High prevalence of missed information related on bone health in orthogeriatric patients with fragility fractures of the pelvis-an institutional register-based analysis.

This is the first study that highlighted the amount of missed information related on bone health in orthogeriatric patients suffering fragility fractures of the pelvis and also evaluated its prevalence and differing etiology in the assessed patients, regarding osteoporosis and/or osteomalacia, based on laboratory and instrumental measurements. This evaluation should become a standardized procedure in the treatment of orthogeriatric patients presenting with a FFP. INTRODUCTION: Fragility fractures of the pelvis (FFP) are common in orthogeriatric patients. Secondary fracture prevention regarding evaluation and treatment of an underlying osteoporosis or osteomalacia is still often neglected. The purpose of this study was to evaluate the amount of missed information related on bone health in older adult FFP patients, the prevalence of vitamin D deficiency in assessed patients, and if fracture type-dependent distribution patterns could be observed. METHODS: A retrospective analysis of prospectively collected data of an institutional register was performed. Patients aged 80 years and older (n = 456) admitted with a FFP from 01/2003 until 12/2019 to a level I trauma center were included. RESULTS: In 456 patients, FFP type II were leading (66.7%). Diagnostics were conducted in 37.1% of the patients regarding measurement of vitamin D levels and 21.7% regarding DXA measurements; vitamin D deficiency was observed in 62.7%, indicators for an underlying osteomalacia in 45.8%, and an osteoporosis in 46.5% of the assessed patients. CONCLUSION: Although FFP are common and will increase, there is still a lack of secondary fracture prevention, starting with information related on bone health. In the assessed patients, a high prevalence of vitamin D deficiency was present, but no significant correlation between vitamin D level and type of fracture was observed. Ongoing education for varying etiology and specific treatment of these fractures is necessary, as surgical treatment was unified, but drug therapy remains different.

ITSN1 regulates SAM68 solubility through SH3 domain interactions with SAM68 proline-rich motifs.

SAM68 is an mRNA-binding protein involved in mRNA processing in the nucleus that forms membraneless compartments called SAM68 Nuclear Bodies (SNBs). We found that intersectin 1 (ITSN1), a multidomain scaffold protein harboring five soluble SH3 domains, interacts with SAM68 proline-rich motifs (PRMs) surrounded by self-adhesive low complexity domains. While SAM68 is poorly soluble in vitro, the interaction of ITSN1 SH3 domains and mRNA with SAM68 enhances its solubility. In HeLa cells, the interaction between the first ITSN1 SH3 domain (SH3A) and P0, the N-terminal PRM of SAM68, induces the dissociation of SNBs. In addition, we reveal the ability of another SH3 domain (SH3D) of ITSN1 to bind to mRNAs. ITSN1 and mRNA may thus act in concert to promote SAM68 solubilization, consistent with the absence of mRNA in SNBs in cells. Together, these results support the notion of a specific chaperoning of PRM-rich SAM68 within nuclear ribonucleoprotein complexes by ITSN1 that may regulate the processing of a fraction of nuclear mRNAs, notably SAM68-controlled splicing events related to higher neuronal functions or cancer progression. This observation may also serve as a putative model of the interaction between other PRM-rich RBPs and signaling proteins harboring SH3 domains.

[S3 guidelines on the diagnosis and treatment of carcinoma of the endometrium : Requirements for pathology]. / S3-Leitlinie Diagnostik und Therapie des Endometriumkarzinoms : Anforderungen an die Pathologie.

The present article summarises the relevant aspects of the S3 guidelines on endometrioid carcinomas. The recommendations include the processing rules of fractional currettings as well as for hysterectomy specimens and lymph node resections (including sentinel lymph nodes). Besides practical aspects, the guidelines consider the needs of the clinicians for appropriate surgical and radiotherapeutic treatment of the patients. Carcinosarcomas are assigned to the endometrial carcinoma as a special variant. For the first time, an algorithmic approach for evaluation of the tumour tissue for Lynch syndrome is given. Prognostic factors based on morphologic findings are summarised.

Harvester ant colonies differ in collective behavioural plasticity to regulate water loss.

