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Objectives: To analyze Australia's high-cited papers (HCPs) receiving ≥100 citations in pharmacology during 2002–2021 and examine the research characteristics, study performance of the top 30 leading participating organizations and authors, and identification of top 30 journals publishing in this area and sub-fields of their research. Materials and Methods: Australia's HCPs on pharmacology research from the top 30 most productive organizations were identified and extracted from the Scopus database from 2002 to 2021 on 21 September 2022 using a search strategy. Select bibliometric measures were utilized to evaluate the publication productivity of important players in this area. The network analysis was performed to evaluate the collaborative interactions amongst the countries, organizations, authors, and keywords. Results: Of the 19,418 Australia's publications (articles) in pharmacology from the top 30 most productive organizations during 2002–2022, only 685 (3.53%) were HCPs, which together received 1,14,623 citations, averaging 164.4 citations per paper (CPP) and the citations ranged from 100 to 1,230. Two papers had more than 1,000 citations and 16 papers had 500 citations. Of the 685 HCPs, 40.58% (278) and 11.39% (78) received external funding support and were international collaboratives. The most productive organizations were Monash University (n = 155), the University of Queensland (n = 111) and the University of Melbourne (n = 97). The most impactful organizations in terms of CPP and relative citation index (RCI) were James Cook University (203.22 and 1.21), Australian National University (196.67 and 1.18) and Queensland University of Technology (193.45 and 1.16). The most productive authors were J. Li (n = 24), C. J. H. Porter (n = 24) and R. L. Nation (n = 23) (Monash University, Melbourne); and the most impactful authors in terms of CPP were A. Christopoulos (Monash Institute of Pharmaceutical Sciences, Melbourne) (288.21), C.W. Pouton (Monash University, Melbourne) (241.50), and D.L. Peterson (University of Queensland, Brisbane) (225.58). The most productive journals were Antimicrobial Agents and Chemotherapy (n = 59), Environmental Pollution (n = 43) and Journal of Medicinal Chemistry (n = 42). The most impactful journals in terms of CPP were Nature Reviews Drug Discovery (371.8), Antiviral Research (286.86) and European Journal of Pharmaceutical Sciences (253.0). The most important keywords with their frequency of appearances were Animal Experiments (108), Metabolism (76), Drug Effects (67), Animal Models (65), Protein Expression (64), Anti-Bacterial Agents (62), Drug Delivery Systems (54), Drug Formulation (44), Signal Transduction (42), and so on. Conclusion: There is an urgent need to increase national funding and expand international collaboration in priority areas, which will help to increase and diversify research output and improve research impact. [ABSTRACT FROM AUTHOR]

The article discusses the laws governing the scientific procedures on animal experimentation and testing in Great Britain. Conventional wisdom asserts that law does not generally mix well with science, at least not if its role is to define and permit only what society considers to be acceptable scientific experiments. Laws have been in effective to regulate the nature and circumstances of experiments using animals and to control and limit any associated pain.

The article discusses the implications of developmental dyslexia, which is also called the congenital word-blindness, as well as recent speculations which have yet to be confirmed. These are derived from experiments conducted on normal humans and monkeys, as well as humans suffering from the experiments of nature. The notion that linguistic competence depends upon associations between vision and hearing implies that the mechanism employed in reading may not be unique to the reading-process.

This systematic review, conducted according to the PRISMA guidelines, focuses on genotoxicity of oxidative hair dye precursors. The search for original papers published from 2000 to 2021 was performed in Medline, Web of Science, Cochrane registry, Scientific Committee on Consumer Safety of the European Commission and German MAK Commission opinions. Nine publications on genotoxicity of p -phenylenediamine (PPD) and toluene-2,5-diamine (p -toluylenediamine; PTD) were included, reporting results of 17 assays covering main genotoxicity endpoints. PPD and PTD were positive in bacterial mutation in vitro assay, and PPD tested positive also for somatic cell mutations in the Rodent Pig-a assay in vivo. Clastogenicity of PPD and PTD was revealed by in vitro chromosomal aberration assay. The alkaline comet assay in vitro showed DNA damage after PPD exposure, which was not confirmed in vivo , where PTD exhibited positive results. PPD induced micronucleus formation in vitro, and increased micronucleus frequencies in mice erythrocytes following high dose oral exposure in vivo. Based on the results of a limited number of data from the classical genotoxicity assay battery, this systematic review indicates genotoxic potential of hair dye precursors PPD and PTD, which may present an important health concern for consumers and in particular for professional hairdressers. [ABSTRACT FROM AUTHOR]

Objective: Brain-derived nerve growth factor (BDNF) plays an important role in cochlear development so it is plausible that it could restore hearing loss if delivered directly into the cochlea. We wished to confirm our previous report that a single intracochlear injection of brain-derived nerve growth factor (BDNF) was beneficial for hearing in guinea pigs. We wished to assess the reproducibility of our results and assess possible improved methods with a view to developing a clinical treatment for sensorineural hearing loss. Methods: CDDP was used to create partial hearing loss in 25 guinea pigs. After 30 days the animals underwent ABR testing and unilateral BDNF injection through the round window in one ear and saline injection into the other ear. After allowing possible effects to stabilize, thirty days later, ABR threshold testing was repeated to assess change in threshold. Results: Final ABR thresholds were 60–70 dB and were about 11 dB better in the ears treated with BDNF. Conclusion: Our original finding that Intracochlear BDNF can improve hearing in guinea pigs was confirmed, but the improvement demonstrated by the methods in this paper is too small for clinical application. [ABSTRACT FROM AUTHOR]

Learning about research ethics and research integrity is greatly facilitated by case studies, which illuminate, ground and personalise abstract questions. This paper argues that fiction can provide similar learning experiences, incarnating ethical dilemmas through a medium that is highly accessible yet sophisticated in its depictions of how researchers behave. Examples of fictional illustrations are given to illustrate various themes such as animal experimentation, exploitation of the vulnerable, researcher bias and research fraud. [ABSTRACT FROM AUTHOR]

