Breathing, swallowing and voice in laryngeal disorsers

The aim of this work was to examine how breathing, swallowing and voicing are affected in different laryngeal disorders. For this purpose, we examined four different patient groups: patients who had undergone total laryngectomy, anterior cervical decompression (ACD), or injection laryngoplasty with autologous fascia (ILAF), and patients with dyspnea during exercise. We studied the problems and benefits related to the automatic speech valve used for the rehabilitation of speech in laryngectomized patients. The device was given to 14 total laryngectomized patients who used the traditional valve especially well. The usefulness of voice and intelligibility of speech were assessed by speech pathologists. The results demonstrated better performance with the traditional valve in both dimensions. Most of the patients considered the automatic valve a helpful additional device but because of heavier breathing and the greater work needed for speech production, it was not suitable as a sole device in speech rehabilitation. Dysphonia and dysphagia are known complications of ACD. These symptoms are caused due to the stretching of tissue needed during the surgery, but the extent and the recovery from them was not well known before our study. We studied two patient groups, an early group with 50 patients who were examined immediately before and after the surgery and a late group with 64 patients who were examined 3 9 months postoperatively. Altogether, 60% reported dysphonia and 69% dysphagia immediately after the operation. Even though dysphagia and dysphonia often appeared after surgery, permanent problems seldom occurred. Six (12 %) cases of transient and two (3 %) permanent vocal cord paresis were detected. In our third study, the long-term results of ILAF in 43 patients with unilateral vocal cord paralysis were examined. The mean follow-up was 5.8 years (range 3 10). Perceptual evaluation demonstrated improved results for voice quality, and videostroboscopy revealed complete or partial glottal closure in 83% of the patients. Fascia showed to be a stable injection material with good vocal results. In our final study we developed a new diagnostic method for exertional laryngeal dyspnea by combining a cardiovascular exercise test with simultaneous fiberoptic observation of the larynx. With this method, it is possible to visualize paradoxal closure of the vocal cords during inspiration, which is a diagnostic criterion for vocal cord dysfunction (VCD). We examined 30 patients referred to our hospital because of suspicion of exercise-induced vocal cord dysfunction (EIVCD). Twenty seven out of thirty patients were able to perform the test. Dyspnea was induced in 15 patients, and of them five had EIVCD and four high suspicion of EIVCD. With our test it is possible to set an accurate diagnosis for exertional laryngeal dyspnea. Moreover, the often seen unnecessary use of asthma drugs among these patients can be avoided.Hengityksen, äänentuoton ja nielemisen häiriintymättömän toiminnan kannalta kurkunpään merkitys on keskeinen. Tässä kurkunpään sairauksia käsittelevässä väitöskirjatyössä tutkittiin näitä toimintoja neljässä eri potilasryhmässä. Kurkunpään poistoleikkauksessa (laryngektomia) ääntä tuottavat rakenteet poistetaan, ja potilaalle tehdään hengitysavanne. Ääni tuotetaan leikkauksen jälkeen henkitorven ja ruokatorven väliin asetetun ääniproteesin avulla. Perinteinen ääniproteesi vaatii toimiakseen hengitysavanteen sulun sormin. Äänen tuoton apuvälineeksi on kehitetty automaattinen puheläppä, joka mahdollistaa puheen ilman sormisulkua. Laitteen käyttökelpoisuudesta puheen kuntoutuksessa ei ole aiemmin ollut riittävästi tietoa. Tutkimuksessamme automaattinen puheläppä annettiin 14 potilaalle, jotka käyttivät perinteistä puheläppää ongelmitta. Automaattinen puheläppä osoittautui hyödylliseksi puheentuoton apuvälineeksi, mutta jopa näiden valikoitujen potilaiden mukaan hengitys ja puhuminen oli raskaampaa automaattisella puheläpällä kuin perinteisellä puheläpällä. Kaularankaleikkaus on yleinen toimenpide välilevypullistuman ja nikamasiirtymän hoidossa. Recurrens- hermon vaurio on tunnettu kaularankakirurgian komplikaatio, joka aiheuttaa käheyttä ja nielemisvaikeutta. Tarkkoja tietoja sen yleisyydestä, vaurion pysyvyydestä tai potilaalle aiheutuvasta haitasta ei ole aiemmin tunnettu. Lähes 70 %:lla potilaista oli ääni- ja nielemisvaikeuksia heti leikkauksen jälkeen, mutta melkein kaikki potilaat toipuivat 3kk seurannan aikana. Ohimeneviä äänihuulihalvauksia todettiin 12 %:lla ja pysyviä halvauksia 3 %:lla potilaista. Tutkimustulosten perusteella potilaille voidaan kertoa odotettavissa olevista ääni- ja nielemisvaikeuksista sekä niistä toipumisesta aiempaa tarkemmin. Äänihuulihalvaus syntyy recurrens- hermon vaurioituessa esimerkiksi kirurgisen komplikaation seurauksena, ja osa potilaista tarvitsee äänikirurgiaa vaikean käheyden korjaamiseksi. Leikkauksessa halvaantunut äänihuuli yleensä medialisoidaan eli tuodaan keskiviivaan, jolloin liikkuva äänihuuli saa siihen taas kontaktin ja soinnikas ääni palautuu. Faskiainjektiossa reiden fascia latasta irrotettava lihaskalvo (faskia) pilkotaan massaksi, joka ruiskutetaan mikroskooppitarkkailussa halvaantuneeseen äänihuulilihakseen sen medialisoimiseksi. Tutkimuksessamme äänihuulten täydellinen tai osittainen sulku voitiin todeta 83 %:lla potilaista, ja 56 % heistä ilmoitti äänen olevan normaali tai lähes normaali kun faskiainjektiosta oli kulunut 3-10 vuotta. Tulokset osoittivat faskiainjektion turvalliseksi, käyttökelpoiseksi ja pysyväksi lievien ja keskivaikeiden äänihuulihalvausten kirurgiseksi hoitomenetelmäksi. Toiminnallisella äänihuulisalpauksella tarkoitetaan kurkunpään toimintahäiriötä, jossa äänihuulet paradoksaalisesti lähentyvät toisiaan sisäänhengityksen aikana. Tämä aiheuttaa sisäänhengitysvaikeutta ja hengityksen vinkunaa. Rasituksessa oireilevat potilaat voidaan tutkia kehittämämme menetelmän, rasituslaryngoskopian, avulla. Siinä ergometrirasitus yhdistetään taipuisan tähystimen avulla nenän kautta tehtävään kurkunpään tarkkailuun. Hengenahdistus ilmaantui testin aikana viidelletoista (56%) potilaalle ja heistä viidellä (33 %) todettiin toiminnallinen äänihuulihalvaus ja neljällä (27 %) vahva epäilys siitä. Testin avulla rasitushengenahdistusoireita voidaan diagnosoida entistä tarkemmin. Toiminnallinen äänihuulisalpaus sekoitetaan helposti rasitusastmaan, joten parantunut diagnostiikka auttaa välttämään turhaa astmalääkitystä

