Muscle Evaluation and Hospital-Associated Disability in Acute Hospitalized Older Adults.

OBJECTIVES: We aimed to examine the association of muscle evaluation, including muscle ultrasound, with hospital-associated disability (HAD), focusing on ADL categories. DESIGN: A prospective observational cohort study. SETTING AND PARTICIPANTS: We recruited patients aged 65 years or older who were admitted to the geriatric ward of an acute hospital between October 2019 and September 2021. MEASUREMENTS: Handgrip strength, bioimpedance analyzer-determined skeletal muscle mass, bilateral thigh muscle thickness (BATT), and the echo intensity of the rectus femoris on muscle ultrasound were performed as muscle assessments. HAD was evaluated separately for mobility impairments and self-care impairments. RESULTS: In total, 256 individuals (mean age, 85.2 years; male sex, 41.8%) were analyzed. HAD in mobility was more common than HAD in self-care (37.5% vs. 30.0%). Only BATT was independently associated with HAD in mobility in multiple logistic regression analysis. There was no significant association between muscle indicators and HAD in self-care. CONCLUSION: A lower BATT was associated with a higher prevalence of HAD in mobility, suggesting the need to reconsider muscle assessment methods in hospitalized older adults. In addition, approaches other than physical may be required, such as psychosocial and environmental interventions to improve HAD in self-care.

Mixed Tb/Dy coordination ladders based on tetra(carboxymethyl)thiacalix[4]arene: a new avenue towards luminescent molecular nanomagnets.

The macrocyclic ligand calix[4]arene (L1) and its sulphur-containing analogue thia[4]calixarene (L2) are promising precursors for functional molecular materials as they offer rational functionalization with various organic groups. Here, we present the first example of lanthanide-based coordination polymers built from the macrocyclic thiacalix[4]arene backbone bearing four carboxylic moieties, namely, ligand H4L3. The combination of H4L3 with the Tb3+ and Dy3+ cations led to the formation of 1D ladder-type coordination polymers with the formula [LnIIIHL3DMF3]·(DMF) (where DMF = dimethylformamide and Ln = Tb or Dy, denoted as HL3-Tb and HL3-Dy), which resulted from the coordination of the lanthanide cations with the partially deprotonated ligand HL33- that behaved as a T-shape connector. The coordination sphere around the metal was completed by the coordinated DMF solvent molecules. By combining both Tb3+ and Dy3+ cations, isostructural heterobimetallic solid solutions HL3-Tb1- x Dy x were also prepared. HL3-Tb and HL3-Dy showed visible light photoluminescence originating from the f-f electronic transitions of pale green emissive Tb3+ and pale yellow emissive Dy3+ with efficient sensitization by the functionalized thia[4]calixarene ligand HL3. In the HL3-Tb1- x Dy x solid solutions, the Tb/Dy ratio governed both the emission colour as well as the emission quantum yield, which reached even 28% at room temperature for HL3-Tb. Moreover, HL3-Dy exhibited a slow magnetic relaxation effect related to the magnetic anisotropy of the dodecahedral Dy3+ complexes, which were well isolated in the crystal lattice by expanded organic spacers.

Role of Neuron-Glial Interaction Mediated by IL-1ß in Ectopic Tooth Pain.

