The lived experience of young adults with Fetal Valproate Spectrum Disorder, and the perspective of their parents: A qualitative study.

BACKGROUND: While research has investigated the physical and neurodevelopmental consequences following prenatal exposure to valproate, our understanding of individuals with a formal diagnosis of Fetal Valproate Spectrum Disorder (FVSD), particularly in the context of adulthood, remains limited. AIM: To investigate how symptoms and challenges of FVSD present in adulthood. METHODS: 30 people took part in the study, including 13 young adults aged between 21 and 37 years, 15 mothers, and 2 fathers. In all cases, valproate had been used for the treatment of maternal epilepsy. Data were collected using semi-structured interviews and analysed using thematic analysis. RESULTS: Six broad themes were identified: 1. Health and development, 2. Employment, 3. Daily living and independence, 4. Social skills and relationships, 5. Access to services, and 6. Impact on families. Individuals with FVSD live with an array of physical, mental, and developmental challenges that extend well beyond childhood, significantly altering their life course and that of their families. Challenges in obtaining employment, achieving independent living, and navigating social and romantic relationships become increasingly significant as individuals with FVSD age. Despite their persistent need for support, services for adults with FVSD are either limited or entirely absent. Recommendations from families were provided regarding optimized support systems. CONCLUSION: This study highlights the lifelong physical, cognitive, emotional, social and behavioural symptoms associated with FVSD. Young adults and their parents desire further research regarding the condition along with improved support and health services in adulthood.

Assessment and validation of enrichment and target capture approaches to improve Mycobacterium tuberculosis WGS from direct patient samples.

Within-host Mycobacterium tuberculosis (Mtb) diversity may detect antibiotic resistance or predict tuberculosis treatment failure and is best captured through sequencing directly from sputum. Here, we compared three sample pre-processing steps for DNA decontamination and studied the yield of a new target enrichment protocol for optimal whole-genome sequencing (WGS) from direct patient samples. Mtb-positive NALC-NaOH-treated patient sputum sediments were pooled, and heat inactivated, split in replicates, and treated by either a wash, DNase I, or benzonase digestion. Levels of contaminating host DNA and target Mtb DNA were assessed by quantitative PCR (qPCR), followed by WGS with and without custom dsDNA target enrichment. The pre-treatment sample has a high host-to-target ratio of DNA (6,168 ± 1,638 host copies/ng to 212.3 ± 59.4 Mtb copies/ng) that significantly decreased with all three treatments. Benzonase treatment resulted in the highest enrichment of Mtb DNA at 100-fold compared with control (3,422 ± 2,162 host copies/ng to 11,721 ± 7,096 Mtb copies/ng). The custom dsDNA probe panel successfully enriched libraries from as little as 0.45 pg of Mtb DNA (100 genome copies). Applied to direct sputum the dsDNA target enrichment panel increased the percent of sequencing reads mapping to the Mtb target for all three pre-processing methods. Comparing the results of the benzonase sample sequenced both with and without enrichment, the percent of sequencing reads mapping to the Mtb increased to 90.95% from 1.18%. We demonstrate a low limit of detection for a new custom dsDNA Mtb target enrichment panel that has a favorable cost profile. The results also demonstrate that pre-processing to remove contaminating extracellular DNA prior to cell lysis and DNA extraction improves the host-to-Mtb DNA ratio but is not adequate to support average coverage WGS without target capture.

Biocide resistant and antibiotic cross-resistant potential pathogens from sewage and river water from a wastewater treatment facility in the North-West, Potchefstroom, South Africa.

