Bifidobacterium exopolysaccharides: new insights into engineering strategies, physicochemical functions, and immunomodulatory effects on host health.

Bifidobacteria are a prominent type of bacteria that have garnered significant research attention for their exceptional probiotic properties and capacity to produce exopolysaccharides (EPSs). These compounds exhibit diverse physical, chemical, and biological characteristics, prompting numerous investigations into their potential applications. Researchers have noted their beneficial effects as immune modulators within the host's body across various industries. Extensive research has been conducted on the immunomodulatory effects of bifidobacteria-derived EPSs, with emerging engineering strategies aimed at enhancing their immune-modulating capabilities. Understanding the structure, physicochemical properties, and biological activities of these compounds is crucial for their effective utilization across different industries. Our review encompassed numerous studies exploring Bifidobacterium and its metabolites, including EPSs, across various sectors, drawing from diverse databases. The distinctive properties of EPSs have spurred investigations into their applications, revealing their potential to bolster the immune system, combat inflammation, and treat various ailments. Additionally, these compounds possess antioxidant and antimicrobial properties, making them suitable for incorporation into a range of products spanning food, health, and medicine.

Predictive value of serum albumin and calcium levels in burn patients with Pseudomonas aeruginosa infection: A comprehensive analysis of clinical outcomes.

In the ongoing challenge to reduce burn-associated mortality rates, this study explores the predictive capacity of clinical factors in burn patients, focusing on vitamin D, calcium, and serum albumin levels during hospitalisation in cases with Pseudomonas aeruginosa infection. Our research involves a comprehensive analysis of 100 burn patients, encompassing crucial clinical parameters such as the burn severity index, serum albumin, vitamin D, and calcium levels at admission. Data were meticulously entered into IBM Statistics SPSS software version 28 and subjected to statistical analysis. The study reveals an average patient age of 39.75 years and a notable 34% mortality rate. Additionally, the average lengths of hospital and intensive care unit (ICU) stays are determined to be 11.33 and 7.79 days, respectively. Significantly, a correlation between calcium and albumin variables and treatment outcomes is established, showcasing their potential to predict variable changes in patient mortality rates. Furthermore, a noteworthy association is observed between serum calcium levels and the duration of ICU hospitalisation. In conclusion, albumin and calcium variables emerge as sensitive and specific indicators for predicting outcomes in burn patients. Importantly, the independence of these factors from the physician's experience and diagnosis reduces human error and thus increases the accuracy of mortality prediction in this patient population.

Effect of vitamin D on clinical outcomes in patients with thermal injury.

Evaluating complications and mortality risks in burn patients is crucial for effective treatment planning and improving survival rates. This study investigated the relationship between the serum vitamin D level and the clinical outcomes of adult burns patients. This was a prospective cohort of adult patients hospitalized due to thermal burns at a burn centre in the north of Iran. Based on the level of 25 hydroxyvitamin D measured upon admission, patients were divided into two groups of patients with sufficient 25 hydroxyvitamin D level and insufficient 25 hydroxyvitamin D level. Descriptive statistics were used for baseline demographics. Univariate analysis was conducted using Mann-Whitney U, Chi-square, independent samples, and Fisher's exact tests. A multivariate logistic regression was performed to adjust for the effects of confounding variables. Statistical analyses were conducted using SPSS 28.0 software. A total of 220 patients were included in the study. The average total body surface area burned was 30.52 ± 9.34. Patients with insufficient vitamin D levels had longer hospital stays (12.53 vs. 11.45) and longer stays in the intensive care unit (ICU) (3.32 vs. 2.40) than those with appropriate vitamin D levels. Participants with insufficient vitamin D levels exhibited a numerically higher incidence of infections than those with adequate levels (p < 0.05). The multivariate regression found that vitamin D deficiency levels were associated with increased infection rates and prolonged hospital stay. This study suggests that vitamin D deficiency is a significant risk factor for adverse clinical outcomes in burn patients. Further research is needed to confirm these associations and to explore potential interventions to optimize vitamin D status in this patient population.