Background: Various suture materials are available for arthroscopic rotator cuff repair. More recently, suture tapes have become popular as they are perceived to be easier to use with less soft tissue irritation. However, little is known about their biomechanical and clinical properties compared with conventional sutures in rotator cuff repairs. Purpose: To perform a systematic review and meta-analysis on whether suture tapes are biomechanically superior to conventional sutures in arthroscopic rotator cuff repairs and whether this translates to superior functional outcomes and a lower incidence of retears. Study Design: Meta-analysis. Methods: The Cochrane Controlled Register of Trials, PubMed, Medline, and Embase were used to perform a systematic review and meta-analysis using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria with the following search terms: (rotator cuff repair OR arthroscopic rotator cuff repair) AND ("tape" OR "wire" OR "cord" OR "suture"). Data pertaining to certain biomechanical properties (contact area, contact pressure, gap formation, load to failure, and stiffness), retears, and patient-reported outcome measures (PROMs) were extracted. The pooled outcome data were analyzed by random- and fixed-effects models. Results: After abstract and full-text screening, 7 biomechanical and 6 clinical studies were included. All biomechanical studies were on animals, with 91 suture tapes and 91 conventional sutures compared. Suture tapes had higher contact pressure (mean difference [MD], 0.04 MPa; 95% CI, 0.01-0.08; P =.02), higher load to failure (MD, 52.62 N; 95% CI, 27.34-77.90; P <.0001), greater stiffness (MD, 4.47 N/mm; 95% CI, 0.57-8.38; P =.02), and smaller gap formation (MD, −0.30 mm; 95% CI, −0.45 to −0.15; P <.0001) compared with conventional sutures. From the clinical analysis of the 681 rotator cuff repairs treated with a suture tape (n = 380) or conventional suture (n = 301), there were no differences in retear rates between the groups (16% vs 20% suture tape and wire, respectively; P =.26) at a mean of 11.2 months. Qualitatively, there were no differences in PROMs between the groups at a mean of 36.8 months. Conclusion: Although biomechanically superior, suture tapes showed similar retear rates and postoperative function to conventional sutures. However, higher-quality clinical studies are required to investigate whether there are no true differences. [ABSTRACT FROM AUTHOR]

Background: Postpartum fatigue is a common disorder worldwide and affects both physical and mental functioning. In breastfeeding women, Prolactin (PRL) is not only involved in immunoregulation, but also responsible for lactation. Prolactin levels in women with chronic fatigue are higher than normal, but a chronic fatigue state inhibits postpartum lactation in humans. Objectives: This paper explored the inhibition mechanism of lactation by postpartum fatigue in rats. Methods: Postpartum fatigue models were built by forcing mother rats to stand in water and divided into 3-hour, 9-hour and 15-hour per day fatigue groups according to the underwater time. Mother rats and their offspring were reunited in a dry cage for 90 minutes every 3 hours for feeding. The expression of PRL, PRL receptor (PRLR), Janus Kinase 2 (JAK 2), and Signal transducers and activators of transcription 5 (STAT5) mRNA were analyzed and the microstructure of mammary gland were observed under light and electron microscopy. Results: The expression of pituitary PRL mRNA and its downstream signaling pathway JAK2 and STAT5 mRNA were down-regulated in the severe postpartum fatigue rats. PRL mRNA responses were dose-related to duration of fatigue. The expression of PRLR mRNA increased. Postpartum fatigue led to functional degeneration of mammary gland. The breast lobules were shrunk and the number of alveoli were decreased. Few milk protein granules and fat droplets were observed in the cytoplasm under transmission electron microscope. Conclusion: Postpartum fatigue inhibits the lactation by down-regulating the expression of PRL and PRL-dependent signaling pathway in rats. [ABSTRACT FROM AUTHOR]

Bivariate responses with mixed continuous and binary variables arise commonly in applications such as clinical trials and genetic studies. Statistical methods based on jointly modeling continuous and binary variables have been available. However, such methods ignore the effects of response mismeasurement, a ubiquitous feature in applications. It has been well studied that in many settings, ignorance of mismeasurement in variables usually results in biased estimation. In this paper, we consider the setting with a bivariate outcome vector which contains a continuous component and a binary component both subject to mismeasurement. We propose estimating equation approaches to handle measurement error in the continuous response and misclassification in the binary response simultaneously. The proposed estimators are consistent and robust to certain model misspecification, provided regularity conditions. Extensive simulation studies confirm that the proposed methods successfully correct the biases resulting from the error-in-variables under various settings. The proposed methods are applied to analyze the outbred Carworth Farms White mice data arising from a genome-wide association study. [ABSTRACT FROM AUTHOR]

The article discusses the effectiveness of selection in producing laboratory stocks that are genetically uniform to be resistant to dental caries. The author details methods to avoid breeding that is somewhat selective because of small sample numbers as well as ways to ensure that random mating produces genetic equilibrium.

QTL mapping is an important tool for identifying regions in chromosomes which are relevant to explain a response of interest. It is a special case of the regression model where an unknown number of missing (non-observable) covariates is involved leading to a complex variable selection procedure. Although several methods have been proposed to identify QTLs and to estimate parameters in the associated model, minimum attention has been devoted to the estimated model adequacy. In this paper, we present an overview of a few methods for residual and diagnostic analysis in the context of Bayesian regression modeling and adapt them to work with QTL mapping. The motivation of this study is to identify QTLs associated with the blood pressure of F2 rats and check the fitted model adequacy. [ABSTRACT FROM AUTHOR]

Projections of both the short- and long-term course of the variant Creutzfeldt-Jakob disease (vCJD) epidemic in Great Britain have demonstrated great uncertainty due to the lack of knowledge of key aspects of the biology and epidemiology of this new disease. Such projections are sensitive to assumptions made regarding the pattern of exposure to BSE-infected animals, the effectiveness of control measures introduced in 1989 and 1996 in reducing this exposure, the functional form of the incubation period distribution and patterns of age-dependent susceptibility/exposure. This paper provides short-term projections for vCJD onsets using the time- and age-distributed onset data to the end of 2000, with results that are directly comparable to the other papers in this issue. These results demonstrate the continued uncertainty in the future scale of this disease. [ABSTRACT FROM AUTHOR]

Phytolacca dodecandra (L' Herit), or 'Endod', is one of the widely known medicinal plants in Ethiopia. Berries of the endod have been used as a detergent for centuries. The present study was aimed to test the hepatoprotective effects of the plant against acetaminophen (APAP)-induced liver injury in rats. Mice of either sex were used for oral acute toxicity tests and APAP-induced lethality tests. Hepatoprotective experiments were done on male rats using 2 g/kg of APAP to induce liver damage. Liver enzymes, total bilirubin (TB), and lipid profile were determined. Liver tissues were also examined histopathologically to see a morphologic change in the control and experiment groups. The protective effect of the plant extract was also tested through sodium pentobarbital (SPB)-induced sleeping time. A significant increase in serum levels of liver enzymes, TB, low-density lipoprotein (LDL), and triglycerides (TGs) was seen from oral administration of 2 g/kg APAP. Total cholesterol (TC) and high-density lipoprotein (HDL) levels were decreased. Serum levels of all parameters were reversed to normal after administration of silymarin 100 mg/kg and, 100, 200, and 400 mg/kg doses of the extract. A significant dose-dependent hepatoprotective effect of Phytolacca dodecandra Methanol Root Extract (PDME) was seen in terms of LDL. Histopathological investigations and SPB-induced sleeping time confirmed the findings of biochemical analysis. The findings of the present study indicate that PDME protected the liver from APAP injury. [ABSTRACT FROM AUTHOR]

