Short-term Treatment Research Articles

Simulated warming reduced greenhouse gas emissions by lowering soil moisture in a Pinus tabulaeformis forest of the temperate zone

The forest soil carbon represents the largest carbon pool in the terrestrial ecosystem. To clarify the effect of climate warming on the soil carbon pool of a Pinus tabulaeformis plantation in the northern temperate zone, an Open-Top Chamber was used to study the effects of warming on soil temperature and moisture, soil enzyme activity, soil active organic carbon, and greenhouse gas emissions in different soil layers. The results showed that (1) warming increased the temperature and decreased the moisture content of the atmosphere and soil. Atmospheric temperature increased by 0.9°C on average, and atmospheric moisture decreased by 0.05%. (2) Warming had no significant effect on soil active organic carbon or enzyme activity, but had a significant effect on the active organic carbon content and enzyme activity in individual soil layers in individual months. (3) Warming reduced soil CO2 emissions from the control treatment, from 996.35 to 781.57 g·m−2. The soil of the P. tabulaeformis forest in Daqing Mountain is a sink of atmospheric CH4. Therefore, after the short-term warming treatment, the soil moisture was reduced; greenhouse gas emissions were significantly reduced, and the warming formed a negative feedback with soil greenhouse gas flux.

Short-Term Treatment of Melatonin Improves the Expression of Cell Adhesion Molecules in the Testis of the Mouse Cryptorchidism Model.

Melatonin plays a major role in regulating the sleep-wake cycle and enhancing testosterone production. We investigated the short-term effects of melatonin treatment for 14 consecutive days in the cryptorchidism model. We categorized experimental mice into Sham (S), Orchiopexy (O), Melatonin (Mel), and Orchiopexy + Melatonin (OMel) groups. Surgery involved inducing cryptorchidism in the left testis for seven days, followed by orchiopexy. The Mel group's testes did not descend, but they received melatonin injections after seven days of cryptorchidism. The OMel group underwent both orchiopexy and melatonin treatment. Both O and Mel groups exhibited decreased sperm and round-headed sperm in the epididymis. Significant increases were observed in the numbers of giant cells and negative Nectin-3 cells at p-value<0.05. The pattern of Cadm1 expression changed, and Nectin-2 and Nectin-3 co-expression was lacking in abnormal spermatids. Sertoli cell cytoplasm in both O and Mel groups exhibited autophagosomes and multivesicular bodies, which correlated with increased cyclooxygenase-2 expression. However, Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cell numbers increased significantly in all treatment groups compared to the S group. Our study found that the combination of orchiopexy and melatonin positively influenced the expression of cell adhesion molecules (Cadm1, Nectin-2, and Nectin-3) involved in spermatogenesis, while reducing giant cells, autophagosomes, and apoptosis.

Phloretin inhibits the growth of Arabidopsis shoots by inducing chloroplast damage and programmed cell death

Phloretin is a key secondary metabolite produced by apple trees. Known for its strong antioxidant properties, this dihydrochalcone has been extensively studied in animals but less so in plants. Recently, we identified phloretin as a phytotoxic allelochemical that inhibits growth in the model plant Arabidopsis by disrupting auxin metabolism and distribution in the roots. In this study, we found that phloretin significantly hinders the growth of Arabidopsis seedlings' aerial parts after a short-term treatment (10 days) and causes their decay after long-term exposure (28 days). These effects result from ultrastructural damage in the mesophyll cells of the leaves, including chloroplast displacement and swelling, lesions, and alterations in thylakoid and cell wall organization. Interestingly, phloretin-treated plants showed a decrease in malondialdehyde levels and antioxidant enzyme activities, while hydrogen peroxide and proline levels remained unchanged. This suggests that phloretin-induced chlorosis and seedling decay are not due to oxidative stress but rather to severe chloroplast structural damage, leading to inefficient photosynthesis, starch degradation, starvation, and activation of micro- and macroautophagic processes for self-preservation. Ultimately, these processes result in programmed cell death. These new insights into the phytotoxic effects of phloretin on Arabidopsis shoots could pave the way for future research into phloretin as a potential multitarget bioherbicide and enhance our understanding of autoallelopathy in apple trees.