Knowledge, attitude, and sources of information towards burn first aid among people referred to a burn centre in the north of Iran.

Optimal management of burns begins with first aid from the first hours of injury. Adequate knowledge of how to perform first aid for burns can reduce the consequences of injury. Therefore, this study aims to determine the knowledge, attitude, and sources of information assessment towards burn First aid among people referred to a burn centre in the north of Iran. A questionnaire-based survey was conducted to assess knowledge, attitude, and sources of information towards burn first aid among people referred to a burn centre in the north of Iran in 2023. In this survey, a convenience sampling method was adopted. The variables consisted of four items on socio-demographic information, 15 items on knowledge, ten items on attitude, and one item on sources of information related to burn First aid. A total of 371 individuals responded to the survey. The mean age of participants was 31.90 ± 8.49 years old. The mean score of the total knowledge of the participants in the research was 6.04 ± 3.05. There was a statistically significant relationship between the variables of age, sex, marital status, place of residence, level of education, and history of receiving first aid training with the participants' knowledge level. The average score of the total attitude of the participants was 44.08 ± 3.88. Out of 371 participants, 214 people (57.7%) had an average attitude, and 157 people (42.3%) had a good attitude towards burn first aid. There was a statistically significant relationship between place of residence, level of education, and history of receiving first aid training with the participants' attitudes in the research. In addition, the level of knowledge had a statistically significant relationship with the participants' attitude level in the research (p-value <0.001). The majority of participants have limited knowledge of burn first aid. This lack of knowledge could lead to severe consequences. Therefore, healthcare organizations should review and promote consistent guidelines for burn first aid to tackle and minimize the effect of this grave injury.

IL-31-dependent neurogenic inflammation restrains cutaneous type 2 immune response in allergic dermatitis.

Despite robust literature associating IL-31 with pruritic inflammatory skin diseases, its influence on cutaneous inflammation and the interplay between inflammatory and neurosensory pathways remain unmapped. Here, we examined the consequences of disrupting Il31 and its receptor Il31ra in a mouse model of house dust mite (HDM)-induced allergic dermatitis. Il31-deficient mice displayed a deficit in HDM dermatitis-associated scratching, consistent with its well-established role as a pruritogen. In contrast, Il31 deficiency increased the number and proportion of cutaneous type 2 cytokine-producing CD4+ T cells and serum IgE in response to HDM. Furthermore, Il4ra+ monocytes and macrophages capable of fueling a feedforward type 2 inflammatory loop were selectively enriched in Il31ra-deficient HDM dermatitis skin. Thus, IL-31 is not strictly a proinflammatory cytokine but rather an immunoregulatory factor that limits the magnitude of type 2 inflammatory responses in skin. Our data support a model wherein IL-31 activation of IL31RA+ pruritoceptors triggers release of calcitonin gene-related protein (CGRP), which can mediate neurogenic inflammation, inhibit CD4+ T cell proliferation, and reduce T cell production of the type 2 cytokine IL-13. Together, these results illustrate a previously unrecognized neuroimmune pathway that constrains type 2 tissue inflammation in the setting of chronic cutaneous allergen exposure and may explain paradoxical dermatitis flares in atopic patients treated with anti-IL31RA therapy.

Polyacrylic acid/ polyvinylpyrrolidone hydrogel wound dressing containing zinc oxide nanoparticles promote wound healing in a rat model of excision injury.

