Correlation between integration of high-risk HPV genome into human DNA detected by molecular combing and the severity of cervical lesions: first results of the EXPL-HPV-002 study.

OBJECTIVES: The aim of the EXPL-HPV-002 study is to evaluate the integration of 14 high-risk HPV as a biomarker of the severity and the progression of cervical lesions. Such a „triage biomarker“ would help to reduce the number of unnecessary colposcopies, to avoid over-treatment of lesions that spontaneously regress and to better target the lesions requiring treatment. DESIGN: EXPL-HPV-002 is a prospective, open-label, single arm, GCP study conducted at 2 clinical sites in the Czech Republic. SETTINGS: Investigations centers: Private Gynecology Center, Brno; Gynecological and Obstetrical Clinic, Brno; Genotyping central lab: NRL for Papillomaviruses and polyomaviruses, IHBT, Prague; Histology Central reading: Aeskulab Pathology, Prague; Molecular combing HPV test: Genomic Vision, Bagneux. METHODS: From June 2016 to May 2018, 688 patients aged 25-65, referred to colposcopy after an abnormal Pap-smear, were enrolled in the study. Among them 60% were found HPV high-risk. The study is divided in two phases: 1. a cross-sectional phase using data collected at first visit (colposcopy images ± histology, pap-smear for HPV genotyping and molecular combing) to study the association between HPV integration status versus colposcopy and histology grades; 2. a longitudinal phase using data collected in follow-up visits: cytology at 6, 18 and 30 months and colposcopy ± histology at 12, 24 and 36 months. A pap-smear collected at 12, 24 and 36 months allows to perform genotyping and molecular combing. HPV integration status is analyzed in comparison with the evolution of lesions, viral clearance and HPV genotype. HPV genotyping and molecular combing were performed on pap-smear samples in central laboratories. Histology data were reviewed by central reading. RESULTS: The transversal phase of the study is achieved and shows that the HPV integration into the human DNA, monitored by molecular combing, can significantly differentiate normal subjects from women with cervical lesions or cancer. CONCLUSION: HPV integration into the host genome, monitored by Genomic Visions technology, is a reliable diagnostic biomarker that will greatly help clinicians to improve their medical decision tree.

Electrochemically controlled winding and unwinding of substrate-supported carbon nanoscrolls.

Carbon nanoscrolls (CNSs) formed spontaneously on the basal plane of highly ordered pyrolytic graphite (HOPG) show winding and unwinding movements when potential steps from 0 V to -0.5 V, -0.6 V and -0.9 V are applied on HOPG immersed in an aqueous electrolyte solution (0.1 M H2SO4). Reversible changes in CNS radial dimensions exceeding 10 nm in the axial direction and 50 nm in the lateral direction are ascribed to variations in the surface tension and electric double-layer structure under applied potentials. Radial motion is observed exclusively on scrolled tube-shaped nanostructures, while other parts of the HOPG surface including planar areas, simple bended and lifted step edges, and kinks remain intact. The mechanism explaining the observed phenomenon is proposed and its significance for prospective applications in electrochemically controlled nanomechanical actuators is outlined.

[Doctors specialty training in obstetrics and gynecology at university medical schools: 2012-2013]. / Specializacní vzdelávání v gynekologii a porodnictví na lékarských fakultách: 2012-2013.

OBJECTIVE: The paper addresses transfer of doctors specialty training from the national Institute of postgraduate medical education (IPVZ) to University Medical Schools (UMS) with the special focus to Obstetrics and Gynecology (OG). METHODS: The National Specialty Board (NSB) has been established. NSB tasks include definition of inclusion criteria and process of specialty choice at UMS. In OG specialty there are defined mid-term and final postgraduate training courses and other requirements for final specialty exam (FSE) - in particular trainees scientific work and surgery done with the supervision of NTB member. The system of FSE, its content, application, reimbursement and mechanisms are described in details. RESULTS: In the whole country in 2012 there have been done 864 FSE in all basic medical specialties, which took place at seven UMS. Autumn semester terms has been utilized significantly more than spring terms (57% vs. 43%). There have been differences in the numbers of specialties and also numbers of candidates in each specialty among different UMS. In total 94% of applicants succeed in the FSE. In 2012 within OG specialty training there has been held 56 FSE - 24 exams on five UMS in spring term and 32 (57%) exams only on two UMS in autumn term. In the spring 2013 FSE were organized on 1st LF UK in Prague with 23 applicants, from which 22 successfully passed. During autumn 2013 the FSE in OG will be held on LF UP in Olomouc with 44 applicants for final postgraduate training course and 39 candidates for FSE. CONCLUSION: Within OG specialty the transfer of doctors specialty training from IPVZ to UMS has been successfully managed. The NSB in OG specialty closely cooperates with past IPVZ and the Accreditation Commission of the Czech Ministry of Health. Thus continuity, quality and continuous enhancement of specialty training program in OG in Czech Republic is assured.

