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Abstract Background Nonspecific low back pain (LBP) has become a significant worldwide public health problem. It is estimated that 84% of people present it at some point in their lives, in which 23% experience its chronic form, negatively affecting their daily lives. Because pain management tool that doesn’t require a firm diagnosis, the development of a device, as SOLIO Alfa Cure Plus, that emanates low level laser therapy, radio frequency and heat with the goal of easing chronic back pain was highly expected. Methods randomized, single blinded, controlled trial. Measures: Numeric Pain Rating Scale (NPRS), the Oswestry Disability Index (ODI) and the Schober’s test. Thirty-seven patients completed pain, disability, and lower back flexibility scales. Randomization was obtained by having an equal amount of sham and real devices and distributing them randomly to patients out of a box where the devices were. Results We observed a larger pain relief in the SOLIO group (42% vs. 23% p = 0.03), and a higher improvement in flexibility (13%) compared to a worsening in the sham group (6.5%; p = 0.04). Conclusion We concluded that utilizing the SOLIO Alfa Cure Plus device may dramatically reduce back pain and allow patients to experience an improvement in quality of life as a result. Trial registration: The clinical trials registration is 8475-21-SMC.

The article discusses the technique of Laterally Extended Parametrectomy (LEP) procedure that was introduced in 1993, which was used to treat femoral artery embolism in patients. Results of the LEP-Wertheim procedure combined proved a better chance for survival and a smaller risk for severe side-effects. Risks of morbidity and hysterectomy includes bladder dysfunction and blood loss. Early detection and emergency intervention is necessary for prevention of this complication.

Abstract Background The HIV viral genome mutates at a high rate and poses a significant long term health risk even in the presence of combination antiretroviral therapy. Current methods for predicting a patient's response to therapy rely on site-directed mutagenesis experiments and in vitro resistance assays. In this bioinformatics study we treat response to antiretroviral therapy as a two-body problem: response to therapy is considered to be a function of both the host and pathogen proteomes. We set out to identify potential responders based on the presence or absence of host protein and DNA motifs on the HIV proteome. Results An alignment of thousands of HIV-1 sequences attested to extensive variation in nucleotide sequence but also showed conservation of eukaryotic short linear motifs on the protein coding regions. The reduction in viral load of patients in the Stanford HIV Drug Resistance Database exhibited a bimodal distribution after 24 weeks of antiretroviral therapy, with 2,000 copies/ml cutoff. Similarly, patients allocated into responder/non-responder categories based on consistent viral load reduction during a 24 week period showed clear separation. In both cases of phenotype identification, a set of features composed of short linear motifs in the reverse transcriptase region of HIV sequence accurately predicted a patient's response to therapy. Motifs that overlap resistance sites were highly predictive of responder identification in single drug regimens but these features lost importance in defining responders in multi-drug therapies. Conclusion HIV sequence mutates in a way that preferentially preserves peptide sequence motifs that are also found in the human proteome. The presence and absence of such motifs at specific regions of the HIV sequence is highly predictive of response to therapy. Some of these predictive motifs overlap with known HIV-1 resistance sites. These motifs are well established in bioinformatics databases and hence do not require identification via in vitro mutation experiments.

Abstract Background Host protein-protein interaction networks are altered by invading virus proteins, which create new interactions, and modify or destroy others. The resulting network topology favors excessive amounts of virus production in a stressed host cell network. Short linear peptide motifs common to both virus and host provide the basis for host network modification. Methods We focused our host-pathogen study on the binding and competing interactions of HIV-1 and human proteins. We showed that peptide motifs conserved across 70% of HIV-1 subtype B and C samples occurred in similar positions on HIV-1 proteins, and we documented protein domains that interact with these conserved motifs. We predicted which human proteins may be targeted by HIV-1 by taking pairs of human proteins that may interact via a motif conserved in HIV-1 and the corresponding interacting protein domain. Results Our predictions were enriched with host proteins known to interact with HIV-1 proteins ENV, NEF, and TAT (p-value < 4.26E-21). Cellular pathways statistically enriched for our predictions include the T cell receptor signaling, natural killer cell mediated cytotoxicity, cell cycle, and apoptosis pathways. Gene Ontology molecular function level 5 categories enriched with both predicted and confirmed HIV-1 targeted proteins included categories associated with phosphorylation events and adenyl ribonucleotide binding. Conclusion A list of host proteins highly enriched with those targeted by HIV-1 proteins can be obtained by searching for host protein motifs along virus protein sequences. The resulting set of host proteins predicted to be targeted by virus proteins will become more accurate with better annotations of motifs and domains. Nevertheless, our study validates the role of linear binding motifs shared by virus and host proteins as an important part of the crosstalk between virus and host.