Collective behavioural plasticity allows ant colonies to adjust to changing conditions. The red harvester ant (Pogonomyrmex barbatus), a desert seed-eating species, regulates foraging activity in response to water stress. Foraging ants lose water to evaporation. Reducing foraging activity in dry conditions sacrifices food intake but conserves water. Within a year, some colonies tend to reduce foraging on dry days while others do not. We examined whether these differences among colonies in collective behavioural plasticity persist from year to year. Colonies live 20-30 years with a single queen who produces successive cohorts of workers which live only a year. The humidity level at which all colonies tend to reduce foraging varies from year to year. Longitudinal observations of 95 colonies over 5 years between 2016 and 2021 showed that differences among colonies, in how they regulate foraging activity in response to day-to-day changes in humidity, persist across years. Approximately 40% of colonies consistently reduced foraging activity, year after year, on days with low daily maximum relative humidity; approximately 20% of colonies never did, foraging as much or more on dry days as on humid days. This variation among colonies may allow evolutionary rescue from drought due to climate change.

p53 is correlated with low BMI negative progesterone receptor status and recurring disease in patients with endometrial cancer.

OBJECTIVE: P53 tumor suppressor gene plays a role in endometrial carcinogenesis. Former studies described correlations between p53 protein overexpression in endometrial cancer and prognostic factors, measured by immunohistochemistry. But data is still controversial. The aim of this study was to measure p53 and phospho-p53 overexpression by Western blot and evaluate correlations between overexpression and prognostic and clinical factors. Phospho-p53 seems to be the functional p53 protein and was examined for the first time in endometrial cancer. METHODS: 40 patients with endometrial cancer were included in the study. A control group of 20 patients with normal endometrial tissue samples was used. Western blot was performed for detection of p53 and phospho-p53. Clinical and pathological parameters were obtained from medical records. Statistical analysis was performed using the log-rank test, the Mann-Whitney test for two independent groups and the Fisher's exact test for dichotomous groupings. RESULTS: In 17.5% of the patients with endometrial cancer a p53 overexpression could be evaluated. There was a correlation between a p53 overexpression and recurring disease (p: 0.014), a negative progesterone receptor status (p: 0.021) and a low BMI (p: 0.022). Only one of 40 patients had a phospho-p53 expression. CONCLUSION: Western blot is a valid method for the detection of p53 overexpression. As other authors described before, p53 overexpression seems to correlate with negative prognostic factors. The correlation between p53 overexpression and a low BMI may underline the relationship between p53 alterations and biological aggressive endometrial carcinomas.

Morphological and tissue characterization of the medicinal fungus Hericium coralloides by a structural and molecular imaging platform.

In this study the potential of new imaging techniques such as Magnetic Resonance Imaging (MRI), Matrix-Assisted Laser Desorption/Ionization (MALDI) profiling mass spectrometry ("MALDI Profiling") and Fourier Transform Infrared (FTIR) spectroscopic imaging was evaluated to study morphological and molecular patterns of the potential medicinal fungus Hericium coralloides. For interpretation, the MALDI profiling, FTIR imaging and MRI results were correlated with histological information gained from Scanning Electron Microscopy (SEM) and Light Microscopy (LM). Additionally we tested several evaluation processes and optimized the methodology for use of complex FTIR images to monitor molecular patterns. It is demonstrated that the combination of these spectroscopic methods enables to gain a more distinct picture concerning morphology and distribution of active ingredients. We were able to obtain high quality FTIR imaging and MALDI-profiling results and to distinguish different tissue types with their chemical ingredients. Beside this, we have created a 3-D reconstruction of a mature Hericium basidioma, based on the MRI dataset: analyses allowed, for the first time, a realistic approximation of the "evolutionary effectiveness" of this bizarrely formed basidioma type, concerning the investment of sterile tissue and its reproductive output (production of basidiospores).

Reference values for blood flow velocity in the uterine artery in normal pregnancies from 18 weeks to 42 weeks of gestation calculated by automatic Doppler waveform analysis.

