Demodex mites is a common occurrence, especially in adults and the elderly. More recent attention has been paid to the presence of Demodex spp. mites in children, even ones without comorbidities. It causes both dermatological and ophthalmological problems. The presence of Demodex spp. is often asymptomatic, thus it is suggested to include parasitological investigation tests in dermatological diagnostics, in addition to bacteriological analysis. Literature reports show that Demodex spp. are related to the pathogenesis of numerous dermatoses, including rosacea or demodicosis gravis, and common eye pathologies reported by patients such as dry eye syndrome or ocular surface inflammatory conditions, such as blepharitis, chalazia, Meibomian gland dysfunction, and keratitis. Treatment of patients is a challenge and is usually prolonged, therefore it is important to carefully diagnose and properly select the therapy regimen for the treatment to be successful, and with minimal side effects, especially for young patients. Apart from the use of essential oils, research is ongoing for new alternative preparations active against Demodex sp. Our review was focused on the analysis of the current literature data on the available agents in the treatment of demodicosis in adults and children.Infestation with  Demodex spp. mites. They are considered to be one of the most common microscopic ectoparasites [Demodex mites have been described that are associated with human demodicosis: D. folliculorum  and D. brevis  [Demodex spp. in humans is the subject of much debate since these microorganisms can be present in humans without showing any symptoms. It was found that this microorganism occurs in the majority of people over 60 years of age (84% of the population tested) and in all people over 70 (100%) [Demodex spp. play an important role in the development of many skin and eye diseases [Demodex spp. [Demodex folliculitis/abscess, demodectic prurigo, vesicular and follicular eczematidis, and demodectic post-inflammatory pigmentation. However, the exact prevalence of demodicosis in the human population has not yet been estimated [Demodex spp. mites on eyelashes were found in 12%. Microorganisms were present both in children without eye discomfort and in children with diagnosed eyelash abnormalities  associated with progressive demodicosis. Moreover, the relationship between living conditions and the higher incidence of Demodex spp. in children from rural areas was emphasized [Demodex spp. mites can also occur in humans as saprophytes, a therapeutic problem also arises. The search for the most effective treatment has been ongoing for years. In the case of ocular demodicosis, standard eyelid hygiene was used, sometimes with sulfur ointment, yellow mercury ointment, pilocarpine gel or local antibiotics, and anthelmintics. Therefore, there are attempts to develop alternative therapies that will be simultaneously effective and their potential for side effects minimized, e.g., with topical treatment based on tea tree oil (TTO) and terpinen-4-ol (T4O) [The human body is colonized by many microorganisms, including bacteria, fungi, and ectoparasites, often related only to the human body. The multicellular, external microorganisms inhabiting the human skin and other mammals include the arasites . The extm Simon, 842 and Dstimated , malignaDemodex spp. belong to a large group of mites with a very wide geographical range, covering many climatic zones. Currently, over 100 species are known, and the most significant species for humans are D. folliculorum and D. brevis. They are highly specialized parasites closely connected to their host, attacking different skin areas of one host  [Demodex spp. mites have a worm-like shape, and their surface is covered with a thin cuticle. Elongated D. folliculorum can be 0.3 to 0.4 mm long. Its presence is found in the outlets of hair follicles, in which it forms clusters composed of several individuals. Shorter and spindly in its shape, D. brevis reaches a length of 0.2–0.3 mm and also has shorter legs. It usually attacks alone and locates itself deep in the apocrine and sebaceous glands of the face, chest, Meibomian gland (causing its destruction), in the external auditory canal (causing periodic leakage and unpleasant odor from the ears), or in the genital area [tal area ,12.The life cycle of the parasite  is approDemodex has a gnathosoma with mouthparts, while the rest of the body is made up of podosome and opisthosoma. The Demodex folliculorum has chelicerae located on the gnathosoma, which are sharp, dagger-like, and more developed than in Demodex brevis. The function of chelicerae is to absorb and grind food, while legs are supported by pedipalps. Both Demodex species have four pairs of legs on the podosome [The anterior body of podosome . It is epodosome ,14. The podosome .Demodex spp. mites prefer moist and warm environments. Humans become infected with the parasite that penetrates healthy skin and looks for sebaceous glands in hair follicles rich in sebum. Ocular signs may include eyelash debris such as waxy debris, scaly debris, cylindrical dandruff, or erythema and telangiectasia of the eyelid [e eyelid ,16.Demodex sp., the life cycle, the mode of transmission, and its pathogenicity and coinfections in different age groups. Risk factors for infestations and accompanying symptoms, as well as prophylaxis, were taken into account. An analysis of routinely used diagnostic methods and available alternative therapeutic options was undertaken. Although there are more and more reports on this microorganism, opinions on its pathogenicity still vary. Therefore, the primary goal of our article was to review the literature reports on the currently used and alternative treatment options for Demodex sp. infestations, as well as the available, particularly routine, diagnostic methods in the diagnosis of demodicosis. A literature search was performed using PubMed and the Cochrane Library. Articles on the potential therapeutic possibilities of demodicosis have been limited to the years 1980–2022. The search covered original studies, guidelines, and syntheses. We also included some in vitro analyses of alternative preparations based on essential oils that can become helpful and effective in the fight against this microorganism. The analyses varied in both quality and design, some of which were randomized controlled trials.This review presents the anatomical features of Demodex sp. mites on humans causes direct damage. It leads to distension of the hair follicles, microabrasion, epithelial hyperplasia, and reactive hyperkeratinization (D. folliculorum), as well as mechanical blockage of the Meibomian glands and granulomatous reactions due to the presence of a chitinous skeleton (D. brevis). There are many factors involved in hair loss from Demodex spp. infestations and the process likely needs more research. Demodex spp. produce an immunologically active lipase that stimulates inflammation [Demodex spp. can lead to degradation of the follicle epithelium, and consequently, increased invasion causes excessive destruction of the hair follicles and perifollicular inflammation [Demodex spp., and extra-alveolar mites may induce a granulomatous reaction to the chitinous skeleton [Demodex spp. feed on sebum and keratinocyte debris [Demodex spp. and associated bacteria  acnes, Staphylococcus aureus) that are present in the hair follicles, and they induce these processes [Demodex spp., which correlates with a decrease in type 2 cytokines (IL-2). Research by Ricardo-Gonzalez et al., 2022 [Demodex spp. mite infestation. It was observed that as a result of their dysfunction and the loss of such a barrier, colonization of Demodex spp. resulted in increased epithelial proliferation and, through the current inflammation, genetic changes in repair programs, which consequently led to the depletion of the hair follicles [Demodex spp. acts as a vector for bacteria such as Streptococci, Staphylococci (on their surface), and Bacillus oleronius . They are believed to be a potential cause of chalazion and MGD. Additionally, Demodex spp. can induce an inflammatory response in the host through delayed hypersensitivity or an innate immune response of the host, due to the action of proteins present inside the mite, their debris, or waste [It is believed that the effect of ammation . In the ammation . In addiskeleton . An exame debris , and alte debris . Althouge debris , are yetrocesses . It is ior waste .Demodex spp. crawl, multiply, and excrete feces, and their entire life cycle takes place in the sebaceous gland. Dead individuals decompose into sebum and, together with the remaining feces, lead to mechanical and chemical irritation of the skin and hypersensitivity reactions. In addition, they trigger an immune response in the form of cellular activity with the participation of T lymphocytes and an increase in the production of pro-inflammatory cytokines, primarily IL-17. Kim et al. suggested that in the tears of patients with eyelid margin inflammation and ocular surface due to a Demodex sp. infestation, the concentration of IL-17 is higher in comparison to the people without Demodex spp. infestation [Demodex folliculorum activates IL-17/MMP-9 signaling and thus may even enhance the function of the corneal epithelial barrier [Demodex spp. infestation of a human host, the immune system response is stimulated with the participation of Toll-like receptors (TLR) [Demodex spp. exoskeleton, i.e., chitin [Demodex spp. are capable of secreting bioactive molecules, influencing the immune reactivity of sebaceous cells, and therefore they can modulate the TLR signaling pathway of the immortalized human sebocyte lineage. It was shown that the increase in the number of Demodex spp. influenced the secretion of interleukin-8 by these cells [estation . Zhang eestation  have sho barrier . Il-17 c barrier . Moreove barrier . During rs (TLR) . It is s, chitin . The enz, chitin . Lacey ese cells .Demodex spp. infection is known for its coincidence with bacterial and fungal infections, as it can facilitate the transmission of other microbes to adjacent tissues or other people [r people . ExampleDemodex sp. such as Acinetobacter calcoaceticus, Novosphingobium, and the Anoxybacillus and Pseudomonas genera [Demodex sp. infestation in patients with herpetic keratitis [Demodex spp. papulopustular rosacea or ocular rosacea, stimulation of the inflammatory response is observed due to the antigenic proteins and stimulation of cathelicidin production of B. oleronius [Demodex spp. [S. epidermidis [S. aureus with pathogenic potential [S. epidermidis is modified, leading to its participation in skin inflammation, as the antigens of this bacterium are recognized by TLR-2 [The studies of Liang et al., 2021  emphasizs genera . It has s genera . Moreoves genera  on coexieratitis . Due to leronius , bacteridex spp. . In addidex spp. ,43. Thesdex spp. . Moreovedermidis  or S. auotential . In the otential , the depotential . Therefootential . The actby TLR-2 . Therefoby TLR-2 . Demodex spp. Some studies indicate a 13% share of Demodex spp. infestations between the ages of 3 and 15 years, and at the age of 19–25, the percentage increases to 34% [Demodex spp. was demonstrated, with Demodex folliculorum dominance. The higher detection rate of Demodex spp. was correlated with the autumn–winter period. Children with Demodex spp. infection usually did not report any discomfort. In the subgroup aged 3–6, a higher percentage of infections was found in children from rural areas. On the other hand, in the subgroup of older children aged 7–14, the symptoms of demodicosis were found more often, e.g., abnormalities of the eyelashes, cylindrical dandruff, or a scaly discharge at the root of the eyelashes [It is now believed that children under 16 are relatively rarely affected by s to 34% . In a sts to 34%  on eyelaDemodex sp., but due to the low production of sebum, the density of this microorganism is low [Demodex spp. infestation. Dermatological demodicosis develops in young patients with primary or secondary immune suppression due to disease or drugs [Demodex spp. infestation may lead to severe inflammation of the face and eyelids [Demodex spp. infestation. Studies have shown that Demodex spp. is involved in infestations of up to one-quarter of malnourished children and one-third of children with cancer [Demodex spp. infestation, especially in children, are known. An example is the case of a 7-year-old immunocompetent girl described by Guerrero-Gonzalez