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A large number of studies have confirmed the anti-inflammatory effects of acupuncture, and some of the mechanisms and pathways regulating inflammatory response have been revealed. However, most of these researches focused on the effect of acupuncture on systemic anti-inflammation, and there is no consensus about the effect characteristics of different acupoints on regulating inflammatory response. It is noteworthy that increasing attention and exploration have been paid to the neuro-immune interactions and regulation of immune-inflammatory homeostasis. Importantly, the understanding of local neuroimmune regulation of non-immune organs has been deepening, which was known as the regional immunity. This new concept lays a scientific foundation for elucidating the characteristics of acupoints on the inflammation, especially the modulation of target visceral organs by the relevant acupoint stimulation. In this paper, the local effects (e.g. activating regional nerve components to induce local neuroimmuno-inflammatory regulation, etc), target visceral organ effects (e.g. regulating activities of visceral resident immune cells to initiate regional immunity regulation mediated by locally resident lymphocytes to promote inflammatory response degradation and to restore the homeostasis of regional immunity in the internal organs, via somato-visceral neuro-segmental connection, etc.) and systemic anti-inflammatory effects (e.g. regulating cholinergic anti-inflammatory pathway, including activating the vagus nerve to exert systemic anti-inflammatory effects through neuroimmune regulatory network, etc.) of acupoint stimulation were analyzed from different levels of neuroimmunological regulation, so as to provide new insights for clarifying the role of acupoints in improving inflammatory diseases.

Capsaicin, the most prominent pungent compound of chilli peppers, has been used in traditional medicine systems for centuries; it already has a number of established clinical and industrial applications. Capsaicin is known to act through the TRPV1 receptor, which exists in various tissues; capsaicin is hepatically metabolised, having a half-life correlated with the method of application. Research on various applications of capsaicin in different formulations is still ongoing. Thus, local capsaicin applications have a pronounced anti-inflammatory effect, while systemic applications have a multitude of different effects because their increased lipophilic character ensures their augmented bioavailability. Furthermore, various teams have documented capsaicin's anti-cancer effects, proven both in vivo and in vitro designs. A notable constraint in the therapeutic effects of capsaicin is its increased toxicity, especially in sensitive tissues. Regarding the traditional applications of capsaicin, apart from all the effects recorded as medicinal effects, the application of capsaicin in acupuncture points has been demonstrated to be effective and the combination of acupuncture and capsaicin warrants further research. Finally, capsaicin has demonstrated antimicrobial effects, which can supplement its anti-inflammatory and anti-carcinogenic actions.

The electrochemical reduction of CO 2  to diverse value-added chemicals is a unique, environmentally friendly approach for curbing greenhouse gas emissions while addressing sluggish catalytic activity and low Faradaic efficiency (FE) of electrocatalysts. Here, zeolite-imidazolate-frameworks-8 (ZIF-8) containing various transition metal ions-Ni, Fe, and Cu-at varying concentrations upon doping are fabricated for the electrocatalytic CO 2 reduction reaction (CO 2 RR) to carbon monoxide (CO) without further processing. Atom coordination environments and theoretical electrocatalytic performance are scrutinized via X-ray absorption spectroscopy (XAS) and density functional theory (DFT) calculations. Upon optimized Cu doping on ZIF-8, Cu 0.5 Zn 0.5 /ZIF-8 achieves a high partial current density of 11.57 mA cm -2 and maximum FE for CO of 88.5% at -1.0 V (versus RHE) with a stable catalytic activity over 6 h. Furthermore, the electron-rich sp 2 C atom facilitates COOH* promotion after Cu doping of ZIF-8, leading to a local effect between the zinc-nitrogen (Zn-N 4 ) and copper-nitrogen (Cu-N 4 ) moieties. Additionally, the advanced CO 2 RR pathway is illustrated from various perspectives, including the pre-H-covered state under the CO 2 RR. The findings expand the pool of efficient metal-organic framework (MOF)-based CO 2 RR catalysts, deeming them viable alternatives to conventional catalysts., (© 2022 Wiley-VCH GmbH.)

