Molybdenum-Copper Antagonism In Metalloenzymes And Anti-Copper Therapy.

The connection between 3d (Cu) and 4d (Mo) via the "Mo-S-Cu" unit is called Mo-Cu antagonism. Biology offers case studies of such interactions in metalloproteins such as Mo/Cu-CO Dehydrogenases (Mo/Cu-CODH), and Mo/Cu Orange Protein (Mo/Cu-ORP). The CODH significantly maintains the CO level in the atmosphere below the toxic level by converting it to non-toxic CO2 for respiring organisms. Several models were synthesized to understand the structure-function relationship of these native enzymes. However, this interaction was first observed in ruminants, and they convert molybdate (MoO4 2- ) into tetrathiomolybdate (MoS4 2- ; TTM), reacting with cellular Cu to yield biological unavailable Mo/S/Cu cluster, then developing Cu-deficiency diseases. These findings inspire the use of TTM as a Cu-sequester drug, especially for treating Cu-dependent human diseases such as Wilson diseases (WD) and cancer. It is well known that a balanced Cu homeostasis is essential for a wide range of biological processes, but negative consequence leads to cell toxicity. Therefore, this review aims to connect the Mo-Cu antagonism in metalloproteins and anti-copper therapy.

Cerebrospinal Creatine Kinase BB Isoenzyme: A Biomarker for Predicting Outcome After Cardiac Arrest.

BACKGROUND: Cerebrospinal fluid creatine kinase BB isoenzyme (CSF CK-BB) after cardiac arrest (CA) has been shown to have a high positive predictive value for poor neurological outcome, but it has not been evaluated in the setting of targeted temperature management (TTM) and modern CA care. We aimed to evaluate CSF CK-BB as a prognostic biomarker after CA. METHODS: We performed a retrospective cohort study of patients with CA admitted between 2010 and 2020 to a three-hospital health system who remained comatose and had CSF CK-BB assayed between 36 and 84 h after CA. We examined the proportion of patients at hospital discharge who achieved favorable or intermediate neurological outcome, defined as Cerebral Performance Category score of 1-3, compared with those with poor outcome (Cerebral Performance Category score 4-5) for various CSF CK-BB thresholds. We also evaluated additive value of bilateral absence of somatosensory evoked potentials (SSEPs). RESULTS: Among 214 eligible patients, the mean age was 54.7 ± 4.8 years, 72% of patients were male, 33% were nonwhite, 17% had shockable rhythm, 90% were out-of-hospital CA, and 83% received TTM. A total of 19 (9%) awakened. CSF CK-BB ≥ 230 U/L predicted a poor outcome at hospital discharge, with a specificity of 100% (95% confidence interval [CI] 82-100%) and sensitivity of 69% (95% CI 62-76%). When combined with bilaterally absent N20 response on SSEP, specificity remained 100% while sensitivity increased to 80% (95% CI 73-85%). Discordant CK-BB and SSEP findings were seen in 13 (9%) patients. CONCLUSIONS: Cerebrospinal fluid creatine kinase BB isoenzyme levels accurately predicted poor neurological outcome among CA survivors treated with TTM. The CSF CK-BB cutoff of 230 U/L optimizes sensitivity to 69% while maintaining a specificity of 100%. CSF CK-BB could be a useful addition to multimodal neurological prognostication after CA.

Effects of the nutrition education intervention on food security, anthropometry, and body composition in women: A randomized controlled trial.

