Lipids and oocyte developmental competence: the role of fatty acids and β-oxidation.
Metabolism and ATP levels within the oocyte and adjacent cumulus cells are associated with quality of oocyte and optimal development of a healthy embryo. Lipid metabolism provides a potent source of energy and its importance during oocyte maturation is being increasingly recognised. The triglyceride and fatty acid composition of ovarian follicular fluid has been characterised for many species and is influenced by nutritional status (i.e. dietary fat, fasting, obesity and season) as well as lactation in cows. Lipid in oocytes is a primarily triglyceride of specific fatty acids which differ by species, stored in distinct droplet organelles that re-localise during oocyte maturation. The presence of lipids, particularly saturated vs unsaturated fatty acids, in in vitro maturation systems affects oocyte lipid content as well as developmental competence. Triglycerides are metabolised by lipases that have been localised to cumulus cells as well as oocytes. Fatty acids generated by lipolysis are further metabolised by β-oxidation in mitochondria for the production of ATP. β-oxidation is induced in cumulus-oocyte complexes (COCs) by the LH surge, and pharmacological inhibition of β-oxidation impairs oocyte maturation and embryo development. Promoting β-oxidation with l-carnitine improves embryo development in many species. Thus, fatty acid metabolism in the mammalian COC is regulated by maternal physiological and in vitro environmental conditions; and is important for oocyte developmental competence.


Are people at risk of psychosis also at risk of suicide and self-harm? A systematic review and meta-analysis.
Suicide and self-harm are prevalent in individuals diagnosed with psychotic disorders. However, less is known about the level of self-injurious thinking and behaviour in those individuals deemed to be at ultra-high risk (UHR) of developing psychosis, despite growing clinical interest in this population. This review provides a synthesis of the extant literature concerning the prevalence of self-harm and suicidality in the UHR population, and the predictors and correlates associated with these events. A search of electronic databases was undertaken by two independent reviewers. A meta-analysis of prevalence was undertaken for self-harm, suicidal ideation and behaviour. A narrative review was also undertaken of analyses examining predictors and correlates of self-harm and suicidality. Twenty-one eligible studies were identified. The meta-analyses suggested a high prevalence of recent suicidal ideation (66%), lifetime self-harm (49%) and lifetime suicide attempts (18%). Co-morbid psychiatric problems, mood variability and a family history of psychiatric problems were among the factors associated with self-harm and suicide risk. Results suggest that self-harm and suicidality are highly prevalent in the UHR population, with rates similar to those observed in samples with diagnosed psychotic disorders. Appropriate monitoring and managing of suicide risk will be important for services working with the UHR population. Further research in this area is urgently needed considering the high rates identified.


Oxycodone withdrawal induces HDAC1/HDAC2-dependent transcriptional maladaptations in the reward pathway in a mouse model of peripheral nerve injury.
The development of physical dependence and addiction disorders due to misuse of opioid analgesics is a major concern with pain therapeutics. We developed a mouse model of oxycodone exposure and subsequent withdrawal in the presence or absence of chronic neuropathic pain. Oxycodone withdrawal alone triggered robust gene expression adaptations in the nucleus accumbens, medial prefrontal cortex and ventral tegmental area, with numerous genes and pathways selectively affected by oxycodone withdrawal in mice with peripheral nerve injury. Pathway analysis predicted that histone deacetylase (HDAC) 1 is a top upstream regulator in opioid withdrawal in nucleus accumbens and medial prefrontal cortex. The novel HDAC1/HDAC2 inhibitor, Regenacy Brain Class I HDAC Inhibitor (RBC1HI), attenuated behavioral manifestations of oxycodone withdrawal, especially in mice with neuropathic pain. These findings suggest that inhibition of HDAC1/HDAC2 may provide an avenue for patients with chronic pain who are dependent on opioids to transition to non-opioid analgesics.


The gene encoding atrial natriuretic peptide and the risk of human stroke.
Recent evidence from an animal model of stroke, the stroke-prone spontaneously hypertensive rat, implicated the gene encoding atrial natriuretic peptide (ANP) as a possible candidate contributing to the likelihood of experiencing a stroke. The purpose of the present study was to investigate the role of ANP in the pathogenesis of cerebrovascular accidents in humans. We investigated 2 previously known markers at ANP, G1837A and T2238C, for their possible association with the occurrence of stroke. This was the largest matched case-controlled sample studied thus far; the sample was drawn from a large prospective study (the Physician's Health Study). When assuming a dominant mode of inheritance, a statistically significant positive association was observed for the 1837A allele, indicating an odds ratio of 1.64 (95% confidence interval, 1.01 to 2.65) for stroke. This observation led to the discovery of a new molecular variant in exon 1, G664A, which was responsible for a valine-to-methionine substitution in the proANP peptide. This mutation, which was in linkage disequilibrium with the G1837A marker, was associated with the occurrence of stroke (odds ratio, 2.0; 95% confidence interval, 1.17 to 3.19; P=0.01). Our findings suggest that molecular variants of the ANP gene may represent an independent risk factor for cerebrovascular accidents in humans. The strong parallelism to the experimental data obtained in the stroke-prone animal model provides assurance for the relevance of our observation.


Correcting high anisometropia: two case reports.
In the cases reported, the anisometropia had not been corrected previously. Despite the common belief that such a correction would induce intolerable symptoms in adults, both patients successfully adapted to the full correction within a few days, showing marked improvement in binocular vision skills.


Hyperthermic and hypothermic effects of morphine in mice: interactions with apomorphine and pilocarpine and changes in sensitivity after caudate nucleus lesions.
In mice, both apomorphine and pilocarpine either potentiated a hypothermic effect of a high dose of morphine or reversed a hyperthermic effect of a low dose of morphine to a hypothermic effect. Haloperidol paritally blocked the hypothermic effect but not the hyperthermic effect of morphine. Scopolamine partially blocked the hyperthermic but not the hypothermic effect of morphine. Bilateral lesions of the caudate nuclei produced no changes in sensitivity to either the acute hyperthermic or hypothermic effect of morphine but did selectively facilitate the developement of tolerance to morphine-induced hypothermia. The results suggest that morphine's temperature effects are determined by the interaction of several mechanisms and that the caudate nucleus may have a specific role in drug tolerance.


The free energy landscape of small molecule unbinding.
The spontaneous dissociation of six small ligands from the active site of FKBP (the FK506 binding protein) is investigated by explicit water molecular dynamics simulations and network analysis. The ligands have between four (dimethylsulphoxide) and eleven (5-diethylamino-2-pentanone) non-hydrogen atoms, and an affinity for FKBP ranging from 20 to 0.2 mM. The conformations of the FKBP/ligand complex saved along multiple trajectories (50 runs at 310 K for each ligand) are grouped according to a set of intermolecular distances into nodes of a network, and the direct transitions between them are the links. The network analysis reveals that the bound state consists of several subbasins, i.e., binding modes characterized by distinct intermolecular hydrogen bonds and hydrophobic contacts. The dissociation kinetics show a simple (i.e., single-exponential) time dependence because the unbinding barrier is much higher than the barriers between subbasins in the bound state. The unbinding transition state is made up of heterogeneous positions and orientations of the ligand in the FKBP active site, which correspond to multiple pathways of dissociation. For the six small ligands of FKBP, the weaker the binding affinity the closer to the bound state (along the intermolecular distance) are the transition state structures, which is a new manifestation of Hammond behavior. Experimental approaches to the study of fragment binding to proteins have limitations in temporal and spatial resolution. Our network analysis of the unbinding simulations of small inhibitors from an enzyme paints a clear picture of the free energy landscape (both thermodynamics and kinetics) of ligand unbinding.


DNA repair and resistance to topoisomerase I inhibitors: mechanisms, biomarkers and therapeutic targets.
Irinotecan and topotecan are derivatives of the naturally occurring cytotoxic compound camptothecin that are used in the treatment of patients with colorectal cancer, either as single agents or in combination with radiotherapy and/or other chemotherapy drugs. They are inhibitors of DNA topoisomerase I (Top I) and exert their cytotoxic effects in replicating cells by inducing DNA strand breaks. A wide range of DNA repair proteins is involved in the recognition and repair of these breaks, and depletion or inhibition of some of these proteins increases the cytotoxic effects of Top I inhibitors. Building on these laboratory observations, ongoing translational research is aiming to establish whether this mechanistic information can be used to improve the treatment of patients with certain types of cancer. Two potential strategies are under investigation: (1) individualising treatment by evaluating levels and/or patterns of expression of DNA repair proteins that predict clinical response to Top I inhibitors, and (2) developing small molecule inhibitors of these repair enzymes to overcome tumour resistance and improve outcomes. This review summarises the current status of these research endeavours, focusing on the key roles of tyrosyl DNA phosphodiesterase 1 (Tdp1) and poly(ADP-ribose) polymerase (PARP), and examines the pre-clinical and clinical data that support the potential value of these and other DNA repair proteins as predictive markers and therapeutic targets. Since irinotecan is increasingly being combined with radiotherapy, the potential for these proteins to act as predictive biomarkers for both Top I inhibitors and radiation is proposed, and the possibility of synergistic potentiation of chemoradiation regimes by Tdp1 and/or PARP inhibitors is considered.


Linking genotype to phenotype: the International Rice Information System (IRIS).
The International Rice Information System (IRIS, http://www.iris.irri.org) is the rice implementation of the International Crop Information System (ICIS, http://www.icis.cgiar.org), a database system for the management and integration of global information on genetic resources and germplasm improvement for any crop. Building upon the germplasm genealogy and field data components of ICIS, IRIS is being extended to handle diverse rice genomics data including: genetic mapping, genome annotation, genotype, mutant, transcripteome, proteome and metabolomic data. Users can access information in the database through stand-alone programs and WWW interfaces offering specialist views to researchers with different interests.


A novel compartmental model to capture the nonlinear trend of COVID-19.
The COVID-19 pandemic took the world by surprise and surpassed the expectations of epidemiologists, governments, medical experts, and the scientific community as a whole. The majority of epidemiological models failed to capture the non-linear trend of the susceptible compartment and were unable to model this pandemic accurately. This study presents a variant of the well-known SEIRD model to account for social awareness measures, variable death rate, and the presence of asymptomatic infected individuals. The proposed SEAIRDQ model accounts for the transition of individuals between the susceptible and social awareness compartments. We tested our model against the reported cumulative infection and death data for different states in the US and observed over 98.8% accuracy. Results of this study give new insights into the prevailing reproduction number and herd immunity across the US.