PURPOSE: The goal of the present study was to establish new Doppler reference ranges for maternal heart rate, intensity-weighted mean blood flow velocities (Vmean) and impedance indices (PI, RI) for the uterine artery by automated waveform analysis. MATERIALS AND METHODS: A cross-sectional prospective study of 921 low-risk pregnancies was performed at 18 - 42 weeks of gestation. Uterine blood flow velocities were derived with pulsed-wave color Doppler. Measurements were carried out 1 to 2 cm above the crossing of the uterine and external iliac arteries. Reference ranges for the individual measuring parameters were constructed based on a growth function from a four-parameter class of monotonic continuous functions according to the smallest square principle. RESULTS: A significant increase in intensity-weighted mean uterine blood flow velocities was observed at 18 - 42 weeks of gestation (Vmean = 43 cm/s to 50 cm/s (p < 0.001)). Reference curves for the pulsatility and resistance indices (PI, RI) significantly decreased with progressing gestation (PI: 18 weeks: 0.89; 42 weeks: 0.65 and RI: 18 weeks: 0.45; 42 weeks: 0.35). No significant PI and RI differences were observed when different placental locations were compared. The maternal heart rate decreased from 88 bpm to 77 bpm. CONCLUSION: Normal ranges for blood flow velocities and impedance indices in the uterine artery were established by Doppler ultrasound antenatal examinations of a large population of low-risk pregnancies. The data are proposed as reference curves to allow the early diagnosis of maternal and fetal risks.

ESTRO-ACROP guideline on surface guided radiation therapy.

Surface guidance systems enable patient positioning and motion monitoring without using ionising radiation. Surface Guided Radiation Therapy (SGRT) has therefore been widely adopted in radiation therapy in recent years, but guidelines on workflows and specific quality assurance (QA) are lacking. This ESTRO-ACROP guideline aims to give recommendations concerning SGRT roles and responsibilities and highlights common challenges and potential errors. Comprehensive guidelines for procurement, acceptance, commissioning, and QA of SGRT systems installed on computed tomography (CT) simulators, C-arm linacs, closed-bore linacs, and particle therapy treatment systems are presented that will help move to a consensus among SGRT users and facilitate a safe and efficient implementation and clinical application of SGRT.

Surface guided radiation therapy: An international survey on current clinical practice.

Introduction: Surface Guided Radiation Therapy (SGRT) is being increasingly implemented into clinical practice across a number of techniques and irradiation-sites. This technology, which is provided by different vendors, can be used with most simulation- and delivery-systems. However, limited guidelines and the complexity of clinical settings have led to diverse patterns of operation. With the aim to understand current clinical practice a survey was designed focusing on specifics of the clinical implementation and usage. Materials and methods: A 32-question survey covered: type and number of systems, quality assurance (QA), clinical workflows, and identification of strengths/limitations. Respondents from different professional groups and countries were invited to participate. The survey was distributed internationally via ESTRO-membership, social media and vendors. Results: Of the 278 institutions responding, 172 had at least one SGRT-system and 136 use SGRT clinically. Implementation and QA were primarily based on the vendors' recommendations and phantoms. SGRT was mainly implemented in breast RT (116/136), with strong but diverse representation of other sites. Many (58/135) reported at least partial elimination of skin-marks and a third (43/126) used open-masks. The most common imaging protocol reported included the combination of radiographic imaging with SGRT. Patient positioning (115/136), motion management (104/136) and DIBH (99/136) were the main applications.Main barriers to broader application were cost, system integration issues and lack of demonstrated clinical value. A lack of guidelines in terms of QA of the system was highlighted. Conclusions: This overview of the SGRT status has the potential to support users, vendors and organisations in the development of practices, products and guidelines.

Neoadjuvant chemoradiotherapy is superior to chemotherapy alone in surgically treated stage III/N2 non-small-cell lung cancer: a retrospective single-center cohort study.

