Transcriptomic profiling of trophoblast fusion using BeWo and JEG-3 cell lines.

In human placenta, alteration in trophoblast differentiation has a major impact on placental maintenance and integrity. However, little is known about the mechanisms that control cytotrophoblast fusion. The BeWo cell line is used to study placental function, since it forms syncytium and secretes hormones after treatment with cAMP or forskolin. In contrast, the JEG-3 cell line fails to undergo substantial fusion. Therefore, BeWo and JEG-3 cells were used to identify a set of genes responsible for trophoblast fusion. Cells were treated with forskolin for 48 h to induce fusion. RNA was extracted, hybridised to Affymetrix HuGene ST1.0 arrays and analysed using system biology. Trophoblast differentiation was evaluated by real-time PCR and immunocytochemistry analysis. Moreover, some of the identified genes were validated by real-time PCR and their functional capacity was demonstrated by western blot using phospho-specific antibodies and CRISPR/cas9 knockdown experiments. Our results identified a list of 32 altered genes in fused BeWo cells compared to JEG-3 cells after forskolin treatment. Among these genes, four were validated by RT-PCR, including salt-inducible kinase 1 (SIK1) gene which is specifically upregulated in BeWo cells upon fusion and activated after 2 min with forskolin. Moreover, silencing of SIK1 completely abolished the fusion. Finally, SIK1 was shown to be at the center of many biological and functional processes, suggesting that it might play a role in trophoblast differentiation. In conclusion, this study identified new target genes implicated in trophoblast fusion. More studies are required to investigate the role of these genes in some placental pathology.

Renal pseudoaneurysm: a rare and potentially fatal complication following ureteroscopy and laser fragmentation of stones.

Ureteroscopy and laser fragmentation of stones is a commonly used method to treat ureteric and renal calculi. We report the exceedingly rare finding of a renal pseudoaneurysm in an interpolar renal artery following ureteroscopy and laser stone fragmentation, which was successfully managed with angioembolisation.

A randomised controlled double-blind clinical trial of 17-hydroxyprogesterone caproate for the prevention of preterm birth in twin gestation (PROGESTWIN): evidence for reduced neonatal morbidity.

OBJECTIVE: To determine whether 17 alpha-hydroxyprogesterone caproate (17OHPC) prolongs gestation beyond 37 weeks of gestation (primary outcome) and reduces neonatal morbidity (secondary outcome) in twin pregnancy. DESIGN: Randomised controlled double-blind clinical trial. SETTING: Tertiary-care university medical centre. POPULATION: Unselected women with twin pregnancies. METHODS: Participants received weekly injections of 250 mg 17OHPC (n = 194) or placebo (n = 94), from 16-20 to 36 weeks of gestation. Randomisation was performed using the permuted-block randomisation method. Data were analysed on an intention-to-treat basis. MAIN OUTCOME MEASURE: Preterm birth (PTB) rate before 37 weeks of gestation. RESULTS: There were no significant differences in the average gestational age at delivery, or in the rates of PTB before 37, 32, and 28 weeks of gestation, between the two groups. The proportion of very-low-birthweight neonates (<1500 g) was significantly lower in the 17OHPC group (7.6%) compared with placebo (14.3%) (relative risk, RR 0.5; 95% confidence interval, 95% CI 0.3-0.9; P = 0.01). Progestogen-treated neonates had a significantly lower composite neonatal morbidity (19.1%) compared with placebo (30.9%) (odds ratio, OR 0.53; 95% CI 0.31-0.90; P = 0.02), with significantly lower odds for respiratory distress syndrome (14.4 versus 23.4%; OR 0.55; 95% CI 0.31-0.98; P = 0.04), retinopathy of prematurity (1.1 versus 4.6%; OR 0.21; 95% CI 0.05-0.96; P = 0.04), and culture-confirmed sepsis (3.4 versus 12.8%; OR 0.24; 95% CI 0.10-0.57; P = 0.00). CONCLUSIONS: Intramuscular 17OHPC therapy did not reduce PTB before 37 weeks of gestation in unselected twin pregnancies. Nonetheless, 17OHPC significantly reduced neonatal morbidity parameters and increased birthweight.

Impact of pre-existing left ventricular dysfunction on kidney transplantation outcomes: implications for patient selection.