et al., 2014 [Demodex sp. as an etiological agent in the development of eyelid inflammation and conjunctivitis in pediatric patients without reduced immunity, even in the first decade of life [Demodex spp. infestation in the pediatric population should be of particular concern. In eyelash studies by Huang et al., 2022 [Demodex spp. infestation occurred significantly more often  compared to the control group of children with non-inflammatory eye diseases (0%). Chalazia is considered a common pediatric problem due to its recurrence, higher frequency in children than in adults at a level of up to 25% [Demodex spp. as a risk factor for the development of chalazia in children is emphasized. In addition, special attention should be paid to preventive check-ups and comprehensive treatment in the case of an infestation in order to prevent the recurrence of a chalazion in children [Demodex spp. were found to influence its severity [Demodex spp. infestation in the pediatric population is also indicated by studies by Liang et al., 2010 [Demodex spp. in all analyzed patients, and the implemented treatment with TTO (tea tree oil) resulted in the resolution of eye irritation and inflammation and a reduction in the number of Demodex spp. Hence, even in the case of children without accompanying immunological disorders, it is worth considering demodicosis in blepharitis and conjunctivitis, especially in the case of therapeutic failures with conventional methods [It is believed that even close contact with the newborn in the first days of life or contact with the mother’s skin during breastfeeding is associated with the transmission of m is low . Moreoveor drugs ,51. In i eyelids . In the  eyelids  in immunh cancer . Not alll., 2014 . Long-tel., 2014 . There a of life . In chill., 2022  on 446 cp to 25% , poor cochildren . Xiao etchildren  also shoseverity . The impl., 2010  in patie methods . Demodex sp. increases with age, hence in middle-aged and older adults, it reaches 100%. Moreover, it reaches 84% of the total population over 60 and 100% of the total population over 70 [Demodex sp. in the general population is less than <5 Demodex sp./cm2. The average rate of infestation with Demodex spp. in the world population is estimated at approximately 60%. It can occur in the skin of people without any symptoms, and the infestation rate does not equal its incidence [Demodex spp. individuals on the human skin and the condition of the immune system [Demodex spp. in humans occurs primarily through direct contact with an infected person, e.g., contact with the skin of the face, kisses, shaking hands, using shared towels, bed linen, pillows, blankets, cosmetics , and hairbrushes at home, at a hotel, or at a hairdresser or beauty salon. Demodex spp., as well as other mites, can also spread through used clothes  [Demodex sp. among users [Demodex spp. was highlighted [Demodex spp. infestation was shown in 62% of people. The study found an increase in the incidence of Demodex spp. in patients over 50 years of age and in those who reported itchy eyes [Demodex spp. The analyses highlight the importance of such symptoms as helpful in determining the Demodex spp. etiology. Furthermore, it has been shown that the eye pathology of Demodex spp. etiology is attributed to individuals in the presence of mite numbers ≥ 2 [Demodex spp. as the etiological agent. Further under consideration is the potential use of corticosteroids in demodicosis or in the case of unrecognized demodicosis, which would alleviate inflammation and granulomatous reactions but, by impairing immunity, result in delayed clearance of the mites from the host’s body [Demodex spp. proliferation leads to demodicosis development, it may present a wide variety of non-specific symptoms, e.g., unexplained itching, dry and blotchy facial skin, hypersensitivity, or non-specific papulopustular and nodular lesions, while also imitating other dermatoses [Demodex sp. infestation is considered much more common in the elderly, the role of the patient’s age has not been fully explained, especially in ocular demodicosis. The study by Li et al., 2021 [D. brevis infestation, more severe corneal lesions, and MGL in young patients with demodicosis of the eye (<35 years of age) than in older patients (>45 years of age) with D. folliculorum dominance. In the study, differences in the symptoms presented by the patients were observed. For the elderly, eye dryness, eye fatigue, itching, and MGD (Meibomian gland dysfunction), which led to ocular surface discomfort, predominate. In younger patients, however, blurred and disturbed vision, eye pain, severe MGL (Meibomian gland loss), and corneal lesions were reported [Demodex sp. in ocular inflammation and blepharitis, it is believed that the increase in the number of Demodex sp. mites causes or worsens symptoms, although the minimum number necessary to induce symptoms has not been demonstrated so far [Demodex spp. infestation, and the contribution of age requires further analysis. Therefore, regardless of the patient’s age, appropriate diagnostics for Demodex spp. should be performed, if there are grounds for this.It is estimated that the incidence of  over 70 . It is encidence . The ince system ,58. Howee system . Spreadiclothes) . In studclothes) , it has ng users . Studieshlighted  of patiechy eyes . Researcchy eyes  in patiebers ≥ 2 . Therefot’s body . As Demormatoses ,62. Althl., 2021  showed hreported . Hence, d so far . Many scDemodex spp. has been considered the etiological factor of rosacea, chronic inflammatory dermatosis of the facial skin since the 1930s. Symptoms of facial dermatosis are manifested by the presence of many small, domed erythematous and maculopapular papules that arise against the background of permanent inflammatory erythema. It has been suggested that an increase in mite density per cm2 (>5) correlates with the pathogenic potential. Therefore, there is also a seasonal exacerbation of rosacea in the warmer spring and summer months, associated with the increase in the number of Demodex spp. Temperatures in the range of 16 °C to 20 °C have been found optimal for the development of Demodex spp. Additionally, it has been observed that temperatures below 0 °C and above 45 °C have a destructive effect on these parasites, and a temperature of 54 °C is lethal [s lethal .Demodex spp. also include follicular dandruff (associated with excessive use of make-up), perioral dermatitis (as a rash), scabies-like lesions, hairless scalp eruptions, Demodex folliculitis, demodicosis gravis (with skin granulomas), and sometimes even association with basal cell carcinoma. In the case of basal cell carcinoma (BCC), apart from UV radiation as the main cause, local factors, e.g., inflammation, irritation, or chronic trauma, are emphasized. Hence, the role of Demodex spp. in the etiopathogenesis of BCC is suggested, due to the main location of skin areas colonized by these mites, e.g., around the nose and eye sockets, most often affected by BCC and association with chronic inflammation. Therefore, due to the irritating/traumatic effect inducing chronic inflammation, the importance of demodicosis as one of the factors stimulating carcinogenesis in BCC of the eyelids in predisposed people is also emphasized [Skin diseases caused by phasized . Furtherphasized  showed tphasized . In addition, the relationship between the development of demodicosis in patients with a reduced state of the immune system, e.g., in connection with the use of steroid drugs or immunosuppressive preparations, and in the course of leukemia or HIV infection, is emphasized . Demodex mites from the skin of the face to the surface of the eyelids, many eye diseases have been observed. The following species are dominant: D. folliculorum  and D. brevis (deep in the Zeiss’ glands—sebaceous glands of the eyelashes and Meibomian glands). The presence of these microorganisms is not necessarily related to the disease state, as they can sometimes also appear in small numbers in asymptomatic individuals [Demodex spp. mites can be isolated in people who do not present symptoms of dermatological diseases, they constitute a conditionally pathogenic microbiome of the facial skin [Demodex spp. mites does not have to lead to symptoms such as acne vulgaris, rosacea, seborrheic dermatitis, or eyelid inflammation [Demodex spp. [Due to the possibility of the spread of ividuals . Some scial skin . On the ammation ,67, and ammation . Moreoveammation . Howeverdex spp. . Figure Demodex mites. In the case of the skin, the development of an infestation with Demodex spp. is initially characterized by small flaky lumps on the skin of the face, as well as a feeling of dryness and itching. The skin lesions of the face are most often located on the cheeks, paranasal areas, and eyelids. Demodex spp., primarily D. folliculorum, is the etiological factor of demodicosis (rosacea-like demodicodis), recognized as a disease since 1961. The existence of Demodex spp. is more often observed on the skin of patients with rosacea [Demodex sp. easier than men [Demodex folliculorum causes skin erythema, peeling, and dryness [2. In the course of rosacea, another characteristic symptom may be the maculopapular rash, and in this case, the number of mites is estimated at 36/cm2 [Clinical symptoms may also depend on the species of the  rosacea . It is s rosacea . Moreovethan men . Demodex dryness . Changest 36/cm2 ,76,77. Demodex spp. include exposure to sunlight, temperature changes, skin phototype, stress, and using stimulants, e.g., alcohol and tobacco [Demodex species D. folliculorum and D. brevis can lead to eyelid margin inflammation. Demodex folliculorum primarily causes the so-called “anterior blepharitis”, which is manifested by the characteristic keratin-fatty cuff at the base of the eyelashes. In addition, numerous telangiectasias are observed covering the edges of the eyelids with persistent itching, burning and redness, dryness, foreign body sensation and unusual visual disturbances, brittle eyelashes, and irritation leading to damage to the eye structures, e.g., the cornea. Eyelash growth may be impaired and eyelash loss may be observed, in addition to corneal lesions, Meibomian gland dysfunction (mainly in the case of Demodex brevis), and peripheral cloudiness [Demodex brevis, the so-called “posterior blepharitis” and symmetrical maculopapular eruptions are observed [Demodex folliculorum and Demodex brevis), is also an infection/colonization with bacteria  and fungi. MGD is caused by blocking the gland orifices and, in consequence, blocking the outflow of the secretions with the participation of, among others, Demodex brevis. A granulation reaction occurs, and a link between Demodex sp. and the formation of recurrent chalazions and styes has been suggested. Other changes related to the Demodex spp. infestation include, among others, dry eye syndrome, ulcerations, keratitis, and endophthalmitis. Recent literature reports the presence of the Demodex mite as one of the etiological factors in the development of basal cell carcinoma of the eyelids [The state of the immune system plays an important role. Additional factors predisposed to increased human colonization by  tobacco . The cou tobacco . Both Deoudiness . In the observed . The conobserved ,80,81. T eyelids ,64,82. TDemodex spp. detection in a patient’s biological material is based primarily on microscopic examination. Samples taken from the patient’s skin, hair, eyebrows, or eyelashes are used. The skin/epidermis samples are obtained from a surface biopsy using cyanoacrylate adhesive glue, skin biopsy, skin scrapings, or using adhesive tape. Eyelashes, eyebrows, hair, or pubic hair are collected via depilation/epilation [Demodex spp.: D. brevis from 100 to 200 μm and D. folliculorum from 200 to 400 μm, at the level of the spinous layer of the epidermis [Demodex spp. Superficial skin scraping (SSS) and tape imprint (TI), which are also applied to detect other parasites, can also be used as diagnostic tools [2 and allows the identification of living, moving parasites of Demodex spp. The analysis is performed using a microscope slide with a designated 1 cm2 spot containing a drop of cyanoacrylate glue placed on the skin in the affected area. Then, after approximately 30 s, the glass is removed and the material is covered with an immersion oil and a coverslip, and the analysis is performed under an immersion microscope [In the diagnosis of demodicosis, the most common method of pilation ,90. Othepilation ,87, and pidermis ,88. The pidermis ,92. Skinic tools . At timecroscope ,89,93. Acroscope .Demodex spp. infestation and confirmed demodicosis, the therapy is very complex. It is usually a difficult and lengthy process, lasting up to several months. The choice of drugs is an individual matter. Without an accurate diagnosis and effective treatment to eliminate Demodex mites from infected areas, microorganisms can continue to reproduce, causing recurring inflammation, the formation of uneven scars, dilated pores, dilated capillaries, extensive swelling, and pustules [Demodex spp. density reduction in the application of metronidazole systemic therapy, even in a short cycle, is indicated. The effectiveness of local therapy with permethrin, as well as crotamiton and benzyl benzoate, has also been demonstrated. However, the use of such agents may be associated with skin irritation in patients. Moreover, there are no unequivocal results of studies that standardize the treatment regimen and indicate its long-term effectiveness [In the case of a pustules . The goapustules . The imppustules . One of pustules . The systiveness .In addition, apart from antibiotics, various medicinal oils are used in therapy including camphor oil, bergamot oil, tea tree oil, peppermint oil, and salvia oil, as well as sulfur ointment, yellow or white mercury ointment, and choline esterase inhibitors ,98. AddiSome of the most commonly applied therapies, both conventional and alternative, have been summarized in Demodex mites externally and internally. Ivermectin is used alone or in combination with metronidazole, which leads to a higher effectiveness of the therapy in the treatment of ocular and skin lesions of Demodex spp. [Ivermectin works by combating dex spp. . Metronidex spp. . In the dex spp. . Demodex spp. [An alternative or complementary form of demodicosis therapy is the use of preparations of natural plant origin in the form of essential oils (EO). They are even more than 80% of a mixture of volatile compounds from the group of (a) terpenes and terpenoids and (b) aromatic and aliphatic components. Due to their antimicrobial and anti-inflammatory properties, they have found use in many therapies, although dosing must be strictly controlled . Researcdex spp. . Demodex spp. mites also plays an important role, e.g., cleansing the face twice a day with soap-free make-up remover, avoiding mineral oil-based preparations and oily makeup, and periodic exfoliation of dead skin [Demodex spp. occurrence. Therefore, preparations are sought to counteract the invasion and kill mites. Hence, essential oils or their active compounds, e.g., terpenes, provide great opportunities, in various forms, e.g., lotions, shampoos, ophthalmic liquids, gels, or ointments.Long-term treatment of demodicosis often has a short-term effect, therefore the prevention of excessive multiplication of ead skin . Skin hyTea tree oil exhibits strong antiseptic, antibacterial, antifungal, antiviral, and antiparasitic properties. It has been found to be effective against aerobic and anaerobic bacteria, molds, and dermatophytes. It has anti-inflammatory and regenerative properties, accelerates the renewal of the epidermis and the process of wound healing, and has the potential to heal ulcers. It supports the treatment of acne, eczema, lichen, and redness, especially in the course of demodicosis. Treatment (lasting approximately 4–6 weeks) using 50% of tea tree oil for intensive massages of the eyelids and daily hygiene and using a shampoo with tea tree extract has been shown to be very effective. It is intended for external use, although it is used in the form of aromatherapy or inhalation. It can also be used as an antitoxin against Australian spider venom. Safe application time is between 1 and 2 days in concentrations of 1–10%, and it can be applied for up to 6 months. In the case of demodicosis, the action of tea tree oil causes the expansion of mites to the surface of the eyelids, which, in turn, enables their thorough removal. The oil in a concentration of 50% used regularly (once a week) was found to have an excellent eradication effect. Studies by Gao et al. demonstrated effective control of ocular demodicosis using a weekly eyelid peel containing 50% TTO and daily peeling of the eyelids with a tea tree shampoo [1.  shampoo ,105,106.Salvia oil has a broad spectrum of applications. In general, salvia was reported to be used in the treatment of eye and skin diseases and oropharyngeal inflammation and possesses mosquito larvicidal properties [Demodex spp. effectively and rapidly, while salvia extract was found to be less effective, most likely due to the low content of the essential oils. The authors suggest that the terpenes in essential oils are responsible for the decreasing vitality of Demodex mites when applying Salvia preparations. [2. operties . Antitumoperties . Accordioperties , essentirations. . Peppermint oil has a broad application range, especially as a flavoring agent in the cosmetic and food industries. It is also proven to exhibit antiseptic properties [Staphylococcus aureus ATCC 25923, Enterococcus fecalis ATCC 29212, Escherichia coli ATCC 25922, and Candida albicans ATCC 90028 [Demodex mites when compared to tea tree oil and salvia oil [Listeria monocytogenes Scott A and Staphylococcus aureus ATCC 25923, two known foodborne pathogens [Demodex mites to match the inhibitory effect of more irritating oils, such as tea tree oil. 3. operties . Accordioperties , peppermCC 90028 . In the athogens . This caCastor oil is a natural derivative of the Ricinus communis plant. It is widely used in cosmetic products in the form of emollients  due to the ease of penetration through human skin, but also, among others, in dressings. It contains fatty acid, which facilitates the regeneration and reconstruction of eyelashes, stimulates their growth, and inhibits the process of hair loss. Castor oil is considered safe and well-tolerated. It has strong properties, including antibacterial, anti-inflammatory, analgesic, antioxidant, wound-healing, and vasoconstrictor aspects. Its important role in replenishing the physiological lipid deficiencies of the tear film, due to ricinolein acid, is indicated. As a result, when applied topically to the eye surface, it is characterized by extended residence time, stability, and an effect on the thickening of the lipid layer of the tear film. Castor oil can be used in the treatment of demodicosis with symptoms of eyelash and eyebrow loss [Demodex sp. mites, inflammatory processes, and clinical symptoms of eye dryness and discomfort, is characterized by therapeutic potential [4. row loss . A promirow loss , where crow loss . Hence, otential .Black seed oil—Nigella sativa L. (Ranunculaceae), also known as black cumin or black seeds, is a medicinal plant with historical value in traditional medicine used as an essential oil, but also as a paste, powder, or extract, indicated for the treatment of many diseases/conditions. Numerous scientific studies have shown the effectiveness of therapy with the use of black cumin seeds in the treatment of chronic diseases, including inflammation and parasitic infestations, and bacterial, fungal, and viral infections. Nigella sativa oil’s main active component, thymoquinone, plays an important role [Demodex spp. mites. It is widely used in the case of skin problems of various etiologies, including acne, blackheads, oily skin, pimples, discoloration, lack of firmness, and signs of aging. The oil softens the skin, soothes irritations, and improves its color. It has been shown to accelerate wound healing and moisturization by accelerating the formation of collagen and the rate of epithelialization. Moreover, it has an antipsoriatic effect [5. ant role , in addiant role . It has c effect . Topicalc effect  and in ac effect , withoutc effect . In addic effect .Bergamot oil (BEO) is primarily used as a fragrance oil, especially in aromatherapy. However, in addition to relaxing properties, it is used to treat skin problems and has antiseptic, cooling, toning, and soothing properties. BEO has remarkable biological activity, including pain relief, wound healing, and neuroprotective effects, as well as antimicrobial and anti-inflammatory and even anti-cancer properties [6. operties ,116,117.operties , which cDemodex spp. in humans, its role as a major contributor to human diseases, and the background of developing demodicosis with varied courses of disease. The vast majority of research studies concern adults and the elderly, although recently, more analyses also cover young adults, adolescents, and young children. There are many considerations about the presence of Demodex spp. is usually low in number and is considered a microorganism, sometimes referred to as a commensal sebaceous unit. However, when it occurs, it may develop a primary eruption or exacerbate facial dermatosis, with the dominance of maculopapular lesions, often on the skin of the face (including the nose) [Demodex spp. was found in 12% of respondents with eyelash abnormalities, including trichiasis, cylindrical dandruff, or flaky discharge at the base of the eyelashes [Demodex spp. infestation can cause severe inflammation of the face and eyelids as shown in a study by Damian et al., 2003 [Demodex spp. Therefore, in severe demodicosis, it is suggested that effective therapy should include the use of, for example, oral ivermectin in combination with topical treatment with permethrin [Demodex sp. was shown. They did not respond to conventional treatment only after introducing demodicosis infestation in pediatric blepharitis and conjunctivitis. Patients were treated with therapy lasting several weeks based on the use of 50% tea tree oil (TTO) in the form of eyelid peels or eyelid massage with 5% TTO ointment. In all patients, after a week of TTO treatment, an improvement in eye irritation and inflammation was noted, and the number of Demodex sp. decreased. It was also shown that corneal symptoms were essentially resolved within 2 weeks. Furthermore, although one of the patients had a recurrence of demodicosis, the re-introduction of TTO therapy was already successful. Therefore, the application of such a therapeutic model may be beneficial and effective, especially in the case of pediatric patients [In children and adolescents, he nose) . Zhang ehe nose)  conducteyelashes . In immul., 2003  in a 6-yrmethrin . In the rmethrin  in patiepatients . Demodex spp. not only with reduced immunity but also with malnutrition was indicated. Approximately one-quarter of malnourished children were infected with Demodex spp. A 6-month analysis based on the elimination of poor nutritional status led to the elimination of demodicosis in at least some of the patients [Demodex spp., especially in children. The condition of the immune system of an infected patient has a crucial impact on the development of the disease and the severity of symptoms . An incrDemodex spp. in the group of children with cancer, and maintenance treatment is necessary in order to prevent delays in the implementation of appropriate therapy [It is also worth mentioning the treatment-resistant maculopapular eruptions resistant to antibiotics caused by  therapy . Demodex spp. occurrence in patients in different age groups, there are certain factors that favor the multiplication of these mites and predispose individuals to the development of consequences of varying severity, including local immunodeficiency [In studies by Wu et al., 2019  BKC patificiency . The basficiency . Sometimficiency  emphasizficiency .Demodex sp. are related to the density of mite individuals, which include blocking of the mouth of the hair follicles. In addition, inflammation and the development of further complications are often associated with the transmission of bacterial infections, e.g., B. oleronius, S. aureus, or fungal infections carried along with the Demodex spp. [Demodex spp. and the formation of rosacea have a mutual influence, which can be considered in the development of effective therapies [Demodex spp. influence the innate and acquired immune response, and the cellular immunity of the attacked organism plays a key role [Demodex spp. mites [Researchers suggest that clinical changes resulting from infestation with dex spp. . In demodex spp.  showed therapies . It is skey role . Additiop. mites  on the ap. mites . On the p. mites .Demodex spp. in 1% of sage oil with paraffin was observed than in the case of triglycerides [Demodex spp. [Demodex species (D. folliculorum and D. brevis) that cause diseases in humans [Demodex spp. [In the treatment of demodicosis, various therapies are proposed, based on, among others, medications such as metronidazole, ivermectin, and permethrin, and antibiotics that work against possible bacterial co-infections. The importance of proper diagnosis and the implementation of effective therapy is emphasized, which, especially in the case of dermatoses, disfigures and stigmatizes patients . Currentycerides . TTO witycerides  on blephdex spp. . In addidex spp. , castor dex spp. , black sdex spp. , chia (Sn humans . In the dex spp. . Currentdex spp. . Demodex spp. can cause dermatological and ophthalmological problems. Infestation is reported as rather common in adults and the elderly, but more attention has been paid recently to the presence of Demodex sp. mites in children, even without comorbidities. The presence of Demodex spp. is often asymptomatic and, in many cases, patients struggle with undiagnosed ailments for a long time. Literature reports show that Demodex spp. are related to the pathogenesis of numerous dermatoses, including rosacea or demodicosis gravis [s gravis  and comm