Pharmacodynamics (PD) is discussed in relation to inhalation exposure to inhaled pharmaceutical and toxic agents. Clearly PD is closely related to pharmacokinetics, and this relation is illustrated with reference to inhaled insulin. PD can be related to pharmacologic responses, and some examples are cited. However, PD can also be thought of as the improvement or deterioration in lung disease state. Some of the major PD endpoints, including histopathology, pulmonary function, and bronchoalveolar lavage are reviewed. Brief reference is also given to other specialty biomarkers of PD response.

Envenomation caused by venomous animals may trigger significant local complications such as pain, edema, localized hemorrhage, and tissue necrosis, in addition to complications such as dermonecrosis, myonecrosis, and even amputations. This systematic review aims to evaluate scientific evidence on therapies used to target local effects caused by envenomation. The PubMed, MEDLINE, and LILACS databases were used to perform a literature search on the topic. The review was based on studies that cited procedures performed on local injuries following envenomation with the aim of being an adjuvant therapeutic strategy. The literature regarding local treatments used following envenomation reports the use of several alternative methods and/or therapies. The venomous animals found in the search were snakes (82.05%), insects (2.56%), spiders (2.56%), scorpions (2.56%), and others (jellyfish, centipede, sea urchin-10.26%). In regard to the treatments, the use of tourniquets, corticosteroids, antihistamines, and cryotherapy is questionable, as well as the use of plants and oils. Low-intensity lasers stand out as a possible therapeutic tool for these injuries. Local complications can progress to serious conditions and may result in physical disabilities and sequelae. This study compiled information on adjuvant therapeutic measures and underscores the importance of more robust scientific evidence for recommendations that act on local effects together with the antivenom.

Thermal discomfort due to accumulated sweat increasing head skin wettedness may contribute to low wearing rates of bicycle helmets. Using curated data on human head sweating and helmet thermal properties, a modelling framework for the thermal comfort assessment of bicycle helmet use is proposed. Local sweat rates (LSR) at the head were predicted as the ratio to the gross sweat rate (GSR) of the whole body or by sudomotor sensitivity (SUD), the change in LSR per change in body core temperature (Δt re ). Combining those local models with Δt re and GSR output from thermoregulation models, we simulated head sweating depending on the characteristics of the thermal environment, clothing, activity, and exposure duration. Local thermal comfort thresholds for head skin wettedness were derived in relation to thermal properties of bicycle helmets. The modelling framework was supplemented by regression equations predicting the wind-related reductions in thermal insulation and evaporative resistance of the headgear and boundary air layer, respectively. Comparing the predictions of local models coupled with different thermoregulation models to LSR measured at the frontal, lateral and medial head under bicycle helmet use revealed a large spread in LSR predictions predominantly determined by the local models and the considered head region. SUD tended to overestimate frontal LSR but performed better for lateral and medial head regions, whereas predictions by LSR/GSR ratios were lower and agreed better with measured frontal LSR. However, even for the best models root mean squared prediction errors exceeded experimental SD by 18-30%. From the high correlation (R > 0.9) of skin wettedness comfort thresholds with local sweating sensitivity reported for different body regions, we derived a threshold value of 0.37 for head skin wettedness. We illustrate the application of the modelling framework using a commuter-cycling scenario, and discuss its potential as well as the needs for further research., Competing Interests: Declarations of competing interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Here, we used a novel approach to analyze the trends in the concentrations of six national criteria air pollutants, carbon monoxide (CO), sulfur dioxide (SO 2 ), nitrogen dioxide (NO 2 ), PM 10 , PM 2.5 , and surface ozone (O 3 ), between 2001 and 2018, and the factors affecting the concentrations of CO and SO 2 at the district level in South Korea (Korea) between 2011 and 2016. We considered four factors affecting the concentrations of CO and SO 2 : (1) concentration-to-emission ratio, (2) air pollutant-to-CO 2 emission ratio, (3) carbon intensity, and (4) area-weighted energy supply. We found that the most influencing factors determining the concentrations of CO and SO 2  in Korea were the air pollutant-to-CO 2  emission ratio and the concentration-to-emission ratio. The annual mean concentrations of CO, SO 2 , PM 10 , PM 2.5 , and NO 2 generally decreased, while O 3 levels showed an increasing trend, over the last 18 years in Korea. We also found that NO 2 concentration had strong positive and negative correlations with PM 2.5 and O 3 concentrations, respectively. However, the relationship between O 3 and NO 2 levels showed an inverted U shape under NO 2 super-rich condition (e.g., > 55 ppb in Seoul), and the daily maximum 8-h values (MDA8O 3 ) increased in proportion to the NO 2 level under poor NO 2 conditions (e.g., < 25 ppb in Seoul)., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

