Primula veris (Primulaceae) is a valuable medicinal plant. The main characteristics for assessing the reproductive potential  and the genetic diversity of populations of the species from Bulgaria were studied. The anthers are tetrasporangiate. Their wall development follows the Dicotyledonous-type and consists of: epidermis, a fibrous endothecium, an ephemeral middle layer and a secretory (glandular) tapetum. After meiosis in pollen mother cells and simultaneous microsporogenesis tetrahedral tetrads are formed predominantly in the anthers. Many ovules (approximately 20) develop in the unilocular ovary and are anatropous, tenuinucellate and bitegmic. The embryo sac (ES) develops after Polygonum (monosporic)-type from the chalazal cell of linear megaspore tetrad in the ovule. After double fertilization, a Caryophyllad-type embryo and initially nuclear endosperm form. In the studied populations, high pollen viability of more than 95% was established. Extremely low viability (about 4%) of the seeds obtained from natural populations was established. The results reveal P. veris to be a predominantly amphimictic  species, although rare vegetative propagation is also observed. As a result of this study, essential data were obtained about the reproductive structures and processes and for assessing the reproductive potential of P. veris. Primula L. includes six subgenera with 37 sections [Primula is represented by only 34 species, included in four sections [The genus sections , and is sections ,2. In Eusections . The gensections , and in sections , includiPrimula veris L.   belongs to the section Primula. The latter is phylogenetically quite isolated from the other sections in the genus and includes a total of seven species [Primula is represented by eight species [Primula is represented by three species: P. veris, P. elatior and P. vulgaris. species . This se species ,9. In Bu species ,11. SpecPrimula is used as a model for a broad area of studies: evolutionary [The section utionary , ecologiutionary , moleculutionary ,15, phytutionary ,17, as wutionary , reproduutionary , reproduutionary , geneticutionary ,14,20, eP. veris is a Euro-Siberian Temperate element [Primula, it is entomophilous with a great affinity between its flowers. Insect pollinators belong to Hymenoptera (mainly bumblebees and bees), Lepidoptera and Diptera [ element  distribu element . As with Diptera ,23.P. veris has a long history of medicinal use. It is a species with an economic significance that is also used as a decorative and melliferous plant. In the European Red List of Medicinal Plants, P. veris is included under the category (LC) “Least Concern” [P. elatior, this species is listed in the European Pharmacopoeia as a source of Primula roots [P. veris is included in the Biodiversity Act, Annex 4 [P. veris, P. elatior and P. vulgaris are cited in the “List of Medicinal Plants Falling under the Provisions of this Act”. P. veris is a species collected as a herb with a commercial designation from its natural habitats, outside the territories of the Bulgarian national parks, determined by the Bulgarian Ministry of Environment and Water (MEW). The above-ground parts (exclusively flowers) and roots of P. veris are permitted to be harvested but only in accordance with the annual quotas of MEW.Concern” . Togethela roots . In Bulg Annex 4 , in part Annex 4  in whichPrimula flowers and roots [Phenolic compounds, including flavonoids, phenolic acids, phenolic glycosides and triterpen saponins, are the main active compounds in nd roots ,29.P. veris and closely related species, specifically P. elatior, are used for the production of herbal teas and as dietary supplements. They exhibit various pharmacological activities, particularly secretolytic, expectorant, anti-inflammatory, diuretic, antimicrobial, antifungal, and sedative [P. veris is used for treating bronchial catarrhs of the respiratory tract, pertussis, asthma, colds and influenza [Many authors ,30 have sedative ,29. In onfluenza ,31.Primula in all aspects mentioned above, the embryological studies involve a small number of species. The data in them are usually scarce or incomplete.Contrary to the intensive studies undertaken on the members of the genus P. veris.The present study aimed to reveal the manner of reproduction, peculiarities of male and female generative spheres. The main parameters of reproductive biology (pollen and seed viability) support the reproductive success of Bulgarian populations of the valuable medicinal plant P. veris reproductive potential can be used for its future successful introduction in culture. This is especially important, as its stocks as a valuable medicinal plant in Bulgaria are declining because the populations of P. veris are usually fragmented, small in size, and often subjected to anthropological or other adverse influences.In the present work, Bulgarian populations of this species were studied for the first time with respect to embryological features, pollen and seed viability and genetic diversity. On the basis of the results, the possibilities of realization of Primula has become a textbook example of floral heteromorphy [P. veris has a typical “distylous syndrome” [The distyly in genus romorphy . The stuyndrome” ,33—a repyndrome” .P. veris show clear distyly, expressed in the presence of long-styled (pin morph) and short-styled (thrum morph) flowers illustrated in P. vulgaris facilitates reciprocal pollination by insects [P. veris, both belonging to the section Primula.Our observation on the flower morphology of individuals of the two studied Bulgarian populations of  insects  as in P.P. allionii [P. mistassinica [It is important to note that in distyly, the long-styled floral morphs produce smaller in size but larger in amount pollen grains than the short-styled morphs. This was observed in allionii , P. mistassinica  and alsoassinica ,39.P. officinalis (syn. P. veris), were reported by [P. veris are almost lacking. Data for Bulgarian populations of the species were obtained for the first time in the present work.Some embryological features on species of the family Primulaceae, including orted by . Since tP. veris are tetrasporangiate, a typical feature in all representatives of the family Primulaceae [Primula species. Thus, initially, the four-layered wall of the anthers in P. veris becomes five-layered. After forming microspore tetrads in the anthers, both endothecium layers develop fibrous thickenings  morphs are more variable in size than those of “pin” (long-styled) morphs [P. veris, a distylous species, the differences in the floral morphology do not influence the success of the insect pollination [Observations on the morphology of pollen from natural and cultivated Polish populations of ) morphs . In the lination .P. veris is superior, unilocular, in which approximately 20 ovules with free central placentation being formed and developed (P. vulgaris [P. nutans [P. veris a solitary style and papilous capitate stigma (with) were observed  inner integument  in it, the cells of the innermost layer of the inner integument lengthen radially becoming tabular in form, forming so-called endothelium (integumentary tapetum) [Anagallis pumila [P. veris.The cells of the epidermal layer of the outer integument in tapetum) , which as pumila . Anderbes pumila  that theContrary to Anderberg’s assertion, in important treatises on Angiosperm embryology, for the family Primulaceae, the formation of only one archaesporium cell in the ovule is indicated ,42.P. veris, as in other Primula species, namely P. bayernii [P. algida and P. amoena [Polygonum (monosporic)-type ES , with the typical shape and location of the nuclei in them , the lower end of the central cell enlarges considerably, forming an outgrowth with dense cytoplasm haustorizing to the chalaza . Similar. amoena . In Primal cells . The forg plants ,42,46.P. veris is a diploid, sexually reproducing (amphimictic) species that reproduces mainly by seeds. However, rarely it may reproduce vegetatively during the growing season by the formation of lateral rosettes. This has already been announced for the species [P. veris [P. veris is represented by such populations.This study shows that  species , and is P. veris  show thaP. veris  also poiP. veris, neither apomixis nor formation of additional embryos  was observed. As a result, the species is considered sexually reproducing, which correlates with its diploid status. However, polyembryony is found in other Primula species. Therefore, in P. auricula the additional 2–3 globular embryos are formed by the zygote [P. amoena, besides the zygotic embryo from the fertilized egg cell, an apomictic embryo also forms [It is important to note that in our study of the generative sphere of e zygote  and thise zygote . In P. aso forms  from thePollen viability (fertility) is an important factor in whether a population will undergo effective pollination and subsequent sexual reproduction to ensure the survival of each plant species. Different terms in pollen testing criteria based on the stages of pollen development in which it is tested are suggested . In our P. veris was estimated after acetocarmine testing: red-colored pollen grains were determined as viable, and colorless ones as nonviable  mature pollen is that which, when falling on the stigma under normal conditions, would start growing a pollen tube and finally discharge its male gametes in the embryo sac in an ovule to perform fertilization. A comparative study on “pin” and “thrum” floral morphs in humidity . In the humidity  found thas found , the datA viable seed is a seed that is capable of germinating and producing a “normal” seedling . A relatP. veris  viability was made after testing with tetrazolium solution in the two studied populations (both in situ and ex situ collected seeds) of P. veris . The evaP. veris . The colP. veris, only cross-pollination between the two genetically determined individuals (“pin” and “thrum” morphs) produces a successful seed set [P. veris have also shown an exclusively low (0.01%) seed viability [P. veris. It is a prerequisite for the successful growth of the species in culture.In distylous species such as seed set . The estiability ,63. The P. veris, and one of the probable reasons for this may be seed dormancy [P. veris continues during the last several months of its development [The exclusively low seed viability assumes a slow rate of germination. It decreases the successful growth of the seedling progeny in dormancy . It has dormancy . The seeelopment ,66. The elopment .Primula veris were polymorphic. The mean number of bands per primer was 10.7. These data are similar to those obtained by Crema et al. [Primula apennina, but there the authors used many more primers (twenty-five primers).In total, 63% of the primers scored for the initial pilot study of a et al.  for the The percentage of polymorphic bands was the highest in the population of Western Rhodopes (74), which is due probably to the larger number of the studied individuals. The same percentage in the population of Petrohan was 72, in the population of Slavyanka 69, and in the population of Gorno Harsovo (Rila) 67. The number of polymorphic bands is only approximately characteristic of the genetic diversity, and is analogous to the mean number of alleles in other markers . Much more informative are the characteristics of genetic diversity [The Shannon’s polymorphic index showed similar trends and again the highest values had the population from the Western Rhodopes, followed