Treatment "non-responders": the experience of short-term psychoanalytic psychotherapy among depressed adolescents, their parents and therapists.

Short-term psychoanalytic psychotherapy (STPP) is an evidence-based treatment for adolescents with depression, but like all treatment approaches, not all patients benefit from it. Previous investigations of the process of STPP have mostly focused on successful cases, and only a few studies have included the perspectives of young people, their parents, and therapists in the understanding of treatment non-response. Semi-structured interviews were carried out with young people who were considered "non-responders" to STPP, as well as with their parents and therapists. These cases were analyzed using a descriptive-interpretative approach. The data analysis revealed three themes: (1) Therapy as a safe space; (2) Can short-term psychotherapy ever be enough?; and (3) Therapists making links and connections that did not make sense to the young people. This study's findings indicate that "poor outcome" psychotherapy does not necessarily equate to a "poor experience" of psychotherapy, with different stakeholders appreciating the treatment setting as a "safe space." However, they also suggest that some felt that a relatively short-term treatment could not lead to substantial change and that young people in STPP might have a more negative view of their outcomes compared to their parents and therapists. Finally, the findings indicate that some interventions made by clinicians in STPP feel wrong or do not make sense to young people, potentially affecting the therapy process.

Overexpression of SIMK in menadione-treated alfalfa enhances antioxidant machinery and leads to oxidative stress resistance

Mitogen-activated protein kinases (MAPKs) transduce stress and developmental signals related to the production of reactive oxygen species (ROS). Alfalfa (Medicago sativa L.) is a valuable forage and human nutrition crop, however, the involvement of MAPKs in plant resistance to oxidative stress is poorly understood in this species. Therefore, we elucidated the role of STRESS-INDUCED MAPK (SIMK) in alfalfa response to menadione, a compound inducing ROS generation, exploiting transgenic alfalfa lines with contrasting SIMK abundance. SIMK was activated by short-term menadione treatment and relocated from the nucleus to the cytoplasm. Proteomic analysis revealed that menadione caused changes in the abundance of proteins involved in metabolism, oxidative stress, biotic stress response, detoxification of carbonyl species, glutathione homeostasis, chloroplast protein turnover, photosynthesis, and membrane trafficking. Genetic manipulations of SIMK altered the abundance of proteins involved in mitochondrial and chloroplast protein import and processing, as well as GLUTATHIONE S-TRANSFERASES (GSTs). Increased GST abundance and activity in roots, and modifications in mitochondrial and chloroplast protein turnover might be responsible for the elevated oxidative stress resistance of alfalfa line overexpressing SIMK. This was supported by the reduced ROS levels in this line. These results reveal a complex nature of plant stress response and suggest a new role of SIMK in the alfalfa resistance to menadione-induced oxidative stress.

Incremental predictive value of genetic risk and functional brain connectivity in determining antipsychotic response in schizophrenia

We aimed to assess the incremental value of schizophrenia polygenic risk score (PgRS) and resting-state functional brain connectivity (rsFC) when added to clinical data in predicting the six-week response to oral risperidone (Risperdal) in schizophrenia. Fifty-seven, 54, and 43 individuals in a group of never-before-treated first-episode schizophrenia had good quality whole-genome sequencing (10x), rsFC, and both genomic and rsFC data, respectively, at baseline. Symptom severity ratings were obtained at baseline and six-weeks of oral risperidone (Risperdal) treatment. The primary outcome was the percentage change in the Positive and Negative Syndrome Scale Total scores after risperidone (Risperdal) treatment. Clinical, PgRS, and rsFC determinants of treatment response were first evaluated independently. Subsequently, three blocks of hierarchical multiple regression analyses with leave-one-out cross-validation (n = 43), were implemented to study clinical, clinical + PgRS and clinical + PgRS + rsFC determinants of treatment response. While the combined clinical variables did not show a statistically significant prediction of treatment response, adding PgRS (9 % R2 change) and rsFC (26 % R2 change) in hierarchical steps, significantly improved the overall proportion of variance explained in treatment response. This proof-of-concept investigation underscores the incremental benefits offered by genetic and neuroimaging metrics over clinical measures in determining prospectively-ascertained short-term treatment response in first-episode schizophrenia.

