Integration of a recent infection testing algorithm into HIV surveillance in Ireland: improving HIV knowledge to target prevention.

Recent infection testing algorithms (RITA) for HIV combine serological assays with epidemiological data to determine likely recent infections, indicators of ongoing transmission. In 2016, we integrated RITA into national HIV surveillance in Ireland to better inform HIV prevention interventions. We determined the avidity index (AI) of new HIV diagnoses and linked the results with data captured in the national infectious disease reporting system. RITA classified a diagnosis as recent based on an AI < 1.5, unless epidemiological criteria (CD4 count <200 cells/mm3; viral load <400 copies/ml; the presence of AIDS-defining illness; prior antiretroviral therapy use) indicated a potential false-recent result. Of 508 diagnoses in 2016, we linked 448 (88.1%) to an avidity test result. RITA classified 12.5% of diagnoses as recent, with the highest proportion (26.3%) amongst people who inject drugs. On multivariable logistic regression recent infection was more likely with a concurrent sexually transmitted infection (aOR 2.59; 95% CI 1.04-6.45). Data were incomplete for at least one RITA criterion in 48% of cases. The study demonstrated the feasibility of integrating RITA into routine surveillance and showed some ongoing HIV transmission. To improve the interpretation of RITA, further efforts are required to improve completeness of the required epidemiological data.

Modeling underwater noise propagation from marine hydrokinetic power devices through a time-domain, velocity-pressure solution.

Marine hydrokinetic (MHK) devices generate electricity from the motion of tidal and ocean currents, as well as ocean waves, to provide an additional source of renewable energy available to the United States. These devices are a source of anthropogenic noise in the marine ecosystem and must meet regulatory guidelines that mandate a maximum amount of noise that may be generated. In the absence of measured levels from in situ deployments, a model for predicting the propagation of sound from an array of MHK sources in a real environment is essential. A set of coupled, linearized velocity-pressure equations in the time-domain are derived and presented in this paper, which are an alternative solution to the Helmholtz and wave equation methods traditionally employed. Discretizing these equations on a three-dimensional (3D), finite-difference grid ultimately permits a finite number of complex sources and spatially varying sound speeds, bathymetry, and bed composition. The solution to this system of equations has been parallelized in an acoustic-wave propagation package developed at Sandia National Labs, called Paracousti. This work presents the broadband sound pressure levels from a single source in two-dimensional (2D) ideal and Pekeris wave-guides and in a 3D domain with a sloping boundary. The paper concludes with demonstration of Paracousti for an array of MHK sources in a simple wave-guide.

New insights into the photochemistry of carotenoid spheroidenone in light-harvesting complex 2 from the purple bacterium Rhodobacter sphaeroides.

Light-harvesting complex 2 (LH2) from the semi-aerobically grown purple phototrophic bacterium Rhodobacter sphaeroides was studied using optical (static and time-resolved) and resonance Raman spectroscopies. This antenna complex comprises bacteriochlorophyll (BChl) a and the carotenoid spheroidenone, a ketolated derivative of spheroidene. The results indicate that the spheroidenone-LH2 complex contains two spectral forms of the carotenoid: (1) a minor, "blue" form with an S2 (11B u+ ) spectral origin band at 522 nm, shifted from the position in organic media simply by the high polarizability of the binding site, and (2) the major, "red" form with the origin band at 562 nm that is associated with a pool of pigments that more strongly interact with protein residues, most likely via hydrogen bonding. Application of targeted modeling of excited-state decay pathways after carotenoid excitation suggests that the high (92%) carotenoid-to-BChl energy transfer efficiency in this LH2 system, relative to LH2 complexes binding carotenoids with comparable double-bond conjugation lengths, derives mainly from resonance energy transfer from spheroidenone S2 (11B u+ ) state to BChl a via the Qx state of the latter, accounting for 60% of the total transfer. The elevated S2 (11B u+ ) â†’ Qx transfer efficiency is apparently associated with substantially decreased energy gap (increased spectral overlap) between the virtual S2 (11B u+ ) â†’ S0 (11A g- ) carotenoid emission and Qx absorption of BChl a. This reduced energetic gap is the ultimate consequence of strong carotenoid-protein interactions, including the inferred hydrogen bonding.

