Structure and Function Analysis of an Antibody Recognizing All Influenza A Subtypes.

Influenza virus remains a threat because of its ability to evade vaccine-induced immune responses due to antigenic drift. Here, we describe the isolation, evolution, and structure of a broad-spectrum human monoclonal antibody (mAb), MEDI8852, effectively reacting with all influenza A hemagglutinin (HA) subtypes. MEDI8852 uses the heavy-chain VH6-1 gene and has higher potency and breadth when compared to other anti-stem antibodies. MEDI8852 is effective in mice and ferrets with a therapeutic window superior to that of oseltamivir. Crystallographic analysis of Fab alone or in complex with H5 or H7 HA proteins reveals that MEDI8852 binds through a coordinated movement of CDRs to a highly conserved epitope encompassing a hydrophobic groove in the fusion domain and a large portion of the fusion peptide, distinguishing it from other structurally characterized cross-reactive antibodies. The unprecedented breadth and potency of neutralization by MEDI8852 support its development as immunotherapy for influenza virus-infected humans.

Mechanism for the initiation of spliceosome disassembly.

Precursor-mRNA (pre-mRNA) splicing requires the assembly, remodelling and disassembly of the multi-megadalton ribonucleoprotein complex called the spliceosome1. Recent studies have shed light on spliceosome assembly and remodelling for catalysis2-6, but the mechanism of disassembly remains unclear. Here we report cryo-electron microscopy structures of nematode and human terminal intron lariat spliceosomes along with biochemical and genetic data. Our results uncover how four disassembly factors and the conserved RNA helicase DHX15 initiate spliceosome disassembly. The disassembly factors probe large inner and outer spliceosome surfaces to detect the release of ligated mRNA. Two of these factors, TFIP11 and C19L1, and three general spliceosome subunits, SYF1, SYF2 and SDE2, then dock and activate DHX15 on the catalytic U6 snRNA to initiate disassembly. U6 therefore controls both the start5 and end of pre-mRNA splicing. Taken together, our results explain the molecular basis of the initiation of canonical spliceosome disassembly and provide a framework to understand general spliceosomal RNA helicase control and the discard of aberrant spliceosomes.

mRNA recognition and packaging by the human transcription-export complex.

Newly made mRNAs are processed and packaged into mature ribonucleoprotein complexes (mRNPs) and are recognized by the essential transcription-export complex (TREX) for nuclear export1,2. However, the mechanisms of mRNP recognition and three-dimensional mRNP organization are poorly understood3. Here we report cryo-electron microscopy and tomography structures of reconstituted and endogenous human mRNPs bound to the 2-MDa TREX complex. We show that mRNPs are recognized through multivalent interactions between the TREX subunit ALYREF and mRNP-bound exon junction complexes. Exon junction complexes can multimerize through ALYREF, which suggests a mechanism for mRNP organization. Endogenous mRNPs form compact globules that are coated by multiple TREX complexes. These results reveal how TREX may simultaneously recognize, compact and protect mRNAs to promote their packaging for nuclear export. The organization of mRNP globules provides a framework to understand how mRNP architecture facilitates mRNA biogenesis and export.

Congenital adrenal hyperplasia.

Congenital adrenal hyperplasia is a group of autosomal recessive disorders leading to multiple complex hormonal imbalances caused by various enzyme deficiencies in the adrenal steroidogenic pathway. The most common type of congenital adrenal hyperplasia is due to steroid 21-hydroxylase (21-OHase, henceforth 21OH) deficiency. The rare, classic (severe) form caused by 21OH deficiency is characterised by life-threatening adrenal crises and is the most common cause of atypical genitalia in neonates with 46,XX karyotype. After the introduction of life-saving hormone replacement therapy in the 1950s and neonatal screening programmes in many countries, nowadays neonatal survival rates in patients with congenital adrenal hyperplasia are high. However, disease-related mortality is increased and therapeutic management remains challenging, with multiple long-term complications related to treatment and disease affecting growth and development, metabolic and cardiovascular health, and fertility. Non-classic (mild) forms of congenital adrenal hyperplasia caused by 21OH deficiency are more common than the classic ones; they are detected clinically and primarily identified in female patients with hirsutism or impaired fertility. Novel treatment approaches are emerging with the aim of mimicking physiological circadian cortisol rhythm or to reduce adrenal hyperandrogenism independent of the suppressive effect of glucocorticoids.

