SAFETY AND EFFICACY OF THYMIC PEPTIDES IN THE TREATMENT OF HOSPITALIZED COVID-19 PATIENTS IN HONDURAS.

Coronavirus disease 2019 (Covid-19) active cases continue to demand the development of safe and effective treatments. This is the first clinical trial to evaluate the safety and efficacy of oral thymic peptides. ; We conducted a nonrandomized phase 2 trial with a historic control group to evaluate the safety and efficacy of a daily 250-mg oral dose of thymic peptides in the treatment of hospitalized Covid-19 patients. Comparisons based on standard care from registry data were performed after propensity score matching. The primary outcomes were survival, time to recovery, and number of participants with treatment-related adverse events or side effects by day 20. ; A total of 44 patients were analyzed in this study: 22 in the thymic peptide group and 22 in the standard care group. There were no deaths in the intervention group compared to 24% mortality in standard care by day 20 (log-rank P=0.02). Kaplan-Meier analysis showed a significantly shorter time to recovery by day 20 in the thymic peptide group than in the standard care group (median, 6 days vs. 12 days; hazard ratio for recovery, 2.75 [95% confidence interval, 1.34 to 5.62]; log-rank P=0.002). No side effects or adverse events were reported. ; In patients hospitalized with Covid-19, the use of thymic peptides resulted in no side effects, adverse events, or deaths by day 20. Compared with the registry data, a significantly shorter time to recovery and mortality reduction were measured.

Physical multimorbidity and cancer prevalence in the National Health and Nutrition Examination Survey.

OBJECTIVES: As the US population ages, both cancer and multimorbidity become more common and pose challenges to the healthcare system. Limited studies have examined the association between multimorbidity and cancer prevalence in the US adult population. To help address this gap, we evaluated the associations between individual chronic conditions and all-site cancer, multimorbidity and all-site cancer, and multimorbidity and site-specific cancers. STUDY DESIGN: This is a cross-sectional study. METHODS: Data from 10,731 adults aged 20 years or older who participated in the 2013-2016 National Health and Nutrition Examination Survey were used in our study. Self-reported demographics, smoking status, sedentary behavior, body mass index, individual chronic conditions, multimorbidity status, cancer history, and cancer sites were assessed. RESULTS: In our sample, the prevalence of having any type of cancer or multimorbidity was 9% (N = 861) and 38% (N = 4248), respectively. Respiratory conditions (multivariable-adjusted odds ratio [OR]: 1.3; 95% confidence interval [CI]: 1.1-1.6) and arthritis (multivariable-adjusted OR: 1.5; 95% CI: 1.2-1.8) were observed to be statistically significantly associated with having all-site cancer after adjusting for potential confounders. Having multimorbidity was also statistically significantly associated with having all-site cancer (multivariable-adjusted OR: 1.4; 95% CI: 1.2-1.7), cervical cancer (multivariable-adjusted OR: 2.6; 95% CI: 1.2-5.4), and bladder cancer (multivariable-adjusted OR: 2.8; 95% CI: 1.0-7.6). CONCLUSIONS: Multimorbidity was associated with all-site cancer, cervical cancer, and bladder cancer. The present study provides new evidence of the potential relationships between multimorbidity and cancer. Future longitudinal studies are warranted to clarify the temporality and potential biological mechanisms of the associations between multimorbidity and cancer.

Medical education from the point of view of medical students: Results from four participatory Delphi panels in Quito, Ecuador.

BACKGROUND: Medical curricula have historically been designed in a top-down approach, usually excluding students. While Delphi panels have been used as a tool for medical education curricula design, none have been conducted in Ecuador. In addition, no such approach has ever included students both as panelists and researchers. MATERIAL AND METHODS: Four Delphi panels were developed and conducted using a participatory approach that allowed medical students to take part both as expert panelists and researchers: specifically, students developed the questionnaire and conducted a qualitative synthesis. Questionnaire responses were anonymized and dispatched online to panelists. The information was organized and collected to develop the qualitative syntheses and prepare the final statements. RESULTS: Thirty-two medical students participated between February and May 2018. A total of 32 questions were developed, corresponding to five different categories. For some questions, consensus was reached; for other questions, general statements were obtained.Discussion and conclusion: Developing the questionnaire, responding to it and analyzing the answers allowed students to raise significant concerns regarding medical education topics proposing relevant policy and curricula change. Participatory Delphi panels can be an efficient tool to obtain organized feedback, improve student class involvement, and promote research skills.

