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Achieving Sustainable Development Goal 7 (SDG-7) by exploring bioenergy production from peat-moss derived hydrothermal aqueous phase (HAPs) through anaerobic digestion (AD). This study investigated six combinations of hydrothermal conversion temperature (HCT) and residence time (HCRT). Methane yields varied significantly, with the highest (256 mL/g COD) achieved at 200 °C:4h, while the lowest (97 mL/g COD) was at 320 °C:4h due to formation of toxic and refractory organics. Microtox analysis showed acute toxicity > 98 % for all HAPs. Notably, higher HCT and HCRT led to more complex and diverse organic patterns, promoting the formation of humus-like substances, ester, alkane alcohols, and aromatics. GC-MS analysis revealed a 23 % increase in aldehyde and ketone compounds at 320 °C:4h. Continuous experiments confirmed 29 % COD removal efficiency at 320 °C:4h and identified 13 refractory organics, highlighting challenges in biodegradability. These findings provided valuable insights for optimizing AD processes, enhancing bioenergy production, and advancing sustainable energy solutions in alignment with SDG-7., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

With rapid industrial expansion, environmental pollution from emerging contaminants has increased, posing severe ecosystem threats. Laccases offer an eco-friendly solution for degrading hazardous substances, but their use as free-form biocatalysts face challenges. This study immobilized laccase (PersiLac1) on green-synthesized Si@Fe nanoparticles (MSFM NPs) to remove pollutants like Malachite Green-containing wastewater and degrade plastic films. Characterization techniques (FTIR, VSM, XRD, SEM, EDS, BET) confirmed the properties and structure of MSFM NPs, revealing a surface area of 31.297 m 2 .g -1 and a pore diameter of 12.267 nm. The immobilized PersiLac1 showed enhanced activity across various temperatures and pH levels, retaining over 82 % activity after 15 cycles at 80°C with minimal leaching. It demonstrated higher stability, half-life, and decimal reduction time than free laccase. Under 1 M NaCl, its activity was 1.8 times higher than the non-immobilized enzyme. The immobilized laccase removed 98.11 % of Malachite Green-containing wastewater and retained 82.92 % activity over twenty cycles of dye removal. Additionally, FTIR and SEM confirmed superior plastic degradation under saline conditions. These findings suggest that immobilizing PersiLac1 on magnetic nanoparticles enhances its function and potential for contaminant removal. Future research should focus on scalable, cost-effective laccase immobilization methods for large-scale environmental applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A plantar wart is a benign hyperplasia that appears on the feet due to the human papillomavirus (HPV). One method used for the treatment of recalcitrant plantar warts, those lasting over 2 years or persisting after at least two treatment attempts, is the cantharidin (1%), podophyllin (5%), and salicylic acid (30%) formulation, also known as the CPS formulation. Although this method is in use, there are few studies on it. This study's objective was to ascertain its cure rate. For this retrospective observational study, we reviewed the medical records of patients treated with the CPS formulation at a podiatric clinic specializing in plantar wart treatment. Our sample size was 48 subjects. The CPS formulation had a cure rate of 62.5%. Out of the cured patients, 86.67% (26/30) required one or two applications. There was no observable correlation (p > 0.05) between wart resolution and virus biotype, evolution time, patient's morphological and clinical attributes, location, number of warts, or preceding treatments. The CPS formulation presents a relatively high efficacy rate for treating recalcitrant HPV plantar warts. Still, additional studies are necessary to evaluate its safety and efficiency., (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)

Trichophyton indotineae has emerged as a novel dermatophyte species resulting in treatment recalcitrant skin infections. While the earliest reports came from India, T. indotineae has now spread to many parts of the world and is rapidly becoming a global health concern. Accurate identification of T. indotineae requires elaborate mycological investigations which is beyond the domain of routine microbiology testing. Extensive, non-inflammatory and atypical presentations are commonly seen with this novel species. T. indotineae shows an alarmingly high rate of mutations in the squalene epoxidase gene leading to lowered in vitro susceptibility to terbinafine. This has also translated into a lowered clinical response and requirement of a higher dose and much longer durations of treatment with the drug. Although the species remains largely susceptible to itraconazole, prolonged treatment durations are required to achieve cure with itraconazole. Fluconazole and griseofulvin do not have satisfactory in vitro or clinical activity. Apart from requirement of prolonged treatment durations, relapse postsuccessful treatment is a distressing and yet unexplained consequence of this "species-shift." Use of third generation azoles and combinations of systemic antifungals is unwarranted as both have not demonstrated clear superiority over itraconazole given alone, and the former is an important class of drugs for invasive mycoses., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Improper use of over-the-counter (OTC) steroid medication has been linked to recalcitrant dermatophytosis. There is proven evidence of HPA axis suppression by the use of long-term oral steroids. This study aims to determine the prevalence and pattern of inappropriate OTC steroid use and its effects on the hypothalamus-pituitary-adrenal (HPA) axis in adults with recalcitrant dermatophytosis., Materials and Methods: This cross-sectional study of 2 months was conducted in a hospital setting and included patients of recalcitrant dermatophytosis with a history of OTC steroid use. Clinico-demographic details and basal serum cortisol levels were recorded in all and analyzed., Result: Of a total of 103 patients, 59.22% ( n = 61/103) were males, and the mean duration of steroid abuse was 17.78 months. About 48.54% ( n = 50/103), 3.88% ( n = 4/103), and 47.57% ( n = 49/103) patients reported the use of topical steroids, oral steroids, and both oral and topical steroids, respectively. Among all the topical steroid users ( n = 99), clobetasol propionate 48.48% ( n = 48/99), while among oral steroid users ( n = 53), prednisolone 45.28% ( n = 24/53) were the most commonly used agents, respectively. The morning serum cortisol levels (8-9 AM) were found to be decreased in 42.7% ( n = 44/103), with a mean value of 44.28 ± 17.34 μg/dL., Conclusion: Improper OTC steroid use in recalcitrant dermatophytosis leads to HPA axis suppression. This highlights the need for intervention from apex health officials., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Family Medicine and Primary Care.)

SCLC is refractory to conventional therapies; targeted therapies and immunological checkpoint inhibitor (ICI) molecules have prolonged survival only marginally. In addition, ICIs help only a subgroup of SCLC patients. Different types of kinases play pivotal roles in therapeutics-driven cellular functions. Therefore, there is a significant need to understand the roles of kinases in regulating therapeutic responses, acknowledge the existing knowledge gaps, and discuss future directions for improved therapeutics for recalcitrant SCLC. Here, we extensively review the effect of dysregulated kinases in SCLC. We further discuss the pharmacological inhibitors of kinases used in targeted therapies for recalcitrant SCLC. We also describe the role of kinases in the ICI-mediated activation of antitumor immune responses. Finally, we summarize the clinical trials evaluating the potential of kinase inhibitors and ICIs. This review overviews dysregulated kinases in SCLC and summarizes their potential as targeted therapeutic agents. We also discuss their clinical efficacy in enhancing anticancer responses mediated by ICIs.

