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The primary objective of this study was to investigate if extended antibiotic treatment against bacterial vaginosis (BV) together with adjuvant lactobacilli treatment could cure BV and, furthermore, to investigate factors that could cause relapse.
In all, 63 consecutive women with bacterial vaginosis diagnosed by Amsel criteria were offered a much more aggressive treatment of BV than used in normal clinical practice with repeated antibiotic treatment with clindamycin and metronidazole together with vaginal gelatine capsules containing different strains of lactobacilli both newly characterised and a commercial one (109 freeze-dried bacteria per capsule). Oral clindamycin treatment was also given to the patient's sexual partner.
The cure rate was 74.6% after 6 months. The patients were then followed as long as possible or until a relapse. The cure rate was 65.1% at 12 months and 55.6% after 24 months. There was no significant difference in cure rate depending on which Lactobacillus strains were given to the women or if the women were colonised by lactobacilli. The most striking factor was a new sex partner during the follow up period where the Odds Ratio of having a relapse was 9.3 (2.8-31.2) if the patients had a new sex partner during the observation period.
The study shows that aggressive treatment of the patient with antibiotics combined with specific Lactobacillus strain administration and partner treatment can provide long lasting cure. A striking result of our study is that change of partner is strongly associated with relapse of BV.
Trial registration
ClinicalTrials.gov: NCT01245322
Bacterial vaginosis (BV) is a disease with unknown aetiology, characterised by loss or reduction of lactobacilli and increased numbers of anaerobes and Gram-negative rods [1]. It is one of the most frequent vaginal infections, and the most common symptom is malodours discharge.
The currently recommended treatment regimes for BV are oral or vaginal metronidazole or vaginal clindamycin [2]. Treatment efficacy is supposed to be high. In a Meta-analysis, the expected cure rate after one month was 70%-80% for metronidazole [3] and 82% for clindamycin [4]. However, in clinical practice these high efficacy rates are rarely observed. Based on our own review of published data, the efficacy is not more than 60% after 4 weeks [5]. Likewise in a follow up study, only 42% were BV free 12 months after therapy [6]. In order to reduce the number of patients who experienced relapse, Sobel et al treated women with recurrent BV with vaginal metronidazole gel for ten days, compared to the normal five days [7]. Women who responded to therapy were then treated with metronidazole gel twice weekly or placebo for 4 months, followed for another 3 months without therapy. By the end of 4 months, 75% were cured in the treatment group compared to 59% in the placebo group, but after 7 months only 49% in the treatment group versus 25% in the placebo group remained cured.
Lactic acid-producing bacilli are part of the normal bacterial microbiota of the vagina and have a physiological role in maintaining a low pH (<4.5), thus protecting against invasion by other micro-organisms [8]. Recent studies, using not only traditional phenotypic methods but also genotyping, have convincingly shown the most common vaginal lactobacilli species to be L. crispatus, L. gasseri, L. iners and L. jensenii [9] where L. crispatus is associated to a normal flora and L. iners more often to BV [10].
The treatment suggestion by Reid et al. [11] i.e. giving oral capsules of L. reuteri (formerly L. fermentum) and L. casei var. rhamnosus, was reported to be successful in 37% of the treated women as compared to 13% given placebo. In a study from Nigeria, the same strains of lactobacilli given orally after a one week course of oral metronidazole cured 88% of women with BV after 30 days compared to 45% in the metronidazole/placebo group [12]. These efficacy results have not been obtained by any other group.
We have previously performed a treatment study with addition of vaginal lactobacilli that did not improve the initial cure rate but the relapse rate was nearly 20% lower in the Lactobacillus treated group [13]. Because of the lower relapse rate noted in this study, we designed a new explorative study with novel, well characterised Lactobacillus strains of human vaginal origin [9].
The primary objectives of this study were to characterise lactobacilli of human vaginal origin and to investigate if more extended antibiotic treatment against BV, together with adjuvant lactobacilli treatment, could increase the cure rate and furthermore, to investigate factors that could influence relapse.
Lactobacillus strains
A total of 110 isolates (51 L. crispatus, 45 L. gasseri and 14 L. jensenei) previously isolated from the vaginal tract of 15 healthy Swedish women [9] were initially included in the study for characterisation and selection of strains for a colonisation study (Table 1). Lactobacillus iners isolates were discarded since these bacteria require special growth requirements, precluding future large scale production and commercial application. Lactobacilli were grown in MRS or Rogosa agar in anaerobiose or in MRS broth in a standing condition at 37°C.
Table 1. Typing of vaginal Lactobacillus isolatesa
Genotyping by REP-PCR and AP-PCR
The Lactobacillus strains were initially typed using PCR amplification on the bacterial repetitive extragenic palindromic DNA sequences (REP-PCR). Chromosomal DNA was isolated from lactobacilli grown in MRS using the DNAeasy kit (Qiagen GmbH, Hilden, Germany) according to the manufacturer protocol for gram positive bacteria. The primers REP1R-I (5'-IIIICGICGICATCIGGC-3') and REP2-I (5'-ICGICTTATCIGGCCTAC-3') were used based on the reproducibility, band intensity and discriminative power [14]. The amplification mixture contained 25 ng template DNA, 1 μM of each primer, 1 X Green GoTaq™ Flexi reaction buffer (Promega, Madison, Wisconsin, USA) and 200 μM of each dNTP, 3 mM MgCl2, and 2.5 U GoTaq™ DNA Polymerase for a total of 50 μl. Bacterial DNA was amplified by PCR using the same thermocycler (GeneAmp® PCR System 9700, Applied Biosystem) and the cycling parameters described by Ventura and Zink [14]. Ten μl of the PCR product was electrophoresised on a 2% agarose gel containing 1 × TAE (Tris acetate-EDTA) and the DNA was visualised by UV transillumination using a Molecular Imager Gel Doc™ system (BioRad, Hercules, CA).
As the L. crispatus strains from women 4, 21 and 23 shared identical REP-PCR profiles, the strains were further differentiated using RAPD (Rapid amplified polymorphic DNA)-PCR with the primers RAPD3 (5'-ACGAGGCAC-3') (primer OPL-5, [15] and RAPD4 (5'-CCGCAGCCAA-3') (primer 1254, [16]). Furthermore, during the colonisation study, positive profile results obtained by REP-PCR were confirmed by two different RAPD PCR using two primers: RAPD3 and RAPD4 for L. crispatus strains; RAPD4 and RAPD6 (5'-TGGGCGTCAA-3') (primer OPL-2, [15]) for L. gasseri strains; and RAPD1 (5'-ATGTAACGCC-3') (primer P2, [17]) and RAPD4 for L. rhamnosus. Each primer was used at 0.5 μM employing the same PCR mixture as described for the REP-PCR. The cycling program was: initial denaturation at 94°C for 2 min; 35 cycles of denaturation at 94°C for 1 min; annealing at 35°C for 1 min; extension at 72°C for 2 min and a final extension at 72°C for 8 min. Ten μl of PCR reaction was electrophoresised on a 2% agarose gel containing 1 X TAE (Tris acetate-EDTA).
Characterisation of Lactobacillus strains
Eighteen Lactobacillus strains isolated from Swedish women and showing different REP- and RAPD PCR profiles were selected and tested for growth rate, aggregation, H2O2 production, hemolysis, antibiotic susceptibility and the presence of plasmids.
The growth rate was evaluated by inoculating a 10 ml MRS tube adjusted to an OD600 of 0.04 and measuring the time of growth from OD600 0.04 to OD 1.0 (late exponential phase). The value was used to calculate an approximate doubling time.
In order to measure aggregation, bacteria were grown until an OD600 1.0 in 10 ml MRS. The tubes were vortexed for 1 min and the aggregation was scored after 30 min in a standing position. The aggregation was scored as follows: no aggregation (0), presence of flakes (1), sedimented flakes but cloudy supernatant (2), sedimented flakes and clear supernatant (3).
H2O2 production by Lactobacillus strains was tested with MRS agar supplemented with 0.25 mg of tetramethylbenzidine (Sigma, St. Louis, Mo.) per ml and 0.01 mg of horseradish peroxidase (Sigma) per ml [18]. H2O2 production was visually scored as strongly positive (3), intermediate positive (2) weakly positive (1), or negative (0) according to the intensity of blue colour development.
The haemolytic activity was evaluated on Columbia blood agar plates containing 5% human or sheep blood following 48 h incubation at 37°C in aerobic, microaerobic (5% CO2) and anaerobic conditions. Two Streptococcus pyogenes clinical isolates (S. pyogenes PU1735 and S. pyogenes svt) obtained from Clinical Microbiology, Department of Clinical and Experimental Medicine clinical University of Linköping were used as positive controls.
The minimum inhibitory concentration (MICs) of ten antibiotics was determined by the E-test method according to the manufacturer's instruction for lactobacilli (AB Biodisk; Solna, Sweden). The breakpoints (susceptible/resistant) were determined in accordance with the Clinical and Laboratory Standards Institute guidelines for gram-positive microorganisms [19].
Plasmids were isolated from a 10-ml culture grown until OD600 0.8 using the following steps: treatment of cells with lysozyme (10 mg/ml) and mutanolysin (80 u/ml), cell lysis, neutralisation, extraction with phenol/chloroform/iso-amylalcohol and precipitation with ethanol. The nucleic acid pellet was washed once with 70% ethanol, dissolved in 100 μl of TE buffer (10 mM Tris-HCl, pH 8.0 and 1 mM EDTA) containing 100 μg/ml of RNase A. Ten μl was run on a 1% agarose gel and the presence of plasmids was visualized by UV transillumination.
Lactobacilli used for treatment
