The Global Task Force for Chronic Pain in People with HIV (PWH): Developing a research agenda in an emerging field.

Chronic pain is a common comorbidity in people with HIV (PWH), with prevalence estimates of 25-85%. Research in this area is growing, but significant gaps remain. A Global Task Force of HIV experts was organized to brainstorm a scientific agenda and identify measurement domains critical to advancing research in this field. Experts were identified through literature searches and snowball sampling. Two online questionnaires were developed by Task Force members. Questionnaire 1 asked participants to identify knowledge gaps in the field of HIV and chronic pain and identify measurement domains in studies of chronic pain in PWH. Responses were ranked in order of importance in Questionnaire 2, which was followed by a group discussion. 29 experts completed Questionnaire 1, 25 completed Questionnaire 2, and 21 participated in the group. Many important clinical and research priorities emerged, including the need to examine etiologies of chronic pain in PWH. Pain-related measurement domains were discussed, with a primary focus on domains that could be assessed in a standardized manner across various cohorts that include PWH in different countries. We collaboratively identified clinical and research priorities, as well as gaps in standardization of measurement domains, that can be used to move the field forward.

Mid-infrared emissivity of partially dehydrated asteroid (162173) Ryugu shows strong signs of aqueous alteration.

The near-Earth asteroid (162173) Ryugu, the target of Hayabusa2 space mission, was observed via both orbiter and the lander instruments. The infrared radiometer on the MASCOT lander (MARA) is the only instrument providing spectrally resolved mid-infrared (MIR) data, which is crucial for establishing a link between the asteroid material and meteorites found on Earth. Earlier studies revealed that the single boulder investigated by the lander belongs to the most common type found on Ryugu. Here we show the spectral variation of Ryugu's emissivity using the complete set of in-situ MIR data and compare it to those of various carbonaceous chondritic meteorites, revealing similarities to the most aqueously altered ones, as well as to asteroid (101955) Bennu. The results show that Ryugu experienced strong aqueous alteration prior to any dehydration.

Generation of functional human serotonergic neurons from fibroblasts.

The brain's serotonergic system centrally regulates several physiological processes and its dysfunction has been implicated in the pathophysiology of several neuropsychiatric disorders. While in the past our understanding of serotonergic neurotransmission has come mainly from mouse models, the development of pluripotent stem cell and induced fibroblast-to-neuron (iN) transdifferentiation technologies has revolutionized our ability to generate human neurons in vitro. Utilizing these techniques and a novel lentiviral reporter for serotonergic neurons, we identified and overexpressed key transcription factors to successfully generate human serotonergic neurons. We found that overexpressing the transcription factors NKX2.2, FEV, GATA2 and LMX1B in combination with ASCL1 and NGN2 directly and efficiently generated serotonergic neurons from human fibroblasts. Induced serotonergic neurons (iSNs) showed increased expression of specific serotonergic genes that are known to be expressed in raphe nuclei. iSNs displayed spontaneous action potentials, released serotonin in vitro and functionally responded to selective serotonin reuptake inhibitors (SSRIs). Here, we demonstrate the efficient generation of functional human serotonergic neurons from human fibroblasts as a novel tool for studying human serotonergic neurotransmission in health and disease.

COMETARY SCIENCE. The structure of the regolith on 67P/Churyumov-Gerasimenko from ROLIS descent imaging.

The structure of the upper layer of a comet is a product of its surface activity. The Rosetta Lander Imaging System (ROLIS) on board Philae acquired close-range images of the Agilkia site during its descent onto comet 67P/Churyumov-Gerasimenko. These images reveal a photometrically uniform surface covered by regolith composed of debris and blocks ranging in size from centimeters to 5 meters. At the highest resolution of 1 centimeter per pixel, the surface appears granular, with no apparent deposits of unresolved sand-sized particles. The thickness of the regolith varies across the imaged field from 0 to 1 to 2 meters. The presence of aeolian-like features resembling wind tails hints at regolith mobilization and erosion processes. Modeling suggests that abrasion driven by airfall-induced particle "splashing" is responsible for the observed formations.

[Is the Intrahepatic Sound Speed an Indicator of the Fat Content of the Liver in Children?]. / Die intrahepatische Schallgeschwindigkeit als möglicher Parameter zur Abschätzung der Steatosis hepatis bei Kindern?

