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Intrauterine devices block luteolysis in cyclic mares, but the underlying mechanism is unknown. To clarify the mechanisms, the protein profile of the endometrial secretome was analyzed using two-dimensional difference gel electrophoresis (2D-DIGE). Twenty-seven mares were classified according to whether they were inseminated (AI) or had an intrauterine device (IUD), a water-filled plastic sphere, inserted into the uterus on Day 3 after ovulation. Uterine lavage fluids were collected on Day 15 from pregnant inseminated mares (AI-P; n = 8), non-pregnant inseminated mares (AI-N; n = 4), and mares with IUD (n = 15). The IUD group was further divided into prolonged (IUD-P; n = 7) and normal luteal phase (IUD-N; n = 8) groups on the basis of ultrasound examinations, serum levels of progesterone and PGFM on Days 14 and 15, and COX-2 results on Day 15. Four mares from each group were selected for the 2D-DIGE analyses. Ten proteins had significantly different abundance among the groups, nine of the proteins were identified. Malate dehydrogenase 1, increased sodium tolerance 1, aldehyde dehydrogenase 1A1, prostaglandin reductase 1, albumin and hemoglobin were highest in pregnant mares; T-complex protein 1 was highest in non-pregnant mares; and annexin A1 and 6-phosphogluconolactonase were highest in IUD mares. The results suggest that the mechanism behind the intrauterine devices is likely related to inflammation. [Display omitted] • Uterine devices modify the protein composition of endometrial secretome in mares. • MDH1, IST1, ALDH1A1 and PTGR1 are up-regulated on Day 15 of pregnancy in mares. • Annexin A1 is up-regulated in mares inserted with an intrauterine device. • Intrauterine devices block luteolysis probably by inducing endometrial inflammation. [ABSTRACT FROM AUTHOR]

The aim was to study the association between snoring and development of occlusion, maxillary dental arch, and soft tissue profile in children with newly completed deciduous dentition. Thirty-two (18 female, 14 male) parent-reported snorers (snoring ≥3 nights/week) and 19 (14 female, 6 male) nonsnorers were recruited. Breathing preference (nose or mouth) was assessed at the mean age of 27 months by otorhinolaryngologist. At the mean age of 33 months, an orthodontic examination was performed, including sagittal relationship of second deciduous molars, overjet, overbite, and occurrence of crowding and lateral crossbite. Bite index was obtained to measure maxillary dental arch dimensions (intercanine and intermolar width, arch length). A profile photograph was obtained to measure facial convexity. No significant differences were found between nonsnorers and snorers in any of the studied occlusal characteristics or in measurements of maxillary dental arch dimensions. Snorers were found to have a more convex profile than nonsnorers. Occurrence of mouth breathing was more common among snorers. Parent-reported snoring (≥3 nights/week) does not seem to be associated with an adverse effect on the early development of deciduous dentition, but snoring children seem to have more convex profile than nonsnorers. Snoring is a mild sign of sleep-disordered breathing, and in the present study its short time lapse may not have had adequate functional impact on occlusion. • Association between snoring and occlusion was studied in 33-month-old children. • Studied children formed a homogenous group in terms of occlusal development. • Parent-reported snoring (≥3 nights/week) does not seem to be associated with an adverse effect on the early development of primary dentition. • Snoring children seem to have more convex profile than nonsnorers. [ABSTRACT FROM AUTHOR]