The mechanism of improving the flavor quality of bighead carp (Aristichthys nobilis) by the short-term micro-flowing water treatment

The short-term micro-flowing water treatment (STMF) has been proven to improve the taste quality of bighead carp. However, few studies have focused on its impact on the aroma quality of bighead carp muscle and the underlying mechanism. This study investigated the effect of STMF on the aroma quality of bighead carp muscle using UPLC–MS/MS-based metabolomics and gas chromatography–mass spectrometry (SAFE–GC–MS) combined with semi-quantitative methods. A total of 56 volatile compounds were found in the bighead carp muscle by SAFE–GC–MS. During the STMF, the contents of hexanal and (E,E)-2,4-heptadienal decreased significantly, which decreased by 24.09 % and 20.80 % after 6 days of the STMF, respectively. However, the contents of (E)-2-octenal and (E)-2-nonenal showed a trend of rising first and then falling, with maximum values at the 6th day of the STMF. The Pearson’s correlation coefficient showed a good correlation between some sensory attributes and aroma compounds. The fatty acid, amino acid, and glutathione metabolism of bighead carp muscle were significantly changed after 2 days of the STMF, with the contents of carnitine and acylcarnitine increased and then the contents of glutamic acid and glutamine increased. The improvement of flavor quality could be related to metabolism of carnitine, glutamic acid, glutamine, and glutathione. This study may help to understand the mechanism of STMF in enhancing the aroma quality of aquatic products.

Treatment outcome of modified endoscopic assisted sinus surgery for treating maxillary sinus diseases with three dimensional volumetric analysis

This retrospective study aimed to analyze volumetric changes of the maxillary sinus after modified endoscopic-assisted sinus surgery (MESS) and to assess short-term treatment outcomes. The volumes of the total maxillary sinus, aeration, and sinus pathology were calculated using computed tomography data obtained prior to surgery and six months after surgery. Postoperative radiological improvement was assessed using the Lund–Mackay score. Bone regeneration around the bony window was evaluated during plate removal. A total of 32 patients were evaluated. Compared with before surgery, air and sinus pathology volumes improved significantly (air, increase by 6.0 cm3, p < 0.001; sinus pathology, decrease by 6.4 cm3, p < 0.001). However, there was no statistically significant change in the total maxillary sinus volume after surgery. The preoperative Lund–Mackay score was 2.9, decreasing to 0.4 six months after surgery (p < 0.001). The only predictors of postoperative aeration rate and Lund–Mackay score were preoperative sinus pathology volume (p = 0.049) and Lund–Mackay score (p = 0.015), respectively. The continuity between the bony window and surrounding sinus wall was restored in all patients. The results of this study suggest that MESS can be a successful, effective, and minimally invasive surgical treatment option for treating maxillary sinus diseases.

Protracted Febrile Myalgia Syndrome: A Rare and Difficult Manifestation of Familial Mediterranean Fever.

Protracted febrile myalgia syndrome (PFMS) is characterized by severe myalgia, fever, abdominal pain, and arthralgia/arthritis episodes lasting for several weeks in patients with familial Mediterranean fever. Treatment options include nonsteroidal anti-inflammatory drugs, corticosteroids, and anti-interleukin-1 therapy. This study aimed to share our experiences of PFMS so as to shed light on this rare and elusive condition. This cross-sectional analysis included 17 patients diagnosed with PFMS at our pediatric rheumatology clinic between January 2018 and September 2023. In our clinic, 17 (1%) of 1663 familial Mediterranean fever patients presented with PFMS, and it was the initial manifestation in 10 patients (58.8%) in the cohort. Eight of the 17 patients had an M694V homozygous mutation in the MEFV gene. A magnetic resonance imaging showed myositis and fasciitis in just 1 patient, and myositis alone was evident in 5 others. Symptoms improved in 2 patients with nonsteroidal anti-inflammatory drugs, whereas prednisolone improved symptoms in 12 patients and anakinra was required in 3 patients. Patients who received anakinra had another severe attack and required long-term anakinra or canakinumab. Syndrome for PFMS is difficult to recognize as it can sometimes be the first manifestation of familial Mediterranean fever. The syndrome is not accompanied by fever in some patients, even though the word febrile is part of its name. Most patients respond dramatically to nonsteroidal anti-inflammatory drugs or corticosteroids. In some patients with PFMS, long-term anakinra or canakinumab treatment may be more useful in preventing severe attacks of PFMS than short-term (5 to 7 days) anakinra treatment.

