A neuropsychological rehabilitation service delivery model for South African adults with acquired brain injury (RSDM-SA).

In low- and- middle- income countries (LMICs) such as South Africa, a high number of Acquired Brain Injuries (ABIs) and a lack of accessibility to healthcare lead to many survivors of brain injury not receiving the level of healthcare and rehabilitation required. Further, in LMICs life-saving or acute care is prioritized with an inadequate focus on the lifelong effects of ABI. This study used Program Theory to develop a Rehabilitation Service Delivery Model for South African Adults with Acquired Brain Injury (RSDM-SA) that caters for the unique nuances of a resource-constrained and culturally diverse context. The RSDM-SA has four interdependent levels, namely (i) Integration of Relevant Aspects of Explanatory Frameworks (ii) South African Contextual Influences on the Model (iii) Systemic Role players Necessary for the Model and (iv) Evidence-Based Guidelines in a Holistic Rehabilitation Process. The Model is a valuable resource in guiding future research endeavors and its contribution lies in the Model's focus on quality, accessibility, relevance, and efficiency, all of which are needed in healthcare internationally.

I36T↑T mutation in South African subtype C (C-SA) HIV-1 protease significantly alters protease-drug interactions.

The efficacy of HIV-1 protease (PR) inhibition therapies is often compromised by the emergence of mutations in the PR molecule that reduces the binding affinity of inhibitors while maintaining viable catalytic activity and affinity for natural substrates. In the present study, we used a recombinant HIV-1 C-SA PR and a recently reported variant for inhibition (Ki, IC50) and thermodynamic studies against nine clinically used inhibitors. This is the first time that binding free energies for C-SA PR and the mutant are reported. This variant PR harbours a mutation and insertion (I36T↑T) at position 36 of the C-SA HIV-1 PR, and did not show a significant difference in the catalytic effect of the HIV-1 PR. However, the nine clinically approved HIV PR drugs used in this study demonstrated weaker inhibition and lower binding affinities toward the variant when compared to the wild type HIV-1 PR. All the protease inhibitors (PIs), except Amprenavir and Ritonavir exhibited a significant decrease in binding affinity (p<0.0001). Darunavir and Nelfinavir exhibited the weakest binding affinity, 155- and 95-fold decreases respectively, toward the variant. Vitality values for the variant PR, against the seven selected PIs, confirm the impact of the mutation and insertion on the South African HIV-1 subtype C PR. This information has important clinical implications for thousands of patients in Sub-Saharan Africa.

Neuroprotective potential of Linezolid: a quantitative and distribution study via mass spectrometry.

A study was undertaken to determine the neuroprotective potential of Linezolid (LIN) in an animal model. Female Sprague-Dawley rats were either given a single (100 mg/kg) dose or treated daily for 4 weeks. A validated LC-MS/MS method was used to measure LIN levels in plasma and brain, this was paired with mass spectrometry imaging to determine the tissue spatial distribution of the drug. The results showed that after a single dose there was poor penetration of the drug into the brain. With multiple doses there were high tissue levels, with the drug reaching steady state in subsequent weeks. LIN displayed a promising distribution pattern with localisation in the brainstem. Systemic circulation is fed into the brain by the carotid and vertebral arteries which enter through the brain stem, therefore high drug concentrations is this area may protect against infectious agents entering via this route.

Small molecule distribution in rat lung: a comparison of various cryoprotectants as inflation media and their applicability to MSI.

Given the recent explosion of mass spectrometric imaging (MSI), it has become easier to assess drug tissue localisation without the use of radiolabeling and other more complex methods (such as PET and MRI). For MSI tissue preparation is of utmost importance, however, the lung in particular does pose some difficulties with imaging since it is made up of a number of air-filled alveoli. These organs are known to collapse when the thoracic cavity is pierced, losing its structural integrity and giving poor histological representation for drug distribution analysis. The use of cryoprotectants as a tissue inflation media will aid in the preservation of the lung's structural integrity during MSI experiments involving small molecule distribution. Various established cryoprotectants (DMSO, PvP, ethylene glycol, sucrose, DMEM, control serum, OCT) were selected as lung inflation media for MSI analysis of gatifloxacin (GAT). Female Sprague-Dawley rats were treated with GAT (10 mg/kg b.w) via i.p. injection. After 15 min the animals were terminated by halothane overdose, and each set of tissue inflated with a specific agent. Cryosections were made and MSI conducted to determine drug tissue distribution. During the early stages of the experimental procedure some crypreservatives were eliminated due to difficulties with sample preparation. While others displayed excellent preservation of the tissue structure and integrity. Following MSI analysis, some agents showed homogenous drug distribution while some displayed heterogeneous distribution favoring the basal periphery. Taking into account the physiology of the lung and previous MRI investigations of its perfusion, it is expected that a systemically administered drug would localize in the basal areas. DMSO and DMEM proved to display this distribution pattern while keeping structural integrity intact. However, the later was ruled out since it showed complete suppression of GAT in solution. From the cryoprotectants selected for this study, DMSO is the most promising lung inflation media focusing on small molecule distribution via MSI.

