Loss of Personal Autonomy and Dignity-Related Distress in End-Of-Life Cancer Patients.

The objective of this cross-sectional study is to investigate Dignity-Related Loss of Personal Autonomy (DR-LPA) intended as loss of relational independence causing dignity-related distress. Moreover, it analyzes its possible relationships with demoralization, spirituality, quality of life, hope, and coping styles in a sample composed of 207 end-of-life cancer patients. These variables have been assessed through the following rating scales: Patient Dignity Inventory - Italian version, Demoralization Scale - Italian version, Functional Assessment of Cancer Therapy Scale - General Measure, Functional Assessment of Chronic Illness Therapy - Spiritual Well-Being, Brief Coping Orientation to Problem Experienced, and Herth Hope Index. The results have shown that most of the DR-LPA items were considered a problem by most patients. Functional, social, emotional, and spiritual wellbeing, disheartenment, age, and sex emerged as significant predictors of DR-LPA. In conclusion, this study showed that DR-LPA can be a relevant concern for patients at the end-of-life and for this reason it becomes necessary for psychosocial provides to consider it to deliver better dignity conserving care.

Synthesis and vectorial functionalisation of pyrazolo[3,4-c]pyridines.

Heterocycles are a cornerstone of fragment-based drug discovery (FBDD) due to their prevalence in biologically active compounds. However, novel heterocyclic fragments are only valuable if they can be suitably elaborated to compliment a chosen target protein. Here we describe the synthesis of 5-halo-1H-pyrazolo[3,4-c]pyridine scaffolds and demonstrate how these compounds can be selectively elaborated along multiple growth-vectors. Specifically, N-1 and N-2 are accessed through protection-group and N-alkylation reactions; C-3 through tandem borylation and Suzuki-Miyaura cross-coupling reactions; C-5 through Pd-catalysed Buchwald-Hartwig amination; and C-7 through selective metalation with TMPMgCl.LiCl followed by reaction with electrophiles or transmetalation to ZnCl2 and Negishi cross-coupling. Linking multiple functionalisation strategies emulates a hit-to-lead pathway and demonstrates the utility of pyrazolo[3,4-c]pyridines to FBDD.

Re-learning mental representation of walking after a brain lesion. Effects of a cognitive-motor training with a robotic orthosis.

Introduction: Stroke-related deficits often include motor impairments and gait dysfunction, leading to a limitation of social activities and consequently affecting the quality of life of stroke survivors. Neurorehabilitation takes advantage of the contribution of different techniques in order to achieve more benefits for patients. Robotic devices help to improve the outcomes of physical rehabilitation. Moreover, motor imagery seems to play a role in neurological rehabilitation since it leads to the activation of the same brain areas as actual movements. This study investigates the use of a combined physical and cognitive protocol for gait rehabilitation in stroke patients. Methods: Specifically, we tested the efficacy of a 5-week training program using a robotic orthosis (P.I.G.R.O.) in conjunction with motor imagery training. Twelve chronic stroke patients participated in the study. We evaluated balance and gait performance before and after the training. Six of them underwent fMRI examination before and after the training to assess the effects of the protocol on brain plasticity mechanisms in motor and imagery tasks. Results: Our results show that the rehabilitation protocol can effectively improve gait performance and balance and reduce the risk of falls in stroke patients. Furthermore, the fMRI results suggest that rehabilitation is associated with cerebral plastic changes in motor networks. Discussion: The present findings, if confirmed by future research, have the potential to advance the development of new, more effective rehabilitation approaches for stroke patients, improving their quality of life and reducing the burden of stroke-related disability.

Tandem Transesterification-Esterification Reactions Using a Hydrophilic Sulfonated Silica Catalyst for the Synthesis of Wintergreen Oil from Acetylsalicylic Acid Promoted by Microwave Irradiation.

SiO2-SO3H, with a surface area of 115 m2/g and pore volume of 0.38 cm3g-1, and 1.32 mmol H+/g was used as a 20% w/w catalyst for the preparation of methyl salicylate (wintergreen oil or MS) from acetylsalicylic acid (ASA). A 94% conversion was achieved in a microwave reactor over 40 min at 120 °C in MeOH. The resulting crude product was purified by flash chromatography. The catalyst could be reused three times.

Catalytic Transformation of Triglycerides to Biodiesel with SiO2-SO3H and Quaternary Ammonium Salts in Toluene or DMSO.