Exophiala spp. is increasingly reported as a pathogen causing the cutaneous, subcutaneous or invasive infection. In this report, we present a case of cutaneous phaeohyphomycosis due to E. jeanselmei on the right hand of a farmer, who suffered from this disease three years ago which had not been definitely diagnosed until he was admitted to our hospital. In our hospital, a potential fungal pathogen was observed by histopathological examination, and then was recovered and identified as E. jeanselmei by sequencing its internal transcribed spacer region. After 4 weeks of antifungal treatment, his hand recovered very well. To investigate the in vitro susceptibility of E. jeanselmei isolates to antifungal agents and compare the characteristics of their related infections among immunocompetent and immunocompromised patients, we reviewed 84 cases published in PubMed database between 1980 and 2020. Alternaria spp. Phialophora spp. and Exophiala spp. . InE. jeanselmei was diagnosed based on the clinical features, histopathological examination, culture and ITS sequencing of the isolate.Accurate identification of the pathogen can provide an important basis for precise diagnosis and treatment of phaeohyphomycosis. Otherwise, prolonged disease process, disseminated or relapsed situation, even poor clinical outcomes might be brought about , 101. TrE. jeanselmei isolates to antifungal agents were also reviewed. As shown in Table E. jeanselmei [In our study, in vitro susceptibility of anselmei .Though ianselmei , 104. Voanselmei . Echinocanselmei . Terbinaanselmei . The lacanselmei .E. jeanselmei. The surgical resection was recommended for treating the phaeohyphomycosis in immunocompromised host, because the recurrence of the infection occurred in about 30.0% of these patients [According to ESCMID/ECMM guidelines, antifungal therapy combination with surgical excision was recommended for managing phaeohyphomycosis . In our patients . The surpatients . Modifyipatients , 96, 108patients .We also found that more than 80.0% of the cases occurred in the patients over 50 years old and 95.2% of the related infections presented as localized subcutaneous or cutaneous lesions. The trauma, particularly in the face and extremity (61.9%), might be the common cause of the infections, which could lead to the inoculation of the fungus in the cutaneous or subcutaneous tissue as described previously , 110.E. jeanselmei. As listed in Table In addition, we payed attention to the correlation between immunity status and clinical characteristics of the infections caused by E. jeanselmei, as demonstrated in our case. The findings of our review based on the cases reported in PubMed database indicated that E. jeanselmei isolates had good in vitro susceptibility to antifungal agents and immune status of the patients might not be correlated to the characteristics of the infections.In all, the results of histopathological examination, culture and species identification can provide the important basis for precise diagnosis and effective treatment of the infection due to


This article has been retracted: In July of 2020, the Academic Committee of Jiangsu Normal University launched an investigation of this paper and requested that the major authors provide the original experimental records and data for verification. To date, however, the authors have failed to provide the requested documents. The committee has concluded that this paper violates academic integrity. In light of this, the paper is retracted.101345-101361. https://doi.org/10.18632/oncotarget.21167Original article: Oncotarget. 2017; 8:101345–101361.


Agaricus bisporus, Agaricus subrufescens, Pleurotus eryngii and Pleurotus ostreatus, during batch culture in shaking flasks, was studied. Fungi were cultured for 26 days in defined media with glucose as carbon source and were primarily evaluated for their ability to consume glucose and produce mycelial mass and intracellular polysaccharides (IPS). Results showed that on the 26th day of cultivation, P. ostreatus produced the maximum biomass (16.75 g/L), whereas P. eryngii showed the maximum IPS concentration (3.82 g/L). All strains presented a similar pattern in total protein production, with A. bisporus having the highest percentage of total proteins . The calculated correlation coefficients among ribonucleic acid (RNA) vs. biomass (0.97) and RNA vs. protein (0.97) indicated a very strong relation between RNA and biomass/protein synthesis. The studied strains exhibited an increase in total glucan and glucanase  production during cultivation, with A. bisporus reaching the highest glucan percentage  and glucanase activity (12.7 units/g biomass). Subsequently, processed analytical data were used in contour-graph analysis for data extrapolation to optimize future continuous culture. The production of various biochemical compounds such as proteins, glucans and glucanases, from the mycelium of four strains of Basidiomycetes species,  Agaricus and Pleurotus being well-established in food and industrial uses  and observed that the maximum biomass, 4.5 g/L, was produced on 9th day. In contrast, when the fungus was grown on a substrate containing glucose (40 g/L) and extract (20 g/L) in flasks at an agitation rate of 120 rpm, the weight of the dry biomass was 20.49 g/L [P. ostreatus AMRL 150 was grown for 16 days in a similar medium to this study. In similar experiments with the same fungal species, it was also noticed that there is great variation in the produced biomass. For example, Sarris et al.  reporteda et al.  cultivatand Wang  used a m11.2 g/L . Kim et 11.2 g/L  culturedy et al. , culture0.49 g/L ,36. Fina0.49 g/L  achievedThe reported in literature variation in biomass production indicates that beyond genetic differences among strains of the same genus, there is also a need for additional studies to optimize media composition and culture conditions in order to establish large-scale continuous cultures for potential commercial production. A. bisporus, A. subrufescens, P. eryngii and P. ostreatus are presented in P. eryngii and P. ostreatus, reaching the maximum values of 3.82–3.56 g/L, whereas in A. bisporus cultures the respective values were stabilized between the 16th and 21st day and reduced afterwards, probably due to degradation. For A. subrufescens, a small amount of IPS was produced at the end of the cultivation period (1.3 g/L). It is also observed that all cultures resulted in IPS ranging between 20 and 40% w/w of the total biomass. Specifically, P. eryngii synthesized the highest IPS amount  exhibiting a small decline in the last days of culture, followed by A. subrufescens, A. bisporus and P. ostreatus. However, as reported by Krüzselyi et al. [w/w) compared to that of 62.77% in pileus and 78.36% w/w in stipes of fruiting bodies of P. eryngii. Additionally, it was observed that although A. subrufescens produced the lowest biomass of all strains, it produced a high IPS amount , similar to those of A. bisporus . It is also noticeable that in all cases, the highest values of IPS were produced in the early stages of cultivation, when biomass concentration was low, and as the mycelium mass was increasing, the concentration of IPS was decreasing. This indicates that part of IPS was used for cell structures, such as cell walls, leading to the observed increase in biomass. IPS accumulation and degradation, occurring when growth was limited by glucose depletion has been also reported in liquid cultures on glucose-based media with C/N 20 for Volvariella volvacea [Morchella esculenta and Flammulina velutipes [Tuber sinense [Ganoderma lucidum [Grifola umbellata [Mean absolute (g/L) and relative (mg/g) values of IPS produced by strains i et al. , the carvolvacea ,68, Morc sinense , Ganoder lucidum  and Grifmbellata . Differembellata . w/w values) are presented in w/w), except A. subrufescens in which protein levels were low . The maximum protein concentration was recorded for A. bisporus , followed by P. ostreatus  on the 21st day of culture, but no significant difference was observed between them. However, these values showed a significant difference compared to the maximum protein concentration of the rest two fungi. It is noticeable that P. ostreatus on the 6th day of culture had already reached a protein percentage of 8.17% (w/w), when the rest of the fungi presented values of 0.5–4% (w/w), being efficient in the production of proteins from the very first stages of culture when biomass concentration was still low. A. bisporus exhibited the highest rate of protein production between 6th and 12th day of culture, reaching almost its peak value on 12th day. In regard to protein production of P. eryngii, it is noticed that even though the carbon source was not completely consumed on the 21st day of culture, protein content was satisfactory . Results are comparable to those reported in literature, where according to Chang and Miles [P. ostreatus carposome is between 10.5 and 30.4%, w/w, while that of mycelial mass ranged from 14.31 to 29.76% w/w [P. eryngii was 24.52% w/w, which is higher than the protein content (18.91% in pileus and 11.34% w/w in stipes) of carposomes [w/w) protein content for A. bisporus mycelium. These data reveal that the protein content in biomass of P. ostreatus, P. eryngii and A. bisporus produced in the nonoptimized medium of this study was satisfactory. However, Chang et al. [w/w) proteins produced in the mycelium of A. blazei, a value relatively higher than that of A. subrufescens, which was used in the present study. The results of protein production of the fungi  where it is visually also noticed that its signal increases with biomass increase, reflecting the growth profile of each fungus during batch culture. It has to be mentioned that determined absolute RNA quantities by purification do not reveal actual RNA content, as purification technologies mainly aim to isolation of large RNA molecules for subsequent use in other analytical procedures with loss of short or degraded RNA ,77. The A. bisporus 0.435 and P. eryngii 0.379 mg/g) and the 26th day (A. subrufescens 0.372 and P. ostreatus 0.443 mg/g) of culture , indicating that production efficiency of this fungus is low at the early stages of culture. It has to be noted that although RNA values per unit biomass (mg/g) tend to be similar at the end of the culture, the actual RNA yield of each fungus varies significantly (Maximum purified RNA quantity per dry weight (mg/g) appeared on the 21st  were observed in A. bisporus after 21 days  and P. ostreatus after 26 days  of culture. The max value of A. bisporus was significantly different to the corresponding values of the three rest fungi, while the maximum values of A. subrufescens and P. eryngii were similar (not significantly different), 4.7%, w/w and were achieved at the end of the cultivation period. Since most of the glucose is consumed during the last stages of fermentation, producing biomass, the positive correlation of glucan production with biomass production was expected . These data indicate that the mycelium of A. subrufescens is quite high in glucans and this fact may increase interest in the wide cultivation of this mushroom [w/w mainly reflects metabolic behaviors but may not correspond to final yields. A decrease in the concentration of glucans was detected for mushroom . FinallyP. ostreatus contained 4.64 w/w of β-glucans, while the