Safety of biologic therapy in combination with methotrexate in moderate to severe psoriasis: a cohort study from the BIOBADADERM registry.

BACKGROUND: Safety is an important consideration in decisions on treatment for patients with moderate-to-severe psoriasis and the study of drug safety is the main purpose of the BIOBADADERM registry. The combination of a biologic agent and a conventional systemic drug [generally methotrexate (MTX)] is a common treatment in clinical practice. However, there is a paucity of evidence from real-world practice on the safety of such combination regimens in the treatment of psoriasis. OBJECTIVES: The primary objective of this study was to ascertain whether the use of regimens combining biologic drugs with MTX in the management of moderate-to-severe psoriasis increases the risk of adverse events (AEs) or serious AEs (SAEs). We compared monotherapy using tumour necrosis factor (TNF), interleukin (IL)-17 and IL-23 inhibitors with the use of the same drugs in combination with MTX. METHODS: Using data from the BIOBADADERM registry, we compared biologic monotherapies with therapies that were combined with MTX. We estimated adjusted incidence rate ratios (aIRR) using a random effects Poisson regression with 95% confidence intervals for all AEs, SAEs, infections and serious infections and other AEs by system organ class. RESULTS: We analysed data from 2829 patients and 5441 treatment cycles, a total of 12 853 patient-years. The combination of a biologic with MTX was not associated with statistically significant increases in overall risk of AEs or SAEs in any treatment group. No increase in the total number of infections or serious infections in patients receiving combined therapy was observed for any group. However, treatment with a TNF inhibitor combined with MTX was associated with an increase in the incidence of gastrointestinal AEs (aIRR 2.50, 95% CI 1.57-3.98; P < 0.002). CONCLUSIONS: The risk of AEs and SAEs was not significantly increased in patients with moderate-to-severe psoriasis receiving different classes of biologic drugs combined with MTX compared with those on biologic monotherapy.

Screening of Phosphate Solubilization Identifies Six Pseudomonas Species with Contrasting Phytostimulation Properties in Arabidopsis Seedlings.

The interaction of plants with bacteria and the long-term success of their adaptation to challenging environments depend upon critical traits that include nutrient solubilization, remodeling of root architecture, and modulation of host hormonal status. To examine whether bacterial promotion of phosphate solubilization, root branching and the host auxin response may account for plant growth, we isolated and characterized ten bacterial strains based on their high capability to solubilize calcium phosphate. All strains could be grouped into six Pseudomonas species, namely P. brassicae, P. baetica, P. laurylsulfatiphila, P. chlororaphis, P. lurida, and P. extremorientalis via 16S rRNA molecular analyses. A Solibacillus isronensis strain was also identified, which remained neutral when interacting with Arabidopsis roots, and thus could be used as inoculation control. The interaction of Arabidopsis seedlings with bacterial streaks from pure cultures in vitro indicated that their phytostimulation properties largely differ, since P. brassicae and P. laurylsulfatiphila strongly increased shoot and root biomass, whereas the other species did not. Most bacterial isolates, except P. chlororaphis promoted lateral root formation, and P. lurida and P. chlororaphis strongly enhanced expression of the auxin-inducible gene construct DR5:GUS in roots, but the most bioactive probiotic bacterium P. brassicae could not enhance the auxin response. Inoculation with P. brassicae and P. lurida improved shoot and root growth in medium supplemented with calcium phosphate as the sole Pi source. Collectively, our data indicate the differential responses of Arabidopsis seedlings to inoculation with several Pseudomonas species and highlight the potential of P. brassicae to manage phosphate nutrition and plant growth in a more eco-friendly manner.

Secukinumab is effective and safe in the long-term treatment of plaque psoriasis in a daily practice setting: Multicenter study in 384 Spanish patients.

