In humans, insulo-striate structural connectivity is largely biased toward either striosome-like or matrix-like striatal compartments.

The insula is an integral component of sensory, motor, limbic, and executive functions, and insular dysfunction is associated with numerous human neuropsychiatric disorders. Insular afferents project widely, but insulo-striate projections are especially numerous. The targets of these insulo-striate projections are organized into tissue compartments, the striosome and matrix. These striatal compartments have distinct embryologic origins, afferent and efferent connectivity, dopamine pharmacology, and susceptibility to injury. Striosome and matrix appear to occupy separate sets of cortico-striato-thalamo-cortical loops, so a bias in insulo-striate projections towards one compartment may also embed an insular subregion in distinct regulatory and functional networks. Compartment-specific mapping of insulo-striate structural connectivity is sparse; the insular subregions are largely unmapped for compartment-specific projections. In 100 healthy adults, we utilized probabilistic diffusion tractography to map and quantify structural connectivity between 19 structurally-defined insular subregions and each striatal compartment. Insulo-striate streamlines that reached striosome-like and matrix-like voxels were concentrated in distinct insular zones (striosome: rostro- and caudoventral; matrix: caudodorsal) and followed different paths to reach the striatum. Though tractography was generated independently in each hemisphere, the spatial distribution and relative bias of striosome-like and matrix-like streamlines were highly similar in the left and right insula. 16 insular subregions were significantly biased towards one compartment: seven toward striosome-like voxels and nine toward matrix-like voxels. Striosome-favoring bundles had significantly higher streamline density, especially from rostroventral insular subregions. The biases in insulo-striate structural connectivity we identified mirrored the compartment-specific biases identified in prior studies that utilized injected tract tracers, cytoarchitecture, or functional MRI. Segregating insulo-striate structural connectivity through either striosome or matrix may be an anatomic substrate for functional specialization among the insular subregions.

Benzodiazepine exposures among women of reproductive age in the US, 2004-2018.

Benzodiazepines, often used to treat anxiety, insomnia, and other conditions, are prescribed more frequently to women than men, and emergency department visits and overdose deaths involving benzodiazepines have increased significantly among women in recent years. This study describes characteristics and trends associated with benzodiazepine exposures among women of reproductive age (15-49 years old) that were reported to United States poison control centers from 2004 through 2018. The National Poison Data System recorded 258,370 first-ranked benzodiazepine exposures among women 15-49 years old during the study period. More than one-half (56.9%) of exposures involved a single-substance and one-third (34.0%) occurred among women 20-29 years old. The majority were categorized as "intentional, suspected suicide" (73.2%) or "intentional" (12.9%). Exposures frequently resulted in admission to a psychiatric facility (20.6%), critical care unit (18.1%), or non-critical care unit (9.3%). Twenty percent of cases resulted in a serious medical outcome, including 205 deaths. The substantial percentage of benzodiazepine exposures among women of reproductive age that were intentional and associated with suicide attempts or suicide deaths indicate that increased prevention efforts are needed to address this issue.

[Summary of the S3 guideline on abdominal aortic aneurysm from an anesthesiological perspective]. / Zusammenfassung der S3-Leitlinie Bauchaortenaneurysma aus anästhesiologischer Sicht.

The current article is a summary of the 2018 revised S3 guideline on screening, diagnosis, therapy, and follow-up of the abdominal aortic aneurysm (AAA) from an anesthesiological point of view. It is the only interdisciplinary guideline that describes in particular the perioperative anesthesiological and intensive care management.

Increased recurrence rates of hepatocellular carcinoma after DAA therapy in a hepatitis C-infected Egyptian cohort: A comparative analysis.

In Egypt, hepatocellular carcinoma (HCC) is the most common form of cancer and direct-acting antivirals (DAA) are administered on a large scale to patients with chronic HCV infection to reduce the risk. In this unique setting, we aimed to determine the association of DAA exposure with early-phase HCC recurrence in patients with a history of HCV-related liver cancer. This was a prospective cohort study of an HCV-infected population from one Egyptian specialized HCC management centre starting from the time of successful HCC intervention. The incidence rates of HCC recurrence between DAA-exposed and nonexposed patients were compared, starting from date of HCC complete radiological response and censoring after 2 years. DAA exposure was treated as time varying. Two Poisson regressions models were used to control for potential differences in the exposed and nonexposed group; multivariable adjustment and balancing using inverse probability of treatment weighting (IPTW). We included 116 patients: 53 treated with DAAs and 63 not treated with DAAs. There was 37.7% and 25.4% recurrence in each group after a median of 16.0 and 23.0 months of follow-up, respectively. Poisson regression using IPTW demonstrated an association between DAAs and HCC recurrence with an incidence rate ratio of 3.83 (95% CI: 2.02-7.25), which was similar in the multivariable-adjusted model and various sensitivity analyses. These results add important evidence towards the possible role of DAAs in HCC recurrence and stress the need for further mechanistic studies and clinical trials to accurately confirm this role and to identify patient characteristics that may be associated with this event.