Transfer function analysis of the circulation: unique insights into cardiovascular regulation.
We have demonstrated previously that transfer function analysis can be used to precisely characterize the respiratory sinus arrhythmia (RSA) in normal humans. To further investigate the role of the autonomic nervous system in RSA and to understand the complex links between respiratory activity and arterial pressure, we determined the transfer functions between respiration, heart rate (HR), and phasic, systolic, diastolic, and pulse arterial pressures in 14 healthy subjects during 6-min periods in which the respiratory rate was controlled in a predetermined but erratic fashion. Pharmacological autonomic blockade with atropine, propranolol, and both, in combination with changes in posture, was used to characterize the sympathetic and vagal contributions to these relationships, as well as to dissect the direct mechanical links between respiration and arterial pressure from the effects of the RSA on arterial pressure. We found that 1) the pure sympathetic (standing + atropine) HR response is characterized by markedly reduced magnitude at frequencies greater than 0.1 Hz and a phase delay, whereas pure vagal (supine + propranolol) modulation of HR is characterized by higher magnitude at all frequencies and no phase delay; 2) both the mechanical links between respiration and arterial pressure and the RSA contribute significantly to the effects of respiration on arterial pressure; 3) the RSA contribution to arterial pressure fluctuations is significant for vagal but not for sympathetic modulation of HR; 4) the mechanical effects of respiration on arterial pressure are related to the negative rate of change of instantaneous lung volume; 5) the mechanical effects have a higher magnitude during systole than during diastole; and 6) the mechanical effects are larger in teh standing than the supine position. Most of these findings can be explained by a simple model of circulatory control based on previously published experimental transfer functions from our laboratory.


Out-of-pocket expenditure by Australian seniors with chronic disease: the effect of specific diseases and morbidity clusters.
Out of pocket expenditure (OOPE) on healthcare is related to the burden of illness and the number of chronic conditions a patient experiences, but the relationship of these costs to particular conditions and groups of conditions is less studied. This study examines the effect on OOPE of various morbidity groupings, and explores the factors associated with a 'heavy financial burden of OOPE' defined by an expenditure of over 10% of equivalised household income on healthcare. Data were collected from 4,574 senior Australians using a stratified sampling procedure by age, rurality and state of residence. Natural clusters of chronic conditions were identified using cluster analysis and clinically relevant clusters based on expert opinion. We undertook logistic regression to model the probability of incurring OOPE, and a heavy financial burden; linear regression to explore the significant factors of OOPE; and two-part models to estimate the marginal effect of factors on OOPE. The mean OOPE in the previous three months was AU$353; and 14% of respondents experienced a heavy financial burden. Medication and medical service expenses were the major costs. Those who experienced cancer, high blood pressure, diabetes or depression were likely to report higher OOPE. Patients with cancer or diabetes were more likely than others to face a heavy burden of OOPE relative to income. Total number of conditions and some specific conditions predict OOPE but neither the clusters nor pairs of conditions were good predictors of OOPE. Total number of conditions and some specific conditions predict both OOPE and heavy financial burden but particular comorbid groupings are not useful in predicting OOPE. Low-income patients pay a higher proportion of income than the well-off as OOPE for healthcare. Interventions targeting those who are likely to face severe financial burdens due to their health could address some of these differences.


Role of consolidation with yttrium-90 ibritumomab tiuxetan in patients with advanced-stage follicular lymphoma.
Non-Hodgkin's lymphoma (NHL) accounts for 4% of all cancers diagnosed in the United States. Follicular lymphoma (FL) is the most common type of indolent NHL with a survival from 5 to 15 years. Although it is very sensitive to chemotherapy and radiotherapy, relapses are the main cause of therapeutic failure, and currently there is no consensus on the first-line treatment and optimal therapeutic strategies for patients with FL. Immediate treatment offers any survival benefit for asymptomatic and more indolent disease. In order to improve outcomes in FL, extend the remission, postpone the need for chemotherapy and improve OS, maintenance therapies with rituximab and consolidation treatments represent very attractive strategies. (90)Y-ibritumomab tiuxetan ((90)Y-IT, Zevalin®) is approval as consolidation therapy in previously untreated FL patients who achieve response to first-line chemotherapy. Consolidation therapy with (90)Y-IT after initial induction treatment has shown improved activity compared with induction chemotherapy alone, even in patients previously treated with rituximab, in one phase III and several phase II trials, improving progression-free survival (PFS) and rate of conversion from partial response (PR) to complete response (CR). The phase III international FIT trial shows an improvement in PFS that is maintained after a median follow up of 7.3 years. Several phase II trials show high rate of conversion from PR to CR and a significant improvement in PFS. Treatment is feasible and well tolerated although myelodysplastic syndrome cases has been observed in some trials. (90)Y-IT should be considered for the initial treatment of FL in patients who are unable to tolerate standard chemotherapy, e.g., elderly or frail patients and otherwise in high-risk patients who achieve a PR or CR due to improvements in CR rate and PFS.


Staphylococcus aureus Bacteremia in Children: Antibiotic Resistance and Mortality.
Staphylococcus aureus (SA) is a major cause of bacteremia in children. Methicillin-resistant SA (MRSA) is considered a public health threat; however, the differences in the prognosis of children with methicillin-susceptible SA (MSSA) versus MRSA bacteremia are not well defined. Data from all SA bacteremia events in children (0-16 years) from 2002 to 2016 in a single Israeli tertiary center were collected. Positive cultures within 48 hours of hospitalization were considered community associated (CA). Those obtained afterward or from children hospitalized within the previous year were considered health-care associated (HA). We recorded 427 events, 284 (66%) were HA, 64 (15%) were MRSA and 9 (2%) were CA-MRSA. There was no increase in MRSA during the study period. In-hospital, 30-day and 1-year mortality were 3% (12 cases), 3.5% (16 cases), and 12% (50 cases), respectively. A multivariable analysis controlling for demographics, admitting department and prior morbidity showed an increased 1-year mortality in children with HA bacteremia (hazard ratio [HR] 4.1; 95% confidence interval [CI]: 1.3-12) and prior chronic disease (HR 3.4; 95% CI 1.2 to 9.0). MRSA was not independently associated with increased one-year mortality compared with MSSA: HR (95% CI: 1.4 [0.6-3.1]). Short-term pediatric mortality after SA bacteremia is low. HA-SA bacteremia has an increased long-term risk for mortality, particularly in children with chronic diseases. Our data suggest mortality was not increased for MRSA compared with MSSA bacteremia. The very low rate of CA-MRSA bacteremia justifies the current practice not to include glycopeptides in the empiric treatment of CA bacteremia in Israel.


Coronary air embolism during removal of a central venous catheter.
Acute air embolism has been described during central venous cannulation, but it may also occur during catheter removal in a spontaneously breathing patient. We describe an episode of acute coronary ischaemia that occurred during CV catheter removal. A 23-year-old male, multiple trauma patient was treated over 27 days in an ITU. He required a tracheostomy, two weeks of mechanical ventilation, and several surgical interventions. On the 27th day, he was scheduled to be transferred to a low-dependency area and his CVC was removed from the left subclavian vein. After five minutes, the pressure pad was released from the site of cannulation; the patient started coughing and became dyspnoeic. He developed tachyarrhythmia with ST depression in the 2nd, 3rd and aVF leads, followed by marked ST elevation, and subsequently, ventricular fibrillation. The patient was placed in the Trendelenburg position and CPR was started. Normal sinus rhythm returned after three defibrillations. Echocardiography revealed the presence of a large amount of air bubbles within the left ventricle, which disappeared spontaneously within one minute. The patient quickly regained consciousness and his condition returned to normal within 12 h, with transient elevation of heart enzymes. Five days later, he was decannulated and transferred to the orthopaedic ward in a satisfactory condition. Air embolism during CV catheter removal is a rare event, but it may occur when a persistent tunnel remains after prolonged cannulation, associated with negative intrathoracic pressure created by a spontaneously breathing or coughing patient. In the case described, acute myocardial ischaemia occurred in the region supplied by the right coronary artery, which is located higher than the left one and is therefore more exposed to air bubbles. We could not demonstrate, however, the presence of a persistent foramen ovale, however some connection had to exist between the right and left sides of the heart in our patient. Special caution should be exercised during CV catheter removal, and the procedure should be always done with the patient placed in the Trendelenburg position.


Phytochemical characterisation of green beans (Phaseolus vulgaris L.) by using high-performance liquid chromatography coupled with time-of-flight mass spectrometry.
Although green beans (Phaseolus vulgaris L.) constitute a major agro-industrial crop worldwide and involve many bean varieties, the phytochemical composition and how this fluctuates among varieties is not well known. The purpose of this work was to conduct a comprehensive characterisation of the phytochemical compounds found in three varieties of green bean. Hydromethanol extracts from green beans were analysed by high-performance liquid chromatography (HPLC) coupled with electrospray time-of-flight mass spectrometry (ESI-TOF-MS) in order to characterise phytochemical compounds from different varieties of P. vulgaris L. The compounds were characterised based on interpreting their mass spectrum provided by the TOF-MS as well as by comparison with information from the literature (some compounds have been described previously in Fabaceae). In this work, 72 phytochemical compounds were tentatively characterised by HPLC-ESI-TOF-MS. These compounds were classified as, 10 phenolic acids, 59 flavonoids, two lignans and an iridoid. Notably, out of the 72 compounds, 54 are new and their isomers have been characterised for the first time in green beans. The phytochemical composition of three different varieties of P. vulgaris L have been characterised using HPLC-ESI-TOF-MS. A total of 72 phytochemical compounds were characterised, 54 being reported in green beans for the first time. Among these were the main flavonoids detected. These results highlight the influence that variety can exert on the quality of phytochemicals. Given that new phytochemical compounds have been characterised, this study offers a useful approach for improving and updating the food-composition tables.