Characterization of intestine-specific TRPM6 knockout C57BL/6J mice: effects of short-term omeprazole treatment.

The transient receptor potential melastatin type 6 (TRPM6) is a divalent cation channel pivotal for gatekeeping Mg2+ balance. Disturbance in Mg2+ balance has been associated with the chronic use of proton pump inhibitors (PPIs) such as omeprazole. In this study, we investigated if TRPM6 plays a role in mediating the effects of short-term (4days) omeprazole treatment on intestinal Mg2+ malabsorption using intestine-specific TRPM6 knockout (Vill1-TRPM6-/-) mice. To do this, forty-eight adult male C57BL/6J mice (50% TRPM6fl/fl and 50% Vill1-TRPM6-/-) were characterized, and the distal colon of these mice was subjected to RNA sequencing. Moreover, these mice were exposed to 20mg/kg bodyweight omeprazole or placebo for 4days. Vill1-TRPM6-/- mice had a significantly lower 25Mg2+ absorption compared to control TRPM6fl/fl mice, accompanied by lower Mg2+ serum levels, and urinary Mg2+ excretion. Furthermore, renal Slc41a3, Trpm6, and Trpm7 gene expressions were higher in these animals, indicating a compensatory mechanism via the kidney. RNA sequencing of the distal colon revealed a downregulation of the Mn2+ transporter Slc30a10. However, no changes in Mn2+ serum, urine, and feces levels were observed. Moreover, 4days omeprazole treatment did not affect Mg2+ homeostasis as no changes in serum 25Mg2+ and total Mg2+ were seen. In conclusion, we demonstrate here for the first time that Vill1-TRPM6-/- mice have a lower Mg2+ absorption in the intestines. Moreover, short-term omeprazole treatment does not alter Mg2+ absorption in both Vill1-TRPM6-/- and TRPM6fl/fl mice. This suggests that TRPM6-mediated Mg2+ absorption in the intestines is not affected by short-term PPI administration.

Effects of acupuncture on shoulder impingement syndrome: A systematic review and meta-analysis.

Shoulder impingement syndrome (SIS) is a common condition that causes chronic shoulder pain. The effectiveness of acupuncture in treating chronic shoulder pain has been documented in previous studies; however, existing systematic reviews and meta-analyses have often excluded Chinese databases and combined different types of acupuncture interventions, such as electroacupuncture, warm acupuncture, pharmacopuncture, and acupotomy. Thus, this study specifically examines the exclusive impact of manual acupuncture on SIS. Several databases, including PubMed, Cochrane Central, Embase, 1 Chinese database (China National Knowledge Infrastructure), and 5 Korean databases (ScienceON, Oriental Medicine Advanced Searching Integrated System, KoreaMed, Korean Studies Information Service System, and KMBASE), were systematically searched for relevant studies. The quality of the included studies was evaluated using the Cochrane Assessment Tool for Risk of Bias Version 2. Data collected from the selected studies were synthesized for meta-analysis. The primary outcome was a pain scale score, and the secondary outcomes were shoulder function and disability. This study included 5 randomized controlled trials. The primary outcome assessment revealed significantly reduced pain (standardized mean difference [SMD] = -0.50, 95% confidence interval [CI] = -0.74 to -0.27) and improvements in shoulder function and disability (SMD = -0.57, 95% CI = -0.96 to -0.19). A subgroup analysis based on treatment duration indicated that short-term acupuncture treatment (≤4 weeks) exhibited a high level of confidence with low heterogeneity (SMD = -0.37, 95% CI = -0.73 to -0.02). Manual acupuncture is effective for relieving pain and improving shoulder function and disability in patients with SIS. However, further research is necessary to validate these findings owing to the limited number of patients and heterogeneity among the studies reviewed.

Aberrant growth and expansion in Penium margaritaceum triggered by disruption of microtubules and the cell wall.