carposome contained 9.05; values higher than those of A. bisporus that were 3.79 and 6.00 w/w, respectively. Toledo et al. [P. ostreatus contained larger amounts of glucans, followed by P. eryngii and A. subrufescens, which had similar values, and then A. bisporus. Finally, the mycelium of P. eryngii was the poorest in glucans, compared to those of the above fungi . Total glucan-production patterns of the four fungi in relation to biomass are presented in A. bisporus appeared to be the most efficient of the studied strains in regard to its content of glucans. On the contrary, P. ostreatus, having consumed 99% of the carbon substrate at the end of the culture, produced the maximum biomass and had the highest yield of glucans among all strains. Production of polysaccharides such as glucans from P. ostreatus species is important and is under thorough investigation not only for their nutritional properties, but also for their biological value in medicinal applications. They are investigated as immunomodulators, antigens in the formulation of vaccines for cancer therapies, as well as for cholesterol reduction [A. subrufescens on the 26th day of culture exhibited a higher percentage of glucans than P. eryngii, despite the fact that its biomass production was almost half that of P. eryngii. These data indicate that the mycelium of A. subrufescens, contrary to its low biomass production, is efficient in glucan synthesis, and this is one of the reasons for the increasing interest in the cultivation of this mushroom [In previous studies, the concentration of glucans in the mycelium has been compared to that of the carposomes. According to Nitschke et al. , the myco et al.  analyzededuction ,13,14. Imushroom . β-glucamushroom .A. bisporus and P. ostreatus  had reached the certain day with almost two-fold higher activity, which is significantly different in comparison to the rest of the fungi. Their maximum glucanase activity coincides with their maximum protein concentration and RNA quantity of that day. A. subrufescens had much lower and delayed production of glucanases until the 16th day. Instead, P. eryngii showed a low increase in the enzyme activity values presenting a maximum at 26th day. It appears that the production of glucanases is a process related to the growth stage of the fungus, as these enzymes were highly produced during the later log and the stationary phase of biomass production. The activity of the fungal glucanases might be triggered in response to carbon-source reduction in the growth medium. These enzymes hydrolyze glycosidic linkages of sugars, thereby might release glucose units in their environment from fungal cell walls. In the present study, glucose was used as a main carbon source, consumed during culture to produce biomass. It seems that fungi perceive the decrease in available glucose levels and scavenge carbon sources by increased enzymatic activity. Glucanases are enzymes that are specialized in the hydrolysis of specific glycosidic bonds. Endo-1,3-β-D glucanase production of the four fungi, expressed as units of enzyme activity per g biomass, is presented in A. bisporus and P. ostreatus, the total glucose amount in the growth media was mostly consumed on the last day of culture, while A. subrufescens and P. eryngii had consumed around half of their glucose source at the same day.As has been already mentioned, the production of glucanases increased from the first days of cultivation when the carbon source was not a limiting factor . This phA. bisporus, exhibiting a wider flexibility in the combinations of biomass-production rate with carbon-source-utilization rate, while P. ostreatus shows the potency for the highest glucanase production of all strains. However, these observations need further experimental verification in continuous cultures.It is noticed from the data of the batch fungal cultures that there is significant variability in the production of glucans and glucanases among the studied fungi. Thus, optimization for future continuous cultures will need large-scale experimental designs that become cumbersome and costly. As a first step for optimizing future continuous production, batch-culture results were further statistically analyzed using response 3D surfaces and contour graphics to extrapolate potential culture parameters . ResultsA. bisporus strain seems to be the most efficient in glucan and glucanase  production. RNA analysis also showed that RNA production can be a valuable prognostic biomarker of successful cultures, as it is strongly correlated with fungal growth. The yields of the fungi in terms of the studied characteristics are not related to the genera of the fungi, but each fungus is an independent case. Since the medium and culture conditions were identical in all cases, differences observed in the biomass production, growth rate and substrate consumption reflect mainly the genetic diversity of the fungal strains. However, this conclusion would be clear if more species of fungi were compared per genus.All fungi showed the ability to produce glucans and glucanases. Based on the results from the batch cultures and extrapolated-data analysis, the


Children has a significant publication record on the topic of Atopic Dermatitis (AD) the past four years. In this commentary, the author highlights those specific articles and provides clinical pearl(s)/perspectives taken from the review of the article. The journal Children has included an excellent group of manuscripts and reviews of AD, and future reviews can include more recent and potential therapies. The biggest obstacle in pediatric AD care is the slow expansion  of approved medication/therapies for the younger pediatric AD population, especially biologics. The author provides perspective on each manuscript and thoughts on the status of AD therapy in children.The journal New Cosmetic Formulation for the Treatment of Mild to Moderate Infantile Atopic Dermatitis. de Lcas R et al. [R et al. .Comment: There is probably nothing more vexing for caregivers and healthcare providers than picking a moisturizer for base therapy in AD children. The authors used an extensive subjective and objective data collection to monitor the benefits for a new complex topical agent. Less relevant to their product is a good review of the underlying skin dysfunction in AD children and the multiple components of their benefits to their product. The product is in lotion form and attempts to repair the multitude of skin barrier issues seen in AD. The small sample size and its eventual international availability limits the usefulness of the product.The Role of Probiotics in Preventing Allergic Disease. Wang, H.T. et al. [. et al. .Comment: In this relatively up-to-date review of probiotics in general in allergic diseases, with an emphasis on AD and food allergy, the authors report on three systematic studies of probiotics in AD with encouraging results and two studies with more contradictory data. They conclude that further studies are warranted.Biologic Treatment Options for Pediatric Psoriasis and Atopic Dermatitis. Cline, A. et al. [. et al. .Comment: A now somewhat dated review of biologic therapies for AD.Pathophysiology of Atopic Dermatitis and Psoriasis: Implications for Management in Children. Chovatiya, R. and Silverberg, J.I. [rg, J.I. .Comment: A excellent and concise review of pathophysiology and therapy options for AD. Extensive references. Worthy of attention for interested parties.Complementary and Integrative Therapies for Childhood Atopic Dermatitis. Adler-Neal, A.L. et al. [. et al. .Comment: A Pub-Med approach to what is known or available on alternative therapies for pediatric AD. A very extensive list of probiotics used in AD is presented. A much shorter discussion on vitamins, minerals, and herbal products is presented. Interestingly, no mention of Vitamin D was included. References are limited to searched publications.Topical and Oral Therapies for Childhood Atopic Dermatitis and Plaque Psoriasis. Frantz, T. et al. [. et al. .Comment: Both AD and psoriasis are intermingled in the review. It provides a good companion to the review of Chovatiya and Silverberg [lverberg . There iQuality of Life and Disease Impact of Atopic Dermatitis and Psoriasis on Children and Their Families. Na, C.H. et al. [. et al. .Comment: There are few greater complexities as a Pediatric Allergist than to explain the complex pathophysiology of asthma and its effect on pulmonary function, especially when severe asthma is present, as patients may facilitate to their internal disease. Not as difficult is AD, when the disease’s consequences are so visible. The indices of Quality of Life (QoL) scales in AD are discussed. Good references are provided.The Role of the Microbiome in Food Allergy: A Review. Nance, C.L. et al. [. et al. .Comment: The skin in patients with atopic dermatitis (AD) has a significant skewing to an abnormal microbiological population. It is conceivable that a GI bacteria or skin-applied bacterial transplant could have a future role(s) in AD therapy or earlier resolution.Breastfeeding and Allergic Disease: What’s New? Nuzzi, G. et al. [. et al. .Comment: The role of breast feeding as a protection from AD is limited. In some circumstances, partially digested food transferring from the breast milk to the child may be a cause for sensitization or potentially triggering atopic dermatitis flares in infants, and this topic has been reviewed recently [recently .Addressing Common Misconceptions in Food Allergy: A Review. Anagnostou, A. [stou, A. .Comment: Sensitization to food is not uncommon in AD in children. Food allergy becomes a true IgE-mediated disease with immediate and potentially significant outcomes. The astute clinician needs to separate sensitization from AD causation but also be aware of concomitant sensitization and food allergy in an AD patient.Atopic Manifestations in Children Born Preterm: A Long-Term Observational Study. Pagano, F. et al. [. et al. .Comment: In a case–control study, gestational diabetes was significantly associated with AD, and pre-term birth before 29 weeks was negatively associated with AD. The relatively small numbers from a single neonatal center may not hold up in large populations, but extensive references provide some perspective.The Association between the Concentration of Heavy Metals in the Indoor Atmosphere and Atopic Dermatitis Symptoms in Children Aged between 4 and 13 Years: A pilot study. Choi, H.S. et al. [Comment: A selected population in cities on a Korean island served as the study basis. Indoor pollutants and heavy metals were measured in homes of children with or without AD. Significant differences for children’s AD were found in volatile organic compounds (VOC) and lead in their homes (elevated for both). The small sample size limits the applicability.Skin Disease in Children: Effects on Quality of Life, Stigmatization, Bullying, and Suicide Risk in Pediatric Acne, Atopic Dermatitis, and Psoriasis Patients. Kelly, K.A. et al. [. et al. .Comment: Using a Pub-Med search strategy, quality of life, bullying, and suicide risk were explored in several chronic skin conditions, including AD. These issues are important but often overlooked downsides to the lives of children with AD. They also explored the potential that allergic inflammation has CNS effects.Barrier Impairment and Type 2 Inflammation in Allergic Diseases: The Pediatric Perspective. Ghezzi, et al. [, et al. .Comment: Although not directly about AD, this review discussed an under-recognized component of AD: the barrier defect that maybe intrinsic to AD but certainly becomes worse with AD. This is a review worthy of mention for its background review of the barrier dysfunction in AD but also asthma and eosinophilic esophagitis. A worthy read.Atopic dermatitis, along with asthma and eosinophilic esophagitis are exceedingly complex allergic diseases. A small consolation is the greater potential for resolution of AD during the pediatric years , althougThe prevention of atopic dermatitis is an incomplete picture, with parental atopic dermatitis having a strong genetic predilection, although the co-factor of filaggrin mutations also has a strong association. Overcoming genetic factors allowing AD to occur may be difficult . PotentiThe early childhood presentation of eczematoid skin conditions, coupled with underlying filaggrin mutations presents a perplexing scenario for halting the atopic march . AlthougEarly moisturizers addition has had a role as a prevention product. This approach was recently summarized . It is pOther pre-AD development strategies, in part, could include vitamin D supplementation, pro-biotics, or nutritional modifications. Whether aggressive microbiome adjustment in highly susceptible children might be of future value has been postulated . Bleach-At present, biological modifiers are not approved in the United States for atopic dermatitis until age 6. Duplimab, an anti-IL-/IL-13 monoclonal antibody, is, however, in clinical trial in children as young as 6 months, with preliminary data presented at the Revolutionizing Atopic Dermatitis Conference in 2021 . Future Consider the pre-biologic medication sphere  physicians live in when taking care of moderate to severe pediatric AD patients . TopicalChildren, particularly Reviews on chronic skin conditions in children and especially atopic dermatitis. Topics have ranged from basic pathophysiology to treatment to psychological components of chronic skin disease. This has been an outstanding grouping of articles, with the potential to add to the care of children with AD. However, major limitations persist in AD prevention and early childhood therapy. With new therapies forthcoming, additional publications in Children on the atopic dermatitis care of children and adolescents are welcomed.With a current 2020 impact factor of 2.863, the past four years has seen an impressive group of manuscripts in


