Energy Expenditure in Humans: Principles, Methods, and Changes Throughout the Life Course.

Humans require energy to sustain their daily activities throughout their lives. This narrative review aims to (a) summarize principles and methods for studying human energy expenditure, (b) discuss the main determinants of energy expenditure, and (c) discuss the changes in energy expenditure throughout the human life course. Total daily energy expenditure is mainly composed of resting energy expenditure, physical activity energy expenditure, and the thermic effect of food. Total daily energy expenditure and its components are estimated using variations of the indirect calorimetry method. The relative contributions of organs and tissues determine the energy expenditure under different physiological conditions. Evidence shows that energy expenditure varies along the human life course, at least in part due to changes in body composition, the mass and specific metabolic rate of organs and tissues, and levels of physical activity. This information is crucial to estimate human energy requirements for maintaining health throughout the life course.

Evaluation of selected natural sesquiterpenes as sensitizing agents of ß-lactam-resistant bacterial strains.

AIMS: To evaluate the capacity of fourteen sesquiterpenes to enhance the action of known antibiotics against two ß-lactam resistant strains, and to determine a possible mechanism of antibiotic sensitization by assessing their ability to inhibit a ß-lactamase enzyme. METHODS AND RESULTS: The broth microdilution method was used to determine the minimum inhibitory concentration (MIC) of ß-lactams cefuroxime (CEFM) and cefepime (CPM) against Staphylococcus aureus 23MR and Escherichia coli 82MR strains in the absence and presence of subinhibitory concentrations of fourteen natural sesquiterpenes. (1R,4R)-4H-1,2,3,4-tetrahydro-1-hydroxycadalen-15-oic acid (5), xerantolide (8), estafiatin (11), and ambrosin (12) exhibited the best sensitizing effects in both strains. These compounds were able to reduce the MIC of CEFM by 2-fold (from 15.0 to 7.5 µg/mL) and CPM by 15-fold (from 0.9 to 0.06 µg/mL) in S. aureus 23MR. For E. coli 82MR, the MIC of CEFM was reduced up to 8-fold (from 120.0 to 15.0 µg/mL). In this strain, the activity of 8 and 11 surpassed that of clavulanic acid (positive reference), which reduced the MIC of CEFM from 120.0 to 60.0 µg/mL. To elucidate a possible mechanism of antibiotic sensitization, molecular docking studies were conducted with ß-lactamases. These studies revealed an affinity with the enzymes (energies > -4.93 kcal/mol) by the formation of hydrogen bonds with certain conserved amino acid residues within the active sites. However, the in vitro results indicated only marginal inhibition, with percentages <50%. CONCLUSIONS: The bioevaluations indicate that nine of fourteen sesquiterpenes enhance the action of CEFM and CPM against the ß-lactam resistant strains, and these compounds displayed moderate activity as inhibitors of ß-lactamase.

Larvicidal Activity against Spodoptera frugiperda of some Constituents from two Diospyros Species. In silico Pesticide-likeness Properties, Acetylcholinesterase Activity and Molecular Docking.

This report informs for the first time the chemical constituents of Diospyros xolocotzii and Diospyros digyna, the pesticidal and the acetylcholinesterase (AChE) inhibition potential of some compounds calculated by in silico approaches, the larvicidal activity against Spodoptera frugiperda of available compounds, the AChE inhibition of selected compounds, and the results of the molecular docking of the most active ones with this receptor. From the aerial parts of D. xolocotzii were isolated pentacyclic triterpenes (1-4, 6, 10, 11-13), phytosterols (15-17), and isodiospyrin (18), whereas the analysis of aerial parts of D. digyna conducted to the isolation of pentacyclic triterpenes (4, 5, 7-9, 11-14), (4S)-shinanolone (19), and scopoletin (20). For comparison purposes, origanal (21) was chemically prepared from 11. The in silico analysis showed that the tested compounds have pesticide potential. The larvicidal activities of 11>13>12 indicated that the increase of the oxidation degree at C-28 increases their bioactivity. Compounds 11 and 21 presented the higher inhibition in the acetylcholinesterase assay, and the higher binding energies, and for the interactionswith AChE by molecular docking. Both Diospyros species are sources of triterpenes with pesticidal potential and the molecular changes in lupane triterpenes correlate with the observed bioactivity and molecular docking.