Diagnostic evaluation and considerations in hypocellular bone marrow failure-A focus on genomics.
Hypocellular bone marrow failure (BMF) has myriad differential diagnoses, most simply considered as acquired and inherited disorders, which are frequently indistinguishable upon morphologic examination of the blood and bone marrow. Accurate diagnosis is critical to optimization of management and begins with a detailed history (including family history) and physical examination. Next-generation sequencing technologies complement traditional testing techniques (such as chromosomal fragility and telomere length assessment) and have a broad application in the diagnosis and prognostication of BMF, with the importance of detection of both germline changes and also somatic variants increasingly well understood and appreciated. There is increasing awareness of germline predisposition to haematological malignancy, which incorporates but is not limited to the traditional inherited BMF syndromes and which raises challenges for counselling, monitoring and treatment of people who harbour a germline lesion. There are many benefits to both patients and their kindred of accurate determination of the precise germline change underlying heritable bone marrow diseases, along with its associated mode of inheritance. While individually, these diseases are rare, collectively they are not so and there are many collaborative efforts underway to document the natural history of these disorders, the associated phenotypes and the ever-increasing list of variants which have sufficient evidence to warrant the ascription of a pathogenic classification. We describe the many diagnostic considerations when evaluating newly presenting patients with hypocellular BMF, with a focus on genomic assessment, which is relevant in both germline and acquired diseases.


Ifugao males, learning and teaching for the improvement of maternal and child health status in the Philippines: an evaluation of a program.
Improving Maternal and Child Health (MCH) is a prioritized global agenda in achieving the United Nations Millennium Development Goal 5. In this challenge, involving males has been an important agenda, and a program with such intent was conducted in Alfonso Lista, Ifugao, of the Philippines. The objectives of this study were: (1) to evaluate the effectiveness in knowledge, attitude, and practice before and after a MCH session; (2) to evaluate the session's effectiveness in relation to socio-demographic characteristics; and (3) to examine if males who have learned about MCH topics can teach another group of males. A male community representative who received a lecture from the health office staff was assigned to teach a group of community males [Group 1, N = 140] in 5 sessions, using educational materials. 10 male volunteers from Group 1 then taught a different group of males [Group 2, N = 105] in their own barangays (villages). To evaluate its effectiveness, a self-administered questionnaire survey pertaining knowledge, attitude and practice regarding MCH was conducted at three different time points: before the session (Time 1, T1), after the session (Time 2, T2), and 3 months following the session (Time 3, T3). A repeated measures analysis of variance was conducted to test for changes over time and its interaction effect between specific socio-demographic variables. In Group 1, there was a significant positive increase in knowledge score over time at T1-T2 and T1-T3 (p < 0.001). For attitude, the score increased only at T1-T2 (p = 0.027). The effectiveness in knowledge and attitude did not vary by socio-demographic characteristics. As for practice, majority of the participants reported that they had talked about MCH topics in their community and assisted a pregnant woman in some ways. A comparison between Group 1 and Group 2 revealed that Group 2 had similar effectiveness as Group 1 in knowledge improvement immediately after the session (p < 0.001), but no such improvement in the attitude score. Although the change in attitude needs further assessment, this strategy of continuous learning and teaching of MCH topics within community males is shown to improve knowledge and has a potential to uplift the MCH status, including the reduction of maternal deaths, in Alfonso Lista, Ifugao, Philippines.


Substernal oxyphil parathyroid adenoma producing PTHrP with hypercalcemia and normal PTH level.
Parathyroid adenoma is the most common cause of primary hyperparathyroidism. Preoperative serum calcium and intact-parathyroid hormone levels are the most useful diagnostic parameters that allow differentiating primary hyperparathyroidism from non-parathyroid-dependent hypercalcemia. Parathyroidectomy is the definitive treatment for primary hyperparathyroidism. Approximately 5% of patients who underwent parathyroidectomy present with persistent or recurrent hyperparathyroidism due to ectopic localization of the adenoma. Functioning oxyphil parathyroid adenoma is an uncommon histological form, seldom causing primary hyperparathyroidism. Parathyroid adenoma with hypercalcemia exhibiting normal parathyroid hormone level is rare. An incidence of 5% to 33% has been documented in the literature; no etiologic explanation has been given. In 1987, parathyroid-hormone-related peptide was isolated as a causative factor of humeral hypercalcemia of malignancy. The presence of parathyroid-hormone-related peptide in parathyroid tissue under normal and pathological conditions has been described in the literature; however, its role in causing hyperparathyroidism has not yet been defined. We present a case of persistent hypercalcemia with a normal level of intact-parathyroid hormone due to a substernal parathyroid adenoma, treated with radioguided parathyroidectomy. The final histological diagnosis was oxyphil adenoma, positive for parathyroid-hormone-related peptide antigens. In clinical practice, this atypical biochemical presentation of primary hyperparathyroidism should be considered in the differential diagnosis of hypercalcemia. The parathyroid-hormone-related peptide should be considered not only in the presence of malignancy.


Isolation and characterization of microcrystalline cellulose from an agro-waste tamarind (Tamarindus indica) seeds and its suitability investigation for biofilm formulation.
The exploration of potential bio-fillers for bio-film application is a promising approach to ensure biodegradable, eco-friendly, good-quality materials with high-performance applications. This is a comprehensive study executed to establish the utility of an agro-waste Tamarindus indica seeds for microcrystalline cellulose production and to assess its feasibility for biofilm fabrication. The extraction was carried out through consecutive chemical-mediated alkalization, acid hydrolysis and bleaching. The isolated microcrystalline cellulose from Tamarindus indica seeds (TSMCC) was characterized through chemical, thermal and morphological characterization to validate the cellulose contribution, thermal resistance, and compatibility of the material. The physical parameters as density and yield percentage were assessed to evaluate its light-weight utility and economic productivity. These examinations revealed that TSMCC has good specific properties such as high cellulose content (90.57 %), average density (1.561 g/cm3), feasible average roughness (12.161 nm), desired particle size (60.40 ± 21.10 μm), good crystallinity (CI-77.6 %) and thermal stability (up to 230 °C); which are worthwhile to consider TSMCC for bio-film formulation. Subsequently, bio-films were formulated by reinforcing TSMCC in polylactic acid (PLA) matrix and the mechanical properties of the bio-films were then studied to establish the efficacy of TSMCC. It is revealed that the properties of pure PLA film increased after being incorporated with TSMCC, where 5 %TSMCC addition showed greater impact on crystalline index (26.16 % to 39.62 %), thermal stability (333oc to 389 °C), tensile strength (36.11 ± 2.90 MPa to 40.22 ± 3.22 MPa) and modulus (2.62 ± 0.55GPa to 4.15 ± 0.53GPa). In light of all promising features, 5 % TSMCC is recommended as a potential filler reinforcement for the groundwork of good quality bio-films for active packaging applications in future.


Quantification of Exposure to Risk Postures in Truck Assembly Operators: Neck, Back, Arms and Wrists.
The study assessed the proportion of time in risky postures for the main joints of the upper limbs in a truck assembly plant and explored the association with musculoskeletal symptoms. Fourteen workstations (13 individuals) of a truck assembly plant were selected, and seven sensors were placed on the body segments of the participants. The sensors included tri-axial accelerometers for the arms and back, inclinometers for the neck and electro-goniometry for quantifying flexion/extension of the right and left hands. The proportions of time in moderate awkward postures were high at all workstations. Neck and wrist excessive awkward postures were observed for most workstations. The average values of the 91st percentile for back flexion and right/left arm elevation were 25°, 62°, and 57°, respectively. The 91st and 9th percentile averages for neck flexion/extension were 35.9° and -4.7°, respectively. An insignificant relationship was found between the percentage of time spent in awkward upper limb posture and musculoskeletal symptoms. The findings provide objective and quantitative data about time exposure, variability, and potential risk factors in the real workplace. Quantitative measurements in the field provide objective data of the body postures and movements of tasks that can be helpful in the musculoskeletal disorders (MSDs) prevention program.


Paramedic decision making: prehospital thrombolysis and beyond.
Mortality from acute myocardial infarction is influenced by the speed at which reperfusion therapy is delivered. In the U.K., prehospital thrombolysis (PHT), administered by paramedics, has been developed to improve call to needle (CTN) times. Recently, it has been shown in randomised trials that mortality can be further reduced by primary percutaneous coronary intervention (PPCI). This project was developed to assess current ST-elevation myocardial infarction practice in a district general hospital and to prepare paramedics for PPCI. Data were collected prospectively over a 12-month period for all patients who received thrombolysis for a presumed myocardial infarct. The primary outcome measures for each case were who delivered the thrombolysis, either the paramedic crew or the hospital, and if the patient did not receive PHT the reason why not. Secondary outcome measures included the CTN time. 153 patients received thrombolysis over the time period (99 men, 54 women, mean age 66 ± 15 years). Of this group, 55 patients received PHT (35.9%) with a median CTN time of 36 min (inter-quartile range (IQR) 30-42 min). The commonest reason for exclusion from receiving PHT was that the patient's history did not fit the eligibility criteria (25% of cases). Paramedics are able to deliver PHT promptly and safely. With the focus now on PPCI, it is anticipated that not only will paramedics be able to select patients for delivery to a heart attack centre for PPCI, they will be selecting many more patients for this treatment than have up to now received PHT.


Validity of the Rapid Eating Assessment for Patients for assessing dietary patterns in NCAA athletes.
Athletes may be at risk for developing adverse health outcomes due to poor eating behaviors during college. Due to the complex nature of the diet, it is difficult to include or exclude individual food items and specific food groups from the diet. Eating behaviors may better characterize the complex interactions between individual food items and specific food groups. The purpose was to examine the Rapid Eating Assessment for Patients survey (REAP) as a valid tool for analyzing eating behaviors of NCAA Division-I male and female athletes using pattern identification. Also, to investigate the relationships between derived eating behavior patterns and body mass index (BMI) and waist circumference (WC) while stratifying by sex and aesthetic nature of the sport. Two independent samples of male (n = 86; n = 139) and female (n = 64; n = 102) collegiate athletes completed the REAP in June-August 2011 (n = 150) and June-August 2012 (n = 241). Principal component analysis (PCA) determined possible factors using wave-1 athletes. Exploratory (EFA) and confirmatory factor analyses (CFA) determined factors accounting for error and confirmed model fit in wave-2 athletes. Wave-2 athletes' BMI and WC were recorded during a physical exam and sport participation determined classification in aesthetic and non-aesthetic sport. Mean differences in eating behavior pattern score were explored. Regression models examined interactions between pattern scores, participation in aesthetic or non-aesthetic sport, and BMI and waist circumference controlling for age and race. A 5-factor PCA solution accounting for 60.3% of sample variance determined fourteen questions for EFA and CFA. A confirmed solution revealed patterns of Desserts, Healthy food, Meats, High-fat food, and Dairy. Pattern score (mean ± SE) differences were found, as non-aesthetic sport males had a higher (better) Dessert score than aesthetic sport males (2.16 ± 0.07 vs. 1.93 ± 0.11). Female aesthetic athletes had a higher score compared to non-aesthetic female athletes for the Dessert (2.11 ± 0.11 vs. 1.88 ± 0.08), Meat (1.95 ± 0.10 vs. 1.72 ± 0.07), High-fat food (1.70 ± 0.08 vs. 1.46 ± 0.06), and Dairy (1.70 ± 0.11 vs. 1.43 ± 0.07) patterns. REAP is a construct valid tool to assess dietary patterns in college athletes. In light of varying dietary patterns, college athletes should be evaluated for healthful and unhealthful eating behaviors.