Developing and designing efficient wound dressings have gained increasing attention and shown beneficial results in improved wound healing effects. This study was conducted to improve wound healing properties and introduce a novel potential wound dressing. A novel hydrogel based on polyvinylpyrrolidone/poly acrylic acid containing Zinc oxide nanoparticles was prepared as an antibacterial wound dressing and examined in a rat excisional wound model. This hydrogel prepared by free radical polymerization using potassium persulfate (KPS) as an initiator, N, N-methylene bisacrylamide (MBA) as a cross-linker, poly acrylic acid (PAA) as a monomer in the presence of polyvinylpyrrolidone (PVP) and Zinc oxide nanoparticles (ZnO NPs). Analyses such as Scanning Electron Microscope (SEM), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction analysis (XRD), and Thermal gravimetric analysis (TGA) were used to study morphology structure. After choosing the optimal sample, in vivo characterization of excisional wound injury on a rat model was done. The healing rate and histological analysis were calculated and compared among the groups. The therapeutic potential of the PAA-PVP-ZnO-%2 was investigated in a rat model of excisional injury compared to the control group. Results showed that the polyacrylic acid/polyvinylpyrrolidone hydrogel wound dressing containing zinc oxide nanoparticles accelerated wound contraction, had antibacterial effects, and promoted wound healing compared to other groups.

Antibiofilm and antimicrobial activity of Lactobacillus cell free supernatant against Pseudomonas aeruginosa isolated from burn wounds.

The present study investigated the antimicrobial and anti-biofilm effects of indigenous Lactobacillus probiotic strains on Pseudomonas aeruginosa isolated from burn wound infection in laboratory conditions. The effect of 7 probiotic strains isolated from infant faeces on the pathogenicity factors of P. aeruginosa, including protease, elastase, antibiofilm and antipyocyanin was measured. Also, diffusion methods in the well and micro broth dilution were used to evaluate the antimicrobial activity of probiotics. All tests were performed in triplicate. A negative control and a positive control were used for each test. SPSS version 22 software was used for statistical analysis, and a p < 0.05 was considered statistically significant. A total of 30 clinical isolates of P. aeruginosa were isolated. The elastolytic activity of P. aeruginosa isolates decreased after adding Cell free supernatant (CFS) of each Lactobacillus. L1, L4, L5, and L6 strains had a 100% inhibitory effect on pathogen isolates. L3 and L7 strains had the lowest inhibitory effect. The inhibitory effect of CFS extracted from lactobacilli on protease production by P. aeruginosa. L1, L4, L5, and L6 strains had an inhibitory effect on all tested isolates. L2, L3, and L7 strains had a less inhibitory effect. L4 strain had the highest inhibitory effect on pyocyanin production by P. aeruginosa (50%), followed by L5 (43.3%), L1 (40%), and L6 (23.3%) strains. L3 and L7 strains had no inhibitory effect on the pyocyanin production of P. aeruginosa isolates. It was found that the CFS of 4 isolates (L1, L4, L5, and L6) was the most active extract and had a 100% inhibitory effect against biofilm formation of all P. aeruginosa strains. The L3 strain had the least inhibitory effect against the biofilm formation of pathogens. Overall, this study showed that probiotics could be promising alternatives to combat the pathogenicity of P. aeruginosa in burn wounds.

An 11-year retrospective study on the epidemiology of paediatric burns in the north of Iran.

Burn injuries in children are distressing physical and emotional events with long-term disability. However, there is little research on the epidemiology of paediatric burns. This information is essential for the development of prevention intervention and acute management. This study aimed to describe epidemiologic characteristics and clinical outcomes of paediatric burns in a burn center in the north of Iran. A retrospective, single-center study was conducted of children (<18 years) admitted to the burns center between 2011 and 2021. The data were analysed by SPSS 24.0 software. The chi-squared test and Fisher's exact test were used to assess categorical variables, and Student's t-tests or One-Way ANOVA was used to evaluate continuous variables. 2951 paediatric burns with mean age 5.30 ± 5.27 years, were admitted during the 11 years, with 1777 boys (60.2%) and 1174 girls (39.8%). By age groups, the majority of children (59.7%) were between 0 and 4 years old, followed by 5 to 8 years (15.7%), 13 to 18 years (14.6%), and 9 to 12 years (10.0%), respectively. The most cause of injury was Hot liquids & vapours (1604, 54.4%). The mean age for burns with fire & flames, hot liquids & vapours, contact, chemical, and electrical was 4.46 ± 4.84, 5.70 ± 5.39, 5.44 ± 5.42, 3.93 ± 3.86, and 3.53 ± 4.06 years, respectively. The total body surface area (TBSA) burned was 14.96 ± 11.94. The longest length of stay (LOS) related to fire and flame was 5.63 ± 7.57 days. The mortality rate was 1.56%. There were significant differences among aetiology groups for the cost per % TBSA (F = 15.784, P < 0.001), which correlated with the burn depth, TBSA, aetiology, LOS, and age. The Ministry of Health should establish strategies for burn prevention and incorporate data surveillance for burn injuries. Community education on kitchen and cooking safety could positively impact the prevalence and outcomes of paediatric burns.