BACKGROUND: Food insecurity as a social determinant of health is associated with adverse physical health outcomes such as obesity. AIM: This study aimed to evaluate the effects of nutrition education intervention based on the transtheoretical model (TTM) on food security, anthropometry, and body composition status. METHODS: In this randomized controlled trial, an intervention was conducted over months (five weeks) using the TTM among 160 women aged 19-64 years. Food security status, anthropometry, and body composition were determined three times: at baseline, three months, and six months after the intervention. RESULTS: In the intervention group, food insecurity significantly decreased before, immediately after, and six months after the intervention, these changes were significant in follow-up time and treatment effect. After six months of follow-up, the intervention group significantly decreased weight (-1.29 kg), body mass index (-0.54), and waist circumference (-3.48 cm). Although differences between the two groups were not statistically significant except in the interaction between follow-up time and intervention groups. Also, the mean of fat mass and total body water decreased in the intervention group and differences between the two groups were statistically significant in follow-up time (p < 0.001 and p = 0.01, respectively) and interaction between follow-up time and intervention group (p < 0.001 and p = 0.005, respectively). CONCLUSION: In the current study, the findings of a six-month TTM-based intervention among women were positive that revealed to be a strategy that may improve anthropometric and nutritional status. Therefore, government programs that offer nutrition counseling should be prioritized to help the population to improve their eating habits.

Triphosphate Tunnel Metalloenzyme 2 Acts as a Downstream Factor of ABI4 in ABA-Mediated Seed Germination.

Seed germination is a complex process that is regulated by various exogenous and endogenous factors, in which abscisic acid (ABA) plays a crucial role. The triphosphate tunnel metalloenzyme (TTM) superfamily exists in all living organisms, but research on its biological role is limited. Here, we reveal that TTM2 functions in ABA-mediated seed germination. Our study indicates that TTM2 expression is enhanced but repressed by ABA during seed germination. Promoted TTM2 expression in 35S::TTM2-FLAG rescues ABA-mediated inhibition of seed germination and early seedling development and ttm2 mutants exhibit lower seed germination rate and reduced cotyledon greening compared with the wild type, revealing that the repression of TTM2 expression is required for ABA-mediated inhibition of seed germination and early seedling development. Further, ABA inhibits TTM2 expression by ABA insensitive 4 (ABI4) binding of TTM2 promoter and the ABA-insensitive phenotype of abi4-1 with higher TTM2 expression can be rescued by mutation of TTM2 in abi4-1 ttm2-1 mutant, indicating that TTM2 acts downstream of ABI4. In addition, TTM1, a homolog of TTM2, is not involved in ABA-mediated regulation of seed germination. In summary, our findings reveal that TTM2 acts as a downstream factor of ABI4 in ABA-mediated seed germination and early seedling growth.

Mild hypothermia and neurologic outcomes in patients undergoing venoarterial extracorporeal membrane oxygenation.

BACKGROUND: Patients with venoarterial extracorporeal membrane oxygenation (VA-ECMO) are at risk of cerebral reperfusion injury after prolonged hypoperfusion and immediate restoration of systemic blood flow. We aimed to examine the impact of mild hypothermia during the first 24 h post-ECMO on neurological outcomes in VA-ECMO patients. METHODS: This was a retrospective study of adult VA-ECMO patients from a tertiary care center. Mild hypothermia was defined as 32-36°C during the first 24 h post-ECMO. The primary outcome was a good neurological function at discharge measured by a modified Rankin Scale ≤3. Multivariable logistic regression analysis was performed for primary outcome adjusting for pre-specified covariates. RESULTS: Overall, 128 consecutive patients with VA-ECMO support (median age: 60 years and 63% males) were included. Within the first 24 h of VA-ECMO cannulation, we found a median of 71 readings per patient (interquartile range 45-88). Eighty-eight patients (68.8%) experienced mild hypothermia within the first 24 h while 18 of those 88 patients (14.2%) had a mean temperature <36°C. ECMO indications included post-cardiotomy shock (39.8%), cardiac arrest (29.7%), and cardiogenic shock (26.6%). Duration of mild hypothermia, but not mean temperature, was independently associated with increased odds of good neurological outcome at discharge (odds ratio [OR] = 1.16, 95% confidence interval [CI] = 1.04-1.31, p = .01) after adjusting for age, the severity of illness, post-ECMO systemic hemorrhage, post-cardiotomy shock, acute brain injury, and mean 24-h PaO2 . Neither duration of mild hypothermia (OR = 0.93, CI = 0.84-1.03, p = .17) nor mean temperature (OR = 0.78, CI = 0.29-2.08, p = .62) was significantly associated with mortality. Similarly, duration of mild hypothermia (p = .47) and mean 24-h temperature (p = .76) were not significantly associated with the frequency of systemic hemorrhages. CONCLUSIONS: In this single-center study, a longer duration of mild hypothermia during the first 24 h of ECMO support was significantly associated with improved neurological outcomes. Mild hypothermia was not associated with an increased risk of systemic hemorrhage or improved survival.