Association of adiposity, telomere length and mortality: data from the NHANES 1999-2002.

BACKGROUND/OBJECTIVES: Telomere shortening is associated with age and risk of medical comorbidity. We assessed the relationship between measures of adiposity, leukocyte telomere length, and mortality and whether it is modified by age. SUBJECTS/METHODS: Subjects with dual-energy X-ray absorptiometry measures were identified using the National Health and Nutrition Examination Survey 1999-2002. Obesity was categorized using two body fat definitions (BF1%: men ⩾25%; females ⩾35%; BF2% ⩾28% and ⩾38%, respectively), body mass index (BMI) and waist circumference (WC; men ⩾102 cm; females ⩾88 cm). Telomere length relative to standard reference DNA (T/S ratio) was assessed using quantitative PCR. Weighted multivariable regression models evaluated the association of telomere length with adiposity, both continuously and categorically (low/normal BF%, low/high WC and standard BMI categories). Differences in telomere length by age and adiposity were ascertained and subsequent models were stratified by age. Proportional hazard models assessed the risk of mortality by adiposity status. A telomere by adiposity interaction was tested in the entire cohort and by age category (<60 vs ⩾60 years; <70 vs ⩾70 years). RESULTS: We identified 7827 subjects. Mean age was 46.1 years. Overall telomere length was 1.05±0.01 (s.e.) that differed by BF1% (low/high: 1.12±0.02 vs 1.03±0.02; P<0.001), BF2% (1.02±0.02 vs 1.11±0.02; P<0.001), BMI (underweight 1.08±0.03; normal 1.09±0.02; overweight 1.04±0.02; and obese 1.03±0.02;P<0.001) and WC (low/high 1.09±0.02 vs 1.02±0.02; P<0.001). Adjusted ß-coefficients evaluating the relationship between telomere length and adiposity (measured continuously) were as follows: BF1% (ß=-0.0033±0.0008; P<0.001), BF2% (-0.041±0.008; P<0.001), BMI (ß=-0.025±0.0008; P=0.005) and WC (ß=-0.0011±0.0004; P=0.007). High BF% (BF1%: ß=-0.035±0.011; P=0.002; BF2%: ß=-0.041±0.008; P<0.001) and WC (ß=-0.035±0.011; P=0.008) were inversely related to telomere length (TL). Stratifying by age, high BF1% (-0.061±0.013), BF2% (-0.065±0.01), BMI-obesity (-0.07±0.015) and high WC (-0.048±0.013) were significant (all P<0.001). This association diminished with increasing age. In older participants, TL was inversely related to mortality (hazard ratio 0.36 (0.27, 0.49)), as were those classified by BF1% (0.68 (0.56, 0.81)), BF2% (0.75 (0.65, 0.80)), BMI (0.50 (0.42, 0.60)) and WC (0.72 (0.63, 0.83)). No interaction was observed between adiposity status, telomere length and mortality. CONCLUSIONS: Obesity is associated with shorter telomere length in young participants, a relationship that diminishes with increasing age. It does not moderate the relationship with mortality.

Predictive factors of flares in systemic lupus erythematosus patients: data from a multiethnic Latin American cohort.

