Masked hypertension risk as condition of arterial stiffness in cardiovascular risk patients: a pilot single-stage screening observational study

Background. Masked arterial hypertension (MAH) is associated with asymptomatic injury of both heart and kidneys. Links between MAH and arterial stiffness are unclear, with debates ongoing on their mutual causative relation. Research into the arterial stiffness contribution to MAH development is a perspective area of cardiology.Objectives. The MAH risk assessment as a condition of arterial stiffness in patients at cardiovascular risk (CVR) without a verified cardiovascular disease (CVD).Methods. A single-stage screening observational study included a total of 92 CVR patients without a verified cardiovascular disease. The trial conducted general clinical examination, daily blood pressure monitoring (DBPM), volumetric sphygmoplethysmography with reading cardio-ankle vascular index (CAVI1), aortic and carotid artery pulse wave velocity (PWV), carotid-femoral PWV (CFV) and augmentation index.Results. Patients were assigned in two cohorts by MAH presence, the primary MAH (58; 63.0%) and normal BP in DBPM (34; 37.0% patients) cohorts. The cohorts did not discord by age, major CVR factors, comorbidity or clinical profile. Men prevailed over women in the MAH cohort (p = 0.028). The cohorts had similar CFV, aortic PWV and augmentation index. Carotid PWV was higher in the MAH cohort both in mean values and elevation rate (p = 0.002 and p = 0.035, respectively). OR and HR were 3.29 and 2.35 (95% CI for OR 1.08–10.49, HR 1.05– 6.02), respectively. MAH was associated with increased CAVI1 for mean values and CAVI1 > 8 incidence rate (p = 0.010 and 0.049, respectively); OR 3.29 (95% CI 1.00–11.41), HR 2.46 (95% CI 1.00–7.10). Correlation analysis revealed a moderate direct dependence between the MAH presence and elevation rate of C-PWV (Q = 0.53) and CAVI1 > 8 (Q = 0.53).Conclusion. The risk of MAH development in CVR patients is both gender and arterial stiffness-dependent. MAH development is associated with increased CAVI1 and carotid PWV.

The Role of Microbiome and Virome in Idiopathic Pulmonary Fibrosis

The interest in the lung microbiome and virome and their contribution to the pathogenesis, perpetuation and progression of idiopathic pulmonary fibrosis (IPF) has been increasing during the last decade. The utilization of high-throughput sequencing to detect microbial and/or viral genetic material in bronchoalveolar lavage fluid or lung tissue samples has amplified the ability to identify and quantify specific microbial and viral populations. In stable IPF, higher microbial burden is associated with worse prognosis but no specific microbe has been identified to contribute to this. Additionally, no causative relation has been established. Regarding viral infections, although in the past they have been associated with IPF, causation has not been proved. Although in the past the diagnosis of acute exacerbation of IPF (AE-IPF) was not considered in patients with overt infection, this was amended in the last few years and infection is considered a cause for exacerbation. Besides this, a higher microbial burden has been found in the lungs of patients with AE-IPF and an association with higher morbidity and mortality has been confirmed. In contrast, an association of AE-IPF with viral infection has not been established. Despite the progress during the last decade, a comprehensive knowledge of the microbiome and virome in IPF and their role in disease pathogenesis are yet elusive. Although association with disease severity, risk for progression and mortality has been established, causation has not been proven and the potential use as a biomarker or the benefits of antimicrobial therapeutic strategies are yet to be determined.

The Causative in Indonesian

In the Principle and Parameter approach, the Indonesian suffix –kan can be treated as an inflection that functions to create a causative relation between the arguments which the verb takes. Along with the treatment, the voice affixes (Vc) meng-, di-, and ter- also heads a phrase, a Voice Phrase (VcP), and a verbal sentence in Indonesian, which really has the status of a Complementizer Phrase (CP), has a VcP as its main element. Vc may take a VP or any other phrase category including a Causative Phrase (CsP) headed by the suffix –kan as its complement. A CsP can also become the complement or adjunct or a VP or another category phrase which becomes the complement of a VcP. The analysis of the suffix –kan as an inflection can explain the similarity of the pairs of sentences which are syntactically similar and have the same meaning, solve the problem of meaning which usually accompanies the discussion of the suffix, and explain the production of Indonesian sentences which contain the suffix –kan. Furthermore, the study may also provide insights for English and Indonesian course designers to develop materials which can present the topic clearly and for Indonesian and English translators to arrive at a good translation equivalent.

