Assessing and Managing Unintentional Weight Loss: A Global Survey of Geriatrician Practice and Their Use of Ice Cream to Address It.

OBJECTIVES: Unintentional weight loss (UIWL) is common among older adults but lacks standardized methods for its diagnosis and management. With a limited understanding on how geriatricians actually address UIWL, we conducted a survey to examine how they diagnose and manage it, and their opinions regarding the use of ice cream to address it. DESIGN, SETTING, AND PARTICIPANTS: An international descriptive, cross-sectional, online survey conducted over a 16-week period in 2019 involving 1131 geriatricians in clinical practice across 51 countries. MEASUREMENTS: We collected information around respondent demographics, use of screening tools and diagnostic investigations, and pharmacological and non-pharmacological approaches to address UIWL. RESULTS: 89.1% of respondents reported frequently seeing UIWL. The most common methods reportedly used to evaluate UIWL were performing a comprehensive history and physical examination (97.4%) and assessing for cognitive impairment (86.5%). 74.2% noted that they routinely prescribed oral nutritional supplements and 71.6% involved non-medical professional(s) to help manage UIWL. While 50.4% reported recommending ice cream to their patients with UIWL, only 30.6% reported being aware of other colleagues recommending it. Geriatricians in practice for 30+ years were significantly more likely to recommend ice cream (P < 0.05). A thematic analysis of qualitative responses identified that prescribing ice cream tended to align both with patient preferences and socio-economic realities. CONCLUSION: While a majority of geriatricians surveyed routinely prescribe ONS and involve others to manage UIWL, at least half are also recommending ice cream. A key practice amongst experienced geriatricians, the use of ice cream could be better acknowledged as a practical and cost-effective way to address UIWL.

Carnitine supplementation induces long-chain acylcarnitine production--studies in the VLCAD-deficient mouse.

Carnitine supplementation does not affect carnitine concentrations in tissues of wild-type and very long-chain acyl-CoA dehydrogenase-deficient mice, but results in an increase in long-chain acylcarnitine production.

The kringle 4 domain of chicken plasminogen.

The kringle 4 unit of chicken plasminogen is similar to mammalian kringle 4 domains in possessing a lysine-binding site. Chicken kringle 4 shows 73-77% sequence identity with the fourth kringle units of porcine, bovine and human plasminogens. A major difference between mammalian and chicken kringle 4 species is that in the latter a glucosamine-based carbohydrate substituent is linked to asparagine-34. Complexation of this carbohydrate with concanavalin A does not interfere with the binding of kringle 4 to lysine-Sepharose, suggesting that in the kringle-fold the glycosylated region is distant from the entrance of the lysine-binding pocket.

Distribution of Gs-alpha activating mutations in human thyroid tumors measured by subcloning.

In the search for the prevalence and distribution pattern of Gs-alpha gene mutations in differentiated thyroid tumors we examined 66 tumor tissue samples for the presence of mutations at "hot-spot" codons 201 and 227 using methods based on the polymerase chain reaction, subcloning and sequencing. The prevailing type of single-base substitution at codon 201 (71.4%) corresponded to the replacement of the wild-type sequence CGT (Arg) with TGT (Cys). The fragments of the Gs-alpha gene, including codon 201 or 227 from five follicular carcinomas and one follicular adenoma, were subcloned in Escherichia coli and it was found that the proportion of alleles with mutated codon 201 varied from 3.2% to 43%. Sequencing of the corresponding region has confirmed preliminary data indicating that the single-base changes CGT (Arg) to TGT (Cys) or CGT to CAT (His) occurred. There was only a weak correlation between the prevalence of cells bearing a mutation in the Gs-alpha gene and the level of Gs-alpha protein expression in the corresponding thyroid tumors.

Age-dependent decrease of the passive Rb+ and K+ permeability of the nerve cell membranes in rat brain cortex as revealed by in vivo measurement of the Rb+ discrimination ratio.