SiO2-SO3H, with a surface area of 115 m2·g-1, pore volumes of 0.38 cm3·g-1 and 1.32 mmol H+/g, was used as a transesterification catalyst. Triglycerides of waste cooking oil reacted with methanol in refluxing toluene to yield mixtures of diglycerides, monoglycerides and fatty acid methyl esters (FAMEs) in the presence of 20% (w/w) catalyst/oil using the hydrophilic sulfonated silica (SiO2-SO3H) catalyst alone or with the addition of 10% (w/w) co-catalyst/oil [(Bun4N)(BF4) or Aliquat 336]. The addition of the ammonium salts to the catalyst lead to a decrease in the amounts of diglycerides in the products, but the concentrations of monoglycerides increased. Mixtures of (Bun4N)(BF4)/catalyst were superior to catalyst alone or Aliquat 336/catalyst for promoting the production of mixtures with high concentrations of FAMEs. The same experiments were repeated using DMSO as the solvent. The use of the more polar solvent resulted in excellent conversion of the triglycerides to FAME esters with all three-catalyst media. A simplified mechanism is presented to account for the experimental results.

Selective Metalation and Functionalization of Fluorinated Nitriles Using 2,2,6,6-Tetramethylpiperidyl Bases.

We have accomplished regioselective deprotometalation of aromatic and heteroaromatic nitriles via (TMP)2Zn·2MgCl2·2LiCl and TMPMgCl·LiCl (TMP = 2,2,6,6-tetramethylpiperidyl) with the exploration of new and scarcely investigated metalation positions. Regioselectivity was rationalized by DFT calculations. The quenching of the generated organozinc and organomagnesium intermediates with various electrophiles gave access to 47 highly functionalized nitriles with yields up to 95%. Additionally, we report a difunctionalization strategy and the use of functionalized nitriles as building blocks to construct relevant heterocycles.

Synthesis of 7-Chloroquinoline Derivatives Using Mixed Lithium-Magnesium Reagents.

We have prepared a library of functionalized quinolines through the magnesiation of 7-chloroquinolines under mild conditions, employing both batch and continuous flow conditions. The preparation involved the generation of mixed lithium-magnesium intermediates, which were reacted with different electrophiles. Mixed lithium-zinc reagents allowed the synthesis of halogenated and arylated derivatives. Some of the synthesized 4-carbinol quinolines have shown interesting antiproliferative properties, their hydroxyl group being a suitable amino group bioisostere. We also report a two-step approach for optically active derivatives.

Roux-en-Y Gastric Bypass Downregulates Angiotensin-Converting Enzyme 2 (ACE2) Gene Expression in Subcutaneous White Adipose Tissue: A Putative Protective Mechanism Against Severe COVID-19.

The angiotensin-converting enzyme 2 (ACE2) is the receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is highly expressed in adipose tissue, possibly associated with progression to severe coronavirus disease 2019 (COVID-19) in obese subjects. We searched the Gene Expression Omnibus (GEO) and reanalyzed the GSE59034 containing microarray data from subcutaneous white adipose tissue (sWAT) biopsies from 16 women before and 2 years after RYGB, and 16 controls matched by sex, age, and BMI. After RYGB, there was a significant decrease in sWAT ACE2 gene expression (logFC=-0.4175, P=0.0015). Interestingly, after RYGB the sWAT ACE2 gene expression was significantly lower than in non-obese matched controls (LogFC=-0.32875, P=0.0014). Our data adds to the well-known benefits of RYGB, a potential protective mechanism against COVID-19.

Efficient N-arylation of 4-chloroquinazolines en route to novel 4-anilinoquinazolines as potential anticancer agents.

Microwave-mediated N-arylation of 4-chloroquinazolines in THF/H2O rapidly and efficiently afforded a library of novel 6-halo-2-phenyl-substituted 4-anilinoquinazolines. The methodology was compatible with numerous ortho-, meta-, and para-substituted N-methylanilines as well as substituted anilines and furnished the corresponding 4-anilinoquinazolines in good yields. Preliminary screening of the synthesized compounds against tumor cells (HCT-116 and T98G) showed promising antiproliferative properties.

Regioselective Functionalization of Ester-, Amide-, Carbonate-, and Carbamate-Substituted 2-Phenyl-2-oxazolines with Mixed Lithium-Magnesium Amides.

We have prepared novel highly functionalized benzene derivatives by regioselective metalation of ester-, amide-, carbamate-, and carbonate-substituted 2-phenyl-2-oxazolines with mixed lithium-magnesium amides followed by reaction with different electrophiles. While a complementary metalation site can be accessed by using different bases, steric and electronic effects promoted by the aromatic ring substituents also play an important role in reaction regioselectivity. Computational calculations of the aromatic hydrogen pKa values have helped us to rationalize the metalation preference by the complex-induced proximity effect concept.

