Integrative phylogenetic, phylogeographic and morphological characterisation of the Unio crassus species complex reveals cryptic diversity with important conservation implications.

The global decline of freshwater mussels and their crucial ecological services highlight the need to understand their phylogeny, phylogeography and patterns of genetic diversity to guide conservation efforts. Such knowledge is urgently needed for Unio crassus, a highly imperilled species originally widespread throughout Europe and southwest Asia. Recent studies have resurrected several species from synonymy based on mitochondrial data, revealing U. crassus to be a complex of cryptic species. To address long-standing taxonomic uncertainties hindering effective conservation, we integrate morphometric, phylogenetic, and phylogeographic analyses to examine species diversity within the U. crassus complex across its entire range. Phylogenetic analyses were performed using cytochrome c oxidase subunit I (815 specimens from 182 populations) and, for selected specimens, whole mitogenome sequences and Anchored Hybrid Enrichment (AHE) data on âˆ¼ 600 nuclear loci. Mito-nuclear discordance was detected, consistent with mitochondrial DNA gene flow between some species during the Pliocene and Pleistocene. Fossil-calibrated phylogenies based on AHE data support a Mediterranean origin for the U. crassus complex in the Early Miocene. The results of our integrative approach support 12 species in the group: the previously recognised Unio bruguierianus, Unio carneus, Unio crassus, Unio damascensis, Unio ionicus, Unio sesirmensis, and Unio tumidiformis, and the reinstatement of five nominal taxa: Unio desectusstat. rev., Unio gontieriistat. rev., Unio mardinensisstat. rev., Unio nanusstat. rev., and Unio vicariusstat. rev. Morphometric analyses of shell contours reveal important morphospace overlaps among these species, highlighting cryptic, but geographically structured, diversity. The distribution, taxonomy, phylogeography, and conservation of each species are succinctly described.

[Traumatology-an interdisciplinary task: exclusively for educational purposes?] / Traumatologie ­ eine interdisziplinäre Aufgabe: nur in der Lehre?

BACKGROUND: Traumatology of the head and neck region is not only a part of otorhinolaryngology, but also has a large overlap with neighboring disciplines of the head and neck region. In Freiburg, an interdisciplinary lecture on "ENT emergencies" was implemented in the 21/22 winter semester. The aim was to provide an even more realistic view on interdisciplinary patient care and to make evident the areas of intersection of four of the major head disciplines (otorhinolaryngology, neurosurgery, ophthalmology, and maxillofacial surgery). MATERIALS AND METHODS: A new, special lecture in otorhinolaryngology was implemented as part of the regular online lecture series accompanying the semester. With reference to the clinical care of ENT emergencies, possible overlaps with neighboring disciplines were identified and explained by the discipline representatives or discussed in front of and with the auditorium. At the end of the semester, all participating students (n = 173) were invited to evaluate the seminar using the survey tool "EvaSys" (EvaSys GmbH, Lüneburg, Germany). In total, 78 students participated in the evaluation process. RESULTS: The new lecture concept was very well accepted and immediately ranked top among the interdisciplinary lecture titles within the ENT lecture series. The clear communication of the term "interdisciplinarity" in the sense of a complementary clinical cooperation was also very successful and was appreciated accordingly by students during the evaluation process. CONCLUSION: Pragmatic presentation of ideal clinical patient care using an interdisciplinary approach is possible within the regular ENT lecture series. This realistic portrayal, beyond any technical and/or professional differences, is of great interest to students and is considered clinically relevant. Thus, interdisciplinary lectures provide a valuable tool to teach the fundamental values of clinical interdisciplinary management for the best possible patient care.

Highly accurate response prediction in high-risk early breast cancer patients using a biophysical simulation platform.

