Pyrazinamide (PZA) is a cornerstone antimicrobial drug used exclusively for the treatment of tuberculosis (TB). Due to its ability to shorten drug therapy by 3 months and reduce disease relapse rates, PZA is considered an irreplaceable component of standard first-line short-course therapy for drug-susceptible TB and second-line treatment regimens for multidrug-resistant TB. Despite over 60 years of research on PZA and its crucial role in current and future TB treatment regimens, the mode of action of this unique drug remains unclear. Defining the mode of action for PZA will open new avenues for rational design of novel therapeutic approaches for the treatment of TB. In this review, we discuss the four prevailing models for PZA action, recent developments in modulation of PZA susceptibility and resistance, and outlooks for future research and drug development.

Technologies allowing genetic sequencing of the human microbiome are opening new realms to discovery. The host microbiota substantially impacts immune responses both in immune-mediated inflammatory diseases (IMIDs) and in tumors affecting tissues beyond skin and mucosae. However, a mechanistic link between host microbiota and cancer or IMIDs has not been well established. Here, we propose T helper 17 (T_H17) lymphocytes as the connecting factor between host microbiota and rheumatoid or psoriatic arthritides, multiple sclerosis, breast or ovarian cancer, and multiple myeloma. We theorize that similar mechanisms favor the expansion of gut-borne T_H17 cells and their deployment at the site of inflammation in extraborder IMIDs and tumors, where T_H17 cells are driving forces. Thus, from a pathogenic standpoint, tumors may share mechanistic routes with IMIDs. A review of similarities and divergences in microbiota-T_H17 cell interactions in IMIDs and cancer sheds light on previously ignored pathways in either one of the two groups of pathologies and identifies novel therapeutic avenues.

Viruses and mobile genetic elements are molecular parasites or symbionts that coevolve with nearly all forms of cellular life. The route of virus replication and protein expression is determined by the viral genome type. Comparison of these routes led to the classification of viruses into seven "Baltimore classes" (BCs) that define the major features of virus reproduction. However, recent phylogenomic studies identified multiple evolutionary connections among viruses within each of the BCs as well as between different classes. Due to the modular organization of virus genomes, these relationships defy simple representation as lines of descent but rather form complex networks. Phylogenetic analyses of virus hallmark genes combined with analyses of gene-sharing networks show that replication modules of five BCs (three classes of RNA viruses and two classes of reverse-transcribing viruses) evolved from a common ancestor that encoded an RNA-directed RNA polymerase or a reverse transcriptase. Bona fide viruses evolved from this ancestor on multiple, independent occasions via the recruitment of distinct cellular proteins as capsid subunits and other structural components of virions. The single-stranded DNA (ssDNA) viruses are a polyphyletic class, with different groups evolving by recombination between rolling-circle-replicating plasmids, which contributed the replication protein, and positive-sense RNA viruses, which contributed the capsid protein. The double-stranded DNA (dsDNA) viruses are distributed among several large monophyletic groups and arose via the combination of distinct structural modules with equally diverse replication modules. Phylogenomic analyses reveal the finer structure of evolutionary connections among RNA viruses and reverse-transcribing viruses, ssDNA viruses, and large subsets of dsDNA viruses. Taken together, these analyses allow us to outline the global organization of the virus world. Here, we describe the key aspects of this organization and propose a comprehensive hierarchical taxonomy of viruses.

Although enteroviruses are associated with a wide variety of diseases and conditions, their mode of replication is well conserved. Their genome is carried as a single, positive-sense RNA strand. At the 5' end of the strand is an approximately 90-nucleotide self-complementary region called the 5' cloverleaf, or the oriL. This noncoding region serves as a platform upon which host and virus proteins, including the 3B, 3C, and 3D virus proteins, assemble in order to initiate replication of a negative-sense RNA strand. The negative strand in turn serves as a template for synthesis of multiple positive-sense RNA strands. Building on structural studies of individual RNA stem-loops, the structure of the intact 5' cloverleaf from rhinovirus has recently been determined via nuclear magnetic resonance/small-angle X-ray scattering (NMR/SAXS)-based methods, while structures have also been determined for enterovirus 3A, 3B, 3C, and 3D proteins. Analysis of these structures, together with structural and modeling studies of interactions between host and virus proteins and RNA, has begun to provide insight into the enterovirus replication mechanism and the potential to inhibit replication by blocking these interactions.

