Does gene therapies clinical research in rare diseases reflects the competitivity of the country: Example of France.

Rare diseases are chronic, serious and generally genetic conditions affecting a small number of people, and their therapeutic management is a real challenge. They represent a considerable burden for patients, caregivers and society alike. Compared with existing symptomatic treatments, gene therapies represent a promising new approach aimed at treating these diseases by replacing a defective gene, or by abolishing or reviving a gene-derived function. France is considered one of the leading countries in the research and development of drugs for rare diseases, yet the position of French public and private stakeholders in the research and development of gene therapies for rare diseases at global and European level remains unclear. To answer this question, we used the GENOTRIAL FR database developed by OrphanDev to clarify France's involvement and competitiveness in this field. The results show that France is actively involved in gene therapy clinical trials, with a dense international collaboration network and solid expertise. However, the French medical infrastructure is mainly involved in clinical research on gene therapy candidates sponsored by several foreign countries. To a lesser extent, French public and private entities are also developing their own gene therapy candidates for various rare diseases, some of which have already reached advanced clinical phases. In conclusion, a number of technical and financial challenges need to be overcome if France is to maintain its position as a European and world leader and increase its contribution to reducing the economic and social burden of rare diseases by developing revolutionary and effective new therapies.

Cefepime vs carbapenems for treating third-generation cephalosporin-resistant AmpC ß-lactamase-hyperproducing Enterobacterales bloodstream infections: a multicenter retrospective study.

OBJECTIVES: AmpC ß-lactamase-hyperproducing Enterobacterales (ABLHE) bloodstream infections (BSI) are emerging and leading to therapeutic challenges worldwide. Prescriptions of carbapenems may lead to the emergence of resistance. This study aimed to compare cefepime with carbapenems for the treatment of third-generation cephalosporin-resistant ABLHE BSI. METHODS: This retrospective multicenter study included patients with ABLHE BSI from two tertiary hospitals in France, between July 2017 and July 2022. Non-AmpC-producing Enterobacterales, extended-spectrum ß-lactamase, and carbapenemase-producing Enterobacterales were excluded. Cefepime was prescribed only in case of minimal inhibitory concentration ≤1 mg/l. The primary outcome was 30-day in-hospital mortality from the date of index blood culture. Secondary outcomes were infection recurrence and treatment toxicity. An inverse probability of treatment weighting approach was used to balance the baseline characteristics between the two groups. RESULTS: We analyzed 164 BSI, which included 77 in the cefepime group and 87 in the carbapenem group. In the weighted cohort, the 30-day mortality rates were similar between the cefepime group (23.3%) and the carbapenem group (19.6%) with a relative risk of 1.19 (95% confidence interval, 0.61-2.33 P = 0.614). No significant difference in recurrence or toxicity was found between the two groups. CONCLUSION: This study adds evidence in favor of the use of cefepime for treating third-generation cephalosporin-resistant ABLHE BSI in case of minimal inhibitory concentration ≤ 1 mg/l, which could spare carbapenems.

The sunny butterflies: new species of high montane pierids of the Catasticta poujadei group from the Peruvian Andes (Pieridae, Pierinae, Aporiina).

The Catasticta poujadei group, within the subgenus Hesperochoia Reissinger, is revised. Two new species, C. copernicus Pyrcz & Fhraeus sp. nov., and C. buszkoi Boyer & Pyrcz sp. nov. occurring near the timberline in Junn and Apurmac are described. Catasticta eximia Rber is reinstated as a species separate from C. poujadei, and a new subspecies, C. eximia tapuna ssp. nov., is described. The affinities of the species of the C. poujadei group are evaluated based on COI barcodes. Their distribution and habitats are described.

Taxonomic discoveries enabled by genomic analysis of butterflies.