Background: Animal models that use open surgical transection of the anterior cruciate ligament (ACL) do not accurately simulate the clinical condition regarding the pivot-shift mechanism and the associated inflammatory response that occurs before reconstruction. Purpose/Hypothesis: The purpose was to characterize a reproducible manual, nonsurgical method to mimic an isolated ACL tear in a clinically relevant model and to evaluate the development of progressive posttraumatic osteoarthritis due to ACL injury. It was hypothesized that the ACL could be reproducibly torn with minimal damage to other ligaments and that there would be progressive development of degenerative joint disease after ACL injury. Study Design: Controlled laboratory study. Methods: A total of 37 mice (strain C57BL/6) were used to compare the manual procedure with sham surgery (sham group; n = 10) and with the established surgical ACL transection (ACLT) procedure (surgical group; n = 27). In the sham group, a closed manual procedure was performed on the right knee and sham surgery on the left knee. In the surgical group, the closed manual procedure was performed on the right knee and surgical ACLT on the left knee. Dissection using India ink, histological assessment with safranin O and hematoxylin-eosin staining, radiological evaluation through radiographs and microfocus computed tomography scans, and gait analyses were performed to assess cartilage/ligament status. Osteoarthritis Research Society International (OARSI) and synovitis scores, anterior tibial translation, range of motion, bone microstructure, osteophyte volume, and pain were assessed at 2, 4, and 8 weeks postoperatively. Results: The manual procedure successfully resulted in an ACL rupture and associated meniscal injury. The posterior cruciate, lateral collateral, and medial collateral ligaments were intact in all dissected knees. Two weeks after ACL tear, the surgical group showed a significantly higher synovitis score, whereas 8 weeks after ACL tear, the manual group showed a significantly higher volume of osteophytes. No significant differences were found between the groups in terms of OARSI score, anterior tibial translation, range of motion, bone microstructure computed tomography values, and stride distance/irregularity. Conclusion: This procedure can be used to create an ACL tear model without causing grossly evident injuries to other ligaments and avoiding the risk of cartilage damage from surgical instruments. Clinical Relevance: This procedure offers a more clinically relevant ACL tear model and facilitates simple, inexpensive, and reproducible development of posttraumatic osteoarthritis. [ABSTRACT FROM AUTHOR]

Aims: Endovenous microwave ablation (EMWA) is an endovenous thermoablation (EVTA) system to ablate incompetent truncal veins. Early results suggest that EMWA uses more power than endovenous laser ablation (EVLA) to get the same results. We aimed to define the parameters for EMWA, which give the same tissue ablation as EVLA, using the validated porcine liver model. Methods: EVLA (1470 nm 600 micron radial fibre) treatments were performed at 6 W, 8 W and 10 W, at pullback speeds of 6, 7, 8 and 9 s/cm, giving Linear Endovenous Energy Densities (LEEDs) between 36 - 90 J/cm. Each combination of power and pullback was repeated 5 times. We then used EMWA in the same model. Powers of 35-75 W and pullback speeds of 4-9 s/cm were used (LEEDs 140-675 J/cm). Ablation tracts from both devices were analysed by 2 blinded observers, noting thermal spread and carbonisation. Results: For each commonly used parameter for EVLA, we identified a range of parameters for EMWA that produced similar tissue ablation in the porcine liver model. To keep the pullback speeds within the usual range, powers of 35-75 W were needed with EMWA, with mean EMWA LEEDs 3.9 - 5.8 times higher than EVLA LEEDs. We found the quicker the pullback speed, the higher the multiple of EMWA LEED we needed to get the same effect. Conclusion: We have identified parameters for EMWA that gave equivalent tissue ablation in the porcine liver model to commonly used parameters used for EVLA. These need to be validated clinically, but as the model used has already been validated against clinical outcome in endovenous thermal ablation, there is little reason to suspect that these results would not be valid. As the power during EMWA is higher than EVLA, EVMA LEEDs are approximately 4-6 times higher than EVLA LEEDs to achieve the same thermal effect on the tissues. [ABSTRACT FROM AUTHOR]

Recently, scholars have focused on a growing number of social movement consequences. However, one important type of intended outcome has been neglected: the development of new technologies. Connecting to key insights from Science and Technology Studies, the aim of this article is to contribute to the literature on the effects of activism in two specific ways. First, I present and discuss four causal mechanisms that show how activists trigger the development of new technologies. Second, I demonstrate how the development of new technologies is a highly contested goal among activists, leading to divisions within social movements. Based on novel empirical research, this paper analyzes a crucial and understudied case of a movement pushing for new technologies: the animal rights movement and its efforts to push for alternatives to animal experimentation. Methodologically, I rely on semistructured interviews with activists from different social movement organizations, publications of social movement organizations, and secondary literature. [ABSTRACT FROM AUTHOR]

For stochastic effects such as cancer, linear-quadratic models of dose are often used to extrapolate from the experience of the Japanese atomic bomb survivors to estimate risks from low doses and low dose rates. The low dose extrapolation factor (LDEF), which consists of the ratio of the low dose slope (as derived via fitting a linear-quadratic model) to the slope of the straight line fitted to a specific dose range, is used to derive the degree of overestimation (if LDEF > 1) or underestimation (if LDEF < 1) of low dose risk by linear extrapolation from effects at higher doses. Likewise, a dose rate extrapolation factor (DREF) can be defined, consisting of the ratio of the low dose slopes at high and low dose rates. This paper reviews a variety of human and animal data for cancer and non-cancer endpoints to assess evidence for curvature in the dose response (i.e. LDEF) and modifications of the dose response by dose rate (i.e. DREF). The JANUS mouse data imply that LDEF is approximately 0.2-0.8 and DREF is approximately 1.2-2.3 for many tumours following gamma exposure, with corresponding figures of approximately 0.1-0.9 and 0.0-0.2 following neutron exposure. This paper also cursorily reviews human data which allow direct estimates of low dose and low dose rate risk. [ABSTRACT FROM AUTHOR]

Background: The tendon-bone interface (TBI) in the rotator cuff has a poor intrinsic capacity for healing, which increases the risk of retear after rotator cuff repair (RCR). However, facilitating regeneration of the TBI still remains a great clinical challenge. Herein, the authors established a novel strategy based on magnetic seeding to enhance the TBI regeneration. Hypothesis: Magnetic seeding bone marrow mesenchymal stem cells labeled with superparamagnetic iron oxide (SPIO-BMSCs) into a biphasic scaffold can promote tendon-bone healing after RCR. Study Design: Controlled laboratory study. Methods: BMSCs were labeled with SPIOs. Prussian blue staining, CCK-8 tests, Western blot, and quantitative reverse transcription polymerase chain reaction (PCR) were used to determine the optimal effect concentration of SPIOs on cell bioactivities and abilities. Then SPIO-BMSCs were magnetically seeded into a biphasic scaffold under a magnetic field. The seeding efficacy was assessed by a scanning electron microscope, and the potential mechanism in chondrogenic differentiation after seeding SPIO-BMSCs into the scaffold was evaluated by Western blot and PCR. Furthermore, the effect of SPIO-BMSC/biphasic scaffold on tendon-bone healing after RCR using a rat model was examined using histological analysis, enzyme-linked immunosorbent assay, and biomechanical evaluation. Results: BMSCs labeled with 100 μg/mL SPIO had no effect on cell bioactivities and the ability of chondrogenic differentiation. SPIO-BMSCs were magnetically seeded into a biphasic scaffold, which offered a high seeding efficacy to enhance chondrogenic differentiation of SPIO-BMSCs via the CDR1as/miR-7/FGF2 pathway for TBI formation in vitro. Furthermore, in vivo application of the biphasic scaffold with magnetically seeded SPIO-BMSCs showed their regenerative potential, indicating that they could significantly accelerate and promote TBI healing with superior biomechanical properties after RCR in a rat rotator cuff tear model. Conclusion: Magnetically seeding SPIO-BMSCs into a biphasic scaffold enhanced seeding efficacy to promote cell distribution and condensation. This construct enhanced the chondrogenesis process via the CDR1as/miR-7/FGF2 pathway and further promoted tendon-bone healing after RCR in a rat rotator cuff tear model. Clinical Relevance: This study provides an alternative strategy for improving TBI healing after RCR. [ABSTRACT FROM AUTHOR]