Young, adult and old male CFY rats (2, 12 and 24 mth of age, respectively) were treated with a daily dose of 30 mg RbCl/100 g body weight, in form of aqueous solution injected intraperitoneally for 14 days. A considerable part of the intracellular K+-content of the body was replaced by Rb+ during this treatment. After cessation of the RbCl injections, a relative steady state came into being in each age group, called Rb+-release period. During this period Rb+ and K+ contents of the blood serum and the cisternal CSF were measured by atomic absorption spectrophotometry, and of the intracellular space of brain cortical cells by energy-dispersive X-ray microanalysis. Ultrastructural features of the brain cortex were also checked by transmission electron microscopy. For X-ray microanalysis, the L-line of Rb at 1.694 keV energy was used at 10 kV accelerating voltage in a scanning electron microscope equipped with an EDAX System F. Rb+ and K+ concentrations were obtained for the cellular dry mass and converted into wet concentrations on the basis of intracellular water contents known from former experiments. Rb+-replacement of K+ did not cause any ultrastructural alteration in the brain cortex. However, the Rb+ accumulation displayed a very significant age-dependent increase: at the beginning of release, adult and old rats had 32.6 and 44.7 mM Rb+ in their intracellular water as against the 8.6 mM found in the young group, and similar proportional difference persisted during 20 days of the release. Rb+ discrimination ratios (DR) calculated either for the blood or the CSF displayed very considerable age-dependent increase: the values of the adult and old groups were 191 and 242% of the young one, indicating that the passive Rb+ (and K+) permeability of the nerve cell membrane decreases throughout the life span of rats. These results give further support to the membrane hypothesis of aging.

Transcellular delta -mu H+ in Valonia ventricosa and its effect on delayed fluorescence.

The possible effect of the illumination-induced transcellular H+-gradient between the central vacuole and the external medium, on both the intensity and the kinetics of delayed fluorescence was studied by measuring both the membrane potentials and H+ fluxes across the plasmatic membranes, and the millisecond component of delayed fluorescence in single cells of the marine alga Valonia ventricosa. The kinetics of the formation of transcellular delta -mu H+ was shown to correlate with the induction kinetics of the millisecond component of delayed fluorescence. Disturbances of transcellular delta -mu H+ by electrical breakdown of the cell or by acidification of the external medium resulted in a decrease of the steady-state level of the light emission and in a decline of the minute oscillations observed in intact cells. The possible involvement of the membrane connections between the chloroplasts and the plasmatic membranes in the formation of transcellular delta-mu H+ is discussed.

Detection of Pseudomonas aeruginosa in water samples using a novel synthetic medium and impedimetric technology.

AIMS: To investigate whether the use of a novel synthetic medium in conjunction with impedimetric technology could provide a rapid and automated detection of Pseudomonas aeruginosa in water samples. METHODS AND RESULTS: A selective synthetic medium (Z-broth) in which the only carbon and nitrogen source is acetamide was applied in direct impedimetric examination for the selective isolation of P. aeruginosa. A total of 1036 tap-water, well-water, swimming-pool water and dialysis water samples were investigated, and any P. aeruginosa contamination was detected in 7-24 h. Neither false-negative nor false-positive results were observed. CONCLUSIONS: The results of the present evaluation demonstrate that impedance measurement with the use of Z-broth is suitable for the rapid and automatic detection of P. aeruginosa in water. SIGNIFICANCE AND IMPACT OF THE STUDY: The main advantages of the method: 240 samples can be examined in one step, the procedure is fully automated, the results are obtained quickly and the labour and media requirements are low.

Prostanoid release by Kupffer cells upon hypoxia-reoxygenation: role of pHi and Cai2+.

Primary cultures of rat Kupffer cells liberated significant amounts of prostaglandin (PG) D2, PGE2, and thromboxane (measured as thromboxane B2) when exposed to reoxygenation after 4 h of hypoxia. After a delayed onset, prostanoids were released at high rates for at least 8 h and after that time 700 pmol PGD2, 280 pmol PGE2, and 200 pmol thromboxane per 10(6) cells had been liberated. Unlike prostanoid release, leukotriene B4 production in reoxygenated cell cultures was only twice as much as in aerobic controls. Superoxide dismutase and catalase had no effect on PGD2, PGE2, and thromboxane production, indicating that prostanoid formation was independent of reactive oxygen species generated extracellularly and of cell injury. On the other hand, diphenyliodonium, as well as amiloride, blocked hypoxia-reoxygenation-induced PGD2, PGE2, and thromboxane release. The elevated prostanoid synthesis was preceded by increases in intracellular pH (from 7.23 to 7.38) and in intracellular Ca2+ (from 55 nM to a maximum level of 807 nM). These observations suggest a participation of NADPH oxidase and a related Na(+)-H+ exchange in the enhanced prostanoid synthesis, probably through the induction of an increased intracellular Ca2+ concentration.

Analysis of the aliphatic 1H-NMR spectrum of plasminogen kringle 4. A comparative study of human, porcine, bovine and chicken homologs.