The comparative genomics of butterflies yields additional insights into their phylogeny and classification that are compiled here. As a result, 3 genera, 5 subgenera, 5 species, and 3 subspecies are proposed as new, i.e., in Hesperiidae: Antina Grishin, gen. n. (type species Antigonus minor O. Mielke, 1980), Pompe Grishin and Lamas, gen. n. (type species Lerema postpuncta Draudt, 1923), and Curva Grishin, gen. n. (type species Moeris hyagnis Godman, 1900); in Lycaenidae: Fussia Grishin, subgen. n. (type species Polyommatus standfussi Grum-Grshimailo, 1891) and Pava Grishin, subgen. n. (type species Thecla panava Westwood, 1852); in Hesperiidae: Monoca Grishin, subgen. n. (type species Tagiades monophthalma Plötz, 1884), Putuma Grishin, subgen. n. (type species Tisias putumayo Constantino and Salazar, 2013), and Rayia Grishin, subgen. n. (type species Mastor perigenes Godman, 1900); Cissia wahala Grishin, sp. n. (Nymphalidae; type locality in Mexico: Oaxaca); in Hesperiidae: Hedone mira Grishin and Lamas, sp. n. (type locality in Peru: Apurímac), Vidius pompeoides Grishin, sp. n. (type locality in Brazil: Amazonas), Parphorus hermieri Grishin, sp. n. (Hesperiidae; type locality in Brazil: Rondônia), and Zenis par Grishin, sp. n. (Hesperiidae; type locality in Peru: Cuzco); in Pieridae: Glutophrissa drusilla noroesta Grishin, ssp. n. (type locality in USA: Texas, Cameron Co.) and Pieris marginalis siblanca Grishin, ssp. n. (type locality in USA: New Mexico, Lincoln Co.), and Argynnis cybele neomexicana Grishin, ssp. n. (Nymphalidae; type locality in USA: New Mexico, Sandoval Co.). Acidalia leto valesinoides-alba Reuss, [1926] and Acidalia nokomis valesinoides-alba Reuss, [1926] are unavailable names. Neotypes are designated for Mylothris margarita Hübner, [1825] (type locality in Brazil) and Papilio coras Cramer, 1775 (type locality becomes USA: Pennsylvania, Montgomery Co., Flourtown). Mylothris margarita Hübner, [1825] becomes a junior objective synonym of Pieris ilaire Godart, 1819, currently a junior subjective synonym of Glutophrissa drusilla (Cramer, 1777). Lectotypes are designated for Hesperia ceramica Plötz, 1886 (type locality in Indonesia: Seram Island), Pamphila trebius Mabille, 1891 (type locality Colombia: Bogota), Methionopsis modestus Godman, 1901 and Papias microsema Godman, 1900 (type locality in Mexico: Tabasco), Hesperia fusca Grote & Robinson, 1867 (type locality in USA: Georgia), Goniloba corusca Herrich-Schäffer, 1869, and Goniloba devanes Herrich-Schäffer, 1869; the type localities of the last two species, together with Pamphila stigma Skinner, 1896 and Carystus (Argon) lota (Hewitson, 1877), are deduced to be in South America. Type locality of Junonia pacoma Grishin, 2020 is in Sinaloa, not Sonora (Mexico). Abdomen is excluded from the holotype of Staphylus ascalon (Staudinger, 1876). Furthermore, a number of taxonomic changes are proposed. Alciphronia Koçak, 1992 is treated as a subgenus, not a synonym of Heodes Dalman, 1816. The following genera are treated as subgenera: Lafron Grishin, 2020 of Lycaena [Fabricius], 1807, Aremfoxia Real, 1971 of Epityches D'Almeida, 1938, Placidina D'Almeida, 1928 of Pagyris Boisduval, 1870, and Methionopsis Godman, 1901 of Mnasinous Godman, 1900. Polites (Polites) coras (Cramer, 1775) is not a nomen dubium but a valid species. The following are