BACKGROUND: Trichophyton mentagrophytes ITS genotype VII (TMVII) has recently been identified in France as the causative agent of dermatophyte infections transmitted during sexual activity among men who have sex with men (MSM). OBJECTIVES: Our objective was to provide new insights into the epidemiology, clinical presentation and treatment of TMVII infections based on cases diagnosed from October 2022 to September 2023 in three medical mycology laboratories in Paris. Additionally, we aimed to perform molecular characterization of TMVII strains collected in Paris, as well as in Switzerland. METHODS: We identified all isolates from skin and hair belonging to the T. mentagrophytes complex by sequencing the ITS region. For isolates corresponding to TMVII, clinical data were retrieved from medical records. For all available TMVII strains that we isolated since January 2021, we sequenced tef1α and tubb and determined the MAT locus idiomorph. RESULTS: We identified 32 cases of TMVII Infections. All cases occurred in men, 30 of whom reported having sex with men. Fifteen cases were sporadic cases including four among sex workers. The other 17 cases belonged to a single cluster involving a tantric masseur who infected 15 clients and his roommate. The median time from massage to lesion onset was 16 [2-52] days. Except for one patient, all other patients received systemic antifungal treatment with terbinafine. We observed five patients whose cultures remained positive even after 3-4 weeks of treatment and five patients experienced a relapse of the infection after discontinuing antifungal treatment. All French isolates exhibited identical tef1α and tubb sequences, as well as the same MAT idiomorph locus. They displayed variations in the tef1α sequence compared to isolates from Switzerland and the Czech Republic. CONCLUSIONS: We confirm the active circulation of TMVII among MSM in France, which is associated with challenges in diagnosis, treatment and prevention.
- MeSH
- Antifungal Agents * therapeutic use MeSH
- Arthrodermataceae MeSH
- Adult MeSH
- Genotype * MeSH
- Homosexuality, Male MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Terbinafine therapeutic use MeSH
- Tinea * microbiology epidemiology drug therapy MeSH
- Trichophyton * genetics isolation & purification MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- France MeSH
Ciele: Cieľom pilotného projektu bolo zvýšiť testovanie ako aj prepojenie so zdravotnou starostlivosťou o novodiagnostikované osoby s infekciou HIV/HCV/syfilisu a tiež zlepšiť zber a prenos údajov pomocou štandardných nástrojov zberu údajov z komunitných centier poskytujúcich dobrovoľné poradenstvo a testovanie (CBVCT) do národného epidemiologického a monitorovacieho systému. Metódy: Integrované dobrovoľné anonymné testovanie z krvi na HIV, HCV a syfilis bolo realizované pomocou rýchlych testov v období 6 mesiacov (03/2019 až 8/2019). Účastníkom s reaktívnymi výsledkami sa odporučilo, aby navštívili špecialistu za účelom potvrdenia diagnózy a nasadenia terapie. Výsledky: Otestovaných bolo 675 klientov na HIV, 410 na HCV a 457 na syfilis. Medián veku účastníkov sa pohyboval od 24 do 35,6 (IQR:24), 75,3 % z nich bolo mužov, 23,7 % žien a 0,6 % transrodových ľudí. Z hľadiska rizika akvírovania testovaných infekcii 48,9 % zo 675 klientov boli muži majúci styk s mužmi (MSM), 0,3 % osoby pracujúce v sex-biznise (SW), 9,0 % injekční užívatelia drog (PWID), 2,4 % migranti (Mi) a 8,3 % klientov uvádzalo kombináciu týchto rizík. Pilotný projekt odhalil infekciu HIV u 0,4 %, HCV u 2,4 % a T. pallidum u 1,8 % klientov. Len 2 klienti, s potvrdenou HIV infekciou boli prepojení s následnou zdravotnou starostlivosťou. Najvyššia prevalencia HIV bola zistená u MSM/Mi (4,2 %), HCV u PWID (30,8 %) a syfilisu u SW/PWID (7,1 %). Bezkondómový styk so SW, PWID, MSM a HIV pozitívnymi za posledných 12 mesiacov uviedlo 5/92, 41/82, 3/78 a 0/88 odpovedajúcich klientov. Výsledky štúdie boli zahrnuté do ročnej národnej epidemiologickej správy. Záver: Pilotný projekt odhalil potrebu podpory integrovaného testovania v CBVCT, prekonania prekážok pri potvrdzujúcom testovaní a prepojení so zdravotnou starostlivosťou ako aj potrebu integrácie základných údajov v rámci monitorovania a hodnotenia (M&E) testovania v CBVCT do národných systémov surveillance na Slovensku.
