Ancient Plasmodium genomes shed light on the history of human malaria.

Malaria-causing protozoa of the genus Plasmodium have exerted one of the strongest selective pressures on the human genome, and resistance alleles provide biomolecular footprints that outline the historical reach of these species1. Nevertheless, debate persists over when and how malaria parasites emerged as human pathogens and spread around the globe1,2. To address these questions, we generated high-coverage ancient mitochondrial and nuclear genome-wide data from P. falciparum, P. vivax and P. malariae from 16 countries spanning around 5,500 years of human history. We identified P. vivax and P. falciparum across geographically disparate regions of Eurasia from as early as the fourth and first millennia BCE, respectively; for P. vivax, this evidence pre-dates textual references by several millennia3. Genomic analysis supports distinct disease histories for P. falciparum and P. vivax in the Americas: similarities between now-eliminated European and peri-contact South American strains indicate that European colonizers were the source of American P. vivax, whereas the trans-Atlantic slave trade probably introduced P. falciparum into the Americas. Our data underscore the role of cross-cultural contacts in the dissemination of malaria, laying the biomolecular foundation for future palaeo-epidemiological research into the impact of Plasmodium parasites on human history. Finally, our unexpected discovery of P. falciparum in the high-altitude Himalayas provides a rare case study in which individual mobility can be inferred from infection status, adding to our knowledge of cross-cultural connectivity in the region nearly three millennia ago.

Preclinical assessment of an anti-HTLV-1 heterologous DNA/MVA vaccine protocol expressing a multiepitope HBZ protein.

BACKGROUND: Human T-lymphotropic virus 1 (HTLV-1) is associated with the development of several pathologies and chronic infection in humans. The inefficiency of the available treatments and the challenge in developing a protective vaccine highlight the need to produce effective immunotherapeutic tools. The HTLV-1 basic leucine zipper (bZIP) factor (HBZ) plays an important role in the HTLV-1 persistence, conferring a survival advantage to infected cells by reducing the HTLV-1 proteins expression, allowing infected cells to evade immune surveillance, and enhancing cell proliferation leading to increased proviral load. METHODS: We have generated a recombinant Modified Virus Vaccinia Ankara (MVA-HBZ) and a plasmid DNA (pcDNA3.1(+)-HBZ) expressing a multiepitope protein based on peptides of HBZ to study the immunogenic potential of this viral-derived protein in BALB/c mice model. Mice were immunized in a prime-boost heterologous protocol and their splenocytes (T CD4+ and T CD8+) were immunophenotyped by flow cytometry and the humoral response was evaluated by ELISA using HBZ protein produced in prokaryotic vector as antigen. RESULTS: T CD4+ and T CD8+ lymphocytes cells stimulated by HBZ-peptides (HBZ42-50 and HBZ157-176) showed polyfunctional double positive responses for TNF-α/IFN-γ, and TNF-α/IL-2. Moreover, T CD8+ cells presented a tendency in the activation of effector memory cells producing granzyme B (CD44+High/CD62L-Low), and the activation of Cytotoxic T Lymphocytes (CTLs) and cytotoxic responses in immunized mice were inferred through the production of granzyme B by effector memory T cells and the expression of CD107a by CD8+ T cells. The overall data is consistent with a directive and effector recall response, which may be able to operate actively in the elimination of HTLV-1-infected cells and, consequently, in the reduction of the proviral load. Sera from immunized mice, differently from those of control animals, showed IgG-anti-HBZ production by ELISA. CONCLUSIONS: Our results highlight the potential of the HBZ multiepitope protein expressed from plasmid DNA and a poxviral vector as candidates for therapeutic vaccine.

Technical details for a robot-assisted hand-sewn esophago-gastric anastomosis during minimally invasive Ivor Lewis esophagectomy.

