Structural domains required for Caenorhabditis elegans G protein-coupled receptor kinase 2 (GRK-2) function in vivo.
G protein-coupled receptor kinases (GRKs) are key regulators of signal transduction that specifically phosphorylate activated G protein-coupled receptors (GPCRs) to terminate signaling. Biochemical and crystallographic studies have provided great insight into mammalian GRK2/3 interactions and structure. However, despite extensive in vitro characterization, little is known about the in vivo contribution of these described GRK structural domains and interactions to proper GRK function in signal regulation. We took advantage of the disrupted chemosensory behavior characteristic of Caenorhabditis elegans grk-2 mutants to discern the interactions required for proper in vivo Ce-GRK-2 function. Informed by mammalian crystallographic and biochemical data, we introduced amino acid substitutions into the Ce-grk-2 coding sequence that are predicted to selectively disrupt GPCR phosphorylation, Gα(q/11) binding, Gβγ binding, or phospholipid binding. Changing the most amino-terminal residues, which have been shown in mammalian systems to be required specifically for GPCR phosphorylation but not phosphorylation of alternative substrates or recruitment to activated GPCRs, eliminated the ability of Ce-GRK-2 to restore chemosensory signaling. Disrupting interaction between the predicted Ce-GRK-2 amino-terminal α-helix and kinase domain, posited to stabilize GRKs in their active ATP- and GPCR-bound conformation, also eliminated Ce-GRK-2 chemosensory function. Finally, although changing residues within the RH domain, predicted to disrupt interaction with Gα(q/11), did not affect Ce-GRK-2 chemosensory function, disruption of the predicted PH domain-mediated interactions with Gβγ and phospholipids revealed that both contribute to Ce-GRK-2 function in vivo. Combined, we have demonstrated functional roles for broadly conserved GRK2/3 structural domains in the in vivo regulation of organismal behavior.


A Randomized, Double-Blind, Placebo-Controlled, Phase 2a Study to Evaluate the Efficacy and Safety of RIST4721 in Subjects with Palmoplantar Pustulosis.
Palmoplantar pustulosis (PPP) is a chronic inflammatory skin condition with neutrophilic infiltration of the epidermis. RIST4721 antagonizes CXC chemokine receptor type 2, which is important in neutrophil recruitment and migration. In this study, the efficacy and safety of RIST4721 versus placebo were assessed in adult subjects with moderate to severe PPP. This phase 2a, multicenter, randomized, double-blind, placebo-controlled study investigated RIST4721 versus placebo in subjects with moderate to severe PPP. Key eligibility criteria included: Palmoplantar Pustulosis Area and Severity Index (PPPASI) ≥ 8 and Palmoplantar Pustulosis Physician Global Assessment ≥ 3. Subjects were randomized 1:1 to RIST4721 300 mg or placebo once daily for 28 days. The primary efficacy endpoints were relative change from baseline in fresh and total pustule count at day 28. Fifteen subjects received RIST4721 and 19 subjects received placebo. Treatment with RIST4721 was found to be generally well tolerated. At day 28, the mean ± standard deviation (SD) relative change from baseline in fresh pustule count was 0.86 ± 0.692 and 0.53 ± 0.561 (P = 0.240) and in total pustule count was 0.99 ± 0.667 and 0.96 ± 0.672 (P = 0.804) for RIST4721 and placebo groups, respectively. Subgroup analysis of subjects with progressing disease demonstrated that subjects with a PPPASI-50 at day 28 was significantly higher for subjects treated with RIST4721 (71%) than placebo (15%) (P = 0.022). Preliminary data suggest RIST4721 is well tolerated and may be a potential therapy for patients with PPP. RIST4721-201 was registered in June 2019 at clinicaltrials.gov: NCT03988335.


Pericentric inversion and partial monosomy 4q associated with congenital anomalies.
A case of complex structural rearrangement of chromosome 4 identified by R-banding as 46,XX,del(4),inv(4)(pter leads to 16::q24 leads to p16::q32 leads to qter) is reported in an infant with congenital anomalies and psychomotor retardation.