A TEST OF SHARKEY AND SINGELIS' (1995) MODEL OF SELF-CONSTRUAL AND EMBARRASSABILITY: SITUATIONAL VERSUS DISPOSITIONAL FACTORS.

Sharkey and Singelis (1995 ) tested a model of embarrassment focusing on strength of independent self-construal, sensitivity to evaluation, and strength of interdependent self-construal. Their findings indicated social anxiety and self-construal explained 28% of the variance in embarrassability. Separately, social anxiety contributed 5.8%, with independent and interdependent self-construal explaining 6.6 and 5.2%, respectively, thus supporting the model. Sharkey and Singelis used Modigiliani's ( 1968 ) Embarrassability Scale, which focuses on embarrassing situations. The current study repeated the analysis but measured embarrassability as a disposition on a sample of Black African (59.8%), Colored (6.1%), Asian/Indian (5.9%), and White (28.2%) first-year psychology students (139 men, 485 women) between 18 and 51 years old (M = 19.5, SD = 2.9). The three constructs together explained about 47% of dispositional embarrassability. Social anxiety explained 25% of the variance, when controlling for independent and interdependent self-construal. Sharkey and Singelis' model may be more applicable to the explanation of situational embarrassability than dispositional embarrassability.

Experimental climate warming enforces seed dormancy in South African Proteaceae but seedling drought resilience exceeds summer drought periods.

Two hypotheses-that elevated night-time temperatures due to climate warming would enforce post-fire dormancy of Proteaceae seed due to low moisture, and that periods without rain during summer would exceed desiccation periods tolerated by Proteaceae seedlings-were tested empirically. Enforced dormancy, i.e., the inability to germinate due to an environmental restraint, was tested by measuring seed germination in 11 Proteaceae species in experimental mesocosms whose soils were artificially elevated by 1.4 and 3.5 °C above ambient by far-red wavelength filtered infrared lamps. Diminished totality of germination and velocities were observed in 91 and 64%, respectively, of the Proteaceae species tested. Drought resilience was tested in one-year-old seedlings of 16 Proteaceae species by withholding water from potted plants during summer in a greenhouse. The most drought-resilient Proteaceae species displayed the lowest initial transpiration rates at field capacity, the smallest declines in transpiration rate with decreasing soil water content, and the lowest water losses by transpiration. Projected drought periods leading to the complete cessation of transpiration in all Proteaceae species greatly exceeded the number of days without rain per month during summer in the current distribution ranges of those species. It was therefore concluded that enforced seed dormancy induced by elevated night-time temperatures is the post-fire recruitment stage of Proteaceae that is most sensitive to climate warming.

A critical survey of average distances between catalytic carboxyl groups in glycoside hydrolases.

Published X-ray crystallographic structures for glycoside hydrolases (GHs) from 39 different families are surveyed according to some rigorous selection criteria, and the distances separating 208 pairs of catalytic carboxyl groups (20 α-retaining, 87 ß-retaining, 38 α-inverting, and 63 ß-inverting) are analyzed. First, the average of all four inter-carboxyl O…O distances for each pair is determined; second, the mean of all the pair-averages within each GH family is determined; third, means are determined for groups of GH families. No significant differences are found for free structures compared with those complexed with a ligand in the active site of the enzyme, nor for α-GHs as compared with ß-GHs. The mean and standard deviation (1σ) of the unimodal distribution of average O…O distances for all families of inverting GHs is 8 ± 2Å, with a very wide range from 5Å (GH82) to nearly 13Å (GH46). The distribution of average O…O distances for all families of retaining GHs appears to be bimodal: the means and standard deviations of the two groups are 4.8 ± 0.3Å and 6.4 ± 0.6Å. These average values are more representative, and more likely to be meaningful, than the often-quoted literature values, which are based on a very small sample of structures. The newly-updated average values proposed here may alter perceptions about what separations between catalytic residues are "normal" or "abnormal" for GHs.