Nine of the vaginal Lactobacillus strains isolated from healthy Swedish women and characterised in the present study were selected for the clinical trial. The lactobacilli were fermented, lyophilised, and dispensed as a mixture of three different strains (109/capsule) in gelatin capsules according to GMP standard (Gruppo Clerici SACCO SS.r.l., Cadorago Italy together with Bifodan A/S, Hundested, Denmark). Other strains from commercial products, currently used for treatment of BV, were also tested for comparison. These strains include L. gasseri (Lba EB01-DSM 14869) and L. rhamnosus (Lbp PB01-DSM 14870) contained in the commercially available EcoVag® vaginal capsules (108 CFU/capsules) (Bifodan A/S, Denmark). Both these Lactobacillus strains were initially isolated from healthy women in Norway. Capsules containing the EcoVag® strains plus another one, L. gasseri DSM 15527, also isolated from healthy women at the same time and characterised by Bifodan. The second probiotic preparation used was LaciBios® (oral capsules containing Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 (around 109/capsule)). These Lactobacillus strains have been described in the studies by Reid and collaborators [11,20].
Women were divided in seven groups that received capsules containing two to three Lactobacillus strains as follows. Group 0: EcoVag® capsule containing L. gasseri DSM 14869 and L. rhamnosus DSM 14870; Group 1: L. crispatus 4R5, L. gasseri 20M39, and L. jenseneii 22B42; Group 2: L. crispatus 23B33, L. gasseri 6M9, L. jenseneii 12B1; Group 3: L. crispatus 21M49, L. gasseri 6M9 and L. crispatus 8R6; Group 4: L. gasseri DSM 14869, L. rhamnosus DSM 14870 and L. gasseri DSM 15527; Group 5: L. gasseri DSM 14869, L. rhamnosus DSM 14870, L. gasseri DSM 15527; Group 6: LaciBios® femina containing L. rhamnosus GR-1 and L. reuteri RC-14. Group 0 to 4 received capsules intra vaginally while groups 5 and 6 took the capsules orally.
Clinical Study
The study was conducted at an outpatient private gynaecological clinic in Drammen, Norway from January 2007 until January 2011. All women with symptomatic BV fulfilling the inclusion criteria were consecutively offered to participate in a prospective study of adjuvant lactobacilli given in addition to antibiotics. Women included were regularly menstruating women, 18 years or older, with normal gynaecological status, not pregnant or breast-feeding and without signs of other genital tract infections. Exclusion criteria were patients with hormonal IUD without regular menstruation; women infected with Chlamydia trachomatis, or Trichomonas vaginalis, or with a clinical candida infection.
Study sample
A total of 76 patients were included in the study. The mean age was 33.7 years with a range of 18-55 years. The diagnosis of BV was based on Amsel criteria. Of the 76 patients, 13 were lost to follow up so that the study at hand consists of 63 patients.
Clinical method
At inclusion, women had a routine gynaecological examination with a non-lubricated speculum and a vaginal ultrasound. A sample of vaginal secretion was analysed for vaginal pH using special pH strips (range 3.8-5.0). The diagnosis of BV was based on Amsel criteria [21], i.e. fulfilling at least 3 of 4 criteria; thin homogenous discharge, vaginal pH above 4.5, positive amine test, and presence of clue cell during microscopical investigation using a phase contrast microscope. A vaginal sample was taken and air-dried. At inclusion, vaginal samples for determining Chlamydia trachomatis infection were performed using strand-displacement amplification (CT amplified DNA assay; Becton-Dickinson) according to the local laboratory routine. Samples for Neisseria gonorhoeae culture were only taken when deemed clinically motivated.
After signing the informed consent form, women were given a seven days course of daily 2% vaginal clindamycin cream (Dalacin vaginal cream 2%, Pfizer Norway Ltd) together with oral clindamycin 300 mg BID for 7 days (Dalacin 300 mg, Pfizer Norway Ltd). Oral clindamycin treatment was also given to the patient's sexual partner [22], however the patient's partner did not sign any informed consent forms. Directly after the clindamycin treatment, a new treatment with vaginal gelatine capsules containing 108-109 freeze-dried lactobacilli for 5 days was started. If menstruation was to occur during treatment, it was suggested that the patient would wait until next menstrual cycle before she started the treatment. After the next menstruation, a new treatment with vaginal metronidazole for 5 days (Zidoval gel 75 g, Meda AS, Norway) was initiated followed by 5 more days with Lactobacillus instillation. After the second menstruation, the patients were given a new course of vaginal metronidazole gel (Figure 1). The evaluation of treatment efficacy was performed after the last treatment course.
Figure 1. Time schedule of the treatment and follow up. Even if the patient had a relapse at the self taken samples (3-6 months) she did not receive treatment until the clinical visit that determined with Amsel criteria at the clinical visit after 6 months.
Follow up
After every menstruation the patients took a self swabbed vaginal culture and a glass smear that was air dried and sent in a sealed envelope to the laboratory using the same method as in an earlier study [23]. The vaginal sample was collected after the bleeding had ceased and before the start of treatment.
The vaginal samples were sent by regular mail from Norway to the Clinical Microbiology laboratory, Linköpings University, Sweden where it was cultured. All recovered lactobacilli were identified to the genus level Lactobacillus by Gram staining, colony morphology and negative catalase test and were subsequently frozen at -70°C and transported to the Clinical Immunology laboratory at the Karolinska hospital in Huddinge where additionnal characterisation was performed. All recovered lactobacilli isolates were again cultured and identified to the species level by amplifications of 16S rDNA regions using species-specific primers. Identification to the strain level was carried out using REP-PCR and RAPD PCR (as described above) to test if they were the same strains as those provided in the lactobacilli-containing capsules. These tests were performed blindly, without knowledge of the treatment the women had received.
Every woman was followed up by a phone call from the investigation nurse and asked about treatment complications and concomitant medication. If the patient had failed to send a sample, it was recorded as missing but she was reminded and asked to send in a new sample after the next menstruation. Each patient collected a total of 6 vaginal samples.
After six menstrual cycles, women were scheduled for a follow up visit to the clinic. Normally the vaginal samples were taken once every 28th day and the follow up time of 6 menstrual cycles would be 5 and half month but for some women 6 menstruation cycles could take longer than 6 months, thus, we report this as a 6-month follow up.
The women were then followed up to 12 months and they were offered a new visit at 24 months, or before, in the case of symptomatic relapse.
Microscopical investigation
Each vaginal sample was rehydrated with normal saline and investigated under a phase contrast microscope with 400 times magnification and with a microscopic area of 0.016 mm2. The approximate numbers of bacteria were recorded as well as the presence of clue cells together with the number of vaginal leucocytes. Each slide was classified according to Hay/Ison classification [24,25] to either normal, intermediate or BV. All microscopic evaluations were performed after that the women had been on clinical visits.
Definition of cure
To be considered cured, the women had to have none of Amsels critera fulfilled at the clinical visit after 6-9 months. All women with clinical relapse (fulfilment of Amsel criteria) at the clinical visit were regarded as treatment failures and were re-treated with clindamycin and metronidazole. Treatment efficacy is reported both as cure after 6, 12 and 24 months, and as time to relapse illustrated with survival analysis with Life table analysis. Some women had treatment failure already at the third month as seen on the self taken sample. These were considered as treatment failures if the Hay/Ison score was 3, a Hay/Ison score of 2 was designated as improved and a score of 1 as cure. A Hay/Ison score of 0 and 4 were regarded as equal to a score of 1 during the follow up periods. As all microscopic investigations were performed after that the women had been on a clinic visit and re-treatment was not initiated on the microscopic results.
Study design
The study was performed as a consecutive treatment, open label, follow-up study.
Statistical methods
Not all patients collected a vaginal smear every month and in case of missing data during the first follow up month, the procedure "last observation carried forward" (LOCF) was used. "Time from treatment to relapse" has been calculated in months and was used to explore differences in time to relapse between groups by survival analysis with Kaplan Meier procedure. A logistic regression analysis was performed and an Odds ratio (OR) with 95% confidence interval (CI) was calculated. All comparisons both between and within groups was performed two-tailed with a significance level of 5%. All the analyses in this study were performed in PASW (SPSS) v.18 and in accordance with the principal of intention to treat (ITT).
Ethical approval
The study was approved by the southeast regional Ethics Committee in Oslo, Norway. To recruit women with BV, we advertised in local newspapers asking for women suffering from malodorous discharge.
Typing and characterisation of vaginal lactobacilli
Analysis of the lactobacilli previously isolated from healthy women showed that only one Lactobacillus species of the same REP-PCR type was generally found among the isolates from each woman. The only exceptions were the women E and P who both carried L. gasseri isolates with two different REP-PCR profiles and woman M who carried two species (L. gasseri and L. crispatus) (Table 1). Strains from different women showed different REP-PCR profiles apart from the L. crispatus strains from woman C, Q and S. These L. crispatus strains could further be differentiated by performing two RAPD-PCR with the primers RAPD3 and RAPD4 (Table 1). A total of 18 different genotypes were identified by using a combination of REP-PCR and RAPD-PCR.