Gender-affirming hormonal therapy induces a gender-concordant fecal metagenome transition in transgender individuals.

BACKGROUND: Limited data exists regarding gender-specific microbial alterations during gender-affirming hormonal therapy (GAHT) in transgender individuals. This study aimed to investigate the nuanced impact of sex steroids on gut microbiota taxonomy and function, addressing this gap. We prospectively analyzed gut metagenome changes associated with 12 weeks of GAHT in trans women and trans men, examining both taxonomic and functional shifts. METHODS: Thirty-six transgender individuals (17 trans women, 19 trans men) provided pre- and post-GAHT stool samples. Shotgun metagenomic sequencing was used to assess the changes in gut microbiota structure and potential function following GAHT. RESULTS: While alpha and beta diversity remained unchanged during transition, specific species, including Parabacteroides goldsteinii and Escherichia coli, exhibited significant abundance shifts aligned with affirmed gender. Overall functional metagenome analysis showed a statistically significant effect of gender and transition (R2 = 4.1%, P = 0.0115), emphasizing transitions aligned with affirmed gender, particularly in fatty acid-related metabolism. CONCLUSIONS: This study provides compelling evidence of distinct taxonomic and functional profiles in the gut microbiota between trans men and women. GAHT induces androgenization in trans men and feminization in trans women, potentially impacting physiological and health-related outcomes. TRIAL REGISTRATION: Clinicaltrials.gov NCT02185274.

Molecular mechanism of promoter opening by RNA polymerase III.

RNA polymerase III (Pol III) and transcription factor IIIB (TFIIIB) assemble together on different promoter types to initiate the transcription of small, structured RNAs. Here we present structures of Pol III preinitiation complexes, comprising the 17-subunit Pol III and the heterotrimeric transcription factor TFIIIB, bound to a natural promoter in different functional states. Electron cryo-microscopy reconstructions, varying from 3.7 Å to 5.5 Å resolution, include two early intermediates in which the DNA duplex is closed, an open DNA complex, and an initially transcribing complex with RNA in the active site. Our structures reveal an extremely tight, multivalent interaction between TFIIIB and promoter DNA, and explain how TFIIIB recruits Pol III. Together, TFIIIB and Pol III subunit C37 activate the intrinsic transcription factor-like activity of the Pol III-specific heterotrimer to initiate the melting of double-stranded DNA, in a mechanism similar to that of the Pol II system.

Paediatric spine injuries in the thoracic and lumbar spine-results of the German multicentre CHILDSPINE study.

BACKGROUND: Paediatric thoracolumbar spine injuries are rare, and meaningful epidemiological data are lacking. OBJECTIVES: The aim of this study was to provide epidemiological data for paediatric patients with thoracolumbar spinal trauma in Germany with a view to enhancing future decision-making in relation to the diagnostics and treatment of these patients. MATERIALS AND METHODS: A retrospective multicentre study includes patients up to 16 years of age who were suffering from thoracolumbar spine injuries who had been treated in six German spine centres between 01/2010 and 12/2016. The clinical database was analysed for patient-specific data, trauma mechanisms, level of injury, and any accompanying injuries. Diagnostic imaging and subsequent treatment were investigated. Patients were divided into three age groups for further evaluation: age group I (0-6 years), age group II (7-9 years) and age group III (10-16 years). RESULTS: A total of 153 children with 345 thoracolumbar spine injuries met the inclusion criteria. The mean age at the time of hospitalization due to the injury was 12.9 (± 3.1) years. Boys were likelier to be affected (1:1.3). In all age groups, falls and traffic accidents were the most common causes of thoracolumbar spine injuries. A total of 95 patients (62.1%) were treated conservatively, while 58 (37.9%) of the children underwent surgical treatment. Minimally invasive procedures were the most chosen procedures. Older children and adolescents were likelier to suffer from higher-grade injuries according to the AOSpine classification. The thoracolumbar junction (T11 to L2) was the most affected level along the thoracolumbar spine (n = 90). Neurological deficits were rarely seen in all age groups. Besides extremity injuries (n = 52, 30.2%), head injuries represented the most common accompanying injuries (n = 53, 30.8%). Regarding spinal injuries, most of the patients showed no evidence of complications during their hospital stay (96.7%). CONCLUSIONS: The thoracolumbar junction was more frequently affected in older children and adolescents. The majority of thoracolumbar spinal column injuries were treated conservatively. Nevertheless, 37.9% of hospitalized children had to be treated surgically, and there was an acceptable complication rate for the surgeries that were performed.