Preclinical evaluation of 68Ga-labeled 1,4,7-triazacyclononane-1,4,7-triacetic acid-ubiquicidin as a radioligand for PET infection imaging.

UNLABELLED: Antimicrobial peptides such as ubiquicidin (UBI) are believed to differentiate between mammalian and bacterial or fungal cells. (99m)Tc-UBI29-41 was previously tested for detecting infection in humans using SPECT. For the present study, the UBI fragment UBI29-41 (TGRAKRRMQYNRR) was conjugated to 1,4,7-triazacyclononane-triacetic acid (NOTA), radiolabeled with (68)Ga, and investigated in a rabbit infection model. METHODS: (68)Ga was obtained from a 1.85-GBq (68)Ge/(68)Ga generator. New Zealand White rabbits were anesthetized with ketamine/medetomidine before tracer administration and placed in a clinical PET/CT scanner. (68)Ga-1,4,7-triazacyclononane-1,4,7-triacetic-acid-ubiquicidin29-41 ((68)Ga-NOTA-UBI29-41) was formulated in saline solution, and 101 ± 41 MBq were administered intravenously. The tracer distribution was studied by PET/CT imaging in animals (a) that were healthy, (b) bearing muscular Staphylococcus aureus infections and turpentine oil-induced muscular inflammations, and (c) bearing ovalbumin-induced lung inflammations. Static PET/CT imaging was performed at different time intervals up to 120 min after injection. For calculation of target-to-nontarget ratios, standardized uptake values were normalized against healthy thigh muscle, representing nontargeted tissue. RESULTS: PET/CT images of healthy animals showed predominant distribution in the kidneys, liver, and bladder; heart and spleen showed moderate, declining uptake, only. The biologic half-life in blood was 29 min. Urinary accumulation of (68)Ga-NOTA-UBI29-41 peaked at 3.8 ± 0.91 percentage injected dose per gram (%ID) at 120 min, and 88 ± 5.2 %ID was recovered in total urine. (68)Ga-NOTA-UBI29-41 imaging in (b) selectively visualized the muscular infection site and was differentiated from sterile inflammatory processes. Standardized uptake value ratios for muscles (infected/inflamed) were 2.9 ± 0.93, 2.9 ± 0.50, 3.5 ± 0.86, and 3.8 ± 0.90 at 5, 30, 60, and 90 min after injection, respectively. Rabbit lungs with asthma showed insignificant uptake. CONCLUSION: (68)Ga-NOTA-UBI29-41 was strongly localized in bacteria-infected areas and minimally detected in a sterile inflammation area in rabbit muscles. The findings propose this compound to be an excellent first-line PET/CT tracer to allow the distinguishing of infection from inflammation.

Butane-1,4-diammonium bis(perchlorate).

The butane-1,4-diammonium cation of the title compound, C(4)H(14)N(2) (2+)·2ClO(4) (-), lies on a special position of site symmetry 2/m, whereas the perchlorate anion is located on a crystallographic mirror plane. An intricate three-dimensional hydrogen-bonding network exists in the crystal structure with each H atom of the ammonium group exhibiting bifurcated inter-actions to the perchlorate anion. Complex hydrogen-bonded ring and chain motifs are also evident, in particular a 50-membered ring with graph-set notation R(10) (10)(50) is identified.

Assessment of changes in photosystem II structure and function as affected by water deficit in Amaranthus hypochondriacus L. and Amaranthus hybridus L.

The present study describes the behaviour of photosystem II (PSII) in Amaranthus hypochondriacus and Amaranthus hybridus under water stress conditions, assessed by the analyses of the polyphasic rise in chlorophyll a fluorescence (O-J-I-P). We determined the adaptive behaviour in relation to the regulation of the different functional and structural parameters of PSII, which was a direct and rapid response due to changes in soil water status indicated by a decrease in leaf water potential and relative water content. It allows for the identification of specific key or limiting chlorophyll fluorescence parameters which could be used to identify traits conveying tolerance. For the above partial processes of PSII function studied, it seems that A. hybridus remained the more stable upon water stress (after 17 days of withholding water), concerning the specific energy fluxes of absorption/reaction centre (ABS/RC) apparent (antenna size) and trapping/reaction centre (TR/RC) (maximum trapping flux), as well as the density of the reaction centres/cross section (RC/CS) and the phenomenological trapping flux/cross section (TR(o)/CS). It was clear that amaranth adjusts the non-photochemical (k(n)) deactivation constant of PSII and to a less extend also the photochemical (k(p)) deactivation constant by means of photoregulation, which forms the basis of the quenching of chlorophyll a fluorescence. Although drought stress caused the deactivation of RCs leading to a decrease in the density of active RCs, the plants compensated by increasing the efficiency of the conversion of trapped excitation energy to electron transport beyond Q(A) (efficiency of exciton trapping/reaction centre: ET(o)/TR(o)). Subsequent damage to PSII might be the reason for the slow, or lack of recovery, for most of the parameters measured.