by Petrohan, Gorno Harsovo, and the lowest value was recorded in the population of Slavyanka.The dendrogram constructed based on the genetic distances among populations revealed that there is no relationship between the geographic and genetic distances . The popP. apennina [P. heterochroma [Primula veris was high both at species and at population levels , Sofia. In Bulgaria, this species is widespread in the plains, foothills, and mountains, from sea level to above 2500 m altitude [P. veris is a diploid species with chromosome number 2n = 22. This chromosome number is also shown for populations from the Znepole Region [The study of embryological characteristics, pollen and seed viability was carried out on two natural populations of altitude . It is oe Region  and Pirie Region .The material used for the embryological study is collected from the two native populations (above mentioned), as well as from plants transferred and grown in greenhouse conditions at the Institute of Biodiversity and Ecosystem Research, Bulgarian Academy of Sciences, Sofia . The vouP. veris was made after using the acetocarmine test [The estimation of pollen viability of the two studied populations of ine test . For thiAssessment of the pollen viability was performed by direct counting, using the light microscope “Olympus” CX21 .To assess seed viability (fertility), the tetrazolium test  was applThe genetic study was performed in four natural populations distributed throughout the whole range of the species’ distribution in Bulgaria : PetrohaDNA was extracted by Invisorb Spin Plant Mini Kit , following the protocol of the producer. DNA quantity and quality before the analysis were measured by the spectrophotometer Nanodrop Lite (Thermo Fisher Scientific).Primula species [Six primers for obtaining Internal simple sequence repeats (ISSR) genetic markers were applied in the study . The mar species . The amp species .Binary matrix was constructed using presence (1) and absence (0) of particular band. Based on the matrix, the following parameters were calculated: expected heterozygosity and the percent of polymorphic bands. Nei’s genetic distances among the population pairs were calculated for revealing the inter-population variation. Cluster analysis was applied by using UPGMA method and by means of the software ClustVis .Primula veris are established, in order to reveal the reproductive potential of this valuable medicinal plant. It should be noted that some new important reproductive characteristics have been identified in this species, as follows: development of two fibrous layers in the anther wall instead of one and formation of hypostase as an additional structure in the chalasal part of the ovules. Considering that the embryological features are very conservative, the established new features enrich the data on embryology and reproductive biology of this species and the genus Primula. The study revealed P. veris is exclusively sexually reproducing in the Bulgarian populations. No apomixis or at least some of its elements is found which correlates with the diploid status of the species.In this study, for the first time, the peculiarities of the generative processes and structures of the Bulgarian populations of P. veris is exclusively determined by the fact that it is a distylous, and therefore a self-incompatible, species. Therefore, it is sensitive to pollen limitation [P. veris, widespread in Bulgaria.The normal (without deviations) course of the processes of formation of the male and female gametophyte, with relatively few observed degenerations of ovules and embryo sacs, combined with the formation of large quantity of fertile pollen (over 95%), provide high reproductive potential and successful reproduction of the species, especially under appropriate conditions. The specificity of mitation , and lowmitation . Consequmitation , and in P. veris exhibits similar patterns of variation to those of closely related species with similar life-history characteristics. The revealed high genetic variability in the studied populations corresponds to that established in other Primula species and allows the conclusion that the high genetic diversity is a common feature of Primula species, due to their outcrossing mode of reproduction. However, a more complete picture can be obtained by studying more populations from the whole species range.The study on genetic diversity revealed that The results on the reproductive potential show that the species can be successfully cultivated in ex situ conditions to obtain medicinal drugs. This option is especially valuable, bearing in mind that the species, although widespread throughout the whole country, is represented by populations that are small in size and fragmented.Primula veris must be carried out in a context of preservation of the size and character of its natural populations.Therefore, we consider that further thorough investigations on morph-specific reproductive processes in


Mycoplasma agalactiae, Mycoplasma mycoides subsp. capri, Mycoplasma capricolum subsp. capricolum and Mycoplasma putrefaciens which were previously thought to produce clinically similar diseases. Today, with major advances in diagnosis enabling the rapid identification by molecular methods of causative mycoplasmas from infected flocks, it is time to revisit this issue. In this paper, we discuss and argue the reasons to support Mycoplasma agalactiae infection as the sole cause of contagious agalactia.For over thirty years, contagious agalactia has been recognized as a mycoplasma disease affecting small ruminants caused by four different pathogens: Mycoplasma agalactiae which was first isolated from sheep in 1923. Over the last thirty years, three other mycoplasmas  have been added to the etiology of CA because they can occasionally cause clinically similar outcomes though nearly always in goats. However, only M. agalactiae is subject to animal disease regulations nationally and internationally. Consequently, it makes little sense to list mycoplasmas other than M. agalactiae as causes of the OIE-listed CA when they are not officially reported by the veterinary authorities and unlikely to be so in the future. Indeed, encouraging countries just to report M. agalactiae may bring about a better understanding of the importance of CA. In conclusion, we recommend that CA should only be diagnosed and confirmed when M. agalactiae is detected either by isolation or molecular methods, and that the other three mycoplasmas be removed from the OIE Manual of Diagnostic Tests and Vaccines in Terrestrial Animals and associated sources.Contagious agalactia (CA) is suspected when small ruminants show all or several of the following clinical signs: mastitis, arthritis, keratoconjunctivitis and occasionally abortion. It is confirmed following mycoplasma isolation or detection. The historical and major cause is  Mycoplasma agalactiae, M. mycoides subsp. capri (previously named M. m. mycoides large colony), M. capricolum subsp. capricolum and M. putrefaciens—should be recognized as causal agents of CA because the clinical disease they cause can be similar and includes mastitis, arthritis, keratoconjunctivitis and, occasionally, abortion [M. agalactiae, the main and historical cause, were sufficiently similar to those of M. m. capri and M. c. capricolum to be considered CA. As a result, these were listed in the OIE Manual of Diagnostic Tests and Vaccines in Terrestrial Animals in 1988 [M. putrefaciens, mainly based on a few reports including one from Da Massa et al. in 1987 describing a severe outbreak of mastitis and arthritis in goats requiring the slaughter of nearly 700 goats [M. putrefaciens and, indeed, M. c. capricolum, the four mycoplasmas have continued to be listed in their manual by the OIE ever since as etiological agents of CA. The inclusion of all four mycoplasmas has not been without argument with the OIE Collaborating Centre for International Cooperation in Animal Biologics at Iowa State University commenting in 2004: “Some authorities consider infections with all of these agents to be CA; others prefer to reserve the term for infections with (only) M. agalactiae. Until this issue has been resolved, reports of CA outbreaks should specify the species involved” [In 1999, the consensus of the working group on contagious agalactia (CA) of the EC COST Action 826 on ruminant mycoplasmoses, which met in Toulouse, France, agreed that four mycoplasmas— in 1988 . Further00 goats . Despitenvolved” . UnfortuM. agalactiae is recognized nationally and internationally and subject to animal disease regulations covering CA. While M. m. capri is a widespread and probably underestimated respiratory pathogen, the disease it causes is, in most cases, clinically distinct from that caused by M. agalactiae. M. c. capricolum also favors the respiratory system and is rarely reported, while M. putrefaciens can cause reduction in milk production but affected animals are often without clinical signs. Moreover, M. m. capri, M. c. capricolum and M. putrefaciens are pathogens of goats rarely affecting sheep, which are by far the most economically important small ruminant species worldwide, particularly in the EU, where sheep numbers are seven times higher than those of goats [M. agalactiae should be considered the sole cause of classical CA.Today, with major advances in diagnosis enabling the rapid identification by molecular methods of causative mycoplasmas from infected small ruminants, which is required to confirm diagnosis of CA, it is belatedly time to revisit this issue. This is important because only of goats . For theM. agalactiae are mastitis which can involve 60–80% of lactating females, followed by arthritis, keratoconjunctivitis and abortion in less than 10% of affected animals. Clinical signs can be seen at various stages during the evolution of the disease, not necessarily in the same animal but in individuals in the affected flock or herd [M. agalactiae accounts for 90% of outbreaks of CA in goats [M. agalactiae and, where it has been reported, may have been the result of a mixed infection with other pathogens, in particular M. m. capri [The main clinical signs of CA caused by  or herd . M. agalin goats ; it is cm. capri .M. mycoides group, M. m. capri and M. c. capricolum, are more often isolated from pneumonic goats [The three other mycoplasmas which have been added to the etiology of CA can occasionally cause clinically similar outcomes, though exclusively in goats. However, the two pathogens belonging to the ic goats  or from ic goats  and onlyic goats .M. m. capri and other pulmonary mycoplasmas in goats from CA, Thiaucourt and Bolske used the rather awkward term MAKePs syndrome standing for mastitis, arthritis, keratoconjunctivitis and pneumonia [In an effort to separate diseases caused by neumonia . Outbreaneumonia .M. putrefaciens is a very infrequent isolate from goats with questionable pathogenicity as it is often isolated from healthy goats but has been found occasionally in goat herds presenting agalactia. It is often found with M. agalactiae where it may play little role in disease progression [The fourth listed mycoplasma gression ,17. Howegression , reporteM. agalactiae as the unique or major pathogen in CA. Some European countries also report to national authorities some or all of the three mycoplasmas, which may not always be linked to outbreaks of mastitis and/or falls in milk production. An investigation carried out between 2004 and 2012 in Sardinia, which has the highest sheep population