Systematic review with meta-analysis: the risk of mother-to-child transmission of hepatitis B virus infection in sub-Saharan Africa.

BACKGROUND: The risk of mother-to-child transmission of hepatitis B virus (HBV) has been quoted as 70-90% among women positive for hepatitis B surface antigen (HBsAg) and e antigen (HBeAg), and 5-30% among HBsAg-positive HBeAg-negative women. These risks are derived from Asia; little is known about sub-Saharan Africa. AIM: To determine the risk of mother-to-child transmission in sub-Saharan Africa, according to maternal HBeAg and type of prophylaxis. METHODS: We searched Medline, Global Health, Embase, African Journals Online and African Index Medicus. We included observational or interventional studies that enrolled infants of HBV-infected women, and that tested for HBsAg or HBV DNA between 3 and 12 months of age. RESULTS: Fifteen articles from 11 African countries were included. Among HBeAg-positive women, the pooled risk was 38.3% (95% CI: 7.0-74.4%) without prophylaxis, which was significantly lower than the lower bound of 70-90% risk in the literature (P = 0.007). Among HBeAg-negative women, the pooled risk was 4.8% (95% CI: 0.1-13.3%) without prophylaxis, which lays within the lower range of the 5-30% risk in Asia. By extrapolating the pooled transmission risks to the number of births to infectious mothers, an estimated 1% of newborns (n = 367 250) are annually infected with HBV at birth in sub-Saharan Africa. CONCLUSIONS: Compared to Asia, the risk of mother-to-child transmission is low in sub-Saharan Africa. However, the annual number of infants perinatally infected with HBV is twice the number of incident paediatric HIV infections in sub-Saharan Africa (n = 190 000). This highlights the importance of preventing mother-to-child transmission of HBV in sub-Saharan Africa, which has been long neglected.

[Langerhans cell histiocytosis of the stomach with BRAF-V600E-mutation: case report and review of the literature]. / Langerhans-Zellhistiozytose des Magens mit BRAF-V600E-Mutation: Fallbericht und Literaturübersicht.

Langerhans cell histiocytosis is a disease with different clinical presentations and a wide spectrum of organ involvements. Rarely Langerhans cell histiocytosis can involve the gastrointestinal tract of adult patients. A case of infiltration of gastric mucosa by Langerhans cell histiocytosis is presented. The neoplastic nature of this infiltrate is underlined by the detection of a BRAF-V600E-mutation. Additionally, an overview of the so far 5 cases published in the English literature is provided. The published clinical experience indicates a benign curse of the disease.

Disease Management Project Breast Cancer in Hesse - 5-Year Survival Data: Successful Model of Intersectoral Communication for Quality Assurance.

Introduction: The Disease Management Project Breast Cancer (DMP Breast Cancer) was first launched in Hesse in 2004. The project is supported by the health insurance companies in Hesse and the Professional Association of Gynaecologists in Hesse. The aim is to offer structured treatment programmes to all women diagnosed with breast cancer in Hesse by creating intersectoral cooperations between coordinating clinics, associated hospitals and gynaecologists in private practice who registered in the DMP programme. Method: Between 1 January 2005 and 30 June 2011, 13 973 women were enrolled in the DMP programme. Results: After data cleansing, survival rates were calculated for a total of 11 214 women. The 5-year overall survival (OS) rate was 86.3 %; survival rates according to tumour stage on presentation were 92.2 % (pT1) and 82.3 % (pT2), respectively. The impact of steroid hormone receptor status on survival (87.8 % for receptor-positive cancers vs. 78.9 % for receptor-negative cancers) and of age at first diagnosis on survival (≤ 35 years = 91 %) were calculated. Conclusion: The project showed that intersectoral cooperation led to significant improvements in the quality of treatment over time, as measured by quality indicators and outcomes after treatment.

