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Pain research continues to face the challenge of poor translatability of pre-clinical studies. In this short primer, we are summarizing the possible causes, with an emphasis on practical and constructive solutions. In particular, we stress the importance of increased heterogeneity in animal studies; formal or informal pre-registration to combat publication bias; and increased statistical training in order to help pre-clinical scientists appreciate the usefulness of available experimental design and reporting guidelines.
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Dolor , Proyectos de Investigación , Animales , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: Biosynthesis of metallic nanoparticles using microorganisms are a fabulous and emerging eco-friendly science with well-defined sizes, shapes and controlled monodispersity. Copper nanoparticles, among other metal particles, have sparked increased attention due to their applications in electronics, optics, catalysis, and antimicrobial agents. RESULTS: This investigation explains the biosynthesis and characterization of copper nanoparticles from soil strains, Niallia circulans G9 and Paenibacillus sp. S4c by an eco-friendly method. The maximum reduction of copper ions and maximum synthesis CuNPs was provided by these strains. Biogenic formation of CuNPs have been characterized by UV-visible absorption spectroscopy, X-ray diffraction, Fourier transform infrared spectroscopy, X-ray analysis and transmission electron microscopy analysis. Using UV-visible spectrum scanning, the synthesised CuNPs' SPR spectra showed maximum absorption peaks at λ304&308 nm. TEM investigation of the produced CuNPs revealed the development of spherical/hexagonal nanoparticles with a size range of 13-100 nm by the G9 strain and spherical nanoparticles with a size range of 5-40 nm by the S4c strain. Functional groups and chemical composition of CuONPs were also confirmed. The antimicrobial activity of the biosynthesized CuNPs were investigated against some human pathogens. CuNPs produced from the G9 strain had the highest activity against Candida albicans ATCC 10,231 and the lowest against Pseudomonas aeruginosa ATCC 9027. CuNPs from the S4c strain demonstrated the highest activity against Escherichia coli ATCC 10,231 and the lowest activity against Klebsiella pneumonia ATCC 13,883. CONCLUSION: The present work focused on increasing the CuNPs production by two isolates, Niallia circulans G9 and Paenibacillus sp. S4c, which were then characterized alongside. The used analytics and chemical composition techniques validated the existence of CuONPs in the G9 and S4c biosynthesized nano cupper. CuNPs of S4c are smaller and have a more varied shape than those of G9 strain, according to TEM images. In terms of antibacterial activity, the biosynthesized CuNPs from G9 and S4c were found to be more effective against Candida albicans ATCC 10,231 and E. coli ATCC 10,231, respectively.
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Cobre , Nanopartículas del Metal , Paenibacillus , Paenibacillus/metabolismo , Nanopartículas del Metal/química , Cobre/química , Antiinfecciosos/farmacología , Antiinfecciosos/química , Antiinfecciosos/metabolismo , Pruebas de Sensibilidad Microbiana , Antibacterianos/biosíntesis , Antibacterianos/farmacología , Antibacterianos/química , Ascomicetos/efectos de los fármacos , Ascomicetos/metabolismoRESUMEN
The increasing interest in environmental protection laws has compelled companies to regulate the disposal of waste organic materials. Despite efforts to explore alternative energy sources, the world remains heavily dependent on crude petroleum oil and its derivatives. The expansion of the petroleum industry has significant implications for human and environmental well-being. Bioremediation, employing living microorganisms, presents a promising approach to mitigate the harmful effects of organic hydrocarbons derived from petroleum. This study aimed to isolate and purify local yeast strains from oil-contaminated marine water samples capable of aerobically degrading crude petroleum oils and utilizing them as sole carbon and energy sources. One yeast strain (isolate B) identified as Candida tropicalis demonstrated high potential for biodegrading petroleum oil in seawater. Physiological characterization revealed the strain's ability to thrive across a wide pH range (4-11) with optimal growth at pH 4, as well as tolerate salt concentrations ranging from 1 to 12%. The presence of glucose and yeast extract in the growth medium significantly enhanced the strain's biomass formation and biodegradation capacity. Scanning electron microscopy indicated that the yeast cell diameter varied based on the medium composition, further emphasizing the importance of organic nitrogenous sources for initial growth. Furthermore, the yeast strain exhibited remarkable capabilities in degrading various aliphatic and aromatic hydrocarbons, with a notable preference for naphthalene and phenol at 500 and 1000 mg/l, naphthalene removal reached 97.4% and 98.6%, and phenol removal reached 79.48% and 52.79%, respectively. Optimization experiments using multi-factorial sequential designs highlighted the influential role of oil concentration on the bioremediation efficiency of Candida tropicalis strain B. Moreover, immobilized yeast cells on thin wood chips demonstrated enhanced crude oil degradation compared to thick wood chips, likely due to increased surface area for cell attachment. These findings contribute to our understanding of the potential of Candida tropicalis for petroleum oil bioremediation in marine environments, paving the way for sustainable approaches to address oil pollution.