Neuroblastoma Amplified Sequence Gene Mutations Inducing Acute Kidney and Liver Injury in an Adolescent Female

Acute liver injury (ALI) in children is a life-threatening event, and a definitive etiology can be identified in approximately 50% of cases. Neuroblastoma amplified sequence (NBAS) gene mutations have been associated with a broad phenotypic spectrum of this disease, ranging from recurrent episodes of fever-induced liver injuries to multiorgan involvement, including frequent infections as well as skeletal and immunological abnormalities. Here, we describe an adolescent female with a confirmed compound heterozygous NBAS gene mutation who presented with an episode of ALI complicated by severe acute kidney injury (AKI). The kidney injury was most probably driven by an intrinsic insult, as noted by elevated neutrophil gelatinase-associated lipocalin levels and a kidney biopsy demonstrating severe tubular damage consistent with acute tubular necrosis. While the patient’s liver function and mental status showed significant improvement with supportive care, recovery of kidney function was delayed, and the patient required acute hemodialysis. We suggest a causative relation between the NBAS gene mutation and severe AKI.

Osteosarcoma of the Mandible in a Patient with Florid Cemento-Osseous Dysplasia and Li–Fraumeni Syndrome: A Rare Coincidence

Cemento-osseous dysplasia (COD) is the most common benign fibro-osseous lesion of the jaws and generally considered non-neoplastic and self-limited. Here, we present a 30-year old female who noticed a bilateral swelling of her posterior mandible with irregular periapical mineralization and incomplete root resorption on panoramic radiographs. A biopsy revealed florid COD and no further treatment was initiated. 9 years later, she presented with a progressive expansion of her left posterior mandible after being treated for bilateral breast cancer 4 and 8 years before. CT scans showed expansile and densely mineralized lesions in all four quadrants with the left posterior mandible showing a focal penetration of the buccal cortical bone. Biopsies revealed an osteoblastic high-grade osteosarcoma in the left and a COD in the right mandible, notably with cellular atypia in the spindle cell component. The patient underwent segmental resection of the left mandible with clear margins and adjuvant chemotherapy. Subsequent genetic testing identified a heterozygous germline TP53 mutation (p.V173G) which confirmed the clinically suspected Li–Fraumeni syndrome (LFS). 3 years after the resection, the patient is free of disease and the other foci of COD remained stable in size on follow-up imaging analyses. Our case illustrates LFS-related osteosarcoma developing within florid COD. Given the rarity of this coincidence, a causative relation between the two lesions seems unlikely but in patients with tumor predisposition syndromes it might be advisable to closely monitor even benign lesions like COD.

Neurological manifestations of severe acute respiratory syndrome coronavirus 2—a controversy ‘gone viral’

Severe acute respiratory syndrome coronavirus 2 first appeared in December 2019 in Wuhan, China, and developed into a worldwide pandemic within the following 3 months causing severe bilateral pneumonia (coronavirus disease 2019) with in part fatal outcomes. After first experiences and tentative strategies to face this new disease, several cases were published describing severe acute respiratory syndrome coronavirus 2 infection related to the onset of neurological complaints and diseases such as, for instance, anosmia, stroke or meningoencephalitis. Of note, there is still a controversy about whether or not there is a causative relation between severe acute respiratory syndrome coronavirus 2 and these neurological conditions. Other concerns, however, seem to be relevant as well. This includes not only the reluctance of patients with acute neurological complaints to report to the emergency department for fear of contracting severe acute respiratory syndrome coronavirus 2 but also the ethical and practical implications for neurology patients in everyday clinical routine. This paper aims to provide an overview of the currently available evidence for the occurrence of severe acute respiratory syndrome coronavirus 2 in the central and peripheral nervous system and the neurological diseases potentially involving this virus.