IR spectroscopy on isolated Co(n)(alcohol)m cluster anions (n=1-4, m=1-3): structures and spin states.

Isolated cobalt-alcohol cluster anions containing n=1-4 cobalt and m=1-3 alcohol molecules (alcohol=methanol, ethanol, propanol) are produced in a supersonic beam by using a laser ablation source. By applying IR photodissociation spectroscopy vibrational spectra in the OH stretching region are obtained. Several structures in different spin states are discussed for the (n,m) clusters. In comparison with density functional theory calculations applied to both the Co/alcohol clusters and the naked Co cluster anions, an unambiguous structural assignment is achieved. It turns out that structures are preferred with a maximum number of hydrogen bonds between the OH groups and the Co···Co units. These hydrogen bonds are typical for anionic species leading to an activation of the OH groups which is indicated by large red-shifts of the OH stretching frequencies compared to the naked alcohols. For each (n,m) cluster, the frequency shifts systematically with respect to the different alcohols, but the type of structure is identical for all alcohol ligands. The application of IR spectroscopy turns out to be an ideal tool not only as a probe for structures but also for spin states which significantly influence the predicted OH stretching frequencies.

Extraction of many-body configurations from nonlinear absorption in semiconductor quantum wells.

Detailed electronic many-body configurations are extracted from quantitatively measured time-resolved nonlinear absorption spectra of resonantly excited GaAs quantum wells. The microscopic theory assigns the observed spectral changes to a unique mixture of electron-hole plasma, exciton, and polarization effects. Strong transient gain is observed only under cocircular pump-probe conditions and is attributed to the transfer of pump-induced coherences to the probe.

IR spectroscopy applied subsequent to a proton transfer reaction in the excited state of isolated 3-hydroxyflavone and 2-(2-naphthyl)-3-hydroxychromone.

IR/R2PI-spectroscopy has been applied to the electronic ground and electronically excited states of 3-hydroxyflavone (3-HF) and 2-(2-naphthyl)-3-hydroxychromone (2-NHC) in a supersonic jet yielding direct structural information on the educt and product of a proton transfer reaction. We show that IR spectra of the electronically excited states can be recorded subsequent to a photoinduced chemical reaction, in this case a proton transfer. In combination with DFT and TDDFT calculations structural assignments are performed.

IR/UV spectroscopy on jet cooled 3-hydroxyflavone (H2O)n (n = 1,2) clusters along proton transfer coordinates in the electronic ground and excited states.

The structure and reactivity of isolated 3-hydroxyflavone (3-HF) aggregates with one and two water molecules has been investigated by applying combined infrared/ultraviolet (IR/UV) spectroscopy in a supersonic jet both for the electronic ground and excited states. In combination with density functional theory (DFT) calculations, the IR spectra of the S(0) states recorded from the upper fingerprint region to the OH stretching vibrations are assigned to the most stable isomers of the clusters. For the first electronically excited (pi pi(*)) state of the 3-HF(H(2)O)(2) cluster structural information are obtained from the IR spectra in combination with time-dependent-DFT (TD-DFT) calculations. No proton transfer structure is observed in the case of a low excess energy within the electronically excited state. By raising the excitation energy, additional bands appear that can be assigned to a tautomeric form indicating the induction of a proton transfer reaction.

Strong and selective inhibitors of hepatitis B virus replication among novel N4-hydroxy- and 5-methyl-beta-L-deoxycytidine analogues.

Novel N(4)-hydroxy- and 5-methyl-modified beta-L-deoxycytidine analogues were synthesized and evaluated as anti-hepatitis B virus (HBV) agents. Their in vitro efficiencies were investigated in HepG2.2.15 cells stably transfected with HBV. beta-L-2',3'-Didehydro-2',3'-dideoxy-N(4)-hydroxycytidine (beta-L-Hyd4C) was most effective in reducing secreted HBV DNA (50% effective concentration [EC(50)], 0.03 microM), followed by beta-L-2',3'-dideoxy-3'-thia-N(4)-hydroxycytidine (EC(50), 0.51 microM), beta-L-2',3'-dideoxy-N(4)-hydroxycytidine (EC(50), 0.55 microM), and beta-L-5-methyl-2'-deoxycytidine (EC(50), 0.9 microM). The inhibition of the presumed target, the HBV DNA polymerase, by the triphosphates of some of the beta-L-cytidine derivatives was also assessed. In accordance with the cell culture data, beta-L-Hyd4C triphosphate was the most active inhibitor, with a 50% inhibitory concentration of 0.21 microM. The cytotoxicities of some of the 4-NHOH-modified beta-L-nucleosides were dramatically lower than those of the corresponding cytidine analogues with the unmodified 4-NH(2) group. The 50% cytotoxic concentrations for beta-L-Hyd4C in HepG2 and HL-60 cells were 2,500 microM and 3,500 microM, respectively. In summary, our results demonstrate that at least beta-L-Hyd4C can be recommended as a highly efficient and extremely selective inhibitor of HBV replication for further investigations.