While flagella have been studied extensively as motility organelles, with a focus on internal structures such as the axoneme, more recent research has illuminated the roles of the flagellar surface in a variety of biological processes. Parasitic protists of the order Kinetoplastida, which include trypanosomes and Leishmania species, provide a paradigm for probing the role of flagella in host-microbe interactions and illustrate that this interface between the flagellar surface and the host is of paramount importance. An increasing body of knowledge indicates that the flagellar membrane serves a multitude of functions at this interface: attachment of parasites to tissues within insect vectors, close interactions with intracellular organelles of vertebrate cells, transactions between flagella from different parasites, junctions between the flagella and the parasite cell body, emergence of nanotubes and exosomes from the parasite directed to either host or microbial targets, immune evasion, and sensing of the extracellular milieu. Recent whole-organelle or genome-wide studies have begun to identify protein components of the flagellar surface that must mediate these diverse host-parasite interactions. The increasing corpus of knowledge on kinetoplastid flagella will likely prove illuminating for other flagellated or ciliated pathogens as well.

CRISPR-Cas systems have been engineered as powerful tools to control gene expression in bacteria. The most common strategy relies on the use of Cas effectors modified to bind target DNA without introducing DNA breaks. These effectors can either block the RNA polymerase or recruit it through activation domains. Here, we discuss the mechanistic details of how Cas effectors can modulate gene expression by blocking transcription initiation or acting as transcription roadblocks. CRISPR-Cas tools can be further engineered to obtain fine-tuned control of gene expression or target multiple genes simultaneously. Several caveats in using these tools have also been revealed, including off-target effects and toxicity, making it important to understand the design rules of engineered CRISPR-Cas effectors in bacteria. Alternatively, some types of CRISPR-Cas systems target RNA and could be used to block gene expression at the posttranscriptional level. Finally, we review applications of these tools in high-throughput screens and the progress and challenges in introducing CRISPR knockdown to other species, including nonmodel bacteria with industrial or clinical relevance. A deep understanding of how CRISPR-Cas systems can be harnessed to control gene expression in bacteria and build powerful tools will certainly open novel research directions.

Acetylation is a conserved modification used to regulate a variety of cellular pathways, such as gene expression, protein synthesis, detoxification, and virulence. Acetyltransferase enzymes transfer an acetyl moiety, usually from acetyl coenzyme A (AcCoA), onto a target substrate, thereby modulating activity or stability. Members of the GCN5-N-acetyltransferase (GNAT) protein superfamily are found in all domains of life and are characterized by a core structural domain architecture. These enzymes can modify primary amines of small molecules or of lysyl residues of proteins. From the initial discovery of antibiotic acetylation, GNATs have been shown to modify a myriad of small-molecule substrates, including tRNAs, polyamines, cell wall components, and other toxins. This review focuses on the literature on small-molecule substrates of GNATs in bacteria, including structural examples, to understand ligand binding and catalysis. Understanding the plethora and versatility of substrates helps frame the role of acetylation within the larger context of bacterial cellular physiology.

The substantial discrepancy between the strong effects of functional foods and various drugs, especially traditional Chinese medicines (TCMs), and the poor bioavailability of these substances remains a perplexing problem. Understanding the gut microbiota, which acts as an effective bioreactor in the human intestinal tract, provides an opportunity for the redefinition of bioavailability. Here, we discuss four different pathways associated with the role of the gut microbiota in the transformation of parent compounds to beneficial or detrimental small molecules, which can enter the body’s circulatory system and be available to target cells, tissues, and organs. We further describe and propose effective strategies for improving bioavailability and alleviating side effects with the help of the gut microbiota. This review also broadens our perspectives for the discovery of new medicinal components.

