Knowledge-based computational methods for identifying or designing novel,non-homologous antimicrobial peptides

We describe computational approaches for identifying promising lead candidates for the development of peptide antibiotics, in the context of quantitative structure–activity relationships (QSAR) studies for this type of molecule. A first approach deals with predicting the selectivity properties of generated antimicrobial peptide sequences in terms of measured therapeutic indices (TI) for known antimicrobial peptides (AMPs). Based on a training set of anuran AMPs, the concept of sequence moments was used to construct algorithms that could predict TIs for a second test set of natural AMPs and could also predict the effect of point mutations on TI values. This approach was then used to design peptide antibiotics (adepantins) not homologous to known natural or synthetic AMPs. In a second approach, many novel putative AMPs were identified from DNA sequences in EST databases, using the observation that, as a rule, specific subclasses of highly conserved signal peptides are associated exclusively with AMPs. Both anuran and teleost sequences were used to elucidate this observation and its implications. The predicted therapeutic indices of identified sequences could then be used to identify new types of selective putative AMPs for future experimental verification.     

Prevalence of severe retinopathy of prematurity in a geographically defined population in Croatia

The aim of this study was to evaluate the prevalence of stage III of retinopathy of prematurity (ROP) among newborns of birth weight < 1500 g and gestational age (GA) < or = 32 weeks, and to compare these prevalences during two time periods (1998-2002 and 2003-2007). The investigation was conducted at the Department of Gynecology and Obstetrics, University Hospital in Rijeka, Croatia. The screening for ROP was performed by an ophthalmologist using a binocular indirect ophthalmoscope. Over a period of 10 years, there were 28,627 liveborn newborns, with 136 (0.48%) premature newborns with a birth weights < 1500 g and 226 (0.79%) newborns with GA at birth < or = 32 weeks. The proportions of survivors among newborns with birth weights < 1500 g (51.1% vs. 70.5%) and among newborns with GA at birth < or = 32 weeks (67.9% vs. 77.0%) were significantly higher in the later period. During the period 2003-2007, the proportion examined for ROP was higher among newborns with birth weight < 1500 g (52.9% vs. 97.1%) and among newborns with GA at birth < or = 32 weeks (46.5% vs. 96.9%). The prevalence of stage III ROP was significantly lower in 2003-2007 compared to that in 1998-2002 among newborns with birth weight < 1500 g (30.6% vs. 14.0%) and newborns with GA at birth < or = 32 weeks (22.4% vs. 8.8%). The prevalence of total ROP among newborns was significantly lower in 2003-2007 compared with 1998-2002. This decrease in prevalence may be explained by advances in neonatal intensive care unit, increased survival of very low birth weight infants and carefully timed retinal examinations.     

The role of omega6 to omega3 ratio in development and progression of age-related macular degeneration

The aim of this study is to investigate possible connection between omega-6/omega-3 fatty acid ratio and development and progression of Age-Related Macular Degeneration (ARMD). We examined 125 patients diagnosed with ARMD and divided into 5 groups of 25 patients according to CARMS (Clinical Age-Related Maculopathy Staging System). Control group consists of 51 patients with similar ages, without ARMD. All of them underwent stereobiomicroscopy, fundus photography and fluorescein angiography. Dietary fatty acids intake was measured using food frequency questionnaire (FFQ). The FFQ was based on previously validated questionnaire (DIETQ, Tinuviel Software, Warington, Ches, UK) and FFQ2 from Blue MountainEye Study. The data were analysed using food nutritient dana from McCance and Widdowson's Food Composition Tables, supplemented with a food fatty acid content database (Foodbase, London, UK). We noticed statistically significant difference between omega-6/omega-3 ratio in neovascular ARMD (stage 5) and all other groups including control group (p = 0.000020). The ratio in Stage 5 was about 11:1 like in Western diet. Stage 4-geographic atrophy (GA) has statistically significant difference in o-mega-6/omega-3 ratio compared with stage 1 (p = 0.000571), stage 2 (p = 0.000112) and stage3 (p = 0.000430). The ratio in first three groups is about 7-7.5:1 (greater then Mediteran-4-5:1, but lower then Western Diet-10-20:1). There is no statistically significant difference between first three stages (p > 0.05) and stage 4 and control group (p = 0.172388). Omega-6/omega-3 ratio is connected with development of neovascular ARMD. Decreased ratio protects against neovascular ARMD. On the contrary, GA seems to be connected with prolonged sunlight exposure (the ratio is about 6:1). It is good to know that changing nutrition habits someone can prevent development of severe neovascular form of ARMD because intravitreal anti-VEGF therapy limitations.     

