Association Between Concurrent Use of Benzodiazepines and Opioids and Health Care Utilization Among Patients With Cancer in Puerto Rico.

PURPOSE: To evaluate the association between concurrent use of opioids and benzodiazepines (BZDs) and emergency room (ER) visits and hospital admissions in patients with cancer. METHODS: Data were obtained from the Puerto Rico Central Cancer Registry-Health Insurance Linkage. Odds ratios (ORs) with 95% CIs and incidence rate ratio (IRR) were estimated using logistic and negative binomial regression analyses to assess the association between concurrent use of opioids and BZDs (overlap of at least 7 days) and ER visits and hospital admissions. RESULTS: A total of 9,259 patients were included in the main analysis. The logistic regression results showed a significant association between concurrent use of opioids and BZDs and at least one ER visit (OR, 1.28 [95% CI, 1.07 to 1.54]) or hospital admission (OR, 1.42 [95% CI, 1.18 to 1.71]) compared with individuals with BZDs alone, after adjusting for age, sex, comorbidity index, cancer stage, health insurance, and health region. Compared with individuals with opioid use alone, the association did not reach significance. In the negative binomial regression, a significant association was observed for ER visits (IRR, 1.52 [95% CI, 1.31 to 1.76]) and hospitalizations (IRR, 1.34 [95% CI, 1.20 to 1.50]) when compared with individuals with BZDs alone. Compared with individuals with opioids alone, it only reached significance for ER visits (IRR, 1.39 [95% CI, 1.20 to 1.61]). CONCLUSION: Careful evaluation must be done before prescribing concurrent opioids and BZDs in patients with cancer, as the results suggest that coprescribing may increase the odds of ER visits and hospitalizations.

A multi-country survey on the impact of COVID-19 on dental practice and dentists' feelings in Latin America.

BACKGROUND: The COVID-19 pandemic has significantly influenced the routine of healthcare workers. This study investigated the impact of the pandemic on dental practice and dentists' feelings in Latin America. METHODS: A survey was conducted with dentists from 11 Spanish-speaking Latin American countries in September-December 2020. Professionals were invited by email and via an open campaign promoted on social media. The questions investigated dental care routines, practice changes, and feelings about the pandemic. Descriptive statistics were used to identify frequencies and distributions of variables. Proportions were compared using chi-square tests. RESULTS: A total of 2127 responses were collected from a sample with diverse demographic, sex, work, and education characteristics. The impact of COVID-19 was considered high/very high by 60% of respondents. The volume of patients assisted weekly was lower compared with the pre-pandemic period (mean reduction = 14 ± 15 patients). A high rate of fear to contracting the COVID-19 at work was observed (85%); 4.9% of participants had a positive COVID-19 test. The main professional challenges faced by respondents were reduction in the number of patients or financial gain (35%), fear of contracting COVID-19 (34%), and burden with or difficulty in purchasing new personal protective equipment (22%). The fear to contracting COVID-19 was influenced by the number of weekly appointments. A positive test by the dentists was associated with their reports of having assisted COVID-19 patients. The most cited feelings about the pandemic were uncertainty, fear, worry, anxiety, and stress. Negative feelings were more prevalent for professionals who did not receive training for COVID-19 preventive measures and those reporting higher levels of fear to contract the disease. CONCLUSION: This multi-country survey indicated a high impact of the pandemic on dental care routines in Latin America. A massive prevalence of bad feelings was associated with the pandemic.

Patterns of End-of-Life Care as Measured by Emergency Room Visits Among Cancer Patients in Puerto Rico.

BACKGROUND: Community palliative care (PC) services are scarce in Puerto Rico (PR). Patients with advanced cancer commonly visit the emergency department(ED) at the end of life (EoL). Recognition of patients with limited life expectancies and PC needs may improve the EoL trajectory of these patients. Our objective was to characterize ED visits of cancer patients at the EoL by examining the patterns of ED visits in PR using the PR Central Cancer Registry-Health Insurance Linkage Database (PRCCR-HILD). METHODS: The cohort consisted of patients aged ≥18 years with a primary invasive that died between 2011- 2017, with a recorded date of death, and who had insurance claims during their last three months. EoL indicators were ED visits, ED death, and hospice care use. RESULTS: The study cohort included 10,755 cancer patients. 49.6% had ≥1 ED visit, 20.3% had ≥2 ED visits, and 9.7% died in the ED. In the adjusted model, female patients (aOR 0.80; 95% CI 0.68-0.93; p-value < 0.01), patients aged ≥80 years (aOR 0.47; 95% CI 0.36-0.63; p-value < 0.01), being enrolled in Medicare (aOR 0.74; 95% CI 0.61-0.90; p-value < 0.01) or being enrolled in Medicaid/Medicare (aOR 0.76; 95% CI 0.62-0.93; p-value = 0.01) were less likely to have an ED visit the date of death. Patients with distant stage are more likely to have ED ≥ 2visits (p-value < 0.05). Conclusions: ED visits at EoL can be interpreted as poor quality cancer care and awareness of the potential of ED-initiated PC is needed in PR.