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Candida tropicalis , Petróleo , Humanos , Candida tropicalis/metabolismo , Biodegradación Ambiental , Levaduras/metabolismo , Petróleo/metabolismo , Hidrocarburos/metabolismo , Fenol/metabolismo , Naftalenos/metabolismoRESUMEN
OBJECTIVE: This study aimed to investigate the ultraviolet (UV) protection/repair benefits of a patented Amino Acid Complex (AAComplex). METHODS: I) AAComplex was incubated with dermal fibroblasts, with/without UVA, and collagen I was measured with a GlasBoxPlus device. II) A lotion, with/without AAComplex (1%) was applied topically to skin explants, following UVA irradiation, and quantified for health-related biomarkers (TNFalpha, histamine, and MMP-1). III) A broad spectrum sunscreen with SPF 46 and a skincare serum containing AAComplex (2%) were assessed using epidermal equivalents, in the presence of UV irradiation, for effects on IL-1alpha, thymine dimers, Ki-67, filaggrin and Nrf2. RESULTS: I) Collagen I synthesis in dermal fibroblasts was significantly decreased after UVA compared to without UV. The presence of AAComplex prevented this decrease. II) UVA irradiation of skin explants increased histamine, TNFα, and MMP-1. Hydrocortisone aceponate cream significantly decreases all 3 biomarkers. AAComplex contained lotion also significantly decreased all 3 biomarkers, the no AAComplex control lotion only reduced histamine. III) With the regimen of sunscreen + AAComplex contained skincare serum, the significant reduction in IL-1alpha was observed along with a complete recovery of Ki-67 and stimulation of filaggrin and Nrf2T. No thymine dimer positive cell was observed indicating the most positive skin impact from the regiment. Conclusion: This research using different human skin models demonstrated that AAComplex can provide protection and damage repair caused by UV, at the ingredient level also when formulated in a serum or lotion formula. Skin may be best protected from UV damage when the regimen is used. J Drugs Dermatol. 2024;23(5):366-375. doi:10.36849/JDD.7916.
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Fibroblastos , Proteínas Filagrina , Metaloproteinasa 1 de la Matriz , Factor 2 Relacionado con NF-E2 , Factor de Necrosis Tumoral alfa , Rayos Ultravioleta , Humanos , Rayos Ultravioleta/efectos adversos , Fibroblastos/efectos de los fármacos , Fibroblastos/efectos de la radiación , Fibroblastos/metabolismo , Metaloproteinasa 1 de la Matriz/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Piel/efectos de la radiación , Piel/efectos de los fármacos , Piel/metabolismo , Protectores Solares/administración & dosificación , Protectores Solares/química , Protectores Solares/farmacología , Aminoácidos/administración & dosificación , Aminoácidos/farmacología , Aminoácidos/química , Interleucina-1alfa/metabolismo , Histamina/sangre , Crema para la Piel/administración & dosificación , Biomarcadores/metabolismo , Colágeno Tipo I , Proteínas de Filamentos Intermediarios/metabolismo , Antígeno Ki-67/metabolismo , Dímeros de Pirimidina , Células CultivadasRESUMEN
Chronic pain is a constantly recurring and persistent illness, presenting a formidable healthcare challenge for patients and physicians alike. Current first-line analgesics offer only low-modest efficacy when averaged across populations, further contributing to this debilitating disease burden. Moreover, many recent trials for novel analgesics have not met primary efficacy endpoints, which is particularly striking considering the pharmacological advances have provided a range of highly relevant new drug targets. Heterogeneity within chronic pain cohorts is increasingly understood to play a critical role in these failures of treatment and drug discovery, with some patients deriving substantial benefits from a given intervention while it has little-to-no effect on others. As such, current treatment failures may not result from a true lack of efficacy, but rather a failure to target individuals whose pain is driven by mechanisms which it therapeutically modulates. This necessitates a move towards phenotypical stratification of patients to delineate responders and non-responders in a mechanistically driven manner. In this article, we outline a bench-to-bedside roadmap for this transition to mechanistically informed personalised pain medicine. We emphasise how the successful identification of novel analgesics is dependent on rigorous experimental design as well as the validity of models and translatability of outcome measures between the animal model and patients. Subsequently, we discuss general and specific aspects of human trial design to address heterogeneity in patient populations to increase the chance of identifying effective analgesics. Finally, we show how stratification approaches can be brought into clinical routine to the benefit of patients.
