Treatment of horizontal neck wrinkles by Endolift laser: Biometric measurement.

BACKGROUND: One of the common esthetic complaints of patients is horizontal neck wrinkles that have limited treatment modality. AIM: In the present study, we evaluated the efficacy of the Endolift laser on the horizontal neck wrinkles. METHODS: Totally, 10 healthy female and male patients suffering horizontal neck wrinkles were joined in this study. All patients are treated with Endolift laser. The effect of the Endolift methods on the horizontal neck wrinkles was evaluated by biometric parameter changed results with Cutometer, Visioface, and the Skin Ultrasound Imaging system. Also, three blinded dermatologists and patients' satisfaction were evaluated. RESULTS: The Visoface results showed that the Endolift laser treatment significantly decline the depth and area of horizontal neck wrinkle. The skin ultrasonography results reported the epidermis and dermis density and thickness were significantly increased. Also, the cutometer outcomes displayed that the Endolift laser treatment can increase skin elasticity. Also, significantly a greater number of patients were well satisfied with the technique. CONCLUSION: In conclusion, Endolift laser is a safe and effective method for decreasing the horizontal neck wrinkles and improving the appearance of the neck. This procedure does not require general anesthesia and recovery time.

Evaluation of the effects of adding an adipose tissue-derived stromal vascular fraction to platelet-rich plasma injection in the treatment of androgenetic alopecia: A randomized clinical trial.

BACKGROUND: Stromal vascular fraction (SVF) cells derived from adipose tissue and platelet-rich plasma (PRP) are among novel treatments for androgenetic alopecia (AGA). We aimed to investigate the effect of adding SVF to PRP and compare it to administering PRP injection alone. METHODS: Eighteen patients were randomly divided into two groups of nine. The PRP group was treated with PRP at all three visits at 1-month intervals, while the SVF-PRP group received an SVF injection on the first visit and a PRP injection on the second and third visits. Each group was evaluated at baseline and 20 weeks after the therapy's initiation. RESULTS: Changes in mean hair diameter and hair count compared to baseline were significant in both groups. The PRP group experienced a greater increase in mean hair count than the SVF-PRP group, and the SVF-PRP group had a marginally greater increase in hair diameter than the PRP group. These differences were not statistically significant compared to each other. The patient and physician assessment scores exceeded the mean (on a scale from 0: poor to 3: excellent) in both groups. CONCLUSION: Adding one SVF injection to two PRP treatment sessions versus three PRP injections alone had no significant difference in evaluated variables. If additional research demonstrates the same results, we suggest that multiple SVF injection sessions may be required to produce a statistically significant difference compared to PRP injection alone. Moreover, considering lower cost and greater accessibility of PRP, it can be used before SVF in the treatment of AGA.

Evaluation of the efficacy of mesenchymal stem cells derived conditioned medium in the treatment of striae distensae: a double blind randomized clinical trial.

BACKGROUND: Striae distensae is a disfiguring atrophic skin condition that impairs the body's aesthetic image. Despite the variety of conducted studies, there is controversy regarding the best modalities. Human mesenchymal stem cells are considered a rich source for scar treatment. Skin needling is among the most efficient and safe aesthetic and therapeutic devices. This study aimed to evaluate the efficacy of the combination of needling and intradermal injection of mesenchymal stem cells compared to skin needling alone for treating striae distensae. METHOD: This study was a randomized, double-blind clinical trial involving 10 women aged 18-60. Each striae lesion was divided into two parts, with one side receiving needling and intradermal injection of conditioned medium, while the other side received needling and intradermal injection of normal saline. This treatment was administered in three sessions with three-week intervals. Patients were evaluated before the first intervention and three months after the final session. Three months after the completion of the intervention, patients' lesions were evaluated using biometric criteria, physician evaluation, and patient self-assessment. RESULTS: The results demonstrated a significant improvement in dermal and complete thickness and skin density in patients treated with microneedling. All skin ultrasound parameters improved significantly in patients receiving the combination of needling and conditioned medium. When comparing the two groups, significantly higher physician and patient satisfaction was observed in the combination group. However, the comparison of biometric indices improvement wasn't significant between these groups. CONCLUSION: The combination of human mesenchymal stem cells with microneedling could be considered a novel effective option for stretch marks.