Exposure to antibiotics, biocides, chemical preservatives, and heavy metals in different settings such as wastewater treatment plants (WWTPs) may apply selective pressure resulting in the enrichment of multiple resistant, co- and cross-resistant strains of bacteria. The purpose of this study was to identify and characterize potentially pathogenic triclosan (TCS) - and/or, chloroxylenol (PCMX) tolerant bacteria from sewage and river water in the North-West, Potchefstroom, South Africa. Several potential pathogens were identified, with Aeromonas isolates being most abundant. Clonal relationships between Aeromonas isolates found at various sampling points were elucidated using ERIC-PCR. Selected isolates were characterized for their minimum inhibitory concentrations against the biocides, as well as antibiotic resistance profiles, followed by an evaluation of synergistic and antagonistic interactions between various antimicrobials. Isolates were also screened for the presence of extracellular enzymes associated with virulence. High-performance liquid chromatography revealed the presence of both biocides in the wastewater, but fingerprinting methods did not reveal whether the WWTP is the source from which these organisms enter the environment. Isolates exhibited various levels of resistance to antimicrobials as well as several occurrences of synergy and antagonisms between the biocides and select antibiotics. Several isolates had a very high potential for virulence but further study is required to identify the specific virulence and resistance genes associated with the isolates in question.

What is the evidence for the use of parenteral nutrition (PN) in critically ill surgical patients: a systematic review and meta-analysis.

BACKGROUND: Malnutrition is associated with poor outcomes in surgical patients and corrective enteral feeding may not be possible. This is a particular problem in the acute setting where malnutrition is prevalent. The aim of this systematic review was to evaluate the use of parenteral nutrition (PN) in critically ill surgical patients. METHODS: This review was registered with PROSPERO (CRD42017079567). Searches of the CENTRAL, EMBASE, and MEDLINE databases were performed using a predefined strategy. Randomised trials published in English since 1995, reporting a comparison of PN vs any comparator in a critically ill surgical population were included. The primary outcome was mortality. Risk of bias was assessed using the Cochrane risk of bias tool and the Grading of Recommendations Assessment, Development and Evaluation assessment. Meta-analysis was performed using a random effects model to assess variation in mortality and length of stay. RESULTS: Fourteen RCTs were identified; standard PN was compared vs other forms of PN in ten studies, to PN with variable dose amino acids in one, and to enteral nutrition (EN) in three. In trials comparing glutamine-supplemented PN (PN-GLN) to PN, a non-significant reduction in mortality was noted (risk difference - 0.08. 95% CI - 0.17, 0.01, p = 0.08). A trend for a reduction in length of stay was seen in PN-GLN to PN comparator (mean reduction - 2.4, 95% CI - 7.19 to 2.32 days, I2 = 92%). Impact on other outcome measures varied in direction of effect. CONCLUSIONS: PN may offer benefit in critically ill surgical patients. The size and quality of studies lead to uncertainty around the estimates of clinical effect, meaning a robust trial is required.

Randomised crossover trial of telemonitoring in chronic respiratory patients (TeleCRAFT trial).

DESIGN: Randomised crossover trial with 6 months of standard best practice clinical care (control group) and 6 months with the addition of telemonitoring. PARTICIPANTS: 68 patients with chronic lung disease (38 with COPD; 30 with chronic respiratory failure due to other causes), who had a hospital admission for an exacerbation within 6 months of randomisation and either used long-term oxygen therapy or had an arterial oxygen saturation (SpO2) of <90% on air during the previous admission. Individuals received telemonitoring (second-generation system) via broadband link to a hospital-based care team. OUTCOME MEASURES: Primary outcome measure was time to first hospital admission for an acute exacerbation. Secondary outcome measures were hospital admissions, general practitioner (GP) consultations and home visits by nurses, quality of life measured by EuroQol-5D and hospital anxiety and depression (HAD) scale, and self-efficacy score (Stanford). RESULTS: Median (IQR) number of days to first admission showed no difference between the two groups­77 (114) telemonitoring, 77.5 (61) control ( p=0.189). Hospital admission rate at 6 months increased (0.63 telemonitoring vs 0.32 control p=0.026). Home visits increased during telemonitoring; GP consultations were unchanged. Self-efficacy fell, while HAD depression score improved marginally during telemonitoring. CONCLUSIONS: Telemonitoring added to standard care did not alter time to next acute hospital admission, increased hospital admissions and home visits overall, and did not improve quality of life in chronic respiratory patients. TRIAL REGISTRATION NUMBER: NCT02180919 (ClinicalTrials.gov).