Penium margaritaceum, a unicellular zygnematophyte (Streptophyta), was employed to elucidate changes in cell expansion when cells were challenged with the fungal pectinolytic enzyme, pectate lyase, and/or the microtubule disrupting agent, amiprophos-methyl (APM). Microtubule disruption by APM results in significant swelling at expansion zones. These swollen zones provide an easy marker for the location of expansion zones, particularly in cells with altered cell wall pectin. Short term treatment with pectate lyase shows pectin degradation primarily at the isthmus expansion zone and two satellite bands, corresponding with the location of future expansion in daughter cells. When the homogalacturonan lattice of the cell wall is removed by treatment with pectate lyase during long treatments, cell division is maintained, but daughter cell products are considerably smaller. Treatment of cells with a mixture of both pectate lyase and APM results in a distinct phenotype, consisting of "dumbbell"-shaped cells, as APM-induced swelling occurs at the novel expansion centers exposed by pectate lyase treatment. These cells also possess other curious alterations including an extensive, chloroplast-free cytoplasmic zone at the center of the cell, a septum containing ß-glycan, arabinogalactan and homogalacturonan epitopes, unique stacks of ER, displaced Golgi bodies and an extensive network of vacuoles. These results provide insight into the importance of cell wall integrity in defining the location of cell growth and division in P. margaritaceum. Understanding these processes in a unicellular zygnematophyte may provide insights into steps involved in the evolution of land plants.

Therapeutic Effect of Thymoquinone on Melatonin, Ferritin, and Renal Function in Renal Ischemia/Reperfusion Injury in Rats

Objective: Ischemia/reperfusion (I/R) injury is the period of tissue or organ damage that develops after the tissue's blood flow is restored. The extent of damage varies according to the severity of tissue and cell damage. Thymoquinone (TQ) has a wide therapeutic spectrum. The effect of thymoquinone on melatonin and ferritin in I/R can regulate renal function by combining these two mechanisms to improve damage. Therefore, the effect of thymoquinone on melatonin and ferritin levels in renal I/R as well as its regulatory role in renal functions have been investigated. Methods: Thirty-six male Sprague Dawley rats were included in the study (250-300 g, 8-10 weeks). The rats were randomly assigned to 6 groups with 6 animals in each group. Groups; 1- Control, 2- Sham, 3- Solvent, 4- Renal ischemia/reperfusion injury (I/R), 5- I/R+ Thymoquinone (TQ) (5 mg/kg/day), 6- TQ (5 mg/kg/day). The dorsal region of the rats was surgically opened, and the left renal artery was clamped for 30 minutes and then reperfused for 24 hours. TQ (i.p) was applied to the treatment groups for 15 days. At the end of the experiment, blood samples were taken from all groups, and kidney function tests (Na+, K+, Creatinine, urea, BUN) were performed. Melatonin and ferritin levels were analyzed by the ELISA method from kidney tissue samples. Results: Data showed that short-term TQ treatment was effective on serum K+ (P = 0.010) and melatonin and ferritin levels in kidney tissue. Melatonin and iron activity, which were normal in healthy groups, melatonin decreased and ferritin increased significantly in the I/R group. TQ treatment positively regulated the dysregulation of these two molecules in I/R. Conclusion: TQ may contribute to the healing of the damage by improving the K+ levels, which indicates the insufficiency of kidney functions in I/R damage. Melatonin and ferritin, as interacting molecules in I/R, are regulated by TQ, indicating that they may contribute to the management of I/R damage.

Long-term CXCR3 antagonist AMG487 mitigated acute graft-versus-host disease by inhibiting T cell activation in a murine model

BackgroundLymphocyte migration plays a key role in the development of acute graft-versus-host disease (aGVHD). Blocking lymphocyte migration by targeting chemokine receptors, such as CXCR3, may be a promising strategy for preventing and treating aGVHD. Our previous studies have shown that short-term CXCR3 antagonist treatment combined with cyclosporine A alleviated aGVHD. However, the effect of long-term AMG487 treatment on aGVHD survival has not been thoroughly investigated. MethodsA murine aGVHD model was used to examine the expression of CXCR3 in donor T cells. The effects of short- and long-term AMG487 treatment on aGVHD survival were assessed. The infiltration of donor T cells into the liver and spleen tissues and the activation of donor T cells in splenic tissues were also examined. ResultsCXCR3 was consistently highly expressed in donor T cells in a murine aGVHD model. Long-term AMG487 treatment, but not short-term, improved survival and aGVHD outcomes (p < 0.05). Furthermore, long-term AMG487 administration reduced the number of donor T cells in the liver but increased the number of donor T cells in the spleen (p < 0.05). Long-term AMG487 treatment also inhibited donor T cell activation in the spleen (p < 0.05). ConclusionThis study demonstrates that long-term AMG487 treatment has a potential therapeutic effect on aGVHD and could be used as a novel therapy.