PURPOSE: Can the sonographically estimated intrahepatic sound speed give hints on the hepatic fat content in children? MATERIALS AND METHODS: In 75 children and adolescents the intrahepatic sound speed was estimated during routine sonography of the liver as a result of an image reconstruction algorithm. It was correlated with weight, age, size, and body mass index (BMI) oft he children, respectively. RESULTS: The average hepatic sound speed in children of normal weight was 1 566 m/s (standard deviation (STD) 29 m/s, in overweight or obese children it was 1 501 m/s (STD 22 m/s), and in obese children it was 1 497 ms (STD 24 m/s). The strongest correlation was found between sound speed and BMI of the children, respectively. The difference of sound speed in normal weighing subjects and overweight/obese children was statistically significant. CONCLUSION: There is a good correlation between the estimated intrahepatic sound speed and the fat content of the liver. Further examinations are encouraged.

[Metastases from a malignant melanoma as extensive, space-occupying lesion in the trachea]. / Metastasen eines malignen Melanoms als ausgedehnte Raumforderung in der Trachea.

We report the case of a 71-year-old man, who was transferred to our clinic with rapidly increasing dyspnea. On examination by flexible bronchoscopy the trachea was found to be almost completely obstructed by metastatic masses of a malignant melanoma. After endoscopic removal of the obstruction, we inserted a covered nitinol stent which led to instantaneous relief of symptoms. Chemotherapy and local radiotherapy were instituted. During the next 9 months there were no signs of recurrence of the tumour in regular pneumological control exams.

[Sentinel lymph node dissection in prostate cancer. Experience after more than 800 interventions]. / Sentinel-Lymphadenektomie beim Prostatakarzinom. Erfahrungen nach über 800 Eingriffen.

There is no consensus on which prostate cancer patients should undergo lymph node removal and which lymph nodes should be included. Therefore, most clinicians rely on nomograms and dispense with lymph node dissection in patients with low-risk disease. Meanwhile, there are some studies which prove that there are also lymph node metastases in patients with low-risk prostate cancer and that lymph node metastases are predominantly localized outside the region of standard lymphadenectomy. In more than 800 men we could show that lymph node metastases were found more often than shown in the Partin tables. These lymph node metastases were detected by sentinel lymph node dissection outside the region of standard and extended lymphadenectomy. Because of insufficient preoperative diagnostics it is unclear which patients have positive lymph nodes. Therefore, it is useful to perform lymph node dissection in every patient. Men with positive nodes could have a better prognosis, when sentinel and extended lymph node dissection are performed.

[Nocardia brasiliensis leg ulcer and nodular lymphangitis in France]. / Ulcère de jambe et lymphangite nodulaire à Nocardia brasiliensis en France métropolitaine.

INTRODUCTION: Nocardia brasiliensis is a very rarely reported cause of chronic phagedenic ulcerations. We report the case of an elderly woman who developed such an infection after falling on her right leg on the road in the Bresse country (an essentially agricultural and bovine-cattle breading region) and developed a chronic phagedenic ulcer secondarily complicated by nodular lymphangitis of the thigh. CASE REPORT: A 75 year-old woman fell on her right leg on the side of the main road outside her hamlet in the Bresse country and secondarily developed a chronique phagedenic ulceration. We first considered her as suffering from pyoderma gangrenosum. A complete scanning only revealed an autoimmune thyroiditis and a rapidly healing gastric ulceration, and none of the treatments, either local or systemic, helped the skin condition to heal. After 3 weeks of application of a local corticoid ointment, the patient developed fever, general malaise, an exacerbation of her wound and an infiltration of the skin round her knee, together with nodular lymphangitic dissemination. A supplementary bacterial swab disclosed massive proliferation of a slow-growing Gram-positive bacillus, which proved to be Nocardia brasiliensis, together with a methicillino-sensitive Staphylococcus aureus. The treatment with sulfamethoxazole-trimetoprim gave a rash after 12 hours and was changed to amoxicillin and clavulanic acid, which rapidly proved to be permanently effective. DISCUSSION: The revelation of this particular slow-growing bacteria is difficult and requires bacterial swabs. Nocardia brasiliensis is relatively rare in primary skin ulcerations and we discuss the reasons why an elderly women should find this bacteria on the road outside her hamlet in the French countryside. This particular infectious condition requires general scanning, to make sure that the primary skin condition does not extend to other organs. We review the therapeutical options for patients who exhibit allergic reactions to the classically effective antibiotic drugs.

Correlation between mouse potency and in vitro relative potency for human papillomavirus Type 16 virus-like particles and Gardasil vaccine samples.

