Lymphatic drainage of sinonasal malignancies and the role of sentinel node biopsies.

BACKGROUND: Locoregional recurrence is a critical factor in the prognosis of sinonasal malignancies. Due to the rarity of these tumours, as well as the heterogeneity of histologies and anatomical subsites, there is little evidence regarding the rate and location of regional metastases in sinonasal malignancies. Elective regional lymph node dissection in the therapy of sinonasal malignancies has become controversial. On the one hand, elective regional lymph node dissection is considered to be an overtreatment in the cN0 cases. On the other hand, undetected occult lymphatic metastases are associated with a poor prognosis. In this study, we discuss the role of sentinel lymph node biopsy as a minimally invasive procedure in the treatment of sinonasal malignancies based on our two years of practical experience and the currently available data. RESULTS: This is a descriptive, monocentric, retrospective study, including 20 cases of cN0 malignant sinonasal neoplasm, that underwent a surgical therapy between 2020 and 2022. The following aspects were investigated: tumour entity, localisation of the primary tumour, tumoral stage, localisation of the sentinel lymph nodes, and postoperative complications. Squamous cell carcinoma was the most frequently diagnosed tumour entity (50%), followed by adenocarcinoma (20%) and malignant melanoma (15%), adenoid cystic carcinoma and mucoepidermoid carcinoma. Sentinel lymph nodes were most frequently found in the ipsilateral neck region I (45%), followed by the ipsilateral neck region II (40%). In all cases, the removed lymph nodes were free of malignancy. There were no postoperative complications due to lymph node biopsy. There were no recurrences during the study period. CONCLUSION: Sentinel node biopsy could add more safety to the management of cN0 sinonasal malignancies due to its low morbidity. Whether SNB could provide an alternative to elective neck dissection in the management of SNM should be investigated in further studies.

Psilocybin and Other Classic Psychedelics in Depression.

Psychedelic drugs such as psilocybin and ketamine are returning to clinical research and intervention across several disorders including the treatment of depression. This chapter focusses on psychedelics that specifically target the 5-HT2A receptor such as psilocybin and DMT. These produce plasma-concentration related psychological effects such as hallucinations and out of body experiences, insightful and emotional breakthroughs as well as mystical-type experiences. When coupled with psychological support, effects can produce a rapid improvement in mood among people with depression that can last for months. In this chapter, we summarise the scientific studies to date that explore the use of psychedelics in depressed individuals, highlighting key clinical, psychological and neuroimaging features of psychedelics that may account for their therapeutic effects. These include alterations in brain entropy that disrupt fixed negative ruminations, a period of post-treatment increased cognitive flexibility, and changes in self-referential psychological processes. Finally, we propose that the brain mechanisms underlying the therapeutic effect of serotonergic psychedelics might be distinct from those underlying classical serotonin reuptake-blocking antidepressants.

Canalization and plasticity in psychopathology.

This theoretical article revives a classical bridging construct, canalization, to describe a new model of a general factor of psychopathology. To achieve this, we have distinguished between two types of plasticity, an early one that we call 'TEMP' for 'Temperature or Entropy Mediated Plasticity', and another, we call 'canalization', which is close to Hebbian plasticity. These two forms of plasticity can be most easily distinguished by their relationship to 'precision' or inverse variance; TEMP relates to increased model variance or decreased precision, whereas the opposite is true for canalization. TEMP also subsumes increased learning rate, (Ising) temperature and entropy. Dictionary definitions of 'plasticity' describe it as the property of being easily shaped or molded; TEMP is the better match for this. Importantly, we propose that 'pathological' phenotypes develop via mechanisms of canalization or increased model precision, as a defensive response to adversity and associated distress or dysphoria. Our model states that canalization entrenches in psychopathology, narrowing the phenotypic state-space as the agent develops expertise in their pathology. We suggest that TEMP - combined with gently guiding psychological support - can counter canalization. We address questions of whether and when canalization is adaptive versus maladaptive, furnish our model with references to basic and human neuroscience, and offer concrete experiments and measures to test its main hypotheses and implications. This article is part of the Special Issue on "National Institutes of Health Psilocybin Research Speaker Series".

Perseverance rover reveals an ancient delta-lake system and flood deposits at Jezero crater, Mars.

Observations from orbital spacecraft have shown that Jezero crater on Mars contains a prominent fan-shaped body of sedimentary rock deposited at its western margin. The Perseverance rover landed in Jezero crater in February 2021. We analyze images taken by the rover in the 3 months after landing. The fan has outcrop faces, which were invisible from orbit, that record the hydrological evolution of Jezero crater. We interpret the presence of inclined strata in these outcrops as evidence of deltas that advanced into a lake. In contrast, the uppermost fan strata are composed of boulder conglomerates, which imply deposition by episodic high-energy floods. This sedimentary succession indicates a transition from sustained hydrologic activity in a persistent lake environment to highly energetic short-duration fluvial flows.

