The Effect of Early Rehabilitation on COVID-19: A Prospective, Observational Study

Objective:The aim of this study was to investigate the effect of early pulmonary rehabilitation (PR) on the course of the disease, respiratory functions, physical activity, fatigue, and discharge time in Coronavirus disease-2019 (COVID-19) patients in the intensive care unit (ICU) setting.Method:A total of 31 patients (20 females, 11 males) with COVID-19 confirmed by real-time polymerase chain reaction who were admitted to the ICU were included. Demographic, clinical, and laboratory data of the patients were recorded. Physical activity, dyspnea, and fatigue of all patients were evaluated before and after PR program. All patients were evaluated on the day of PR in the ICU, the day of discharge from ICU to the ward, and on the day of discharge from hospital. Functional status was evaluated using the functional disability questionnaire (FDQ), the ambulation status using the functional ambulation classification (FAC), dyspnea using the modified Borg scale (MBS), and fatigue using the fatigue severity scale.Results:The mean length of ICU and hospital stay was 17.93±11.54 days and 18.29±8.41 days, respectively. The mean number of sessions was 8.87±7.66. The mean time from hospitalization to recovery was 13.00±9.62 days. Median FDQ and MBS scores were significantly higher during the ICU stay than the ward stay and at the time of discharge (p<0.05). Median FAC scores were significantly higher at the time of discharge than the ward and ICU scores (p<0.05). There was a positive and statistically significant correlation between the FDQ scores during the ward stay and C-reactive protein (CRP) values during the ICU stay (r=0.382, p=0.034) and CRP values during the ward stay (r=0.379, p=0.035). There was a negative and statistically significant correlation between the FDQ scores at the time of discharge and ferritin levels during the ICU stay (r=-0.421, p=0.018). A positive and statistically significant correlation was observed between MBS scores at the time of discharge and CRP values during the ward stay (p=0.418, p=0.019).Conclusion:Our study suggests that PR is an effective and safe approach with improved physical and functional results and COVID-19 survivors should undergo a PR program in an individualized manner using a multidisciplinary approach to improve short- and long-term outcomes

Selective determinants of inositol 1,4,5-trisphosphate and adenophostin A interactions with type 1 inositol 1,4,5-trisphosphate receptors

BACKGROUND AND PURPOSE: Adenophostin A (AdA) is a potent agonist of inositol 1,4,5-trisphosphate receptors (IP 3R). AdA shares with IP 3 the essential features of all IP 3R agonists, namely structures equivalent to the 4,5-bisphosphate and 6-hydroxyl of IP 3, but the basis of its increased affinity is unclear. Hitherto, the 2'-phosphate of AdA has been thought to provide a supra-optimal mimic of the 1-phosphate of IP 3. EXPERIMENTAL APPROACH: We examined the structural determinants of AdA binding to type 1 IP 3R (IP 3R1). Chemical synthesis and mutational analysis of IP 3R1 were combined with 3H-IP 3 binding to full-length IP 3R1 and its N-terminal fragments, and Ca 2+ release assays from recombinant IP 3R1 expressed in DT40 cells. KEY RESULTS: Adenophostin A is at least 12-fold more potent than IP 3 in functional assays, and the IP 3-binding core (IBC, residues 224-604 of IP 3R1) is sufficient for this high-affinity binding of AdA. Removal of the 2'-phosphate from AdA (to give 2'-dephospho-AdA) had significantly lesser effects on its affinity for the IBC than did removal of the 1-phosphate from IP 3 (to give inositol 4,5-bisphosphate). Mutation of the only residue (R568) that interacts directly with the 1-phosphate of IP 3 decreased similarly (by -30-fold) the affinity for IP 3 and AdA, but mutating R504, which has been proposed to form a cation-Π interaction with the adenine of AdA, more profoundly reduced the affinity of IP 3R for AdA (353-fold) than for IP 3 (13-fold). CONCLUSIONS AND IMPLICATIONS: The 2'-phosphate of AdA is not a major determinant of its high affinity. R504 in the receptor, most likely via a cation-Π interaction, contributes specifically to AdA binding

Systemic zinc redistribution and dyshomeostasis in cancer cachexia

Cachexia affects up to two thirds of all cancer patients and is a significant cause of morbidity and mortality. It is a complex metabolic syndrome associated with the underlying illness and characterized by loss of skeletal muscle tissue with or without loss of fat mass. Cachexia’s other prominent clinical symptoms include anorexia, systemic inflammation, pediatric growth failure, and hypogonadism. The relationship between the symptoms of cancer cachexia and the underlying illness is unclear, and there is an urgent need for a better understanding of the pathophysiology of this syndrome. Normal Zn metabolism is often disrupted in cancer patients, but the possible effects of systemic Zn dyshomeostasis in cachexia have not been investigated. We propose that the acute phase response can mediate Zn redistribution and accumulation in skeletal muscle tissue and contribute to the activation of the ubiquitin–proteasome pathway that regulates protein catabolism. This chronic redistribution deprives Zn from other tissues and organs and compromises critical physiological functions in the body. The cardinal symptoms of Zn deficiency are anorexia, systemic inflammation, growth failure in children, and hypogonadism. These symptoms also prominently characterize cancer cachexia suggesting that the role of systemic Zn dyshomeostasis in cachexia should be investigated