BACKGROUND: Minimally invasive Ivor Lewis esophagectomy (MIILE) provides better outcomes than open techniques, particularly in terms of post-operative recovery and pulmonary complications. However, in addition to requiring advanced technical skills, thoracoscopic access makes it hard to perform esophagogastric anastomosis safely, and the reported rates of anastomotic leak vary from 5 to 16%. Several minimally invasive esophago-gastric anastomotic techniques have been described, but to date strong evidence to support one technique over the others is still lacking. We herein report the technical details and preliminary results of a new robot-assisted hand-sewn esophago-gastric anastomosis technique. METHODS: From January 2018 to December 2020, 12 cases of laparoscopic/thoracoscopic Ivor Lewis esophagectomy with robot-assisted hand-sewn esophago-gastric anastomosis were performed. The gastric conduit was prepared and tailored taking care of vascularization with a complete resection of the gastric fundus. The anastomosis consisted of a robot-assisted, hand-sewn four layers of absorbable monofilament running barbed suture (V-lock). The posterior outer layer incorporated the gastric and esophageal staple lines. RESULTS: The post-operative course was uneventful in nine cases. Two patients developed chyloperitoneum, one patient a Sars-Cov-2 infection, and one patient a late anastomotic stricture. In all cases, there were no anastomotic leaks or delayed gastric conduit emptying. The median post-operative stay was 13 days (min 7, max 37 days); the longest in-hospital stay was recorded in patients who developed chyloperitoneum. CONCLUSION: Despite the small series, we believe that our technique looks to be promising, safe, and reproducible. Some key points may be useful to guarantee a low complications rate after MIILE, particularly regarding anastomotic leaks and delayed emptying: the resection of the gastric fundus, the use of robot assistance, the incorporation of the staple lines in the posterior aspect of the anastomosis, and the use of barbed suture. Further cases are needed to validate the preliminary, but very encouraging, results.

In vitro ovicidal activity of Brongniartia montalvoana against small ruminant gastrointestinal nematodes.

Several plants of the Fabaceae family have been assessed regarding their high nutritional value and anthelmintic properties. The ovicidal effect of the hydroalcoholic extract (Bm-HAE) and subfractions from the aerial parts of Brongniartia montalvoana (Fabaceae) against a mixed strain of gastrointestinal nematodes (GIN) (Haemonchus spp., Trichostrongylus spp. and Oesophagostomum spp.) resistant to albendazole sulfoxide, ivermectin and levamisole was evaluated by the egg hatch test (EHT). The Bm-HAE was subjected to liquid-liquid chemical separation with ethyl acetate giving two fractions, an aqueous (Bm-Aq) and an organic (Bm-EtOAct). The purification of the bioactive fraction (Bm-EtOAct) through chromatographic separation resulted in four bioactive subfractions (BmR6, BmR7, BmR8 and BmR10). The treatments were designed as follows: Bm-HAE at 800, 1,500, 3,000 and 6,000 µg/mL, and Bm-Aq, Bm-EtOAct and subfractions (BmR6, BmR7, BmR8 and BmR10) at 100, 200, 400 and 800 µg/mL. Two properly negative controls (distilled water and 2% methanol) and thiabendazole (100 µg/mL) as a positive control were used for each bioassay. The chemical identification of the extract, fractions and subfractions was performed through chromatographic processes like open column chromatography, thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC-PDA). Additionally, the GIN eggs exposed to the bioactive compounds were observed through confocal laser scanning microscopy (CLSM). The Bm-HAE showed 99.5% egg hatching inhibition (EHI) at 6,000 µg/mL with a lethal concentration (LC50) of 1110 µg/mL. The Bm-EtOAc fraction displayed 99.1% EHI at 800 µg/mL with LC50 = 180 µg/mL. The ovicidal activity of the four subfractions was similar at 800 µg/mL: BmR6 (92% EHI); BmR7 (100% EHI); BmR8 (97.8%); and BmR10 (99.1%). The HPLC-PDA analysis of the bioactive subfractions allowed identification of p-coumaric acid, ferulic acid and coumarin derivatives as major compounds. The CLSM analysis allowed observation of morphological alterations in unhatched larvae caused by bioactive compounds present in the Bm-EtOAc and BmR10. In addition, the flavonoids eriodyctiol, luteolin and cynaroside were described for the first time for B. montalvoana.

Systematic review of functional outcomes and quality of life after transanal endoscopic microsurgery and transanal minimally invasive surgery: a word of caution.

