Saccharomyces Boulardii and Bismuth Subsalicylate as Low-Cost Interventions to Reduce the Duration and Severity of Cholera

We conducted a randomised single-blinded clinical trial of 100 cholera patients in Port-au-Prince, Haiti to determine if the probiotic Saccharomyces cerevisiae var. boulardii and the anti-diarrhoeal drug bismuth subsalicylate (BS) were able to reduce the duration and severity of cholera. Subjects received either: S. boulardii 250 mg, S. boulardii 250 mg capsule plus BS 524 mg tablet, BS 524 mg, or two placebo capsules every 6 hours alongside standard treatment for cholera. The length of hospitalisation plus the number and volume of emesis, stool and urine were recorded every 6 hours until the study subject was discharged (n=83), left against medical advice (n=11), or requested removal from the study (n=6). There were no reported deaths or adverse study-related events. There were no statistically significant differences between the study arms and the outcomes of interest

A rare case of recurrent paroxysmal supraventricular tachycardia in pregnancy managed with adenosine, a wonder drug

Paroxysmal supraventricular tachycardia (PSVT) is the most common sustained arrhythmia during pregnancy and a challenging situation due to lack of evidence based guidelines. About 50% of PSVT, who fail to respond to vagal maneuvres, responds to therapies as pharmacologic agents as adenosine and electrocardioversion. We reported a case of 29 years old primigravida women with no organic heart disease who presented at 21 weeks of period of gestation with complaints of palpitations and shortness of breath. Her ECG revealed PSVT for which she received adenosine as anti-arrhythmic for conversion to sinus rhythm. She was started prophylactically on tablet metoprolol 25 mg twice daily, as advised by cardiologist. In third trimester, she had recurrent episodes of PSVT for which she received adenosine in emergency department. She delivered a healthy female baby by an elective caesarean section done under spinal anesthesia. Fortunately, her intraoperative and postpartum was uneventful with no recurrence of PSVT during hospital stay. She was discharged on day 4 of caesarean section on tablet metoprolol 12.5 mg twice daily and followed in postpartum period for complications. To summarize, PSVT occurring during pregnancy, labour or at caesarean section is not uncommon. Treatment remains a challenge though, as clinical decision must be tackled with appropriate consideration of both maternal and fetal factors. So, multi-disciplinary approach is needed for treatment including obstetrician, cardiologists, physician and neonatologists. Our case highlighted the necessity of keeping anti-arrhythmic drugs such as adenosine readily available on the labour ward

Health Impact Assessment of the Proposed Moʻomomi Community-Based Subsistence Fishing Area

Hawai‘i State law provides pathways for island communities to apply for the designation of Community-Based Subsistence Fishing Areas (CBSFAs), allowing for comanagement of culturally significant and/or cologically vulnerable nearshore fisheries by the state and local communities. In the early 1990s residents of the Island of Moloka‘i expressed concern about Native Hawaiians’ rights to exercise traditional cultural fishing practices in nearshore environments. A task force report, commissioned in 1994 by then- Governor John Waihe‘e, recommended that the Mo‘omomi fishery area along the northwest coast of Moloka‘i serve as a demonstration area, in which fishing activities would be managed by the Ho‘olehua Homestead community primarily for subsistence rather than commercial use. The Hawai‘i State Legislature passed Hawai‘i Revised Statute §188-22.6 that same year, authorizing the Department of Land and Natural Resources (DLNR) to designate CBSFAs and implement management strategies “for the purpose of reaffirming and protecting fishing practices customarily and traditionally exercised for the purposes of [N]ative Hawaiian subsistence, culture, and religion.” Fish and other marine life are prominent staples of traditional Hawaiian diets, and overfishing, commercial harvesting methods, and a gradual movement away from the Hawaiian mahele system of sharing and other ancestral practices were identified as threats to community and cultural food security. Despite the passage of legislation more than 20 years ago, the proposed Mo‘omomi CBSFA remained a pilot project. Currently Hui Mālama O Mo‘omomi, a community organization based on Moloka‘i, is in the process of advancing a formal proposal to make traditional subsistence harvesting practices legally enforceable in the designated area of Moloka‘i’s north shore. This Health Impact Assessment seeks to provide information that will help evaluate the CBSFA proposal by taking into consideration potential effects of CBSFA status on community well-being. The authors also hope that the findings and recommendations of an HIA particular to the Mo‘omomi area may also prove relevant to CBSFA proposals from other regions of the state where such co-management strategies are being considered