Reproducibility of the energy metabolism response to an oral glucose tolerance test: influence of a postcalorimetric correction procedure.

PURPOSE: Metabolic flexibility (MetF), which is a surrogate of metabolic health, can be assessed by the change in the respiratory exchange ratio (RER) in response to an oral glucose tolerance test (OGTT). We aimed to determine the day-to-day reproducibility of the energy expenditure (EE) and RER response to an OGTT, and whether a simulation-based postcalorimetric correction of metabolic cart readouts improves day-to-day reproducibility. METHODS: The EE was assessed (12 young adults, 6 women, 27 ± 2 years old) using an Omnical metabolic cart (Maastricht Instruments, Maastricht, The Netherlands) after an overnight fast (12 h) and after a 75-g oral glucose dose on 2 separate days (48 h). On both days, we assessed EE in 7 periods (one 30-min baseline and six 15-min postprandial). The ICcE was performed immediately after each recording period, and capillary glucose concentration (using a digital glucometer) was determined. RESULTS: We observed a high day-to-day reproducibility for the assessed RER (coefficients of variation [CV] < 4%) and EE (CVs < 9%) in the 7 different periods. In contrast, the RER and EE areas under the curve showed a low day-to-day reproducibility (CV = 22% and 56%, respectively). Contrary to our expectations, the postcalorimetric correction procedure did not influence the day-to-day reproducibility of the energy metabolism response, possibly because the Omnical's accuracy was ~ 100%. CONCLUSION: Our study demonstrates that the energy metabolism response to an OGTT is poorly reproducible (CVs > 20%) even using a very accurate metabolic cart. Furthermore, the postcalorimetric correction procedure did not influence the day-to-day reproducibility. Trial registration NCT04320433; March 25, 2020.

Association of meal timing with body composition and cardiometabolic risk factors in young adults.

PURPOSE: To investigate the association of meal timing with body composition and cardiometabolic risk factors in young adults. METHODS: In this cross-sectional study participated 118 young adults (82 women; 22 ± 2 years old; BMI: 25.1 ± 4.6 kg/m2). Meal timing was determined via three non-consecutive 24-h dietary recalls. Sleep outcomes were objectively assessed using accelerometry. The eating window (time between first and last caloric intake), caloric midpoint (local time at which ≥ 50% of daily calories are consumed), eating jetlag (variability of the eating midpoint between non-working and working days), time from the midsleep point to first food intake, and time from last food intake to midsleep point were calculated. Body composition was determined by DXA. Blood pressure and fasting cardiometabolic risk factors (i.e., triglycerides, total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, and insulin resistance) were measured. RESULTS: Meal timing was not associated with body composition (p > 0.05). The eating window was negatively related to HOMA-IR and cardiometabolic risk score in men (R2 = 0.348, ß = - 0.605; R2 = 0.234, ß = - 0.508; all p ≤ 0.003). The time from midsleep point to first food intake was positively related to HOMA-IR and cardiometabolic risk score in men (R2 = 0.212, ß = 0.485; R2 = 0.228, ß = 0.502; all p = 0.003). These associations remained after adjusting for confounders and multiplicity (all p ≤ 0.011). CONCLUSIONS: Meal timing seems unrelated to body composition in young adults. However, a longer daily eating window and a shorter time from midsleep point to first food intake (i.e., earlier first food intake in a 24 h cycle) are associated with better cardiometabolic health in young men. CLINICAL TRIAL REGISTRATION: NCT02365129 ( https://www. CLINICALTRIALS: gov/ct2/show/NCT02365129?term=ACTIBATE&draw=2&rank=1 ).