Bioelectrochemical treatment and recovery of copper from distillery waste effluents using power and voltage control strategies.

Copper recovery from distillery effluent was studied in a scalable bioelectro-chemical system with approx. 6.8 L total volume. Two control strategies based on the control of power with maximum power point tracking (MPPT) and the application of 0.5 V using an external power supply were used to investigate the resultant modified electroplating characteristics. The reactor system was constructed from two electrically separated, but hydraulically connected cells, to which the MPPT and 0.5 V control strategies were applied. Three experiments were carried out using a relatively high copper concentration i.e. 1000 mg/L followed by a lower concentration i.e. 50 mg/L, with operational run times defined to meet the treatment requirements for distillery effluents considered. Real distillery waste was introduced into the cathode to reduce ionic copper concentrations. This waste was then recirculated to the anode as a feed stock after the copper depletion step, in order to test the bioenergy self-sustainability of the system. Approx. 60-95% copper was recovered in the form of deposits depending on starting concentration. However, the recovery was low when the anode was supplied with copper depleted distillery waste. Through process control (MPPT or 0.5 V applied voltage) the amount and form of the copper recovered could be manipulated.

Synthesis of Phenyl Esters Using SiO2-SO3H Catalyst in Conventional Heating and Microwave-Irradiated Esterification Processes.

A SiO2-SO3H amorphous catalyst containing a small surface area of 115.0 m²g-1 and 1.32 mmol H+/g was prepared from fine construction sand and sodium carbonate and sulfonated with H2SO4. In a 10% (w/w) basis, it is very efficient for catalyzing the esterification of carboxylic acids with phenol. The reaction processes were performed using conventional heating and under microwave irradiation. The yields were higher in the microwave-irradiated esterification. The catalyst could be used for three esterification sequences in both processes.

The preparation of benzyl esters using stoichiometric niobium (V) chloride versus niobium grafted SiO2 catalyst: A comparison study.

Two solvent free methods of a one-to-one alcohol/acid mol ratio synthesis of benzyl esters of the formic, acetic, benzoic, salicylic, nicotinic, and oxalic acids are described. The stoichiometric reactions used 1.5 mol ratio solid NbCl5 as the reagent and required from two to three hours for completion at room temperature; for the catalytic processes, NbCl5 was grafted directly, at room temperature, onto a silica gel of specific area of 507 m2g-1, produced from construction sand and sodium carbonate, forming a 5.4% Nb w/w SiO2-Nb gel with a specific area of 412 m2g-1. At 10% w/w catalyst/alcohol ratio, this SiO2-Nb catalyst gave similarly very good yields but required from 6 to 9 hours at the reflux temperature of the slurry. The catalyst could be re-used three times.

Alexithymia and Depression Affect Quality of Life in Patients With Chronic Pain: A Study on 205 Patients With Fibromyalgia.

Pain in fibromyalgia (FM) is accompanied by a heterogeneous series of other symptoms, which strongly affect patients' quality of life and interfere with social and work performance. The present study aimed to evaluate the effects of alexithymia on both the physical and the psychosocial components of the health-related quality of life (HRQoL) of FM patients, controlling for the concomitant effects of depression, anxiety, and pain. In particular, given the strong interconnection between depression and alexithymia, the relationship between alexithymia and HRQoL as mediated by depressive symptoms was further investigated. Data were collected on a consecutive sample of 205 female patients with a main diagnosis of FM. The results showed that about 26% of the patients showed the presence of alexithymia, as assessed by the Toronto Alexithymia Scale (TAS-20). Clinically relevant levels of depressive and anxiety symptoms were present in 61 and 60% of the patients, respectively. The results of the hierarchical multiple regression analyses showed that pain intensity (PI) and depressive symptoms explained the 45% of the variance of the physical component of HRQoL (p < 0.001). Regarding the mental component of HRQoL, depressive and anxiety symptoms, alexithymia, and PI significantly explained 61% of the variance (p < 0.001). The mediation analyses confirmed that alexithymia had a direct effect on the mental component of HRQoL and showed a statistically significant indirect effect on both the physical and the mental components, through the mediation of depressive symptoms. In conclusion, the results of the present study suggested the presence of both a direct and an indirect effect of alexithymia, in particular of the difficulty identifying feeling, on the HRQoL of patients with FM. Indeed, even though the concomitant presence of depressive symptoms is responsible of an indirect effect, alexithymia per se seems to directly contribute to worsen the impact that this chronic pain pathology has on the patients' quality of life, especially regarding the psychosocial functioning.