Sex change and effective population size: implications for population genetic studies in marine fish.

Large variance in reproductive success is the primary factor that reduces effective population size (Ne) in natural populations. In sequentially hermaphroditic (sex-changing) fish, the sex ratio is typically skewed and biased towards the 'first' sex, while reproductive success increases considerably after sex change. Therefore, sex-changing fish populations are theoretically expected to have lower Ne than gonochorists (separate sexes), assuming all other parameters are essentially equal. In this study, we estimate Ne from genetic data collected from two ecologically similar species living along the eastern coast of South Africa: one gonochoristic, the 'santer' sea bream Cheimerius nufar, and one protogynous (female-first) sex changer, the 'slinger' sea bream Chrysoblephus puniceus. For both species, no evidence of genetic structuring, nor significant variation in genetic diversity, was found in the study area. Estimates of contemporary Ne were significantly lower in the protogynous species, but the same pattern was not apparent over historical timescales. Overall, our results show that sequential hermaphroditism may affect Ne differently over varying time frames, and that demographic signatures inferred from genetic markers with different inheritance modes also need to be interpreted cautiously, in relation to sex-changing life histories.

[Robotic Rectal Cancer Surgery]. / Roboterassistierte Rektumkarzinomchirurgie.

BACKGROUND: The oncological outcome of patients with rectal cancer has improved considerably over the past few decades. This is mainly due to the introduction of the surgical concept of total mesorectal excision (TME) and the implementation of multimodal treatment strategies. Additionally, it has recently been demonstrated that the oncological results of open and laparoscopic TME are comparable. For some time there has been an ongoing debate on the potential relevance of robotic assistance systems in visceral surgery. The aim of this study was to evaluate the operative and perioperative outcomes of patients with rectal or rectosigmoid cancer, who were operated on using the Da Vinci Surgical System. PATIENTS AND RESULTS: We retrospectively analysed the outcomes of 202 consecutive patients, who were operated between September 2010 and November 2015 in three Surgical Centers. The cohort consisted of 136 men and 66 women with a mean BMI of 28. We performed the following procedures: 49 anterior rectal resections, 119 low anterior rectal resections, and 34 abdominoperineal excisions. Conversion to an open procedure was required in 13 patients. Non-surgical complications (n = 27) occurred in 24 patients (12%) and surgical complications (n = 67) in 62 patients (31%). Most complications were due to abdominal or sacral wound infections (n = 25) and anastomotic leaks (n = 18). The mortality rate within 30 days was 2%. The rate of R0 resections was 95%, with circumferential resection margins being negative in 98% of the patients. The quality of the mesorectal resection was scored as good in 91% of the patients. CONCLUSIONS: The Da Vinci Surgical System can be used safely and with a low complication rate for surgical treatment of rectal cancer. While primary evidence suggests that the outcome of robotic-assisted surgery is comparable with open and laparoscopic surgery, its definitive value has to be determined upon publication of the prospective randomized ROLARR trial. The main advantages of the Da Vinci system are its endowristed instruments with multiple degrees of freedom and its optimised visualisation (3D, stable camera platform controlled by the surgeon). Another positive feature is the significant ergonomic advantage for the surgeon.

Improved adherence to modern antiretroviral therapy among HIV-infected injecting drug users.