PURPOSE: The introduction of transanal endoscopic or minimally invasive surgery has allowed organ preservation for rectal tumors with good oncological results. Data on functional and quality-of-life (QoL) outcomes are scarce and controversial. This systematic review sought to synthesize fecal continence, QoL, and manometric outcomes after transanal endoscopic microsurgery (TEM) or transanal minimally invasive surgery (TAMIS). METHODS: A systematic review of the literature including Medline, Embase, and the Cochrane Library databases was conducted searching for articles reporting on functional outcomes after TEM or TAMIS between January 1995 and June 2018. The evaluated outcome parameters were pre- and postoperative fecal continence (primary endpoint), QoL, and manometric results. Data were extracted using the same scales and measurement units as from the original study. RESULTS: A total of 29 studies comprising 1297 patients were included. Fecal continence outcomes were evaluated in 23 (79%) studies with a wide variety of assessment tools and divergent results. Ten studies (34%) analyzed QoL changes, and manometric variables were assessed in 15 studies (51%). Most studies reported some deterioration in manometric scores without major QoL impairment. Due to the heterogeneity of the data, it was not possible to perform any pooled analysis or meta-analysis. CONCLUSIONS: These techniques do not seem to affect continence by themselves except in minor cases. The possibility of worsened function after TEM and TAMIS should not be underestimated. There is a need to homogenize or standardize functional and manometric outcomes assessment after TEM or TAMIS.

Statistical mechanical properties of sequence space determine the efficiency of the various algorithms to predict interaction energies and native contacts from protein coevolution.

Studying evolutionary correlations in alignments of homologous sequences by means of an inverse Potts model has proven useful to obtain residue-residue contact energies and to predict contacts in proteins. The quality of the results depend much on several choices of the detailed model and on the algorithms used. We built, in a very controlled way, synthetic alignments with statistical properties similar to those of real proteins, and used them to assess the performance of different inversion algorithms and of their variants. Realistic synthetic alignments display typical features of low-temperature phases of disordered systems, a feature that affects the inversion algorithms. We showed that a Boltzmann-learning algorithm is computationally feasible and performs well in predicting the energy of native contacts. However, all algorithms, when applied to alignments of realistic size, suffer of false positives quite equally, making the quality of the prediction of native contacts with the different algorithm much system-dependent.

Efficacy of local phytotherapy in the nonsurgical treatment of periodontal disease: A systematic review.

Herbal drugs are commonly used in the treatment of several diseases, including periodontitis. So far, no systematic review had evaluated the evidence regarding the efficacy of these agents in the treatment of periodontal disease. Therefore, the purpose of this review was to evaluate the effect of local application of phytotherapic agents as adjuncts to scaling and root planing (SRP), compared to SRP alone, on clinical parameters of chronic periodontal patients. Only randomized controlled trials of at least 3 months follow-up, of SRP alone in association with local phytotherapic agents were included. MEDLINE (PubMed), Google Scholar and LILACS databases were searched for articles published up to October 2016. Random-effects meta-analyses were conducted for clinical attachment level and probing pocket depth (PPD) change after treatment. Of 1861 papers potentially relevant, 7 were included. All studies showed that periodontal treatment in association with local phytotherapic delivery promotes a significant PPD reduction and the majority of them showed clinical attachment level gain. The local use of phytotherapy as an adjunct to SRP may promote additional benefits in PPD reduction and clinical attachment level gain. However, these results must be interpreted with caution due to the small sample size, high risk of bias and heterogeneity of the studies.

The effect of an inhibitor of gut serotonin (LP533401) during the induction of periodontal disease.

BACKGROUND AND OBJECTIVE: LP533401 is an inhibitor of tryptophan hydroxylase 1, which regulates serotonin production in the gut. Previous work indicates that LP533401 has an anabolic effect in bone. Thus, we hypothesized that inhibition of gut serotonin production may modulate the host response in periodontal disease. In this study, we aimed to analyze the effects of LP533401 in a rat periodontitis model to evaluate the role of gut serotonin in periodontitis pathophysiology. MATERIAL AND METHODS: Twenty-four rats were divided into three groups: treated group (T: ligature-induced periodontal disease and LP533401, 25 mg/kg/d) by gavage; ligature group (L: ligature-induced periodontal disease only); and control group (C: without ligature-induced periodontal disease). After 28 d, radiographic alveolar bone support was measured on digital radiographs, and alveolar bone volume fraction, tissue mineral density and trabeculae characteristics were quantified by microcomputed tomography in the right hemi-mandible. Left hemi-mandibles were decalcified and alveolar bone loss, attachment loss and area of collagen in the gingiva were histologically analyzed. RESULTS: Significant difference between the L and C groups was found, confirming that periodontal disease was induced. We observed no difference between the T and L groups regarding alveolar bone destruction and area of collagen. CONCLUSION: LP533401 (25 mg/kg/d) for 28 d does not prevent bone loss and does not modulate host response in a rat model of induced periodontal disease.