The role of BAFF and BAFF-R inhibitors in the treatment of immune thrombocytopenia; a focused review.

Immune thrombocytopenia (ITP) is an autoimmune-driven disease characterized by increased destruction and impaired platelet production resulting in an enhanced risk of bleeding. Immunosuppressant agents are the most common treatment strategies for ITP. Despite their efficacy, these medications often cause unpredictable side effects. Recent investigations revealed that patients with ITP exhibit elevated B-cell activating factor (BAFF) levels in both their spleens and serum. Belimumab, a BAFF inhibitor, illustrated a promising therapeutic avenue for managing ITP by interfering with BAFF activity and long-lived plasma cell production. Both clinical and experimental studies have yielded positive outcomes when combining rituximab with an anti-BAFF monoclonal antibody in treating ITP. In addition, ianalumab, a monoclonal antibody with a dual mechanism that targets BAFF-R and deletes peripheral BAFF-R+ B cells, is currently being used for ITP treatment [NCT05885555]. The upcoming results from novel BAFF inhibitors, such as ianalumab, could offer clinicians an additional therapeutic option for treating ITP.

A systematic review of interleukin-31 inhibitors in the treatment of prurigo nodularis.

BACKGROUND: Prurigo nodularis (PN) is a neuroimmunological skin disease. Severe itching is the most challenging symptom which affects patients' quality of life. T helper 2-derived cytokines, such as interleukin-31 and oncostatin M (OSM), play a crucial role in PN pathogenesis. Nemolizumab and vixarelimab are two biologics acting as IL-31 inhibitors. Vixarelimab also suppresses the OSM activity. This systematic review evaluates the efficacy and safety of nemolizumab and vixarelimab in PN management. METHODS: A systematic search was conducted in PubMed/Medline, Ovid Embase, and Web of Science up to September 17th, 2023. Clinical trials and cohort studies published in English were included. RESULTS: Among a total of 96 relevant records, five were included. The results of four studies with 452 patients using nemolizumab showed that a significantly higher percentage of patients treated with nemolizumab demonstrated a reduction in peak pruritus numerical rating scale (PP-NRS) and investigator's global assessment along with improved sleep disturbance (SD) and quality of life than the placebo group. Moreover, one study administered vixarelimab to 49 PN patients, and their finding illustrated a higher rate of subjects who received vixarelimab experienced ≥ 4-point diminution in worst itch NRS, visual analog scale, healing of representative lesions, and SD quality compared to the placebo group. CONCLUSIONS: IL-31 inhibitors suggest distinct advantages in improving pruritus, sleep quality, and overall quality of life in subjects with moderate-to-severe PN. Further clinical studies are recommended to compare the effectiveness of these biologics to other therapeutic choices.

The FEDBD plasma's quantitative investigation of skin parameters: Skin elasticity, thickness, density, tissue oxygenation, perfusion, and edema.

This study used the FEDBD plasma device for skin rejuvenation in animal samples. There were two groups of six male Wistar rats. Before starting the treatment, immediately after the treatment, the fourth week, and the tenth week of follow-up, biometric tests were performed, including moisture level, evaporation from the skin surface, erythema and melanin, skin elasticity and firmness with an MPA9 device and cutometer. The thickness and density of the epidermis and dermis, an essential indicator in rejuvenation, were evaluated with a skin ultrasound device. Also, the level of oxygen, perfusion, and interstitial water (edema) was checked using a Tivita tissue hyperspectral camera at a depth of 6 mm of the skin.

Exploring the Efficacy of Fractional Carbon Dioxide Laser as an Add-on Combination to Conventional Therapies for Treatment-Resistant Vitiligo (A Review Article).

Introduction: Vitiligo, a dermatological disorder that leads to depigmented skin patches, presents a significant challenge, particularly in resistant areas such as acral regions. Fractional CO2 laser therapy holds promise as an adjunct to conventional treatment, enhancing repigmentation. This review comprehensively explores its efficacy and safety in resistant-to-treatment vitiligo. Methods: We conducted extensive database searches in PubMed, Embase, and Cochrane, focusing on English-language literature published between 2012 and 2023. We included comparative studies that met the following criteria: (1) Participants had non-segmental vitiligo, with resistant-to-treatment localization engagement; (2) The treatment involved the use of fractional CO2 laser in combination with conventional therapies; and (3) Outcomes were assessed based on the repigmentation ratio or significant difference. We excluded studies from which data from published results could not be extracted. Results: After extensive screening of 52 articles, we finally selected five studies. The results showed that fractional CO2 laser therapy, when combined with other treatments, often shows promise in vitiligo treatment in refractory cases. Although individual responses varied, overall efficacy and safety were promising, with minimal adverse effects and no severe complications. Conclusion: The fractional CO2 laser, when used in conjunction with conventional therapies, emerges as a promising option for treating refractory vitiligo. Large-scale randomized trials and a deeper understanding of the underlying mechanisms are vital for future progress in optimizing treatment protocols, case selection, and safety.

