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.

Re-expression of miR-200s in claudin-low mammary tumor cells alters cell shape and reduces proliferation and invasion potentially through modulating other miRNAs and SUZ12 regulated genes.

BACKGROUND: MicroRNAs are a class of non-coding RNAs that regulate gene expression through binding to mRNAs and preventing their translation. One family of microRNAs known as the miR-200 family is an important regulator of epithelial identity. The miR-200 family consists of five members expressed in two distinct clusters; the miR-200c/141 cluster and the miR-200b/200a/429 cluster. We have found that murine and human mammary tumor cells with claudin-low characteristics are associated with very low levels of all five miR-200s. METHODS: To determine the impact of miR-200s on claudin-low mammary tumor cells, the miR-200c/141 cluster and the miR-200b/200a/429 cluster were stably re-expressed in murine (RJ423) and human (MDA-MB-231) claudin-low mammary tumor cells. Cell proliferation and migration were assessed using BrdU incorporation and transwell migration across Matrigel coated inserts, respectively. miRNA sequencing and RNA sequencing were performed to explore miRNAs and mRNAs regulated by miR-200 re-expression while Enrichr-based pathway analysis was utilized to identify cellular functions modified by miR-200s. RESULTS: Re-expression of the miR-200s in murine and human claudin-low mammary tumor cells partially restored an epithelial cell morphology and significantly inhibited proliferation and cell invasion in vitro. miRNA sequencing and mRNA sequencing revealed that re-expression of miR-200s altered the expression of other microRNAs and genes regulated by SUZ12 providing insight into the complexity of miR-200 function. SUZ12 is a member of the polycomb repressor complex 2 that suppresses gene expression through methylating histone H3 at lysine 27. Flow cytometry confirmed that re-expression of miR-200s increased histone H3 methylation at lysine 27. CONCLUSIONS: Re-expression of miR-200s in claudin-low mammary tumor cells alters cell morphology and reduces proliferation and invasion, an effect potentially mediated by SUZ12-regulated genes and other microRNAs.

Investigating surface binding effects: antibacterial efficacy of bound 8-hydroxyquinoline against Staphylococcus aureus and Escherichia coli.

AIMS: To investigate the binding of the antimicrobial compound 8-hydroxyquinoline (8HQ) to a material interface and to determine whether immobilization affects the antibacterial efficacy. METHODS AND RESULTS: The 8HQ derivative 5-carboxy-8-hydroxyquinoline (5C8HQ) was attached to silica beads through amide bond coupling at the carboxyl moiety of 5C8HQ. Attachment of 5C8HQ was confirmed using a combination of mass spectrometry, thermogravimetric analysis, colorimetric testing and Soxhlet extraction. Computational modelling results indicated that this substitution did not compromise the active sites on the molecule, whereas other positions on the ring system could potentially inhibit antimicrobial activity. The antibacterial effect of 8HQ and the 5C8HQ-modified silica complex against Escherichia coli 15597 (ATCC® 25922) and Staphylococcus aureus (ATCC 25923) was evaluated. CONCLUSIONS: The test results show that the immobilized 8HQ continues to exhibit antibacterial activity, however, quantifying the efficacy compared to free 8HQ bears further investigation. The expected antibacterial mechanism requires that the metal chelation site of 8HQ be retained and available after attachment to a surface. The retention of antibacterial activity after surface bonding represents a novel mechanism of action not previously reported. SIGNIFICANCE AND IMPACT OF THE STUDY: Recent changes in regulations due to environmental concerns prompted many companies and organizations to explore antimicrobial treatments that are chemically bound to the product. Chemically bonding biocidal compounds to a surface limits environmental release; however, molecular mechanisms that drive antibacterial activity when compounds are immobilized are limited. The results reported here demonstrate that the 8HQ reactive site retains antibacterial efficacy even after covalent attachment to a surface. This approach supersedes other antimicrobial treatments where the active component is gradually released from the material surface in order to elicit antimicrobial effects. This specific antibacterial activity of bound 8HQ represents a novel mechanism of action not previously reported, and a potential conduit to a new class of bound antimicrobial materials.

A One Health investigation of Salmonella enterica serovar Wangata in north-eastern New South Wales, Australia, 2016-2017.