Eighteen Lactobacillus strains with different PCR types were selected for further characterisation and were scored according to properties that would promote their colonisation (auto aggregation) and antimicrobial capacity (H2O2 production), guarantee their safety for human use (abscence of plasmid, absence of hemolysis and no antibiotic resistance) and possibility for large scale production (growth rate) (Table 2). Four strains containing plasmids (5M8, 13B2, 15M7, 16B2) and one strain with ambiguous blood hemolysis results (18R5) were discarded. Although the hemolysis could not be classified as β-hemolysis, it was decided to not pursue further studies with this strain for potential safety reasons. None of the strains were resistant to ampicillin, cefuroxime, imipenem, gentamicin, erythromycin, chloramphenicol, tetracycline, or rifampicin. All the tested lactobacilli were resistant to metronidazole and several of the strains (10 of 18 strains) were resistant to cefoxitin. High level of resistance to these antibiotics has been previously reported and is considered as natural resistance in lactobacilli [26].
Table 2. Characterisation of vaginal Lactobacillus strains
Nine Lactobacillus strains of different species and presenting the highest scores were selected for the clinical trial: three L. gasseri (6M8, 6M9, 20M39), four L. crispatus (4R5, 8R6, 21M49, 23B33) and two L. jenseneii (12B1, 22B42) strains (Table 3).
Table 3. Demographic and clinical characteristics in the study population at enrolment (n = 63)
Clinical treatment with antibiotics and lactobacilli
Demographic and behavioural characteristics
Of the 76 patients enrolled, 13 were lost during the follow up. Considering that 14 women got pregnant during this period, the 17% drop out rate is comparable to other studies [7,6]. The demographic and behavioural characteristics of the 63 participants that completed the study are shown in Table 3. All the women included were Caucasians. There was no difference in the above characteristics between the women in the different treatment groups.
Twenty-three women (36.5%) had been treated for BV previously with a mean time of 3.8 years before starting the study. There was no data on how many times the women had been previously treated for BV. The median time that the symptoms of BV had started was 5 months before the start of the study with a range of 1-60 months and the average time was 10.8 months.
Women reported that they had met a new partner in 36 cases (57.1%) and 6 women (9.5%) had recently been divorced and only 21 (33.3%) had the same sexual partner. The median time for the new relationship was 6 months with a range of 1-48 months and the mean time was 12 months.
Among the 36 women that had a new partner, one woman reported that she had symptoms of BV before she met her new partner. Among the other 35 patients, it is then possible to calculate an "incubation time". That is the difference between the time that the patient starts her new relationship and the beginning of symptoms of BV. The median time was 2 months with a range of 1-22 months and a mean time of 3.8 months.
Colonisation with any given lactobacilli was observed in 17 out of the 43 patients that received intravaginal lactobacilli (Table 4). Four women were not included in the analysis of colonisation as they did not provide enough samples. The women receiving EcoVag® (Group 0) were colonised by L. rhamnosus 14870 in 6 out of 8 cases (75%). The strain persisted more than 2 months in three patients, i.e. about 2 weeks after stopping its administration, and until Month 3 and 5 in two other patients (one and three months after stopping the treatment respectively). Of the women receiving the characterised lactobacilli isolated from Swedish women (Group 1 to 3), the L. crispatus strains were the ones showing the best colonisation (Table 4). Although colonising a lower proportion of women (around 33%), L. crispatus 4R5 (Group 1), L. crispatus 23B33 (Group 2), and L. crispatus 8R6 (Group 3) persisted until Month 6 in 7 out of 9 women colonised by one of these strains i.e. 4 months after stopping the treatment. Of the women receiving a mixture of L. rhamnosus 14870, L. gasseri 14869 and L. gasseri DSM 15527, only two were colonised either by L. rhamnosus 14870 or L. gasseri 14869. None of the women that took the Lactobacillus preparation orally (Group 5 and 6) got colonised.
Table 4. Colonisation of the vaginal tract by administered Lactobacillus
Clinical outcome
Of the 63 patients that completed the study, 28 had relapses after 24 months. The cure rate was 74.6% after 6 months, 65.1% after 12 months and 55.6% after 24 months (Table 5).
Table 5. Clinical outcome
There was no significant difference in cure rate depending on which lactobacilli were given to the women (Figure 2). Furthermore, no correlation was found between colonisation with administered lactobacilli and the cure rate either at 6, 12 or 24 months after the start of the study.
Figure 2. Survival analysis with Life table showing the difference in cure rate between vaginal and oral administration of different Lactobacillus preparations. No statistical difference is seen. Group 0: EcoVag® capsule containing L. gasseri DSM 14869 and L. rhamnosus DSM 14870; Group 1: L. crispatus 4R5, L. gasseri 20M39, and L. jenseneii 22B42; Group 2: L. crispatus 23B33, L. gasseri 6M9, L. jenseneii 12B1; Group 3: L. crispatus 21M49, L. gasseri 6M9 and L. crispatus 8R6; Group 4: L. gasseri DSM 14869, L. rhamnosus DSM 14870 and L. gasseri DSM 15527; Group 5: Oral (the same group as the vaginal group 4) L. gasseri DSM 14869, L. rhamnosus DSM 14870, L. gasseri DSM 15527; Group 6: oral LaciBios® femina containing L. rhamnosus GR-1 and L. reuteri RC-14.
All patients' sexual partners, except two, accepted the oral clindamycin treatment. In one case, the couple had separated and partner treatment was not indicated. After a year, they started the same relationship again and this case was calculated as a new sexual relationship. In the second case, the partner refused to take any medicine. The patient had a microscopic relapse already at 4 months and a clinical relapse at the 6-month visit. This case is reported as having the same sexual partner. Two women reported the same male sexual partner but a new female sexual partner and are thus reported as having a new sexual partner. During the follow up time, a total of twenty-two patients had changed to new sexual partner. Of the 22 patients with a new partner, only 5 had no relapse (cure of 22.7%) compared to 30 of the 41 (73.2%) that did not change partner, OR = 9.3 (95% CI: 2.8-31.2). Survival analysis (Figure 3) showed that women who reported a new sexual partner during follow-up had significantly shorter time to relapse with a Log Rank test (p < 0.001).
Figure 3. Survival analysis with Kaplan-Meier showing that there were significantly more relapses in patients who report a new sexual partner during follow up. Log rank < 0.001. Patients that are censored means that they have not completed the 24-month follow up. For some women the 24-month follow up is not done until 30 month. That is why some patients are reported as 30 month.
Also a multiple logistic regression show that changed to new sexual partner during follow up was significantly associated to have a relapse but not age, earlier treatment of BV, presence of Mobiluncus before entering the study, a new relation before entering the study, lactobacilli given or whether or not the patient were colonised with any lactobacilli (Table 6). Of the 28 women with relapse, 21 had one relapse and five had two relapes. Two women had 4 and 5 relapses during the follow up period.
Table 6. Multiple logistic regression model where relapse within 24 months was outcome variable.
During the study, only one severe adverse event occurred, a case of diarrhoea in group 1 that caused the patient to stop treatment. There were no more candida infections than expected normally (10%).
The purpose of this study was to optimise the treatment of BV using extended antibiotics administration combined with administration of lactobacilli. By giving the patient a more aggressive treatment, we could obtain a 6-month cure rate of 74.6%, a 12-month cure rate of 65.1% and a 24-month cure rate of 55.6%. Interestingly, we could not find any difference in cure rate whether or not it was a recurrent BV. These findings are surprising as it has always been suggested in the literature that recurrent BV is more difficult to treat [7,27].
There are many treatment studies of BV that report cure rates of 90% but such a high cure rate is not seen in clinical practice [5]. As diagnostic tests for BV are subjective, one can question a cure higher than 70% after one month. From our own meta-analysis, a 4-week cure rate is never better than 60% [5]. Most studies report a 2 week or 4 week cure rate and there are very few studies that report a longer follow up than 4 weeks. As our treatment lasted 2 months, our 6-month cure rate corresponds to 4 months, or 4 menstruations, after the cessation of treatment. Our study could thus be compared to the Sobel study [7] where 88% of the women who clinically responded to a ten days treatment with 0.75% metronidazole gel were randomly assigned to metronidazole or placebo twice weekly for 4 months. Three months after cessation of treatment, the cure rate was 49% in the treatment group and 25% in the placebo group. But as only 88% were initially cured the comparable cure rate would be 43% in the treatment group, and this cure rate should be compared to our cure rate of 74.6%. In another follow up study from Australia, only 31% had a Nugent score of less than 3, 12 months after therapy with one week of oral metronidazole [6]. In comparison to these studies, our 6-month cure rate of nearly 75% is markedly superior.
Recurrence rates for BV beyond 12 months have been reported in very few studies. In one of them, non-pregnant women were treated with oral metronidazole for 10 days. The patients were treated until they were cured at a follow up visit and for some patients, the metronidazole treatment was repeated up to 3 times before all patients were cured. Outpatients' attendance was retrospectively reviewed, and follow-up at 6 years revealed a cumulative recurrence rate of BV of 53% where 73% of the recurrences had occurred within 12 months, i.e. a 12-month cure rate of 63% but starting from only cured patients [28].