In bacterial populations, quorum sensing (QS) systems participate in the regulation of specialization processes and regulate collective behaviors that mediate interactions and allow survival of the species. In Gram-positive bacteria, QS systems of the RRNPP family (Rgg, Rap, NprR, PlcR, and PrgX) consist of intracellular receptors and their cognate signaling peptides. Two of these receptors, Rap and NprR, have regained attention in Bacillus subtilis and the Bacillus cereus group. Some Rap proteins, such as RapH and Rap60, are multifunctional and/or redundant in function, linking the specialization processes of sporulation and competence, as well as global expression changes in the transition phase in B. subtilis. NprR, an evolutionary intermediate between Rap and RRNPP transcriptional activators, is a bifunctional regulator that modulates sporulation initiation and activates nutrient scavenging genes. In this review, we discuss how these receptors switch between functions and connect distinct signaling pathways. Based on structural evidence, we propose that RapH and Rap60 should be considered moonlighting proteins. Additionally, we analyze an evolutionary and ecological perspective to understand the multifunctionality and functional redundancy of these regulators in both Bacillus spp. and non-Bacillus Firmicutes. Understanding the mechanistic, structural, ecological, and evolutionary basis for the multifunctionality and redundancy of these QS systems is a key step for achieving the development of innovative technologies for health and agriculture.

While airway clearance techniques (ACTs) are recommended for individuals with bronchiectasis, many trials have demonstrated inconsistent benefits or failed to reach their primary outcome. This review determined the most common clinical and patient-reported outcome measures used to evaluate the efficacy of ACTs in bronchiectasis. A literature search of five databases using relevant keywords and filtering for studies published in English, up until the end of August 2019, was completed. Studies included randomised controlled trials, using crossover or any other trial design, and abstracts. Studies were included where the control was placebo, no intervention, standard care, usual care or an active comparator. Adults with bronchiectasis not related to cystic fibrosis were included. Extracted data comprised study authors, design, duration, intervention, outcome measures and results. The search identified 27 published studies and one abstract. The most common clinical outcome measures were sputum volume (n=23), lung function (n=17) and pulse oximetry (n=9). The most common patient-reported outcomes were health-related quality of life (measured with St George's Respiratory Questionnaire, n=4), cough-related quality of life (measured with Leicester Cough Questionnaire, n=4) and dyspnoea (measured with Borg/modified Borg scale, n=8). Sputum volume, lung function, dyspnoea and health- and cough-related quality of life appear to be the most common clinical and patient-reported measures of airway clearance treatment efficacy.

Background

People with pulmonary fibrosis often experience a protracted time to diagnosis, high symptom burden and limited disease information. This review aimed to identify the supportive care needs reported by people with pulmonary fibrosis and their caregivers.

ABSTRACTBackground:Some opportunities to routinely capture and improve respectful maternity care (RMC) during facility-based childbirth include quality improvement (QI) initiatives, community-based monitoring efforts through community score cards (CSC), and performance-based financing (PBF) initiatives. But there is limited guidance on which types of RMC indicators are best suited for inclusion in these initiatives. We sought to provide practical evidence-based recommendations on indicators that may be used for routine measurement of RMC in programs.Methods:We used a rapid review approach, which included (1) reviewing existing documents and publications to extract RMC indicators and identify which have or can be used in facility-based QI, CSCs, and PBF schemes; (2) surveying RMC and maternal health experts to rank indicators, and (3) analyzing survey data to select the most recommended indicators.Results:We identified 49 indicators spanning several domains of RMC and mistreatment including dignified/nondignified care, verbal and physical abuse, privacy/confidentiality, autonomy/loss of autonomy, supportive care/lack thereof, communication, stigma, discrimination, trust, facility environment/culture, responsiveness, and nonevidence-based care. Based on the analysis of the survey data, we recommend 33 indicators (between 2 and 6 indicators for each RMC domain) that may be suited for incorporation in both facility-based QI and CSC-related monitoring efforts.Conclusion:Integrating RMC indicators into QI and CSC initiatives, as well as in other maternal and neonatal health programs, could help improve RMC at the facility and community level. More research is needed into whether RMC can be integrated into PBF initiatives. Integration of RMC indicators into programs to improve quality of care and other health system outcomes will facilitate routine monitoring and accountability around experience of care. Measurement and improvement of women's experiences will increase maternal health service utilization and improve quality of care as a means of reducing maternal and neonatal morbidity and mortality.

BACKGROUND

Sex differences have been described in diabetes cardiovascular outcome trials (CVOTs).

BACKGROUND

Continuous glucose monitoring (CGM) provides important information to aid in achieving glycemic targets in people with diabetes.