Highlights • Neurotoxic property of MPTP and rotenone was compared. • Neurotoxicity of MPTP was acute and selective to the dopaminergic neurons. • Rotenone caused glial activation and neuronal loss in the hippocampus. Abstract Animal models for Parkinson's disease (PD) are very useful in understanding the pathogenesis of PD and screening for new therapeutic approaches. 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) and rotenone are common neurotoxins used for the development of experimental PD models, and both inhibit complex I of mitochondria; this is thought to be an instrumental mechanism for dopaminergic neurodegeneration in PD. In this study, we treated mice with MPTP (30 mg/kg/day) or rotenone (2.5 mg/kg/day) for 1 week and compared the neurotoxic effects of these toxins. MPTP clearly produced dopaminergic lesions in both the substantia nigra and the striatum as shown by loss of dopaminergic neurons, depletion of striatal dopamine, activation of glial cells in the nigrostriatal pathway and behavioral impairment. In contrast, rotenone treatment did not show any significant neuronal injury in the nigrostriatal pathway, but it caused neurodegeneration and glial activation only in the hippocampus. MPTP showed no such deleterious effects in the hippocampus suggesting the higher susceptibility of the hippocampus to rotenone than to MPTP. Interestingly, rotenone caused upregulation of the neurotrophic factors and their downstream PI3K-Akt pathway along with adenosine monophosphate-activated protein kinase (AMPK) activation. These results suggest that MPTP-induced dopaminergic neurotoxicity is more acute and specific in comparison to rotenone toxicity, and compensatory brain-derived neurotrophic factor (BDNF) induction and AMPK activation in the rotenone-treated brain might suppress the neuronal injury. [ABSTRACT FROM AUTHOR]

Abstract European Union (EU) strategy on blue growth has directed interest in the debate on utilizing marine resources. At the same time, EU Member States are taking the first steps in doing maritime spatial planning (MSP). For strategic planning such as MSP and prioritizing future investments, governments and policy makers are in need of economic indicators for the blue economy. Although in all parts of the world the sea has traditionally been the driver for the growing economy, research on the economic value of the blue economy has been limited. However, when MSP is becoming the norm, evaluating the existing blue economy becomes more important. In this paper, the economic significance of blue economies is estimated for the Gulf of Bothnia (GoB) region of Finland. By conducting a case study on the current situation of the blue economy in a specific region it is possible to bring the discussion of blue growth to a practical and local level. The GoB was seen as a potential area to study blue growth or the blue economy because of the already existing active maritime sector and the relatively pristine environment. The core problems of defining and quantifying multi-sector resources such as the blue economy will be discussed, and comprehensive data to scrutinize the blue economy sector in the GoB will be provided. This study stresses the importance of local economic data to be able to understand the potential of blue economies. [ABSTRACT FROM AUTHOR]

In spite of the massive research for the identification of neurorestorative or neuroprotective intervention for curing Parkinson's disease (PD), there is still lack of clinically proven neuroprotective agents. Metformin, a common anti-hyperglycemic drug has been known to possess neuroprotective properties. However, specific mechanisms by which metformin protects neurons from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity remain to be elucidated. In this study, we assessed the neuroprotective effects of metformin in the subchronic MPTP model of PD, and explored its feasible mechanisms for neuroprotection. Animals received saline or MPTP injection (30 mg/kg/day) for the first 7 days, and then saline or metformin (200 mg/kg/day) for the next 7 days. Immunohistochemical stainings showed that metformin rescued the tyrosine hydroxylase-positive neurons and attenuated astroglial activation in the nigrostriatal pathway. In parallel, metformin restored dopamine depletion and behavioral impairments exerted by MPTP. Western blot analysis revealed that metformin ameliorated MPTP-induced α-synuclein phosphorylation which was accompanied by increased methylation of protein phosphatase 2A (PP2A), a phosphatase related to α-synuclein dephosphorylation. Moreover, the metformin regimen significantly increased the level of brain derived neurotrophic factor in the substantia nigra, and activated signaling pathways related to cell survival. Proof of concept study revealed that inhibition of PP2A or tropomyosin receptor kinase B reversed neuroprotective property of metformin in SH-SY5Y cells. Our results indicate that metformin provides neuroprotection against MPTP neurotoxicity, which might be mediated by inhibition of α-synuclein phosphorylation and induction of neurotrophic factors. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a neurodegenerative disorder characterized by prominent loss of the nigral dopaminergic neurons and motor symptoms, such as resting tremor and bradykinesia. Evidence suggests that neuroinflammation may play a critical role in PD pathogenesis. Interleukin (IL)-32 is a newly-identified proinflammatory cytokine, which regulates innate and adaptive immune responses by activating p38 MAPK and NF-κB signaling pathways. The cytokine has been implicated in cancers and autoimmune, inflammatory, and infectious diseases. In this study, we attempted to identify the effects of IL-32β on dopaminergic neurotoxicity induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), using IL-32β transgenic mice. Male wild type and IL-32β transgenic mice received intraperitoneal injections of vehicle or MPTP (15 mg/kg × 4). Immunohistochemistry showed that overexpression of IL-32β significantly increased MPTP-mediated loss of dopaminergic neurons in the substantia nigra and deletion of tyrosine hydroxylase-positive fibers in the striatum. Dopamine depletion in the striatum and deficit in locomotor activity were enhanced in IL-32β transgenic mice. These results were accompanied by higher neuroinflammatory responses in the brains of transgenic mice. Finally, we found that IL-32β exaggerated MPTP-mediated activation of p38 MAPK and JNK pathways, which have been shown to be involved in MPTP neurotoxicity. These results suggest that IL-32β exacerbates MPTP neurotoxicity through enhanced neuroinflammatory responses. [ABSTRACT FROM AUTHOR]