In this study, we focused on understanding key storage traits of seeds from Macrozamia fraseri , an unusual though important species that is impacted by mining. To support current restoration activities, large amounts of seed from M. fraseri have been regularly collected and stored for up to 8 years under standard seed banking conditions (5°C and 20% relative humidity), though in situ recruitment from directly sown seed is poor. To investigate the underlying constraints to germination on demand, we set out to assess the viability of M. fraseri seeds that had been stored in a restoration seed bank from 6 to 66 months. Seed moisture content (MC) (fresh weight basis) was also determined for seeds with different storage histories to ascertain whether M. fraseri seeds display traits (i.e. high MC) that might suggest non-orthodox seed storage behaviour. The youngest seed accession (6 months old) was found to have a high MC (45.8 ± 5.4%-fresh weight basis), and >50% viability. In comparison, older (>30 months old) accessions were observed to have a marked reduction in both seed MC (10-35% MC) and viability (0-29.4%). While preliminary, we conclude that M. fraseri seeds appear to lose viability during conventional storage with younger accessions displaying both a higher seed MC and viability, compared to accessions stored for longer. Given the significance of these results, future research activities are recommended to better understand the interplay between seed MC and storage environment and how this relates to the seasonally dry Mediterranean climate where this species naturally occurs. As well, storage and propagation approaches are proposed to increase success when using M. fraseri for conservation and restorative activities., Competing Interests: All authors acknowledge that regarding this manuscript there is no conflict of interest to declare., (© The Author(s) 2023. Published by Oxford University Press and the Society for Experimental Biology.)

Seagrass meadows are declining at a global scale, threatening their capacity as blue carbon sinks. Restoration of seagrasses (via seagrass seeds or plant transplantation) may recover their carbon sequestration capacity. Previous studies have predominantly focused on sediment organic carbon (SOC), while variations in sediment carbon compositions remain poorly understood, limiting our comprehension of the influence of seagrass restoration on sediment carbon stability. Here, we researched the differences in surface (0-3 cm) sediment carbon compositions in response to tropical seagrass transplantation among species (Thalassia hemprichii and Enhalus acoroides); specifically, differences in labile, recalcitrant and refractory SOC, as well as sediment inorganic carbon (SIC) compositions variations under transplanted T. hemprichii and E. acoroides communities. It was found that seagrass transplantation enhanced suspended particle organic matter, and epiphyte and macroalgae input to surface sediment, which recovered the surface SOC concentration and stock rapidly to natural levels (increased ∼1.6-fold) within two years following transplantation. The elevated contribution of epiphyte and macroalgae significantly increased the surface labile sediment organic matter (SOM), but not the recalcitrant and refractory SOM composition after short-term transplantation. Meanwhile, surface SIC was significantly elevated, which might be mainly ascribed to allochthonous carbonate particle trapped under transplanted area with implications for carbon sequestration. The higher canopy and longer leaf seagrass species, E. acoroides, had elevated SOC, SIC and was more labile composition, compared to T. hemprichii transplant. Overall, this research suggests that tropical seagrass transplantation can increase the surface SOC, SIC concentration by increasing the labile organic matter and allochthonous carbonate particle input, respectively, with varying significantly among seagrass species., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: To evaluate whether anti-drug antibodies (ADAs) are present in the ocular fluid of patients with ranibizumab-recalcitrant neovascular age-related macular degeneration (nAMD)., Methods: Two serum ADA-positive ranibizumab-recalcitrant patients and two serum ADA-negative controls were recruited from patients with nAMD treated with ranibizumab monotherapy. Recalcitrance was defined as persistent fluid after ≥6 monthly ranibizumab injections. Serum and aqueous humor ADAs were detected by enzyme-linked immunosorbent assay and immunoprecipitation, respectively., Results: Two of 156 ranibizumab-treated patients were ADA-positive. The patients received six and 14 ranibizumab injections, respectively, up to 4 weeks prior to blood collection. The serum ADA concentration was estimated to be approximately 50,000 ng/mL. Neutralizing ADAs were confirmed in both samples. A specific band was detected by immunoprecipitation only in ADA-positive samples, consistent with the results of enzyme-linked immunosorbent assay. Based on an assessment of the degree of sensitivity of commercially available anti-ranibizumab antibodies, it was estimated that the immunoprecipitation method could detect ADA levels >30 ng. Nevertheless, ADAs were not detected in the aqueous humor of either the experimental or control group., Conclusion: In the aqueous humor, ADAs are either not present or are present at a lower concentration than that which can be detected by immunoprecipitation. This presumably reflects the fact that blood ADA is the product of systemic circulation clearance through anterior elimination of intravitreal ranibizumab. Based on our results, ADAs do not return to the eye in sufficient quantities to interfere with the action of ranibizumab in the vitreous cavity., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Many patients with moderate-to-severe psoriasis may not achieve complete skin clearance with recalcitrant lesions despite being on biologics. We aimed to evaluate the real-world effectiveness and safety of combining topical calcipotriene/betamethasone dipropionate (Cal/BD) foam with biologic therapy for the treatment of recalcitrant psoriatic lesions over the scalp or lower legs. We retrospectively reviewed the medical charts of psoriasis patients receiving adjunctive topical Cal/BD foam with biologics for at least 16 weeks on recalcitrant psoriatic lesions of the scalp or lower legs between 2020 and 2021 at a tertiary referral medical center in southern Taiwan. Among the 18 recruited patients, the severity outcomes of body surface area (BSA), Physician's Global Assessment (PGA), and BSA × PGA of the recalcitrant areas decreased by approximately 31%, 48%, and 50%, respectively, after 4 weeks of once-daily adjunctive Cal/BD foam use. Thereafter, the effect remained nearly constant after dose reduction to twice weekly until week 16. The Dermatology Life Quality Index and the nine-item Treatment Satisfaction Questionnaire for Medication questionnaire revealed improved life quality and a high level of satisfaction, with only a few mild adverse effects reported. In conclusion, adjunctive topical Cal/BD foam might be an effective and safe option for patients with recalcitrant lesions on the scalp and lower legs despite biologics use., (© 2023 Japanese Dermatological Association.)

Introduction: The role of lasers in the treatment of standard therapy-resistant inflammatory dermatoses and connective tissue disorders has been controversial and evidence supporting the role of lasers in this setting is scarce., Objective: To assess the efficacy of lasers in the management of inflammatory dermatoses and connective tissue disorders (CTD)., Materials and Methods: A retrospective case review of all inflammatory dermatoses/connective tissue diseases treated in a tertiary laser clinic between March 2010 and 2020 was undertaken., Results: A total of 60 cases (48 = female) were included and the average age was 51 years (range 21 to 74). The following conditions were treated: scleroderma n = 22 (37%), granuloma faciale n = 10 (17%), sarcoidosis n = 8 (13%), discoid lupus erythematosus n = 7 (12%), and systemic lupus erythematosus n = 2 (3%). Other diagnoses included necrobiosis lipoidica, pyoderma vegetans, hypertrophic lichen planus, and dermatomyositis. The most common type of laser used was pulsed dye laser (PDL) in n = 41 (68%) cases. Eight (13%) patients received treatment with the carbon dioxide (CO 2 ) laser. The most common site treated was the face. A good response with a marked reduction of signs was seen in 62% of patients while 10% of the patients did not respond to laser treatment. Self-limiting complications included purpura and hyperpigmentation., Limitations: Lack of objective assessment and outcome measures., Conclusions: This is the largest cohort of patients to have undergone laser treatment for inflammatory dermatoses/connective tissue disease. Based on this retrospective review, we conclude that lasers can be a useful adjunct in the management of otherwise difficult-to-treat selected inflammatory and connective tissue diseases., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Indian Dermatology Online Journal.)