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BACKGROUND: Respiratory viruses, particularly adenoviruses (ADV), influenza A virus (e.g., H1N1), and coronaviruses (e.g., HCoV-229E and SARS-CoV-2) pose a global public health problem. Therefore, developing natural wide-spectrum antiviral compounds for disrupting the viral life cycle with antioxidant activity provides an efficient treatment approach. Herein, biosurfactant (Sur) and C50 carotenoid pigment (Pig) of haloalkaliphilic archaeon Natrialba sp. M6 which exhibited potent efficacy against hepatitis and anti-herpes simplex viruses, were investigated against pulmonary viruses. METHODS: The cytotoxicity of the extracted Sur and Pig was examined on susceptible cell lines for ADV, HIN1, HCoV-229E, and SARS-CoV-2. Their potential against the cytopathic activity of these viruses was detected with investigating the action modes (including, virucidal, anti-adsorption, and anti-replication), unveiling the main mechanisms, and using molecular docking analysis. Radical scavenging activity was determined and HPLC analysis for potent extract (Sur) was performed. RESULTS: All current investigations stated higher anti-pulmonary viruses of Sur than Pig via mainly virucidal and/or anti-replicative modes. Moreover, Sur had stronger ADV's capsid protein binding, ADV's DNA polymerase inhibition, suppressing hemagglutinin and neuraminidase of H1N1, and inhibiting chymotrypsin-like (3CL) protease of SARS-CoV-2, supporting with in-silico analysis, as well as radical scavenging activity than Pig. HPLC analysis of Sur confirmed the predominate presence of surfactin in it. CONCLUSION: This study declared the promising efficacy of Sur as an efficient pharmacological treatment option for these pulmonary viruses and considered as guide for further in vivo research.
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Coronavirus Humano 229E , Subtipo H1N1 del Virus de la Influenza A , Antivirales/uso terapéutico , Simulación del Acoplamiento Molecular , SARS-CoV-2 , Carotenoides/farmacologíaRESUMEN
Regular usage of cosmetic products and drugs in dermatological vehicles may cause irritant contact dermatitis. For example, aluminum chloride (AlCl3), the most efficacious antiperspirant salt to treat hyperhidrosis, shows high irritancy potential. To mitigate the irritant contact dermatitis caused by topical application of products containing AlCl3, we investigated the anti-irritating effects of aloe extract and taurine in vitro and in vivo. In an in vitro experiment, reconstructed human epidermis model, EpiDerm, was tested with AlCl3 in the presence or absence of taurine and aloe extract. In a human clinical study, 12 adult subjects were tested with two products, a commercial AlCl3 antiperspirant product and a prototype 12% AlCl3 formulation containing 0.1% taurine and 0.1% aloe extract. Skin irritation potential in vitro and in vivo was measured by the release of pro-inflammatory cytokine, IL-1α, and chemokine, IL-8. Taurine and aloe extract significantly (p < 0.05) reduced IL-lα and IL-8 production in vitro and in vivo after topical application of formulations containing AlCl3. The blend of taurine and aloe extract demonstrated boosted anti-irritation benefits on AlCl3 irritated skin both in vitro and in vivo. These results suggest that the combination of these anti-irritating actives may possibly be effective in mitigating irritant contact dermatitis caused by other dermatological vehicles containing irritating agents, but further research is warranted to assess their effects.