A few studies examined the comparative side effects of Coronavirus Disease-19 (COVID-19) vaccines. We compared the extension and severity of self-reported side effects of seven COVID-19 vaccines [BNT162b2 (Pfizer-BioNTech), ChAdOx1 (AstraZeneca), mRNA-1273 (Moderna), CoronaVac (Sinovac Life Sciences), Gam-COVID-Vac (Gamaleya's Sputnik V), Ad5-nCoV (CanSinoBIO), and Ad26.CoV2.S (Johnson & Johnson/Janssen)] in the Mexican population. We also evaluated the association of type of vaccine, sex, age, comorbidity, and history of allergies to the extent and severity of side effects. This was a cross-sectional study carried out online between August 12 and September 3, 2021 in Mexico. The first inclusion criterion was to receive a COVID-19 vaccine and the second, being at least 18 years old. The survey link was distributed via multiple social media platforms. We questioned about the type of vaccine and symptoms based on short-term side effects reported in the literature. Side effect extension was classified as local, systemic, or both. We asked about the need to take medicine, stop activities/miss work, or seek medical attention. Then, a severity index was constructed based on responses. Descriptive and stepwise multivariate logistic ordinal regression analyses were used to calculate odds ratio (OR) and 95% CI for each outcome adjusted by potential confounders. The mean age was 38.9 ± 11.0 years ( n = 4,024). Prevalence of at least one side effect varied between vaccines and by a number of doses. At dose 1, ChAdOx1 was the vaccine with the highest rate of at least one side effect (85%) followed by Gam-COVID-Vac (80%). Both were associated to greater extension (adjusted OR 2.53, 95% CI 2.16, 2.96 and adjusted OR 2.41, 95% CI 1.76, 3.29, respectively) and severity of side effects (adjusted OR 4.32, 95% CI 3.73, 5.00 and adjusted OR 3.00, 95% CI 2.28, 3.94, respectively). Young age (<50 years), female sex, comorbidity, and history of allergies were associated with greater extension and severity, independent of the type of vaccine and potential confounders. At dose 2, mRNA-1273 was the vaccine with the highest rate of side effects (88%) and the only vaccine associated to greater extension (adjusted OR 2.88, 95% CI 1.59, 5.21) and severity of symptoms (adjusted OR 3.14, 95% CI 1.82, 5.43). Continuous studies are necessary to acknowledge more post-vaccine symptoms in different populations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Camacho Moll, Salinas Martínez, Tovar Cisneros, García Onofre, Navarrete Floriano and Bermúdez de León.)

