Safety, tolerability and pharmacokinetics of eteplirsen in young boys aged 6-48 months with Duchenne muscular dystrophy amenable to exon 51 skipping.

Eteplirsen is FDA-approved for the treatment of Duchenne muscular dystrophy (DMD) in exon 51 skip-amenable patients. Previous studies in boys > 4 years of age indicate eteplirsen is well tolerated and attenuates pulmonary and ambulatory decline compared with matched natural history cohorts. Here the safety, tolerability and pharmacokinetics of eteplirsen in boys aged 6-48 months is evaluated. In this open-label, multicenter, dose-escalation study (NCT03218995), boys with a confirmed mutation of the DMD gene amenable to exon 51 skipping (Cohort 1: aged 24-48 months, n = 9; Cohort 2: aged 6 to < 24 months, n = 6) received ascending doses (2, 4, 10, 20, 30 mg/kg) of once-weekly eteplirsen intravenously over 10 weeks, continuing at 30 mg/kg up to 96 weeks. Endpoints included safety (primary) and pharmacokinetics (secondary). All 15 participants completed the study. Eteplirsen was well tolerated with no treatment-related discontinuations, deaths or evidence of kidney toxicity. Most treatment-emergent adverse events were mild; most common were pyrexia, cough, nasopharyngitis, vomiting, and diarrhea. Eteplirsen pharmacokinetics were consistent between both cohorts and with previous clinical experience in boys with DMD > 4 years of age. These data support the safety and tolerability of eteplirsen at the approved 30-mg/kg dose in boys as young as 6 months old.

Indirect positive health outcomes of COVID-19: a systematic review.

OBJECTIVES: The aim of this study was to assess the frequency of indirect positive health outcomes as a result of the COVID-19 pandemic. STUDY DESIGN: This was a systematic review. METHODS: Articles were identified from four online databases (Web of Science, Scopus, PubMed and Google Scholar) using predetermined search terms. After studies were systematically identified, the results were summarised narratively. The indirect positive health outcomes associated with the emergence of COVID-19 and measures taken for its prevention were categorised into four health dimensions (physical, mental, social and digital). RESULTS: After initial screening, 44 articles were assessed for eligibility, and 33 were included in the final sample. Of the included studies, 72.73% noted a benefit from COVID-19 prevention measures in the physical health dimension. In addition, 12.12%, 9.09%, 3.03% and 3.03% of articles reported a positive impact in the digital, mental, social and combined digital and mental health dimensions, respectively. CONCLUSIONS: Despite the catastrophic health, socio-economic and political crises associated with the COVID-19 emergency, it has also resulted in some positive health outcomes. Reduced air pollutants, improved disease prevention practices, increased digital health delivery and improved mental and social health dimensions were reported during the pandemic. Integrated and collaborative activities for the persistence of these health benefits are recommended.

A unified call to action from Australian nursing and midwifery leaders: ensuring that Black lives matter.

Nurses and midwives of Australia now is the time for change! As powerfully placed, Indigenous and non-Indigenous nursing and midwifery professionals, together we can ensure an effective and robust Indigenous curriculum in our nursing and midwifery schools of education. Today, Australia finds itself in a shifting tide of social change, where the voices for better and safer health care ring out loud. Voices for justice, equity and equality reverberate across our cities, our streets, homes, and institutions of learning. It is a call for new songlines of reform. The need to embed meaningful Indigenous health curricula is stronger now than it ever was for Australian nursing and midwifery. It is essential that nursing and midwifery leadership continue to build an authentic collaborative environment for Indigenous curriculum development. Bipartisan alliance is imperative for all academic staff to be confident in their teaching and learning experiences with Indigenous health syllabus. This paper is a call out. Now is the time for Indigenous and non-Indigenous nurses and midwives to make a stand together, for justice and equity in our teaching, learning, and practice. Together we will dismantle systems, policy, and practices in health that oppress. The Black Lives Matter movement provides us with a 'now window' of accepted dialogue to build a better, culturally safe Australian nursing and midwifery workforce, ensuring that Black Lives Matter in all aspects of health care.

Pbx1 is required for Hox D3-mediated angiogenesis.