Repair of transperineal recto-urethral fistula using a fibrin sealant haemostatic patch.

AIM: Recto-urethral fistula (RUF) is a rare complication of radical prostatectomy. We report a transperineal approach using a fibrin sealant haemostatic patch. METHOD: Five consecutive patients who developed RUF following radical prostatectomy had a direct transperineal repair with a haemostatic patch (TachoSil®) and were assessed at a median follow-up of 35.5 (21-45) months. RESULTS: There were no early postoperative complications. The average length of hospital stay was 5 (4-7) days. One patient developed recurrence 4 weeks after removal of the urethral catheter. Following healing in four patients the stoma was reversed at a median interval of 3 months, and 9.5 (7-10) months following the prostatic surgery. In the four patients with successful closure there was no case of recurrence or anorectal or urinary dysfunction at a median follow-up of 35.5 (21-45) months. CONCLUSION: Direct transperineal repair of RUF reinforced with a fibrin haemostatic patch of TachoSil is safe and effective.

Selective approach for upper rectal cancer treatment: total mesorectal excision and preoperative chemoradiation are seldom necessary.

BACKGROUND: The implementation of preoperative chemoradiation combined with total mesorectal excision has reduced local recurrence rates in rectal cancer. However, the use of both types of treatment in upper rectal cancer is controversial. OBJECTIVE: The purpose of this work was to assess oncological results after radical resection of upper rectal cancers compared with sigmoid, middle, and lower rectal cancers and to determine risk factors for local recurrence in upper rectal cancer. DESIGN: This was a retrospective analysis of prospectively collected data. SETTINGS: This study was conducted in a tertiary care referral hospital in Valencia, Spain. PATIENTS: Analysis included 1145 patients who underwent colorectal resection with primary curative intent for primary sigmoid (n = 450), rectosigmoid (n = 70), upper rectal (n = 178), middle rectal (n = 186), or lower rectal (n = 261) cancer. MAIN OUTCOME MEASURES: Oncological results, including local recurrence, disease-free survival, and cancer-specific survival, were compared between the different tumor locations. Univariate and multivariate analyses were performed to identify risk factors for local recurrence in upper rectal cancer. RESULTS: A total of 147 patients (82.6%) with upper rectal tumors underwent partial mesorectal excision, and only 10 patients (5.6%) of that group received preoperative chemoradiation. The 5-year actuarial local recurrence, disease-free survival, and cancer-specific survival rates for upper rectal tumors were 4.9%, 82.0%, and 91.6%. Local recurrence rates showed no differences when compared among all of the locations (p = 0.20), whereas disease-free survival and cancer-specific survival were shorter for lower rectal tumors (p = 0.006; p = 0.003). The only independent risk factor for local recurrence in upper rectal cancer was an involved circumferential resection margin at pathologic analysis (HR, 14.23 (95% CI, 2.75-73.71); p = 0.002). LIMITATIONS: This was a single-institution, retrospective study. CONCLUSIONS: Most upper rectal tumors can be treated with partial mesorectal excision without the systematic use of preoperative chemoradiation. Involvement of the mesorectal fascia was the only independent risk factor for local recurrence in these tumors.

Product analysis and initial reliability testing of the total mesorectal excision-quality assessment instrument.

