Psychological factors and long-term tinnitus handicap in vestibular schwannoma patients after retrosigmoid microsurgery - a cross-sectional study.

OBJECTIVE: This study aimed to investigate the connection between psychological factors and postoperative tinnitus in vestibular schwannoma (VS) patients following retrosigmoid microsurgery. DESIGN: Cross-sectional study. STUDY SAMPLE: Ninety-three VS patients participated, completing questionnaires on demographics, tinnitus severity (THI-12), personality traits (TIPI-G), dizziness impact (DHI), perceived health benefits (GBI), somatisation tendencies (SOMS-2), and psychological distress (HADS-D). Our analysis involved Mann-Whitney U-tests, Spearman's rank-order correlations, and false discovery rate correction. RESULTS: Most participants reported postoperative tinnitus (77/93), with 41 experiencing it preoperatively. Emotional stability correlated negatively with tinnitus presence, while tinnitus severity was associated with emotional distress. Preoperative somatisation tendencies were also positively linked to tinnitus severity. Postoperative Tinnitus was further linked to reduced perceived health benefits and increased anxiety and depression levels. Notably, age and gender showed no significant associations. CONCLUSION: This study uncovers the interplay between postoperative tinnitus and psychological factors in VS patients, highlighting emotional and cognitive dimensions. Tailored psychological interventions addressing tinnitus's psychosomatic impact may enhance patients quality of life.

Unusual coordination mode for 1,3-diphosphete ligands towards a Cr-Cr quintuple bond complex.

The reaction of LCr5̲CrL (L = N2C25H29, 1) with the phosphaalkynes R-C≡P (R = tBu, Me, Ad) yields the neutral dimerisation compounds [L2Cr2(µ,η1:η1:η2:η2-P2C2R2)] (R = tBu (2), Me (3)) and the tetrahedrane complex [L2Cr2(µ,η2:η2-PCAd)] (4). The 1,3-diphosphete ligands in complexes 2 and 3 are the first to possess this structural feature spanned over a metal-metal multiple bond, while the slightly bigger adamantyl phosphaalkyne remains a monomer in 4 with a side-on coordination mode.

Rapid, complete and sustained tumour response to the TRK inhibitor larotrectinib in an infant with recurrent, chemotherapy-refractory infantile fibrosarcoma carrying the characteristic ETV6-NTRK3 gene fusion.

BACKGROUND: The ETV6-NTRK3 gene fusion is present in the majority of cases of infantile fibrosarcoma (IFS) and acts as a potent oncogenic driver. We report the very rapid, complete, and sustained response of an advanced, chemotherapy-refractory, recurrent IFS to targeted treatment with the oral tropomyosin receptor kinase (TRK) inhibitor larotrectinib. PATIENT AND METHODS: A male infant born with a large congenital IFS of the tongue had the tumour surgically resected at age 4 days. Within 2 months, he developed extensive lymph node recurrence that progressed during two cycles of vincristine-doxorubicin-cyclophosphamide chemotherapy. At screening, a large right cervical mass was clinically visible. Magnetic resonance imaging (MRI) revealed bilateral cervical and axillary lymph node involvement as well as infiltration of the floor of the mouth. The largest lesion measured 5.5×4.5×4.4 cm (ca. 55 cm3). The patient started outpatient oral larotrectinib at 20 mg/kg twice daily at age 3.5 months. RESULTS: After 4 days on treatment, the parents noted that the index tumour was visibly smaller and softer. The rapid tumour regression continued over the following weeks. On day 56 of treatment, the first scheduled control MRI showed the target lesion had shrunk to 1.2×1.2×0.8 cm (ca. 0.6 cm3), corresponding to a complete response according to the Response Evaluation Criteria In Solid Tumors version 1.1. This response was maintained over subsequent follow-up visits, and on day 112 at the second control MRI the target lymph node was completely normal. At last follow-up, the disease remained in complete remission after 16 months on larotrectinib, with negligible toxicity and no safety concerns. CONCLUSION(S): Selective TRK inhibition by larotrectinib offers a novel, highly specific and highly effective therapeutic option for IFS carrying the characteristic ETV6-NTRK3 gene fusion. Its use should be considered when surgery is not feasible. (NCT02637687).

Determining how diluted bloodstains were derived: Inferring distinctive characteristics and formulating a guideline.