The aim of the study was to assess the long-term effectiveness and safety of secukinumab in Spanish patients with moderate-to-severe psoriasis in a daily practice setting. Nationwide multicenter, observational, retrospective, non-interventional, single-cohort study including patients who initiated treatment with secukinumab in daily clinical practice conditions. Subjects were followed for a minimum of 3 months and a maximum of 24 months. Psoriasis Area Severity Index (PASI), Body Surface Area and Physician's Global Assessments were collected at baseline and months 3, 6, 12, 18 and 24 during treatment. Adverse events and reasons for secukinumab withdrawal were collected and classified for analyses. A total of 384 patients were enrolled in the study. Median PASI declined rapidly from 14.3 at baseline to 2.7 at month 3, 2.1 at month 12, and remained low (2.8) at month 24. Within the group of patients with PASI ≥10 at baseline (n = 278), 58.3%, 60.4% and 56.5% achieved a PASI90 response at months 3, 12 and 24, respectively. As for absolute PASI, 86.5%, 69.5%, 42.7% and 37% achieved PASI <5, < 3, < 1 and 0, respectively, at month 3. Secukinumab was more effective in biologic-naïve patients and in those with lower Body Mass Index. Secukinumab presented a good long-term safety profile. Secukinumab was effective and safe in a routine clinical setting, in a large cohort of patients with moderate-to-severe plaque psoriasis, in the short-, medium- and long-term (up to 24 months).

Fast and sustained improvement of patient-reported outcomes in psoriatic patients treated with secukinumab in a daily practice setting.

Psoriasis is a chronic dermatological disease with great impact on patients' quality of life (QoL). The main objective of this study was to assess the impact of secukinumab treatment on different patient-reported outcomes (PROs) during a long-term follow-up in Spanish patients with moderate-to-severe psoriasis under real-world conditions. Retrospective, observational, open-label, nationwide multicenter cohort study that included patients who initiated treatment with secukinumab in daily clinical practice conditions. PROs assessing disease impact and QoL included Dermatology Life Quality Index (DLQI), Patient's Global Psoriasis Assessment, Itch Numerical Rating Scale and EuroQoL Thermometer Visual Analogue Scale. Outcomes, including PROs and Psoriasis Area and Severity Index (PASI), were assessed at months 3, 6, 12, 18, and 24 during treatment. A total of 238 patients were enrolled in the study. Patients had a mean DLQI score of 14.9 at baseline; 78.3%, 73.7%, and 71.7% of them achieved a DLQI 0/1 response at months 6, 12, and 24, respectively. DLQI score was lower in the long term for naïve patients. A sharp decrease in mean DLQI was observed during the first 3 months, reaching a plateau that was maintained until the end of follow-up. Similar findings were observed for the rest of QoL assessments. There was a close association between improvement in QoL and skin clearance (PASI), which progressively increased during follow-up. In this study, secukinumab sustainably improved patient's QoL during a 24-month follow-up, with strongest effects in patients naïve to biological therapies and with a direct correlation with PASI improvement.

Effect of Sex in Systemic Psoriasis Therapy: Differences in Prescription, Effectiveness and Safety in the BIOBADADERM Prospective Cohort.

The effect of sex on systemic therapy for psoriasis has not been well studied. The aim of this study was to analyse a large multicentre Spanish cohort of 2,881 patients with psoriasis (58.3% males), followed from January 2008 to November 2018, to determine whether sex influences prescription, effectiveness of therapy, and the risk of adverse events. The results show that women are more likely than men to be prescribed biologics. There were no differences between men and women in effectiveness of therapy, measured in terms of drug survival. Women were more likely to develop adverse events, but the difference in risk was small and does not justify different management. Study limitations include residual confounding and the use of drug survival as a proxy for effectiveness.

Histopathological findings in COVID-19-induced cutaneous lesions. Clinicopathological correlation of SARS-CoV-19 dermatologic patterns: review of the literature.

An increasing number of publications have brought attention to COVID-19-associated cutaneous lesions. Histopathological descriptions and clinical correlation of the histopathological findings of COVID-19 skin lesions are lacking. In this manuscript, we reviewed and described the histopathological characteristics of COVID-19 infection cutaneous patterns reported in the literature.

