Search

Abstract Background Somatic symptoms are common and costly for society and correlate with suffering and low functioning. Nevertheless, little is known about the long-term implications of somatic symptoms. The objective of this study was to assess if somatic symptoms in adolescents with depression and in their matched controls predict severe mental illness in adulthood by investigating the use of hospital-based care consequent to different mental disorders. Methods The entire school population of 16–17-year-olds in the city of Uppsala, Sweden, was screened for depression in 1991–1993 (n = 2300). Adolescents with positive screenings (n = 307) and matched non-depressed controls (n = 302) participated in a semi-structured diagnostic interview for mental disorders. In addition, 21 different self-rated somatic symptoms were assessed. The adolescents with depression and the matched non-depressed controls were engaged in follow-up through the National Patient Register 17–19 years after the baseline study (n = 375). The outcome measures covered hospital-based mental health care for different mental disorders according to ICD-10 criteria between the participants’ ages of 18 and 35 years. Results Somatic symptoms were associated with an increased risk of later hospital-based mental health care in general in a dose–response relationship when adjusting for sex, adolescent depression, and adolescent anxiety (1 symptom: OR = 1.63, CI 0.55–4.85; 2–4 symptoms: OR = 2.77, 95% CI 1.04–7.39; ≥ 5 symptoms: OR = 5.75, 95% CI 1.98–16.72). With regards to specific diagnoses, somatic symptoms predicted hospital-based care for mood disorders when adjusting for sex, adolescent depression, and adolescent anxiety (p

Abstract Background Earlier research has investigated the association between parental separation and long-term health outcomes among offspring, but few studies have assessed the potentially moderating role of mental health status in adolescence. The aim of this study was to analyze whether parental separation in childhood predicts depression in adulthood and whether the pattern differs between individuals with and without earlier depression. Methods A community-based sample of individuals with adolescent depression in 1991–93 and matched non-depressed peers were followed up using a structured diagnostic interview after 15 years. The participation rate was 65% (depressed n = 227; non-depressed controls n = 155). Information on parental separation and conditions in childhood and adolescence was collected at baseline. The outcome was depression between the ages 19–31 years; information on depression was collected at the follow-up diagnostic interview. The statistical method used was binary logistic regression. Results Our analyses showed that depressed adolescents with separated parents had an excess risk of recurrence of depression in adulthood, compared with depressed adolescents with non-separated parents. In addition, among adolescents with depression, parental separation was associated with an increased risk of a switch to bipolar disorder in adulthood. Among the matched non-depressed peers, no associations between parental separation and adult depression or bipolar disorder were found. Conclusions Parental separation may have long-lasting health consequences for vulnerable individuals who suffer from mental illness already in adolescence.

Abstract Background Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease. Three new drugs for AD based on monoclonal antibodies against the amyloid-β peptide (Aβ) have recently been approved because they favor the reduction of the burden of senile plaque in the AD patient’s brain. Nonetheless, both drugs have very limited applicability and benefits and show several side effects. These limitations invite us to find alternative strategies for treating patients with AD. Here, we explored whether tissue-nonspecific alkaline phosphatase (TNAP), an ectoenzyme upregulated in the brain of AD patients and whose inhibition has beneficial effects on tau-induced pathology, is also efficient in reducing senile plaque burden. Methods To evaluate whether TNAP may reduce cerebral senile plaque loading and Aβ-related toxicity, we use both pharmacological and genetic approaches. We analyze postmortem samples from human AD patients, APP/PS1 mice (a mouse model that mimics amyloid pathology observed in AD patients) treated or not with TNAP inhibitors, and the newly generated transgenic mouse line, TNAP-deficient APP/PS1 mice. Results For the first time, we describe that genetic or pharmacological blockade of TNAP effectively reduces senile plaque burden by promoting its clearance, which leads to amelioration of cognitive impairment caused by Aβ-induced toxicity. These beneficial effects of TNAP inhibition occur concomitantly with higher microglial recruitment toward the senile plaque and increased microglial phagocytic capacity of Aβ by a mechanism involving metalloprotease-depending osteopontin processing. In addition, we also found that TNAP blockade favors LRP1-mediated transport of Aβ through the BBB. Conclusions Here, we have shown that TNAP inhibition effectively reduces brain senile plaque burden and associated behavioral defects. Furthermore, given that we had previously reported that TNAP blockade also ameliorates Tau-induced neurotoxicity and increases lifespan of P301S tauopathy mouse model, we can state that TNAP blockade may be a novel and efficient therapy for treating patients with AD.