Purpose The purpose of this paper is to determine the factors predictive of flares in systemic lupus erythematosus (SLE) patients. Methods A case-control study nested within the Grupo Latino Americano De Estudio de Lupus (GLADEL) cohort was conducted. Flare was defined as an increase ≥4 points in the SLEDAI. Cases were defined as patients with at least one flare. Controls were selected by matching cases by length of follow-up. Demographic and clinical manifestations were systematically recorded by a common protocol. Glucocorticoid use was recorded as average daily dose of prednisone and antimalarial use as percentage of time on antimalarial and categorized as never (0%), rarely (>0-25%), occasionally (>25%-50%), commonly (˃50%-75%) and frequently (˃75%). Immunosuppressive drugs were recorded as used or not used. The association between demographic, clinical manifestations, therapy and flares was examined using univariable and multivariable conditional logistic regression models. Results A total of 465 cases and controls were included. Mean age at diagnosis among cases and controls was 27.5 vs 29.9 years, p = 0.003; gender and ethnic distributions were comparable among both groups and so was the baseline SLEDAI. Independent factors protective of flares identified by multivariable analysis were older age at diagnosis (OR = 0.929 per every five years, 95% CI 0.869-0.975; p = 0.004) and antimalarial use (frequently vs never, OR = 0.722, 95% CI 0.522-0.998; p = 0.049) whereas azathioprine use (OR = 1.820, 95% CI 1.309-2.531; p < 0.001) and SLEDAI post-baseline were predictive of them (OR = 1.034, 95% CI 1.005-1.064; p = 0.022). Conclusions In this large, longitudinal Latin American cohort, older age at diagnosis and more frequent antimalarial use were protective whereas azathioprine use and higher disease activity were predictive of flares.

Pleuropulmonary involvement in patients with systemic lupus erythematosus from a Latin American inception cohort (GLADEL).

Objectives The objectives of this study were to examine the demographic and clinical features associated with the occurrence of pleuropulmonary manifestations, the predictive factors of their occurrence and their impact on mortality in systemic lupus erythematosus (SLE) patients. Materials and methods The association of pleuropulmonary manifestations with demographic and clinical features, the predictive factors of their occurrence and their impact on mortality were examined in GLADEL patients by appropriate univariable and multivariable analyses. Results At least one pleuropulmonary manifestation occurred in 421 of the 1480 SLE patients (28.4%), pleurisy being the most frequent (24.0%). Age at SLE onset ≥30 years (OR 1.42; 95% CI 1.10-1.83), the presence of lower respiratory tract infection (OR 3.19; 95% CI 2.05-4.96), non-ischemic heart disease (OR 3.17; 95% CI 2.41-4.18), ischemic heart disease (OR 3.39; 95% CI 2.08-5.54), systemic (OR 2.00; 95% CI 1.37-2.91), ocular (OR 1.58; 95% CI 1.16-2.14) and renal manifestations (OR 1.44; 95% CI 1.09-1.83) were associated with pleuropulmonary manifestations, whereas cutaneous manifestations were negatively associated (OR 0.47; 95% CI 0.29-0.76). Non-ischemic heart disease (HR 2.24; 95% CI 1.63-3.09), SDI scores ≥1 (OR 1.54; 95% CI 1.10-2.17) and anti-La antibody positivity (OR 2.51; 95% CI 1.39-4.57) independently predicted their subsequent occurrence. Cutaneous manifestations were protective of the subsequent occurrence of pleuropulmonary manifestations (HR 0.62; 95% CI 0.43-0.90). Pleuropulmonary manifestations independently contributed a decreased survival (HR: 2.79 95% CI 1.80-4.31). Conclusion Pleuropulmonary manifestations are frequent in SLE, particularly pleuritis. Older age, respiratory tract infection, cardiac, systemic and renal involvement were associated with them, whereas cutaneous manifestations were negatively associated. Cardiac compromise, SDI scores ≥1 and anti-La positivity at disease onset were predictive of their subsequent occurrence, whereas cutaneous manifestations were protective. They independently contributed to a decreased survival in these patients.

Early discoid lupus erythematosus protects against renal disease in patients with systemic lupus erythematosus: longitudinal data from a large Latin American cohort.