ChatGPT With GPT-4 Outperforms Emergency Department Physicians in Diagnostic Accuracy: Retrospective Analysis.

BACKGROUND: OpenAI's ChatGPT is a pioneering artificial intelligence (AI) in the field of natural language processing, and it holds significant potential in medicine for providing treatment advice. Additionally, recent studies have demonstrated promising results using ChatGPT for emergency medicine triage. However, its diagnostic accuracy in the emergency department (ED) has not yet been evaluated. OBJECTIVE: This study compares the diagnostic accuracy of ChatGPT with GPT-3.5 and GPT-4 and primary treating resident physicians in an ED setting. METHODS: Among 100 adults admitted to our ED in January 2023 with internal medicine issues, the diagnostic accuracy was assessed by comparing the diagnoses made by ED resident physicians and those made by ChatGPT with GPT-3.5 or GPT-4 against the final hospital discharge diagnosis, using a point system for grading accuracy. RESULTS: The study enrolled 100 patients with a median age of 72 (IQR 58.5-82.0) years who were admitted to our internal medicine ED primarily for cardiovascular, endocrine, gastrointestinal, or infectious diseases. GPT-4 outperformed both GPT-3.5 (P<.001) and ED resident physicians (P=.01) in diagnostic accuracy for internal medicine emergencies. Furthermore, across various disease subgroups, GPT-4 consistently outperformed GPT-3.5 and resident physicians. It demonstrated significant superiority in cardiovascular (GPT-4 vs ED physicians: P=.03) and endocrine or gastrointestinal diseases (GPT-4 vs GPT-3.5: P=.01). However, in other categories, the differences were not statistically significant. CONCLUSIONS: In this study, which compared the diagnostic accuracy of GPT-3.5, GPT-4, and ED resident physicians against a discharge diagnosis gold standard, GPT-4 outperformed both the resident physicians and its predecessor, GPT-3.5. Despite the retrospective design of the study and its limited sample size, the results underscore the potential of AI as a supportive diagnostic tool in ED settings.

Polarized epidermal growth factor secretion ensures robust vulval cell fate specification in Caenorhabditis elegans.

The anchor cell (AC) in C. elegans secretes an epidermal growth factor (EGF) homolog that induces adjacent vulval precursor cells (VPCs) to differentiate. The EGF receptor in the nearest VPC sequesters the limiting EGF amounts released by the AC to prevent EGF from spreading to distal VPCs. Here, we show that not only EGFR localization in the VPCs but also EGF polarity in the AC is necessary for robust fate specification. The AC secretes EGF in a directional manner towards the nearest VPC. Loss of AC polarity causes signal spreading and, when combined with MAPK pathway hyperactivation, the ectopic induction of distal VPCs. In a screen for genes preventing distal VPC induction, we identified sra-9 and nlp-26 as genes specifically required for polarized EGF secretion. sra-9(lf) and nlp-26(lf) mutants exhibit errors in vulval fate specification, reduced precision in VPC to AC alignment and increased variability in MAPK activation. sra-9 encodes a seven-pass transmembrane receptor acting in the AC and nlp-26 a neuropeptide-like protein expressed in the VPCs. SRA-9 and NLP-26 may transduce a feedback signal to channel EGF secretion towards the nearest VPC.

Odontoid fracture in geriatric patients - analysis of complications and outcome following conservative treatment vs. ventral and dorsal surgery.