Crystal structures of the RNA triphosphatase from Trypanosoma cruzi provide insights into how it recognizes the 5'-end of the RNA substrate.

RNA triphosphatase catalyzes the first step in mRNA cap formation, hydrolysis of the terminal phosphate from the nascent mRNA transcript. The RNA triphosphatase from the protozoan parasite Trypanosoma cruzi, TcCet1, belongs to the family of triphosphate tunnel metalloenzymes (TTMs). TcCet1 is a promising antiprotozoal drug target because the mechanism and structure of the protozoan RNA triphosphatases are completely different from those of the RNA triphosphatases found in mammalian and arthropod hosts. Here, we report several crystal structures of the catalytically active form of TcCet1 complexed with a divalent cation and an inorganic tripolyphosphate in the active-site tunnel at 2.20-2.51 Å resolutions. The structures revealed that the overall structure, the architecture of the tunnel, and the arrangement of the metal-binding site in TcCet1 are similar to those in other TTM proteins. On the basis of the position of three sulfate ions that cocrystallized on the positively charged surface of the protein and results obtained from mutational analysis, we identified an RNA-binding site in TcCet1. We conclude that the 5'-end of the triphosphate RNA substrate enters the active-site tunnel directionally. The structural information reported here provides valuable insight into designing inhibitors that could specifically block the entry of the triphosphate RNA substrate into the TTM-type RNA triphosphatases of T. cruzi and related pathogens.

Heart Rate and Neurological Outcomes in Patients Undergoing Targeted Temperature Management.

INTRODUCTION: There is a paucity of data evaluating the impact of heart rate (HR) during Targeted Temperature Management (TTM) and neurologic outcomes. Current resuscitation guidelines do not specify a HR goal during TTM. We sought to determine the relationship between HR and neurologic outcomes in a single-center registry dataset. METHODS: We retrospectively studied 432 consecutive patients who completed TTM (33°C) after cardiac arrest from 2008 to 2017. We evaluated the relationship between neurologic outcomes and HR during TTM. Pittsburgh Cerebral Performance Categories (CPC) at discharge were used to determine neurological recovery. Statistical analysis included chi square, Student's t-test and Mann-Whitney U. A logistic regression model was created to evaluate the strength of contribution of selected variables on the outcome of interest. RESULTS: Approximately 94,000 HR data points from 432 patients were retrospectively analyzed; the mean HR was 82.17 bpm over the duration of TTM. Favorable neurological outcomes were seen in 160 (37%) patients. The mean HR in the patients with a favorable outcome was lower than the mean HR of those with an unfavorable outcome (79.98 bpm vs 85.67 bpm p < 0.001). Patients with an average HR of 60-91 bpm were 2.4 times more likely to have a favorable neurological outcome compared to than HR's < 60 or > 91 (odds ratio [OR] = 2.36, 95% confidence interval [CI] 1.61-3.46, p < 0.001). Specifically, mean HR's in the 73-82 bpm range had the greatest rate of favorable outcomes (OR 3.56, 95% CI 1.95-6.50), p < 0.001. Administration of epinephrine, a history of diabetes mellitus and hypertension all were associated with worse neurological outcomes independent of HR. CONCLUSION: During TTM, mean HRs between 60-91 showed a positive association with favorable outcomes. It is unclear whether a specific HR should be targeted during TTM or if heart rates between 60-91 bpm might be a sign of less neurological damage.