OBJECTIVES: Adherence to antiretroviral therapy (ART) among injecting drug users (IDUs) is often suboptimal, yet little is known about changes in patterns of adherence since the advent of highly active antiretroviral therapy in 1996. We sought to assess levels of optimal adherence to ART among IDUs in a setting of free and universal HIV care. METHODS: Data were collected through a prospective cohort study of HIV-positive IDUs in Vancouver, British Columbia. We calculated the proportion of individuals achieving at least 95% adherence in the year following initiation of ART from 1996 to 2009. RESULTS: Among 682 individuals who initiated ART, the median age was 37 years (interquartile range 31-44 years) and 248 participants (36.4%) were female. The proportion achieving at least 95% adherence increased over time, from 19.3% in 1996 to 65.9% in 2009 (Cochrane-Armitage test for trend: P < 0.001). In a logistic regression model examining factors associated with 95% adherence, initiation year was statistically significant (odds ratio 1.08; 95% confidence interval 1.03-1.13; P < 0.001 per year after 1996) after adjustment for a range of drug use variables and other potential confounders. CONCLUSIONS: The proportion of IDUs achieving at least 95% adherence during the first year of ART has consistently increased over a 13-year period. Although improved tolerability and convenience of modern ART regimens probably explain these positive trends, by the end of the study period a substantial proportion of IDUs still had suboptimal adherence, demonstrating the need for additional adherence support strategies.

Status and challenges for sustainable billfish fisheries in the Western Indian Ocean.

Billfish species (families Istiophoridae and Xiphiidae) are caught in artisanal, recreational, and commercial fisheries throughout the Western Indian Ocean region. However, data and information on the interactions among these fisheries and the ecology of billfish in the WIO are not well understood. Using an in-depth analysis of peer-reviewed articles, grey literature, observation studies, and authors' insider knowledge, we summarize the current state of knowledge on billfish fisheries in 10 countries. To describe historical and current trends, we examined fisheries statistics from governmental and non-governmental agencies, sportfishing clubs' reports, diaries of sportfishing captains, and the catch and effort databases of the Indian Ocean Tuna Commission. We highlight two key points. First, billfish fisheries in the Western Indian Ocean are highly diverse, comprising two distinct segments-coastal and oceanic. However, data are poor for most countries with significant gaps in information especially for sport and artisanal fisheries. Second, the evidence assembled showed that billfish species have immense social, cultural, and economic value. Swordfish are targeted by both large-scale and semi-industrial fisheries, while other billfish species, particularly marlin, are highly sought after by sport fisheries in most countries. Our paper provides a comprehensive review of billfish fisheries and available information in the context of the WIO underscoring the need to strengthen data collection and reporting, citizen science, and collaborative sustainable development and management of billfish. Supplementary Information: The online version contains supplementary material available at 10.1007/s11160-022-09725-8.

MinION 16S datasets of a commercially available microbial community enables the evaluation of DNA extractions and data analyses.

New advances in sequencing technology and bioinformatics analysis tools have significantly supported the culture-independent analysis of complex microbial communities associated with environmental, plant, animal and human samples. However, previous work has shown that DNA extraction can have a major influence in the community profile. As such there is a constant need for new methods to efficiently and rapidly prepare and analyze DNA for microbiome research, especially in the case new and emerging technology like the Oxford Nanopore Technologies (ONT) MinION. A commercial standard was used, in triplicate, to evaluate three DNA extraction protocols, including two commercially available and one "in-house" DNA extraction method. All DNA extractions were done as per manufacturer's instructions and prepared with the same commercial ONT 16S sample preparation kit, prior to being analysed using MinION sequencing. Eight MinION 16S datasets of this microbial reference community were obtained. Reads were initially base called and demultiplexed using ONT's Guppy™ sequencing software (version 3.2.4), filtered using NanoFilt and then classified using Usearch. A set of R scripts are presented to process sintax files generated from Usearch and produce an OTU table that can be used for further analyses. All datasets were deposited into the SRA (NCBI) database. These datasets will allow future extraction kit comparisons using MinION sequencing since a standardize laboratory process using commercially available components, such as the MinION 16S sample preparation kit, microbial reference community and extraction kits, were used. The current ONT 16S workflow making use of the Epi2me agent only provides QC metrics and the ID's of the main genera identified and does not provide any tools currently for further downstream community comparison. The analyses scripts provided in the supplementary material will thus further enable the testing of new datasets against these reference sets and provide users the ability to compare their workflows with ours, thus standardizing comparisons and workflows.