Challenges of Salinity Intrusion and Drought Stress on Olive Tree Cultivation on Mljet Island.

Understanding genotype-specific responses to environmental stressors is vital for developing resilience strategies that ensure sustainable olive cultivation and productivity. In this work, cultivar 'Oblica' and several olive genotypes from the island of Mljet (Croatia) were exposed to short-term (21 days) salinity and drought treatments. In contrast to other olive genotypes, genotype M29 as well as cultivar 'Oblica' managed to maintain growth and chlorophyll a levels under salinity stress to the same level as the control. Drought, however, significantly reduced the growth parameters in all olive trees. Cultivar 'Oblica' accumulated the greatest amount of Na+ ions in the leaves compared to olive genotypes from the island of Mljet, demonstrating superior resistance by translocating Na+ to leaf vacuoles. The observed reduction in K+ content in the roots of olive trees under all treatments suggests a generalized stress response. On the other hand, effective Ca2+ uptake has been identified as a crucial energy-saving strategy that olive trees use to cope with brief periods of salinity and drought. The proline content and activities of superoxide dismutase (SOD) and guaiacol peroxidase (GPOX) varied among the olive trees, highlighting the importance of antioxidative capacities and stress adaptation mechanisms. According to the obtained results, stress-resistant olive genotypes like 'Oblica' and M29 show potential for breeding resilient varieties.

Chromosome doubling increases PECTIN METHYLESTERASE 2 expression, biomass, and osmotic stress tolerance in kiwifruit

Abstract Chromosome doubling-induced polyploidization is a popular tool for crop breeding. Polyploidy crops commonly have multiple advantages, including increased biomass and stress tolerance. However, little is known about the genes responsible for these advantages. We found kiwifruit (Actinidia chinensis cv. Hongyang) PECTIN METHYLESTERASE 2 (AcPME2)is substantially upregulated in artificially created tetraploid plants that show increased biomass and enhanced tolerance to osmotic stress. Overexpression (OE) of AcPME2 led to increased biomass and enhanced stress tolerance in Arabidopsis (Arabidopsis thaliana), tomato (Solanum lycopersicum), and kiwifruit. Upon short-term osmotic stress treatment, AcPME2-OE plants showed higher levels of demethylesterified pectins and more Ca2+ accumulation in the cell wall than Col-0 plants, which led to increased cell wall stiffness. The stress-induced plasmolysis assays indicated that AcPME2 dynamically mediated the cell wall stiffness in response to osmotic stress, which is dependent on Ca2+ accumulation. Transcriptomic analysis discovered that dozens of stress-responsive genes were significantly upregulated in the AcPME2-OE plants under osmotic stress. Besides, AcPME2-mediated cell wall reinforcement prevented cell wall collapse and deformation under osmotic stress. Our results revealed a single gene contributes to two advantages of polyploidization (increased biomass and osmotic stress tolerance) and that AcPME2 dynamically regulates cell wall stiffness in response to osmotic stress.

Revealing the Causes of Dyslexia through a Differential Diagnosis, a Short-Term Effective Treatment and an Appropriate Conceptual Framework.