in Italy, found a high number of outbreaks of M. m. capri. This was shown to be the result of introductions of goat breeds from Spain and other European countries. The disease was confirmed in 34 goat farms and a single sheep flock [M. m. capri was isolated from the lungs and brains of over 74% of the herds, sites rarely associated with M. agalactiae (7).Overall, most countries involved in small ruminant dairy production identify ep flock . While tClinical signs of the four mycoplasmas are summarized in M. agalactiae vary according to the route of infection. Hasso and colleagues [M. agalactiae testing four different routes of inoculation and observed: acute to chronic mastitis in the intramammary and subcutaneously inoculated groups; acute synovitis in the intravenously inoculated group and, to a lesser extent, in the intramammary inoculated group; and subacute enteritis in the orally inoculated group. No changes were detected in the eyes.It can be difficult to make comparisons between infections caused by these various mycoplasmas because experimental infections do not always mimic natural infection as the pathogen may invade less aggressively either following contamination from the environment or the infected hands of the milkers. However, reports have shown quite distinct pathological changes following infection with different mycoplasmas. Moreover, lesions resulting from experimental infections of lleagues  reportedM. m. capri infection as a disease which involves mainly the thoracic cavity in adults and the joints of young animals. There was no mention of lesions in the mammary glands. Studies carried out in Italy some years ago [M. m. capri infection was a respiratory and poly-arthritic syndrome and only one of ten experimentally infected goats had udder lesions detected by immunohistochemistry. Agnello et al. [M. m. capri where few adult animals showed clinical signs or lesions, whereas a severe poly-arthritic syndrome was found in the 90% of kids with an 80% mortality rate.Other authors ,21 have ears ago  confirmeo et al.  investigM. agalactiae and M. m. capri in goats following natural infection and showed that M. m. capri possessed a greater respiratory tropism than M. agalactiae. In addition, a large number of M. m. capri isolates were found in the ear canal, demonstrating a close connection between the respiratory system and the middle ear.Bergonier et al.  investigM. c. capricolum, M. m. capri and M. m. mycoides (large colony type) showed fatal septicemia within 5 days; histopathological findings consisted of acute diffuse interstitial pneumonia, arthritis and multifocal necrotic purulent splenitis [Pathological and immunohistochemical findings observed in 12 kids experimentally infected with plenitis .M. putrefaciens pathology have shown that only intramammary inoculation can lead to an acute mastitis while other routes failed to produce lesions [M. putrefaciens strains in lactating goats via intramammary inoculation caused an increase of leukocytes in milk within 8 days but no sign of mastitis in spite of a complete halt in lactation after some days [The few studies on  lesions ; this maome days . PatholoM. c. capricolum, a fibrinopurulent polyarthritis and an acute, diffuse interstitial pneumonia. However, lactating goats exposed to low numbers of the organism via the teat canal experienced similar lesions as well as acute mastitis, agalactia and hardened udders.Da Massa  reportedM. agalactiae is isolated. Indeed, few, if any, countries report CA officially when M. m. capri, M. c. capricolum and M. putrefaciens are detected. M. agalactiae and very few reports of the other causative mycoplasmas over the last 20 years [M. m. capri, M. c. capricolum and M. putrefaciens in both sheep and goats have been reported [M. agalactiae appears to be dominant in both sheep and goats. In North and Central Spain, M. agalactiae is widely present in sheep but M. m. capri, M. c. capricolum and M. putrefaciens remain unreported [M. agalactiae (75%) compared to M. m. capri (4%) [M. m. capri in goats is similar to that of M. agalactiae [Of potential significance to our argument is the geographical distribution of the mycoplasmas and identification of regions where CA is reported. Unfortunately, this is difficult to be certain of as reports of CA by the World Animal Health Information System (WAHIS) issued by the OIE do not specify the pathogen involved. Furthermore, many reporting countries do not have the ability or inclination to identify mycoplasmas, so diagnosis is mainly based on clinical disease. In countries where mycoplasma laboratories exist, CA is only declared when 20 years . Many ot20 years . In Bosnreported . In Nortreported  and in Treported , M. agalreported . In Murcpri (4%) . In contalactiae .M. m. capri, M. c. capricolum and M. putrefaciens respectively but rarely detected M. agalactiae in clinically affected goats [M. agalactiae is considered as a dominant pathogen in major sheep-breeding regions [M. m. capri strains were also isolated in goats in Sardinia and Sicily [M. c. capricolum and M. putrefaciens were isolated from a few milk samples in Sardinia in 2018 . In Greece and Cyprus, all reports in both sheep and goats have focused exclusively on M. agalactiae [In France, a national surveillance network estimated a prevalence of 42%, 26% and 15% for ed goats . In Ital regions , whereasalactiae .M. m. capri has been reported in Australia and New Zealand, CA has never been diagnosed despite the large numbers of sheep probably because most are maintained for meat production. In general, M. agalactiae appears to have a more restricted distribution: Southern Europe, West Asia, including Turkey and Iran, and North Africa with occasional reports from parts of South America like Brazil [M. m. capri has been reported on most continents of the world where small ruminants are kept. Reports of M. c. capricolum and M. putrefaciens are much more sporadic and infrequent.More recently, CA has been reported in countries in Western Asia like Iran and Mongolia where automation of the dairy industry is still rare. While isolation of e Brazil . On the M. agalactiae is very closely related to the bovine pathogen, M. bovis, and grouped in the hyorhinis group along with other animal pathogens. The other three mycoplasmas, M. m. capri, M. c. capricolum and M. putrefaciens, belong or are very closely related to the genetically distant mycoides cluster surprisingly located in the spiroplasma group, mollicutes more commonly found in plants and insects. Indeed, M. agalactiae shares only 18% of its genome with the M. mycoides cluster [Mycoplasma spp. showed a marked difference in behavior in vitro. Erythromycin is effective against infection by M. m. capri, M. c. capricolum and M. putrefaciens, but inefficient against M. agalactiae strains [bovis or mycoides groups.It is worth noting that  cluster . Interes strains ,14,27. TM. agalactiae is suspected as was a recent case involving imported goats from France [M. agalactiae is detected. Israel regularly isolates M. agalactiae and M. m. mycoides but only reports this nationally while informing the OIE that CA is present based on clinical findings. In many countries including Turkey and Portugal, cases of CA are not reported possibly because of the complexities of reporting several pathogens as causes of CA. In France, Greece, Iran and Italy as well, action is only taken in the event of the detection of M. agalactiae. Indeed, we do not know of any country that reports or takes action if any of the other causative mycoplasmas are found.In the United Kingdom, like many other disease-free countries, CA is a notifiable disease and is covered by two pieces of legislation: the Specific Diseases (Notification and Slaughter) Order 1992 and the Specific Diseases (Notification) Order 1996 which describe procedures to be taken, including movement restriction, slaughter and disinfection, in the event of an outbreak. However, action is only taken if m France . Poland M. agalactiae represents the most important and prevalent pathogen associated with CA, the disease shows the same clinical course both in sheep and goats. Moreover, in those countries like Italy where often both animal species are kept together in the same group, owners do not report any clinical differences between them. It seems to confirm that the clinical behavior of CA is quite different according to the pathogen involved, target species, breed, farm/husbandry type or degree of domestication. However, from a veterinary point of view, two different diseases are seen. First, the “typical or classical disease” which is very contagious affecting flock milk production and for this reason is called “contagious agalactia”. This disease occurs exclusively in milking/dairy small ruminants. In the ancestral species, the Spanish ibex (Capra pirenaica), the clinical signs are represented by blindness, malnutrition and polyarthritis [In countries where rthritis , but theM. agalactiae as a single cause of CA may help focus attention on this important pathogen and remove the confusion and uncertainty that exists about reporting of this OIE-listed disease. This will also fit better into the OIE ethos of “one disease, one cause”. It is hoped that this paper may cause the EU to reconsider altering the status of CA in future amendments to the regulation as we believe it is an under-reported disease with international significance.The introduction of European Union (EU) regulation 2016/429, which provided a new regulatory framework covering control and surveillance of infectious diseases, animal welfare and animal movements amongst Member States, complements local legislation but also reduces the amount of intervention possible . WorryinM. m. capri and M. c. capricolum: caprine respiratory and articular syndrome (CRAS). This reflects more accurately the main disease signs and separates it from the OIE-listed contagious caprine pleuropneumonia caused by the closely related M. capricolum subsp. capripneumoniae which is confined to the thoracic cavity.Finally, in a further effort to bring about clarity to this complex area we propose a new term for the disease caused by the largely respiratory pathogens M. agalactiae is detected either by isolation or molecular methods such as PCR and the other three mycoplasmas removed from the OIE Manual of Diagnostic Tests and Vaccines in Terrestrial Animals and associated sources.In conclusion, we recommend that CA should only be diagnosed and confirmed when


