Cluster of legionnaires’ disease in an Italian prison

Background: Legionella pneumophila (Lp) is the most common etiologic agent causing Legionnaires’ Disease (LD). Water systems offer the best growth conditions for Lp and support its spread by producing aerosols. From 2015 to 2017, the Regional Reference Laboratory of Clinical and Environmental Surveillance of Legionellosis of Palermo monitored the presence of Lp in nine prisons in Western Sicily. During this investigation, we compared Lp isolates from environmental samples in a prison located in Palermo with isolates from two prisoners in the same prison. Methods: We collected 93 water samples from nine Sicilian prisons and the bronchoalveolar lavages (BALs) of two prisoners considered cases of LD. These samples were processed following the procedures described in the Italian Guidelines for the Prevention and Control of Legionellosis of 2015. Then, genotyping was performed on 19 Lp colonies (17 from water samples and 2 from clinical samples) using the Sequence-Based Typing (SBT) method, according to European Study Group for Legionella Infections (ESGLI) protocols. Results: Lp serogroup (sg) 6 was the most prevalent serogroup isolated from the prisons analyzed (40%), followed by Lp sg 1 (16%). Most of all, in four penitentiary institutions, we detected a high concentration of Lp >104 Colony Forming Unit/Liter (CFU/L). The environmental molecular investigation found the following Sequence Types (STs) in Lp sg 6: ST 93, ST 292, ST 461, ST 728, ST 1317 and ST 1362, while most of the isolates in sg 1 belonged to ST 1. We also found a new ST that has since been assigned the number 2451 in the ESGLI-SBT database. From the several Lp sg 1 colonies isolated from the two BALs, we identified ST 2451. Conclusions: In this article, we described the results obtained from environmental and epidemiological investigations of Lp isolated from prisons in Western Sicily. Furthermore, we reported the first cluster of Legionnaires’ in an Italian prison and the molecular typing of Lp sg 1 from one prison’s water system and two BALs, identified the source of the contamination, and discovered a new ST

Volume regulation by Amphiuma red blood cells. The membrane potential and its implications regarding the nature of the ion-flux pathways

After osmotic perturbation, the red blood cells of Amphiuma exhibited a volume-regulatory response that returned cell volume back to or toward control values. After osmotic swelling, cell-volume regulation (regulatory volume decrease; RVD) resulted from net cellular loss of K, Cl, and osmotically obliged H2O. In contrast, the volume-regulatory response to osmotic shrinkage (regulatory volume increase; RVI) was characterized by net cellular uptake of Na, Cl, and H2O. The net K and Na fluxes characteristic of RVD and RVI are increased by 1-2 orders of magnitude above those observed in studies of volume-static control cells. The cell membrane potential of volume-regulating and volume-static cells was measured by impalement with glass microelectrodes. The information gained from the electrical and ion-flux studies led to the conclusion that the ion fluxes responsible for cell-volume regulation proceed via electrically silent pathways. Furthermore, it was observed that Na fluxes during RVI were profoundly sensitive to medium [HCO3] and that during RVI the medium becomes more acid, whereas alkaline shifts in the suspension medium accompany RVD. The experimental observations are explained by a model featuring obligatorily coupled alkali metal-H and Cl-HCO3 exchangers. The anion- and cation-exchange pathways are separate and distinct yet functionally coupled via the net flux of H. As a result of the operation of such pathways, net alkali metal, Cl, and H2O fluxes proceed in the same direction, whereas H and HCO3 fluxes are cyclic. Data also are presented that suggest that the ion-flux pathways responsible for cell-volume regulation are not activated by changes in cell volume per se but by some event associated with osmotic perturbation, such as changes in intracellular pH

VIRULENCE FACTORS AND ANTIMICROBIAL RESISTANCE OF ESCHERICHIA COLI ST131 IN COMMUNITY-ONSET HEALTHCARE-ASSOCIATED INFECTIONS IN SICILY, ITALY