The aliphatic 1H-NMR spectrum of the kringle 4 domain of human plasminogen has been studied via two-dimensional chemical shift correlated (COSY) and nuclear Overhauser correlated (NOESY) experiments at 300 MHz and 620 MHz. A number of aliphatic proton spin systems have been identified and several definite assignments have been made. This was mainly achieved by comparison of the human kringle 4 spectrum with spectra of the porcine, bovine and chicken homologs and also with that of the kringle 1 from human plasminogen on which we have reported previously. The three valyl and two leucyl residues of human kringle 4 have been assigned. The eleven threonyl spin systems have been identified via a RELAYED-COSY experiment and Thr17 has been assigned. The three alanyl spin systems have been identified and assigned. Six seryl spin systems have been identified and the signals from the seven glycyl residues of human kringle 4 have been located with Gly45 assigned. Furthermore, 24 AMX spin systems have been mapped in the COSY spectrum of human kringle 4 and H alpha-H beta,beta' spin systems of Tyr2, Tyr41, Tyr50, Tyr74, Trp25 and Trp62 have been assigned. From the spectrum of a deglycosylated chicken homolog, the epsilon-methyl singlets of Met28 and Met48 have been assigned. Finally, ligand effects on selected aliphatic resonances were observed which could be analyzed in terms of residues likely to neighbor the kringle lysine-binding site.

"Run-down" of gamma-aminobutyric acidA receptor function during whole-cell recording: a possible role for phosphorylation.

When using whole-cell recording methods and a minimal intracellular medium containing only inorganic ions, ethyleneglycolbis-(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, and N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid, we have observed a time-dependent decrease in the responsiveness of cultured chick spinal cord neurons to gamma-aminobutyric acid (GABA). The current evoked by 30 microM GABA progressively declined to approximately 30% of its initial value after five applications at 10-min intervals. This was accompanied by an equivalent decline in the GABA-evoked membrane conductance. "Run-down" of the response was reduced when Mg2+-ATP was present in the pipet solution. Inclusion of ATP-gamma-S, an analog that donates a thiophosphate group resistant to hydrolysis, also reduced run-down. The nonhydrolyzable analog beta, gamma-imidoadenosine-5'-triphosphate was without effect. These results suggest that an ATP-dependent process, possibly phosphorylation, is involved in the maintenance of GABAA receptor function.

Analysis of the aromatic 1H NMR spectrum of chicken plasminogen kringle 4.

The intact kringle 4 domain of chicken plasminogen has been characterized by 1H NMR spectroscopy at 300 and 620 MHz in both the presence and absence of epsilon-aminocaproic acid, an antifibrinolytic drug. The study focuses on the aromatic resonances. Comparisons with spectra from human, porcine and bovine kringle 4 homologs indicates a strict conservancy of conformation, reflecting the underlying primary sequence homology, and leads to an unambiguous assignment of all the aromatic resonances, including those of Phe15 and His40 which are unique to the chicken domain. Conclusive evidence is found that the Tyr9 ring fluctuates between two states, one in which it flips fast and other in which it is severely hindered. Similarly, the Tyr64 side chain finds itself in a structurally constrained locus. The Trp62, Tyr64, and Trp72 aromatic resonances are most sensitive to ligand presence, supporting a previously reported model of the kringle 4 lysine-binding site. His40, Phe41, and Tyr74 are also perturbed by ligand indicating proximity to the site. In contrast, the Phe15 aromatic spectrum indicates a rather mobile phenyl ring which is insensitive to ligand presence, thus confirming the lesser importance of the corresponding segment within the first kringle loop in determining kringle structure and/or function.

Alterations of markers during hepatocarcinogenesis in rats.

Fischer 344 male rats were treated with N-nitrosodiethylamine, and two weeks later promotion was effected by treatment with N-2-acetylaminofluorene for 14 days. At midpoint of the promotion protocol, one group of rats was subjected to partial hepatectomy (model A); others were treated with either carbon tetrachloride (model B) or thioacetamide (model C). Alterations in the activities of marker enzymes (glucose-6-phosphatase, gamma-glutamyl transpeptidase, cytochrome P-450, N-demethylase) during hepatocarcinogenesis were followed biochemically. The highest incidences of liver foci and of hepatocellular carcinomas were observed in model A, and these showed a good correlation with long-lasting elevated gamma-glutamyl transpeptidase activity. Analysis of the marker alterations suggests that there are three stages in hepatocarcinogenesis: (1) depression resulting from the toxic action of the initiator; (2) recovery and adaptation to cellular injury; and (3) long-lasting adverse alterations in the activities of the marker enzymes after promotion. The loss of certain non-histone proteins soon after promotion was also observed. Comparative studies of the individual actions of initiators and promoters on marker enzymes indicated that both contribute to the marker changes during hepatocarcinogenesis.

