Multimodal decoding of human liver regeneration.

The liver has a unique ability to regenerate1,2; however, in the setting of acute liver failure (ALF), this regenerative capacity is often overwhelmed, leaving emergency liver transplantation as the only curative option3-5. Here, to advance understanding of human liver regeneration, we use paired single-nucleus RNA sequencing combined with spatial profiling of healthy and ALF explant human livers to generate a single-cell, pan-lineage atlas of human liver regeneration. We uncover a novel ANXA2+ migratory hepatocyte subpopulation, which emerges during human liver regeneration, and a corollary subpopulation in a mouse model of acetaminophen (APAP)-induced liver regeneration. Interrogation of necrotic wound closure and hepatocyte proliferation across multiple timepoints following APAP-induced liver injury in mice demonstrates that wound closure precedes hepatocyte proliferation. Four-dimensional intravital imaging of APAP-induced mouse liver injury identifies motile hepatocytes at the edge of the necrotic area, enabling collective migration of the hepatocyte sheet to effect wound closure. Depletion of hepatocyte ANXA2 reduces hepatocyte growth factor-induced human and mouse hepatocyte migration in vitro, and abrogates necrotic wound closure following APAP-induced mouse liver injury. Together, our work dissects unanticipated aspects of liver regeneration, demonstrating an uncoupling of wound closure and hepatocyte proliferation and uncovering a novel migratory hepatocyte subpopulation that mediates wound closure following liver injury. Therapies designed to promote rapid reconstitution of normal hepatic microarchitecture and reparation of the gut-liver barrier may advance new areas of therapeutic discovery in regenerative medicine.

Laparoscopic and open liver resection for hepatocellular carcinoma with Child-Pugh B cirrhosis: multicentre propensity score-matched study.

BACKGROUND: Laparoscopic liver resection for hepatocellular carcinoma (HCC) in Child-Pugh A cirrhosis has been demonstrated as beneficial. However, the role of laparoscopy in Child-Pugh B cirrhosis is undetermined. The aim of this retrospective cohort study was to compare open and laparoscopic resection for HCC with Child-Pugh B cirrhosis. METHODS: Data on liver resections were gathered from 17 centres. A 1 : 1 propensity score matching was performed according to 17 predefined variables. RESULTS: Of 382 available liver resections, 100 laparoscopic and 100 open resections were matched and analysed. The 90-day postoperative mortality rate was similar in open and laparoscopic groups (4.0 versus 2.0 per cent respectively; P = 0.687). Laparoscopy was associated with lower blood loss (median 110 ml versus 400 ml in the open group; P = 0.004), less morbidity (38.0 versus 51.0 per cent respectively; P = 0.041) and fewer major complications (7.0 versus 21.0 per cent; P = 0.010), and ascites was lower on postoperative days 1, 3 and 5. For laparoscopic resections, patients with portal hypertension developed more complications than those without (26 versus 12 per cent respectively; P = 0.002), and patients with a Child-Pugh B9 score had higher morbidity rates than those with B8 and B7 (7 of 8, 10 of 16 and 21 of 76 respectively; P < 0.001). Median hospital stay was 7.5 (range 2-243) days for laparoscopic liver resection and 18 (3-104) days for the open approach (P = 0.058). The 5-year overall survival rate was 47 per cent for open and 65 per cent for laparoscopic resection (P = 0.142). The 5-year disease-free survival rate was 32 and 37 per cent respectively (P = 0.742). CONCLUSION: Patients without preoperative portal hypertension and Child-Pugh B7 cirrhosis may benefit most from laparoscopic liver surgery.

Idiopathic granulomatous mastitis: A diagnostic and therapeutic challenge.

BACKGROUND: Idiopathic granulomatous mastitis is a rare benign breast disease of women of reproductive age. It usually presents as a painful mass. Since the etiology is unclear, directed diagnosis and management is lacking. METHODS: This is a retrospective chart review of 14 patients, over twelve years (2004-2016), identified through query of pathology findings. RESULTS: Two asymptomatic patients were diagnosed after oncologic breast resection following neoadjuvant chemotherapy. The remaining twelve patients were young (31.7 years, range 23-43 years), predominantly non-white (50% African/African-American, 36% Hispanic, 7% Asian), pregnant within the last five years (86%), with no prior granulomatous disease. Evaluation included breast imaging, microbial cultures and staining, and biopsy. Treatment included antibiotics (57%), corticosteroids (21%), methotrexate (7%), and/or surgery (71%). Imaging suggests segmental masses, possibly abscess. CONCLUSION: Granulomatous mastitis is uncommon, and difficult to diagnose and manage. We review our experience, the literature, and propose an algorithm for diagnosis and management.

Midlife managerial experience is linked to late life hippocampal morphology and function.