PURPOSE: Pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) in early breast cancer (EBC) is largely dependent on breast cancer subtype, but no clinical-grade model exists to predict response and guide selection of treatment. A biophysical simulation of response to NAC has the potential to address this unmet need. METHODS: We conducted a retrospective evaluation of a biophysical simulation model as a predictor of pCR. Patients who received standard NAC at the University of Chicago for EBC between January 1st, 2010 and March 31st, 2020 were included. Response was predicted using baseline breast MRI, clinicopathologic features, and treatment regimen by investigators who were blinded to patient outcomes. RESULTS: A total of 144 tumors from 141 patients were included; 59 were triple-negative, 49 HER2-positive, and 36 hormone-receptor positive/HER2 negative. Lymph node disease was present in half of patients, and most were treated with an anthracycline-based regimen (58.3%). Sensitivity and specificity of the biophysical simulation for pCR were 88.0% (95% confidence interval [CI] 75.7 - 95.5) and 89.4% (95% CI 81.3 - 94.8), respectively, with robust results regardless of subtype. In patients with predicted pCR, 5-year event-free survival was 98%, versus 79% with predicted residual disease (log-rank p = 0.01, HR 4.57, 95% CI 1.36 - 15.34). At a median follow-up of 5.4 years, no patients with predicted pCR experienced disease recurrence. CONCLUSION: A biophysical simulation model accurately predicts pCR and long-term outcomes from baseline MRI and clinical data, and is a promising tool to guide escalation/de-escalation of NAC.

Associations between childhood family emotional health, fronto-limbic grey matter volume, and saliva 5mC in young adulthood.

BACKGROUND: Poor family emotional health (FEH) during childhood is prevalent and impactful, and likely confers similar neurodevelopmental risks as other adverse social environments. Pointed FEH study efforts are underdeveloped, and the mechanisms by which poor FEH are biologically embedded are unclear. The current exploratory study examined whether variability in 5-methyl-cytosine (5mC) and fronto-limbic grey matter volume may represent pathways through which FEH may become biologically embedded. RESULTS: In 98 university students aged 18-22 years, retrospective self-reported childhood FEH was associated with right hemisphere hippocampus (b = 10.4, p = 0.005), left hemisphere amygdala (b = 5.3, p = 0.009), and right hemisphere amygdala (b = 5.8, p = 0.016) volumes. After pre-processing and filtering to 5mC probes correlated between saliva and brain, analyses showed that childhood FEH was associated with 49 5mC principal components (module eigengenes; MEs) (prange = 3 × 10-6 to 0.047). Saliva-derived 5mC MEs partially mediated the association between FEH and right hippocampal volume (Burlywood ME indirect effect b = - 111, p = 0.014), and fully mediated the FEH and right amygdala volume relationship (Pink4 ME indirect effect b = - 48, p = 0.026). Modules were enriched with probes falling in genes with immune, central nervous system (CNS), cellular development/differentiation, and metabolic functions. CONCLUSIONS: Findings extend work highlighting neurodevelopmental variability associated with adverse social environment exposure during childhood by specifically implicating poor FEH, while informing a mechanism of biological embedding. FEH-associated epigenetic signatures could function as proxies of altered fronto-limbic grey matter volume associated with poor childhood FEH and inform further investigation into primarily affected tissues such as endocrine, immune, and CNS cell types.

Surgical nodal management in hypopharyngeal and laryngeal cancer.

OBJECTIVE: The aim of this study is to compare pre-therapeutic staging of the loco-regional lymphatic basin and subsequent surgical management in cN0 versus cN+ hypopharyngeal and laryngeal cancer patients. METHODS: We analyzed all hypopharyngeal and laryngeal carcinoma patients treated surgically at a single quaternary medical care and cancer center between 2004 and 2014. We established two groups for patients who underwent neck dissection comparing patients with a low LNR (lymph node ratio) to one with a high LNR. Regarding the cN0 cohort, elective neck dissection was evaluated as a secondary predictor variable. Comorbidities, such as anemia and renal insufficiency, were analyzed as potentially influencing disease-free (DFS) and overall survival (OS). RESULTS: A total of 310 patients (185 glottic and 125 supraglottic/hypopharyngeal carcinoma) were included. Pre-therapeutic neck MRI-/CT-scan and concomitant neck ultrasound revealed cN+ status in 144 patients resulting in a significant over-staging in 63 patients (44%) who were rated as being pN0 after histological examination. 166 patients were staged cN0 and 21 underwent elective neck dissection (11 local advanced glottic and 10 supraglottic/hypopharyngeal carcinoma). Two cN0 patients showed occult cervical lymph node metastases (10%). Furthermore, we could detect a significant negative impact of the LNR divided by the number of dissected lymph nodes and OS. CONCLUSION: The pre-therapeutic clinical evaluation of lymphatic outgrowth is over-staged. OS decreases with increasing LNR divided by the number of dissected lymph nodes. Renal insufficiency and anemia are significant negative factors, decreasing both OS and DFS.