The general framework of landscape genomics for tree conservation as published. We missed the proper citations about plots of FST outlier test, cluster and RONA which were depicted in In the original article, there was a mistake in the legend for In the original article, there was a mistake in Rheum palmatum complex in the Eastern Asiatic Region. Mol. Ecol. 29, 1791-1805. doi: 10.1111/mec.15448 was not cited in the article. The citation has now been inserted in the legend of In the original article Feng, L., Ruhsam, M., Wang, Y. H., Li, Z. H., and Wang, X. M. (2020). Using demographic model selection to untangle allopatric divergence and diversification mechanisms in the FST outlier test and RONA are modified from Du et al. (The general framework of landscape genomics for tree conservation. The plots of cluster, u et al.  and Fengu et al. , respectThe authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Antibiotics, as pollutants of emerging concern, can enter marine environments, rivers, and lakes and endanger ecology and human health. The purpose of this study was to review the studies conducted on the presence of antibiotics in water, sediments, and organisms in aquatic environments . Most of the reviewed studies were conducted in 2018 (15%) and 2014 (11%). Antibiotics were reported in aqueous media at a concentration of <1 ng/L–100 μg/L. The results showed that the highest number of works were conducted in the Asian continent . The highest concentration of antibiotics in water and sea sediments, with a frequency of 49%, was related to fluoroquinolones. According to the results, the highest amounts of antibiotics in water and sediment were reported as 460 ng/L and 406 ng/g, respectively. In rivers, sulfonamides had the highest abundance (30%). Fluoroquinolones (with an abundance of 34%) had the highest concentration in lakes. Moreover, the highest concentration of fluoroquinolones in living organisms was reported at 68,000 ng/g, with a frequency of 39%. According to the obtained results, it can be concluded that sulfonamides and fluoroquinolones are among the most dangerous antibiotics due to their high concentrations in the environment. This review provides timely information regarding the presence of antibiotics in different aquatic environments, which can be helpful for estimating ecological risks, contamination levels, and their management. Today, drugs are an integral part of life and are used to treat diseases of humans and other organisms . AntibioAntibiotic compounds have different mechanisms in cells, such as suppression of cell wall synthesis, inhibition of nucleic acid synthesis, modification of cell membranes, suppression of protein synthesis, and inhibition of DNA, depending on the different functions of the molecule .Some antibiotic molecules are metabolized in the bodies of humans or animals, while most 70–90%) are excreted unchanged via feces and urine ,6. The a0–90% areThe accumulation of antibiotics in different parts of aquatic environments threatens the relevant ecosystems and affects the health of humans and other organisms. Antibiotic residues in marine ecosystems cause the spread of antibiotic-resistance genes, and also lead to serious environmental problems. Connecting antibiotics to pathogens and transferring them to the human body  can cause severe human risks . The preRecently, due to the high production and use of antibiotics and the emergence of antibiotic-resistance genes in aquatic environments, the attention of researchers around the world has been drawn to this issue . To imprThe Web of Science database was used to find published articles related to the present study. Additionally, for a specialized search, keywords such as ‘Antibiotics + Marine environment’, ‘Antibiotics + Sediment’, ‘Live creatures + Antibiotics’, ‘Antibiotic + river + lake + marine + Sea + sediment + organism + water body’, and ‘Review Antibiotics + microorganism + biota’ were used. There were 99 articles on antibiotics in sediments, water, and biota in the environments (aquatic environments), as well as several review studies. To draw the figures, first, the studies were categorized by year, parts of aquatic environments, country, and continent, and then the graphs related to each item were drawn using Excel software. ow), distribution coefficient (Kd), separation constants (pKa), vapor pressure, and Henry’s law constant (KH) [According to their chemical structures, antibiotics are classified into several groups, including macrolides, beta-lactams, tetracyclines, quinolones, fluoroquinolones, sulfonamides, phenicols, and penicillin . The tenant (KH) . Antibioant (KH) . The preant (KH) . Fluoroqant (KH) . Accumulant (KH) . AntibioMacrolide (ML) antibiotics form a group of 12–16 organ lactone rings that are replaced with one or more sugars (amino sugars). Other characteristics of this group include being lipophilic, having low solubility in water, and being weakly acidic. Macrolides are generally bacteriostatic; however, some of these drugs may be bactericidal at very high concentrations ,37. ThisBeta-lactam antibiotics include a wide range of molecules that contain at least one beta-lactam ring in their molecular structures. These drugs are active against many Gram-positive, Gram-negative, and anaerobic organisms, interfering with the cell wall synthesis of reproducing bacteria . The preSulfonamides (SAs) are derived from a p-amino-benzene-sulfonamide functional group. This group has acidic and basic properties . These aTetracyclines are one of the main groups of antibiotics used for veterinary and human medicine, agriculture, and as food additives to enhance the growth of animals. These are amphoteric and degradable antibiotics that are unstable in bases but stable in acids. These antibiotics cause severe environmental problems and serious damage to human health. Since conventional WWTPs are not able to fully eliminate these micropollutants, the removal efficiency of tetracyclines in treatment plants has been reported between 12 and 80% ,43. StudThe quinolones’ properties are fat-solubility and resistance to acidic hydrolysis, alkalinity, high temperatures, and ultraviolet radiation damage. This group has many applications, including the treatment of infectious diseases and the promotion of livestock and aquaculture. They enter aquatic environments through untreated human and animal wastewater or direct discharge from aquaculture products .Over the past decades, the presence of antibiotics in the environment has created concerns around the world. Antibiotics are widely used in human and veterinary medicine and enter the environment through different pathways. The presence of antibiotics in the sludge and effluent of municipal treatment plants, hospitals, industrial centers, and livestock farms has resulted in the occurrence of pollution in marine environments, surface water, soil, and groundwater . ConsumeThe antibiotics SMT (15–328 ng/L), SMZ (20–174 ng/L), and TMP (4–7 ng/L) had the highest concentrations among the 12 studied antibiotics in Vietnamese waters . In a std, s) is used. However, because there is no dynamic adsorption between sediment and water, this value cannot be considered an accurate partition coefficient [Sediments are considered to be reservoirs of pollution and receive large amounts of organic pollutants . Antibiofficient . Negligifficient . Factorsfficient . High cofficient . Other ffficient . The confficient . Zhang efficient . Arikan fficient . AntibioInvestigating the occurrence of antibiotics in aquatic environments helps us to assess their potential threat to ecosystem balance . AntibioAs the use of antibiotics is increasing in industrialized and developing countries, it has led to the identification of these contaminants in surface waters, sediments, and biota around the world. The entry of antibiotics into aqueous media takes place through several sources. Most wastewater treatment plants are not able to effectively remove antibiotics, so their output can contaminate surface waters with antibiotics . The antow partition coefficient. If the degree of ionization is not high and the Kow partition coefficient is not between 2 and 6, the concentrations of antibiotics in oysters decrease [Lutjanus russelli, Lutjanus erythopterus, and Trachinotus ovatus), mollusks , crabs , and shrimps (Fenneropenaeus penicillatus) in southern China, concluded that enrofloxacin was a high-concentration antibiotic in the muscles of the studied samples [Oncorhynchus mykiss) [Antibiotics are widely used to treat bacterial infections in humans and animals. Some are also used as growth stimulants in pigs  and plandecrease . Extensidecrease . Figure  samples . Sulfame samples . In Bang samples . In anot mykiss) . Table 5Detect the concentrations of antibiotics in more aquatic organisms.The function of antibiotics is different in different organisms; therefore, it is necessary to study the concentrations of antibiotics in different organisms  simultaneously.Since antibiotics can accumulate in sediments of aquatic environments, it is recommended that future studies study the concentrations of antibiotics in sediments at different depths.The widespread use of antibiotics and the lack of advanced sewage treatment systems in developing countries have caused the pollution of water sources, necessitating more detection of antibiotic contamination and the improvement of treatment systems to remove pollutants.The present study reviewed the reports of antibiotic concentrations in different parts of aquatic environments . It can be concluded that among the different antibiotics, fluoroquinolones and sulfonamides had the highest concentrations in most of the studied environments. The average concentration of fluoroquinolones in sea, lake, and river sediments was 539.79 ng/g, while in sea and lake water it was 204.85 ng/L and 369.74 ng/L, respectively. Moreover, sulfonamides had the highest concentrations in rivers, with an average concentration of 191.11 ng/L. Antibiotics in aquatic tissues such as shrimp, fish, etc., can threaten the health of humans as consumers of these aquatic organisms. The average concentration of fluoroquinolone, as the most abundant antibiotic in marine organisms , was reported as 145.77 ng/g. Among different countries around the world, the highest concentrations of antibiotics were reported in China. Furthermore, the results of the studies conducted in aquatic environments showed that the environments that are exposed to various effluents  have higher concentrations and a greater variety of different antibiotics. Therefore, it is necessary to take the required approaches to reduce the entry of these pollutants into the environment. The following recommendations can be made for future investigations:Conceptualization, Z.M. and A.M.S.; methodology, T.M. and B.R.; software, M.S.; validation, S.F., B.R., T.N. and M.S.; investigation, Z.M. and T.N.; resources, T.M.; data curation, B.R.; writing—original draft preparation, B.R. and T.M.; writing—review and editing, M.S.; visualization, B.R.; supervision, M.S. All authors have read and agreed to the published version of the manuscript.