Liver cancer is the most common cancer among males in Africa. The disease has a poor prognosis and its treatment is associated with toxicity and resistance. For this reason, numerous herbal combinations are being subjected to anticancer screening to circumvent the shortcomings of the conventional anticancer drugs. In the current study, the in vivo anti-cancer effects of the chloroform root extract of the herb, Clausena excavata Burm were investigated. Liver cancer was induced in mice by a single intraperitoneal injection of diethylnitrosamine (DEN) followed by oral administration of the promoter of carcinogenesis, 2-aminoacetyl fluorine that was mixed with the mice feed. The cytotoxicity of the root extract of C. excavata on liver cancer cells was investigated using liver enzyme, histology, DNA fragmentation and caspases assays. Real time qPCR was conducted to evaluate the effect of the extract on apoptotic genes. The findings revealed that the extract of C. excavata significantly decreased the progression of hepatocarcinogenesis and the toxicity-induced production of the liver enzymes, alanine and aspartate aminotransferases. The histological analyses of the liver tissues revealed evidence of apoptotic cell death. The extract also provoked significant (p <.05) expressions of caspase 9 protein and gene as well as other apoptotic genes (P53, P27, Apaf-1, cytochrome C, bax and bid). Therefore, we postulate that the chloroform root extract of C. excavata induces apoptosis of liver cancer in mice. [ABSTRACT FROM AUTHOR]

Objective: Aqueous extract of unripe Musa paradisiaca fruit is commonly used for the treatment of ulcers in eastern Nigeria. This study aimed to assess the acute and subacute effects of an aqueous extract of unripe fruit on male and female fertility in rats. Methods: Aqueous extracts obtained by maceration were analyzed for acute and subacute toxicity and for the presence of phytochemical constituents using standard procedures. The extract (100, 500, and 1000 mg/kg) was administered daily to rats of both sexes for 28 d. Blood samples collected on days 0 and 28 were assessed for follicle-stimulating hormone (FSH), luteinizing hormone (LH), catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA). Testes and ovaries were harvested for histopathological analysis. Sperm were also collected to determine the sperm count and motility. Results: Phytochemical screening revealed the presence of saponins, tannins, alkaloids, and resins. After an oral dose of up to 5000 mg/kg, there were no deaths in the acute toxicity test. The extract (500 mg/kg) significantly (P <.05) enhanced sperm count and motility relative to the untreated control; significantly (P <.05) reduced SOD, CAT, and glutathione levels, while significantly (P <.05) elevated LH, FSH, and MDA levels in male and female rats. Histological examination revealed significant structural damage to the ovaries. Conclusion: Unripe Musa paradisiaca fruit exhibited an adverse toxicological profile following prolonged administration and caused oxidative stress in rodents. [ABSTRACT FROM AUTHOR]

Garcinia dulcis (GD) extract possesses anti-hypertensive property that are poorly characterized. This study aimed to investigate an anti-inflammatory effect of GD flower extract in the 2-kidney-1-clip (2K1C) hypertensive compared to sham operative (SO) rat. Male Wistar rats were divided into 2 groups; the 2K1C group in which a silver clip was placed around renal artery to induce hypertension, and the SO normotensive group. Four weeks later, each group of rats were further divided into 2 subgroups, each subgroup was orally gavaged of either corn oil (vehicle) or 50 mg/kg BW GD extract daily for 4 weeks. The malondialdehyde (MDA) levels in serum, liver, and kidney were determined. Hematoxylin and eosin staining was carried out for histological examination, Periodic acid – Schiff staining for glomerular injury, Masson's trichrome staining for renal fibrosis, and immunohistochemistry for either tumor necrosis factor alpha (TNF-α) or endothelial nitric oxide synthase (eNOS) investigation. Taken together, our results demonstrated that GD flower extract decreased the MDA level in both serum and liver and kidney tissue and suppressed the expression of TNF-α in both liver and kidney of 2K1C hypertensive rats. Mesangial cell proliferation, expansion of mesangial matrix, widening Bowman's capsule space, congestion of glomerular capillary and vessel, cloudy swelling of renal tubular epithelial cell, and renal fibrosis were observed in the kidneys of 2K1C rats. Therefore, we concluded that GD flower extract can alleviate liver and kidney inflammation in which partially attenuates the glomerular injury in the 2K1C rat. [ABSTRACT FROM AUTHOR]

Background: Muscle edema formation and inflammatory processes are early manifestations of acute rotator cuff lesions in sheep. Histological analysis of affected muscles revealed edema formation, inflammatory changes, and muscle tissue disruption in MRs. Hypothesis: Edema contributes to inflammatory reactions and early muscle fiber degeneration before the onset of fatty infiltration. Study Design: Controlled laboratory study. Methods: Osteotomy of the greater tuberosity, including the insertion of the infraspinatus tendon, was performed on 14 sheep. These experimental animal models were divided into 2 groups: a nontrauma group with surgical muscle release alone (7 sheep) and a trauma group with standardized application of additional trauma to the musculotendinous unit (7 sheep). Excisional biopsy specimens of the infraspinatus muscle were taken at 0, 3, and 4 weeks. Results: Edema formation was histologically demonstrated in both groups and peaked at 3 weeks. At 3 weeks, signs of muscle fiber degeneration were observed. At 4 weeks, ingrowth of loose alveolar and fibrotic tissue between fibers was detected. Fatty tissue was absent. The diameter of muscle fibers increased in both groups, albeit to a lesser degree in the trauma group, and practically normalized at 4 weeks. Immunohistology revealed an increase in macrophage types 1 and 2, as well as inflammatory mediators such as prostaglandin E2 and nuclear factor kappa-light-chain-enhancer of activated B cells. Conclusion: Early muscle edema and concomitant inflammation precede muscle fiber degeneration and fibrosis. Edema formation results from tendon release alone and is only slightly intensified by additional trauma. Clinical Relevance: This study illustrates that early edema formation and inflammation elicit muscle fiber degeneration that precedes fatty infiltration. Should this phenomenon be applicable to human traumatic rotator cuff tears, then surgery should be performed as soon as possible, ideally within the first 21 days after injury. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of electroacupuncture (EA) at ST36 on intestinal microflora and plasma metabolites in a mouse model of type 2 diabetes mellitus (T2DM), to provide a theoretical basis and guidance for the clinical treatment of T2DM by traditional Chinese medicine (TCM). Methods: Sixteen T2DM db/db mice were randomly divided into treatment (T, n = 8) and model (M, n = 8) groups, and a further eight normal db/m+ mice reared under the same conditions served as a non-diabetic control group (C, n = 8). The general conditions of mice were observed weekly. After obtaining blood and stool samples, the mice were euthanized. Fasting blood glucose (FBG) was measured using a glucometer and fasting insulin (FINS) was measured in plasma by enzyme-linked immunosorbent assay (ELISA). Liver and colon tissues were embedded in paraffin and subjected to hematoxylin–eosin (HE) staining to observe pathological changes in these tissues. In addition, 16S ribosomal RNA (rRNA) sequencing was performed to analyze changes in the intestinal flora and metabolomics was employed to assess changes in metabolites in the blood. Results: EA significantly reduced FBG and FINS levels and alleviated pathological damage to the liver and colon. Furthermore, EA increased intestinal community richness and diversity by decreasing the relative abundance of Clostridium and incresasing the relative abundance of Lactobacillus. EA also reduced D-fructose levels in T2DM mice according to plasma metabolomics. Conclusion: EA has a positive regulatory effect on the intestinal flora and can regulate blood glucose and improve insulin resistance in T2DM model mice. [ABSTRACT FROM AUTHOR]

