Strategic Planning and Essential Steps for Establishing a Uterine Transplant and Rehabilitation Program: From Idea to Reality.

UTx is performed to address absolute uterine infertility in the presence of uterine agenesis, a nonfunctional uterus, or after a prior hysterectomy. After the initial success of UTx resulting in a livebirth (2014) in Sweden, there are over 70 reported UTx surgeries resulting in more than 40 livebirths worldwide. Currently, UTx has been performed in over 10 countries. As UTx is transitioning from an "experimental procedure" to a clinical option, an increasing number of centers may contemplate a UTx program. This article discusses essential steps for establishment of a successful UTx program. These principles may be implemented in cis- and transgender UTx candidates.

Catatonia in the medically ill: Differences and parallels in etiology, phenomenology and management.

OBJECTIVE: Catatonia is a disorder characterized by psychomotor symptoms. The etiology, symptomatology, response and outcome of catatonia in the medically ill has not been vigorously studied. Those who have catatonia associated with another mental disorder versus. catatonic disorder due to another medical condition may differ. The aim of this study is to study the causes, phenomenology and outcomes of medically ill patients with catatonia and explore differences among those who have catatonia associated with psychiatric illness vs. systemic medical illness. METHOD: We studied the incidence of catatonic symptoms in medically hospitalized patients to identify any apparent differences in clinical manifestations due to distinctive etiologies. Specifically, we assessed if there are differences between those who had catatonia associated with another mental disorder versus those with catatonic disorder due to another medical condition in their phenomenology, management and likelihood of response to treatment. RESULTS: Of our 40 patients, 18 patients (45%) had catatonia associated with another mental disorder, 17 (42.5%) had catatonic disorder due to another medical condition, and in 5 patients (12.5%) the cause of catatonia was not identified. The most common catatonic symptoms regardless of etiology in our medically ill were mutism, followed by rigidity, and immobility. Bipolar disorder, schizophrenia, major depressive disorder, metabolic abnormalities, anti NMDAR encephalitis were the most frequent causes of catatonia in our medically ill patients. Compared to subjects with catatonic disorder due to another medical condition, those with catatonia associated with another mental disorder had more frequent mannerisms (Chi-square = 4.27; p = 0.039), waxy flexibility (Chi-square = 11.0; p < 0.01), and impulsivity (Chi-square = 4.12, p = 0.042). Nonsignificant trends were noted for posturing (Chi-square = 3.74, p = 0.053), perseveration (Chi-square = 3.37, p = 0.067), and stereotypy (Chi-square = 2.91, p = 0.088) also being more frequent in catatonia associated with a psychiatric cause. DISCUSSION: Our data supports phenomenological differences between medical and psychiatric causes of catatonia in the medically ill.

Neural stem cell delivery of an oncolytic adenovirus in newly diagnosed malignant glioma: a first-in-human, phase 1, dose-escalation trial.