Evaluation of activity meters for estrus detection: A stochastic bioeconomic modeling approach.

Although estrus detection makes a relevant contribution to the reproductive performance of dairy cattle, studies on the economic evaluation of automatic estrus detection systems are rare. The objective of the present study is to provide an economic evaluation of activity meters used for estrus detection. The effect of different estrus detection rates on gross margins was modeled with SimHerd (SimHerd A/S, Viborg, Denmark). The analysis considers all costs associated with the investment in activity meters. The economic evaluation was carried out through simulation of Simmental herds with yearly milk yields of 7,000 or 9,000 kg and Holstein Friesian herds with yearly milk yields of 9,000 or 11,000 kg, each with herd sizes of 70 or 210 cows. Furthermore, we distinguished between 2 investment scenarios. In scenario 1, only cows are equipped with activity meters for estrus detection, whereas scenario 2 assumes that cows and heifers are equipped with activity meters. Because existing empirical information for some variables shows significant variability (estrus detection rates, time for estrus detection), they were modeled with distributions using the Monte Carlo method in @RISK (Palisade Corporation, Ithaca, NY), allowing us to model a probability distribution of net returns (NR) of investment in activity meters for estrus detection. The simulation results show that the average NR of investment in activity meters for estrus detection over all scenarios ranges from +€7 to +€40 per cow per year for the Simmental breed, and from +€19 to +€46 per cow per year for the Holstein Friesian breed. Generally, the NR depends on the milk production level assumed. For the Simmental breed, depending on the scenario, the simulation results show a 54 to 200% larger average NR of investment in activity meters for estrus detection with a milk yield of 9,000 kg/yr compared with 7,000 kg/yr. For the Holstein Friesian breed, the effect of the modeled milk yield on the NR is much less pronounced. Average NR of investment in activity meters are greater for larger herd sizes because of cost degression effects. An additional equipping of heifers has, on average, a positive effect on the economics of activity meters for estrus detection because of the resulting reduction in the age at first calving. Considering all scenarios, the probability of a positive NR of investment in activity meters ranges between 74 and 98% for the Simmental breed and between 85 and 99% for the Holstein Friesian breed.

Novel methods for the assessment of safety pharmacology and toxicology parameters in anesthetized and ventilated dogs receiving inhaled drugs.

INTRODUCTION: For nonclinical drug development, it is optimal if safety pharmacology and toxicology studies are performed in a model that reasonably represents the patient the drug is intended to treat. To simulate prolonged inhalation therapy in ventilated patients, GLP inhalation toxicology methods, including safety pharmacology endpoints, in anesthetized, intubated and mechanically ventilated dogs were developed. This model required establishment of a canine intensive care unit (ICU) capable of providing prolonged anesthesia (propofol infusion and morphine titration) and partial parenteral nutrition (dextrose, amino acids and lipids) while safety parameters were monitored. METHOD: Telemetry was used to continuously monitor heart rate, ECG and blood pressure. Blood gas parameters were periodically measured while oxygen saturation and core temperature were reported continuously. Glucose was measured hourly while other standard clinical pathology (hematology, coagulation, clinical chemistry) samples were evaluated approximately every 12 h. Aerosols were administered continuously over 48 h by inhalation using a mesh nebulizer (Aerogen Solo) fed by a syringe pump into a humidified circuit of a critical care ventilator (LTV® 1000) ending in an endotracheal tube placed in the trachea. Animals were ventilated with pressure control ventilation targeting a respiratory minute volume of 2.0-3.5 l per minute (LPM). Peak inspiratory pressure (PIP) was maintained between 10 and 17 cm H2O and inspiratory time was set to 1 s with an inspiratory:expiratory (I:E) ratio of 1:2. Ventilator parameters and anesthesia were adjusted to maintain normal PaCO2 levels and adequate sedation, respectively. Novel methods were developed to determine dose and particle size in vitro as on-line measurements were not feasible during in vivo aerosol delivery. RESULTS AND DISCUSSION: Acceptable baseline measurements were established for all parameters over the 48-h evaluation period, qualifying the method as appropriate for assessment of GLP safety pharmacology and toxicology studies.

C-Halide bond cleavage by a two-coordinate iron(i) complex.