Rationale: In recent decades, the use of ayahuasca (AYA) - a β-carboline- and dimethyltryptamine-rich hallucinogenic botanical preparation traditionally used by Northwestern Amazonian tribes for ritual and therapeutic purposes - has spread from South America to Europe and the USA, raising concerns about its possible toxicity and hopes of its therapeutic potential. Thus, it is important to analyze the acute, subacute, and long-term effects of AYA to assess its safety and toxicity.Objectives: The purpose of this study was to conduct a systematic review of human studies assessing AYA effects on psychiatric symptoms, neuropsychological functioning, and neuroimaging.Methods: Papers published until 16 December 2015 were included from PubMed, LILACS and SciELO databases following a comprehensive search strategy and pre-determined set of criteria for article selection.Results: The review included 28 full-text articles. Acute AYA administration was well tolerated, increased introspection and positive mood, altered visual perceptions, activated frontal and paralimbic regions and decreased default mode network activity. It also improved planning and inhibitory control and impaired working memory, and showed antidepressive and antiaddictive potentials. Long-term AYA use was associated with increased cortical thickness of the anterior cingulate cortex and cortical thinning of the posterior cingulate cortex, which was inversely correlated to age of onset, intensity of prior AYA use, and spirituality. Subacute and long-term AYA use was not associated with increased psychopathology or cognitive deficits, being associated with enhanced mood and cognition, increased spirituality, and reduced impulsivity.Conclusions: Acute, subacute, and long-term AYA use seems to have low toxicity. Preliminary studies about potential therapeutic effects of AYA need replication due to their methodological limitations. [ABSTRACT FROM AUTHOR]

Here, Reynolds and Neill describe the studies that preceded and followed publication of this paper, which reported a deficit in parvalbumin (PV), a calcium-binding protein found in GABA interneurons known to be reduced in schizophrenia patients, in conjunction with a deficit in reversal learning in an animal model for schizophrenia. This publication resulted from common research interests: Reynolds in the neurotransmitter pathology of schizophrenia, and Neill in developing animal models for schizophrenia symptomatology. The animal model, using a sub-chronic dosing regimen (sc) with the non-competitive NMDA receptor antagonist PCP (phencyclidine), evolved from previous work in rats (for PCP) and primates (for cognition). The hypothesis of a PV deficit came from emerging evidence for a GABAergic dysfunction in schizophrenia, in particular a deficit in PV-containing GABA interneurons. Since this original publication, a PV deficit has been identified in other animal models for schizophrenia, and the PV field has expanded considerably. This includes mechanistic work attempting to identify the link between oxidative stress and GABAergic dysfunction using this scPCP model, and assessment of the potential of the PV neuron as a target for new antipsychotic drugs. The latter has included development of a molecule targeting KV3.1 channels located on PV-containing GABA interneurons which can restore both PV expression and cognitive deficits in the scPCP model. [ABSTRACT FROM AUTHOR]

Objective: To examine for the in vitro existence of contractile nodules on the taut band of muscle fibers where myofascial trigger points (MTrPs) are located (using cell culture). Methods: Sixteen male Sprague–Dawley rats (7 weeks old) were randomly divided into experimental and control groups. A blunt striking injury and eccentric exercise were applied to the gastrocnemius muscle of rats in the experimental group once a week for 8 weeks to establish an MTrP model. Subsequently, the rats were reared normally and rested for 4 weeks. After modeling, the skeletal muscles at the MTrPs (and non-MTrPs at the same anatomical position) were extracted from the two groups of rats for in vitro cell culture experiments of single muscle fibers. Potential contractile nodules in the MTrP group were exposed to different concentrations of acetylcholinesterase, whereas non-MTrP cells were exposed to acetylcholine. The morphological changes of muscle cells in each group were observed. Results: By culturing MTrP cells in vitro, large contractile nodules remained in single MTrP muscle fibers, whereas some contractile nodules were twisted and deformed. After the addition of different acetylcholinesterase concentrations, no obvious morphological changes were observed in the contractile nodules in the MTrP group. After the non-MTrP cells were exposed to different acetylcholine concentrations, no significant morphological changes were observed in the single muscle fibers. Conclusion: MTrP cells can continue to maintain contractile morphology in vitro, but whether the recovery of such contractile nodules is related to acetylcholine remains uncertain. [ABSTRACT FROM AUTHOR]