Escherichia coli ST131 is an emerging resistant agent recently called \u201csuperbug\u201d in England. This strain is responsible of community-acquired urinary tract infections and nowadays showing increasing resistance to antibiotics like fluoroquinolones and cephalosporins. Survey of virulent bacterial clone is relevant to control its spreading in community. We aim to assess the circulation of resistant clones Escherichia coli ST131 outside of the hospital to prompt control of outbreak in our geographical area. We selected 105 E. coli resistant isolates from community-acquired urinary infections and performed a multiplex PCR to evaluate if they belonged to the ST131 type. We investigated their set of virulence factors; in particular, kpsMII, papA, sfaS, focG, iutA, papC, hlyD and afa genes, and finally, we evaluated beta lactamases genes and quinolone resistance determinants. E. coli ST 131 clone was present in 66.6% of our isolates and showed positivity to a wide range of resistance genes, in particular blaCTX-M-15 among beta lactamases and plasmid-related quinolone resistance genes (qnrA, qnrS and aac (6\u2019)-Ib-cr). Moreover, 81% of the strains showed positivity to at least one of the virulence factor genes. Our results suggested a high presence of E. coli ST131 in community. We suggest antibiotic stewardship for outpatient clinicians and facilities to contain the spread of \u201csuperbug\u201d agents

Prehospital transdermal glyceryl trinitrate in patients with ultra-acute presumed stroke (RIGHT-2): an ambulance-based, randomised, sham-controlled, blinded, phase 3 trial

Background High blood pressure is common in acute stroke and is a predictor of poor outcome; however, large trials oflowering blood pressure have given variable results, and the management of high blood pressure in ultra-acute strokeremains unclear. We investigated whether transdermal glyceryl trinitrate (GTN; also known as nitroglycerin), a nitricoxide donor, might improve outcome when administered very early after stroke onset.Methods We did a multicentre, paramedic-delivered, ambulance-based, prospective, randomised, sham-controlled,blinded-endpoint, phase 3 trial in adults with presumed stroke within 4 h of onset, face-arm-speech-time score of 2or 3, and systolic blood pressure 120 mm Hg or higher. Participants were randomly assigned (1:1) to receivetransdermal GTN (5 mg once daily for 4 days; the GTN group) or a similar sham dressing (the sham group) in UKbasedambulances by paramedics, with treatment continued in hospital. Paramedics were unmasked to treatment,whereas participants were masked. The primary outcome was the 7-level modified Rankin Scale (mRS; a measure offunctional outcome) at 90 days, assessed by central telephone follow-up with masking to treatment. Analysis washierarchical, first in participants with a confirmed stroke or transient ischaemic attack (cohort 1), and then in allparticipants who were randomly assigned (intention to treat, cohort 2) according to the statistical analysis plan. Thistrial is registered with ISRCTN, number ISRCTN26986053.Findings Between Oct 22, 2015, and May 23, 2018, 516 paramedics from eight UK ambulance services recruited1149 participants (n=568 in the GTN group, n=581 in the sham group). The median time to randomisation was 71 min(IQR 45–116). 597 (52%) patients had ischaemic stroke, 145 (13%) had intracerebral haemorrhage, 109 (9%) hadtransient ischaemic attack, and 297 (26%) had a non-stroke mimic at the final diagnosis of the index event. In the GTNgroup, participants’ systolic blood pressure was lowered by 5·8 mm Hg compared with the sham group (p<0·0001),and diastolic blood pressure was lowered by 2·6 mm Hg (p=0·0026) at hospital admission. We found no difference inmRS between the groups in participants with a final diagnosis of stroke or transient ischaemic stroke (cohort 1):3 (IQR 2–5; n=420) in the GTN group versus 3 (2–5; n=408) in the sham group, adjusted common odds ratio for pooroutcome 1·25 (95% CI 0·97–1·60; p=0·083); we also found no difference in mRS between all patients (cohort 2:3 [2–5]; n=544, in the GTN group vs 3 [2–5]; n=558, in the sham group; 1·04 [0·84–1·29]; p=0·69). We found nodifference in secondary outcomes, death (treatment-related deaths: 36 in the GTN group vs 23 in the sham group[p=0·091]), or serious adverse events (188 in the GTN group vs 170 in the sham group [p=0·16]) between treatmentgroups. Interpretation Prehospital treatment with transdermal GTN does not seem to improve functional outcome in patientswith presumed stroke. It is feasible for UK paramedics to obtain consent and treat patients with stroke in the ultra acute prehospital settin