The impact of Type 2 diabetes prevention programmes based on risk-identification and lifestyle intervention intensity strategies: a cost-effectiveness analysis.

AIMS: To develop a cost-effectiveness model to compare Type 2 diabetes prevention programmes targeting different at-risk population subgroups with a lifestyle intervention of varying intensity. METHODS: An individual patient simulation model was constructed to simulate the development of diabetes in a representative sample of adults without diabetes from the UK population. The model incorporates trajectories for HbA1c , 2-h glucose, fasting plasma glucose, BMI, systolic blood pressure, total cholesterol and HDL cholesterol. Patients can be diagnosed with diabetes, cardiovascular disease, microvascular complications of diabetes, cancer, osteoarthritis and depression, or can die. The model collects costs and utilities over a lifetime horizon. The perspective is the UK National Health Service and personal social services. We used the model to evaluate the population-wide impact of targeting a lifestyle intervention of varying intensity to six population subgroups defined as high risk for diabetes. RESULTS: The intervention produces 0.0003 to 0.0009 incremental quality-adjusted life years and saves up to £1.04 per person in the general population, depending upon the subgroup targeted. Cost-effectiveness increases with intervention intensity. The most cost-effective options are to target individuals with HbA1c > 42 mmol/mol (6%) or with a high Finnish Diabetes Risk (FINDRISC) probability score (> 0.1). CONCLUSION: The model indicates that diabetes prevention interventions are likely to be cost-effective and may be cost-saving over a lifetime. In the model, the criteria for selecting at-risk individuals differentially impact upon diabetes and cardiovascular disease outcomes, and on the timing of benefits. These findings have implications for deciding who should be targeted for diabetes prevention interventions.

Cost-effectiveness of population-based, community, workplace and individual policies for diabetes prevention in the UK.

AIM: To analyse the cost-effectiveness of different interventions for Type 2 diabetes prevention within a common framework. METHODS: A micro-simulation model was developed to evaluate the cost-effectiveness of a range of diabetes prevention interventions including: (1) soft drinks taxation; (2) retail policy in socially deprived areas; (3) workplace intervention; (4) community-based intervention; and (5) screening and intensive lifestyle intervention in individuals with high diabetes risk. Within the model, individuals follow metabolic trajectories (for BMI, cholesterol, systolic blood pressure and glycaemia); individuals may develop diabetes, and some may exhibit complications of diabetes and related disorders, including cardiovascular disease, and eventually die. Lifetime healthcare costs, employment costs and quality-adjusted life-years are collected for each person. RESULTS: All interventions generate more life-years and lifetime quality-adjusted life-years and reduce healthcare spending compared with doing nothing. Screening and intensive lifestyle intervention generates greatest lifetime net benefit (£37) but is costly to implement. In comparison, soft drinks taxation or retail policy generate lower net benefit (£11 and £11) but are cost-saving in a shorter time period, preferentially benefit individuals from deprived backgrounds and reduce employer costs. CONCLUSION: The model enables a wide range of diabetes prevention interventions to be evaluated according to cost-effectiveness, employment and equity impacts over the short and long term, allowing decision-makers to prioritize policies that maximize the expected benefits, as well as fulfilling other policy targets, such as addressing social inequalities.

Influence of aerobic fitness on vasoreactivity in young men.

