Targeted antimicrobial activity of a specific IgG–SMAP28 conjugate against Porphyromonas gingivalis in a mixed culture

Antimicrobial peptides coupled to a ligand, receptor or antibody for a specific pathogenic bacteria could be used to develop narrow-spectrum pharmaceuticals with ‘targeted’ antimicrobial activity void of adverse reactions often associated with the use of broad-spectrum antibiotics. To assess the feasibility of this approach, in this study sheep myeloid antimicrobial peptide (SMAP) 28 was linked to affinity- and protein G-purified rabbit immunoglobulin G (IgG) antibodies specific to the outer surface of Porphyromonas gingivalis strain 381. The selective activity of the P. gingivalis IgG–SMAP28 conjugate was then assessed by adding it to an artificially generated microbial community containing P. gingivalis, Aggregatibacter actinomycetemcomitans and Peptostreptococcus micros. The specificity of the P. gingivalis IgG–SMAP28 conjugate in this mixed culture was concentration-dependent. The conjugate at 50 μg protein/mL lacked specificity and killed P. gingivalis, A. actinomycetemcomitans and P. micros. The conjugate at 20 μg protein/mL was more specific and killed P. gingivalis. This is an initial step to develop a selective antimicrobial agent that can eliminate a specific periodontal pathogen, such as P. gingivalis, from patients with periodontal disease without harming the normal commensal flora

Overnight olfactory enrichment using an odorant diffuser improves memory and modifies the uncinate fasciculus in older adults

ObjectiveCognitive loss in older adults is a growing issue in our society, and there is a need to develop inexpensive, simple, effective in-home treatments. This study was conducted to explore the use of olfactory enrichment at night to improve cognitive ability in healthy older adults.MethodsMale and female older adults (N = 43), age 60–85, were enrolled in the study and randomly assigned to an Olfactory Enriched or Control group. Individuals in the enriched group were exposed to 7 different odorants a week, one per night, for 2 h, using an odorant diffuser. Individuals in the control group had the same experience with de minimis amounts of odorant. Neuropsychological assessments and fMRI scans were administered at the beginning of the study and after 6 months.ResultsA statistically significant 226% improvement was observed in the enriched group compared to the control group on the Rey Auditory Verbal Learning Test and improved functioning was observed in the left uncinate fasciculus, as assessed by mean diffusivity.ConclusionMinimal olfactory enrichment administered at night produces improvements in both cognitive and neural functioning. Thus, olfactory enrichment may provide an effective and low-effort pathway to improved brain health

Overnight olfactory enrichment using an odorant diffuser improves memory and modifies the uncinate fasciculus in older adults.

OBJECTIVE: Cognitive loss in older adults is a growing issue in our society, and there is a need to develop inexpensive, simple, effective in-home treatments. This study was conducted to explore the use of olfactory enrichment at night to improve cognitive ability in healthy older adults. METHODS: Male and female older adults (N = 43), age 60-85, were enrolled in the study and randomly assigned to an Olfactory Enriched or Control group. Individuals in the enriched group were exposed to 7 different odorants a week, one per night, for 2 h, using an odorant diffuser. Individuals in the control group had the same experience with de minimis amounts of odorant. Neuropsychological assessments and fMRI scans were administered at the beginning of the study and after 6 months. RESULTS: A statistically significant 226% improvement was observed in the enriched group compared to the control group on the Rey Auditory Verbal Learning Test and improved functioning was observed in the left uncinate fasciculus, as assessed by mean diffusivity. CONCLUSION: Minimal olfactory enrichment administered at night produces improvements in both cognitive and neural functioning. Thus, olfactory enrichment may provide an effective and low-effort pathway to improved brain health

Circulating Tumor DNA is Unreliable to Detect Somatic Gene Alterations in Gastrointestinal Peritoneal Carcinomatosis

IntroductionTumor agnostic circulating tumor DNA (ctDNA) is routinely used to guide treatment decisions in gastrointestinal (GI) cancers, especially metastatic cancers. The amount of ctDNA detected in plasma is affected by stage, tumor burden, and tumor vascularization. We hypothesized that peritoneal carcinomatosis (PC) is associated with lower ctDNA levels than other metastatic sites in GI cancers due to the plasma-peritoneal barrier.MethodsWe conducted a retrospective analysis of patients with stage II-IV GI cancers treated at our institution between 2015 and 2020 with available panel-based ctDNA results (Guardant 360TM). ctDNA analysis was performed on early and pretreatment samples. We compared the reported maximum variant allele frequency (mVAF) of somatic mutations across metastatic sites.ResultsOf the 279 patients with GI cancers (colorectal, upper GI, pancreaticobiliary), 212 had stage IV disease (PC: n = 61; visceral metastases: n = 138; other metastases: n = 13). Mean mVAF increased with increasing stages of disease (stage II: 3.6 ± 7; stage III: 6.4 ± 10; stage IV: 28.0 ± 51; p < 0.01). Among patients with stage IV disease, PC was associated with lower ctDNA levels independent of primary tumor site (PC only: 12.1%; PC+ visceral metastases: 26.8%; and visceral metastases only: 35.0%; p < 0.01). In a subset of patients (n = 27, matched pair analysis of genomic alterations (GAs) showed fewer GAs were detected in plasma compared with tissue.ConclusionsPC of GI origin is associated with significantly lower ctDNA levels compared with visceral metastasis. Caution is warranted when interpreting ctDNA results from patients with PC due to lower sensitivity for detecting actionable mutations

Preferences of Type 1 Diabetic Patients on Devices for Islet Transplantation.