Extreme precipitation events can pose great risks to natural ecosystems and human society. Investigating past changes in the frequency, intensity, and duration of such events and understanding the possible driving factors are critical for reliable projections of future changes and for informing adaptation strategies planning. Here we analyze trends in a complete list of extreme precipitation indices (EPIs) over the Yangtze River Basin (YRB) during the period of 1960-2019. Also, we examine the possible influences of global warming, ENSO, and local effects on the spatiotemporal variability of the EPIs. Our results show that average and extreme precipitation intensities, and the frequency of extreme heavy precipitation in the YRB have significantly increased, while precipitation frequency and maximum duration of wet spells have significantly decreased. A regional difference in trend occurrence and magnitude is also observed, showing the intensity and frequency of precipitation extremes over the Middle and Lower reaches are more likely to increase and increase faster, compared with those of the Upper reach of the YRB. Furthermore, our correlation analysis shows global warming, ENSO, and local effects all are significant driving factors that control the spatiotemporal variability of precipitation extremes over the YRB. Global warming tends to enhance the frequency and intensity of precipitation extremes. The La Niña phase of ENSO often corresponds to an increase of frequency and intensity of precipitation extremes in the current year, but a decrease of frequency and intensity in the coming year. Local warming mainly exerts a reducing effect on precipitation extremes, which is likely a response to the significant decrease of relative humidity in the YRB. Our findings highlight the need for a systematic approach to examine global, regional, and local drivers of trends in precipitation extremes in the YRB, and contribute to the understanding of precipitation changes in this region., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Snakebite accidents are considered serious public health problems. They are often neglected, and individuals who have received insufficient treatment are subjected to various disabling alterations. Snake venoms are secretions composed of biologically active molecules capable of triggering local and systemic effects in envenomation victims. Bothropic snakes are responsible for most of the ophidian accidents in Brazil; their venoms are mainly related to local manifestations, due to a composition that is especially rich in proteases and phospholipases A 2 . The most common local damages are inflammation, with consequent cellular activation and release of inflammatory mediators, hemorrhage, edema, pain and (myo)necrosis, which may lead to amputation of the affected areas. Antivenom therapy is the main treatment for snakebites. However, the efficiency is mainly due to the neutralization of the toxins responsible for the systemic alterations. Thus, the local damages can evolve to markedly compromise the tissue. The complexity of these local effects associated with the toxicity of the snake venom components of the genus Bothrops, arouse interest in the study of the biochemical and pathophysiological mechanisms involved with the actions caused by toxins of the venom. Therefore, this review aims to analyze the edematogenic, hyperalgesic and myotoxic effects caused by Brazilian bothropic venoms in order to contribute to the study and elucidation of the mechanisms of action of its components and, consequently, enable discoveries of more effective combined therapies in the treatment of local damages resulting from envenoming., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The study investigates the ability of methanolic extract of Andrographis paniculata (MAP) to supplement polyvalent anti-snake venom (ASV) in inhibiting neurotoxic enzyme acetylcholinesterase (AChE) and 'spreading factor' hyaluronidase from Naja naja (N.N) venom. AChE and hyaluronidase activity were measured in 100 or 200 µg of crude venom, respectively, and designated as 'control'. In Test Group I, enzyme assays were performed immediately after the addition of ASV/MAP/ASV + MAP to the venom. Inhibition of AChE by ASV (100-367 µg) was 12-17%, and of hyaluronidase (22-660 µg) was 33-41%. Under the same conditions, MAP (100-400 µg) inhibited AChE and hyaluronidase to the extent of 17-33% and 17-52%, respectively. When ASV (220 µg) and MAP (100-200 µg) were added together, AChE and hyaluronidase were inhibited to a greater extent from 39-63 to 36-44%, than when either of them was used alone. In Test Group 2, the venom was incubated with ASV/MAP/ASV + MAP for 10-30 min at 37 °C prior to the assay which enhanced AChE inhibition by 6%, 82% and 18% respectively, when compared to Test Group I. Though there was no change in inhibition of hyaluronidase in the presence of ASV, MAP could further increase the extent of inhibition by 27% and ASV + MAP upto 4%. In Test Group III, venom and substrate were incubated for 90 min and hyaluronidase activity was measured after the addition of inhibitors. Here, ASV + MAP caused increased inhibition by 69% compared to ASV alone. The study confirms the ability of phytochemicals in MAP to contribute to a multipronged strategy by supplementing, thereby augmenting the efficacy of ASV., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s) 2020.)