Abstract GPIHBP1 is a membrane protein of endothelial cells that transports lipoprotein lipase (LPL), the key enzyme in plasma triglyceride metabolism, from the interstitial space to its site of action on the capillary lumen. An intrinsically disordered highly negatively charged N-terminal domain of GPIHBP1 contributes to the interaction with LPL. In this work, we investigated whether the plethora of heparin-binding proteins with positively charged regions found in human plasma affect this interaction. We also wanted to know whether the role of the N-terminal domain is purely non-specific and supportive for the interaction between LPL and full-length GPIHBP1, or whether it participates in the specific recognition mechanism. Using surface plasmon resonance, affinity chromatography, and FRET, we were unable to identify any plasma component, besides LPL, that bound the N-terminus with detectable affinity or affected its interaction with LPL. By examining different synthetic peptides, we show that the high affinity of the LPL/N-terminal domain interaction is ensured by at least ten negatively charged residues, among which at least six must sequentially arranged. We conclude that the association of LPL with the N-terminal domain of GPIHBP1 is highly specific and human plasma does not contain components that significantly affect this complex.

When adapting to a new host country, one of the most important issues is social belonging – the question on what basis people feel a sense of belonging. This is a question of group identity. Group identity is based on the group’s shared history and especially on myths of common and special origins. In the narratives of the Estonians of Abkhazia, the main reason for emigration is the difficult economic conditions in the old homeland. These stories are recorded in the written memories and village chronicles of the inhabitants of the Estonian settlements in the Caucasus, which date back to the 19th and 20th centuries, but they can be heard orally even today, because the stories have been heard from parents and grandparents. Both in earlier writings and in today’s oral presentations, the conditions in the old homeland of Estonia are depicted as poor, sometimes quite unbearable. An important figure in these stories is an evil and arrogant German landlord who oppressed the ancestors of the settlers. The first chapter of the article shows the historical background of the confrontation between the Estonian peasants and the German landlords in Estonia and how it was at least partially realized as an emigration movement under the influence of the peasant laws of the 19th century. The topic of the evil landlord was taken by the Estonian settlers to the settlements in Caucasus – these were stories told from personal experiences with the landlords. The formation and transmission of stories from generation to generation as founding narratives was facilitated by the opposition between Estonians and Germans in the Estonian national discourse. The second chapter focuses on the texts that reflect landlord-peasant conflicts in Estonia at the time of emigration – the texts of the leading figures of the national awakening movement in the school- and history books. These texts also influenced the developing identity of the Estonian colonists. The article then discusses the stories about the evil landlord told in various Estonian settlements on the Black Sea coast and finally the meaning of these stories in the formation of social belonging.

The popularity of social networks has reached remarkable heights with users spending extensive time using them. Social networks have become a firm part of society especially in the lives of learners. Changes can be seen throughout the years regarding interest and usage of social networks. Accordingly, this study’s objectives concentrate on the exploration and comparison of freshmen students’ social network usage from the academic years of 2016 and 2022 in the Faculty of Education at Tishk International University. Further, the freshmen respondents were given the same quantitative questionnaire. The data disclosed the social network that was most favored, the device used to access social networks, their perception regarding the effective communicational format, its influence on grades, and difference amid learners considering a temporary social media hiatus from these academic years. Therefore, this study indicated that the freshmen contributors of the academic years of 2016 and 2022 regarded and handled social networks differently.

Abstract Background The contribution of the postoperative process to developing or worsening urinary incontinence (UI) after hip fracture surgery (HFS) remains unclear. We aimed to evaluate UI incidence and worsening among older patients undergoing HFS, and explore associated risk factors. Methods This prospective cohort study included patients ≥ 75 years admitted between October 2019 and October 2021 to the Traumatology Service of three hospitals in the Consorci Sanitari de Alt-Penedès i Garraf (Barcelona, Spain) with hip fracture requiring surgical treatment. UI was assessed using the first two questions of the International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF) at baseline and at days 30 (± 3 days) and 90 (± 3 days) after HFS. Surgery-related data and post-surgical complications were recorded. Results A total of 248 patients with a mean (SD) age of 85.8 (6.78) years were included; 77.8% were female and 154 (62.1%) had UI at baseline. After HFS, 3.24% experienced urinary tract infections (UTIs), 3.64%, acute urinary retention (AUR), 8.57%, constipation, and 53.9%, prolonged catheterization (> 24 h). Fifty-eight patients without baseline UI developed UI at 30 days, resulting in a UI incidence of 61.7% (95% CI 51.1–71.54) between days 0 and 30. Of the 248 patients, 146 (59.1%) experienced worsening of UI. AUR and UTIs were identified as risk factors for UI development and worsening after HFS, respectively. Conclusion The incidence of UI in older patients after HFS is significant. Patient management protocols should consider AUR and UTIs to reduce or eliminate the incidence of UI in older patients undergoing HFS.