Abstract Background De novo eukaryotic promoter prediction is important for discovering novel genes and understanding gene regulation. In spite of the great advances made in the past decade, recent studies revealed that the overall performances of the current promoter prediction programs (PPPs) are still poor, and predictions made by individual PPPs do not overlap each other. Furthermore, most PPPs are trained and tested on the most-upstream promoters; their performances on alternative promoters have not been assessed. Results In this paper, we evaluate the performances of current major promoter prediction programs (i.e., PSPA, FirstEF, McPromoter, DragonGSF, DragonPF, and FProm) using 42,536 distinct human gene promoters on a genome-wide scale, and with emphasis on alternative promoters. We describe an artificial neural network (ANN) based meta-predictor program that integrates predictions from the current PPPs and the predicted promoters' relation to CpG islands. Our specific analysis of recently discovered alternative promoters reveals that although only 41% of the 3' most promoters overlap a CpG island, 74% of 5' most promoters overlap a CpG island. Conclusion Our assessment of six PPPs on 1.06 × 109 bps of human genome sequence reveals the specific strengths and weaknesses of individual PPPs. Our meta-predictor outperforms any individual PPP in sensitivity and specificity. Furthermore, we discovered that the 5' alternative promoters are more likely to be associated with a CpG island.

In the choice of a planned fertility preservation procedure for stage IA1 and IB1 cervical cancer, optimal oncological safety is the main focus of virtually all protocols. The surgeon should remove the appropriate proportion of the cervix for oncological safety, ensuring an adequate tumour-free surgical margin. However, some of the literature on fertility preservation, referring to histological parameters, still considers conisation with excellent fertility results to be optimal for the treatment of tumours with a diameter of 2 cm. With regard to fertility preservation in the case of radical trachelectomy versus simple conisation, we are aware of several ongoing studies, the results of which may provide an answer as to whether a more conservative surgical therapy for smaller tumours (less than 2 cm in diameter) represents an acceptable oncological safety.

Objective: To describe the laterally extended parametrectomy (LEP) surgical technique, emphasizing the main challenges of the procedure., Methods: LEP was designed as a more radical surgical procedure aiming to remove the entire parametrial tissue from the pelvic sidewall. Its initial indications were for lymph node positive Stage Ib (current International Federation of Gynecology and Obstetrics 2018 Stage IIIc) and Stage IIb cervical cancer. Currently, with most guidelines recommending definitive radiochemotherapy for these cases, initial LEP indications have become debatable. LEP is now mainly indicated for removing tumors involving the soft structures of the pelvic sidewall during a pelvic exenteration, aiming to obtain lateral free margins. This expands the lateral borders of the dissection to not only the medial surface of internal iliac vessels, but also to the true limits of the pelvic sidewall., Results: During LEP, the parietal and visceral branches of the hypogastric vessels are divided at the entry and exit level of the pelvis. Consequently, the entire internal iliac system is excised, and no connective or lymphatic tissue remain on the pelvic sidewall. The main technical challenges of LEP are caused by the difficulty in ligating large caliber vessels (internal iliac artery and vein) and the variable anatomic distribution of pelvic sidewall veins., Conclusion: LEP is a feasible technique for removing pelvic sidewall recurrences, aiming to obtain surgical free margins.

Introduction: Recurrence originating from the pelvic lymph node containing fibro-fatty tissue has consistently been identified as the most frequent pattern of treatment failure in early-stage cervical cancer. A surgical technique for the complete removal of the connective tissue content of the pelvis was introduced at St. Stephen Hospital in 1993 to improve oncological outcome by reducing the risk of recurrence from the pelvis. Efficacy and toxicity of the procedure were studied in 563 patients with stage IB cervical cancer with a completed 5-year follow-up., Methods: Final pathology in 492 (87.4%) of 563 consecutive completed radical hysterectomies suggested that all tissue, which could contain tumor dissemination, was removed from the pelvis; thus, no adjuvant treatment was applied. Adjuvant chemoradiotherapy was advised in 71 cases (12.6%), where pathologic finding alluded tumor spread beyond the study criteria., Finding: At completed 5-year follow-up, the overall survival of 492 patients who had surgery without adjuvant therapy was 94.0%. Pathologic stage, lymphovascular space involvement, pelvic lymph node metastases, histology classification, and grade had no significant influence on prognosis. The only factor that influenced the overall survival was International Federation of Gynecology and Obstetrics stage (IB1 or IB2). Five-year overall survival of 71 patients to whom adjuvant therapy was recommended was 56.3%. Five-year overall survival of the whole cohort (n = 563) was 88.8%. The complication rate did not seem to be different from the published data on traditional radical surgery in cervical cancer., Conclusions: Our results (in accordance with other recent publications) suggest that complete excision of the connective tissue content of the pelvis provides equal or better survival chances without any adjuvant treatment for almost 90% of operable patients with stage IB cervical cancer than less radical surgery with or without adjuvant treatment. We suggest this strategy to be mentioned as one alternative in future treatment protocols.