An in vitro relative potency (IVRP) assay has been developed as an alternative to the mouse potency assay used to release Merck's human papillomavirus (HPV) vaccine, Gardasil, for early phase clinical trials. The mouse potency assay is a classical, in vivo assay, which requires 4-6 weeks to complete and exhibits variability on the order of 40% relative standard deviation (RSD). The IVRP assay is a sandwich-type immunoassay that is used to measure relative antigenicity of the vaccine product. The IVRP assay can be completed in three days, has a variability of approximately 10% RSD and does not require the sacrifice of live animals. Because antigen detection is achieved using H16.V5, a neutralizing monoclonal antibody, which binds to a clinically-relevant epitope, the relative antigenicity measured by the IVRP assay is believed to be a good predictor of in vivo potency. In this study, the relationship between immunogenicity, as measured by the mouse potency assay and antigenicity as measured by the IVRP assay, is demonstrated. Freshly manufactured and aged samples produced using two different manufacturing processes were tested using both methods. The results demonstrate that there is an inverse correlation between the IVRP and mouse potency assays. Additionally, clinical results indicate IVRP is predictive of human immunogenicity. Thus, antigenicity, as defined by the H16.V5 epitope, can be used as a surrogate for immunogenicity and the IVRP assay is suitable for use as the sole potency test for Gardasil samples.

Nematic-amorphous polymer interfaces in the presence of a compatibilizer.

We introduce and apply a variant of a dynamic self-consistent field simulation in two dimensions to predict the structure of interfaces between a nematic and an amorphous polymer compatibilized by a diblock copolymer. First, we investigate the effect of the nematic order on the polymer polymer interface without compatibilizer. Then we include the compatibilizer and consider two interfacial setups previously used in experiments, i.e., the bilayer setup and the trilayer setup. In the bilayer setup the diblock copolymer is mixed into the amorphous homopolymer and migrates to the interface in the course of the simulation forming a layered structure. We compare the amount of copolymer at the interface for initial concentrations of the copolymer below and above the critical micelle concentration. In the trilayer setup the initial thickness of the diblock copolymer is varied. The resulting interfacial morphology evolves in the competition between the lamellar structure induced by the interface and a micellar structure, which is intrinsic to the copolymer.

[CT in ureterolithiasis with a radiation dose equal to intravenous urography: results in 209 patients]. / CT der Ureterolithiasis mit der Strahlendosis einer Ausscheidungsurographie: Ergebnisse bei 209 Patienten.

PURPOSE: To evaluate a low-dose, nonenhanced helical CT protocol for the diagnosis of renal colic using an effective dose equivalent of radiation not higher than that of intravenous urography. MATERIALS AND METHODS: A new low-dose helical-CT protocol (120 kV; 70 mA; rotation time 0.75 s; collimation 5 mm, pitch = 2) was used to examine 209 consecutive patients with symptoms of renal colic. The initial CT reports were compared with retrograde ureterography, ureteral endoscopy, stone retrieval, surgical or clinical findings. The effective radiation dose was calculated by the method published by Nagel. The prevalence of ureterolithiasis was 70 %. RESULTS: Sensitivity and specificity of the low-dose-helical CT in detecting ureteral calculi were 97.7 % and 96.8 %, respectively. The positive predictive value was 99.3 % and negative predictive value 92.4 %. The mean effective radiation dose equivalent was 0.97 mSv in male and 1.35 mSv in female patients. CONCLUSIONS: The diagnostic value of the reported CT protocol does no differ from previously published protocols. However, the effective radiation dose equivalent is at least 50 % lower than stated in the published protocols. We recommend the low-dose helical CT protocol as the method of choice.

[Imatinib-induced purpuric vasculitis]. / Vasculite purpurique induite par l'imatinib.

INTRODUCTION: Imatinib (Glivec) is a new molecule that specifically inhibits tyrosine-kinase activity and is used in the treatment of chronic myeloid leukemia. Cutaneous side effects with imatinib are frequent. We report the first case of purpuric vasculitis probably due to this drug. OBSERVATION: A 65 year-old man was treated for chronic myeloid leukemia with imatinib. After two months of treatment, he developed an erythematous and squamatous on the trunk, which regressed spontaneously one week after suspension of the product. Imatinib was reintroduced two months later. The patient immediately developed a painful, infiltrated, purpuric eruption on the legs. Histological examination revealed vasculitis compatible with the diagnosis of toxiderma. Since treatment could not be suspended, oral corticosteroids were introduced and the lesions cleared within three weeks. DISCUSSION: Adverse cutaneous reactions to imatinib are frequent. Their physiopathological mechanism is unknown.

Changes in the cell wall network during the thermal dehydration of alfalfa stems.