Titrimetric determination of muscle buffering capacity (beta mtitr) in biopsy samples.
In vitro titration of muscle homogenates has been used to assess muscle buffering capacity (beta mtitr) in a variety of species. In the present study, factors likely to affect the estimation of beta mtitr were investigated. Also, values of beta mtitr from normal Thoroughbred horses are presented. A non-linear titration curve was obtained with addition of HCl to muscle homogenates. As a result, beta mtitr is expressed as the mumol H+ required to change the pH of 1g of dry muscle or wet muscle from 7.1 to 6.5. An effect of dilution on the initial pH was found below 40 mg wet muscle per ml homogenising reagent (10 mg dry muscle per ml) and on beta mtitr below 10 mg wet muscle. As a result, 40 mg wet muscle or 10 mg dry muscle per ml was chosen as the minimum concentration for determination of beta mtitr. Incubation of homogenates up to 60 mins did not affect beta mtitr significantly. As a mean, beta mtitr in wet muscle was approximately 25 per cent higher compared to dry muscle. The beta mtitr of dry muscle was increased by approximately 18 per cent when HCO3- was added in an amount equivalent to the calculated HCO3- content of wet muscle at rest. The homogenisation process resulted in complete loss of adenosine triphosphate and phosphocreatine with only small changes in adenosine diphosphate and adenosine monophosphate. It was concluded that the estimates of beta mtitr did not include any contribution from 'dynamic' buffering via rephosphorylation of adenosine diphosphate by phosphocreatine, and in dry muscle it was accounted for mainly through physico-chemical buffering by phosphates, proteins and dipeptides. beta mtitr determined in biopsy samples of muscle from 20 Thoroughbred horses ranged from 100.8 to 131.8 mumol H+/g dry muscle pH 7.1 to 6.5 (mean 121.2, sd +/- 7.4).


Helpful ways providers can communicate about persistent medically unexplained physical symptoms.
Communication between patients and providers about persistent "medically unexplained" physical symptoms (MUS) is characterized by discordance. While the difficulties are well documented, few studies have examined effective communication. We sought to determine what veterans with Gulf War Illness (GWI) perceive as the most helpful communication from their providers. Veterans with GWI, a type of MUS, have historically had complex relationships with medical providers. Determining effective communication for patients with particularly complex relationships may help identify the most critical communication elements for all patients with MUS. Two hundred and-ten veterans with GWI were asked, in a written questionnaire, what was the most useful thing a medical provider had told them about their GWI. Responses were coded into three categories with 10 codes. The most prevalent helpful communication reported by patients was when the provider offered acknowledgement and validation (N = 70). Specific recommendations for managing GWI or its symptoms (N = 48) were also commonly reported to be helpful. In contrast, about a third of the responses indicated that nothing about the communication was helpful (N = 63). There were not differences in severity of symptoms, disability or healthcare utilization between patients who found acknowledgement and validation, specific recommendations or nothing helpful. Previous research has documented the discord between patients and providers regarding MUS. This study suggests that most patients are able to identify something helpful a provider has said, particularly acknowledgement and validation and specific treatment recommendations. The findings also highlight missed communication opportunities with a third of patients not finding anything helpful.


Expression of p53, p21/WAF/CIP, Bcl-2, Bax, Bcl-x, and Bak in radiation-induced apoptosis in testicular germ cell tumor lines.
Testicular germ cell tumors (TGCTs) represent one of the few tumor types that are curable by antineoplastic therapy, probably due to the high sensitivity of this neoplasm to induction of apoptosis by chemotherapeutic agents and/or ionizing radiation. Here, we tested cell susceptibility to radiation-induced apoptosis in a panel of TGCT cell lines and attempted to correlate this with the known potentially relevant molecular determinants (p53 gene status and Bcl-2 family proteins) of apoptosis. Induction of apoptosis by gamma-radiation was morphologically recognized in NT2, NCCIT, S2, and 2102 EP using Hoechst/PI staining and additionally confirmed by Western blot analysis of PARP cleavage. The p53 gene status was estimated by sequence analysis. Expression of p21/WAF/CIP was determined by Northern blot analysis and immunoblotting was used to monitor p53, Bax, Bcl-2, Bcl-x, and Bak protein levels. In vitro colony formation was studied to establish clonogenic survival curves. NT2 and NCCIT appeared to be susceptible for radiation-induced apoptosis, contrasting 2102 EP and S2 which were highly resistant. Sequence analysis showed that NT2, S2, and 2102 EP are homozygous for wild-type p53 (wtp53), whereas NCCIT contains mutant p53 (mtp53). NT2 and 2102 EP cells showed radiation-induced p53 upregulation, while NCCIT (mtp53) and S2 (no p53 protein) cells did not. Consistently, gamma-radiation-induced DNA damage resulted in a p53-dependent transactivation of the p21/WAF/CIP gene in NT2 and 2102 EP, but not in mtp53-containing NCCIT cells and p53 nonexpressing S2 cells. Constitutive expression of Bax, Bcl-2, Bcl-x, and Bak was not affected by radiation and showed no correlation with cell susceptibility to radiation-induced apoptosis. A discrepancy was found between apoptosis and reproductive death. The present study revealed that: i) the presence of wtp53 may not be absolutely required for the hypersensitivity for radiation-induced apoptosis in TGCT cell lines, ii) the molecular mechanism underlying the unique radiosensitivity was independent of the expression of Bcl-2 family proteins, and iii) cell susceptibility to apoptosis induction is not sufficiently informative to predict intrinsic radiosensitivity as determined by clonogenic survival.


Chronomic community screening reveals about 31% depression, elevated blood pressure and infradian vascular rhythm alteration.
Depression, which is a risk factor for cardiac morbidity and mortality, is not an unusual occurrence among individuals with coronary heart disease (CHD), but evidence concerning its role in the pathogenesis of this condition is less clear. Ambulatory blood pressure monitoring (ABPM) has become an important tool in the diagnosis and management of hypertension. Several previous studies have indicated that various kinds of target organ damage and cardiovascular morbidity are more strongly associated with a diagnosis by ABPM than through spot-checks in a clinical setting. This study investigated whether depressive mood was associated with changes in the about-weekly (circaseptan) and half-weekly (circasemiseptan) variations in blood pressure (BP) and heart rate (HR), including a BP surge on Mondays, in community-dwelling subjects monitored chronomically for the time structure (chronome) of their BP and HR variabilities. From April 2001 to April 2003, 217 subjects (85 men and 132 women; mean age: 56.8 +/- 11.3 yr) from U town, Hokkaido (latitude: 43.45 degrees N, longitude: 141.85 degrees E), self-monitored their BP and HR for 7 days starting around 11 a.m. on Thursday, and took readings at 30-minute intervals between 7 a.m. and 10 p.m., then at 60-minute intervals between 10 p.m. and 7 a.m. The data were retrieved and analyzed on a PC with appropriate commercial software (TM-2430-15; A&D Co., Japan). Subjects were asked about 15 items on a depression rating scale through a self-administered questionnaire. When the score amounted to 5 or higher, subjects were considered to be depressive. Student's t-test, a one-way analysis of variance (ANOVA), and cosinor methods with parametric tests were also used. A p-value below 0.05 was considered to indicate statistical significance (below 0.10: borderline statistical significance). Depression rating scales were obtained for 192 out of the 217 subjects enrolled in this study. Depression scores were (>) 5 in 72 subjects. The average values of systolic (S) and diastolic (D) BP were statistically significantly higher in depressed subjects (SBP: 129.2 vs 124.5 mmHg; p = 0.034; DBP: 79.0 vs 76.5 mmHg; p = 0.041). The 7-day average for HR did not differ between subjects with depression scores of < 5 or > 5. DBP dipping was less in the depressed subjects (16.30 vs 18.22%; p = 0.048). The dipping ratios of SBP and HR showed no statistically significant difference. In the group with depression scores of < 5, HR variability (estimated by the SD of HR and HR dip) was higher during vacations and lower on Mondays. The 24-h BP measures showed a novelty effect and a surge on Mondays. In the depressed group, a prominent circaseptan rhythm appeared to replace the novelty effect, vacation dip, and Monday surge. The results of this investigation indicate the clinical importance of the monitoring of depressed subjects. Fewer than 7 days of monitoring means a greater risk of false diagnosis, and thus a therapeutic decision including potentially unnecessary or inappropriate long-term treatment. Records shorter than 7 days would not have detected circaseptan BP dysrhythmia associated with a depressive state. Prominent circaseptans can provide new indications on the mechanisms underlying the strong relation between depression and adverse cardiac events. Future studies should aim at determining whether the treatment of depression, especially from the standpoint of a chronodiagnosis and chronotherapy, can reduce the incidence of adverse cardiac events, and whether this depends upon restoring normal BP and HR variability, i.e. anormal BP and HR chronome.


Case Report: Laparoscopic Excision of a Primary Giant Splenic Hydatid Cyst: Literature Review.
Cystic echinococcosis (CE), also known as hydatid cyst, is a zoonosis caused by the tapeworm Echinococcus granulosus. It is a common health problem in many countries. This condition predominantly affects the liver and the lungs, and the spleen to a less extent (splenic hydatid cyst, SHD). Indeed, it is estimated that SHD occurs in less than 2% of abdominal CE and 0.5-8% of CE cases. Here, we present a case of a 44-year-old Chinese woman with primary giant SHD who experienced pain in the left hypochondrium for 10 days. A combination of abdominal ultrasonography and computed tomography (CT) were used for preoperative diagnosis. Laparoscopic splenectomy was performed without any complications, and albendazole (400 mg per day) was administered postoperatively for 3 months. At 3-, 6-, 12-, and 24-month follow-up, the patient remained symptoms free, and abdominal CT found no signs of recurrence. In addition to this case, we review the previous literature on SHD treated by laparoscopy and reveal that laparoscopic approach is safe and effective for SHD. Particularly, we show that laparoscopic splenectomy is feasible for giant cysts (> 10 cm) at high risk of rupture or compressing other vital structures.