Executive functioning and positive psychological characteristics: a replication and extension.

Positive psychological characteristics and executive function are correlated with gratitude, satisfaction with life, and forgiveness. The goal of this study was to replicate these findings while examining two additional constructs, namely, hope and optimism. 113 students (25 men, 88 women) between the ages of 17 to 24 years (M = 19.4, SD = 1.5) volunteered to participate. Positive correlations between executive function and gratitude were found but mixed results were obtained for forgiveness and satisfaction with life. Hope and optimism correlated positively with executive function and hierarchical multiple regression analysis indicated that they contributed significantly to the explanation of executive functioning. Further investigation into relationships between executive functioning, its neurobiological substrates, and positive psychological attributes is recommended.

Ethane-1,2-diammonium dibromide: a redetermination at 100†K.

In the redetermined [for the previous study, see Søtofte (1976 ▶). Acta Chem. Scand. Ser. A, 30, 309-311] crystal structure of the title compound, C(2)H(10)N(2) (2+)·2Br(-), the H atoms have been located and the hydrogen-bonding scheme is described. The ethane-1,2-diammonium cation lies over a crystallographic inversion centre and straddles a crystallographic mirror plane with the C and N atoms in special positions. In the crystal, the cations and anions are linked by N-H⋯Br and N-H⋯(Br,Br) hydrogen bonds, which generate various ring and chain motifs including an R(10) (5)(32) loop.

Effect of trifluoroacetate, a persistent degradation product of fluorinated hydrocarbons, on Phaseolus vulgaris and Zea mays.

The aim of this study was to quantify the effect of the pollutant, trifluoroacetate (TFA), on growth and photosynthesis of Phaseolus vulgaris (C(3)) and Zea mays (C(4)) in order to elucidate the physiological and biochemical basis of its inhibitory action. In whole plant studies, photosynthetic gas exchange, fast phase fluorescence kinetics and Rubisco activity were measured in parallel over a 14-day period in plants cultivated in a water culture system with NaTFA added at concentrations ranging from 0.625 to 160mgl(-1). Although initial stimulation of some photosynthetic parameters was observed at low TFA concentrations early on in the experiment, marked inhibition occurred at higher concentrations. In general Z. mays was affected more severely than P. vulgaris showing a large TFA-induced decrease in both apparent carboxylation efficiency (ACE) and in vitro Rubisco (ribulose-1,5-bisphosphate carboxylase/oxygenase; EC 4.1.1.39) activity. Analysis of photosynthetic gas exchange revealed that besides constraints on mesophyll processes such as Rubisco activity, stomatal limitation also increased with increasing TFA concentration, especially in P. vulgaris. In depth analysis of the fast phase fluorescence transients pointed at TFA-induced uncoupling of the oxygen evolving complex (OEC) and inhibition of electron transport beyond Q(a) including possible constraints on the reduction of end electron acceptors of photosystem I.

Penta-carbonyl-2κC-chlorido-1κCl-bis-[1(η)-cyclo-penta-dien-yl](µ-1-oxido-ethyl-ene-1:2κO:C)chromium(0)zirconium(IV).

The title compound, [CrZr(C(5)H(5))(2)(C(2)H(3)O)Cl(CO)(5)], consists of two metal centres, with a (penta-carbonyl-chromium)oxymethyl-carbene group coordinating as a monodentate ligand to the zirconocene chloride. π-Delocalization through the Zr-O-C=Cr unit is indicated by a short Zr-O distance [2.041 (3) Å] and a nearly linear Zr-O-C angle [170.5 (3)°]. Mol-ecules are aligned with their mol-ecular planes (through Zr, Cl, carbene and Cr) parallel to the ab plane. C-H⋯Cl inter-actions result in zigzag chains of mol-ecules propagating parallel to the b axis.

Hexane-1,6-diammonium dinitrate.