BACKGROUND: Different treatment options are discussed for geriatric odontoid fracture. The aim of this study was to compare the treatment options for geriatric odontoid fractures. METHODS: Included were patients with the following criteria: age ≥ 65 years, identification of seniors at risk (ISAR score ≥ 2), and odontoid fracture type A/B according to Eysel and Roosen. Three groups were compared: conservative treatment, surgical therapy with ventral screw osteosynthesis or dorsal instrumentation. At a follow-up examination, the range of motion and the trabecular bone fracture healing rate were evaluated. Furthermore, demographic patient data, neurological status, length of stay at the hospital and at the intensive care unit (ICU) as well as the duration of surgery and occurring complications were analyzed. RESULTS: A total of 72 patients were included and 43 patients could be re-examined (range: 2.7 ± 2.1 months). Patients with dorsal instrumentation had a better rotation. Other directions of motion were not significantly different. The trabecular bone fracture healing rate was 78.6%. The patients with dorsal instrumentation were hospitalized significantly longer; however, their duration at the ICU was shortest. There was no significant difference in complications. CONCLUSION: Geriatric patients with odontoid fracture require individual treatment planning. Dorsal instrumentation may offer some advantages.

Pediatric cervical spine injuries-results of the German multicenter CHILDSPINE study.

OBJECTIVES: The aim of this study was to provide epidemiological data of pediatric patients suffering from cervical spinal trauma in Germany, in order to integrate these data in future decision-making processes concerning diagnosis and therapy. MATERIALS AND METHODS: Retrospective multicenter study includes all patients up to 16 years suffering from cervical spine injuries who were treated in six German spine centers between 01/2010 and 12/2016. The clinical databases were screened for specific trauma mechanism, level of injury as well as accompanying injuries. Diagnostic imaging and the chosen therapy were analyzed. Patients were divided into three age groups for further evaluation: age group I (0-6 years), age group II (7-9 years), age group III (10-16 years). RESULTS: A total of 214 children with 265 cervical spine injuries were included during the mentioned period. The mean age at the time of injury was 11.9 (± 3.9) years. In age group I, 24 (11.2%) patients were included, age group II consisted of 22 patients (10.3%), and 168 patients belonged to age group III (78.5%). Girls and boys were equally affected. In all age groups, falls and traffic accidents were the most common causes of cervical spine injuries. A total of 180 patients (84.1%) were treated conservatively, while 34 (15.9%) children underwent surgery. Distorsion/whiplash injury was the most common entity (n = 165; 68.2%). Children aged 0-9 years had significantly (p < 0.001) more frequent injuries of the upper cervical spine (C0-C2) compared to older age groups. Patients of age group III were more likely to suffer from injuries in subaxial localizations. Neurological deficits were rarely seen in all age groups. Head injuries did represent the most common accompanying injuries (39.8%, n = 92). CONCLUSIONS: The upper cervical spine was more frequently affected in young children. Older children more often suffered from subaxial pathologies. The majority of cervical spinal column injuries were treated conservatively. Nevertheless, 15% of the hospitalized children had to be treated surgically.

Towards a somatosensory theory of speech perception.

Speech perception is known to be a multimodal process, relying not only on auditory input but also on the visual system and possibly on the motor system as well. To date there has been little work on the potential involvement of the somatosensory system in speech perception. In the present review, we identify the somatosensory system as another contributor to speech perception. First, we argue that evidence in favor of a motor contribution to speech perception can just as easily be interpreted as showing somatosensory involvement. Second, physiological and neuroanatomical evidence for auditory-somatosensory interactions across the auditory hierarchy indicates the availability of a neural infrastructure that supports somatosensory involvement in auditory processing in general. Third, there is accumulating evidence for somatosensory involvement in the context of speech specifically. In particular, tactile stimulation modifies speech perception, and speech auditory input elicits activity in somatosensory cortical areas. Moreover, speech sounds can be decoded from activity in somatosensory cortex; lesions to this region affect perception, and vowels can be identified based on somatic input alone. We suggest that the somatosensory involvement in speech perception derives from the somatosensory-auditory pairing that occurs during speech production and learning. By bringing together findings from a set of studies that have not been previously linked, the present article identifies the somatosensory system as a presently unrecognized contributor to speech perception.

