Search Results (22)

Baseline plasma ACTH concentrations are frequently utilized as part of the diagnostic evaluation of equids when PPID is suspected. Baseline ACTH can be impacted by many factors including time of year, i.e., ACTH has generally been found to be elevated during late summer through early autumn in the northern hemisphere. An understanding of ACTH concentrations in healthy equids over the course of a year is useful for the proper interpretation of concentrations in PPID-suspect animals. Previous studies assessing ACTH concentrations in healthy donkeys (Equus asinus) and hybrids (E. asinus × E. caballus) are limited, often utilizing very small numbers, equids from specific and limited geographical regions, limited timeframes or unspecified donkey types (miniature, standard, or mammoth). We aimed to characterize the seasonal variation in baseline ACTH concentrations in healthy miniature donkeys, standard donkeys and hybrids in the United States (US) and to compare those concentrations across these groups. Following outlier removal, 19 standard donkeys (from California (CA), Massachusetts (MA), New York (NY)), 14 miniature donkeys (CA and NY), and 28 hybrids (Texas (TX) and NY) were utilized for analysis. Samples were collected from each equid twice per month from June to November 2019 and once per month from December 2019 through May 2020. The mean ACTH concentration of all equids was higher from mid-August through the end of October compared to the rest of the year (being the highest in the second half of September with the mean (standard deviation) values of 109.6 (52.6), 134.6 (67.4), and 100.8 (189.6) in standard donkeys, miniature donkeys, and hybrids, respectively). Additionally, ACTH concentrations in hybrids were 23% (95% Confidence Interval (CI): 4–38%) and 51% (95% CI: 36–63%) lower than in standard and miniature donkeys, respectively, from mid-August through October. During the rest of the year, hybrids similarly showed 31% (95% CI: 16–43%) and 30% (95% CI: 15–42%) lower ACTH concentrations compared with standard and miniature donkeys, respectively. Full article

Fifty-two horses aged >15 years, diagnosed with pituitary pars intermedia dysfunction (PPID), and displaying hypertrichosis were recruited via an online survey of PPID horse owners. From mid-December, group T (n = 29) wore Equilume^® light masks extending photoperiod to 15 h daily, while group C1 (n = 23) remained under natural photoperiod. As 85% (44/52) of recruited study horses received pergolide medication, a second unmedicated PPID research herd (C2; n = 17) was recruited and remained under natural photoperiod. Hair coat samples, shedding and body condition scores were collected monthly by owners for 13 months and analysed by the research team. Data related to management, coat condition and PPID clinical signs were collected using bimonthly questionnaires (BMQ). Time (p < 0.001), group (p = 0.025) and time-by-group interaction (p = 0.005) affected hair length. Group differences were attributable to shorter hair lengths in C2, and no differences in hair length occurred between T and C1 (p > 0.05). Time affected shedding scores (p < 0.001) which was advanced by one month in T (p < 0.05). In group T, BMQ responses showed improved coat condition in April (p = 0.035), decreased fat coverage in April and June (p < 0.05), and increased energy/alertness in February (p = 0.022). Improvements in coat condition (p = 0.043), clinical signs of PPID (p = 0.018), and general quality of life (p = 0.035) were reported in T only in a final study questionnaire. Blue light treatment merits further investigation as a complementary treatment for PPID. Full article

Pituitary pars intermedia dysfunction (PPID) is a common, slowly progressive, neurodegenerative disorder of the older horse. Oxidative damage to the hypothalamic periventricular neurons results in loss of dopaminergic inhibition of the pars intermedia region of the pituitary gland. Consequently, there is increased production of the pro-opiomelanocortin (POMC)-derived hormones normally produced by this region, as well as initial melanocyte hypertrophy and hyperplasia, followed by adenomatous change. Clinical signs that are highly suggestive of the disease are generalised and regional hypertrichosis and delayed/abnormal coat shedding. Numerous clinical signs provide a moderate clinical suspicion, including hyperhidrosis, abnormal fat distribution/regional adiposity, epaxial muscle atrophy/loss of topline, laminitis, weight loss, recurrent infections, behavioural changes/lethargy, polyuria and polydipsia, a pot-bellied appearance, bulging supraorbital fat pads, reduced wound healing, lordosis and infertility. In all animals, a diagnosis of PPID is made based on the signalment, clinical signs and results of further diagnostic tests, with age being a crucial factor to consider. Currently recommended further diagnostic tests are measurement of basal adrenocorticotrophic hormone (ACTH) concentrations (all year) and evaluation of the ACTH response to thyrotrophin-releasing hormone (TRH) using seasonally adjusted references intervals (non-autumn). Animals should also be tested for insulin dysregulation, as laminitis risk in PPID is associated with hyperinsulinaemia. PPID can be managed but not cured; it is a lifelong condition. The individual clinical signs can be managed, e.g., clipping the excessive haircoat and providing unrestricted access to water for individuals with polydipsia. Alternatively, pharmacological management can be employed, and the dopamine-2 receptor agonist pergolide is licensed/approved for the treatment of equine PPID. This should be prescribed in combination with dietary recommendations based on the body condition score and insulin sensitivity status of the individual animal. Full article