The effects of heat treatments used to dry alfalfa stems were investigated. Heating at 70 or 100 degrees C caused no major change in the cell wall composition, but xylanase had lower activity on the cell wall of heated material and the amount of xylose released varied with the temperature used. Chemical fractionation of cell wall carbohydrates showed that the main changes occurring during stem dehydration concerned pectic polymers and probably hemicelluloses. There was less material soluble in ammonium oxalate from alfalfa heated at 100 degrees C than from fresh alfalfa. The results suggest that heat processing causes some changes in the cell wall network. Environmental scanning electron microscopy was used to examine fully hydrated tissues at high resolution. There was cell distortion without disruption of cell walls as water was lost.

Radioisotope guided pelvic lymph node dissection for prostate cancer.

PURPOSE: The localization of lymph node metastases in prostate cancer varies enormously. Due to high morbidity complete pelvic lymphadenectomy is often decreased to modified staging lymphadenectomy, resulting in loss of sensitivity for detecting micrometastases. Based on the promising results of intraoperative gamma probe application for identifying sentinel lymph nodes in malignant melanoma, breast and penis cancer, we identified sentinel lymph nodes in prostate cancer using a comparable technique. MATERIALS AND METHODS: In 117 patients 99mtechnetium nanocolloid was transrectally injected directly into the prostate under ultrasound guidance 1 day before pelvic lymphadenectomy. Thereafter dynamic lymphoscintigraphy was done. Initially lymph nodes identified as sentinel lymph nodes by the gamma probe were removed and subsequently modified pelvic lymphadenectomy was performed. RESULTS: Lymphatic metastasis was detected in 28 cases. An average of 4 sentinel lymph nodes were identified per patient in 25 of 27 patients with micrometastasis, of which those in 24 contained micrometastasis for 96% sensitivity. In contrast, sensitivity of modified pelvic lymphadenectomy was 81.5%. In 16 patients only sentinel lymph nodes were positive. An average of 21.8 lymph nodes (range 10 to 51) was dissected per patient at pelvic lymphadenectomy. Lymph node metastasis was noted in 6 of the 46 patients with a prostate specific antigen between 4 and 10 ng./ml. and in 8 of the 64 with a stage pT2 tumor. CONCLUSIONS: Our study shows individual variability of lymphatic drainage of the prostate and limited sensitivity for detecting positive lymph nodes when the pelvic dissection area is limited. Furthermore, our experience implies that the identification of sentinel lymph nodes is feasible, not only in breast cancer and malignant melanoma, but also in prostate cancer using a comparable technique.

[Unenhanced spiral computerized tomography in acute diagnosis of flank pain. Examination in contraindications for contrast medium administration]. / Native Spiral-Computertomographie in der Akutdiagnostik von Flankenschmerzen. Untersuchung bei Kontraindikationen zur Kontrastmittelgabe.

The diagnostic value of unenhanced helical computed tomography was investigated in a prospective study. In 53 patients (aged 35 to 82 years) with acute flank pain tomography was performed in addition to abdominal plain film and ultrasound examination. All 53 patients had a contraindication for intravenous administration of contrast medium. Ureteral calculi were either confirmed or excluded by retrograde ureteropyelography in 44 cases, in 9 patients by asservation of calculi and clinical follow-up. Helical computed tomography was able to precisely identify all of the 34 ureteral calculi, whereas abdominal plain films led to 6 false positive and 17 false negative findings. In 1 patient with retroperitoneal lymphoma (diagnosed by CT) false positive findings occurred. Unenhanced helical computed tomography reaches a distinctively increased diagnostic value (sensitivity 100%, specificity 95%, accuracy 97%) in the evaluation of acute flank pain as compared to conventional radiologic imaging and ultrasound. This non-invasive procedure is to be considered method of choice for patients with contraindications for the application of radiopaque material.

Biochemical course after radical retropubic prostatectomy: preliminary results.

OBJECTIVE: To investigate prognostic factors in localized and lymphatically spread prostate cancer. METHODS: The biochemical course after radical retropubic prostatectomy in 306 patients was subject to a retrospective analysis. RESULTS: Prostate-specific antigen (PSA), Gleason score (prostatectomy specimen) and pathological stage proved to be prognostically relevant (p < 0.0001). PSA, Gleason score and tumor stage also were to be considered as (independent) prognostic factors by means of a multivariate analysis (p < 0.001), whereas perineural invasion (prostatectomy specimen) and preoperative bone marrow findings (CK 2) had no impact on the course of the disease. After a median follow-up of 1,307 days (3.6 years), a biochemical relapse occurred in 41.8%. CONCLUSION: High preoperative PSA values and the resulting high portion of advanced tumor stages are a possible basis for the high biochemical relapse rate in our collective. The learning curves of several surgeons and the previously more restrictive pelvic lymphadenectomy (surgical understaging) may also be considered causes.