Our previous studies showed that the homeobox (Hox) D3 transcription factor induces expression of alphavbeta3 integrin and promotes endothelial cell (EC) migration and angiogenesis. Since binding of Hox 3 factors to target DNA is enhanced by the co-factor Pbx, we investigated whether Pbx1 is also required for angiogenesis. We observed that EC predominantly express the Pbx1b isoform. Nuclear extracts from angiogenic EC express higher levels of active Pbx1 and more effectively form complexes on Pbx1/Hox consensus DNA oligonucleotides as compared to nuclear extracts from quiescent EC. Introduction of anti-sense against Pbx1 impaired the formation of Pbx1/Hox complexes on target DNA consensus in nuclear extracts from angiogenic EC. Anti-sense against Pbx1 also impaired EC migration and blocked angiogenesis induced by bFGF in vivo. Furthermore, although the levels of Hox D3 were unchanged, expression of its target gene, beta3 integrin was reduced, consistent with impaired transcriptional activation by Hox D3. Together, these studies suggest that Pbx1 is required for pro-angiogenic Hox DNA binding and transcriptional activity in endothelial cells.

The cycle of homelessness in the lives of young mothers: the diagnostic phase of an action research project.

This paper presents the findings of the first stage of an action research project designed to explore the experience of repeated homelessness in the lives of young women. An action research strategy was selected because it offered a framework within which to work with and for rather than on this vulnerable group of service users. The women participating in the research developed a conceptual model that captured the essence of their experience, which they named 'Our Cycle'. They also proposed a system for service delivery, 'From trauma to recovery: a non-professional model'. The diagnostic phase of the action research has thus resulted in a sound theoretical and practical framework to guide the implementation and evaluation stages of the project, currently being funded through the United Kingdom Department of Health's Health Action Zone initiative.

The application of technetium-99m hexamethylpropyleneamine oxime (99mTc-HMPAO) labeled white blood cells for the diagnosis of right dorsal ulcerative colitis in two horses.

The application of 99mTc-HMPAO labeled white blood cells to support the diagnosis of right dorsal ulcerative colitis was studied in two horses with a history and clinical signs consistent with phenylbutazone toxicity. These images were compared to a reference horse unaffected by right dorsal ulcerative colitis. Blood was collected aseptically in heparinized syringes from the patients for in vitro white blood cell (WBC) radiolabeling. The buffy coat was separated out and radiolabeled with 99mTc-HMPAO. The radiolabeled blood was re-injected i.v. and four images of the right and left side of the patient's abdomen were acquired at 4 hours and 20 hours post-injection. Results of the nuclear study revealed no abnormal findings in the abdomen at the four-hour post-injection images in any horse. Images obtained 20 hours post-injection revealed a linear uptake of radiolabeled WBCs in the right cranioventral abdomen in the region of the right dorsal colon in both horses with right dorsal ulcerative colitis. The reference horse had no radiopharmaceutical uptake in this region. This nuclear imaging study was a rapid, non-invasive method to identify right dorsal colon inflammation. These findings not only supported the diagnosis of right dorsal ulcerative colitis, but also facilitated appropriate medical management of each horse.

Foaling-management practices associated with the occurrence of enterocolitis attributed to Clostridium perfringens infection in the equine neonate.

Enterocolitis associated with Clostridium perfringens (C. perfringens) infection in neonatal foals is often severe and has been associated with a high case-mortality risk. We designed a premises-based survey to evaluate the associations of regional foaling practices, premises environmental management, periparturient foal and brood-mare management, and periparturient brood-mare ration with the occurrence of neonatal enterocolitis attributed to C. perfringens infection. Potential risk factors individually associated with enterocolitis were breed type, housing type at foaling and in the first three days of life, ground/floor surface type at foaling and in the first three days of life, brood-mare ration before and after foaling, and the presence of livestock other than horses on the premises in the past. From the multivariable-logistic regression models, six variables were significantly associated with an increased risk of the outcome of interest (p<0.05): foals of the stock horse type, housing in a stall or drylot in the first three days of life, other livestock present on the premises in the past, foal born on dirt, sand or gravel surface, and low amounts of grass hay and grain fed post-partum. Low grain amounts fed pre-partum represented a decreased risk of the outcome of interest.