Association between sleep habits and behavioral problems in early adolescence: a descriptive study.
Sleep habits are related to children's behavior, emotions, and cognitive functioning. A strong relationship exists between sleep habits and behavioral problems. However, precisely which sleep habits are associated with behavioral problems remains unclear. Therefore, the purpose of this study is to clarify the relationship between sleep habits and behavioral problems in early adolescence. This study used data from a larger longitudinal research, specifically, data from the year 2021. First-year junior high school students (12-14 years) in Japan were surveyed; their parents (N = 1288) completed a parent-report questionnaire. The main survey items were subject attributes, the Pittsburgh Sleep Quality Index (PSQI), and the Strength and Difficulties Questionnaire (SDQ). Of the 652 valid responses received, 604 individuals who met the eligibility criteria (no developmental disability in the child and completion of all survey items) were included in the analysis. To examine the relationship between sleep habits and behavioral problems, logistic regression analysis using the inverse weighted method with propensity score was conducted with sleep habits (sleep quality, time to fall asleep, sleep duration, sleep efficiency, sleep difficulty, use of sleeping pills, difficulty waking during the day, and sleep disturbances) as explanatory variables and behavioral problems (overall difficulty in SDQ) as objective variables. The propensity score was calculated by employing the logistic regression using the inverse weighted method based on propensity scores. Propensity scores were calculated based on gender, family structure, household income, and parental educational background. The results showed that behavioral problems tended to be significantly higher in the group at risk for sleep quality, sleep difficulties, daytime arousal difficulties, and sleep disturbances than in the group with no risk. The results suggest that deterioration in sleep quality, sleep difficulties, daytime arousal difficulties, and sleep disturbances may increase the risk of behavioral problems in adolescents.


Lipid-saccharide intermediates and glycoprotein biosynthesis in a temperature-sensitive Chinese hamster cell mutant.
The characterization of a temperature-sensitive Chinese hamster cell mutant has been continued with the aim of localizing the apparent defect in glycoprotein synthesis (Tenner et al., '77). Although the mutation is lethal, a demonstration of the ability of the mutant cells to support proliferation of Mengo virus at the nonpermissive temperature indicates that the general metabolic processes of the cells remain intact at a time when glycoprotein synthesis is severely depressed. A quantitative study of protein synthesis on membrane-associated polysomes suggests that the synthesis of the polypeptide portion of the glycoproteins at 40.8 degrees C may be normal. The investigation of lipid-saccharide molecules which have been implicated in the formation and transfer of the oligosaccharide "core" to polypeptide acceptors shows that mutant cells at the nonpermissive temperature are capable of synthesizing these lipid saccharides normally, and that the pool of the dolichyl oligosaccharides is maintained at a constant level independent of the temperature. The rate of formation of the lipid-oligosaccharide, however, is reduced in intact mutant cells at the nonpermissive temperature. Further investigations show this decreased rate to be the result of an increased half life of the lipid-oligosaccharide at 40.8 degrees C. These data indicate that the temperature-sensitive step in glycoprotein biosynthesis is the transfer of the oligosaccharide core from the lipid-oligosaccharide intermediates to the nascent polypeptide chain. The data presented also provide evidence that the lipid-saccharide intermediates, previously described mainly in in vitro systems, are in fact involved in the glycosylation of a majority, if not all, of the mannose-containing glycoproteins in intact, growing hamster cells.


Systematic analysis of gut microbiota in pregnant women and its correlations with individual heterogeneity.
The woman's gut microbiota during pregnancy may support nutrient acquisition, is associated with diseases, and has been linked to infant health. However, there is limited information on gut microbial characteristics and dependence in pregnant women. In this study, we provide a comprehensive overview of the gut microbial characteristics of 1479 pregnant women using 16S rRNA gene sequencing of fecal samples. We identify a core microbiota of pregnant women, which displays a similar overall structure to that of age-matched nonpregnant women. Our data show that the gestational age-associated variation in the gut microbiota, from the ninth week of gestation to antepartum, is relatively limited. Building upon rich metadata, we reveal a set of exogenous and intrinsic host factors that are highly correlated with the variation in gut microbial community composition and function. These microbiota covariates are concentrated in basic host properties (e.g., age and residency status) and blood clinical parameters, suggesting that individual heterogeneity is the major force shaping the gut microbiome during pregnancy. Moreover, we identify microbial and functional markers that are associated with age, pre-pregnancy body mass index, residency status, and pre-pregnancy and gestational diseases. The gut microbiota during pregnancy is also different between women with high or low gestational weight gain. Our study demonstrates the structure, gestational age-associated variation, and associations with host factors of the gut microbiota during pregnancy and strengthens the understanding of microbe-host interactions. The results from this study offer new materials and prospects for gut microbiome research in clinical and diagnostic fields.