Pyoderma gangrenosum (PG) is a rare, autoinflammatory disease leading to aseptic ulcers which carries a significant disease burden and is often difficult to treat, with many patients failing first-line treatment and requiring additional therapies. Such cases are typically referred to in the literature as "recalcitrant", "refractory", or "resistant", though little is known about the clinical characteristics of such cases. We performed a narrative literature review to characterize patient demographics and clinical course associated with difficult to treat pyoderma gangrenosum cases in order to identify trends to guide future clinical management and therapeutic innovation. We identified 148 cases with clinical manifestations and associated patient demographics stratified by ulcer and patient features. Consistent with previous work, a greater prevalence of PG was observed among female patients and those with a history of inflammatory bowel disease, however interestingly despite an aggressive course to their PG, few patients had comorbidities complicating their disease course. Additionally, despite the requirement of three or more treatments for most patients' disease to resolve, the majority healed within the typical window observed in previous clinical studies with low rates of recurrence. Biologics were the most common medication patients were on at time of remission. Collectively, our results suggest a potential benefit for a reduced threshold for biologic initiation in PG patients and a need for standardization of language in the field to facilitate treatment outcomes comparisons and interventions., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Becker et al.)

Eco-friendly treatment of complex textile and dyeing wastewaters poses a pressing environmental concern. An approach adopting different treatment paths and integrated anaerobic-aerobic processes for high-strength and recalcitrant textile dyeing wastewater was examined. The study demonstrated that over 97% of suspended solids (SS) and more than 70% of chemical oxygen demand (COD) were removed by polyaluminum chloride pre-coagulation of suede fabric dyeing stream. Up to 58% of COD and 83% of SS were removed through hydrolysis pretreatment of other low-strength streams. Notable COD removal of up to 99% from a feed of 20,862 mg COD/L was achieved by integrated anaerobic-aerobic treatment of high strength stream. Besides achieving high COD removal of 97%, the anaerobic granular sludge process demonstrated multi-faceted attributes, including high feed loading, smaller footprint, little sludge production, and good stability. The integrated anaerobic-aerobic treatment offers a robust and viable option for highly contaminated and recalcitrant textile dyeing wastewater., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

In plants, phase change from the juvenile stage to maturity involves physiological and anatomical changes, which are initiated and controlled by evolutionary highly conserved microRNAs. This process is of particular significance for the in vitro propagation of woody plant species, as individuals or tissues that have undergone the transition to vegetative maturity are recalcitrant to propagation. Conserved miRNAs differentially expressed between juvenile (including rejuvenated) and mature silver birch tissues were identified using high-throughput sequencing of small RNA libraries. Expression of some miR156 isoforms was high in juvenile tissues and has been previously reported to regulate phase transitions in a range of species. Additional miRNAs, such as miR394 and miR396, that were previously reported to be highly expressed in juvenile woody plant tissues were also differentially expressed in this study. However, expression of miR172, previously reported to be highly expressed in mature tissues, was low in all sample types in this study. The obtained results will provide insight for further investigation of the molecular mechanisms regulating vegetative phase change in silver birch and other perennial woody plant species, by analysing a wider range of genotypes, tissue types and maturation stages. This knowledge can potentially assist in identification of rejuvenated material at an earlier stage than currently possible, increasing the efficiency of silver birch in vitro propagation.

Objective: To establish the safety and effectiveness of subtotal petrosectomy with cochlear implantation in patients affected by chronic middle ear disorders to refractory to previous surgical treatments., Methods: A multicentre, retrospective study was conducted on patients affected by recalcitrant chronic middle ear disorders who underwent cochlear implantation in combination with subtotal petrosectomy. Patients' details were collected from databases of 11 Italian tertiary referral centres. Additionally, a review of the most updated literature was carried out., Results: 55 patients were included with a mean follow-up time of 44 months. Cholesteatoma was the most common middle ear recurrent pathology and 50.9% of patients had an open cavity. 80% of patients underwent a single stage surgery. One case of explantation for device failure was reported among the 7 patients with post-operative complications., Conclusions: Subtotal petrosectomy with cochlear implantation is a benchmark for management of patients with recalcitrant chronic middle ear disorders. A single stage procedure is the most recommended strategy. Optimal follow-up is still debated. Further studies are required to investigate the role of this surgery in paediatric patients., (Copyright © 2023 Società Italiana di Otorinolaringoiatria e Chirurgia Cervico-Facciale, Rome, Italy.)

Chronic hand eczema (CHE) is persistent inflammatory dermatitis that may significantly affect the quality of life, with psychosocial effects, impact on school, work, and leisure activities, influence on socioeconomic status, and high health care costs. Pediatric-CHE (P-CHE) has a high prevalence yet has not been extensively studied in children and adolescents. There is minimal published data on P-CHE in North America, and no specific management guidelines. Limited prevalence data show broad ranges (0.9%-4.4%) in preschool and school children, with 1 study stating up to 10.0% 1-year prevalence for ages 16 to 19 years. Atopic dermatitis and allergic contact dermatitis appear important in the pathogenesis of this disease process, although there is limited pediatric data assessing disease associations and no standardized methodology for evaluating this disorder. Given the potential life-changing consequences of P-CHE, further research into this disease process is warranted to help generate best therapeutic practices and minimize this disease process' morbidity in adulthood., Competing Interests: Dr Eichenfield has served as an advisory board member, and/or speaker, consultant, or clinical trial investigator for AbbVie, Arcutis, Almirall, Arena, Aslan, Bausch, Castle, Dermavant, Eli Lilly, Forte, Galderma, Gelnmark/Ichnos, Incyte, Leo Pharma, Novartis, Pfizer, Regeneron, Sanofi Genzyme, UCB, and Valeant/Ortho Derm. Drs Haft, Park, Lee, and Sprague have no conflicts of interest to declare., (© 2023 by the American Academy of Dermatology, Inc. Published by Elsevier Inc.)