Background: Neurogenic bladder (NB) is a form of neurological bladder dysfunction characterized by excessive contraction of the bladder detrusor. Protein kinase A (PKA) signaling is involved in the contraction of the detrusor muscle. Aims: To investigate whether PKA signaling mediates the effect of electroacupuncture (EA) on the excessive contraction of the bladder detrusor in NB. Methods: Sixty rats were randomly divided into control, sham, NB, NB + EA, and NB + EA + H89 (a PKA receptor antagonist) groups. The modified Hassan Shaker spinal cord transection method was used to generate a NB model. After EA intervention for one week, urodynamic tests were used to evaluate bladder function, hematoxylin and eosin staining was conducted to assess morphological changes, enzyme-linked immunosorbent assay (ELISA) was performed to measure the concentration of PKA, and Western blotting was conducted to measure the protein levels of phosphorylated myosin light chain kinase (p-MLCK)/p-MLC. Results: The results showed that NB resulted in morphological disruption, impairment of urodynamics, and decreases in the concentration of PKA and the protein levels of p-MLCK/p-MLC. EA reversed the changes induced by NB dysfunction. However, the improvement in urodynamics and the increases in the concentration of PKA and the protein levels of p-MLCK/p-MLC were inhibited by H89. Conclusion: Our findings indicate that the PKA signaling pathway mediates the beneficial effect of EA on excessive contraction of the bladder detrusor in a rat model of NB. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus prevalence has reached epidemic levels despite the existence of contemporary treatments. People thus started looking at the possible therapeutic value of natural therapies. Crushed shoot tips of Crinum abyssinicum (Amaryllidaceae) are mixed with water in Ethiopia to treat diabetes, yet this practice is not well supported by science. Objective: In this experiment, mice models were used to verify the blood sugar and lipid-lowering benefits of solvent fractions of C. abyssinicum shoot tips. Materials and Methods: In a single-dose treated Streptozotocin (STZ)-induced diabetic model, mice were randomly grouped into eleven categories which include diabetic negative control, diabetic positive control, and 9 diabetic treatment groups. In repeated daily doses treated STZ-induced model, Mice were divided into 6 groups which included normal and diabetic negative control (TW80), diabetic positive control (5 mg/kg glibenclamide), and three diabetic treatment groups 100, 200, and 400 mg/kg). Finally, blood glucose, lipid level, and body weight were examined. Results: In the single-dose treated diabetic model, there was a significant blood glucose reduction at 200 and 400 mg/kg doses of aqueous fraction and glibenclamide starting from the sixth-hour post-administration unlike ethyl acetate and chloroform fraction compared to baseline and negative control. In repeated daily dose-treated diabetic mice, all three doses (100, 200, and 400 mg/kg of aqueous fraction) resulted in a substantial reduction (P <.001) in blood glucose compared to baseline and negative control on the seventh day and 14th day. Besides the AQF shows improvement in lipid levels and body weight parameters. Conclusion: The results of the study demonstrated that C. abyssinicum shoot tip fractions have the greatest potential to lower blood sugar and lipid levels, supporting conventional claims for the treatment of diabetes. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) is a significant cause of disability worldwide, with limited treatment options. This study investigated the potential of bone marrow-derived mesenchymal stem cells (BMSCs) modified with XIST lentiviral vector to modulate macrophage polarization and affect neural stem cell (NSC) microenvironment reconstruction following SCI. Bioinformatics analysis revealed that MID1 might be crucial for BMSCs' treatment of SCI. XIST overexpression enriched Zmynd8 to the promoter region of MID1 and inhibited MID1 transcription, which promoted macrophage M2 polarization. In vitro experiments showed that BMSCs-XIST promoted NSC proliferation, migration, differentiation, and axonal growth by inducing macrophage M2 polarization, suppressing inflammation, and accelerating the re-establishment of the homeostatic microenvironment of NSCs. In vivo, animal experiments confirmed that BMSCs-XIST significantly alleviated SCI by promoting NSC differentiation and axon formation in the injured area. The study demonstrated the potential of XIST-overexpressing BMSCs for treating SCI by regulating macrophage polarization and homeostasis of the NSC microenvironment. These findings provide new insights into the development of stem cell-based therapies for SCI. [ABSTRACT FROM AUTHOR]

Background: Total meniscectomy for treating massive meniscal tears may lead to joint instability, cartilage degeneration, and even progressive osteoarthritis. The meniscal substitution strategies for advancing reconstruction of the meniscus deserve further investigation. Hypothesis: A decellularized meniscal scaffold (DMS) modified with collagen affinity stromal cell–derived factor (C-SDF1α) may facilitate meniscal regeneration and protect cartilage from abrasion. Study Design: Controlled laboratory study. Methods: The authors first modified DMS with C-SDF1α to fabricate a new meniscal graft (DMS-CBD [collagen-binding domain]). Second, they performed in vitro studies to evaluate the release dynamics, biocompatibility, and differentiation inducibility (osteogenic, chondrogenic, and tenogenic differentiation) on human bone marrow mesenchymal stem cells. Using in vivo studies, they subjected rabbits that received medial meniscectomy to a transplantation procedure to implement their meniscal graft. At postoperative weeks 6 and 12, the meniscal regeneration outcomes and chondroprotective efficacy of the new meniscal graft were evaluated by macroscopic observation, histology, micromechanics, and immunohistochemistry tests. Results: In in vitro studies, the optimized DMS-CBD graft showed notable biocompatibility, releasing efficiency, and chondrogenic inducibility. In in vivo studies, the implanted DMS-CBD graft after total meniscectomy promoted the migration of cells and extracellular matrix deposition in transplantation and further facilitated meniscal regeneration and protected articular cartilage from degeneration. Conclusion: The new meniscal graft (DMS-CBD) accelerated extracellular matrix deposition and meniscal regeneration and protected articular cartilage from degeneration. Clinical Relevance: The results demonstrate that the DMS-CBD graft can serve as a potential meniscal substitution after meniscectomy. [ABSTRACT FROM AUTHOR]

Antidepressants often disrupt sleep. Vortioxetine, a multimodal antidepressant acting through serotonin (5-HT) transporter (SERT) inhibition, 5-HT3, 5-HT7 and 5-HT1D receptor antagonism, 5-HT1B receptor partial agonism, and 5-HT1A receptor agonism, had fewer incidences of sleep-related adverse events reported in depressed patients. In the accompanying paper a polysomnographic electroencephalography (sleep-EEG) study of vortioxetine and paroxetine in healthy subjects indicated that at low/intermediate levels of SERT occupancy, vortioxetine affected rapid eye movement (REM) sleep differently than paroxetine. Here we investigated clinically meaningful doses (80-90% SERT occupancy) of vortioxetine and paroxetine on sleep-EEG in rats to further elucidate the serotoninergic receptor mechanisms mediating this difference. Cortical EEG, electromyography (EMG), and locomotion were recorded telemetrically for 10 days, following an acute dose, from rats receiving vortioxetine-infused chow or paroxetine-infused water and respective controls. Sleep stages were manually scored into active wake, quiet wake, and non-REM or REM sleep. Acute paroxetine or vortioxetine delayed REM onset latency (ROL) and decreased REM episodes. After repeated administration, vortioxetine yielded normal sleep-wake rhythms while paroxetine continued to suppress REM. Paroxetine, unlike vortioxetine, increased transitions from non-REM to wake, suggesting fragmented sleep. Next, we investigated the role of 5-HT3 receptors in eliciting these differences. The 5-HT3 receptor antagonist ondansetron significantly reduced paroxetine's acute effects on ROL, while the 5-HT3 receptor agonist SR57227A significantly increased vortioxetine's acute effect on ROL. Overall, our data are consistent with the clinical findings that vortioxetine impacts REM sleep differently than paroxetine, and suggests a role for 5-HT3 receptor antagonism in mitigating these differences. [ABSTRACT FROM AUTHOR]