Molecular analysis of mutation at the hprt locus of Chinese hamster V79 cells induced by ethyl methanesulphonate and mitomycin C.
Mutations at the hprt locus of Chinese hamster V79 cells were induced by treatment with ethyl methanesulphonate (EMS), considered primarily a point mutagen and mitomycin C (MMC), a potent clastogen. EMS gave a dose-dependent induction of mutants while MMC induced a poor mutagenic response. Mutations were analysed using Southern and Northern blotting. Analysis of 9 EMS-induced and 4 spontaneous mutants yielded no detectable alterations in the hprt locus after digestion of DNA with 6 restriction enzymes. Mutants without detectable changes carried presumptive point mutations. In contrast, 4 out of 12 MMC-induced mutants had detectable alterations. 2 of these appeared to have lost the entire hprt gene while the other 2 had probable partial deletions. For these 4 deletion mutants no hprt mRNA was detected. 3 MMC-induced and 1 EMS-induced mutants had reduced levels of hprt mRNA. All the other mutants showed normal levels of hprt mRNA and the message detected was always of the correct size. It is suggested that the poor mutagenic response induced by MMC may be due to the lethal nature of large deletions involving both the hemizygous hprt locus and adjacent essential genes. This may lead to an underestimate of the mutagenicity of clastogenic agents such as MMC in the V79 HPRT mutation assay.


External validation of the STONE score and derivation of the modified STONE score.
The STONE score is a clinical prediction rule for the presence of uncomplicated ureter stones with a low probability of acutely important alternative findings. This study performed an external validation of the STONE score, focusing on the Korean population, and a derivation of the modified STONE score for better specificity and sensitivity. We retrospectively reviewed medical records of patients complaining of flank pain at a single emergency department from January 2013 to December 2014. Patients were categorized into 3 groups according to their STONE score. The prevalence of ureter stones and other alternative findings were calculated in each group. We derived a modified STONE score based on a multivariable analysis and performed an interval validation. From the 700 patients included in the analysis, 555 patients (79%) had a ureter stone. The area under the receiver operating characteristic curve of the STONE score was 0.92. The sensitivity of the high stone score was 0.56. In the modified STONE score, nausea, vomiting, and racial predictors were substituted by C-reactive protein and previous stone history. The area under the receiver operating characteristic curve and sensitivity of the modified STONE score in the internal validation group significantly increased to 0.94 and 0.80, respectively. The STONE score can be used to predict a ureter stone with a low probability of other alternative findings. The modified STONE score might increase the diagnostic performance in suspicious urinary stone cases. We performed external validation of the STONE score and derivation of the modified STONE score. This scoring system could help the clinicians with radiation reducing decision making.


Spinocerebellar ataxia type 15 caused by missense variants in the ITPR1 gene.
Spinocerebellar ataxia type 15 (SCA15) is a degenerative, adult onset autosomal dominant cerebellar ataxia, caused almost exclusively by deletions in the inositol 1,4,5 triphosphate receptor type 1 (ITPR1) gene (ITPR1). ITPR1 mediates calcium release from the endoplasmic reticulum, and particularly abounds in Purkinje cells. It plays a pivotal role in excitatory and inhibitory actions on Purkinje cells, and alterations in their balance cause cerebellar dysfunction in ITPR1 knockout mice. To date, only two single missense mutations have been reported to cause SCA15. They were considered pathogenic because cosegregation occurred with disease, and haploinsufficiency was hypothesized as their pathogenic mechanism. In this study, three Caucasian kindreds with different heterozygous missense variants in ITPR1 are reported. The main clinical manifestation was a slowly progressive gait ataxia with onset after 40 years of age, with chorea in two patients and hand tremor in another one, concordant with manifestations found in SCA15. The three missense variants identified in ITPR1 were c.1594G>A; p.(Ala532Thr) in Kindred A, c.56C>T; p.(Ala19Val) in Kindred B, and c.256G>A; p.(Ala86Thr) in Kindred C. Every variant was labelled as of unknown significance; however, each one cosegregated with disease and was predicted to be pathogenic by in silico tests. The three ITPR1 missense variants found in this study exhibited cosegregation with disease, a result that sustains their pathogenicity. Further studies are needed to confirm the role of missense mutations in SCA15.