species-level taxa (not subspecies or synonyms of taxa given in parenthesis): Lycaena pseudophlaeas (Lucas, 1866) and Lycaena hypophlaeas (Boisduval, 1852) (not Lycaena phlaeas (Linnaeus, 1761), Satyrium dryope (W. H. Edwards, 1870) (not Satyrium sylvinus (Boisduval, 1852)), Apodemia cleis (W. H. Edwards, 1882) (not Apodemia zela (Butler, 1870)), Epityches thyridiana (Haensch, 1909), comb. nov. (not Epityches ferra Haensch, 1909, comb. nov.), Argynnis bischoffii W. H. Edwards, 1870 (not Argynnis mormonia Boisduval, 1869), Argynnis leto Behr, 1862 (not Argynnis cybele (Fabricius, 1775)), Boloria myrina (Cramer, 1777) (not Boloria selene ([Denis & Schiffermüller], 1775)), Phyciodes jalapeno J. Scott, 1998 (not Phyciodes phaon (W. H. Edwards, 1864)), Phyciodes incognitus Gatrelle, 2004 and Phyciodes diminutor J. Scott, 1998 (not Phyciodes cocyta (Cramer, 1777)), Phyciodes orantain J. Scott, 1998 (not Phyciodes tharos (Drury, 1773)), Phyciodes anasazi J. Scott, 1994 (not Phyciodes batesii (Reakirt, [1866])), Cercyonis silvestris (W. H. Edwards, 1861) (not Cercyonis sthenele (Boisduval, 1852)), Paramacera allyni L. Miller, 1972 and Paramacera rubrosuffusa L. Miller, 1972 (not Paramacera xicaque (Reakirt, [1867])), Cissia cheneyorum (R. Chermock, 1949), Cissia pseudocleophes (L. Miller, 1976), and Cissia anabelae (L. Miller, 1976) (not Cissia rubricata (W. H. Edwards, 1871)), Tarsoctenus gaudialis (Hewitson, 1876) (not Tarsoctenus corytus (Cramer, 1777)), Nisoniades inca (Lindsey, 1925) (not Nisoniades mimas (Cramer, 1775), Xenophanes ruatanensis Godman & Salvin, 1895 (not Xenophanes tryxus (Stoll, 1780)), Lotongus shigeoi Treadaway & Nuyda, 1994, Lotongus balta Evans, 1949, Lotongus zalates (Mabille, 1893), and Lotongus taprobanus (Plötz, 1885) (not Lotongus calathus (Hewitson, 1876)), Oxynthes martius (Mabille, 1889) (not Oxynthes corusca (Herrich-Schäffer, 1869)), Notamblyscirtes durango J. Scott, 2017 (not Notamblyscirtes simius W. H. Edwards, 1881), Hedone praeceps Scudder, 1872, Hedone catilina (Plötz, 1886), and Hedone calla (Evans, 1955) (not Hedone vibex (Geyer, 1832)), Atalopedes huron (W. H. Edwards, 1863) (not Atalopedes campestris (Boisduval, 1852)), Papias microsema Godman, 1900 (not Mnasinous phaeomelas (Hübner, [1829]), comb. nov.), Papias unicolor (Hayward, 1938) and Papias monus Bell, 1942 (not Papias phainis Godman, 1900), Nastra leuconoides (Lindsey, 1925) (not Nastra leucone (Godman, 1900)), Nastra fusca (Grote & Robinson, 1867) (not Nastra lherminier (Latreille, [1824])), Zenis hemizona (Dyar, 1918) and Zenis janka Evans, 1955 (not Zenis jebus (Plötz, 1882)), Carystus (Argon) argus Möschler, 1879 (not Carystus (Argon) lota Hewitson, 1877), and Lycas devanes (Herrich-Schäffer, 1869) (not Lycas argentea (Hewitson, 1866)). Borbo impar ceramica (Plötz, 1886), comb. nov. is not a synonym of Pelopidas agna larika (Pagenstecher, 1884) but a valid subspecies. Parnassius smintheus behrii W. H. Edwards, 1870 and Cercyonis silvestris incognita J. Emmel, T. Emmel & Mattoon, 2012 are subspecies, not species. The following are junior subjective synonyms: Shijimiaeoides Beuret, 1958 of Glaucopsyche Scudder, 1872, Micropsyche Mattoni, 1981 of Turanana Bethune-Baker, 1916, Cyclyrius Butler, 1897 of Leptotes Scudder, 1876, Mesenopsis Godman & Salvin, 1886 of Xynias Hewitson, 1874, Carystus tetragraphus Mabille, 