BACKGROUND: End-stage kidney disease patients with decreased left ventricular ejection fraction (EF) are often denied kidney transplantation (KT) for fear of poor graft and patient survival. METHODS: We retrospectively studied all patients who underwent KT at our center between 2001 and 2005 to determine the impact of low EF on outcomes post KT. Low EF was defined as <50% EF by noninvasive cardiac imaging. Follow-up was for 1 year post KT. Outcomes assessed included hospitalization for congestive heart failure (CHF), cardiac events, and renal allograft and patient survival. RESULTS: Among 254 patients, 37 had low EF (study group) and 217 had normal EF (≥50%; control group). Post KT, the low EF group had a significantly higher rate of hospitalization for CHF. No significant difference was noted in the rate of cardiac events, graft loss, GFR, and all cause death at 12 months post KT. CONCLUSION: Patients with low EF should not be excluded from transplantation, given favorable outcomes.

Burn resuscitation: is it straightforward or a challenge?

Burn shock resuscitation has been extensively studied over the past four decades. Many formulas exist and many parameters have been suggested to assess the adequacy of resuscitation. The most commonly used formula is the Parkland formula, the most commonly used fluids are crystalloids, and the most commonly used parameter is urine output. However, until now, no conclusive evidence has suggested that one formula is superior to another or that one parameter is a better predictor than another. In this article we will review the updated information about the subject and we will look into new advancements in this field. We will pose some questions at the end that will help researchers concentrate their future efforts to solve this important challenge in burn care.

The effect of injections of botulinum toxin type A combined with casting on the equinus gait of children with cerebral palsy.

Our aim was to evaluate the effect of adding inhibitory casting to the treatment of young children with cerebral palsy who received injections of botulinum neurotoxin A (BoNT-A) to gastrocnemius for equinus gait. Of the 20 patients in the series, 11 in group A had inhibitory casts applied on the day of the first set of BoNT-A injections and nine in group B did not have casting. Both groups received another BoNT-A injection four months later. The patients were followed for eight months and examined at five intervals. Both groups showed significant improvement in gait parameters and function (p < 0.0001) and selective motor control (p = 0.041, - 0.036) throughout the study. Group A had significantly better passive dorsiflexion of the ankle (p = 0.029), observational gait score (p = 0.006) and selective motor control (p = 0.036). We conclude that the addition of inhibitory casting enhances and prolongs the results of treatment and mainly influences the passive range of movement, while BoNT-A mostly influences the dynamic motion. The second injection further improved the results of most parameters. The gross motor function measure, the selective motor control test and the modified Tardieu scale correlated well with the results of treatment. We recommend the use of inhibitory casting whenever augmentation of the effect of treatment with BoNT-A is needed.

Burn wound cleansing - a myth or a scientific practice.

Burn wound cleansing is an integral step in every wound management protocol. Yet a lot of this practice is based on myth rather than real scientific basis. The literature is poor in scientific papers comparing the outcome of patients who underwent wound cleansing to those who did not. A survey form was designed by the Mediterranean Council for Burns and Fire Disasters - MBC and sent by e-mail to its members as well as members of the European Burn Association and other burn specialists, and 76 replies were received. Responses showed wide inconsistencies in the methods of burn wound cleansing, the solutions used for cleansing, the added antiseptics or detergents used, and the frequency of cleansing. Wound cleansing and dressing is a process that should be based on evidence and not on a ritualistic behaviour or a personal preference. In order to optimize burn wound care and promote optimal healing, more clinical evidence-based studies are needed to confirm or negate the positive or negative effects of any topical solution currently in use for burn wound cleansing.

Perthes' disease and the search for genetic associations: collagen mutations, Gaucher's disease and thrombophilia.