In patients with cancer-associated venous thromboembolism, knowledge of the estimated rate of recurrent events is important for clinical decision-making regarding anticoagulant therapy. The Ottawa score is a clinical prediction rule designed for this purpose, stratifying patients according to their risk of recurrent venous thromboembolism during the first six months of anticoagulation. We conducted a systematic review and meta-analysis of studies validating either the Ottawa score in its original or modified versions. Two investigators independently reviewed the relevant articles published from 1st June 2012 to 15th December 2018 and indexed in MEDLINE and EMBASE. Nine eligible studies were identified; these included a total of 14,963 patients. The original score classified 49.3% of the patients as high-risk, with a sensitivity of 0.7 [95% confidence interval (CI): 0.6-0.8], a 6-month pooled rate of recurrent venous thromboembolism of 18.6% (95%CI: 13.9-23.9). In the low-risk group, the recurrence rate was 7.4% (95%CI: 3.4-12.5). The modified score classified 19.8% of the patients as low-risk, with a sensitivity of 0.9 (95%CI: 0.4-1.0) and a 6-month pooled rate of recurrent venous thromboembolism of 2.2% (95%CI: 1.6-2.9). In the high-risk group, recurrence rate was 10.2% (95%CI: 6.4-14.6). Limitations of our analysis included type and dosing of anticoagulant therapy. We conclude that new therapeutic strategies are needed in patients at high risk for recurrent cancer-associated venous thromboembolism. Low-risk patients, as per the modified score, could be good candidates for oral anticoagulation. (This systematic review was registered with the International Prospective Registry of Systematic Reviews as: PROSPERO CRD42018099506).

BackgroundSelf-harm is a serious risk factor for suicide, a major public health concern, and a significant burden on the NHS. Rates of self-harm presentation in primary care are rising and GPs interact with patients both before and after they have self-harmed. There is significant public and political interest in reducing rates of self-harm, but there has been no robust synthesis of the existing literature on the role of GPs in the management of patients who self-harm.AimThis study aimed to explore the role of the GP in the management of patients with self-harm behaviour.Design and settingA systematic review and narrative synthesis of primary care literature.MethodThis systematic review was conducted and is reported in line with PRISMA guidance. Electronic databases systematically searched were MEDLINE, PsycINFO, EMBASE, CINAHL, Web of Science, and AMED. Two independent reviewers conducted study screening and selection, data extraction, and quality appraisal of all included studies. Thematic analysis was conducted.ResultsFrom 6976 unique citations, 12 studies met eligibility criteria and were included. These 12 studies, published from 1997–2016, of 789 GPs/family medicine physicians from Europe, the US, and Australia were of good methodological quality. Five themes were identified for facilitating GP management of self-harm: GP training, improved communication, service provision, clinical guidelines, and young people. Four barriers for GP management of self-harm were identified: assessment, service provision, local, and systemic factors.ConclusionGPs recognise self-harm as a serious risk factor for suicide, but some feel unprepared for managing self-harm. The role of the GP is multidimensional and includes frontline assessment and treatment, referral to specialist care, and the provision of ongoing support.

PURPOSE

Operational failures are system-level errors in the supply of information, equipment, and materials to health care personnel. We aimed to review and synthesize the research literature to determine how operational failures in primary care affect the work of primary care physicians.

Caseum, the central necrotic material of tuberculous lesions, is a reservoir of drug-recalcitrant persisting mycobacteria. Caseum is found in closed nodules and in open cavities connecting with an airway. Several commonly accepted characteristics of caseum were established during the preantibiotic era, when autopsies of deceased tuberculosis (TB) patients were common but methodologies were limited. These pioneering studies generated concepts such as acidic pH, low oxygen tension, and paucity of nutrients being the drivers of nonreplication and persistence in caseum. Here we review widely accepted beliefs about the caseum-specific stress factors thought to trigger the shift of Mycobacterium tuberculosis to drug tolerance. Our current state of knowledge reveals that M. tuberculosis is faced with a lipid-rich diet rather than nutrient deprivation in caseum. Variable caseum pH is seen across lesions, possibly transiently acidic in young lesions but overall near neutral in most mature lesions. Oxygen tension is low in the avascular caseum of closed nodules and high at the cavity surface, and a gradient of decreasing oxygen tension likely forms toward the cavity wall. Since caseum is largely made of infected and necrotized macrophages filled with lipid droplets, the microenvironmental conditions encountered by M. tuberculosis in foamy macrophages and in caseum bear many similarities. While there remain a few knowledge gaps, these findings constitute a solid starting point to develop high-throughput drug discovery assays that combine the right balance of oxygen tension, pH, lipid abundance, and lipid species to model the profound drug tolerance of M. tuberculosis in caseum.