OBJECTIVES: The objective of this study was to examine whether early discoid lupus erythematosus (DLE) would be a protective factor for further lupus nephritis in patients with systemic lupus erythematosus (SLE). METHODS: We studied SLE patients from GLADEL, an inception longitudinal cohort from nine Latin American countries. The main predictor was DLE onset, which was defined as physician-documented DLE at SLE diagnosis. The outcome was time from the diagnosis of SLE to new lupus nephritis. Univariate and multivariate survival analyses were conducted to examine the association of DLE onset with time to lupus nephritis. RESULTS: Among 845 GLADEL patients, 204 (24.1%) developed lupus nephritis after SLE diagnosis. Of them, 10 (4.9%) had DLE onset, compared to 83 (12.9%) in the group of 641 patients that remained free of lupus nephritis (hazard ratio 0.39; P = 0.0033). The cumulative proportion of lupus nephritis at 1 and 5 years since SLE diagnosis was 6% and 14%, respectively, in the DLE onset group, compared to 14% and 29% in those without DLE (P = 0.0023). DLE onset was independently associated with a lower risk of lupus nephritis, after controlling for sociodemographic factors and disease severity at diagnosis (hazard ratio 0.38; 95% confidence interval 0.20-0.71). CONCLUSIONS: Our data indicate that DLE onset reduces the risk of further lupus nephritis in patients with SLE, independently of other factors such as age, ethnicity, disease activity, and organ damage. These findings have relevant prognosis implications for SLE patients and their clinicians. Further studies are warranted to unravel the biological and environmental pathways associated with the protective role of DLE against renal disease in patients with SLE.

Lupus in Latin-American patients: lessons from the GLADEL cohort.

The need for comprehensive published epidemiologic and clinical data from Latin American systemic lupus erythematosus (SLE) patients motivated the late Dr Alarcón-Segovia and other Latin American professionals taking care of these patients to spearhead the creation of the G: rupo L: atino A: mericano D: e E: studio del L: upus (GLADEL) cohort in 1997. This inception cohort recruited a total of 1480 multiethnic (Mestizo, African-Latin American (ALA), Caucasian and other) SLE patients diagnosed within two years from the time of enrollment from 34 Latin American centers with expertise in the diagnosis and management of this disease. In addition to the initial 2004 description of the cohort, GLADEL has contributed to improving our knowledge about the course and outcome of lupus in patients from this part of the Americas. The major findings from this cohort are highlighted in this review. They have had important clinical implications for the adequate care of SLE patients both in Latin America and worldwide where these patients may have emigrated.

Systemic fungal infections in patients with human inmunodeficiency virus.

Histoplasmosis is a systemic infection caused by the dimorphic fungus Histoplasma capsulatum. In immunocompromised patients, primary pulmonary infection can spread to the skin and meninges. Clinical manifestations appear in patients with a CD4(+) lymphocyte count of less than 150 cells/µL. Coccidioidomycosis is a systemic mycosis caused by Coccidioides immitis and Coccidioides posadasii. It can present as diffuse pulmonary disease or as a disseminated form primarily affecting the central nervous system, the bones, and the skin. Cryptococcosis is caused by Cryptococcus neoformans (var. neoformans and var. grubii) and Cryptococcus gattii, which are members of the Cryptococcus species complex and have 5 serotypes: A, B, C, D, and AD. It is a common opportunistic infection in patients with human immunodeficiency virus (HIV)/AIDS, even those receiving antiretroviral therapy. Histopathologic examination and culture of samples from any suspicious lesions are essential for the correct diagnosis of systemic fungal infections in patients with HIV/AIDS.

DNA damage and aging on hematopoietic stem cells: Impact of oxidative stress in ApoE-/- mice.

The effects of aging on ROS production and DNA damage were assessed in hematopoietic stem cells (HSCs) from apolipoprotein E-deficient (ApoE-/-) mice (2-, 12- and 24-month-old), a traditional experimental model of atherogenic dyslipidemia. HSCs from aged ApoE-/- mice were associated with increased ROS levels, leading to loss quiescence, DNA damage, apoptosis and telomere shortening. The concurrence of lack of ApoE and aging result in exhaustion and senescence of HSCs accompanied by increased oxidative stress and inflammation. Therefore, our data open avenues to a better understanding of age-related changes and genetic factors, which may synergistically compromise the efficacy of aged HSC recovery and/or transplantation.

Lichen amyloidosis in a dark skinned patient.