Previous work has demonstrated a direct relationship between aerobic fitness and vasodilatory function (i.e., flow-mediated dilation; FMD); however, the relation between aerobic fitness and vasoconstrictor responsiveness (i.e., low flow-mediated constriction; L-FMC), and the overall vasoactive range (FMD + L-FMC) is unclear. PURPOSE: To test the hypothesis that L-FMC and the overall vasoactive range (FMD + L-FMC) will be related to aerobic fitness in young, healthy men. METHODS: Twenty men (age: 23 ± 5 years) were recruited, and divided evenly into a higher (HF) vs. lower (LF) aerobic fitness group, quantified via YMCA cycle ergometry (VO2 peak extrapolation), and a 3-min step test (1-min heart rate recovery). Duplex Doppler-ultrasound was used to assess brachial artery FMD and L-FMC. RESULTS: Estimated VO2 peak (HF = 55 ± 10 vs. LF = 38 ± 5 mL/kg/min) and heart rate recovery (HF = 36 ± 10 vs. LF = 25 ± 8 beats) were greater in the HF group (P < 0.05). FMD and the vasoactive range were similar between groups; however, L-FMC was significantly greater in HF (HF = -2.5 ± 1.6 vs. LF = -0.7 ± 1.8%, P < 0.05; d = 1.18). A correlational analysis revealed an inverse relationship between L-FMC and both HR recovery (r = -0.665, P < 0.01) and estimated VO2 peak (r = -0.5, P < 0.05). CONCLUSIONS: This work supports an association between L-FMC and aerobic fitness in young, healthy men. Longitudinal or interventional studies are warranted to support causality, and to distinguish whether L-FMC is more sensitive to changes in aerobic fitness than FMD.

The cost-effectiveness of changes to the care pathway used to identify depression and provide treatment amongst people with diabetes in England: a model-based economic evaluation.

BACKGROUND: Diabetes is associated with premature death and a number of serious complications. The presence of comorbid depression makes these outcomes more likely and results in increased healthcare costs. The aim of this work was to assess the health economic outcomes associated with having both diabetes and depression, and assess the cost-effectiveness of potential policy changes to improve the care pathway: improved opportunistic screening for depression, collaborative care for depression treatment, and the combination of both. METHODS: A mathematical model of the care pathways experienced by people diagnosed with type-2 diabetes in England was developed. Both an NHS perspective and wider social benefits were considered. Evidence was taken from the published literature, identified via scoping and targeted searches. RESULTS: Compared with current practice, all three policies reduced both the time spent with depression and the number of diabetes-related complications experienced. The policies were associated with an improvement in quality of life, but with an increase in health care costs. In an incremental analysis, collaborative care dominated improved opportunistic screening. The incremental cost-effectiveness ratio (ICER) for collaborative care compared with current practice was £10,798 per QALY. Compared to collaborative care, the combined policy had an ICER of £68,017 per QALY. CONCLUSIONS: Policies targeted at identifying and treating depression early in patients with diabetes may lead to reductions in diabetes related complications and depression, which in turn increase life expectancy and improve health-related quality of life. Implementing collaborative care was cost-effective based on current national guidance in England.

Functional characteristics of spirilloxanthin and keto-bearing Analogues in light-harvesting LH2 complexes from Rhodobacter sphaeroides with a genetically modified carotenoid synthesis pathway.

Light-harvesting 2 (LH2) complexes from a genetically modified strain of the purple photosynthetic bacterium Rhodobacter (Rba.) sphaeroides were studied using static and ultrafast optical methods and resonance Raman spectroscopy. Carotenoid synthesis in the Rba. sphaeroides strain was engineered to redirect carotenoid production away from spheroidene into the spirilloxanthin synthesis pathway. The strain assembles LH2 antennas with substantial amounts of spirilloxanthin (total double-bond conjugation length N=13) if grown anaerobically and of keto-bearing long-chain analogs [2-ketoanhydrorhodovibrin (N=13), 2-ketospirilloxanthin (N=14) and 2,2'-diketospirilloxanthin (N=15)] if grown semi-aerobically (with ratios that depend on growth conditions). We present the photophysical, electronic, and vibrational properties of these carotenoids, both isolated in organic media and assembled within LH2 complexes. Measurements of excited-state energy transfer to the array of excitonically coupled bacteriochlorophyll a molecules (B850) show that the mean lifetime of the first singlet excited state (S1) of the long-chain (N≥13) carotenoids does not change appreciably between organic media and the protein environment. In each case, the S1 state appears to lie lower in energy than that of B850. The energy-transfer yield is ~0.4 in LH2 (from the strain grown aerobically or semi-aerobically), which is less than half that achieved for LH2 that contains short-chain (N≤11) analogues. Collectively, the results suggest that the S1 excited state of the long-chain (N≥13) carotenoids participates little if at all in carotenoid-to-BChl a energy transfer, which occurs predominantly via the carotenoid S2 excited state in these antennas.