Background: Workers in the zinc production and processing of galvanized sheet steel are exposed to a complex mixture of particles and gases, including zinc oxide (ZnO) that can affect human health. We aimed to study the effects of short-term controlled exposure to nano-sized ZnO on airway inflammatory markers in healthy volunteers., Methods: Sixteen subjects (8 females, 8 men; age 19-42, non-smokers) were exposed to filtered air and ZnO nanoparticles (0.5, 1.0 and 2.0 mg/m 3 ) for 4 h, including 2 h of cycling with a low workload. Induced sputum samples were collected during a medical baseline and a final examination and also about 24 h after each exposure. A number of inflammatory cellular and soluble markers were analyzed., Results: Frequency and intensity of symptoms of airway irritation (throat irritation and cough) were increased in some subjects 24 h after ZnO exposures when compared to filtered air. The group comparison between filtered air and ZnO exposures showed statistically significant increases of neutrophils and interleukin-8 (IL-8), interleukin-6 (IL-6), matrix metalloproteinase (MMP-9) and tissue inhibitors of metalloproteinases (TIMP-1) in sputum starting at the lowest ZnO concentration of 0.5 mg/m 3 . However, a concentration-response relationship was absent. Effects were reversible. Strong correlations were found between neutrophil numbers and concentrations of total protein, IL-8, MMP-9, and TIMP-1., Conclusions: Controlled exposures of healthy subjects to ZnO nanoparticles induce reversible airway inflammation which was observed at a concentration of 0.5 mg/m 3 and higher. The lack of a concentration-response relationship warrants further studies.

Many diseases and conditions affect a relatively localized area of the body. They can be treated either by direct deposition of drug in the target area, or by giving the drug systemically. Here we review nanoparticle-based approaches to achieving both. We highlight advantages and disadvantages that nanoscale solutions have for locally administered therapies, with emphasis on the former. We discuss strategies to enable systemically delivered nanoparticles to deliver their payloads at specific locations in the body, including triggering (local and remote) and targeting.

Effects of urban/rural residence on late-stage cancer have long been explored, but remained controversial. Spatial granularity of rural definition, temporal change of rurality, and local variability of such effects may contribute to inconsistent findings, but they have not been fully addressed. We proposed a spatially resolved and temporally comparable rurality index and a geographically weighted regression approach to re-examine this question. Taking Florida as an example, our analyses show that rural effects on late-stage cancer vary dramatically over locations (600-m cells). The odds ratios range from 0.9 to 1.10, and imply that one degree of rurality can increase/decrease local risk of late-stage cancer by up to 10%. Our study is an early attempt to explore local effects of rurality on cancer at a fine spatial scale, and reveals interesting patterns hidden by global multi-level analysis. The new framework and findings can better inform precision interventions to mitigate cancer disparities., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Lung metastases are often resected non-anatomically with a laser using a diode-pumped Nd:YAG laser at a wavelength of 1320 nm with a laser output of up to 60 W. Usually the removal of lesions is carried out in contact mode by means of a bare fibre. We compared the local effects of an Nd:YAG laser at a wavelength of 1064 nm with those at a wavelength of 1320 nm using a 600-μm bare fibre in contact mode in an experimental model. The investigations were carried out on porcine lungs freshly withdrawn at the abattoir. The 600-μm laser fibre was fixed vertically in contact with the lung surface on a fibre holder. The fibre holder was connected to a feeding device that advances the laser fibre at constant speeds (5, 10 or 20 mm/s). In each case, two laser powers were examined: 20 and 60 W. The lung lesions produced by the laser fibre were excised for histological examination. After haematoxylin-eosin staining, the depth of the vaporisation and coagulation zones (in μm) from the laser cuts was measured. For each setting, an average value was calculated. The individual groups were compared for significance using a non-parametric Mann-Whitney U test (p < 0.05). At a low speed of the bare fibre of 5 mm/s and a laser output of 20 W, the average depth of the vaporisation zone was 858 ± 3.3 μm (λ = 1064 nm) compared to 766.0 ± 7.5 μm (λ = 1320 nm) (p < 0.01). Upon faster movement (20 mm/s), the extension of the vaporisation zone decreased to 320.3 ± 7.1 μm (λ = 1064 nm). The depth of the vaporisation zone increased significantly at 60 W, both at λ = 1064 and 1320 nm with 1517.0 ± 1.7 μm and 1414.0 ± 4.9 μm, respectively. The extent of the coagulation zone was significantly smaller at 20 W and the low speed of 5 mm/s, namely, 200.4 ± 3.7 μm (λ = 1064 nm) and 224.1 ± 2.8 μm (1320-nm laser). Upon faster movement of the laser fibre at the same output, the extent of the coagulation zone decreased in both groups. At a laser power of 60 W, the extent of the coagulation zone was significantly less with the 1064-nm laser (110.3 ± 2.4 μm) than with the 1320-nm laser (324.8 ± 1.9 μm; p < 0.001). When the laser fibre moves more rapidly, the extent of the coagulation zone decreases further. The Nd:YAG laser with a wavelength of 1320 nm still has the optimal ratio of cutting and coagulation capacity on the resection surface. With the 1064-nm Nd:YAG laser, a higher cutting capacity is associated with a decrease of the coagulation capacity.