Burkholderia cepacia (formerly Pseudomonas cepacia) was once thought to be a single bacterial species but has expanded to the Burkholderia cepacia complex (Bcc), comprising 24 closely related opportunistic pathogenic species. These bacteria have a widespread environmental distribution, an extraordinary metabolic versatility, a complex genome with three chromosomes, and a high capacity for rapid mutation and adaptation. Additionally, they present an inherent resistance to antibiotics and antiseptics, as well as the abilities to survive under nutrient-limited conditions and to metabolize the organic matter present in oligotrophic aquatic environments, even using certain antimicrobials as carbon sources. These traits constitute the reason that Bcc bacteria are considered feared contaminants of aqueous pharmaceutical and personal care products and the frequent reason behind nonsterile product recalls. Contamination with Bcc has caused numerous nosocomial outbreaks in health care facilities, presenting a health threat, particularly for patients with cystic fibrosis and chronic granulomatous disease and for immunocompromised individuals. This review addresses the role of Bcc bacteria as a potential public health problem, the mechanisms behind their success as contaminants of pharmaceutical products, particularly in the presence of biocides, the difficulties encountered in their detection, and the preventive measures applied during manufacturing processes to control contamination with these objectionable microorganisms. A summary of Bcc-related outbreaks in different clinical settings, due to contamination of diverse types of pharmaceutical products, is provided.

Intrathecal administration of anti-infectives is indicated in central nervous system infections by multiresistant pathogens when drugs that can reach adequate cerebrospinal fluid (CSF) concentrations by systemic therapy are not available. Antibiotics that readily pass the blood-brain and blood-CSF barriers and/or that have low toxicity allowing an increase in the daily dosage should not be used for intrathecal therapy. Intrathecal therapy is accompanied by systemic treatment. Antibacterials indispensable for intrathecal therapy include aminoglycosides, colistin, daptomycin, tigecycline, and vancomycin. Limited experience suggests the utility of the antifungals amphotericin B and caspofungin. Intraventricular administration ensures distribution throughout the CSF compartment, whereas intralumbar dosing often fails to attain adequate antibiotic concentrations in the ventricles. The individual dose is determined by the estimated size of the CSF space and by the estimated clearance from CSF. For moderately lipophilic anti-infectives with a molecular weight above approximately 1,000 g/mol, as well as for hydrophilic drugs with a molecular weight above approximately 400 g/mol, one daily dose is normally adequate. The ventricular drain should be clamped for 15 to 120 min to facilitate the distribution of the anti-infective in the CSF space. Therapeutic drug monitoring of the trough levels is necessary only in cases of therapeutic failure.

Although not as ubiquitous as antibacterial susceptibility testing, antifungal susceptibility testing (AFST) is a tool of increasing importance in clinical microbiology laboratories. The goal of AFST is to reliably produce MIC values that may be used to guide patient therapy, inform epidemiological studies, and track rates of antifungal drug resistance. There are three methods that have been standardized by standards development organizations: broth dilution, disk diffusion, and azole agar screening for Aspergillus. Other commonly used methods include gradient diffusion and the use of rapid automated instruments. Novel methodologies for susceptibility testing are in development. It is important for laboratories to consider not only the method of testing but also the interpretation (or lack thereof) of in vitro data.

In this retrospective study, whole-genome sequencing (WGS) data generated on an Ion Torrent platform was used to predict phenotypic drug resistance profiles for first- and second-line drugs among Swedish clinical Mycobacterium tuberculosis isolates from 2016 to 2018. The accuracy was ~99% for all first-line drugs and 100% for four second-line drugs. Our analysis supports the introduction of WGS into routine diagnostics, which might, at least in Sweden, replace phenotypic drug susceptibility testing in the future.