Iron(i) species are debated as key intermediates during the C-halide activation step in Kumuda type C-C cross-coupling catalysis. However, there is only limited knowledge on the reactivity of isolable iron(i) complexes towards organohalides. Using the known two-coordinate iron(i) complex K{18c6}[FeI(N(SiMe3)2)2] we disclose its proficiency to rapidly cleave different types of carbon halide bonds including even C-F bonds. Mechanistic studies indicate stepwise one-electron processes with the involvement of organoradicals.

Aesthetic and functional outcomes in patients with a nasal prosthesis.

The aim was to evaluate the aesthetic and functional outcomes in patients with a nasal prosthesis after radical tumour resection. A questionnaire with 15 domains was created to evaluate the satisfaction of patients with their nasal prosthesis. Correlations with the results of the University of Washington Quality of Life (UWQOL) questionnaire, which was also completed by the patients, were analyzed. Forty-three patients with a partial or total nasal prosthesis completed the questionnaire. Twenty-seven patients were male and 16 were female; their median age was 62 years. The median follow-up time after tumour resection was 33 months. The best result was obtained for overall function (85.5) and the worst result for nasal crusts (58.5). The average daily duration of prosthesis use was 17.4h. There were sex-dependent and age-dependent differences in the domain 'self-confidence', age-dependent differences in the domain 'stability during sporting activities', and differences in the domain 'nose bleed' depending on the time since tumour resection. All patients would recommend this rehabilitation after rhinectomy. 'Satisfaction with function' had the most influence on UWQOL domains. The nasal prosthesis is a well-accepted rehabilitation after rhinectomy. The results for appearance are comparable to those obtained for nasal reconstruction, and high scores were found for the functional domains.

Examination of the recommended safe and unsafe zone for placement of surgical instruments in thoracentesis and video-assisted thoracic surgery: a cadaveric study.

BACKGROUND: Thoracentesis and video-assisted thoracic surgery procedures can result in haemorrhage as a consequence of severing the collateral branches of the posterior intercostal artery. These branches have been shown to be most common in the 5th intercostal space (ICS). Tortuosity has been shown to be especially prevalent nearer to midline. A group of investigators have recommended the 4th and 7th ICS, 120 mm lateral to midline as a safe zone, least likely to hit branches when cutting into the ICS. The present study aimed to investigate that safe zone as a better entry points for procedures. In addition, investigation of the least safe 5th ICS was also performed. MATERIALS AND METHODS: A total of 56 embalmed human cadavers were selected for the study. With the cadavers laid prone, 2 cm incisions were made at the 4th, 5th and 7th ICS, 120 mm lateral to midline bilaterally. The cadavers were then placed supine and the incisions were dissected. Careful attention was paid to identify if any collateral branches were cut. RESULTS: After thorough dissection of the 4th, 5th and 7th ICS incision sites, it was shown that damage to the 5th intercostal was seen most frequently. CONCLUSIONS: Based on this cadaveric study, a 2 cm incision at the 4th, 5th and 7th ICS 120 mm lateral from midline resulted in the most damage at the level of the 5th ICS. The 4th ICS had the least damage seen. Therefore, it is recommended that insertion should be placed at the level of the 4th ICS bilaterally.

Relapsing high grade mucoepidermoid carcinoma. Long-lasting complete response following reirradiation and EGFR blockade.

BACKGROUND AND PURPOSE: The treatment strategy for inoperable recurrent mucoepidermoid carcinoma (MEC) is not well established. Here, we present a case of a relapsed high grade MEC of the salivary glands of the hard palate that was successfully treated with a reirradiation (re-RT) and cetuximab, an antibody against epidermal growth factor receptor (EGFR). CASE REPORT: Twelve years after resection and adjuvant radiotherapy for high grade MEC of the salivary glands, a patient presented with inoperable recurrent disease. She received another 59.4 Gy. In addition, 400 mg/m(2) cetuximab was administered in the first week, followed by six additional weekly courses at 250 mg/m(2). RESULTS: Treatment was well tolerated. The patient is doing well and continuous radiological complete response (CR) is documented for 25 months after completion of the combined treatment. CONCLUSION: Combined re-RT and targeted inhibition of EGFR with cetuximab may be a valuable therapeutic strategy in patients with recurrent localized high grade MEC who are not candidates for radical surgery.

Diagnostic value of ultrasound-guided core needle biopsy in patients with salivary gland masses.