Main Conclusions: Fully mature acorns of Quercus variabilis, Q. aliena, Q. mongolica, and Q. glandulifera are desiccation-sensitive. X-ray computer tomography showed that cotyledons shrink during drying, but embryos are protected. Information available on recalcitrant acorns of tropical and sub-tropical species of Quercus suggests that an impermeable pericarp, which limits the entry and loss of water only through the hilum (scar), is the underlying mechanism that prevents drying of the embryo axis following dispersal until the germination season. However, there is a lack of consensus supporting this proposition across species, and it is not well understood if such mechanisms occur in temperate Quercus species. This study investigated the significance of the acorn pericarp for temperate oak species and presents an ecological framework based on the post-dispersal climatic conditions. Using Quercus variabilis, Q. aliena, Q. mongolica, and Q. glandulifera acorns, the relationship between moisture content (MC) and germination was established, and X-ray computed tomography (X-ray CT) was used to understand the internal structural changes of cotyledons and embryonic axis occurring during desiccation. Water entry and exit routes through the scar, pericarp and apex were determined by imbibition and drying experiments. Climatic data and acorn morphological characteristics and germination were subjected to a principal component analysis (PCA). Freshly dispersed acorns of all species had a moisture content (MC) above 35% fresh weight (FW) basis, but drying to 15-10% MC resulted in complete loss of viability, implying recalcitrance behaviour. X-ray CT images suggested that the pericarp offers some protection to cotyledons and embryonic axis during desiccation, but it is contingent on MC. Extensive drying to a low MC with the scar and apex covered with vaseline resulted in internal tissues shrinkage, corresponding with viability loss. Water could enter or exit through the pericarp, albeit at a much slower rate than through the scar. A combination of factors including acorn anatomy, moisture content at the time of dispersal, microhabitat, the position of acorns in the soil prevent embryo desiccation below the critical MC and thus promotes survival of acorns on/in the soil during winter in temperate regions. Pericarp anatomy, to some extent, prevents excessive drying of the embryonic axis by slowing water movement, but prolonged drying or predatory pressure could result in pericarp cracks, favouring the absorption of water during sporadic rain. In the latter case, the survival of acorns possibly depends extensively on the continuous erratic rainfall, i.e. continuous wet-dry cycle, but in-situ experiments are yet to be performed to test this hypothesis., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aim: To assess efficacy of intrastromal voriconazole (ISV) in the treatment of fungal keratitis non-responding to conventional antifungals. Methods: Eighteen patients with smear positive fungal keratitis, not responding to conventional topical/ systemic antifungal therapy up to 2 weeks, were included in the study. Afterwards, they were given ISV (50 µg in 0.1 ml) around the ulcer and continued to receive conventional antifungal therapy. Responses to treatment (decrease in size of the ulcer and infiltrates) were recorded daily for 3-days, at 1-week and every 2 weeks for 3-months, or until the ulcer had healed completely. Results: The mean age at presentation was 51 ± 17.83 years. The most common organism isolated was Fusarium (17/ 18), followed by Aspergillus (1/ 18). All the patients were successfully treated in terms of corneal healing, but one case did not improve in vision due to the existence of diabetic macular oedema. 6 patients improved after a single injection, 7 had to receive 2 and 5 improved after 3 injections. The mean number of injections in 17 treated patients was 1.94 ± 0.78. Moreover, the mean resolution time was 18.50 ± 6.25 days. The size of ulcer and height of hypopyon at presentation were noteworthy risk-factors linked to management outcomes. Deeper ulcers required a greater number of injections when compared to superficial ulcers. The mean best-corrected visual acuity improved from 0.94 to 0.25 at 3 months follow-up in all the patients. Conclusion: Intrastromal Voriconazole (50 µg/ 0.1 mL) appears to be an effective adjunct therapy in cases of recalcitrant deep fungal keratitis non-responding to conventional antifungals. Though, some may require repeated injections, timely ISV administration certainly reducing the need for tectonic/ therapeutic keratoplasty. Abbreviations: ISV = Intrastromal Voriconazole, AS-OCT = anterior-segment optical coherence topography, KOH = potassium hydroxide, BCVA = best-corrected visual acuity., (#x00A9; The Authors.Romanian Society of Ophthalmology.)

Linear immunoglobulin A bullous dermatosis (LABD) is an idiopathic or drug-induced vesiculobullous disease typically managed with dapsone or colchicine. We report a case of LABD successfully treated with rituximab in a patient who was intolerant to first-line therapies and recalcitrant to typical immunosuppressants. The patient was initially started on prednisone and mycophenolate mofetil which resulted in minimal response and disease progression. Improvement was seen after two infusions of rituximab 1000 mg at 2 weeks apart with planned maintenance therapy., Competing Interests: Conflict of interest: the authors declare no potential conflict of interest, and all authors confirm accuracy., (©Copyright: the Author(s).)

Seeds are the most commonly used source of storage material to preserve the genetic diversity of plants. However, prior to the deposition of seeds in gene banks, several questions need to be addressed. Here, we illustrate the scheme that can be used to ensure that the most optimal conditions are identified to enable the long-term storage of seeds. The main questions that need to be answered pertain to the production of viable seeds by plants, the availability of proper protocols for dormancy alleviation and germination, seed tolerance to desiccation and cold storage at -20 °C. Finally, it is very important to fully understand the capability or lack thereof for seeds or their explants to tolerate cryogenic conditions. The proper storage regimes for orthodox, intermediate and recalcitrant seeds are discussed.

Background: There has been an emergence of recalcitrant, recurrent, and difficult-to-treat tinea. Monotherapy with oral antifungals leads to partial clearance or high recurrence of lesions. Isotretinoin is a good adjuvant to systemic antifungals in chronic dermatophytosis. Voriconazole could be a future alternative due to its efficacy against dermatophytes and little resistance., Objective: To evaluate the efficacy and safety of oral itraconazole, combined itraconazole/isotretinoin therapy, and voriconazole for recalcitrant tinea., Patients and Methods: This study included 90 patients with chronic, recurrent and/or recalcitrant tinea. They were equally divided into three groups: itraconazole monotherapy, combined itraconazole/isotretinoin therapy, and voriconazole monotherapy. All patients received treatments for 6 weeks. The clinical response was classified as either a complete or incomplete clinical cure. Potassium hydroxide microscopy and culture were performed to identify mycological cure. Patients with complete cure were followed up for another 6 months to detect any recurrence., Results: Complete clinical cure was observed in 53.3% of the itraconazole group, 70% of the itraconazole/isotretinoin group, and 83.3% of the voriconazole group. Mycological cure was detected in 56.7% of the itraconazole group, 83.3% of the itraconazole/isotretinoin group, and 86.7% of the voriconazole group. There was a statistically significant difference between the three groups in favour of voriconazole, then the combined group. No significant adverse effects were observed. The recurrence rate was significantly lower in the voriconazole group compared with the other two groups., Conclusions: Voriconazole could be a future alternative for the treatment of recalcitrant dermatophytosis., (© 2022 Wiley-VCH GmbH.)

