Triggerable tough hydrogels for gastric resident dosage forms

Systems capable of residing for prolonged periods of time in the gastric cavity have transformed our ability to diagnose and treat patients. Gastric resident systems for drug delivery, ideally need to be: ingestible, be able to change shape or swell to ensure prolonged gastric residence, have the mechanical integrity to withstand the forces associated with gastrointestinal motility, be triggerable to address any side effects, and be drug loadable and release drug over a prolonged period of time. Materials that have been primarily utilized for these applications have been largely restricted to thermoplastics and thermosets. Here we describe a novel set of materials, triggerable tough hydrogels, meeting all these requirement, supported by evaluation in a large animal model and ultimately demonstrate the potential of triggerable tough hydrogels to serve as prolonged gastric resident drug depots. Triggerable tough hydrogels may be applied in myriad of applications, including bariatric interventions, drug delivery, and tissue engineering.Bill & Melinda Gates Foundation (Grant OPP1096734)Bill & Melinda Gates Foundation (Grant OPP1139927)National Institutes of Health (U.S.) (Grant EB000244

Photoreceptor degeneration in a new Cacna1f mutant mouse model.

The Cacna1f gene encodes the α1F subunit of an L-type voltage-gated calcium channel, Cav1.4. In photoreceptor synaptic terminals, Cav1.4 channels mediate glutamate release and postsynaptic responses associated with visual signal transmission. We have discovered a new Cacna1f mutation in nob9 mice, which display more severe phenotypes than do nob2 mice. To characterize the nob9 phenotype at different ages, we examined the murine fundus, applied retinal optical coherence tomography, measured flash electroretinograms (ERGs) in vivo, and analyzed the retinal histology in vitro. After identifying the X-linked recessive inheritance trait, we sequenced Cacna1f as the candidate gene. Mutations in this gene were detected by polymerase chain reaction (PCR) and confirmed by restriction fragment length polymorphism. Morphologically, an early-onset of retinal disorder was detected, and the degeneration of the outer plexiform layers progressed rapidly. Moreover, the mutant mice showed drastically reduced scotopic ERGs with increasing age. In 14-month-old nob9 retinas, immunostaining of cone opsins demonstrated a reduction in the number of short-wavelength opsins (S-opsins) to 54% of wild-type levels, and almost no middle-wavelength opsins (M-opsins) were observed. No cone ERGs could be detected from residual cones, in which S-opsins abnormally migrated to inner segments of the photoreceptors. The mutations of the Cacna1f gene in nob9 mice involved both a single nucleotide G to A transition and a 10-nucleotide insertion, the latter resulting in a frame-shift mutation in exon 14

Resistant Maltodextrin Alleviates Dextran Sulfate Sodium-Induced Intestinal Inflammatory Injury by Increasing Butyric Acid to Inhibit Proinflammatory Cytokine Levels

Inflammatory bowel disease (IBD), one kind of intestinal chronic inflammatory disease, is characterized by colonic epithelial barrier injury, overproduction of proinflammatory cytokines, and fewer short-chain fatty acids (SCFAs). The present study is aimed at testing the hypothesis that resistant maltodextrin (RM), a soluble dietary fiber produced by starch debranching, alleviated dextran sulfate sodium- (DSS-) induced colitis in mice. Female C57BL/6 mice with or without oral administration of 50 mg/kg RM for 19 days were challenged with 3% DSS in drinking water to induce colitis (from day 14 to day 19). Although RM could not reverse DSS-induced weight loss or colon shortening, it reduced inflammatory cell infiltration and epithelial damage in colon tissue, as well as the transfer of intestinal permeability indicators including serum diamine oxidase (DAO) and D-lactic acid (D-LA). ELISA analysis indicated that RM significantly suppressed the increase of Th1 cytokines induced by DSS in the colon such as tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). The levels of proinflammatory cytokines interleukin-1β (IL-1β), IL-17, and IL-8 in the DSS group were significantly higher than those in the control group and RM group, but no significant difference was observed in the RM-DSS group compared with the RM group. Interestingly, IL-10 levels of the DSS group were significantly higher than those of the other groups. With respect to SCFAs, DSS administration significantly decreased the concentration of faecal butyric acid while the RM-DSS group showed a tendency to increase (P=0.08). In general, RM alleviated dextran sulfate sodium-induced intestinal inflammation through increasing the level of butyric acid and subsequently inhibiting the expression of proinflammatory cytokines

Datasheet1_Assessment of reporting quality in randomized controlled trials of acupuncture for labor pain.docx

ObjectiveTo evaluate the reporting quality of randomized controlled trials (RCTs) of acupuncture for labor pain, and to explore relevant factors for facilitating reporting transparency and integrity for future RCTs.MethodEight Chinese and English databases were systematically searched from their inception until August 31, 2021. General characteristics and methodological quality of the included reports were evaluated based on the CONSORT statement and the STRICTA guidelines. Descriptive statistical analysis was performed. Cohen's κ-statistics were calculated to assess the agreement of all items between two reviewers.ResultsA total of 84 RCTs were included. Based on the CONSORT statement, a positive reporting rate (greater than 80%) was evident for the items “trial design” “participants” “intervention” “outcomes” “numbers analyzed” and “generalizability”. The quality of reporting for the items “randomized in the title or abstract” “sample size” “allocation concealment” “implementation” “blinding” “recruitment” “ancillary analyses” “harms” “interpretation” “registration” and “protocol” was poor with positive rates less than 10%. Based on the STRICTA guidelines, the items “extent to which treatment varied” “number of needle insertions per subject per session” and “control or comparator interventions” had poor reporting quality with positive rates of less than 10%. Substantial agreement was observed for most items and excellent agreement for some items.ConclusionThe reporting quality of RCTs of acupuncture for labor pain is suboptimal generally. Rigorous adherence to the CONSORT statement and the STRICTA guidelines should be emphasized in future studies to improve the quality of acupuncture RCT reports.</p

Table1_Identification of rare thalassemia variants using third-generation sequencing.XLSX

Routine PCR, Sanger sequencing, and specially designed GAP-PCR are often used in the genetic analysis of thalassemia, but all these methods have limitations. In this study, we evaluated a new third-generation sequencing-based approach termed comprehensive analysis of thalassemia alleles (CATSA) in subjects with no variants identified by routine PCR, Sanger sequencing, and specially designed GAP-PCR. Hemoglobin testing and routine PCR tests for 23 common variants were performed for 3,033 subjects. Then, Sanger sequencing and specially designed GAP-PCR were performed for a subject with no variants identified by routine PCR, no iron deficiency, and positive hemoglobin testing. Finally, the new CATSA method was conducted for the subjects with no variants identified by Sanger sequencing and specially designed GAP-PCR. In the 49 subjects tested by CATSA, eight subjects had variants identified. Sanger sequencing and independent PCR confirmed the CATSA result. In addition, it is the first time that Hb Lepore was identified in Hunan Province. In total, traditional methods identified variants in 759 of the 3,033 subjects, while CATSA identified additional variants in eight subjects. CATSA showed great advantages compared to the other genetic testing methods.</p