Various different impairments and their interactions can cause reading problems referred to as "dyslexia". Since reading requires the interaction of many abilities, the impairment of each of these abilities can result in dyslexia. Therefore, the diagnosis must differentiate various kinds of dyslexia. The diagnosis of a certain kind of dyslexia cannot be delimited to the investigation and description of symptoms but must also include the investigation of the causes of each kind of dyslexia. For this purpose, a scientifically unequivocal concept of causation and appropriate methods are needed to distinguish them from co-existing impairments that have no causal influence on reading performance. The results of applying these methods cannot be adequately accounted for by a non-scientific, intuitive understanding of necessary and sufficient conditions and causation. The methods suitable for revealing the causes of dyslexia are described in detail, and the results of applying these methods in experiments, in which 356 children with developmental dyslexia participated, are reviewed. Since the concepts of "necessary" and "sufficient" conditions and "causation" proposed in the philosophy of science are not suitable for describing causes of dyslexia and their interaction, they are replaced by a more detailed, experimentally based conceptual framework that provides an accurate description of the conditions required for correct reading and the causes of dyslexia.

Effects of Short-Term Treatment of Rabbit Extraocular Muscle With Ciliary Neurotrophic Factor.

Little is known about the effect of ciliary neurotrophic factor (CNTF) on extraocular muscles, but microarray studies suggested CNTF might play a role in the development and/or maintenance of strabismus. The effect of short-term treatment of adult rabbit extraocular muscle with injected CNTF was examined for its ability to alter muscle characteristics. Eight adult New Zealand white rabbits received an injection into one superior rectus muscle of 2 µg/100 µL CNTF on 3 consecutive days. One week after the first injection, the rabbits were euthanized, and the treated and contralateral superior rectus muscles were assessed for force generation capacity and contraction characteristics using an in vitro stimulation protocol and compared to naïve control superior rectus muscles. All muscles were analyzed to determine mean cross-sectional areas and expression of slow twitch myosin heavy chain isoform. Short-term treatment of rabbit superior rectus muscles with CNTF resulted in a significant decrease in muscle force generation, but only at the higher stimulation frequencies. Significantly decreased myofiber cross-sectional areas of the treated muscles correlated with the decreased generated force. In addition, there were significant changes to contractile properties of the treated muscles, as well as a decrease in the number of myofibers expressing slow twitch myosin heavy chain. We show that short-term treatment of a single rabbit superior rectus muscle results in decreased myofiber size, decreased force, and altered contractile characteristics. Further studies are needed to determine if it can play a role in improving alignment in animal models of strabismus.

Zibotentan in Microvascular Angina: A Randomized, Placebo-Controlled, Crossover Trial.

Background: Microvascular angina is associated with dysregulation of the endothelin system and impairments in myocardial blood flow, exercise capacity, and health-related quality of life. The G allele of the noncoding single nucleotide polymorphism RS9349379 enhances expression of the endothelin-1 gene (EDN1) in human vascular cells, potentially increasing circulating concentrations of Endothelin-1 (ET-1). Whether zibotentan, an oral ET-A receptor selective antagonist, is efficacious and safe for the treatment of microvascular angina is unknown. Methods: Patients with microvascular angina were enrolled in this double-blind, placebo-controlled, sequential crossover trial of zibotentan (10 mg daily for 12 weeks). The trial population was enriched to ensure a G allele frequency of 50% for the RS9349379 single nucleotide polymorphism. Participants and investigators were blinded to genotype. The primary outcome was treadmill exercise duration (seconds) using the Bruce protocol. The primary analysis estimated the mean within-participant difference in exercise duration after treatment with zibotentan versus placebo. Results: A total of 118 participants (mean ±SD; years of age 63.5 [9.2 ]; 71 [60.2% ] females; 25 [21.2% ] with diabetes) were randomized. Among 103 participants with complete data, the mean exercise duration with zibotentan treatment compared with placebo was not different (between-treatment difference, -4.26 seconds [95 ] CI, -19.60 to 11.06] P=0.5871). Secondary outcomes showed no improvement with zibotentan. Zibotentan reduced blood pressure and increased plasma concentrations of ET-1. Adverse events were more common with zibotentan (60.2%) compared with placebo (14.4%; P<0.001). Conclusions: Among patients with microvascular angina, short-term treatment with a relatively high dose (10 mg daily) of zibotentan was not beneficial. Target-related adverse effects were common.

Long versus short-term opioid therapy for fibromyalgia syndrome and risk of depression, sleep disorders and suicidal ideation: a population-based, propensity-weighted cohort study

ObjectiveFibromyalgia syndrome (FMS) is characterised by widespread pain and is associated with mood disorders such as depression as well as poor sleep quality. These in turn have been linked to...