Disease characteristics of MCT8 deficiency : an international, retrospective, multicentre cohort study

Background Disordered thyroid hormone transport, due to mutations in the SLC16A2 gene encoding monocarboxylate transporter 8 (MCT8), is characterised by intellectual and motor disability resulting from cerebral hypothyroidism and chronic peripheral thyrotoxicosis. We sought to systematically assess the phenotypic characteristics and natural history of patients with MCT8 deficiency. Methods We did an international, multicentre, cohort study, analysing retrospective data from Jan 1, 2003, to Dec 31, 2019, from patients with MCT8 deficiency followed up in 47 hospitals in 22 countries globally. The key inclusion criterion was genetically confirmed MCT8 deficiency. There were no exclusion criteria. Our primary objective was to analyse the overall survival of patients with MCT8 deficiency and document causes of death. We also compared survival between patients who did or did not attain full head control by age 1·5 years and between patients who were or were not underweight by age 1–3 years (defined as a bodyweight-for-age Z score <–2 SDs or <5th percentile according to WHO definition). Other objectives were to assess neurocognitive function and outcomes, and clinical parameters including anthropometric characteristics, biochemical markers, and neuroimaging findings. Findings Between Oct 14, 2014, and Jan 17, 2020, we enrolled 151 patients with 73 different MCT8 (SLC16A2) mutations. Median age at diagnosis was 24·0 months (IQR 12·0-60·0, range 0·0-744·0). 32 (21%) of 151 patients died; the main causes of mortality in these patients were pulmonary infection (six [19%]) and sudden death (six [19%]). Median overall survival was 35·0 years (95% CI 8·3–61·7). Individuals who did not attain head control by age 1·5 years had an increased risk of death compared with patients who did attain head control (hazard ratio [HR] 3·46, 95% CI 1·76–8·34; log-rank test p=0·0041). Patients who were underweight during age 1–3 years had an increased risk for death compared with patients who were of normal bodyweight at this age (HR 4·71, 95% CI 1·26–17·58, p=0·021). The few motor and cognitive abilities of patients did not improve with age, as evidenced by the absence of significant correlations between biological age and scores on the Gross Motor Function Measure-88 and Bayley Scales of Infant Development III. Tri-iodothyronine concentrations were above the age-specific upper limit in 96 (95%) of 101 patients and free thyroxine concentrations were below the age-specific lower limit in 94 (89%) of 106 patients. 59 (71%) of 83 patients were underweight. 25 (53%) of 47 patients had elevated systolic blood pressure above the 90th percentile, 34 (76%) of 45 patients had premature atrial contractions, and 20 (31%) of 64 had resting tachycardia. The most consistent MRI finding was a global delay in myelination, which occurred in 13 (100%) of 13 patients. Interpretation Our description of characteristics of MCT8 deficiency in a large patient cohort reveals poor survival with a high prevalence of treatable underlying risk factors, and provides knowledge that might inform clinical management and future evaluation of therapies

Zmiana poziomu kredytowania przedsiębiorstw w Polsce w okresie pandemii COVID-19

The main theme undertaken in this paper is the assessment of the impact of the COVID-19 pandemic on corporate lending. The main objective of the article is to analyze the qualitative and quantitative changes in the level of corporate lending in Poland. The author focuses, on the one hand, on the ability of firms to incur liabilities and, on the other hand, on the changes in bank lending rules over the course of a changing economic reality burdened by the crisis caused by the pandemic. The individual analyses also show a broader comparative context by referring to statistical data before the onset of the virus crisis. In the case under review, uncertainty about the health of the MSP sector during the crisis weighed on the tightening of credit policy. An increase in demand for bank financing in the pandemic period was reported by both large companies and micro enterprises. However, only in the case of the former did the availability of loans increase. As a result, the gap between the availability of bank loans to large firms and the MSP sector widened.Tematem przewodnim niniejszego opracowania jest ocena wpływu pandemii COVID-19 na kredytowanie przedsiębiorstw. Głównym celem artykułu jest analiza zmian jakościowych i ilościowych poziomu kredytowania przedsiębiorstw w Polsce. Autorzy skupiają się z jednej strony na możliwościach zaciągnięcia zobowiązań przez firmy, z drugiej zaś na zmiany zasad udzielania pożyczek przez banki na przestrzeni zmieniającej się rzeczywistości gospodarczej, obarczonej kryzysem spowodowanym przez pandemię. W poszczególnych analizach ukazano również szerszy kontekst porównawczy odwołując się do danych statystycznych przed wystąpieniem kryzysu spowodowanego wirusem. W analizowanym przypadku niepewność co do kondycji sektora MSP w okresie kryzysu zaważyła na zaostrzeniu polityki kredytowej. wzrost zapotrzebowania na finansowanie bankowe w okresie pandemii zgłaszały zarówno duże firmy, jak i mikroprzedsiębiorstwa, jednak tylko w przypadku tych pierwszych dostępność kredytów wzrosła. W związku z tym różnica między dostępnością kredytów bankowych dla sektora dużych firm i sektora MSP powiększyła się

Selection of rhizobacteria improving phytoremediation of soil contaminated with heavy metal compounds