[Treatment strategies of the colorectal anastomosis stricture]. / Strategie lécby striktury kolorektální anastomózy.

INTRODUCTION: The treatment of the stenoses of colorectal anastomoses represents a difficult area of colonic surgery. This is partly connected to the introduction of staplers and an increasing amount of sphincter-preserving surgeries. At our clinic, we solve the stenoses of colorectal anastomoses using a surgical rectoscope with a good effect. MATERIAL AND METHODS: We analysed retrospectively a group of 27 patients with benign stenosis of colorectal anastomosis of the medial and upper rectum who underwent surgery at our clinic in the period between January 2004 and December 2011. From the total amount of 27 patients, in 23 patients the stenosis was caused by the dehiscence of anastomosis, and in 4 patients the stenosis had a different etiology. RESULTS: In the group of 27 patients, in 14 patients the stenosis of colorectal anatomosis was solved radiologically using a high pressure balloon. Total of 13 patients underwent surgery, in 10 of them we used the surgical rectoscope and 3 patients underwent an open abdominal procedure. CONCLUSION: The first method of choice in treatment of the stenoses of the colorectal anastomoses is a balloon dilatation. If this is not successful we can use the surgical rectoscope as a minimally invasive though effective and safe method.

A three-headed piriformis muscle: an anatomical case study and narrative review of literature.

The piriformis muscle (PM) is found in the gluteal region, exiting the pelvis through the greater sciatic foramen and dividing it into the suprapiriform and infrapiriform foramina. The piriformis works as part of the hip external rotator muscle group, and is responsible for rotation of the femur upon hip extension and abduction of the femur during flexion of the hip joint. The aim of the present report is to describe a very rare case of the primary three-headed PM. To the best knowledge of the authors, the said variant has not yet been described in the existing literature. The 71-year-old male formalin-fixed cadaver was subjected to routine dissection. After careful removal of the connecting tissue, three separate, primary heads of the PM were identified. The lower head of the PM arose from the middle part of the sacral bone; 87.56 mm long and 9.73 mm wide. The medial head was attached to the internal part of the posterior inferior iliac spine; 121.6 mm long and 20.97 mm wide. The upper head was attached to the external part of the posterior inferior iliac spine; 78.89 mm long and 23.94 mm wide. All heads converged into a common tendon which inserted onto the greater trochanter. The clinical importance of this work comes down to the fact that the aberrant PM may be the reason behind the piriformis syndrome and its associated symptoms. Moreover, knowledge regarding the variant anatomy of the PM is of immense importance to, e.g. anaesthesiologists performing computed tomography- or ultrasound-guided sciatic nerve injection for local anaesthesia, radiologists interpreting imaging studies, and surgeons, especially during posterior approaches to the hip and pelvis.

Extensive pneumatisation of the sphenoid bone: anatomical investigation of the recesses of the sphenoid sinuses and their clinical importance.

BACKGROUND: There is a great variance between the extents of pneumatisation of the sphenoid sinuses that can reach beyond the body of the sphenoid bone. The purpose of this study was to find the prevalence of the recesses of the sphenoid sinuses in Polish adult population. MATERIALS AND METHODS: Two hundred ninety-six computed tomography (CT) scans of patients who did not present any pathology in the sphenoid sinuses were evaluated in this retrospective analysis. Spiral CT scanner (Siemens Somatom Sensation 16) was used to glean the medical images. Standard scan procedure was applied, with Siemens CARE Dose 4D option enabled. No contrast medium was administered. RESULTS: In the majority of the patients (93.92%), the pneumatisation of the sphenoid sinuses expanded beyond the body of the sphenoid bone; hence, there were recesses of the sinuses present. The most common variant was the presence of two recesses - 12.84% of cases. The prevalence of all the 17 recesses was only 0.34%. Amongst the uneven recesses present, the sphenoidal rostrum's recess (61.15% of the patients) and the inferior clinoid recess (56.42%) were the most common. Amongst the even recesses present, the lateral recess was prevalent in the majority (65.88%), whereas the posterior clinoid process' recess was the least common (9.8%). CONCLUSIONS: Presence of the recesses might facilitate access to the cranial fossae; hence, comprehensive evaluation of the sphenoid sinuses is of immense importance in order to avoid unnecessary drills through the hard bone, which could potentially damage the nearby neurovascular structures.