BACKGROUND: There is lack of consensus whether neoadjuvant chemoradiotherapy (CHT/RT) is superior to neoadjuvant chemotherapy (CHT) alone in patients with potentially resectable stage III/N2 non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: We retrospectively evaluated clinical parameters and outcomes in patients with clinical stage III/N2 NSCLC treated with neoadjuvant CHT/RT versus CHT followed by surgery. Nearest-neighbor propensity score (PS) matching was used to correct for pretreatment differences. RESULTS: A total of 84 patients were enrolled. Thirty-four (40%) and 50 (60%) patients received CHT/RT or CHT followed by curative-intent surgery, respectively. Overall 90-day mortality and morbidity were 0% versus 0.04% and 21% versus 18%, respectively, with no significant difference between the CHT/RT and the CHT-alone cohorts (P = 0.51 and P = 0.70). In the PS-matched cohort, complete pathological response was recorded in 25% after CHT/RT versus 0% after CHT at the time of surgery. Patients receiving neoadjuvant CHT/RT exhibited significantly better 5-year disease-free survival (DFS) [45% versus 16% CHT group; hazard ratio (HR) 0.43, P = 0.04]; 5-year overall survival (OS) was 75% after CHT/RT and 21% after CHT (HR 0.37, P = 0.001). CHT/RT more often induced pathological mediastinal downstaging (P = 0.007), but CHT/RT remained the only independent factor for DFS and OS and did not depend on mediastinal downstaging. CONCLUSIONS: In this retrospective PS-matched long-term analysis, neoadjuvant CHT/RT conferred improved DFS and OS compared with CHT alone in stage III/N2 NSCLC. These highly challenging results require confirmation in well-designed randomized controlled trials conducted at highly specialized thoracic oncology centers.

Vaults and the major vault protein: novel roles in signal pathway regulation and immunity.

The unique and evolutionary highly conserved major vault protein (MVP) is the main component of ubiquitous, large cellular ribonucleoparticles termed vaults. The 100 kDa MVP represents more than 70% of the vault mass which contains two additional proteins, the vault poly (ADP-ribose) polymerase (vPARP) and the telomerase-associated protein 1 (TEP1), as well as several short untranslated RNAs (vRNA). Vaults are almost ubiquitously expressed and, besides chemotherapy resistance, have been implicated in the regulation of several cellular processes including transport mechanisms, signal transmissions and immune responses. Despite a growing amount of data from diverse species and systems, the definition of precise vault functions is still highly complex and challenging. Here we review the current knowledge on MVP and vaults with focus on regulatory functions in intracellular signal transduction and immune defence.

A cytological approach to the ordering of events in gene activation using the Sgs-4 locus of Drosophila melanogaster.

The polytene chromosomes of Drosophila strains that differ in the synthesis of the major salivary gland glue protein sgs-4 were examined by indirect immunofluorescence using antisera to several nonhistone chromosomal proteins. The Oregon-R X chromosome, which produces sgs-4 messenger RNA, showed a strong fluorescent band at locus 3C11-12 when stained with anti-RNA polymerase II, whereas the null mutant Berkeley 1 failed to exhibit fluorescence at that locus. The presence of another antigen (Band 2), normally associated with developmentally active loci, was clearly evident at locus 3C11-12 of both transcriptionally competent and null strains, indicating that the association of Band 2 antigen with the chromatin is an event independent of RNA polymerase II binding. Antibodies directed against Drosophila topoisomerase I stained 3C11-12 in the Sgs-4+ (wild-type) strain brightly, but gave significantly less staining in the null strain. This indicates that the high concentrations of topoisomerase I seen at active loci are closely associated with the transcriptional event. In some of these analyses, we have made use of flies heterozygous for the wild-type and null alleles in order to make internally controlled comparisons. The results suggest that this type of analysis will enable conclusions to be drawn concerning the interdependence and order of action of chromosomal proteins involved in developmental gene activation.

The yeast CDC37 gene interacts with MPS1 and is required for proper execution of spindle pole body duplication.

The MPS1 gene from Saccharomyces cerevisiae encodes an essential protein kinase required for spindle pole body (SPB) duplication and for the mitotic spindle assembly checkpoint. Cells with the mps1-1 mutation fail early in SPB duplication and proceed through monopolar mitosis with lethal consequences. We identified CDC37 as a multicopy suppressor of mps1-1 temperature-sensitive growth. Suppression is allele specific, and synthetic lethal interactions occur between mps1 and cdc37 alleles. We examined the cdc37-1 phenotype for defects related to the SPB cycle. The cdc37-1 temperature-sensitive allele causes unbudded, G1 arrest at Start (Reed, S.I. 1980. Genetics. 95: 561-577). Reciprocal shifts demonstrate that cdc37-1 arrest is interdependent with alpha-factor arrest but is not a normal Start arrest. Although the cells are responsive to alpha-factor at the arrest, SPB duplication is uncoupled from other aspects of G1 progression and proceeds past the satellite-bearing SPB stage normally seen at Start. Electron microscopy reveals side-by-side SPBs at cdc37-1 arrest. The outer plaque of one SPB is missing or reduced, while the other is normal. Using the mps2-1 mutation to distinguish between the SPBs, we find that the outer plaque defect is specific to the new SPB. This phenotype may arise in part from reduced Mps1p function: although Mps1p protein levels are unaffected by the cdc37-1 mutation, kinase activity is markedly reduced. These data demonstrate a requirement for CDC37 in SPB duplication and suggest a role for this gene in G1 control. CDC37 may provide a chaperone function that promotes the activity of protein kinases.

