If Mediterranean Diet Could Slow Atherosclerosis Progression, Could Specific Herbal Supplement Achieve the Same?

Dietary Control has been emphasized as an important means to prevent the development of atherosclerosis. It is a form belief without scientific evidence until the early report of the Study on Coronary Diet Intervention with olive oil and Cardiovascular Prevention (CODIOPREV Study on Mediterranean Diet). The current study is using Surrogate market IMT as the objective indicator, to compare the CORDIOPREV volunteers with known cardiovascular disease, which have demonstrated objective reduction in IMT thickness after 5 to 7 years of Mediterranean diet consumption. A study done in Hong Kong since 2003 using a simple twin herb formula for the prevention of progress of atherosclerosis in 4 different groups of patients with cardiovascular diseases, and using the same surrogate marker IMT as the objective indicator, showed comparable results within a much shorter period of 6-12 months. Extensive laboratory tests have also been completed to verify the bioactivities of the twin herb formula on anti-inflammation, anti-oxidation, endothelial protection and regenerative capacity related to atherosclerosis. It is suggested that before more potent therapeutic measures become available to slow atherosclerosis progression are available. The purpose of the paper is to compare the Mediterranean Diet for long term consumption and selective herbal preparations for shorter term or intermittent scheduled intake, and recommend to high-risk individuals.

Blinatumomab Associated Seizure Risk in Patients with Down Syndrome and B-Lymphoblastic Leukemia: An Interim Report from Children's Oncology Group (COG) Study AALL1731

INTRODUCTION Children with Down Syndrome (DS) and B-lymphoblastic leukemia (B-ALL) are at an increased risk of both relapse and treatment-related mortality, compared to those without DS. On COG study AALL1731 for de novo B-ALL, patients with DS and higher risk features (DS-High) are non-randomly treated with a regimen replacing intensive elements of conventional chemotherapy with three 28-day cycles of blinatumomab, with the combined goals of reducing toxicity and enhancing anti-leukemic efficacy. The DS-High group includes all NCI high risk (HR) patients; NCI standard risk (SR) patients with end-induction minimal residual disease positivity (>0.01%), unfavorable cytogenetics, CNS3 status, steroid pre-treatment, neutral cytogenetics with CNS2 status, or testicular disease. Neurotoxicity is a known risk of blinatumomab, with an incidence of 4% in block 1 and 1% in block 2 among pediatric patients with relapsed ALL (Brown et al, JAMA 2021). However, the specific risk in patients with DS has not been described to date. Here, we provide an early report of increased seizure incidence associated with blinatumomab in older DS-High patients enrolled on AALL1731 to date. METHODS We reviewed seizure incidence among patients with DS enrolled on AALL1731 from June 2019 to June 2021 who had proceeded to receive blinatumomab. Blinatumomab was administered at a dose of 15 mcg/m 2/day, using dexamethasone pre-medication in cycle 1. Infusions were interrupted for seizures, with resumption at 5 mcg/m 2/d permitted following full resolution for grade 1-3 seizures. RESULTS Among DS NCI HR patients, 8 of 47 (17%) had a seizure during blinatumomab infusion (Table 1). All 8 seizures occurred in patients over 10 years old. Six of the 8 seizures occurred in the first cycle of blinatumomab, most in the first 3 days of the infusion. Four had concomitant fever or cytokine release syndrome. Seizures were grade 2 (n=2) or grade 3 (n=6), and all resolved with full neurologic recovery. Of the 8 patients, 5 elected to resume blinatumomab; no further seizures occurred in these patients. There was no indication of increased seizure risk among NCI SR DS-High patients (1 seizure among 11 patients), or among DS or non-DS patients receiving blinatumomab on other study strata (0 of 7 DS SR-Avg; 1 of 146 non-DS SR-Avg; and 2 of 120 non-DS SR-High). CONCLUSIONS The incidence of seizures associated with blinatumomab in DS-ALL patients older than 10 years appears higher than previously reported in children without DS. The majority of seizures occurred within the first 3 days, all fully resolved with no sequelae, and no patient who resumed blinatumomab infusion at a lower rate experienced further seizures. Seizure prophylaxis may be advisable in DS patients while receiving blinatumomab, particularly those >10 years of age. Further follow-up and a larger sample size are needed to confirm incidence and identify risk factors predisposing DS patients to neurologic toxicity. Figure 1 Figure 1. Disclosures Li: Novartis Canada: Membership on an entity's Board of Directors or advisory committees. Raetz: Pfizer: Research Funding; Celgene: Other: DSMB member. Loh: MediSix therapeutics: Membership on an entity's Board of Directors or advisory committees. Gupta: Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees. Rau: Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Advisory Board; AbbVie Pharmaceuticals: Other: Spouse is employee and stock holder; Servier Pharmaceuticals: Consultancy. OffLabel Disclosure: This trial includes the use of blinatumomab in combination with chemotherapy for treatment of de novo B-lymphoblastic leukemia.