High-Intensity End-of-Life Care Among Patients With GI Cancer in Puerto Rico: A Population-Based Study.

PURPOSE: High-intensity care with undue suffering among patients with cancer at the end of life (EoL) is associated with poor quality of life. We examined the pattern and predictors of high-intensity care among patients with GI cancer in Puerto Rico. METHODS: This population-based study of data from the Puerto Rico Central Cancer Registry-Health Insurance Linkage Database examined patients with GI cancer who died between 2009 and 2017. EoL care intensity indicators include the following services in the last month before death: emergency room (ER) visits, hospitalizations, intensive care unit (ICU) admissions, life-extending procedures, death in an acute care setting, and the use of chemotherapy in the last 14 days. We used logistic regression models to examine factors associated with EoL care. RESULTS: Four thousand six hundred twenty-nine patients with GI cancer were included in the analysis. We found that 11.0% of patients received chemotherapy, 17.3% had > 1 hospitalization, 9.3% were in the ICU, 18.0% had > 1 ER visit, 39.3% died in an acute care setting, and 8.6% received life-extending procedures. A compound indicator of the aggressiveness of care showed that 54.5% of patients had at least one of the selected aggressive indicators. The multivariable model showed that female patients, patients ≥ 60 years of age, patients enrolled in Medicaid, patients dually eligible for both Medicare and Medicaid, and patients who survived > 1 year were less likely to receive aggressive EoL care. CONCLUSION: Our findings support the urgent need to improve EoL care in Puerto Rico. Further studies are warranted to fully understand EoL care in patients with cancer in Puerto Rico.

Analgesic Effect of Botulinum Toxin A in Myofascial Pain Syndrome Patients Previously Treated with Local Infiltration of Anesthetic and Steroids.

The purpose of this study was to evaluate the analgesic effect of botulinum toxin A (BoNTA) injections in patients with myofascial pain syndrome (MPS) who were previously treated with the local infiltration of anesthetic and steroids (LIAS). The study included a retrospective phase and a longitudinal open-label prospective phase, which were conducted on consecutive patients with MPS previously treated with the local infiltration of anesthetic (levobupivacaíne 0.25%) and steroids (triamcinolone 40 mg). Eligible patients were treated with a single intramuscular injection of BoNTA (Botox; Allergan, Inc., Irvine, CA). The treatment efficacy was determined according to the degree of pain relief obtained. Eighty-two patients met the inclusion/exclusion criteria and were included in the study. Successful results were obtained for 32 (39.0%) and 30 (36.6%) patients, during treatment with BoNTA and LIAS, respectively. The mean (standard deviation) length of the analgesic effect was significantly longer with BoNTA (29.6 [SD = 17.7] weeks) than with LIAS (8.5 [SD = 6.4] weeks), P <.0001. As regards the side effects, 19 (23.2%) patients reported transient soreness at the injection site for 2 to 3 days with BoNTA. The MPS patients previously treated with a local infiltration of anesthetic and steroids who then received a single injection of BoNTA experienced significantly reduced pain for a relatively long time.

Critical urologic skills and procedures in the emergency department.

The evaluation and management of genitourinary emergencies is a fundamental component of the training and practice of emergency physicians. Urologic procedures are common in the emergency room. Emergency physicians play a vital role in the initial evaluation and treatment because delays in management can lead to permanent damage. This article discusses the most common urologic procedures in which emergency physicians must be proficient for rapid intervention to preserve function and avoid complications. An overview of each procedure is discussed as well as indications, contraindications, equipment, technique, and potential complications.

Posttranslational modifications affect the interaction of S100 proteins with tumor suppressor p53.

