27-year-old man • muscle weakness • fatigue • electrolyte abnormalities • Dx?

► Muscle weakness ►Fatigue ► Electrolyte abnormalities.

Effect of Layperson-Delivered, Empathy-Focused Program of Telephone Calls on Loneliness, Depression, and Anxiety Among Adults During the COVID-19 Pandemic: A Randomized Clinical Trial.

Importance: Loneliness is a risk factor for many clinical conditions, but there are few effective interventions deployable at scale. Objective: To determine whether a layperson-delivered, empathy-focused program of telephone calls could rapidly improve loneliness, depression, and anxiety in at-risk adults. Design, Setting, and Participants: From July 6 to September 24, 2020, we recruited and followed up 240 adults who were assigned to receive calls (intervention group) or no calls (control group) via block randomization. Loneliness, depression, and anxiety were measured using validated scales at enrollment and after 4 weeks. Intention-to-treat analyses were conducted. Meals on Wheels Central Texas (MOWCTX) clients received calls in their homes or wherever they might have been when the call was received. The study included MOWCTX clients who fit their service criteria, including being homebound and expressing a need for food. A total of 296 participants were screened, of whom 240 were randomized to intervention or control. Interventions: Sixteen callers, aged 17 to 23 years, were briefly trained in empathetic conversational techniques. Each called 6 to 9 participants over 4 weeks daily for the first 5 days, after which clients could choose to drop down to fewer calls but no less than 2 calls a week. Main Outcomes and Measures: Primary outcome was loneliness (3-item UCLA Loneliness Scale, range 3-9; and 6-item De Jong Giervald Loneliness [De Jong] Scale, range 0-6). Secondary outcomes were depression (Personal Health Questionnaire for Depression), anxiety (Generalized Anxiety Disorder scale), and self-rated health (Short Form Health Survey Questionnaire). Results: The 240 participants were aged 27 to 101 years, with 63% aged at least 65 years (n = 149 of 232), 56% living alone (n = 135 of 240), 79% women (n = 190 of 240), 39% Black or African American (n = 94 of 240), and 22% Hispanic or Latino (n = 52 of 240), and all reported at least 1 chronic condition. Of 240 participants enrolled, 13 were lost to follow-up in the intervention arm and 1 in the control arm. Postassessment differences between intervention and control after 4 weeks showed an improvement of 1.1 on the UCLA Loneliness Scale (95% CI, 0.5-1.7; P < .001; Cohen d of 0.48), and improvement of 0.32 on De Jong (95% CI, -0.20 to 0.81; P = .06; Cohen d, 0.17) for loneliness; an improvement of 1.5 on the Personal Health Questionnaire for Depression (95% CI, 0.22-2.7; P < .001; Cohen d, 0.31) for depression; and an improvement of 1.8 on the Generalized Anxiety Disorder scale (95% CI, 0.44 to 3.2; P < .001; Cohen d, 0.35) for anxiety. General physical health on the Short Form Health Questionnaire Survey showed no change, but mental health improved by 2.6 (95% CI, 0.81 to 4.4; P = .003; Cohen d of 0.46). Conclusions and Relevance: A layperson-delivered, empathy-oriented telephone call program reduced loneliness, depression, and anxiety compared with the control group and improved the general mental health of participants within 4 weeks. Future research can determine whether effects on depression and anxiety can be extended to maximize clinical relevance. Trial Registration: ClinicalTrials.gov Identifier: NCT04595708.

An epifluorescence-based evaluation of the effects of short-term particle association on the chlorination of surface water bacteria.

Investigations into particle-mediated chlorination resistance were undertaken for three different bacteria (Escherichia coli ATCC 25922 and environmental isolates of Pseudomonas fluorescens and Serratia marcescens) and three different surfaces (goethite, environmental particles and surface-modified environmental particles). P. fluorescens demonstrated greater hydrophobicity than both other strains and proved the most adherent bacterium over all substrata investigated. Particle-mediated resistance to chlorination was investigated using short bacteria-particle association times and activity assays that employed sensitive epifluorescent detection. Consistent with adhesive behaviours, the bacterial strain that demonstrated the greatest particle-mediated chlorination resistance was the environmental strain of P. fluorescens. Resistance was observed to vary with both bacteria and particle type, and demonstrated a moderate correlation with adhesion (r(2) ≥ 0.65). The short-term approach employed in our study demonstrates particle-mediated protection without the commonly assumed requirements of extracellular polymeric substances (EPS) or a large particle-based chlorine demand. Consequently, we have linked resistance with adhesion capacities and demonstrated a limit to resistance in the presence of additional particle protective sites (through increased turbidity) which appears to be driven by intra-population variance in bacterial surface characteristics. Finally, we observed important differences between behaviours of environmental versus laboratory-derived bacterial strains and particles, which highlight the importance of employing both approaches in characterising "real world" systems.