Lichen amyloidosis is a primary localized cutaneous amyloidosis without systemic involvement, characterized by a persistent pruritic eruption of multiple discrete hyperkeratotic papules. The etiology is unknown, but chronic irritation of the skin has been proposed as an etiological factor. We herein report a typical case of lichen amyloidosis in a dark skinned patient. Physical examination revealed slightly shiny, brownish and fine uniform papules approximately 1 cm in diameter, with no accompanying macular lesions. Biopsy specimens taken from some of these papules on the legs showed small globular deposits of an amorphous and slightly eosinophilic substance in the dermis. This substance stained positively with Congo red, indicating the presence of amyloid. In addition, amyloid gave an apple green birefringence when viewed with polarized light.

In vitro antimicrobial activity against equine Lawsonia intracellularis strains.

BACKGROUND: Lawsonia intracellularis is the aetiologic agent of equine proliferative enteropathy (EPE). This emerging equine disease leads to diarrhoea, severe protein loss and can result in death if left untreated. Timely treatment of EPE is critical for recovery from the disease, and hence, information about antimicrobial susceptibilities of equine L. intracellularis strains to antimicrobials used in horses is needed. However, L. intracellularis is an obligate intracellular bacterium and so must be isolated and maintained in cell cultures. OBJECTIVES: To determine the in vitro antimicrobial activity of 14 antimicrobials against two equine L. intracellularis strains. STUDY DESIGN: In vitro experiments. METHODS: This study was designed to compare the relative in vitro susceptibility of each strain of L. intracellularis to different antimicrobials which included metronidazole, minocycline hydrochloride, erythromycin, cephalothin sodium salt, combination (4:1) of sulfamethazine and trimethoprim, chloramphenicol, rifampicin, penicillin, ampicillin, doxycycline hydrochloride, cefazolin sodium salt, clarithromycin, ceftiofur hydrochloride and enrofloxacin. The minimum inhibitory concentration (MIC) was based on intracellular and extracellular activity that inhibited 99% of L. intracellularis growth in cell culture as compared to the antimicrobial-free control. RESULTS: Rifampicin and clarithromycin were the most active antimicrobials against the two L. intracellularis strains tested, with MICs of ≤0.125 when tested both intracellularly and extracellularly. Doxycycline, minocycline, erythromycin, chloramphenicol and enrofloxacin showed intermediate to high activity, and activity was generally higher when evaluating intracellular activity. Sulfamethazine/trimethoprim showed variable results. Ampicillin, penicillin and metronidazole had low to moderate activity. L. intracellularis was resistant to cefazolin, cephalothin and ceftiofur in in vitro conditions. MAIN LIMITATIONS: Only two equine isolates of L. intracellularis were available for this study due to the difficulty in isolating this obligate intracellular species from intestinal samples. CONCLUSIONS: This is the first report of antimicrobial susceptibility patterns for equine L. intracellularis strains.

Different effects of spinally applied prostaglandin D2 on responses of dorsal horn neurons with knee input in normal rats and in rats with acute knee inflammation.

Prostaglandin D2(PGD2) is the most produced prostanoid in the CNS of mammals, and in behavioral experiments it has been implicated in the modulation of spinal nociception. In the present study we addressed the effects of spinal PGD2 on the discharge properties of nociceptive spinal cord neurons with input from the knee joint using extracellular recordings in vivo, both in normal rats and in rats with acute inflammation in the knee joint. Topical application of PGD2 to the spinal cord of normal rats did not influence responses to mechanical stimulation of the knee and ankle joint except at a high dose. Specific agonists at either the prostaglandin D2 receptor 1 (DP1) or the prostaglandin D2 receptor 2 (DP2) receptor had no effect on responses to mechanical stimulation of the normal knee. By contrast, in rats with inflamed knee joints either PGD2 or a DP1 receptor agonist decreased responses to mechanical stimulation of the inflamed knee and the non-inflamed ankle thus reducing established inflammation-evoked spinal hyperexcitability. Vice versa, spinal application of an antagonist at DP1 receptors increased responses to mechanical stimulation of the inflamed knee joint and the non-inflamed ankle joint suggesting that endogenous PGD2 attenuated central sensitization under inflammatory conditions, through activation of DP1 receptors. Spinal application of a DP2 receptor antagonist had no effect. The conclusion that spinal PGD2 attenuates spinal hyperexcitability under inflammatory conditions is further supported by the finding that spinal coapplication of PGD2 with prostaglandin E2 (PGE2) attenuated the PGE2-induced facilitation of responses to mechanical stimulation of the normal joint.