In the 17th century two Estonian literary languages were standardised. As literary language was needed primarily for translating ecclesiastical texts and for worship services, it evolved as a church language that was created mainly by German pastors, following the example of the German language. At the end of the 17th century, in connection with the translation of the Bible and the establishment of Estonian schools, there emerged a need to renew the literary language and make it more approachable for the common people. The reforms created a situation where church manuals that differed in dialects, orthography and wording were used simultaneously. The case of Wennekülla Hans in the year 1700 demonstrates how a peasant reacted to that confusion. Wennekülla Hans, who was a self-appointed preacher in the parish of Paistu/Paistel, got caught up in a conflict with the pastor Andreas Hornung, who belonged to the circle of language innovators. The peasant accused the pastor of false teaching because the pastor was using a church manual with a modified language version. The case is one of the earliest examples of the evolution of a literary language into a sociolect that was used not only by clergymen but by peasants as well.

This article presents the results of a multi-proxy study conducted on a triple burial found at a settlement site at Pärnu Road 41, Tallinn, Estonia, dating to 405â360 cal BC (Pre-Roman Iron Age). Through archaeological and chemical analyses, including AMS dating, archaeobotany, osteology, stable isotope analysis, lipid analysis, metallography and XRF analysis, this study proves valuable insights into the provenance, diet, and burial practices of the woman and children buried in the grave at Pärnu Road 41. The stable isotope analysis of strontium, carbon and nitrogen suggests that the individuals were of local origin and did not travel long distances during their lifetime. It is likely that the diet of the woman was mainly based on terrestrial protein, which is also supported by lipid analysis performed of pot sherds. These results correspond with the dietary stable isotope values of individuals from Estonia dated to the second half of the Bronze Age and the Pre-Roman Iron Age. Based on the find context of carbonized grains, the partial burning of the female skeleton and the fire pit built contemporaneously above the grave, it is likely that grains and fire could have played an important role in inhumation burials. However, because of the scarcity of inhumation burials in pit graves, it is unclear whether or not the triple burial at Pärnu Road 41 represents a widespread burial practice alongside the stone graves typical of this period. Moreover, it is possible that the observed rituals are linked to foreign customs, as the buried individuals may have had familial ties to immigrants from different regions of eastern Europe, as indicated by a unique bronze bell-pendant found in the grave. This study also introduces the discovery of the earliest known iron smithing site in Estonia. Spherical magnetic droplets found within the burial soil were proven to be hammer scales, formed as a by-product of iron working. The appearance of hammer scales in the soil of a burial dated to the 4th century BC challenges the previously established timeline of iron working in the region.

This is an in-depth study of a mimicked slotted point, carved from a cervid longbone, found in the lower reaches of the Pärnu River. The 3D digital model, created during this study, provides an interactive and innovative tool for studying the object in detail. The AMS dating places the artefact at the very beginning of human habitation in the present-day territory of Estonia. SEM-EDS, ATR-FT-IR and GC-FID/MS analyses demonstrate that this unique object was probably originally partially covered with a mixture of red ochre and some coniferous resin, possibly as hafting adhesive. As this is a detailed replica of a slotted point, it also demonstrates how people themselves saw slotted points in the Early Mesolithic, also raising the question of the purpose of this replica â was it an ordinary arrowhead or rather a ritual object?