Aim: Aim of the pilot was to increase HIV/HCV/syphilis testing and linkage to care of newly diagnosed persons, improve data collection and transfer using standard data collection tools in CBVCT services. Methods: Integrated anonymous voluntary testing from blood for HIV, HCV and syphilis was realised using rapid tests in the period of 6 months (03/2019–08/2019). Participants with reactive results were advised to see a specialist for confirmatory testing and/or treatment. Results: A total of 675 clients were tested for HIV, 410 for HCV, and 457 for syphilis. Participants’ median age ranged from 24 to 35.6 (IQR: 24), 75.3% of them were men, 23.7% were women, and 0.6% identified as transgender. In terms of groups at risk 48.9 % of 675 clients were men who have sex with men (MSM), 0.3 % sex workers (SW), 9.0 % people who inject drugs (PWID), 2.4 % migrants (Mi) and the rest of clients (8.3 %) belonged to groups at combined risk. Pilot revealed HIV, HCV and T. pallidum infections in 0.4 %, 2.4 % and 1.8 % of clients, respectively. Just 2 clients, confirmed HIV-positive, were linked to care. The highest prevalence of HIV (4.2 %), HCV (30.8 %) and syphilis (7.1 %) was found among MSM/Mi, PWID and SW/PWID, respectively. Condomless intercourse with SW, PWID, MSM and HIV-positive person in the last 12 months was reported by 5/92, 41/82, 3/78 and 0/88 of responding clients, respectively. Core indicators were included in the yearly national epidemiological report. Conclusions: Pilot revealed the need to support integrated CBVCT to overcome barriers in confirmatory testing and linkage to care and to integrate core data of monitoring and evaluation (M&E) testing framework at CBVCT services into a national surveillance and M&E systems in Slovakia.
- MeSH
- Anonymous Testing * MeSH
- Hepatitis C diagnosis epidemiology MeSH
- HIV Infections diagnosis epidemiology MeSH
- Delivery of Health Care, Integrated methods MeSH
- Humans MeSH
- Public Health Surveillance methods MeSH
- Sexually Transmitted Diseases * diagnosis epidemiology MeSH
- Sexual and Gender Minorities MeSH
- Preventive Health Services methods MeSH
- Syphilis diagnosis epidemiology MeSH
- Drug Users * MeSH
- Check Tag
- Humans MeSH
- Geographicals
- Slovakia MeSH
PROBLEM: Up to 75 % of at-risk perinatal women do not receive treatment in Czechia. BACKGROUND: Pregnant women with mental health difficulties are more likely to undergo less controversial nonpharmaceutical treatment during pregnancy, but structural and psychological barriers interfere with their capacity to seek professional help. AIM: We tested the effectiveness of the telephone-based peer support intervention Mom Supports Mom (MSM) in Czech pregnant women at risk of mental disorder. METHODS: The Edinburgh Postnatal Depression Scale (EPDS) was used to assess risk in women (EPDS ≥ 10). Women at risk were randomized into two groups; the intervention group received the MSM, while the control group received the care as usual, which did not contain any psychological support intervention. One month after completing the EPDS, the women's mental statuses were again measured and compared, this time with data before and after the intervention, using the Perinatal Anxiety Screening Scale (PASS) to measure anxiety, the EPDS to measure depression, the Prenatal Psychosocial Profile (PPP) to measure stress, and the Prenatal Attachment Inventory - Revised (PAI-R) to measure attachment. The trial was registered under the name Pregnancy without psychosocial stress (ClinicalTrials.gov ID NCT04853693). FINDINGS: A total of 167 women were included in the study and randomized into two groups. Depressive symptoms did not decrease (Cohen ́s d; 95 % CI = 0.48; 0.17-0.79; p = .002), but levels of anxiety (Cohen ́s d; 95 % CI = 0.44; 0.13-0.75; p = .005) and psychosocial stress (Cohen ́s d; 95 % CI = 0.55; 0.20-0.82; p = .002) were reduced in women in the intervention group compared with women in the control. In addition, prenatal attachment increased among intervened women (Cohen ́s d; 95 % CI = 0.48; 0.17-0.79; p = .002). DISCUSSION: The telephone-based peer support intervention MSM is effective in reducing stress and anxiety and increasing prenatal attachment but does not reduce depression among high-risk women.