Spectroscopic and functional characterization of cyanobacterium Synechocystis PCC 6803 mutants on the cytoplasmic-side of cytochrome b559 in photosystem II.

We performed spectroscopic and functional characterization on cyanobacterium Synechocystis PCC6803 with mutations of charged residues of the cytoplasmic side of cytochrome (Cyt) b559 in photosystem II (PSII). All of the mutant cells grew photoautotrophically and assembled stable PSII. However, R7Eα, R17Eα and R17Lß mutant cells grew significantly slower and were more susceptible to photoinhibition than wild-type cells. The adverse effects of the arginine mutations on the activity and the stability of PSII were in the following order (R17Lß>R7Eα>R17Eα and R17Aα). All these arginine mutants exhibited normal period-four oscillation in oxygen yield. Thermoluminescence characteristics indicated a slight decrease in the stability of the S3QB(-)/S2QB(-) charge pairs in the R7Eα and R17Lß mutant cells. R7Eα and R17Lß PSII core complexes contained predominantly the low potential form of Cyt b559. EPR results indicated the displacement of one of the two axial ligands to the heme of Cyt b559 in R7Eα and R17Lß mutant reaction centers. Our results demonstrate that the electrostatic interactions between these arginine residues and the heme propionates of Cyt b559 are important to the structure and redox properties of Cyt b559. In addition, the blue light-induced nonphotochemical quenching was significantly attenuated and its recovery was accelerated in the R7Lα and R17Lß mutant cells. Furthermore, ultra performance liquid chromatography-mass spectrometry results showed that the PQ pool was more reduced in the R7Eα and R17Lß mutant cells than wild-type cells in the dark. Our data support a functional role of Cyt b559 in protection of PSII under photoinhibition conditions in vivo.

Venous thromboembolism knowledge among older post-hip fracture patients and their caregivers.

Patient education about venous thromboembolism (VTE) prevention is needed to prevent complications and costly re-hospitalization. Nurses are uniquely positioned to provide vital education as patients transition from the inpatient setting to after discharge. Still, little is known about patient knowledge deficits and those of their caregivers. The purpose of this study was to explore VTE prevention knowledge in a sample of older hip fracture patients and family caregivers. At the time of hospital discharge, surveys were completed by hip fracture surgery patients (≥65; n=30) and family caregivers (n=30). Participants reported needs for more prophylactic anticoagulation and side effects education. Mean education satisfaction was 3.49 out of 5 among patients and 3.83 among caregivers. Focused patient education regarding the wisdom of VTE prevention, potential risks involved, and patient and caregiver roles in advocating for better prevention measures is needed for these patients at risk for hospital readmission secondary to VTE.

Perturbing the water cavity surrounding the manganese cluster by mutating the residue D1-valine 185 has a strong effect on the water oxidation mechanism of photosystem II.