Long-term safety of nine systemic medications for psoriasis: A cohort study using the Spanish Registry of Adverse Events for Biological Therapy in Dermatological Diseases (BIOBADADERM) Registry.

BACKGROUND: Registry studies broadly describing the safety of systemic drugs in psoriasis are needed. OBJECTIVE: To describe the safety findings of the systemic drugs acitretin, adalimumab, apremilast, cyclosporine, etanercept, infliximab, methotrexate, secukinumab, and ustekinumab used for the treatment of moderate to severe psoriasis in patients included in the Spanish Registry of Adverse Events for Biological Therapy in Dermatological Diseases (BIOBADADERM) Registry. METHODS: The incidence rate ratio (IRR) and adjusted IRR (including propensity scores) of identified adverse events for each drug, using methotrexate as reference, were determined by means of a prospective cohort. RESULTS: Our study included 2845 patients (8954 treatment cycles; 9642 patient-years). Ustekinumab and secukinumab had the lowest rate of adverse events for several of the system organ classes, with a statistically significant decreased rate ratio (IRR of <1), whereas cyclosporine and infliximab had the highest, with an increased rate ratio (IRR of ≥5). LIMITATIONS: Observational study, drug allocation not randomized, depletion of susceptibles, and prescribed doses not registered. CONCLUSION: Our data provide comparative safety information in the real-life setting that could help clinicians selecting between available products.

To what extend is nail ultrasound discriminative between psoriasis, psoriatic arthritis and healthy subjects?

To assess the discriminative utility of nail features detected by B-mode (BM) and color Doppler (CD) ultrasound (US) between patients with psoriasis (PsO) and psoriatic arthritis (PsA) and healthy controls. Sixty patients with PsA, 21 patients with PsO, and 20 healthy controls were prospectively included. All patients underwent a dermatologic assessment and PsA patients also a rheumatologic assessment. All patients and controls underwent a US assessment of the finger nails that included a BM score for nail plate integrity and four different CD scores based on the amount and location of CD signals in the nail bed/matrix. In addition, we measured the thickness of the nail bed (TNB) and nail plate (TNP). The BM score and the CD score based on the amount of signals in the nail bed in contact with the ventral plate discriminated between the control group (median, range 0.0, 0-4 and 2.0, 0-9, respectively) and the PsO/PsA group (median, range: 7.0, 0-31 and 5.14, 0-13, respectively) (p < 0.05) with or without clinical nail involvement. The CD scores based on the percentage of the nail bed/matrix occupied by Doppler signals did not discriminate between controls and PsO/PsA patients. TNB and TNP were significantly higher in psoriatic nails with or without clinical involvement than in control nails. In PsO/PsA patients, the BM score, TNB and TNP were significantly higher in clinically involved nail than in clinically non-involved nails. Our results showed discriminative utility of BM US and some CD US features for PsO/PsA nails.

Mutations in an antisense RNA, involved in the replication control of a repABC plasmid, that disrupt plasmid incompatibility and mediate plasmid speciation.

The maintenance of large plasmid in a wide variety of alpha-proteobacteria depends on the repABC replication/segregation unit. The intergenic repB-repC region of these plasmids encodes a countertranscribed RNA (ctRNA) that modulates the transcription/translation rate of RepC, the initiator protein. The ctRNA acts as a strong incompatibility factor when expressed in trans. We followed a site directed mutagenesis approach to map those sequences of the ctRNA that are required for plasmid incompatibility and for plasmid replication control. We found that the first three nucleotides of the 5'-end of the ctRNA are essential for interactions with its target RNA. We also found that stretches of 4-5 nucleotides of non-complementarity within the first 10 nucleotides of the left arm of the ctRNA and the target RNA are sufficient to avoid plasmid incompatibility. Additionally, miniplasmid derivatives expressing ctRNAs with mutations in the 5' end or small deletions in the ctRNA are capable of controlling their own replication and coexisting with the parental plasmid. We suggest that a mechanism that could have a crucial role in the speciation process of repABC plasmids is to accumulate enough changes in this small region of the ctRNA gene to disrupt heteroduplex formation between the target RNA of one plasmid and the ctRNA of the other. Plasmids carrying these changes will not have defects in their maintenance.