Methamphetamine (MA) is a extremely addictive psychostimulant drug with a significant abuse potential. Long-term MA exposure can induce neurotoxic effects through oxidative stress, mitochondrial functional impairment, endoplasmic reticulum stress, the activation of astrocytes and microglial cells, axonal transport barriers, autophagy, and apoptosis. However, the molecular and cellular mechanisms underlying MA-induced neurotoxicity remain unclear. MA abuse increases the chances of developing neurotoxic conditions such as Parkinson's disease (PD), Alzheimer's disease (AD) and other neurotoxic diseases. MA increases the risk of PD by increasing the expression of alpha-synuclein (ASYN). Furthermore, MA abuse is linked to high chances of developing AD and subsequent neurodegeneration due to biological variations in the brain region or genetic and epigenetic variations. To date, there is no Food and Drug Administration (FDA)-approved therapy for MA-induced neurotoxicity, although many studies are being conducted to develop effective therapeutic strategies. Most current studies are now focused on developing therapies to diminish the neurotoxic effects of MA, based on the underlying mechanism of neurotoxicity. This review article highlights current research on several therapeutic techniques targeting multiple pathways to reduce the neurotoxic effects of MA in the brain, as well as the putative mechanism of MA-induced neurotoxicity. [Display omitted] • Methamphetamine abuse is linked to increased risk of neurotoxic diseases. • There is no FDA approved therapy for methamphetamine-induced neurotoxicity till date. • Targeting multiple pathways can reduce neurotoxic effects of methamphetamine. • Focuses are now on the development of therapy for reducing MA-induced neurotoxicity. [ABSTRACT FROM AUTHOR]

The European Union (EU) promotes a sustainable blue economy in the coastal and marine regions. In Finland, the regional development objectives are defined at the national and regional levels. Maritime spatial planning (MSP) is a tool to reconcile the sea's different uses. This study considers developing collaborative practices in regional planning to help meet regional development objectives. The MSP participants representing the coastal fishery (fishing and fish farming) in the Satakunta region, Finland, exemplify a local stakeholder group. Coastal fishery is a demanding and highly regulated livelihood, with the potential to grow as local food is trending. A mixed-method approach was used to examine MSP participants' and fishery experts' perceptions about regional cooperation and the MSP process. The semi-structured interviews focused on three main themes: regional cooperation and synergies, conflicts and threats, and interest in regional collaboration or establishing secondary businesses. Questionnaires 2019 and 2021 examined stakeholders' engagement (intrinsic motivation) and social trust towards the planners in the MSP process. The need to tackle the challenges of coastal fishery dictates coastal fishery participants' perceptions regarding the fishery business's development in a regional context. Despite the collaborative approach, the first Finnish MSP round did not make a significant difference in the coastal fishery's status as a stakeholder group. MSP processes and developing the sustainable blue economy are part of the regional development framework, requiring a level playing field and mutual trust among stakeholders. The regional development of marine and coastal areas would benefit from a joint forum for stakeholder interaction built upon MSP. Collaboration could strengthen the integrative and comprehensive management of sea uses and resources. • Coastal fishery participants' perceptions of MSP and regional cooperation studied. • The fishery participants reflect the challenges and complexities of coastal fishery. • The MSP process fulfilled the coastal fishery participants' expectations variedly. • MSP could support regional development by providing a collaboration forum. • MSP collaboration may strengthen the integrative management of marine resources. [ABSTRACT FROM AUTHOR]