The Magnitude and Mechanism of Charge Enhancement of CH∙∙O H-bonds

Quantum calculations find that neutral methylamines and thioethers form complexes, with N-methylacetamide (NMA) as proton acceptor, with binding energies of 2–5 kcal/mol. This interaction is magnified by a factor of 4–9, bringing the binding energy up to as much as 20 kcal/mol, when a CH3+ group is added to the proton donor. Complexes prefer trifurcated arrangements, wherein three separate methyl groups donate a proton to the O acceptor. Binding energies lessen when the systems are immersed in solvents of increasing polarity, but the ionic complexes retain their favored status even in water. The binding energy is reduced when the methyl groups are replaced by longer alkyl chains. The proton acceptor prefers to associate with those CH groups that are as close as possible to the S/N center of the formal positive charge. A single linear CH··O hydrogen bond (H-bond) is less favorable than is trifurcation with three separate methyl groups. A trifurcated arrangement with three H atoms of the same methyl group is even less favorable. Various means of analysis, including NBO, SAPT, NMR, and electron density shifts, all identify the +CH··O interaction as a true H-bond

ETUDE PAR RMN ET POTENTIOMETRIE DES INTERACTIONS INTRAMOLECULAIRES, DES PROPRIETES ACIDO-BASIQUES MICROSCOPIQUES ET CONFORMATIONNELLES DU MYO-INOSITOL 1,4,5-TRIS(PHOSPHATE) ET D'ANALOGUES TRIS-ET TETRAKIS-PHOSPHORYLES

L'OBJET DE CE TRAVAIL EST L'ETUDE DES PROPRIETES ACIDO-BASIQUES ET CONFORMATIONELLES D'ANALOGUES DU MYO-INOSITOL 1,4,5-TRIS(PHOSPHATE) DONT LE ROLE ET L'IMPORTANCE BIOLOGIQUE ONT ETE RAPPELES. LES MICRO ET MACRO-CONSTANTES DE PROTONATION DES LIGANDS ETUDIES ONT ETE DETERMINEES PAR L'INTERMEDIAIRE DE LA POTENTIOMETRIE ET DE TITRAGES RMN EN FONCTION DU PH. CETTE APPROCHE INFRAMOLECULAIRE, RENDANT COMPTE DE L'ETAT DE PROTONATION DE CHAQUE PHOSPHATE, A PERMIS D'EVALUER L'INFLUENCE DE LA NATURE DES SUBSTITUANTS D'UN INOSITOL-PHOSPHATE SUR LE COMPORTEMENT DES NOYAUX 3 1P ET 1H VOISINS. UNE AUGMENTATION DE L'HYDROPHOBIE LOCALE PROVOQUE UNE VARIATION VERS LES CHAMPS FORTS DES SIGNAUX DE CES NOYAUX ET UNE AUGMENTATION DE LA BASICITE D'UN GROUPEMENT PHOSPHATE VOISIN. L'ADENOPHOSTINE A, SEUL LIGAND PLUS ACTIF QUE L'INS(1,4,5)P 3, A EGALEMENT ETE ETUDIEE. DES PROPRIETES ACIDO-BASIQUES PROCHES DE CELLES DE L'INS(1,4,5)P 3 ET LA PRESENCE DE LA PARTIE ADENINE SONT DES ELEMENTS PERMETTANT D'EXPLIQUER SON EXCEPTIONNELLE AFFINITE. PAR AILLEURS, L'ETUDE DES INTERACTIONS ENTRE LES PHOSPHATES ET LES HYDROGENES METHYNIQUES A MIS EN EVIDENCE LA FORMATION DE LIAISONS HYDROGENE FAIBLES DE TYPE C-HO, NOTAMMENT DANS LE CAS DE L'INS(1,4,5)P 3. LES RESULTATS DE HOESY 1H- 3 1P ET DE TITRAGES RMN- 1 3C ONT EGALEMENT REVELE DES INTERACTIONS SIMILAIRES ENTRE DES HYDROGENES DE CE TYPE ET DES GROUPEMENTS PHOSPHATE. EN OUTRE, CES TITRAGES EN 1 3C ONT MONTRE UNE DEFORMATION DU CYCLE DU 3,4,5-TRIDESOXY-INS(1,2,6)P 3. LES TITRAGES RMN- 3 1P ET 1H DE DEUX ANALOGUES DEOXY ONT REVELE DES PHENOMENES SIMILAIRES. LES GROUPEMENTS HYDROXYLES SONT DONC INDISPENSABLES POUR STABILISER LA MOLECULE EN CONFORMATION CHAISE PAR L'INTERMEDIAIRE DE LIAISONS HYDROGENE. LES TITRAGES RMN DE PROTONS HYDROXYLIQUES ONT VERIFIE CETTE HYPOTHESE EN MONTRANT L'EXISTENCE DE LIAISONS HYDROGENE FORTES ENTRE LES GROUPEMENTS PHOSPHATES DEPROTONES ET LES HYDROXYLES. CES LIAISONS STABILISENT LES PROTONS HYDROXYLIQUES JUSQU'A DES VALEURS DE PH ELEVEES ET PEUVENT ENGENDRER DES VARIATIONS DE DEPLACEMENTS CHIMIQUES CONSEQUENTES PUISQUE CERTAINS SIGNAUX ONT ETE OBSERVES A DES VALEURS DE L'ORDRE DE 8 PPM. ENFIN, DANS LA DERNIERE PARTIE, DEDIEE A DES ETUDES DE COMPLEXATION, LE SYSTEME INS(1,2,6)P 3/ZN 2 +/SPERMINE A MONTRE LA FORMATION DE COMPLEXES TERNAIRES STABLES.STRASBOURG-Sc. et Techniques (674822102) / SudocSudocFranceF