Design for fully steerable dual-trap optical tweezers.
A design for complete beam steering (in three dimensions) of one or two optical tweezers traps is presented. The two most important requirements for efficient and stable movement of an optical trap are identified. A detailed recipe for the construction of a movable optical tweezers trap that fulfills these requirements is given (exemplified with an inverted microscope). The system has been found to allow for precise and free movements of both traps in all three dimensions in a dual-trap optical tweezers configuration and to be robust and reliable, as well as forgiving of small misalignments in the optical system.


Superluminal transmission of information through an electromagnetic metamaterial.
A passive, matched two-time-derivative Lorentz material medium is designed to have its equivalent permittivity and permeability smaller than their values in free space over a large range of frequencies. Superluminal pulse propagation in this medium and consequent superluminal information exchange without a violation in causality are demonstrated. Additional properties of this medium are developed including the energy in it and the force characteristics induced on it by electromagnetic field interactions. It is shown that the force on the medium can be made to be attractive or repulsive using a change in frequency or a change in the material characteristics. Potential applications are discussed.


Incidence rates of cystic follicles in Holstein cows according to 15-day and 30-day intervals.
Cystic ovarian follicles occurred in 198 out of 1599 (12.4%) Ontario Holstein lactations. These occurrences were grouped by date of diagnosis into 15-day and 30-day intervals after calving, and only open cows were considered. The incidence rates for the 15-day intervals form zero to 150 days of lactation varied form 0.2% to 3.5%; the highest rate was 31 to 45 days. The incidence rates for the 30-day intervals from zero to 210 days of lactation varied form 1.4% to 6.8%, depending on the method of calculating the denominator of the rate. The consistently highest 30-day rate was at 31 to 60 days (4.7% or 4.8%).


Distribution of complement receptor subtypes in non-Hodgkin's lymphomas of B-cell origin.
Surface receptors specific for either the C4b (CR1) or C3d (CR2) component of complement were examined on the neoplastic cells from 30 cases of non-Hodgkin's lymphoma of B-cell origin and on cells derived from 9 normal lymphoid tissues. Lymphocyte suspensions from non-neoplastic peripheral blood, tonsils, and lymph node contained three categories of complement receptor lymphocytes (CRL): cells with receptors for both C4b and C3d (CR1+, CR2+); cells with receptors for C4b but not C3d (CR1+, CR2-), and cells with receptors for C3d but not C4b (CR1-, CR2+). The mean of the proportion of total CRL expressing receptors only of C3d (CR1-, CR2+) was 0.35 for non-neoplastic tissues and 0.28 for malignant lymphomas of follicular center cell (FCC) origin. However, the proportion of cells with this phenotype was significantly higher in well differentiated lymphocytic lymphomas (WDL) and chronic lymphocytic leukemia (CLL) (0.65) and in intermediately differentiated lymphocytic lymphomas (IDL) (0.59). Histologic compartmentalization of the CRL subtypes was observed in frozen sections of normal lymphoid tissue. CR1+ cells were present in lymphoid follicles interfollicular areas, and in splenic red pulp. CR2+ cells were confined to lymphoid follicles. These findings strongly suggest that complement receptor phenotypes may be useful markers of B-cell differentiation.


Partially ordered sets: ranking and prediction of substances' properties.
There are at least two significant applications of partial order theory in chemistry: Ranking methods and substances' properties prediction. In both cases, a set of objects is endowed with a partial order relation e.g. "more polluting than", "can be obtained from", "more reactive than" etc. The couple of set and partial order relation is known in mathematics as a partially ordered set (poset). Ranking methods, such as the Hasse diagram technique, lead to a partial order where several incomparabilities (lack of order) appear between pairs of objects. This phenomenon is quite common in ranking studies, and it often is circumvented by a combination of object features leading to a total order. However, such a combination introduces subjectivities and bias in the ranking process. Here a step-by-step procedure is shown to turn incomparabilities into comparabilities taking into account all the possible bias by a linear combination of features. In such a manner, it is possible to predict how probable it is to obtain a particular total order from a given poset. Similarly, it is possible to calculate the needed bias over certain attributes to obtain a particular total order. An example application is shown where substances are ranked according to their bioconcentration factor and biodegradation potential. Another application of partial order theory to chemistry has to do with the prediction of properties for a set of substances related in a (preferably systematic) chemical fashion. A customary relation is "can be obtained from"; if such a relation is set up for a given molecular structure e.g. benzene, and all its substituted derivatives (say chlorinated ones) are considered, then the set of benzene and its chlorinated derivatives are partially ordered. Taking advantage of the poset generated, different methods can be applied to predict properties of the substances considered in the poset. Such methods include the poset-average, cluster expansion, and splinoid methods. In this paper we discuss each one of these methods, its advantages and disadvantages and we outline its applicability to estimate cooperative free energies of hemoglobins with different degree of oxygenation.


Structural studies of pulsed-laser deposited nanocomposite metal-oxide films.
Pulsed laser deposition in vacuum has been used to develop metal-oxide nanocomposite films with well controlled structural quality. Results for the copper-aluminium oxide (Cu:Al2O3) system are used to illustrate the main morphological and structural features of these films. High resolution transmission electron microscopy (TEM) analysis shows that the films consist of Cu nanocrystals with average dimensions that can be controlled between 2 nm and 10 nm embedded in an amorphous Al2O3 matrix. It is observed that the in-plane shape of the nanocrystals evolves from circular to elongated, and the number of nanocrystals per unit area decreases as their size increases. This evolution is explained in terms of nucleation at the substrate surface and coalescence during the later stages of growth. The thermal stability of the films has been studied by in situ TEM annealing and no transformation could be observed up to about 800 degrees C when partial crystallization of the Al2O3 starts.


Characterizing regulatory and functional differentiation between maize mesophyll and bundle sheath cells by transcriptomic analysis.
To study the regulatory and functional differentiation between the mesophyll (M) and bundle sheath (BS) cells of maize (Zea mays), we isolated large quantities of highly homogeneous M and BS cells from newly matured second leaves for transcriptome profiling by RNA sequencing. A total of 52,421 annotated genes with at least one read were found in the two transcriptomes. Defining a gene with more than one read per kilobase per million mapped reads as expressed, we identified 18,482 expressed genes; 14,972 were expressed in M cells, including 53 M-enriched transcription factor (TF) genes, whereas 17,269 were expressed in BS cells, including 214 BS-enriched TF genes. Interestingly, many TF gene families show a conspicuous BS preference in expression. Pathway analyses reveal differentiation between the two cell types in various functional categories, with the M cells playing more important roles in light reaction, protein synthesis and folding, tetrapyrrole synthesis, and RNA binding, while the BS cells specialize in transport, signaling, protein degradation and posttranslational modification, major carbon, hydrogen, and oxygen metabolism, cell division and organization, and development. Genes coding for several transporters involved in the shuttle of C(4) metabolites and BS cell wall development have been identified, to our knowledge, for the first time. This comprehensive data set will be useful for studying M/BS differentiation in regulation and function.


Changes in neutrophil-to-lymphocyte ratios in postcardiac arrest patients treated with targeted temperature management.
The prognostic value of changes in neutrophil-to-lymphocyte ratios (NLR) in cardiac arrest survivors receiving targeted temperature management (TTM) is unknown. The current study investigated NLR in postcardiac arrest (PCA) patients undergoing TTM. This retrospective single-center study included 95 patients (59 males, age: 55.0±17.0 years) with in-hospital and out-of-hospital cardiac arrests who underwent TTM for PCA syndrome within 6 h of cardiac arrest. Hypothermia was maintained for 24 h at a target temperature of 33°C. NLR was calculated as the absolute neutrophil count divided by the absolute lymphocyte count. Of the 95 patients, 59 (62%) died during hospital stay. Fewer vasopressors were used in patients who survived. Out-of-hospital cardiac arrest was more frequent in decedents (p=0.005). Length of stay in the hospital and intensive care unit were significantly longer in patients who survived (p=0.0001 and p=0.001, respectively). NLR on admission and during rewarming did not differ between survivors and decedents. NLR during cooling was significantly higher in decedents (p=0.014). Delta NLR cut-off of 13.5 best separated survivors and decedents (AUC=0.68, 95% CI: 0.57-0.79, p=0.003 with a sensitivity and specificity of 64% and 67%, respectively). In multivariate logistic regression analysis, larger increase in NLR was significantly associated with decreased survival (OR: 0.96, 95% CI: 0.94-0.99, p=0.008). Changes in NLR are an independent determinant of survival in patients with return of spontaneous circulation PCA treated with TTM. An NLR change can be used to predict survival in these patients.


Ethical dilemmas in pain management.
Pain management is becoming an increasingly important component of comprehensive wound care. Choices for the best approach in managing the elderly patient with painful wounds can pose ethical dilemmas. Ethical principles such as autonomy, beneficence, and non-maleficence are explored through a case presentation. Suggestions for addressing these ethical dilemmas are examined.


Rhythmic swimming activity in neurones of the isolated nerve cord of the leech.
1. Repeating bursts of motor neurone impulses have been recorded from the nerves of completely isolated nerve cords of the medicinal leech. The salient features of this burst rhythm are similar to those obtained in the semi-intact preparation during swimming. Hence the basic swimming rhythm is generated by a central oscillator. 2. Quantitative comparisons between the impulse patterns obtained from the isolated nerve cord and those obtained from a semi-intact preparation show that the variation in both dorsal to ventral motor neurone phasing and burst duration with swim cycle period differ in these two preparations. 3. The increase of intersegmental delay with period, which is a prominent feature of swimming behaviour of the intact animal, is not seen in either the semi-intact or isolated cord preparations. 4. In the semi-intact preparation, stretching the body wall or depolarizing an inhibitory motor neurone changes the burst duration of excitatory motor neurones in the same segment. In the isolated nerve cord, these manipulations also change the period of the swim cycle in the entire cord. 5. These comparisons suggest that sensory input stabilizes the centrally generated swimming rhythm, determines the phasing of the bursts of impulses from dorsal and ventral motor neurones, and matches the intersegmental delay to the cycle period so as to maintain a constant body shape at all rates of swimming.