Efficacy evaluation of endolift laser for treatment of nasolabial folds and marionette lines.

BACKGROUND: The nasolabial folds are the most marked sign of aging. Endolift laser was used for the treatment of nasolabial folds and marionette lines (one of the facial danger zones). METHODS: Ten female subjects were engaged in this study. Patients underwent Endolift laser for nasolabial folds and marionette lines treatment. The efficacy of the Endolift technique on the nasolabial folds and marionette lines was evaluated by biometric assessment with Cutometer, Visioface, and the Skin Ultrasound Imaging system. Also, patient's satisfaction and blinded dermatologists' assessment were assessed. RESULTS: The Visoface results displayed that the Endolift laser treatment significantly declined the depth and area of the nasolabial wrinkles. The skin ultrasonography results reported that the epidermis and dermis density and thickness were significantly increased. Also, the cutometer outcomes showed that the Endolift laser treatment can increase skin elasticity. The results showed that a large number of patients were very satisfied with the technique. CONCLUSION: In conclusion, Endolift laser has an effective technique for decreasing the nasolabial folds, marionette lines, and improve the appearance of the face without any sever side effect. This technique does not need general anesthesia and recovery time.

The Therapeutic Efficacy of Freeze-Dried Human Amniotic Membrane Allograft Gel for Diabetic Foot Ulcers: A Phase-1 Clinical Trial.

Diabetic foot ulcers (DFUs) are classified as hard-to-heal wounds, which occur in approximately 15% of diabetic patients. Several interventions have shown efficacy in reducing the risk of amputation among patients with DFU, including timely diagnosis and management of infection and ischemia, debridement of necrotic tissues, reducing mechanical pressure on ulcers, and patient education. One major challenge in the management of DFUs is optimizing wound care to improve healing outcomes. Recently, interdisciplinary approaches proposed a new generation of wound dressing which increased efficacy and significantly decreased the healing time. The current study assessed the healing characteristics of chronic DFUs treated with lyophilized amniotic membrane gel (LAMG) in combination with standard care, versus a placebo hydrogel with standard care. In total, 18 patients (8 male, 10 female) were randomly assigned to the control group, which received standard care and a gelatin scaffold (placebo), or the intervention group, which received standard care along with LAMG. We evaluated the reduction in wound size and assessed the patient's health-related quality of life over 9 weeks. In the LAMG group (n = 9) and the Placebo group (n = 9), the wounds were reduced in size by a mean of 73.4% ± 15.3% and 13.1% ± 10.1%, respectively (P = .008). Patients treated with LAMG demonstrated significant improvements in the scores related to physical function, physical limitation, physical pain, general health, social function, emotional problems, and energy levels compared to the control group. The findings of this study indicate that using the LAMG with standard care significantly enhances wound healing.

Treatment of periorbital hyperpigmentation using sublative fractional radiofrequency (SFR).

BACKGROUND: Periorbital hyperpigmentation (POH) is a common cosmetic concern. Numerous techniques of treatment have been assessed with variable results. AIM: The purpose of this research is to assess the efficacy of non-ablative radiofrequency, Sublative fractional Radiofrequency (SFR) on POH treatment. METHODS: In this research study, nine patients with POH and the age range of 25-57 years, were enrolled. The patients were treated by non-ablative radiofrequency SRF. The outcomes were assessed by biometric assessment. The skin lightness and melanin content of the periorbital skin were assessed by colorimeter and Mexameter. Skin elasticity was assessed by Cutometer. The skin ultrasound imaging system was used to evaluate the diameter and density of the epidermis and dermis. Visioface was used to evaluate the skin color and wrinkles. Also, patient's satisfaction and physician's assessment were assessed. RESULTS: The results showed that the lightness and elasticity of the periorbital skin were significantly increased after treatment. Also, the melanin content of the skin was decreased. The denser skin layers were seen in both dermis and epidermis. The Visioface results displayed the reduction in the percent change of the skin color and wrinkle (p < 0.05). Similarly, the physician and patients' assessment confirmed the outcomes. No serious adverse effect was reported. CONCLUSION: In conclusion, the SFR technique is an effective and satisfactory therapeutic choice for treatment of POH.