Pharmacological and behavioral treatment for trichotillomania: An updated systematic review with meta-analysis.

BACKGROUND: Trichotillomania (TTM) is a difficult-to-treat psychiatric condition with no first-line medications approved by the Food and Drug Administration. Individuals with TTM often feel that clinicians know little about this disorder. Here, we present an updated meta-analysis of randomized controlled trials (RCTs) examining treatments for TTM. METHODS: Pubmed, PsychINFO, Embase, and CENTRAL were searched with the terms "Trichotillomania OR Hair Pulling Disorder" to identify randomized controlled clinical trials evaluating treatments for TTM. RESULTS: Twenty-four trials involving 26 comparisons and 857 participants were included in this meta-analysis. Behavioral therapy with habit-reversal training components (BT-HRT) demonstrated a large benefit compared to control conditions (standardized mean difference [SMD] [95% CI] = -1.22 [-1.71, -0.73], p < .0001) for improving TTM symptoms. Clomipramine (SMD [95% CI] = -0.71 [-1.38, -0.05], p = .036), N-acetylcysteine (SMD [95% CI] = -0.75 [-1.36, -0.13], p = .017) and olanzapine (SMD [95% CI] = -0.94 [-1.77, -0.12], p = .025) demonstrated significant benefits compared to placebo in RCTs. CONCLUSIONS: BT-HRT has demonstrated the largest treatment effects and has the strongest evidence base for reducing TTM symptoms. In contrast, several pharmacological agents have demonstrated efficacy in single randomized clinical trials that would benefit from replication. Additional trials are needed to identify other effective medications for TTM and determine the relative efficacy of available agents.

Hypothermia Inhibits Cerebral Necroptosis and NOD-Like Receptor Pyrin Domain Containing 3 Pathway in a Swine Model of Cardiac Arrest.

BACKGROUND: Targeted temperature management (TTM) is commonly used in hypothermia after cardiopulmonary resuscitation (CPR), and its mechanism to improve cerebral function is complex. This study aimed to investigate the effects of TTM on necroptosis and the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome in the brain tissue of pigs after CPR. MATERIALS AND METHODS: Ventricular fibrillation was induced, and CPR was performed 10 min later in nine pigs in the normothermia group and nine pigs in the TTM group. The body temperature in the TTM group was dropped to 33°C after CPR and maintained for 24 h, whereas in the normothermia group, it was maintained at 38°C. Before CPR and at 30 h after CPR, serum neuron-specific enolase and S-100ß were measured. At 30 h after CPR, pigs were euthanized, and brain tissues were collected for measurement of receptor-interacting protein kinase (RIPIK) 1, RIPK3, mixed lineage kinase domain-like (MLKL), NLRP3, cysteinyl aspartate-specific proteinase (caspase)-1, interleukin (IL)-1ß, and IL-18. RESULTS: Serum neuron-specific enolase and S-100ß were increased significantly (P < 0.05) in the two CPR-treated groups compared with the sham group and more obviously in the normothermia group. In addition, the expression of RIPK3, phosphorylated MLKL, and NLRP3 in brain tissues was increased. The expression of RIPK3, phosphorylated MLKL, NLRP3, and caspase-1 as well as the levels of IL-1ß and IL-18 were lower (P < 0.05) in the TTM group compared with the normothermia group. CONCLUSIONS: Necroptosis and the NLRP3 pathway were activated after CPR. TTM may attenuate postresuscitation brain injury through the regulation of necroptosis and the NLRP3 pathway.

Intravascular versus surface cooling for targeted temperature management after out-of-hospital cardiac arrest: an analysis of the TTH48 trial.