The emergence of plasmid-encoded oxacillinase and carbapenemase among uropathogenic Escherichia coli (UPEC) isolated from hospitalized patients in the North of Iran.

Carbapenemase enzyme production is responsible for resistance to carbapenem among Gram-negative bacteria. This study aimed to detect common carbapenemase and oxacilinase genes among uropathogenic E. coli (UPEC) isolated from hospitalized patients in Rasht, north of Iran. In the present study, from 2000 urine samples, 263 UPEC strains were isolated from inpatients with urinary tract infections (UTI) in 2020. The Kirby-Bauer disk diffusion susceptibility test was used to determine the sensitivity or resistance of isolates to antimicrobial compounds. The double-disk test confirmed extended-spectrum ß lactamase (ESBL) production phenotypically, and the presence and distribution of genes encoding carbapenemase and oxacilinase were investigated using polymerase chain reaction (PCR). Based on the findings, 13/263 isolates (8 ESBL and five non-ESBL) showed a non-susceptible phenotype to at least one of the studied carbapenem group antibiotics, and 121 (46%) isolates were ESBL-producers. PCR for oxacilinase and carbapenemase genes was done on all 126 isolates, including ESBL-positive and carbapenem-resistant strains, in which 10 (7.9%) and 25 (19.8%) isolates harbored OXA-1 and IMP genes, respectively. Also, OXA-2, OXA-10, OXA-48, VIM, and NDM genes were not found in any studied isolates. IMP and OXA-1 genes among carbapenemase-producing isolates indicate the possible spread of antibiotic-resistant strains. Hence, identification and control of ESBL and carbapenemase-producing strains, although with almost low frequency due to plasmid genes encoding carbapenemase, is essential for infection control.

Epidemiology of chemical burns: An 11-year retrospective study of 126 patients at a referral burn centre in the north of Iran.

The etiology and outcomes of chemical burns vary worldwide, influenced by the local population structure, industry distribution, and geographical and social environments. The aim of this study was to evaluate the epidemiology of chemical burns among patients referred to a burn centre in the north of Iran. A single-centre, retrospective study was conducted on patients with chemical burns between 2011 and 2021. Data collection was carried out using the hospital information system (HIS), and data collected from medical records included gender, age, marital status, occupations, burn season, place of residence, intention to burn, location of the accident, percent of total body surface area (%TBSA), the primary cause of burns, the body region of the burn, length of hospital stay (days), infection, and discharge status. The data were analysed using descriptive statistical methods and SPSS 24.0 software. Of the 10 133 burn patients treated in a burn centre in the north of Iran between 2011 and 2021, 1.2% had chemical burns. The average age of patients was 34.45 (SD = 22.16) years, and most chemical burns cases were male (70.6%, n = 89). Chemical burns occurred most frequently in patients aged 20 to 49 years (69.8%, n = 107), and most of the burns were accidental (84.9%, n = 107). The home was the most common place of chemical burn injury, accounting for 49.2% (62 cases), followed by the workplace (43.7%, n = 55), respectively. Most chemical burns occurred in the summer season (36.5%, n = 46), and acid (74.6%, n = 94) was the most common cause of chemical burns. The mean TBSA was 16.41 (SD = 15.10). The most common burn area was the lower limb (34.9%, n = 44), and the overall mortality rate was 4.8%. The average length of stay in the hospital was 6.53 (SD = 5.57) days. Community education on household safety, restricting non-specialists' access to chemical substances, and the promotion of early consultation could reduce chemical burn prevalence and improve outcomes.