- MeSH
- Adult MeSH
- Humans MeSH
- Mothers psychology MeSH
- Prenatal Care methods MeSH
- Psychiatric Status Rating Scales MeSH
- Social Support * MeSH
- Pregnancy MeSH
- Pregnant People MeSH
- Peer Group * MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
- Geographicals
- Czech Republic MeSH
BACKGROUND: The aim of the study was to assess socio-demographical characteristics, clinical presentation, and outcomes in patients diagnosed with mpox. METHODS: A survey on patients diagnosed with mpox was performed in 14 countries from Central and Eastern Europe. Data was compared according to HIV status and country of origin (EU vs. non-EU). Mpox diagnosis was confirmed by RT-PCR from oropharyngeal swabs, skin lesions, and other body fluids. RESULTS: Out of 154 patients confirmed with mpox in 2022, 99.3% were males, with a median age (years) of 35 (IQR 30-39), 90.2% MSM and 48.7% PLWH. Compared to HIV-negative subjects, PLWH had more frequent high-risk behaviours:chemsex (p = 0.015), group sex (p = 0.027), and a history of sexually transmitted infections (STIs) (p = 0.004). Persons from EU were more often PLWH (p = 0.042), MSM (p < 0.0001), had multiple sexual partners (p = 0.025), practiced chemsex (p = 0.008) or group-sex (p = 0.005) and had more often history of STIs (p < 0.0001). The median CD4 cell count/mL at mpox diagnosis was 713 (IQR 486-996) and 73.5% had undetectable HIV VL. The commonest clinical features were fever (108 cases), lymphadenopathy (78), and vesiculo-pustular rash: penile (76), perianal (48), limbs (67). Fifty-one (31%) persons were hospitalized due to complications or epidemiological reasons. Three patients received tecovirimat or cidofovir. The outcome was favorable for all patients, including 4 with severe forms. CONCLUSIONS: Mpox was diagnosed predominantly in young MSM, with high-risk behaviors and history of STIs. Effective contact tracing and vaccination are important strategic pillars to control mpox outbreaks.
- MeSH
- Adult MeSH
- Disease Outbreaks * MeSH
- HIV Infections epidemiology MeSH
- Condylomata Acuminata epidemiology MeSH
- Middle Aged MeSH
- Humans MeSH
- Sexually Transmitted Diseases epidemiology diagnosis MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Europe MeSH
- Europe, Eastern MeSH
Exposure to bisphenols has been found to have adverse effects on male reproductive function in animals. Human exposure to bisphenols is widespread. Bisphenol A (BPA) and its analogues, including bisphenol S (BPS), bisphenol F (BPF), and bisphenol AF (BPAF) are utilized in various consumer products such as food contact materials and dental resins. The effects of these compounds on male fertility and spermatogenesis are unclear and findings from human studies are inconsistent. In this cross-sectional study, we evaluated the influence of BPA, BPS, BPF, BPAF (BPs) measured in semen on number of spermatozoa, total motility, progressive motility, morphology, and DNA fragmentation. We also examined the association of bisphenols (BPs) exposure with patients' occupation. A total of 358 patients aged 17-62 years with BMI 18-42 were included in the study from 2019 to 2021. BPs were extracted using solvent extraction followed by preconcentration step and determined by high-performance liquid chromatography and tandem mass spectrometry (LC/MSMS). Bisphenols were detected in 343 from 349 analysed samples (98.3% of all the samples). In 6 samples, the concentration of all BPs was under the limit of detection and in 20 samples under the limit of quantification. We did not find a statistically significant relationship between occupation and BPs. However, we observed significant correlations between the concentration of BPA and a lower motility and normal morphology. For BPS, a significant correlation with a lower ejaculate volume and a lower total sperm count was found. BPF and BPAF were detected only in 14.3% and 23.9% of samples, respectively. For BPF and BPAF, no significant correlations with spermiogram parameters were observed. Our results show that BPs are widespread in the male population (more than 90% of analysed samples), independently of an occupation and in case of BPA and BPS having a negative impact on spermiogram parameters.