In forensic settings, diluted bloodstains are regularly encountered for example when bloodstains are mixed with tap-/rainwater, after deliberate cleaning attempts, or when blood is dropped on a wet surface such as a towel. Such diluted bloodstain scenarios can be subdivided into sequences of events in which a blood drop was either (1) readily diluted (a mixture of blood and water is deposited); (2) deposited on a surface that was readily moistened (first water, then blood) or (3) deposited and subsequently moistened (first blood, then water). Current bloodstain pattern analysis (BPA) lacks data and tools to distinguish these three ways of derivation of a diluted bloodstain that vary in the sequence of deposition of blood and water on textile. In this study, 880 bloodstains were examined for characteristics that can be used to determine the derivation of diluted bloodstains. A guideline to assist BPA-analysts in interpreting diluted bloodstains was extracted. The added value of this guideline was confirmed by conducting two surveys: one survey with and one without the guideline. A third survey confirmed that the characteristics also function on a broader range of textile types that have different weave and knit styles. This guideline can aid BPA-experts to determine, in an objective way, how diluted bloodstains derived which can aid in determining which activities took place at a crime scene.

Rapid, complete and sustained tumour response to the TRK inhibitor larotrectinib in an infant with recurrent, chemotherapy-refractory infantile fibrosarcoma carrying the characteristic ETV6-NTRK3 gene fusion.

BACKGROUND: The ETV6-NTRK3 gene fusion is present in the majority of cases of infantile fibrosarcoma (IFS) and acts as a potent oncogenic driver. We report the very rapid, complete, and sustained response of an advanced, chemotherapy-refractory, recurrent IFS to targeted treatment with the oral tropomyosin receptor kinase (TRK) inhibitor larotrectinib. PATIENT AND METHODS: A male infant born with a large congenital IFS of the tongue had the tumour surgically resected at age 4 days. Within 2 months, he developed extensive lymph node recurrence that progressed during two cycles of vincristine-doxorubicin-cyclophosphamide chemotherapy. At screening, a large right cervical mass was clinically visible. Magnetic resonance imaging (MRI) revealed bilateral cervical and axillary lymph node involvement as well as infiltration of the floor of the mouth. The largest lesion measured 5.5×4.5×4.4 cm (ca. 55 cm3). The patient started outpatient oral larotrectinib at 20 mg/kg twice daily at age 3.5 months. RESULTS: After 4 days on treatment, the parents noted that the index tumour was visibly smaller and softer. The rapid tumour regression continued over the following weeks. On day 56 of treatment, the first scheduled control MRI showed the target lesion had shrunk to 1.2×1.2×0.8 cm (ca. 0.6 cm3), corresponding to a complete response according to the Response Evaluation Criteria In Solid Tumors version 1.1. This response was maintained over subsequent follow-up visits, and on day 112 at the second control MRI the target lymph node was completely normal. At last follow-up, the disease remained in complete remission after 16 months on larotrectinib, with negligible toxicity and no safety concerns. CONCLUSION(S): Selective TRK inhibition by larotrectinib offers a novel, highly specific and highly effective therapeutic option for IFS carrying the characteristic ETV6-NTRK3 gene fusion. Its use should be considered when surgery is not feasible. (NCT02637687).

Unexpected differences in the reactivity between the phosphorus and arsenic derivatives [(CpBIGFe)2(µ,η4:4-E4)] (E = P and As).

Different reaction pathways were determined between thermolysis and photolysis reactions of the butterfly complex [{CpBIGFe(CO)2}2(µ,η1:1-As4)] (1b). The thermolysis leads to novel arsenic-rich compounds [(CpBIGFe)2(µ,η4:4-As4)] (2b), [(CpBIGFe)3(µ3,η4:4:4-As6)] (4) and [CpBIGFe(η5-As5)] (5), whereas the photolysis of [{CpBIGFe(CO)2}2(µ,η1:1-E4)] (1a: E = P; 1b: E = As) exclusively results in the decarbonylation products [(CpBIGFe)2(µ,η4:4-P4)] (2a), 2b and [(CpBIGFe)(µ,η4:1-As4)(CpBIGFe(CO)2)] (3). The E4 complexes 2a and 2b show unique structural differences in the solid state despite their related compositions.

Neutral two-dimensional organometallic-organic hybrid polymers based on pentaphosphaferrocene, bipyridyl linkers and CuCl.

The reaction of the Pn ligand complex [Cp*Fe(η5-P5)] (1: Cp* = η5-C5Me5) with CuCl in the presence of 4,4'-bipyridine or 1,2-di(4-pyridyl)ethylene leads to the formation of three unprecedented neutral 2D organometallic-organic hybrid networks, the constitutional isomers [Cu2Cl2{Cp*Fe(µ3,η5:1:1-P5)}(µ,η1:1-C10H8N2)]n (2 and 3) and the coordination polymer [(CuCl)2{Cp*Fe(µ3,η5:1:1-P5)}(µ,η1:1-C12H10N2)]n (4) with isomeric square (2 and 3) and honeycomb (4) layer topologies.