Treatment of superficial and deep partial width second degree burn's wound with allogeneic cord blood platelet gel.

BACKGROUND: Burns are caused by a variety of mechanisms, including flames, hot liquids, metallurgy, chemicals, electric current, and ionizing and non-ionizing radiation. The most significant burn wound management involves complete repair and regeneration as soon as possible while minimizing infection, contraction, and scarring in the damaged tissue area. Some factors such as delivery of nutrients, growth factors, and oxygen are essential to promote and stimulate the wound healing progress in the burns area. When these factors are not provided, the burn wound undergoes a physiological crisis. The use of growth factors is a promising approach to overcoming this limitation. Umbilical cord blood platelet concentrates are a rich natural source of growth factors. METHODS: This clinical trial used growth factors released from the lysis of umbilical cord blood platelet concentrates that have a key role in promoting re-epithelization and regeneration of damaged tissues by forming a fibrin network. This study evaluated the effectiveness of allogeneic cord blood platelet gel topical dressing in a group of patients diagnosed with superficial and deep partial thickness (second-degree) burn wounds. Clinical outcomes were compared between the intervention group and a control group of patients with superficial second-degree burn wounds who received the standard routine treatment including paraffin gauze wound dressing and silver sulfadiazine ointment. RESULTS: The study's results showed that the increased rate of recovery and tissue granulation completely promoted to wound healing and burn wound closure, decreased the recovery time, and reduced inflammation and scars caused by burn injuries. However, the use of cord blood platelet gel topical dressing is not currently a routine treatment method in patients suffering from burn wounds. However, the study's results showed that allogenic cord blood platelet gel could be used to treat superficial and deep second-degree burns as a routine treatment. It was also shown that allogenic cord blood platelet gel topical dressing could be a candidate for autograft or after autograft skin transplantation surgery (in donor and recipient sites) instead of skin surgery in some patients. CONCLUSION: Allogeneic topical wound dressing provides an effective treatment that offers a faster rate of epithelialization and healing of wounds and also decreases patients' scar and inflammation level as well as the length of recovery time. This, finally, leads to better burn wound management and the improved quality of burn wound treatment.

Efficacy of fractional CO2 laser in combination with stromal vascular fraction (SVF) compared with fractional CO2 laser alone in the treatment of burn scars: a randomized controlled clinical trial.

BACKGROUND: The appearance of skin scars is known as one of the main side effects of skin burns. Stromal vascular fraction (SVF), as a rich source of cell populations with tissue regeneration properties, plays an important role in the healing of skin lesions. Fractional CO2 lasers have occupied a special place in treating skin lesions, particularly skin scars, since their introduction. Our study aimed to compare the combination of SVF and fractional CO2 laser with fractional CO2 laser alone in the treatment of burn scars. METHOD: This double-blind clinical trial study was conducted on ten patients with burn scars that were treated three times with a fractional CO2 laser at site of burn lesions, and one of the two areas studied was randomly injected with SVF. Two months after completion of the procedure, patients' scars were assessed using the Vancouver scar scale (VSS), biometric criteria, and physician and patient satisfaction ratings. RESULTS: The results confirmed a significant improvement in VSS, cutometry, R7 criteria, complete density sonography, and skin density sonography in the fractional CO2 laser-treated group. The VSS criteria, epidermal thickness sonography, complete density sonography, and skin density sonography in the group treated with the combination of fractional CO2 laser and SVF also showed significant improvement. The VSS criteria and melanin index of Mexameter in the group treated with SVF in combination with fractional CO2 laser were significantly better than the group treated with fractional CO2 laser alone. Also, physician and patient satisfaction in the group treated with SVF injection in combination with fractional CO2 laser was significantly higher than the other group. CONCLUSION: The results confirm the efficacy of SVF injection in combination with fractional CO2 laser in the treatment of burn scars and can be considered as a treatment option for better management of these lesions. TRIAL REGISTRATION: The study protocol was retrospectively registered at Iranian Registry of Clinical Trials with code: IRCT20210515051307N1, Registration date: 2021-11-14, URL: https://www.irct.ir/trial/56337 .