Although many reports have demonstrated that ectopic pain develops in the orofacial region following tooth pulp inflammation, which often causes misdiagnosis and inappropriate treatment for patients with pulpitis, the precise mechanism remains unknown. In the present study, we hypothesized that the functional interaction between satellite glial cells and neurons mediated by interleukin 1ß (IL-1ß) in the trigeminal ganglion (TG) is involved in ectopic orofacial pain associated with tooth pulp inflammation. The digastric muscle electromyogram (D-EMG) activity elicited by capsaicin administration into the maxillary second molar tooth pulp was analyzed to evaluate the noxious reflex and was significantly increased in rats with inflammation of the maxillary first molar (M1) versus rats injected with saline. A significant increase in the expression of connexin43 (Cx43), a gap junction containing protein, was observed in activated satellite glial cells surrounding second molar-innervating neurons in the TG after M1 pulpitis. Daily administration of Gap26, a Cx43 mimetic peptide and inhibitor, in the TG significantly suppressed the enhancement of capsaicin-induced D-EMG activity and the percentage of Fluoro-Gold (FG)-labeled cells encircled by glial fibrillary acid protein-immunoreactive (IR) + Cx43-IR cells after M1 pulp inflammation ( P < 0.01). The percentage of FG-labeled cells encircled by glial fibrillary acid protein-IR + IL-1ß-IR cells, IL-1 type I receptor-IR cells labeled with FG, and TRPV1-IR cells labeled with FG significantly increased after M1 pulp inflammation ( P < 0.01). Daily administration of IL-1ra, an IL-1 receptor antagonist, into the TG significantly reduced the enhancement of capsaicin-induced D-EMG activity and the percentage of TRPV1-IR neurons labeled with FG after M1 pulp inflammation ( P < 0.01). The present findings suggest that satellite glial cell is activated in the TG via activated gap junctions composed of Cx43 following tooth pulp inflammation, which leads to the hyperactivation of remote neurons via IL-1ß mechanisms and results in ectopic tooth pulp pain in the adjacent tooth.

Balanitis caused by Streptococcus pyogenes: a report of two cases.

Streptococcus pyogenes (the Lancefield group A streptococcus) is a cause of pharyngitis and impetigo. However, it has rarely been implicated as a sexually transmitted pathogen. We herein report two cases of severe balanitis due to S. pyogenes in sexually active men. It is postulated that penile cellulitis developed following the invasion of S. pyogenes through a traumatic abrasion acquired during fellatio performed by commercial sex workers. Both patients were treated successfully with oral administration of penicillin.

Primary omental gamma/delta T-cell lymphoma involving the central nervous system.

Gamma/delta T-cell lymphoma (GDTL) is an uncommon lymphoma that was initially reported to involve only the liver and spleen. GDTL other than the hepatosplenic type is extremely rare. Frequent primary sites include skin and subcutaneous tissue, intestine, or nasal region. We report a case of GDTL of the omentum in a 54 year-old-man. The tumor cells are CD2-, CD3+, CD4-, CD5-, CD8+, CD56+, TIA-1+, granzyme B+/-. They expressed the identical phenotype of intestinal GDTL. The patient was treated with 2 courses of CHOP which comprised cyclophosphamide, doxorubicin, vincristine and prednisolone, and 3 courses of EPOCH which comprised etoposide, prednisolone, vincristine, cyclophosphamide and doxorubicin. However, he failed to obtain remission. During the fourth course of EPOCH, muscle weakness of the lower extremities developed and intracranial masses were observed by computed tomographic scan of the brain. Dissemination of lymphoma to the central nervous system was considered and it may be attributable to the expression of CD56 in this case. High dose methotrexate (HD-MTX) chemotherapy successfully eliminated the omental tumor and reduced the size of the intracranial masses, thus HD-MTX appears to be an effective treatment against GDTL.

Comparison of the effects of glimepiride and glibenclamide on adipose tissue tumour necrosis factor-alpha mRNA expression and cellularity.