Association between ACTH stimulation test results and clinical signs in dogs with hyperadrenocorticism treated with trilostane.

Trilostane is the recommended medical treatment for dogs with hyperadrenocorticicm (HAC). The objective of this study was to investigate the association between ACTH stimulation test (ACTHST) results, and relevant clinical signs, in dogs treated with trilostane. A disease-specific questionnaire was developed, which included the owner's assessment of polydipsia, polyuria, polyphagia, panting, and satisfaction with the treatment, based on a 5-response category rating scale. Forty-nine dogs with HAC were prospectively enrolled. Dogs were grouped according to their recheck appointment (first recheck, 710 days after commencement of treatment or change of trilostane dose; second recheck, 4 weeks after the first recheck; third recheck, performed at 3-6 months intervals once the dog was well controlled). At the recheck appointment, the owner's questionnaire responses were recorded, and an ACTHST was performed, along with urine specific gravity measurement. Linear mixed effects models were used to assess differences among the three recheck time points and to test possible associations between ACTHST results and clinical signs. Significant differences between rechecks were present for stimulated cortisol (first to third recheck, P < 0.001; second to third recheck, P < 0.01), polydipsia (first to second recheck, P = 0.001), polyuria (first to second recheck, P < 0.001; first to third recheck, P = 0.001), and owner satisfaction (first to second recheck, P < 0.001; first to third recheck, P < 0.001). Backward stepwise variable elimination did not identify any significant associations between ACTHST results and clinical signs. Therefore, clinical signs of HAC were not predicted based on the ACTHST results.

Classification of endonasal HHT lesions using digital microscopy.

BACKGROUND: Recurrent spontaneous epistaxis is the most common clinical manifestation and the most debilitating symptom in hereditary haemorrhagic telangiectasia (HHT) patients. To this date, there exist only a classification of HHT patients by different genetic mutations. There is no standard classification for the mucocutaneous endonasal manifestations of HHT. The aim of the present study was to document the variety of endonasal HHT lesions using digital microscopy and to propose a clinical classification. METHODS: We recorded the endonasal HHT lesions of 28 patients using a digital microscope. We reconstructed the 3D images und videos recorded by digital microscope afterwards and classified the endonasal lesions of HHT in two classes: Grade A, presence of only flat telangiectasias in the mucosa level and Grade B, (additional) presence of raised berry or wart-like telangiectasia spots. We investigated also Haemoglobin level by routine laboratory procedures, plasma VEGF level by ELISA, Severity of epistaxis by epistaxis severity score (ESS) and quality of life by a linear visual analogue scale (VAS). RESULTS: We found a higher quality of life and a lower severity of epistaxis in Grade A patients in comparison to Grade B patients. No difference in plasma VEGF level and in Haemoglobin between Grad A patients and Grade B patients could be detected. Plasma VEGF levels showed no gender specific differences. It could also not be correlated to the extranasal manifestation. CONCLUSION: The classification for endonasal manifestation of HHT proposed in this study indicates severity of epistaxis und quality of life. Digital microscopy with the ability of 3D reconstruction of images presents a useful tool for such classifications. The classification of endonasal HHT lesions using digital microscopy allows to evaluate the dynamic of HHT lesions in the course of time independent of examiner. This allows also to evaluate the efficacy of the different treatment modalities by dynamic of HHT lesions. Moreover digital microscopy is very beneficial in academic teaching of rare diseases.

Network-driven discovery yields new insight into Shox2-dependent cardiac rhythm control.

The homeodomain transcription factor SHOX2 is involved in the development and function of the heart's primary pacemaker, the sinoatrial node (SAN), and has been associated with cardiac conduction-related diseases such as atrial fibrillation and sinus node dysfunction. To shed light on Shox2-dependent genetic processes involved in these diseases, we established a murine embryonic stem cell (ESC) cardiac differentiation model to investigate Shox2 pathways in SAN-like cardiomyocytes. Differential RNA-seq-based expression profiling of Shox2+/+ and Shox2-/- ESCs revealed 94 dysregulated transcripts in Shox2-/- ESC-derived SAN-like cells. Of these, 15 putative Shox2 target genes were selected for further validation based on comparative expression analysis with SAN- and right atria-enriched genes. Network-based analyses, integrating data from the Mouse Organogenesis Cell Atlas and the Ingenuity pathways, as well as validation in mouse and zebrafish models confirmed a regulatory role for the novel identified Shox2 target genes including Cav1, Fkbp10, Igfbp5, Mcf2l and Nr2f2. Our results indicate that genetic networks involving SHOX2 may contribute to conduction traits through the regulation of these genes.