BACKGROUND: The aim of this study was to explore the performance and outcomes for intravascular (IC) versus surface cooling devices (SFC) for targeted temperature management (TTM) after out-of-hospital cardiac arrest. METHODS: A retrospective analysis of data from the Time-differentiated Therapeutic Hypothermia (TTH48) trial (NCT01689077), which compared whether TTM at 33 °C for 48 h results in better neurologic outcomes compared with standard 24-h duration. Devices were assessed for the speed of cooling and rewarming rates. Precision was assessed by measuring temperature variability (TV), i.e., the standard deviation (SD) of all temperature measurements in the cooling phase. Main outcomes were overall mortality and poor neurological outcome, including death, severe disability, or vegetative status. RESULTS: A total of 352 patients had available data and were included in the analysis; of those, 218 (62%) were managed with IC. A total of 114/218 (53%) patients with IC and 61/134 (43%) with SFC were cooled for 48 h (p = 0.22). Time to target temperature (≤ 34 °C) was significantly shorter for patients treated with endovascular devices (2.2 [1.1-4.0] vs. 4.2 [2.7-6.0] h, p < 0.001), but temperature was also lower on admission (35.0 [34.2-35.6] vs. 35.3 [34.5-35.8]°C; p = 0.02) and cooling rate was similar (0.4 [0.2-0.8] vs. 0.4 [0.2-0.6]°C/h; p = 0.14) when compared to SFC. Temperature variability was significantly lower in the endovascular device group when compared with SFC methods (0.6 [0.4-0.9] vs. 0.7 [0.5-1.0]°C; p = 0.007), as was rewarming rate (0.31 [0.22-0.44] vs. 0.37 [0.29-0.49]°C/hour; p = 0.02). There was no statistically significant difference in mortality (endovascular 65/218, 29% vs. others 43/134, 32%; p = 0.72) or poor neurological outcome (endovascular 69/218, 32% vs. others 51/134, 38%; p = 0.24) between type of devices. CONCLUSIONS: Endovascular cooling devices were more precise than SFC methods in patients cooled at 33 °C after out-of-hospital cardiac arrest. Main outcomes were similar with regard to the cooling methods.

Confirmatory Factor Analysis of the Malay-Language Transtheoretical Model of Physical Activity among Malaysian Primary School Children.

INTRODUCTION: The transtheoretical model (TTM) is an integrative model of intentional change consisting of stages of change, processes of change, decisional balance and self-efficacy. This study aimed at validating the TTM questionnaires on physical activity for Malaysian children using confirmatory factor analysis. METHODS: The participants were 381 Malay students (188 male; 193 female), aged 10-12 years old, with a mean age of 10.94 (SD = 0.81). The original version of the TTM was translated into the Malay language using forward and backward translation. Certain phrases were adapted based on the local culture and vocabulary suitable for primary school students. RESULTS: The final measurement models and their fit indices were: processes of change (CFI = 0.939, TLI = 0.925, SRMR = 0.040, RMSEA = 0.030); decisional balance (CFI = 0.897, TLI = 0.864, SRMR = 0.045, RMSEA = 0.038); and self-efficacy (CFI = 0.934, TLI = 0.915, SRMR = 0.042, RMSEA = 0.032). CONCLUSION: Care must be taken when using the TTM with children, as it has been prevalently validated with adults. The final version of the TTM questionnaire for Malay primary school children had 24 items for process of changes, 13 items for self-efficacy and 10 items for decisional balance.

A systematic review of transfusion-transmitted malaria in non-endemic areas.