An active cognitive lifestyle has been suggested to have a protective role in the long-term maintenance of cognition. Amongst healthy older adults, more managerial or supervisory experiences in midlife are linked to a slower hippocampal atrophy rate in late life. Yet whether similar links exist in individuals with Mild Cognitive Impairment (MCI) is not known, nor whether these differences have any functional implications. 68 volunteers from the Sydney SMART Trial, diagnosed with non-amnestic MCI, were divided into high and low managerial experience (HME/LME) during their working life. All participants underwent neuropsychological testing, structural and resting-state functional MRI. Group comparisons were performed on hippocampal volume, morphology, hippocampal seed-based functional connectivity, memory and executive function and self-ratings of memory proficiency. HME was linked to better memory function (p = 0.024), mediated by larger hippocampal volume (p = 0.025). More specifically, deformation analysis found HME had relatively more volume in the CA1 sub-region of the hippocampus (p < 0.05). Paradoxically, this group rated their memory proficiency worse (p = 0.004), a result correlated with diminished functional connectivity between the right hippocampus and right prefrontal cortex (p < 0.001). Finally, hierarchical regression modelling substantiated this double dissociation.

Therapeutically relevant structural and functional mechanisms triggered by physical and cognitive exercise.

Physical and cognitive exercise may prevent or delay dementia in later life but the neural mechanisms underlying these therapeutic benefits are largely unknown. We examined structural and functional magnetic resonance imaging (MRI) brain changes after 6 months of progressive resistance training (PRT), computerized cognitive training (CCT) or combined intervention. A total of 100 older individuals (68 females, average age=70.1, s.d.±6.7, 55-87 years) with dementia prodrome mild cognitive impairment were recruited in the SMART (Study of Mental Activity and Resistance Training) Trial. Participants were randomly assigned into four intervention groups: PRT+CCT, PRT+SHAM CCT, CCT+SHAM PRT and double SHAM. Multimodal MRI was conducted at baseline and at 6 months of follow-up (immediately after training) to measure structural and spontaneous functional changes in the brain, with a focus on the hippocampus and posterior cingulate regions. Participants' cognitive changes were also assessed before and after training. We found that PRT but not CCT significantly improved global cognition (F(90)=4.1, P<0.05) as well as expanded gray matter in the posterior cingulate (Pcorrected <0.05), and these changes were related to each other (r=0.25, P=0.03). PRT also reversed progression of white matter hyperintensities, a biomarker of cerebrovascular disease, in several brain areas. In contrast, CCT but not PRT attenuated decline in overall memory performance (F(90)=5.7, P<0.02), mediated by enhanced functional connectivity between the hippocampus and superior frontal cortex. Our findings indicate that physical and cognitive training depend on discrete neuronal mechanisms for their therapeutic efficacy, information that may help develop targeted lifestyle-based preventative strategies.

Emergency treatment of papaverine priapism.

We report a case of vasoactive-agent-induced priapism successfully treated in the emergency department with 10 mg of metaraminol injected into the corpora cavernosa.

The introduction of local anaesthesia in Australia, January 19, 1885.

Medical journals in Australia between 1856 and 1884 were wont to publish many references to forms of local anaesthesia, probably because this form of pain relief was of assistance to lone practitioners in isolated country towns. Some of these methods are described, as is the first use of cocaine by A. S. Gray and J. T. Rudall on January 19, 1885. As in journals elsewhere there followed a spate of articles reporting various aspects of cocaine and its usage, including an abortive attempt to find an alternative agent.

Normal EEG of the restrained twenty-four-hour-old Japanese quail (Coturnix coturnix japonica).

A new method for obtaining bipolar electroencephalographic (EEG) recordings from day-old Japanese quail (Coturnix coturnix japonica) is described. The electrodes are chronically placed stainless steel suture wires sewn into the skull and secured with dental acrylic. Using this arrangement, recordings were made over the hyperstriatum accessorum and dorsoarchistriatum regions of the brain. These records showed a preponderance of high amplitude slow waves. Transitions to low amplitude fast waves were also evident, and rare instances of paradoxical sleep were noted. computerized frequency analyses of the recordings divided wave numbers into distinct groups over the 1 to 17 Hz range: 1 to 4 Hz, 4 to 8 Hz, 8 to 13 Hz, and 13 to 17 Hz. Frequencies of waves detectable across the hyperstriatum accessorum were primarily confined to the 1 to 7 Hz range, whereas waves generated around the dorsoarchistriatus showed more abundant high frequency patterns. Mean amplitude of the waves (10 to 50 muV) showed an inverse exponential relationship with frequency. The method described produced an EEG of good quality on unanesthetized birds with the electrode placement procedures requiring less than 30 min.

Development and evaluation of social skills training for schizophrenic patients in remission.

Investigated were measures of self-esteem, self-perceived attitudinal dimensions and locus of control to assess the effects of group social skills training for schizophrenic psychiatric inpatients. A pretest, posttest control group design was employed utilizing forty subjects currently in treatment. It was hypothesized that short-term cognitively structured group therapy would realize significant improvement in self-esteem, internal locus of control and assertive attitude change. Significant mean differences between the treatment group's level of self-esteem, perceived assertive behavior and internal locus of control as a result of treatment were realized. Discussion of training methodology, issues and import for clinical applications and research are discussed.

Binary assessment of early approach-behaviour in the Japanese quail.

Visually-elicited early approach-behaviour was studied in 1013 Japanese quail chicks (Coturnix coturnix japonica) by a newly developed, binary assessment procedure. This procedure was shown to be highly effective for identifying approach preferences and related indivisual differences in early approach-behaviour. Experimental results show that quail chicks exhibit approach-responses to a flashing light. Within various paired intensity-combinations of the tested intensity-range of approximately two log units, they consistently preferred the higher intensity stimulus.