Letermovir in lung transplant recipients with cytomegalovirus infection: A retrospective observational study

Letermovir is a new antiviral drug approved for the prophylaxis of CMV infection in allogeneic stem cell transplants. The aim of the study was to assess the therapeutic efficacy of letermovir in difficult to treat CMV infections in lung transplant recipients. All lung transplant recipients between March 2018 and August 2020, who have been treated with letermovir for ganciclovir-resistant or refractory CMV infection were included in the study and analysed retrospectively. In total, 28 patients were identified. CMV disease was present in 15 patients (53.6%). In 23 patients (82.1%), rapid response was noticed, and CMV-viral load could be significantly decreased (>1 log₁₀) after a median of 17 [14–27] days and cleared subsequently in all of these patients. Five patients (17.9%) were classified as non-responder. Thereof, development of a mutation of the CMV UL56 terminase (UL-56-Gen: C325Y) conferring letermovir resistance could be observed in three patients (60%). Common side effects were mild and mostly of gastrointestinal nature. Mild adjustments of the immunosuppressive drugs were mandatory upon treatment initiation with letermovir. In addition to other interventions, letermovir was effective in difficult to treat CMV infections in lung transplant recipients. However, in patients with treatment failure mutation conferring letermovir, resistance should be taken into account.     

Interleukin-6 and selected plasma proteins in healthy persons of different ages

In the present study, interleukin-6(IL-6) and several acute phase proteins were measured in healthy participants (23–87 years of age). A linear correlation between IL-6 and age was established with an increase of 0.016 pg/ml(00.004) per year of life. Whereas CRP remained below 0.5 mg/dl in all participants, an increase with age for fibrinogen and an inverse relation for albumin as well as transferrin were obtained. However, the increase of IL-6 did not correlate with any of these changes. IL-6 associated diseases may therefore occur more often with advancing age, but in healthy participants IL-6 does not explain the changing plasma protein pattern resembling that of an acute phase reaction.     

Demonstration of pro-opiomelanocortin mRNA in pituitary adenomas and para-adenomatous gland in cushing's disease and Nelson's syndrome

Pro-opiomelanocortin (POMC) mRNA was demonstrated in pituitary adenomas from 16 patients with Cushing's disease and 10 with Nelson's syndrome. The intensity of signal was significantly greater in Nelson's syndrome than in Cushing's disease and there was a trend towards a greater proportion of positive cells. This probably reflects inhibition of POMC gene expression by the high circulating levels of cortisol in Cushing's disease. In the para-adenomatous gland, the intensity of signal was variable in cells showing Crooke's hyaline change, ranging from negative to strongly positive, in keeping with the functional heterogeneity of corticotrophs. In one case, junctional corticotrophs were present and these were more intensely stained than anterior lobe corticotrophs in the same gland. This supports the concept that these cells are subject to different regulatory influences from corticotrophs in the anterior lobe. Whether this is related to differences in embryological origins or to local factors is at present unclear.     

Progress in the treatment of congenital malformations of the hand

Treatment of congenital malformations of the hand and forearm has progressed not only from new procedures, but especially due to a new technique, namely microsurgery. Microsurgery enables skilled hand surgeons to operate on the tiny hands of babies without damaging the anatomical structures. The optimal time for the correction of many deformities is during the first 2 years of life. This gives excellent adaptation of the corrected structures to their altered function, especially in combination with a long period of further growth. Several new procedures are described which have been made possible only since the introduction of microsurgery, either by microvascular anastomoses or by meticulous dissection technique (toe transplantation, proximal toe phalanx transplantation, nail wall formation in complex syndactyly, transposition of digital parts in polydactyly and radial club hand).

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Resumen El tratamiento de las malformaciones congénitas de la mano y el antebrazo ha progresado no sólo en términos de nuevos procedimientos, sino, especialmente, en razón de una nueva técnica, la microcirugía. La microcirugía permite que los cirujanos de mano idoneos puedan operar sobre las pequeñas manos de bebés sin causar daño a las estructuras anatómicas. La época óptima para la corrección de muchas deformaciones es durante los 2 primeros años de vida. Esto hace posible una excelente adaptatión, de las estructuras que han sido corregidas a la función alterada, especialnmente durante períodos prolongados del crecimiento. Se describen algunos nuevos procedimientos que han sido factibles sólo desde la introducción de la microcirugía, bien sea por anastomosis microvascular o por una meticulosa técnica de disecci [trasplante de un artejo, transplante de la falange proximal, formación de la uña en sindatilia compleja, transposición de partes de dígitos en polidactilia y en mano zamba radial (club hand)].