Nail position has an influence on anterior knee pain after tibial intramedullary nailing

Our aim was to determine the possible relationship between anterior knee pain (AKP) and nail position marked as a distance from tip of nail to tibial plateau (NP) and to the tuberositas tibiae (NT). Nail position has an influence on anterior knee pain after tibial intramedullary nailing. We evaluated postoperative outcome results of 50 patients in the last 3 years with healed fractures initially treated with intramedullary (IM) reamed nails with 2 or 3 interlocking screws on both parts of the nail and with the use of medial paratendinous incision for nail entry portal. Patients marked a point on the visual analog scale (VAS) that corresponded to the level of postoperative AKP felt. Two groups of patients were formed on the basis of AKP (pain level was neglected): groups A and B, with and without pain, respectively. The difference between the two groups concerning NP measurements was statistically significant (p < 0.05), but not concerning NT measurements at the p < 0.05 level. Patients were classified by pain with high accuracy (98%) according to a classification tree. Symptoms of AKP did not appear if the tip of the nail position was more than 6.0 mm from the NP and more than 2.6 mm from the NT. However, for better evaluation of these results it will be necessary to examine a larger number of postoperative patients with AKP.     

Influence of psychical trauma through transgenerational transfer on the development of traumatic reactions in women with diagnosed breast cancer

Earlier experience of psychological trauma of a close person can through a transgenerational transfer influence traumatic reactions of a person going through a trauma at present, resulting in a repetition of earlier traumatic experiences and a development of a variety of mental disturbances. Purpose of our study was to evaluate the influence of transgenerational transfer on the development of Posttraumatic stress disorder (PTSD) in women with diagnosed breast cancer that had a family member with diagnosed cancer. The sample mainly consisted of 120 women treated in a Department of Oncology, Osijek University Hospital Center with diagnosis of newly discovered breast cancer, during the conduction of radio therapy having values Hamilton depression scale (HAM-D) from > or = 8 to < or = 24 or values Hamilton anxiety scale (HAM-A) from > or = 17 to < or = 30. Psychotherapeutic interview with a detailed clinical overview and with applying diagnostic criteria according to DSM-IV for mental disorders, specially structured non-standardized questionnaire for etiologic factors evaluation of the beginning of examinees' mental disorder, Los Angeles Symptom Checklist of PTSD symptoms (LASC), Hamilton's scale for anxiety evaluation (HAM-A) and Hamilton's scale for depression evaluation (HAM-D) were used. Results show that 61 (51%) of patients have a family member with diagnosed cancer. The average total value on LASC for examinees that had a family member with diagnosed cancer was slightly higher (22.92) in comparison to those who had no such family member (20.88). No statistically significant connection was found between having a family member with diagnosed cancer and the average total value on LASC. Although no connection was established between having a family member with diagnosed cancer and the average value on LASC in women with diagnosed breast cancer, transgenerational transfer of emotions seems to be important in their traumatic reactions, but it is still insufficiently researched and it is a challenge for future researches leaving many complicated issues open.     

Influence of in-hospital cardiac rehabilitation on psychological status after myocardial infarction in patients with D-type personality

The aim of this study was to determine the number of D-type personality patients in the group with a history of myocardial infarction (MI) and the influence of comprehensive in-hospital cardiac rehabilitation (iCR) on their psychological status (PS). The study included 316 consecutive patients aged 18 to 65 with MI in the last six months admitted into the programme of iCR. Surgical revascularized patients, clinically unstable patients and patients with sever chronic diseases and disorders were excluded. At the beginning and in the end of iCR diagnostic exam, hematological/biochemical blood analysis, ergometric testing was conducted. At the beginning and four weeks after the finish of the iCR estimation of PS was conducted. Distress scale 14 (DS14) questioner was used for that purpose. In the period of three weeks, patients were included in the programme of comprehensive iCR. Out of 316 patients in the study group 83.2% were male, while 16.8% were female. Average age of the patient was 51.3 +/- 7.2. When being admitted to iCR 42.7% patients had characteristics of D-type personality. Those patients had substantially lower level of body mass and body mass index. In the same time there were no differences among groups in risk factors, values of clinical, laboratory and diagnostic parameters. During iCR study group had more complications in comparison to the control group. At the end of iCR substantial rise of functional capacity of patients, improvement of lipid profile and lowering of glycaemia was recorded. Also at the end of iCR antiarrhythmics and psychopharmaceutical medicaments were more often prescribed to the patients in the study group. Four weeks after the iCR share of D-type personality patients was 41% and 71% of study group patients kept their D-type structure.     