Adherence to prescribing restrictions for HER2-positive metastatic breast cancer in Australia: A national population-based observational study (2001-2016)

Background: Targeted cancer therapy is often complex, involving multiple agents and chemotherapeutic partners. In Australia, prescribing restrictions are put in place to reflect existing evidence of cost-effectiveness of these medicines. As therapeutic options continue to expand, these restrictions may not be perceived to align with best practice and it is not known if their use in the real-world clinic adheres to these restrictions. We examined the treatment of women receiving trastuzumab for HER2-positive metastatic breast cancer (HER2+MBC) to determine the extent to which treatment adhered to national prescribing restrictions. Patients and methods: Our population-based, retrospective cohort study used dispensing records for every Australian woman initiating publicly-subsidised trastuzumab for HER2+MBC between 2001±2013, followed through 2016. We used group-based trajectory models (GBTMs) to cluster patients, first on their patterns of trastuzumab exposure, and then on their patterns of lapatinib and chemotherapy exposure. We described the characteristics of patients within each cluster, and examined their treatments and combinations of treatments to determine restriction adherence. Results: Of 5,052 patients initiating trastuzumab, 1,795 (36%) received at least one non-adherent HER2-targeted treatment. The most common non-adherent treatments were trastuzumab combinations involving vinorelbine (24% of non-adherent treatments); capecitabine (24%); and anthracyclines (10%). Non-adherent lapatinib use was observed in 4% of patients. GBTM identified three trastuzumab exposure clusters, each containing three further subclusters. The largest proportions of non-adherent treatments were in sub-clusters with longer trastuzumab exposure and more non-taxane chemotherapy. Patients in these sub-clusters were younger than those in sub-clusters with less non-adherent treatment. Conclusions: Our study highlights that, even during the relatively simpler treatment era of our study period, a substantial amount of treatment did not adhere to prescribing restrictions. As more trials are conducted exploring pertuzumab and T-DM1 in combination with different chemotherapies and other HER2-targeted therapies, the regulation and funding of HER2-targeted treatment will become more challenging