Transplantation of pancreatic islets within a biomaterial device is currently under investigation in clinical trials for the treatment of patients with type 1 diabetes (T1D). Patients' preferences on such implants could guide the designs of next-generation implantable devices; however, such information is not currently available. We surveyed the preferences of 482 patients with T1D on the size, shape, visibility, and transplantation site of islet containing implants. More than 83% of participants were willing to receive autologous stem cells, and there was no significant association between implant fabricated by one's own stem cell with gender (χ2 (1, n = 468) = 0.28; P = 0.6) or with age (χ2 (4, n = 468) = 2.92; P = 0.6). Preferred location for islet transplantation within devices was under the skin (52.7%). 48.3% preferred microscopic disks, and 32.3% preferred a thin device (like a credit card). Moreover, 58.4% preferred the implant to be as small as possible, 25.4% did not care about visibility, and 16.2% preferred their implants not to be visible. Among female participants, 81% cared about the implant visibility, whereas this number was 64% for male respondents (χ2 test (1, n = 468) = 16.34; P < 0.0001). 22% of those younger than 50 years of age and 30% of those older than 50 did not care about the visibility of implant (χ2 test (4, n = 468) = 23.69; P < 0.0001). These results suggest that subcutaneous sites and micron-sized devices are preferred choices among patients with T1D who participated in our survey

Misdiagnosis of appendiceal neoplasms as ovarian tumors: Impact of prior gynecologic surgery on definitive cytoreduction and HIPEC.

BackgroundFemale patients with pelvic/adnexal masses often undergo gynecologic operations due to presumed ovarian origin. The diagnosis of an appendiceal tumor is often only made postoperatively after suboptimal cytoreduction has been performed. We hypothesized that an index gynecological procedure increases the morbidity of definitive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) in patients with appendiceal mucinous tumors.MethodsA single-center retrospective review was performed to identify female patients undergoing CRS/HIPEC for appendiceal tumors from 2012 to 2020.ResultsDuring the 8-year period, CRS/HIPEC was performed in 36 female patients with appendiceal mucinous tumors. Eighteen patients (50.0%) had received a prior pelvic operation by gynecologists (PPO Group) for presumed ovarian origin before referral for definitive CRS/HIPEC. The median peritoneal cancer index (PCI) was higher in the PPO group (21 vs. 9, p = 0.04). The median number of days from gynecologic procedure to definitive CRS/HIPEC was 169 days. Compared to patients who did not undergo a prior gynecologic operation, those in the PPO group had higher intraoperative blood loss (650 vs 100 mL, p < 0.01) during CRS/HIPEC as well as longer length of stay (12 vs 8 days, p = 0.02) and higher overall morbidity (72.3% vs 33.3%, p = 0.02). After controlling for PCI, prior gynecologic operation increased risk of 30-day morbidity after definitive CRS/HIPEC (OR 11.6, p < 0.01).ConclusionA multi-disciplinary approach is needed for the primary evaluation of patients with pelvic masses of undetermined origin. A gynecological resection is associated with increased morbidity during definitive cytoreduction and HIPEC for appendiceal mucinous tumors

Impact of an automated large vessel occlusion detection tool on clinical workflow and patient outcomes.

PurposeAutomated large vessel occlusion (LVO) tools allow for prompt identification of positive LVO cases, but little is known about their role in acute stroke triage when implemented in a real-world setting. The purpose of this study was to evaluate the automated LVO detection tool's impact on acute stroke workflow and clinical outcomes.Materials and methodsConsecutive patients with a computed tomography angiography (CTA) presenting with suspected acute ischemic stroke were compared before and after the implementation of an AI tool, RAPID LVO (RAPID 4.9, iSchemaView, Menlo Park, CA). Radiology CTA report turnaround times (TAT), door-to-treatment times, and the NIH stroke scale (NIHSS) after treatment were evaluated.ResultsA total of 439 cases in the pre-AI group and 321 cases in the post-AI group were included, with 62 (14.12%) and 43 (13.40%) cases, respectively, receiving acute therapies. The AI tool demonstrated a sensitivity of 0.96, a specificity of 0.85, a negative predictive value of 0.99, and a positive predictive value of 0.53. Radiology CTA report TAT significantly improved post-AI (mean 30.58 min for pre-AI vs. 22 min for post-AI, p < 0.0005), notably at the resident level (p < 0.0003) but not at higher levels of expertise. There were no differences in door-to-treatment times, but the NIHSS at discharge was improved for the pre-AI group adjusted for confounders (parameter estimate = 3.97, p < 0.01).ConclusionImplementation of an automated LVO detection tool improved radiology TAT but did not translate to improved stroke metrics and outcomes in a real-world setting