The hexane-1,6-diammonium cation of the title compound, C(6)H(18)N(2) (2+)·2NO(3) (-), lies across a crystallographic inversion centre and shows significant deviation from planarity in the hydro-carbon chain. This is evident from the torsion angle of -64.0°(2) along the N-C-C-C bond and thse torsion angle of -67.1°(2) along the C-C-C-C bonds. An intricate three-dimensional hydrogen-bonding network exists in the crystal structure, with each H atom on the ammonium group exhibiting bifurcated inter-actions to the nitrate anion. Complex hydrogen-bonded ring and chain motifs are also evident, in particular a 26-membered ring with graph-set notation R(4) (4)(26) is observed.

Hydrogen-bonding motifs and thermotropic polymorphism in redetermined halide salts of hexamethylenediamine.

The redetermined crystal structures of hexane-1,6-diammonium dichloride, C(6)H(18)N(2)(2+) x 2 Cl(-), (I), hexane-1,6-diammonium dibromide, C(6)H(18)N(2)(2+) x 2 Br(-), (II), and hexane-1,6-diammonium diiodide, C(6)H(18)N(2)(2+) x 2 I(-), (III), are described, focusing on their hydrogen-bonding motifs. The chloride and bromide salts are isomorphous, with both demonstrating a small deviation from planarity [173.89 (10) and 173.0 (2) degrees, respectively] in the central C-C-C-C torsion angle of the hydrocarbon backbone. The chloride and bromide salts also show marked similarities in their hydrogen-bonding interactions, with subtle differences evident in the hydrogen-bond lengths reported. Bifurcated interactions are exhibited between the N-donor atoms and the halide acceptors in the chloride and bromide salts. The iodide salt is very different in molecular structure, packing and intermolecular interactions. The hydrocarbon chain of the iodide straddles an inversion centre and the ammonium groups on the diammonium cation of the iodide salt are offset from the planar hydrocarbon backbone by a torsion angle of 69.6 (4) degrees. All three salts exhibit thermotropic polymorphism, as is evident from differential scanning calorimetry analysis and variable-temperature powder X-ray diffraction studies.

Penta-carbonyl-2κC-chlorido-1κCl-bis-[1(η)-cyclo-penta-dien-yl][µ(2)-oxido(meth-yl)methyl-ene-1:2κO:C]tungsten(0)zirconium(IV).

The title compound, [ZrW(C(5)H(5))(2)(C(2)H(3)O)Cl(CO)(5)] or [W(CO)(5)C(CH(3))OZr(C(5)H(5))(2)Cl], consists of two metal centres, with a (tungsten penta-carbon-yl)oxymethyl-carbene group coordinating as a monodentate ligand to the chloridozirconocene. The two halves of the mol-ecule are related by a crystallographic mirror plane. Delocalization through the Zr-O-C=W unit is indicated by a short Zr-O distance and a nearly linear Zr-O-C angle.

Variable-temperature powder X-ray diffraction of aromatic carboxylic acid and carboxamide cocrystals.

The effect of temperature on the cocrystallization of benzoic acid (BA), pentafluorobenzoic acid (FBA), benzamide (BAm), and pentafluorobenzamide (FBAm) is examined in the solid state. BA and FBA formed a 1:1 complex 1 at ambient temperature by grinding with a mortar and pestle. Grinding FBA and BAm together resulted in partial conversion into the 1:1 adduct 2 at 28 degrees C and complete transformation into the product cocrystal at 78 degrees C. Further heating (80-100 degrees C) and then cooling to room temperature gave a different powder pattern from that of 2. BAm and FBAm hardly reacted at ambient temperature, but they afforded the 1:1 cocrystal 3 by melt cocrystallization at 110-115 degrees C. Both BA+FBAm (4) and BA+BAm (5) reacted to give new crystalline phases upon heating, but the structures of these products could not be determined owing to a lack of diffraction-quality single crystals. The stronger COOH and CONH2 hydrogen-bonding groups of FBA and FBAm yielded the equimolar cocrystal 6 at room temperature, and heating of these solids to 90-100 degrees C gave a new crystalline phase. The X-ray crystal structures of 1, 2, 3, and 6 are sustained by the acid-acid/amide-amide homosynthons or acid-amide heterosynthon, with additional stabilization from phenyl-perfluorophenyl stacking in 1 and 3. The temperature required for complete transformation into the cocrystal was monitored by in situ variable-temperature powder X-ray diffraction (VT-PXRD), and formation of the cocrystal was confirmed by matching the experimental peak profile with the simulated diffraction pattern. The reactivity of H-bonding groups and the temperature for cocrystallization are in good agreement with the donor and acceptor strengths of the COOH and CONH2 groups. It was necessary to determine the exact temperature range for quantitative cocrystallization in each case because excessive heating caused undesirable phase transitions.