Transformation of nortricyclane type cage compounds P4S3, P4Se3 and As4S3 by [Cp''2Zr(CO)2].

The complex [Cp''2Zr(CO)2] (Cp'' = C5H3tBu2) was used to transform the nortricyclane type cage compounds E4Q3 (E = P, Q = S, Se; E = As, Q = S) resulting in unprecedented complexes [(Cp''2Zr)2(µ,η1:1:1:1-E2Q4)] possessing bridging ligands that represent the anions of the so far unknown tetrachalcogenohypodiphosphorous acid (HQ)2PP(QH)2 and tetrathiohypodiarsenous acid (HS)2AsAs(SH)2, respectively.

Facile synthesis of one-dimensional organometallic-organic hybrid polymers based on a diphosphorus complex and flexible bipyridyl linkers.

The selective synthesis of a series of new "ladderlike" one-dimensional organometallic-organic hybrid polymers is shown. The polymers are obtained from the reaction of the diphosphorus ligand complex [Cp2Mo2(CO)4(η(2)-P2)] with the copper salt [Cu(CH3CN)4]BF4 in the presence of flexible organic bipyridyl linkers in high selectivity. This unique behaviour is supported by DFT calculations.

Diminished electron density in the Vaska-type rhodium(I) complex trans-[Rh(NCBH3)(CO)(PPh3)2].

Vaska-type complexes, i.e. trans-[RhX(CO)(PPh3)2] (X is a halogen or pseudohalogen), undergo a range of reactions and exhibit considerable catalytic activity. The electron density on the Rh(I) atom in these complexes plays an important role in their reactivity. Many cyanotrihydridoborate (BH3CN(-)) complexes of Group 6-8 transition metals have been synthesized and structurally characterized, an exception being the rhodium(I) complex. Carbonyl(cyanotrihydridoborato-κN)bis(triphenylphosphine-κP)rhodium(I), [Rh(NCBH3)(CO)(C18H15P)2], was prepared by the metathesis reaction of sodium cyanotrihydridoborate with trans-[RhCl(CO)(PPh3)2], and was characterized by single-crystal X-ray diffraction analysis and IR, (1)H, (13)C and (11)B NMR spectroscopy. The X-ray diffraction data indicate that the cyanotrihydridoborate ligand coordinates to the Rh(I) atom through the N atom in a trans position with respect to the carbonyl ligand; this was also confirmed by the IR and NMR data. The carbonyl stretching frequency ν(CO) and the carbonyl carbon (1)JC-Rh and (1)JC-P coupling constants of the Cipso atoms of the triphenylphosphine groups reflect the diminished electron density on the central Rh(I) atom compared to the parent trans-[RhCl(CO)(PPh3)2] complex.

[Neurofeedback in the Treatment of Anorexia Nervosa: a Case Report]. / Der Einsatz von Neurofeedback bei Anorexia nervosa: ein Fallbeispiel.

Anorexia nervosa has been related to alterations in brain activity in terms of hyperactive EEG patterns. This case report illustrates the principles and results of a five-week neurofeedback treatment in a 29-year-old woman suffering from anorexia nervosa. A neurofeedback protocol to enhance alpha activity (8 - 12 Hz) was developed and conducted additionally to the standardized treatment for eating disorders in training sessions twice a week. Pre- and post-test measurements included resting state EEG measurements and a psychological test battery. The results show improvements from pre- to post-test in eating disorder psychopathology including psychological wellbeing, emotional competence, and eating behavior traits. In addition, a decrease in theta power (4 - 7 Hz), a well-known trait marker of anorexia nervosa, was measured. However, our data should be interpreted with caution because this is a single case study. Nevertheless, this report documents the practicability and method of neurofeedback as treatment adjunct in eating disorders from the clinical perspective. Although the use of neurofeedback in the treatment of anorexia nervosa is recommended in literature, empirical studies are still lacking. Randomized controlled trials to evaluate short- and long-term effects of neurofeedback are needed.

Probing Charges on the Atomic Scale by Means of Atomic Force Microscopy.