The protozoan parasite Trichomonas vaginalis (Tv) causes trichomoniasis, the most common non-viral sexually transmitted infection in the world. Although Tv has been linked to significant health complications, only two closely related 5-nitroimidazole drugs are approved for its treatment. The emergence of resistance to these drugs and lack of alternative treatment options poses an increasing threat to public health, making development of novel anti-Trichomonas compounds an urgent need. The proteasome, a critical enzyme complex found in all eukaryotes has three catalytic subunits, β1, β2, and β5 and has been validated as a drug target to treat trichomoniasis. With the goal of developing tools to study the Tv proteasome, we isolated the enzyme complex and identified inhibitors that preferentially inactivate either one or two of the three catalytic subunits. Using a mass spectrometry-based peptide digestion assay, these inhibitors were used to define the substrate preferences of the β1, β2 and β5 subunits. Subsequently, three model fluorogenic substrates were designed, each specific for one of the catalytic subunits. This novel substrate profiling methodology will allow for individual subunit characterization of other proteasomes of interest. Using the new substrates, we screened a library of 284 peptide epoxyketone inhibitors against Tv and determined the subunits targeted by the most active compounds. The data show that inhibition of the Tv β5 subunit alone is toxic to the parasite. Taken together, the optimized proteasome subunit substrates will be instrumental for understanding the molecular determinants of proteasome specificity and for accelerating drug development against trichomoniasis.
- MeSH
- Proteasome Inhibitors pharmacology chemistry MeSH
- Catalytic Domain * MeSH
- Proteasome Endopeptidase Complex * metabolism chemistry MeSH
- Protozoan Proteins chemistry metabolism antagonists & inhibitors genetics MeSH
- Substrate Specificity MeSH
- Trichomonas vaginalis * enzymology MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Simultaneous comparisons of multiple disease-modifying therapies for relapsing-remitting multiple sclerosis (RRMS) over an extended follow-up are lacking. Here we emulate a randomised trial simultaneously comparing the effectiveness of six commonly used therapies over 5 years. METHODS: Data from 74 centres in 35 countries were sourced from MSBase. For each patient, the first eligible intervention was analysed, censoring at change/discontinuation of treatment. The compared interventions included natalizumab, fingolimod, dimethyl fumarate, teriflunomide, interferon beta, glatiramer acetate and no treatment. Marginal structural Cox models (MSMs) were used to estimate the average treatment effects (ATEs) and the average treatment effects among the treated (ATT), rebalancing the compared groups at 6-monthly intervals on age, sex, birth-year, pregnancy status, treatment, relapses, disease duration, disability and disease course. The outcomes analysed were incidence of relapses, 12-month confirmed disability worsening and improvement. RESULTS: 23 236 eligible patients were diagnosed with RRMS or clinically isolated syndrome. Compared with glatiramer acetate (reference), several therapies showed a superior ATE in reducing relapses: natalizumab (HR=0.44, 95% CI=0.40 to 0.50), fingolimod (HR=0.60, 95% CI=0.54 to 0.66) and dimethyl fumarate (HR=0.78, 95% CI=0.66 to 0.92). Further, natalizumab (HR=0.43, 95% CI=0.32 to 0.56) showed a superior ATE in reducing disability worsening and in disability improvement (HR=1.32, 95% CI=1.08 to 1.60). The pairwise ATT comparisons also showed superior effects of natalizumab followed by fingolimod on relapses and disability. CONCLUSIONS: The effectiveness of natalizumab and fingolimod in active RRMS is superior to dimethyl fumarate, teriflunomide, glatiramer acetate and interferon beta. This study demonstrates the utility of MSM in emulating trials to compare clinical effectiveness among multiple interventions simultaneously.