Microneedle fractional radiofrequency in the treatment of periorbital dark circles.

BACKGROUND: Periorbital hyperpigmentation (POH) is a common disorder in the patients. Women are more upset with POH in compare to males. Several methods have been used to the POH, with different efficacy and adverse reactions. AIM: The aim of the present study is to evaluate the efficacy of microneedle fractional radiofrequency (MRF) in treating POH. METHODS: So, nine patients with POH and the age range of 25-57 years, were treated by microneedle fractional radiofrequency (MRF). The outcome was evaluated via biometric assessment. The colorimeter was used to assess the skin lightness. Mexameter was used for evaluated the amount of Melanin in the periorbital skin. Cutometer was used for skin elasticity assessment. The skin ultrasound imaging system was utilized to estimate the epidermis and dermis diameter and density. Furthermore, Visioface was applied to assessed the skin color and wrinkles. Also patient's satisfaction and physician's assessment were evaluated. RESULTS: The results displayed that the periorbital skin lightness 32.38% ± 5.67 and elasticity of the R2: 40.29% ± 8.18, R5: 39.03 ± 5.38 and R7: 42.03% ± 14.16 were significantly improved after treatment (p < 0.05). Also the melanin content of the skin was decreased (49.41% ± 9.12). The skin layers were denser in the dermis and also in the epidermis (skin density: 30.21% ± 10.16 and skin thickness: 41.12% ± 13.21) (p < 0.05). The results revealed the decrease in the percent change of the skin color (30.34% ± 9.30) and wrinkle (area: 25.84% ± 6.43 and volume: 30.66% ± 8.12) (p < 0.05). Similarly, the physician and patient's assessment were confirmed the obtained outcomes. CONCLUSION: In conclusion, the microneedle RF technique is practicable, effective and safe method for periorbital dark circles treatment.

The quantitative investigation of spark plasma on skin parameters with skin elasticity, thickness, density, and biometric characteristics.

Cold atmospheric plasma has been developed and utilized as a novel technique for skin rejuvenation because of its various effects on cells and living things. This study investigated the accuracy of this claim and any possible side effects of using spark plasma to rejuvenate skin. The present work is the first quantitative investigation using animal models. 12 Wistar rats were divided into two groups for this investigation. To compare the skin's natural process with the treated skin, the first group underwent a single session of plasma therapy, while the second group served as the control group. The back of the necks of the samples was shaved for 20 cm. Before beginning treatment, the MPA9 multifunctional skin tester was used to determine the melanin index, erythema index, and transepidermal water loss (TEWL). The skin's thickness and density were assessed using sonography, and its elasticity index was calculated using a Cutometer. The samples were exposed to plasma radiation in the designated area (in a triangular pattern). The abovementioned signs were examined immediately after the following therapy and at the weekly appointment 2-4 weeks later. Optical spectroscopy was also used to demonstrate the presence of active species. In this study, we found that a plasma spark therapy session significantly boosts skin elasticity, and the ultrasound results revealed a significantly increased skin thickness and density. The plasma increased the amount of skin surface evaporation, erythema, and melanin immediately following the treatment. However, 4 weeks later, it recovered to its former state and did not differ significantly from before the therapy.

Chlamydia pneumoniae Seropositivity in the Iranian Patients with the Skin Inflammatory Disorder of Rosacea.