At the end of the 19th century, Estonian settlers encountered malaria in the Volga region and Siberia, but outbreaks with the most serious consequences hit Estonians in the Black Sea coastal region of the Caucasus. The article looks at the first contact of the local Estonians with malaria, how the disease affected migrations and settlement activities, what the Estonians’ descriptions of the disease were, what the causes of the disease were believed to be, how malaria was treated, and what preventive measures were used against the disease. Although malaria had also been present in many parts of Europe in earlier centuries, it had almost disappeared in the second half of the 19th century due to improved hygiene and sanitation. Europeans encountered malaria mainly in colonial countries, and so did Estonians. While in Estonia there were still several outbreaks of malaria in the first half of the 19th century, it was no longer a problem in the second half of the century. Now, Estonians came into contact with malaria mainly abroad – in warmer and wetter regions, where Estonian men had been conscripted into military service (e.g., the Russo-Turkish War, the Crimean War; cf. the Turkish disease) or where they had emigrated and established settlements. The resettling of Estonians to the Caucasus, which took place in the last quarter of the 19th century, cannot be described without mentioning malaria. Malaria hit Estonians primarily in settlements built in coastal areas, where there were sufficiently moist conditions for the development of malaria mosquitoes. Estonian colonists fell very ill in the first years of settlement, and their mortality rates were high. Many Estonians decided to return to their homeland due to malaria. The struggle of the Estonian settlers of the Black Sea coast of the Caucasus with malaria occurred at a time when science had not yet discovered either the plasmodium that causes malaria or the role of mosquitoes in the transmission of the disease. The colonial authorities had introduced quinine as an antimalarial agent, which was distributed to the settlers, including Estonians, and began to drain the land, but the mechanisms of the disease’s origin and spread were unknown. This is also reflected in the disease explanations and treatment methods that were common among Estonian settlers. Folk names and magical healing methods for malaria were brought from Estonia, and were applied in combination with methods from conventional medicine. Neither the first nor the others corresponded to the true nature of the disease. Although malaria has been familiar in Estonia as well, also as a mythological disease, the mythological aspect has not been thoroughly thematized in the material of Caucasian Estonians, which does not mean that it was unknown. Although there are no surviving legends related to malaria as a mythological disease, and malaria is not presented as a disease demon, this may be due to the choice of the medium: our knowledge of Estonians’ struggle with malaria comes from reports sent to Estonian newspapers by the settlers, but the newspapers preferred to publish rational texts – the mythological side of the malaria lore, if it was known, was not present in the articles published in the newspapers. However, some treatment techniques have been preserved that convince that malaria was also explained mythologically. The treatment methods also betray the fact that the line between rational and mythological explanations may have been blurred: both old magical treatment methods and new medications offered by conventional medicine were used. As malaria was one of the main factors hindering settlement activities in the Caucasus, which is reflected by a rather extensive return migration, it acquired an important place in the so-called founding narrative of the settlements over time. Malaria was part of the wild nature that had to be conquered in order to achieve a stable existence and future for ourselves and future generations. The cutting down of dense forests and the struggle with wild animals threatening the settlers’ households was marked by hard work, which in turn testified to the settlers’ work ethic. Malaria was also attributed to intensive work. This confirmed the self-image of Estonians, for whom hard work has an important role. Information about the discovery of the causative plasmodium of malaria at the end of the 19th century, which proved the role of mosquitoes in the spread of malaria, reached the Caucasus with a slight time lag. It especially concerns the late arrival of new knowledge among the colonists – earlier knowledge about the connection of malaria with humidity and poisonous vapours remained among Estonian settlers even in the 20th century. Based on the new knowledge, the authorities improved the previous anti-malaria measures – during the Soviet times, a certain type of fish was cultivated in the water bodies, which destroyed the mosquito larvae. Swamp drainage, anti-humidity measures in building architecture, deforestation for farmlands and eucalyptus planting were in use in the late 19th century and destroyed the breeding grounds for mosquitoes even before the connection between mosquitoes and malaria was discovered. These methods are still in use today, because malaria has not really been eradicated from the Caucasus.