In this work, we examined some biochemical and biological activities of Bothrops fonsecai venom, a pitviper endemic to southeastern Brazil, and assessed their neutralization by commercial bothropic antivenom (CAv). Cross-reactivity of venom with CAv was also assessed by immunoblotting and size-exclusion high performance chromatography (SE-HPLC). Bothrops fonsecai venom had PLA 2 , proteolytic and esterase activities that were neutralized to varying extents by venom:antivenom ratios of 5:1 and 5:2 (PLA 2 and esterase activities) or not significantly by either venom:antivenom ratio (proteolytic activity). The minimum hemorrhagic dose (69.2μg) was totally neutralized by both ratios. Clotting time in rat citrated plasma was 33±10.5s (mean±SD; n=5) and was completely neutralized by a 5:2 ratio. Edema formation was dose-dependent (1-30μg/site) and significantly inhibited by both ratios. Venom (10-300μg/mL) caused neuromuscular blockade in extensor digitorum longus preparations; this blockade was inhibited best by a 5:2 ratio. Venom caused myonecrosis and creatine kinase release in vivo (gastrocnemius muscle) and in vitro (extensor digitorum longus) that was effectively neutralized by both venom:antivenom ratios. Immunoblotting showed that venom components of ~25-100kDa interacted with CAv. SE-HPLC profiles for venom incubated with CAv or specific anti-B. fonsecai antivenom raised in rabbits (SAv) indicated that CAv had a higher binding capacity than SAv, whereas SAv had higher affinity than CAv. These findings indicate that B. fonsecai venom contains various activities that are neutralized to different extents by CAv and suggest that CAv could be used to treat envenoming by B. fonsecai., (Copyright © 2016. Published by Elsevier Inc.)

The present publication describes an integrative grouping concept to derive threshold values for inhalation exposure. The classification scheme starts with differences in toxicological potency and develops criteria to group compounds into two potency classes, namely toxic (T-group) or low toxic (L-group). The TTC concept for inhalation exposure is based on the TTC RepDose data set, consisting of 296 organic compounds with 608 repeated-dose inhalation studies. Initially, 21 structural features (SFs) were identified as being characteristic for compounds of either high or low NOEC values (Schüürmann et al., 2016). In subsequent analyses these SF groups were further refined by taking into account structural homogeneity, type of toxicological effect observed, differences in absorption, metabolism and mechanism of action (MoA), to better define their structural and toxicological boundaries. Differentiation of a local or systemic mode of action did not improve the classification scheme. Finally, 28 groups were discriminated: 19 T-groups and 9 L-groups. Clearly distinct thresholds were derived for the T- and L-toxicity groups, being 2 × 10(-5) ppm (2 μg/person/day) and 0.05 ppm (4260 μg/person/day), respectively. The derived thresholds and the classification are compared to the initial mainly structure driven grouping (Schüürmann et al., 2016) and to the Cramer classification., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The elucidation of the mutual influence between peptide bond geometry and local conformation has important implications for protein structure refinement, validation, and prediction. To gain insights into the structural determinants and the energetic contributions associated with protein/peptide backbone plasticity, we here report an extensive analysis of the variability of the peptide bond angles by combining statistical analyses of protein structures and quantum mechanics calculations on small model peptide systems. Our analyses demonstrate that all the backbone bond angles strongly depend on the peptide conformation and unveil the existence of regular trends as function of ψ and/or φ. The excellent agreement of the quantum mechanics calculations with the statistical surveys of protein structures validates the computational scheme here employed and demonstrates that the valence geometry of protein/peptide backbone is primarily dictated by local interactions. Notably, for the first time we show that the position of the H(α) hydrogen atom, which is an important parameter in NMR structural studies, is also dependent on the local conformation. Most of the trends observed may be satisfactorily explained by invoking steric repulsive interactions; in some specific cases the valence bond variability is also influenced by hydrogen-bond like interactions. Moreover, we can provide a reliable estimate of the energies involved in the interplay between geometry and conformations., (© 2015 Wiley Periodicals, Inc.)