Prevalence and Related Factors of Electrical Burns in Patients Referred to Iranian Medical Centers: A Systematic Review and Meta-Analysis.

BACKGROUND: Electrical burn, one of the serious public health challenges, is considered one of the most devastating due to higher mortalities. Burn injuries impose a high economic burden on patients, the health system, and society. We aimed to determine the prevalence of electrical burn injury among burn patients hospitalized in Iran. METHODS: A systematic literature search was conducted to identify articles published from Iran in the electronic databases of Scopus, PubMed, Embase, Google Scholar, Web of Science, and SID from Jan 2000 to Dec 2020. Next, eight publications from international databases and ten articles from the Persian SID database that met our inclusion criteria were selected for data extraction and meta-analysis. The inclusion criteria were articles done among the Iranian population with burn patients. RESULTS: In all studies, the pooled prevalence of electrical burn was estimated at 3.8% (95% CI: 3.1% - 4.5%) in burn patients. Occurrence of electrical burn-in males and females was 92.3% (95% CI: 87.9% - 95.2%) and 7.7% (95% CI: 4.8% - 12.1%) respectively. Also, the mortality rate was 3.5% (95% CI: 2.2% - 5.6%). CONCLUSION: The epidemiological study of electrical burns helps determine the effective factors in the occurrence of this type of damage.

Performance measurement of construction suppliers under localization, agility, and digitalization criteria: Fuzzy Ordinal Priority Approach.

The suppliers' performance plays a vital role, with a domino effect, in project success, organizational competitiveness, protecting supply chain and construction industry from disruptions and PESTEL risks (political, economic, social, technological, environmental, and legal). Therefore, measuring the performance of the construction suppliers has become the primary focus of project-oriented organizations and the core of business decision-making, especially during global megatrends. The question that may arise here is, "How can the performance of the construction suppliers be determined under uncertainties considering the post-COVID-19 era?" Organizations need eligible suppliers for the rapid recovery of the supply chain and construction sector at this critical stage. Given the importance of the issue, this study aims to propose a novel approach for measuring the performance of construction suppliers using the fuzzy ordinal priority approach (OPA-F). OPA-F is a recent development in multiple criteria decision-making (MCDM) that can determine the criteria weights for performance measurement using fuzzy linguistic variables. We do not always have access to a complete data set in real-world situations and business environments. Nevertheless, OPA-F can handle this dilemma, even with incomplete input data. This research intends to consider three main aspects of the construction suppliers, known as (L-A-D) capabilities, including localization, agility, and digitalization. In this regard, we bring up a case study from the construction industry to demonstrate the application of the proposed framework. The findings show that the most critical criterion is "digitalization" for the case study. This criterion covers "supply chain automation" and "virtualization and dematerialization" of services/products. The proposed approach is practical and straightforward, particularly for academicians and decision-makers; it can also incorporate uncertainties.

Dual mechanical and pharmacological thromboprophylaxis decreases risk of pulmonary embolus after laparotomy for gynecologic malignancies.