Representatives of the genus Bifidobacterium are widely used as probiotics to modulate the gut microbiome and alleviate various health conditions. The action mechanisms of probiotics rely on their direct effect on the gut microbiota and the local and systemic effect of its metabolites. The main purpose of this animal experiment was to assess the biosafety of the Bifidobacterium longum strain BIOCC1719. Additional aims were to characterise the influence of the strain on the intestinal microbiota and the effect on several health parameters of the host during 15- and 30-day oral administration of the strain to mice. The strain altered the gut microbial community, thereby altering luminal short-chain fatty acid metabolism, resulting in a shift in the proportions of acetic, butyric, and propionic acids in the faeces and serum of the test group mice. Targeted metabolic profiling of serum revealed the possible ability of the strain to positively affect the hosts’ amino acids and bile acids metabolism, as the cholic acid, deoxycholic acid, aspartate, and glutamate concentration were significantly higher in the test group. The tendency to increase anti-inflammatory polyamines (spermidine, putrescine) and neuroprotective 3-indolepropionic acid metabolism and to lower uremic toxins (P-cresol-SO4, indoxyl-SO4) was registered. Thus, B. longum BIOCC1719 may exert health-promoting effects on the host through modulation of the gut microbiome and the host metabolome via inducing the production of health-promoting bioactive compounds. The health effects of the strain need to be confirmed in clinical trials with human volunteers.

The transition from foraging to farming was a key turning point in ancient socio-economies. Yet, the complexities and regional variations of this transformation are still poorly understood. This multi-proxy study provides a new understanding of the introduction and spread of early farming, challenging the notions of hierarchical economies. The most extensive biological and biomolecular dietary overview, combining zooarchaeological, archaeobotanical, dietary stable isotope and pottery lipid residue analyses is presented, to unravel the nature and extent of early farming in the 3rd millennium cal BCE in the northeast Baltic. Farming was introduced by incoming Corded Ware cultural groups (CWC), but some dietary segregation existed within these communities, with some having more access to domesticates, others incorporating more wild resources into their diet. The CWC groups coexisted in parallel with local hunter–fisher–gatherers (HFG) without any indication of the adoption of domesticates. There was no transition from foraging to farming in the 3rd millennium cal BCE in the NE Baltic. Instead, we see a complex system of parallel worlds with local HFGs continuing forager lifeways, and incoming farmers practising mixed economies, with the continuation of these subsistence strategies for at least a millennium after the first encounter with domesticated animals.

In the minds of Estonians Abkhazia is associated mainly with Estonians living there. When the Georgian-Abkhazian war broke out in August 1992, the Estonian state evacuated about 170 Estonians and their families from Abkhazia in the autumn of the same year. The reception of the war itself in the Estonian media was low and related to the situation of Estonians there, but the motives and direct causes of the war and the development of war events were also examined. One Baltic News Service journalist observed the evacuation of Estonians and wrote about the events of the war on the spot, but most of the authors operated in Estonia and used various sources. In today’s context, it may seem surprising to what extent materials from Russian information channels were used, but at that time it was understandable: Russia covered events in its border countries more actively than Western agencies. Materials translated directly from Russian newspapers were also published in the Estonian press. The choice of sources also influenced the framing in which the events of that time were mediated. The coverage of the war in the Estonian media has undergone significant developments over the decades. The articles published during the war presented the events in a neutral way, rather sympathizing with the Abkhazians than the aggressor. While in the first half of the war the fighters of the Confederation of Mountain People of the Caucasus were presented as allies of the Abkhazians, the articles published at the end of the war sometimes included Russians, although the contribution of the Russians was not explained. However, even at the end of the war, the coverage remained largely neutral, conveying the views of both Georgians and Abkhazians. From the middle of 1994, the reception of the war began to change, which was related to Georgia’s international self-assertion. Reports from international organizations increasingly highlighted the issue of Georgian war refugees and Georgia’s claim to territorial integrity. This was also reflected in the Estonian media, where Abkhazians were increasingly called separatists without the right to independence. However, until the end of the 1990s, some articles were published that also provided Abkhaz views on events. Estonia had taken a clear direction towards integration with the West, but there was no clear understanding of Georgia’s orientation, which also influenced the attitudes of Estonian media towards Georgia-Abkhazia relations. Georgia’s leader, Eduard Shevardnadze, maneuvered between the West and Russia, pushing Abkhazia into an economic blockade and concluding agreements with Russia, while seeking integration with NATO and the European Union. The situation changed dramatically after the Rose Revolution in Georgia, when Mikhail Saakashvili, who had come to power, began to move unequivocally on the path of Western integration. At the same time, Georgia’s relations with Russia deteriorated. Georgia, a small brave country in conflict with Russia, suddenly became Estonians’ ally and friend. The common enemy unites, and when Saakashvili’s rhetoric gained a firm foothold in Georgia’s territorial integrity, Abkhazia was clearly positioned in the Estonian mainstream media as a separatist Russian puppet. Retrospectively, the reception of the Georgian-Abkhazian war changed – the pluralistic approach of the 1990s was replaced by the Georgian version. In this connection, the portrayal of the role of the Russians in the war also changed: peace mediators in the early 1990s or postcolonial implementers of the divide et impera principle now became allies of the Abkhaz. After the Law of Occupied Territories was adopted in Georgia on 23 October 2008, the concept “occupied Georgian territory” as an epithet of Abkhazia appeared in the Estonian media. As Russia continues to be in the position of a negative external “stranger” for the Estonian media, Russia’s relations with Georgia continue to influence our media attitudes towards Abkhazia and interpretations of the Georgian-Abkhazian war.