The aromatic 1H-NMR spectrum of plasminogen kringle 4. A comparative study of human, porcine and bovine homologs.

The isolated kringle 4 domain of human plasminogen has been compared with homologous structures from bovine and porcine sources, both free and in the presence of the ligand 6-aminohexanoic acid, by two-dimensional 1H-NMR spectroscopies at 300 MHz and 600 MHz. The chemical-shift-correlated, spin-echo-correlated, and double-quantum-correlated aromatic spectra of the three proteins reveal that the globular conformation of the fourth kringle is closely maintained throughout the set of homologs. Direct comparison shows that the three conserved Trp residues (at sites 25, 62 and 72) which exhibit highly non-degenerate subspectra, find themselves in similar intramolecular environments. In particular, proton Overhauser experiments reveal that the close steric interaction between the Trp-II (Trp62 or Trp25) indole group and the aromatic ring at site 74 (Tyr74 or Phe74) is strictly preserved. This feature forces the kringle inner loop, closed by the Cys51-Cys75 link, to fold back onto itself so as to place the site 74 residue proximal to the Cys22-Cys63 bridge. Single-residue substitutions enable unambiguous assignments of His-I to His3, Tyr-III to Tyr41 and Tyr-IV to Tyr74. From this direct evidence, comparison with the kringle 1 spectrum, and the previously reported chemical modification of Tyr-II (Tyr50) [Trexler M., Bányai L., Patthy L., Pluck N. D. & Williams R. J. P. (1985) Eur. J. Biochem. 152, 439-446], Tyr-I and Tyr-V (the latter, an immobile ring on the 600-MHz time scale) could be assigned to Tyr2 and Tyr9, respectively. Since Trp-III has previously been assigned to Trp72 at the lysine-binding site, the present study completes the assignment of 10 out of 12 aromatic spin systems in the kringle 4 1H-NMR spectrum; the only ambiguity which remains concerns the Trp-I and Trp-II indole spin systems, which are totally identified but as yet only tentatively assigned to Trp25 and Trp62, respectively.

Engineering clinician leadership and success in tobacco control: recommendations for policy and practice in Hungary and Central Europe.

Decades of research and advocacy to control tobacco use and related public-health harm have not counterbalanced the tobacco industry's successful stronghold, which is ever-increasing in countries with weaker anti-tobacco leadership. Current rates of tobacco use and harm in Hungary and other Central European countries mark them as some of the industry's greater successes. Following the Behavioural Ecological Model, a framework for behavioural and cultural change, this paper reviews important ways that dentists, physicians and other healthcare providers can counter the tobacco industry's influence on patients, communities, and the nation. The analysis includes policies and practices shown to be effective in controlling and undermining the tobacco industry, and outlines new policies and practices that show promise based on the behavioural change framework. The components of an all-encompassing tobacco-control programme are described through explicit recommendations for research, practice and policy that are necessary to establish a professional and societal culture that extinguishes the influence and harm of the tobacco industry in Hungary, Central Europe and developing countries worldwide.

The collagen-binding site of type-II units of bovine seminal fluid protein PDC-109 and fibronectin.

A single type-II domain has been isolated by limited proteolysis of the collagen-binding bovine seminal fluid protein, PDC-109. The 45-residue fragment corresponding to the second type-II domain of the parent molecule was found to have retained affinity for immobilized collagen, indicating that this minidomain carries critical regions of the collagen-binding site. Studies on various fragments of fibronectin have also implicated the two type-II units of this molecule in collagen-binding. In the present work we have found that type-II domains of human fibronectin, expressed in Escherichia coli as beta-galactosidase fusion proteins, bind specifically to immobilized collagen.

Negative modulation of the gamma-aminobutyric acid response by extracellular zinc.