BACKGROUND: Product analysis of rectal cancer resection specimens before specimen fixation may provide an immediate and relevant evaluation of surgical performance. We tested the interrater reliability (IRR) of a product analysis tool called the Total Mesorectal Excision-Quality Assessment Instrument (TME-QA). METHODS: Participants included two gold standard raters, five pathology assistants, and eight pathologists. Domains of the TME-QA reflect total mesorectal excision principles including: (1) completeness of mesorectal margin; (2) completeness of mesorectum; (3) coning of distal mesorectum; (4) physical defects; and (5) overall specimen quality. Specimens were scored independently. We used the generalizability theory to assess the tool's internal consistency and IRR. RESULTS: There were 39 specimens and 120 ratings. Mean overall specimen quality scores for the gold standard raters, pathologists, and assistants were 4.43, 4.43, and 4.50, respectively (p > 0.85). IRR for the first nine items was 0.68 for the full sample, 0.62 for assistants alone, 0.63 for pathologists alone, and 0.74 for gold standard raters alone. IRR for the item overall specimen quality was 0.67 for the full sample, 0.45 for assistants, 0.80 for pathologists, and 0.86 for gold standard raters. IRR increased for all groups when scores were averaged across two raters. CONCLUSIONS: Assessment of surgical specimens using the TME-QA may provide rapid and relevant feedback to surgeons about their technical performance. Our results show good internal consistency and IRR when the TME-QA is used by pathologists. However, for pathology assistants, multiple ratings with the averaging of scores may be needed.

Catecholamines promote the expression of virulence and oxidative stress genes in Porphyromonas gingivalis.

BACKGROUND AND OBJECTIVE: Stress has been identified as an important risk factor in the development of many infectious diseases, including periodontitis. Porphyromonas gingivalis, a gram-negative oral anaerobic bacterium, is considered an important pathogen in chronic periodontitis. Microorganisms, including P. gingivalis, that participate in infectious diseases have been shown to respond to catecholamines released during stress processes by modifying their growth and virulence. Therefore, the purpose of this study was to evaluate the effects of adrenaline and noradrenaline on the growth, antimicrobial susceptibility and gene expression in P. gingivalis. MATERIAL AND METHODS: P. gingivalis was incubated in the presence of adrenaline and noradrenaline (100 µm) for different time-periods in rich (Tryptic soy broth supplemented with 0.2% yeast extract, 5 µg/mL of hemin and 1 µg/mL of menadione) and poor (serum-SAPI minimal medium and serum-SAPI minimal medium supplemented with 5 µg/mL of hemin and 1 µg/mL of menadione) media, and growth was evaluated based on absorbance at 660 nm. Bacterial susceptibility to metronidazole was examined after exposure to adrenaline and noradrenaline. The expression of genes involved in iron acquisition, stress oxidative protection and virulence were also evaluated using RT-quantitative PCR. RESULTS: Catecholamines did not interfere with the growth of P. gingivalis, regardless of nutritional or hemin conditions. In addition, bacterial susceptibility to metronidazole was not modified by exposure to adrenaline or noradrenaline. However, the expression of genes related to iron acquisition (hmuR), oxidative stress (tpx, oxyR, dps, sodB and aphC) and pathogenesis (hem, hagA and ragA) were stimulated upon exposure to adrenaline and/or noradrenaline. CONCLUSION: Adrenaline and noradrenaline can induce changes in gene expression related to oxidative stress and virulence factors in P. gingivalis. The present study is, in part, a step toward understanding the stress-pathogen interactions that may occur in periodontal disease.

[Laparoscopic approach of achalasia. Long-term clinical and functional results and quality of life]. / Abordaje laparoscópico de la acalasia. Resultados clínicos, de calidad de vida y funcionales a largo plazo.

INTRODUCTION: Laparoscopic Heller myotomy has become the gold standard procedure for patients with achalasia. This study evaluates the clinical status, quality of life, and functional outcomes after laparoscopic Heller myotomy. MATERIAL AND METHODS: We analyzed patients who underwent laparoscopic Heller myotomy with an associated anti-reflux procedure from October 1998 to December 2010. Before surgery, we administered a clinical questionnaire and as of 2002, we also evaluated quality of life using a specific questionnaire (GIQLI). In 2011, we performed a follow up for all available patients. We administered the same clinical questionnaire and quality of life test as before surgery and performed manometry and 24-hour pH monitoring. According to the length of follow up, patients were divided into 3 groups. Group 1 with a follow-up between 6 and 47 months; group 2 follow-up between 48 and 119 months, and group 3 with a follow-up of more than 120 months). Moreover, 27 patients had already been evaluated with this same protocol in 2003. Pre- and postoperative data were compared for the 3 groups and for patients who completed follow up in 2003 and 2011. RESULTS: Ninety-five patients underwent laparoscopic Heller myotomy. Seventy-six (80%) were available for follow-up. Mean follow-up was 56 months (range 6-143). Global improvement in dysphagia was 89%. Total DeMeester score decreased in the 3 groups. GIQLI scores improved after surgery, reaching normal values. Manometric determinations showed normal LES pressures after myotomy in the 3 groups. Ten percent of overall 24-hour pH monitoring was abnormal. The group of patients followed up in 2003 and in 2011 showed no impairment in the variables studied in the long term. CONCLUSIONS: Long-term follow up of the laparoscopic approach to achalasia showed good results concerning clinical status and quality of life, with normal sphincteric pressures and a low incidence of gastroesophageal reflux.