BACKGROUND: Malignant glioma is the most common and lethal primary brain tumour, with dismal survival rates and no effective treatment. We examined the safety and activity of NSC-CRAd-S-pk7, an engineered oncolytic adenovirus delivered by neural stem cells (NSCs), in patients with newly diagnosed high-grade glioma. METHODS: This was a first-in-human, open-label, phase 1, dose-escalation trial done to determine the maximal tolerated dose of NSC-CRAd-S-pk7, following a 3 + 3 design. Patients with newly diagnosed, histologically confirmed, high-grade gliomas (WHO grade III or IV) were recruited. After neurosurgical resection, NSC-CRAd-S-pk7 was injected into the walls of the resection cavity. The first patient cohort received a dose starting at 6·25 × 1010 viral particles administered by 5·00 × 107 NSCs, the second cohort a dose of 1·25 × 1011 viral particles administered by 1·00 × 108 NSCs, and the third cohort a dose of 1·875 × 1011 viral particles administered by 1·50 × 108 NSCs. No further dose escalation was planned. Within 10-14 days, treatment with temozolomide and radiotherapy was initiated. Primary endpoints were safety and toxicity profile and the maximum tolerated dose for a future phase 2 trial. All analyses were done in all patients who were included in the trial and received the study treatment and were not excluded from the study. Recruitment is complete and the trial is finished. The trial is registered with ClinicalTrials.gov, NCT03072134. FINDINGS: Between April 24, 2017, and Nov 13, 2019, 12 patients with newly diagnosed, malignant gliomas were recruited and included in the safety analysis. Histopathological evaluation identified 11 (92%) of 12 patients with glioblastoma and one (8%) of 12 patients with anaplastic astrocytoma. The median follow-up was 18 months (IQR 14-22). One patient receiving 1·50 × 108 NSCs loading 1·875 × 1011 viral particles developed viral meningitis (grade 3) due to the inadvertent injection of NSC-CRAd-S-pk7 into the lateral ventricle. Otherwise, treatment was safe as no formal dose-limiting toxicity was reached, so 1·50 × 108 NSCs loading 1·875 × 1011 viral particles was recommended as a phase 2 trial dose. There were no treatment-related deaths. The median progression-free survival was 9·1 months (95% CI 8·5-not reached) and median overall survival was 18·4 months (15·7-not reached). INTERPRETATION: NSC-CRAd-S-pk7 treatment was feasible and safe. Our immunological and histopathological findings support continued investigation of NSC-CRAd-S-pk7 in a phase 2/3 clinical trial. FUNDING: US National Institutes of Health.

Safety and toxicology assessment of sodium nitrite administered by intramuscular injection.

Intramuscular (IM) injection of nitrite (1-10 mg/kg) confers survival benefit and protects against lung injury after exposure to chlorine gas in preclinical models. Herein, we evaluated safety/toxicity parameters after single, and repeated (once daily for 7 days) IM injection of nitrite in male and female Sprague Dawley rats and Beagle dogs. The repeat dose studies were performed in compliance with the Federal Drug Administration's (FDA) Good Laboratory Practices Code of Federal Regulations (21 CFR Part 58). Parameters evaluated consisted of survival, clinical observations, body weights, clinical pathology, plasma drug levels, methemoglobin and macroscopic and microscopic pathology. In rats and dogs, single doses of ≥100 mg/kg and 60 mg/kg resulted in death and moribundity, while repeated administration of ≤30 or ≤ 10 mg/kg/day, respectively, was well tolerated. Therefore, the maximum tolerated dose following repeated administration in rats and dogs were determined to be 30 mg/kg/day and 10 mg/kg/day, respectively. Effects at doses below the maximum tolerated dose (MTD) were limited to emesis (in dogs only) and methemoglobinemia (in both species) with clinical signs (e.g. blue discoloration of lips) being dose-dependent, transient and reversible. These signs were not considered adverse, therefore the No Observed Adverse Effect Level (NOAEL) for both rats and dogs was 10 mg/kg/day in males (highest dose tested for dogs), and 3 mg/kg/day in females. Toxicokinetic assessment of plasma nitrite showed no difference between male and females, with Cmax occurring between 5 mins and 0.5 h (rats) or 0.25 h (dogs). In summary, IM nitrite was well tolerated in rats and dogs at doses previously shown to confer protection against chlorine gas toxicity.

Use of a new RNA next generation sequencing approach for the specific detection of virus infection in cells.

The utilization of the current combination of in vitro, in vivo and PCR assays for the identification of adventitious viruses in production cells has a limited range of detection. While Next Generation Sequencing (NGS) has a broader breadth of detection, it is unable to differentiate sequences from replicating viruses versus background inert sequences. In order to improve NGS specificity, we have designed a new NGS approach which targets subsets of viral RNAs only synthesized during cell infection. In order to evaluate the performance of this approach for detecting low levels of adventitious viruses, we selected two difficult virus/cell systems. This included B95-8 cells persistently infected by Human herpesvirus 4 (HHV-4) and serially diluted into HHV-4 negative Ramos cells and Madin-Darby bovine kidney cells with an early infection produced via a low dose of Bovine viral diarrhea virus. We demonstrated that the sensitivity of our RNA NGS approach was equivalent to targeted PCR with an increased specificity for the detection of viral infection. We were also able to identify a previously undetected Murine Leukemia Virus contaminant in Ramos cells. Based on these results, we conclude that this new RNA NGS approach is suitable for conducting viral safety evaluations of cells.

