Hyaluronic Acid Bioconjugates for the Delivery of Bioactive Molecules

Hyaluronic acid (HA) has currently several therapeutic applications: in ophthalmology, osteoarthritis, wound healing, tissue regeneration, postoperative anti-adhesion and anesthetic medicine. In the last ten years, it has also been successfully investigated in the field of drug delivery, in the form of conjugates or hydrogel depot systems. HAylation, the covalent conjugation of HA to bioactive molecules, allows the overcoming of disadvantages associated with some pharmaceuticals, such as insolubility, instability and fast kidney clearance. These issues can be addressed also by covalent attachment of polyethylene glycol (PEGylation), but HA has the relevant advantages of biodegradability, high loading and specific targeting. In this review, the novel HA derivatives and the latest advances in HA-based drug delivery with a particular focus on the chemistry of conjugation will be discussed. Although, so far, there are no HA-drug conjugates on the market, several derivatives are presently under clinical investigation, and the promising results encourage further investigations and the exploitation of this versatile polysaccharide

Asiakaspysyvyyden parantaminen palveluita kehittämällä : Koronapandemian tuomat haasteet kuntosaliliiketoimintaan

Koronapandemia on sysännyt liikunta-alan toimijoita kehittämään uusia tuote- ja palveluvalikoimia sekä uudistamaan jo olemassa olevia toimintapoja sekä –malleja. Poikkeuksellinen tilanne on tuonut haasteita liikunta-alan operatiiviseen toimintaan ja yritysten ensisijaiseksi tavoitteeksi on noussut asiakaspysyvyyden säilyttäminen. Tämän pro gradu -tutkielman tarkoituksena on muodostaa ymmärrys siitä, miten kuntosaliliiketoiminnassa voidaan parantaa asiakaspysyvyyttä palveluita kehittämällä. Tutkielma tarkastelee etenkin poikkeusoloihin soveltuvia liikunta-alan palveluita sekä asiakaspitoa. Tutkielman teoriaosuus käsittelee asiakasymmärryksen johtamista, palveluliiketoiminnan kehittämistä ja asiakaspysyvyyden merkitystä palveluliiketoiminnassa. Teoriaa on täydennetty disruptiivisten innovaatioiden teorialla. Teoriakatsauksista on johdettu tämän pro gradu – tutkielman teoreettinen viitekehys, joka havainnollistaa sitä, mistä näkökulmasta tutkittavaa ilmiötä ollaan lähestytty. Tutkimus edustaa luonteeltaan kvalitatiivista tutkimushaaraa. Koska tutkittavan ilmiön lähestymistapa on ongelmakeskeinen ja käytännönläheinen, tutkimuksen lähestymistavassa sovelletaan toimintatutkimusta. Tutkimuksen aineisto kerättiin teemahaastatteluin ja se analysoitiin sisällönanalyysin keinoin. Tutkimus nosti esille tarpeen tarjota poikkeusoloihin soveltuvia palveluita, kuten virtuaalisia etäryhmäliikuntatunteja, etänä järjestettäviä PT-tapaamisia ja ulkotunteja. Myös digitaaliset asiointimahdollisuudet korostuivat. Pandemia-aikana kuntosaliharjoittelusta piti luoda mahdollisimman turvallista kuntosalin yleisen siisteyden ja hygieniatason kautta. Tutkimus nosti esille myös tarpeen tarkastella asiakaspysyvyyttä syvemmällä tasolla. Liikunta-alan asiakaspysyvyyteen vaikuttivat etenkin asiakasuskollisuus, palvelun laatu, asiakastyytyväisyys, harjoittelukertojen tiheys, sisäinen motivaatio, palvelun hinta ja kuntosalin sijainti sekä monet muut tekijät. Ohjatuissa liikuntapalveluissa korostui etenkin suhteiden tärkeys ja tunteellisen komponentin merkitys. Asiakkaiden nähtiin pysyvän jäseninä myös, mikäli yritys ja brändi resenoivat kohderyhmässä. Tulosten perusteella voidaan todeta, että alan yritysten tulee nähdä markkinointi vielä vahvemmin strategisena liikkeenjohtona. Tällöin yrityksillä on mahdollisuus tunnistaa asiakaslogiikoita, luoda sopivia asiakaslähtöisiä palveluita sekä yhdenmukaistaa kokonaisprosesseja. Kuntosaliliiketoiminta tulee luoda asiakkaan ympärille, jolloin liiketoiminnan pohjana toimii asiakaskeskeinen logiikka (CDL). Tämä korostaa etenkin kokemuksien merkitystä, joiden avulla yrityksillä on mahdollisuus erottautua kilpailijoista. Oleellista on myös ymmärtää monikanavaisten asiakaspolkujen ja -pisteiden merkitys

