Gregersensecher3735

This forum presents the current state of research in the screening and identification of people with eating disorders in community and primary care, taking a longer-term perspective that highlights the slow rate of progression in development of instruments, and impact on polices and practice.

An historical overview is presented, followed by a critique of contemporary instruments and practice, and barriers to case detection and appropriate referral pathways.

There are now many instruments but all lack high levels of positive predictive power. However, some do have high sensitivity. Barriers contributing to poor detection and the treatment gap include need for improved education and support for primary care professionals and lack of confidence of individuals with eating disorders to initiate a discussion with health professionals. The best screening instrument would not overcome either of these barriers.

We purport there is an urgent need to improve current screening instruments (not to develop more), power consumers to navigate care pathways.

To investigate the likelihood of missing a vestibular schwannoma (VS) diagnosis in patients who present with a sudden hearing loss (SHL) that does not meet the most accepted audiometric criteria for sudden sensorineural hearing loss (SSNHL) (a decrease of ≥30 dB at three consecutive frequencies).

All adult patients (>18 years) diagnosed with SHL of any severity in a tertiary care referral medical center between 2015 and 2020 and who underwent an MRI scan to rule out VS were included. Statistical analyses were conducted to evaluate the difference between the rate of VS among patients with an initial audiogram, which met the abovementioned criteria, and those who did not. Other audiometric criteria for SNHL were also evaluated (≥10 dB at ≥2 frequencies and ≥ 15 dB at one frequency).

Of the 332 patients included in the study, 152 met the audiometric criteria for SSNHL, and 180 did not. Both groups had a similar VS rate (8.6% vs. 8.9%, p=0.914). Similar results were found when other audiometric criteria for asymmetric SNHL were analyzed. In a subgroup analysis of patients with VS-associated SSNHL, neither the tumor size nor the Koos classification was associated with any of the audiometric criteria systems.

There should be a high index of suspicion for the presence of VS in patients with an SHL of any severity.

3 Laryngoscope, 2022.

3 Laryngoscope, 2022.Programmed death (PD)-1/PD-ligand 1 (PD-L1) antibodies have shown an intense clinical effect in some patients with PD-L1+ tumors, and their applications have rapidly expanded to various cancer types with or without the application of new companion diagnostics (CDx) with a lower cutoff value and inclusion of macrophage evaluation. However, the pathological background explaining the difference in the cutoff value remains unknown. To address this, we evaluated tissue array samples from 231 patients with lung adenocarcinoma, 186 with lung squamous cell carcinoma, and 38 with renal cell carcinoma (RCC) who were not receiving PD-1/PD-L1 antibodies to investigate the relationship between PD-L1 expression on tumor cells and CD8+ T-cell infiltration in tumor tissues. PD-L1 expression in RCC was clearly lower than that in non-small-cell lung cancer (NSCLC) tissue, whereas CD8+ T-cell infiltration was low in all cancers. We next analyzed PD-L1 expression by interferon (α, β, and γ) and LPS stimulation in both macrophages and 41 cancer cell lines derived from various organs and histological types. The PD-L1 expression patterns were classified into three types, which differed depending on each organ or tissue type. Interestingly, NSCLC cell lines showed highly diverse PD-L1 expression patterns compared with RCC cell lines. Conversely, PD-L1 expression was stronger and more prolonged in macrophages than in typical cell lines. Here, we revealed the diversity of the PD-L1 expression patterns in tumor cells and macrophages, demonstrating the pathological and cytological significance of the transition of cutoff values in PD-L1 CDx for PD-1/PD-L1 antibody administration.

Although phonatory glottal posture and airflow pulse shape affect voice quality, studies to date have been limited by visualization of vocal fold (VF) vibration from a superior view. We performed a 3D reconstruction of VF vibratory motion during phonation from a medial view and assessed the glottal volume waveform and resulting acoustics as a function of neuromuscular stimulation.

In vivo canine hemilarynx phonation.

Across 121 unique combinations of the superior laryngeal nerve (SLN) and recurrent laryngeal nerve (RLN) stimulation, the hemilarynx was excited to the oscillation with airflow. VF medial surface reference points were tracked on high-speed video, mapped into 3D space, and surface shape was restored using cubic spline interpolation. Glottal surface shape, reconstruction-based parameters, and glottal volume waveform were calculated. Fundamental frequency (F0), cepstral peak prominence (CPP), and harmonic amplitude (H1-H2) were measured from high-quality audio samples.

The glottis was convergent during opening and divergent during closing. Neuromuscular activation changed phonatory glottal shape and reduced glottal volume. Significant reduction in glottal volume and closing quotient were present with SLN stimulation. RLN stimulation significantly increased F0 and CPP and decreased H1-H2 (constricted glottis), while SLN effects were similar and synergistic with concurrent RLN stimulation.