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Aloe/química , Dermatitis por Contacto/prevención & control , Extractos Vegetales/química , Piel/efectos de los fármacos , Taurina/química , Adulto , Cloruro de Aluminio , Compuestos de Aluminio/efectos adversos , Antitranspirantes/efectos adversos , Astringentes , Supervivencia Celular/efectos de los fármacos , Cloruros/efectos adversos , Cosméticos/efectos adversos , Citocinas/biosíntesis , Femenino , Humanos , Técnicas In Vitro , Queratinocitos/efectos de los fármacos , Masculino , Extractos Vegetales/farmacocinética , Absorción Cutánea , Taurina/farmacocinéticaRESUMEN
The goal of the current work was to optimize the growth parameters needed to manufacture agarase enzyme from a non-marine PI strain of Bacillus subtilis on an agar-based medium. Using Plackett-Burman design (PBD), nine process parameters were evaluated, and agar, peptone, and yeast-extract were identified as the most significant independent factors influencing agarase production with confidence levels more than 90%. To evaluate the optimal concentrations of the indicated process parameters on agarase production, the Box-Behnken design (BBD) was applied. After optimization, B. subtilis strain PI produced 119.8 U/ml of agarase, representing a 1.36-fold increase. In addition the agar hydrolysate fermented products contain the liberated oligosaccharide acts as strong antioxidant which has 62.4% scavenging activity. Also, the agarase yields increased (1141.12, 1350.253, 1684.854 and 1921.863 U/ml) after substitution the agar with algal biomass of Carolina officinalis at different concentrations (2, 5, 10 and 15%), respectively. After completing the saccharification process, the resulted hydrolysate was used to produce ethanol through fermentation with Pichia pastoris yeast strain as an economical method giving yields (6.68317, 7.09748, 7.75648 and 8.22332 mg/ml), that are higher than using yeast extract peptone dextrose (YPD) medium (4.461 mg/ml).
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Bacillus subtilis , Biomasa , Etanol , Fermentación , Glicósido Hidrolasas , Bacillus subtilis/metabolismo , Bacillus subtilis/crecimiento & desarrollo , Bacillus subtilis/enzimología , Etanol/metabolismo , Glicósido Hidrolasas/metabolismo , Medios de Cultivo/química , Agar/química , Hidrólisis , Antioxidantes/metabolismoRESUMEN
ABSTRACT: In the peripheral nervous system, spontaneous activity in sensory neurons is considered to be one of the 2 main drivers of chronic pain states, alongside neuronal sensitization. Despite this, the precise nature and timing of this spontaneous activity in neuropathic pain is not well-established. Here, we have performed a systematic search and data extraction of existing electrophysiological literature to shed light on which fibre types have been shown to maintain spontaneous activity and over what time frame. We examined both in vivo recordings of preclinical models of neuropathic pain, as well as microneurography recordings in humans. Our analyses reveal that there is broad agreement on the presence of spontaneous activity in neuropathic pain conditions, even months after injury or years after onset of neuropathic symptoms in humans. However, because of the highly specialised nature of the electrophysiological methods used to measure spontaneous activity, there is also a high degree of variability and uncertainty around these results. Specifically, there are very few directly controlled experiments, with less directly comparable data between human and animals. Given that spontaneous peripheral neuron activity is considered to be a key mechanistic feature of chronic pain conditions, it may be beneficial to conduct further experiments in this space.