Salmonella enterica serovar Wangata (S. Wangata) is an important cause of endemic salmonellosis in Australia, with human infections occurring from undefined sources. This investigation sought to examine possible environmental and zoonotic sources for human infections with S. Wangata in north-eastern New South Wales (NSW), Australia. The investigation adopted a One Health approach and was comprised of three complimentary components: a case-control study examining human risk factors; environmental and animal sampling; and genomic analysis of human, animal and environmental isolates. Forty-eight human S. Wangata cases were interviewed during a 6-month period from November 2016 to April 2017, together with 55 Salmonella Typhimurium (S. Typhimurium) controls and 130 neighbourhood controls. Indirect contact with bats/flying foxes (S. Typhimurium controls (adjusted odds ratio (aOR) 2.63, 95% confidence interval (CI) 1.06-6.48)) (neighbourhood controls (aOR 8.33, 95% CI 2.58-26.83)), wild frogs (aOR 3.65, 95% CI 1.32-10.07) and wild birds (aOR 6.93, 95% CI 2.29-21.00) were statistically associated with illness in multivariable analyses. S. Wangata was detected in dog faeces, wildlife scats and a compost specimen collected from the outdoor environments of cases' residences. In addition, S. Wangata was detected in the faeces of wild birds and sea turtles in the investigation area. Genomic analysis revealed that S. Wangata isolates were relatively clonal. Our findings suggest that S. Wangata is present in the environment and may have a reservoir in wildlife populations in north-eastern NSW. Further investigation is required to better understand the occurrence of Salmonella in wildlife groups and to identify possible transmission pathways for human infections.

Participation of children on the autism spectrum in home, school, and community.

BACKGROUND: Children on the autism spectrum participate less frequently, and in a narrower range of activities, than their nonautistic peers, but little is known about exact participation patterns across contexts or how this is perceived by caregivers. This study aimed to document patterns of participation and caregiver views with regard to frequency and intensity of activities. METHOD: Caregivers of children on the spectrum aged 5 (n = 90) and 9-10 years (n = 128) completed the Participation and Environment Measure for Children and Youth for home, school, and community. Caregivers reported on frequency of child's participation, level of involvement, and caregivers' desire for change in participation patterns. RESULTS: Item-level analyses revealed similar patterns of participation across home, school, and community for both cohorts with some small age-appropriate differences. Caregivers generally desired increased diversity, frequency, and involvement in activities but a decreased use of electronics (computers, games, TV, and DVDs). CONCLUSION: The possibility of autism-specific participation patterns could inform future interventions aimed at enhancing social inclusion. This warrants further investigation through multiinformant designs that seek the perspectives of the child and caregivers.

Altered fatty acid metabolism and reduced stearoyl-coenzyme a desaturase activity in asthma.

BACKGROUND: Fatty acids and lipid mediator signaling play an important role in the pathogenesis of asthma, yet this area remains largely underexplored. The aims of this study were (i) to examine fatty acid levels and their metabolism in obese and nonobese asthma patients and (ii) to determine the functional effects of altered fatty acid metabolism in experimental models. METHODS: Medium- and long-chain fatty acid levels were quantified in serum from 161 human volunteers by LC/MS. Changes in stearoyl-coenzyme A desaturase (SCD) expression and activity were evaluated in the ovalbumin (OVA) and house dust mite (HDM) murine models. Primary human bronchial epithelial cells from asthma patients and controls were evaluated for SCD expression and activity. RESULTS: The serum desaturation index (an indirect measure of SCD) was significantly reduced in nonobese asthma patients and in the OVA murine model. SCD1 gene expression was significantly reduced within the lungs following OVA or HDM challenge. Inhibition of SCD in mice promoted airway hyper-responsiveness. SCD1 expression was suppressed in bronchial epithelial cells from asthma patients. IL-4 and IL-13 reduced epithelial cell SCD1 expression. Inhibition of SCD reduced surfactant protein C expression and suppressed rhinovirus-induced IP-10 secretion, which was associated with increased viral titers. CONCLUSIONS: This is the first study to demonstrate decreased fatty acid desaturase activity in humans with asthma. Experimental models in mice and human epithelial cells suggest that inhibition of desaturase activity leads to airway hyper-responsiveness and reduced antiviral defense. SCD may represent a new target for therapeutic intervention in asthma patients.

Identification of Mucosa-Invading and Intravascular Bacteria in Feline Small Intestinal Lymphoma.