Transcriptional and Metabolic Response of a Strain of Escherichia coli PTS- to a Perturbation of the Energetic Level by Modification of [ATP]/[ADP] Ratio.

The intracellular [ATP]/[ADP] ratio is crucial for Escherichia coli's cellular functions, impacting transport, phosphorylation, signaling, and stress responses. Overexpression of F1-ATPase genes in E. coli increases glucose consumption, lowers energy levels, and triggers transcriptional responses in central carbon metabolism genes, particularly glycolytic ones, enhancing carbon flux. In this contribution, we report the impact of the perturbation of the energetic level in a PTS- mutant of E. coli by modifying the [ATP]/[ADP] ratio by uncoupling the cytoplasmic activity of the F1 subunit of the ATP synthase. The disruption of [ATP]/[ADP] ratio in the evolved strain of E. coli PB12 (PTS-) was achieved by the expression of the atpAGD operon encoding the soluble portion of ATP synthase F1-ATPase (strain PB12AGD+). The analysis of the physiological and metabolic response of the PTS- strain to the ATP disruption was determined using RT-qPCR of 96 genes involved in glucose and acetate transport, glycolysis and gluconeogenesis, pentose phosphate pathway (PPP), TCA cycle and glyoxylate shunt, several anaplerotic, respiratory chain, and fermentative pathways genes, sigma factors, and global regulators. The apt mutant exhibited reduced growth despite increased glucose transport due to decreased energy levels. It heightened stress response capabilities under glucose-induced energetic starvation, suggesting that the carbon flux from glycolysis is distributed toward the pentose phosphate and the Entner-Duodoroff pathway with the concomitant. Increase acetate transport, production, and utilization in response to the reduction in the [ATP]/[ADP] ratio. Upregulation of several genes encoding the TCA cycle and the glyoxylate shunt as several respiratory genes indicates increased respiratory capabilities, coupled possibly with increased availability of electron donor compounds from the TCA cycle, as this mutant increased respiratory capability by 240% more than in the PB12. The reduction in the intracellular concentration of cAMP in the atp mutant resulted in a reduced number of upregulated genes compared to PB12, suggesting that the mutant remains a robust genetic background despite the severe disruption in its energetic level.

Jatropha curcas L. root structure and growth in diverse soils.

Unlike most biofuel species, Jatropha curcas has promise for use in marginal lands, but it may serve an additional role by stabilizing soils. We evaluated the growth and structural responsiveness of young J. curcas plants to diverse soil conditions. Soils included a sand, a sandy-loam, and a clay-loam from eastern Mexico. Growth and structural parameters were analyzed for shoots and roots, although the focus was the plasticity of the primary root system architecture (the taproot and four lateral roots). The sandy soil reduced the growth of both shoot and root systems significantly more than sandy-loam or clay-loam soils; there was particularly high plasticity in root and shoot thickness, as well as shoot length. However, the architecture of the primary root system did not vary with soil type; the departure of the primary root system from an index of perfect symmetry was 14 ± 5% (mean ± standard deviation). Although J. curcas developed more extensively in the sandy-loam and clay-loam soils than in sandy soil, it maintained a consistent root to shoot ratio and root system architecture across all types of soil. This strong genetic determination would make the species useful for soil stabilization purposes, even while being cultivated primarily for seed oil.

Glucose Transport in Escherichia coli: From Basics to Transport Engineering.