The assembly of dihaploid rice plants through anther culture was constrained due to the recalcitrant properties. A comprehensive investigation of gene expression patterns among rice varieties with recalcitrant and non-recalcitrant anthers will help to understand the cellular mechanisms and biological processes of recalcitrant properties in rice anther cultures. Therefore, we performed RNA sequencing and analysis on the anthers of three selected Indonesian rice varieties with opposite recalcitrant properties. The varieties are Fatmawati with non-recalcitrant properties, IR64 recalcitrant and Tarabas unknown. The Illumina NextSeq PE150 sequencer was used to generate a total crude nucleotide of approximately 41.21 Gb in size. From 272,239,682 total paired final raw reads, 137,343,391 total net reads were obtained and uploaded to NCBI's Sequence Read Archive (SRA) repository under BioProject accession number PRJNA856048. This dataset allowed us to identify and profile all expressed genes with functions associated with recalcitrant and non-recalcitrant properties. In addition, the transcriptome data obtained will be valuable for the discovery of potential gene markers and functional SNPs associated with functional traits to assist rice breeding programs through the development of Marker Assisted Selection (MAS)., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Background: Acral lesions of vitiligo are most likely recalcitrant to the known lines of treatment. Ablative fractional CO 2 has shown efficacy in treatment of vitiligo in combination with other modalities., Methods: Thirty non-segmental vitiligo patients with acral lesion were included in the study. Each patient was subjected to fractional Carbon Dioxide Laser Treatment followed by application of 5 fluorouracil (5FU) cream for five consecutive days. Evaluation was done 3 weeks from the start of treatment and 12 weeks after the last treatment session using VESTA score, evaluation of patients' photos by blinded investigation in addition to patients' satisfaction scores., Results: Patients showed significant improvement of Vitiligo extent score for a target area (VESTA) score and developed considerable degree of repigmentation as assessed by blinded investigators., Conclusion: The combination of fractional ablative CO 2 and 5FU is an effective and safe procedure for the treatment of acral vitiligo with promising results offering patients a new therapeutic window., (© 2022 Wiley Periodicals LLC.)

Polycyclic aromatic hydrocarbons (PAHs) are one of the major toxic constituents of crude oil and therefore, an understanding on PAHs associated risks and their relationship with soil biological parameters are necessary for adopting effective risk-based and site specific remediation strategies in the contaminated soil. Here, risks evaluation of eight detected PAHs in terms of toxic equivalent concentration (TEQ C ), benzo(a)pyrene equivalent (BaPeq), contamination factor (CF), pollution load index (PLI), hazard quotient (HQ), hazard index (HI), toxic unit for individual PAHs (TU) and PAHs mixture (TU m ) have been evaluated. Besides, the effect of PAHs contamination on soil biological properties has also been investigated and correlated with PAHs concentrations. The TEQc of eight PAHs was recorded in the range of 0.06-5.0 mg kg -1 soil , whereas the BaPeq value was 25.3 mg kg -1 soil which exceed the permissible limit. Similarly, CF (85.5-1668.2), PLI (322.8), HQ (311.7-8340.9), HI (26,443.8), TU (227.9-3821.6) and TU m (7916.2) also exceed the permissible values for non-toxic conditions indicating carcinogenic risk for humans. Besides, activities of soil dehydrogenase, urease, alkaline-phosphatase, catalase, amylase and cellulase were decreased by 1.5-2.3 folds in the contaminated soil than control. The results of Pearson's correlation matrix also established negative impact of PAHs on the soil's biological properties., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Acute generalized exanthematous pustulosis (AGEP) is a severe cutaneous adverse reaction (SCAR) characterized by sterile nonfollicular pustules on an erythematous base that form rapidly after drug exposure. AGEP is mediated by numerous cytokines produced by drug-specific T cells that mediate neutrophilic intracorneal, subcorneal, or intraepidermal pustule development. Though genetic susceptibility is not fully understood, individuals with mutations in IL-36RN may be at increased risk of AGEP development. AGEP commonly presents with leukocytosis and fever in the acute pustular phase and follows a self-limited desquamative recovery phase upon removal of offending drug. Severe cases of AGEP may have multisystem organ involvement. Atypical presentations of AGEP include localized eruptions and cases with overlapping clinical and histopathologic features associated with Stevens-Johnson syndrome/toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, and generalized pustular psoriasis. Most cases of AGEP clear rapidly with systemic corticosteroids, but severe or recalcitrant cases may require other systemic therapies, such as cyclosporine, and intravenous immunoglobulin., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Approximately 5% of patients experience recurrent symptoms after carpal tunnel release (CTR) and need revision surgery. Several surgical techniques have been described for recurrent carpal tunnel syndrome (CTS) and the abductor digiti minimi (ADM) flap is one of them. Literature concerning clinical results of the ADM flap for recurrent CTS is lacking. The aim of this study is to evaluate the outcomes of the ADM flap for recurrent CTS. Methods: We treated seven patients with the ADM flap (eight hands) between July 2016 and February 2019. Patient characteristics were assessed, and patients were asked about their symptoms (pain, sensation and paresthesia) before and after surgery. Postoperatively, we administered CTS symptoms, satisfaction with the surgery, patient-reported outcome measurements (BCTQ and QuickDASH) and whether they would undergo the same surgery again. Complications were also recorded Results: The median follow-up was 14 months. The success rate measured by CTS symptoms was 88%. Seven out of eight patients were satisfied with the results and two patients would not elect to undergo the same procedure again. Two patients reported having a weaker grip at the donor site. The median BCTQ symptom and function scores were 2.9 (1.7-3.5) and 2.6 (1.8-3.0) respectively. The median QuickDASH score was 41 (IQR 22-52). Complications reported were wound dehiscence ( n = 1) and hypertrophic scar ( n = 1). Conclusions: The outcomes of the ADM flap in patients with recurrent CTS were like other commonly used procedures in recurrent CTS. Level of Evidence: Level IV (Therapeutic).

This study aimed to evaluate an activated sludge system as a post-treatment step of anaerobic effluents from the co-digestion of sugarcane vinasse and hemicelluloses hydrolysate. The system consisted, initially, of a two-stage anaerobic system followed by a continuously fed activated sludge, all in bench scale. After adaptation of aerobic microorganisms to effluent conditions, the anaerobic digestion was conducted in a single-stage anaerobic reactor, increasing the influent organic loading rate (OLR) of activated sludge from 0.73 to an average of 2.36 gCOD/L·day. Under optimal conditions (12-h hydraulic retention time [HRT]), a 62 ± 9% efficiency was observed on the aerobic post-treatment, resulting in effluent chemical oxygen demand (COD) of 414.3 ± 95 mg/L. Overall efficiency of the combined system (anaerobic + aerobic) averaged 88 ± 3%. Influent and effluent characteristics were then analyzed by Folin-Ciocalteau method, UV-Vis spectrophotometry, and gas chromatography-mass spectrometry (GC-MS) for identification of potentially toxic and recalcitrant compounds. Compounds that absorb light within the visible spectra were well removed by the combined treatment system. Most compounds identified by GC-MS in the influent were completely removed by aerobic microorganisms. Saturated fatty acids such as adipic acid, hexadecanoic acid, and octadecanoic acid were observed in the final effluent, as well as other potentially toxic compounds such as stigmasterol, di-isobutyl phthalate, and benzene. Activated sludge proved to be an efficient post-treatment for anaerobic co-digestion, able to cope with changes of anaerobic effluent quality and providing a final effluent of stable organic load. However, phenol removal was not efficient and further studies could be performed to optimize its degradation. PRACTITIONER POINTS: Conventional activated sludge with a 12-h HRT was capable of handling significant OLR variation, providing a final effluent with lower and stable COD concentration. Glucose addition for carbon supplementation was necessary during the start-up of activated sludge. Compounds that absorb light within the visible spectra were mostly removed by the combined (anaerobic-aerobic) treatment system. Most potentially toxic compounds were well removed in the post-treatment system. Saturated fatty acids, VFA, phenols, and low molecular weight aromatic compounds remained in the final effluent., (© 2022 Water Environment Federation.)