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Résumé Le traitement des malformations congénitales de la main et de l'avant-bras a progressé non seulement grâce à de nouveaux procédés mais surtout grâce à l'apparition de toute une technique nouvelle: la microchirurgie. Celle-ci permet à des chirurgiens de la main expérimentés d'opérer les toutes petites mains des jeunes enfants sans compromettre la fonction des structures anatomiques. Les 2 premières années de la vie sont la meilleure période pour corriger la plupart des malformations: elles permettent une adaptation excellente des structures de fonction auparavant altérée, en se combinant avec la longue période de croissance à venir. Plusieurs procédés nouveaux sont répertoriés. Ils sont devenus possibles seulement depuis l'introduction de la microchirurgie: il s'agit notamment des anastomoses microvasculaires ou des techniques méticuleuses de dissection comme le transfert d'orteil ou de la phalange proximale de l'orteil, la création du mur latéral d'ongle dans un cas de syndactylie complexe ou la transposition de segments des doigts pour polydactylie ou main bote radiale.

     

Factors associated with insomnia symptoms: A cross-sectional study during a Covid-19 fully restrictive lockdown

Insomnia is the most frequent sleep disorder and a public health concern that increased during the Covid 19 pandemic. Fully restrictive lockdowns during Covid are interesting periods to examine the impact of environmental and behavioural changes on the emergence of insomnia symptoms. In this cross-sectional study we aimed to (1) determine the main factors associated with insomnia symptoms during a Covid-19 fully restrictive lockdown examining the associated daily life alterations and (2) create a predictive model of insomnia symptoms. We used the data drawn from the “Covid-RythmE” study that reached volunteers from the general French population through an online survey during the last 2 weeks of the 2 month full lockdown. Associations with insomnia symptoms were tested and significant associations were entered in a Backward Stepwise Logistic Regression (BSLR) to assess the best combination to classify individuals with or without insomnia symptoms. From the 1624 participants, 50.64% suffered from mild to severe insomnia symptoms as assessed by the ISI. The best combination for explaining insomnia symptoms with 74.26% of accuracy included: age (OR = 1.15), females (OR = 1.26), smaller home sizes (OR = 0.77), environmental noises (OR = 1.59), anxiety symptoms (OR = 1.24), depressive symptoms (OR = 1.15), regularity of sleep–wake schedules (OR = 1.25), exposure to screen during the morning (OR = 1.13), and LED light during the evening (OR = 1.17). Thus, lifestyle schedule and exposure to natural synchronizers such as light, are primordial in considering in insomnia physiopathology, prevention and treatment, as well as the associated mental health status.     

Chloride Ion-Containing Polymeric Ionic Liquids for Application as Electrolytes in Solid-State Batteries

Organic, solid-state batteries require efficient solid electrolytes able to provide stable ion conduction. Here, solid electrolytes based on ionic liquid (IL) polymers with chloride counterions as electrolyte materials for batteries are presented. Acrylic monomers with imidazolium substituents with alkyl side groups that are linked by alkyl spacers to the acrylic group are employed. The IL monomers with chloride counterions are either converted by thermally initiated radical polymerization into linear homopolymers or incorporated into polymer networks by UV-initiated copolymerization utilizing a bifunctional, non-ionic cross-linker. Both procedures successfully yielded the desired materials, which is confirmed by NMR spectroscopy (linear homopolymers) or Raman spectroscopy (IL networks). The ionic conductivities at room temperature are measured by Electrochemical Impedance Spectroscopy. The ionic conductivities of the linear homopolymers are in the range of 10⁻⁴ to 10⁻⁶ S cm⁻¹, while those of the IL networks are about two orders of magnitude lower. They increase to 10⁻⁴ S cm⁻¹ at 70 °C. The electrochemical stability is examined by Linear Sweep Voltammetry and is proven in the voltage range of −2 to +2 V. The results reveal that the materials represent promising electrolytes for potential solid-state battery applications.     

DNA measurement,proliferation markers,and other factors in pituitary adenomas

To assess the proliferative activity of pituitary adenomas, 36 surgically removed adenomas were studied by light microscopical parameters; mitotic count; expression of PCNA, Ki-67, cathepsin D, and EGF; and image cytometry. Three adenomas (9%) showed high, 11 (34%) medium, 17 (53%) moderate, and 1 (3%) low structural differentiation. In 10 adenomas (31%), no mitosis was observed. The average was 2.4 mitoses/100 HPF; the highest count was 7.1 mitoses/100 HPF. Eleven adenomas (33.3%) were PCNA-negative; in 20 adenomas (60.6%), between 0.05 and 3.9, and in 2 adenomas (6.0%), between 10.5 and 16.4 PCNA-positive nuclei were observed. Only a recurrent null-cell adenoma (9%) was Ki-67-negative. Three adenomas (9.1%) were EGF-negative, 28 (84.8%) showed up to 10% positive cells, and 2 (6.1 %) showed between 10 and 30% positive cells; 19 adenomas (68%) were cathepsin D-negative, including all endocrine-inactive adenomas. Half the adenomas had an euploid DMA stem line. Endocrine-inactive adenomas displayed a higher rate of euploid DNA stem lines than endocrine-active adenomas. The S-phase fraction varied between 2.97 and 28%, with a mean value of 14.4%. Half the adenomas showed an S-phase fraction of 11.65% or lower.     