Measurement of first- and second-order modulation detection thresholds in listeners with cochlear hearing loss.
First- and second-order modulation detection thresholds were measured in normal hearing and hearing-impaired listeners. 'First-order' modulation detection thresholds correspond to the ability of listeners to detect sinusoidal amplitude modulation (SAM); they are measured as a function of the frequency of that modulation, f(m). 'Second-order' modulation detection thresholds correspond to the ability to detect sinusoidal modulation applied to the modulation depth of a SAM signal; they are measured as a function of the frequency of the modulation applied to the modulation depth (referred to as f(m)'). In this case, the SAM signal acts as a 'carrier' stimulus of frequency f(m) and sinusoidal modulation of the SAM-signal's modulation depth (at rate f(m)') generates two additional components in the modulation spectrum at f(m)-f(m)' and f(m)+f(m)'. In both groups of listeners, first-order modulation detection thresholds were measured for modulation frequencies f(m) ranging between 4 Hz and 32 Hz, and second-order modulation detection thresholds were measured for second-order modulation frequencies f(m)' ranging between 1 Hz and 11 Hz, using a fixed first-order modulation frequency f(m) of 16 Hz. The results showed that, in hearing-impaired listeners: first-order modulation detection thresholds were within the normal range up to f(m) = 16 Hz and poorer than normal at f(m) = 32 Hz; second-order modulation detection thresholds were within the normal range at f(m)' = 3, 5 and 11 Hz, and poorer than normal at f(m)' = 1 Hz and 7 Hz. These results suggest that cochlear damage has little effect on the detection of both sinusoidal and complex temporal envelopes.


Klippel-Trenaunay-Weber syndrome: Oro-dental manifestations and management.
Klippel-Trenaunay-Weber syndrome (KTWS) is a rare congenital systemic disease characterized by a classic typical triad: cutaneous haemangioma, arterio-venous fistulas or varicosities (or both) and unilateral hypertrophy of hard and soft tissue with different localizations. First described by the French physicians Marcel Klippel and Paul Trenaunay, in 1900, KTWS has a clinically incidence of 2-5/100000. The complete triad (port-wine stains, varicose veins, and soft tissue and/or bony hypertrophy) occurs in almost 2/3 of the patients. Moreover, these features may be present at birth or develops during growing becoming more evident with age. Typical orofacial manifestations include facial asymmetry, jaw enlargement and malocclusion. A previously diagnosed 55-year-old male patient was referred to the Department of Cranio-Maxillofacial Surgery presenting with extended mandibular ramus exostosis on the left side and concomitant malocclusion. Surgical removal of the hypertrophic bone was performed due to progressive mouth opening restriction, limited oral hygiene ability and increased mandible deviation. Bleeding complications and wound healing disorders were not observed. Consistent mouth opening training resulted in an improvement in mouth opening. It is suggested to consider KTWS as one of the differential diagnoses if vascular syndromes in the head and neck region occur. Special attention must be given to dental treatment due to eventual excessive haemorrhage that might occur after oral surgical procedures.