Persistent bacterial infections of the gastrointestinal mucosa are causally linked to gastric carcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma in people and laboratory animals. We examined the relationship of mucosa-associated bacteria to alimentary lymphoma in cats. Intestinal biopsies from 50 cats with alimentary lymphoma (small cell, n = 33; large cell, n = 17) and 38 controls without lymphoma (normal to minimal change on histopathology, n = 18; lymphocytic-plasmacytic enteritis, n = 20) were evaluated. The number and spatial distribution of bacteria (ie, in luminal cellular debris, villus-associated mucus, adherent to epithelium, mucosal invasion, intravascular, or serosal) were determined by fluorescence in situ hybridization with the eubacterial probe EUB-338. Mucosa-invasive bacteria were more frequently observed in cats with large cell lymphoma (82%, P ≤ .001) than in cats with small cell lymphoma (18%), normal to minimal change on histopathology, and lymphocytic-plasmacytic enteritis (3%). Intravascular bacteria were observed solely in large cell lymphoma (29%), and serosal colonization was more common in cats with large cell lymphoma (57%) than with small cell lymphoma (11%, P ≤ .01), normal to minimal change (8%, P ≤ .01), and lymphocytic-plasmacytic enteritis (6%, P ≤ .001). The high frequency of invasive bacteria within blood vessels and serosa of cats with large cell lymphoma may account for the sepsis-related complications associated with large cell lymphoma and inform clinical management. Further studies are required to determine the role of intramucosal bacteria in the etiopathogenesis of feline alimentary lymphoma.

Tumourigenic non-small-cell lung cancer mesenchymal circulating tumour cells: a clinical case study.

BACKGROUND: Over the past decade, numerous reports describe the generation and increasing utility of non-small-cell lung cancer (NSCLC) patient-derived xenografts (PDX) from tissue biopsies. While PDX have proven useful for genetic profiling and preclinical drug testing, the requirement of a tissue biopsy limits the available patient population, particularly those with advanced oligometastatic disease. Conversely, 'liquid biopsies' such as circulating tumour cells (CTCs) are minimally invasive and easier to obtain. Here, we present a clinical case study of a NSCLC patient with advanced metastatic disease, a never smoker whose primary tumour was EGFR and ALK wild-type. We demonstrate for the first time, tumorigenicity of their CTCs to generate a patient CTC-derived eXplant (CDX). PATIENTS AND METHODS: CTCs were enriched at diagnosis and again 2 months later during disease progression from 10 ml blood from a 48-year-old NSCLC patient and implanted into immunocompromised mice. Resultant tumours were morphologically, immunohistochemically, and genetically compared with the donor patient's diagnostic specimen. Mice were treated with cisplatin and pemetrexed to assess preclinical efficacy of the chemotherapy regimen given to the donor patient. RESULTS: The NSCLC CDX expressed lung lineage markers TTF1 and CK7 and was unresponsive to cisplatin and pemetrexed. Examination of blood samples matched to that used for CDX generation revealed absence of CTCs using the CellSearch EpCAM-dependent platform, whereas size-based CTC enrichment revealed abundant heterogeneous CTCs of which ∼80% were mesenchymal marker vimentin positive. Molecular analysis of the CDX, mesenchymal and epithelial CTCs revealed a common somatic mutation confirming tumour origin and showed CDX RNA and protein profiles consistent with the predominantly mesenchymal phenotype. CONCLUSIONS: This study shows that the absence of NSCLC CTCs detected by CellSearch (EpCAM(+)) does not preclude CDX generation, highlighting epithelial to mesenchymal transition and the functional importance of mesenchymal CTCs in dissemination of this disease.

Increased Nicotiana tabacum fitness through positive regulation of carotenoid, gibberellin and chlorophyll pathways promoted by Daucus carota lycopene ß-cyclase (Dclcyb1) expression.