A new sequential injection analysis-capillary electrophoresis system with amperometric detection.

A novel and fully automated sequential injection analysis manifold coupled to a capillary electrophoresis apparatus with amperometric detection, is described. The sequential injection manifold was isolated from the high voltage by inserting an air plug into the circuit. Small buffer reservoirs were used to avoid the need to pump fresh buffer to the interface during the electrophoretic separation. No decoupling device was used to mitigate the interference from the high voltage electric field, instead the potential shift induced by the separation voltage, was accounted for. The new hydrodynamic injection method presented is based on the overpressure created in the circuit when a pinch valve is closed for a predetermined time. The injection method yields RSD values of peak height and area below 2.55 and 1.82%, respectively, at different durations of valve closure (n = 5). The capillary and working electrode alignment was achieved by adapting a commercial available capillary union. When the electrode was replaced, the alignment method proved to be very reliable, yielding RSD values of peak height and area lower than 2.64 and 2.08%, respectively (n = 8). Using this system with a gold microelectrode, dopamine, and epinephrine could be quantified within the concentration range of 1-500 µM and detected at a concentration of 0.3 µM. The methods here presented could be applied for the development of new capillary electrophoresis systems with amperometric detection and/or to the design of fully automated systems for online process monitoring purposes.

Base-Controlled Regioselective Functionalization of Chloro-Substituted Quinolines.

We prepared a number of di- and trifunctionalized quinolines by selective metalation of chloro-substituted quinolines with metal amides followed by reaction with different electrophiles. Metalation of the C-3 position of the quinolinic ring with lithium diisopropylamide at -70 °C is easy to achieve, whereas reaction with lithium-magnesium and lithium-zinc amides affords C-2 or C-8 functionalized derivatives in a regioselective fashion. These complementary methods could be rationalized by DFT calculations and are convenient strategies toward the synthesis of bioactive quinoline derivatives such as chloroquine analogues.

Oxygen Saturation in the Dental Pulp of Maxillary Premolars in Different Age Groups - Part 1.

The aim of this study was to determine oxygen saturation levels in the dental pulp of maxillary premolars in different age groups. A total of 120 human maxillary premolars with normal dental pulps were selected covering the following age groups: 20-24, 25-29, 30-34, 35-39 and 40-44 years (n=24 each group). Oxygen saturation was assessed using pulse oximetry. Analysis of variance was used to assess differences in oxygen saturation levels and Tukey's test was used to identify the age groups that differed from each other. Significance was set at 0.05. Mean oxygen saturation of 120 premolars was 86.20% considering all age groups. Significantly reduced levels were found in the oldest group compared to the other groups: 40 to 44 years - 80.00% vs. 89.71, 87.67, 88.71, and 84.80% for age groups 20-24, 25-29, 30-34, 35-39 years, respectively. The mean oxygen saturation levels were similar between 20 and 39 years of age (86.20%) in the whole sample, but reduced significantly in the 40-44-year age group, suggesting that older patients present lower oxygen saturation results even in the absence of pulp tissue injury.

Oxygen Saturation in the Dental Pulp of Maxillary Premolars in Different Age Groups - Part 1

Abstract The aim of this study was to determine oxygen saturation levels in the dental pulp of maxillary premolars in different age groups. A total of 120 human maxillary premolars with normal dental pulps were selected covering the following age groups: 20-24, 25-29, 30-34, 35-39 and 40-44 years (n=24 each group). Oxygen saturation was assessed using pulse oximetry. Analysis of variance was used to assess differences in oxygen saturation levels and Tukey's test was used to identify the age groups that differed from each other. Significance was set at 0.05. Mean oxygen saturation of 120 premolars was 86.20% considering all age groups. Significantly reduced levels were found in the oldest group compared to the other groups: 40 to 44 years - 80.00% vs. 89.71, 87.67, 88.71, and 84.80% for age groups 20-24, 25-29, 30-34, 35-39 years, respectively. The mean oxygen saturation levels were similar between 20 and 39 years of age (86.20%) in the whole sample, but reduced significantly in the 40-44-year age group, suggesting that older patients present lower oxygen saturation results even in the absence of pulp tissue injury.