OBJECTIVES: Patients with gynecologic malignancies have high rates of post-operative venous thromboembolism. Currently, there is no consensus for peri-operative thromboprophylaxis specific to gynecologic oncology. We aimed to compare rates of symptomatic pulmonary embolus within 30 days post-operatively, and to identify risk factors for pulmonary embolus. METHODS: The Division of Gynecologic Oncology at Sunnybrook Health Sciences Centre implemented dual thromboprophylaxis for laparotomies in December 2017. We conducted a prospective study of laparotomies for gynecologic malignancies from December 2017 to October 2018, with comparison to historical cohort from January 2016 to November 2017 using the institutional National Surgical Quality Improvement Program database (NSQIP). Pre-intervention, patients received low molecular weight heparin during admission and extended 28-day prophylaxis was continued at the surgeon's discretion. Post-intervention, all patients received both mechanical thromboprophylaxis with sequential compression devices during admission and 28-day prophylaxis with low molecular weight heparin. RESULTS: There were 371 and 163 laparotomies pre- and post-intervention, respectively. Patient characteristics (age, body mass index, diabetes, smoking, tumor stage), rate of malignant cases, operative blood loss and duration, and length of stay were similar between groups. After implementation, pulmonary emboli rates decreased from 5.1% to 0% (p=0.001). There were more cytoreductive procedures pre-intervention (p≤0.0001) but surgical complexity scores were similar (p=0.82). Univariate analysis revealed that surgery pre-intervention (OR 4.25, 95% CI 1.04 to 17.43, p=0.04), length of stay ≥5 days (OR 11.94, 95% CI 2.65 to 53.92, p=0.002), and operative blood loss ≥500 mL (OR 2.85, 95% CI 1.05 to 7.8, p=0.04) increased risk of pulmonary embolus. On multivariable analysis, surgery pre-intervention remained associated with more pulmonary emboli (OR 4.16, 95% CI 1.03 to 16.79, p=0.045), when adjusting for operative blood loss. CONCLUSION: Dual thromboprophylaxis after laparotomy significantly reduced rates of pulmonary embolus in this high-risk patient population.

ɑO-Conotoxin GeXIVA isomers modulate N-type calcium (CaV 2.2) channels and inwardly-rectifying potassium (GIRK) channels via GABAB receptor activation.

αO-Conotoxin GeXIVA is a 28 amino acid peptide derived from the venom of the marine snail Conus generalis. The presence of four cysteine residues in the structure of GeXIVA allows it to have three different disulfide isomers, that is, the globular, ribbon or bead isomer. All three isomers are active at α9α10 nicotinic acetylcholine receptors, with the bead isomer, GeXIVA[1,2], being the most potent and exhibiting analgesic activity in animal models of neuropathic pain. The original report of GeXIVA activity failed to observe any effect of the isomers on high voltage-activated (HVA) calcium channel currents in rat dorsal root ganglion (DRG) neurons. In this study, we report, for the first time, the activity of globular GeXIVA[1,3] at G protein-coupled GABAB receptors (GABAB R) inhibiting HVA N-type calcium (Cav2.2) channels and reducing membrane excitability in mouse DRG neurons. The inhibition of HVA Ba2+ currents and neuroexcitability by GeXIVA[1,3] was partially reversed by the selective GABAB R antagonist CGP 55845. In transfected HEK293T cells co-expressing human GABAB R1 and R2 subunits and Cav2.2 channels, both GeXIVA[1,3] and GeXIVA[1,4] inhibited depolarization-activated Ba2+ currents mediated by Cav2.2 channels, whereas GeXIVA[1,2] had no effect. The effects of three cyclized GeXIVA[1,4] ribbon isomers were also tested, with cGeXIVA GAG being the most potent at human GABAB R-coupled Cav2.2 channels. Interestingly, globular GeXIVA[1,3] also reversibly potentiated inwardly-rectifying K+ currents mediated by human GIRK1/2 channels co-expressed with GABAB R in HEK293T cells. This study highlights GABAB R as a potentially important receptor target for the activity of αO-conotoxin GeXIVA to mediate analgesia.

Adopting distributed ledger technology for the sustainable construction industry: evaluating the barriers using Ordinal Priority Approach.