Kelvin probe force spectroscopy was used to characterize the charge distribution of individual molecules with polar bonds. Whereas this technique represents the charge distribution with moderate resolution for large tip-molecule separations, it fails for short distances. Here, we introduce a novel local force spectroscopy technique which allows one to better disentangle electrostatic from other contributions in the force signal. It enables one to obtain charge-related maps at even closer tip-sample distances, where the lateral resolution is further enhanced. This enhanced resolution allows one to resolve contrast variations along individual polar bonds.

Synthesis of arsenic-rich As n ligand complexes from yellow arsenic.

The reaction of [{η5-Cp'''Co}2{µ,η4:4-toluene}] with yellow arsenic yields the arsenic-rich As n ligand complexes [{Cp'''Co(µ,η2:2-As2)}2] (1), [(Cp'''Co)4(µ4,η4:4:2:2:1:1-As10)] (2) and [(Cp'''Co)3(µ3,η4:4:2:1-As12)] (3), which were comprehensively characterized. The molecular structure of 1 show a triple-decker complex with two As2 units forming the middle-deck; compound 2 contains an all-arsenic As10 analogue of dihydrofulvalene in the molecular structure. The As12 ligand in 3 represents the largest As n ligand complex reported so far.

Production of inflammatory mediators and extracellular traps by carp macrophages and neutrophils in response to lipopolysaccharide and/or interferon-γ2.

Neutrophilic granulocytes and macrophages are crucial for the innate immune response against infections. They migrate into the focus of inflammation, where they efficiently bind, engulf and kill bacteria by proteolytic enzymes, antimicrobial peptides, reactive oxygen (ROS) and nitrogen (RNS) species. Moreover, activated neutrophils and macrophages can form extracellular traps (ETs). Fish neutrophils and macrophages are morphologically, histochemically, and functionally similar to their mammalian counterparts, but their significance for regulation of inflammatory responses and pathogen killing needs further elucidation. We compared the activity of head kidney monocytes/macrophages and neutrophilic granulocytes of common carp and established that upon lipopolysaccharide stimulation, not only neutrophils, but also carp monocytes/macrophages release extracellular DNA and are capable to form macrophage extracellular traps (METs). To clarify whether many specific LPS functions reported for piscine phagocytes might be due to impurities in the commonly used LPS preparations we studied expression of inflammatory mediators, release of DNA, ROS and RNS in cells stimulated with LPS or its highly purified form (pLPS). Also IFN-γ2 stimulation and its synergism with LPS/pLPS in stimulating expression of pro-inflammatory mediators was studied. Results substantiate that a classical stimulation of TLR4 by LPS may indeed be absent in carp as most of the classically reported LPS effects are abolished or diminished when pLPS is used. Interestingly, we also observed a potent IL-10 expression in neutrophilic granulocytes upon LPS stimulation, which, apart from their pro-inflammatory function, clearly indicates a role in restrictive control of the inflammatory reaction.

Low temperature activation of S8, Se(red) and α-Te with [Cp(BIG)Fe(CO)2] radicals.

The bulky dimeric iron complex, [Cp(BIG)Fe(CO)2]2, readily activates elemental chalcogens (S8, Se(red) and α-Te) under mild conditions at room temperature. Six compounds containing Q2(2-) ligands (Q = S, Se) and a Te(2-) ligand, respectively, were isolated and completely characterized, including by X-ray diffraction techniques.

Characterization and expression analysis of an interferon-γ2 induced chemokine receptor CXCR3 in common carp (Cyprinus carpio L.).

Chemokine and chemokine receptor signalling pairs play a crucial role in regulation of cell migration, morphogenesis, and cell activation. Expressed in mammals on activated T and NK cells, chemokine receptor CXCR3 binds interferon-γ inducible chemokines CXCL9-11 and CCL21. Here we sequenced the carp CXCR3 chemokine receptor and showed its relationship to CXCR3a receptors found in other teleosts. We found high expression of the CXCR3 gene in most of the organs and tissues of the immune system and in immune-related tissues such as gills and gut, corroborating a predominantly immune-related function. The very high expression in gill and gut moreover indicates a role for CXCR3 in cell recruitment during infection. High in vivo expression of CXCR3 at later stages of inflammation, as well as its in vitro sensitivity to IFN-γ2 stimulation indicate that in carp, CXCR3 is involved in macrophage-mediated responses. Moreover, as expression of the CXCR3 and CXCb genes coincides in the focus of inflammation and as both the CXCb chemokines and the CXCR3 receptor are significantly up-regulated upon IFN-γ stimulation it is hypothesized that CXCb chemokines may be putative ligands for CXCR3.