Resumo Este estudo determinou os níveis de saturação de oxigênio (SaO2) em polpas dentárias de pré-molares superiores em diferentes faixas etárias. Foram selecionados 120 pré-molares superiores humanos com polpas dentárias normais, abrangendo os seguintes grupos etários: 20-24, 25-29, 30-34, 35-39 e 40-44 anos (n=24 para cada grupo). A saturação de oxigênio foi avaliada utilizando oximetria de pulso. A análise de variância foi utilizada para avaliar diferenças nos níveis de saturação de oxigênio, e o teste de Tukey foi utilizado para identificar os grupos etários que diferiam uns dos outros. A significância foi estabelecida em 0,05. A saturação média de oxigênio foi de 86,20% considerando todos os grupos etários. Níveis significativamente reduzidos foram encontrados no grupo de indivíduos de maior idade em comparação aos outros grupos: 40 a 44 anos - 80,00% vs. 89,71, 87,67, 88,71 e 84,80% para os grupos etários 20-24, 25-29, 30-34, 35-39 anos. Os níveis médios de saturação de oxigênio foram semelhantes entre os 20 e os 39 anos de idade (86,20%), mas reduziram-se significativamente na faixa etária de 40-44 anos, sugerindo que os pacientes mais idosos apresentam menor saturação de oxigênio mesmo na ausência de lesão do tecido pulpar.

Anodic electro-fermentation of 3-hydroxypropionic acid from glycerol by recombinant Klebsiella pneumoniae L17 in a bioelectrochemical system.

BACKGROUND: 3-Hydroxypropionic acid (3-HP) is an important platform chemical which can be produced biologically from glycerol. Klebsiella pneumoniae is an ideal biocatalyst for 3-HP because it can grow well on glycerol and naturally synthesize the essential coenzyme B12. On the other hand, if higher yields and titers of 3-HP are to be achieved, the sustained regeneration of NAD+ under anaerobic conditions, where coenzyme B12 is synthesized sustainably, is required. RESULTS: In this study, recombinant K. pneumoniae L17 overexpressing aldehyde dehydrogenase (AldH) was developed and cultured in a bioelectrochemical system (BES) with the application of an electrical potential to the anode using a chronoamperometric method (+0.5 V vs. Ag/AgCl). The BES operation resulted in 1.7-fold enhancement of 3-HP production compared to the control without the applied potential. The intracellular NADH/NAD+ ratio was significantly lower when the L17 cells were grown under an electric potential. The interaction between the electrode and overexpressed AldH was enhanced by electron shuttling mediated by HNQ (2-hydroxy-1,4-naphthoquinone). CONCLUSIONS: Enhanced 3-HP production by the BES was achieved using recombinant K. pneumoniae L17. The quinone-based electron transference between the electrode and L17 was investigated by respiratory uncoupler experiments. This study provides a novel strategy to control the intracellular redox states to enhance the yield and titer of 3-HP production as well as other bioconversion processes.

Concomitant Use of Transcranial Direct Current Stimulation and Computer-Assisted Training for the Rehabilitation of Attention in Traumatic Brain Injured Patients: Behavioral and Neuroimaging Results.

Divided attention (DA), the ability to distribute cognitive resources among two or more simultaneous tasks, may be severely compromised after traumatic brain injury (TBI), resulting in problems with numerous activities involved with daily living. So far, no research has investigated whether the use of non-invasive brain stimulation associated with neuropsychological rehabilitation might contribute to the recovery of such cognitive function. The main purpose of this study was to assess the effectiveness of 10 transcranial direct current stimulation (tDCS) sessions combined with computer-assisted training; it also intended to explore the neural modifications induced by the treatment. Thirty-two patients with severe TBI participated in the study: 16 were part of the experimental group, and 16 part of the control group. The treatment included 20' of tDCS, administered twice a day for 5 days. The electrodes were placed on the dorso-lateral prefrontal cortex. Their location varied across patients and it depended on each participant's specific area of damage. The control group received sham tDCS. After each tDCS session, the patient received computer-assisted cognitive training on DA for 40'. The results showed that the experimental group significantly improved in DA performance between pre- and post-treatment, showing faster reaction times (RTs), and fewer omissions. No improvement was detected between the baseline assessment (i.e., 1 month before treatment) and the pre-training assessment, or within the control group. Functional magnetic resonance imaging (fMRI) data, obtained on the experimental group during a DA task, showed post-treatment lower cerebral activations in the right superior temporal gyrus (BA 42), right and left middle frontal gyrus (BA 6), right postcentral gyrus (BA 3) and left inferior frontal gyrus (BA 9). We interpreted such neural changes as normalization of previously abnormal hyperactivations.