Effects of benzodiazepine receptor partial inverse agonists in the elevated plus maze test of anxiety in the rat

The present series of experiments examined the effects of five benzodiazepine receptor (BZR) partial inverse agonists on the behaviour of rats on an elevated plus maze. The drugs were tested in a standard plus maze with 3-cm walls added to the open arms, as this has been shown to increase the sensitivity of the plus maze to anxiogenic-like drug effects (Jones and Cole 1995). The drugs tested were FG 7142 (0–100 mg/kg),-CCE (0–30 mg/kg), ZK 132 556 (0–100 mg/kg), ZK 90 886 (0–30 mg/kg) and Ro 15–4513 (0–30 mg/kg). In addition, to allow a comparison with previous studies, the effects of three reference substances, DMCM (0–2.5 mg/kg), pentylenetetrazol (PTZ; 0–30 mg/kg) and yohimbine (0–5 mg/kg), were also examined. These three reference compounds produced a dose-dependent reduction in the duration of open arm exploration and the total number of open arm entries, indicative of anxiogenic-like effects. DMCM produced significant effects at the doses of 1.25 and 2.5 mg/kg, PTZ at 30 mg/kg, and yohimbine at 5 mg/kg. The BZR partial inverse agonist FG 7142 (10, 30 and 100 mg/kg) also reduced the duration of open arm exploration and the total number of arm entries. The minimally effective dose resulted in a receptor occupancy of approximately 80%. Ro 15–4513 also produced anxiogenic-like effects, but only at a dose (30 mg/kg) that resulted in a receptor occupancy of approximately 95%. In contrast, the other BZR partial inverse agonists, ZK 132 553 and ZK 90 886, did not significantly reduce the duration of open arm exploration, even at doses that produced greater than 95% receptor occupancies.-CCE also did not reduce open arm exploration at any dose tested (0–30 mg/kg). The GABA shift, a biochemical index of intrinsic activity, indicates that these latter three compounds are more inverse agonistic than Ro 15–4513. In summary, these results demonstrate that not all BZR receptor partial inverse agonists have anxiogenic-like activity in the rat plus maze, and that the GABA shift, a biochemical index of intrinsic efficacy, does not predict which BZR partial inverse agonists are anxiogenic.     

Parasite communities of the Salzhaff (Northwest Mecklenburg, Baltic Sea). I. Structure and dynamics of communities of littoral fish, especially small-sized fish

The parasites of ten fish species, including four Gobiidae, three Gasterosteidae, two Syngnathidae, and one Zoarcidae from the Salzhaff region, Northwest Mecklenburg, Baltic Sea, were investigated in 1995 and 1996. As many as 36 parasite species, represented by diverse groups of helminths and protozoans as well as annelids and copepods, are found during 4 seasons in these hosts. By far the most abundant group is represented by digeneans, comprising 15 species, followed by 7 cestodans and 6 nematodes. With regard to component communities, 8 host-parasite combinations are core and secondary species with more than 40% prevalence in which generalists such as the digeneans Podocotyle atomon and Cryptocotyle concavum (in 3 hosts). C. lingua, Diplostomum spathaceum, and Acanthostomum balthicum, and the nematode Hysterothylacium are involved. Also, specialists such as Aphalloides timmi in Pomatoschistus microps as well as Magnibursatus caudofilamentosa and Thersitina gasterostei in Gasterosteus aculeatus attain high levels of prevalence. A comparison of different investigations reveals greater prevalence of allogenic and autogenic parasite species with 3 host cycles in the Rerik-Riff (free Baltic) and higher levels of prevalence of autogenic parasite species with 1 or 2 host cycles in the entire Salzhaff. The component communities of gobies from Dahmeshöved, Lübeck Bight, attain generally lower degrees of prevalence than those of the Salzhaff region. The infracommunities consist mostly of 1–3 parasite species per host specimen; this value is surpassed on occasion in P. microps (maximum 7 species) and in G. aculeatus (maximum 9 species, which may compete for 5 microhabitats in a host specimen). In this context the theory of empty niches propagated by some parasitologists is critically discussed and substituted by the assumption of variable niche widths. The seasonality of the more abundant parasites is either unclear – as in the case of C. concavum– or evident – as in the case of P. atomon, which prevail in early spring and summer, or A. timmi, which dominate in late summer, as do M. caudofilamentosa, which is absent in spring. The main causes of the infestation of fish hosts may be their ages and the availability of parasites due to the presence of intermediate hosts.