Background: According to traditional Chinese medicine (TCM) theory, acupoints are specifically chosen sites of acupuncture manipulation, and also the basis for studying the mechanism of acupuncture. Stimulating different acupoints on the body surface could provide various therapeutic benefits. However, what is the acupoint? This question is not clear., Review Summary: We focuse on examining the function of acupoints from different perspectives, including the local and the systemic effects of stimulating acupoints. For example, acupoints may release certain substances or incur some changes, which could adjust the function of organs, maintain homeostasis. Furthermore, the therapeutic effects of verum acupoints versus sham acupoints were discussed. However, due to insufficience in evidence and in current methodologies, research into mechanisms of acupuncture is still incomplete., Conclusion: This review might explain, to some extent, what an acupoint is. Further research into the identity of acupoints is warranted, and multidisciplinary methods using novel technologies may yield significant advances over existing knowledge., (Wiley Periodicals, Inc.)

Bothrops leucurus venom causes significant local effects, such as necrosis, pain, hemorrhage and edema. These effects are important because of their high frequency and severity. The treatment of these local effects is not simple because of their quick triggering and a variety of components that induce these effects. Myonecrosis, dermonecrosis and edema are primarily caused by the action of hemorrhagins and myotoxins. A number of investigators have demonstrated the influence of thyroid hormones on inflammatory processes, particularly on wound healing. We investigated the edematogenic, hemorrhagic and necrotic activity of the B. leucurus venom in the hypothyroid, hyperthyroid and euthyroid of rats. The CK (creatine kinase) plasma level decreased in the animals in a hypothyroid state. The hypothyroid condition also significantly reduced the hemorrhagic and dermonecrotic area compared to the euthyroidism and hyperthyroidism states. It also mitigated the rat paw edema compared to that found in the euthyroid and hyperthyroid animals. The hyperthyroid animals showed no significant differences in the three treatments compared to the euthyroid animals. Our results suggest that the triggering of local effects induced by envenomation by B. leucurus is attenuated in hypothyroid animals, possibly by the effect of hypothyroidism on the immune system and blood flow., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

In natural populations, mating between relatives can have important fitness consequences due to the negative effects of reduced heterozygosity. Parental level of inbreeding or heterozygosity has been also found to influence the performance of offspring, via direct and indirect parental effects that are independent of the progeny own level of genetic diversity. In this study, we first analysed the effects of parental heterozygosity and relatedness (i.e. an estimate of offspring genetic diversity) on four traits related to offspring viability in great tits (Parus major) using 15 microsatellite markers. Second, we tested whether significant heterozygosity-fitness correlations (HFCs) were due to 'local' (i.e. linkage to genes influencing fitness) and/or 'general' (genome-wide heterozygosity) effects. We found a significant negative relationship between parental genetic relatedness and hatching success, and maternal heterozygosity was positively associated with offspring body size. The characteristics of the studied populations (recent admixture, polygynous matings) together with the fact that we found evidence for identity disequilibrium across our set of neutral markers suggest that HFCs may have resulted from genome-wide inbreeding depression. However, one locus (Ase18) had disproportionately large effects on the observed HFCs: heterozygosity at this locus had significant positive effects on hatching success and offspring size. It suggests that this marker may lie near to a functional locus under selection (i.e. a local effect) or, alternatively, heterozygosity at this locus might be correlated to heterozygosity across the genome due to the extensive ID found in our populations (i.e. a general effect). Collectively, our results lend support to both the general and local effect hypotheses and reinforce the view that HFCs lie on a continuum from inbreeding depression to those strictly due to linkage between marker loci and genes under selection., (© 2014 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.)