The role of heritable thrombophilic risk factors in the pathogenesis of the Perthes' disease is controversial. The clinical and radiological findings of Perthes' disease may be indistinguishable from those of Gaucher's disease, and the most common Jewish N370S Gaucher mutation is threefold greater in patients with Perthes' disease. Familial osteonecrosis of the femoral head is associated with variant mutations of collagen type II (COL2A1 mutations). We therefore studied the potential role of genetic thrombophilia and the Gaucher and COL2A1 mutations in children with Perthes' disease. Genomic DNA of 119 children with radiologically-confirmed Perthes' disease diagnosed between 1986 and 2005 was analysed for the thrombophilic polymorphisms Factor V Leiden, 677T-MTHFR and FIIG20210A. The results were compared with those of a group of 276 children without Perthes' disease. DNA was also analysed for the Gaucher mutations N370S, G insertion (84GG), L444P, Intron 2 (IVS2+1G>A) and R496H. Enzymic assays confirmed the Gaucher disease status. Collagen (COL2A1) mutations of the 12q13 gene were also analysed. The prevalence of thrombophilic markers was similar among the 119 patients with Perthes' disease and the 276 control subjects. The prevalence of the Gaucher mutation was consistent with Israeli population carriership data and did not confirm an earlier-claimed association with Perthes' disease. All 199 patients were negative for the studied COL2A1 mutations. We found no genetic association between Perthes' disease and either Gaucher's disease or COL2A1 mutations or increased genetic thrombophilia among our patients compared with the control group. A systematic review of case-control studies suggested that there was a positive association between Perthes' disease and Factor V Leiden. The impact of this association upon the disease, although not consistent across the studies, remains unclear.

Numeric expression of aesthetics and beauty.

Debate over what constitutes beauty, particularly beauty of the human body, has raged since philosophy began. Interested scholars have debated the meaning of beauty for centuries. However, it seems that numbers and the resulting numeric relationships play a fundamental role in the classification of the human body, and that a harmonic profile or body shape is produced only at certain definite numeric relationships. The beauty of individual features depends on "ideal" proportions, and it is suggested that expressing beauty in terms of geometry is possible. As the demand for aesthetic surgery has increased tremendously over the past few decades, it is becoming essential to be able to assess the possible satisfaction that can be expected after an aesthetic surgery procedure and to determine the beauty of the final result as precisely as possible.

[Quality assurance in biometry before cataract surgery: which patients have an increased risk of aberrance from target refraction?]. / Qualitätssicherung in der Biometrie vor Kataraktoperationen: Welche Patienten haben ein erhöhtes Risiko für Abweichungen von der Zielrefraktion?

BACKGROUND: An important factor for patient satisfaction after cataract surgery is the achievement of the planned target refraction. The formulae which are used to calculate the necessary refractive power of the intraocular lens (IOL) to be implanted have been improved over time in order to deliver exact predictions even in those cases in which the measurements of an eye deviate greatly from the norm. We examined which of the routinely measured biometric values have an influence on reaching target refraction. PATIENTS AND METHODS: This retrospective investigation reports on a case series of 153 eyes of 146 patients within 6 months in which a cataract operation was performed. The average age at the time of operation was 73.5 years. Four measurements were taken preoperatively: refraction (Ref), axial length (AL), corneal refractive power (CR) and anterior chamber depth (ACD). Each of these measurements was examined regarding its influence on the refractive outcome. One of three end points was possible for each eye: achievement of target refraction within +/- 0.5 dpt, aberrance from target refraction by more than + 0.5 dpt and aberrance from target refraction by more than - 0.5 dpt. A multivariate regression analysis was performed in which aberrance from target refraction was defined as the dependent variable and the four mentioned measurements were set as independent variables. RESULTS: Of the 153 eyes, in 91 eyes the target refraction was achieved within 0.5 dpt (group 1). In 37 eyes the aberrance from target refraction was more than - 0.5 dpt (group 2) and in 25 eyes it was more than + 0.5 dpt (group 3). The mean measurement values in groups 1, 2 and 3 were as follows: for preoperative refraction 0.0 dpt/0.5 dpt/0.625 dpt, for corneal refractive power 42.84 dpt/42.29 dpt/42.67 dpt, for axial length 23.41 mm/23.36 mm/23.73 mm and for anterior chamber depth 3.07 mm/3.00 mm/3.20 mm. No statistically significant relation between the respective measured values or a combination thereof and the refractive result could be demonstrated. CONCLUSIONS: The formulae for calculating IOL power available today are highly developed and integrate preoperative biometries in a non-linear way, so that there is little difference between measurements within the norm and outlying ones concerning their influence on the refractive result. When conducting quality assurance efforts, we recommend to direct attention to factors influencing anterior chamber depth.

First clinical experience with anecortave acetate (Retaane).