Carotenoids, chlorophylls and gibberellins are derived from the common precursor geranylgeranyl diphosphate (GGPP). One of the enzymes in carotenoid biosynthesis is lycopene ß-cyclase (LCYB) that catalyzes the conversion of lycopene into ß-carotene. In carrot, Dclcyb1 is essential for carotenoid synthesis in the whole plant. Here we show that when expressed in tobacco, increments in total carotenoids, ß-carotene and chlorophyll levels occur. Furthermore, photosynthetic efficiency is enhanced in transgenic lines. Interestingly, and contrary to previous observations where overexpression of a carotenogenic gene resulted in the inhibition of the synthesis of gibberellins, we found raised levels of active GA4 and the concommitant increases in plant height, leaf size and whole plant biomass, as well as an early flowering phenotype. Moreover, a significant increase in the expression of the key carotenogenic genes, Ntpsy1, Ntpsy2 and Ntlcyb, as well as those involved in the synthesis of chlorophyll (Ntchl), gibberellin (Ntga20ox, Ntcps and Ntks) and isoprenoid precursors (Ntdxs2 and Ntggpps) was observed. These results indicate that the expression of Dclcyb1 induces a positive feedback affecting the expression of isoprenoid gene precursors and genes involved in carotenoid, gibberellin and chlorophyll pathways leading to an enhancement in fitness measured as biomass, photosynthetic efficiency and carotenoid/chlorophyll composition.

Costs of adverse events among patients with HIV infection treated with nonnucleoside reverse transcriptase inhibitors.

OBJECTIVES: The aim of the study was to assess the incidence and costs of adverse events (AEs) among patients with HIV infection treated with nonnucleoside reverse transcriptase inhibitors (NNRTIs) from the health care system perspective. METHODS: US medical and pharmacy claims during 2004-2009 were examined to select adult new NNRTI users with HIV infection. The incidence of selected AEs and time to occurrence were assessed during the first year. Episodes of care for each AE were identified using claims associated with AE management. For each AE, a propensity score model was used to match patients with an AE to those without (1:4) based on the propensity of having an AE. Mean total health care costs, AE-associated costs and incremental costs per episode, and annual total health care costs per patient were calculated. RESULTS: Of the 2548 NNRTI-treated patients, 29.3% experienced AEs. The incidence ranged from 0.4 episodes/1000 person-years for suicide/self-injury to 14.9 episodes/1000 person-years for dizziness, 49.8 episodes/1000 person-years for depression and 150.3 episodes/1000 person-years for lipid disorder. The mean AE-associated cost (duration) per episode ranged from $586 (88 days) for lipid disorder to $975 (33 days) for rash, $2760 (73 days) for sleep-related symptoms and $4434 (41 days) for nausea/vomiting. The mean incremental cost per episode ranged from $1580 for rash to $2032 for lipid disorder, $8307 for sleep-related symptoms and $12 833 for nausea/vomiting. During the 12 months following NNRTI initiation, the mean annual total health care cost was $27 299 (efavirenz: $26 185; other NNRTIs: $34 993) and AE-associated costs were $608 (efavirenz: $554; other NNRTIs: $979) among all NNRTI users. CONCLUSIONS: With treatment increasing patient survival, comparisons of therapeutic regimens should consider treatment-associated AEs. Findings from this study could be informative for clinicians and payers in managing HIV infection with NNRTIs.

Immune biomarker evaluation of sequential tyrosine kinase inhibitor and nivolumab monotherapies in renal cell carcinoma: the phase I TRIBE trial.

Background: Predictive biomarkers for immune checkpoint blockade in the second-line treatment of metastatic renal cell carcinoma (mRCC) are lacking. Materials and methods: Patients with histologically confirmed RCC who started nivolumab after at least 4 months of tyrosine kinase inhibitors (TKIs) were recruited for this study. Serial tissue and blood samples were collected for immune biomarker evaluation. The primary endpoint was to determine the association of specific T-cell subsets with clinical outcomes tested using Wilcoxon rank sum for clinical benefit rate (CBR) and log-rank test for progression-free survival (PFS). Results: Twenty patients were included in this trial with a median age of 64 years and followed-up for a median of 12 months. The median PFS for patients who received TKI was 13.8 months, while for those subsequently treated with nivolumab following TKI therapy, the median PFS was 2.6 months. CBR of nivolumab was 20% with two partial responses. Functionally active programmed cell death protein 1+ CD4+ T cells were enriched in non-responders (q = 0.003) and associated with worse PFS on nivolumab (P = 0.04). Responders showed a significant reduction in the effector CD4+T-cell (TEF) fraction compared to non-responders at 3 months on nivolumab (0.40 versus 0.80, P = 0.0005). CD127+CD4+ T cells were enriched in patients who developed immune-related adverse effects (q = 0.003). Using in-house validated multiplex immunohistochemistry for six markers, we measured tumour-associated immune cell densities in tissue samples. Responders to nivolumab showed a significantly higher mean of immune cell densities in tissue samples compared to non-responders (346 versus 87 cells/mm2, P = 0.04). Conclusions: In this small study, analysis of tissue-based and peripheral blood immune cell subsets predicted clinical outcomes of nivolumab. Further studies are warranted with larger populations to validate these observations.