The active site of water oxidation in Photosystem II (PSII) is a Mn4CaO5 cluster that is located in a cavity between the D1 and CP43 protein subunits by which it is coordinated. The remainder of this cavity is filled with water molecules, which serve as a source of substrate and participate in poorly understood hydrogen bond networks that may modulate the function of the Mn4CaO5 cluster. These water molecules interact with the first and second sphere amino acid ligands to the Mn4CaO5 cluster and some water interacts directly with the Mn4CaO5 cluster. Here, the results of mutations to the amino acids that line the walls of several predicted cavities in the immediate vicinity of the Mn4CaO5 cluster were examined in Synechocystis sp. PCC 6803. Of these, mutations of Val185 in the D1 subunit resulted in the most interesting functional alterations. The hydrophobic D1-Val185 occupies a location contacting water molecules that are positioned between the redox active tyrosine (YZ) and the putative proton gate residue, D1-Asp61, and at a position opposite the oxo bridge atom, O5, of the cluster. Mutations of the residue D1-Val185 were produced, with the intention that the substitute residue would extend into the water cavity that includes H2O molecules that interact with the Mn4CaO5 cluster, amino acid ligands of the Mn4CaO5 cluster, YZ and the chloride co-factor of PSII. Three of these mutants, D1-Val185Asn, D1-Val185Thr, and D1-Val185Phe, were able to accumulate significant levels of charge separating PSII and were characterized using polarographic and fluorescent techniques. Of the three substitutions, the phenylalanine substitution was the most severe with a complete inability to evolve oxygen, despite being able to accumulate PSII and to undergo stable charge separation. The threonine substitution had no apparent effect on oxygen evolution other than a 40% reduction in the steady state rate of O2 production compared to the case of wild-type Synechocystis , due to a reduced ability to accumulate PSII centers. The asparagine substitution produced the most complex phenotype with respect to O2 evolution. Although still able to evolve oxygen, D1-Val185Asn does so less efficiently than wild-type PSII, with a higher miss factor than that for the wild type. Most significantly, asparagine substitution dramatically retards the rate of O2 release and results in an extension of the kinetic lag phase prior to O2 release that is highly reminiscent of the effects of mutations produced at D1-Asp61. The observed effects of the D1-Val185Phe and D1-Val185Asn mutations may be due to alterations in the environment of nearby chloride co-factor of PSII and/or alterations in the hydrogen bond network, perhaps impeding the movement of water to a binding site on the metal cluster.

Participation of glutamate-333 of the D1 polypeptide in the ligation of the Mn4CaO5 cluster in photosystem II.

In the 1.9 Å structural model of photosystem II (PDB: 3ARC), the amino acid residue Glu333 of the D1 polypeptide coordinates to the oxygen-evolving Mn4CaO5 cluster. This residue appears to be highly significant in that it bridges the two Mn ions (Mn(B3) and the "dangling" Mn(A4)) that are also bridged by the oxygen atom O5. This oxygen atom has been proposed to be derived from one of two substrate water molecules and to become incorporated into the product dioxygen molecule during the final step in the catalytic cycle. In addition, the backbone nitrogen of D1-Glu333 interacts directly with a nearby Cl⁻ atom. To further explore the influence of this structurally unique residue on the properties of the Mn4CaO5 cluster, the D1-E333Q mutant of the cyanobacterium Synechocystis sp. PCC 6803 was characterized with a variety of biophysical and spectroscopic methods, including polarography, EPR, X-ray absorption, and FTIR difference spectroscopy. The kinetics of oxygen release in the mutant were essentially unchanged from those in wild-type. In addition, the oxygen flash yields exhibited normal period-four oscillations having normal S state parameters, although the yields were lower, indicative of the mutant's lower steady-state dioxygen evolution rate of approximately 30% compared to that of the wild-type. The S1 state Mn-XANES and Mn-EXAFS and S2 state multiline EPR signals of purified D1-E333Q PSII core complexes closely resembled those of wild-type, aside from having lower amplitudes. The S(n+1)-minus-S(n) FTIR difference spectra showed only minor alterations to the carbonyl, amide, and carboxylate stretching regions. However, the mutation eliminated a negative peak at 3663 cm⁻¹ in the weakly H-bonding O-H stretching region of the S2-minus-S1 FTIR difference spectrum and caused an approximately 9 cm⁻¹ downshift of the negative feature in this region of the S1-minus-S0 FTIR difference spectrum. We conclude that fully functional Mn4CaO5 clusters assemble in the presence of the D1-E333Q mutation but that the mutation decreases the yield of assembled clusters and alters the H-bonding properties of one or more water molecules or hydroxide groups that are located on or near the Mn4CaO5 cluster and that either deprotonate or form stronger hydrogen bonds during the S0 to S1 and S1 to S2 transitions.

Proton transport facilitating water-oxidation: the role of second sphere ligands surrounding the catalytic metal cluster.