Methods of palaeogeographical modelling of possible freshwater bodies based on open access datasets provided by the Estonian Land Board are discussed, along with the landscape use of the recently surveyed palaeolagoons at the mouths of the rivers Vihterpalu, Teenuse and Velise (western Estonia) after Litorina Sea transgression maximum (ca 5300 BC). The site clusters by the Vihterpalu palaeolagoon can be dated to the Pre-Pottery Mesolithic or Narva stage (until 5200 BC and 5200â3900 BC, respectively). Human activity by the Velise lagoon probably started at the same time and intensified during the Comb Ware stage (3900â1750 BC). Two mineral surface depressions, sufficient to accommodate remnant lakes and presently covered by peat layers of mires deserve further attention. They are located in the Seljaküla, Variku and Keedika villages behind the coastal formations observable by the road connecting the Keilaâ Haapsalu main road with Nõva village. Similar depressions behind the coastal formations in the TeenuseâVelise area are not sufficient for freshwater bodies. The spatial pattern of small- scale aceramic settlement sites by the tributaries of the present-day River Kasari up to 10 km from the palaeocoastline suggests a highly persistent seasonal land use during the Comb Ware stage, comparable to the Neolithic settlement phase of Kunda Lammasmägi.

The settlement site of Jägala Jõesuu V is located in northern Estonia in the village of Jõesuu, about 200 m from the eastern bank of the Jägala River and about 2 km from the present-day coast of the Baltic Sea. It was discovered during the fieldwork in 2011, and 275 m2 was researched during rescue excavations in the course of road renovation. The remains of one pit-house (partly excavated), several pits and fireplaces were found. The collection of finds (11 454 artefacts and ecofacts) consists of potsherds of Comb Ware, tools and debris of quartz and flint, burnt bones, hazelnut shells, etc. The excavation technique, as well as the fact that the site was a relatively short-term and undisturbed complex, provided a good basis for spatial analysis that identified at least five concentration zones of finds. The largest concentration (61% of all finds) is related to the filling of the pit-house, >2.8 à 5.3 m in size and with pits inside it. The second large concentration zone (10% of all finds) contains the same find categories as the pit-house, but in different proportions, and it is assumed to be the remains of an above-ground construction measuring about 6 à 3 m. Three other concentrations, which in one case mostly contain flint and quartz artefacts (diameter ca 2.5 m) and quartz in the other two cases (ca 1.5 and 3 m in diameter) can be associated with outdoor activities.

Abstract Background Permanent progression of paternal age and development of reproductive medicine lead to increase in number of children conceived with assisted reproductive techniques (ART). Although it is uncertain if ARTs have direct influence on offspring health, advanced paternal age, associated comorbidities and reduced fertility possess significant risks of genetic disorders to the offspring. With a broad implementation of a non-invasive prenatal testing (NIPT), more cases of genetic disorders, including sex discordance are revealed. Among biological causes of sex discordance are disorders of sexual development, majority of which are associated with the SRY gene. Case presentation We report a case of a non-invasive prenatal testing and ultrasound sex discordance in a 46,XY karyotype female fetus with an SRY pathogenic variant, who was conceived through an intracytoplasmic sperm injection (ICSI) due to severe oligozoospermia of the father. Advanced mean age of ICSI patients is associated with risk of de novo mutations and monogenic disorders in the offspring. Additionally, ICSI patients have higher risk to harbour infertility-predisposing mutations, including mutations in the SRY gene. These familial and de novo genetic factors predispose ICSI-conceived children to congenital malformations and might negatively affect reproductive health of ICSI-patients’ offspring. Conclusions Oligozoospermic patients planning assisted reproduction are warranted to undergo genetic counselling and testing for possible inherited and mosaic mutations, and risk factors for de novo mutations.