Kleine–Levin syndrome (KLS) is characterized by episodes of hypersomnia. Additionally, these patients can present with hyperphagia, hypersexuality, abnormal behavior, and cognitive dysfunction. Functional neuroimaging studies such as fMRI-BOLD, Positron Emission Tomography (PET) or SPECT help us understand the neuropathological bases of different disorders. We conducted a systematic review to investigate the neuroimaging features of KLS patients and their clinical correlations. This systematic review was conducted by following the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) and PRISMA protocol reporting guidelines. We aim to investigate the clinical correlation with neuroimaging among patients with KLS. We included only studies written in the English language in the last 20 years, conducted on humans; 10 studies were included. We excluded systematic reviews, metanalysis, and case reports. We found that there are changes in functional imaging studies during the symptomatic and asymptomatic periods as well as in between episodes in patients with K.L.S. The areas most reported as affected were the hypothalamic and thalamic regions, which showed hypoperfusion and, in a few cases, hyperperfusion; areas such as the frontal, parietal, occipital and the prefrontal cortex all showed alterations in cerebral perfusion. These changes in cerebral blood flow and regions vary according to the imaging  and the task performed while imaging was performed. We encountered conflicting data between studies. Hyper insomnia, the main feature of this disease during the symptomatic periods, was associated with decreased thalamic activity. Other features of K.L.S., such as apathy, hypersexuality, and depersonalization, were also correlated with functional imaging changes. There were also findings that correlated with working memory deficits seen in this stage during the asymptomatic periods. Hyperactivity of the thalamus and hypothalamus were the main features shown during the asymptomatic period. Additionally, functional imaging tends to improve with a longer course of the disease, which suggests that K.L.S. patients outgrow the disease. These findings should caution physicians when analyzing and correlating neuroimaging findings with the disease. The first cases of Kleine–Levin syndrome (K.L.S.) were described by Kleine and Levin separately, in 1925 and 1929, respectively . K.L.S. The disorder is characterized by episodic hypersomnia; each episode lasts ten days and recurs every 3.5 months on average . PatientThe cases also report normal periods of cognition and behavior in between these episodes . A studyThe etiology of this syndrome is not well understood. It is hypothesized that hypothalamic pathology plays a role in the development of the syndrome, but an exact association has not been made . Other pThis syndrome is diagnosed using the International Classification of Sleep Disorders. Radiological investigations conducted in cases of K.L.S. were mostly to identify and treat potential causes such as meningitis or encephalitis (CSF), focal brain lesions (brain imaging), or epilepsy (E.E.G.) .Among all the treatment modalities available, no definitive treatment has been found. In one study, 41% of patients showed termination of episodes and a “clear mind” with amantadine, an antiviral with dopamine reuptake inhibitory capacity . Their sThis systematic review was conducted by following the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) and PRISMA protocol reporting guidelines ,11.We included observational studies, defined as case–control studies and cohorts, conducted on humans and written in the English language. Animal studies were excluded. We excluded papers that did not fulfill the aims of our study. After screening the studies, we included papers with one of the following characteristics: (1) patients with KLS; (2) intervention: use of functional imaging to evaluate the patients such as fMRI, SPECT; (3) comparator: there was not a comparison because of the low prevalence of the disease; and (4) outcomes: areas of the brain with hypo/hypermetabolism, hypo/hyperactivity, during episodes and between the episodes of KLS.We used the PubMed and Google Scholar databases for this systematic review. The search was conducted between December 2021 and January 2022. We used an advanced search strategy with the following terms: (“Kleine Levin Syndrome” [Title/Abstract] AND “MRI” [Title/Abstract]) OR (“Kleine Levin Syndrome” [Title/Abstract] AND “SPECT” [Title/Abstract]) OR (“Kleine Levin Syndrome” [Title/Abstract] AND “fMRI” [Title/Abstract]) OR (“Kleine Levin Syndrome” [Title/Abstract] AND “Imaging” [Title/Abstract]).We collected from each paper in the first table the following information: the author, year, country, age, sex, number of participants, and methods of the study.We collected from each paper in the second table the following information: the author, year, country, functional study, and areas with hyper/hypometabolism or hypo/hyperactivity. We used the Robins-1 analysis for bias assessment in each study . We found 10 observational studies that specifically discussed the role of functional imaging in patients with K.L.S.; There were five studies that reported cases in the asymptomatic period, one study in the symptomatic period, and four studies in both periods. Hypometabolism, less activity or hypoperfusion were found in seven studies such as Engstrom et al. in 2016, Engstrom et al. in 2009, Huang et al. in 2005, Dauvilliers et al. in 2014, Dudoignon et al. in 2021, Ket et al. in 2014, Engstet et al. in 2014. This hypometabolism was located mainly in the frontal, temporal, occipital, lobe, thalami, and cingulate zone. On the other hand, hypermetabolism, greater activity or hyperperfusion was established in five studies: Engstrom et al. in 2009, Dauvilliers et al. in 2014, Dudoignon et al. in 2021, Engstrom et al. in 2014, Vigren et al. in 2013. The increased of activity was presented mostly in the thalamus and prefrontal cortex. A total of 4 out of the 10 studies established limitations; a major limitation was the absence of a matched control group in Vigren et al., 2014 and Dudoignon et al., 2021. A heterogeneous group of patients participated; they had no similarities in state of disease, some were assessed while having K.L.S. episodes, while, others were in remission. Symptomatology and disease duration were not similar either. Due to these features, perfusion patterns could change and be associated with specific symptom patterns such as those found in Vigren et al., 2014. Additionally, in Dudoignon et al., 2021, the FDG-PET/CT was performed in a single expert center that is highly experienced in K.L.S., which means they were more capable of detecting subtle changes in K.L.S. brain imaging, unlike many other studies. Another limitation was found in Engstrom et al., 2014, where there was no adjustment for the time when the patients had their last episode in the data analysis. Finally, Vigren et al., 2013 includes some limitations, such as technical issues in Magnetic Resonance Spectography (M.R.S). Technology at the time of the study design. Additionally, the latter presented different limitations related to the analysis of the results, as the use of a voxel of interest in the M.R.S. study—including the entire thalamus and not only the anterior-medial parts—may also cause individual variation of N acetyl aspartic acid (NAA)-concentrations in both groups and could contribute to a variable distribution of the thalamic neurons. Furthermore, the absence of a significant difference in thalamic levels of N.A.A. between patients and controls is an argument against a primary thalamic dysfunction. We found multiple relationships between K.L.S. clinical features and the different affected areas of the brain with different neuroimaging studies. The asymptomatic period in K.L.S. is free of hypersomnolence attacks but working memory task deficits remain. Additionally, functional imaging is abnormal between episodes . Functional imaging in patients with K.L.S. is similar to other central parasomnias such as narcolepsy. Patients with narcolepsy have decreased activity in the frontal, anterior cingulate, and parietal areas. At the same time, the parietal region of patients with K.L.S. seems to be unaffected ,27. AddiThree studies showed increased thalamic activity during the asymptomatic period, correlating with working memory task deficits using fMRI ,22,23. HIn the first two studies, thalamic hyperactivity correlated with lower activation in the anterior cingulate and dorsomedial prefrontal cortex . The autIn Dudoignon et al.’s study, more patients with hippocampal hypometabolism had working memory deficits than those without hippocampal metabolism . ExecutiN-acetyl aspartate (NAA) is a biomarker of neuronal loss and malfunction, so a decrease in the NAA levels suggests neuronal deficit . Vigren Significant connections between the pons and the frontal eye field have been established before. In 2016 Engstrom et al. found decreased connectivity between the frontal eye fields and the pons compared to controls , while nA previous case report found a disrupted connection between the thalamus and the pons . Still, The study by Engstrom 2014 analyzed working memory pathways in patients with K.L.S., specifically the executive network and the salience networks during the asymptomatic phase . The salRegarding the executive network, K.L.S. patients had increased activation in the left dorsolateral prefrontal cortex (DLPFC) and the left hemisphere in the region of the posterior parietal cortex (PPC) tested . This fiRegarding the salience network, K.L.S. patients have increased activation of the left thalamus, more activation of the right anterior cingulate cortex (ACC), and decreased activation left insular cortex (AIC) . The lonDecreased perfusion in the temporal and occipital cortex was related to depersonalization and derealization. The more the patients suffered from depersonalization/derealization, the greater the affected area . The corIn the Dudoignon study, hypometabolism in the posterior associative cortex and hippocampus and increased metabolism in the prefrontal cortex was associated with the younger onset of age and shorter course of the disease . HypometDecreased level of consciousness can be explained by the involvement of the reticular activating system because there might be disruption between the connection in the thalamus  and cerebral cortex. Lesions of the thalamic nuclei also have been reported to cause limbic symptoms . AnotherOther studies suggest that the connections between the brainstem and the thalamus can be diminished during a hyper somnolent state. This finding suggests a relationship between the thalamus and the brainstem, which regulate sleep and wakefulness . The ascWhile imaging modalities have revealed hypoperfusion of both thalami on SPECT imaging during the symptomatic period in K.L.S. patients, its potential clinical implications have not been thoroughly investigated . In contDepersonalization and derealization were correlated with hypoperfusion in the left and right parietal-temporal junction . The angThere was more hypoperfusion as compared to control in the right dorsomedial prefrontal cortex . PatientAs suggested by AlShareef et al., abnormal sexual behavior may orientate towards hypothalamic dysfunction; however, the hypothalamus seems to be intact . This suThere have been many reports showing the hypermetabolism of the striatum during the symptomatic period of patients with K.L.S. Some authors, such as Haba-Rubio et al., explain that this enhanced activity in the striatum occurs due to compensatory mechanisms surrounding the primarily affected regions ; howeverThe disease seems to improve over time. In one study, there was less activation in the asymptomatic period in the anterior cingulate cortex, left precuneus, and left occipital cortex in the second examination compared to the first examination using fMRI . A seconRegarding remission, almost half of the patients that have undergone remission showed the persistence of the same pattern. This may imply that some patients could have chronic and persistent cognitive deficits and maybe a non-basic course of the disease . KLS patVirgen et al. concluded that SPECT may be a diagnostic aid only for experienced neurologists able to recognize and consider K.L.S. and its differential diagnoses as potential causes of hypersomnia in young patients. SPECT has a low sensitivity (48%) and should not be used as the only diagnostic tool for K.L.S. . In the Our findings reflect that there are changes in functional imaging studies during symptomatic, asymptomatic, and between episodes in patients with K.L.S. These changes vary according to the study  used to identify these modifications; some of them are conflicting.Hyper insomnia, the main feature of this disease during the symptomatic periods, was associated with decreased thalamic activity. Other features of K.L.S., such as apathy, hypersexuality, and depersonalization, were also correlated with functional imaging changes. Some findings correlated with working memory deficits seen in this stage during the asymptomatic periods. Hyperactivity of the thalamus and hypothalamus were the main features shown with these working memory deficits during the asymptomatic periods. Additionally, functional imaging tends to improve with a longer course of the disease, suggesting that K.L.S. patients outgrow the disease. These findings should caution physicians when analyzing and correlating neuroimaging findings with the disease.


