Myocardial Infarction Rates in Women Vs Men With ST-Elevation Myocardial Infarction.

Women and patients with incomplete revascularization (IR) have a worse prognosis after ST elevation myocardial infarction (STEMI). However, the extent to which IR affects outcomes for women with STEMI compared with men is not well characterized. Thus, we examined late outcomes of 589 consecutive STEMI patients who received percutaneous coronary intervention and assessed SYNTAX scores (SS), both at baseline and after all procedures (residual SS). A residual SS >8 defined IR. The primary end point was cardiac death or myocardial infarction (MI), with median follow-up of 3.6 years [interquartile range [IQR] 2.6 to 4.7]. Women (n = 123) had lower baseline SSs 15.0 [IQR 9 to 20], than men (n = 466), 16.0 [IQR 9 to 20; p = 0.02. After all planned procedures, the residual SS was 5.0 [IQR 0 to 9] in women and 5.0 (IQR 1 to 11] in men, p = 0.37. Cardiac death or MI occurred in (97/589) patients (16%), 24% (30/123) in women and 14% (67/466) in men (hazard ratio [HR] 1.75; 95% confidence intervals [CI] 1.14 to 2.69; p = 0.01). In patients with residual SYNTAX score (rSS) >8 cardiac death or MI occurred in 43% (15/35) of women and 23% 36/158 men (HR 2.14; 95% CI 1.17 to 3.91; p = 0.01). In patients with rSS = 0 to 8 cardiac death or MI occurred in 17% (15/88) of women and 10% of men (31/308) (HR 1.68; 95% CI 0.91 to 3.12; p = 0.10; interaction p value 0.58). Multivariate analysis found women were 1.77 times more likely than men to experience cardiac death or MI (95% CI 1.13 to 2.77; p = 0.01). In conclusion, we found despite a lower burden of disease at presentation and no difference in rates of IR between men and women, outcome differences were substantial. Women with rSS >8 were twice as likely as men with the same rSS to experience cardiac death or MI post-STEMI. Differences remained significant postrisk adjustment.

Role of Serotonin Transporter in Eye Development of Drosophila melanogaster.

Serotonin transporter (SerT) in the brain is an important neurotransmitter transporter involved in mental health. However, its role in peripheral organs is poorly understood. In this study, we investigated the function of SerT in the development of the compound eye in Drosophila melanogaster. We found that SerT knockdown led to excessive cell death and an increased number of cells in S-phase in the posterior eye imaginal disc. Furthermore, the knockdown of SerT in the eye disc suppressed the activation of Akt, and the introduction of PI3K effectively rescued this phenotype. These results suggested that SerT plays a role in the healthy eye development of D. melanogaster by controlling cell death through the regulation of the PI3K/Akt pathway.

Anti-Inflammatory Effects of Lasia spinosa Leaf Extract in Lipopolysaccharide-Induced RAW 264.7 Macrophages.

Lasia spinosa (L.) Thwaites was used as a traditional medicine to treat many inflammatory diseases for centuries. However, its effects on the inflammatory response are not yet characterized. In this study, we investigated the anti-inflammatory activities of L. spinosa leaf extract in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. We found that ethanol extracts of L. spinosa leaves showed anti-oxidant activity due to the presence of high levels of polyphenolic compounds. Treatment with the leaf extract significantly repressed the production of inflammatory mediators such as nitric oxide and reactive oxygen species and the expression of pro-inflammatory cytokines in the LPS-stimulated RAW 264.7 cells. Moreover, L. spinosa leaf extract treatment prevented activation of the nuclear factor-kappa B pathway by inhibiting nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) degradation. Furthermore, the mitogen-activated kinase and phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) pathways were suppressed upon treatment with the leaf extract. In addition to suppressing inflammatory factors, the extract also activated the nuclear factor erythroid 2-related factor 2/heme-oxygenase-1 pathway. We propose that L. spinosa leaf extract has the potential as an effective therapeutic agent for alleviating oxidative stress and excessive inflammation.

Mortality at 5 Years Among Very Elderly Patients Undergoing High Sensitivity Troponin T Testing for Suspected Acute Coronary Syndromes.

BACKGROUND: Patients aged ≥80 years old often present to Emergency Departments (ED) with symptoms potentially due to an acute coronary syndrome (ACS). This study aimed to evaluate associations between baseline level(s) of high sensitivity troponin T (HsTnT), adjudicated diagnoses and outcomes. METHODS: Consecutive patients aged ≥80 years were studied, who presented to the ED at Liverpool Hospital, NSW, Australia during the 4 months period March to June 2014 (inclusive) with symptoms suggestive of an ACS, and who had at least one HsTnT assay performed. Diagnoses were based on the fourth universal definition of MI (myocardial infarction) including type-1 MI, type-2 MI, acute myocardial injury, chronic myocardial injury; the rest were termed "other diagnoses". Patients were categorised by baseline HsTnT levels 1) ≤14 ng/L, 2) 15-29 ng/L, 3) 30-49 ng/L and 4) ≥50 ng/L. RESULTS: Of 2,773 patients screened, 545 were aged ≥80 years (median age 85 [IQR 82-88]); median follow-up was 32 months (IQR 5-56). The respective rates of adjudicated diagnoses were type-I MI 3.1%, type-2 MI 13%, acute myocardial injury 9.5%, chronic myocardial injury 56% and 18.6% had other diagnoses. Mortality rates increased, irrespective of adjudicated diagnoses with increasing HsTnT levels (ng/L): 17% (16/96) for ≤14; 35% (67/194) for 15-29; 51% (65/127) for 30-49; and 64% (82/128) for ≥50 ng/L; log rank p≤0.001. On multi-variable analyses, after adjusting for potential confounding factors including age, hypertension, chronic kidney disease (CKD) and chronic obstructive pulmonary disease (COPD), MI type was not associated with late mortality. CONCLUSIONS: Among patients aged ≥80 years higher HsTnT levels, irrespective of adjudicated diagnoses, were associated with increased mortality. Most very elderly patients presenting with symptoms suggestive of an ACS undergoing HsTnT testing in EDs had elevated levels most commonly due to chronic myocardial injury. Whether any interventions can modify outcomes require prospective evaluation.