The salivary glands are unique in the diversity and complexity of their pathologies. Because fine needle aspiration cytology and frozen section are associated with major diagnostic difficulties, the authors analyzed the use of core needle biopsy (CNB) for the histologic assessment of salivary gland lesions. A systematic observational clinicopathologic quality assessment study was performed over 81 months including 161 CNB procedures in 76 patients with salivary gland pathologies. Adequate samples containing the target tissue were obtained in 73 patients. These samples revealed malignant disease in 45 (62%) patients, benign disease in 26 (36%) patients, and were inconclusive in 2 (3%) patients. Follow-up uncovered no false-positive or false-negative results. On the basis of secondary histologic and clinical follow-up, the statistical parameters were calculated as follows: sensitivity 94%; specificity 100%; accuracy 96%; positive predictive value 100%; negative predictive value 90%. The advantages and potential limitations of CNB in patients with salivary gland masses are discussed. CNB is a reliable biopsy technique for the assessment of salivary gland pathologies, although limitations remain for the subclassification of some neoplastic lesions. The authors recommend CNB as the biopsy technique of choice for a selection of indications.

[Recommendations on therapy for chronic constipation--working group for functional diagnosis and psychosomatics of the austrian society of gastroenterology and hepatology]. / Empfehlungen zur Therapie der chronischen Obstipation der Arbeitsgruppe für Funktionsdiagnostik und Psychosomatik der Österreichischen Gesellschaft für Gastroenterologie und Hepatologie.

Constipation is one of the most frequent gastroenterological problems, especially among elderly people. Chronic constipation is now defined by the new Rome III criteria. Life style counselling is usually only effective in early stages of disease and for mild types. In patients with constipation one should actively screen for possible causative, medically adverse events. Recently new effective opioid antagonists were introduced to act against constipation in patients on long-term opioid therapy. If these actions fail, medical therapy with polyethylene glycol or lactulose should be favoured in the long-term treatment. Psychodiagnostic queries concerning fear should be included in the diagnostic procedures. Biofeedback is an effective therapy in these cases and especially with pelvic floor dyssynergia. Surgical interventions are rarely indicated or successful with the exception of chronic outlet obstruction with severe anatomic changes.

[Persistent extramedullary plasmacytoma of the nose after radiotherapy]. / Persistierendes extramedulläres Plasmozytom der Nase nach Radiatio.

Solitary extramedullary plasmacytomas of the head and neck are rare tumors. These tumors are known to be very radiosensitive and therefore radiotherapy is often considered as the treatment of choice. We present the case of a solitary extramedullary plasmacytoma of the nose which did not respond sufficiently to radiotherapy, i.e. persistence of the tumor led to surgical treatment. After a discussion of the recent literature we primarily recommend the excision of this type of tumor whenever possible.

[Intraluminal surgical procedures for glottic enlargement in bilateral vocal fold paralysis in adduction]. / Intraluminäre Verfahren der Glottiserweiterung bei bilateraler Stimmlippenparese.

Bilateral vocal fold paralysis with paramedian position of the vocal chords can result from iatrogenic or traumatic nerve injuries, neurologic disorders and extralaryngeal malignancies and usually causes significant shortness of breath while the voice is only slightly affected. Only about 10% of the affected patients tolerate the narrowed airway caused by bilateral vocal fold paralysis in adduction, so most patients are candidates for a surgical intervention. Today, a range of intraluminal surgical procedures for enlargement of the glottis in bilateral vocal fold paralysis have been described which intend to avoid or supersede tracheostomy and which have replaced time-consuming external approaches to the glottis. This report provides an overview of the most important intraluminal surgical procedures for bilateral vocal fold paralysis in adduction and comments in detail on indications, surgical techniques, advantages and potential complications of the presented procedures for temporary or definitive enlargement of the glottis.

[Nuchal swelling]. / Nuchale Schwellung.

In the unusual case of a 68-year-old woman with one-sided painless lateral neck swelling, the ENT examination showed a firm nuchal mass (4 × 4 cm) on the right side with no other pathological findings. Angio-MRI confirmed a solid, sharply demarcated tumor with arterial hyperperfusion. Core needle aspiration biopsy was performed, revealing well-circumscribed tufts showing the typical "cannonball" aspect. After preoperative embolisation we performed extirpation of the mass. Histological examination showed an acquired tufted angioma. Clinical as well as radiological follow-up examination detected neither local relapse nor metastases.