Role of tumor proteinases in tumor cell-induced platelet aggregation.
In a previous work we found a correlation between in vivo metastatic potential of cancer cells and their platelet aggregating activity in sublines of the mFS6 murine fibrosarcoma. In the present study the effects of different proteinase inhibitors on platelet aggregation induced by these cells were investigated. When the platelets were incubated with the inhibitors, only those effective against cysteine proteinases strongly reduced platelet aggregation by cancer cells; serine protease inhibitors, including hirudin, had no effect on platelet response. Incubation of neoplastic cells with the same inhibitors gave similar, though less evident results. Addition of neoplastic cells to platelet-rich plasma also caused significant production of fibrinopeptide A, more by the less malignant cells. Thus, in this experimental model a cysteine proteinase of the neoplastic cells appears to play an important role in the platelet aggregation induced by them, and this property was detected in the M4 cells with high metastatic in vivo activity.


Programmable transdermal delivery of nicotine in hairless guinea pigs using carbon nanotube membrane pumps.
A compact switchable transdermal nicotine patch device was demonstrated to be effective in vivo in a hairless guinea pig animal model. This required the development and validation of a quantitative method for the simultaneous determination of cotinine and nicotine in hairless guinea pig plasma by liquid chromatography-mass spectrometry. Nicotine metabolism in hairless guinea pigs is rapid and cotinine was found to be the viable nicotine marker. The portable carbon nanotube membrane device, powered by a 1.5 V watch battery, was demonstrated to be a power efficient method to pump nicotine at levels six to eight times that of passive diffusion. Cotinine blood plasma levels in hairless guinea pigs were seen to increase from 6 to 12 ng/mL when the patch was turned from passive diffusion to an active pumping state. These nicotine patch devices are highly promising for potential clinical applications, with programmed delivery based on remote counseling, in order to improve smoking cessation treatments.


DNA variation in MSR1, RNASEL and E-cadherin genes and prostate cancer in Poland.
We investigated whether or not inherited variation in MSR1, RNASEL and E-cadherin contribute to prostate cancer risk in Poland. We sequenced the coding region of these three genes in individuals from Poland and identified five common DNA variants (R462Q and D541E in RNASEL, R293X and P275A in MSR1, and 2076C>T (A692A) in E-cadherin). These five variants and the -160C>A promoter change in E-cadherin were genotyped in 737 prostate cancer cases and 511 controls. The frequencies of genotyped variants in MSR1, RNASEL and E-cadherin genes in cases and controls were similar. We did not see any association for the studied variants when cases were stratified by age of diagnosis, by family history, by prostate-specific antigen level at the time of diagnosis, by Gleason sore or by tumor stage. Inherited variation in RNASEL, MSR1 and E-cadherin genes do not seem to contribute to prostate cancer development in Poland.


Affine invariants of convex polygons.
In this correspondence, we prove that the affine invariants, for image registration and object recognition, proposed recently by Yang and Cohen (see ibid., vol.8, no.7, p.934-46, July 1999) are algebraically dependent. We show how to select an independent and complete set of the invariants. The use of this new set leads to a significant reduction of the computing complexity without decreasing the discrimination power.


Human immunodeficiency virus-associated dementia: a link between accumulation of viral proteins and neuronal degeneration.
In the late stage of human immunodeficiency virus-1 (HIV) infection, a subset of individuals develops HIV associated neurocognitive disorders (HAND), which in its severe form, is characterized by motor and cognitive dysfunction. Dendritic pruning, synaptic abnormalities and neuronal apoptosis are observed in these patients. There are numerous advances in our understanding of HIV interactions with cells of the central nervous system. However, the underlying causes of neurological symptoms and pathological alterations observed in HIV positive subjects are poorly understood. Moreover, little is still known about the molecular mechanisms by which HIV induces synaptic dysfunction and degeneration. HAND resembles other common neurological diseases such as Alzheimer's and Huntington's diseases. These neurodegenerative disorders are characterized by accumulation of toxic proteins such as tau and huntingtin, respectively, which promote axonal degeneration by impairing axonal transport. Axonal degeneration precedes neuronal death. Therefore, a better understanding of the mechanisms whereby HIV triggers axonal degeneration has potential implications for developing therapeutic compounds to prevent synaptic failure in HAND. This article highlights and reviews evidence showing that neuronal accumulation of viral proteins promotes axonal damage.


Expression of HSP70 in healing wounds of diabetic and nondiabetic mice.
Heat shock proteins (HSPs) stabilize intracellular processes of cells under stress. Little is known about the role of HSPs in wound healing, or whether their expression is altered by systemic disease. The focus of this study was to examine the local heat shock response to wounding in diabetic mice. Congenitally diabetic and phenotypically normal mice underwent standardized full-thickness cutaneous wounding. Mice were sacrificed at sequential time points and the wound beds excised. Tissues underwent immunohistochemical (IHC) and RT-PCR analyses for inducible HSP70. HSP70 protein expression in the wound bed by IHC peaked at 24 h in the nondiabetic mice. Expression of HSP70 was delayed in the diabetic mice until Day 3, which correlates with the clinical delay in healing seen in this model. The protein was especially prominent in the epithelium and in inflammatory cells migrating into the granulation tissue matrix. RT-PCR demonstrated upregulation of HSP70 mRNA within 12 h after wounding, lasting until Day 3, and decreasing thereafter in both the nondiabetic and the diabetic animals. Cutaneous wounding produces a HSP response in inflammatory cells, and expression of inducible HSP70 is delayed in diabetic mice. This delay may be related to the impaired inflammatory response of diabetics, and may contribute to impaired wound healing. The wound may be a continuing source of the heat shock response in inflammatory cells after injury.


Cytotoxic effect of buckwheat (Fagopyrum esculentum Moench) hull against cancer cells.
Buckwheat (Fagopyrum esculentum Moench) hull was extracted with 70% ethanol and then further fractionated with n-hexane, chloroform, ethyl acetate, and water stepwise. In the in vitro test (SRB assay), hexane and ethyl acetate fractions showed higher inhibition effects against MCF-7 cells than other samples at the 1 mg/mL level: 89% and 93.2%, respectively. They also displayed higher inhibition rates against Hep3B cells of 83.6% and 75.3%, respectively, at 1 mg/mL. The ethyl acetate fraction yielded the highest inhibition rate against A549 cells with the level of 0.25 mg/mL, but it showed a lower inhibition rate than the hexane and chloroform fractions at higher levels of sample, i.e., 0.75 and 1.0 mg/mL. All samples showed higher inhibition effects against AGS human gastric carcinoma than any other cancer cells. The inhibition rates against HeLa cells were 81.2% and 82.0% for the chloroform and butanol fraction with 0.5 mg/mL, respectively. However, all samples yielded an inhibition rate of less than 35% against normal cells, at all treatment levels, except the ethanol extract. All extracts at doses of 25 and 50 mg/kg showed decreases of more than 20% and 42%, respectively, in tumor formation in sarcoma-180 implanted mice except for the aqueous fraction. From these results, it is suggested that buckwheat hull possesses anticancer properties against a variety of different cancer cell lines.


The domino effect: the impact of gender on operative self-efficacy.
Studies suggest that there are key differences in operative experience based on a trainee's gender. A large-scale self-efficacy (SE) survey, distributed to general surgery residents after the American Board of Surgery In-Training Examination in 2020, found that female gender was associated with decreased SE in graduating PGY5 residents for all 4 laparoscopic procedures included on the survey (cholecystectomy, appendectomy, right hemicolectomy, and diagnostic laparoscopy). We sought to determine whether these differences were reflected at the case level when considering operative performance and supervision using an operative assessment tool (SIMPL OR). Supervision and performance data reported through the SIMPL OR platform for the same 4 laparoscopic procedures included in the SE survey were aggregated for residents who were PGY5s in 2020. Independent t-tests and multiple linear regression were used to determine the relationship between trainee gender and supervision/performance ratings. For laparoscopic cases in aggregate (n = 2708), male residents rated their performance higher than females (3.57 vs. 3.26, p < 0.001, 1 = critical deficiency, 5 = exceptional performance) and reported less supervision (3.15 vs. 2.85, p < 0.001, 1 = show and tell, 4 = supervision only); similar findings were seen when looking at attending reports of resident supervision and performance. A multiple linear regression model showed that attending gender did not significantly predict resident-reported supervision or performance levels, while case complexity and trainee gender significantly affected both supervision and performance (p < 0.001). Female residents perceive themselves to be less self-efficacious at core laparoscopic procedures compared to their male colleagues. Comparison to more case-specific data confirm that female residents receive more supervision and lower performance ratings. This may create a domino effect in which female residents receive less operative independence, preventing the opportunity to establish SE. Further research should identify opportunities to break this cycle and consider gender identity beyond the male/female construct.


Fast reflective optic-based rotational anisotropy nonlinear harmonic generation spectrometer.
We present a novel Rotational Anisotropy Nonlinear Harmonic Generation (RA-NHG) apparatus based primarily upon reflective optics. The data acquisition scheme used here allow for fast accumulation of RA-NHG traces, mitigating low frequency noise from laser drift, while permitting real-time adjustment of acquired signals with significantly more data points per unit angle rotation of the optics than other RA-NHG setups. We discuss the design and construction of the optical and electronic components of the device and present example data taken on a GaAs test sample at a variety of wavelengths. The RA-second harmonic generation data for this sample show the expected four-fold rotational symmetry across a broad range of wavelengths, while those for RA-third harmonic generation exhibit evidence of cascaded nonlinear processes possible in acentric crystal structures.


Augmentation of thyrotropin responses to thyrotropin-releasing hormone following small decreases in serum thyroid hormone concentrations.
To determine whether slight decreases in serum thyroid hormone concentrations resulted in augmentation of the thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH), TSH responses to TRH were determined before and after 13 days of iodide treatment in 20 normal subjects. Slight reductions in serum thyroxine (t4) and/or triiodothyronine (T3) concentrations and slight increases in basal serum TSH concentrations occurred in normal subjects treated with 50 or 250 mg iodide daily, though serum T4, T3 and TSH concentrations remained within their respective normal range. In contrast, TSH responses to TRH were significantly greater at the end of the iodide treatment period. In the subjects who received 50 mg iodide daily, mean basal serum TSH concentrations were 3.1 and 3.2 muU/ml before and 4.9 and 4.6 muU/ml after iodide. Post-TRH mean peak serum TSH concentrations were 14.2 muU/ml before and 27.4 muU/ml after iodide (P smaller than 0.01). A very similar augmentation of peak serum TSH was found in the subjects who received 250 mg iodide daily (before iodide, peak TSH 17.2 muU/ml; after iodide, peak TSH 28.7 muU/ml). No changes in serum T4, T3 or TSH concentrations or TSH responses to TRH followed iodide administration in 4 thyroxine-treated hypothyroid patients. These results indicate that slight reductions in serum T4 AND T3 concentrations result in increased pituitary sensitivity to TRH, just as small increases in serum T4 and T3 concentrations decrease sensitivity to TRH.