Hobit and Blimp-1 regulate TRM abundance after LCMV infection by suppressing tissue exit pathways of TRM precursors.
Tissue-resident memory T cells (Trm) are retained in peripheral tissues after infection for enhanced protection against secondary encounter with the same pathogen. We have previously shown that the transcription factor Hobit and its homolog Blimp-1 drive Trm development after viral infection, but how and when these transcription factors mediate Trm formation remains poorly understood. In particular, the major impact of Blimp-1 in regulating several aspects of effector T-cell differentiation impairs study of its specific role in Trm development. Here, we used the restricted expression of Hobit in the Trm lineage to develop mice with a conditional deletion of Blimp-1 in Trm, allowing us to specifically investigate the role of both transcription factors in Trm differentiation. We found that Hobit and Blimp-1 were required for the upregulation of CD69 and suppression of CCR7 and S1PR1 on virus-specific Trm precursors after LCMV infection, underlining a role in their retention within tissues. The early impact of Hobit and Blimp-1 favored Trm formation and prevented the development of circulating memory T cells. Thus, our findings highlight a role of Hobit and Blimp-1 at the branching point of circulating and resident memory lineages by suppressing tissue egress of Trm precursors early during infection.


The involvement of bulbospinal pathways in fentanyl-induced inhibition of spinal withdrawal reflexes in the decerebrated rabbit.
The selective opioid OP3(mu)-receptor agonist fentanyl was administered via the intravenous, intrathecal and intraventricular routes to decerebrated rabbits in doses from 1-30 microg/kg. Reflexes evoked in medial gastrocnemius motoneurones by electrical stimulation of the sural nerve were depressed by fentanyl given by all three routes. The opioid was most potent when given intrathecally and least potent when given into the fourth ventricle. Blockade of spinal alpha2-adrenoceptors by intrathecal RX 821002 (100 microg) reduced the effectiveness of intrathecal and low (<3 microg/kg) intravenous doses of fentanyl, but did not affect or enhanced responses to high intraventricular and intravenous doses. Spinalization reduced the effectiveness of intrathecal and intravenous fentanyl and abolished inhibition from intraventricular dosing. These data show that fentanyl acts in the spinal cord and in the brain stem to suppress spinal reflexes, although very high doses were required for effects from the latter site. It appears that low intravenous doses of fentanyl act mainly in the spinal cord and that increasing the dosage recruits descending inhibition. The results of alpha2-adrenoceptor blockade indicate that the spinal inhibitory effects of opioids are enhanced by an interaction with endogenous noradrenaline in the spinal cord. Thus, the full expression of the spinal inhibitory effects of fentanyl is dependent on brain stem cell groups, either as a source of noradrenaline input to the spinal cord, or as a site from which opioids can activate descending inhibitory systems.


Synthesis Of PEG-Coated, Ultrasmall, Manganese-Doped Iron Oxide Nanoparticles With High Relaxivity For T1/T2 Dual-Contrast Magnetic Resonance Imaging.
Beyond magnetic resonance imaging (MRI), which has been widely used clinically, molecular MRI (mMRI) can further provide qualitative and quantitative information at the cellular and molecular levels. However, the diagnostic accuracy may not be satisfactory via single-contrast mMRI due to some interferences in vivo. T1/T2 dual-contrast MRI using the same contrast agent (CA) could significantly improve the detection accuracy. Therefore, in this study, we fabricated poly(ethylene glycol) (PEG)-coated, manganese-doped iron oxide nanocomposites (Mn-IONPs@PEG) as T1/T2 dual-contrast CA, and evaluated its feasibility of T1/T2 dual-contrast MRI in vitro and in vivo. Mn-IONPs were prepared by the thermal decomposition of iron-eruciate and manganese-oleate complexes and were coated with 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-N-(methoxy[polyethylene glycol]-2000) (DSPE-PEG 2000). The physicochemical properties and cytotoxicity of the Mn-IONPs were fully characterized, followed by MRI in vitro and in vivo. Ultrasmall 3 nm-sized nanoparticles were successfully prepared and were identified using transmission electron microscopy (TEM), high-resolution TEM, and X-ray diffraction. After coating with DSPE-PEG, the Mn-IONPs@PEG displayed excellent hydrophilicity and good biocompatibility. Due to the manganese-doping and PEG coating, the Mn-IONPs@PEG showed good relaxivity in vitro. Especially, the Mn-IONPs@PEG coated with DSPE-PEG following a mass ratio to Mn-IONPs of 1:20 showed harmonious longitudinal relaxivity (r 1 = 7.1 mM-1s-1) and transversal relaxivity (r 2 = 120.9 mM-1s-1), making it a better candidate for T1/T2 dual-contrast mMRI. After administrated via a caudal vein, the Mn-IONPs@PEG can induce significant enhancement in both T1-weighted and T2-weighted MR images and the time at 10 mins after injection was regarded as a suitable time for imaging because both the T1 and T2 enhancement were optimum at that time. The obtained Mn-IONPs@PEG exhibited good r 1 and r 2 and was a reasonable candidate for T1/T2 dual-contrast mMRI.