Mastigimas anjosi is an important pest of Cedrela fissilis in the southeastern and southern regions of Brazil. The objective of the present study was to investigate the effect of the temperature, relative humidity, rainfall and natural enemies on the flight activity of adults and the movement of M. anjosi nymphs, with two sampling methods, yellow sticky traps and direct collections on the leaves of C. fissilis trees. The sex ratio of this pest was also assessed. The number of M. anjosi individuals was negatively correlated with the minimum and maximum temperatures, with a population peak in late May and early June 2017. The numbers of individuals of this psyllid was positively correlated with the relative humidity and rainfall. Larvae and adults of Cycloneda sanguinea, Hippodamia convergens adults and Atopozelus opsimus nymphs and adults preyed upon M. anjosi adults and nymphs on C. fissilis leaves in the field. Mastigimas anjosi sex ratio was 0.46. Information about sampling methods of M. anjosi and its natural enemies is presented and can contribute to the integrated management of this pest in the field. Key message —Mastigimas anjosi on Cedrela fissilis have to be understood for effective control of this pest.The factors favouring infestation of  —Mastigimas anjosi in C. fissilis forests were provided.Important data to promote monitoring and biological control programmes of  —Atopozelus opsimus, Cycloneda sanguinea and Hippodamia convergens individuals in the yellow sticky traps and the predation on C. fissilis show the importance of these natural enemies in the integrated management of M. anjosi.The high numbers of  —M. anjosi adults and its natural enemies and can be used to monitor populations of these insects in the C. fissilis plantations.Yellow sticky traps were efficient in sampling of  —Cedrela fissilis leaves was inefficient to survey insect predators of M. anjosi.Sampling of . 1Cedrela fissilis Vell. , of arboreal size and native to Brazil  = 0.6478 > α = 0.05. This shows that it is possible to affirm, with a 5% significance level, that the distribution of the data in this sample is normal. However, this was rejected for M. anjosi adults, Wcalculated = 0.8404 < W = 0.905, with p-value calculated by p[W < Wcalculated] = 0.0014 < α = 0.05 . The hypothesis that data on population variances are similar (homogeneity) was rejected, that is, the means and medians of the M. anjosi nymph and adult populations differ according to ANOVA (p = 1.362 × 10−36) and the Kruskal–Wallis test (p = 2.2 × 10−16), respectively.The normality test showed that the Hα = 0.05 a,b. The M. anjosi adults, respectively, from the variation of the dataset . The PCA retained all factors with eigenvalues higher than one  for nymphs and PC4 (5.2%) for adults of this pest  and maximum (r = −0.93) temperatures for nymphs (r = −0.93) and adults (r = −0.97) of M. anjosi, respectively, moderate and direct for relative humidity  and weak and inversely proportional for rainfall  and natural enemies , respectively  and the explanatory minimum (TMIN) and maximum (TMAX) temperatures with the population fluctuation of this psyllid. The number of nymphs (r = 0.88 and r = 0.75) and adults (r = 0.90 and r = 0.72) of M. anjosi correlated with the variables rainfall and relative humidity and the axis of PC2, high and direct correlation, respectively, in addition to low and inversely proportional correlation with natural enemies   with the M. anjosi adult numbers  and adults  of M. anjosi showed the fit of the regression analysis line with the dataset .The variable natural enemies, in the PC3, showed a moderate and direct correlation  for nymphs and adults (F = 2.8786) of M. anjosi was significant, but reduced , sea pumpkin, Arctotheca nivea (L. fil.) Lewin , parrot bush, Banksia sessilis Knight  and garden pea, Pisum sativum L.  in Australia [Austroasca viridigrisea Paoli, 1936 (Hemiptera: Cicadellidae) adults in Narrabri, New South Wales, Australia [Ctenarytaina thysanura Ferris & Klyver, 1932  in Hobart, Tasmania, Australia [Aphis fabae Scopoli, 1763, the cabbage aphid, Brevicoryne brassicae L., 1758 and the green peach aphid, Myzus persicae Sulzer, 1776 (Hemiptera: Aphididae) in a laboratory in England [M. anjosi nymphs and adults in the autumn confirm the effect of climatic conditions on the capture of hemipterans, as reported for the highest number of individuals of sharpshooters, Acrogonia citrina Marucci & Cavichioli, 2002, Bucephalogonia xanthophis Berg, 1879 and Dilobopterus costalimai Young, 1977 (Hemiptera: Cicadellidae) during periods of high rainfall (207.8 mm) in November 2003 in Viçosa, state of Minas Gerais, Brazil [The attractiveness of ustralia , as prefustralia . Green, ustralia . In addi England . The gre England . The gre, Brazil .M. anjosi nymphs population in the 20th evaluation and that of adults in the following is due to the nymphs of this insect completing the development cycle in approximately 20 days [M. anjosi individuals, collected in Sorocaba, in May and June, a period with rainfall above 100 mm after the dry period [C. fissilis plants and, consequently, in the reproduction and development of this insect [The peak of  20 days  and the y period , confirms insect .M. anjosi number due to the population dynamics of natural enemies being directly related to that of their prey or hosts. Larger pest populations support a greater number of natural enemies due to the increased supply of food/host, as observed for onion thrips, Thrips tabaci Lindeman, 1889 (Thysanoptera: Thripidae) and their predators from five families, including Aeolothripidae (Thysanoptera) on common onion plants, Allium cepa L. , with population peaks, respectively, in late July and early August in the central and western regions of New York, USA in 2011 and 2012 [The highest number of individuals of natural enemies, collected in October, follows the same trend as the and 2012 .M. anjosi nymphs and adults numbers with a population peak in late May and early June was similar to that reported for G. brimblecombei nymphs per Eucalyptus L'Hér.  leaf in Botucatu and São Simão, state of São Paulo, Brazil [G. brimblecombei adult numbers and temperature was also inverse in collections with yellow sticky traps on river redgum, Eucalyptus camaldulensis Dehnh, 1832 trees in January to June 2005 in Luiz Antônio, state of São Paulo, Brazil [M. anjosi individuals collected on C. fissilis trees in August 2015 during a period with low rainfall and high temperatures with yellow sticky traps in Sorocaba [M. anjosi individuals, captured in the summer, and higher in the winter months, characterize the impact of temperature on the population dynamics of this insect.The inverse linear correlation between the explanatory variables minimum (TMIN) and maximum (TMAX) temperatures with the , Brazil . The cor, Brazil  and for M. anjosi nymphs, indicate their greater preference to feed on nymphs than on adults of this pest, because they are smaller, apterous and low mobile [A. opsimus, C. sanguinea and H. convergens preying upon M. anjosi on C. fissilis leaves in Sorocaba shows the importance of these natural enemies as reported for those preying the Asian citrus psyllid, Diaphorina citri Kuwayama, 1980 (Hemiptera: Liviidae) on Citrus  in China [Triozoida limbata Enderlein, 1918 (Hemiptera: Triozidae) on common guava, Psidium guajava L.  in Petrolina, state of Pernambuco, Brazil [Atopozelus opsimus, Chrysopidae and Syrphidae species are generalist natural enemies, and they were reported preying M. anjosi on T. ciliata trees in 2013 and 2015 in Conselheiro Lafaiete and Ouro Branco, state of Minas Gerais, Brazil [Atopozelus opsimus preyed upon M. anjosi nymphs and adults on C. fissilis trees in Montes Claros, state of Minas Gerais, Brazil, and their nymphs feed on honeydew produced by this pest. This predator did not prevent damage to C. fissilis, which may be related to the high temperatures in this region, reducing its reproduction and increasing its development period [The numbers of natural enemies, negatively correlated with that of w mobile ,16. The in China  and the , Brazil . Atopoze, Brazil . Atopoze0 hypothesis acceptance shows normal distribution of data on the M. anjosi nymph numbers and that their base can be accepted and compatible with approximately 65% of the residue data and that the W value should be rejected for the adult numbers of this insect. On the other hand, the lack of normality in the frequency distribution of this dataset may be related to the behaviour of the M. anjosi adults with reduced body size and wings that facilitate their rapid locomotion within C. fissilis plants [W value, as some individuals, randomly, may not have been captured by the sticky traps, while the low mobility of nymphs of M. anjosi facilitates to sample this stage by direct collection of the leaves in the field.The Hs plants . In addiM. anjosi nymphs, related to maximum and minimum temperatures and rainfall, and their relationship with the PC1 and PC2 of the PCA axes confirm an increase in their numbers in the drier months and a reduction with the temperature increases. The lower number of M. anjosi individuals in periods with rainfall above 100 mm is due to the relationship between accumulated rainfall and the total nymph numbers of this species as reported for G. brimblecombei nymphs at temperatures between 22 and 26°C and rainfall above 80 mm in Brazil [Glycaspis baileyi Moore, 1961 (Hemiptera: Psyllidae) and other psyllids species on forest red gum, Eucalyptus tereticornis Sm. plants in Mauritius [The number of n Brazil ,20,22,53auritius .T. limbata increased with minimum, average and maximum temperatures and accumulated rainfall. However, the latter parameter increased the rate of vegetative growth of the plants and, consequently, the development and vigour of this psyllid due to the greater nutrient availability and leaf turgidity [Psyllids can have several generations per year, with all stages present, although with varying numbers between them . The numurgidity . Torrenturgidity .M. anjosi adult numbers can be explained by the greater difficulty of these predators to capturing adults of this psyllid with reduced body size and rapid locomotion within the leaves of the C. fissilis plants [The moderate and direct correlation between natural enemies and s plants .F value for M. anjosi nymphs and adults from the analysis of main components, may be related to the restrictions on the values of the observations, strictly positive [The low relationship between the variables analysed, normality of the data and the positive . This hapositive , for exaM. anjosi adults in Sorocaba was similar to that of other psyllids, with amphitoky parthenogenesis, but it differs from that of the jumping plant lices, Cacopsylla myrtilli Wagner, 1947 [Cacopsylla rare Tuthill, 1944, Glycaspis atkinsoni Moore, 1984, and Glycaspis operta Moore, 1984 (Hemiptera: Psyllidae) [The sex ratio of er, 1947 , Cacopsyyllidae) , with th. 5M. anjosi nymphs and adults was negatively correlated with maximum and minimum temperatures and positively with relative humidity and rainfall with population peaks between the end of May and the beginning of June 2017. The high numbers of A. opsimus, C. sanguinea and H. convergens individuals in the yellow sticky traps and the predation of M. anjosi adults and nymphs on C. fissilis trees show the importance of these natural enemies in the integrated management of this psyllid. Yellow sticky traps were efficient in sampling of M. anjosi adults and its natural enemies and can be used to monitor these populations in the field. Sampling of C. fissilis leaves was inefficient to survey C. sanguinea, H. convergens and A. opsimus. The sex ratio of M. anjosi adults was 0.46.The number of


Correction to: BMC Neurol 21, 231 (2021)https://doi.org/10.1186/s12883-021-02233-5Following publication of the original article , the autThe original article  has beenAdditional file 2. This is the statistical analysis, provided in .pdf format. This contains the R code used in the analysis and so parts of this are likely to be hard to understand for the reader not familiar with this language. The file provides the results given in the main article. It includes some additional analyses and images which, for reasons of space, do not form part of the main article. In particular, it provides details of all of the MTs assessed. For each gene assessed, we also provide hyperlinks (where possible), to the relevant entry at the NCBI Gene database (https://www.ncbi.nlm.nih.gov/gene).