Proteins of the S100 family bind to the intrinsically disordered transactivation domain (TAD; residues 1-57) and C-terminus (residues 293-393) of the tumor suppressor p53. Both regions provide sites that are subject to posttranslational modifications, such as phosphorylation and acetylation, that can alter the affinity for interacting proteins such as p300 and MDM2. Here, we found that S100A1, S100A2, S100A4, S100A6, and S100B bound to two subdomains of the TAD (TAD1 and TAD2). Both subdomains were mandatory for high-affinity binding to S100 proteins. Phosphorylation of Ser and Thr residues increased the affinity for the p53 TAD. Conversely, acetylation and phosphorylation of the C-terminus of p53 decreased the affinity for S100A2 and S100B. In contrast, we found that nitrosylation of S100B caused a minor increase in binding to the p53 C-terminus, whereas binding to the TAD remained unaffected. As activation of p53 is usually accompanied by phosphorylation and acetylation at several sites, our results suggest that a shift in binding from the C-terminus in favor of the N-terminus occurs upon the modification of p53. We propose that binding to the p53 TAD might be involved in the stimulation of p53 activity by S100 proteins.

Reversal of coenzyme specificity of 2,3-butanediol dehydrogenase from Saccharomyces cerevisae and in vivo functional analysis.

Saccharomyces cerevisiae NAD(H)-dependent 2,3-butanediol dehydrogenase (Bdh1), a medium chain dehydrogenase/reductase is the main enzyme catalyzing the reduction of acetoin to 2,3-butanediol. In this work we focused on altering the coenzyme specificity of Bdh1 from NAD(H) to NADP(H). Based on homology studies and the crystal structure of the NADP(H)-dependent yeast alcohol dehydrogenase Adh6, three adjacent residues (Glu(221), Ile(222), and Ala(223)) were predicted to be involved in the coenzyme specificity of Bdh1 and were altered by site-directed mutagenesis. Coenzyme reversal of Bdh1 was obtained with double Glu221Ser/Ile222Arg and triple Glu221Ser/Ile222Arg/Ala223Ser mutants. The performance of the triple mutant for NADPH was close to that of native Bdh1 for NADH. The three engineered mutants were able to restore the growth of a phosphoglucose isomerase deficient strain (pgi), which cannot grow on glucose unless an alternative NADPH oxidizing system is provided, thus demonstrating their in vivo functionality. These mutants are interesting tools to reduce the excess of acetoin produced by engineered brewing or wine yeasts overproducing glycerol. In addition, they represent promising tools for the manipulation of the NADP(H) metabolism and for the development of a powerful catalyst in biotransformations requiring NADPH regeneration.

Engineering of 2,3-butanediol dehydrogenase to reduce acetoin formation by glycerol-overproducing, low-alcohol Saccharomyces cerevisiae.

Engineered Saccharomyces cerevisiae strains overexpressing GPD1, which codes for glycerol-3-phosphate dehydrogenase, and lacking the acetaldehyde dehydrogenase Ald6 display large-scale diversion of the carbon flux from ethanol toward glycerol without accumulating acetate. Although GPD1 ald6 strains have great potential for reducing the ethanol contents in wines, one major side effect is the accumulation of acetoin, having a negative sensory impact on wine. Acetoin is reduced to 2,3-butanediol by the NADH-dependent 2,3-butanediol dehydrogenase Bdh1. In order to investigate the influence of potential factors limiting this reaction, we overexpressed BDH1, coding for native NADH-dependent Bdh1, and the engineered gene BDH1(221,222,223), coding for an NADPH-dependent Bdh1 enzyme with the amino acid changes 221 EIA 223 to 221 SRS 223, in a glycerol-overproducing wine yeast. We have shown that both the amount of Bdh1 and the NADH availability limit the 2,3-butanediol dehydrogenase reaction. During wine fermentation, however, the major limiting factor was the level of synthesis of Bdh1. Consistent with this finding, the overproduction of native or engineered Bdh1 made it possible to redirect 85 to 90% of the accumulated acetoin into 2,3-butanediol, a compound with neutral sensory characteristics. In addition, the production of diacetyl, a compound causing off-flavor in alcoholic beverages, whose production is increased in glycerol-overproducing yeast cells, was decreased by half. The production of higher alcohols and esters, which was slightly decreased or unchanged in GPD1 ald6 cells compared to that in the control cells, was not further modified in BDH1 cells. Overall, rerouting carbons toward glycerol and 2,3-butanediol represents a new milestone in the engineering of a low-alcohol yeast with desirable organoleptic features, permitting the decrease of the ethanol contents in wines by up to 3 degrees.

Modulation of the oligomerization state of p53 by differential binding of proteins of the S100 family to p53 monomers and tetramers.