Wiele spośród bakterii ryzosferowych charakteryzuje się wysoką opornością na jony metali ciężkich i odgrywa ważną rolę w promowaniu wzrostu roślin w ich obecności. W badaniach przeanalizowano szczepy bakterii Bacillus sp. (ML 1-2), Bacteroidetes bacterium (RI 116-1), Flavobacterium sp. (RI 111-11), Pseudomonas fluorescens (LI C1), Serratia entomophila (RI 111-21) i Variovorax sp. (ML 3-12), wyizolowane z gleb skażonych związkami metali ciężkich lub zdegradowanych antropogenicznie. W warunkach in vitro wyselekcjonowano bakterie oporne na jony wybranych metali ciężkich (Cd, Cu, Zn i Pb). Wykazano, że S. entomophila (RI 111-21) i P. fluorescens (LI C1) należą do bakterii o najwyższym stopniu oporności na obecność jonów metali ciężkich w podłożu, zwłaszcza cynku i ołowiu. Szczepami o najwyższej wrażliwości na przeanalizowane jony metali cięż-kich okazały się B. bacterium (RI 116-1) i Flavobacterium sp. (RI 111-11). Stwierdzono, że na wzrost i rozwój siewek rzepaku negatywnie wpływały jony metali ciężkich uszeregowane w kolejności: Pb>Zn>Cu>Cd. Inokulacja rzepaku ozimego (Brassica napus L. odmiana Kronos) wykazała, że niektóre bakterie promowały wzrost i rozwój siewek w obecności jonów metali ciężkich, zwłaszcza miedzi i kadmu. Szczepy Bacillus sp. (ML 1-2) i B. bacterium (RI 116-1) najsilniej promowały wzrost siewek rzepaku w środowisku zawierającym jony metali ciężkich, stąd też wydają się mieć największy potencjał w procesach fitoremediacji gleb.Many soil bacteria show a high tolerance to heavy metals and play a vital role in promoting plant growth in a heavy-metal-contaminated environment. In the study reported on in this paper the bacterial strains being analyzed included Bacillus sp. (ML 1-2), Bacteroidetes bacterium (RI 116-1), Flavobacterium sp. (RI 111-11), Pseudomonas fluorescens (LI C1), Serratia entomophila (RI 111-21), and Variovorax sp. (ML 3-12), which had been isolated from soils contaminated by heavy metal compounds, or degraded due to anthropogenic activity. Under in-vitro conditions selected were bacteria tolerant to Cd, Cu, Zn and Pb. It has been demonstrated that among the strains examined S. entomophila (RI 111-21) and P. fluorescens (LI C1) are endowed with the highest tolerance to the heavy metals in the substrate, specifically to Zn and Pb, whereas B.?bacterium (RI 116-1) and Flavobacterium sp. (RI 111-11) display the highest vulnerability to heavy metals. Taking into account their negative influence on the growth and development of rape seedlings, the four heavy metals have been listed in the following order: Pb>Zn>Cu>Cd. Inoculation of winter rape (Brassica napus L. var. Kronos) has shown that some of the bacterial strains promote the growth and development of seedlings in the presence of heavy metals, especially copper and cadmium. The strains Bacillus sp. (ML 1-2) and B. bacterium (RI 116-1), which were parti-cularly active in promoting rape seedling growth in an environment containing heavy metals, seem to have the greatest potential for the phytoremediation of soils

Pain rating is worth a thousand words. Nocebo hyperalgesia induced by verbal modeling prevails over the effects of symbolic modeling and verbal suggestion

This study compares the effectiveness of verbal modeling, symbolic modeling, and verbal suggestion in inducing nocebo hyperalgesia. It is the first study to examine the contribution of stress to observationally induced nocebo hyperalgesia. This study’s experimental groups represented various sources of social information: a group of people participating in the study (verbal modeling), a single participant (symbolic modeling), and an experimenter (verbal suggestion). During the experiment, participants received electrocutaneous stimuli at the same intensity, half of which were applied with a placebo (sham device). Participants in the verbal modeling group were acquainted with pain ratings that had allegedly been provided by other participants. The ratings suggested that other participants experienced more pain in the placebo trials than in the control trials. In the symbolic modeling group, participants observed a model experiencing more pain in the placebo than in the control trials. In the verbal suggestion group, participants received a verbal suggestion of hyperalgesia in the placebo trials and no suggestion in the control trials. No manipulations were used in the control group. To investigate whether nocebo hyperalgesia is stable over time, an additional extinction phase was conducted. Nocebo hyperalgesia was induced by verbal modeling only and was mediated by expectancy. Stress was a significant moderator of the induced effect. Nocebo hyperalgesia was extinguished during the extinction phase. The obtained results provide potential implications for minimizing nocebo hyperalgesia in clinical practice by, for instance, controlling patients’ expectancies and stress levels

Placebo hypoalgesia and nocebo hyperalgesia induced by observational learning may be difficult to disentangle in a laboratory setting

Observational learning (OBL) can evoke placebo hypoalgesia and nocebo hyperalgesia, however, these effects have rarely been systematically compared. Healthy participants (n=105) were randomised to: 1) placebo OBL, 2) nocebo OBL, or 3) a no-observation control group. During OBL, a videotaped model simulated pain relief or increase after a sham ointment was applied. Thermal pain was evoked on two arms (ointment, control) at baseline and post-OBL. A three-way interaction confirmed that OBL modulates pain: F(2,93)=6.08, p=.003, ηp2=.12. Pain increased after nocebo OBL, with a bigger increase for the ointment arm (both p≤.007). After placebo OBL, pain increased for the control arm only (p&lt;.001). Expectations mediated these effects. That pain for the control stimuli increased after placebo OBL could reflect nocebo learning. Experimental paradigms typically examine relative differences between ointment and control stimuli. Our results show that this can complicate disentangling placebo hypoalgesia and nocebo hyperalgesia in laboratory settings