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Dolor Crónico , Neuralgia , Animales , Humanos , Dolor Crónico/complicaciones , Neuralgia/etiología , Nervios Periféricos , Sistema Nervioso Periférico , Células Receptoras Sensoriales/fisiología , Enfermedad CrónicaRESUMEN
ABSTRACT: Combat trauma can lead to widespread tissue damage and limb loss. This may result in chronic neuropathic and post amputation pain, including phantom limb pain (PLP) and residual limb pain (RLP). The military population is distinct with respect to demographic, injury, and social characteristics compared with other amputation and trauma cohorts. We undertook a systematic review of studies of military personnel, with a history of combat injury, that reported a prevalence of any type of postamputation pain or chronic neuropathic pain, identified from Embase and MEDLINE databases.Using the inverse variance method with a random-effects model, we undertook a meta-analysis to determine an overall prevalence and performed exploratory analyses to identify the effect of the type of pain, conflict, and time since injury on prevalence. Pain definitions and types of pain measurement tools used in studies were recorded. Thirty-one studies (14,738 participants) were included. The pooled prevalence of PLP, RLP, and chronic neuropathic pain were 57% (95% CI: 46-68), 61% (95% CI: 50-71), and 26% (95% CI: 10-54), respectively. Between-study heterogeneity was high (I 2 : 94%-98%). Characterisation of duration, frequency, and impact of pain was limited. Factors reported by included studies as being associated with PLP included the presence of RLP and psychological comorbidity. The prevalence of postamputation pain and chronic neuropathic pain after combat trauma is high. We highlight inconsistency of case definitions and terminology for pain and the need for consensus in future research of traumatic injury.
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Dolor Crónico , Personal Militar , Neuralgia , Humanos , Neuralgia/epidemiología , Neuralgia/etiología , Personal Militar/estadística & datos numéricos , Prevalencia , Dolor Crónico/epidemiología , Amputación Quirúrgica/efectos adversos , Amputación Quirúrgica/estadística & datos numéricos , Miembro Fantasma/epidemiologíaRESUMEN
BACKGROUND: The magnitude of placebo effects from physical and psychological 'sham' is unknown but could impact efficacy trials and treatment understanding. To quantify placebo effects, this systematic review of three-armed randomised controlled trials (RCTs) of physical and psychological interventions for pain compared outcomes in 'sham' control intervention and non-exposure arms. METHODS: RCTs with treatment, 'sham' control intervention, and non-exposure groups were included, enrolling adults with any pain. A protocol was pre-registered (PROSPERO: CRD42023413324), and twelve databases searched from 2008 to July 2023. Trial methods and blinding were analysed descriptively and risk of bias assessed. Meta-analysis of pain measures at short-, medium- and long-term was performed with random-effects models of standardised mean differences (SMD).Studies were sub-grouped according to control intervention type. RESULTS: Seventeen RCTs were included. The average short-term placebo effect was small (0.21 SMD, 0.1-0.33 95% CI, p = 0.0002, 1440 participants). It showed no heterogeneity (Tau2 = 0.1, I2 = 11%, p = 0.3), preventing meta-regression analyses of effect modifiers. However, sub-group analyses revealed larger placebo effects in manual control interventions compared to disabled devices and miscellaneous control interventions. Overall, placebo analgesia accounted for 39% of treatments' short-term effectiveness. No placebo effects were found at medium-term (7 RCTs, 381 participants) or long-term follow-up (3 RCTs, 173 participants). CONCLUSIONS: The observed placebo analgesia has mechanistic and methodological implications, though its clinical importance may be limited. Control intervention design affects placebo effects, highlighting the importance of considering methodology in RCT interpretation. Review limitations include a small number of long-term studies and sample heterogeneity. SIGNIFICANCE: This systematic review directly quantifies placebo effects from physical and psychological 'sham' control interventions and compares them to treatments' overall effectiveness. By doing so, the review enhances our understanding of placebo effects, their relative contribution in clinical trials, and their susceptibly to trial design. It poses further questions regarding the influence of blinding, participant expectations, and features of the therapeutic context. Overall, the insights provided by this review carry methodological significance and are important for the interpretation and synthesis of efficacy trials in this field.