Prevalence of endocrine disease in sport horses has been sparsely reported. They often compete well into their teenage years; thus, diagnosis and control of endocrine disease could be important to maintain performance and optimise health and welfare. The aim was to compare the prevalence of pituitary pars intermedia dysfunction (PPID), insulin dysregulation (ID) and metabolic obesity between sport and non-sport type breeds and assess disease progression. Blood samples submitted for plasma adrenocorticotropic hormone (ACTH), serum insulin or adiponectin were included in this study. Horses were grouped according to their breed into sport horses, which are typically used for athletic purposes, and non-sport horses, which are less-athletic breeds typically used for leisure. Cases included 1365 non-sport horse initial samples with 1850 non-sport horse follow-up samples and 1022 sport horse initial samples with 1081 sport horse follow-up samples. PPID and metabolic obesity were found to be as prevalent in the sport horse population, but non-sport horses were more likely to have ID. Upon follow up examination PPID was more prevalent with higher median ACTH in sport horses. This was also true of metabolic obesity in sport horses at follow-up, although median adiponectin was higher, perhaps indicating that the population is less severely affected than non-sport horses. Screening for endocrinopathies should be considered in sport horses presenting with poor performance. Full article

Bisphenol A (BPA) is a common synthetic chemical compound classified as an endocrine disruptor. It affects multiple physiological systems in the body, including the female reproductive system, particularly granulosa cells (GCs) in the ovaries, where steroidogenesis occurs. This study investigated the impact of various BPA concentrations (environmentally relevant concentrations of 0.001 µM and 0.1 µM and toxicological concentration of 100 µM) and exposure times (24 and 72 h) on cell viability and counts and in vitro production of estradiol and progesterone in human GCs collected from waste follicular fluid of IVF patients. Gene expression analysis of 182 genes associated with steroidogenesis and apoptosis was performed in GCs using PCR arrays, followed by protein expression analysis by Western blot. Our results demonstrate that after longer BPA exposure (72 h), a higher concentration of BPA (100 µM) negatively affects the cellular viability and counts and significantly alters steroid hormone biosynthesis in vitro, leading to reduced concentrations of estradiol and progesterone in the culture medium. We found that all BPA concentrations altered the expression of different steroidogenesis- and apoptosis-related genes in GCs. At 0.001 μM, BPA exposure decreased the expression of TRIM25, UGT2B15, CASP3, and RPS6KA3 genes and increased the expression of NR6A1 and PPID genes. At 0.1 μM, BPA increased the expression of AR, HSD3B1, BID, IKBKG, and PPID genes while reducing the expression of TRIM25 and CASP3 genes. At the highest concentration of 100 μM, BPA upregulated the expression of AR, GPER30, BID, IKBKG, and PPID genes and downregulated the expression of FOXO1 and UGT2B15 genes. These results highlight BPA’s concentration-specific effects on steroidogenesis and apoptosis and show its potential to compromise GC function, with possible negative implications for female fertility and ovarian health, even at environmentally relevant concentrations. Full article