Impaired lung function in multiple sclerosis: a single-center observational study in 371 persons.

INTRODUCTION: Abnormal lung function in people with multiple sclerosis (PwMS) could be considered as the result of muscle weakness or MS-specific structural central nervous system (CNS) abnormalities as a precipitant factor for the worsening of motor impairment or cognitive symptoms. METHODS: This is a cross-sectional observational study in PwMS. Forced spirometry was conducted, and normative metrics of forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and the relation FEV1/FVC were calculated. Qualitative and quantitative brain magnetic resonance imaging (MRI) examinations were carried out. RESULTS: A total of 371 PwMS were included in the study. Of those, 196 (53%) had RRMS, 92 (25%) SPMS, and 83 (22%) PPMS. Low FVC and FEV1 was present in 16 (8%), 16 (19%), and 23 (25%) of the patients in the RRMS, PPMS, and SPMS, respectively. PwMS with T2-FLAIR lesions involving the corpus callosum (CC) had a significantly higher frequency of abnormally low FVC and FEV1 (OR 3.62; 95% CI 1.33-9.83; p = 0.012) than patients without lesions in that region. This association remained significant in the RRMS group (OR 10.1; 95% CI 1.3-67.8; p 0.031) when the model excluded PPMS and SPMS. According to our study, for every increase of 1 z score of FVC, we observed an increase of 0.25 cm3 of hippocampal volume (ß 0.25; 95% CI 0.03-0.47; p 0.023) and 0.43 cm3 of left hippocampus volume (ß 0.43; 95% CI 0.16-0.71; p 0.002). CONCLUSIONS: We observed an incremental prevalence of abnormally low pulmonary function tests that parallels a sequence from more early relapsing courses to long-standing progressive courses (RRMS to PPMS or SPMS).

A bout of endurance and resistance exercise transiently decreases plasma levels of bile acids in young, sedentary adults.

Circulating bile acids (BA) are signaling molecules that control glucose and lipid metabolism. However, the effects of acute exercise on plasma levels of BA in humans remain poorly understood. Here, we evaluate the effects of a bout of maximal endurance exercise (EE) and resistance exercise (RE) on plasma levels of BA in young, sedentary adults. Concentration of eight plasma BA was measured by liquid chromatography-tandem mass spectrometry before and 3, 30, 60, and 120 min after each exercise bout. Cardiorespiratory fitness (CRF) was assessed in 14 young adults (21.8 ± 2.5 yo, 12 women); muscle strength was assessed in 17 young adults (22.4 ± 2.5 yo, 11 women). EE transiently decreased plasma levels of total, primary, and secondary BA at 3 and 30 min after exercise. RE exerted a prolonged reduction in plasma levels of secondary BA (p < 0.001) that lasted until 120 min. Primary BA levels of cholic acid (CA) and chenodeoxycholic acid (CDCA) were different across individuals with low/high CRF levels after EE (p ≤ 0.044); CA levels were different across individuals with low/high handgrip strength levels. High CRF individuals presented higher levels of CA and CDCA 120 min after exercise vs baseline (+77% and +65%) vs the low CRF group (-5% and -39%). High handgrip strength levels individuals presented higher levels of CA 120 min after exercise versus baseline (+63%) versus the low handgrip strength group (+6%). The study findings indicate that an individual's level of physical fitness can influence how circulating BA respond to both endurance and resistance exercise. Additionally, the study suggests that changes in plasma BA levels after exercising could be related to the control of glucose homeostasis in humans.

Effect of a 24-Week Concurrent Exercise Intervention on Neck Adiposity and Its Distribution in Young Adults: The ACTIBATE Randomized Controlled Trial.