Occult osseous metastasis of a colonic adenocarcinoma visualized with technetium tc 99m hydroxymethylene diphosphate scintigraphy in a horse.

A 5-year-old Arabian horse was admitted with a 5-day history of undulant pyrexia of unknown origin, inappetence, obtundation, and acute collapse. Physical examination results were unremarkable except for a grade II/VI left-sided systolic cardiac murmur and abdominal splinting. Mild chronic inflammatory changes were evident on clinicopathologic evaluation. Echocardiography revealed moderate aortic insufficiency. A solitary soft tissue opacity was found on thoracic radiography but not on ultrasonography. Palliative treatment was ineffective. Nuclear scintigraphy with WBC labeled with technetium Tc 99m hexamethylpropyleneamine oxime did not identify abnormalities, but a second nuclear scan with technetium Tc 99m hydroxymethylene diphosphate identified polyostotic disease. Examination of a biopsy specimen from an affected rib revealed disseminated adenocarcinoma. The horse was euthanatized. Necropsy and histologic examination revealed a colonic adenocarcinoma with osseous metaplasia that had disseminated to multiple parenchymal organs, muscle, and bone.

Enterocolitis associated with Clostridium perfringens infection in neonatal foals: 54 cases (1988-1997).

OBJECTIVE: To identify clinical signs, physical examination findings, results of diagnostic tests, treatments administered, and clinical outcome of neonatal foals with enterocolitis associated with Clostridium perfringens infection. DESIGN: Retrospective study. ANIMALS: 54 neonatal foals. RESULTS: Most foals had acute onset of obtunded mentation, colic, or diarrhea and developed leukopenia, neutropenia, an abnormally high number of band neutrophils, toxic WBC, and hypoproteinemia within 24 hours after admission, despite high serum IgG concentrations (> 800 mg/dl). Abdominocentesis and abdominal radiography of some foals revealed exudative peritonitis and gaseous distention of the small and large intestine, respectively. Cytologic examination of feces revealed spores or gram-positive rods in 8 of 10 foals. The most common genotypes of C perfringens isolates were type A and C, alone or in combination. Treatment did not alter mortality rate for most foals that had a positive culture for C perfringens type C. Of 54 foals, 29 (54%) that had C perfringens-associated enterocolitis died. Foals that had a culture that yielded C perfringens had higher sepsis scores, IgG concentrations, and mortality rates, compared with the overall hospital population of neonatal foals. CLINICAL IMPLICATIONS: Foals less than 7 days old that have enterocolitis associated with C perfringens infections, especially type C, have a guarded prognosis. Cytologic examination of feces to determine spore counts and detect rods may be a means for early identification of C perfringens infections. Polymerase chain reaction assays to determine genotype are important for designing preventive treatment regimens.

Abdominal neoplasia (excluding urogenital tract).

Neoplasia of the equine gastrointestinal tract and abdominal organs occurs predominantly in geriatric horses, although lymphoma and hepatocellular carcinoma and a few other neoplasms can be found in young horses. This article discusses diagnostics that can be used in weight-loss situations, suspicious of neoplasia, as well as tumors themselves including clinical signs, diagnostic tools, histopathologic appearance, and management.

Change in process: bringing about change in health care through action research.

A 2-year action-research project aiming to facilitate the management of change was carried out in a district general hospital. Hospital managers and senior ward nurses had very different views concerning the source of challenges and problems within the hospital organization. A case-study of nurses' experience of change at ward level was produced as part of the diagnostic phase of the action research. The results of the case-study indicated that general managers and professionals had different agendas for change but that there is common ground between them.

[125I] Glucagon binding by liver membranes from young and adult rats.

We have previously shown that adipocytes from adult (between four and five months old) rats have reduced glucagon binding and glucagon-stimulated lipolytic activity when compared with cells from young (1.5 months old) animals. In the present study we measured specific [125I] glucagon binding by purified liver plasma membranes isolated from young and adult rats. When expressed on the basis of membrane protein content, 5'-nucleotidse activity, or specific [125I] insulin binding, the extend of [125I] glucagon binding by liver membranes was not influenced by aging. Furthermore, the degree of [125I] glucagon degradation was the same in both membrane preparations. These data describe a unique condition in which glucagon binding and hormone sensitivity diminish in one tissue but remain unaltered in another.