Rhipicephalus sanguineus s.l. , the brown dog tick, is the most widely distributed tick species in the world. The two dominant lineages, a temperate group and a tropical group, are recognized as important disease vectors for both dogs and humans. The temperate and tropical lineages overlap in range in some regions of the world, including the southwestern United States, where recent outbreaks of Rocky Mountain spotted fever are linked to R. sanguineus s.l. While it is unclear to what extent they may differ in their capacity to transmit pathogens, finer-scale resolution of temperate and tropical lineage distribution may provide insight into the ecology of these two tick groups and the epidemiology of R. sanguineus s.l.-vectored diseases. Using diagnostic polymerase chain reaction assays, we examined the geospatial trends in R. sanguineus s.l. lineages throughout Arizona. We found the temperate and tropical lineages were well delineated, with some overlap in the eastern part of the state. In one county, tropical and temperate ticks were collected on the same dog host, demonstrating that the two lineages are living in sympatry in some instances and may co-feed on the same host. Rickettsia rickettsii, which kills more people within North America than any other tickborne disease [Dermacentor variabilis, and Montana, Idaho, and Wyoming, where the principal vector is D. andersoni.Ticks (Acari: Ixodida: Ixodidae) are important vectors of many human and animal diseases, especially within North America. Among the most significant of these diseases is Rocky Mountain spotted fever (RMSF), a bacterial infection caused by  disease . In 2018 disease . Most ofRhipicephalus sanguineus sensu lato-vectored RMSF has been recognized in Mexico since the 1930s, though data on estimated incidence is limited [ limited . Since t limited ,6,7. WhiR. sanguineus s.l., but the ticks will feed on humans as incidental hosts and can transmit R. rickettsii at all life stages. The close relationship between domestic dogs and humans enables infestations of R. sanguineus s.l. in and around human homes and allows the tick to complete its entire life cycle indoors [R. sanguineus s.l. with RMSF may have important implications for the epidemiology and expansion of this disease to other parts of the world and should be explored in greater detail.Dogs are the preferred hosts of  indoors . Through indoors . Affecte indoors ,6,8. TheR. sanguineus s.l. refers to a complex of 11–17 related species or subspecies with a worldwide distribution [R. sanguineus s.l. lineages  and other Rhipicephalus species  are minute, further complicating the taxonomic status [R. sanguineus sensu stricto. The aforementioned tropical lineage within the Americas is currently under revision, with specimens from Australia and southern Asia declared a separate species, R. linnaei, by Šlapeta et al. (2021) [R. sanguineus species complex, ticks will be referred to in terms of temperate and tropical lineage throughout this text.ribution ,10,11. Tribution . Historiribution ,14. Morpc status . In 2018c status  designat. (2021) . To dateR. sanguineus s.l. lineages occupy distinct ecological niches [Rickettsia spp. bacteria, but to date, only the tropical lineage has been associated with the distribution of RMSF in Mexico [R. sanguineus s.l. lineages differ in their capacity to transmit R. rickettsii. However, various experimental transmission studies suggest that the temperate and tropical lineages do differ in their ability to transmit a variety of other pathogens, including Ehrlichia canis, Hepatozooan canis, and Anaplasma platys [R. sanguineus s.l. species complex ticks within Arizona may, therefore, provide insight into the epidemiological distribution of R. sanguineus s.l.-vectored diseases across the state in the future.While it has been suggested that the two main l niches ,20,21,22l niches ,22,23. An Mexico ,19,24. Ia platys ,28,29,30R. sanguineus species complex. Given the higher rate of base substitution relative to most nuclear genes, mitochondrial DNA sequences are useful phylogenetic markers for clades with relatively recent divergence [R. sanguineus s.l. taxa [R. sanguineus s.l. ticks with those of Hyalomma dromedarii [R. sanguineus complex after finding that nuclear markers, specifically ITS2, were insufficiently variable and therefore not informative or robust enough to provide resolution on the necessary scale [Much work has been done to investigate the molecular dissimilarities between divergent populations within the vergence . A systevergence . The mit.l. taxa ,17,23,33.l. taxa ,36,37,38omedarii . The autry scale ,16.R. sanguineus s.l. lineages within Arizona. A diagnostic polymerase chain reaction (PCR) protocol was developed using lineage-specific primers to differentiate between the temperate and tropical lineages of R. sanguineus s.l. based on the mitochondrial 12S rRNA gene with Sanger sequencing confirmation on a subset of samples. Given the current understanding of the global distribution of R. sanguineus s.l. ticks, it was hypothesized that the temperate lineage will be more abundant, particularly in northern latitudes and higher elevations across Arizona. However, the presence of the tropical lineage in the six regions of the state where historic and ongoing transmission of RMSF is occurring was predicted.The aim of this work was to determine the spatial distribution of R. sanguineus s.l. ticks of all life stages and engorgement levels were solicited throughout the year as a convenience sample from animal shelters, tribal vector control agencies, and University of Arizona Cooperative Extension offices across Arizona. Most ticks included in this study were collected from dogs at animal shelters  or in collaboration with local stakeholders during vector control activities, such as RMSF prevention campaigns and mobile rabies clinics. The majority of ticks were collected during peak tick activity, during the months of March through August. Ticks were identified to species complex using standard taxonomic keys [In 2018 and 2019, mic keys , and theTicks were placed in a 1.5 mL tube, submerged in liquid nitrogen, homogenized with a sterile pestle, and treated with 20 mg/mL lysozyme solution . DNA was isolated using the Qiagen QiaAmp DNA Mini Kit, with an AE buffer elution volume of 50 μL.R. sanguineus s.l. were based on differences of two bp at the binding sites for both the forward and reverse primers, and amplified a sequence of the mitochondrial 12S rRNA approximately 350–360 base pairs in length . Presence/absence data were recorded for the two lineages at each sampling site, and elevation and latitude data were inferred based on nearest city/town utilizing the ArcGIS Data and Maps global databases.R. sanguineus s.l. ticks were included in this study from eleven counties in Arizona  of the samples amplified using the temperate primers, whereas 72% (n = 220) amplified using the tropical primers. Occasionally, there was low amplification with the second lineage-specific primer set, resulting in a faint band in the second lane for a sample . This may have been due to non-specific binding, contamination, or an indication of hybridization and paternal leakage of mitochondrial DNA [As expected, positive controls for the temperate and tropical lineages amplify with the appropriate lineage-specific primer but not the other . Twenty-rial DNA . HoweverSanger sequencing was performed on the 12S PCR amplicon of 117 (38.2%) samples from eleven counties in Arizona and compared against lineage-specific diagnostic PCR results. Four samples (two larvae and two nymphs) were removed from the analysis due to low DNA concentrations and subsequent low-quality Sanger sequencing reads. These samples amplified using the lineage-specific primers but could not be verified with sequencing. For the remaining samples, there was 100% consensus between amplification with lineage-specific primers and sequencing-based identification.R. sanguineus s.l. lineages were surprisingly well-delineated across the state. However, both lineages were found in two counties—Gila and Cochise—indicating some overlap in their ranges. The distributions of the two R. sanguineus s.l. ticks were collected between 31.5° and 34° latitude  a. On theR. sanguineus s.l. lineage demonstrates that the two lineages overlap in range in Arizona. While this study utilized a convenience sampling method and therefore the lack of a lineage in a county may not be representative of an actual absence, the results support the published literature on the distribution of the temperate lineage [The spatial analysis of  lineage ,34. We f lineage , where t lineage  that the lineage  further R. sanguineus s.l. lineages is necessary to assess future risks of tickborne diseases vectored by this tick species complex in a warming world.It is well established that vector-borne diseases, including those transmitted by ticks, increase in incidence as the global climate warms . The resR. sanguineus s.l. ticks without the need for additional sequencing. While not sufficient for phylogenetic analyses, it may prove useful for researchers seeking to identify R. sanguineus s.l. ticks to lineage without additional investments in time and resources. This protocol may be especially useful in regions where both lineages have been found to screen large numbers of ticks and define the distribution of R. sanguineus s.l. with high resolution.The diagnostic PCR protocol described here quickly and reliably distinguishes between temperate and tropical lineages of R. sanguineus s.l. populations [R. sanguineus s.l. populations showed reproductive success, and also indicated the occurrence of paternal inheritance of mitochondria and mitochondrial heteroplasmy [R. sanguineus s.l. lineages has also been observed experimentally, although most of the hybrid progeny did not produce viable offspring [R. sanguineus s.l. lineages, and whether an R. sanguineus s.l. tick may behaviorally present as one lineage while mitochondrial DNA determines it to be the other. Identification of a nuclear genetic marker with sufficient resolution at this taxonomic level would aid in this line of research.Due to lingering taxonomic questions, several hybridization experiments have been conducted using geographically isolated, allopatric ulations ,45. A crffspring ,45. HoweR. sanguineus s.l. is the primary vector of RMSF in Arizona, much remains to be investigated. The temperate and tropical R. sanguineus s.l. lineages are present in Arizona and living in sympatry in some areas. A systematic assessment of the presence/absence of each lineage across the state using non-convenience sampling strategies may highlight additional areas of sympatry. Future research on this topic should focus on whether the two lineages differ in their vectorial capacity for RMSF. Additionally, a more thorough assessment of climatic variables relevant to range limitation and overlap may be helpful to better understand the distribution of the temperate and tropical R. sanguineus s.l. ticks in this region of the United States. Finally, researchers should seek evidence of hybridization among sympatric temperate and tropical R. sanguineus s.l. lineages to further understand the implications of this on the epidemiology of RMSF and other tickborne diseases.While R. sanguineus s.l., temperate and tropical, at a fine scale in Arizona. We were able to sample ticks from eleven of fifteen counties in the state, including regions of the state affected by R. sanguineus s.l.-transmitted RMSF. The data presented here demonstrates a clear pattern of R. sanguineus s.l. lineage distribution across both latitude and elevation within Arizona. We also verify the presence of both lineages in two counties in the eastern part of the state. Our findings are somewhat limited by convenience sampling and limited access to dog hosts in some counties, as it is possible that our dog sample sizes in some areas were insufficient to obtain a representative sample of lineage.This research explores the distribution of the two recognized lineages of