Neck adipose tissue (NAT) accumulation and neck circumference are independent predictors of cardiometabolic risk (CMR) and low-grade chronic inflammation in young adults. The present study examines whether a 24-week concurrent exercise intervention can reduce NAT volume and neck circumference in young adults, and whether any changes in these variables are related to changes in body composition, CMR, and the inflammatory profile. Seventy-four participants (51 women, age 22 ± 2 years) were included in the main analyses, after being randomly assigned to either a (a) control (n = 34), (b) moderate-intensity exercise (n = 19), or (c) vigorous-intensity exercise (n = 21) group. Participants in the exercise groups trained 3-4 days/week (endurance + resistance exercise training). NAT volume and NAT distribution across different depots were estimated using computed tomography before and after the intervention. Anthropometric variables, body composition (determined by dual-energy X-ray absorptiometry), and CMR/inflammatory markers were also recorded. The exercise intervention did not reduce the total NAT volume, nor was NAT distribution affected (p > .05). However, it did reduce neck circumference in the vigorous-intensity exercise group compared with the moderate-intensity exercise and control groups (by 0.8 and 1 cm, respectively, p ≤ .05). Changes in total NAT and neck circumference were positively, albeit weakly, related (adj. R2: .05-.21, all p ≤ .05) to changes in body weight and adiposity, leptin (only total NAT), and CMR (only neck circumference). Altogether 24 weeks of concurrent exercise does not appear to reduce NAT accumulation in young adults, but may slightly reduce neck circumference in those who partake in vigorous exercise.

Effect of Moderate Versus Vigorous Exercise Intensity on Body Composition in Young Untrained Adults: The Activating Brown Adipose Tissue Through Exercise (ACTIBATE) Randomized Controlled Trial.

The present study aimed to investigate the effect of a 24-week aerobic + resistance training programs at moderate versus vigorous intensity on body composition, and the persistence of the changes after a 10-month free-living period, in young untrained adults. This report is based on a secondary analysis from the activating brown adipose tissue through exercise (ACTIBATE) single-center unblinded randomized controlled trial. A total of 144 young adults (65.6% women) aged 18-25 years were randomly allocated to three different groups: (a) aerobic + resistance exercise training program based on the international physical activity recommendations at vigorous intensity (Ex-Vigorous group), (b) at moderate intensity (Ex-Moderate group), and (c) control group (no exercise). Body composition outcomes were determined by a dual-energy X-ray absorptiometry scanner. Both Ex-Vigorous and Ex-Moderate decreased body weight, fat mass, and visceral adipose tissue mass in a similar manner (all p < .04). After a 10-month free-living period, these parameters returned to baseline levels in both exercise groups (all ps < .03). No differences between the exercise groups and the control group were noted in lean mass changes (all ps > .1). A 24-week aerobic + resistance training intervention based on the international physical activity recommendations was enough to improve body weight, fat mass, and visceral adipose tissue mass in untrained young adults, independently of the exercise intensity (moderate vs. vigorous).

Synthesis, biological evaluation, molecular docking studies and In-silico ADMET evaluation of pyrazines of pentacyclic triterpenes.

The semisynthesis of novel derivatives of lupeyl palmitate and 3ß-palmitoyloxy-olean-12-ene by introduction of a pyrazine at C-2 / C-3 and modifications of the relatively unexplored C-30 position of lupeol derivatives was conducted, and their cytotoxic and anti-inflammatory activities were evaluated. The derivatives 7, 10 and 11 significantly inhibited the tumor cell lines U251, K562, HCT-15, MCF-7 and SKLU-1, and compounds 7 and 11 were more active (IC50 25.4 ± 2.0 µM and 7.1 ± 0.4 µM, respectively) than the positive control (etoposide (IC50 31.5 ± 2.2 µM) in the tumor line PC-3. Introduction of the pyrazine at C-2 / C-3 in compounds 1 and 2 or modification at C-30 of compound 1 decreased the anti-inflammatory activity in the TPA-induced mouse ear edema. Following the results of the PASS online evaluation of the potential biological activity of the natural compounds and their derivatives, the inhibition of pNF-κB translocation to the prostate cancer (PC-3) cell nucleus was investigated and the binding mode of compounds 7, 10 and 11 with the human NF-κB receptor was explored by a molecular docking study. These derivatives bound directly or close to the amino acids that form the DNA recognition site. The ADMET physicochemical parameters of the fifteen compounds were further analyzed in silico using Molinspiration calculations indicating the potential of compounds 7, 10 and 11 for further investigation.