Thermal-chemical pre-treatment has proven to facilitate the solubilization of organics and improvement in biogas generation from the organic fraction of municipal solid waste (OFMSW). However, the production of recalcitrant is inevitable when OFMSW is pretreated at high temperatures and alkali dosage. This study develops a strategy to use Fe 3+ to reduce the formation of recalcitrant compounds, i.e., 5-HydroxyMethyl Furfural (5-HMF), furfurals, and humic acids (HA) during thermal-alkali pre-treatment. It was postulated that the formation of the recalcitrant compound during pre-treatment can be reduced by Fe 3+ dosing to oxidize intermediates of Maillard reactions. A decrease in 5-HMF (45-49%) and furfurals (54-66%) was observed during Fe 3+ (optimum dose: 10 mg/L) mediated thermal-alkali pre-treatment owing to the Lewis acid behavior of FeCl 3 . The Fe 3+ mediated assays show a substantial improvement in VS removal (28%) and biogas yield, i.e., 31% (292 mL/gVS added ) in 150 °C + 3 g/L NaOH, 34% (316 mL/gVS added ) in 175 °C + 3 g/L NaOH, and 36% (205 mL/gVS added ) in 200 °C + 3 g/L NaOH assays, over their respective controls (no Fe 3+ dosing). The reducing property of Fe 3+ rendered a low ORP (-345 mV) in the system than control, which is beneficial to the anaerobic microbiome. Electrical conductivity (EC) also shows a three-fold increase in Fe 3+ mediated assays over control, promoting direct interspecies electron transfer (DIET) amongst microbes involved in the electrical syntrophy. The score plot and loading plots from principal component analysis (PCA) showed that the results obtained by supplementing 10 mg/L Fe 3+ at 150, 175, and 200 °C were significantly different. The correlation of the operational parameters was also mutually correlated. This work provides a techno-economically and environmentally feasible option to mitigate the formation of recalcitrant compounds and enhance biogas production in downstream AD by improving the degradability of pretreated substrate., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Desiccation sensitive (DS) seeds are shed at high water contents (WC) and metabolically active, but WC thresholds vary broadly among species even in the same genus. Eugenia is an important ecological genus that has high occurrence in several Brazilian morphoclimatic domains. In this study, we assessed seed desiccation tolerance of five Eugenia species collected in specific meteorological conditions. We reported the species geographical ranges and verified the rainfall and temperature of species sites in the year prior to seed collection. We also assessed initial WC, seed germination and vigor and seedling growth upon desiccation. Eugenia uniflora was the widest spread among the five species, while E. astringens was the most restricted. In this specific study, widespread species showed a higher WC threshold than restricted species. In the same way, the WC of fresh seeds was not correlated to the desiccation tolerance threshold. Seed desiccation tolerance was species dependent and correlated with the environmental status of seed collection sites. Wetter and warmer conditions were correlated to the E. uniflora higher DS threshold. Low rainfall and temperature corresponded to a lower desiccation sensitivity of E. astringens seeds. Seeds of the five species lost half viability between 0.44 and 0.25 g H 2 O g DW - 1 and after 65-270 h of desiccation. Our results indicate that abiotic factors impact plant populations during the seed production season and can drive seed desiccation tolerance threshold and physiological behavior. These results should be taken into account in ex-situ plant conservation programs and tropical species management., (© 2022. The Author(s) under exclusive licence to The Botanical Society of Japan.)

Introduction: There is no consensus on treatment of recalcitrant lateral epicondylitis (RLE). This is a prospective, non-randomized, interventional study comparing pain scores and functional outcomes between arthroscopic extensor carpi radialis brevis release and continued intensive conservative treatment., Materials and Methods: The study compared two groups: Group 1, consisting of 25 patients undergoing continued conservative treatment for 24 months, and Group 2, consisting of 25 patients undergoing arthroscopic extensor carpi radialis brevis release with decortication (ARD). VAS (Visual Analogue Scale) score for lateral elbow pain at rest and after routine daily activities were compared at 6 weeks, 24 weeks, 12 months and 24 months. Functional outcomes were compared with grip strength, and patients reported functional outcome scores, pre-intervention and 24 months post-intervention., Results: There was a significant improvement in VAS scores for pain, functional outcome scores, and grip strength in both the groups post-intervention ( P  < 0.05). VAS scores for pain at rest in both the groups were significantly better after the interventions, at all follow-up durations ( P  < 0.001). VAS scores for pain after routine daily activities were significantly better in group 2 at 24 weeks ( P  = 0.002) and afterward ( P  < 0.001). Group 2 had significantly better functional outcome scores at 24 months ( P  < 0.001) though the difference in grip strength was not statistically significant ( P  = 0.121)., Conclusion: The present study shows favourable functional outcomes and pain scores of ARD compared to continued intensive conservative treatment for RLE., Level of Study: II, Non-randomized comparative study., Supplementary Information: The online version contains supplementary material available at 10.1007/s43465-022-00649-w., Competing Interests: Conflict of interestAll authors (s) declare that they do not have any competing interest concerning this research, authorship, and/or publication of this article., (© Indian Orthopaedics Association 2022.)

Syzygium maire is a highly threatened Myrtaceae tree species endemic to New Zealand. Due to its recalcitrant seed storage behaviour, cryopreservation is the only viable long-term ex situ conservation option for this species. This study investigated viability, oxidative stress, thermal properties, and ultrastructure of zygotic embryo axes (EAs) desiccated to various moisture contents (MC). Fresh EAs had a MC of c. 1.9 g/g with 100% viability but rapid desiccation to MC < 0.3 g/g significantly reduced viability and decreased the activities of the enzymatic antioxidants superoxide dismutase, catalase and glutathione peroxidase, with a sevenfold increase in the production of protein carbonyls and lipid peroxides. Differential Scanning Calorimetry analysis showed no thermal events in EAs desiccated to a MC of <0.2 g/g, indicating that all freezable water had been removed, but this was lethal to both EAs and enzymatic antioxidants. The ultrastructure of desiccated EAs showed signs of plasmolysis, while fully hydrated EAs exposed to cryogenic temperature had ultrastructural disintegration and membrane damage. The decline in enzymatic antioxidant activities and the increase in lipid peroxidation suggest that S. maire EA viability loss is due to oxidative stress rather than structural impacts.