Interlaboratory comparison 09/2017 - VOC measurement from indoor air samples

Proftest SYKE carried out the interlaboratory comparison for TVOC thermodesorption measurements (ISO 16000-6) from native indoor air samples in Tenax TA thermodesorption tubes (IDA 09/17) in October-November 2017. 2EH (2-ethyl-1-hexanol), naphthalene, styrene, toluene, and TXIB (2,2,4-trimethyl-1,3-pentanediol diisobutyrate) measurements were also tested with synthetic sample. In total 10 participants took part in the intercomparison. In total 68 % of the participants reported satisfactory results, when deviation of 20–30 % from the assigned value was accepted. The calculated values were used as the assigned values for the synthetic sample for the results reported as compound specific responses. For the other measurands and samples the average of the results of the homogeneity measurements and the test results of the expert laboratory were used as the assigned value. The evaluation was based on the z scores. Warm thanks to all the participants of this interlaboratory comparison

Interlaboratory Proficiency Test 10/2019 VOC - measurement from indoor air samples

Proftest SYKE carried out the interlaboratory comparison in cooperation with Finnish Institute of Occupational Health (FIOH) for VOC thermodesorption measurements (ISO 16000-6) from native indoor air samples in Tenax TA thermodesorption tubes in October 2019 (IAVOC 10/2019). Further, the measurements of alpha-pinene, 1-butanol, 2-butoxyethanol, 2EH (2-ethyl-1-hexanol), naphthalene, styrene, tetrachloroethylene, toluene, and TXIB (2,2,4-trimethyl-1,3-pentanediol diisobutyrate) were tested from the synthetic sample. In total ten participants took part in the comparison. In total 77 % of the results reported by the participants were satisfactory when deviation of 20–40 % from the assigned value was accepted. The calculated values were used as the assigned values for the results of the synthetic sample reported as compound specific responses. For the other measurands and samples mainly the mean of the results of the homogeneity measurements and the test results of the expert laboratory was used as the assigned value. The performance evaluation was based on the z scores. Warm thanks to all the participants in this interlaboratory comparison

Interlaboratory Comparison 11/2020. VOC measurements from indoor air samples

Proftest SYKE carried out the interlaboratory comparison in cooperation with Finnish Institute of Occupational Health (FIOH) for VOC thermodesorption measurements (ISO 16000-6) from native indoor air samples in Tenax TA thermodesorption tubes in September-October 2020 (IAVOC 11/2020). Further, the measurements of alpha-pinene, 1-butanol, 2-butoxyethanol, decane, ethylbenzene, 2EH (2-ethyl-1-hexanol), naphthalene, styrene, tetrachloroethylene, toluene, 1,2,4-trimethylbenzene, and TXIB (2,2,4-trimethyl-1,3-pentanediol diisobutyrate were tested from the synthetic sample. In total eight participants took part in the comparison. In total 71 % of the results reported by the participants were satisfactory when deviation of 15–35 % from the assigned value was accepted. The calculated values were used as the assigned values for the results of the synthetic sample reported as compound specific responses. For the other measurands and samples the mean of the results of the homogeneity measurements and the test results of the expert laboratory was used as the assigned value. The performance evaluation was based on the z scores. Warm thanks to all the participants in this interlaboratory comparison

Interlaboratory comparison 09/2018 - VOC measurement from indoor air samples

Proftest SYKE carried out the interlaboratory comparison in cooperation with Finnish Institute of Occupational Health (FIOH) for VOC thermodesorption measurements (ISO 16000-6) from native indoor air samples in Tenax TA thermodesorption tubes (IDA 09/2018) in October 2018. Further, the measurements of alpha-pinene, 1-butanol, 2-butoxyethanol, 2EH (2-ethyl-1-hexanol), naphthalene, styrene, tetrachloroethylene, toluene, and TXIB (2,2,4-trimethyl-1,3-pentanediol diisobutyrate) were tested from the synthetic sample. In total eight participants took part in the comparison. In total 70 % of the results reported by the participants were satisfactory when deviation of 20–30 % from the assigned value was accepted. The calculated values were used as the assigned values for the results of the synthetic sample reported as compound specific responses. For the other measurands and samples the mean of the results of the homogeneity measurements of the expert laboratory were used as the assigned value. The performance evaluation was based on the z scores. Warm thanks to all the participants of this interlaboratory comparison