Hypoglycemic Toxins and Enteroviruses as Causes of Outbreaks of Acute Encephalitis-Like Syndrome in Children, Bac Giang Province, Northern Vietnam.

We investigated the cause of seasonal outbreaks of pediatric acute encephalitis-like syndrome associated with litchi harvests (May-July) in northern Vietnam since 2008. Nineteen cerebrospinal fluid samples were positive for human enterovirus B, and 8 blood samples were positive for hypoglycemic toxins present in litchi fruits. Patients who were positive for hypoglycemic toxins had shorter median times between disease onset and admission, more reports of seizures, more reports of hypoglycemia (glucose level <3 mmol/L), lower median numbers of leukocytes in cerebrospinal fluid, and higher median serum levels of alanine aminotransferase and aspartate transaminase than did patients who were positive for enteroviruses. We suggest that children with rapidly progressing acute encephalitis-like syndrome at the time of the litchi harvest have intoxication caused by hypoglycemic toxins, rather than viral encephalitis, as previously suspected. These children should be urgently treated for life-threatening hypoglycemia.

Characteristics and resource utilization of patients presenting to the ED from mass gathering events.

INTRODUCTION: At many mass gathering events (MGEs), emergency medical services decrease the number of patient transfers to the hospital; however, little information is known regarding the characteristics of attendees presenting to or requiring transfer to the emergency department (ED). The purpose of this study is to describe the characteristics of patients presenting from MGEs to the ED. A secondary aim of this study is to describe ED resources utilized by these patients. METHODS: This was a single-center, retrospective review evaluating patients attending MGEs who presented to the ED. Electronic medical records of patients seen in the ED of a tertiary academic medical center between October 13, 2013 and December 31, 2015 were reviewed and a descriptive analysis performed. RESULTS: We reviewed and included 209 patients. The majority of patients presenting to the ED were from large outdoor concerts (n=186, 89%), young (median age 20years), single (n=156, 87%) and had no past medical history (n=114, 63%). Alcohol use was reported in a majority (n=140, 78%) and polysubstance use in over a quarter of patients (n=55, 31%). The most frequently administered medications were intravenous fluids (n=94, 52%) and antiemetics (n=59, 33%). The majority of patients (n=161, 89%) were discharged directly from the ED, and median length of stay in the ED was 3.3h [IQR 2.3 to 5.3]. CONCLUSION: Patients presenting to the ED from MGEs generally required minimal medical care beyond supportive management with low rates of hospital admission. Further controlled studies are needed to confirm these findings.

Single dose GLP toxicity and biodistribution study of a conditionally replicative adenovirus vector, CRAd-S-pk7, administered by intracerebral injection to Syrian hamsters.

BACKGROUND: CRAd-S-pk7 is a conditionally replicative oncolytic adenoviral vector that contains a survivin promoter and a pk7 fiber modification that confer tumor-specific transcriptional targeting and preferential replication in glioma while sparing the surrounding normal brain parenchyma. METHODS: This IND-enabling study performed under GLP conditions evaluated the toxicity and biodistribution of CRAd-S-pk7 administered as a single intracerebral dose to Syrian hamsters, a permissive model of adenoviral replication. Two hundred and forty animals were stereotactically administered either vehicle (n = 60) or CRAd-S-pk7 at 2.5 × 10(7), 2.5 × 10(8), or 2.5 × 10(9) viral particles (vp)/animal (each n = 60) on day 1. The animals were closely monitored for toxicology evaluation, assessment of viral distribution, and immunogenicity of CRAd-S-pk7. RESULTS: Changes in hematology, clinical chemistry, and coagulation parameters were minor and transient, and consistent with the inflammatory changes observed microscopically. These changes were considered to be of little toxicological significance. The vector remained localized primarily in the brain and to some degree in the tissues at the incision site. Low levels of vector DNA were detected in other tissues in a few animals suggesting systemic circulation of the virus. Viral DNA was detected in brains of hamsters for up to 62 days. However, microscopic changes and virus-related toxicity to the central nervous system were considered minor and decreased in incidence and severity over time. Such changes are not uncommon in studies using adenoviral vectors. CONCLUSION: This study provides safety and toxicology data justifying a clinical trial of CRAd-S-pk7 loaded in FDA-approved HB1.F3.CD neural stem cell carriers administered at the tumor resection bed in humans with recurrent malignant glioma.