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Analgesia , Adulto , Humanos , DolorRESUMEN
Bacterioruberin and its rare glycosylated derivatives are produced by Arthrobacter agilis as an adaptation strategy to low temperature conditions. The high antioxidant properties of bacterioruberin held great promise for different future applications like the pharmaceutical and food industries. Microbial production of bacterioruberin via a cost-effective medium will help increase its commercial availability and industrial use. The presented study aims to optimize the production of the rare C50 carotenoid bacterioruberin and its derivatives from the psychotrophic bacteria Arthrobacter agilis NP20 strain on a whey-based medium as a cost effective and readily available nutritious substrate. The aim of the study is extended to assess the efficiency of whey treatment in terms of estimating total nitrogen content in treated and untreated whey samples. The significance of medium ingredients on process outcome was first tested individually; then the most promising factors were further optimized using Box Behnken design (BBD). The produced carotenoids were characterized using UV-visible spectroscopy, FTIR spectroscopy, HPLC-DAD chromatography and HPLC-APCI-MS spectrometry. The maximum pigment yield (5.13 mg/L) was achieved after a 72-h incubation period on a core medium composed of 96% sweet whey supplemented with 0.46% MgSO4 & 0.5% yeast extract and inoculated with 6% (v/v) of a 24 h pre-culture (109 CFU/mL). The cost of the formulated medium was 1.58 $/L compared with 30.1 $/L of Bacto marine broth medium. The extracted carotenoids were identified as bacterioruberin, bis-anhydrobacteriouberin, mono anhydrobacterioruberin, and glycosylated bacterioruberin. The presented work illustrates the possibility of producing bacterioruberin carotenoid from Arthrobacter agilis through a cost-effective and eco-friendly approach using cheese whey-based medium.
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It is crucial to identify more biological adsorbents that can efficiently uptake metals from wastewater. Dry haloalkaliphilic archaea Natronolimnobius innermongolicuswas evaluated for Cd ions biosorption. The optimal operating conditions (pH, biomass dose, initial metal concentration, contact time, and isotherms models) were tested. Biosorption process is influenced by the metal's solution pH with maximum removal of 83.36% being achieved at pH 8. Cadmium ions uptake reaches equilibrium in about 5 min of biosorption process. The Langmuir model was determined to better fit the Cd(II) biosorption by dry archaea. The maximal uptake capacity (qmax) of Cd(II) was 128.21 mg/g. The effect of multi-component system on biosorption behaviour of Pb, Ni, Cu, Fe, and Cd ions by immobilized dried archaeal cells, dried archaeal cells, and dried bryozoa was studied using Plackett-Burman experimental design. The investigated biosorbents were effective at removing metals from contaminated systems, particularly for Fe, Pb, and Cd ions. Moreover, the interaction behaviour of these metals was antagonistic, synergistic, or non-interactive in multi-metals system. SEM, EDX, and FTIR spectra revealed changes in surface morphology of the biomass through the biosorption process. Finally, continuous adsorption experiment was done to examine the ability of immobilized biomass to adsorb metals from wastewater.
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Cadmio , Contaminantes Químicos del Agua , Cadmio/análisis , Aguas Residuales , Cinética , Adsorción , Plomo , Concentración de Iones de Hidrógeno , Biomasa , IonesRESUMEN
BACKGROUND: As a white biotechnological trend, esterases are thought to be among the most active enzymes' classes in biocatalysis and synthesis of industrially importance organic compounds. Esterases are used in many applications such as the manufacture of pharmaceuticals, cosmetics, leather, textile, paper, food, dairy products, detergents, and treatment of some environmental pollutants. RESULTS: A poly-histidine moiety was added to the C-terminal end of the Geobacillus sp. gene encoding carboxyl esterase (EstB, ac: KJ735452) to facilitate one-step purification. This recombinant protein was successfully expressed in Escherichia coli (E. coli) under control of Lambda promoter (λ). An open reading frame (ORF) of 1500 bps encoding a polypeptide of 499 amino acid residues and a calculated molecular weight (54.7 kD) was identified as carboxyl-esterase B due to its conserved glycine-X-serine-X-glycine motif (G-X-S-X-G) and its high similarity toward other carboxyl esterases, where the 3-D tertiary structure of EstB was determined based on high homology % (94.8) to Est55. The expression was scaled up using 7-L stirred tank bioreactor, where a maximum yield of enzyme was obtained after 3.5 h with SEA 51.76 U/mg protein. The expressed protein was purified until unity using immobilized metal affinity chromatography (IMAC) charged with cobalt and then characterized. The purified enzyme was most active at pH 8.0 and remarkably stable at pH (8-10). Temperature optimum was recorded at 65 °C, and it kept 70% of its activity after 1-h exposure to 60 °C. The active half-live of enzyme was 25 min at 70 °C and a calculated T melting (Tm) at 70 °C. The determined reaction kinetics Michaelis-Menten constant (Km), maximum velocity rate (Vmax), the turnover number (Kcat), and catalytic efficiency (Kcat/Km) of the pure enzyme were found 22.756 mM, 164.47 U/ml (59.6 min-1), and (2.619 mol/ min), respectively. CONCLUSION: Creation of a recombinant 6 × -His estB derived from a thermophile Geobacillus sp. was performed successfully and then overexpressed under λ-promoter. In a bench scale bioreactor, the overexpression was grown up, followed by one-step purification and biochemical characterization. The recorded promising pH and temperature stability properties suggest that this expressed carboxyl esterase could be used in many industrial sectors.