Observations, Meteorites, and Models: A Preflight Assessment of the Composition and Formation of (16) Psyche.

Some years ago, the consensus was that asteroid (16) Psyche was almost entirely metal. New data on density, radar properties, and spectral signatures indicate that the asteroid is something perhaps even more enigmatic: a mixed metal and silicate world. Here we combine observations of Psyche with data from meteorites and models for planetesimal formation to produce the best current hypotheses for Psyche's properties and provenance. Psyche's bulk density appears to be between 3,400 and 4,100 kg m-3. Psyche is thus predicted to have between ~30 and ~60 vol% metal, with the remainder likely low-iron silicate rock and not more than ~20% porosity. Though their density is similar, mesosiderites are an unlikely analog to bulk Psyche because mesosiderites have far more iron-rich silicates than Psyche appears to have. CB chondrites match both Psyche's density and spectral properties, as can some pallasites, although typical pallasitic olivine contains too much iron to be consistent with the reflectance spectra. Final answers, as well as resolution of contradictions in the data set of Psyche physical properties, for example, the thermal inertia measurements, may not be resolved until the NASA Psyche mission arrives in orbit at the asteroid. Despite the range of compositions and formation processes for Psyche allowed by the current data, the science payload of the Psyche mission (magnetometers, multispectral imagers, neutron spectrometer, and a gamma-ray spectrometer) will produce data sets that distinguish among the models.

Altered T cell receptor beta repertoire patterns in pediatric ulcerative colitis.

The antigenic specificity of T cells occurs via generation and rearrangement of different gene segments producing a functional T cell receptor (TCR). High-throughput sequencing (HTS) allows in-depth assessment of TCR repertoire patterns. There are limited data concerning whether TCR repertoires are altered in inflammatory bowel disease. We hypothesized that pediatric ulcerative colitis (UC) patients possess unique TCR repertoires, resulting from clonotypical expansions in the gut. Paired blood and rectal samples were collected from nine newly diagnosed treatment-naive pediatric UC patients and four healthy controls. DNA was isolated to determine the TCR-ß repertoire by HTS. Significant clonal expansion was demonstrated in UC patients, with inverse correlation between clinical disease severity and repertoire diversity in the gut. Using different repertoire variables in rectal biopsies, a clear segregation was observed between patients with severe UC, those with mild-moderate disease and healthy controls. Moreover, the overlap between autologous blood-rectal samples in UC patients was significantly higher compared with overlap among controls. Finally, we identified several clonotypes that were shared in either all or the majority of UC patients in the colon. Clonal expansion of TCR-ß-expressing T cells among UC patients correlates with disease severity and highlights their involvement in mediating intestinal inflammation.

Associations of postoperative mortality with the time of day, week and year.

Studies that have investigated circadian, weekday and seasonal variation in postoperative mortality have been relatively small or have been for scheduled surgery. We retrospectively tested a large mixed surgical cohort from a German tertiary care university hospital for the presence of cyclical variation in all-cause in-hospital mortality after operations performed between 2006 and 2013. We analysed mortality rates after 247,475 operations, adjusted for age, sex, comorbidities, location, urgency and duration of the surgery, and intra-operative blood transfusions. The mortality odds ratio (95%CI) after operations started in the morning (08:00-11:00) were lowest, 0.73 (0.66-0.80), p < 0.001 and highest for operations started in the afternoon (13:00-17:00), 1.29 (1.18-1.40), p < 0.001. Mortality at the weekend was the same as during the week. There was no seasonal variation in mortality, p = 0.12. However, the interference of four-yearly and ten-monthly cycle amplitudes resulted in higher mortality odds ratio (95%CI) in winter 2008-2009, 1.41 (1.18-1.69), p < 0.001, and lower mortality in spring 2011 and 2012, 0.70 (0.56-0.85) and 0.67 (0.53-0.85), p < 0.001 and p = 0.001, respectively. The ability to predict cyclical phenomena would facilitate the design of interventional studies, aimed at reducing mortality following surgery in the afternoon and when cycles interfere constructively.

Neuroplasticity following short-term strength training occurs at supraspinal level and is specific for the trained task.