High-temperature thermal pretreatment alone or in conjugation with chemical pretreatment (highly acidic or alkaline) produced recalcitrant compounds, which inhibits the anaerobic digestion (AD) process performance. This study aims to develop a strategy to use carbon-based conductive materials to mitigate the recalcitrant toxicity and enhance the methane generation in the downstream AD. The formation of recalcitrant compounds, mainly the furan derivatives, i.e., furfural and 5-HydroxyMethyl furfurals (5-HMF) during thermo-chemical pretreatment of OFMSW at 150 °C, 175 °C, 200 °C with 3 g/L-NaOH dose, and the alleviation of their inhibitory effects by adding 25 g/L of each of granular activated carbon (GAC) and granular biochar (GBC) during mesophilic AD were studied. The addition of conductive materials resulted in the highest biogas yield of 462 mL/gVS added (GAC) and 449 mL/gVS added (GBC) for 175°C-3g/L-NaOH pretreatment, which was >45% higher over control. The highest improvement of >65% in biogas yield was observed for 200°C-3g/L-NaOH pretreatment despite the lower biogas yield. The conductive materials amended digester shows a significant decrease in the 5-HMF and furfurals concertation. The highest reduction in 5-HMF (44%) and furfural (51%) concentrations were observed for 200°C-3g/L-NaOH pretreatment, and 25 g/L GBC amended tests. The score plots from the principal component analysis (PCA) of the characterization of the digestate showed that the data were significant, whereas the loading plots depicted the correlation of different experimental parameters studied (like fate of recalcitrant, biogas yield and other parameters post AD of OFMSW when aided with conductive materials). Application of regression models in all the batch assays depicted that a lag phase of 2-4 days was observed in Modified Gompertz Model (MGM), 4-5 days in Logistic Model (LM) and a rapid hydrolysis was proven with the value of hydrolysis coefficient being between 0.003 and 0.029 from the first-order (FO) model., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Increasing energy demands and environmental issues have stressed the importance of sustainable methods of energy production. Anaerobic digestion (AD) of the biodegradable waste, i.e., agricultural residues, organic fraction of municipal solid waste (OFMSW), sewage sludge, etc., results in the production of biogas, which is a sustainable and cost feasible technique that reduces the dependence on fossil fuels and also overcomes the problems associated with biomass waste management. To solubilize the organic matter and enhance the susceptibility of hardly biodegradable fraction (i.e., lignocellulosic) for hydrolysis and increase methane production, several pretreatments, including physical, chemical, biological, and hybrid methods have been studied. However, these pretreatment methods under specific operating conditions result in the formation of recalcitrant compounds, such as sugars (xylose, Xylo-oligomers), organic acids (acetic, formic, levulinic acids), and lignin derivatives (poly and mono-phenolic compounds), causing significant inhibitory effects on anaerobic digestion. During the scaling up of these techniques from laboratory to industrial level, the focus on managing inhibitory compounds formed during pretreatment is envisaged to increase because of the need to use recalcitrant feedstocks in anaerobic digestion to increase biogas productivity. Therefore, it is crucial to understand the production mechanism of inhibitory compounds during pretreatment and work out the possible detoxification methods to improve anaerobic digestion. This paper critically reviews the earlier works based on the formation of recalcitrant compounds during feedstocks pretreatment under variable conditions, and their detrimental effects on process performance. The technologies to mitigate recalcitrant toxicity are also comprehensively discussed., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Lateral epicondylitis of the elbow is a common degenerative disorder in middle-aged patients. Surgery is reserved for patients who do not respond to nonoperative treatment., Purpose: To evaluate hand-grip strength and return to heavy manual activities in patients engaged in work requiring heavy lifting after arthroscopic release of refractory lateral epicondylitis., Study Design: Case series; Level of evidence, 4., Methods: The study included consecutive patients who underwent arthroscopic release of the extensor carpi radialis brevis tendon to treat recalcitrant lateral epicondylitis of the elbow, with a minimum 48-month follow-up. Functional outcome measures included assessment of hand-grip strength, visual analog scale for pain, and Mayo elbow performance score. The recorded measurements were compared at postoperative 1 and 6 months and the final assessment. Pre- and postoperative data were compared using the paired t test, and the various postoperative assessments were compared using 1-way analysis of variance., Results: A total of 22 patients (mean ± SD; age, 34.6 ± 5.9 years) with a mean follow-up of 60.5 ± 4.7 months were included in our study. There were highly significant improvements between preoperative and 1-month postoperative results regarding hand-grip strength (17.5 ± 4.1 kg to 34.4 ± 6.8 kg), visual analog scale score for pain (7.86 ± 1.2 to 1.8 ± 1.09), and Mayo score (57.1 ± 7.9 to 89.3 ± 4.9; P < .00001 for all). Significant improvements were found on all 3 functional measures between 1 and 6 months postoperatively ( P ≤ .05 was statistically significant), and there were nonsignificant improvements on all measures from 6-month to final follow-up. The patients regained 96.4% of their hand strength as compared with the unaffected side and returned to their previous activities without reporting serious complications., Conclusion: Minimally invasive arthroscopic release of recalcitrant lateral epicondylitis of the elbow provided a satisfactory functional result, as shown by regaining of hand-grip strength in patients engaged in heavy manual occupations without significant morbidities., Competing Interests: The authors declared that there are no conflicts of interest in the authorship and publication of this contribution. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2022.)

Introduction: The treatment of recalcitrant nongenital cutaneous warts has always been challenging for dermatologists as they often recur and relapse. Multiple treatment options have been investigated to improve the outcome. This review provides an overview of the current treatment modalities and summarizes the efficacy and side effects of each treatment option for recalcitrant nongenital cutaneous warts., Methods: A PubMed search was performed through July 2019 to include all English language reports investigating the treatment for recalcitrant nongenital cutaneous warts, regardless of design., Results: A total of 144 studies were included in this review. The treatment options for recalcitrant nongenital cutaneous warts can be divided into three groups: destructive treatment, immunotherapy, and cytotoxic agents. Although both destructive therapies and cytotoxic agents demonstrated high complete response rates, immunotherapy, which is a minimally invasive method, was superior in terms of the clearance of distant warts. Intralesional mumps-measles-rubella injections and purified protein derivatives currently demonstrate high efficacy with well-established clinical evidence., Conclusions: Many upcoming treatment modalities, especially immunotherapy, are promising. However, more comparative studies are required to verify the efficacy and safety profile.

Background: Recalcitrant auricular keloids are keloids that have recurred after any previous treatment. They have been shown to have an increased likelihood of recurrence. There is no consensus on how best to treat recalcitrant auricular keloids. Here, we perform the first systematic review and meta-analysis investigating the evidence for treating recalcitrant auricular keloids., Methods: We searched MEDLINE, EMBASE, CINAHL, and EBM Reviews using specific keywords. Prespecified inclusion and exclusion criteria were used to assess article eligibility. Data were extracted for number of recalcitrant keloids, treatment modality, recurrence, and minimum follow-up time. Included articles were stratified by treatment and assigned a level of evidence (LOE) based on the Oxford Centre for Evidence-Based Medicine guidelines. A meta-analysis was performed to estimate recurrence rates with 95% confidence intervals for each treatment modality., Results: A total of 887 unique articles were identified and 13 included. Eleven were LOE III and 2 were LOE IV. Recurrence rates were found to be 9% (95% CI: 3%-25%) for excision with adjuvant brachytherapy, 14% (95% CI: 12%-17%) for excision with adjuvant compression therapy, 17% (95% CI: 3%-56%) for excision with adjuvant external beam radiation, and 18% (95% CI: 4%-53%) for excision with adjuvant steroid injections. No statistical significant difference was found., Conclusions: Data for treatment of auricular keloids are heterogeneous with few high-quality studies. Excision with adjuvant brachytherapy has the lowest recurrence rate in our analysis. Narrow confidence intervals reported here for brachytherapy and compression therapy may help surgeons more confidently recommend either of these treatment modalities to patients., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2021 The Author(s).)