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Limb trauma remains the most prevalent survivable major combat injury. In the First World War, more than 700,000 British soldiers received limb wounds and more than 41,000 underwent an amputation, creating one of the largest amputee cohorts in history. Postamputation pain affects up to 85% of military amputees, suggesting that up to 33,000 British First World War veterans potentially reported postamputation pain. This qualitative systematic review explores the professional medical conversation around clinical management of chronic postamputation pain in this patient cohort, its development over the 20th century, and how this information was disseminated among medical professionals. We searched The Lancet and British Medical Journal archives (1914-1985) for reports referring to postamputation pain, its prevalence, mechanisms, descriptors, or clinical management. Participants were First World War veterans with a limb amputation, excluding civilians and veterans of all other conflicts. The search identified 9809 potentially relevant texts, of which 101 met the inclusion criteria. Reports emerged as early as 1914 and the discussion continued over the next 4 decades. Unexpected findings included early advocacy of multidisciplinary pain management, concerns over addiction, and the effect of chronic pain on mental health emerging decades earlier than previously thought. Chronic postamputation pain is still a significant issue for military rehabilitation. Similarities between injury patterns in the First World War and recent Iraq and Afghanistan conflicts mean that these historical aspects remain relevant to today's military personnel, clinicians, researchers, and policymakers.
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Introduction: Although pre/pro/postbiotics have become more prevalent in dermatologic and cosmetic fields, the mode of action when topically applied is largely unknown. A multi-omic approach was applied to decipher the impact of the skincare products with pre/postbiotics on skin microbiome and metabolome. Methods: Subjects with dry skin applied a body wash and body lotion with or without pre/postbiotics for 6 weeks. Skin hydration was measured at baseline, 3 and 6 weeks. Skin swabs were collected for 16S rRNA gene sequencing, metagenomics and metabolomics analysis. Results: Skin hydration significantly increased in both groups. The prebiotic group significantly reduced opportunistic pathogens, e.g., Pseudomonas stutzeri and Sphingomonas anadarae, and increased the commensals, e.g., Staphylococcus equorum, Streptococcus mitis, Halomonas desiderata. Bacterial sugar degradation pathways were enriched in the prebiotic group, while fatty acid biosynthesis pathways were reduced in control. The changes on skin metabolome profiles by the products were more prominent. The prebiotic group performed greater modulation on many clinically-relevant metabolites compared to control. Correlation analysis showed H. desiderata and S. mitis positively correlated with skin hydration, P. stutzeri and S. anadarae negatively correlated with the metabolites that are positively associated with skin hydration improvement. Conclusion: This holistic study supported a hypothesis that the pre/postbiotics increased skin hydration through the modulation of skin microbiome, metabolic pathways and metabolome.