Pregnancy outcome in maternal Crigler-Najjar syndrome type II: a case report and systematic review of the literature.

OBJECTIVE: To report a case of maternal Crigler-Najjar syndrome (CNS) type II in pregnancy, systematically review the literature for similar case reports, and to evaluate whether pregnancy is safe in patients with the disease. Data sources included the PubMed and up to date databases. RESULTS: A 37-year-old mother with CNS type II was treated with phenobarbital during her pregnancy and her bilirubin levels were monitored. Her newborn had mild direct hyperbilirubinemia, did not require any treatment and his postnatal follow-up showed normal growth and development as well as normal hearing. CONCLUSION: CNS type II is rare, and only a few pregnancies with this condition have been reported. Maternal treatment with phenobarbital lowers the unconjugated bilirubin and avoids fetal and newborn sequelae.

[The patient's satisfaction in relation with the treatment in hospital psychiatry: a comparison between Italy and Germany]. / Behandlungszufriedenheit und Einflussfaktoren in der stationären Psychiatrie: ein deutsch/italienischer Vergleich.

The aim of this study is to compare psychiatric patients' satisfaction with their treatment in Munich and in South Tirol. For this purpose, besides clinical and social-demographic factors, for each sample-group of patients, their general satisfaction, their valuation of the different aspects of hospital treatment and life quality were considered and compared. The relevance of these elements in the global satisfaction was examined with linear multiple regression models. The results of the research show a rather high level of global satisfaction in both sample-groups, even if statistically relevant differences occur in evaluations of several aspects of the treatment. In Munich's sample-group a higher rate of satisfaction emerged in relation with the treatment: the attitude of the medical staff, the psycho-pharmacological treatments, the clinic's image and the conduct of the nursing staff. In both groups the most relevant factor for patients' satisfaction, besides the positive results of the treatment, was the attitude of the doctor, and in particular way his empathy with the patient. In regard to the age, the diagnosis and the duration of the hospitalization, it was not possible to demonstrate, in both sample-groups, any statistically relevant connection with the general satisfaction rate, while a high rate of trust in the doctors and in the medicines was found to be, in each group, a significant condition for a positive evaluation of the treatment. The influence of the personal life-quality was proven statistically relevant but weak. Altogether, regardless of the medical structure that was examined, the results underline the predominant importance of the curing doctor's social and emotional skills for patients' satisfaction.

Role of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) for prognosis in endometrial cancer.

BACKGROUND: Urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) contribute to the invasiveness of many carcinomas. Here, we studied a possible association between cytosolic uPA and PA-1 concentrations in tumor tissue with prognosis in patients with endometrial cancer. METHODS: Cytosolic concentrations of uPA and PAI-1 were determined in 69 primary endothelial adenocarcinomas using an enzyme-linked immunoassay (ELISA). A possible influence of uPA and PAI-1 was studied by multivariate Cox regression adjusting for the established clinical prognostic factors FIGO-stage, grading, depth of invasion, diabetes mellitus and age. RESULTS: Both uPA (p=0.011) and PAI-1 (p=0.003) were associated with relapse free time using the multivariate proportional hazards model. Association with overall survival was less pronounced with p=0.021 for uPA and p=0.358 for PAI-1. Concentrations of PAI-1 increased with FIGO stage (p=0.003) and with histological grading (p=0.005). Both uPA and PAI-1 concentrations were negatively correlated with estrogen and progesterone receptor levels. CONCLUSION: The combination of high cytosolic concentrations of uPA (>5 ng/mg total protein) and high PAI-1 (>20 ng/mg total protein) may reveal a group of patients with increased risk of progression.