The ability of PSII to extract electrons from water, with molecular oxygen as a by-product, is a remarkable biochemical and evolutionary innovation. From an evolutionary perspective, the invention of PSII approximately 2.7 Ga led to the accelerated accumulation of biomass in the biosphere and the accumulation of oxygen in the atmosphere, a combination that allowed for the evolution of a much more complex and extensive biosphere than would otherwise have been possible. From the biochemical and enzymatic perspective, PSII is remarkable because of the thermodynamic and kinetic obstacles that needed to have been overcome to oxidize water as the ultimate photosynthetic electron donor. This article focuses on how proton release is an integral part of how these kinetic and thermodynamic obstacles have been overcome: the sequential removal of protons from the active site of H2O-oxidation facilitates the multistep oxidation of the substrate water at the Mn4CaOx, the catalytic heart of the H2O-oxidation reaction. As noted previously, the facilitated deprotonation of the Mn4CaOx cluster exerts a redox-leveling function preventing the accumulation of excess positive charge on the cluster, which might otherwise hinder the already energetically difficult oxidation of water. Using recent results, including the characteristics of site-directed mutants, the role of the second sphere of amino acid ligands and the associated network of water molecules surrounding the Mn4CaOx is discussed in relation to proton transport in other systems. In addition to the redox-leveling function, a trapping function is assigned to the proton release step occurring immediately prior to the dioxygen chemistry. This trapping appears to involve a yet-to-be clarified gating mechanism that facilitates to coordinated release of a proton from the neighborhood of the active site thereby insuring that the backward charge-recombination reaction does not out-compete the forward reaction of dioxygen chemistry during this final step of H2O-oxidation.

Synthesis and photophysical properties of chlorins bearing 0-4 distinct meso-substituents.

The presence of substituents at designated sites about the chlorin macrocycle can alter the spectral properties, a phenomenon that can be probed through synthesis. Prior syntheses have provided access to chlorins bearing distinct aryl substituents (individually or collectively) at the 5, 10, and 15-positions, but not the 20-position. A new Western half (5-phenyl-2,3,4,5-tetrahydro-1,3,3-trimethyldipyrrin) has been employed in condensation with an Eastern half (9-bromodipyrromethane-1-carboxaldehyde) followed by oxidative cyclization to give (5% yield) the zinc(II) 20-phenylchlorin. Condensation of the same Western half and a diaryl-substituted Eastern half provided (11% yield) the zinc(II) 5,10,20-triarylchlorin; demetalation with TFA followed by 15-bromination and Suzuki coupling gave the free base 5,10,15,20-tetraarylchlorin. Altogether, 10 new synthetic chlorins have been prepared. The near-UV (B) absorption band of the free base chlorins shifts bathochromically from 389 to 429 nm and that for the zinc chlorins from 398 to 420 nm as the number of meso-aryl rings is increased stepwise from 0-4. The long-wavelength (Q(y)) absorption band undergoes a bathochromic and hypochromic shift upon increase in number of meso-aryl groups. Regardless of the number and positions of the meso-aryl substituents (including "walking a phenyl group around the ring"), the respective fluorescence quantum yields (0.17 to 0.27) and singlet excited-state lifetimes (9.4 to 13.1 ns) are comparable among the free base chlorins and the same is true for the zinc chelates (0.057 to 0.080; 1.2 to 1.6 ns). Density functional theory calculations show that of the frontier molecular orbitals of the chlorin, the energy of the HOMO-1 is the most affected by meso-aryl substituents, undergoing progressive destabilization as the number of meso-aryl groups is increased. The availability of chlorins with 0-4 distinct meso-aryl substituents provides the individual stepping-stones to bridge the known unsubstituted chlorin and the meso-tetraarylchlorins.

Contributors to depressive symptoms among Korean immigrants with type 2 diabetes.