Viral diversity in swine intestinal mucus used for the manufacture of heparin as analyzed by high-throughput sequencing.

Heparin is one of the main pharmaceutical products manufactured from raw animal material. In order to describe the viral burden associated with this raw material, we performed high-throughput sequencing (HTS) on mucus samples destined for heparin manufacturing, which were collected from European pigs. We identified Circoviridae and Parvoviridae members as the most prevalent contaminating viruses, together with viruses from the Picornaviridae, Astroviridae, Reoviridae, Caliciviridae, Adenoviridae, Birnaviridae, and Anelloviridae families. Putative new viral species were also identified. The load of several known or novel small non-enveloped viruses, which are particularly difficult to inactivate or eliminate during heparin processing, was quantified by qPCR. Analysis of the combined HTS and specific qPCR results will influence the refining and validation of inactivation procedures, as well as aiding in risk analysis of viral heparin contamination.

Unbiased analysis by high throughput sequencing of the viral diversity in fetal bovine serum and trypsin used in cell culture.

Fetal bovine serum (FBS) and trypsin are reagents used in cell culture and have been the source of viral contamination of pharmaceutical products. We performed high throughput sequencing (HTS) of two pools of commercial batches of FBS and three commercial batches of trypsin. Taxonomies were assigned by comparing sequences of contigs and singletons to the entire NCBI nucleic acid and protein databases. The same major viral species were evidenced between batches of a given reagent but the proportion of viral reads among total reads varied markedly between samples (from 0.002% to 22.7%). In FBS, the sequences found were mainly from bovine viral diarrhea virus (BVDV) 1 to 3 and bovine parvovirus 3 (BPV3). The BVDV sequences derived from FBS showed only minor discrepancies with primers generally used for the screening of BVDV. Viral sequences in trypsin were mainly from porcine circovirus type 2. Other known viral sequences at lower read counts and potential new viral species (bovine parvovirus and bovine pegivirus) were evidenced. The load of some known and new viruses detected by HTS could be quantified by qPCR. Results of HTS provide a framework for evaluating the pertinence of control measures including the design of PCRs, bioassays and inactivation procedures.

Analysis by high throughput sequencing of Specific Pathogen Free eggs.

Specific Pathogen Free (SPF) embryonated eggs are used for the production of many veterinary and human vaccines. We have used High Throughput Sequencing to screen allantoic fluids and embryos for the presence of encapsidated viral genomes and viral transcripts, respectively. SPF eggs from two different producers were tested. We evidenced sequences corresponding to known endogenous retroviruses and sequences of Avian Leukosis Virus, but no sequence that might suggest a productive infection of eggs with a virus even distant from known viruses. Our results strongly suggest that SPF eggs such as those used for this study represent a safe substrate for the production of vaccines.

Symptoms of Anxiety, Depression, and Stress among Families of Critically Ill Patients with COVID-19: A Longitudinal Clinical Trial.