Sri Lankan Tamil refugees have endured over four decades of protracted displacement in southern India. This paper synthesizes findings from four studies conducted between 2005 and 2018 among refugees residing in the Gummidipoondi and Trichy refugee camps in the state of Tamil Nadu, India. Framed by a Community Based Participatory Research, in collaboration with the Organization for Eelam Refugee Rehabilitation (OfERR) and Community Advisory Board, these studies aimed to investigate the challenges related to migration stressors, mental health, family dynamics, and resource utilization of the Sri Lankan refugees living in India. The association of Psychological Distress and Migration Stress (PDMS) study examined migration stressors influencing psychological distress among refugees. The intergenerational Conflict and Community Readiness (ICCR study) assessed community readiness for repatriation and intergenerational conflict employing semi-structured qualitative interviews. The Family Dynamics (FD) mixed-method study investigated longitudinal associations between migration stressors, resource utilization, family dynamics, and health outcomes among Sri Lankan Tamil refugees. The Parenting Processes and Intervention Development (PPID) Study incorporated perspectives of community health workers through qualitative exploratory research. Integrating these findings, the research developed (1) Conceptual Model of Refugee Family Dynamics and (2) Framework for Refugee Health Intervention. These models provide a culturally sensitive framework for future interventions to improve family well-being among refugee populations. Full article

The goal of this meta-analysis was to (i) identify any potential differences in the apparent and true digestibility, renal excretion, and retention between ponies and horses and (ii) examine the impact of work on these parameters. Additionally, the study aimed to (iii) evaluate the effects of water deficiency. This meta-analysis used data from 33 studies and plotted them in diagrams similar to the Lucas test against mineral intake. Three studies involved ponies that were later diagnosed with pituitary pars intermedia dysfunction (PPID). These were compared with other data to identify quantitative differences, as they may have clinical significance. If any significant difference was observed, the data were not used for the evaluation of the aforementioned goals. Data were compared within certain intake ranges using t-tests and ANOVA, followed by Holm–Sidak post hoc tests. Working equines showed significantly higher apparent and true Na digestibility and lower endogenous faecal Na losses compared to non-working ponies and horses, suggesting a rather important role of the gastrointestinal tract in the regulation of Na metabolism in equines. The true K digestibility was also significantly higher in working animals than in non-working ones, but the differences were quantitatively smaller than for Na. Retention plus sweat losses for Na, K and Cl were higher in working animals compared to equines in maintenance. Horses showed higher Na and K retention plus sweat losses compared to ponies. These effects are likely attributable to greater sweat losses in working equines, particularly horses. The apparent and true Cl digestibility was significantly higher in ponies than in horses. A clinical relevance of this observation is rather unlikely, as the digestibility remained very high in both. Water deprivation influenced serum Cl levels and increased renal K excretion, which subsequently led to reduced K retention. Compared to other animal species, no effects on blood K levels or Na metabolism were observed. The ponies diagnosed with PPID exhibited a significantly lower apparent K digestibility compared to healthy animals, which could be an important factor to consider when feeding soaked hay, due to potential electrolyte losses during soaking. Full article

Background/Objectives: Posterior neck, trapezius, and interscapular pain, exacerbated by poor posture such as forward head and rounded shoulders, is common. In this study, we aimed to assess the clinical outcomes of isotonic saline injections at nerve entrapment points (NEPs) within the sternocleidomastoid (SCM) and scalenus medius (SM) muscles for alleviating spinal accessory nerve (SAN) and dorsal scapular nerve (DSN) compression in patients suffering from posterior neck, trapezius, and interscapular pain. Methods: In this retrospective study, 68 patients were included, with 34 receiving isotonic saline injections and 34 undergoing Extracorporeal Shock Wave Therapy (ESWT) as a control. The clinical outcomes were evaluated using the Visual Analog Scale (VAS) and Percent Pain Intensity Difference (PPID) before and after therapy. The effectiveness of isotonic saline injections targeting NEPs in the SCM and SM muscles in relieving pain associated with SAN and DSN entrapment was assessed. Results: Both treatments significantly reduced VAS and PPID scores, with injection therapy showing a larger treatment effect size (Cohen’s d: 3.521 for VAS and 3.521 for PPID) compared to ESWT (Cohen’s d: 1.379 for VAS and 1.710 for PPID). The mean clinically important difference observed for VAS was 4.2, exceeding the expected value of 2.6, indicating a substantial improvement in pain and patient quality of life. Conclusions: Isotonic saline injections at the NEPs of SAN and DSN within the SCM and SM muscles might potentially reduce posterior neck, trapezius, and interscapular pain associated with possible nerve entrapment, without causing complications. Further research is needed to validate these findings in larger, controlled trials. Full article