A new cooling method to store and transport semen in Styrofoam boxes at a temperature of 15°C to 20°C was developed. The new system was compared with the standard procedure in a field trial using pregnancy rate (PR) of inseminated mares as the benchmark. The standard transport method (F) involved the use of an overnight frozen cooling device, which resulted in a temperature range of 1°C to 8°C inside the syringe containing the semen. The test method (R) involved a cooling device kept in the refrigerator overnight to achieve temperatures inside the semen syringe of 15°C to 20°C. A total of 409 ejaculates from 15 stallions housed at two stud farms were cooled and then transported to inseminate 195 mares one to three times per estrus during one to four cycles in the same breeding season. Altogether, 255 inseminations were carried out using semen cooled by the F method and 154 cooled by the R method. The PRs were not significantly different between the two cooling methods (per cycle PR in the F group = 45.0% vs. 44.6% in the R group). In experiment 2, 13 mares were inseminated in 25 cycles using F semen (n = 12) and R semen (n = 13) stored for 12 hours. The mares were administered hCG 12 hours after artificial insemination (AI) and scanned every 12 hours to determine the time of ovulation. The semen temperature had no effect on PR. All mares that ovulated within 12 hours of AI (4 of 4) conceived. However, only two of 21 mares (9.5%) that ovulated >36 hours after AI conceived. [ABSTRACT FROM AUTHOR]

• PwMS on certain DMTs have attenuated response to initial COVID-19 vaccination. • Booster vaccinations result in seroconversion in one third. • Almost half of pwMS on fingolimod seroconverted after a booster vaccine. • COVID-19 T-cell responses are often present in people on ocrelizumab. People with MS treated with anti-CD20 therapies and fingolimod often have attenuated responses to initial COVID-19 vaccination. However, uncertainties remain about the benefit of a 3rd (booster) COVID-19 vaccine in this group. PwMS without a detectable IgG response following COVID-19 vaccines 1&2 were invited to participate. Participants provided a dried blood spot +/- venous blood sample 2–12 weeks following COVID-19 vaccine 3. Humoral and T cell responses to SARS-CoV-2 spike protein and nucleocapsid antigen were measured. Of 81 participants, 79 provided a dried blood spot sample, of whom 38 also provided a whole blood sample; 2 provided only whole blood. Anti-SARS-CoV-2-spike IgG seroconversion post-COVID-19 vaccine 3 occurred in 26/79 (33%) participants; 26/40 (65%) had positive T-cell responses. Overall, 31/40 (78%) demonstrated either humoral or cellular immune response post-COVID-19 vaccine 3. There was no association between laboratory evidence of prior COVID-19 and seroconversion following vaccine 3. Approximately one third of pwMS who were seronegative after initial COVID-19 vaccination seroconverted after booster (third) vaccination, supporting the use of boosters in this group. Almost 8 out of 10 had a measurable immune response following 3rd COVID-19 vaccine. [ABSTRACT FROM AUTHOR]

• Clinical trial populations do not fully reflect routine practice. The power of routinely collected data to inform clinical practice is increasingly recognised. • The OPTIMISE:MS pharmacovigilance study is a prospective, pragmatic observational study, conducted across 13 UK MS centres. • 342 clinical events were reported during follow up of 2112 participants • We demonstrate how routinely collected healthcare data can be used to evaluate the safety of DMT for people with MS, and that it is possible to distinguish drug-related and disease-activity related risks. Clinical trial populations do not fully reflect routine practice. The power of routinely collected data to inform clinical practice is increasingly recognised. The OPTIMISE:MS pharmacovigilance study is a prospective, pragmatic observational study, conducted across 13 UK MS centres. Data were collected at the time of routine clinical visits. The first participant was recruited on 24th May 2019; data were extracted on 11th November 2021. 2112 participants were included (median age 44.0 years; 1570 (72%) female; 1981 (94%) relapsing-remitting MS). 639 (30%) were untreated at study entry, 205 (10%) taking interferon beta/copaxone, 1004 (47%) second/third generation DMT first line and 264 (13%) had escalated from a platform DMT. 342 clinical events were reported, of which 108 infections. There was an increased risk of adverse events in people taking second/third generation DMT (RR 3.45, 95%CI 1.57-7.60, p<0.01 vs no DMT). Unadjusted Poisson regression demonstrated increased incident adverse events in people taking natalizumab (IRR 5.28, 95%CI 1.41-19.74, p<0.05), ocrelizumab (IRR 3.24, 95%CI 1.22-8.62, p<0.05), and GA biosimilar (Brabio) (IRR 4.89, 95%CI 1.31-18.21, p<0.05) vs no DMT. Routinely collected healthcare data can be used to evaluate DMT safety in people with MS. These data highlight the potential of pragmatic studies to guide understanding of risks and benefits associated with DMT. [ABSTRACT FROM AUTHOR]