Long-term results of cryopreserved allografts in aortoiliac graft infections.

OBJECTIVE: Different graft materials have been proposed for in situ reconstruction in the setting of vascular graft infection (VGI). We analyzed the long-term outcomes after in situ aortoiliac reconstruction with cryopreserved allografts. METHODS: We performed a retrospective analysis of patients who had undergone in situ aortoiliac reconstruction with cryopreserved arterial allografts for VGI from 2000 to 2015. The end points were the perioperative and long-term mortality and graft-related complications, including stenosis, occlusion, pseudoaneurysm, and reinfection. RESULTS: A total of 33 patients (91% male) with a median age of 67 years (range, 53-83 years) had undergone in situ aortoiliac reconstruction with cryopreserved allografts. The 30-day mortality was 6% (n = 2); both deaths were related to the allograft (one early allograft-enteric fistula and one graft rupture). Another two patients had experienced early (≤30 days) graft-related events (one allograft-enteric fistula and one graft limb occlusion), for an early graft-related complication rate of 12% (n = 4). Of the 31 discharged patients, 13 (42%) had died after a median of 47 months (range, 2-97 months). The median follow-up for the 18 remaining patients was 96 months (range, 10-146 months). The estimated survival at 1, 3, and 5 years was 88%, 81%, and 66%, respectively. Nine patients (29%) had experienced at least one of the following graft-related events during follow-up, including graft stenosis requiring intervention in five (16%), graft occlusion in four (13%), pseudoaneurysm in three (10%), and reinfection in two patients (6%). The estimated freedom from any first graft-related event at 1, 3, and 5 years was 78%, 71%, and 62%, respectively. The estimated primary patency and primary assisted patency at 1 and 3 years was 87% and 79%, and 90% and 83%, respectively. CONCLUSIONS: In situ aortoiliac reconstruction with cryopreserved allografts to treat VGI was associated with relevant perioperative graft-related complications. Although the reinfection rate was acceptable, other graft-related complications were frequent in the long term, in particular, graft occlusion and stenosis.

Mid-regional pro-atrial natriuretic peptide independently predicts short-term mortality in COVID-19.

BACKGROUND: Mid-regional pro-atrial natriuretic peptide (MR-proANP) is a strong prognostic marker in several inflammatory, respiratory and cardiovascular conditions, but has not been studied in COVID-19 yet. METHODS: This prospective, observational study of patients with COVID-19 infection was conducted from 6 June to 26 November 2020 in different wards of a tertiary hospital. MR-proANP, N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitive cardiac troponin I levels on admission were collected and tested for their association with disease severity and 28-day mortality. RESULTS: A total of 213 eligible patients with COVID-19 were included in the final analyses of whom 13.2% (n = 28) died within 28 days. Median levels of MR-proANP at admission were significantly higher in nonsurvivors (307 pmol/L IQR, [161 - 532] vs 75 pmol/L [IQR, 43 - 153], P < .001) compared to survivors and increased with disease severity and level of hypoxaemia. The area under the ROC curve for MR-proANP predicting 28-day mortality was 0.832 (95% CI 0.753 - 0.912, P < .001). An optimal cut-off point of 160 pmol/L yielded a sensitivity of 82.1% and a specificity of 76.2%. MR-proANP was a significant predictor of 28-day mortality independent of clinical confounders, comorbidities and established prognostic markers of COVID-19 (HR 2.77, 95% CI 1.21 - 6.37; P = .016), while NT-proBNP failed to independently predict 28-day mortality and had a numerically lower AUC compared to MR-proANP. CONCLUSION: Higher levels of MR-proANP at admission are associated with disease severity of COVID-19 and act as a powerful and independent prognostic marker of 28-day mortality.

Effect of marathon and ultra-marathon on inflammation and iron homeostasis.