SARS-CoV-2 vaccination patterns in a private hematology and internal medicine outpatient clinic.

OBJECTIVE: Determine the proportion of vaccinated patients in a private hematology and internal medicine outpatient clinic and potential factors in adherence in at-risk patients (due to onco-hematological diseases). MATERIALS AND METHODS: This is a cross-sectional study of outpatients from a private clinic. We applied a non-validated instrument to all patients attending the outpatient clinic from May to October 2021. According to the primary diagnosis, we classified patients into onco-hematological and non-onco-hematological patients. Since national authorities exclusively executed and planned the rollout of vaccines, the order and eligibility defined by authorities of vaccination was considered when conducting the analysis and patients were classified according to the their corresponding group. RESULTS: 397 participants were accrued, 269 (68%) had an onco-hematological condition. In the whole group, 73 (18.3%) had a history of infection. Vaccination history was present in 286 persons (72%); 82% had two doses. In the subset of 269 persons with an onco-hematological condition, 191 (71%) were vaccinated, whereas 95 participants with non-hematological conditions (73%) had received the vaccine. Vaccination status was associated with age (OR 1.07, 95%CI: 1.03,1.10, p<0.0001) and body mass index (OR 1.11, 95%CI: 1.04,1.17, p<0.0001). CONCLUSIONS: According to our study, vaccination adherence at our center is significantly different from the nationwide proportion of vaccines.

Association of shivering threshold time with body composition and brown adipose tissue in young adults.

PURPOSE: Brown adipose tissue (BAT) increases metabolic heat production in response to cold exposure. Body size and composition are involved in the human cold response, yet the influence of BAT herein have not fully been explored. Here, we aimed to study the association of the cold-induced shivering threshold time with body composition, BAT, the perception of shivering and skin temperature in young adults. METHODS: 110 young healthy adults (81 females; age = 21.7 ± 2.1 years, BMI = 24.2 ± 4.3 kg/m2) underwent 2 h of individualized cooling, followed by the quantification of BAT using a18F-fluorodeoxyglucose ([18F]FDG) positron emission tomography-computed tomography (PET-CT) scan. Body mass index (BMI), lean mass, fat mass and body surface area (BSA) were also measured. Shivering threshold time was defined as the time until shivering occurred using an individualized cooling protocol. RESULTS: The shivering threshold time was on average 116.1 min for males and 125.8 min for females, and was positively associated to BMI (ß = 3.106; R2 = 0.141; p = 0.001), lean mass (ß = 2.295; R2 = 0.128; p = 0.001) and fat mass (ß = 1.492; R2 = 0.121; p = 0.001) in females, but not in males (all p ≥ 0.409). The shivering threshold time was positively associated with BSA in males (p = 0.047) and females (p = 0.001), but it was not associated with BAT volume or [18F]FDG uptake nor with the perception of shivering and skin temperature perception in both sexes. CONCLUSION: The shivering threshold time is positively associated with whole-body adiposity and lean mass in females, but not in males. The shivering threshold time was positively associated with BSA, but no association was observed with BAT nor with the perception of shivering or skin temperature. Future research should consider the influence of body composition when applying cooling protocols among individuals with different phenotypical features.

Short- and Mid-Term Impact of Tobacco Smoking on Donor Renal Function Following Living Kidney Donation at a Tertiary Referral Hospital.