Juniperus L. is the second-largest genus of conifers, having the widest distribution of all conifer genera. Its phytogeographic history is, however, obscure due to its very poor fossil record. We described a wood of Juniperus sp. from the lower Maeotian sediments of the Popov Kamen section, Taman Peninsula, South Russia, in order to clarify its taxonomic position shedding light on the phytogeographic history of the genus. This fossil wood was well-preserved by mummification, which allowed for it to be studied by the same methods as used for the anatomical examination of modern woods. The wood from the Popov Kamen section shows the greatest similarity to the extant Mediterranean species J. excelsa, belonging to the section Sabina. This is the first reliable macrofossil evidence of the sect. Sabina from Eurasia convincingly dated to the Miocene. The age of the mummified wood from the Popov Kamen section is consistent with molecular dating of diversification of the lineage comprising juniper species of the sect. Sabina from Europe, Asia and eastern Africa. The wood of Juniperus sp. has not been buried in situ, as it was found in the relatively deep-water marine sediments. The available coeval pollen series and macrofossils of Cupressaceae from the surrounding regions suggest that this wood was likely transferred by sea current from the northwestern side of the Black Sea, which was a part of the Eastern Paratethys. Juniperus L. is the second-largest genus of conifers, and the largest member of the family Cupressaceae. Comprising 75 species Genus Sabina Spach, 1841Section Juniperus sp.Material: PK-2020, three fragments of well-preserved mummified wood from an entire fossil stem, discovered from the Late Miocene sediments of the Popov Kamen section, Taman Peninsula, South Russia, deposited at the Laboratory of Paleobotany, Komarov Botanical Institute, St. Petersburg, Russia. Duplicates of these samples were deposited at the Department of Paleontology, Geological Faculty, Moscow State University, Moscow, Russia .Growth rings are distinct, 0.19–1.60 mm wide; the transition from earlywood to latewood is gradual A. EarlywThe axial parenchyma is abundant, tangentially zonate A and occRays are exclusively uniseriate D, compleDark-stained compounds are common in axial parenchyma cells and occur in ray cells. Crystals are not found.Fitzroya cupressoides (Molina) I.M. Johnst. and eight speices of Juniperus . Among these species, the presence of marginal axial parenchyma has been reported only in J. drupacea [J. excelsa and J. oxycedrus [J. drupacea and J. oxycedrus are distinctive, however, from the fossil wood from Taman Peninsula by larger pits on tangential tracheid walls  and also by the occurrence of higher  rays. The latter species also differs from the wood sample under study by fewer (mostly 1–2) pits per cross-fields [J. excelsa shows greater similarity with the Miocene wood, but it differs from the fossil wood in thinner horizontal walls of the ray cells, and the occasional occurrence of biseriate rays [The fossil sample from Taman Peninsula represents a typical homoxylic wood, showing the tracheids bearing large (up to 24 µm in diameter) circular bordered pits on radial walls as well as exclusively uniseriate rays. This suite of traits occurs only in conifers. The InsideWood  search fdrupacea , J. excexycedrus ,20. J. ds-fields . J. exceate rays ,20,21.Juniperus species having this trait. Apart from J. drupacea, J. excelsa and J. oxycedrus, marginal axial parenchyma has been reported in J. conferta [J. monosperma (Engelm.) Sarg., J. thurifera L., J. scopulorum Sarg. and J. tibetica Kom. [J. scopulorum and J. thurifera differ from the fossil wood from Taman Peninsula by the occurrence of larger pits (>10 µm in diameter) on tangential walls of tracheids [J. thurifera is also distinctive by much more numerous rays , lower ray cells , and the lack of indentures [J. conferta has mostly unpitted end walls of ray cells [J. scopulorum, J. monosperma, and J. tibetica share the occurrence of higher rays  than the fossil wood from Taman Peninsula. The latter two species and J. conferta are also distinctive from the sample under study in having fewer (up to three) pits on cross-fields [As the presence of marginal axial parenchyma is a prominent feature of the fossil sample from Taman Peninsula, which is uncommon in the wood of conifers, we compared it with other extant conferta , J. monoica Kom. ,20. J. sracheids . J. thurdentures . Unlike ay cells . Then, Js-fields .Juniperus, but it cannot be convincingly placed into any modern species that have been examined to date by wood anatomists. It shows the greatest similarity to the Mediterranean species J. excelsa, belonging to the section Sabina.In summary, our fossil wood belongs to the genus Juniperoxylon Houlbert [Juniperus [Juniperoxylon pottoniense (Stopes) Kräusel from the early Cretaceous of England [J. wagneri Süss & Rathner from the Miocene of Germany [Juniperoxylon, including J. zamunerae Ruiz & Bodnar from the Middle Triassic of Argentina [J. breviparenchmatosum Watari & Nishida from the Eocene of Hokkaido, Japan [Juniperoxylon acarcae Akkemik, from the early Miocene of the central Turkey [J. juniperoides (Kownas) Huard, J. pachyderma (Göppert) Kräusel, J. rhenanum Burgh from North Rhine-Westphalia [J. schneiderianum Dolezych from Lusatia [Juniperus sp. from the early Miocene of the Galatean Volcanic Province, northwestern Turkey [The fossil homoxylic woods showing a combination of spaced arrangement of circular pits on radial tracheid walls, cupressoid cross-field pits, nodular transverse walls of axial parenchyma cells and usually also nodular walls of ray cells have been ascribed to the genera Houlbert ,23 and Juniperus ,24. Juni England  and the  England  and J. w Germany  are distrgentina ; J. brevo, Japan ; Juniperl Turkey ; and foustphalia  and J. s Lusatia , differ n Turkey , show grSabina of the genus Juniperus, as well as to the early Miocene woods from the northwestern Turkey assigned to the Juniperus sp. Although the studied sample is distinctive from any woods of modern or extinct junipers described to date, its anatomical traits are not sufficient for its reliable taxonomic attribution. Thus, we do not consider the fossil wood as a new species of this genus, but designate it as Juniperus sp. seemingly belonging to the section Sabina.Overall, the mummified wood from the late Miocene deposits of the Taman Peninsula shows a close affinity to some extant species from the section Juniperus sp. from the lower Maeotian sediments of Taman Peninsula is the first reliable macrofossil evidence of the section Sabina from Eurasia whose age is convincingly dated to the Miocene. The most ancient fossils of junipers attributed to this group have been described from the Eocene/Oligocene boundary of north Bohemia, the Czech Republic [Sabina includes three extinct species from the Oligocene to the middle Miocene of the North America [J. foetidissima from the Miocene–Pliocene boundary from the Sofia Basin, Bulgaria [J. sabina from Bashkortostan, Russia [Juniperus sp. from the Popov Kamen section shows that the species of this lineage occurred in the regions adjacent to Eastern Paratethys at least since the early Maeotian age.The mummified wood of Republic . More re America ,9,10,11 Bulgaria , and the, Russia . The mumJuniperus sp. has not been buried in situ, as it was found in relatively deep-water marine sediments. The only coeval occurrence of the pollen grains ascribed to Juniperus sp. has been reported from the lower Maeotian deposits of Odessa Oblast, southern Ukraine [J. bessarabica Negru has been described from the lower Sarmatian of Moldova [Juniperus, i.e., to another lineage of junipers than the fossil wood under study attributed to the section Sabina. Cupressaceae have not been reported, however, in other pollen series studied in the Sarmatian and Maeotian deposits of the Eastern Paratethys regions, including those from the Taman Peninsula [Juniperus have also been found in coeval paleofloras in southern Ukraine [Juniperus sp. was likely transferred by sea current from the northwestern side of the Black Sea, which was a part of the Eastern Paratethys in the Miocene. Transportability of driftwoods over large distances has been supported by strong evidence [Obviously, the wood of  Ukraine . More an Ukraine . As for  Moldova  (Figure eninsula ,36, the eninsula , Bulgarieninsula , Abkhazieninsula  and seveeninsula . No macr Ukraine , Krasnod Ukraine  and Geor Ukraine ,42,43. Tevidence .Juniperus sp. shows the greatest similarity to the extant Mediterranean species J. excelsa, belonging to a well-supported “clade IV” within the section Sabina [J. thurifera, the Asian J. chinensis and J. polycarpus, as well as J. procera from east Africa and south Arabia. As suggested by molecular dating [Juniperus sp. from the Popov Kamen section. The reported fossil records of this group, up to now, are too sparse, however, for detailed reconstruction of its phytogeographic history.The fossil wood of n Sabina . This lir dating , this liThree fragments of totally mummified portion of entire tree trunk, 23 cm in length and 7 cm in diameter, without any traces of organisms feeding , were coSince its first description by Andrusov , this geThe fossil wood in this study was well-preserved by mummification. This specimen was processed and sectioned using the same methods as used for modern wood. The wood samples were boiled in water for about one hour and sectioned with a sledge microtome. Transverse, radial and tangential microtome sections of 20–30 µm in thickness were stained with alcian blue/safranin  or left