Marcone et al have carried out adjuvant treatment with lactobacilli following treatment with oral metronidazole for 7 days [29]. The cure rate at 6 and 12 months was higher (>80%) than in the present study. However, the cure rate in women receiving the traditional treatment with metronidazole only was also much higher (around 70%) than the one previously reported in other studies (less than 36%) (Table 7) [6,7]. The definition of cure in their study was not based on Nugent or Hay/Isons scoring and only women who use natural methods of contraception were included, making it difficult to compare with other studies. The women selected in their study were probably engaged in a more stable relationship and less prone to change of partners and relapses. In a subsequent study by Marcone et al, long-term treatment with lactobacilli for 6 months resulted in a cure rate of 91% 6 months after stopping the treatment [30]. The study could be criticized for the same reason as the earlier study [29] but it could also be that the two courses of lactobacilli for 5 days used in the present study is a too short treatment and that a long-term treatment is necessary to obtain a stable biofilm in the vagina.
Table 7. Study results of suppressive treatment of BV.
If we exclude studies that report a 2 or 4-week cure rate, the treatment proposed in the present study describes one of the best cure rates that has ever been reported. Our treatment suggestion is extremely aggressive and one must ask if this aggressive treatment is justified. For many patients, however, BV is a burden that causes a high morbidity and it takes a long time and much effort in order to be cured. Often the women are treated with many courses of antibiotics so in the end, the difference to our aggressive treatment is that we give all antibiotics at one time instead of spreading it out over a longer time. The risk associated with aggressive antibiotic treatment is subsequent infection with Clostridium difficile. Clindamycin is a drug that is often associated with a risk for colitis but other antibiotics such as penicillin, ampicillin, cephalosporin and fluoroquinolones can all precipitate this disorder when used long term. As we only gave one course of treatment for 7 days with clindamycin, followed by two vaginal treatments with metronidazole, we think that our treatment regimen does not carry a high risk of acquiring Clostridium difficile infection [31] and during our study, only one patient had to withdraw treatment because of diarrhoea. Recurrent BV is troublesome and there have been only a few published studies on how to handle recurrent BV [6,27,32-36] with different suggestions as how to handle this problem. Women are often given treatment similar to suppressive treatment of chronic vulvo-vaginal candida infection [37].
It is not easy to perform a study in young women that continues for a period of 24 month. During this follow up, 14 women became pregnant and 5 underwent major surgery such as hysterectomy (data not shown). This could certainly influence the results of our 24 month cure rate at follow up and this has to be taken into consideration. As some patients still come to our clinic we have registered 4 more relapses (2 because of a new relationship) but these have been after more than 30 months after the first treatment. As we give the same aggressive treatment in the case of a relapse, only 2 women had more than 2 relapses. In at least one case, she had a sexual partner that was not monogamous.
Several clinical trials have been performed to investigate whether specific strains of lactobacilli, administered either orally or intra-vaginally, in combination with antibiotics or not, are able to colonise the vaginas of women with bacterial vaginosis and to improve symptoms and/or signs of bacterial vaginosis [12,29,38,39]. Our previous study with adjuvant EcoVag® vaginal capsule treatment showed that lactobacilli could increase the cure rate at 6 months by nearly 20% (from 46% to 65%). However, only the women who responded to treatment were included in that study [13]. If we consider the women who were re-treated already after the first month, the cure rate drops to 53% in women treated with lactobacilli compared to 39% in the placebo treated group. Since a placebo group was included in the previous study, we did not include this group in the present one for ethical reasons. However, the cure rate obtained with vaginal administration of the new preparation tested was similar to the results obtained with EcoVag® capsules. Among the new characterised Lactobacillus strains tested, only the L. crispatus strains were able to colonise. The strains colonised a lower number of individuals than L. rhamnosus DSM 16870 from the Ecovag® capsule (30% vs 75%) but for a longer period (up to four months after stopping the treament). In comparison, the well studied probiotic strains L. crispatus CTV-05, L. rhamnosus GR-1 and L. fermentum RC-14 have been reported to colonise between 20 and 40% of the non antibiotic treated women 4-weeks post intravaginal administration [40-42]. In a more recent study, vaginal capsules containing a mixture of L. gasseri LN40, L. fermentum LN99, L. casei subsp. rhamnosus LN113 and P. acidilactici LN23 were administered for five days to women after conventional treatment with clindamycin. Following the first menstruation after Lactobacillus administration, 53% of the women were colonised by any of the five strains but only 26% after the second menstruation. In accordance with our results, no correlation was found between colonisation and treatment result of BV. The difference in colonisation of the vaginal tract by the probiotic lactobacilli might depend on factors such as vaginal intercourse and the microflora at enrollement [40].
Oral treatment with Lactobacillus rhamnosus (GR-1) and Lactobacillus reuteri (RC-14) have been shown to be extremely effective over a four week follow up period with a 90% cure [12]. In our study, however, oral treatment with the same lactobacilli did not performed as well over a long follow up period (67% cure).
Verstraelen et al. have reviewed the epidemiology of BV in relation to sexual behavior and concluded that BV in some acts as an STD or SED (sexually enhanced disease) and with frequency of intercourse being the critical factor [43]. A striking result of our study is that change of partner is strongly associated with BV, giving strong support to the notion of BV as a STD associated condition with consequence for treatment/partner treatment. In the study of Bradshaw [6], the authors found that having a regular sex partner was associated with a higher recurrence rate whereas having a new sex partner was associated with a lower recurrence. They suggested that women treated for BV are reinfected by their regular partner but not by new partners who would then be less likely to carry the causative agent for BV. The discrepancies between these two studies could be explained by the fact that we treated the partners with clindamycin. However, according to published studies, there is no evidence that partner treatment is efficacious [44]. The most quoted studies are the Scandinavian studies by Vejtorp [45] and Moi [46] where the authors used 2 grams of metronidazole at day 1 and 3 given to the female and to the male either as placebo or metronidazole in the same dose. They reported cure rates of 75-77% regardless of whether the partner was treated or not. Both studies were carried out at a STD clinic and none of the studies controlled for a new partner during the follow up period. This treatment regimen of metronidazole (2 grams, day 1 and 3) has been used worldwide but in fact this treatment has never been evaluated in a placebo-controlled study. Three other studies have reported a tendency towards a better cure rate if the partner was treated [47-49]. The only study that used clindamycin reported a 10%, non-significant, increase in cure rate after treating the partner with oral clindamycin [22]. So as a conclusion from our study and from the critical review of the literature we suggest that partner treatment should be used more often.
It is surprising that women tend not to seek care for symptoms of BV directly when symptoms appear. The mean time of beginning of symptoms was 11.3 months (median time 6 months) with a range of 1-60 months, prior to diagnosis. We have no explanation for this but if this is the same in all countries it could be a possible explanation why STI clinics have difficulties to find a possible connection between a new sexual partners and symptoms of BV. As 35 women reported that they had symptoms of BV after they started a new relationship it was possible to calculate an "incubation time". This "incubations time" is only speculative but nevertheless interesting, since it is only a median of 2 months.
The study shows that aggressive treatment of the patient with antibiotics combined with Lactobacillus administration can provide a long lasting cure. A striking result of our study is that a change of partner is strongly associated with relapse of BV giving support for the notion that BV is an STD and that the patient's sexual partner needs to be treated. The new Lactobacillus preparation tested were as good as the commercial EcoVag® product when administered intra vaginally but vaginal colonisation observed for some strains did not seem to influence the cure rate. Further studies with extended treatment with different preparations of lactobacilli and larger cohorts will have to be performed to evaluate the relationship between colonisation by lactobacilli and cure of BV.
Competing interests
This study has been performed with the economical support from Bifodan AS. The company has had no influence on study design, data interpretation or content of the article.
Authors' contributions
P-GL, UF and LH have contributed to the study design; P-G L, collection of clinical data and analysis of air-dried smears, KKA and HM to the characterisation of the lactobacilli; HM, UF and SP to the cultivation and typing of the lactobacilli and SN to statistical analysis. EB have performed the encapsulation of the freezed-dried lactobacilli. All have contributed to the writing of manuscript and all authors read and approved the final manuscript.
This study has received financial support from Bifodan AS Denmark and the Swedish research Council in Sweden.
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Pre-publication history
The pre-publication history for this paper can be accessed here:


text: Tagged: related post, single quote, tooltip Viewing 4 posts - 1 through 4 (of 4 total) Author Posts July 25, 2013 at 9:05 am #26716 Yiannis GirodParticipant Hi, When a post have a title with a single quote inside, the tooltip hover related post image doesn't show all the right part of title since single quote. Any idea ? Thanks and best regards. July 25, 2013 at 11:06 am #131370 DudeModerator Hey! Yes try to escape the quote. Instead of ' type ' . You can also try the html entity: " Regards, Peter August 9, 2013 at 10:14 am #131371 Yiannis GirodParticipant ' doesn't work and " is not a simple quote… ;-) It a little bug to fix. I don't want to "tinker" with my blog titles… Any other idea ? Thanks and regards. August 10, 2013 at 4:24 am #131372 IsmaelModerator Hi, Try this instead. For example you have a post called "This is a test'. Add this: & #39; Remove the space after &. Regards, Ismael Author Posts Viewing 4 posts - 1 through 4 (of 4 total) The topic 'Simple quote not supported in related post image tooltip' is closed to new replies.

subset: commoncrawl


text:
Psi-Ops: The Mindgate Conspiracy for PS2On: PS2, PC, Xbox
The mind is a great thing. Use it to move objects, start fires and have out of body experiences.
Review Verdict Read Review
8Out of 10
Stuck on Psi-Ops: The Mindgate Conspiracy? We've got you covered!
Don't panic! Our cheats will see you through.


text:
Add NBA.com to the list of haters. They did their grades of every team in the league so far this summer and both us and Cleveland received the lowest grade with an overall "D". What do you think? Are they accurate?
- Bargnani unlikely to benefit from Bosh's exit
- Pondering frontcourt lineups, Kleiza's usage


text:
- Detail Images
Reward your feet after a day of roughing it.
There is nothing better than slipping out of your hiking, mountaineering, or ski boots and into a pair of the lightweight Western Mountaineering Men's Flash Booties at the end of the day. These babies are packed with warm goose down insulation to help thaw out cold feet and give them some good ol' TLC. The Flash Bootie is primarily intended for use indoors, in your tent, or even in your sleeping bag, but a reinforced sole does allow for quick trips outdoors.
Share your thoughts
Western Mountaineering Flash Bootie
- Familiarity:I've used it once or twice and have initial impressions
- Fit:Runs large
- Height: 5'7"Weight: 155 lbsSize Purchased: medium
Run a tad large, but if your wearing them in your bag.... who cares. 1st time backpacking in the snow and I was toasty as can be. What a great addition to my gear and they add next to nothing in weight.
Leta Kalfas, Vendor Rep
Hey Shirley, Leta with Western Mountaineering here. What shoe size are you? I am a women's 9 and I fit into the unisex medium ok... I am wondering if we can do better on our sizing chart. Anyway, these booties do kick some ass - I've used mine in the hut, at home, and around the campsite - amazing warmth and almost no weight!!
Thanks for the review,
I agree with Shirley, these run large. The chart is off by about 2 sizes. I wish I read these reviews before buying.
I wear a Mens Size 8, 41.5 euro. I bought two sets, one small for my wife and a medium for me. I fit perfect in the size small. In fact, I can actually stick my Croc Size 8 shoe inside of the Medium bootie. That makes it fit better when walking outside at snow camp. I actually cannot walk around in the Medium bootie by itself without it sloshing all over the place.
Perfect for inside the bag, but for $70 I want to wear these at snow camp and not have to rely on bringing Crocs or some other footwear in addition to mountaineering boots and booties.
I think these booties could use an upgraded lightweight firm foam sole that is foot shaped like the Croc (but 1/2 the thickness on the sole and no upper). Closed-cell foam is warm, light and moldable. This would be more durable compared to the current foam sole with fabric outer cover.
Me Likie
These are great! I bought them for hanging around camp and sleeping in while ski mountaineering. I am a cold sleeper to begin with and even in a 0 degree bag my feet will get cold. Not any more :) These are comfy to wear and especially sleep in. Your foot does slide around in them a little while walking around but I do not move around too much in them anyway while I have them on. They are super lightweight and not noticeable when stuffed in the bottom of my pack. The only thing is they are made in the large side. I am a straight up men's 10 shoe size and the medium fits me well. There is even about an extra inch or so of space. If I had gotten the large they definitely would have been way too big.
Kyle, Gearhead
Light and Warm
- Familiarity:I've used it several times
I wear an 8.5 and I bought the Med. I think they fit the way they are supposed to. They are light, fluffy and warm. I bought these for mostly cold weather camping. You can venture outside but do it quickly and carefully. If you're looking for something that is more rugged, try the expedition or bootie models by Western Mountaineering. Honestly, beside the oven effect, you barely know they are on.
1-800-409-4502 ext 4420
I wear a Mens 8 1/2, occasionally size 9....
I wear a Mens 8 1/2, occasionally size 9. Would the "Medium" be tight? Would the "Large" be too loose?
I wear a size 9.5-10 and just got the large and they are huge. I have more than an inch and a half to move around in. I'm going to swap them for mediums. I'm not sure if I would go with a medium or small if I were you but I'd say that medium you'd definitely have room.
-- edit--
I'm noticing a discrepency between the EU sizing and US sizing on their sizing chart and I feel like the EU sizing is definitely more accurate to what I got so I would recommend going with that.
Feather Light
- Familiarity:I gave it as a gift but have feedback to share
- Fit:True to size
I got these for my GF for casual use because she likes my somewhat beefier WM down booties. The red color is very feminine and she loves them.
However, on a functional note: these are so ridiculously lightweight that I would recommend them for any backcountry enthusiast with cold feet. The warmth-to-weight ratio is as good as it gets. I would make sure not to walk around much at all in these, though, as they are the most delicate bootie WM makes.
Will you be getting in more sizes any time...
Will you be getting in more sizes any time soon?
Hey Greg,
You're in luck! We more of all sizes in throughout the next month or so, just keep checking back!
Well Made but slippery bottom
- Gender:Male
- Familiarity:I gave it as a gift but have feedback to share
Bought this product for my wife. Very well made and very light. Had to send it back because the bottom was too slippery for her. She almost fell twice after wearing them for about an hour.
Wicked warm and compressible.
Got to use these for the first time last night cold camping in northern Minnesota. I put them on inside my tent and instant comfort! I love them. So warm I had to take them off in the middle of the night because my feet were too warm. I only plan to use them inside my sleeping bag. It was 0° F and I was happy.
Flash booties
I got the flash booties for my wife, she loves them.
Good for in the Sleeping Bag
First of all, I got these to take with me winter alpine climbing. My feet tend to get quite cold in my sleeping bag within my bivy bag within a snow trench laying on the snow. I got these guys because they're smaller than the others and I assumed they'd compress very well. And they do! They are also very warm. They have definitely achieved my purpose in getting them. I had no intentions (and still don't) on using them to walk around camp in the snow. They wouldn't work well for that (but that's what the others are for). Walking around camp I tend to wear my boots loosened up. So if this is what you're looking for, these guys will give you a super lightweight option that will serve you well.