Rationale: Families of critically ill patients with coronavirus disease (COVID-19) may be at particularly high risk for anxiety, depression, and post-traumatic stress disorder after hospital discharge. Objectives: To assess symptoms of anxiety, depression, and stress among families of patients with COVID-19 during and after intensive care unit (ICU) admissions and to use qualitative methods to determine the sources of emotional distress. Methods: Families of patients with COVID-19 who participated in an ICU study were approached for participation in this post-hospital discharge study. Participants completed the Hospital Anxiety and Depression Scale (HADS) and the Impact of Events Scale-Revised (IES-R) at up to three points during the ICU stay and once after the ICU stay. Mixed-effects models were used to compare trajectories of HADS and IES-R scores over the ICU and post-ICU periods. Telephone interviews with participants were evaluated using thematic content analysis. Results: Among the 90 families that participated from September 2020 to April 2021, 47 respective patients were alive and 43 were deceased. Average HADS anxiety, HADS depression, and IES-R scores after hospital discharge were significantly higher (greater symptom burden) among families of deceased versus surviving patients: 9.2 (95% confidence interval [CI], 7.8-10.6) versus 6.3 (95% CI, 4.9-7.6) (P < 0.01), 7.1 (95% CI, 5.7-8.6) versus 3.2 (95% CI, 2.3-4.1) (P < 0.001), and 36.1 (95% CI, 31.0-41.2) versus 20.4 (95% CI, 16.1-24.8) (P < 0.001), respectively. HADS anxiety and HADS depression scores began to diverge during the ICU stay, whereas IES-R scores diverged after the stay for families of surviving versus deceased patients. Qualitative analysis confirmed a higher burden of psychological symptoms among families of deceased patients. Memories from the ICU stay became a focal point for participants who lost their loved ones, whereas families of surviving patients were able to look positively toward the future. In addition, families of deceased patients often viewed friends and family as sources of stress, whereas families of surviving patients typically viewed their community as a source of support. Conclusions: Patient death was associated with symptoms of anxiety, depression, and post-traumatic stress disorder among families of ICU patients with COVID-19. Psychological support interventions may be most beneficial for families of patients who died of COVID-19. Clinical trial registered with www.clinicaltrials.gov (NCT04501445).

Splicing-independent recruitment of U1 snRNP to a transcription unit in living cells.

Numerous non-coding RNAs are known to be involved in the regulation of gene expression. In this work, we analyzed RNAs that co-immunoprecipitated with human RNA polymerase II from mitotic cell extracts and identified U1 small nuclear RNA (snRNA) as a major species. To investigate a possible splicing-independent recruitment of U1 snRNA to transcription units, we established cell lines having integrated a reporter gene containing a functional intron or a splicing-deficient construction. Recruitment of U snRNAs and some splicing factors to transcription sites was evaluated using fluorescence in situ hybridization (FISH) and immunofluorescence. To analyze imaging data, we developed a quantitative procedure, 'radial analysis', based on averaging data from multiple fluorescence images. The major splicing snRNAs (U2, U4 and U6 snRNAs) as well as the U2AF65 and SC35 splicing factors were found to be recruited only to transcription units containing a functional intron. By contrast, U1 snRNA, the U1-70K (also known as snRNP70) U1-associated protein as well as the ASF/SF2 (also known as SFRS1) serine/arginine-rich (SR) protein were efficiently recruited both to normally spliced and splicing-deficient transcription units. The constitutive association of U1 small nuclear ribonucleoprotein (snRNP) with the transcription machinery might play a role in coupling transcription with pre-mRNA maturation.

Neuropsychiatric sequelae of brain radiation therapy: A review of modality, symptomatology, and treatment options.

OBJECTIVE: Consultation-liaison psychiatrists frequently evaluate cancer patients with brain involvement, and brain irradiation is often a mainstay of treatment for this population. A comprehensive review of the neuropsychiatric effects of brain radiotherapy is lacking in the psychiatric literature. This review aims to provide an in depth discussion of existing literature with guidance about treatments for radiation-induced neurocognitive decline. METHODS: Narrative synthesis of available published literature retrieved from PubMed and MEDLINE databases. Particular focus was given to neuropsychiatric manifestations after radiotherapy, dose-response relationships, differential effects of whole versus stereotactic regimens, and studies investigating possible pharmacological treatments. RESULTS: Brain irradiation induces cognitive, mood, and other symptoms that evolve in a time-dependent manner and adversely affect quality of life. Available data implicates loss of hippocampal neurogenesis and repair in post-radiotherapy changes. Clinical factors affecting incidence of neuropsychiatric compromise include total radiation dose, whole brain radiation, among others. Efficacy of pharmacological interventions is mixed for certain agents (ie, methylphenidate) but promising for others (ie, memantine). CONCLUSIONS: Neuropsychiatric consequences of brain irradiation are common. Although our understanding of clinical manifestations and pathogenesis has advanced considerably, treatment options are poorly researched and use of any psychopharmacological intervention should therefore be tailored to individual patient needs.