AIM: The aim of this study was to compare the effects of glimepiride and glibenclamide on tumour necrosis factor (TNF)-alpha expression and adipocyte cellularity in spontaneously diabetic, obese rats. METHODS: Eight-week-old male Otsuka Long-Evans Tokushima Fatty (OLETF) rats were randomized to receive glimepiride, glibenclamide or control treatment for 12 weeks, after which TNF-alpha mRNA levels, adipose tissue cellularity and physiological parameters were measured. RESULTS: TNF-alpha mRNA expression in retroperitoneal fat tissue was significantly greater in the glibenclamide group (2.2 +/- 1.1), compared with the control group (0.9 +/- 0.4; p<0.05) or the glimepiride group (0.9 +/- 0.2; p<0.01). The mean fat-cell area in retroperitoneal fat tissue was increased at study endpoint in the glibenclamide group (13,764 +/- 7036 microm2), compared with both the control and glimepiride groups (10,755 +/- 6193 microm2 and 11,317 +/- 5646 microm2 respectively; p<0.05). Investigation of cellularity revealed a decrease in the frequency of small fat cells and an increase in the frequency of large fat cells in both the glibenclamide and glimepiride groups compared with the control group, with a greater increase in large fat cells in the glibenclamide group. At study endpoint, insulin and triglyceride values were significantly higher in the active treatment groups compared with the control group; however, insulin levels were significantly greater in glibenclamide-treated animals compared with glimepiride-treated animals. An oral glucose tolerance test performed at the end of the study showed that there were no significant differences among the three groups in terms of plasma glucose and insulin concentrations. CONCLUSIONS: This study suggests that although both glibenclamide and glimepiride may have a hypertrophisizing effect on fat cells in adipose tissues, this effect is greater with glibenclamide, leading to augmentation of TNF-alpha mRNA expression and possible exacerbation of insulin resistance.

Spontaneous firing activity of cortical neurons in adult cats with reorganized tonotopic map following pure-tone trauma.

We hypothesized that moderate sensorineural hearing loss resulting from acoustic trauma would cause (i) a change in the cortical tonotopic map, (ii) an increase in spontaneous activity in the reorganized region and (iii) increased inter-neuronal synchrony within the reorganized part of the cortex. Five kittens were exposed to a 126 dB sound pressure limit tone of 6 kHz for 1 h at both 5 and 6 weeks of age. Recordings were performed 7-16 weeks after the exposure. Auditory brainstem response thresholds for frequencies above 12 kHz were increased by 30 dB on average relative to those in normal cats. Tonotopic maps in the primary auditory cortex were reorganized in such a way that the area normally tuned to frequencies of 10-40 kHz was now entirely tuned to 10 kHz. Spontaneous firing rates were significantly higher in reorganized areas than in normal areas. In order to test for changes in inter-neuronal synchrony, cross-correlation analysis was done on 225 single-unit pairs recorded in the traumatized cats. For the single- and dual-electrode pairs there was no significant difference in peak cross-correlation coefficients for the firings of simultaneously recorded cells between normal and reorganized areas. However, the percentage of correlations that differed significantly from zero was higher in the reorganized area than in the normal area. This suggests a potential correlation between cortical reorganization, increased spontaneous firing rate and inter-neuronal synchrony that might be related to tinnitus found in high-frequency hearing loss induced by acoustic trauma.

Neuronal responses in cat primary auditory cortex to natural and altered species-specific calls.

We investigated how natural and morphed cat vocalizations are represented in primary auditory cortex (AI). About 40% of the neurons showed time-locked responses to major peaks in the vocalization envelope, 60% only responded at the onset. Simultaneously recorded multi-unit (MU) activity of these peak-tracking neurons on separate electrodes was significantly more synchronous during stimulation than under silence. Thus, the representation of the vocalizations is likely synchronously distributed across the cortex. The sum of the responses to the low and high frequency part of the meow, with the boundary at 2.5 kHz, was larger than the neuronal response to the natural meow itself, suggesting that strong lateral inhibition is shaping the response to the natural meow. In this sense, the neurons are combination-sensitive. The frequency-tuning properties and the response to amplitude-modulated tones of the MU recordings can explain the responses to natural, and temporally and spectrally altered vocalizations. Analysis of the mutual information in the firing rate suggests that the activity of at least 95 recording sites in AI would be needed to reliably distinguish between the nine different vocalizations. This suggests that a distributed representation based on temporal stimulus aspects may be more efficient than one based on firing rate.

The steroid receptor coactivator SRC-3 (p/CIP/RAC3/AIB1/ACTR/TRAM-1) is required for normal growth, puberty, female reproductive function, and mammary gland development.