Background: Dopamine has been suggested to be a stop signal for eye growth and affects the development of myopia. Acupuncture is known to increase dopamine secretion and is widely used to treat myopia clinically. Objective: The aim of this study was to determine if acupuncture inhibits myopia progression in form deprived Syrian hamsters by inducing rises in dopamine content that in turn suppress inflammasome activation. Methods: Acupuncture was applied at LI4 and Taiyang every other day for 21 days. The levels of molecules associated with the dopamine signaling pathway, inflammatory signaling pathway and inflammasome activation were determined. A dopamine agonist (apomorphine) was used to evaluate if activation of the dopaminergic signaling pathway suppresses myopia progression by inhibiting inflammasome activation in primary retinal pigment epithelial (RPE) cells. A dopamine receptor 1 (D1R) inhibitor (SCH39166) was also administered to the hamsters. Results: Acupuncture inhibited myopia development by increasing dopamine levels and activating the D1R signaling pathway. Furthermore, we also demonstrated that nucleotide-binding oligomerization domain (NOD)-, leucine-rich repeat (LRR)- and pyrin domain-containing protein 3 (NLR) family pyrin domain-containing 3 (NLRP3) inflammasome activation was inhibited by activation of the D1R signaling pathway. Conclusion: Our findings suggest that acupuncture inhibits myopia development by suppressing inflammation, which is initiated by activation of the dopamine—D1R signaling pathway. [ABSTRACT FROM AUTHOR]

Objective: Insomnia is the most common sleep disorder and is often comorbid with mental and physical diseases. The present study was designed to investigate the hypnotic effect of electroacupuncture (EA) of the cymba concha to stimulate the auricular branch of the vagus nerve (ABVN). Methods: Mice were intraperitoneally injected with p-chlorophenylalanine (PCPA, 300 mg/kg·d) for 2 days to induce insomnia and subsequently received EA or manual acupuncture (MA) of the cymba concha for 30 min once daily for 5 consecutive days, or no treatment. The phenobarbital-induced sleep test was used to analyze the hypnotic effects and the open field test was used to analyze the locomotor activities and anxiolytic effects of EA/MA of the cymba concha. In addition, the levels of gamma-aminobutyric acid (GABA) and glutamate (Glu) in the hypothalamus and peripheral blood were determined by enzyme-linked immunosorbent assay (ELISA). Results: PCPA injection significantly decreased sleep duration, increased sleep latency and induced anxiety-like behaviors in mice. In PCPA-insulted mice, EA of the cymba concha improved the sleep disturbance by significantly prolonging sleep duration, while no change in sleep latency was observed. Moreover, EA of the cymba concha improved PCPA-induced anxiety-like behaviors without decreasing locomotor activities in the open field test. EA of the cymba concha increased the level of GABA in the hypothalamus and peripheral blood, while Glu concentrations remained unchanged. Conclusion: These findings indicate that EA of the region innervated by the ABVN upregulates GABA levels in the hypothalamus and ameliorates the symptoms of insomnia and anxiety, suggesting that EA of the cymba concha might have potential value as an intervention for insomnia. [ABSTRACT FROM AUTHOR]

Amaranthus dubius is a vegetable consumed for its nutritional content in Kenya. In herbal medicine, A. dubius is utilized to relief fever, anemia and hemorrhage. Additionally, it is utilized to manage cognitive dysfunction and is considered to augment brain function, but there is no empirical evidence to support this claim. The contemporary study investigated cognitive enhancing potential of A. dubius in mice model of Alzheimer's disease (AD)-like dementia induced with ketamine. Cognitively damaged mice were treated with aqueous extract of A. dubius leaf upon which passive avoidance task (PAT) was used to assess the cognitive performance. At the end of passive avoidance test, brains of the mice were dissected to evaluate the possibility of the extract to inhibit hallmarks that propagate AD namely oxidative stress and acetylcholinesterase activity. Additionally, characterization of secondary metabolites was done using liquid chromatograph- mass spectrometry analysis. During PAT test, extract-treated mice showed significantly increased step-through latencies than AD mice, depicting ability of A. dubius to reverse ketamine-induced cognitive decline. Further, the extract remarkably lowered malondialdehyde levels to normal levels and effectively inhibited acetylcholinesterase enzyme. The study showed that A. dubius extract is endowed with phytoconstituents that possess anti-oxidant and anticholinesterase activities. Thus, this study confirmed promising therapeutic effects of 200, 300 and 400 mg/kg bw of A. dubius extract with potential to alleviate cognitive disarray observed in AD. [ABSTRACT FROM AUTHOR]

Background: Biocompatibility and stability of three-dimensional printed polycaprolactone mesh grafts for nasal surgery are proven in both animal and human models. However, their safety and durability as batten grafts for caudal septal deviation has not been documented. This study was designed to investigate the efficacy and safety of three-dimensional printed polycaprolactone mesh batten graft in septoplasty using the wedge resection technique for the correction of caudal septal deviation. Methods: This retrospective study reviewed the medical records of 20 patients aged ≥ 18 years with caudal septal deviation who underwent septoplasty with wedge resection and three-dimensional printed polycaprolactone mesh graft from a tertiary medical center in South Korea, between December 1, 2019 and May 31, 2021. Those without nasal obstruction before surgery or with a short follow-up period (< 28 days) were excluded from the survey analysis. Results: Of the 20 patients (mean age, 48.0 [range, 19–65] years), 17 (85.0%) were male, and three (15.0%) were female. A significant change was noted in the mean nasal obstruction symptom evaluation score (68.2 vs. 15.0, P <.001) in the 17 patients included in the analysis. Postoperative endoscopic evaluation revealed a straight septum in 19/20 (95.0%) patients, and no complications were noted in the postoperative follow-up period of up to 364 days. Conclusions: The three-dimensional printed polycaprolactone nasal mesh is safe and provides adequate support to resist the intrinsic memory of the cartilage of the caudal septum. In addition to nasal surgeries, it has great potential as a graft in other reconstructive surgeries. Trial registration Retrospectively registered. [ABSTRACT FROM AUTHOR]

MLN8237, a specific inhibitor of Aurora-A kinase, is proved to be a potential treatment strategy for hepatocellular carcinoma (HCC). Nanogels improve the efficacy of doxorubicin. Therefore, this study aims to investigate the increase in the effect of nanogels on MLN8237 in inhibiting HCC. Doxorubicin or MLN8237 was used as an anti-tumor drug models which were packaged by organic solvent volatilization method to obtain the doxorubicin-loaded nanogel and the MLN8237-loaded nanogel. Subsequently, CCK8 assay, cell cycle assay, apoptosis assay, real-time PCR, western blotting assay and animal experiments were used to detect the effects of MLN8237 nanogel on the proliferation, cell cycle, apoptosis, tumor growth, mRNA and protein levels of aurora-A and PUMA, and AKT phosphorylation levels in HCC cell lines. The results show that the nanogels can realize pH-regulated hydrophobicity reversal, have certain stability, and can realize lysosomal escape. Moreover, the MLN8237-loaded nanogel has a stronger ability to inhibit HCC cell proliferation, block cell cycle, promote apoptosis and inhibit tumor growth than free MLN8237 by suppressing aurora-A and AKT phosphorylation. In short, nanogel can enhance the efficacy of MLN8237. [ABSTRACT FROM AUTHOR]