Piloting Group-Based Behavioral Activation Therapy for Families of Deceased COVID-19 Patients.

Surrogate decision-making is a stressful process for many family members of critically ill patients. The COVID-19 pandemic may have amplified the risk for anxiety, depression, and posttraumatic stress disorder (PTSD) symptoms in ICU surrogates. OBJECTIVES: This study piloted an online group-based behavioral intervention with family members of deceased COVID-19 patients. Participant engagement, perceptions, and responses related to the intervention were assessed. DESIGN: A single-arm pilot study was conducted with bereaved families. Quantitative analysis of measures of anxiety, depression, and PTSD symptoms was conducted with mixed models. Qualitative data were analyzed to identify themes in surrogates' experiences with the intervention. SETTING: Participants were recruited from ICUs at a tertiary academic medical center. Participants completed the intervention, measures, and interviews online. SUBJECTS: Participants were family members of patients who died from COVID-19. INTERVENTIONS: The intervention involved six online group-based behavioral activation sessions. Sessions covered topics pertinent to grieving and engagement in personally meaningful activities. MEASUREMENTS AND MAIN RESULTS: Semi-structured interviews explored participants' experiences with the intervention. Surrogates also completed measures of anxiety, depression, and PTSD symptoms before and after the intervention. Nineteen of 26 participants (73.1%) completed the study. Thematic analysis suggested that surrogates found the group helpful for overcoming perceived isolation, receiving validation, and developing coping skills. Significant pre-to-post reductions were observed in symptoms of Hospital and Anxiety Disorder Scale (HADS) anxiety (pre-mean = 9.27, sd = 5.30 vs post-mean = 6.80, sd = 4.16; p = 0.0271), HADS depression (pre-mean =6 .65, sd = 4.58 vs post- mean = 4.89, sd = 3.40; p = 0.0436), and Impact of Events Scale-Revised PTSD (pre-mean = 36.86, sd = 16.97 vs post-mean = 24.14, sd = 13.49; p = 0.0008). LIMITATIONS: This was a preliminary study based on qualitative and self-report measures. Future studies should include a control group. CONCLUSIONS: Online group-based behavioral activation therapy appears to be a potentially useful intervention for family members of ICU patients who died from COVID-19.

Multidisciplinary inpatient rehabilitation for Functional Movement Disorders: A prospective study with long term follow up.

INTRODUCTION: Functional Movement Disorders (FMDs) are challenging to treat. We assessed the effect of multidisciplinary inpatient rehabilitation, involving motor retraining, psychotherapy and psychotropic medication on FMD patient function and maintenance of improvement after one year. METHODS: FMD patients in a movement disorders clinic were referred for inpatient rehabilitation. Baseline, discharge and one year follow-up measures included: Clinical Global Impression (CGI-severity, CGI-change); Depression and Somatic Symptom Scale (DSSS); Generalized Anxiety Disorder-7 (GAD-7); Patient Health Questionnaire-9 (PHQ-9); Post-traumatic stress disorder check-list for DSM-5 (PCL-5). Outcomes were analyzed with non-parametric models. RESULTS: Seventeen patients completed rehabilitation. Thirteen completed one-year follow-up. Median CGI-severity was "markedly ill." At discharge, movement disorder improved in 93% (median CGI-change = 2, "much improved") as assessed by neurologist and patient. Psychiatrist ratings showed improvement among 86.7%; physiatrist and psychologist ratings were 66.7% and 53.3%, respectively. Symptoms improved on DSSS (Wilcoxon Z = -2.914, p ≤ 0.004); GAD-7 (Z = -3.045, p ≤ 0.002); PHQ-9 (Z = -3.415, p ≤ 0.01) but not PCL-5 (Z = -1.506, p = 0.132). At 1 year, 54% maintained at least minimal improvement by neurologist rating and 77% by patient rating (median CGI-change = 3, "minimally improved"). Improvement was not maintained for DSSS (Wilcoxon Z = -0.385. p = 0.701), GAD-7 (Z = -0.943, p = 0.357) or PHQ-9 (Z = -0.55, p = 0.582). CONCLUSIONS: Multidisciplinary inpatient rehabilitation improved FMD patient function, depression, anxiety and somatic symptoms. One-year follow-up demonstrated minimal sustained improvement and worsening psychopathology, reflecting chronic debility despite initial rehabilitative success.