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Thigmotaxis is an innate predator avoidance behaviour of rodents. To gain insight into how injury and disease models, and analgesic drug treatments affect thigmotaxis, we performed a systematic review and meta-analysis of studies that assessed thigmotaxis in the open field test. Systematic searches were conducted of 3 databases in October 2020, March and August 2022. Study design characteristics and experimental data were extracted and analysed using a random-effects meta-analysis. We also assessed the correlation between thigmotaxis and stimulus-evoked limb withdrawal. This review included the meta-analysis of 165 studies We report thigmotaxis was increased in injury and disease models associated with persistent pain and this increase was attenuated by analgesic drug treatments in both rat and mouse experiments. Its usefulness, however, may be limited in certain injury and disease models because our analysis suggested that thigmotaxis may be associated with the locomotor function. We also conducted subgroup analyses and meta-regression, but our findings on sources of heterogeneity are inconclusive because analyses were limited by insufficient available data. It was difficult to assess internal validity because reporting of methodological quality measures was poor, therefore, the studies have an unclear risk of bias. The correlation between time in the centre (type of a thigmotactic metric) and types of stimulus-evoked limb withdrawal was inconsistent. Therefore, stimulus-evoked and ethologically relevant behavioural paradigms should be viewed as two separate entities as they are conceptually and methodologically different from each other.
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Prueba de Campo Abierto , Roedores , Ratas , Animales , Ratones , Dolor , Trastorno de Personalidad Antisocial , Bases de Datos FactualesRESUMEN
ABSTRACT: Blinding is challenging in randomised controlled trials of physical, psychological, and self-management therapies for pain, mainly because of their complex and participatory nature. To develop standards for the design, implementation, and reporting of control interventions in efficacy and mechanistic trials, a systematic overview of currently used sham interventions and other blinding methods was required. Twelve databases were searched for placebo or sham-controlled randomised clinical trials of physical, psychological, and self-management treatments in a clinical pain population. Screening and data extraction were performed in duplicate, and trial features, description of control methods, and their similarity to the active intervention under investigation were extracted (protocol registration ID: CRD42020206590). The review included 198 unique control interventions, published between 2008 and December 2021. Most trials studied people with chronic pain, and more than half were manual therapy trials. The described control interventions ranged from clearly modelled based on the active treatment to largely dissimilar control interventions. Similarity between control and active interventions was more frequent for certain aspects (eg, duration and frequency of treatments) than others (eg, physical treatment procedures and patient sensory experiences). We also provide an overview of additional, potentially useful methods to enhance blinding, as well as the reporting of processes involved in developing control interventions. A comprehensive picture of prevalent blinding methods is provided, including a detailed assessment of the resemblance between active and control interventions. These findings can inform future developments of control interventions in efficacy and mechanistic trials and best-practice recommendations.
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Dolor Crónico , Automanejo , Humanos , Dolor Crónico/terapiaRESUMEN
ABSTRACT: Sham interventions in randomized clinical trials (RCTs) of physical, psychological, and self-management (PPS) therapies for pain are highly variable in design and believed to contribute to poor internal validity. However, it has not been formally tested whether the extent to which sham controls resemble the treatment under investigation consistently affects trial outcomes, such as effect sizes, differential attrition, participant expectancy, and blinding effectiveness. Placebo- or sham-controlled RCTs of PPS interventions of clinical pain populations were searched in 12 databases. The similarity of control interventions to the experimental treatment was rated across 25 features. Meta-regression analyses assessed putative links between employed control interventions, observed effect sizes in pain-related outcomes, attrition, and blinding success. The sample included 198 unique control interventions, dominated by manual therapy and chronic musculoskeletal pain research. Meta-analyses indicated small-to-moderate benefits of active treatments over control interventions, across subgroups of manual therapies, exercise, and rehabilitation, and psychological intervention trials. Multiple meta-regression modelling demonstrated that similarity between sham control and tested interventions predicted variability in pain-related outcomes, attrition, and blinding effectiveness. Influential variables were differences relating to the extent of intervention exposure, participant experience, and treatment environments. The results support the supposed link between blinding methods and effect sizes, based on a large and systematically sourced overview of methods. However, challenges to effective blinding are complex and often difficult to discern from trial reports. Nonetheless, these insights have the potential to change trial design, conduct, and reporting and will inform guideline development.