3D reconstruction of in vivo medial surface vibration revealed effects of laryngeal nerve stimulation on glottal vibratory pattern and acoustic correlates of voice quality. SLN activation resulted in significantly quicker glottal closure per cycle, decreased glottal volume, and higher-pitched, less breathy, and less noisy voice. RLN had a similar effect on acoustic measures.

N/A, Basic Science Laryngoscope, 2022.

N/A, Basic Science Laryngoscope, 2022.Predation is widely regarded as an important selective force in the evolution and maintenance of dermal armour; yet, the basic premise that predation and armour are strongly linked to each other has proven to be difficult to assess. In this concept, I put forward the fighting-advantage hypothesis, the view that aggressive interactions with conspecifics, not predation, might have been a key selective pressure in the evolution of dermal armour. Considering intraspecific competition as a potential explanation could not only reveal previously overlooked aspects of the functional and evolutionary significance of dermal armour, but also advance the emerging field of biomimetics in which such knowledge forms the starting point of technological innovation.Preclinical forms of gastrointestinal stromal tumor (GIST), small asymptomatic lesions, called microGIST, are detected in approximately 30% of the general population. Gastrointestinal stromal tumor driver mutation can be already detected in microGISTs, even if they do not progress into malignant cancer; these mutations are necessary, but insufficient events to foster tumor progression. Here we profiled the tissue microbiota of 60 gastrointestinal specimens in three different patient cohorts-micro, low-risk, and high-risk or metastatic GIST-exploring the compositional structure, predicted function, and microbial networks, with the aim of providing a complete overview of microbial ecology in GIST and its preclinical form. Comparing microGISTs and GISTs, both weighted and unweighted UniFrac and Bray-Curtis dissimilarities showed significant community-level separation between them and a pronounced difference in Proteobacteria, Firmicutes, and Bacteroidota was observed. Akt inhibitor Through the LEfSe tool, potential microbial biomarkers associated with a specific type of lesion were identified. In particular, GIST samples were significantly enriched in the phylum Proteobacteria compared to microGISTs. Several pathways involved in sugar metabolism were also highlighted in GISTs; this was expected as cancer usually displays high aerobic glycolysis in place of oxidative phosphorylation and rise of glucose flux to promote anabolic request. Our results highlight that specific differences do exist in the tissue microbiome community between GIST and benign lesions and that microbiome restructuration can drive the carcinogenesis process.Niche variation at population level mediates niche packing (i.e. patterns of species' spread within the niche space) and species coexistence at community level. Competition and ecological opportunity (resource diversity) are two of the main mechanisms underlying niche variation. Dense niche packing could occur through increased niche partitioning or increased niche overlap. In this study, we used stable carbon and nitrogen isotope data of 635 individual rodents from four species across nine sites in the montane region of a subtropical island to test the effects of competition and ecological opportunity on population isotope niche size, inter-individual niche difference within population and interspecific niche overlap within community. We used the Bayesian Standard Ellipse Area (SEAB, the ellipse area enclosed by carbon and nitrogen isotope values of organisms on a bi-plot) to estimate population niche size and interspecific niche overlap. Inter-individual niche difference within population was quantified as al niche difference and interspecific niche overlap within communities. Under strong intraspecific competition and limited ecological opportunity for niche expansion, individuals may choose to increase their isotopic uniqueness from conspecifics at the cost of overlapping with heterospecifics of different trophic roles within the community niche space as overall competition increases. Denser niche packing of these rodent communities might be achieved through increased niche overlap.New treatments, particularly second-line options, are needed to improve outcomes for patients with recurrent/metastatic cervical cancer (r/mCC). Tisotumab vedotin (TV) is an antibody-drug conjugate directed to tissue factor, a transmembrane protein commonly expressed in cancer cells, to deliver cytotoxic monomethyl auristatin E. This single-arm, open-label phase 1/2 trial evaluated the consistency of safety and efficacy outcomes of TV in Japanese patients with r/mCC to bridge the current findings with those reported in previous trials in non-Japanese patients in the United States and Europe. In part 1 (dose escalation; N = 6), patients with advanced solid tumors received TV 1.5 or 2.0 mg/kg once every 3 weeks to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). Part 2 (dose expansion; N = 17) evaluated the RP2D in r/mCC patients with 1-2 prior lines of therapy. In part 1, no dose-limiting toxicities were observed, the MTD was not reached, and TV 2.0 mg/kg was established as the RP2D. In part 2, the most common treatment-emergent adverse events were anemia (58.8%), nausea (58.8%), alopecia (47.1%), epistaxis (47.1%), and diarrhea (35.3%); adverse events of special interest were bleeding (76.5%), ocular events (35.3%), and peripheral neuropathy (17.6%), and were mostly grade 1/2. In part 2, confirmed objective response rate was 29.4%, median duration of response was 7.1 months, and median time to response was 1.2 months. In Japanese patients with r/mCC, TV demonstrated a manageable and tolerable safety, pharmacokinetics, and efficacy profile consistent with that observed in non-Japanese patients.