We investigated the ways S100B, S100A1, S100A2, S100A4, and S100A6 bind to the different oligomeric forms of the tumor suppressor p53 in vitro, using analytical ultracentrifugation and multiangle light scattering. It is established that members of the S100 protein family bind to the tetramerization domain (residues 325-355) of p53 when it is uncovered in the monomer, and so binding can disrupt the tetramer. We found a stoichiometry of one dimer of S100 bound to a monomer of p53. We discovered that some S100 proteins could also bind to the tetramer. S100B bound the tetramer and also disrupted the dimer by binding monomeric p53. S100A2 bound monomeric p53 as well as tetrameric, whereas S100A1 only bound monomeric p53. S100A6 bound more tightly to tetrameric than to monomeric p53. We also identified an additional binding site for S100 proteins in the transactivation domain (1-57) of p53. Based on our results and published observations in vivo, we propose a model for the binding of S100 proteins to p53 that can explain both activation and inhibition of p53-mediated transcription. Depending on the concentration of p53 and the member of the S100 family, binding can alter the balance between monomer and tetramer in either direction.

Sedimentación en comunidades arrecifales de Bahías de Huatulco, Oaxaca, México

Sedimentation on reef communities at Bahías de Huatulco, Oaxaca, Mexico. Although coral reef sedimentation is important because it modifies processes like symbioses, reproduction, recruitment and coral growth, Mexican Pacific studies are lacking. On this regard, spatio-temporal variations in sedimentation rate were investigated in six coral reef communities from Oaxaca. During February 2006-January 2007 (excluding April, July and August) two sediment structures, with four sediment traps each, were randomly installed. Sediment traps were replaced with a mean periodicity of 38 days, and the sediments were washed, filtered, dried and weighted in order to calculate sedimentation rate. Sedimentation rate was heterogeneous among localities 7.06, P < 0.01). It was high at Isla Montosa (653.31 kg m-2 year-1) and Isla Cacaluta (450.09 kg m-2 (F5,36 = year-1), intermediate at San Agustín, Jicaral-Chachacual and Dos Hermanas (155.18-92.53 kg m-2 year-1) and low at La Entrega (14.33 kg m-2 year-1). Sedimentation rate was homogeneous through time (F7,34 = 0.85, P > 0.5); nonetheless, during the dry season (November-March) sedimentation rate in the area oscillated between 6.8-73.5 mg cm-2 day-1, whereas during the rainy season (May-October) the values were 141-1088 % higher (74.5-147.6 mg cm-2 day-1, Mann-Whitney U = 137, n = 42, P = 0.03). There was a significant relationship between sedimentation rate and pluvial precipitation (Spearman R = 0.83, n = 8, P = 0.009), suggesting that the amount of sediment reaching coral communities is closely tied to regional precipitation. Sedimentation rates recorded at Isla Montosa (366.64 mg cm-2 day-1) and Isla Cacaluta (366.03 mg cm-2 day-1) during the rainy season can be considered lethal-sublethal considering sediment tolerance and rejection efficiency of stony corals. The absence of coral mortality during the rainy season may result from: a) high efficiency of active sediment removal, b) increased physiological tolerance to sediments, and c) a high degree of passive sediment removal via turbulence. Nonetheless, the combined effect of natural and anthropogenic induced sedimentation may cause a shift in coral community structure and eventually a loss of the reef areas in Bahías de Huatulco. Rev. Biol. Trop. 56 (3): 11791187. Epub 2008 September 30.

Aún cuando la sedimentación en arrecifes es importante pues sus efectos alteran procesos como la simbiosis, reproducción, reclutamiento y crecimiento, se carece de estudios en el Pacífico mexicano. Debido a lo anterior, se evaluó la tasa de sedimentación y su variación espacio-temporal en seis comunidades coralinas de Oaxaca. Durante febrero 2006- enero 2007 (exceptuando abril, julio y agosto), instalamos al azar dos estructuras con cuatro recolectores de sedimento cada una. Los recolectores fueron reemplazados aproximadamente cada 38 días y los sedimentos fueron enjuagados, filtrados, secados y pesados. La tasa de sedimentación fue heterogénea entre localidades 7.06, P < 0.01); fue alta en Isla Montosa (653.31 (F5,36 = kg m-2 año-1) e Isla Cacaluta (450.09 kg m-2 año-1), inter-media en San Agustín, Jicaral-Chachacual y Dos Hermanas (155.18-92.53 kg m-2 año-1) y baja en La Entrega (14.33 kg m-2 año-1). La tasa de sedimentación no varió a lo largo del año (F7,34 = 0.85, P > 0.5); no obstante, durante la temporada de secas (noviembre-marzo) la tasa de sedimentación en la zona osciló entre 6.8-73.5 mg cm-2 día-1, mientras que durante lluvias (mayo-octubre) osciló entre 74.5-147.6 mg cm-2 día-1, es decir, durante la temporada de lluvias la tasa de sedimentación fue 141-1088 % mayor que durante secas (Mann-Whitney U = 137, n = 42, P = 0.03). La relación entre la cantidad de sedimento y la precipitación pluvial fue significativa (Spearman R = 0.83, n = 8, P = 0.009), sugiriendo que el aporte de sedimento está relacionado con la escorrentía regional. La tasa de sedimentación registrada en Isla Montosa (366.64 mg cm-2 día-1) e Isla Cacaluta (366.03 mg cm-2 día-1) durante la temporada de lluvias, puede ser considerada como letal-subletal en función de la tolerancia y de la capacidad de rechazo de sedimento por parte de los corales; no obstante, la ausencia de mortalidad coralina, en respuesta a los niveles de sedimentación registrados durante la época de lluvias, y el desarrollo coralino observado en la región pudiera estar relacionado al efecto combinado de: a) la eficiencia de la remoción activa de sedimento, b) el posible incremento en la tolerancia fisiológica al sedimento por parte de los corales pétreos de Bahías de Huatulco, y c) la remoción pasiva de sedimentos vía la turbulencia de la zona. No obstante, el efecto combinado de la sedimentación natural aunado a la sedimentación resultado de actividades antropogénicas en la región, podría promover un cambio en la estructura arrecifal provocando la eventual pérdida de las comunidades coralinas en Bahías de Huatulco.