Construction 4.0 has become a buzzword since the penetration of building information modeling (BIM), cyber-physical systems, and digital and computing technologies into the construction industry. Among emerging technologies, distributed ledger technology (DLT), or blockchain, is a powerful business enhancer whose potential can disrupt projects, AEC (architecture, engineering, and construction) firms, and construction supply chain, and in a broader sense, the whole construction industry. This technology has not reached the plateau of productivity due to several barriers and challenges. Previous studies have started to investigate the barriers to implementing DLT in various sectors and segmentations. However, we still need further surveys in the construction industry. This study evaluates the applicability of identified challenges and barriers based on a sustainability perspective. Precisely, we will answer which challenges need to be addressed for the sustainability of the construction industry. To meet the research objective, the ordinal priority approach (OPA) in multiple attributes decision-making (MADM) was utilized. This novel method determines the weight of sustainability attributes and barriers simultaneously. The results show that DLT implementation needs (i) infrastructure for data management, (ii) advanced applications and archetypes, and (iii) customers' demand, interest, and tendency, and (iv) taxation and reporting. Solving high-ranked challenges is the key to social sustainability from the aspects of "supply chain management and procurement"; "transparency, anti-corruption, and anti-counterfeiting"; and "fair operation and honest competition."

Contribution of dorsal horn CGRP-expressing interneurons to mechanical sensitivity.

Primary sensory neurons are generally considered the only source of dorsal horn calcitonin gene-related peptide (CGRP), a neuropeptide critical to the transmission of pain messages. Using a tamoxifen-inducible CalcaCreER transgenic mouse, here we identified a distinct population of CGRP-expressing excitatory interneurons in lamina III of the spinal cord dorsal horn and trigeminal nucleus caudalis. These interneurons have spine-laden, dorsally directed, dendrites, and ventrally directed axons. As under resting conditions, CGRP interneurons are under tonic inhibitory control, neither innocuous nor noxious stimulation provoked significant Fos expression in these neurons. However, synchronous, electrical non-nociceptive Aß primary afferent stimulation of dorsal roots depolarized the CGRP interneurons, consistent with their receipt of a VGLUT1 innervation. On the other hand, chemogenetic activation of the neurons produced a mechanical hypersensitivity in response to von Frey stimulation, whereas their caspase-mediated ablation led to mechanical hyposensitivity. Finally, after partial peripheral nerve injury, innocuous stimulation (brush) induced significant Fos expression in the CGRP interneurons. These findings suggest that CGRP interneurons become hyperexcitable and contribute either to ascending circuits originating in deep dorsal horn or to the reflex circuits in baseline conditions, but not in the setting of nerve injury.

The ability to sense pain is critical to our survival. Normally, pain is provoked by intense heat or cold temperatures, strong force or a chemical stimulus, for example, capsaicin, the pain-provoking substance in chili peppers. However, if nerve fibers in the arms or legs are damaged, pain can occur in response to touch or pressure stimuli that are normally painless. This hypersensitivity is called mechanical allodynia. A protein called calcitonin gene-related peptide, or CGRP, has been implicated in mechanical allodynia and other chronic pain conditions, such as migraine. CGRP is found in, and released from, the neurons that receive and transmit pain messages from tissues, such as skin and muscles, to the spinal cord. However, only a few distinct groups of CGRP-expressing neurons have been identified and it is unclear if these nerve cells also contribute to mechanical allodynia. To investigate this, Löken et al. genetically engineered mice so that all nerve cells containing CGRP produced red fluorescent light when illuminated with a laser. This included a previously unexplored group of CGRP-expressing neurons found in a part of the spinal cord that is known to receive information about non-painful stimuli. Using neuroanatomical methods, Löken et al. monitored the activity of these neurons in response to various stimuli, before and after a partial nerve injury. This partial injury was induced via a surgery that cut off a few, but not all, branches of a key leg nerve. The experiments showed that in their normal state, the CGRP-expressing neurons hardly responded to mechanical stimulation. In fact, it was difficult to establish what they normally respond to. However, after a nerve injury, brushing the mice's skin evoked significant activity in these cells. Moreover, when these CGRP cells were artificially stimulated, the stimulation induced hypersensitivity to mechanical stimuli, even when the mice had no nerve damage. These results suggest that this group of neurons, which are normally suppressed, can become hyperexcitable and contribute to the development of mechanical allodynia. In summary, Löken et al. have identified a group of nerve cells in the spinal cord that process mechanical information and contribute to touch-evoked pain. Future studies will identify the nerve circuits that are targeted by CGRP released from these nerve cells. These circuits represent a new therapeutic target for managing chronic pain conditions related to nerve damage, specifically mechanical allodynia, which is the most common complaint of patients with chronic pain.