1891 of Lotongus calathus parthenope (Plötz, 1886), Parnara bipunctata Elwes & J. Edwards, 1897 of Borbo impar ceramica (Plötz, 1886), Hesperia peckius W. Kirby, 1837 of Polites (Polites) coras (Cramer, 1775), and Lerodea neamathla Skinner & R. Williams, 1923 of Nastra fusca (Grote & Robinson, 1867). The following transfers are proposed: of species between genera (i.e., revised genus-species combinations): Nervia niveostriga (Trimen, 1864) (not Kedestes Watson, 1893), Leona lota Evans, 1937 (not Lennia Grishin, 2022), Leona pruna (Evans, 1937) and Leona reali (Berger, 1962) (not Pteroteinon Watson, 1893), Mnasinous phaeomelas (Hübner, [1829]) (not Papias Godman, 1900), Saturnus jaguar (Steinhauser, 2008) (not Parphorus Godman, 1900), Parphorus harpe (Steinhauser, 2008) (not Saturnus Evans, 1955), Parphorus kadeni (Evans, 1955) (not Lento Evans, 1955), and Calpodes chocoensis (Salazar & Constantino, 2013) (not Megaleas Godman, 1901); of subspecies between species (i.e., revised species-subspecies combinations): Melitaea sterope W. H. Edwards, 1870 of Chlosyne palla (Boisduval, 1852) (not Chlosyne acastus (W. H. Edwards, 1874)) and Panoquina ocola distipuncta Johnson & Matusik, 1988 of Panoquina lucas (Fabricius, 1793); and junior subjective synonym transferred between species: Rhinthon zaba Strand, 1921 of Conga chydaea (A. Butler, 1877), not Cynea cynea (Hewitson, 1876), Pamphila stigma Skinner, 1896 of Hedone catilina (Plötz, 1886), not Hedone praeceps Scudder, 1872, and Pamphila ortygia Möschler, 1883 of Panoquina hecebolus (Scudder, 1872), not Panoquina ocola (W. H. Edwards, 1863). Proposed taxonomic changes result in additional revised species-subspecies combinations: Lycaena pseudophlaeas abbottii (Holland, 1892), Satyrium dryope putnami (Hy. Edwards, 1877), Satyrium dryope megapallidum Austin, 1998, Satyrium dryope itys (W. H. Edwards, 1882), Satyrium dryope desertorum (F. Grinnell, 1917), Argynnis bischoffi opis W. H. Edwards, 1874, Argynnis bischoffi washingtonia W. Barnes & McDunnough, 1913, Argynnis bischoffi erinna W. H. Edwards, 1883, Argynnis bischoffi kimimela Marrone, Spomer & J. Scott, 2008, Argynnis bischoffi eurynome W. H. Edwards, 1872, Argynnis bischoffi artonis W. H. Edwards, 1881, Argynnis bischoffi luski W. Barnes & McDunnough, 1913, Argynnis leto letona (dos Passos & Grey, 1945), Argynnis leto pugetensis (F. Chermock & Frechin, 1947), Argynnis leto eileenae (J. Emmel, T. Emmel & Mattoon, 1998), Boloria myrina nebraskensis (W. Holland, 1928), Boloria myrina sabulocollis Kohler, 1977, Boloria myrina tollandensis (W. Barnes & Benjamin, 1925), Boloria myrina albequina (W. Holland, 1928), Boloria myrina atrocostalis (Huard, 1927), Boloria myrina terraenovae (W. Holland, 1928), Phyciodes anasazi apsaalooke J. Scott, 1994, Polites coras surllano J. Scott, 2006, and Curva darienensis (Gaviria, Siewert, Mielke & Casagrande, 2018). Specimen curated as the holotype of Acidalia leto valesinoides-alba Reuss, [1926] is Argynnis leto letona (dos Passos & Grey, 1945) (not A. leto leto Behr, 1862) from USA: Utah, Provo. A synonymic list of available genus-group names for Lycaeninae [Leach],[1815] is given. Unless stated otherwise, all subgenera, species, subspecies and synonyms of mentioned genera and species are transferred with their parent taxa, and others remain as previously classified.