Hospice or Hospital: The Costs of Dying of Cancer in the Oncology Care Model.

Background: End-of-life management is a difficult aspect of cancer care. With the oncology care model (OCM), we have data to assess both clinical outcomes and total cost of care (TCOC). Objective: To measure and characterize the TCOC for those who received less than three days of hospice care (HC) at the end of life compared with those who received three days or more. Design: Assess data on costs and site and date of death from Medicare claims on patients identified in the OCM who received chemotherapy in the six months before death. Standard statistical methods were used to characterize both populations. Setting/Subjects: Subjects were Medicare patients with cancer who died while managed by U.S. oncology practices in the OCM. Measurements were TCOC in 30-day intervals for the last months of life, cost by site of care at the end of life, and demographic characteristics of the population and association with HC. Results: There were 7329 deaths. Dying in the hospital was twice the cost of dying at home under HC ($20,113 vs. $10,803). Of demographic groups measured, only black race and a lymphoma diagnosis had <50% hospice enrollment for three days or more before death. Conclusions: This study reinforces previous studies regarding costs in the last 30 days of life. The graphic representation highlights the dollar cost and the costs of lost opportunity. Using these data to improve communication, addressing socioeconomic support, and formal palliative care integration are potential strategies to improve care.

Protective effects of a carbon monoxide-releasing molecule (CORM-3) during hepatic cold preservation.

UNLABELLED: There is increasing evidence that carbon monoxide (CO), a signaling molecule generated during the degradation of heme by heme oxygenase-1 (HO-1) in biological systems, has a variety of cytoprotective actions, including anti-hypoxic effects at low temperatures. However, during liver cold preservation, a direct effect needs to be established. Here, we designed a study to analyze the role of CO, delivered via a carbon monoxide-releasing molecule (CO-RM) in the maintenance of liver function, and integrity in rats during cold ischemia/reperfusion (CI/R) injury. We used an isolated normothermic perfused liver system (INPL) following a clinically relevant model of ex vivo 48 h cold ischemia stored in a modified University of Wisconsin (UW) solution, to determine the specific effects of CO in a rat model. CO was generated from 50 microM tricarbonylchloro ruthenium-glycinato (CORM-3), a water-soluble transition metal carbonyl that exerts pharmacological activities via the liberation of controlled amounts of CO in biological systems. The physiological effects of CORM-3 were confirmed by the parallel use of a specific inactive compound (iCORM-3), which does not liberate CO in the cellular environment. CORM-3 addition was found to prevent the injury caused by cold storage by improving significantly the perfusion flow during reperfusion (by almost 90%), and by decreasing the intrahepatic resistance (by 88%) when compared with livers cold preserved in UW alone. Also, CORM-3 supplementation preserved good metabolic capacity as indicated by hepatic oxygen consumption, glycogen content, and release of lactate dehydrogenase. Liver histology was also partially preserved by CORM-3 treatment. CONCLUSIONS: These findings suggest that CO-RM could be utilized as adjuvant therapeutics in UW solutions to limit the injury sustained by donor livers during cold storage prior to transplantation, as has been similarly proposed for the heart, and kidney.

A prospective bicenter study investigating the diagnostic value of procalcitonin in patients with acute appendicitis.

