Focal nodular hyperplasia: a review of current indications for and outcomes of hepatic resection

Background

Focal nodular hyperplasia (FNH) is a common benign disease of the liver with no recognized potential for malignant transformation. The term describes an entity of lobular proliferation of normally differentiated hepatocytes, frequently around a central fibrous scar. Two key issues influence surgical decision making in FNH: diagnostic certainty, and symptomatic assessment.

Methods

A systematic review of studies reporting hepatic resections of FNH was performed. Indications and outcomes in adult populations were examined with a focus on diagnostic workup, patient selection and operative mortality and morbidity.

Results

Diagnostic modalities in the majority of studies involved ultrasound and computed tomography. Fewer than half employed magnetic resonance imaging (MRI). In instances in which MRI was not available, diagnostic accuracy was inferior.

Conclusions

Percutaneous biopsy should be avoided to prevent the risk for tumour seeding. Patients presenting with asymptomatic definitive FNH can be safely managed conservatively. In symptomatic patients surgical resection is a safe and effective treatment for which acceptable rates of morbidity (14%) and zero mortality are reported. However, evidence of symptom resolution is reported with conservative strategies. Diagnostic uncertainty remains the principal valid indication for FNH resection, but only in patients in whom contrast-enhanced MRI forms part of preoperative assessment.     

Altered lysophosphatidic acid (LPA) receptor expression during hepatic regeneration in a mouse model of partial hepatectomy

Background

Hepatic regeneration requires coordinated signal transduction for efficient restoration of functional liver mass. This study sought to determine changes in lysophosphatidic acid (LPA) and LPA receptor (LPAR) 1–6 expression in regenerating liver following two-thirds partial hepatectomy (PHx).

Methods

Liver tissue and blood were collected from male C57BL/6 mice following PHx. Circulating LPA was measured by enzyme-linked immunosorbent assay (ELISA) and hepatic LPAR mRNA and protein expression were determined.

Results

Circulating LPA increased 72 h after PHx and remained significantly elevated for up to 7 days post-PHx. Analysis of LPAR expression after PHx demonstrated significant increases in LPAR1, LPAR3 and LPAR6 mRNA and protein in a time-dependent manner for up to 7 days post-PHx. Conversely, LPAR2, LPAR4 and LPAR5 mRNA were barely detected in normal liver and did not significantly change after PHx. Changes in LPAR1 expression were confined to non-parenchymal cells following PHx.

Conclusions

Liver regeneration following PHx is associated with significant changes in circulating LPA and hepatic LPAR1, LPAR3 and LPAR6 expression in a time- and cell-dependent manner. Furthermore, changes in LPA–LPAR post-PHx occur after the first round of hepatocyte division is complete.     

Community use of face masks and similar barriers to prevent respiratory illness such as COVID-19: a rapid scoping review

BackgroundEvidence for face-mask wearing in the community to protect against respiratory disease is unclear.AimTo assess effectiveness of wearing face masks in the community to prevent respiratory disease, and recommend improvements to this evidence base.MethodsWe systematically searched Scopus, Embase and MEDLINE for studies evaluating respiratory disease incidence after face-mask wearing (or not). Narrative synthesis and random-effects meta-analysis of attack rates for primary and secondary prevention were performed, subgrouped by design, setting, face barrier type, and who wore the mask. Preferred outcome was influenza-like illness. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) quality assessment was undertaken and evidence base deficits described.Results33 studies (12 randomised control trials (RCTs)) were included. Mask wearing reduced primary infection by 6% (odds ratio (OR): 0.94; 95% CI: 0.75–1.19 for RCTs) to 61% (OR: 0.85; 95% CI: 0.32–2.27; OR: 0.39; 95% CI: 0.18–0.84 and OR: 0.61; 95% CI: 0.45–0.85 for cohort, case–control and cross-sectional studies respectively). RCTs suggested lowest secondary attack rates when both well and ill household members wore masks (OR: 0.81; 95% CI: 0.48–1.37). While RCTs might underestimate effects due to poor compliance and controls wearing masks, observational studies likely overestimate effects, as mask wearing might be associated with other risk-averse behaviours. GRADE was low or very low quality.ConclusionWearing face masks may reduce primary respiratory infection risk, probably by 6–15%. It is important to balance evidence from RCTs and observational studies when their conclusions widely differ and both are at risk of significant bias. COVID-19-specific studies are required.     