Background: The mulga snake (Pseudechis australis) is the largest terrestrial venomous snake in Australia. It is capable of inflicting severe and occasionally fatal envenoming, but there have been few studies of P. australis bites., Objectives: To highlight and reinforce the main features of P. australis envenoming and to provide a clearer picture of the epidemiology of bites from this species., Methods: Selected case records kept by the Toxinology Dept. (Women's and Children's Hospital, Adelaide, Australia) were reviewed retrospectively to determine definite P. australis bites., Inclusion Criteria: definite cases where the snake was identified by a competent person and/or lab specimens (bite site/urine) tested positive for "black snake" using CSL snake venom detection kit in a locality within the known range of P. australis, but without sympatry with other Pseudechis spp., Exclusion Criteria: where the snake could not be clearly identified under criteria above. Epidemiological and clinical information was recorded and analysed for the definite cases., Results: A total of 27 cases were identified as definite P. australis bites; there were no fatalities. The median age was 35.5 years (IQR 51-23) and 80% of bites occurred in males. More bites occurred in the warmer months (Dec-March) and in those handling/interfering with snakes. Seven people were bitten whilst asleep at night. 21/27 patients developed systemic envenoming (based on signs, symptoms and laboratory results) and 17 cases received antivenom. Local bite site pain (18) and swelling (17) were common as were non-specific generalised symptoms such as nausea, vomiting and headache. Myotoxicity (11) and anticoagulant coagulopathy (10) occurred frequently; haemolysis was seen in fewer cases (3). Two patients developed local tissue injury around the bite site requiring further treatment., Conclusions: This study confirms previous reports about P. australis bites with respect to high rates of envenoming, commonly associated with pain and swelling and systemic effects of rhabdomyolysis and anticoagulant coagulopathy. Systemic envenoming, even severe cases, responds well to antivenom therapy. Compared to other Australian snakes, a high proportion of bites occur in people asleep at night. Medically significant local tissue injury around the bite site may occur and may be associated with inappropriate first-aid, particularly the vascular occlusive type., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Correlations between fitness and genome-wide heterozygosity (heterozygosity-fitness correlations, HFCs) have been reported across a wide range of taxa. The genetic basis of these correlations is controversial: do they arise from genome-wide inbreeding ("general effects") or the "local effects" of overdominant loci acting in linkage disequilibrium with neutral loci? In an asexual thelytokous lineage of the Cape honey bee (Apis mellifera capensis), the effects of inbreeding have been homogenized across the population, making this an ideal system in which to detect overdominant loci, and to make inferences about the importance of overdominance on HFCs in general. Here we investigate the pattern of zygosity along two chromosomes in 42 workers from the clonal Cape honey bee population. On chromosome III (which contains the sex-locus, a gene that is homozygous-lethal) and chromosome IV we show that the pattern of zygosity is characterized by loss of heterozygosity in short regions followed by the telomeric restoration of heterozygosity. We infer that at least four selectively overdominant genes maintain heterozygosity on chromosome III and three on chromosome IV via local effects acting on neutral markers in linkage disequilibrium. We conclude that heterozygote advantage and local effects may be more common and evolutionarily significant than is generally appreciated., (© 2013 The Author(s). Evolution © 2013 The Society for the Study of Evolution.)

Most polypeptides originally assigned to a specific organ and a specific effect seem to occur in many different parts of the body, in neurons as well as in endocrine cells. Thus gastrin and insulin, or very similar peptides can be demonstrated in extracts of the vagal nerves and of peripheral somatic nerves. Electrical stimulation of the sciatic nerve of a perfused cat leg causes appearance of gastrin and insulin like immunoreactivity in the perfusates. This gastrin and insulin like immunoreactivity might originate from nervous depots. If so it might be assumed that insulin and other peptides are released in response to activation of autonomic or somatic nerves and that they might exert local metabolic effects in response to the acute needs of energy in eg. striated or smooth muscles.