Tristetraprolin regulates Cyclin D1 and c-Myc mRNA stability in response to rapamycin in an Akt-dependent manner via p38 MAPK signaling.

The differential expression of the critical cell cycle control proteins cyclin D1 and c-myc has been shown to result in Akt-dependent hypersensitivity of tumor cells to mTOR inhibitors. We have previously demonstrated that the differential utilization of internal ribosome entry sites within the mRNAs of these transcripts allows maintenance of protein synthesis in the face of rapamycin (rapa) exposure in an Akt-dependent manner. Here, we demonstrate that in addition to this mechanism, cyclin D1 and c-myc mRNA stability is also coordinately regulated following rapa treatment depending on Akt activity status. We identify A/U-rich response elements within the 3' untranslated regions (UTRs) of these transcripts, which confer the observed differential stabilities and show that the RNA-binding protein, tristetraprolin (TTP), interacts with these elements. We also present evidence that TTP accumulates in response to rapa exposure, binds to the cis-acting elements within the cyclin D1 and c-myc 3' UTRs and is differentially serine phosphorylated in an Akt-dependent manner. Furthermore, the differential phosphorylation status of TTP results in its sequestration by 14-3-3 proteins in quiescent Akt-containing cells. Finally, siRNA-mediated knockdown of TTP expression or inhibiting a known regulator of TTP phosphorylation, p38 MAP kinase, abolishes the effects on cyclin D1 and c-myc mRNA stability. We assume that the differential control of cyclin D1 and c-myc mRNA stability and translational efficiency constitutes a coordinate response to rapa contributing to the maintenance of expression of these determinants in rapa-resistant quiescent Akt-containing cells following exposure.

Spread of hepatitis B viruses in vitro requires extracellular progeny and may be codetermined by polarized egress.

Viruses can spread by different mechanisms: via intracellular particles through cell junctions to neighboring cells or via secreted virions to adjacent or remote cells. The observation of clusters of hepadnavirus-infected cells both in vivo and in primary hepatocytes neither proves the first mechanism nor excludes the second. In order to test which mechanism, if not both, is used by hepatitis B viruses in order to spread, we used primary duck hepatocytes and duck hepatitis B virus (DHBV) as an infection model. If extracellular progeny virus alone determines spreading, neutralizing antisera or drugs blocking virus binding to hepatocytes should abolish secondary infection. In order to test this, we used DHBV envelope-specific neutralizing antisera, as well as suramin, a known inhibitor of infection. Both reagents strongly reduced hepatocellular attachment of viral particles and almost completely abolished primary infection, whereas an ongoing intracellular infection was not affected as long as no progeny virus was released. In contrast, incubation of infected primary hepatocytes with these reagents during release of progeny virus completely prevented secondary infection. Moreover, the combination of electron and immunofluorescence microscopy analyses revealed the residence of viral particles in cytoplasmic vesicles preferentially located near the basolateral membrane of infected hepatocytes. Taken together, these data strongly suggest that hepatitis B viruses mainly spread by secreted, extracellular progeny and point to polarized egress of viral particles into intercellular compartments, which restricts their diffusion and favors transmission of virus to adjacent cells.

[Prostate carcinoma (PC)--an organ-related specific pathological neoplasm]. / Prostatakarzinom (PC)--eine organspezifische Neoplasie aus der Sicht der Pathologie.