The physiological response to high-level endurance exercise, such as running a marathon, poses several beneficial but also potentially harmful metabolic changes. The objective of this study was to determine the impact of marathon (M) and ultra-marathon (UM) on inflammation and iron homeostasis in paired samples. Fifteen well-trained, non-professional endurance athletes (14 males, 1 female) performed both a 130 km ultra-marathon and a traditional 42.195 km marathon. We determined markers of inflammation and iron homeostasis before, immediately after, and within 5 days after finishing each run, respectively. Biomarkers of inflammation (leucocytes, neutrophil granulocytes, monocytes, and c-reactive protein [CRP]) increased significantly after both marathon and ultra-marathon with higher levels of CRP after ultra-marathon compared with marathon both immediately after the race (18.15 ± 12.41 vs 5.58 ± 9.65 mg/L, P < .001) and at follow-up (15.67 ± 16.97 vs 7.19 ± 7.75 mg/L, P = .045) Concentrations of ferritin also increased significantly after both races and remained high at follow-up. Higher levels of ferritin immediately after the race (111.5 ± 103.2 vs 84.8 ± 86.3, P = .001) and at follow-up (102.7 ± 79.5 vs 74.6 ± 65.6, P = .001) were found in ultra-marathon finishers. The observed increase of serum iron and transferrin saturation (TSAT) after marathon and the decrease of serum iron and TSAT after ultra-marathon resulted in a significant absolute difference between the two races. The present data suggest a higher degree of inflammation after ultra-marathon compared with marathon. Markers of iron homeostasis also showed different response patterns with regard to running distance.

Long-term outcome and survival rate of monopolar radial head replacement.

BACKGROUND: The purposes of this study were (1) to report functional outcomes; (2) to assess complications, revisions, and survival rate; and (3) to assess differences in functional outcomes between removed and retained radial head arthroplasties (RHAs), early and delayed treatment, and type of RHA used at long-term follow-up after monopolar RHA for unreconstructible radial head fractures or their sequelae. METHODS: Seventy-eight patients (mean age, 59.2 years) who were at least 6 years postoperatively after monopolar RHA for unreconstructible RHFs or their sequelae were included. The Mayo Elbow Performance Score (MEPS); Quick Disability of the Arm, Shoulder, and Hand (QuickDASH) score; visual analog scale; postoperative satisfaction (1-6, 6 = highly unsatisfied); range of motion; complications; and revisions were assessed. Radiographic findings were reported. Kaplan-Meier survival analysis was performed. Subgroups (RHA type, early vs. delayed surgery, RHA removed vs. retained) were compared. RESULTS: At a median clinical follow-up of 9.5 years (range: 6.0-28.4 years), median MEPS was 80.0 (interquartile range [IQR]: 60.0-97.5), median QuickDASH was 22.0 (IQR: 4.6-42.6), median visual analog scale was 1 (IQR: 0-4), median postoperative satisfaction was 2 (IQR: 1-3), and median arc of extension/flexion was 110° (IQR: 80°-130°). Radiographic follow-up was available for 48 patients at a median of 7.0 years (range: 2.0-15.0 years). Heterotopic ossifications were seen in 14 (29.2%), moderate-to-severe capitellar osteopenia/abrasion in 3 (6.1%), moderate-to-severe ulnohumeral degeneration in 3 (6.1%), and periprosthetic radiolucencies in 17 (35.4%) patients. Twenty-nine patients (37.2%) had complications and 20 patients (25.6%) underwent RHA exchange or removal. Kaplan-Meier analysis with failure defined as RHA exchange or removal demonstrated survival of 75.1% (95% confidence interval: 63.7-83.3) at 18 years. The highest annual failure rate was observed in the first year in which the RHAs of 7 patients (9%) were exchanged or removed. No significant differences were detected between type of RHA in MEPS (Mathys: 82.5 [75.0-100] vs. Evolve: 80.0 [60.0-95.0]; P = .341) and QuickDASH (Mathys: 12.5 [0-34.4] vs. Evolve: 26.7 [6.9-46.2]; P = .112). Early surgery (≤3 weeks) yielded significantly superior MEPS (80.0 [70.0-100.0] vs. 52.5 [30.0-83.8]; P = .014) and QuickDASH (18.6 [1.5-32.6] vs. 46.2 [31.5-75.6]; P = .002) compared with delayed surgery (>3 weeks). Patients with retained RHAs had significantly better MEPS (80.0 [67.5-100] vs. 70.0 [32.5-82.5]; P = .016) and QuickDASH (18.1 [1.7-31.9] vs. 49.1 [22.1-73.8]; P = .007) compared with patients with removed RHAs. CONCLUSIONS: Long-term outcomes for RHA are satisfactory; however, there is a high complication and revision rate, resulting in implant survival of 75.1% at 18 years with the highest annual failure rate observed in the first postoperative year.