Birth of 16 healthy children after ICSI in cases of nonmosaic Klinefelter syndrome.

STUDY QUESTION: Does the health status of infants fathered by nonmosaic Klinefelter syndrome (KS) patients whose partners underwent ICSI with sperm obtained from testicular dissection reveal any genetic risk for the offspring?. SUMMARY ANSWER: KS patients undergoing testicular sperm extraction (TESE) are capable of conceiving healthy children. WHAT IS KNOWN ALREADY: Paternity has been successfully achieved in nonmosaic KS patients (47,XXY karyotype) by ICSI using either ejaculated or testicular spermatozoa. A crucial concern is the potential transmission of genetic abnormalities to the offspring. Some studies reported that 47,XXY spermatogonia are capable of completing spermatogenesis leading to the production of mature spermatozoa with increased aneuploidies. Other authors showed that where focal spermatogenesis is present in nonmosaic KS males, it originates from euploid germ cells and, therefore, produces normal mature gametes. In support of this finding, at present, the great majority of children born from nonmosaic KS patients are chromosomally normal. STUDY DESIGN, SIZE, DURATION: From April 2004 to June 2010, 38 azoospermic patients with nonmosaic KS were examined for the presence of testicular spermatozoa. Spermatozoa were retrieved from 15 patients and 26 ICSI cycles were done (16 with cryopreserved sperm). There were 15 pregnancies leading to the birth of 16 babies who were karyotyped at amniocentesis and after birth. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were recruited from couples attending the European Hospital, Rome, and Clinica MAR&Gen, Granada, for infertility treatment. Both the European Hospital and Clinica MAR&Gen are private clinics. Testicular tissue was extracted with TESE or micro-TESE. After retrieval, fresh sperm was used for ICSI or it was cryopreserved for future use. MAIN RESULTS AND THE ROLE OF CHANCE: Spermatozoa were retrieved from 15 patients (14 TESE and 1 micro-TESE) out of 38 (39.5%). A total of 26 ICSI cycles were performed: 10 with fresh and 16 with cryopreserved-thawed sperm. Mean ages (y) of patients with positive and negative sperm retrieval were, respectively, 34.8 ± 1.72 and 35.6 ± 4.08 (NS, nonsignificant). Comparing ICSI cycles performed with fresh sperm (n = 10) to those performed with frozen-thawed sperm (n = 16): Fertilization rates per injected oocyte were 53.0% (44 of 83) and 47.8% (32 of 67), respectively (NS). The cleavage rate per injected oocyte was 90.6% (29 of 32) versus 68.2% (30 of 44); P = 0.026. Clinical outcomes were not significantly different between the fresh and the frozen-thawed sperm group: clinical pregnancy rates were 7 of 10 (70.0%) and 8 of 16 (50.0%); implanted embryos (per transferred embryo) were 8 of 23 (34.8%) and 8 of 29 (27.6%); delivery rates were 6 of 10 (60.0%) and 5 of 16 (31.3%). Sixteen babies were born, all of them are healthy with a normal karyotype, eight from the fresh sperm group and eight from the frozen-thawed sperm group. LIMITATIONS, REASONS FOR CAUTIONS: The small numbers available for study mean that only common problems can be excluded. WIDER IMPLICATIONS OF THE FINDINGS: This study provides further reassurance that KS men can father healthy children and that pre-implantation genetic diagnosis on embryos conceived with their sperm is not strongly indicated. However, until conclusive information is available, such couples should be offered extensive genetic counseling. STUDY FUNDING/COMPETING INTEREST(S): No external funding was obtained for the present study. None of the authors has any conflict of interest to declare. TRIAL REGISTRATION NUMBER: Not applicable.