Validation of the emergency surgery score (ESS) in a UK patient population and comparison with NELA scoring: a retrospective multicentre cohort study.

INTRODUCTION: Accurate risk scoring in emergency general surgery (EGS) is vital for consent and resource allocation. The emergency surgery score (ESS) has been validated as a reliable preoperative predictor of postoperative outcomes in EGS but has been studied only in the US population. Our primary aim was to perform an external validation study of the ESS in a UK population. Our secondary aim was to compare the accuracy of ESS and National Emergency Laparotomy Audit (NELA) scores. METHODS: We conducted an observational cohort study of adult patients undergoing emergency laparotomy over three years in two UK centres. ESS was calculated retrospectively. NELA scores and all other variables were obtained from the prospectively collected Emergency Laparotomy and Laparoscopic Scottish Audit (ELLSA) database. The primary and secondary outcomes were 30-day mortality and postoperative intensive care unit (ICU) admission, respectively. RESULTS: A total of 609 patients were included. Median age was 65 years, 52.7% were female, the overall mortality was 9.9% and 23.8% were admitted to ICU. Both ESS and NELA were equally accurate in predicting 30-day mortality (c-statistic=0.78 (95% confidence interval (CI), 0.71-0.85) for ESS and c-statistic=0.83 (95% CI, 0.77-0.88) for NELA, p=0.196) and predicting postoperative ICU admission (c-statistic=0.76 (95% CI, 0.71-0.81) for ESS and 0.80 (95% CI, 0.76-0.85) for NELA, p=0.092). CONCLUSIONS: In the UK population, ESS and NELA both predict 30-day mortality and ICU admission with no statistically significant difference but with higher c-statistics for NELA score. Both scores have certain advantages, with ESS being validated for a wider range of outcomes.

Pilot project and evaluation of delivering diabetes work-based education using video conferencing.

CONTEXT: Diabetes is a chronic long-term disease with an increasing incidence. There is a need to increase access to effective care and to ensure such care is delivered as locally as possible. The geographical spread of NHS Highland Scotland presents additional challenges to ensuring a skilled workforce given education is normally work-based tuition and assessment. The aim of this pilot project was to deliver teleconferenced diabetes training to healthcare and allied healthcare professionals who provide basic level care for, and management of, people with diabetes and to evaluate this training. ISSUE: Work-based diabetes education was designed to be delivered by a diabetes educator through videoconferencing or face to face (F2F) for healthcare professionals in peripheral settings in the Scottish Highlands region over two half-days. The education covered theoretical and practical training in diabetes. The evaluation of the project was through post-course questionnaires and assessment instruments to capture views of the content and delivery mode, as well as student performance. LESSONS LEARNED: Feedback from participants indicated that the educational content was relevant and that the use of videoconferencing (VC) could provide accessibility to training where distance, cost and other issues may make access difficult. Student performance on the assessment instruments did not differ between those who received the training through video conferencing and those who received the training through F2F delivery. Video conferencing can counteract the difficulties of accessing training for clinical peripherally based professionals. Training through VC did not compromise student acquisition of learning outcomes. Feedback indicates that VC can reduce the interactive nature of the learning and teaching experience.

Equine stomachs harbor an abundant and diverse mucosal microbiota.