Escherichia coli is the best-known model for the biotechnological production of many biotechnological products, including housekeeping and heterologous primary and secondary metabolites and recombinant proteins, and is an efficient biofactory model to produce biofuels to nanomaterials. Glucose is the primary substrate used as the carbon source for laboratory and industrial cultivation of E. coli for production purposes. Efficient growth and associated production and yield of desired products depend on the efficient sugar transport capabilities, sugar catabolism through the central carbon catabolism, and the efficient carbon flux through specific biosynthetic pathways. The genome of E. coli MG1655 is 4,641,642 bp, corresponding to 4702 genes encoding 4328 proteins. The EcoCyc database describes 532 transport reactions, 480 transporters, and 97 proteins involved in sugar transport. Nevertheless, due to the high number of sugar transporters, E. coli uses preferentially few systems to grow in glucose as the sole carbon source. E. coli nonspecifically transports glucose from the extracellular medium into the periplasmic space through the outer membrane porins. Once in periplasmic space, glucose is transported into the cytoplasm by several systems, including the phosphoenolpyruvate-dependent phosphotransferase system (PTS), the ATP-dependent cassette (ABC) transporters, and the major facilitator (MFS) superfamily proton symporters. In this contribution, we review the structures and mechanisms of the E. coli central glucose transport systems, including the regulatory circuits recruiting the specific use of these transport systems under specific growing conditions. Finally, we describe several successful examples of transport engineering, including introducing heterologous and non-sugar transport systems for producing several valuable metabolites.

Anti-interleukin-17 therapies for moderate/severe psoriasis in clinical practice: effectiveness, safety and association with clinical patient factors.

OBJECTIVES: Interleukin-17 (IL-17) contributes to the pathogenesis of psoriasis. Secukinumab, ixekizumab, and brodalumab are monoclonal antibodies anti-IL-17 antibodies, approved for the treatment of moderate/severe plaque psoriasis.The aim of the study was to describe the effectiveness and safety of anti-IL-17 agents in moderate/severe plaque psoriasis in clinical practice. We also analysed anti-IL-17 therapies' survival, dose adjustment, and clinical patients' factors associated with their effectiveness and safety. METHODS: A retrospective, longitudinal study was conducted at a tertiary hospital. We included patients with moderate/severe psoriasis treated with anti-IL-17 agents. The effectiveness was evaluated with Psoriasis Area and Severity Index (PASI) score and safety through the adverse drug reactions (ADRs) collected. RESULTS: 38 patients were studied (median age=47.4 years, 71.0% male). The mean number of biological therapies that patients received was 2.6, and anti-IL-17 therapy was the first biological therapy for 36.8% of patients. The median years in treatment were 2.5 (95% CI 1.95 to 2.98) for secukinumab, 1.2 (95% CI 0.36 to 1.47) for ixekizumab, and 0.7 (IQR 0.71) for brodalumab. The median PASI score after 6 months of treatment was 0 (IQR 0) and 85.3% of patients achieved a PASI of 90 (84.0% with secukinumab, 87.5% with ixekizumab, and 100% with brodalumab). Dose adjustment was associated with the line of treatment (p=0.034 for naïve patients), age (p=0.044 for younger patients), and concomitant pathologies (p=0.015 without more diseases).24 patients suffered from ADRs, mainly infections of the upper respiratory tract, and there were no statistically significant differences between the three therapies. CONCLUSIONS: Anti-IL-17 agents constitute an effective treatment for patients with moderate/severe plaque psoriasis and for longer. Dose reductions were associated with fewer lines of treatment, younger patients and absence of concomitant pathologies. ADR were minor and similar among the anti-IL-17.

The risk of hepatic adverse events of systemic medications for psoriasis: a prospective cohort study using the BIOBADADERM registry.