The molecular mechanism of how the infecting DNA of bacteriophage T4 passes from the capsid through the bacterial cell wall and enters the cytoplasm is essentially unknown. After adsorption, the short tail fibers of the infecting phage extend from the baseplate and trigger the contraction of the tail sheath, leading to a puncturing of the outer membrane by the tail tip needle composed of the proteins gp5.4, gp5 and gp27. To explore the events that occur in the periplasm and at the inner membrane, we constructed T4 phages that have a modified gp27 in their tail tip with a His-tag. Shortly after infection with these phages, cells were chemically cross-linked and solubilized. The cross-linked products were affinity-purified on a nickel column and the co-purified proteins were identified by mass spectrometry, and we found that predominantly the inner membrane proteins DamX, SdhA and PpiD were cross-linked. The same partner proteins were identified when purified gp27 was added to Escherichia coli spheroplasts, suggesting a direct protein–protein interaction. Full article

Donkey medicine is gaining attention due to their increased use as companion animals, in shows, asinotherapy, etc. The increasing demand and unique aspects call for specialized care, requiring new information (physiology, infectious disorders, pharmacology, etc.). Since obesity is common in this species, hyperlipemia, metabolic syndrome and insulin dysregulation (ID) are common disorders in donkeys, in some cases with high mortality, either directly (multiorgan dysfunction) or indirectly due to poor quality of life (chronic laminitis). Donkeys have long-life expectancy and are often afflicted with pituitary pars intermedia dysfunction (PPID), a neurodegenerative and endocrine disease. Hyperlipemia is diagnosed based on high plasma triglyceride concentration in association with clinical findings and laboratory abnormalities from affected tissues (liver, kidney and pancreas). The measurement of resting serum insulin and plasma ACTH concentrations is the first step in ID and PPID diagnosis. In donkeys with clinical signs of ID (obesity or recurrent laminitis) or PPID (hypertrichosis, regional adiposity, laminitis and weight loss), where these hormones are in the normal or non-diagnostic range (donkey-specific cut-off values and reference ranges need to be established), dynamic tests are recommended (oral sugar test or thyrotropin-releasing hormone, respectively). Equine treatment protocols apply to donkeys, although pharmacological studies for most drugs, except pergolide, are lacking. Full article

The Hippo signaling pathway is a highly conserved pathway that plays important roles in the regulation of cell proliferation and apoptosis. Transcription factors TEAD1-4 and transcriptional coregulators YAP/TAZ are the downstream effectors of the Hippo pathway and can modulate Hippo biology. Dysregulation of this pathway is implicated in tumorigenesis and acquired resistance to therapies. The emerging importance of YAP/TAZ-TEAD interaction in cancer development makes it a potential therapeutic target. In the past decade, disrupting YAP/TAZ-TEAD interaction as an effective approach for cancer treatment has achieved great progress. This approach followed a trajectory wherein peptidomimetic YAP–TEAD protein-protein interaction disruptors (PPIDs) were first designed, followed by the discovery of allosteric small molecule PPIDs, and currently, the development of direct small molecule PPIDs. YAP and TEAD form three interaction interfaces. Interfaces 2 and 3 are amenable for direct PPID design. One direct YAP–TEAD PPID (IAG933) that targets interface 3 has entered a clinical trial in 2021. However, in general, strategically designing effective small molecules PPIDs targeting TEAD interfaces 2 and 3 has been challenging compared with allosteric inhibitor development. This review focuses on the development of direct surface disruptors and discusses the challenges and opportunities for developing potent YAP/TAZ-TEAD inhibitors for the treatment of cancer. Full article

This work presents a silicon-based capacitively transduced width extensional mode (WEM) MEMS rectangular plate resonator with quality factor (Q) of over 10,000 at a frequency of greater than 1 GHz. The Q value, determined by various loss mechanisms, was analyzed and quantified via numerical calculation and simulation. The energy loss of high order WEMs is dominated by anchor loss and phonon-phonon interaction dissipation (PPID). High-order resonators possess high effective stiffness, resulting in large motional impedance. To suppress anchor loss and reduce motional impedance, a novel combined tether was designed and comprehensively optimized. The resonators were batch fabricated based on a reliable and simple silicon-on-insulator (SOI)-based fabrication process. The combined tether experimentally contributes to low anchor loss and motional impedance. Especially in the 4th WEM, the resonator with a resonance frequency of 1.1 GHz and a Q of 10,920 was demonstrated, corresponding to the promising f × Q product of 1.2 × 10¹³. By using combined tether, the motional impedance decreases by 33% and 20% in 3rd and 4th modes, respectively. The WEM resonator proposed in this work has potential application for high-frequency wireless communication systems. Full article