Currently, the expansion of the novel human respiratory coronavirus (known as SARS-CoV-2 [severe acute respiratory syndrome coronavirus 2], COVID-2019 [coronavirus disease 2019], or 2019-nCoV [2019 novel coronavirus]) has stressed the need for therapeutic alternatives to alleviate and stop this new epidemic. The previous epidemics of infections by high-morbidity human coronaviruses, such as SARS-CoV in 2003 and the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, prompted the characterization of compounds that could be potentially active against the currently emerging novel coronavirus, SARS-CoV-2. The most promising compound is remdesivir (GS-5734), a nucleotide analog prodrug currently in clinical trials for treating Ebola virus infections. Remdesivir inhibited the replication of SARS-CoV and MERS-CoV in tissue cultures, and it displayed efficacy in nonhuman animal models. In addition, a combination of the human immunodeficiency virus type 1 (HIV-1) protease inhibitors lopinavir/ritonavir and interferon beta (LPV/RTV–IFN-β) was shown to be effective in patients infected with SARS-CoV. LPV/RTV–IFN-β also improved clinical parameters in marmosets and mice infected with MERS-CoV. Remarkably, the therapeutic efficacy of remdesivir appeared to be superior to that of LPV/RTV–IFN-β against MERS-CoV in a transgenic humanized mouse model. The relatively high mortality rates associated with these three novel human coronavirus infections, SARS-CoV, MERS-CoV, and SARS-CoV-2, have suggested that proinflammatory responses might play a role in the pathogenesis. It remains unknown whether the generated inflammatory state should be targeted. Therapeutics that target the coronavirus alone might not be able to reverse highly pathogenic infections. This minireview aims to provide a summary of therapeutic compounds that have shown potential in fighting SARS-CoV-2 infections.

The poor prognosis for patients with pancreatic ductal adenocarcinoma (PDAC) impels an improved understanding of disease biology to facilitate the development of better therapies. PDAC typically features a remarkably dense stromal reaction, featuring and established by a prominent population of cancer-associated fibroblasts (CAF). Genetically engineered mouse models and increasingly sophisticated cell culture techniques have demonstrated important roles for fibroblasts in PDAC progression and therapy response, but these roles are complex, with strong evidence for both tumor-supportive and tumor-suppressive or homeostatic functions. Here, we review the recent literature that has improved our understanding of heterogeneity in fibroblast fate and function in this disease including the existence of distinct fibroblast populations, and highlight important avenues for future study.

Ovarian cancer imposes a substantial health and economic burden. We systematically reviewed current health-economic evidence for ovarian cancer early detection or prevention strategies. Accordingly, we searched relevant databases for cost-effectiveness studies evaluating ovarian cancer early detection or prevention strategies. Study characteristics and results including quality-adjusted life years (QALY), and incremental cost-effectiveness ratios (ICER) were summarized in standardized evidence tables. Economic results were transformed into 2017 Euros. The included studies (N = 33) evaluated ovarian cancer screening, risk-reducing interventions in women with heterogeneous cancer risks and genetic testing followed by risk-reducing interventions for mutation carriers. Multimodal screening with a risk-adjusted algorithm in postmenopausal women achieved ICERs of 9,800–81,400 Euros/QALY, depending on assumptions on mortality data extrapolation, costs, test performance, and screening frequency. Cost-effectiveness of risk-reducing surgery in mutation carriers ranged from cost-saving to 59,000 Euros/QALY. Genetic testing plus risk-reducing interventions for mutation carriers ranged from cost-saving to 54,000 Euros/QALY in women at increased mutation risk. Our findings suggest that preventive surgery and genetic testing plus preventive surgery in women at high risk for ovarian cancer can be considered effective and cost-effective. In postmenopausal women from the general population, multimodal screening using a risk-adjusted algorithm may be cost-effective.

BACKGROUND AND PURPOSE:

Computed tomography angiography offers a non-invasive alternative to DSA for the assessment of cerebral vasospasm following subarachnoid hemorrhage but there is limited evidence regarding its reliability. Our aim was to perform a systematic review (Part I) and to assess (Part II) the inter- and intraobserver reliability of CTA in the diagnosis of cerebral vasospasm.

SUMMARY:

The cerebral ventricles have been studied since the fourth century BC and were originally thought to harbor the soul and higher executive functions. During the infancy of neuroradiology, alterations to the ventricular shape and position on pneumoencephalography and ventriculography were signs of mass effect or volume loss. However, in the current era of high-resolution cross-sectional imaging, variation in ventricular anatomy is more easily detectable and its clinical significance is still being investigated. Interpreting radiologists must be aware of anatomic variations of the ventricular system to prevent mistaking normal variants for pathology. We will review of the anatomy and development of the lateral ventricles and discuss several ventricular variations.