BACKGROUND: Limited information is available regarding the risk of incident liver disease in patients with psoriasis receiving systemic therapies. OBJECTIVES: To describe the liver safety findings of conventional and modern systemic therapies for moderate-to-severe psoriasis, and to compare the relative incidence rates of hepatic adverse events (AEs) for each drug. METHODS: All the patients on the BIOBADADERM registry were included. Crude and adjusted incidence rate ratios (cIRR and aIRR, respectively) of hepatic AEs, using anti-TNF drugs as reference, were determined. Outcomes of interest were hypertransaminasemia, nonalcoholic fatty liver disease (NADFLD) and a group of other, less represented, hepatic AEs. RESULTS: Our study included 3,171 patients exposed to systemic drugs (6279 treatment cycles). Incident hypertransaminasemia was the most frequent hepatic AE (incidence rate of 21 per 1000 patients-years [CI 95% 18-23]), followed by NAFLD (8 cases per 1000 patients-years [95% CI 6-10]). Methotrexate (aIRR 3.06 [2.31-4.4]; p = 0.000) and cyclosporine (aIRR 2.37 [1.05-5.35]; p = .0378) were associated with an increased risk for hypertransaminasemia when compared to anti-TNF-α agents. No differences were observed between different groups of biologics. Conventional therapies were not associated with new incident NAFLD. CONCLUSIONS: Comparative information of the incidence of hepatic AEs could facilitate drug selection in moderate-to-severe psoriasis.

Characterization of plant growth-promoting bacteria associated with avocado trees (Persea americana Miller) and their potential use in the biocontrol of Scirtothrips perseae (avocado thrips).

Plants interact with a great variety of microorganisms that inhabit the rhizosphere or the epiphytic and endophytic phyllosphere and that play critical roles in plant growth as well as the biocontrol of phytopathogens and insect pests. Avocado fruit damage caused by the thrips species Scirtothrips perseae leads to economic losses of 12-51% in many countries. In this study, a screening of bacteria associated with the rhizosphere or endophytic phyllosphere of avocado roots was performed to identify bacterial isolates with plant growth-promoting activity in vitro assays with Arabidopsis seedlings and to assess the biocontrol activity of the isolates against Scirtothrips perseae. The isolates with beneficial, pathogenic and/or neutral effects on Arabidopsis seedlings were identified. The plant growth-promoting bacteria were clustered in two different groups (G1 and G3B) based on their effects on root architecture and auxin responses, particularly bacteria of the Pseudomonas genus (MRf4-2, MRf4-4 and TRf2-7) and one Serratia sp. (TS3-6). Twenty strains were selected based on their plant growth promotion characteristics to evaluate their potential as thrips biocontrol agents. Analyzing the biocontrol activity of S. perseae, it was identified that Chryseobacterium sp. shows an entomopathogenic effect on avocado thrips survival. Through the metabolic profiling of compounds produced by bacteria with plant growth promotion activity, bioactive cyclodipeptides (CDPs) that could be responsible for the plant growth-promoting activity in Arabidopsis were identified in Pseudomonas, Serratia and Stenotrophomonas. This study unravels the diversity of bacteria from the avocado rhizosphere and highlights the potential of a unique isolate to achieve the biocontrol of S. perseae.

Seedling Characteristics of Three Oily Species before and after Root Pruning and Transplant.

Moringa oleifera Lam. (Moringa), Jatropha curcas L. (Jatropha), and Ricinus communis L. (Ricinus) are oily species known by their capability to grow in tropical and subtropical lands. However, there are no studies comparing their growth and recovery capabilities after root pruning and transplant. The purpose of this research was to compare and analyze propagation, growth, and recovery performance of these species after root pruning and transplant. We sowed 100 seeds per species and monitored their survival and growth during a 63-day period; after this, we uprooted the plants and pruned their roots 4.0 cm from their base and transplanted them. We monitored their recovery over 83 days, and then uprooted plants and measured above- and belowground data, digitized their roots in three dimensions, and calculated biomass fractions. With this information, we established allometric equations to estimate biomass fractions and root distribution models. Results indicated that Ricinus had the highest propagation capabilities. Jatropha and Ricinus had similar recovery after root pruning and transplant. Moringa had the lowest propagation and recovery from transplant. Concerning belowground data, root pruning increased root density more than three times in Moringa, four times in Ricinus, and six times in Jatropha. Nevertheless, the three species maintained natural root trays. Ricinus had the longest and thinnest roots and the highest number of branches, followed by Jatropha, and finally Moringa, with the smallest quantity and the shortest and thickest roots. We concluded that the three species recovered well from root pruning and transplant, with improved root structure upon applying these practices.