Considerations on the Systematics of Neotropical Pierina, with the Description of Two New Species of Phulia Herrich-Schäffer from the Peruvian Andes (Lepidoptera: Pieridae, Pierinae, Pierini).

A comparative analysis of high-Andean Pierina was carried out, including a total of 25 species. Based on morphological evidence, with an emphasis on venation and genitalia and molecular data, using three genetic markers, we confirm the recent subjective synonymy of the generic names Tatochila Butler, 1870, Piercolias, Staudinger, 1894, Hypsochila Ureta, 1955, Infraphulia Field, 1958, Pierphulia Field, 1958, and Theochila Field, 1958 with Phulia Herrich-Schäffer, 1867. Two new species are described, namely Phulia stoddardi Pyrcz & Cerdeña n. sp., from the Andes of Central Peru, which occurs at an unusually high altitude of close to 5000 m a.s.l. in dry puna habitat, and Phulia phantasma Lamas, Willmott & Boyer n. sp., from dry montane forests in northern Peru and southern Ecuador. An overview of high-elevation butterflies is presented, with some discussion on adaptations to this environment.

Primary Adrenal Lymphoma as a Rare Cause of Primary Adrenal Insufficiency: Challenges in Management and a Review of the Literature.

Background/Objective: Primary adrenal lymphoma (PAL) is an aggressive form of lymphoma associated with adrenal insufficiency (AI) in most cases. It requires a histologic confirmation unlike other cases of primary AI. Case Report: We report a case of a 66-year-old man who presented with AI with symptomatic hypotension and hypo-osmolar hyponatremia. Ultrasound and computed tomography scans revealed bilateral bulky adrenal masses that were avid on fluorodeoxyglucose positron emission tomography scan. The diagnosis of PAL was confirmed with adrenal biopsy. He was treated with rituximab-based chemotherapy, which was complicated by several endocrine challenges, including worsening diabetes, multiple adrenal crises, prolonged hyponatremia, and refractory hypokalemia requiring spironolactone. He eventually developed central nervous system disease and was treated with palliative intent. Discussion: AI in the setting of PAL can constitute both diagnostic and therapeutic challenges, including significant electrolyte imbalances as discussed in this case report. Conclusion: It is important to have a high suspicion for PAL, especially in the presence of bilateral adrenal masses and AI. Early adrenal biopsy is required for diagnosis. Multidisciplinary care is vital to manage complications that arise during the disease course and treatment.

A new high-altitude species of Penaincisalia Johnson, 1990 (Lepidoptera, Lycaenidae) from the Peruvian Andes.

A new Penelfin species, Penaincisalia jadwigae sp. nov. is described from very high elevations, 45104620 m, in the Department of Huancavelica, Peru. Superficially it is somewhat similar to P. perezi Blint, 2001, but can easily be recognized by wing colour and pattern. A key for the identification of species in the Penaincisalia s. str. group with orange dorsal wing surface colouration is provided. A list of the local butterfly fauna is given, and spatial distribution, thermal regulation and discoloration are briefly discussed. The taxon Shapiroana matusikorum Johnson, 1992 is reinstated from synonymy with Penaincisalia aurulenta Johnson, 1990, as Rhamma matusikorum (Johnson, 1992), stat. rev., comb. n. 17 figures are provided.

Distribution of Achromobacter Species in 12 French Cystic Fibrosis Centers in 2020 by a Retrospective MALDI-TOF MS Spectrum Analysis.