Use of a pattern recognition technique to control a multifunctional prosthesis.
Various kinds of command source can be used to control an above-elbow prosthesis. But none of them can be used to perform a specified task easily. The research is devoted to investigation of the potential effectiveness of applying the kinematic data of the shoulder joint to control an upper-limb prosthesis. Using these data as input signals, an appropriate signal processing technique, pattern recognition, is utilised to derive control commands. The purpose of the investigation is to use these commands to control a multifunctional prosthesis so that an amputee can perform a few tasks. For testing performance accuracy, a goniometer is worn by a subject with intact arm. It is also interfaced to a digital computer. Next, he is asked to do one of the predefined tasks for which the joint angle trajectories have already been derived and stored. Almost as soon as the shoulder joint angles are sampled and sent to the computer, the program calculates the elbow and wrist angles. These values are compared with actual elbow and wrist angles, which are monitored by the goniometer.


Early postoperative arterial oxygen desaturation. Determining factors and response to oxygen therapy.
Oxygen arterial saturation (SaO2) was measured with a pulse oximeter in 209 patients after elective surgery. Measurements were made upon arrival in the recovery room (RR) and 1 hr later. On each occasion, the patients randomly and alternately breathed--for 10 min at a time--room air or 35% O2. Factors that might influence the incidence of postoperative hypoxemia were analyzed. After breathing room air for 10 min after arrival in the RR, the mean SaO2 was 90.7 +/- 3.9% (+/- SD). Twenty min after and 1 hr after arrival in the RR, mean SaO2 increased significantly to 92.4 +/- 3.5% (P less than 0.001) and 93.2 +/- 3.0% (P less than 0.001), respectively. Postoperative hypoxemia (SaO2 less than or equal to 90%) after breathing room air for 10 min at 10 min, 20 min, and 1 hr after arrival in the RR occurred in 43.8%, 26.9%, and 16.9% of the patients, respectively. Breathing 35% O2 for 10 min 10 min after arrival in the RR, as well as 20 min and 1 hr after arrival, significantly increased SaO2 above the SaO2 level after breathing room air by 5.7% (P less than 0.001), 4.3% (P less than 0.001), and 4.0% (P less than 0.001), respectively. A significant multiple correlation was found between low SaO2 levels while breathing room air on arrival in the RR and fentanyl dose, age, and concentration of halothane used intraoperatively (R = 0.46; P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)


Chest applications of magnetic resonance imaging: an update.
Accumulated experience with MR applications in the chest has helped to define its role relative to other modalities. Technical advances improving image quality, newer fast scans, and cine methods are expanding the information available from MR. This discussion reviews the useful applications and limitations of MR in evaluating thoracic disorders. Physicians should be knowledgeable and selective in their utilization of this modality.


Improved method for the histochemical demonstration of glucose-6-phosphatase activity.
Methodological studies on the histochemical technique for the demonstration of G6Pase activity showed that the occurrence of common artifacts: morphological destruction, extracellular precipitation of reaction product and nuclear staining are dependent on the concentration of lead nitrate, buffer and substrate. By studying the effects of systematic variation of the incubation media on the histochemical reaction optimal concentrations of either of these components were determined. An improved medium containing 3.6 mM lead nitrate, 40 mM tris-maleate buffer, pH 6.5, 10 mM G6P and 300 mM sucrose was used for the study of G6Pase distribution patterns in liver acini of juvenile and adult rats of both sexes and in those of starved adult female rats. The results obtained indicate sex dependent differences in the functional organization of the liver acinus and furthermore demonstrate the rapid functional adaptability of liver parenchyma to changes of the nutritional situation.