A comparative analysis of hepatocellular carcinoma after hepatic resection in young versus elderly patients.
The aim of this study was to investigate the clinical outcomes after surgical treatment of hepatocellular carcinoma (HCC) in the elderly patients compared with younger patients. Clinicopathological data and treatment outcomes in 61 elderly (≥70 years old) and 90 younger (≤40 years old) patients with HCC who underwent curative liver resection between 2000 and 2010 were retrospectively collected and compared using various parameters. The older HCC group was more likely to have hepatitis C virus and non-B non-C hepatitis virus infection, higher values of indocyanine green retention at 15 min (ICGR)(15), more preoperative comorbidities, and more postoperative complications. There were no significant differences in intraoperative parameters and pathologic features. The recurrence rate, overall survival and disease-free survival rates were similar amongst the two groups. The only independent prognostic factor of overall survival was postoperative complications. Our findings suggest that age by itself does not have an adverse effect on operative outcomes, including long-term prognosis. For young and elderly HCC patients, hepatic resection is a safe and effective treatment.


[Classics textual research and using situation investigation of Tibetan medicine "Zha-xun"].
In this article the classics textual research to the origin of "Zha-xun" was carried out, the ethnobotanical research methods, the origin of visits, key informant interviews, sample collection and textual research were applied in the research. The results showed that the hypothesis of Zha-xun"s origin mainly included "source of mine", "source of feces", "source of monkey menstrual blood" in China. There were "source of fossil", "source of the plant secretion" abroad. The authors had interviewed the villagers at origin, herbalists, Tibetan doctors, herb dealers, foreign scholars for a total of 18 people, and collecting 45 batches medicinal materials. According to ancient Tibetan classics textual and Tibetan medicine doctors' views, medicinal materials were divided into the genuine and the substitutes. The genuine was identified as ancient so-called "iron" type "Zha-xun", and the substitute was fecal pellet bonding briquette. According to the field survey and literature research, "source of fossil" more in line with substance of Zha-xun was derived from the rock. As the results, the author believed that Zha-xun was the mixture of organic fossils from the rock seepage with flying squirrel, pika feces. So it is needed to be set up Zha-xun classification standard to evaluate the quality of medicinal materials. Meanwhile, it was necessary to further clarify fecal pellet substitute rationality. Above all, this article clarified the status of the use of Tibetan medicine-"Zha-xun", and laid the foundation of species systematics and quality standards research of "Zha-xun".


Gene expression reversal toward pre-adult levels in the aging human brain and age-related loss of cellular identity.
It was previously reported that mRNA expression levels in the prefrontal cortex at old age start to resemble pre-adult levels. Such expression reversals could imply loss of cellular identity in the aging brain, and provide a link between aging-related molecular changes and functional decline. Here we analyzed 19 brain transcriptome age-series datasets, comprising 17 diverse brain regions, to investigate the ubiquity and functional properties of expression reversal in the human brain. Across all 19 datasets, 25 genes were consistently up-regulated during postnatal development and down-regulated in aging, displaying an "up-down" pattern that was significant as determined by random permutations. In addition, 113 biological processes, including neuronal and synaptic functions, were consistently associated with genes showing an up-down tendency among all datasets. Genes up-regulated during in vitro neuronal differentiation also displayed a tendency for up-down reversal, although at levels comparable to other genes. We argue that reversals may not represent aging-related neuronal loss. Instead, expression reversals may be associated with aging-related accumulation of stochastic effects that lead to loss of functional and structural identity in neurons.


Nucleotide substrate binding characterization in human pancreatic-type ribonucleases.
Human genome contains a group of more than a dozen similar genes with diverse biological functions including antiviral, antibacterial and angiogenesis activities. The characterized gene products of this group show significant sequence similarity and a common structural fold associated with binding and cleavage of ribonucleic acid (RNA) substrates. Therefore, these proteins have been categorized as members of human pancreatic-type ribonucleases (hRNases). hRNases differ in cell/tissue localization and display distinct substrate binding preferences and a wide range of ribonucleolytic catalytic efficiencies. Limited information is available about structural and dynamical properties that influence this diversity among these homologous RNases. Here, we use computer simulations to characterize substrate interactions, electrostatics and dynamical properties of hRNases 1-7 associated with binding to two nucleotide substrates (ACAC and AUAU). Results indicate that even with complete conservation of active-site catalytic triad associated with ribonucleolytic activity, these enzymes show significant differences in substrate interactions. Detailed characterization suggests that in addition to binding site electrostatic and van der Waals interactions, dynamics of distal regions may also play a role in binding. Another key insight is that a small difference in temperature of 300 K (used in experimental studies) and 310 K (physiological temperature) shows significant changes in enzyme-substrate interactions.


Predicting cryptic ligand binding sites based on normal modes guided conformational sampling.
To greatly expand the druggable genome, fast and accurate predictions of cryptic sites for small molecules binding in target proteins are in high demand. In this study, we have developed a fast and simple conformational sampling scheme guided by normal modes solved from the coarse-grained elastic models followed by atomistic backbone refinement and side-chain repacking. Despite the observations of complex and diverse conformational changes associated with ligand binding, we found that simply sampling along each of the lowest 30 modes is near optimal for adequately restructuring cryptic sites so they can be detected by existing pocket finding programs like fpocket and concavity. We further trained machine-learning protocols to optimize the combination of the sampling-enhanced pocket scores with other dynamic and conservation scores, which only slightly improved the performance. As assessed based on a training set of 84 known cryptic sites and a test set of 14 proteins, our method achieved high accuracy of prediction (with area under the receiver operating characteristic curve >0.8) comparable to the CryptoSite server. Compared with CryptoSite and other methods based on extensive molecular dynamics simulation, our method is much faster (1-2 hours for an average-size protein) and simpler (using only pocket scores), so it is suitable for high-throughput processing of large datasets of protein structures at the genome scale.


A Comprehensive Analysis of Selenium-Binding Proteins in the Brain Using Its Reactive Metabolite.
The intracellular metabolism of selenium in the brain currently remains unknown, although the antioxidant activity of this element is widely acknowledged to be important in maintaining brain functions. In this study, a comprehensive method for identifying the selenium-binding proteins using PenSSeSPen as a model of the selenium metabolite, selenotrisulfide (RSSeSR, STS), was applied to a complex cell lysate generated from the rat brain. Most of the selenium from L-penicillamine selenotrisulfide (PenSSeSPen) was captured by the cytosolic protein thiols in the form of STS through the thiol-exchange reaction (R-SH+PenSSeSPen→R-SSeSPen+PenSH). The cytosolic protein species, which reacted with the PenSSeSPen mainly had a molecular mass of less than 20 kDa. A thiol-containing protein at m/z 15155 in the brain cell lysate was identified as the cystatin-12 precursor (CST12) from a rat protein database search and a tryptic fragmentation experiment. CST12 belongs to the cysteine proteinase inhibitors of the cystatin superfamily that are of interest in mechanisms regulating the protein turnover and polypeptide production in the central nervous system and other tissues. Consequently, CST12 is suggested to be one of the cytosolic proteins responsible for the selenium metabolism in the brain.


Deep-Reaching Hydrodynamic Flow Confinement: Micrometer-Scale Liquid Localization for Open Substrates With Topographical Variations.
We present a method for nonintrusive localization and reagent delivery on immersed biological samples with topographical variation on the order of hundreds of micrometers. Our technique, which we refer to as the deep-reaching hydrodynamic flow confinement (DR-HFC), is simple and passive: it relies on a deep-reaching hydrodynamic confinement delivered through a simple microfluidic probe design to perform localized microscale alterations on substrates as deep as 600 μm. Designed to scan centimeter-scale areas of biological substrates, our method passively prevents sample intrusion by maintaining a large gap between the probe and the substrate. The gap prevents collision of the probe and the substrate and reduces the shear stress experienced by the sample. We present two probe designs: linear and annular DR-HFC. Both designs comprise a reagent-injection aperture and aspiration apertures that serve to confine the reagent. We identify the design parameters affecting reagent localization and depth by DR-HFC and study their individual influence on the operation of DR-HFC numerically. Using DR-HFC, we demonstrate localized binding of antihuman immunoglobulin G (IgG) onto an activated substrate at various depths from 50 to 600 μm. DR-HFC provides a readily implementable approach for noninvasive processing of biological samples applicable to the next generation of diagnostic and bioanalytical devices.


Elevated aortic pulse wave velocity, a marker of arterial stiffness, predicts cardiovascular events in well-functioning older adults.
Aging results in vascular stiffening and an increase in the velocity of the pressure wave as it travels down the aorta. Increased aortic pulse wave velocity (aPWV) has been associated with mortality in clinical but not general populations. The objective of this investigation was to determine whether aPWV is associated with total and cardiovascular (CV) mortality and CV events in a community-dwelling sample of older adults. aPWV was measured at baseline in 2488 participants from the Health, Aging and Body Composition (Health ABC) study. Vital status, cause of death and coronary heart disease (CHD), stroke, and congestive heart failure were determined from medical records. Over 4.6 years, 265 deaths occurred, 111 as a result of cardiovascular causes. There were 341 CHD events, 94 stroke events, and 181 cases of congestive heart failure. Results are presented by quartiles because of a threshold effect between the first and second aPWV quartiles. Higher aPWV was associated with both total mortality (relative risk, 1.5, 1.6, and 1.7 for aPWV quartiles 2, 3, and 4 versus 1; P=0.019) and cardiovascular mortality (relative risk, 2.1, 3.0, and 2.3 for quartiles 2, 3, and 4 versus 1; P=0.004). aPWV quartile was also significantly associated with CHD (P=0.007) and stroke (P=0.001). These associations remained after adjustment for age, gender, race, systolic blood pressure, known CV disease, and other variables related to events. Among generally healthy, community-dwelling older adults, aPWV, a marker of arterial stiffness, is associated with higher CV mortality, CHD, and stroke.