Introduction: In 2003, we published our preliminary experience with the use of an operative technique (laterally extended parametrectomy, the LEP procedure) without adjuvant therapy, in the treatment of 29 stage IB, cervical cancer patients with pelvic lymph node metastases. In our present paper, by an extended recruiting period, with a completed 5 year follow up, we studied the outcome of LEP operations, used with the same indications., Methods: In 70 out of 106 LEP-Wertheim operated patients, no adjuvant treatment was used. In 36 patients, where histology suggested tumor spread beyond the threshold of our surgery, adjuvant chemo-radiotherapy was advised. 5 year follow up was completed (without any patient lost for follow up) for the whole cohort of patients., Results: In 70 patients treated by LEP procedure alone, the overall 5-year survival was 91.4%. For those 36 patients, who were excluded due to disease spread above study criteria, 5 year survival was 44%. Complications in 10% of the cases necessitated a second operation. Apart from transient hyper continence and one case of permanent incontinence, no severe quality of life consequence of the operation was observed., Conclusions: Our results suggest that in two-thirds of pelvic lymph node positive, stage IB cervical cancer cases surgery alone could provide equal or better survival (without the toxicity of chemo-radiotherapy), than any kind of multimodality treatment alternatives. LEP procedure should be considered a treatment option for stage IB cervical cancer patients with pelvic lymph node metastases., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Over the past few decades the number of young, reproductive age cancer survivors has increased as a result of improved and less destructive cancer treatments. Certain types of cancers are predominantly diagnosed among reproductive age women and a small proportion of cancers originating in the reproductive tract are also detected in this age group. Treatment in the past used to be definitive and in most cases led to sterility. In recent years, improved medical treatments and more conservative surgical approaches have been introduced increasing the number of young survivors of cancer treatment. These less invasive treatments seem to be associated with similar survival rates and fertility can be preserved in most cases. This has led to studies evaluating the reproductive options of these women. Conservative surgical techniques, the use of chemotherapeutic agents with a reduced gonadotoxic side-effect profile, and the application of more focused radiation therapy are associated with maintenance of fertility. In addition, assisted reproductive technology (ART) has undergone tremendous improvements and now offers several alternatives to those who wish to maintain fertility before or even after cancer therapy. This review summarizes the fertility sparing medical and surgical as well as ART options that reproductive age women desiring to maintain fertility may utilize if they face cancer therapy.

Objective: Discussion of current experiences with abdominal radical trachelectomy in the treatment of early stages of cervical cancer in fertile women., Design: Case-reports., Setting: Department of Obstetrics and Gynecology, General Faculty Hospital and 1st Medical Faculty, Charles University, Prague., Methods: Presentation of 4 cases of abdominal radical trachelectomy and pelvic lymphadenectomy. Discussion with published data., Results: Three cases of open abdominal and one case of laparoscopic abdominal radical trachelectomies together with pelvic lymphadenectomies are presented. All procedures were indicated for cervical cancer stages IA2-IB1. Frozen section of pelvic nodes and a slice of upper margin of cervix revealed no metastasis or infiltration. In total 22-43 pelvic nodes were removed, being negative in all cases. Operative time ranged between 148 and 270 min. in laparotomy and 250 min. in laparoscopy. Blood loss reached 350-3500 ml. There were no intraoperative complications, postoperatively one case of bladder atony was treated by suprapubic drainage for 30 days, one case of ileus was managed pharmacologically. Vaginal suture healed properly in all cases. No complications occurred within limited follow-up of 1-5 months., Conclusion: Abdominal radical trachelectomy with pelvic lymphadenectomy is a rational alternative in the treatment of stages IA2-IIA cervical cancer in women of fertile age. Standard radicality in parametria resection and easy incorporation into armamentarium of oncogynecological centers are main advantages of such approach. Laparotomy can be avoided using laparoscopy.