Achromobacter spp. are nonfermenting Gram-negative bacilli mainly studied among cystic fibrosis (CF) patients. The identification of the 19 species within the genus is time-consuming (nrdA-sequencing), thus data concerning the distribution of the species are limited to specific studies. Recently, we built a database using MALDI-TOF mass spectrometry (MS) (Bruker) that allows rapid and accurate species identification and detection of the multiresistant epidemic clones: A. xylosoxidans ST137 spreading among CF patients in various French and Belgium centers, and A. ruhlandii DES in Denmark. Here, we first assessed whether species identification could be achieved with our database solely by analysis of MS spectra without availability of isolates. Then, we conducted a multicentric study describing the distribution of Achromobacter species and of the clone ST137 among French CF centers. We collected and analyzed with our local database the spectra of Achromobacter isolates from 193 patients (528 samples) from 12 centers during 2020. In total, our approach enabled to conclude for 502/528 samples (95.1%), corresponding to 181 patients. Eleven species were detected, only five being involved in chronic colonization, A. xylosoxidans (86.4%), A. insuavis (9.1%), A. mucicolens (2.3%), A. marplatensis (1.1%) and A. genogroup 3 (1.1%). This study confirmed the high prevalence of A. xylosoxidans in chronic colonizations and the circulation of the clone A. xylosoxidans ST137 in France: four patients in two centers. The present study is the first to report the distribution of Achromobacter species from CF patients samples using retrospective MALDI-TOF/MS data. This easy approach could enable future large-scale epidemiological studies.

Management of a Major Carbapenem-Resistant Acinetobacter baumannii Outbreak in a French Intensive Care Unit While Maintaining Its Capacity Unaltered.

We describe bundle measures implemented to overcome a protracted carbapenem-resistant Acinetobacter baumannii (CRAB) outbreak in an 18-bed trauma Intensive Care Unit (ICU) at Strasbourg University Hospital, a tertiary referral center in France. Outbreak cases were defined by a positive CRAB sample with OXA-23 profile during or after ICU say. To sustain the capacity of the busy trauma ICU, infection control bundles were purposely selected to control the outbreak without closing the ICU. During the outbreak, from May 2015 to January 2019, 141 patients were contaminated by CRAB, including 91 colonized and 50 infected patients. The conventional infection and prevention control (IPC) measures implemented included weekly active surveillance of patients' samples, enhancement of environmental cleaning, interventions to improve hand hygiene compliance and antibiotic stewardship with audits. Supplemental measures were needed, including environmental samplings, health care workers' (HCWs) hand sampling, chlorhexidine body-washing, relocation of the service to implement Airborne Disinfection System (ADS), replication of crisis cells, replacement of big environmental elements and improvement of HCW organization at the patient's bedside. The final measure was the cohorting of both CRAB patients and HCW caring for them. Only the simultaneous implementation of aggressive and complementary measures made it possible to overcome this long-lasting CRAB epidemic. Facing many CRAB cases during a rapidly spreading outbreak, combining simultaneous aggressive and complementary measures (including strict patients and HCW cohorting), was the only way to curb the epidemic while maintaining ICU capacity.

Human Co-Infections between Borrelia burgdorferi s.l. and Other Ixodes-Borne Microorganisms: A Systematic Review.

When it comes to tick-borne diseases, co-infections are often mentioned. This concept includes several entities. On the one hand, tick vectors or vertebrate reservoir host can harbor several microorganisms that can be pathogenic for humans. On the other hand, human co-infections can also be understood in different ways, ranging from seropositivity without clinical symptoms to co-disease, i.e., the simultaneous clinical expression of infections by two tick-borne microorganisms. The latter, although regularly speculated, is not often reported. Hence, we conducted a systematic review on co-infections between B. burgdorferi s.l., the etiological agent of Lyme borreliosis, and other microorganisms potentially transmitted to humans by Ixodes spp. ticks. A total of 68 relevant articles were included, presenting 655 cases of possible co-infections. Most cases of co-infections corresponded to patients with one tick-borne disease and presenting antibody against another tick-borne microorganism. Co-disease was particularly frequent in two situations: patients with clinical symptoms of high fever and erythema migrans (EM), and patients with neurological symptoms linked to the TBEv or a neuroborreliosis. No impact on severity was evidenced. Further studies are needed to better appreciate the frequency and the impact of co-infections between several tick-borne microorganisms.