Health Numeracy and Relative Risk Comprehension in Perioperative Patients and Physicians.
Helping patients to understand relative risks is challenging. In discussions with patients, physicians often use numbers to describe hazards, make comparisons, and establish relevance. Patients with a poor understanding of numbers-poor "health numeracy"-also have difficulty making decisions and coping with chronic conditions. Although the importance of "health literacy" in perioperative populations is recognized, health numeracy has not been well studied. Our aim was to compare understanding of numbers, risk, and risk modification between a patient population awaiting surgery under general anesthesia and attending physicians at the same center. We performed a single-center cross-sectional survey study to compare patients' and physicians' health numeracy. The study instrument was based on the Schwartz-Lipkus survey and included 3 simple health numeracy questions and 2 risk reduction questions in the anesthesiology domain. The survey was mailed to patients over the age of 18 scheduled for elective surgery under general anesthesia between June and September 2019, as well as attending physicians at the study center. Two hundred thirteen of 502 (42%) patient surveys sent and 268 of 506 (53%) physician surveys sent were returned. Median patient score was 4 of 5, but 32% had a score of ≤3. Patients significantly overestimated their total scores by an average of 0.5 points (estimated [mean ± standard deviation (SD)] = 4.3 ± 1.2 vs actual 3.8 ± 1.3; P < .001). Health numeracy was significantly associated with higher educational level (gamma = 0.351; P < .001) and higher-income level (gamma = 0.397; P < .001). Physicians' health numeracy was significantly higher than the patients' (median [interquartile range {IQR}] = 5 [4-5] vs 4 [3-5]; P < .001). There was no significant difference between physicians' self-estimated and actual total numeracy score (mean ± SD = 4.8 ± 0.6 vs 4.7 ± 0.6; P = .372). Simple health numeracy (questions 1-3) was predictive of correct risk reduction responses (questions 4, 5) for both patients (gamma = 0.586; P < .001) and physicians (gamma = 0.558; P = .006). Patients had poor health numeracy compared to physicians and tended to overrate their abilities. A small proportion of physicians also had poor numeracy. Poor health numeracy was associated with incomprehension of risk modification, suggesting that some patients may not understand treatment efficacy. These disparities suggest a need for further inquiry into how to improve patient comprehension of risk modification.


Male-driven biased gene conversion governs the evolution of base composition in human alu repeats.
Regional biases in substitution pattern are likely to be responsible for the large-scale variation in base composition observed in vertebrate genomes. However, the evolutionary forces responsible for these biases are still not clearly defined. In order to study the processes of mutation and fixation across the entire human genome, we analyzed patterns of substitution in Alu repeats since their insertion. We also studied patterns of human polymorphism within the repeats. There is a highly significant effect of recombination rate on the pattern of substitution, whereas no such effect is seen on the pattern of polymorphism. These results suggest that regional biases in substitution are caused by biased gene conversion, a process that increases the probability of fixation of mutations that increase GC content. Furthermore, the strongest correlate of substitution patterns is found to be male recombination rates rather than female or sex-averaged recombination rates. This indicates that in addition to sexual dimorphism in recombination rates, the sexes also differ in the relative rates of crossover and gene conversion.


Maternal Consumption of Non-Nutritive Sweeteners during Pregnancy Is Associated with Alterations in the Colostrum Microbiota.
Non-nutritive sweeteners (NNSs) provide a sweet taste to foods and beverages without significantly adding calories. Still, their consumption has been linked to modifications in adult's and children's gut microbiota and the disruption of blood glucose control. Human milk microbiota are paramount in establishing infants' gut microbiota, but very little is known about whether the consumption of sweeteners can alter it. To address this question, we sequenced DNA extracted colostrum samples from a group of mothers, who had different levels of NNS consumption, using the Ion Torrent Platform. Our results show that the "core" of colostrum microbiota, composed of the genera Bifidobacterium, Blautia, Cutibacteium, Staphylococcus, and Streptococcus, remains practically unchanged with the consumption of NNS during pregnancy, but specific genera display significant alterations, such as Staphylococcus and Streptococcus. A significant increase in the unclassified archaea Methanobrevibacter spp. was observed as the consumption frequency of NNS increased. The increase in the abundance of this archaea has been previously linked to obesity in Mexican children. NNS consumption during pregnancy could be related to changes in colostrum microbiota and may affect infants' gut microbiota seeding and their future health.


Hepatitis C virus infection among dialysis patients in United arab emirates.
To evaluate the incidence of positivity of anti-hepatitis C virus (anti-HCV) antibodies in the hemodialysis (HD) patients, and the impact of isolation of the anti-HCV positive patients, we studied 262 HD patients in our unit between January 1991 and December 1993. There were 64 patients with anti-HCV positivity. Forty nine of them were males, and 15 were females, with mean ages of 41.8 +/- 8.6 years. The mean dialysis period was 20.9 +/- 2.5 months. The serum anti-HCV antibodies were detected with second generation HCV enzyme linked immunosorbent assay. The test was repeated every three months for the patients, and every six months for the dialysis staff members. Dialyzers were not reused. Isolation of the positive patients by using designated HD machines was performed, besides adopting the universal precautions of infection. At the time of the inclusion to the study 45 patients out of 64 (70.3%) were anti-HCV positive. In this group 42% received blood transfusions, 17.5% started hemodialysis in another dialysis unit. Nineteen patients (29.7%) seroconverted during the study period. In this group, nine patients (47.6%) received blood transfusions (1.7 + 0.5 units). Of the seroconverted patients, eight (42%) travelled abroad and received HD during their holidays. Eight of the seroconverted patients did not have identifiable risk factors except HD. The overall seroconversion rate was 0.95 per 100 patient months. The rate decreased to 0.4 per 100 patient months if the identifiable causes for seroconversion (blood transfusion, duration of dialysis, holiday dialysis) were excluded. We conclude that HCV infection is frequent in hemodialysis patients. Strict follow up of the universal precautions together with isolation of anti-HCV positive patients with designated machines may be sufficient to prevent nosocomial transmission of HCV infection. The risk of transfusion may be minimized by using r-Human erythropoietin in the treatment of anemia in this population.


HIV-associated primary effusion lymphoma presenting as a paracardial mass.
Primary effusion lymphoma (PEL), a rare type of non-Hodgkin's lymphoma, is an AIDS-defining illness and always associated with human herpesvirus 8 (HHV-8). Classic presentations involve the pleural, pericardial or peritoneal cavities. Infrequently, extracavitary solid tumours develop. Treatment of PEL requires chemotherapy and highly active antiretroviral therapy (HAART). We report a case of a 46-year-old man, who presented with right-sided chest pain, dyspnoea and night sweats. Evaluation revealed decreased breath sounds and dullness to percussion on the right side of the chest. Imaging demonstrated a 6.1 cm×6.3 cm right paracardial mass and right-sided pleural effusion. Pleural fluid was HHV-8 positive. The patient was diagnosed with PEL with extracavitary involvement and treated with chemotherapy and concurrent HAART. This case is the first reported case of extracavitary paracardial involvement and adds new insight to the accepted treatment for PEL with extracavitary lesions.


An inducible phosphoenolpyruvate: dihydroxyacetone phosphotransferase system in Escherichia coli.
A phosphoenolpyruvate: dihydroxyacetone phosphotransferase was induced in Escherichia coli grown on dihydroxyacetone as sole carbon source or in its presence. This is the first example of a triose which can be acted upon by the membrane complex to provide a central intermediate in glycolysis. The presence of this system explains the ability of a mutant, in which the ATP-dependent glycerol kinase is genetically replaced by a glycerol: NAD 2-oxidoreductase, to grow on glycerol.


Single-dose pharmacokinetics of orally administered terbinafine in bearded dragons (Pogona vitticeps) and the antifungal susceptibility patterns of Nannizziopsis guarroi.
To identify the antifungal susceptibility of Nanniziopsis guarroi isolates and to evaluate the single-dose pharmacokinetics of orally administered terbinafine in bearded dragons. 8 healthy adult bearded dragons. 4 isolates of N guarroi were tested for antifungal susceptibility. A compounded oral solution of terbinafine (25 mg/mL [20 mg/kg]) was given before blood (0.2 mL) was drawn from the ventral tail vein at 0, 4, 8, 12, 24, 48, 72, and 96 hours after administration. Plasma terbinafine concentrations were measured with high-performance liquid chromatography. The antifungal minimum inhibitory concentrations against N guarroi isolates ranged from 4,000 to > 64,000 ng/mL for fluconazole, 125 to 2,000 ng/mL for itraconazole, 125 to 2,000 ng/mL for ketoconazole, 125 to 1,000 ng/mL for posaconazole, 60 to 250 ng/mL for voriconazole, and 15 to 30 ng/mL for terbinafine. The mean ± SD peak plasma terbinafine concentration in bearded dragons was 435 ± 338 ng/mL at 13 ± 4.66 hours after administration. Plasma concentrations remained > 30 ng/mL for > 24 hours in all bearded dragons and for > 48 hours in 6 of 8 bearded dragons. Mean ± SD terminal half-life following oral administration was 21.2 ± 12.40 hours. Antifungal susceptibility data are available for use in clinical decision making. Results indicated that administration of terbinafine (20 mg/kg, PO, q 24 to 48 h) in bearded dragons may be appropriate for the treatment of dermatomycoses caused by N guarroi. Clinical studies are needed to determine the efficacy of such treatment.


[Diurnal dynamics of urinary excretion of potassium during one- and two-shift work].
Four groups of constructive and industry workers--men aged 19-20--were examined. Group 1 and 3 subjects (10 subjects in each group) worked for 1 or 2 years, respectively, in the day shift only. Group 2 (5 subjects) and 4 (10 subjects) subjects worked for 1 or 2 years, respectively, in the day and night shifts, with the shift alternating every week. The day shift was from 8.00 a.m. to 5.00 p.m. and the night shift was from 5.00 p.m. to 1.00 a.m. The test subjects were examined in a hospital on the day following the working week. Group 1, 3 and 4 subjects were examined once (Group 4 after the night shift), and Group 2 subjects twice (after the day and night shifts). Urine was collected every odd hour with a two-hour interval from 7.00 a.m. to 7.00 a.m. of the next day. The day shift in both groups was accompanied by an early increase in potassium excretion. The shift transition was attended by a change of the daily maximum toward later hours. As compared to the one-shift work, the two-shift work increased the amplitude of the diurnal potassium excretion. This can be considered as a stressful effect of the two-shift work. This effect was very distinct after a week of the day-shift work. Therefore, when assessing the physiological effects of the two-shift work, with respect to daily variations in renal potassium excretion, it is necessary to carry out pertinent examinations after the day-shift work.