Preoperative ultrasound to identify distribution of the lateral femoral cutaneous nerve in total hip arthroplasty using the direct anterior approach.
Recently, the branching pattern of the lateral femoral cutaneous nerve (LFCN) named Fan type has been reported that LFCN injury cannot be avoided in surgical dissections that use the direct anterior approach to the hip joint in the cadaveric study. We hypothesized that the Fan type can be identified by ultrasound The aim of this study was to investigate whether LFCN injury occurs in DAA-THA in cases identified as the Fan type based on preoperative ultrasound of the proximal femur. Ultrasonography of the proximal femur on the surgical side was performed before surgery and the LFCN distribution was judged as the Fan type or Non-Fan type. A self-reported questionnaire was sent to the patients at two months after surgery, and the presence or absence of LFCN injury was prospectively surveyed. After application of exclusion criteria, 45 hips were included. LFCN injury was observed after surgery in 9 of the 10 patients judged as the Fan type based on the ultrasound of the proximal femur (positive predictive value: 90%), and no LFCN disorder was actually observed in 25 of the 26 patients judged as Non-Fan type (specificity: 96.2%). To prevent injury of the LFCN in patients judged as the Fan type on the ultrasound test before surgery, the risk of direct injury of the LFCN may be reduced through the approach in which an incision is made in the fascia which is opposite to the radial spreading, i.e., between the sartorius and tensor fasciae latae muscles or slightly medial from it.


Mecamylamine-precipitated nicotine withdrawal syndrome and its prevention with baclofen: an autoradiographic study of α4β2 nicotinic acetylcholine receptors in mice.
A previous study from our laboratory showed that baclofen (BAC, GABAB receptor agonist) was able to prevent the behavioral expression of nicotine (NIC) withdrawal syndrome. To further investigate the mechanisms underlying this effect, we conducted this study, with the aims of analyzing α4β2 nicotinic receptor density during NIC withdrawal and, in case we found any changes, of determining whether they could be prevented by pretreatment with BAC. Swiss Webster albino mice received NIC (2.5 mg/kg, s.c.) 4 times daily, for 7 days. On the 8th day, NIC-treated mice received the nicotinic antagonist mecamylamine (MEC; 2 mg/kg, i.p.) 1 h after the last dose of NIC. A second group of NIC-treated mice received BAC (2 mg/kg, i.p.) prior to MEC administration. Thirty minutes after MEC, mice were sacrificed and brain autoradiography with [(3)H]epibatidine was carried out at five different anatomical levels. Autoradiographic mapping showed a significant increase of α4β2 nicotinic receptor labeling during NIC withdrawal in the nucleus accumbens shell (AcbSh), medial habenular nucleus (HbM), thalamic nuclei, dorsal lateral geniculate (DLG) nucleus, fasciculus retroflexus (fr), ventral tegmental area, interpeduncular nucleus and superior colliculus. BAC pretreatment prevented the increased α4β2 nicotinic receptor binding sites in the AcbSh, MHb, thalamic nuclei, DLG nucleus and fr. The present results suggest a relationship between BAC's preventive effect of the expression of NIC withdrawal signs, and its ability to restore the changes in α4β2 nicotinic receptor labeling, evidenced in specific brain areas in NIC withdrawn animals.


Burden of Chronic Kidney Disease by KDIGO Categories of Glomerular Filtration Rate and Albuminuria: A Systematic Review.
The Kidney Disease: Improving Global Outcomes (KDIGO) 2012 guidelines recommend classifying patients by glomerular filtration rate (GFR) and albuminuria to predict chronic kidney disease (CKD) prognosis. The aim of this systematic review was to explore the epidemiological burden of CKD stratified by the KDIGO 2012 categories. MEDLINE® and Embase were searched for observational studies of patients with CKD with results stratified according to the KDIGO 2012 classification. Investigated outcomes were prevalence, incidence, and risk factors and complications of CKD, including mortality. The review included ten observational studies with 3033 to 46,949 participants, conducted in the USA, China, France, Italy and Spain. The most frequently reported outcome was the prevalence of CKD (GFR categories G3-5), ranging from 2% to 17%. Most participants were normoalbuminuric, with 0.4-3.2% macroalbuminuric, and most fell within the KDIGO 2012 low-risk or moderate-risk groups, with 0.9-5.6% in the high-risk and 0.3-4.8% in the very high-risk groups. Although scarce, data on the prevalence of comorbidities in CKD according to the KDIGO classification suggest that they increase with albuminuria severity. Patients with CKD frequently have complications, but only a small proportion have severely increased albuminuria or fall within the KDIGO high-risk or very high-risk groups. These groups, however, are associated with the highest burden of disease, as comorbidities are more prevalent with increasing albuminuria severity. New studies framed by the KDIGO 2012 classification are needed to address key gaps in the understanding of CKD burden and outcomes.