Background: There is growing interest in nonoperative treatment for the management of Achilles tendon ruptures (ATRs). However, nonoperative treatment is limited by the risk of tendon reruptures and low satisfaction rates. Recently, atelocollagen injections have been reported to have beneficial effects on tendon healing. Purpose: To evaluate the beneficial effects of injected atelocollagen on Achilles tendon healing and investigate the mechanism of atelocollagen on tendon healing. Study Design: Controlled laboratory study. Methods: Percutaneous tenotomy of the right Achilles tendon in 66 rats was performed. The animals were equally divided into the noninjection group (NG) and the collagen injection group (CG). At 1, 3, and 6 weeks, the Achilles functional index, cross-sectional area, load to failure, stiffness, stress, and the modified Bonar score were assessed. Transmission electron microscopy, western blotting, and immunohistochemistry were also performed. Results: The Achilles functional index (–6.8 vs −43.0, respectively; P =.040), load to failure (42.1 vs 27.0 N, respectively; P =.049), and stiffness (18.8 vs 10.3 N/mm, respectively; P =.049) were higher in the CG than those in the NG at 3 weeks. There were no significant differences in histological scores between the 2 groups. Transmission electron microscopy analysis showed that the mean diameter of collagen fibrils in the CG was greater than that in the NG at 3 weeks (117.2 vs 72.6 nm, respectively; P <.001) and 6 weeks (202.1 vs 144.0 nm, respectively; P <.001). Western blot analysis showed that the expression of collagen type I in the CG was higher than that in the NG at 1 week (P =.005) and 6 weeks (P =.001). Conclusion: An atelocollagen injection had beneficial effects on the healing of nonoperatively treated Achilles tendon injuries. The Achilles tendon of CG rats exhibited better functional, biomechanical, and morphological outcomes compared with NG rats. The molecular data indicated that the mechanism of atelocollagen injections may be associated with an increased amount of collagen type I. Clinical Relevance: An atelocollagen injection might be a good adjuvant option for the nonoperative treatment of ATRs. [ABSTRACT FROM AUTHOR]

InVivoStat is a free-to-use statistical software package for analysis of data generated from animal experiments. The package is designed specifically for researchers in the behavioural sciences, where exploiting the experimental design is crucial for reliable statistical analyses. This paper compares the analysis of three experiments conducted using InVivoStat with other widely used statistical packages: SPSS (V19), PRISM (V5), UniStat (V5.6) and Statistica (V9). We show that InVivoStat provides results that are similar to those from the other packages and, in some cases, are more advanced. This investigation provides evidence of further validation of InVivoStat and should strengthen users’ confidence in this new software package. [ABSTRACT FROM AUTHOR]

Background: The anterior cruciate ligament (ACL) has poor regenerative capacity, and an injury leads to loss of function, limiting quality of life and increasing the incidence of osteoarthritis. Surgical interventions can stabilize the joint and improve functional recovery. The delivery of growth factors (GFs) enhances the healing process; however, this is complex in its regulation, is high in costs, has side effects, and can only be accomplished with supraphysiological concentrations and thus is currently not clinically feasible. However, the immobilization of a patient’s endogenous GFs in biomaterials can overcome these problems. Purpose: To develop a method to capture endogenous bone morphogenetic protein–2 (BMP-2) and ultimately show enhanced ACL healing in vivo using this novel methodology. Study Design: Controlled laboratory study. Methods: BMP-2 binding peptides were synthetized, purified, and immobilized on polycaprolactone (PCL) films. The affinity between the peptide and human BMP-2 (hBMP-2) was confirmed with immunofluorescence and enzyme-linked immunosorbent assay. The C2C12 Luc reporter cell line was used to confirm the bioactivity of immobilized BMP-2. For in vivo experiments, the same functionalization technology was applied to the commercially available Polytape, and the functionalized tape was sutured together with the graft used for ACL reconstruction in rats. Each animal underwent reconstruction with either native Polytape (n = 3) or Polytape with BMP-2 binding peptides (n = 3). At 2 and 6 weeks after surgery, the graft was assessed by histology and micro–computed tomography. Results: The covalent immobilization of the peptide in PCL was successful, allowing the peptide to capture hBMP-2, which remained bioactive and led to the osteogenic differentiation of C2C12. In vivo experiments confirmed the potential of the Polytape functionalized with the BMP-2 binding peptide to capture endogenous BMP-2, leading to enhanced bone formation inside the femoral and tibial tunnels and ultimately improving the graft’s quality. Conclusion: The incorporation of BMP-2 binding peptides into materials used for ACL reconstruction can capture endogenous hBMP-2, which enhances the healing process inside the bone tunnels. Clinical Relevance: These results demonstrate the potential of using synthetic peptides to endow biomaterials with novel biological functions, namely to capture and immobilize endogenous GFs. [ABSTRACT FROM AUTHOR]

Recent representations of human-animal relationships in farming have tended to focus on human experience, and to essentialise animal subjectivity in granting them a centred subjectivity akin to that assumed to be possessed by humans. Instead, this paper develops an understanding of the coproduction of domestic livestock animal subjectivities and the technologies used in farming domestic livestock animals, based on an analysis of texts produced by agricultural scientists, farmers, and equipment manufacturers relating to the effects of introducing new robotic milking technologies into dairy farming. Drawing particularly on Foucault's conceptions of subjectivity and biopower, I explore the emergence of particular forms of bovine subjectivity associated with robotic milking. Through an analysis of a wide range of secondary sources, the paper shows that, although robotic technologies have been presented as offering cows `freedom', better welfare, and a more `natural' experience, other relations of domination come into effect in association with such technologies and their spatialities. These are expressed through the manipulation of animal bodies and behaviours, in expectations that cows move and act in particular ways, and through normalisation and individualisation processes. I argue that nonhuman animal subjectivities in agriculture are thus heterogeneous, fluid, and contingent on specific sets of relationships between animals, humans, and technologies and on specific agricultural microgeographies. The paper ends by acknowledging that these relationships need further empirical exploration in terms of both attempts to understand animals' changed experiences and ways of being, and their ethical implications in particular situations. [ABSTRACT FROM AUTHOR]

Pulsed radiofrequency is a growingly popular pain treatment modality. However, its clinical efficacy remains controversial. In this review, the available literature on pulsed radiofrequency is critically analysed to determine its clinical efficacy. Our search of the literature for pulsed radiofrequency yielded 341 citations; after reviewing the abstracts we found 51 relevant articles. There were 4 review articles: 44 articles pertained to the application of pulsed radiofrequency by an electrode placed in the vicinity of a neural structure. Of these only two were randomised controlled trials. Of the remaining 42 articles, one was a non-randomised controlled trial, three were prospective uncontrolled trials: there were six retrospective studies, 11 case reports, eight laboratory studies, two position papers, five editorials and seven items of correspondence, while one publication reported two studies. Three articles pertained to transcutaneous application of pulsed radiofrequency. Of the two randomised controlled trials, one reported efficacy of the pulsed radiofrequency while the other reported it to be ineffective. The majority of the uncontrolled and observational studies reported clinical efficacy of pulsed radiofrequency, however many of these studies had limitations. Further randomised controlled clinical trials are recommended in order for the practising pain physician to clearly understand the role of pulsed radiofrequency in the treatment of various chronic pain syndromes. [ABSTRACT FROM AUTHOR]