Inflammatory Pseudotumor of the Anal Canal Mimicking Colorectal Cancer: Case Report and Hints to Improve a Patient’s Fitness for Treatment and Prevention

: Background and Clinical Significance: Men who engage in anal fisting may experience full rectal and colon thickness injury resulting in an endoscopic emergency. The endoscopist does not routinely question patients about their sexual habits, nor are patients compliant with counseling during the endoscopy procedure as indicated by the infectious disease clinician. Case Presentation: A 47-years-old HIV- and monkeypox virus (MPXV)-negative Caucasian gay man underwent colonoscopy because of changes in bowel habits with anal discomfort and rectal bleeding. The first colonoscopy showed a vegetative annular neoformation of the anal canal. There was a concentric stenosis of the lumen. The endoscopist suspected the diagnosis of anal squamous cell carcinoma and a histopathology investigation was requested. Biopsy histology excluded a frank neoplasm or anal intraepithelial neoplasia (AIN). Then, the patient was referred to a multidisciplinary team. With adequate counseling, the patient disclosed his habitual anal fisting. Laboratory identification of L1-L3 Chlamydia trachomatis (CT) genovars was positive for CT L1, L2, real-time PCR for Neisseria gonorrhoeae (NG), and Mycoplasma hominis. Human Papillomavirus (HPV)-DNA detection identified HPV type 70, 68, and 61. We illustrate this case with plenty of histology and immunohistochemistry. We also review the differential diagnosis of AIN according to the 5th edition (2019) WHO Classification of Digestive System Tumours. Conclusions: Our patient emphasizes two important aspects of endoscopy and pathology: first, the significance of understanding patients' sexual behaviors in diagnosing rectal and colon injuries, as well as the need for sexually transmitted infections (STI) screening especially for CT; and second, the effectiveness of a multidisciplinary communication model that encourages private discussions to alleviate patients' fears and improve prevention efforts

Socio-Demographic Characteristics and Sexual Behavioral Factors of Patients with Sexually Transmitted Infections Attending a Hospital in Southern Italy

Sexually transmitted infections (STIs) are a serious global health problem. In Italy, data describing the vulnerability to STIs of specific sexual minorities and the influence of sociodemographic and behavioral determinants are limited, as most infections are not subject to mandatory notification. This retrospective study describes the sociodemographic profile and main sexual behaviors of patients attending a hospital in Palermo (Sicily, Italy) from January 2018 to March 2019 as predictors of STI risk. Patients were divided in subgroups: men-who-have-sex-with-men (MSM), men-who-have-sex-with-women (MSW), bisexual men and females. Data were obtained through an anonymous questionnaire. Patients were tested for chlamydia, syphilis, Mycoplasma genitalium infection, genital herpes and HPV infection. A total of 294 subjects with STIs (male/female ratio about 2:1) were screened. Of the total sample, 79.6% of patients were Italian. MSM accounted for 34.3%, MSW for 29.6%, bisexual men for 5.8% and females for 30.3%. A total of 44.5% of patients had a high education level, 42.5% reported irregular use of condoms, 20.7% reported having had 5-10 partners in the six months prior to the visit and 32.9% were HIV-positive. HPV infection and syphilis were the most prevalent STIs. Conclusions: The most common profile of patients attending our clinic was that of an adult, Italian man with a high level of education, poor use of condoms and a high number of partners. MSM had the highest sex-behavior-related risk for STIs. In addition, our results suggest that all STD teams need to implement counselling topics and recommendations to share with patients, as well as tips on how to approach sexual health education/counselling, thereby promoting patient-centered approaches and educational programs