[Diagnosis of inherited diseases of platelet function. Interdisciplinary S2K guideline of the Permanent Paediatric Committee of the Society of Thrombosis and Haemostasis Research (GTH e. V.)]. / Diagnose angeborener Störungen der Thrombozytenfunktion. Interdisziplinäre S2K-Leitlinie der Ständigen Kommission Pädiatrie der Gesellschaft für Thrombose- und Hämostaseforschung e. V.

Congenital disorders of platelet function are a heterogeneous group of disorders that are often not detected until bleeding occurs. In clinical settings only a few methods have proven to be useful for identification and classification of inherited platelet disorders. For a rational diagnostic approach, a stepwise algorithm is recommended. Patient history and clinical investigation are mandatory. Von Willebrand disease and other coagulation disorders should always be ruled out prior to specific platelet testing. Platelet count, size, volume (MPV) and morphology may guide further investigations. The PFA-100® CT is suited for screening for severe platelet defects. Platelet aggregometry allows assessment of multiple aspects of platelet function. Flow cytometry enables diagnosis of thrombasthenia Glanzmann, Bernard-Soulier syndrome and storage pool defects. Molecular genetics may confirm a putative diagnosis or pave the way for identifying new defects. We present an unabridged version of the interdisciplinary guideline.

Single bunch X-ray pulses on demand from a multi-bunch synchrotron radiation source.

Synchrotron radiation facilities routinely operate in a multi-bunch regime, but applications relying on time-of-flight schemes require single bunch operation. Here we show that pulse picking by resonant excitation in a storage ring creates in addition to the multi-bunch operation a distinct and separable single bunch soft X-ray source. It has variable polarization, a photon flux of up to 10(7)-10(9) ph s(-1)/0.1%BW at purity values of 10(4)-10(2) and a repetition rate of 1.25 MHz. The quasi-resonant excitation of incoherent betatron oscillations of electrons allows horizontal pulse separation at variable (also circular) polarization accessible for both, regular 30 ps pulses and ultrashort pulses of 2-3 ps duration. Combined with a new generation of angularly resolving electron spectrometers this creates unique opportunities for time-resolved photoemission studies as confirmed by time-of-flight spectra. Our pulse picking scheme is particularly suited for surface physics at diffraction-limited light sources promising ultimate spectral resolution.

Histopathological assessment of tumour regression, nodal stage and status of resection margins determines prognosis in patients with oral squamous cell carcinoma treated with neoadjuvant radiochemotherapy.

OBJECTIVES: In advanced oral squamous cell carcinoma (OSCC), tumour regression after neoadjuvant radiochemotherapy seems to be an important prognostic factor. In this study, we intended to compare regression grading according to two previously described regression models and to analyse the association of tumour regression and other tumour characteristics with patients' characteristics and overall survival. METHODS: The retrospective study included 63 treatment-naive patients with primary OSCC of stages II-IV, who were treated with a concomitant neoadjuvant radiochemotherapy followed by radical surgery. Assessment of histopathological features was performed, there under regression grading according to two previously described regression models. RESULTS: Both tumour regression models provided comparable results in terms of distribution of different regression grades. In univariate analysis regression gradings (P = 0.003 and P = 0.007), ypT-stage, ypN-stage and status of resection margins (P < 0.001) were significantly associated with the 5-year overall survival (OS). None of the pretreatment clinicopathological parameters showed association with histopathological tumour regression. Multivariate analysis revealed the status of resection margins and of lymph node metastasis as statistically significant features for OS (P = 0.020 and P = 0.003, respectively). CONCLUSION: Tumour regression grading, nodal stage and status of resection margins predict prognosis in patients after neoadjuvant treatment. Currently, there are no pretreatment clinicopathological parameters, which predicting good tumour response to therapy. Thus, identifying non-responding patients, which might benefit from an intensified systemic therapy, requires surgical resection and consecutive histopathological assessment. Therefore, further investigation and validation of new, especially, molecular predictors of tumour response to radiochemotherapy remains an unmet, future clinical need.

First observation of photons carrying orbital angular momentum in undulator radiation.

Photon beams of 99 eV energy carrying orbital angular momentum (OAM) have been observed in the 2nd harmonic off-axis radiation of a helical undulator at the 3rd generation synchrotron radiation light source BESSY II. For detection, the OAM carrying photon beam was superimposed with a reference beam without OAM. The interference pattern, a spiral intensity distribution, was recorded in a plane perpendicular to the propagation direction. The orientation of the observed spiral structure is related to the helicity of the undulator radiation. Excellent agreement between measurements and simulations has been found.