Steroid receptor coactivator-3 (SRC-3) is a coactivator of nuclear receptors in the SRC family as assayed in vitro. Here, we show that mouse SRC-3 is expressed in a tissue-specific fashion and distributed mainly in the oocytes, mammary glands, hippocampus, olfactory bulb, smooth muscle, hepatocytes, and vaginal epithelium. Genetic disruption of SRC-3 in mice results in a pleiotropic phenotype showing dwarfism, delayed puberty, reduced female reproductive function, and blunted mammary gland development. Hormonal analysis indicates that SRC-3 plays a role in both the growth hormone regulatory pathway and the production of estrogen, which may explain the observed phenotypes. These results suggest that the physiological role of SRC-3 is different from that of SRC-1 and prove the diversity among coactivator family members.

Moderate noise trauma in juvenile cats results in profound cortical topographic map changes in adulthood.

Cortical topographic map changes have been reported after profound drug-induced hearing loss in neonates, after progressive high-frequency hearing loss, and after mechanically induced lesions in the cochlea of adult animals. The present study demonstrates that exposure of 5-week-old kittens to a loud 6 kHz tone, producing mild to moderate high-frequency hearing loss, induces a profound reorganization of the frequency map in auditory cortex. In the reorganized cortical region, the frequency-tuning curves were of normal sharpness with near normal thresholds. Inhibitory tuning curve bandwidths were similar to those in control animals. Spontaneous activity in the reorganized part of the cortex was significantly increased. In contrast, the strength of the cross-correlation of the spontaneous activity of units recorded on different electrodes was the same in the normal and reorganized part. Minimum first-spike latency was significantly increased in trauma cats, largely for units at the dorsal side of the sampled region. Because most other neural response properties are normal in the reorganized part of cortex, sub-cortical topographic map changes are likely involved in producing the altered cortical topographic maps.

A case of aortitis syndrome and IgA nephropathy: possible role of human leukocyte antigens in both diseases.

A 51-year-old woman, who had both aortitis syndrome (Takayasu arteritis) and IgA nephropathy, presented with hypertension, fever, a high erythrocyte sedimentation rate, high C-reactive protein and serum IgG levels, proteinuria, and renal dysfunction. Renal arteriography showed stenosis and poststenotic dilatation at the origin of the right renal artery, as well as tortuosity of the left renal artery branches and marked atrophy of the left kidney. Renal biopsy showed IgA nephropathy with deposits of IgA, C3, and fibrinogen in the glomeruli and arteriolosclerosis. The present patient had human leukocyte antigen (HLA)-B 52, which is reported to be related to the aortitis syndrome, as well as HLA-DR 4, which is possibly related to IgA nephropathy, suggesting that HLA status may be involved in the pathogenesis of both diseases.

Thiomenthol derivatives as novel percutaneous absorption enhancers.

Thiomenthol derivatives were synthesized and their promoting activity on the percutaneous absorption of ketoprofen from hydrogels was evaluated in rats. The apparent penetration rate (Rp) of ketoprofen absorbed from the hydrogel was estimated by the pharmacokinetic model derived under the assumption of a constant penetration rate through the skin after a lag time. As an index of promoting activity of thiomenthol derivatives, an enhancement factor (Ef) was defined as the ratio of the Rp value with enhancer to the value obtained with the control not containing enhancer. Skin irritancy evoked by these derivatives was investigated microscopically by using a cross-section of the excised skin onto which ketoprofen hydrogel was applied. Total irritation score (TIS) was estimated by summation of each irritation score in several parts of the skin. The physicochemical parameters of thiomenthol derivatives such as a partition coefficient (log P) and a steric energy were calculated and the quantitative relationships between these parameters and the Ef values or TIS values were investigated on the basis of multiple regression analysis. As a result, a parabolic relationship between log P and Ef was noted. A similar relationship was also observed in the case of TIS.

Mannose-binding molecules of rat spermatozoa and sperm-egg interaction.