[Sedimentation on reef communities at Bahías de Huatulco, Oaxaca, Mexico]. / Sedimentación en comunidades arrecifales de Bahías de Huatulco, Oaxaca, México.

Although coral reef sedimentation is important because it modifies processes like symbioses, reproduction, recruitment and coral growth, Mexican Pacific studies are lacking. On this regard, spatio-temporal variations in sedimentation rate were investigated in six coral reef communities from Oaxaca. During February 2006-January 2007 (excluding April, July and August) two sediment structures, with four sediment traps each, were randomly installed. Sediment traps were replaced with a mean periodicity of 38 days, and the sediments were washed, filtered, dried and weighted in order to calculate sedimentation rate. Sedimentation rate was heterogeneous among localities (F,36 = 7.06, P < 0.01). It was high at Isla Montosa (653.31 kg m(-2) year(-1)) and Isla Cacaluta (450.09 kg m(-2) year(-1)), intermediate at San Agustin, Jicaral-Chachacual and Dos Hermanas (155.18-92.53 kg m(-2) year(-1)) and low at La Entrega (14.33 kg m(-2) year(-1)). Sedimentation rate was homogeneous through time (F7,34 = 0.85, P > 0.5); nonetheless, during the dry season (November-March) sedimentation rate in the area oscillated between 6.8-73.5 mg cm(-2) day(-1), whereas during the rainy season (May-October) the values were 141-1088 % higher (74.5-147.6 mg cm(-2) day(-1), Mann-Whitney U = 137, n = 42, P = 0.03). There was a significant relationship between sedimentation rate and pluvial precipitation (Spearman R = 0.83, n = 8, P = 0.009), suggesting that the amount of sediment reaching coral communities is closely tied to regional precipitation. Sedimentation rates recorded at Isla Montosa (366.64 mg cm(-2) day(-1)) and Isla Cacaluta (366.03 mg cm(-2) day(-1)) during the rainy season can be considered lethal-sublethal considering sediment tolerance and rejection efficiency of stony corals. The absence of coral mortality during the rainy season may result from: a) high efficiency of active sediment removal, b) increased physiological tolerance to sediments, and c) a high degree of passive sediment removal via turbulence. Nonetheless, the combined effect of natural and anthropogenic induced sedimentation may cause a shift in coral community structure and eventually a loss of the reef areas in Bahiás de Huatulco.

Chronic zinc deficiency induces an antioxidant adaptive response in rat lung.

Few studies are available about the role of dietary zinc (Zn) in respiratory diseases. Adult male rats were divided into 2 groups and fed respectively a moderate Zn-deficient diet and a Zn-adequate control diet. In lung tissue at 2 months, thiobarbituric acid-reactive species (TBARS), total glutathione, glutathione disulfide, protein carbonyls, metallothionein, and the activities of glutathione peroxidase (GPx), catalase, CuZn-superoxide dismutase (CuZnSOD) and glucose-6-phosphate dehydrogenase (G-6-PDH) were increased, but protein thiols decreased. In lung tissue at 4 months, TBARS, metallothionein, and the activities of CuZnSOD, Mn-superoxide dismutase (MnSOD) increased. The activities GPx, catalase, G-6-PDH were lower than control group. The changes were accompanied by histological alterations in Zn-deficient lung. The results provide evidence of the pro-oxidative effects of Zn-deficiency in lung, and suggest that the time of treatment play a key role in determining lung susceptibility to oxidative stress.