The Call of the Wild – Movie Review Rating: A- (Great) Trailer/Thumbnail Courtesy 20th Century Studios Jack London’s novel The Call of the Wild is a stirring and page turning adventure that puts the reader into the point-of-view of a dog. Buck’s journey from domesticated pooch to a dog understanding where he came from is […]

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The Jesus Rolls – Movie Review Rating: D+ (Bad) Trailer/Thumbnail Courtesy Level Film Joel and Ethan Coen’s The Big Lebowski has rightfully become a beloved cult film and with that comes calls to make a sequel. The Coen Brothers have correctly asserted that the Dude is better suited to one stand-alone story. However, that hasn’t […]

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The Invisible Man – Movie Review Rating: A- (Great) Trailer/Thumbnail Courtesy Universal Pictures The horror genre doesn’t get nearly enough recognition for how it handles certain subject matter. Some can be gratuitous, while others are able to comment on society’s ills in a way that provokes a needed reaction from the audience. Director/writer Leigh Whannell […]

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Run This Town – Movie Review Rating: C (Average) Trailer/Thumbnail Courtesy Elevation Pictures The scandal surrounding Toronto Mayor Rob Ford was so massive, it even managed to receive worldwide attention. That’s rather unprecedented in Canadian politics, but it was an unusual story not in sync with peoples’ stereotypical view of Canada. A movie about Ford […]

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Onward – Movie Review Rating: B+ (Very Good) Trailer/Thumbnail Courtesy Walt Disney Studios Part of the appeal of fantasy films is seeing the different magical creatures that populate the world created by the authors and filmmakers. Director Dan Scanlon seems to have latched onto that in devising the story for Onward, which cleverly brings those […]

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The Hunt – Movie Review Rating: B- (Okay) Trailer/Thumbnail Courtesy Universal Pictures Within the current political climate, both sides have never been more divided. This is especially amplified in the age of the Internet, where everyone has a place to voice their opinion. The Hunt takes the curious approach of making the stereotypical alt-right wingers […]

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Bloodshot – Movie Review Rating: D (Very Bad) Trailer/Thumbnail Courtesy Sony Pictures Watching Bloodshot, one is almost reminded of the loud, absurd and moronic action movies that once starred the likes of Jean-Claude Van Damme and Sylvester Stallone. It’s just a bunch of over-the-top action scenes loosely tied together by the thinnest of plots. In […]

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My Spy – Movie Review Rating: B (Good) Trailer/Thumbnail Courtesy Elevation Pictures The premise for My Spy isn’t the most original concept in the world. There have been any number of comedies centered on muscled men tasked with watching over children and the humour that ensues. It was probably inevitable that Dave Bautista would be […]

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Never Rarely Sometimes Always – Movie Review Rating: A- (Great) Trailer/Thumbnail Courtesy Universal Pictures Getting pregnant can be a tricky event for any teenager and how they approach this can often depend on their environment. In exploring the topic, director/writer Eliza Hittman has opted for a realistic portrayal. The journey taken by Autumn and her […]

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The Willoughbys – Movie Review Rating: B+ (Very Good) Trailer/Thumbnail Courtesy Netflix There is something strangely appealing about stories that mix childlike fantasy with macabre humour. It’s why Roald Dahl’s books continue to resonate with readers, young and old. The Willoughbys brings us a colourful world with dark themes and wicked comedy. Director/co-writer Kris Pearn […]

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A new movie reimagines H.G. Wells's novel The Invisible Man. We still can't make people invisible, but it is possible to make tiny objects completely disappear

Adrian Tchaikovsky's latest novel The Doors of Eden rewrites Earth's evolutionary history, with highlights including fish that upload their minds to supercomputers and cats that rule over primates

Westworld is soon to return with season three. Four episodes in to the impossibly glamorous, highly urbanised future, I can't wait to find out what's going on, writes Emily Wilson

Doom Eternal does contain gratuitous violence, but the evidence suggests violence in video games doesn't affect people's behaviour in the real world, says Jacob Aron

Is our love affair with AI really about building a new kind of deity to meet human needs no amount of rationality can fill? Max Barry's disturbing novel Providence lays out the case, says Sally Adee

The video game Resident Evil 3 was in development long before the coronavirus outbreak, but it holds up a mirror to the strange times we live in today

Martha Wells's action-packed novel Network Effect puts you inside the head of a Murderbot. It raises fascinating questions you will think about for a long time, says Sally Adee