Postnatal Effects of Gestational and Lactational Gavage Exposure to Boric Acid in the Developing Sprague Dawley Rat.

Human exposure to boron occurs primarily through diet and drinking water sources. Animal studies have found that reduced fetal weight following gestational exposure to boron (as boric acid) is the most sensitive toxicological effect. However, recent studies suggest that newborns in areas with elevated boron in drinking water may receive levels of exposure that exceed the U.S. EPA oral reference dose for B. Currently, there are no data to inform a boron risk assessment accounting for this developmental window. To address this knowledge gap, the National Toxicology Program evaluated developmental toxicity following pre- and postnatal boron exposure. Time-mated female Sprague Dawley (Hsd: Sprague Dawley SD) rats were administered 0-20 mg B/kg/day (as boric acid) via gavage from gestation day 6 to 21; offspring were dosed via gavage at the same respective dose level from postnatal day (PND) 1 to 28. There were no dose-related effects on dam bodyweight, bodyweight gain, or feed consumption. Clinical findings were limited to low incidences of umbilical hernia in the 20 mg B/kg pups which resolved by study completion. Pup plasma boron concentrations increased in dose-proportional manner and were similar between PND 4 and PND 28. Postnatal weight gain was significantly reduced at 20 mg B/kg, with male and female pups weighing 23% less than the controls on PND 28. These findings demonstrate that postnatal growth in the Sprague Dawley rat is sensitive to boron exposure and highlights the importance of evaluating the potential toxicity of agents with known human exposures during early life stages.

Pixel: a content management platform for quantitative omics data.

BACKGROUND: In biology, high-throughput experimental technologies, also referred as "omics" technologies, are increasingly used in research laboratories. Several thousands of gene expression measurements can be obtained in a single experiment. Researchers are routinely facing the challenge to annotate, store, explore and mine all the biological information they have at their disposal. We present here the Pixel web application (Pixel Web App), an original content management platform to help people involved in a multi-omics biological project. METHODS: The Pixel Web App is built with open source technologies and hosted on the collaborative development platform GitHub (https://github.com/Candihub/pixel). It is written in Python using the Django framework and stores all the data in a PostgreSQL database. It is developed in the open and licensed under the BSD 3-clause license. The Pixel Web App is also heavily tested with both unit and functional tests, a strong code coverage and continuous integration provided by CircleCI. To ease the development and the deployment of the Pixel Web App, Docker and Docker Compose are used to bundle the application as well as its dependencies. RESULTS: The Pixel Web App offers researchers an intuitive way to annotate, store, explore and mine their multi-omics results. It can be installed on a personal computer or on a server to fit the needs of many users. In addition, anyone can enhance the application to better suit their needs, either by contributing directly on GitHub (encouraged) or by extending Pixel on their own. The Pixel Web App does not provide any computational programs to analyze the data. Still, it helps to rapidly explore and mine existing results and holds a strategic position in the management of research data.

Bad metallic transport in a cold atom Fermi-Hubbard system.

Strong interactions in many-body quantum systems complicate the interpretation of charge transport in such materials. To shed light on this problem, we study transport in a clean quantum system: ultracold lithium-6 in a two-dimensional optical lattice, a testing ground for strong interaction physics in the Fermi-Hubbard model. We determine the diffusion constant by measuring the relaxation of an imposed density modulation and modeling its decay hydrodynamically. The diffusion constant is converted to a resistivity by using the Nernst-Einstein relation. That resistivity exhibits a linear temperature dependence and shows no evidence of saturation, two characteristic signatures of a bad metal. The techniques we developed in this study may be applied to measurements of other transport quantities, including the optical conductivity and thermopower.