Alkyne-Bridged α-Conotoxin Vc1.1 Potently Reverses Mechanical Allodynia in Neuropathic Pain Models.

Several Conus-derived venom peptides are promising lead compounds for the management of neuropathic pain, with α-conotoxins being of particular interest. Modification of the interlocked disulfide framework of α-conotoxin Vc1.1 has been achieved using on-resin alkyne metathesis. Although introduction of a metabolically stable alkyne motif significantly disrupts backbone topography, the structural modification generates a potent and selective GABAB receptor agonist that inhibits Cav2.2 channels and exhibits dose-dependent reversal of mechanical allodynia in a behavioral rat model of neuropathic pain. The findings herein support the hypothesis that analgesia can be achieved via activation of GABABRs expressed in dorsal root ganglion (DRG) sensory neurons.

PERMA model vs. integrative-behavioral couple therapy for fertility problems: A randomized clinical trial protocol.

BACKGROUND: Psychological interventions may reduce fertility problems. Positive emotion, engagement, meaning, positive relationship and accomplishment (PERMA) is a cognitive intervention and integrative-behavioral couple therapy (IBCT) is a behavioral intervention. Appropriate mental interventions are important in infertility treatment. OBJECTIVE: To investigate the effect of the PERMA model vs. IBCT in reducing the fertility problems of couples. MATERIALS AND METHODS: The content of the interventions was developed and adjusted based on a literature review and the opinions of experts. In this three-arm parallel randomized clinical trial, 42 couples undergoing infertility treatment will be allocated randomly into three groups (n = 14 couples/each). Group 1 will receive the PERMA intervention, group 2 will receive the IBCT intervention, and group 3 as the control group will receive an infertility treatment training program intervention. The primary outcome will be the fertility problems, which will be measured by completing a fertility problem inventory at baseline, as well as in the 5 th and 9 th wk as a follow-up. Another primary outcome, satisfaction with the intervention, will also be assessed in the 5 th and 9 th wk. The secondry outcome will be a positive pregnancy test at wk 12. The interventions will be conducted through a combination of face-to-face and online via WhatsApp. CONCLUSION: This study will assess social, sexual, and parenthood concerns. A combination of online and face-to-face interventions will be appropriate given the COVID-19 pandemic. Couple's counseling may provide better counseling outcomes for fertility problems in comparison with group counseling. This study will try to optimize resilience during infertility treatment through learning better relationship and problem-solving skills, and may have an indirect impact on pregnancy rate, burden of infertility, and costs of treatment due to increased effectiveness.

Venom-Derived Peptides Inhibiting Voltage-Gated Sodium and Calcium Channels in Mammalian Sensory Neurons.

Pain management is a serious worldwide problem that affects the physical and mental health of all affected humans. As an alternative to opioids, pharmaceutical companies are seeking other sources of potential analgesics that have fewer adverse side effects. Animal venoms are a natural cocktail of a complex mixture of salts, peptides, and proteins. Most animals that produce venoms release them for the purpose of prey capture and/or defense against other vertebrates. Over the last 30 years, many venom-derived peptides have been shown to be active against numerous voltage-gated ion channels in the mammalian somatosensory nervous system. Voltage-gated ion channels and in particular sodium, potassium, and calcium channels are fundamental to the transmission of all somatosensory information from the periphery to the central nervous system. This information can be chemical, mechanical, or thermal sensation that can result from touch to a more painful sensation of tissue injury. These voltage-gated ion channels open or close in response to changes in membrane potential to permit ion movement across the cell membrane. In this chapter, we screened the scientific literature characterizing venom-derived peptides that target voltage-gated sodium and calcium channels and exhibit analgesic properties. Depending on peptide activity, these can either inhibit voltage-gated sodium or calcium channels completely by binding to the pore of the channel or modulate the activity by binding to other regions such as the voltage sensor of the channel.