BACKGROUND: The negative impact of tobacco smoking on renal function has been widely studied. However, there is limited knowledge about the effect of smoking on pre-operative and post-operative renal function in living kidney donors. OBJECTIVE: The objective of the study was to evaluate the short- and mid-term impact of smoking on donor renal function. METHODS: This is a retrospective study of 308 patients who underwent living donor nephrectomy (LDN) at a tertiary referral hospital. We compared baseline characteristics as well as functional outcomes following LDN according to history of tobacco smoking. Estimated glomerular filtration rate (eGFR) was calculated with the modification of diet in renal disease equation in 6 time periods: pre-operative, 1 week, 1 month, 6 months, 12 months, and 24 months after surgery. We performed a Kaplan-Meier analysis for chronic kidney disease (CKD) outcome and binary logistic regression analysis to identify risk factors associated with CKD at 24 months of follow-up. RESULTS: Among donors, 106 (34.4%) reported a smoking history before nephrectomy. Smoking donors had worse pre-operative eGFR than non-smokers (90 ± 26.3 mL/min/1.73m2 vs. 96 ± 27 mL/min/1.73 m2, respectively; p = 0.02) and lower eGFR at 1 week (p = 0.01), 1 month (p ≤ 0.01), 6 months (p = 0.01), and 12 months (p = 0.01) after LDN. Tobacco smoking (OR 3.35, p ≤ 0.01) and age ≥ 40 years at donation (OR 6.59, p ≤ 0.01) were associated with post-operative development of CKD at 24 months after LDN. CONCLUSIONS: Living kidney donors with a tobacco smoking history had an increased risk of developing chronic kidney disease following nephrectomy. Smoking-cessation strategies should be implemented.

Assessment of energy expenditure: are calories measured differently for different diets?

PURPOSE OF REVIEW: The prevalence and burden of obesity has reached alarming levels. The assessment of human energy expenditure enables the identification of obesity-prone and obesity-resistant individuals and helps to explain the short and long-term success of weight loss treatments. In this review, we describe the state-of-the-art methods used in the assessment of human energy expenditure and the impact of dietary intake on the interpretation of the data. RECENT FINDINGS: The reference techniques to assess energy expenditure in humans have not significantly changed during the last century. Today, indirect calorimetry, either using a metabolic chamber or a metabolic cart, is the favored method to assess human energy expenditure and is the only method enabling the assessment of macronutrient oxidation. The doubly labeled water method however provides accurate assessment of human energy expenditure under free living conditions. SUMMARY: Although energy expenditure and macronutrient oxidation can be assessed by simple calculations from oxygen consumption and carbon dioxide production, these calculations can provide erroneous results or require corrections and/or more complex interpretation when several biochemical pathways are simultaneously engaged. Such physiological mechanisms are often elicited by dietary interventions including, among other, gluconeogenesis, lipogenesis, ketogenesis, alcohol oxidation and under or overfeeding.

Endocrine Mechanisms Connecting Exercise to Brown Adipose Tissue Metabolism: a Human Perspective.

PURPOSE OF REVIEW: To summarize the state-of-the-art regarding the exercise-regulated endocrine signals that might modulate brown adipose tissue (BAT) activity and/or white adipose tissue (WAT) browning, or through which BAT communicates with other tissues, in humans. RECENT FINDINGS: Exercise induces WAT browning in rodents by means of a variety of physiological mechanism. However, whether exercise induces WAT browning in humans is still unknown. Nonetheless, a number of protein hormones and metabolites, whose signaling can influence thermogenic adipocyte's metabolism, are secreted during and/or after exercise in humans from a variety of tissues and organs, such as the skeletal muscle, the adipose tissue, the liver, the adrenal glands, or the cardiac muscle. Overall, it seems plausible to hypothesize that, in humans, exercise secretes an endocrine cocktail that is likely to induce WAT browning, as it does in rodents. However, even if exercise elicits a pro-browning endocrine response, this might result in a negligible effect if blood flow is restricted in thermogenic adipocyte-rich areas during exercise, which is still to be determined. Future studies are needed to fully characterize the exercise-induced secretion (i.e., to determine the effect of the different exercise frequency, intensity, type, time, and volume) of endocrine signaling molecules that might modulate BAT activity and/or WAT browning or through which BAT communicates with other tissues, during exercise. The exercise effect on BAT metabolism and/or WAT browning could be one of the still unknown mechanisms by which exercise exerts beneficial health effects, and it might be pharmacologically mimicked.