The organ- and tumour-related specific characteristics of prostate carcinoma (PC) are presented in an overview under various aspects. It is the key for understanding pathological changes, including PC, to consider the subdivision of the prostate into anatomically and functionally distinguishable zones, especially the transitional zone (TZ) and the peripheral zone (PZ). The pseudoneoplastic hyperplasia of the TZ, combined with inflammatory consequences and age-related changes, forms a differential diagnostic challenge to both clinico-radiological diagnosis and macroscopic and microscopic examination. High-degree prostatic intra-epithelial neoplasia (PIN III) and atypical adenomatous hyperplasia (AAH) are presented as precursor lesions of PC with varying significance and assessment. Moreover, there are discussed the following characteristic features of PC: localisation types, focality, volume, progression, double-graduation according to Gleason, tumour stage, and prognosis. The most important prognosis factors of PC (category I) include the categories of the TNM system, such as stage, surgical marginal situation, degree and also the preoperative PSA level as a (poor) substitute for the tumour volume. Potential prognosis parameters (category II) show the tumour volume and the DNS ploidy, while there continues to exist a large number of non-established parameters (category III). The prognostic validity of the pathological examinations depends, on the one hand, on the tissue extent (needle biopsy, transurethral resection (TURP), so-called simple prostatectomy, radical prostatectomy (RPE)) and the prostate zones covered. On the other hand, the prognostic certainty also depends on the tumour-adequate macroscopic and microscopic assessment of an RPE that can only be a partial or complete handling in transversal large-area sections.

[Criteria of dignity in ultrasound mammography using a 10-MHz-transducer, also with regard to tumor size]. / Mammasonographische Dignitätskriterien unter besonderer Berücksichtigung der Tumorgrösse.

AIM: Ongoing technical progress has increased the accuracy of imaging in ultrasound mammography. Using a 10-MHz-transducer, eight different criteria of dignity were evaluated for validity, also with regard to the size of a tumor. MATERIALS AND METHODS: Over a period of three years, 446 breast tumors were ultrasonographically examined by two experienced medical doctors. The study comprised only suspicious lesions detected by mammography and/or manual palpation. Diagnostic validity was quantified by means of sensitivity, specificity, positive and negative predictive value, as well as the ODDS-ratio. RESULTS: Ultrasound mammography demonstrated a sensitivity of 94.0 %, specificity of 91.4 %, positive predictive value of 95.9 %, and a negative predictive value of 99.1 %. Eight different sonographic criteria were validated separately. The most important signs of malignancy were (in descending order): a highly echogenic halo, spikes, jagged contour, posterior acoustic shadowing, and discontinuity of tissue structure. Features of benign disease were: smooth edge, posterior acoustic enhancement, displacement margin, bilateral acoustic shadowing and continuity of tissue structure. Furthermore, it appeared that the size of a tumor only had consequences on posterior shadowing (p = 0.017). All other features did not show significant variation in relation to tumor size. CONCLUSION: We were able to prove that ultrasound mammography is an excellent medium for the differentiation of benign and malignant breast lesions, when precise indication criteria were adhered to, even in cases of small tumor size.

[Significance of detecting impaired uteroplacental perfusion for diagnosis of antiphospholipid antibody syndrome--a case report]. / Die Bedeutung des Nachweises einer uteroplazentaren Perfusionseinschränkung für die Diagnose eines Antiphospholipid-Antikörpersyndromes--ein Fallbericht.

INTRODUCTION: The antiphospholipid antibody syndrome (APA) is a potentially life-threatening disease in pregnancy, associated with spontaneous abortion, intrauterine growth retardation (IUGR), preeclampsia and foetal death in utero. One of the sequelae of the antiphospholipid-antibodies is an impaired uteroplacental circulation. We present a case where we diagnosed an antiphospholipid antibody syndrome (APA) on the basis of a highly pathological Doppler flow in both uterine arteries. CASE REPORT: A 35-year-old G2P0 with a history of intrauterine foetal death in the 24th week was seen at 15 weeks in her second pregnancy for an ultrasound scan. The Doppler study of both uterine arteries showed highly pathological resistance indices and bilateral notching. Laboratory studies revealed elevated levels of antibodies against Cardiolipin and phospholipids. Therapy trials with low-dose aspirin, heparin, corticosteroids, hemodilution therapy and immunoglobulin remained unsuccessful. The foetus developed severe IUGR, anhydramnios and foetal distress. In the 26th week the parents insisted on a caesarean section because of a pathological heart rate pattern. The birth weight was 365 grams and the infant died immediately. DISCUSSION: There are several mechanisms which impair the uteroplacental circulation in an APA syndrome. Therefore it is essential to perform laboratory tests when detecting a pathological blood flow in both uterine arteries. In this case all therapies failed, and the preterm infant died due to severe IUGR and distress. The diagnosis, however, facilitated the introduction of early anticoagulation therapy for the mother, the exclusion of systemic lupus erythematodes and the counselling of the parents with regard to further pregnancies.