- MeSH
- Dimethyl Fumarate therapeutic use MeSH
- Fingolimod Hydrochloride therapeutic use MeSH
- Glatiramer Acetate therapeutic use MeSH
- Immunosuppressive Agents therapeutic use MeSH
- Interferon-beta therapeutic use MeSH
- Humans MeSH
- Natalizumab therapeutic use MeSH
- Recurrence MeSH
- Multiple Sclerosis, Relapsing-Remitting * drug therapy MeSH
- Multiple Sclerosis * drug therapy MeSH
- Pregnancy MeSH
- Check Tag
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Randomized Controlled Trial MeSH
Antimicrobial resistance (AMR) is one of the top public health threats nowadays. Among the most important AMR pathogens, Escherichia coli resistant to extended spectrum cephalosporins (ESC-EC) is a perfect example of the One Health problem due to its global distribution in animal, human, and environmental sources and its resistant phenotype, derived from the carriage of plasmid-borne extended-spectrum and AmpC β-lactamases, which limits the choice of effective antimicrobial therapies. The epidemiology of ESC-EC infection is complex as a result of the multiple possible sources involved in its transmission, and its study would require databases ideally comprising information from animal (livestock, companion, wildlife), human, and environmental sources. Here, we present the steps taken to assemble a database with phenotypic and genetic information on 10,763 ESC-EC isolates retrieved from multiple sources provided by 13 partners located in eight European countries, in the frame of the DiSCoVeR Joint Research project funded by the One Health European Joint Programme (OH-EJP), along with its strengths and limitations. This database represents a first step to help in the assessment of different geographical and temporal trends and transmission dynamics in animals and humans. The work performed highlights aspects that should be considered in future international efforts, such as the one presented here.
- Publication type
- Journal Article MeSH
Cieľ: Cieľom štúdie bolo popísať výskyt HIV-1 subtypov a HIV-1 kmeňov rezistentných na antiretrovírusovú liečbu (ART) u HIV pozitívnych osôb novo diagnostikovaných na Slovensku v rokoch 2019–2021. Materiál a metódy: Študijnú skupinu tvorilo 184 HIV pozitívnych naivných pacientov novo diagnostikovaných na Slovensku v rokoch 2019–2021. Vírusová HIV-1 RNA bola izolovaná z plazmy pomocou QIAamp Viral RNA Mini Kit (QIAGEN, Nemecko). Pre RT-PCR a sekvenovanie oblasti HIV pol sme použili interné postupy podľa protokolu ANRS AC11 pre RT (reverzná transkriptáza), PRO (proteáza) a IN (integráza) (ANRS AC11 Resistance Study Group, 2015). Analýzu sekvencií sme uskutočnili pomocou softvéru Sequencing Analysis Software v5.3 (Applied Biosystems®). HIV sekvencie boli manuálne upravené pomocou BioEdit (verzia 7.2.5), porovnané s konsenzuálnymi HIV-1 sekvenciami v Los Alamos Sequence Database (URL 2), zarovnané pomocou CLUSTAL W (Labarga et al., 2007) a softvérových balíkov BioEdit (verzia 7.2 .5) (Hall, 1999). Na vyhodnotenie sekvencie sme použili algoritmus HIVDB (verzia 9.0) Stanfordskej databázy HIV liekovej rezistencie (URL 1.). Na analýzu HIV-1 subtypov sme použili nástroj REGA HIV-1 Subtyping Tool (De Oliviera et al., 2005) a fylogenetickú analýzu sme vypracovali pomocou programu MEGA X (Kumar et al., 2018). Výsledky: Fylogenetickú analýzu sme vykonali zo vzoriek 184 osôb, kde sme odhalili najrozšírenejší subtyp B (129/184, 70,11 %) prevládajúci v populácii u mužov, ktorí majú sex s mužmi (MSM) (96/129 74,42 %). Čo sa týka non-B subtypov (55/184, 29,89 %), najrozšírenejší bol subtyp A (48/184, 26,09 %) v porovnaní so subtypom F (F1) (3; 1,63 %), C (1; 0,54 %) a cirkulujúcimi rekombinantnými formami CRF02_AG (2; 1,09 %), CRF01_AE (1; 0,54 %). U 9,24 % (17/184) vzoriek sme zistili prítomnosť 25 mutácií asociovaných s HIV rezistenciou na ART, z toho 7,07 % (13/184) na inhibítory reverznej transkriptázy, 1,66 % (3/181) na inhibítory proteázy a 1,32 % (2/151) na inhibítory integrázy. Okrem toho u 1,63 % (3/184) pacientov bola prítomná viactriedna rezistencia. Mutácie asociované s rezistenciou HIV na ART sa našli u 9,30 % osôb infikovaných podtypom B. Záver: Naša štúdia potvrdila pretrvávajúci najvyšší výskyt subtypu B s mierne klesajúcou tendenciou v porovnaní s minulými rokmi. Detekcia mutácií vytvárajúcich rezistenciu HIV na ART podčiarkuje potrebu testovania rezistencie u naivných pacientov ešte pred začatím ART na Slovensku.