Molecular determinants of insulin resistance, cell apoptosis and lipid accumulation in non-alcoholic steatohepatitis.

BACKGROUNDS AND AIMS: Non-alcoholic-steatohepatitis (NASH) is closely related to insulin resistance, but it is unknown whether insulin resistance may be localized in hepatocytes. This study investigates insulin signalling in liver tissue from NASH, and the molecular mechanisms by which insulin-resistance could lead to liver damage (apoptosis). Moreover, to investigate the mechanisms of lipid overload we studied key enzymes in hepatocytes lipid metabolism. METHODS AND RESULTS: In liver specimens from 11 patients with NASH and 7 histological normal livers, we measured total and phosphorylated Akt (active form), Bax and Bcl-2 by Western-blot analysis. In addition, we studied AMP-activated protein Kinase and Carnitine-Palmitoyl-Transferase-1 gene expression, key regulators of non-esterified fatty acid synthesis and oxidation, by reverse transcription polymerase chain reaction. In NASH, phosphorylated Akt was impaired (104.3+/-10.6 vs 152.6+/-22.4 AU, p<0.002) and correlated with necroinflammatory score (r=-0.62; p<0.05). Bax/Bcl-2 ratio was increased in NASH. Moreover, we observed a decrease of AMP-activated protein Kinase (10.74+/-6 vs 144.7+/-41.6 AU, p<0.0001) and Carnitine-Palmitoyl-Transferase-1 gene expression (38.7+/-14.6 vs 192.1+/-26.2 AU, p<0.0001), and both were correlated with steatosis score (r=-0.56, p<0.05, r=-0.87, p<0.05 respectively). CONCLUSIONS: Akt, a key molecule of insulin signalling and cell apoptosis is impaired in NASH, suggesting an important role of hepatic insulin resistance in liver failure. Moreover, decreased non-esterified fatty acid oxidation may cause hepatic lipid overload.

Phantom reflexes: muscle contractions at a frequency not physically present in the input stimuli.

In the motor system, the periodic stimulation of one Ia-afferent input produces reflex muscle contractions at the input frequency. However, we observed that when two Ia monosynaptic reflex-afferent inputs are involved the periodic muscle contractions may occur at a frequency physically not present in the afferent inputs even when these inputs are sub-threshold. How can the muscles respond with such phantom reflex contractions at a frequency physically absent in the sub-threshold Ia-afferent input stimuli? Here we provide an explanation for this phenomenon in the cat spinal cord, that we termed "ghost motor response". We recorded monosynaptic reflexes in the L7 ventral root, intracellular potentials in the motoneurons, and the associated muscular contractions elicited by stimulation of the lateral and medial gastrocnemius nerves. By stimulating with periodic pulses of sub-threshold intensities and distinct frequencies of 2 and 3 Hz the lateral and medial gastrocnemius nerves, respectively, we observed monosynaptic responses and phantom reflex muscle contractions occurring at the fundamental frequency (1 Hz), which was absent in the input stimuli. Thus we observed a reflex ghost motor response at a frequency not physically present in the inputs. We additionally studied the inharmonic case for sub-threshold stimuli and observed muscular contractions occurring at much lower frequencies, which were also conspicuously absent in the inputs. This is the first experimental evidence of a phantom reflex response in the nervous system. The observed behavior was modeled by numerical simulations of a pool of neurons subjected to two different input pulses.

Short-term outcomes of the multi-institutional bladder exstrophy consortium: Successes and complications in the first two years of collaboration.