Prevalence of severe/morbid obesity and other weight status and anthropometric reference standards in Spanish preschool children: The PREFIT project.

BACKGROUND: Childhood obesity has become a major health problem in children under the age of 5 years. Providing reference standards would help paediatricians to detect and/or prevent health problems related to both low and high levels of body mass and to central adiposity later in life. Therefore, the aim of this study was to examine the prevalence of different weight status categories and to provide sex- and age-specific anthropometry reference standards for Spanish preschool children. METHODS: A total of 3178 preschool children (4.59±0.87 years old) participated in this study. Prevalence of different degrees of obesity (mild, severe, and morbid) and other weight status categories were determined. RESULTS: Reference standards were obtained. Prevalence of overweight and obese preschool children in the Spanish population ranged from 21.4 to 34.8%. Specifically, the obesity prevalence was 3.5, 1.2, and 1.3% of these subjects were categorized as mild, severe, and morbid obese. Sex- and age-specific reference standards for anthropometric parameters are provided for every 0.25 years (i.e. every trimester of life). CONCLUSION: Our results show a high prevalence of overweight/obese preschoolers. The provided sex- and age-specific anthropometric reference standards could help paediatricians to track and monitor anthropometric changes at this early stage in order to prevent overweight/obesity.

Treatment of Persons with Multiple Myeloma in Underprivileged Circumstances: Real-World Data from a Single Institution.

BACKGROUND: The treatment of patients with multiple myeloma (MM) has evolved in recent years, and the disease-associated prognosis has improved substantially. This improvement has been driven largely by the approval of novel agents, many of which are expensive and not universally available. Less expensive but effective approaches would be of value globally. PATIENTS AND METHODS: All consecutive MM patients diagnosed in the Centro de Hematología y Medicina Interna de Puebla after 1993 were included in this study. Patients were given oral thalidomide (100 mg/day), oral dexamethasone (36-40 mg/week), and aspirin 100 mg/day. Bor-tezomib (1.75 mg s.c. every week) was administered to those who could afford it. After 4-6 weeks of treatment, patients were offered an outpatient-based hematopoietic cell transplant (HCT). After the recovery of granulocytes following HCT, patients continued indefinitely on thalidomide; those who failed to tolerate thalidomide were switched to lenalidomide (25 mg/day). RESULTS: The median overall survival (OS) for all patients has not been reached and is >157 months. Median follow-up of the patients lasted 14 months (range 1.3-157). The median OS of patients with and without HCT was similar. The response rate (complete remission or very good partial remission) was 72% for those given thalidomide plus dexamethasone versus 88% for those given bortezomib, thalidomide, and dexamethasone before HCT, but OS was not different. As post-HCT maintenance, 37 patients received thalidomide; 26 of those (70%) could be maintained indefinitely on thalidomide, whereas 11 were switched to lenalidomide after a median of 7 months; median OS of patients maintained on thalidomide or lenalidomide after HCT was not different. CONCLUSION: In this series, a regimen incorporating low-cost novel agents and outpatient HCT was associated with excellent long-term survival in the treatment of MM patients. This approach may be a model for MM treatment in underprivileged circumstances.

Hopane-type triterpenes from Cnidoscolus spinosus and their bioactivities.