BACKGROUND: Transfusion-transmitted malaria (TTM) is an accidental Plasmodium infection caused by whole blood or a blood component transfusion from a malaria infected donor to a recipient. Infected blood transfusions directly release malaria parasites in the recipient's bloodstream triggering the development of high risk complications, and potentially leading to a fatal outcome especially in individuals with no previous exposure to malaria or in immuno-compromised patients. A systematic review was conducted on TTM case reports in non-endemic areas to describe the epidemiological characteristics of blood donors and recipients. METHODS: Relevant articles were retrieved from Pubmed, EMBASE, Scopus, and LILACS. From each selected study the following data were extracted: study area, gender and age of blood donor and recipient, blood component associated with TTM, Plasmodium species, malaria diagnostic method employed, blood donor screening method, incubation period between the infected transfusion and the onset of clinical symptoms in the recipient, time elapsed between the clinical symptoms and the diagnosis of malaria, infection outcome, country of origin of the blood donor and time of the last potential malaria exposure. RESULTS: Plasmodium species were detected in 100 TTM case reports with a different frequency: 45% Plasmodium falciparum, 30% Plasmodium malariae, 16% Plasmodium vivax, 4% Plasmodium ovale, 2% Plasmodium knowlesi, 1% mixed infection P. falciparum/P. malariae. The majority of fatal outcomes (11/45) was caused by P. falciparum whilst the other fatalities occurred in individuals infected by P. malariae (2/30) and P. ovale (1/4). However, non P. falciparum fatalities were not attributed directly to malaria. The incubation time for all Plasmodium species TTM case reports was longer than what expected in natural infections. This difference was statistically significant for P. malariae (p = 0.006). A longer incubation time in the recipient together with a chronic infection at low parasite density of the donor makes P. malariae a subtle but not negligible risk for blood safety aside from P. falciparum. CONCLUSIONS: TTM risk needs to be taken into account in order to enhance the safety of the blood supply chain from donors to recipients by means of appropriate diagnostic tools.

Pre-existing medical comorbidity is not associated with neurological outcomes in patients undergoing targeted temperature management following cardiac arrest.

The prognostic significance of chronic medical illness in comatose survivors of cardiac arrest who undergo targeted temperature management (TTM) remains largely unknown. We sought to assess the association between overall burden of pre-existing medical comorbidity and neurological outcomes in survivors of cardiac arrest undergoing TTM. We analyzed a prospectively collected cohort of 314 patients treated with TTM following cardiac arrest at a tertiary care hospital between 2007 and 2014. Overall burden of medical comorbidity was approximated with the use of the Charlson Comorbidity Index (CCI). Poor neurological outcome at hospital discharge, defined as a cerebral performance category (CPC) score >2, was the primary outcome. Secondary outcomes included death prior to hospital discharge and at 1 year following cardiac arrest. Multivariable logistic regression was used to assess the association between CCI scores and outcomes. A poor neurological outcome at hospital discharge was observed in 193 (61%) patients. One hundred and seventy-nine (57%) patients died prior to hospital discharge and a total of 195 (62%) patients had died at 1-year post-arrest. In multivariable logistic regression, elevated CCI scores were not associated with increased odds of poor neurological outcomes (OR 1.04, 95% CI 0.90-1.19, p = 0.608) or death (OR 0.99, 95% CI 0.86-1.13, p = 0.816) at hospital discharge. No association was seen between CCI scores and death at 1-year post-arrest (OR 1.09, 95% CI 0.95-1.26, p = 0.220). Increasing burden of medical comorbidity, as defined by CCI scores, is not associated with neurological outcomes or survival in patients treated with TTM.

Temperature variability during targeted temperature management is not associated with neurological outcomes following cardiac arrest.