Resting state fMRI reveals a default mode dissociation between retrosplenial and medial prefrontal subnetworks in ASD despite motion scrubbing

In resting state functional magnetic resonance imaging (fMRI) studies of autism spectrum disorders (ASDs) decreased frontal-posterior functional connectivity is a persistent finding. However, the picture of the default mode network (DMN) hypoconnectivity remains incomplete. In addition, the functional connectivity analyses have been shown to be susceptible even to subtle motion. DMN hypoconnectivity in ASD has been specifically called for re-evaluation with stringent motion correction, which we aimed to conduct by so-called scrubbing. A rich set of default mode subnetworks can be obtained with high dimensional group independent component analysis (ICA) which can potentially provide more detailed view of the connectivity alterations. We compared the DMN connectivity in high-functioning adolescents with ASDs to typically developing controls using ICA dual-regression with decompositions from typical to high dimensionality. Dual-regression analysis within DMN subnetworks did not reveal alterations but connectivity between anterior and posterior DMN subnetworks was decreased in ASD. The results were very similar with and without motion scrubbing thus indicating the efficacy of the conventional motion correction methods combined with ICA dual-regression. Specific dissociation between DMN subnetworks was revealed on high ICA dimensionality, where networks centered at the medial prefrontal cortex and retrosplenial cortex showed weakened coupling in adolescents with ASDs compared to typically developing control participants. Generally the results speak for disruption in the anterior-posterior DMN interplay on the network level whereas local functional connectivity in DMN seems relatively unaltered

Hepsin regulates TGF beta signaling via fibronectin proteolysis

Transforming growth factor-beta (TGF beta) is a multifunctional cytokine with a well-established role in mammary gland development and both oncogenic and tumor-suppressive functions. The extracellular matrix (ECM) indirectly regulates TGF beta activity by acting as a storage compartment of latent-TGF beta, but how TGF beta is released from the ECM via proteolytic mechanisms remains largely unknown. In this study, we demonstrate that hepsin, a type II transmembrane protease overexpressed in 70% of breast tumors, promotes canonical TGF beta signaling through the release of latent-TGF beta from the ECM storage compartment. Mammary glands in hepsin CRISPR knockout mice showed reduced TGF beta signaling and increased epithelial branching, accompanied by increased levels of fibronectin and latent-TGF beta 1, while overexpression of hepsin in mammary tumors increased TGF beta signaling. Cell-free and cell-based experiments showed that hepsin is capable of direct proteolytic cleavage of fibronectin but not latent-TGF beta and, importantly, that the ability of hepsin to activate TGF beta signaling is dependent on fibronectin. Altogether, this study demonstrates a role for hepsin as a regulator of the TGF beta pathway in the mammary gland via a novel mechanism involving proteolytic downmodulation of fibronectin.Peer reviewe

Nanoscale Metallic Iron for Environmental Remediation: Prospects and Limitations

The amendment of the subsurface with nanoscale metallic iron particles (nano-Fe0) has been discussed in the literature as an efficient in situ technology for groundwater remediation. However, the introduction of this technology was controversial and its efficiency has never been univocally established. This unsatisfying situation has motivated this communication whose objective was a comprehensive discussion of the intrinsic reactivity of nano-Fe0 based on the contemporary knowledge on the mechanism of contaminant removal by Fe0 and a mathematical model. It is showed that due to limitations of the mass transfer of nano-Fe0 to contaminants, available concepts cannot explain the success of nano-Fe0 injection for in situ groundwater remediation. It is recommended to test the possibility of introducing nano-Fe0 to initiate the formation of roll-fronts which propagation would induce the reductive transformation of both dissolved and adsorbed contaminants. Within a roll-front, FeII from nano-Fe0 is the reducing agent for contaminants. FeII is recycled by biotic or abiotic FeIII reduction. While the roll-front concept could explain the success of already implemented reaction zones, more research is needed for a science-based recommendation of nano- Fe0 for subsurface treatment by roll-front