Chemical investigation of the aerial parts of Cnidoscolus spinosus resulted in the isolation of relatively infrequent hopane-type triterpenes, 3ß-acetoxy-hop-22(29)-ene (1), first reported here as natural product, together with 3-oxo-hop-22(29)-ene (2), and 3ß-hydroxy-hop-22(29)-ene (3). ß-Amyrin palmitate and three phytosterols were also characterized. The structures of the compounds were established using spectroscopic methods, and those of 1 and 2 were confirmed by crystallographic analysis. Selected biological activities for the isolated hopane-type triterpenes were tested through a series of assays for determining the cytotoxic, anti-inflammatory, α-glucosidase inhibition and antiparasitic activities. Compounds 1-3 did not show cytotoxic activity, compound 1 displayed an important inhibitory effect in the mouse ear induced inflammation assay, and significantly inhibited the yeast α-glucosidase activity in vitro and in silico. Additionally, compounds 2 and 3 showed marginal activities against Trypanosoma cruzi and Leishmania mexicana. Therefore, the bioactivities of hopane-type triterpenes deserve further investigation, particularly their anti-inflammatory properties.

Mantle cell lymphoma may have a different clinical course in Mexican Mestizos: Real-world data from a single center.

BACKGROUND: The biology of some hematological diseases varies among different populations. No previous studies have evaluated the clinical behavior of mantle cell lymphoma (MCL) in México. OBJECTIVE AND METHODS: This is a retrospective review of MCL cases seen in Mexico from January 2003 to June 2020. A total of 12 cases were identified. RESULTS: There were nine males and three females; median age was 56 years. Eight patients had a high MCL international prognostic index score, one was intermediate, and three were low. Five patients had circulating malignant monoclonal cells. Initial treatment included rituximab, cyclophosphamide, daunorubicin, vincristine, and prednisone (R-CHOP) and CHOP. Subsequent treatment included hematopoietic stem cell transplantation in five patients; two were given maintenance therapy. Splenectomy was done in four patients. Median overall survival (OS) for all the patients has not been reached and exceeds 162 mos: OS at 162 mos was 56%. Achieving a complete remission (CR) after the first treatment was a significant prognostic factor, with a median OS exceeding 141 mos in patients achieving CR, and 16 mos among those not achieving CR (p = 0.0006). CONCLUSION: Some of MCL patients in Mexico have an indolent clinical course, particularly patients who achieve a CR to initial treatment and who undergo splenectomy.

INFUSION OF CONVALESCENT PLASMA IS ASSOCIATED WITH CLINICAL IMPROVEMENT IN CRITICALLY ILL PATIENTS WITH COVID-19: A PILOT STUDY.

BACKGROUND: The ideal treatment of coronavirus disease (COVID)-19 has yet to be defined, but convalescent plasma (CoPla) has been successfully employed. OBJECTIVE: The objective of the study was to study the safety and outcomes of the administration of CoPla to individuals with severe COVID-19 in an academic medical center. METHODS: Ten patients were prospectively treated with plasma from COVID-19 convalescent donors. RESULTS: Over 8 days, the sequential organ failure assessment score dropped significantly in all patients, from 3 to 1.5 (p = 0.014); the Kirby index (PaO2/FiO2) score increased from 124 to 255, (p < 0.0001), body temperature decreased significantly from 38.1 to 36.9°C (p = 0.0058), and ferritin levels also dropped significantly from 1736.6 to 1061.8 ng/ml (p = 0.0001). Chest X-rays improved in 7/10 cases and in 6/10, computerized tomography scans also revealed improvement of the lung injury. Decreases in C-reactive protein and D-dimer levels were also observed. Three of five patients on mechanical ventilation support could be extubated, nine were transferred to conventional hospital floors, and six were sent home; two patients died. The administration of CoPla had no side effects and the 24-day overall survival was 77%. CONCLUSIONS: Although other treatments were also administered to the patients and as a result data are difficult to interpret, it seems that the addition of CoPla improved pulmonary function.