Meccus' taxonomy has been quite complex since the first species of this genus was described by Burmeister in 1835 as Conorhinus phyllosoma. In 1859 the species was transferred to the genus Meccus and in 1930 to Triatoma. However, in the twentieth century, the Meccus genus was revalidated  and, in the twenty-first century, through a comprehensive study including more sophisticated phylogenetic reconstruction methods, Meccus was again synonymous with Triatoma. Events of natural hybridization with production of fertile offspring have already been reported among sympatric species of the T. phyllosoma subcomplex, and experimental crosses demonstrated reproductive viability among practically all species of the T. phyllosoma subcomplex that were considered as belonging to the genus Meccus, as well as between these species and species of Triatoma. Based on the above, we carried out experimental crosses between T. longipennis (considered M. longipennis in some literature) and T. mopan  to evaluate the reproductive compatibility between species of the T. phyllosoma complex. In addition, we have grouped our results with information from the literature regarding crosses between species that were grouped in the genus Meccus with Triatoma, in order to discuss the importance of experimental crosses to confirm the generic reorganization of species.T. mopan female and T. longipennis male resulted in viable offspring. The hatching of hybrids, even if only in one direction and/or at low frequency, demonstrates reproductive compatibility and homeology between the genomes of the parents.The crosses between T. phyllosoma subcomplex species considered in the Meccus genus with species of the Triatoma genus shows that there is “intergeneric” genomic compatibility, which corroborates the generic reorganization of Meccus in Triatoma.Considering that intergeneric crosses usually do not result in viable offspring in Triatominae, the reproductive compatibility observed between the  Trypanosoma cruzi  , the etiological agent of Chagas disease , together with T. bolivari Carcavallo, Martínez & Pelaez, 1987, T. mexicana  and T. ryckmani Zeledón & Ponce, 1972, form the T. phyllosoma subcomplex , form the T. phyllosoma complex  also resulted in the production of hybrids [Events of natural hybridization with production of fertile offspring have already been reported among sympatric species of the bcomplex . Experimterature , 18. In  hybrids , 20.Triatoma species of the T. phyllosoma (T. longipennis) and T. dimidiata (T. mopan) subcomplexes, to evaluate the reproductive compatibility between species of the T. phyllosoma complex. In addition, we have grouped our results with information from the literature regarding crosses between species that were initially grouped in the genus Meccus with Triatoma, in order to discuss the importance of experimental crosses to confirm the generic reorganization of species.The study of reproductive barriers by experimental crossings was used in taxonomy T. longipennis and T. mopan. These two species were chosen because both belong to the T. phyllosoma complex [T. mopan has never been considered as belonging to Meccus, unlike T. longipennis. The insects used in the experiment came from colonies kept in the Triatominae insectary of the School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, São Paulo, Brazil. The experimental crosses were conducted in the Triatominae insectary, according to the experiments of Correia et al. [Reciprocal experimental crosses were conducted between  complex , 14, 15,a et al.  and Menda et al. : the insT. recurva and T. phyllosoma (as M. phyllosomus) [T. mexicana and T. longipennis [T. mopan female and T. longipennis male resulted in viable offspring (Table As observed for the crosses between losomus)  and betwgipennis , only thng Table . The hatng Table , demonstPanstrongylus and Triatoma, Panstrongylus and Nesotriatoma, Rhodnius Stål, 1859 and Psammolestes Bergroth, 1911  and Rhodnius and Triatoma [T. phyllosoma subcomplex species considered in the Meccus genus with species of the Triatoma genus , as noted for the crossings between Triatoma . The repTriatoma is a paraphyletic group comprising 82 species [Triatoma related phylogenetically to the genera Panstrongylus, Paratriatoma, Linshcosteus and Hermanlentia [Meccus in Triatoma rescues a discussion about the application of the morphological characteristics used for a long time as diagnoses for the genera of the subfamily Triatominae .Meccus has been changed to Triatoma, several authors continued publishing articles using the Meccus nomenclature as valid [Triatoma (Meccus) pallidipennis [Meccus after the genus Triatoma (between parentheses) represents a subgenus and, so far, there are no valid subgenera in the subfamily Triatominae.Taxonomy is a fundamental science for the entomo-epidemiology of Chagas disease, because correctly classifying triatomines can assist in the activity of vector control programs . Even thas valid , 29–46 adipennis –49—sinceMeccus in Triatoma proposed by Justi et al. [T. phyllosoma subcomplex into this genus to avoid future misunderstandings by the scientific community and vector control programs.Thus, through reproductive compatibility, we confirm the generic reorganization of i et al. . In addi


Culicoides imicola (C. imicola), which was the main vector of African horse sickness virus.African horse sickness, a transboundary and non-contagious arboviral infectious disease of equids, has spread without any warning from sub-Saharan Africa towards the Southeast Asian countries in 2020. It is imperative to predict the global distribution of C. imicola were mainly obtained from the published literature and the Global Biodiversity Information Facility database. The maximum entropy algorithm was used to model the current distribution suitability and future dynamics of C. imicola under climate change scenarios.The occurrence records of C. imicola were distributed in most of the southern part areas of America, southwestern Europe, most of Africa, the coastal areas of the Middle East, almost all regions of South Asia, southern China, a few countries in Southeast Asia, and the whole Australia. Our model also revealed the important environmental variables on the distribution of C. imicola were temperature seasonality, precipitation of coldest quarter, and mean temperature of wettest quarter. Representative Concentration Pathways (RCPs) is an assumption of possible greenhouse gases emissions in the future. Under future climate change scenarios, the area of habitat suitability increased and decreased with time, and RCP 8.5 in the 2070s gave the worst prediction. Moreover, the habitat suitability of C. imicola will likely expand to higher latitudes. The prediction of this study is of strategic significance for vector surveillance and the prevention of vector-borne diseases.The modeling results showed that the currently suitable habitats for  Culicoides biting midges play an important role in the spread of vector-borne infectious diseases worldwide, transmitting disease agents to humans, domestic and wild animals. Among them, African horse sickness is a transboundary and non-contagious infectious disease of equids and is one of the most lethal equine virus infections known. The pathogenic virus is African horse sickness virus (AHSV), which belongs to the genus Orbivirus, the family Reoviridae (oviridae . The Woroviridae .Culicoides bolitinos is a proven vector of AHSV in South Africa. Culicoides imicola (C. imicola) is another important vector for field transmission of AHSV  from the literature (https://www.gbif.org/). All the occurrence data were spatially filtered at 10 km2 grid cells , 2050s (average for 2041–2060), and 2070s (average for 2061–2080).To determine the influence of the environmental variables on the he model . The curhe model , which oVariance inflation factors were calculated to avoid the multi-collinearity of environmental variables, it is considered that variables with variance inflation factors greater than 10 were highly collinear , and eachttp://biodiversityinformatics.amnh.org/open_source/maxent/). MaxEnt model is a machine learning method, which is used to analyze with the presence-only point data (The maximum entropy (MaxEnt) model was used for modelling (int data . In the int data . To accoint data .The AUC (the area under the receiver operating characteristic curve) assesses the predictive performance of the model. The range of AUC value is 0–1, and a higher value corresponds to a better predictive model . To evalC. imicola distribution was reclassified: unsuitable (less than 0.05), low suitability (0.05–0.33), medium suitability (0.33−0.67), and high suitability (greater than 0.67).The result maps were visualized using ArcGIS 10.2 . According to the Intergovernmental Panel on Climate Change Assessment Report , the conC. imicola distribution  in the current model for ribution , indicatC. imicola  was greater than 0.5, the variation range represented by the horizontal axis was the optimal range , the predicted habitat suitability for C. imicola was better for values of optimal range from 403 to 631 . It is worth noting that the suitable areas under the RCP 8.5 scenario hardly increased in the 2070s, but decreased sharply.The areas of different habitat suitability under current and future climate scenarios were shown in Culicoides  belongs to the same genus as AHSV and mainly infects ruminants. Recently, cases of BTV infection have been confirmed in C. imicola in Yunnan Province of China (The predicted map showed that the neighboring countries, India, Myanmar, Southern China, Laos, Cambodia, and Vietnam were all in the suitable areas for of China , suggestC. imicola will likely expand to higher latitudes, and the predicted map even showed that there were low suitability areas in high latitudes in Norway, Sweden, Finland, and the Kola Peninsula. C. imicola to expand northward. Moreover, it is worth noting that the Americas and Australasia have large areas of low suitability and medium suitability, and if C. imicola were translocated to these areas, there are increasing risks for C. imicola to expand the activity range. This will lead to a wider geographical distribution of the AHSV, thereby increasing the risk of exposure to diseases.In the future scenario, the habitat suitability of C. imicola is of great significance for the prevention and control of African horse sickness because AHSV was transmitted to domestic and wild populations through C. imicola biting. In domestic populations, the horses of AHSV infection have obvious clinical signs, a short period of viremia, and high mortality (C. imicola and Culicoides bolitinos were less reluctant to enter enclosed space (The surveillance of ortality . In wildortality . Zebra rortality . In 2020ed space . Stablined space . Therefoed space .C. imicola occurrence data were obtained from the published literature, which might suffer from underreporting. However, the results could be related to differences in reporting rather than the true ecological habits of Culicoides. In the future, it will be interesting to model the impact of the geographical expansion of Culicoides on disease distribution. Simultaneously, it is of great significance if the prediction model includes Culicoides survivability under high temperatures.This study still has a limitation, for most of C. imicola occurrence records and bioclimatic variables, the current and future suitable habitat of C. imicola all over the world was modeled using MaxEnt model. Three bioclimatic variables were revealed to have important effects on C. imicola distribution. In the 21st century, the habitat suitability of C. imicola may be different with climate change. The prediction of this study is of strategic significance for vector surveillance and the prevention of vector-borne diseases.Based on 10.7717/peerj.12308/supp-1Supplemental Information 1Click here for additional data file.