We have studied the effects of divalent cations on the gamma-aminobutyric acid (GABA) response of voltage-clamped spinal cord neurons, using the whole-cell recording configuration. Zn, Cd, Ni, and Mn (but not Ba, Ca, or Mg) inhibit GABA-induced whole-cell currents when applied extracellularly. Although Zn is an effective inhibitor when applied extracellularly, it is ineffective when applied intracellularly. Inhibition by these cations is mediated by a common saturable recognition site that is distinct from the recognition sites for GABA, benzodiazepines, barbiturates, picrotoxin, or steroids. The maximal inhibition, or efficacy of inhibition, of GABA-induced currents is greater for Zn than for Cd, Ni, or Mn. The order of potency is Cd greater than Zn much greater than Ni much greater than Mn. Inhibition by Zn is partially surmountable by GABA, consistent with a decrease in both the maximum response and the affinity for GABA. The dose-response curve for inhibition of the GABA response by Zn is shifted to the right at a high GABA concentration but is unaffected by the presence of chlordiazepoxide, pentobarbital, or 5 beta-pregnan-3 alpha-ol-20-one. The results are consistent with a model in which a Zn-sensitive modulatory site exerts negative allosteric control over GABA receptor function.

[Differences in the mechanisms of damage to Kupffer cells and liver endothelial cells during preservation in UW solution]. / Unterschiede im Mechanismus der Schädigung von Kupfferzellen und Leberendothelzellen während der Konservierung in UW-Lösung.

AIM OF THE STUDY: The predominant injury during cold preservation of the liver appears to affect the non-parenchymal cells. Therefore we studied the contribution of hypoxia and the effect of the University of Wisconsin (UW) solution on the injury to cultured liver endothelial and Kupffer cells. METHODS: Cultured endothelial cells and Kupffer cells of the rat liver were incubated in Krebs-Henseleit buffer at 37 degrees C and in both, Krebs-Henseleit buffer and UW solution, at 4 degrees C. Hypoxic conditions were simulated by the addition of cyanide (1 mM), to some of the cultures glucose (10 mM) was added. Cell injury was assessed by the uptake of the vital dye trypan blue and by the release of cytosolic lactate dehydrogenase. RESULTS: Kupffer cells as well as endothelial cells exhibited a high hypoxia tolerance in Krebs-Henseleit buffer at both 37 degrees C and 4 degrees C. A large difference between both cell types, however, was seen during cold incubation in UW solution: whereas only 35 +/- 10% of Kupffer cells lost viability during 24 hrs under aerobic control conditions, the loss of viability of liver endothelial cells was already 83 +/- 12% under the same conditions. The addition of KCN increased the Kupffer cell injury to 75 +/- 8% but strongly decreased the endothelial cell injury to 3 +/- 2%. The addition of glucose to the cyanide-containing UW solution decreased the injury to Kupffer cells but increased the injury to endothelial cells. CONCLUSION: During cold incubation in UW solution cultured liver endothelial cells are affected by an energy-dependent injury. This type of injury is not detectable in Kupffer cells.

Phosphorylation factors control neurotransmitter and neuromodulator actions at the gamma-aminobutyric acid type A receptor.

Whole-cell and patch-voltage clamp experiments were carried out on cultured chick spinal cord neurons to investigate the dependence of gamma-aminobutyric acid (GABA)A receptor function on intracellular phosphorylation factors. Without ATP in the intracellular solution, repeated application of 30 microM GABA results in a progressive decline (run-down) of the currents evoked by GABA in standard whole-cell recordings but not when the nystatin-perforated patch method is used. Run-down is also observed in outside-out excised patch recordings, indicating that any enzymatic factors required for run-down must be closely associated with the plasma membrane. Run-down is associated with decreases in both the maximum GABA-induced current and the GABA EC50. Inclusion of magnesium adenosine-5'-O-(3-thio)triphosphate in the intracellular buffer prevents the decline in the maximum GABA response but the GABA EC50 still decreases, resulting in a "run-up" of the response at low (3 microM) GABA concentrations. Run-down is use dependent, requiring repeated activation of the GABAA receptor by high (30 microM) GABA concentrations. However, use-independent run-down can be induced by the inclusion of alkaline phosphatase in the intracellular buffer. The response to 3 microM GABA does not normally run down, but run-down is observed when the response to 3 microM GABA is potentiated with pentobarbital or allopregnanolone, suggesting that run-down is consequence of GABA receptor activation and/or desensitization. Run-down of the potentiated GABA response can be prevented by addition of magnesium adenosine-5'-O-(3-thio)triphosphate to the intracellular solution. Strikingly, run-down results in a significant decrease in the potentiating effects of positive modulators, whereas the inhibitory effects of negative modulators such as pregnenolone sulfate and ZnCl2 are unchanged. The results demonstrate that phosphorylation factors have the capacity to control GABAA receptor pharmacology, affecting the potency and efficacy of GABA, the kinetics of GABAA receptor desensitization, and the sensitivity of the receptor to modulators such as steroids, benzodiazepines, and barbiturates.