text:
Staff report
NEW CASTLE, Pa.
Two Boston terrier puppies were stolen Wednesday during a morning home invasion in New Castle.
According to 21 WFMJ-TV, The Vindicator's broadcast partner, 75-year-old homeowner Irene Matas is fearful that the people responsible for the crime may sell the 11-week-old puppies to make quick cash.
"They could have emptied my house out, and I wouldn't care. But to take those two precious little animals, what goes through people's minds?" Matas said.
Matas, who is undergoing treatment for cancer, only had the puppies for three weeks. She got them after her dog Patches became ill and had to be put down.
Matas and her brother were at home at the time, asleep in back bedrooms. The invaders entered the home through the back door, not only taking the puppies, but a 42-inch flat screen TV, the victim's purse and a digital camera, sometime between midnight and 6:30 a.m.
The puppies were stolen from an enclosed playpen in the family room.
"Whoever has them, please, please, please return them to me," Matas says. "But if you do have them and for some reason you cannot do this, then please take care of them."
The New Castle woman said the pups respond to the names "Peanuts" and "Sissy."
Peanuts, a male Boston terrier weighing only about two and a half pounds, has a distinctive black mark on his nose that looks like a tiny dog bone.
Sissy, a female Boston terrier weighing just over four pounds, has a tiny black mark on her forehead, and has four white boots, or four white legs, which is said to be unusual for a Boston terrier whose back legs are normally black.
Matas is offering a reward, no questions asked for the return of the puppies. Call (724) 658-8855 or (724) 714-8084.
The lowest form of life on our planet...stealing puppies from a sick woman.
Since Vindy always seems way behind...this is from WKBN
Puppies stolen from a home in Lawrence County have been returned.
Two Boston terrier puppies were taken from the Mahoning Township home of Irene Matas Wednesday morning. Along with the dogs, the burglars took her T.V. And digital camera.
Matas said she received several tips on the dogs' whereabouts after media coverage of the story. Because of that information, police were able to track the dogs down Friday night to two separate locations near New Castle.
According to Matas, a woman called and told her that someone had tried to sell her a puppy and she thought it might be one of the terriers that was taken. Matas alerted police, which led them to a home south of New Castle. One dog was recovered there, while the other was found at a home in Neshannock Township.
"I'm so thrilled to have them back. They are so happy to be back, and they are just playing with each other and are just so happy," said Matas. "Without the help of the public, these dogs would not be home right now."
No word yet if any arrests have been made in connection to the stolen dogs.
"The "invaders" entered the home through the back door....
Invaders? More like the lowest piece of human garbage! Have to steal because there to damn lazy to get off there useless DNA a@#es and actually work for something, instead of taking things that others work hard for. Can't stand these filthy pieces of human filth! Hopefully, KARMA, does work.......


text:
December 9, 2013
Put on Your Riot Gear and Push Your Way to the Rockefeller Center Christmas Tree
Christmas time again at Rockefeller Center in Midtown, Manhattan. Swam through the hoards of visitors and people hustling tours to get to the tree. I managed to snap a couple pictures as I passed through- enjoy the intentional blur and the ultra wide angle.
1 comment:
- Eliza GoJanuary 26, 2015 at 7:01 PM
Nothing beats the precious moments of starring at the city lights. The good side of having a condo unit at the central business district is that it gives you an easy access to all the amenities like entertainment, shopping mall, and restaurants. This is the reason why I have bought a Dover Parkview condo in Singapore. Know more here http://www.doverpark.sg/ReplyDelete


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The up side is that by my maliciously killing that clown above, the young lady might just be grateful enough to overlook my being old and overweight to thank me in a fantasy sort of a way.....away from the sight of the dead clown.
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Definitions for unsubstantiated
This page provides all possible meanings and translations of the word unsubstantiated
Princeton's WordNet
uncorroborated, unsubstantiated(adj)
unsupported by other evidence
Lacking substantiation; without evidence.
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- αβάσιμοςGreek
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text:
Author(s): Prof. D. K. Chavan, Priyanka A. Chinchorkar, Sachin V. Margaje
Published in: International Journal of Engineering Research & Technology
License: This work is licensed under a Creative Commons Attribution 4.0 International License.
Website: www.ijert.org
Volume/Issue: Vol.1 - Issue 10 (December - 2012)
e-ISSN: 2278-0181
In continuous search of clean, safe and renewable energy sources, wind power is certainly one of the most attractive solutions. Wind power was used earlier for several centuries for propelling ships, driving wind mills, pumping water, irrigating field and numerous other purposes.
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Mission Statement
The Mizzou Tiger Club - St. Louis is a non-profit organization funded by private contributions to support the University of Missouri - Columbia Athletic Department and the Tiger Scholarship Fund.
The primary goals of the Club are to:
Work directly with the Athletic Department on all Club projects.
Create a network to support the development efforts of the Tiger Scholarship Fund through events, activities and personal contacts.
Serve as a vehicle to recruit new donors and season ticket holders for the University.
Create an enthusiastic atmosphere of support and goodwill for the Athletic Department and all of the University's athletic programs.
Encourage good sportsmanship by setting an example for others to follow.
STL Tiger Talk Lunches
The Mizzou Tiger Club - St. Louis is excited to announce its monthly STL Tiger Talk Lunches on the first Tuesday of each month during the 2016 calendar year!
Tuesday, January 5, 2016
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Cost $20 per person, which covers a choice of burger/sandwich, side, soft drink and gratuity.
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"John Carter of Mars" Moving Ahead!
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Jack Bauer
Fleet Admiral
Location: Jack Bauer
Re: "John Carter of Mars" Moving Ahead!
And some casting news:
Hollywood Reporter
Taylor Kitsch and Lynn Collins will star in "John Carter of Mars," the adaptation of the Edgar Rice Burroughs book series that Andrew Stanton is directing for Disney.
Kitsch will play the title character, Carter, while Collins is playing Dejah Thoris, the heir to the throne of Mars' Helium kingdom.
"See you in another life, brotha." - Desmond David Hume - Lost
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Orson Scott Card
Revolving Door (0)
Sightings (3)
The Top 100 Books on Facebook - Posted September 10, 2014
The Facebook Data Science Team curled up with ... [AllFacebook]
Ender's Game Trailer Released - Posted May 8, 2013
The first trailer for the movie adaptation of Orson Scott Card's Ender's Game has been released. We've embedded the trailer above--what do you think? Here's more about the film, from the release: In the near future, a hostile alien race called the Formics have attacked Earth. If not for the legendary heroics of... [semanticweb.com]
Internet Privacy Documentary Gets Off to Roaring Start in Sonoma - Posted April 15, 2013
After world premiering at SLAMdance in January, Cullen Hoback's documentary Terms and Conditions May Apply re-upped on the film festival circuit this past weekend at the Sonoma International Film Festival. And in what is likely the first of several such prizes, it snagged the event's Best Documentary Feature nod. ... [FishbowlLA]