CRP subunit association and hinge conformation changes in response to cAMP binding: analysis of C-helix cysteine-substituted CRP.

We investigated the characteristics of 13 CRP variants having cysteine substituted at positions 113, 115, 116, 117, 118, 120, 122, 124, 126, 127, 129, 130, or 131, positions that span the length of the CRP C alpha-helix. Under reducing conditions, the WT and all Cys-substituted forms of CRP migrated as 23.5 kDa CRP monomer species on SDS-PAGE gels. In the absence of a reductant, 9 of 13 Cys-substituted forms of CRP including the L113C, S117C, M120C, L124C, V126C, T127C, E129C, K130C, and V131C CRP contained protein that migrated as 47 kDa CRP dimer species on SDS-PAGE gels. CNBr digestion of the protein preparations followed by MALDI-TOF MS analysis of the peptide fragments showed these 47 kDa species to be CRP dimers that originated from disulfide bonds formed between positional-pair C alpha-helix Cys residues. The ratio of monomer CRP and disulfide cross-linked CRP within a Cys-substituted CRP preparation was found to be independent of cAMP for Cys-substituted CRP preparations denatured and renatured in the presence of various cAMP concentrations. This finding suggests that there is no large-scale concerted motion (i.e., scissoring) of the CRP subunits in response to cAMP binding. In addition, we have identified three amino acid residues located along the CRP C alpha-helix that play a role in facilitating the conformation transition of the CRP hinge from that characteristic of apo-CRP to that characteristic of the CRP.cAMP complex.

Characterisation of antibacterial Australian medicinal plant extracts by investigation of the mechanism of action and the effect of interfering substances.

Propidium iodide (PI) uptake and salt tolerance assays were used to investigate the mechanism of antibacterial action of an extract of the leaves of Eremophila duttonii, a traditional Australian medicinal plant previously shown to have potent bactericidal activity against Gram positive bacteria. The extract compromised the integrity of the cytoplasmic membrane of Staphylococcus aureus , leading to increased membrane permeability (indicated by uptake of PI) and a decrease in ability to exclude NaCl. The bactericidal action of the E. duttonii extract was concluded to be due to its membrane-active properties. The effect of contaminants on the efficacy of this extract and other medicinal plant extracts was also investigated. Organic contaminants (bakers' yeast and skim milk powder) decreased the efficacy of all extracts investigated, while hard water had no effect. Greater understanding of the biocidal properties of the plant extracts investigated may determine if they have medical, industrial or environmental applications. ((c) 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim).

Interaction of CRP L124 with cAMP affects CRP cAMP binding constants, cAMP binding cooperativity, and CRP allostery.

A cyclic nucleotide-binding pocket of the CRP dimer is composed of amino acid residues contributed by both subunits. Leucine (L) 124 of one subunit packs against the adenine ring of cAMP bound to the opposing subunit. We have undertaken a study designed to evaluate the role of L124 in CRP allostery. Wild-type (WT) apo-CRP is a 47 kDa protease-resistant dimer composed of identical subunits that exhibits a biphasic isotherm in cAMP titration studies. The WT CRP-cAMP complex is a protease-sensitive dimer degraded by protease to a dimer core that ranges between 26.5 and 30.5 kDa. Substitution of L124 with isoleucine (I), valine (V), cysteine (C), or alanine (A) generated a series of CRP variants that exhibited unique differences in apo-CRP resistance to protease, the mass of the core fragments generated in protease digestion reactions, cAMP-mediated allostery, and CRP-cAMP complex functionality. Differences in the affinity of the position 124 CRP variants for cAMP were observed. The binding constants that drive the formation of the WT and L124I CRP-cAMP complexes deviated by not more than a factor of 1.5. In contrast, the L124V, L124A, and L124C forms of CRP exhibited both a decreased K(cAMP1)(app) and an increased K(cAMP2)(app) to produce 2.4-, 55-, and 204-fold reductions, respectively, in the difference between these two parameters compared to that observed for WT CRP. The data indicate that the van der Waals volume and/or the hyrophobicity of the L124 side chain are important determinants of CRP cAMP binding properties and affect, either directly or indirectly, cAMP-mediated conformation changes in CRP.