Utility of Botulinum Injections in Stiff-Person Syndrome.

Stiff-person syndrome (SPS) is an uncommon neurological disorder characterized by significant rigidity and muscle spasms primarily affecting the truncal and proximal musculature. Furthermore, a wide-based gait with functional impairment is generally seen. High-dose benzodiazepines or baclofen are widely considered the optimal initial therapy; however, major adverse effects often preclude adequate dosing. Refractory cases may be treated with intravenous immunoglobulins (IVIG), plasma exchange, or B-cell depletion with rituximab, although these are also associated with major, sometimes fatal, adverse reactions. Several reports have validated the safety and utility of botulinum injections in this setting, yet botulinum remains markedly underutilized in this cohort. Below, a case report and review of the literature show botulinum can decrease pain and stiffness, improve gait and balance, and decrease dependence on powerful systemic treatments in this group.

Cerebral Venous Sinus Thrombosis in a Patient with Ulcerative Colitis Flare.

Inflammatory bowel disease is characterized by a chronic inflammatory state and is therefore associated with abnormalities in coagulation and a hypercoagulable state. Cerebral venous sinus thrombosis is a rare complication of inflammatory bowel disease yet contributes significant morbidity and mortality to those affected. Early diagnosis is critical, as a delay in diagnosis portends a worse prognosis. This paper seeks to highlight the increased risk of venous sinus thrombosis in patients with inflammatory bowel disease. We start by discussing the case of a seventeen-year-old female who presented with ulcerative colitis flare and developed new-onset seizures, found to be caused by a large venous sinus thrombosis.

[Myxoma and myxoid chondrosarcoma of the nasal septum: two case reports]. / Myxomatöse Neoplasien des Nasenseptums: 2 Fallberichte.

Myxoid neoplasms are histopathologically divided into true myxomas and other tumors of myxomatous character. In the region of the nasal septum, this tumor entity is extremely rare. In the following two case reports, the unusual findings of a myxoma and a myxoid chondrosarcoma of the nasal septum are presented and discussed. At first visit, both patients reported a slowly progressing, bilateral nasal obstruction. In nasal endoscopy, both showed a smoothly surfaced, spheroid, soft tissue mass in the dorsal nasal septum. On CT-scans, a displacing growth was described for the first patient; in the second patient, a bony arrosion of the floor of the sphenoid sinus was suspected. Both lesions were surgically completely removed. The histopathological diagnosis was myxoma in the first and myxoid chondrosarcoma in the second patient. An early, locally recurrent tumor in the second patient could also be surgically removed. Both patients have been in full remission for more than a year. In spite of the similar symptoms and clinical findings, histopathologically different myxoid neoplasms of the nasal septum show marked variations in growth and recurrence.

Ho:YAG laser treatment of hyperplastic inferior nasal turbinates.

OBJECTIVES: Although preliminary studies about the successful use of the Ho:YAG laser in nasal turbinate surgery have been reported, no clinical study has been performed on this procedure. The aim of this prospective clinical study was to assess the long-term effect of Ho:YAG laser in the treatment of hyperplastic inferior nasal turbinates. METHODS: Eighty-five patients with nasal obstruction who did not respond to conservative medical treatment were treated with a pulsed Ho:YAG laser (wavelength of =2080 nm). Fifty-two of these patients were included in this clinical study and were followed for 1 year. RESULTS: Within the first 2 weeks, nasal obstruction was correlated to the extent of nasal crusting. Six months after laser treatment, the mucociliary function test showed no variation compared with the preoperative measurements. One year after laser treatment 77% of the patients demonstrated improved nasal airflow on rhinomanometry and questionnaire. CONCLUSIONS: Ho:YAG-laser treatment of hyperplastic turbinates can be performed as outpatient surgery under local anesthesia and offers controllable ablation of soft tissue in a short operation time with satisfactory results and excellent patient acceptance.

Evidence of complex formation between alkaline phosphatase and a pro-apoptotic hemoprotein cytochrome c.