There is a growing quantity of evidence on how skin and gut microbiome composition impacts the course of various dermatological diseases. The strategies involving the modulation of bacterial composition are increasingly in the focus of research attention. The aim of the present review was to analyze the literature available in PubMed (MEDLINE) and EMBASE databases on the topic of microbiome modulation in skin diseases. The effects and possible mechanisms of action of probiotics, prebiotics and synbiotics in dermatological conditions including atopic dermatitis (AD), psoriasis, chronic ulcers, seborrheic dermatitis, burns and acne were analyzed. Due to the very limited number of studies available regarding the topic of microbiome modulation in all skin diseases except for AD, the authors decided to also include case reports and original studies concerning oral administration and topical application of the pro-, pre- and synbiotics in the final analysis. The evaluated studies mostly reported significant health benefits to the patients or show promising results in animal or ex vivo studies. However, due to a limited amount of research and unambiguous results, the topic of microbiome modulation as a therapeutic approach in skin diseases still warrants further investigation. In 1683, Antoni van Leuwenhoek made the first microscopic observation of bacteria colonizing the surface of the human skin .spp.) present in the vaginal tract  in contrast to children delivered by Cesarean section, that acquire microbiome associated with the skin   vs. 31/68 [46%]) ) . Wickenstization . Anothertization . In 2006 placebo . Six yeaobiotics . Schmidtobiotics  Kim et aobiotics . Lau et L. reuteri) in the group of pregnant women and infants was evaluated by Abrahamsson et al. Despite the cumulative incidence of AD was similar in the L. reuteri and the placebo groups (36% vs. 34%), IgE-associated eczema was less common in the L. reuteri group, although the difference was only statistically significant during the second year of life (8% vs. 20%) [B. longi and L. rhamnosus). The incidence of eczema in the probiotic group was similar to that in the placebo group (22% vs. 25%). The median SCORAD at 12 months was 17.10 in the probiotic group and 11.60 in the placebo group [L. acidophilus in their study, Taylor et al. showed no difference in the probiotic  and placebo  groups [However, 13 out of 21 trials showed that the administration of probiotics had no impact on prevalence of AD. Studies by Allen et al., Dotterud et al., Huurre et al. and Plummer et al. showed that a mix of bacterial strains was given and revealed a similar frequency of diagnosed AD both in the study and control groups. They also showed no effect of the use of probiotics in pregnant mother and infants to avoid the development of AD ,36,41,44vs. 20%) . Conclusvs. 20%) ,37,39,42 36% vs. %, IgE-as) groups .Prebiotics in the prevention of atopic dermatitis. The number of studies on prebiotics in the prevention of AD is limited and they present inconsistent results. Studies investigated only a few prebiotic compounds: combination of galacto-oligosaccharide (GOS) and fructo-oligosahccaride (FOS), acidic oligosaccharides, polydextrose (PDX), different content of lactose, oligofructose plus inulin. Among the nine studies included in this review, five have shown the positive effect of prebiotics in the prevention of the development of eczema. The rest of the studies showed no significant differences in group of infants fed with or without prebiotics.Positive effects of the administration of prebiotics has been shown by Ziegler et al., who investigated the administration of a GOS and PDX mix and found a statistical difference in the occurrence of eczema (prebiotics vs. control: 18 vs. 7%) . The samRole of probiotics and prebioticsin AD treatment. 20 of 27 studies on probiotics revealed improving SCORAD in AD patients compared to placebo. One of the first studies on probiotic treatment in AD, that found using probiotics may have positive impact on the course of AD, was the study by Isolauri et al. The aim of their study was to evaluate the effects of probiotics use with Bb-12 or LGG on infants with AD. The results showed that by using probiotics, the skin condition improves. SCORAD decreased in the Bb-12 group to 0, and in the LGG group to 1 versus the SCORAD of 13.4 in the placebo group [S. thermophilus ST10 and tara gum on the SCORAD score. The score decreased significantly in the probiotic group after one month and the index was significantly lower in the probiotic group than in the placebo group [Streptococcus thermophilus for 4 weeks. The results showed significant improvement of SCORAD in the probiotic group compared to blacebo [L. salivarus LS01, were also those conducted by Drago et al. [L. acidofilus DDS-1—by Gerasimov et al. [L. plantarum—by Han et al. [L. fermentum—by Weston et al. [L. sakei—by Woo et al. [L. casei, L. rhamnosus, L. plantarum, and B. lactis) or placebo groups for six weeks. The result of their trial was a significant clinical improvement in the skin condition among the probiotic groups [B. breve. Taniuchi et al. and Yoshida et al. showed a significant improvement in skin conditions during the study in the probiotic group [bo group . Drago ebo group . Ivakhne blacebo . Wu et a blacebo . Brouwer blacebo ,63,64. So et al.  and Iemoo et al.  L. acidov et al. , L. plann et al. , L. fermn et al.  and L. so et al.  Yang et c groups . Two of ic group ,88. Threic group ,86,87.B. bifidum group versus controls [L. rhamnosus and B. lactic. Their findings stated that there is no significant difference between probiotic and placebo groups [Lactobacillus strains (lyophilized L. rhamnosus 19070-2 and L. reuteri DSM 122460) in combination for six weeks in 1- to 13-year-old children with AD. The total SCORAD index in this trial did not change significantly [L. acidophilus and B. lactis Bi-07 (Bi-07) were that there was no benefit for the probiotics on the severity of AD. However, a post hoc analysis showed a significant reduction in severity of AD in the Bi-07 group and possible positive effects of this probiotic strain could be of further interest [B. lactis and L. paracasei. No significant differences were observed between the groups after 12-week treatment-period [Seven out of 27 studies in children showed no significant differences in SCORAD scores between the probiotic and placebo groups after treatment. Lin et al. proved that the SCORAD index was not significantly reduced in the controls . Grüber controls . Similarcontrols . Sistek o groups . Rosenfeficantly . The resinterest . Gore ett-period .Bifidobacterium animalis subsp. lactis LKM512 may reduce pruritus by increasing expression of metabolite kynurenic acid [Five out of 36 studies did not estimate the SCORAD score, but evaluated other factors, such as puritus. Matsumo et al. in their study found that nic acid . The resnic acid . Studiesnic acid , as wellnic acid . Nermes nic acid .Synbiotics. Five publications on the use of synbiotics were found; however, only one of them by Farid et al. reported a significant reduction of the SCORAD score [L. rhamnosus Lcr35) and synbiotics in children over two years old. The study showed no statistical differences regarding SCORAD scores between the two groups [L. salivarius and FOS resulted in lower SCORAD in a comparison with the control [AD score . Passeroo groups . Shafieio groups . A signio groups  Wu et al control .S.aureus plays an important role in AD, a promising new perspective of displacing it with more desirable species is also considered [The role of microbiome composition in allergic diseases is well-known, with lower biodiversity found as a factor inducing their development. Modulating the microbiome with probiotics balances the gut microflora, protects the function of intestinal barrier and lowers the level of pro-inflammatory cytokines produced. Probiotics also influence Toll-like receptors, which play an important role in T-cell differentiation and the development of allergic reactions. As skin colonization with nsidered .Streptococcus spp., Corynebacterium spp., Cutibacterium spp., Staphylococcus spp., Finegoldia spp. and Neisseria spp. can be found. The biodiversity of microbiota is generally decreased in moderate-to-severe psoriatic patients in contrary to mild psoriatic patients [Psoriasis is a common inflammatory disease that affects around 2–3% of the population . It manipatients .L. sporogenes for 15 days allieviated the symptoms accompanying the sudden onset of generalised pustular psoriasis in a 47-year-old female [B. infantis 35264 for 8 weeks [B. longum CECT 7347,  B. lactis CECT 8145 and L. rhamnosus CECT 8361 for 12 weeks resulted in a significant reduction in PASI scores [L. pentosus GMNL-77, both for five or seven days, causes a reduction in erythaematous scaling lesions, decreases TNF-α, IL-6, IL-23, IL-17A/F and IL-22 levels in the skin, decreases spleen weight and reduces the number of IL-17- and IL-22-producing CD4+ T cells in the spleen [B. adolescentis CCFM667, B. breve CCFM1078, Lacticaseibacillus paracasei CCFM1074, and Limosilactobacillus reuteri CCFM1132 ameliorated psoriasis-like pathological characteristics and suppressed the release of IL-23/T helper cell 17 (Th17) axis-related inflammatory cytokines. On the contrary, B. animalis CCFM1148, L. paracasei CCFM1147 and L. reuteri CCFM1040 neither alleviated the pathological characteristics nor reduced the levels of inflammatory cytokines [Leuconostoc mesenteroides NTM048 to imiquimod-induced mice suppressed erythema, scaling, upregulated IL-17 production, increased the levels of plasma deoxycholic acid and altered the faecal microbiota composition. Changes in the gut microbiome were indicated by the increased abundance of Akkermansia and a decreased abundance of Staphylococcus and Streptococcus [L. sakei proBio-65 resulted in an inhibition of the imiquimod-induced changes in the skin, as well as decreased IL-19, IL-17A and IL-23 levels [Bacteroidetes and decreased levels of Firmicutes, Proteobacteria and Actinobacteria, probably altering the intestinal barrier integrity, T-cell response and population-type balance, chemotaxis along with carbohydrate, cobalamin, and iron metabolism [Based on the reported alterations in gut microbiome, attempts were made to use probiotics and prebiotics in the treatment of psoriasis. Two original studies, one case report and four mice studies were published. In the case report described by Vijayashankar and Raghunath, a supplementation with d female . Groeger 8 weeks . In the I scores . In three spleen . In the ytokines . Ogawa etococcus . The onl3 levels . It was tabolism .L. acidophilus, L. casei, L. fermentum, B. bifidum), it had beneficial effects on the DFU size. It also decreased the serum total cholesterol and CRP and increased plasma nitric oxide (NO) and total plazma antioxidant capacity [The use of probiotics as a novel treatment for diabetic foot ulcers (DFU) was first published in 2014. It was suggested that the application of probiotic agents would enable the healing of diabetic ulcers and would prevent diabetic foot infections by activating Toll-like receptors and producing β-defensins, which stimulate skin immune functions . Mohsenicapacity .L. rhamnosus and L. paracasei strains in a 1:1 ratio against microorganisms previously isolated from chronic ulcerative lesions. Following the administration of probiotics, the growth of bacteria, compared to the control, was lower in the case of such bacteria as P. aeruginosa, C. striatum, A. baumanii, S. aureus, P. mirabilis in 75%, in the case of Candida parapsilosis in 93.75%, while in the case of E. faecalis 18.75%, and 50% for the mixed flora of the mentioned pathogens. The ability to co-aggregate all pathogens that could prevent adhesion and invasion was also shown [L. casei shirota topically and systemically during the onset of the healing of traumatic ulcers in Wistar rats. The number of fibroblasts and new blood vessels were significantly higher in the two intervention