Little is known about the gastric mucosal microbiota in healthy horses, and its role in gastric disease has not been critically examined. The present study used a combination of 16S rRNA bacterial tag-encoded pyrosequencing (bTEFAP) and fluorescence in situ hybridization (FISH) to characterize the composition and spatial distribution of selected gastric mucosal microbiota of healthy horses. Biopsy specimens of the squamous, glandular, antral, and any ulcerated mucosa were obtained from 6 healthy horses by gastroscopy and from 3 horses immediately postmortem. Pyrosequencing was performed on biopsy specimens from 6 of the horses and yielded 53,920 reads in total, with 631 to 4,345 reads in each region per horse. The microbiome segregated into two distinct clusters comprised of horses that were stabled, fed hay, and sampled at postmortem (cluster 1) and horses that were pastured on grass, fed hay, and biopsied gastroscopically after a 12-h fast (cluster 2). The types of bacteria obtained from different anatomic regions clustered by horse rather than region. The dominant bacteria in cluster 1 were Firmicutes (>83% reads/sample), mainly Streptococcus spp., Lactobacillus spp. and, Sarcina spp. Cluster 2 was more diverse, with predominantly Proteobacteria, Bacteroidetes, and Firmicutes, consisting of Actinobacillus spp. Moraxella spp., Prevotella spp., and Porphyromonas spp. Helicobacter sp. sequences were not identified in any of 53,920 reads. FISH (n = 9) revealed bacteria throughout the stomach in close apposition to the mucosa, with significantly more Streptococcus spp. present in the glandular region of the stomach. The equine stomach harbors an abundant and diverse mucosal microbiota that varies by individual.

A brief report on perceptions of alcohol and society among Scottish medical students.

AIMS: To assess perceptions on alcohol misuse and addiction among medical students prior to in-depth training in order to determine areas of the curriculum that need to be reshaped or focused on. METHODS: A questionnaire assessment of first- and second-year medical students' perceptions of alcohol misuse. RESULTS: Students had some misconceptions about current alcohol misuse rates, including a perception that addiction is common among health professionals, that the under-25s had the fastest increasing rate of alcohol addiction and that British women had a more rapidly increasing rate of alcohol addiction than British men. CONCLUSION: Encouragingly, students overwhelmingly felt that alcohol addiction was something to which they could make a difference. It highlights that early education about alcohol misuse is important in terms of teaching students how to recognize hazardous and harmful drinkers and how to manage them.

CCK, PYY and PP: the control of energy balance.

The control of food intake consists of neural and hormonal signals between the gut and central nervous system (CNS). Gut hormones such as CCK, PYY and PP signal to important areas in the CNS involved in appetite regulation to terminate a meal. These hormones can act directly via the circulation and activate their respective receptors in the hypothalamus and brainstem. In addition, gut vagal afferents also exist, providing an alternative pathway through which gut hormones can communicate with higher centres through the brainstem. Animal and human studies have demonstrated that peripheral administration of certain gut hormones reduces food intake and leads to weight loss. Gut hormones are therefore potential targets in the development of novel treatments for obesity and analogue therapies are currently under investigation.

Relationship between surface dissolved iron inventories and net community production during a marine heatwave in the subarctic northeast Pacific.

From winter 2013-14 to the end of 2015-16, a high pressure atmospheric system induced elevated sea surface temperatures in the offshore subarctic northeast Pacific, resulting in a marine heatwave. Increased stratification due to the heatwave resulted in shoaling of the winter mixed layer and a decrease in nutrient re-supply to the euphotic zone. Here, we investigate relationships between dissolved iron (dFe) and macronutrients, net community production (NCP), (micro)nutrient uptake ratios, and phytoplankton community composition in the winter and summer from 2012 to 2015 to gain insight into coupled biogeochemical responses to the heatwave. Our investigation highlights the importance of external dFe supply during marine heatwave events, as a more shallow mixed layer reduces the transport of essential (micro)macronutrients to the surface layer. We conclude that recycled dFe did not contribute to NCP in 2014, but rather the vertical displacement of dFe rich water unrelated to mixed layer deepening played a major role. In 2015, such transport was not detected, resulting in abnormally low dFe and shift toward higher biomass of pico- and nano-phytoplankton size-classes.

Parry Romberg Syndrome in a Young Ghanaian: A Case Report and a Literature Review.

Parry Romberg syndrome (PRS), also known as progressive hemifacial atrophy, is a very rare self-limiting disease, which affects the skin and subcutaneous tissues, underlying musculature, cartilage, and bony structures of one half of the face with a resultant hemiatrophy and alopecia areata. It presents in children and young adults, with a slow progression of the atrophy for several years, and then becomes stable. Magnetic resonance imaging (MRI) or computed tomography (CT) scan of the cranium demonstrates the radiological feature of hemiatrophy very clearly. We report a case of PRS in a nine-year-old girl with characteristic features which was diagnosed based on medical history, clinical signs, and radiological findings on cranial CT scan and MRI.