BACKGROUND: Patients with diabetes have a higher prevalence of depression than the general population. Korean immigrants with type 2 diabetes are understudied. OBJECTIVES: The aim of this study was to identify the prevalence and correlates of depressive symptoms in Korean immigrants. METHODS: In this cross-sectional descriptive study, a community sample of 164 Korean immigrant adults with type 2 diabetes were assessed for depressive symptoms using the Center for Epidemiological Studies Depression scale. Predictors of depression were grouped into three categories: demographic (age, gender, education, English proficiency), clinical (duration of diabetes, comorbidities, insulin use), and psychosocial (general health, diabetes-related quality of life [QOL], family support). RESULTS: Approximately 56% of participants had Center for Epidemiological Studies Depression Scale scores of ≥16. Higher levels of depression were associated with greater impact of diabetes on QOL (b = 5.68, p = .001), worse overall health (b = -0.09, p = .012), and less family support (b = -4.02, p = .042). The relationship between depression and diabetes impact on QOL was stronger for men than women (b = 6.67, p = .020). DISCUSSION: Depressive symptoms are common among Korean immigrants with type 2 diabetes. Assessing diabetes-related QOL, general health, and family support may be of value in better understanding depressive symptoms among this population. Among Korean immigrant men with type 2 diabetes, specific attention should be paid to diabetes-related QOL.

Forgiveness and health: assessing the mediating effect of health behavior, social support, and interpersonal functioning.

Religiousness and spirituality are important to most Americans and while beneficial associations between forgiveness and health are consistently observed, little is known regarding the mechanism of association. Cross-sectional multiple mediation-based analyses of associations between dimensions of forgiveness and physical and mental health were conducted using a sample of 363 undergraduate students from rural Southern Appalachia. Controlling for demographic variables (i.e., gender, age, education, ethnicity, and marital status) and lifetime religiousness, multivariable analyses reflected associations of forgiveness of self and forgiveness of others, but not feeling forgiven by God, with physical health status, somatic symptoms, mental health status, and psychological distress. All such associations operated through health behavior and/or social support; however, only in the context of forgiveness of self did such associations also operate through interpersonal functioning (problems). While forgiveness of self and forgiveness of others each appear to have a robust indirect relationship with health, mediation-based associations involving forgiveness of self were nearly twice as frequent. It may be that forgiveness of self is relatively more important to health-related outcomes.

The D1-D61N mutation in Synechocystis sp. PCC 6803 allows the observation of pH-sensitive intermediates in the formation and release of O2 from photosystem II.

The active site of photosynthetic water oxidation by Photosystem II (PSII) is a manganese-calcium cluster (Mn(4)CaO(5)). A postulated catalytic base is assumed to be crucial. CP43-Arg357, which is a candidate for the identity of this base, is a second-sphere ligand of the Mn(4)-Ca cluster and is located near a putative proton exit pathway, which begins with residue D1-D61. Transient absorption spectroscopy and time-resolved O(2) polarography reveal that in the D1-D61N mutant, the transfer of an electron from the Mn(4)CaO(5) cluster to Y(Z)(OX) and O(2) release during the final step of the catalytic cycle, the S(3)-S(0) transition, proceed simultaneously but are more dramatically decelerated than previously thought (t(1/2) of up to ~50 ms vs a t(1/2) of 1.5 ms in the wild type). Using a bare platinum electrode to record the flash-dependent yields of O(2) from mutant and wild-type PSII has allowed the observation of the kinetics of release of O(2) from extracted thylakoid membranes at various pH values and in the presence of deuterated water. In the mutant, it was possible to resolve a clear lag phase prior to the appearance of O(2), indicating formation of an intermediate before the onset of O(2) formation. The lag phase and the photochemical miss factor were more sensitive to isotope substitution in the mutant, indicating that proton efflux in the mutant proceeds via an alternative pathway. The results are discussed in comparison with earlier results obtained from the substitution of CP43-Arg357 with lysine and in regard to hypotheses concerning the nature of the final steps in photosynthetic water oxidation. These considerations led to the conclusion that proton expulsion during the initial phase of the S(3)-S(0) transition starts with the deprotonation of the primary catalytic base, probably CP43-Arg357, followed by efficient proton egress involving the carboxyl group of D1-D61 in a process that constitutes the lag phase immediately prior to O(2) formation chemistry.

Copper transporter 2 regulates endocytosis and controls tumor growth and sensitivity to cisplatin in vivo.