Allium stent for treatment of ureteral stenosis.

AIM: The aim of our study is to value the efficacy of self-expanding Allium ureteral stent in the treatment of ureteral stenosis. METHODS: From 2010 to 2013, we treated 12 patients, aged from 23 to 64 years. Six patients were affected by congenital UPJ obstruction, four patients by iatrogenic unilateral ureteral stenosis and two patients by bilateral ureteral stenosis. All the patients showed hydronephrosis before the stenotic lesion and pain. In all the patients, we use a 30 Fr, 10 cm length self-expanding Allium ureteral stent. The medium follow-up is 10 months after Allium stent removal. RESULTS: All the patients were immediately free of pain after the procedure. We didn't experience intra, peri and postoperative complications. In all the patients, a complete correction of the stenotic lesion was obtained. No recurrence of stenosis occurred during follow-up. CONCLUSION: Self-expanding allium ureteral stent represents an effective treatment of ureteral stenosis in patients not suitable for surgery.

A pioneer of public health, Bernardino Ramazzini.

2014 marks the tercentenary of the death of Bernardino Ramazzini, an academic who lived in the Duchy of Modena in the second half of the seventeenth century. This event represents an occasion to remember his thinking, which is remarkably anticipatory of some concepts and trends of modern public health. Although the main merit of Bernardino Ramazzini lies in his contribution to the knowledge of occupational diseases, which granted him the title of father of Occupational Medicine, his work deserves a more detailed and complete consideration. In fact, the systematic approach to the clinical presentation of diseases and their relationship to work, gathered in the famed treatise De Morbis Artificum Diatriba, resulted in little attention being paid to the preventive aspects of his thinking. The free spirit, the tension for searching, the love for the discussion characterize his scientific attitude, which spans from the anticipation of an epidemiologic approach to studies on the impact of air and climate, from workplace surveillance to suggestions for the protection of health, from proposals of primary prevention tools to recommendations of lifestyle behaviour, from educational issues to health promotion. His scientific, cultural and humanitarian stature is evidenced by his overall scientific works revealing the modernity of his thinking in the light of the present trend of public health focusing on the needs of people and promoting occupational health as an integral component of the health concept.

Occupation and breast cancer: fitness for work is an aspect that needs to be addressed.

Much progress has been made in breast cancer prevention, treatment and rehabilitation and there is evidence that the majority of breast cancer survivors are able to continue working. Although several studies suggest that environmental and occupational factors (certain chemicals and circadian rhythm changes) contribute to the onset of breast cancer, current management of individuals susceptible to breast cancer and breast cancer survivors does not focus on either occupational exposure or working conditions. A more active role of physicians in informing patients about occupational hazards and of occupational health physicians in making appropriate fitness for work judgments would lead to a more complete assessment ofthe health risk of susceptible workers and workers resuming their activity after sick leave for breast cancer treatment.

[The cultural, economic and social context of Ramazzini's Diatriba in the second half of the 17th century--in memory of Pericle Di Pietro on occasion of the third centenary of the publication of the final edition of the Diatriba (Padua, 1713)]. / Il contesto culturale, economico e sociale della Diatriba ramazziniana nella seconda metà del seicento--in memoria di Pericle Di Pietro in occasione del trecentesimo anniversario della pubblicazione dell'edizione definitiva della Diatriba (Padova, 1713).

The paper aims at analyzing the development of Ramazzini's train of thought in Diatriba within the cultural, economic and social context of the Duchy of Modena in the second half of the seventeenth century. The period was characterized by a deep recession affecting every aspect of life in the territory: culture was mostly at the service of the court's image, the economy, mainly based on agriculture, was in crisis and many crafts depended on the demands of the nobility. The culture of the Este court had, however, little influence on Ramazzini's ideas, whereas social and economic aspects were the stimulus to his experimentalism via observation. In this context, Ramazzini was an illuminated nonconformist, who analysed the vulnerability of the population with an anthropological approach that embraced individuals, environment, social and economic status.