INTRODUCTION: Recent studies on comatose survivors of cardiac arrest undergoing targeted temperature management (TTM) have shown similar outcomes at multiple target temperatures. However, details regarding core temperature variability during TTM and its prognostic implications remain largely unknown. We sought to assess the association between core temperature variability and neurological outcomes in patients undergoing TTM following cardiac arrest. METHODS: We analyzed a prospectively collected cohort of 242 patients treated with TTM following cardiac arrest at a tertiary care hospital between 2007 and 2014. Core temperature variability was defined as the statistical variance (i.e. standard deviation squared) amongst all core temperature recordings during the maintenance phase of TTM. Poor neurological outcome at hospital discharge, defined as a Cerebral Performance Category (CPC) score>2, was the primary outcome. Death prior to hospital discharge was assessed as the secondary outcome. Multivariable logistic regression was used to examine the association between temperature variability and neurological outcome or death at hospital discharge. RESULTS: A poor neurological outcome was observed in 147 (61%) patients and 136 (56%) patients died prior to hospital discharge. In multivariable logistic regression, increased core temperature variability was not associated with increased odds of poor neurological outcomes (OR 0.38, 95% CI 0.11-1.38, p=0.142) or death (OR 0.43, 95% CI 0.12-1.53, p=0.193) at hospital discharge. CONCLUSION: In this study, individual core temperature variability during TTM was not associated with poor neurological outcomes or death at hospital discharge.

Protective effect of Trillium tschonoskii saponin on CCl4-induced acute liver injury of rats through apoptosis inhibition.

To explore hepatoprotective role and underlying mechanisms of Trillium tschonoskii Maxim (TTM), 36 rats were randomly divided into control, CCl4-induced liver injury model, and biphenyl dimethyl dicarboxylate (DDB) and low-, moderate-, and high-dose TTM treatment groups. After CCl4-induced model establishment, the rats from DDB and TTM groups were administrated with DDB at 0.2 g/kg per day and TTM at 0.1, 0.5, and 1.0 g/kg per day, while the rats from control and model groups were administrated with saline. After 5 days of treatments, all rats were sacrificed for determining serum ALT and AST levels and liver index, examining histopathological changes in liver through HE and TUNEL staining, and evaluating TNF-α and IL-6 mRNA expression by real-time PCR, and caspase-3, Bcl-2, and Bax expression by Western blot. Results indicated that CCl4 could induce acute liver injury and abnormal liver function in rats with obvious hepatomegaly, increased liver index, high ALT and AST levels, up-regulated TNF-α and IL-6, and overexpressed Bax and caspase-3. However, DDB and TTM could execute protective role in CCl4-induced liver injury in rats through reducing ALT and AST levels, rescuing hepatomegaly, down-regulating inflammatory factors and inhibiting hepatocyte apoptosis in a dose-dependent manner. Therefore, TTM has obvious protective role in CCl4-induced liver injury of rats through inhibiting hepatocyte apoptosis.

Stages and Processes of Change Utilized by Female Sex Workers Participating in an Alcohol-Reduction Intervention in Mombasa, Kenya.

BACKGROUND: According to the transtheoretical model (TTM) behavior change occurs through a series of steps when an individual becomes aware of a behavior, prepares to change, and executes those changes using certain processes. This model has not yet been used to describe alcohol-reduction behavior change processes in resource-limited settings. OBJECTIVE: This qualitative analysis aimed to describe and characterize the stages and processes of change employed by female sex workers in Mombasa, Kenya during the course of their participation in a 6-month alcohol reduction intervention. METHODS: In 2011-2012, clinical interviews were conducted with 45 female sex workers. One interview was conducted each month during the intervention period, resulting in a total of six transcripts per participant. During each interview, the counselor noted the participant's stage of change and recent alcohol use. The clinical notes were analyzed via qualitative coding techniques and organized into matrices to classify alcohol reduction strategies discussed by participants. RESULTS: Participants discussed using the stage-specific processes of change described by the TTM to reduce their alcohol use and maintain the behavior change. Participants who were HIV-positive at the start of the intervention seemed to progress to the action/maintenance stage more quickly than HIV-negative participants. CONCLUSIONS/IMPORTANCE: Results suggest that the TTM constructs may be relevant in understanding the alcohol reduction behavior change process of an at-risk population in a resource-limited setting. Future quantitative research should seek to validate the TTM's application internationally. Alcohol interventions should consider tailoring content to participants' stages of change and HIV-status for increased effectiveness.

Structural determinants of specificity and catalytic mechanism in mammalian 25-kDa thiamine triphosphatase.