Impact of Different Anthropogenic Environments on Ticks and Tick-Associated Pathogens in Alsace, a French Region Highly Endemic for Tick-Borne Diseases.

Ticks and tick-borne diseases have spread over the last decades. In parallel, the incidence in humans, accidental hosts for most of these zoonotic diseases, has increased. This epidemiological intensification can be associated with anthropogenic alterations of forest ecosystems and animal biodiversity, but also with socioeconomic changes. Their proliferation is largely due to human-induced effects on the factors that favor the circulation of these infectious agents. We selected different types of anthropogenic environments in Alsace, a region endemic for tick-borne diseases in France, to better understand the impact of human interventions on tick populations and tick-borne disease incidence. Ticks were collected in one golf course, three urban parks, one mid-mountain forest, and one alluvial forest that is currently part of a protected natural area. Ixodes ricinus was found primarily in humid vegetation, which is favorable for tick survival, such as grounds populated with trees and covered with leaf litter. We also observed that reforestation and high animal biodiversity in a protected area such as the alluvial forest led to a greater number of ticks, including both Ixodes ricinus and Dermacentor reticulatus, as well as to a higher prevalence of pathogens such as Borrelia burgdorferi sensu lato, Anaplasma phagocytophilum, Borrelia miyamotoi, and Rickettsia raoulti.

A new species of the enigmatic genus Oressinoma Doubleday from the Andes of central Peru (Lepidoptera: Nymphalidae, Satyrinae).

A new, and only the third known species of the Neotropical montane genus Oressinoma Doubleday is describedO. sorina n. sp., from the Andes of central Peru. It is distinguishable immediately from the other two congeners by the shape of the hindwing underside submarginal orange band, and by the male genitalia. The systematics of Oressinoma are reviewed. A preliminary analysis is carried out based on COI barcode confirming the separate specific status of O. sorina n. sp. in relation to other two congeners. Both barcode and genital morphology data suggest that the widespread O. typhla Doubleday may be a complex of allopatric or, locally parapatric species. The genus Oressinoma is the only neotropical member of the predominantly Australian subtribe Coenonymphina, represented in the entire Holarctic by one genus onlyCoenonympha Hbner, considered as the putative sister-genus of Oressinoma. Their origins and relationships are briefly discussed.

Case Report: Acquired Disseminated BCG in the Context of a Delayed Immune Reconstitution After Hematological Malignancy.

Context: Disseminated infections due to Mycobacterium bovis Bacillus Calmette-Guérin (BCG) are unusual and occur mostly in patients with inborn error of immunity (IEI) or acquired immunodeficiency. However, cases of secondary BCGosis due to intravesical BCG instillation have been described. Herein, we present a case of severe BCGosis occurring in an unusual situation. Case Description: We report one case of severe disseminated BCG disease occurring after hematological malignancy in a 48-year-old man without BCG instillation and previously vaccinated in infancy with no complication. Laboratory investigations demonstrated that he was not affected by any known or candidate gene of IEI or intrinsic cellular defect involving IFNγ pathway. Whole genome sequencing of the BCG strain showed that it was most closely related to the M. bovis BCG Tice strain, suggesting an unexpected relationship between the secondary immunodeficiency of the patient and the acquired BCG infection. Conclusion: This case highlights the fact that, in addition to the IEI, physicians, as well as microbiologists and pharmacists should be aware of possible acquired disseminated BCG disease in secondary immunocompromised patients treated in centers that administrate BCG for bladder cancers.

Broth Microdilution and Gradient Diffusion Strips vs. Reference Agar Dilution Method: First Evaluation for Clostridiales Species Antimicrobial Susceptibility Testing.