Studies on Zn(II) and Cd(II) heteroligand complexes with RC(S)NHP(O)(OiPr)2 (R = Ph, NH2, PhNH) and α-diimine (bpy and phen) ligands. C-Cl bond cleavage of CH2Cl2 by [Zn(phen){PhC(S)NP(O)(OiPr)2}2]

The reaction of [ZnL^I,II₂] (L^I = [NH₂C(S)NP(O)(OiPr)₂]⁻; L^II = [PhNHC(S)NP(O)(OiPr)₂]⁻) or [Cd₂L^IV₄] (L^IV = [PhC(S)NP(O)(OiPr)₂]⁻) with 2,2′-bipyridine (bpy) or 1,10-phenanthroline (phen) leads to the heteroligand complexes [Zn(bpy)L^I,II₂], [Zn(phen)L^I,II₂], [Cd(bpy)L^IV₂] or [Cd(phen)L^IV₂], respectively. The introduction of the diimine ligands into the coordination sphere of the metal cation provokes a change from 1,5-O,S- to 1,3-N,S-coordination of the anionic ligands for Zn but not for the Cd species. The reaction of [Zn(phen)L^IV₂] (L^IV = PhC(S)NP(O)(OiPr)₂⁻) with CH₂Cl₂ cleaves the chlorine atoms from CH₂Cl₂ and leads to the formation of [Zn(phen)L^IVCl] and S,S′-bis(benzimidothio-N-diisopropoxyphosphoryl)methane (L^IV-CH₂-L^IV) in high yields. Using CHCl₃ or CCl₄ instead of CH₂Cl₂ does not lead to the formation of chlorine substituted products even under reflux conditions. The new compounds were investigated by ¹H and ³¹P{¹H} NMR, IR spectroscopy and microanalysis. Crystal structures of [ZnL^II₂], [Cd(phen)L^IV₂]·CH₂Cl₂, [Zn(bpy)L^I₂] and [Zn(phen)L^IVCl] were elucidated by X-ray diffraction.     

The antibacterial threaded-lasso peptide capistruin inhibits bacterial RNA polymerase

Capistruin, a ribosomally synthesized, post-translationally modified peptide produced by Burkholderia thailandensis E264, efficiently inhibits growth of Burkholderia and closely related Pseudomonas strains. The functional target of capistruin is not known. Capistruin is a threaded-lasso peptide (lariat peptide) consisting of an N-terminal ring of nine amino acids and a C-terminal tail of 10 amino acids threaded through the ring. The structure of capistruin is similar to that of microcin J25 (MccJ25), a threaded-lasso antibacterial peptide that is produced by some strains of Escherichia coli and targets DNA-dependent RNA polymerase (RNAP). Here, we show that capistruin, like MccJ25, inhibits wild type E. coli RNAP but not mutant, MccJ25-resistant, E. coli RNAP. We show further that an E. coli strain resistant to MccJ25, as a result of a mutation in an RNAP subunit gene, exhibits resistance to capistruin. The results indicate that the structural similarity of capistruin and MccJ25 reflects functional similarity and suggest that the functional target of capistruin, and possibly other threaded-lasso peptides, is bacterial RNAP.     

Non linear anthropometric predictors in swimming

In this paper we have tried to identify the significance and character of the linear and non-linear relations between simple anthropometric predictors: body height (BH), body weight (BW), and body mass index, and swimming performance: freestyle swimming 50 (FS50) and 400 meters (FS400), in a sample of young (15 years old on average) male (N = 40) and female (N = 28) swimmers. Linear (general model: y = a+bx) and nonlinear regression (general model: y = a+bx+cx2) were calculated simultaneously. Morphological variables are a significantly better predictor of the FS50 in males (BH mostly), and FS400 in females (BW mostly). This study emphasized some of the main advantages in the nonlinear regression calculation (including an interpretation of the relationships at a more superior level), and consequently allowed a precise anthropometric modeling in swimming using simple and easily measurable variables. For example, the best results in FS400 can be expected for the subjects that are average in BW (which guarantees solid muscle mass--the generator of force), but above average in BH (because of the physical law of lever). In conclusion, nonlinear regressions allow one to define the real nature of the relationships between variables, but only if compared with the linear ones. Additionally, this study emphasized one of the most important factors in defining possible specification-equation (e.g. structure of the influence of the different dimensions on the sport achievement) in different sports. In short, it underlines the importance of sampling the appropriate sample of the subject--highly skilled athletes exclusively.     

Ovarian cancer: PCD and brain metastases

Paraneoplastic cerebellar degeneration (PCD), the one of the most common paraneoplastic syndromes, refer to clinical disorders associated mostly with lung, ovarian and breast cancer, but not directly caused by the cancer or its metastases. Pathologic finding is an extensive loss of Purkinje cells in the cerebellum. Immunohistochemically, the auto-antibodies on the Purkinje cells had been detected. Clinically, PCD is characterized by sub-acutely evolving pancerebellar symptoms. Neurological dysfunction may appear before the detection of the underlying cancer. Therefore, the surgical exploration is necessary for the final diagnosis. The patient undergoes specific therapy. Soon, neurological status of the patient gets irreparable worse. Death come usually 2-3 years after the first symptoms of the PCD occurs. Case of a 63-years old woman with PCD as the first evidence of her cancer is reported. The patient developed brain metastases and died almost 3 years after the first symptoms of PCD occur