text:
June 10, 2011
IMG Academies are in a class by themselves
Dallas Jackson
BRADENTON, Fla. - IMG Baseball Academy Director Ken Bolek isn't cocky, he's convinced. And with the impressive results of the various IMG training schools - one-of-a-kind training and teaching centers - why shouldn't he be?
"There is nothing like this anywhere," he said. "No other place has our facilities, our instructors or our success."
Bolek is one of eight directors that represent the different specialized branches of the private boarding school set on 400 acres of property on the Gulf Coast in Central Florida. The other training schools are the Leadbetter Golf Academy, Bollettieri Tennis Academy, Madden Football Academy, Basketball, Soccer, Softball, and Lacrosse Academy as well as the IMG Performance Institute.
Bolek, who has been at the school for over 15 years, has seen IMG grow into what it is today. Its facilities include:
And still with plans to expand.
It also houses one of the most extensive off-the field training programs an athlete can find.
"For an old school guy like me, it is rewarding," Bolek said. "We have been pushing hard the last couple of years to make improvements and it will be great for everyone."
He also has taken the time to stop and smell the roses.
"We are the largest sports academy in the world," he said. "That is fantastic and should be celebrated."
Because of the lack guaranteed games and the programs elite reputation, IMG often must take games wherever it can get them - and that includes tournaments.
Like it or not.
"We struggle to get games," Bolek said. "It is good and bad. We aren't bound by a percent of games in the state or in a district, but we also have a tough time filling our schedule.
"And we do not like to take too many tournaments or trips because it affects the kids in the classroom."
This season, the IMG team did participate in a tournament: The Hard Nine National Classic in Anaheim, California.
The team was accompanied by a teacher and the players were expected to be focused on schoolwork.
"They do not mess around with school here," Bonilla said. "It is emphasized."
It is emphasized as much as anything else at the school.
"We have the best," Bolek said. "Our pitching coach is a former pitcher. He teaches pitching, not base running. Our weightlifting guy trained athletes in weight lifting; he is not our speed and agility coach. Our teachers are the same. They are not math majors teaching English. IMG will always be exclusive because there are a small percentage of people to prescribe to our specific needs. If we are to hold our kids to a set of standards, we have to hold ourselves to that same set."
- Dallas Jackson
"What folks still need to know is that the great majority of our graduates will not make a living as a professional athlete and we teach much more than just athletics here," he said. "We prepare kids with life skills that will help make them a better person."
The Total Athlete Approach was developed by the IMG Performance Institute and breaks down into three schools of thought with eight total development techniques.
Athletic body management, physical conditioning, vision training, nutrition, mental conditioning, communication skills, life skills and college preparation and placement are all part of the curriculum.
All of that is in addition to the school load each must maintain within the Pendleton School.
The communications skill curriculum for the students, developed by a company called Game On, was founded by Steve Shenbaum to aid professional athletes. It is now based out of IMG Academy.
Blair Bloomston, the associate director of Game On, thinks this expanded approach helps the kids not only make friends, but helps the teens find themselves through the process.
"We have kids from all over the globe here," she said. "It not only helps them cross over the sport-specific barriers, it allows them to open up to others and themselves."
The Game On model uses role-playing, improvising and other techniques to help with interpersonal communication as well as media relations.
"There is a boisterous, vivacious eight (on a scale to 10) inside of all of us," she said. "There is also a quiet and professional three. We try to help people feel comfortable with both."
Game On also emphasizes that being comfortable in your own skin is more important than being what the media may want you to be.
"Sometimes other media training will create a paradox," she said. "We want each person to build their own brand and make sure it is consistent. Being caught in a lie is one of the worst things that can happen when dealing with the media."
A current member of the IMG Baseball Academy, Brandon Bonilla, is fighting public perception as he grows into a potential major league baseball player.
His father, Bobby, was a polarizing player in the late 1980's and early 90's. The younger Bonilla was drafted by the Colorado Rockies in Round No. 33 of the MLB Rule IV Draft.
Brandon says that his experience at IMG has been amazing.
"It is much different [than Greenwich (Conn.) High]," Bonilla said. "I am blessed to be here. To be in a focused school for three hours a day, get hands on baseball training from former professionals and all of the other benefits that are here is wonderful."
His teammate Alfredo Escalara, a thirdbaseman, says his experience has been night-and-day compared to where he grew up in Puerto Rico.
"We didn't even have fields there," Escalara said. "Here we have perfectly manicured fields. It is perfect."
Florida State commit despite not starting on the varsity team at IMG, said that the disadvantages of a boarding school are far offset by the Academies' benefits.
"Once you are on campus, you are on campus," he said, although he lives off campus with his parents. "But my parents knew if I stayed home I could not achieve my goals. I was 11 and playing with 15 year-olds. Here I am surrounded by good athletes and get training by the best."
Part of surrounding the players with the best comes down to the philosophy of the school.
"We don't accept everyone," Bolek said. "Our screening process is simple. We want to know the goals and objectives of the family and the player before we take the next step. From there, we will do an evaluation and a projection and share that with the families. If the two do not align, then this is likely not the place for them."
With nearly 1,000 students on campus, IMG Academies are not for everyone.
"We only deal with reality here," Bolek said. "If a family thinks their kid will come here get an education and sign a pro contract, but we do not see that ceiling for them, we communicate that very clearly. I'd say that 98 percent of our families come in knowing that they are paying for a professional learning experience to help their children become professionals. And that doesn't mean professional athletes that means professionals."
Getting in is difficult.
"We have a system, a process, an environment that has been tested and proven effective," Bolek said. "At some point we will have to ask how big is big, but until then we will take the folks who come here for the right reasons. If people think that they can get in and just make their own way through without being a part of the big picture then they will find out they are wrong."
The most important part of all will happen once you are on campus.
"People think that just because we pay the tuition here that it makes us better," Bonilla said. "Those people are wrong. We have so much more work to do once we are here than they would believe."
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text:
An interview with CEO Bob Beauchamp
These tips can help you save money
Join the NASDAQ Community today and get free, instant access to portfolios, stock ratings, real-time alerts, and more!
Jack Henry & Associates, Inc. (
) will begin trading ex-dividend on February 22, 2013. A cash
dividend payment of $0.13 per share is scheduled to be paid on
March 12, 2013. Shareholders who purchased JKHY stock prior to the
ex-dividend date are eligible for the cash dividend payment. This
represents an 13.04% increase over the prior quarter.
The previous trading day's last sale of JKHY was $43.84,
representing a -1.08% decrease from the 52 week high of $44.32 and
a 36.28% increase over the 52 week low of $32.17.
JKHY is a part of the Technology sector, which includes
companies such as Infosys Limited (
) and Automatic Data Processing, Inc. (
). JKHY's current earnings per share, an indicator of a company's
profitability, is $1.88. Zacks Investment Research reports JKHY's
forecasted earnings growth in 2013 as 14.19%, compared to an
industry average of -5%.
For more information on the declaration, record and payment
dates, visit the
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The views and opinions expressed herein are the views and opinions of the author and do not necessarily reflect those of Nasdaq, Inc.
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text:
FreeBSD Bugzilla – Bug 88260
Update port: net/poptop Update version 1.2.1 to 1.2.3
Last modified: 2005-11-28 12:46:23 UTC
Maintainer of net/poptop,
Please note that PR ports/88260 just has been submitted.
If it contains a patch for an upgrade, an enhancement or a bug fix
you agree on, reply to this email stating that you approve the patch
and a committer will take care of it.
The full text of the PR can be found at:
Edwin Groothuis
Responsible Changed
From-To: freebsd-ports-bugs->lawrance
This patchset is being tested currently.
It needs some time. Wait please.
Any progress on this PR?
State Changed
From-To: open->closed
Committed, thanks! If you are interested in maintaining the port,
can you please coordinate with the current maintainer and file
a separate PR.


text:
Careful, honey. He looks hungry.
Jesus he is top heavy…looks like Austin Powers standing on Mini Me's shoulders
His body shape is very interesting
It's never good to vomit up your peanut M&Ms in the middle of a date.
I think he might have just thrown up a little in his mouth.
I know, right? He always looks like that!
It just occurred to me that I've never seen Jonah Hill and Chris Christie in the same place at the same time.
Wait until she finds out he isn't a furry.
The first human in history to achieve the "Inverted Bowling Pin" body type.
It's a race, it's a chase, hurry up and feed their face!
Who will win? No one knows! Feed the hungry hip-ip-pos!
Hungry Hungry Hippos!
HA, I love that movie +1
Someone just told him that Judd Apatow is retiring.
Why does everyone suddenly look like an Oompa Loompa? I need to check a mirror, STAT.
Shouldn't she be the one throwing up a little at the thought of sex?
Too late, Hitchcock was already cast.
Say what you want, but Fat Jonah Hill looks better than Skinny Jonah Hill. When he was skinny, he looked like that weird Man/Kid from Children of the Corn!
she fiine. FML.
He's dating her to look straight and she's dating him to look anorexic.
Wanna be in my wolf pack?
2/3rds of a Chris Christie.
Isn't that his girlfriend from The Sitter?
Fuck, now you know I watched The Sitter.


text:
by John Bell
A record 32 boats and 175 anglers landing nearly 2,000 pounds of wahoo competed in the Bimini Big Game Club Resort & Marina's second season Wahoo Smackdown III two-day tournament this past weekend.
Competitor leaving Big Game Club marina
Taking home over $7,500 in cash and prizes for top team (193.8 pounds of wahoo) and largest catch (51.6 pounds) was Captain Edward Garcia and team Brizzo Fishing from Coral Gables, Florida.
Team Time Less of West Palm Beach Captained by Tristen Hunt took second place team honors ($1,500) with 189.8 pounds. Finishing third with 152.1 pounds was Fishin' a Loan captained by Kevin Marsh of Palm Coast, Florida winning $1,000.
Team Time Less Second Place
Overall, according to tournament director Capt. Paul Cameron, more than $60,000 in cash and prizes were awarded. Documenting the action was legendary angler Larry Dahlberg, whose 'The Hunt For Big Fish' airs on the NBC Sports Network.
'There was an incredible turnout of anglers and despite some high winds the first day, everyone had a great time competing and enjoying the camaraderie of fishermen and fisherwomen,' said Michael Weber, BBGC General Manager. 'Along with our great food and drink this made for a record breaking weekend for the Big Game Club's Wahoo Smackdown III.'
Wahoo Weigh-In
Team Brizzo Fishing First Place
Weber said the Bimini Big Game Club Resort & Marina will be hosting another wahoo tournament in February 2014.
Big Game Club Bimini


text:
Lutz, Robert H
Today:8:30 am - 5:00 pm
Tomorrow:8:30 am - 5:00 pm
310 E Graham St,
Shelby, NC 28150
(704) 751-4438
Business Details
YP Qualified
- Hours:
Regular HoursSat - SunClosed
- General Info:
- Serving clients in Cleveland County and the surrounding areas since 1990 If you are looking for an experienced North Carolina attorney to handle your bankruptcy, corporate law or criminal law matter, the Lutz Law Firm is fully prepared to take on your case. Based out of Shelby, North Carolina, Attorney Robert Lutz has more than 20 years of experience serving individuals and businesses across Cleveland County and the surrounding counties of Rutherford, Polk, McDowell, Lincoln and Gaston. And as a former prosecutor for the District Attorney's Office for Cleveland and Lincoln Counties, Attorney Lutz has the knowledge and experience necessary for your case to succeed.
- Services/Products:
- Bankruptcy — Robert has spent more than 15 years in bankruptcy courts across North Carolina. This knowledge of the Federal Bankruptcy Code can help you get the resolution you need. • Corporate law — Whether dealing with a buy-and-sell agreement, contract negotiations or anything in between, Robert's corporate law services can get your business moving again. • Criminal law & traffic violations — Robert's familiarity with criminal law & traffic violations across North Carolina is an invaluable tool if your case goes to court.
- Payment method:
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- Other Link:
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- Bankruptcy Law Attorneys, Business Bankruptcy Law Attorneys, Corporation & Partnership Law Attorneys, Family Law Attorneys, General Practice Attorneys, Traffic Law Attorneys, Wills, Trusts & Estate Planning Attorneys, Attorneys, Business Law Attorneys, Transportation Law Attorneys