The study aimed to determine the effects of red clover (Trifolium pratense) silage with high phyto-oestrogen content on ewe performance during their first breeding season. Red clover silage containing formononetin, biochanin A, genistein, and daidzein was fed to 10 nulliparous ewes of the prolific Finnish Landrace breed before, during and after the breeding season, for a total of 5 months. A control group of 10 ewes was fed with grass silage. The mean numbers of foetuses per pregnancy were 2.1±0.7 and 2.2±0.8 for the red clover and control groups, respectively. The total mass of the uterus with its contents was significantly greater in ewes of the red clover group compared with those of the control group. This difference was mainly explained by the greater volume of foetal fluids. Serum progesterone concentration in the red clover group was significantly lower over the entire period analysed than in the control group. In conclusion, the fecundity of the ewes was not reduced by red clover feed with high phyto-oestrogen concentrations. The volume of foetal fluids increased that could increase the risk for vaginal prolapse before the term. [ABSTRACT FROM PUBLISHER]

The article looks at a double-blind experiment on the effectiveness and safety of monotherapy with the extended-release formulation of the antipsychotic drug quetiapine fumarate (quetiapine XR) in older major depression disorder patients. Subjects were evaluated with the Montgomery Asberg Depression Rating Scale (MADRS) before and after quetiapine XR or placebo treatment. The results indicated that quetiapine XR quickly improved depression symptoms and was tolerated with few adverse effects.

Abstract: Racing and fertility are connected with each other in many ways. Stress and increased body temperature induced by racing may have negative effects on fertility, but on the other hand, high quality nutrition and management of racing horses may have positive effects. Fertility may also be genetically associated with racing performance. The analysed data consisted of Finnish mating records of Standardbreds (n =33,679) and Finnhorses (n =32,731), from 1991 to 2005, and the harness racing records of both mares and stallions. Fertility was measured by foaling outcome, and racing performance was measured by best time and number of races. We used racing results from the mating year and from the entire career, to study both short-term and long-term effects of racing on fertility. The analyses were conducted with a linear mixed model, where racing was fitted as a fixed factor. In a separate bivariate analysis we measured the genetic correlation of racing and fertility, applying a threshold model for the fertility trait. For mares, racing after the first mating or more than 10 times during the mating year diminished the foaling outcome. However, racing only before the first mating or 1–5 times during the mating year had positive effects on mare fertility. Stallion fertility did not suffer from racing during the mating year. The mares with the best career racing records had the highest foaling rates, but this was probably due to preferential treatment. The genetic correlation between best racing record and fertility was favourable but weak in the Finnhorse (−0.24±0.08), and negligible in the Standardbred (−0.15±0.11). [Copyright &y& Elsevier]