Two proteins, alkaline phosphatase (AP) and cytochrome c (cyt c) which seem to be involved in the apoptotic cell death program were examined on their interaction. Intestinal AP affects ferricytochrome c (cyt c(FeIII)) by changing its optical properties, redox state and conformation. The effect proceeded over the course of hours with a gradual decrease in free cyt c(FeIII) as the AP concentration increased. A heme containing high molecular species was created in the first stage of interaction of the proteins in neutral, acidic (pH 2.6), alkaline (pH 8.3), low ionic strength (10 mmol/l phosphate), and high ionic strength (0.5 mol/l NaCl) media. Further complexation was favored by higher pH values and temperature. Differential scanning calorimetry revealed a decrease in enthalpy of the thermodenaturation temperature (Tm) of cyt c at 84.5 degrees C due to the AP addition. Increments of AP in the mixtures resulted in the appearance of Tm peaks at 68 degrees C and 61 degrees C. Electrophoretic analysis of the commercial samples of intestinal APs showed main fractions from 63.2 kDa to 72.9 kDa and from 172.9 up to 179.0 kDa. Changes in positions and intensities of the bands were detected upon longer incubation (24 h) with cyt c. The electrophoretic pattern of the bacterial AP was homogeneous with one fraction of 43.7 kDa showing no alteration due to the cyt c presence. Gel permeation chromatography of incubated mixtures of intestinal APs and cyt c confirmed the creation of new heme containing complexes.

[Long-term treatment with desmopressin in children with primary nocturnal enuresis. An international multicenter study]. / Dlouhodobá lécba desmopresinem u detí s primární nocní enurézou. Mezinárodní multicentrická studie.

BACKGROUND: Desmopressin (an analogue of antidiuretic hormone) holds an important place in the treatment of primary nocturnal enuresis. According to some long-term trials its action is mainly symptomatic. The benefit of treatment and persistence of the effect in relation to the expected decline of enuresis in 15% children/1 year is discussed. METHODS AND RESULTS: The open multicentre trial lasted 42 months. In the first stage 265 patients (164 boys, 101 girls) aged 9.4 +/- 2.8 (5-18 years) were given desmopressin (nasal drops) to achieve a 4-week dry integral. Enuresis stopped in 207/265 (78.1%) children within six (median) weeks of treatment after an effective dose of 10.5 micrograms (median) based on titration. During the second stage 55/265 children (25 boys and 30 girls) proceeded with treatment for 2-30 (median 12) months, one boy did not complete the trial. An effective dose was administered for 3.5 months (median) and then the dose declined depending on the effect by 3.5 micrograms (1 drop) per months (median). In the titration stage enuresis receded in 89.1% (49/55) children. After the first year of the trial there were 72.7% responders (p < 0.001, as compared with the assumed decline), after two years 70.9% (p < 0.01) and after three years 61.1% children (p < 0.05). The trial was completed by 61.1% (33/54) children as respondents. 23 of them 17-38 months after termination of treatment. 29.6% (16/54) patients were relapsing responders on long-term treatment, 5.6% (3/54) patients completed the trial as partial responders and 3.7% (2/54) children as non-responders. Minor side-effects were recorded during the titration stage in 4.5% children, during long-term treatment 5.4% children. The osmolality of morning urine increased during treatment regardless of the final effect (p < 0.01). The authors did not find a significant relationship between age, sex, familial incidence of enuresis, period of treatment and the achieved effect. CONCLUSIONS: The authors provided evidence of a rapid onset of the effect of desmopressin and a high effectiveness throughout the trial. The osmolality of the morning urine was not a reliable predictive factor of the effect. In the authors opinion long-term treatment is important for development of regulation and regression of complaints. During a relapse the authors recommend return to maintenance treatment and gradual discontinuation after 6-12 months. Desmopressin treatment is in the authors' opinion safe, well tolerated and very useful.

Nanobubble assisted nanopatterning utilized for ex situ identification of surface nanobubbles.

Nanobubble assisted nanopatterning of polystyrene (PS) film allows visualization of nanobubble positions and identification of their appearance on the surface ex post by atomic force microscopy (AFM) imaging ex situ. Due to the PS nanograin size, ∼10(1) nm, nanobubbles of diameter less than 50 nm can be resolved, as well as microbubbles and micropancakes. The time scale of the nanopattern formation was found to be in the seconds range. This relatively short exposure time thus provides the possibility of also resolving some aspects of microbubble and nanobubble dynamics. In this work we demonstrate that ex post, ex situ AFM imaging of a PS surface after its exposure to deionized water allows us to examine nanobubble and microbubble formation, distribution and arrangement without any influence of the AFM scanning tip and under experimental conditions where in situ AFM imaging is not feasible, e.g. in liquid flow.