BACKGROUND: Thiamine triphosphate (ThTP) is present in most organisms and might be involved in intracellular signaling. In mammalian cells, the cytosolic ThTP level is controlled by a specific thiamine triphosphatase (ThTPase), belonging to the CYTH superfamily of proteins. CYTH proteins are present in all superkingdoms of life and act on various triphosphorylated substrates. METHODS: Using crystallography, mass spectrometry and mutational analysis, we identified the key structural determinants of the high specificity and catalytic efficiency of mammalian ThTPase. RESULTS: Triphosphate binding requires three conserved arginines while the catalytic mechanism relies on an unusual lysine-tyrosine dyad. By docking of the ThTP molecule in the active site, we found that Trp-53 should interact with the thiazole part of the substrate molecule, thus playing a key role in substrate recognition and specificity. Sea anemone and zebrafish CYTH proteins, which retain the corresponding Trp residue, are also specific ThTPases. Surprisingly, the whole chromosome region containing the ThTPase gene is lost in birds. CONCLUSIONS: The specificity for ThTP is linked to a stacking interaction between the thiazole heterocycle of thiamine and a tryptophan residue. The latter likely plays a key role in the secondary acquisition of ThTPase activity in early metazoan CYTH enzymes, in the lineage leading from cnidarians to mammals. GENERAL SIGNIFICANCE: We show that ThTPase activity is not restricted to mammals as previously thought but is an acquisition of early metazoans. This, and the identification of critically important residues, allows us to draw an evolutionary perspective of the CYTH family of proteins.

Simulations of Femtosecond-Laser Near-Field Ablation Using Nanosphere under Dynamic Excitation.

Femtosecond lasers have garnered widespread attention owing to their subdiffraction processing capabilities. However, their intricate natures, involving intrapulse feedbacks between transient material excitation and laser propagation, often present significant challenges for near-field ablation predictions and simulations. To address these challenges, the current study introduces an improved finite-difference time-domain method (FDTD)-plasma model (plasma)-two-temperature model (TTM) framework for simulating the ablation processes of various nanospheres on diverse substrates, particularly in scenarios wherein dynamic and heterogeneous excitations significantly influence optical-field distributions. Initially, FDTD simulations of a single Au nanosphere on a Si substrate reveal that, with transitions in the excitation states of the substrate, the field-intensity distribution transforms from a profile with a single central peak to a bimodal structure, consistent with experimental reports. Subsequently, simulations of a polystyrene nanosphere array on a SiO2 substrate reveal that different excitation states of the nanospheres yield two distinct modes, namely near-field enhancement and masking. These modes cannot be adequately modeled in the FDTD simulations. Our combined model also considers the intrapulse feedback between the electromagnetic-field distribution resulting from near-field effects and material excitations. Furthermore, the model can quantitatively analyze subsequent electron-phonon coupling and material removal processes resulting from thermal-phase transitions. Consequently, our model facilitates predictions of the femtosecond-laser ablation of single nanospheres or nanosphere arrays with varying sizes and materials placed on substrates subjected to near-field effects.

Targeted Temperature Management for Traumatic Asphyxia: A Case Report.

Traumatic asphyxia (TA) is a rare condition due to severe crush injury to the upper abdomen or chest region. Elevated intrathoracic pressure causes impaired venous return, which damages the small vessels. Consciousness is reportedly lost in many TA cases. In the most severe cases, hypoxic encephalopathy occurs. Since TA patients usually have other traumatic complications such as thoracic or abdominal injury, the mortality rate of this syndrome is quite variable. Hypothermia is a risk factor for mortality in trauma patients, and targeted temperature management (TTM) is rarely performed for trauma cases. There are scattered articles reporting the usefulness of TTM in severe traumatic brain injury. To our best knowledge, there have been no reports of TTM in TA cases. We herein report a TA case with decorticate rigidity having a good neurological outcome after TTM.