Pituitary pars intermedia dysfunction is one of the most common diseases of aged horses and ponies. In Parkinson’s disease, which is, similar to PPID, a disease that involves oxidative damage to dopaminergic pathways but with different clinical signs, alterations to the serum amino acid profile have been reported. To examine changes in the plasma amino acid profile in horses with PPID, EDTA plasma of horses that were presented for various reasons that required laboratory examinations of blood anticoagulated with EDTA was collected. With this plasma, the basal ACTH concentration as well as the amino acid profile was determined. Horses were considered PPID patients if the ACTH concentration was ≥ 100 pg/mL, i.e., they would be considered affected at any time. Horses were defined as non-PPID (nPPID) patients if the ACTH concentration was below 30 pg/mL. Horses receiving pergolide with ACTH ≤ 30 pg/mL were allocated to the group PPIDrr (PPID, ACTH in reference range) and horses receiving pergolide with ACTH ≥ 100 pg/mL to the group PPIDarr (PPID, ACTH above reference range). In total, 93 horses were examined, including 88 horses at the clinic and 5 horses at a private practice. Of these, 53 horses fulfilled the inclusion criteria (ACTH ≤ 30 pg/mL or ACTH ≥ 100 pg/mL). A total of 25 horses were diagnosed as nPPID, 20 as PPID, 5 as PPIDrr, and 3 as PPIDarr. Arginine was significantly higher in PPIDrr than in PPID and nPPID, asparagine was significantly higher in PPID, PPIDrr, and PPIDarr than in nPPID, citrulline was significantly higher in PPIDrr than in nPPID and PPID, cysteine was significantly lower in PPIDrr than in PPID, nPPID, and PPIDarr, and glutamine was significantly higher in PPID and PPIDarr than in nPPID. Especially, asparagine, citrulline, and glutamine may be potential diagnostic markers and may offer interesting approaches for research regarding amino supplementation in PPID. Full article

Poor recognition of subtle clinical abnormalities and equivocal ACTH concentrations make early diagnosis of PPID difficult. Progressive clinical findings and corresponding ACTH concentrations in horses transitioning to PPID over time have not been documented. Seven horses with ACTH concentrations equivocal for PPID (utilizing locally derived, seasonally adjusted diagnostic-cut off values (DCOV)) and no clinical signs of PPID were selected. Sequential measurement of basal and thyrotropin-releasing hormone (TRH)-stimulated ACTH concentrations and recording of clinical findings occurred from October 2017 to November 2021 in a prospective case series. In two horses, marked hypertrichosis developed. Although 1/11 basal ACTH concentrations were below DCOV in 2018, subsequently all basal ACTH concentrations in these two horses without treatment were greater than DCOV. One horse was treated with pergolide which normalized basal ACTH concentrations. Four horses developed intermittent, mild hypertrichosis, and one horse never developed hypertrichosis. Basal ACTH concentrations in these five horses were greater than DCOV in 63/133 (47.4%) of testing points. TRH-stimulated ACTH concentrations in these five horses were greater than DCOV in 77/133 (57.9%) of testing points, sometimes markedly increased and greater than the assay upper limit of detection (LoD) of 1250pg/mL. TRH-stimulated ACTH concentrations were most frequently positive in late summer and early autumn, with 24/37 (64.9%) of TRH-stimulated ACTH concentrations greater than the DCOV in February and March. Horses transitioning to PPID can have subtle clinical signs and equivocal ACTH concentrations. However, TRH-stimulated ACTH concentrations can be markedly greater than DCOV, especially in late summer and early autumn (February and March) allowing for identification of subclinical and transitional cases. Full article

Substantial morbidity results from pituitary pars intermedia dysfunction (PPID) which is often underestimated by owners and veterinarians. Clinical signs, pathophysiology, diagnostic tests, and treatment protocols of this condition are reviewed. The importance of improved recognition of early clinical signs and diagnosis are highlighted, as initiation of treatment will result in improved quality of life. Future research should be targeted at improving the accuracy of the diagnosis of PPID, as basal adrenocorticotropic hormone (ACTH) concentration can lack sensitivity and thyrotropin releasing hormone (TRH) used to assess ACTH response to TRH stimulation is not commercially available as a sterile registered product in many countries. The relationship between PPID and insulin dysregulation and its association with laminitis, as well as additional management practices and long-term responses to treatment with pergolide also require further investigation. Full article