Genetic and Epigenetic Analysis Revealing Variants in the NCAM1–TTC12–ANKK1–DRD2 Cluster Associated Significantly With Nicotine Dependence in Chinese Han Smokers

Backgrounds Although studies have demonstrated that the NCAM1–TTC12–ANKK1–DRD2 gene cluster plays essential roles in addictions in subjects of European and African origin, study of Chinese Han subjects is limited. Further, the underlying biological mechanisms of detected associations are largely unknown. Methods Sixty-four single-nucleotide polymorphisms (SNPs) in this cluster were analyzed for association with Fagerstrőm Test for Nicotine Dependence score (FTND) and cigarettes per day (CPD) in male Chinese Han smokers (N = 2616). Next-generation bisulfite sequencing was used to discover smoking-associated differentially methylated regions (DMRs). Both cis-eQTL and cis-mQTL analyses were applied to assess the cis-regulatory effects of these risk SNPs. Results Association analysis revealed that rs4648317 was significantly associated with FTND and CPD (p = .00018; p = .00072). Moreover, 14 additional SNPs were marginally significantly associated with FTND or CPD (p = .05–.01). Haplotype-based association analysis showed that one haplotype in DRD2, C-T-A-G, formed by rs4245148, rs4581480, rs4648317, and rs11214613, was significantly associated with CPD (p = .0005) and marginally associated with FTND (p = .003). Further, we identified four significant smoking-associated DMRs, three of which are located in the DRD2/ANKK1 region (p = .0012–.00005). Finally, we found five significant CpG–SNP pairs (p = 7.9 × 10–9–6.6 × 10–6) formed by risk SNPs rs4648317, rs11604671, and rs2734849 and three methylation loci. Conclusions We found two missense variants (rs11604671; rs2734849) and an intronic variant (rs4648317) with significant effects on ND and further explored their mechanisms of action through expression and methylation analysis. We found the majority of smoking-related DMRs are located in the ANKK1/DRD2 region, indicating a likely causative relation between non-synonymous SNPs and DMRs. Implications This study shows that there exist significant association of variants and haplotypes in ANKK1/DRD2 region with ND in Chinese male smokers. Further, this study also shows that DNA methylation plays an important role in mediating such associations.

Unique Case of Bilateral Exudative Retinal Detachment following Creatine Supplementation in a Patient with Autosomal Dominant Bestrophinopathy

We report a case of bilateral serous retinal detachment in a patient with rod-cone dystrophy caused by mutation of BEST1. This followed creatine monohydrate use as a dietary supplement. A 39-year-old male with rod-cone dystrophy and low hyperopia developed extensive bilateral exudative retinal detachment following creatine monohydrate diet supplementation. Five days after stopping creatine use, the bilateral retinal detachments resolved completely. This may indicate a causative relation of creatine supplementation to development of serous retinal detachment in a susceptible patient with pre-existing retinal dystrophy.

Marked Causative Structures of Chinese Verb-Resultative Construction

This paper aims to study the syntactic and semantic features of ‘marked VRC causative structures’, those special syntactic-semantic structures formed by verb-resultative constructions (VRCs) which violate both the Uniformity of Theta Assignment Hypothesis and the Thematic Hierarchy. Their syntactic and semantic features are defined as follows: 1) VRC has a causative relation within itself; 2) the argument in the object position is the causee and the only argument of the resultative complement; 3) the causer in the subject position is any conceptual component from the cause event other than the agent of the predicate verb. This paper then attempts to propose an extended account to expound how they are formed syntactically and semantically. On this account, a marked VRC causative structure is re-causativization of a VRC when the VRC is self-causative; it enables other conceptual components of the cause event than the agent to become the causer when a VRC is not self-causative. There are some constraints on what becomes the causer of a marked VRC causative structure.

The Mapping of Thematic Roles to Grammatical Functions in Mandarin BA Construction Denoting Causation: From the Perspective of Lexical Mapping Theory

NP1 in the position of the subject of the mandarin BA construction denoting causation is usually occupied by patientlike roles and NP2 immediately following BA is usually occupied by agentlike roles. The causative relation between NP1 and NP2, with the former being the Cause, and the latter the Affectee, derives from the word BA, which triggers in the lexicon the morpholexical operation of causativization when it unites with the predicate. The operation involves either assignment of causative roles Cause and Affectee to the existent thematic roles or insertion of a new role Cause to the thematic structure, with the prominence of Cause or the thematic role assigned Cause always being over the other roles. Having undergone this morpholexical operation, the thematic structure correctly maps to and generates the grammatical functional structure according to the general principles and conditions stipulated by the Lexical Mapping Theory (LMT). The result of this research shows that even for a construction as unique as the mandarin BA construction denoting causation compared with any other languages, LMT is still well applicable in explaining its role-function mapping.