BACKGROUND: Procalcitonin (PCT) is an established laboratory marker for disease severity in patients with infection and sepsis. In addition, PCT has been shown to be an effective marker for a limited number of localized infections. However, whether or not PCT has any diagnostic value for acute appendicitis, still remains unclear. The purpose of this prospective bicenter study was, therefore, to determine whether or not the PCT levels in the serum of patients with acute appendicitis have any diagnostic value. METHODS: This prospective study included 103 patients who received an appendectomy, based on the clinical diagnosis of acute appendicitis, in a surgical department of an academic teaching hospital in Germany or in a county hospital in Spain. White blood cell count (WBC), C-reactive protein (CRP) and procalcitonin (PCT) values were determined preoperatively. All appendectomy specimens were sent for routine histopathological evaluation. Based on this information, the patients were assigned to 1 of 5 groups that reflected the severity of the appendicitis. RESULTS: Of the 103 patients who were included in the study, 98 had appendicitis. Fourteen (14.3%) showed an increase in PCT values. Of those 14, 4 had a serum PCT >0.5 ng/ml, 9 had a PCT value >2-10 ng/ml and 1 had a PCT value >10 ng/ml. The sensitivity of PCT was calculated to be 0.14. The mean WBC value was 13.0/nl (+/- 5.2, 3.4-31), and for CRP it was 8.8 mg/dl (+/- 13, 0-60.2). The values of CRP, WBC and PCT increased with the severity of the appendicitis. CONCLUSIONS: PCT is potentially increased in rare cases of severe inflammation and, in particular, after appendiceal perforation or gangrenous appendicitis. However, its remarkably low sensitivity prohibits its routine use for the diagnosis of appendicitis.

Distribution of Eg5 and TPX2 in mitosis: Insight from CRISPR tagged cells.

The mitotic spindle is a dynamic bipolar structure that mediates chromosome segregation in mitosis. In most organisms, spindle formation requires the action of kinesin-5 motor proteins that generate outward force on antiparallel microtubules to establish spindle bipolarity. Previous work has shown that Eg5 and TPX2, a spindle microtubule-associated protein that suppresses Eg5 motor activity, are enriched on parallel microtubules near spindle poles. This distribution is inconsistent with the requirement for Eg5-dependent force production during mitosis. To investigate this, we used CRISPR/Cas9 gene editing to tag Eg5 and TPX2 with EGFP and quantify protein distribution throughout mitosis. The results show that at metaphase both Eg5-EGFP and TPX2-EGFP are enriched toward spindle poles, but only TPX2-EGFP is enriched relative to microtubules. Eg5-EGFP and TPX2-EGFP show distinct localization patterns in anaphase, with Eg5-EGFP relocalizing to the midzone earlier than TPX2-EGFP. Analysis of spindles oriented at 90° to the coverslip confirmed that Eg5-EGFP was present on bridge microtubules in metaphase and anaphase; in contrast, TPX2 was not enriched, or enriched at later times, on these microtubules. Overall, TPX2 was present at 3.6X the level of Eg5 on the spindle and Eg5 was locally enriched at the prophase centrosome (~7×) compared to the whole cell. Our results show that using cells with fluorescent tags at the endogenous locus can provide novel insight into protein distribution during mitosis.

Canadian Stroke Best Practice Recommendations for Acute Stroke Management: Prehospital, Emergency Department, and Acute Inpatient Stroke Care, 6th Edition, Update 2018.