The chemistry and pharmacology of putative synthetic cannabinoid receptor agonist (SCRA) new psychoactive substances (NPS) 5F‐PY‐PICA, 5F‐PY‐PINACA,and their analogs

5F‐PY‐PICA and 5F‐PY‐PINACA are pyrrolidinyl 1‐(5‐fluoropentyl)ind (az)ole‐3‐carboxamides identified in 2015 as putative synthetic cannabinoid receptor agonist (SCRA) new psychoactive substances (NPS). 5F‐PY‐PICA, 5F‐PY‐PINACA, and analogs featuring variation of the 1‐alkyl substituent or contraction, expansion, or scission of the pyrrolidine ring were synthesized and characterized by nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography–quadrupole time‐of‐flight–mass spectrometry (LC–QTOF–MS). In competitive binding experiments against HEK293 cells expressing human cannabinoid receptor type 1 (hCB₁) or type 2 (hCB₂), all analogs showed minimal affinity for CB₁ (pK_i < 5), although several demonstrated moderate CB₂ binding (pK_i 5.45–6.99). In fluorescence‐based membrane potential assays using AtT20‐hCB₁ or ‐hCB₂ cells, none of the compounds (at 10 μM) produced an effect >50% of the classical cannabinoid agonist CP55,940 (at 1 μM) at hCB₁, although several showed slightly higher relative efficacy at hCB₂. Expansion of the pyrrolidine ring of 5F‐PY‐PICA to an azepane ( 8 ) conferred the greatest hCB₂ affinity (pK_i 6.99) and activity (pEC₅₀ 7.54, E_max 72%) within the series. Unlike other SCRA NPS evaluated in vivo using radio biotelemetry, 5F‐PY‐PICA and 5F‐PY‐PINACA did not produce cannabimimetic effects (hypothermia, bradycardia) in mice at doses up to 10 mg/kg.     

Gonadotropin-inhibitory hormone (GnIH) secretion into the ovine hypophyseal portal system

GnIH was first identified in avian species, and there is now strong evidence that it is operant in mammals as an inhibitor of reproduction. Mammalian gonadotropin-inhibitory hormone (GnIH)-3 is encoded by the RFRP gene in neurons of the dorsomedial nucleus. These neurons project to the median eminence, predicting a role as a secreted neurohormone and regulation of the pituitary gonadotropes. To determine whether GnIH-3 is a secreted neurohormone, we measured its concentration in hypophyseal portal blood in ewes during the nonbreeding (anestrous) season and during the luteal and follicular phases of the estrous cycle in the breeding season. Paired portal and jugular blood samples were collected and plasma prepared for RIA using an ovine GnIH-3 antibody. Pulsatile GnIH-3 secretion was observed in the portal blood of all animals. Mean GnIH-3 pulse amplitude and pulse frequency was higher during the nonbreeding season. GnIH-3 was virtually undetectable in peripheral blood plasma. There was a lack of association between secretory pulses of GnIH-3 (portal) and LH (peripheral). To determine the role of secreted GnIH-3, we examined its effects on GnRH-stimulated LH secretion in hypothalamo-pituitary-disconnected ewes; a significant reduction in the LH response to GnRH was observed. Finally, to identify cellular targets in the pituitary, the expression of GnIH receptor [G protein-coupled receptor 147 (GPR147)] in fractions enriched for gonadotropes somatotropes, and lactotropes was examined; expression was observed in each cell type. These data show GnIH-3 is secreted into portal blood to act on pituitary gonadotropes, reducing the action of GnRH.     

Visual attention and the acquisition of information in human crowds

Pedestrian crowds can form the substrate of important socially contagious behaviors, including propagation of visual attention, violence, opinions, and emotional state. However, relating individual to collective behavior is often difficult, and quantitative studies have largely used laboratory experimentation. We present two studies in which we tracked the motion and head direction of 3,325 pedestrians in natural crowds to quantify the extent, influence, and context dependence of socially transmitted visual attention. In our first study, we instructed stimulus groups of confederates within a crowd to gaze up to a single point atop of a building. Analysis of passersby shows that visual attention spreads unevenly in space and that the probability of pedestrians adopting this behavior increases as a function of stimulus group size before saturating for larger groups. We develop a model that predicts that this gaze response will lead to the transfer of visual attention between crowd members, but it is not sufficiently strong to produce a tipping point or critical mass of gaze-following that has previously been predicted for crowd dynamics. A second experiment, in which passersby were presented with two stimulus confederates performing suspicious/irregular activity, supports the predictions of our model. This experiment reveals that visual interactions between pedestrians occur primarily within a 2-m range and that gaze-copying, although relatively weak, can facilitate response to relevant stimuli. Although the above aspects of gaze-following response are reproduced robustly between experimental setups, the overall tendency to respond to a stimulus is dependent on spatial features, social context, and sex of the passerby.