Antimicrobial susceptibility testing of anaerobes is challenging. Because MIC determination is recommended by both CLSI and EUCAST, commercial broth microdilution and diffusion strip tests have been developed. The reliability of broth microdilution methods has not been assessed yet using the agar dilution reference method. In this work, we evaluated two broth microdilution kits (MICRONAUT-S Anaerobes® MIC and Sensititre Anaerobe MIC®) and one gradient diffusion strip method (Liofilchem®) for antimicrobial susceptibility testing of 47 Clostridiales isolates (Clostridium, Clostridioides and Hungatella species) using the agar dilution method as a reference. The evaluation focused on comparing six antimicrobial molecules available in both microdilution kits. Analytical performances were evaluated according to the Food and Drug Administration (FDA) recommendations. Essential agreements (EA) and categorical agreements (CA) varied greatly according to the molecule and the evaluated method. Vancomycin had values of essential and categorical agreements above 90% for the three methods. The CA fulfilled the FDA criteria for three major molecules in the treatment of Gram-positive anaerobic infections (metronidazole, piperacillin/tazobactam and vancomycin). The highest rate of error was observed for clindamycin. Multicenter studies are needed to further validate these results.

The emerging tick-borne pathogen Neoehrlichia mikurensis: first French case series and vector epidemiology.

Neoehrlichia mikurensis is an intracellular bacterium transmitted in Europe and Asia by ticks of the Ixodes ricinus complex. Interest in this bacterium has increased since it was demonstrated to be responsible for febrile syndromes in patients. To date, most clinical cases have been reported in northern Europe, but case series have also been described in central Europe and China. Notably, thrombotic events occurred during the course of the disease. We investigated the presence of N. mikurensis in 10,885 I. ricinus nymphs in two regions of France (Alsace and Brittany) collected between 2013 and 2020 and in 934 patients suspected of human granulocytic anaplasmosis in Alsace, an endemic area for Lyme borreliosis, using a specific PCR assay. N. mikurensis was detected in 5.42% of the ticks from Alsace, whereas only one (0.03%) tick was found to be positive in Brittany. Spatiotemporal disparities were also noticed within the Alsace region over the four collection sites investigated, and a significant increase in the prevalence of nymphs carrying N. mikurensis was also observed in the last three years of collection. Four out of 934 screened patients were found to be positive for N. mikurensis. Two had malignancies, and the other two were apparently immunocompetent. Superficial thrombosis was noticed in one patient, and long-lasting bacteremia was noted in another patient. These four patients are the first clinical cases of neoehrlichiosis described in France. We suggest including N. mikurensis in the differential diagnosis of post-tick bite febrile syndromes to treat patients and prevent the occurrence of thrombotic complications.

Microwell Array Based Opto-Electrochemical Detections Revealing Co-Adaptation of Rheological Properties and Oxygen Metabolism in Budding Yeast.

Microdevices composed of microwell arrays integrating nanoelectrodes (OptoElecWell) are developed to achieve dual high-resolution optical and electrochemical detections on single Saccharomyces cerevisiae yeast cells. Each array consists of 1.6 × 105 microwells measuring 8 µm in diameter and 5 µm height, with a platinum nanoring electrode for in situ electrochemistry, all integrated on a transparent thin wafer for further high-resolution live-cell imaging. After optimizing the filling rate, 32% of cells are effectively trapped within microwells. This allows to analyse S. cerevisiae metabolism associated with basal respiration while simultaneously measuring optically other cellular parameters. In this study, the impact of glucose concentration on respiration and intracellular rheology is focused. It is found that while the oxygen uptake rate decreases with increasing glucose concentration, diffusion of tracer nanoparticles increases. The OptoElecWell-based respiration methodology provides similar results compared to the commercial gold-standard Seahorse XF analyzer, while using 20 times fewer biological samples, paving the way to achieve single cell metabolomics. In addition, it facilitates an optical route to monitor the contents within single cells. The proposed device, in combination with the dual detection analysis, opens up new avenues for measuring cellular metabolism, and relating it to cellular physiological indicators at single cell level.