We have previously reported the occurrence and partial characterisation of an alpha-D-mannosidase activity on plasma membranes of rat, mouse, hamster and human spermatozoa. A soluble isoform of the rat sperm surface mannosidase was purified and polyclonal antibody raised. Since several reports have suggested that mannosyl residues on the rat, mouse and human zona pellucida may be involved in sperm-zona binding, studies were undertaken to examine the receptor-like role of mannose-binding molecules on rat spermatozoa. Sprague-Dawley rats (25-30-days old) were superovulated and eggs collected from the oviduct were treated with 0.3% hyaluronidase to remove the cumulus cells. Spermatozoa, collected from the cauda epididymis were capacitated for 5 h at 37 degrees C in 5% CO2 in air. The sperm-zona binding assay was performed in the presence of increasing concentrations of several sugars as well as preimmune and immune (anti-mannosidase or anti-mannose binding protein) IgG. Data from these studies show that: (1) significantly fewer sperm bound per egg in the presence of competitive inhibitors of mannosidase; (2) among the sugars examined, D-mannose was the most potent inhibitor causing 70% reduction in the number of sperm bound per egg; (3) anti-mannosidase or anti-mannose binding protein (but not preimmune) IgG showed a dose-dependent reduction in the number of sperm bound per egg; (4) anti-mannosidase IgG (but not anti-mannose binding protein IgG) showed a dose-dependent inhibition of sperm surface mannosidase activity; (5) the competitive inhibitors of mannosidase or the immune IgG had no effect on sperm motility or the sperm acrosome reaction. These result suggest that mannose-binding molecule(s) such as alpha-D-mannosidase or mannose-binding protein on the spermatozoa may recognise mannosyl residues on zona pellucida, and play a receptor-like role in sperm-egg interaction in the rat.

Rat zona pellucida glycoproteins: molecular cloning and characterization of the three major components.

The zona pellucida (ZP), the extracellular glycocalyx that surrounds the oocyte, is well known to mediate homologous gamete interaction. In a previous study from our laboratories, we reported the qualitative characterization of the rat ZP. The ZP in this species, like the mouse, hamster, and human, was found to contain three glycoproteins, namely rZP1, rZP2, and rZP3 (Araki et al. [1992] Biol Reprod 46:912-919). In this study, cDNAs encoding whole rat ZP major components have been isolated and characterized. A rat ovary cDNA library was screened with the mouse ZP3 and ZP2 cDNA probes, respectively. For rZP1 cDNA cloning, cDNAs generated using reverse transcriptase-polymerase chain reaction and rapid amplification of 5' and 3' cDNA ends, were isolated and sequenced. The rZP3 cDNA showed 1338 bp with a coding region containing 1272 bp, that translates into 424 amino acids. The total translation of rZP3 peptide has a molecular weight of 45,820, containing six potential N-glycosylation sites and 75 Ser/Thr residues, possible O-glycosylation sites. The amino acid sequence derived from the cDNA sequence shares high sequence homologies to mouse (90%), hamster (78%), and human (65%) ZP3 (ZPC) glycoproteins, indicating that the rat and mouse ZP3 have quite a conserved amino acid sequence, including the potential glycosylation sites. The total transcript of the rZP2 was 2154 nucleotides and the largest open reading frame was 695 amino acids. This would translate into a protein of 78.4 kDa. In the case of rZP1, the cDNA clone consisted of 1960 bp, and the coding region contained 1851 bp translating into 617 amino acids. Significant homologies were observed between rZP2 and ZPA family from various mammalian species. The rZP1 also showed a sequence homology to mouse ZP1, known as a mouse orthologue of ZPB family, suggesting that the rZP2 and rZP1 are members of ZPA and ZPB families, respectively. The message distributions for each zona components were limited within the ovary and the signal was detectable in the growing oocytes. The present results will further our understanding of the structure of rat zona components and lead to a better understanding of species-specificity observed during sperm-egg interaction.

In situ localization of messenger ribonucleic acid for an oviduct-specific glycoprotein during various hormonal conditions in the golden hamster.