Aim: The aim of the study was to describe the prevalence of HIV-1 subtypes and HIV-1 strains resistant to antiretroviral therapy (ART) in HIV-positive persons newly diagnosed in Slovakia in 2019–2021. Materials and Methods: The study group consisted of 184 HIV-positive na?ve patients newly diagnosed in Slovakia from 2019 to 2021. The viral HIV-1 RNA was isolated from plasma by the QIAamp Viral RNA Mini Kit (QIAGEN, Germany). For RT-PCR and sequencing of the HIV pol region, in-house procedures were used according to the ANRS AC11 protocol for RT (reverse transcriptase), PRO (protease), and IN (integrase) [ANRS AC11 Resistance Study Group, 2015]. Analysis of sequences was performed using Sequencing Analysis Software v5.3 (Applied Biosystems®). HIV sequences were manually edited using BioEdit (version 7.2.5), compared with consensus HIV-1 sequences in the Los Alamos Sequence Database (URL 2), aligned using CLUSTAL W [Labarga et al., 2007] and BioEdit software packages (version 7.2 .5) [Hall, 1999]. HIVDB Algorithm (version 9.0) of the Stanford HIV Drug resistance database (URL 1.) was used for sequence evaluation. For HIV-1 subtype analysis, the REGA HIV-1 Subtyping Tool [De Oliviera et al., 2005] and phylogenetic analysis MEGA X [Kumar et al., 2018] were used. Results: Phylogenetic analyses performed in samples of 184 persons revealed the most prevalent subtype B (129/184, 70.11%), detected to the greatest extent in the population of men who have sex with men (MSM) (96/129 74.42%). Concerning non-B subtypes (55/184, 29.89%), subtype A was found with the highest prevalence (48/184, 26.09%) compared to subtype F (F1) (3; 1.63%), C (1; 0.54%) and circulating recombinant forms CRF02_AG (2; 1.09%), CRF01_AE (1; 0.54%). In 9.24% (17/184) of samples, 25 mutations clinically relevant and associated with HIV resistance ART were detected, of which 7.07% (13/184) to reverse transcriptase inhibitors, 1.66% (3/181) to protease inhibitors and 1.32% (2/151) to integrase inhibitors. In addition, multiclass resistance was present in 1.63% (3/184) of patients. Mutations associated with HIV resistance to ART were found in 9.30 % of persons infected with subtype B. Conclusion: Our study confirmed ongoing highest prevalence of subtype B with a slightly decreasing trend compared to last years. Detection of mutations causing HIV resistance to ART underlines the need for resistance testing in na?ve patients even before the initiation of ART in Slovakia.
- MeSH
- Anti-Retroviral Agents therapeutic use MeSH
- Genetic Techniques MeSH
- Genotype MeSH
- HIV Infections * epidemiology drug therapy transmission MeSH
- HIV-1 genetics drug effects MeSH
- Clinical Studies as Topic MeSH
- Humans MeSH
- Mutation genetics MeSH
- Drug Resistance, Viral MeSH
- Check Tag
- Humans MeSH
- Geographicals
- Slovakia MeSH