Recurrence and complications after laparoscopic versus open inguinal hernia repair: results of a prospective randomized multicenter trial.

BACKGROUND: The aim of this prospective randomized multicenter trial was to evaluate the recurrence rates and complications of open versus laparoscopic repairs of inguinal hernias. METHODS: Patients with primary unilateral inguinal hernias were randomized to Shouldice repair, Bassini operation, tension-free hernioplasty (Lichtenstein repair), laparoscopic transabdominal extraperitoneal hernioplasty (TEP), or laparoscopic transabdominal preperitoneal hernioplasty (TAPP). The primary outcome parameter was the rate of recurrence at 3 years. The secondary outcome was the rate of intraoperative, perioperative, and long-term complications. Follow-up comprised of clinical examination after 1, 2, and 3 years. RESULTS: Three hundred and sixty-five patients were randomly assigned to one of the five procedures. The intention-to-treat analysis showed that the cumulative 3-year recurrence rate was 3.4% in the Bassini group, 4.7% in the Shouldice group, 0% in the Lichtenstein group, 4.7% in the TAPP group, and 5.9% in the TEP group (p = 0.48). Comparing open (Bassini, Shouldice, Lichtenstein) versus laparoscopic (TAPP, TEP) techniques (p = 0.29) and comparing the use of mesh prostheses (Lichtenstein, TAPP, TEP) versus suturing techniques (Bassini, Shouldice) (p = 0.74) showed no significance in the rate of recurrence. The rates of intraoperative (p = 0.15), perioperative (p = 0.09), and long-term complications (p = 0.13) were without significance between the five groups. Comparing mesh techniques (Lichtenstein, TAPP, TEP) versus suturing techniques (Bassini, Shouldice) showed no significance in the rate of complications. The per-protocol analysis for the comparison of mesh (Lichtenstein, TAPP, TEP) versus suturing (Bassini, Shouldice) techniques revealed that recurrences (p = 0.74), intraoperative (p = 0.64), perioperative (p = 0.27), and long-term complications (p = 0.91) were evenly distributed. CONCLUSIONS: In this multicenter study, no significant difference in the recurrence rate and complications between laparoscopic and open methods of hernia repair was revealed.

Fetal urogenital sinus with consecutive hydrometrocolpos because of labial fusion: prenatal diagnostic difficulties and postpartal therapeutic management.

OBJECTIVE: To elucidate the differential diagnoses of tumorous dilations in the fetal pelvic region detected by prenatal ultrasound and the postnatal management demonstrated on a fetus with 29 weeks of gestation with a retrovesical located bottle-like cystic structure measuring 54 x 31 x 27 mm within the pelvis. Postnatal findings were a labial fusion and a consecutive hydrometrocolpos due to a urethrovaginal fistula. METHOD: Case report of a fetus affected by an intricate cloacal anomaly. RESULTS: The long-term prognosis for this nonsyndromic form of hydrometrocolpos without any other structural defects or organic failures after operative sanitation is excellent. Final reconstruction is planned at about 12 months of age. CONCLUSION: Prenatal diagnosis of tumorous dilations in the fetal pelvic region often involves difficulties because of numerous differential diagnoses and possible presentation in late pregnancy. Magnetic resonance imaging could be a useful complementary tool for assessing these anomalies when ultrasonography is inconclusive. In some cases, the final diagnosis cannot be confirmed until after delivery.

Diabetes mellitus is a multivariate independent prognostic factor in endometrial carcinoma: a clinicopathologic study on 313 patients.

OBJECTIVE: The aim of this study was to analyse the influence of diabetes mellitus as a prognostic factor for overall survival in endometrial cancer. MATERIALS AND METHODS: Charts were reviewed from patients with endometrial carcinoma from 1985 to 2003. Data on clinicopathologic variables, adjuvant treatment, site of recurrence and survival were collected. The chi-square test was used to examine associations between variables. The Kaplan-Meier method was used for survival analysis and Cox's proportional hazards model for multiple regression analysis. RESULTS: Multivariate analysis revealed that diabetes mellitus, FIGO stage and depth of myometrial invasion were significantly associated with overall survival.