groups in a comparison with the control group [S. aureus and treated with L. fermentum, which secrets gaseous NO. The day after the procedure, treatment with the patch with a probiotic agent started and lasted for 21 or 20 days. Morphometric analysis of the ulcer healing revealed that it was significantly accelerated with this treatment method in both infected and uninfected ischemic wounds [Faecalibacterium prausnitzii (SPA and SPAH) for immune cell activity and wound healing in mice. They found that the presence of these strains in the gut exhibited significantly higher patterns of reepithelialization compared to controls by inhibiting NF-kβ activation. It resulted in decreased wound proinflammatory cytokine expression and induced myofibroblast and collagen transitions [L. reuteri was transformed with a plasmid containing the genetic material of the C-X-C Motif Chemokine Ligand 12 chemokine involved in accelerated wound healing. Additionally, the lactic acid produced by the probiotic bacterium lowered the pH and increased the bioavailability of the chemokine. This strain was applied to wounds in mice, accelerating ulcer healing, epithelialization, and wound closure [Most research was carried out using in vitro models, e.g., the effectiveness of a probiotic based on so shown . Kusumanol group . A furthc wounds . Stefia nsitions . In anot closure .L. plantarum was used in the treatment of chronic leg ulcers. The probiotic was applied to ulcers in 14 patients with diabetes and 20 non-diabetic patients. After 30 days of follow-up, 90% of the extent of ulceration had resolved in 43% of diabetic patients and 50% of non-diabetic patients. A decrease in CFU of S. aureus, S. epidermidis and P. aeruginosa was also noted. It was found that probiotics disrupt biofilm, regulate IL-8 levels and modulate the immune system [K. pneumoniae, E. faecalis and P. mirabilis) chronic wound. The patient received a mixture of probiotics  three times/week [The most relevant original work was published in 2010. e system . In addimes/week .Malassezia spp. [Malassezia strains in the seborrheic area and a satisfactory therapeutic effect of antifungal formulas [M. furfur, which elicit an inflammatory response from keratinocytes [M. furfur also possesses the ability to produce metabolites, which stimulate the aryl hydrocarbon receptor and thus may modulate the function of antigen-presenting cells [Seborrheic dermatitis (SD) characterized by erythematous, scaling plaques on the the face, chest and scalp ,147. It zia spp. . Researcinocytes ,149. M. ng cells .Vitreoscilla filiformis preparation in a double-blind study involving 60 patients with SD resulted in a reduction of itching, erythema and scaling. At the cellular and subcellular level, the lysate of these bacteria resulted in an increase in the activity of IL-10 produced by dendritic cells of the skin and an increase in the activity of regulatory T lymphocytes [There are limited data on the effects of probiotics and the modulation of the cutaneous microbiome on the course of SD. The use of superficial phocytes . Anotherphocytes . These eThe analysis of studies conducted both in animal models and in clinical trials, mostly showed at aleast partial positive effect of the use of probiotics on the healing of infected wounds by inhibiting microbiome growth, microfilm formation and interbacterial communication .L. plantarum. Peral et al. established the effectiveness of L. plantarum probiotic treatment with a topical application in human patients. L. plantarum would compete with bacterial pathogens and would be able to promote tissue repair [L. fermentum and L. delbruekii treatment in pediatric post-burn patients. They conclude that probiotic administration is safe to use and improves wound healing [L. casei resulted in the appearance of multi-drug sensitive P. aeruginosa instead of an extremely drug-resistant strain [B. infantis 35624 single-strain probiotics were more effective compared to Lactobacillus reuteri protectis in altering intestinal immunity [Among the various used bacterial strains, the most evidence exists for e repair . El-Ghaz healing . In a cat strain . Perdanaimmunity .L. plantarum and/or its by-products could be a potential therapeutic agent for P. aeruginosa burn infections [L. plantarum reduced P. aeruginosa in a rat model of burns [L. plantarum) suppressed the induction of TNF-α, IL-6 and IL-10 in liver and inhibited the accumulation of the pathogen in remote organs [L. plantarum as a therapeutic agent alleivates burn wound infection and scaring after burn injury in rabbits [L. plantarum has a protective role in non-infected burn wounds against meticillin-resistant Staphylococcus aureus (MRSA). Additionally, the therapeutic effect of L. plantarum was not shown in MRSA infection [Saccharomyces boulardii could effectively decrease the incidence of antibiotic-induced bacterial translocation in burned rats [Valdez et al. has been shown in adult inbred BALB/c mice that fections . Brachkoof burns . Argentae organs . Satish  rabbits . Sürmelinfection . Herek ened rats .Khan et al. demonstrated the importance of the method of probiotic application in a thermal burn mouse model. The use of the bioskeleton compared to traditional forms of probiotic application resulted in acceleration of epithelialization, collagen production and formation of hair follicles, as well as an inhibiton on the growth of pathogenic bacteria, reducing infection and accelerating wound healing . As a reC. difficile colitis by giving probiotics to burned patients in a critical condition. Otherwise, they found no significant difference in C. difficile infection between the control group and the intervention group [Fleming et al. performed a retrospective study in connection with preventing potential antibiotic-associated on group . Olguin on group .Due to the damaged intestinal barrier and the impaired immune system function caused by burns, there is a potential risk that probiotic bacteria may translocate and ultimately result in infection. Mayes et al. demonstrated the efficacy and safety of probiotics in the pediatric population hospitalized due to skin burns . HoweverCutibacterium acnes has been implicated as an important pathogenic factor. Fitz-Gibbon et al. compared the Cutibacterium strains in patients suffering from acne and healthy individuals, finding remarkable differences [Firmicutes, Clostridium, Clostridiales, Lachnospiraceae, Ruminococcaceae increased Bacteroides levels) [Acne is a chronic skin disease, affecting the pilosebaceous units, with multifactorial pathogenesis including hormonal influence, the immunological state of the host, diet, deregulation of insulin-like growth factor, excessive sebum production and FoxO1 deficiency ,153. Conferences . More anferences . The rol levels) .L. rhamnosus SP1 (LSP1) had been reported to bring health benefits to the patients such as LSP1 normalized skin expression of genes involved in insulin signalling and an improvement in the appearance of adult acne [B.lactis W51, B. lactis W52, L. acidophilus W55, L. casei W56, L. salivarius W57, and L. lactis W58 was reported to be a trigger for elevated IL-10 serum levels [E. faecalis SL-5 [Nitrosomonas eutropha [L. acidophilus showed improvement in the skin condition. L. acidophilus was also reported to decrease the population of C. acnes [C. acnes growth [L. reuteri on the proliferation of C. acnes and S. epidermidis [Bifidobacterium spp. [S. salivarius strains and one L. plantarum strain, were also reported to show antimicrobal activity in in vitro studies against C. acnes and other pathogens [A limited number of studies concerning probiotics and prebiotics use in acne is available. Yet, it is known that the beneficial components of the microflora may ameliorate skin lesions via the suppression of the Treg cell population. In addition, the suppression of B and Th cells due to the modulation of inflammatory cytokine production along with increasing IgA and butyrate secretion may also have an important effect . A cliniult acne . Howeverm levels . The resm levels ,128. Toplis SL-5 , Nitrosoeutropha  or L. acC. acnes . These fs growth . Similardermidis . Bifidobium spp. . as wellathogens .The present review focuses on a subject that is relatively new and is still not investigated in full detail. One of the major limitations is the small number of publications reporting clinical studies, especially multi-center, double-blinded, placebo-controlled clinical trials. The number of patients in the presented studies were usually low and many studies involved animal models, which cannot be extrapolated to humans. Since the exact pattern composition of a “healthy microbiome” is impossible to establish, there are no objective measures to investigate a universal model. The bacteria used in different studies presented various genera and properties; moreover, they were derived from different sources, often with no exact information on the method of production, storage and other properties. Moreover, the skin diseases presented in the paper were chosen based on their duration and the number of studies available; however, single studies show that the microbiome modulation, e.g., via a fecal microbiota transplant, may be also effective in the treatment of other dermatological conditions, for example in alopecia areata .It can be stated that the microbiome plays an important role in dermatological diseases, at the same time as being an attractive target of therapeutic interaction. This may contribute to the promotion of beneficial (from the point of view of inflammation) activation of the immune system, a reduction of the inflammatory state and, above all, could constitute a physical barrier to the colonization of the skin by pathogenic bacteria. The perspective of treating skin diseases with microbiome modulation via oral and topical probiotics, prebiotics or synbiotics are becoming a part of reality.L. plantarum and has showed at least a partial positive effect of the use of probiotics on the healing of infected wounds by inhibiting pathogen growth, microfilm formation and interbacterial communication. Concerning SD and acne, the very limited available data on probiotic administration have showed inconsistent results.There is a growing number of studies into the beneficial effects of probiotics in patients with atopic diseases. It is estimated that the oral application of probiotics or prebiotics during delivery or in the first months of life could delay or alleviate the appearance of AD in infants. From another point of view, probiotics could have the potential to reduce the SCORAD index as a treatment method. On the basis of the available evidence, a recommendation on probiotic intake in order to avoid AD cannot be currently made. Administering probiotics may influence the composition of the gut microbiome, which is more and more often considered to be a factor in the development of psoriasis. The suspected efficacy of probiotics in alleviating the course of psoriasis may be connected to lowering the levels of plasma pro-inflammatory cytokines. Since the data and the amount of research on this topic are limited, it still requires new, randomized, placebo-controlled trials, which would gain an insight into the pathogenesis and novel strategies of psoriasis treatment. There are very limited data available at the moment in the context of chronic ulcers. The positive effects of probiotics were shown mainly in studies focusing on ulcers resulting from diabetes complications. Probiotics may prevent or reduce the infection of burned wounds. Most research has focused on the The studies have shown that probiotics and prebiotics both administered orally or applied topically may have a positive influence on the course of skin diseases. Despite the continuous increase in promising data on the effectiveness of the use of probiotics and prebiotics, further clinical trials are needed to assess the efficacy and long-term safety profile of probiotics and prebiotics in the treatment of patients with dermatological diseases.