A hybridization of managed aquifer recharge (MAR) with pre-oxidation processes was conducted in this study to investigate changes in dissolved organic matter characteristics and the attenuation of selected trace organic contaminants (TrOCs). Potassium permanganate, chlorine, and ozone treatments were used for pre-oxidation, which effectively attenuated some TrOCs, particularly the combination of MAR with ozone achieved 84-99% attenuation. The pre-oxidation step using potassium permanganate showed high removal of carbamazepine (96%). Moreover, MAR was also combined with nanofiltration (NF) as a multi-barrier concept for the removal of persistent TrOCs after MAR. A short-chain polyfluoroalkyl substance (PFAS) was effectively removed after combining MAR columns with NF membranes. Thus, pre-oxidation coupled with MAR followed by NF could potentially enhance the removal of selected TrOCs., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The post-genomic tool metabolomics is a great advancement in science and technology which acquires novel strategies and pathways to analyze various biological compounds. Metabolomics aids in retrieving the qualitative and quantitative data from the various biological system. The current review is focused on the application of metabolomics in bioremediation and helps to focus on the xenobiotic compounds which are discharged into the environment and have long term impact. The microbial based biodegradation can be effectively used along with the combination of metabolomic approach for a better understanding of the breakdown of certain recalcitrant. Additionally, this review also discusses the candidate gene approach which helps to comprehend the functional analysis of microbial genes in response to different contaminants. Therefore, this review intends to discuss the metabolomics in bioremediation by studying the complete set of metabolites involved during the process of degradation and their interaction with the environment.

Topical cyclosporine (CSA) has been reported as an alternative treatment in steroid-refractory oral lichen planus (OLP), but evidence is limited and conflicting. An N-of-1 trial setting could be appropriate to evaluate interindividual differences in treatment response. We studied a series of 21 open-label, biphasic single-patient observations. Patients (15 women, 6 men) with OLP recalcitrant to topical steroids received four weeks of CSA mouth rinse (200 mg/twice daily) followed by four weeks of drug withdrawal. Pain (visual analogue scale (VAS) score), disease extent (physicians' global assessment (PGA) score) and quality of life (Dermatology Life Quality Index (DLQI) score,) were assessed at baseline (T0), after four weeks of treatment (T1) and after another four weeks without treatment (T2). Median age was 58 years (interquartile range/IQR = 52-67) and median disease duration was 18 months (IQR = 12-44). Median baseline VAS score decreased significantly at T1 ( p = 0.0003) and increased at T2 ( p = 0.032) (T0 = 5 (IQR = 3-6.5); T1 = 2 (IQR = 0.5-3.4); T2 = 3 (IQR = 2-4.8)). Similarly, median baseline PGA score decreased significantly at T1 ( p = 0.001) and increased at T2 ( p = 0.007) (T0 = 2 (IQR = 1.3-2.5); T1 = 1 (IQR = 1-2); T2 = 2 (IQR = 1-2)). Median baseline DLQI score also decreased significantly at T1 ( p =.027) but did not change at T2 ( p = 0.5) (T0 = 2.5 (IQR = 1-5.8); T1 = 1 (IQR = 0-3); T2 = 1 (IQR = 1-4)). CSA responders ( n = 16) had significantly higher median baseline VAS scores (5.2 (IQR = 5-6.5)) than nonresponders ( n =5) (2 (IQR = 2-3.5) ( p = 0.02). In our study, pain, disease extent and quality of life of patients with OLP improved significantly during therapy with low-dose CSA mouth rinse and exacerbated after drug withdrawal. Remarkably, patients with high initial VAS scores seemed to profit most.

Objectives: Previous work showed that higher polyp mast cell load correlated with worse postoperative endoscopic appearance in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Polyp epithelial mast cells showed increased expression of T-cell/transmembrane immunoglobulin and mucin domain protein 3 (TIM-3), a receptor that promotes mast cell activation and cytokine production. In this study, CRSwNP patients were followed post-operatively to investigate whether mast cell burden or TIM-3 expression among mast cells can predict recalcitrant disease., Methods: Nasal polyp specimens were obtained via functional endoscopic sinus surgery (FESS) and separated into epithelial and stromal layers via enzymatic digestion. Mast cells and TIM-3-expressing mast cells were identified via flow cytometry. Mann-Whitney U tests and Cox proportional hazard models assessed whether mast cell burden and TIM-3 expression were associated with clinical outcomes, including earlier recurrence of polypoid edema and need for treatment with steroids., Results: Twenty-three patients with CRSwNP were studied and followed for 6 months after undergoing FESS. Higher mast cell levels were associated with earlier recurrence of polypoid edema: epithelial HR = 1.283 ( P  = .02), stromal HR = 1.103 ( P  = .02). Percent of mast cells expressing TIM-3 in epithelial or stromal layers was not significantly associated with earlier recurrence of polypoid edema. Mast cell burden and TIM-3+ expression were not significantly associated with need for future treatment with steroids post-FESS., Conclusions: Mast cell load in polyp epithelium and stroma may predict a more refractory postoperative course for CRSwNP patients. The role of TIM-3 in the chronic inflammatory state seen in CRSwNP remains unclear.

Ulnar tunnel syndrome is the second most common upper-limb peripheral nerve compression syndrome. Recurrence or persistence of symptoms after primary surgery is found in 9.9%-21% of cases. The main cause of failure is peri- and endo-neural fibrosis, and management is difficult and controversial. Revision of nerve neurolysis combined with freestyle adipofascial flap provides nerve decompression and coverage with vascularized tissue, which prevents scar tissue formation around the nerve and restores glide. We performed a preliminary vessel-injected cadaver study. The perforating vessels from the posterior recurrent ulnar artery vascularize the medial adipose and fascial tissues of the elbow, allowing elevation of an adipofascial flap which is able to reach the ulnar nerve. Eight patients with neuropathic ulnar nerve pain in recalcitrant ulnar tunnel syndrome due to peri- and/or endo-neural fibrosis were treated by neurolysis, and the nerve was covered with an ulnar adipofascial flap. All patients were evaluated by percussion test, visual analog scale for pain, electromyography, electroneurography and ultrasound, and were classified according to the McGowan classification as modified by Goldberg. The study was approved by the review board. All patients had good 4-year outcome, with complete return to daily activity, work and sports 4 months after surgery. The results of this novel surgical technique were encouraging, without complications or donor site morbidity. Adipofascial flap combined with neurolysis could be a valid solution in the treatment of recalcitrant ulnar tunnel syndrome., (Copyright © 2021 SFCM. Published by Elsevier Masson SAS. All rights reserved.)