Structural damage at Florida Cando Complex – An Overview

In this paper the structural damage at Florida complex is being discussed. Inspite of an early report by engineering consultant, giving evidence of possible structural damage and necessity of repairs required, the delay in repair works resulted in a catastrophic collapse of the building in the middle of the night. The study on this collapse of the building opens the discussion on timely actions to be taken during the construction as well as maintenance of the buildings. Keywords: Structural damage, collapse, deteriorating, repair, corrosion, water seepage.

Ketogenic Diet for KARS-Related Mitochondrial Dysfunction and Progressive Leukodystrophy

KARS encodes lysyl-tRNA synthetase, which is essential for protein translation. KARS mutations sometimes cause impairment of cytoplasmic and mitochondrial protein synthesis, and sometimes lead to progressive leukodystrophies with mitochondrial signature and psychomotor regression, and follow a rapid regressive course to premature death. There has been no disease-modifying therapy beyond supportive treatment. We present a 5-year-old male patient with an asymmetrical leukodystrophy who showed overt evidence of mitochondrial dysfunction, including elevation of lactate on brain MR spectroscopy and low oxygen consumption rate in fibroblasts. We diagnosed this patient's condition as KARS-related leukodystrophy with cerebral calcification, congenital deafness, and evidence of mitochondrial dysfunction. We employed a ketogenic diet as well as multiple vitamin supplementation with the intention to alleviate mitochondrial dysfunction. The patient showed alleviation of his psychomotor regression and even partial restoration of his abilities within 4 months. This is an early report of a potential disease-modifying therapy for KARS-related progressive leukodystrophy without appreciable adverse effects.

A squalene–hopene cyclase in Schizosaccharomyces japonicus represents a eukaryotic adaptation to sterol-limited anaerobic environments

Biosynthesis of sterols, which are key constituents of canonical eukaryotic membranes, requires molecular oxygen. Anaerobic protists and deep-branching anaerobic fungi are the only eukaryotes in which a mechanism for sterol-independent growth has been elucidated. In these organisms, tetrahymanol, formed through oxygen-independent cyclization of squalene by a squalene–tetrahymanol cyclase, acts as a sterol surrogate. This study confirms an early report [C. J. E. A. Bulder, Antonie Van Leeuwenhoek, 37, 353–358 (1971)] that Schizosaccharomyces japonicus is exceptional among yeasts in growing anaerobically on synthetic media lacking sterols and unsaturated fatty acids. Mass spectrometry of lipid fractions of anaerobically grown Sch. japonicus showed the presence of hopanoids, a class of cyclic triterpenoids not previously detected in yeasts, including hop-22(29)-ene, hop-17(21)-ene, hop-21(22)-ene, and hopan-22-ol. A putative gene in Sch. japonicus showed high similarity to bacterial squalene–hopene cyclase (SHC) genes and in particular to those of Acetobacter species. No orthologs of the putative Sch. japonicus SHC were found in other yeast species. Expression of the Sch. japonicus SHC gene (Sjshc1) in Saccharomyces cerevisiae enabled hopanoid synthesis and stimulated anaerobic growth in sterol-free media, thus indicating that one or more of the hopanoids produced by SjShc1 could at least partially replace sterols. Use of hopanoids as sterol surrogates represents a previously unknown adaptation of eukaryotic cells to anaerobic growth. The fast anaerobic growth of Sch. japonicus in sterol-free media is an interesting trait for developing robust fungal cell factories for application in anaerobic industrial processes.

Early report on percutaneous endoscopic gastrostomy at Owerri, Nigeria

Objectives: Percutaneous endoscopic gastrostomy (PEG) is a well-established endoscopic procedure that is used predominantly to create enteral access for feeding. Its use has not been widespread in Nigeria despite its efficacy. This study is done to review the early experiences in the use of PEG in Federal Medical Centre, Owerri and Carez Clinic, Owerri. Material and Methods: This is a 4-year retrospective cross-sectional study of patients who had PEG from January 2015 to December 2018. The indications, complications, and outcomes of the procedure were analyzed. Results: A total of 13 patients had pull-type gastrostomy during this period. Six (46.1%) patients had the procedure on account of neurologic disorders, 4 (30.8%) patients had esophageal tumors, while 3 (23.1%) patients had esophageal motility disorders. The overall success rate for PEG tube placement was 100%. The most common complication was superficial skin infection 30.8% (4/13). No mortality was attributable to the procedure. Conclusion: PEG is still not commonly done in our setting, but it is a relatively safe procedure. Physicians should be encouraged to offer it to our teeming patients with neurologic disorders who may benefit from it.