The oviductal epithelium secretes specific glycoproteins that associate with the egg after ovulation. Several published reports including our preliminary studies have suggested that ovarian steroids regulate the secretion of oviduct-specific glycoproteins in several mammalian species. The objective of this study, using golden hamsters, was to analyze the hormonal effects on gene expression of these molecules more precisely during various hormonal conditions (estrous cycle, ontogeny, pregnancy, GnRH analogue treatment, and ovariectomy) by in situ hybridization. The message for the hamster oviduct-specific glycoprotein (HOGP) was detected by a digoxigenin-labeled single-strand specific DNA probe in paraffin sections. Data from these studies show the following. 1) In the oviduct, the signal was detected in both the perinuclear region and the basal region in the ampulla but was predominantly detected in the basal region in the isthmus. 2) The signal intensity was high in the ampulla compared with the isthmus. 3) During a normal estrous cycle, the message level was significantly altered between the estrous and diestrous stages in the ampulla but not in the isthmus. In addition, the signal did not disappear at any stage in either the isthmus or ampulla. 4) The HOGP message was first observed from around 14 days of age and then decreased in parallel with serum estradiol levels during aging. 5) The signal was also observed in the oviductal epithelium of pregnant animals at term and of postpartum animals. 6) When we treated the animals with TAP-144-SR (GnRH analogue) or performed an ovariectomy, which caused diminution of serum estradiol and progesterone levels, the message of HOGP was significantly decreased. Moreover, the message expression was greatly induced after estradiol administration to GnRH analogue-treated animals, whereas a high level of serum progesterone slightly inhibited HOGP message expression. These results suggest that elevation of the serum estradiol/ progesterone level affects the HOGP gene expression in the ampulla. However, a high serum estradiol level did not induce the gene expression rapidly, suggesting that an adequate serum hormonal level over a given period of time may be important for the HOGP gene expression.

Molecular cloning and characterization of a mouse oviduct-specific glycoprotein.

In the present study, we have isolated the cDNA for the mouse oviduct-specific glycoprotein (MOGP) by screening the mouse oviduct cDNA library with the bovine oviduct-specific glycoprotein (BOGP)-cDNA probe and by the 5' rapid amplification of the cDNA end (5'RACE). The total length of cDNA was determined to be 2525 base pairs (bp) by sequence analysis. The coding region contained 2163 bp translating to 721 amino acids. Based on comparisons with the N-terminal amino acid sequences of purified-BOGP and of hamster oviduct-specific glycoprotein (oviductin), it was inferred that the derived amino acid sequence contained a signal peptide region of 21 amino acids and a mature MOGP (core protein) region of 700 amino acids (76,515 daltons). It was also inferred that the mature MOGP contained three potential N-linked glycosylation sites and 24 possible O-linked glycosylation sites, and had the unique seven-residue repeat sequence (21 repeats) within the predicted sequence in the C-terminal side. The amino acid sequence of a portion of MOGP was highly homologous to that of BOGP (71% identity), baboon oviduct-specific glycoprotein (61% identity), and human oviduct-specific glycoprotein (77% identity). Significant homologies were also observed with two mammalian secretory proteins that were reported as a mammalian member of a chitinase protein family. Northern blot hybridization with a DIG-labeled probe indicated that a single message of 2.8 kb was present in total RNA prepared from oviductal tissue. In situ hybridization using MOGP-cDNA showed that a MOGP message was only detected in the oviductal epithelial cells. These results strongly suggest that a significant degree of homology exists among oviduct-specific glycoproteins of various mammalian species.

Accumulation of hydroxyapatite in the kidney of streptozotocin-induced diabetic rat fed a low-zinc diet.

Calcification occurred in the kidney of streptozotocin (STZ)-induced diabetic rats fed a low-zinc diet. The deposits were stained by the von Kossa method and were detected intracellularly in the tubular cells, mainly in the cortico-medullar region. The deposits were found to be a heterogenous substance on electron microscopy. There were various sizes of deposits, and the surfactant was very much distorted. Many deposits grew up to bind small particles, and the core-like substance was observed in the center of the deposit. The component of the deposit was analyzed by an X-ray microanalyzer, and was found to be calcium and phosphorus. The ratio of calcium to phosphorus was 2.159, which coincided with the ratio of standard hydroxyapatite. From these observations, the deposit is believed to be hydroxyapatite. It is thought that the core is formed at first, many particles are then bound to the core, and deposits grow up.