BACKGROUND: Anecortave acetate is an angiostatic cortisene which is injected as a posterior juxtascleral depot and has been shown to be effective in the treatment of exudative age-related macular degeneration (AMD). The compound is not yet approved in Switzerland but can be used as "compassionate use" in individual cases. PATIENTS AND METHODS: An uncontrolled case series with standardised documentation of ETDRS visual acuity, near acuity, need for magnification and fluorescein angiography was performed. RESULTS: 22 eyes of 19 patients (8 male, 11 female, average age 78.8 years) were treated with a posterior juxtascleral depot injection (PJD) of 15 mg anecortave acetate. The mean change in visual acuity after 3 months in eyes treated with anecortave acetate was -2.6 ETDRS letters corresponding to 0.52 Snellen lines. 3/20 eyes gained more than 1 line. 11/20 eyes showed stable visual acuity (+/- 1 Snellen line, +/- 5 ETDRS letters). 5/20 eyes developed moderate vision loss (one to two Snellen lines, 6-10 ETDRS letters). 1/20 lost 18 ETDRS letters (> 3 Snellen lines). There were no moderate or severe adverse events. CONCLUSIONS: A PJD of 15 mg anecortave acetate is safe and well tolerated. In eyes with occult CNV without recent progression or with residual neovascular activity after photodynamic therapy anecortave acetate may be an alternative therapeutic option before considering intravitreal anti-VEGF agents due to the much less invasive character and lower risk profile.

Military and civilian burn injuries during armed conflicts.

Burn injury is a ubiquitous threat in the military environment, and war burns have been described for more than 5,000 years of written history. Fire was probably utilized as a weapon long before that. With the ever-increasing destructive power and efficiency of modern weapons, casualties, both fatal and non-fatal, are reaching new highs, particularly among civilians who are becoming the major wartime targets in recent wars, accounting for most of the killed and wounded. Even though medical personnel usually believe that a knowledge of weaponry has little relevance to their ability to effectively treat injuries and that it may in some way be in conflict with their status, accorded under the Geneva and Hague treaties, it is imperative that they know how weapons are used and understand their effects on the human body. The present review explores various categories of weapons of modern warfare that are unfamiliar to most medical and paramedical personnel responsible for burn treatment. The mechanisms and patterns of injury produced by each class of weapons are examined so that a better understanding of burn management in a warfare situation may be achieved.

An elevated PSA, which normalizes, does not exclude the presence of prostate cancer.

The purpose of this study was to determine the incidence of prostate cancer in patients who have an elevated referral prostate-specific antigen (PSA), which subsequently falls to within their normal age-specific reference range prior to prostate biopsy. The study demonstrated that of the 160 patients recruited, 21 (13%) had a repeat PSA level which had fallen back to within their normal range. Five of these 21 patients (24%) were diagnosed with prostate cancer following biopsy, two of whom had a benign prostate examination. The study, therefore, demonstrates that normalisation of the PSA level prior to biopsy does not exclude the presence of prostate cancer even when the prostate feels benign.

Armed conflict and burn injuries: a brief review*.

Burns and fire disasters are sad but common and obligatory components of armed conflicts, and with the increasing sophistication of weaponry and of chemical and nuclear devices the problem is not set to disappear; on the contrary. Indeed, with the (fortunate) decrease of major international wars but with the (unfortunate) increase of smaller ethnic and sectarian but equally treacherous conflicts, burns are bound to remain a constant problem. Yet the profession is ill prepared for such dark challenges.

Marjolin's Ulcer of the Scalp: a Reconstructive Challenge.

In the year 1828 Jean-Nicolas Marjolin described the formation of ulcers specifically in chronic burn scars, and in 1903 De Costa coined the term "Marjolin's ulcer", applying it to tumours arising in simple leg ulcers. The causes of this condition are described, as also treatment protocols, and a case report is presented.

Women's lower urinary tract function and dysfunction: definitions and epidemiology.

This review focuses on females' lower urinary tract dysfunction (LUTD). It summarises the definitions agreed by the International Continence Society (ICS), investigates the reasons behind the disparity between previous publications related to LUTD and tries to pool their results into subgroups. As urinary incontinence is the main LUTD in women, its prevalence, incidence and risk factors has been studied intensively. However, the review also looks at other LUTD including voiding dysfunction and nocturia.