[The position of the head during treatment in the emergency room-an explorative analysis of immobilization of the cervical spine]. / Die Lagerung des Kopfes während der Behandlung im Schockraum ­ eine explorative Analyse über die Immobilisation der Halswirbelsäule.

BACKGROUND: Immobilization of the cervical spine is a standard procedure in emergency medicine mostly achieved via a cervical collar. In the emergency room other forms of immobilization are utilized as cervical collars have certain drawbacks. The present study aimed to provide preliminary data on the efficiency of immobilization in the emergency room by analyzing the residual spinal motion of the patient's head on different kinds of head rests. METHODS: In the present study biomechanical motion data of the cervical spine of a test subject were analyzed. The test subject was placed in a supine position on a mobile stretcher (Stryker M1 Roll-In System, Kalamazoo, MI, USA) wearing a cervical collar (Perfit ACE, Ballerup, Denmark). Three different head rests were tested: standard pillow, concave pillow and cavity pillow. The test subject carried out a predetermined motion protocol: right side inclination, left side inclination, flexion and extension. The residual spinal motion was recorded with wireless motion trackers (inertial measurement unit, Xsens Technologies, Enschede, The Netherlands). The first measurement was performed without a cervical collar or positioning on the pillows to measure the physiological baseline motion. Subsequently, three measurements were taken with the cervical collar applied and the pillows in place. From these measurements, a motion score was calculated that can represent the motion of the cervical spine. RESULTS: When the test subject's head was positioned on a standard pillow the physiological motion score was reduced from 69 to 40. When the test subject's head was placed on concave pillow the motion score was further reduced from 69 to 35. When the test subject's head was placed on cavity pillow the motion score was reduced from 69 to 59. The observed differences in the overall motion score of the cervical spine are mainly due to reduced flexion and extension rather than rotation or lateral inclination. CONCLUSION: The motion score of the cervical spine using motion sensors can provide important information for future analyses. The results of the present study suggest that trauma patients can be immobilized in the early trauma phase with a cervical collar and a head rest. The application of a cervical collar and the positioning on the concave pillow may achieve a good immobilization of the cervical spine in trauma patients in the early trauma phase.

Rotation in an Enantiospecific Self-Assembled Array of Molecular Raffle Wheels.

Tailored nano-spaces can control enantioselective adsorption and molecular motion. We report on the spontaneous assembly of a dynamic system-a rigid kagome network with each pore occupied by a guest molecule-employing solely 2,6-bis(1H-pyrazol-1-yl)pyridine-4-carboxylic acid on Ag(111). The network cavity snugly hosts the chemically modified guest, bestows enantiomorphic adsorption and allows selective rotational motions. Temperature-dependent scanning tunnelling microscopy studies revealed distinct anchoring orientations of the guest unit switching with a 0.95 eV thermal barrier. H-bonding between the guest and the host transiently stabilises the rotating guest, as the flapper on a raffle wheel. Density functional theory investigations unravel the detailed molecular pirouette of the guest and how the energy landscape is determined by H-bond formation and breakage. The origin of the guest's enantiodirected, dynamic anchoring lies in the specific interplay of the kagome network and the silver surface.

Steroid 17-Hydroxyprogesterone in Hair Is a Potential Long-Term Biomarker of Androgen Control in Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency.