A Systematic Review of Sodium Disorders in HHV-6 Encephalitis.

Human herpesvirus 6 (HHV-6) encephalitis has a high mortality rate. Among those who survive, ~80% develop some type of permanent neurologic disorder. Early diagnosis and treatment may help prevent long-term sequelae. There have been several case reports as well as retrospective and prospective studies associating HHV-6 encephalitis with some form of sodium imbalance, either hyponatremia or hypernatremia; however, the exact frequency post-HCT is unknown, with reports ranging from 30% to 100%. We performed a systematic review of the literature and found 34 cases of HHV-6 encephalitis reported in conjunction with sodium imbalance that documented the timing of that imbalance relative to the onset of encephalitis. Sodium imbalance occurred before or at the onset of HHV-6 encephalitis in all but 2 cases (94%). This finding supports previous suggestions that sodium imbalance can be considered an early indicator of the potential development or presence of HHV-6 encephalitis in at-risk patient populations.

Evaluation of liver failure in a pediatric transplant recipient of a liver allograft with inherited chromosomally integrated HHV-6B.

BACKGROUND: Active infections of human herpesvirus 6B (HHV-6B) are frequent in immunocompromised recipients after transplantation. Nevertheless, they need to be distinguished from latent inherited chromosomally integrated genomes (iciHHV-6) present in about 1% of the population to avoid unnecessary administration of toxic antivirals. METHODS: A 5-year-old child presented with acute liver allograft rejection associated with HHV-6 DNA in plasma, which led to an unfavorable outcome. We investigated the possibility of HHV-6 infection derived from an iciHHV-6 present in the donor's liver using molecular and histopathology studies in various tissues, including quantification of HHV-6 DNA, genotyping, sequencing for antiviral resistance genes, relative quantification of viral transcripts, and detection of gB and gH viral proteins. RESULTS: The presence of iciHHV-6B was evidenced in the donor with signs of reactivation in the gallbladder and transplanted liver (detection of HHV-6B mRNA and late proteins). This localized expression could have played a role in liver rejection. Low viral loads in the recipient's plasma, with identical partial U39 sequences, were in favor of viral DNA released from the transplanted liver rather than a systemic infection. CONCLUSIONS: Determination of iciHHV-6 status before transplantation should be considered to guide clinical decisions, such as antiviral prophylaxis, viral load monitoring, and antiviral therapy.

Type-II myocardial infarction and chronic myocardial injury rates, invasive management, and 4-year mortality among consecutive patients undergoing high-sensitivity troponin T testing in the emergency department.

AIMS: As assessment of patients with suspected acute coronary syndromes (ACS) in emergency departments (EDs) represents a major workload because high-sensitivity troponin (HsTn) T and I levels are frequently measured, and a minority of patients have final diagnosis of myocardial infarction (MI). We determined the relative frequencies of three patients groups: Type-I MI, Type-II MI (including acute myocardial injury). METHODS AND RESULTS: Among 2738 consecutive patients with suspected ACS presenting to ED at Liverpool Hospital, Australia, between March and June 2014. We studied the use of invasive and pharmacological therapies, and 4-year outcomes. Adjudication of MI was according to the 4th universal definition as follows: (i) Type-I MI; (ii) Type-II MI (including acute myocardial injury), and (iii) chronic myocardial injury. Of 995 patients (36%) [median age 76 years (interquartile range 65-83)] with ≥2 HsTnT measurements and one >14 ng/L, 727 (73%) had chronic myocardial injury, 171 (17%) had Type-II MI, and 97 (9.7%) had Type-I MI; respective late mortality rates to 48 months were 33%, 43%, and 14% (P < 0.001). In-hospital angiography rates were 95% for patients with Type-I MI, [62% had percutaneous coronary intervention (PCI)] 24% (7% PCI) for those with Type-II MI, and 3.4% for chronic myocardial injury. On Cox modelling for mortality relative to Type 1 MI, adjusted hazard ratios were 1.94 [95% confidence intervals (CIs) 1.06-3.57]; P = 0.032 for Type 2 MI, and for chronic myocardial injury 1.14 (95% CIs 0.64-2.02); P = 0.66. CONCLUSION: Among unselected patients undergoing HsTnT testing in EDs, Type-II MI including acute myocardial injury was more common than Type-I MI. Chronic myocardial injury, which occurred in three of four patients. Whereas patients with Type-II MI had higher late mortality than those with Type-I MI, after multivariable analyses mortality rates were marginally different.

Drosophila model for studying the link between lipid metabolism and development.

Developmental processes are cascades of biological changes linked with information transfer, growth, and differentiation during the life cycle of an organism. Lipid metabolism plays a vital role in the life cycle of organisms. Drosophila models grant numerous advantages in investigating the underlying mechanisms of each process as well as their connections. In each section of this review, we will discuss multiple studies revealing the function of lipid-related genes in different stages of early development: spermatogenesis, oogenesis, embryogenesis along with late development in life cycle of Drosophila.