INTRODUCTION/BACKGROUND: Bladder exstrophy is a rare diagnosis that presents major reconstructive challenges. To increase experience and proficiency in the care of bladder exstrophy (BE), the Multi-Institutional BE Consortium (MIBEC) was formed, with a focus on refining technical aspects of complete primary repair of bladder exstrophy (CPRE) and subsequent care. OBJECTIVE: Outcome measures included successful CPRE (absence of dehiscence), complications, and integrated points of technique and care over the short-term. STUDY DESIGN: Boston Children's Hospital, Children's Hospital of Philadelphia and Children's Hospital of Wisconsin alternately served as the host, with observation, commentary and critique by visiting collaborating surgeons. CPRE with bilateral iliac osteotomy was performed at 1-3 months of age. High-definition video capture of the surgery allowed local and distant broadcast to facilitate real-time observation and teaching, and recording of all procedures. RESULTS: From February 2013 to February 2015, MIBEC participating surgeons performed CPRE on 27 consecutive patients (22 classic BE, five epispadias). There were no dehiscences in 27 patients (0%, 95% CI 0-12.5%). Thirteen girls and 14 boys underwent CPRE at a median age of 2.3 months (range 0.1-51.6). One boy had a hypospadiac urethral meatus at CPRE completion. Hydronephrosis of mild or moderate grade was present postoperatively in eight girls and two boys. Additional results, per gender, are presented in the Summary table below. DISCUSSION: Absence of dehiscence in this cohort was comparable or compared favorably with the literature. However, several girls had significant obstructive complications following CPRE. The rate of bladder outlet obstruction (BOO) in girls was increased compared with published reports. A low complication rate was noted in the boys following CPRE, which was comparable to reports in the literature, and early signs of continence and spontaneous voiding were noted in some boys and girls. Limitations included variation in patient age at presentation, thereby introducing a wide age range at CPRE. Outcome data were limited by short follow-up regarding voiding with continence. CONCLUSION: This collaborative effort proved beneficial regarding significantly increased surgeon exposure to CPRE, refinement of CPRE technique, surgeon learning and expertise. Technical refinement of CPRE is ongoing.

The colon revisited or the key to wellness, health and disease.

The hypothesis being advanced in this paper is that there is a new medical paradigm emerging from the biomedical research carried out in this century, mainly due to the explosion of the so called "omics" and associated techniques. The main idea is that there is a common pathway from wellbeing and health to chronic disease ("chronopathy") and even to death, which comprises following steps: 1) unhealthy diet, sedentary life style and permanent exposition to xenobiotics and all kinds of noxious stimuli;→2) intestinal dysbiosis;→3) alteration of the intestinal mucus layer (especially that of the colon);→4) disruption of the endothelial tight junctions;→5) metabolic endotoxemia+bacterial translocation;→6) inflammation;→7) exacerbation of the enteric nervous system (ENS) and consequent maladaptation and malfunctioning of the colon;→8) epigenetic manifestations;→9) "chronopathy" and premature death. Therefore, in order to maintain a good health or to improve or even reverse chronic diseases in a person, the main outcome to look for is a homeostatic balance of the intestinal microbiota (eubiosis), most of which is located in the colon. Lynn Margulis was one of the main scientists to highlight the importance of the role played by bacteria not only in the origin of all biological species now present on earth, but also on their role in global homeostasis. Bacteria do not rely on other living beings for their existence, while the latter depend completely on the former. Humans are no exemption, and new evidence emerges each day about the pivotal role of intestinal microbiota in human health, disease and, in general, in its wellbeing. The following facts about intestinal microbiota are nowadays generally accepted: there are about 10 times more bacteria in the gut than human cells in every human being; the microbioma is about 100-150 times bigger that the human genome, and there is a clear link between intestinal microbiota and many of the most common chronic diseases, from obesity and diabetes to depression and Parkinson disease and different kinds of cancer. The main implication of this theory is that we should become a sort of microbiota farmers, that is, we ought to be more conscious of our intestinal microbiota, take care of it and monitor it permanently. Thus, as part of our good life habits (healthy eating, physical exercise), we should probably undergo periodic seasons of fasting and colon cleansing, as it was common in older times.