INTRODUCTION: To evaluate scalp hair steroid concentrations as a monitoring tool for androgen control and metabolic outcomes in adults with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. METHODS: 17-hydroxyprogesterone (17-OHP), androstenedione, testosterone, cortisol, cortisone, progesterone, prednisolone, and prednisone concentrations were measured in scalp hair by means of LC-MS/MS in 27 women and 15 men with CAH and controls (37 women, 42 men). RESULTS: In CAH men and women, 17-OHP levels in hair showed a significant positive correlation with corresponding levels in serum (ρ = 0.654; p = 0.01; ρ = 0.553, p = 0.003 respectively), while total testosterone levels were only significantly correlated in CAH men (ρ = 0.543; p = 0.036). Androstenedione levels did not show a significant correlation. Receiver-operating characteristic (ROC) curve analysis indicated that a cutoff value of 21.7 pg/mg for 17-OHP in hair provided a sensitivity of 100% and a specificity of 88.9% for identifying men with elevated serum androstenedione. Hair 17-OHP in women showed a poorer performance in terms of identifying those with elevated androstenedione serum levels. However, when applying a cutoff value of 5.5 for the free androgen index as a marker of significant hyperandrogenism in CAH women, 17-OHP >27.6 pg/mg in hair provided a sensitivity of 100% and a specificity of 95.8% (AUC 0.986, 95% CI 0.945-1.000; p < 0.001). Neither hair cortisol nor markers of adrenal androgen control in hair showed significant associations with cardiometabolic outcome or bone health. CONCLUSION: This study shows that scalp hair 17-OHP concentrations may be a promising noninvasive long-term parameter for treatment monitoring in adult patients with CAH.

Sexual Behavior, Desire, and Psychosexual Experience in Gynephilic and Androphilic Trans Women: A Cross-Sectional Multicenter Study.

BACKGROUND: One of the most prominent etiological theories of gender incongruence in trans women proposes a paraphilic erotic target location error (ie, autogynephilia) as a causal factor in gynephilic (ie, exclusively gynephilic and bisexual) trans women. We hypothesized that a paraphilic erotic target location should manifest itself in various aspects of sexual behavior, solitary and dyadic sexual desire, and psychosexual experience. AIM: To compare sexual behavior, sexual desire, and psychosexual experience of exclusively gynephilic and bisexual trans women with that of androphilic trans women to explore whether their sexuality differs substantially. METHODS: Trans women diagnosed with gender dysphoria (Diagnostic and Statistical Manual of Mental Disorders-5) were recruited at 4 transgender healthcare centers in Germany. The present study analyzed items on sexual behavior, desire, and experience of a self-report questionnaire, collected as part of a cross-sectional multicenter study. MAIN OUTCOMES: Multiple aspects of sexuality were examined using self-constructed items. Sexual desire was measured using the Sexual Desire Inventory and psychosexual experience using the Multidimensional Sexuality Questionnaire. RESULTS: Significantly more exclusively gynephilic than androphilic trans women reported a history of sexual arousal in relation to cross-dressing. However, little evidence was found that gynephilic and androphilic sexual desire, behavior, and psychosexual experience differ profoundly. Interestingly, a statistically non-significant trend indicated that gynephilic trans women who had not yet undergone gender affirming surgery showed the highest levels of sexual desire (solitary and dyadic), whereas the opposite was the case for androphilic trans women. CLINICAL TRANSLATION: Data of this study indicate that sexual orientation does not appear to be a good predicator for sexual behavior, desire, and psychosexual experience in trans women. STRENGTHS AND LIMITATIONS: We investigated sexual desire and experience using standardized and evaluated measures such as the Sexual Desire Inventory and Multidimensional Sexuality Questionnaire. Future studies with a larger sample size should investigate how different gender affirming medical intervention might have diverging influences on sexual behavior, desire, and experience. CONCLUSION: Ultimately, this study found little evidence for the hypothesis that sexual behavior, sexual desire, and psychosexual experience differ substantially in gynephilic (exclusively gynephilic and bisexual) and androphilic trans women. Laube JS, Auer M, Biedermann SV, et al. Sexual Behavior, Desire, and Psychosexual Experience in Gynephilic and Androphilic Trans Women: A Cross-Sectional Multicenter Study. J Sex Med 2020;17:1182-1194.