Background: Rosacea is a skin chronic inflammation with an unknown cause and cure. Environmental and genetic factors could not entirely explain the disease pathogenesis. Recently, infections like Chlamydia pneumoniae are of more attention in the rosacea progression. This study investigated the relationship between the C. pneumoniae seropositivity and the rosacea disorder. Materials and Methods: We aimed at a cohort of 100 patients with the rosacea disorder (60 active and 40 inactive) and from 100 sex- and age-matched healthy controls in Isfahan and determined the immunoglobulin M (IgM)/IgG antibodies titers to C. pneumoniae in the serum using the enzyme-linked immunosorbent assay method. The groups were compared using the analysis of variance procedure at the significant level of P < 0.05, statistically. Results: The mean of IgG in the controls was significantly higher than the levels in both the active and the inactive rosacea patients (p < 0.022). Also, the titer of serum IgM to C. pneumoniae in the controls was different, compared with the active (p < 0.019) and the inactive (p < 0.02) rosacea patients. In addition, the median titer of serum IgG (not IgM) to C. pneumoniae in the females with the inactive rosacea disorder was lower than the active rosacea disorder (p < 0.019) and controls women (p < 0.008). Furthermore, the serum level of IgG or IgM to C. pneumoniae in the controls males was higher than the males with the rosacea disorder (p < 0.05) and (p < 0.02), alternatively. Conclusion: C. pneumoniae seropositivity in the rosacea patients and controls was insignificant.

Assessment of quality of life and self-esteem in male patients with androgenetic alopecia before and after hair transplantation.

BACKGROUND: Patients with androgenetic alopecia experience a significant decrease in self-esteem and quality of life. There are several methods by which these factors may be improved. AIMS: Determining whether patients feel better about themselves with a better quality of life after undergoing hair transplant procedure. PATIENTS/METHODS: 35 people were chosen from Jordan Skin and Hair Clinic in Tehran, Iran. Following hair transplant, follow-up subjects had their quality of life and level of self-esteem assessed using the Rosenberg Self-Esteem Scale (RSES) and Dermatology Life Quality Index (DLQI), respectively. The means of quantitative results were compared using paired T-test. The chi-square test was done to compare preoperative and postoperative characteristics qualitatively. Differences were regarded significant if p < 0.05. Analysis of covariance was applied to evaluate the effect of marital status and educational level on outcome variables (ANCOVA). RESULTS: Our findings showed a statistically significant difference (p < 0.001) between pre- and post-operative hair transplantation for quality of life, and mean score increased to 2.17. There was a statistically significant difference between the two groups, with an average self-esteem score on RSES rising to 5.35 (p < 0.001). A statistically significant link between educational achievement and quality of life was found (p < 0.001). CONCLUSION: This study found postoperative psychological aspects of AGA patients significantly improve than preoperative. Our results show that there is a statistically significant difference between the self-esteem and quality of life of AGA patients before and after hair restoration surgery.

Efficacy of Endolift laser for arm and under abdomen fat reduction.

BACKGROUND: Noninvasive laser for body fat contouring is a quickly growing field in the cosmetic dermatology. Surgical options carry disadvantages, such as the usage of anesthetics, swelling, pain and long time for recovery, so there is a growing public request for the techniques with fewer side effects and shorter recovery periods. Several new noninvasive body contouring ways have been advanced such as, cryolipolysis radiofrequency energy, suction-massage, high-frequency focused ultrasound, and laser therapy. Noninvasive laser improves the body's appearance by the elimination of excess adipose tissue, specifically in areas in which fat perseveres in spite of diet and exercise. METHODS: In this study the efficacy of Endolift laser was evaluated for reduction of excess fat in the arms and under abdomen. Ten patients with excess fat in the arms and under abdomen were enrolled in this study. The patients were treated by Endolift laser in the arms and under abdomen areas. The outcomes were evaluated by two blinded board certified dermatologists and by patients' satisfaction. The circumference of each arm and under abdomen was measured using a flexible tape measure. RESULTS: The results showed reduction in the fat and circumference of arms and under abdomen after treatment. The treatment was considered as effective methods with high patient satisfaction. Also no severe adverse effects were reported. CONCLUSION: Endolift laser can be a good alternative to surgical body fat contouring due to its efficacy, safety, minimal recovery time, low cost. Also Endolift laser does not require general anesthetics.

SWI/SNF complex, promising target in melanoma therapy: Snapshot view.

Therapeutic strategies based on epigenetic regulators are rapidly increasing in light of recent advances in discovering the role of epigenetic factors in response and sensitivity to therapy. Although loss-of-function mutations in genes encoding the SWItch/Sucrose NonFermentable (SWI/SNF) subunits play an important role in the occurrence of ~34% of melanomas, the potential of using inhibitors and synthetic lethality interactions between key subunits of the complex that play an important role in melanoma progression must be considered. Here, we discuss the importance of the clinical application of SWI/SNF subunits as a promising potential therapeutic in melanoma.