Neoadjuvant and Adjuvant Systemic Therapy for Newly Diagnosed Stage II–IV Epithelial Ovary,Fallopian Tube,or Primary Peritoneal Carcinoma: A Practice Guideline

Background: This study aims to provide guidance for the use of neoadjuvant and adjuvant systemic therapy in women with newly diagnosed stage II–IV epithelial ovary, fallopian tube, or primary peritoneal carcinoma. Methods: EMBASE, MEDLINE, and Cochrane Library were investigated for relevant systematic reviews and phase III trials. Articles focusing on consolidation and maintenance therapies were excluded. Results: For women with potentially resectable disease, primary cytoreductive surgery, followed by six to eight cycles of intravenous three-weekly paclitaxel and carboplatin is recommended. For those with a high-risk profile for primary cytoreductive surgery, neoadjuvant chemotherapy can be an option. Adjuvant chemotherapy with six cycles of dose-dense weekly paclitaxel plus three-weekly carboplatin can be considered for women of Japanese descent. In women with stage III or IV disease, the incorporation of bevacizumab concurrent with paclitaxel and carboplatin is not recommended for use as adjuvant therapy unless bevacizumab is continued as maintenance therapy. Intravenous paclitaxel plus intraperitoneal cisplatin and paclitaxel can be considered for stage III optimally debulked women who did not receive neoadjuvant chemotherapy. However, intraperitoneal administration of chemotherapy with bevacizumab should not be considered as an option for stage II–IV optimally debulked women. Discussion: The recommendations represent a current standard of care that is feasible to implement and valued by both clinicians and patients.     

Molecular Organisation of Tick-Borne Encephalitis Virus

Tick-borne encephalitis virus (TBEV) is a pathogenic, enveloped, positive-stranded RNA virus in the family Flaviviridae. Structural studies of flavivirus virions have primarily focused on mosquito-borne species, with only one cryo-electron microscopy (cryo-EM) structure of a tick-borne species published. Here, we present a 3.3 Å cryo-EM structure of the TBEV virion of the Kuutsalo-14 isolate, confirming the overall organisation of the virus. We observe conformational switching of the peripheral and transmembrane helices of M protein, which can explain the quasi-equivalent packing of the viral proteins and highlights their importance in stabilising membrane protein arrangement in the virion. The residues responsible for M protein interactions are highly conserved in TBEV but not in the structurally studied Hypr strain, nor in mosquito-borne flaviviruses. These interactions may compensate for the lower number of hydrogen bonds between E proteins in TBEV compared to the mosquito-borne flaviviruses. The structure reveals two lipids bound in the E protein which are important for virus assembly. The lipid pockets are comparable to those recently described in mosquito-borne Zika, Spondweni, Dengue, and Usutu viruses. Our results thus advance the understanding of tick-borne flavivirus architecture and virion-stabilising interactions.     

Hemodynamic effects of pindolol and atenolol at rest and during isometric exercise: A noninvasive study with healthy volunteers

Summary Hemodynamic effects of intravenous and oral pindolol and atenolol were assessed in ten healthy volunteers by left ventricular echocardiography and systolic time intervals. Measurements were made at rest and during hand-grip-induced isometric exercise. Drug doses were pindolol 0.015 mg/kg intravenously and 10 mg/day orally, atenolol 0.1 mg/kg intravenously, and 50 mg/day orally.Heart rate at rest was reduced by both drugs. The reduction caused by atenolol during oral treatment was significantly greater (p<0.01). Intravenously only pindolol reduced mean arterial pressure. During oral treatment atenolol reduced the mean arterial pressure nonsignificantly. Both drugs lowered heart rate during isometric exercise, atenolol being significantly more effective. During oral treatment atenolol blunted the heart-rate reaction to exercise. Mean arterial pressure during isometric exercise rose slightly with both drugs after intravenous administration. During oral treatment only atenolol reduced the mean arterial pressure significantly. Intravenous atenolol reduced cardiac contractility at rest, indicated by significant decreases in fractional shortening, ejection fraction, and the mean velocity of circumferential fiber shortening. In contrast, intravenous pindolol and oral therapy with either drug did not change contractility. Intravenous atenolol raised total peripheral resistance. The preejection period/left ventricular ejection time ratio decreased with intravenous pindolol, while atenolol increased it.In conclusion, atenolol had more negative inotropic and chronotropic effects, especially after acute intravenous administration. Only atenolol reduced cardiac output and increased peripheral resistance. After repeated oral administration, these effects were less apparent.     