The 2018 update of the Canadian Stroke Best Practice Recommendations for Acute Stroke Management, 6th edition, is a comprehensive summary of current evidence-based recommendations, appropriate for use by healthcare providers and system planners caring for persons with very recent symptoms of acute stroke or transient ischemic attack. The recommendations are intended for use by a interdisciplinary team of clinicians across a wide range of settings and highlight key elements involved in prehospital and Emergency Department care, acute treatments for ischemic stroke, and acute inpatient care. The most notable changes included in this 6th edition are the renaming of the module and its integration of the formerly separate modules on prehospital and emergency care and acute inpatient stroke care. The new module, Acute Stroke Management: Prehospital, Emergency Department, and Acute Inpatient Stroke Care is now a single, comprehensive module addressing the most important aspects of acute stroke care delivery. Other notable changes include the removal of two sections related to the emergency management of intracerebral hemorrhage and subarachnoid hemorrhage. These topics are covered in a new, dedicated module, to be released later this year. The most significant recommendation updates are for neuroimaging; the extension of the time window for endovascular thrombectomy treatment out to 24 h; considerations for treating a highly selected group of people with stroke of unknown time of onset; and recommendations for dual antiplatelet therapy for a limited duration after acute minor ischemic stroke and transient ischemic attack. This module also emphasizes the need for increased public and healthcare provider's recognition of the signs of stroke and immediate actions to take; the important expanding role of paramedics and all emergency medical services personnel; arriving at a stroke-enabled Emergency Department without delay; and launching local healthcare institution code stroke protocols. Revisions have also been made to the recommendations for the triage and assessment of risk of recurrent stroke after transient ischemic attack/minor stroke and suggested urgency levels for investigations and initiation of management strategies. The goal of this updated guideline is to optimize stroke care across Canada, by reducing practice variations and reducing the gap between current knowledge and clinical practice.

Structure and content of the Entamoeba histolytica genome.

The intestinal parasite Entamoeba histolytica is one of the first protists for which a draft genome sequence has been published. Although the genome is still incomplete, it is unlikely that many genes are missing from the list of those already identified. In this chapter we summarise the features of the genome as they are currently understood and provide previously unpublished analyses of many of the genes.

The structural gene for a phosphorus-repressible phosphate permease in Neurospora crassa can complement a mutation in positive regulatory gene nuc-1.

van+, a gene encoding a phosphorus-repressible phosphate permease, was isolated by its ability to complement nuc-1, a positive regulatory locus that normally regulates van+ expression. This was unexpected because the nuc-1 host already contained a resident van+ gene. Plasmids carrying van+ complemented a nuc-2 mutation as well. Probing of RNA from untransformed wild-type (nuc-1+) and constitutive (nuc-1c) strains by van+ probes indicated that levels of the van+ transcript were subject to control by nuc-1+. Probing of the same RNAs with a cosmid clone, containing approximately 15 kilobases of upstream and downstream DNA, revealed no other detectable phosphorus-regulated transcripts within this 40-kilobase region of the chromosome.

Regulation of adherence and virulence by the Entamoeba histolytica lectin cytoplasmic domain, which contains a beta2 integrin motif.

Killing of human cells by the parasite Entamoeba histolytica requires adherence via an amebic cell surface lectin. Lectin activity in the parasite is regulated by inside-out signaling. The lectin cytoplasmic domain has sequence identity with a region of the beta2 integrin cytoplasmic tail implicated in regulation of integrin-mediated adhesion. Intracellular expression of a fusion protein containing the cytoplasmic domain of the lectin has a dominant negative effect on extracellular lectin-mediated cell adherence. Mutation of the integrin-like sequence abrogates the dominant negative effect. Amebae expressing the dominant negative mutant are less virulent in an animal model of amebiasis. These results suggest that inside-out signaling via the lectin cytoplasmic domain may control the extracellular adhesive activity of the amebic lectin and provide in vivo demonstration of the lectin's role in virulence.

Bilateral cheek-to-nose advancement flap: an alternative to the paramedian forehead flap for reconstruction of the nose.

Skin cancer on the nose is commonly treated with surgical excision resulting in defects that require closure. The surgeon is faced with many reconstructive options. The paramedian forehead flap is one commonly used technique. In this study we describe the bilateral cheek-to-nose advancement flap as an alternative to the paramedian forehead flap in patients with strong nasolabial folds and prominent cheek tissue laxity, who require closure of MOHS surgery defects on the nasal dorsum and sidewall. Twelve patients were treated with the latter flap and evaluated after 2 weeks and 6 months. The patients' subjective and the surgeons' objective evaluation after 6 months were either completely satisfied or satisfied. The bilateral cheek-to-nose advancement flap is a reliable tool in the interventional portfolio of the reconstructive surgeon.