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1996 Chevrolet Camaro Coupe RS 2dr Coupe
I love my camaro ! 220,000 mile and its in hirrble conditions. Tell you the truth? dont buy this car if you want to spen money. Parts are expencive and gas sucks. Why do i still own it? because i love my camaro and i will own it and put more money then its worth because to me its worth so much more then any thing else.
I bought the car new and still drive it everyday. The car has had no major mechanical repairs to it in all these years. I had to change an alternator once, and fixed the electric windows twice. That is it! It now has 158,000 miles on it. I will never sell my baby and will drive it for many years to come. If you are going to buy one, get one from an adult owner like myself who maintained the car. Kids just beat on them.
Reliability. I could drive this car cross country tomorrow and not have a care in the world.
i had a camaro 1983, love it, and after got a thunderbird, and a chevy lumina, great cars chevy, other not that much, and then i want another camaro again, and its the best, great driving experience, power on v-6, fuel economy, t-tops, great design, great for my two kids, they are comfortable in the small back space.
t-tops, v-6 power and fuel economy, exterior design, features, interior space, love all
the camaro doesn't need anything
I got my camaro as my first car about and a half years ago... The previous owner didn't take care of the car, which caused problems for me. There was a lot of things that needed to be replaced, AC, Transmission, 02 sensors, water pump, and the egr valve. I was able to drive the car for a year without problems. However, when I started college, I was driving 30 miles to and from school everyday. That's when the car started to give me problems. The car overheated 4 times within 2 months, and each time it was something different that caused it. Replaced the thermostat, hose and radiator. Other minuscule things like leaky t-tops and broken console henge. The car has some design flaws.
T-top, power, and the appearance is just great.
this model was expensive and hard to work on. Hopefully the 09 camaro will be more refined...
I bought the car used in 2000. The BOSE was blown but a new custom sound system has me rockin'. I like to put on my reflector sunglasses and drive around slowly. It still gets looks and comments. It corners like it's on rails and the 3.8 has plenty of power for the light body. I love the car. My girlfriend thinks it's too low. Mechanically it's been good but interior quality is kind of iffy. Overall, I love the car. At 118,000 I expect to drive her for a while longer.
The looks and comments I get from admirers.
Interior integrity could be better.
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Thursday, October 14, 2010
*&^%$# Madonna, She HATES Chicago . . .
That's right, Her Madgesty had the nerve to diss our city, but apparently she expressed these views in 1991 when she was filming "A League of Our Own."
Huffington Post has uncovered a letter that the pop star wrote to a friend complaining about "the lack of hot guys" in Chicago: ". . . when God decided where the beautiful men were going to live in the world, he did not choose Chicago."
Served deliciously by 312 Dining Diva at 12:15 PM
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Hunt Phelan Weddings and Events Venue
Have your wedding or event at Memphis' most elegant historic wedding and event venue. We can host the smallest intimate gatherings to the largest of corporate events. Beautiful gardens, elegant decor, and historic furnishings will set the scene for an event to remember.
This Greek Revival mansion displays a rich and elegant civil war past, with host to 5 presidents. The grounds have lush gardens and many beautiful backdrops that will make your day a memorable delight. Hunt Phelan is perfect for a variety of weddings and events with a commercial kitchen, amazing dinning, spacious bar area, and more.


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One of the Greitest person in the history
1 Year ago on The Springboks and N… »
1 Year ago on The Springboks and N… »
I was in stadium, it was very good and dramatic match. Georgia were missing many players too - ( first line . zirakashvili (klermon); bregvadze (Tuluza); kakovin (tuluza); therd line - basilaia (edinburg); kolelishvili (Lion); wings - Todua (albi) and capitan Matchkhaneli.) Thenks the both teams.
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Narrow your search
With monitors that go beyond the norm, HP attempts to make a splash at CES 2015.
Each week, Iyaz Akhtar scours CNET's sites to see what people are looking at and talking about, and then counts down the most popular trends in tech. From the most popular products to must have gadgets to the most downloaded software, Iyaz brings a witty, informative look at each week's list.
The accessory company unveils a 3,840x2,160-pixel monitor for less than you'd expect to pay.
As a big-screen upscale all-in-one with touch and decent gaming chops, the latest version of Dell's XPS 27 is a great all-around home PC that covers a lot of bases.
Pricing not available
With a high price-to-performance ratio, the Monoprice IPS-Glass Panel Pro will satisfy most bargain hunters; however, there are better options for a few dollars more.
Pricing not available
The HP Envy 27-inch IPS monitor with Beats Audio goes long on sound while still giving image quality its due.
As long as you have no advanced demands, the Pavilion 27xi will meet your basic needs with aplomb.
Pricing not available
The advance model monitor is designed for color-critical work with a 2,560x1,600-pixel resolution and 16:10 aspect ratio.
The new line of monitors will come in three screen sizes,
Well-priced and powerful, the Asus PB278Q is the best entry point for those seeking an extreme-definition monitor at a not-so-extreme price.
The monitor features a 2,560x1,440-pixel IPS display that rotates 90 degrees.


text:
Anti-Corn Law League, British organization founded in 1839, devoted to fighting England's Corn Laws, regulations governing the import and export of grain. It was led by Richard Cobden, who saw the laws as both morally wrong and economically damaging. The league mobilized the industrial middle classes against the landlords, and Cobden won over the prime minister, Sir Robert Peel. The Corn Laws were repealed in 1846.
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Cecil J. Hare
Position: B
Height: 5-11 Weight: 195 lbs.
Born: March 2, 1919 in Glenbush, Canada
Died: April 14, 1963 in Spokane, WA
High School: Sheridan
College: Gonzaga (school history)
Weighted Career AV (100-95-...): 0 (14739th overall since 1950)
Relatives: Brother of Ray Hare
2-time Pro Bowler (fine print)
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text: I don't know that you need to "see past" the aesthetic. It is its own justification, and it is certainly emblematic of its time period. When you see certain kinds of Pictorialist images, you think "oh, Art Nouveau", and when you see others, "oh.... that crap". But period-original Pictorialism, just like period-original Modernism or post-Modernism, stands by itself as an artifact of its time. Someone doing Pictorialist images today, however, needs to have an artistic justification for doing it, because it IS no longer current. Not saying you can't have a creative justification for using it, but you have to have a clear, articulate reason. Otherwise you are a dilettante hobbyist just aping a dead style because you can't think creatively on your own.


text:
With Instructables you can share what you make with the world, and tap into an ever-growing community of creative experts.
In this instructible i will teach you how to color you xbox 360 controller with sharpies (that what i used) or spray paint. Its quite simple really.WARNING- In ...
Okay to take apart the Xbox 360 controller you will need a torex 8 screwdriver. (but you can actually get away with using a small flat head). There ...
Now that you have it taken apat gut it out! take everything and put it somewhere safe.
Okay you now how two options. You can Draw you own design on it or can can spray paint it a boring color. If you decide to spray ...
IF YOU ARE GOING TO SPRAY PAIN I T THEN LOOK AT BOTTOM. Okay once you done with you awesome design markers the you need to tape it ...
Now that it is taped up. And you design is all done, you now need to take you controller part and place it on newspaper and spray it ...
Remove the tape and put it back together! Once back together test all buttons and if some are sticky then take it apart and scrape around the holes ...
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Review: "Orange is the New Black"
Movie Moles Frann Michel and Iven Hale take a critical, yet appreciative, look at "Orange is the New Black," the Netflix series that has just finished its first season. They point out its failures to fully represent prison life, while finding much to admire in the show. For a summary of Frann's and Iven's review, and links to other critical reviews, check out Frann Michel's blog.
- Title: Review: "Orange is the New Black"
- Album: August 19, 2013
- Length: 9:12 minutes (5.27 MB)
- Format: MP3 Mono 44kHz 80Kbps (CBR)
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