Effects of the implementation of the web‐based patient support system on staff’s attitudes towards computers and IT use: a randomised controlled trial

Scand J Caring Sci; 2010; 24; 592–599
Effects of the implementation of the web‐based patient support system on staff’s attitudes towards computers and IT use: a randomised controlled trial Utilisation of information technology (IT) in the treatment of people with severe mental health problems is an unknown area in Europe. Use of IT and guiding patients to relevant sources of health information requires that nursing staff have positive attitudes toward computers and accept IT use as a part of daily practises. The aim of the study was to assess the effects of the implementation of a web‐based patient support system on staff’s attitudes towards computers and IT use on psychiatric wards. Hundred and forty‐nine nurses in two psychiatric hospitals in Finland were randomised to two groups to deliver patient education for patients with schizophrenia and psychosis with a web‐based system (n = 76) or leaflets (n = 73). After baseline nurses were followed‐up for 18 months after the introduction of the system. The primary outcome was nurses’ motivation to utilise computers, and the secondary outcomes were nurses’ beliefs in and satisfaction with computers, and use of computer and internet. There were no statistically significant differences between study groups in attitudes towards computers (motivation p = 0.936, beliefs p = 0.270, satisfaction p = 0.462) and internet use (p = 0.276). However, nurses’ general computer use (p = 0.029) increased more in the leaflet group than in the IT intervention group. We can conclude that IT has promise as an alternative method in patient education, as the implementation of the web‐based patient support system in daily basis did not have a negative effect on nurses’ attitudes towards IT.     

Human papillomavirus prevalence and type distribution in male anogenital sites and semen.

BACKGROUND: Human papillomavirus (HPV) is sexually transmitted and causes cervical cancer. Although HPV can infect men and women, little is known about infection in men. Specifically, the prevalence of type-specific HPV infection and the distribution of infections by anogenital anatomic site in men are incompletely characterized. METHODS: We tested 463 men ages 18 to 40 years for HPV at the glans/corona, penile shaft, scrotum, urethra, perianal area, anal canal, and in a semen sample. Eligible men acknowledged no history of genital warts and had sexual intercourse with a woman within the past year. HPV testing by PCR and reverse line blot genotyping for 37 types was conducted on each of the specimens from the seven sampling sites. RESULTS: When HPV results from any sampling site were considered, 237 (51.2%) men were positive for at least one oncogenic or nononcogenic HPV type, and another 66 (14.3%) men were positive for an unclassified HPV type. The types with the highest prevalence were HPV-16 (11.4%) and 84 (10.6%). External genital samples (glans/corona, shaft, and scrotum) were more likely than anal samples to contain oncogenic HPV (25.1% versus 5.0%). HPV-positive penile shaft and glans/corona samples were also more likely to be infected with multiple HPV types than other sites. CONCLUSIONS: More complete anogenital sampling and sensitive detection for 37 HPV types resulted in a higher HPV prevalence in primarily asymptomatic men than reported previously. The penile shaft was the site most likely to be HPV positive and harbored the greatest proportion of multiple type and oncogenic infections. These results have implications for research of HPV among men and transmission between partners.     

Somatic mutation analysis of <Emphasis Type="Italic">MYH11</Emphasis>in breast and prostate cancer

Background  

MYH11 (also known as SMMHC) encodes the smooth-muscle myosin heavy chain, which has a key role in smooth muscle contraction. Inversion at the MYH11 locus is one of the most frequent chromosomal aberrations found in acute myeloid leukemia. We have previously shown that MYH11 mutations occur in human colorectal cancer, and may also be associated with Peutz-Jeghers syndrome. The mutations found in human intestinal neoplasia result in unregulated proteins with constitutive motor activity, similar to the mutant myh11 underlying the zebrafish meltdown phenotype characterized by disrupted intestinal architecture. Recently, MYH1 and MYH9 have been identified as candidate breast cancer genes in a systematic analysis of the breast cancer genome.