Flipping the Classroom to Train Citizen Scientists in Invasive Species Detection and Response

Extension educators are increasingly using flipped classrooms, wherein online content delivery precedes in-person learning. We have applied this approach to two Extension programs in which citizen scientists are trained in early detection of invasive species. Our goal in using the tool of flipped classrooms is to accommodate large amounts of content while focusing classroom time on skills development. In 2017, we assessed efficacy of the flipped classroom through knowledge tests and surveys completed by 174 participants and 106 participants, respectively. Results demonstrated large knowledge gains and high participant satisfaction. We encourage Extension professionals to consider whether use of the flipped classroom format could advance achievement of their programs\u27 learning objectives

Cobalt nanoparticles trigger ferroptosis-like cell death (oxytosis) in neuronal cells : Potential implications for neurodegenerative disease

Abstract The neurotoxicity of hard metal-based nanoparticles (NPs) remains poorly understood. Here, we deployed the human neuroblastoma cell line SH-SY5Y differentiated or not into dopaminergic- and cholinergic-like neurons to study the impact of tungsten carbide (WC) NPs, WC NPs sintered with cobalt (Co), or Co NPs versus soluble CoCl2. Co NPs and Co salt triggered a dose-dependent cytotoxicity with an increase in cytosolic calcium, lipid peroxidation, and depletion of glutathione (GSH). Co NPs and Co salt also suppressed glutathione peroxidase 4 (GPX4) mRNA and protein expression. Co-exposed cells were rescued by N-acetylcysteine (NAC), a precursor of GSH, and partially by liproxstatin-1, an inhibitor of lipid peroxidation. Furthermore, in silico analyses predicted a significant correlation, based on similarities in gene expression profiles, between Co-containing NPs and Parkinson's disease, and changes in the expression of selected genes were validated by RT-PCR. Finally, experiments using primary human dopaminergic neurons demonstrated cytotoxicity and GSH depletion in response to Co NPs and CoCl2 with loss of axonal integrity. Overall, these data point to a marked neurotoxic potential of Co-based but not WC NPs and show that neuronal cell death may occur through a ferroptosis-like mechanism.Peer reviewe

The importance of microtubule-dependent tension in accurate chromosome segregation

Accurate chromosome segregation is vital for cell and organismal viability. The mitotic spindle, a bipolar macromolecular machine composed largely of dynamic microtubules, is responsible for chromosome segregation during each cell replication cycle. Prior to anaphase, a bipolar metaphase spindle must be formed in which each pair of chromatids is attached to microtubules from opposite spindle poles. In this bipolar configuration pulling forces from the dynamic microtubules can generate tension across the sister kinetochores. The tension status acts as a signal that can destabilize aberrant kinetochore-microtubule attachments and reinforces correct, bipolar connections. Historically it has been challenging to isolate the specific role of tension in mitotic processes due to the interdependency of attachment and tension status at kinetochores. Recent technical and experimental advances have revealed new insights into how tension functions during mitosis. Here we summarize the evidence that tension serves as a biophysical signal that unifies multiple aspects of kinetochore and centromere function to ensure accurate chromosome segregation

Approvals and Timing of New Formulations of Novel Drugs Approved by the US Food and Drug Administration Between 1995 and 2010 and Followed Through 2021

New formulations of prescription drugs can improve convenience and tolerability for patients, but they also constitute manufacturer strategies to extend brand-name drug market exclusivity periods. We examined whether new formulations of brand-name novel drugs were associated with novel drugs’ sales and/or therapeutic value, as well as characterized first new formulations’ approval timing relative to the novel drug’s generic approval. We found that manufacturers are several times more likely to secure Food and Drug Administration approval for a new formulation for existing drugs that have reached blockbuster status. (Blockbuster drugs are the most profitable drugs with more than $1 billion in annual sales, but are not necessarily the most innovative or clinically meaningful drugs.) Manufacturers also dramatically reduced pursuing approval for new formulations once their drugs began to face generic competition. In contrast, companies did not develop new formulations for drugs that were considered the most therapeutically valuable, innovative, or clinically useful. Thus, while the modified formulations may not be innovative or clinically meaningful themselves, drug manufacturers frequently do not alter drugs that are particularly valuable and innovative to begin with. Our study shows that drugs’ revenue, as opposed to patient benefit, is the clear driver for reformulating drugs