Copper transporter 2 (CTR2) is one of the four copper transporters in mammalian cells that influence the cellular pharmacology of cisplatin and carboplatin. CTR2 was knocked down using a short hairpin RNA interference. Robust expression of CTR2 was observed in parental tumors grown in vivo, whereas no staining was found in the tumors formed from cells in which CTR2 had been knocked down. Knockdown of CTR2 reduced growth rate by 5.8-fold, increased the frequency of apoptotic cells, and decreased the vascular density, but it did not change copper content. Knockdown of CTR2 increased the tumor accumulation of cis-diamminedichloroplatinum(II) [cisplatin (cDDP)] by 9.1-fold and greatly increased its therapeutic efficacy. Because altered endocytosis has been implicated in cDDP resistance, uptake of dextran was used to quantify the rate of macropinocytosis. Knockdown of CTR2 increased dextran uptake 2.5-fold without reducing exocytosis. Inhibition of macropinocytosis with either amiloride or wortmannin blocked the increase in macropinocytosis mediated by CTR2 knockdown. Stimulation of macropinocytosis by platelet-derived growth factor coordinately increased dextran and cDDP uptake. Knockdown of CTR2 was associated with activation of the Rac1 and cdc42 GTPases that control macropinocytosis but not activation of the phosphoinositide-3 kinase pathway. We conclude that CTR2 is required for optimal tumor growth and that it is an unusually strong regulator of cisplatin accumulation and cytotoxicity. CTR2 regulates the transport of cDDP in part through control of the rate of macropinocytosis via activation of Rac1 and cdc42. Selective knockdown of CTR2 in tumors offers a strategy for enhancing the efficacy of cDDP.

Psychometric validation of a short acculturation scale for Korean immigrants.

BACKGROUND: Acculturation has been identified as a determinant of health behavior and outcome among ethnic minorities. The high prevalence of lifestyle-related chronic diseases and risk factors among Korean immigrants calls for a valid short acculturation scale to use in clinical practice and health research settings. OBJECTIVES: The aim of this study was to validate the psychometric properties of a short acculturation scale originally developed for Hispanics after translating the scale to Korean (SAS-K) to determine its suitability for use with Korean immigrants. METHODS: A self-administered questionnaire was completed by 143 Korean immigrants with Type 2 diabetes aged 30-80 years from a Korean community in Southern California. Confirmatory factor analysis, criterion validity, and internal reliability were utilized to evaluate the psychometric properties of the SAS-K. RESULTS: Using a second-order confirmatory factor analysis, a 3-factor structure, χ(51) = 121.49, p < .001 (comparative fit index = .950, standardized root mean squared residual = .055, root mean square error of approximation = .099), was confirmed. The SAS-K was associated positively with length of residence, age of arrival, and English proficiency. Reliability for the total SAS-K was .93. Cronbach's alpha coefficients for each subscale of the SAS-K ranged from .80 (Ethnic Social Relations) to .95 (Media). DISCUSSION: The 12-item, easy-to-use SAS-K showed satisfactory reliability and validity and, thus, is an appropriate instrument for measuring acculturation in Korean immigrants. The short nature and ease of administration of the SAS-K make it an ideal choice for healthcare providers and researchers to assess acculturation levels quickly and easily and to further the development and use of more culture-appropriate interventions.

The fine line of defensive medicine.

Defensive medicine is a practice that has been utilized by clinicians in efforts of preventing patient dissatisfaction and malpractice claims and may be done through either omission or commission. As much as 57% of physicians have disclosed that they practice defensive medicine. However, this practice does not necessarily prevent malpractice claims and more importantly, neither does it equate to good medical practice, with some leading to poor outcomes. Unfortunately, there is a high percentage of malpractice claims lodged against clinicians in both primary care and hospital settings. Specialists such as surgeons, obstetricians, and gynecologists face the highest claims. In particular, during the SARS CoV-2 pandemic, with new challenges and limited treatment algorithms, there is an even greater concern for possible bourgeoning claims. Counteracting defensive medicine can be accomplished through decriminalizing malpractice claims, leaving physician oversight up to state medical boards and hospital claims management committees. Additional tort reform measures must also be taken such as caps on noneconomic damages to ensure emphasis on beneficence and nonmaleficence. Once these are in place, it may well serve to increase clinician-patient trust and improve patient independence in the shared decision-making process of their treatment, allowing clinicians to practice their full scope of practice without feeling wary of potential malpractice claims.