AIMS: Different modalities of strength training cause performance enhancements, which are specific for the trained task. However, the involved mechanisms are still largely unknown. It has been demonstrated that strength training could induce neuroplasticity, which might underlie the performance improvements during the first training sessions. Thus, we hypothesized to find task-specific neuroplasticity after a short-term strength training of two distinct strength tasks. METHODS: Young healthy male subjects were exposed to 4 sessions of either maximal isometric explosive (EXPL group, N = 9) or slow sustained (SUS group, N = 10) knee extensions. Pre- and post-training, we measured H-reflexes and motor evoked potentials (MEPs) in the vastus lateralis (VL) at the onset of both strength tasks. RESULTS: Pre- and post-training, H-reflexes remained unchanged in both groups. MEP areas were lower in the trained task in both groups and remained unchanged in the untrained task. CONCLUSION: This study demonstrated that short-term strength training induces specific neuroplasticity for the trained task only. The fact that MEPs were lower but H-reflex amplitudes remained unchanged at the onset of the trained tasks suggests that strength training elicited neuroplasticity at supraspinal level that most likely reflect an improved task-specific corticospinal efficiency.

Effectiveness of a standardized patient education program on therapy-related side effects and unplanned therapy interruptions in oral cancer therapy: a cluster-randomized controlled trial.

PURPOSE: Oral agents for cancer treatment are increasingly prescribed due to their benefits. However, oral cancer medications are difficult to handle and have a considerable potential for side effects. This type of therapy requires a high level of self-management competence by the patient. A standardized patient education program provided by physicians and oncology nurses may positively influence the handling of oral agents. The aim of the study was to evaluate the impact of a standardized patient education program provided by specially trained oncology nurses on therapy management regarding side effects and unplanned therapy interruptions. METHODS: One hundred sixty-five patients from 28 office-based oncology practices from all over Germany participated in this cluster-randomized controlled study. Patients of both intervention (n = 111) and standard care groups (n = 54) received the usual oncologist counseling; in addition, the patients from the intervention group (k = 17 practices) received an education from specially trained oncology nurses. The time of observation was 3 months per patient. RESULTS: The patients of the intervention group reported fewer side effects (skin rash, pain, fatigue, nausea, vomiting). Patients in the standard care group interrupted the therapy more frequently without informing their oncologist, compared to the intervention group. CONCLUSIONS: Patients benefit from a standardized patient education program provided by specially trained oncology nurses. They tend to handle side effects and critical situations better.

Development of a home-based auditory training to improve speech recognition on the telephone for patients with cochlear implants: A randomised trial.

OBJECTIVES: Speech recognition on the telephone poses a challenge for patients with cochlear implants (CIs) due to a reduced bandwidth of transmission. This trial evaluates a home-based auditory training with telephone-specific filtered speech material to improve sentence recognition. DESIGN: Randomised controlled parallel double-blind. SETTING: One tertiary referral centre. PARTICIPANTS: A total of 20 postlingually deafened patients with CIs. MAIN OUTCOME MEASURES: Primary outcome measure was sentence recognition assessed by a modified version of the Oldenburg Sentence Test filtered to the telephone bandwidth of 0.3-3.4 kHz. Additionally, pure tone thresholds, recognition of monosyllables and subjective hearing benefit were acquired at two separate visits before and after a home-based training period of 10-14 weeks. For training, patients received a CD with speech material, either unmodified for the unfiltered training group or filtered to the telephone bandwidth in the filtered group. RESULTS: Patients in the unfiltered training group achieved an average sentence recognition score of 70.0%±13.6% (mean±SD) before and 73.6%±16.5% after training. Patients in the filtered training group achieved 70.7%±13.8% and 78.9%±7.0%, a statistically significant difference (P=.034, t10 =2.292; two-way RM ANOVA/Bonferroni). An increase in the recognition of monosyllabic words was noted in both groups. The subjective benefit was positive for filtered and negative for unfiltered training. CONCLUSIONS: Auditory training with specifically filtered speech material provided an improvement in sentence recognition on the telephone compared to training with unfiltered material.

[Delirium, analgesia, and sedation in intensive care medicine : Development of a protocol-based management approach]. / Delir, Analgesie und Sedierung in der Intensivmedizin : Entwicklung eines protokollbasierten Managements.

Intensive care treatment has long-term consequences that are often not immediately apparent to the health care providers. The combination of muscle weakness, cognitive damage, and psychological disorders is comprised under the term post-intensive care syndrome (PICS). Analgesia and sedation protocols, as well as nonpharmacological preventive and therapeutic approaches, are effective tools for avoiding complications and improving long-term survival. The principle of "early goal-directed therapy" is fundamental. Here, a treatment target is defined and continuously re-evaluated by validated monitoring methods. Evidence clearly supports a paradigm shift towards patients that are awake, attentive, and able to participate in their therapy. Individualized analgesia and (non)sedation approaches allow a Richmond Agitation-Sedation Scale (RASS) target value of 0/-1 for the majority of patients. Should sedation indeed be necessary, there must be a focus on avoiding oversedation, especially an early deep sedation.