Environmental factors and non-chemical methods to suppress growth of the invasive plant Gutenbergia cordifolia

A research article was published by Acta Oecologica Volume 119, August 2023Little is known about preferred environmental conditions and non-chemical control of invasive Gutenbergia cordifolia. We assessed the effects of different A. annua crude extract concentrations, synthetic herbicide (glyphosate), fire regime and shade to G. cordifolia germination, shoot and root dry biomass, seedling height and leaf chlorophyll. High concentrations (75%) of A. annua crude extracts significantly reduced germination percentage of G. cordifolia by 25% (F2,4=77.2, p < 0.001), and suppressed shoot and root dry biomass (F2,4 = 80.3, p < 0.001; F2,4=46.104, p < 0.001, respectively) as well as seedling height and leaf chlorophyll (F2,4 = 12.02, p < 0.002; F2,4 = 15.9, p < 0.001), respectively. Medium temperature (60 °C) and long exposure time (5 min) significantly increased G. cordifolia germination percentage (F2,7 = 32.6, p < 0.001) while extreme temperatures (≥150 °C) at both (1 min) short and (5 min) long exposure time completely suppressed germination of G. cordifolia. Under high shade, while germination percentage was a third that of other treatments (F 2, 4 = 20.9, p = 0.008), mean germination took twice as long (F2, 4 = 17.9, p = 0.010) and shoot fresh biomass was reduced by half (F 2, 4 = 16.92, p = 0.004). Shoot and root dry biomass were reduced to more than a third under high shade, seedling height reduced to half but leaf chlorophyll content was not affected (F 2,4 = 6.3, p = 0.030; F 2,4 = 9.1, p = 0.020; F 2,4 = 18.3, p = 0.003; F 2,4 = 3.02, p = 0.120, respectively). We suggest using A. annua as a potential bio-herbicide and highlight considering fire and shade as suppressor tools to control G. cordifolia, but first include in-situ trials to assess their impacts to both native plants and animals

A site-selective hyaluronan-interferonα2a conjugate for the treatment of ovarian cancer

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Polyethylene glycol (PEG)-dendron phospholipids as innovative constructs for the preparation of super stealth liposomes for anticancer therapy.

Pegylation of nanoparticles has been widely implemented in the field of drug delivery to prevent macrophage clearance and increase drug accumulation at a target site. However, the shielding effect of polyethylene glycol (PEG) is usually incomplete and transient, due to loss of nanoparticle integrity upon systemic injection. Here, we have synthesized unique PEG-dendron-phospholipid constructs that form super stealth liposomes (SSLs). A \u3b2-glutamic acid dendron anchor was used to attach a PEG chain to several distearoyl phosphoethanolamine lipids, thereby differing from conventional stealth liposomes where a PEG chain is attached to a single phospholipid. This composition was shown to increase liposomal stability, prolong the circulation half-life, improve the biodistribution profile and enhance the anticancer potency of a drug payload (doxorubicin hydrochloride)

Polyethylene glycol (PEG)-dendron phospholipids as innovative constructs for the preparation of super stealth liposomes for anticancer therapy

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Loss of ap4s1 in zebrafish leads to neurodevelopmental defects resembling spastic paraplegia 52.

Autosomal recessive spastic paraplegia 52 is caused by biallelic mutations in AP4S1 which encodes a subunit of the adaptor protein complex 4 (AP-4). Using next-generation sequencing, we identified three novel unrelated SPG52 patients from a cohort of patients with cerebral palsy. The discovered variants in AP4S1 lead to reduced AP-4 complex formation in patient-derived fibroblasts. To further understand the role of AP4S1 in neuronal development and homeostasis, we engineered the first zebrafish model of AP-4 deficiency using morpholino-mediated knockdown of ap4s1. In this model, we discovered several phenotypes mimicking SPG52, including altered CNS development, locomotor deficits, and abnormal neuronal excitability

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

A ingestão de substâncias cáusticas na infância: A construção e divulgação de vídeo educativo sobre medidas de prevenção / The ingestion of caustic substances in childhood: The construction and dissemination of an educational video on prevention measures

A ingestão de substâncias cáusticas na infância é um problema de saúde pública e acarreta alta morbidade aos pacientes, que geralmente desenvolvem estenose esofágica. Os tratamentos disponíveis para estenose cáustica são pouco satisfatórios e por isso realizamos um trabalho para divulgação de medidas de prevenção. Trata-se de vídeo explicativo sobre os perigos da ingestão de substâncias cáusticas e como evitar tais acidentes com crianças. O vídeo foi produzido a partir do relato de familiares de pacientes vítimas da ingestão acidental de soda cáustica