Phenotypic and genomic analysis of Zymomonas mobilis ZM4 mutants with enhanced ethanol tolerance.

Zymomonas mobilis ZM4 is an ethanol-producing microbe that is constitutively tolerant to this solvent. For a better understanding of the ethanol tolerance phenomenon we obtained and characterized two ZM4 mutants (ER79ap and ER79ag) with higher ethanol tolerance than the wild-type. Mutants were evaluated in different ethanol concentrations and this analysis showed that mutant ER79ap was more tolerant and had a better performance in terms of cell viability, than the wild-type strain and ER79ag mutant. Genotyping of the mutant strains showed that both carry non-synonymous mutations in clpP and spoT/relA genes. A third non-synonymous mutation was found only in strain ER79ap, in the clpB gene. Considering that ER79ap has the best tolerance to added ethanol, the mutant alleles of this strain were evaluated in ZM4 and here we show that while all of them contribute to ethanol tolerance, mutation within spoT/relA gene seems to be the most important.

Antifungal potential of Lauraceae rhizobacteria from a tropical montane cloud forest against Fusarium spp.

The occurrence of pests and diseases can affect plant health and productivity in ecosystems that are already at risk, such as tropical montane cloud forests. The use of naturally occurring microorganisms is a promising alternative to mitigate forest tree fungal pathogens. The objectives of this study were to isolate rhizobacteria associated with five Lauraceae species from a Mexican tropical montane cloud forest and to evaluate their antifungal activity against Fusarium solani and F. oxysporum. Fifty-six rhizobacterial isolates were assessed for mycelial growth inhibition of Fusarium spp. through dual culture assays. Thirty-three isolates significantly reduced the growth of F. solani, while 21 isolates inhibited that of F. oxysporum. The nine bacterial isolates that inhibited fungal growth by more than 20% were identified through 16S rDNA gene sequence analysis; they belonged to the genera Streptomyces, Arthrobacter, Pseudomonas, and Staphylococcus. The volatile organic compounds (VOC) produced by these nine isolates were evaluated for antifungal activity. Six isolates (Streptomyces sp., Arthrobacter sp., Pseudomonas sp., and Staphylococcus spp.) successfully inhibited F. solani mycelial growth by up to 37% through VOC emission, while only the isolate INECOL-21 (Pseudomonas sp.) inhibited F. oxysporum. This work provides information on the microbiota of Mexican Lauraceae and is one of the few studies identifying forest tree-associated microbes with inhibitory activity against tree pathogens.

Association between clinical factors and dose modification strategies in the treatment with ustekinumab for moderate-to-severe plaque psoriasis.

PURPOSE: The aim of this study was to identify clinical factors associated with dose reduction and dose escalation in the treatment with ustekinumab in patients with moderate-to-severe plaque psoriasis. MATERIALS AND METHODS: An observational, longitudinal and retrospective study was conducted using patients with moderate-to-severe plaque psoriasis. We reviewed clinical histories and variables were recorded on a database (patients' characteristics, pharmacotherapeutics, effectiveness and safety). We evaluated correlation between dose reduction, dose escalation and used dose with other variables. RESULTS: Of the study's 62 patients, Ustekinumab dose was adjusted in 45.2% (22.6% with reduced doses and 22.6% with increased doses). We found a statistically significant correlation between extending the dosing interval and the absence of psoriatic arthritis, no concomitant systemic therapies, treatment time with ustekinumab, lower PASI at week 28 and achieving PASI75 at week 28. There was also a statistically significant correlation between dose escalation and diabetes mellitus, psoriatic arthritis, prior biological treatments, concomitant systemic therapies, concomitant phototherapy and not achieving PASI75 at week 28. CONCLUSIONS: Dose-reduction strategies would increase ustekinumab efficiency in patients that achieve PASI 75 without psoriatic arthritis, diabetes mellitus, previous BT and concomitant treatment with conventional systemic drugs.