Cell entry of a host targeting protein of oomycetes requires gp96

This work is supported by the [European Community’s] Seventh Framework Programme [FP7/2007–2013] under grant agreement no. [238550] (L.L., J.D.-U., C.J.S., P.v.W.); BBSRC [BBE007120/1, BB/J018333/1 and BB/G012075/1] (F.T., I.d.B., C.J.S., S.W., P.v.W.); Newton Global Partnership Award [BB/N005058/1] (F.T., P.v.W.), the University of Aberdeen (A.D.T., T.R., C.J.S., P.v.W.) and Deutsche Forschungsgemeinschaft [CRC1093] (P.B., T.S.). We would like to acknowledge the Ministry of Higher Education Malaysia for funding INA. We would like to thank Brian Haas for his bioinformatics support. We would like to acknowledge Neil Gow and Johannes van den Boom for critical reading of the manuscript. We would like to acknowledge Svetlana Rezinciuc for technical help with pH-studies.Peer reviewedPublisher PD

Molecular Analyses of Circadian Gene Variants Reveal Sex-Dependent Links Between Depression and Clocks

An extensive literature links circadian irregularities and/or sleep abnormalities to mood disorders. Despite the strong genetic component underlying many mood disorders, however, previous genetic associations between circadian clock gene variants and major depressive disorder (MDD) have been weak. We applied a combined molecular/functional and genetic association approach to circadian gene polymorphisms in sex-stratified populations of control subjects and case subjects suffering from MDD. This approach identified significant sex-dependent associations of common variants of the circadian clock genes hClock, hPer3 and hNpas2 with major depression and demonstrated functional effects of these polymorphisms on the expression or activity of the hCLOCK and hPER3 proteins, respectively. In addition, hCLOCK expression is affected by glucocorticoids, consistent with the sex-dependency of the genetic associations and the modulation of glucocorticoid-mediated stress response, providing a mechanism by which the circadian clock controls outputs that may affect psychiatric disorders. We conclude that genetic polymorphisms in circadian genes (especially hClock and hPer3, where functional assays could be tested) influence risk of developing depression in a sex- and stress-dependent manner. These studies support a genetic connection between circadian disruption and mood disorders, and confirm a key connection between circadian gene variation and major depression

Predictors and outcomes of neurological deterioration in intracerebral hemorrhage: results from the TICH-2 randomised controlled trial

Neurological deterioration is common after intracerebral hemorrhage (ICH). We aimed to identify the predictors and effects of neurological deterioration and whether tranexamic acid reduced the risk of neurological deterioration. Data from the Tranexamic acid in IntraCerebral Hemorrhage-2 (TICH-2) randomized controlled trial were analyzed. Neurological deterioration was defined as an increase in National Institutes of Health Stroke Scale (NIHSS) of ≥ 4 or a decline in Glasgow Coma Scale of ≥ 2. Neurological deterioration was considered to be early if it started ≤ 48 h and late if commenced between 48 h and 7 days after onset. Logistic regression was used to identify predictors and effects of neurological deterioration and the effect of tranexamic acid on neurological deterioration. Of 2325 patients, 735 (31.7%) had neurological deterioration: 590 (80.3%) occurred early and 145 (19.7%) late. Predictors of early neurological deterioration included recruitment from the UK, previous ICH, higher admission systolic blood pressure, higher NIHSS, shorter onset-to-CT time, larger baseline hematoma, intraventricular hemorrhage, subarachnoid extension and antiplatelet therapy. Older age, male sex, higher NIHSS, previous ICH and larger baseline hematoma predicted late neurological deterioration. Neurological deterioration was independently associated with a modified Rankin Scale of > 3 (aOR 4.98, 3.70–6.70; p [less than] 0.001). Tranexamic acid reduced the risk of early (aOR 0.79, 0.63–0.99; p = 0.041) but not late neurological deterioration (aOR 0.76, 0.52–1.11; p = 0.15). Larger hematoma size, intraventricular and subarachnoid extension increased the risk of neurological deterioration. Neurological deterioration increased the risk of death and dependency at day 90. Tranexamic acid reduced the risk of early neurological deterioration and warrants further investigation in ICH