The Finnish mating records of Standardbred trotters (SB; n=33 679) and Finnhorses (FH; n=32 731) were analysed to study the effect of the level of inbreeding on foaling rates and to estimate the heritability of foaling rate. A linear mixed model was assumed, with the outcome of the foaling (foal or no foal) as the trait of the study. A restricted maximum likelihood-based method was used to calculate the estimates of the variance components. Predictions of breeding values and estimates of fixed effects were also calculated. The average level of inbreeding was 9.9% in the SB and 3.6% in the FH. The average foaling rates were better in the SB (72.6%) than in the FH (66.3%), but within each breed intense inbreeding had a statistically significant negative effect on foaling rate ( P<0.05). Also, the mating type, the age and breeding type of the mare, and the age of the stallion had statistically significant effects on foaling rate ( P<0.001). The heritability of foaling rate was between 3.4% and 3.7% in SBs and between 5.5% and 9.8% in FHs, when the outcome of the foaling was considered to be a trait of the expected foal. With the same model, the estimates of maternal genetic effect were 4.7% for SBs and 3.2% for FHs, and the estimates of the permanent environmental effects of the stallion were between 1.3% and 1.7%. Avoiding matings with very high inbreeding coefficients would improve foaling rates. It would also be possible to devise a breeding program for better equine fertility, but because the heritability is low, improvement of environmental factors deserves special attention. [ABSTRACT FROM AUTHOR]

Background: Microbial colonization of the airways and intestine during birth might have an effect on the risk of asthma and allergic diseases later in life. Objective: We sought to evaluate the association between intrauterine microbial growth at the time of delivery and the development of asthma and allergic sensitization among offspring. Methods: Intrauterine bacterial culture results were recorded at the time of cesarean delivery of 460 children who were born at Kuopio University Hospital during 1990–1992. When the children reached the age of 15 to 17 years, self-administered questionnaires were sent to the mothers, and 382 of the children were also examined by using skin prick tests. Results: Intrauterine growth of potential pathogenic anaerobic bacteria and Streptococcus species at birth was associated with an increased risk of doctor-diagnosed asthma ever (odds ratio [OR], 4.51 [95% CI, 1.56–13.0]; OR, 2.53 [95% CI, 1.19–5.38]) and doctor-diagnosed current asthma (OR, 7.34 [95% CI, 2.44–22.03]; OR, 3.37 [95% CI, 1.46–7.76]) at the age of 15 to 17 years compared with the risk seen in subjects with negative microbial cultures. These findings remained significant also after applying the Bonferroni correction. No significant association after the Bonferroni correction was detected between intrauterine microbial growth and allergic sensitization among offspring. Conclusion: The results of this study indicated that specific intrauterine microbial growth at the time of birth might increase the risk of asthma among offspring through inflammatory mechanisms. These results indicate new potential targets for future studies on the effects of maternal vaginal microflora and intrauterine infection in the development of asthma among children [Copyright &y& Elsevier]

Abstract: Prostaglandin F2α (PGF2α) and GnRH treatments, when administered 24h apart during early diestrus, cause short estrous cycles in some dairy cows and heifers [J. Taponen, M. Kulcsar, T. Katila, L. Katai, G. Huszenicza, H. Rodriguez-Martinez, Short estrous cycles and estrous signs after premature ovulations induced with cloprostenol and gonadotropin-releasing hormone in cyclic dairy cows, Theriogenology 2002; 58, 1291–1302]. We investigated the effect of a time interval between PGF2α and GnRH administration on the appearance of short cycles. Estrus was induced in heifers with dexcloprostenol. A second luteolysis was induced similarly on day 7 after ovulation, and either 0 (T0) or 24h (T24) later an injection of GnRH (0.1mg of gonadorelin) was administered. We monitored ovarian activity with progesterone analyses from blood plasma samples and with ultrasonography. Fourteen cases (12 in T0 and 2 in T24) were excluded due to either incomplete luteolysis (2 cases) or unresponsiveness to GnRH (10 in T0 and 2 in T24). Short estrous cycles (7 to 8 d) were detected in 11/11 and 8/17 heifers in groups T0 and T24, respectively, with a significant difference in the incidence of short cycles (P <0.01). In Experiment 2, estrus was induced in cows on day 8 (D8, n =18), 9 (D9, n =5), or 10 (D10, n =3) with cloprostenol and gonadorelin administered simultaneously. Daily milk samples were collected for progesterone analysis until subsequent estrus was detected and ovarian ultrasound examinations were performed. Eight cases had to be excluded due to unresponsiveness to GnRH, leaving 18 cases eligible for the study. Short estrous cycles (7–12d) were detected in 14/18 cows. In conclusion, shortening the time interval between PGF2α and GnRH treatments increased the incidence of short estrous cycles and appeared to increase the proportion of females unresponsive to GnRH treatment. [Copyright &y& Elsevier]