Lipoprotein lipase (LPL), a crucial enzyme in the intravascular hydrolysis of triglyceride-rich lipoproteins, is a potential drug target for the treatment of hypertriglyceridemia. The activity and stability of LPL are influenced by a complex ligand network. Previous studies performed in dilute solutions suggest that LPL can appear in various oligomeric states. However, it was not known how the physiological environment, that is blood plasma, affects the action of LPL. In the current study, we demonstrate that albumin, the major protein component in blood plasma, has a significant impact on LPL stability, oligomerization, and ligand interactions. The effects induced by albumin could not solely be reproduced by the macromolecular crowding effect. Stabilization, isothermal titration calorimetry, and surface plasmon resonance studies revealed that albumin binds to LPL with affinity sufficient to form a complex in both the interstitial space and the capillaries. Negative stain transmission electron microscopy and raster image correlation spectroscopy showed that albumin, like heparin, induced reversible oligomerization of LPL. However, the albumin induced oligomers were structurally different from heparin-induced filament-like LPL oligomers. An intriguing observation was that no oligomers of either type were formed in the simultaneous presence of albumin and heparin. Our data also suggested that the oligomer formation protected LPL from the inactivation by its physiological regulator angiopoietin-like protein 4. The concentration of LPL and its environment could influence whether LPL follows irreversible inactivation and aggregation or reversible LPL oligomer formation, which might affect interactions with various ligands and drugs. In conclusion, the interplay between albumin and heparin could provide a mechanism for ensuring the dissociation of heparan sulfate-bound LPL oligomers into active LPL upon secretion into the interstitial space.

Abstract Background Diabetic foot and lower limb complications are an important cause of morbidity and mortality among persons with diabetes mellitus. Very few studies have been carried out in the primary care settings. The main objective was to assess the prognosis of diabetic foot ulcer (DFU) in patients from primary care centers in Catalonia, Spain, during a 12‐month follow‐up period. Methods We included participants with type 2 diabetes and a new DFU between February 2018 and July 2019. We estimated the incidence of mortality, amputations, recurrence and healing of DFU during the follow‐up period. A multivariable analysis was performed to assess the association of these outcomes and risk factors. Results During the follow‐up period, 9.7% of participants died, 12.1% required amputation, 29.2% had a DFU recurrence, and 73.8% healed. Having a caregiver, ischemia or infection were associated with higher mortality risk (hazard ratio [HR]:3.63, 95% confidence interval [CI]:1.05; 12.61, HR: 6.41, 95%CI: 2.25; 18.30, HR: 3.06, 95%CI: 1.05; 8.94, respectively). Diabetic retinopathy was an independent risk factor for amputation events (HR: 3.39, 95%CI: 1.37; 8.39). Increasing age decreased the risk for a DFU recurrence, while having a caregiver increased the risk for this event (HR: 0.97, 95%CI: 0.94; 0.99). The need for a caregiver and infection decreased the probability of DFU healing (HR: 0.57, 95%CI: 0.39; 0.83, HR: 0.64, 95%CI: 0.42; 0.98, respectively). High scores for PEDIS (≥7) or SINBAD (≥3) were associated with an increased risk for DFU recurrence and a lower probability of DFU healing, respectively. Conclusions We observed high morbidity among subjects with a new DFU in our primary healthcare facilities. Peripheral arterial disease, infection, and microvascular complications increased the risk of poor clinical outcomes among subjects with DFU.

Project Based Learning has a long history which received contributions from many famous names. Projects are of great importance in the process of education due to the helpful features it provides for the teachers and students. The type of projects used can vary, but that does not change the fact that it can be used by teachers to have students apply the knowledge they have learned. The purpose of this research was to explore the perspectives of students on Project Based Learning to determine whether this method was viewed positively. This study transpired in the Education Departments of Tishk International University in Erbil, Kurdistan. A survey of seven questions was administered in this research, and the total number of 100 surveys was gathered from students of the Tishk International University Education Faculty. The students were members of the English Language Teaching, Biology, Physics, and Math departments and varied within stages, which ranged from 2nd, 3rd, and 4th. Their participation in the survey did not affect their grades and was strictly voluntary. The statistics analyzed in this study presented that students perceive Project Based Learning as effective, and the majority recommend this method of teaching and learning.