Renal transplantation using ileal conduits in 5 cases.
We report our experience with 5 cases of renal transplantation into ileal conduits and review the literature. In 2 cases a modified surgical procedure was used, which combines a groin extraperitoneal approach for the vascular portion of the operation and a peritoneal window for the anastomosis between the urinary collecting system and the ileal loop. Of our 5 patients 3 are alive with functioning grafts, 1 has undergone retransplantation and 1 with a functioning kidney died of sepsis originating in a decubitus ulcer. Two patients had conduit-related complications. In our literature review of 16 reports 52 per cent of 68 patients were alive with functioning grafts and 32 per cent had conduit-related complications, usually involving urosepsis, calculous disease or stenosis. With a high index of suspicion, and an aggressive diagnostic and therapeutic approach to these problems, a good prognosis can be expected when transplantation is performed in these patients.


Role of cell-matrix interactions in osteoclast differentiation.
Osteoclast and their mononuclear cell precursors are present within the bone microenvironment at sites of physiologic and pathologic bone resorption. Analysis of tissues from sites of bone resorption reveal that cells expressing the full morphological and functional properties of mature osteoclasts are restricted to the immediate bone surface. We hypothesize that in addition to cytokines, components of the bone matrix and specific cell surface receptors on osteoclasts and their precursors play an essential role in determining the genetic profile and functional properties of fully differentiated resorbing osteoclasts. We have employed expression profiling, with an in vitro model of matrix-dependent osteoclast differentiation, to identify the molecular pathways by which bone matrix-interactions induce terminal osteoclast differentiation and activation. In preliminary studies, we have identified unique genes and transcriptional pathways that are induced by interaction of osteoclast precursors with specific components of the mineralized bone matrix. The authenticity of the gene profiles, as markers of osteoclast differentiation and activation, have been provisionally validated using an in vivo animal bone implantation model and by examination of tissues from patients with specific forms of pathologic osteoclast-mediated bone resorption. The ultimate goal of our studies is to identify new molecular targets for inhibiting osteoclast-mediated bone loss in disorders of pathologic bone loss. The early work of Walker et al. (Walker 1972) in parabiotic animals, and the subsequent studies of Burger et al. (Burger, Van der Meer, van de Gevel, et al. 1982) using a co-culture model with fetal bone rudiments and bone marrow-derived cells, have helped to establish that osteoclasts are derived from macrophage precursors of colony forming unit-macrophage (CFU-M lineage). As such, they share a common hematopoietic origin with other CFU-M lineage cells, including tissue macrophages that populate the lung (alveolar macrophages), liver (Kupfer cells), synovium (synovial macrophages) and other organs. They also share a common lineage


The processing of the sounds and meanings of ongoing speech by aphasic subjects.
The ability of aphasic subjects to process the sounds and meanings of ongoing speech was tested. Subjects, 10 aphasic and 20 control, heard test sentences which contained one member of phonemically similar word pairs in one of three semantic contexts: congruent, neutral, and noncongruent. Immediately after hearing a sentence, subjects were to indicate which member of the word pair had been in the sentence. All subject groups had similar overall patterns of response to the different semantic contexts. The division of aphasic subjects into groups of high and low comprehenders revealed response differences. High comprehending aphasic subjects, like control subjects, demonstrated interactive processing of the sounds and meaning of speech while low comprehending aphasic subjects did not.


Managing surgical demand when needs outstrip resource: qualitative investigation of colorectal cancer surgery provision in the first wave of the COVID-19 pandemic.
At the onset of the COVID-19 pandemic, elective surgical provision was severely affected by the need for hospital reorganization to care for critically ill patients. In response, National Health Service (NHS) England issued national guidance proposing acceptable time intervals for postponing different types of surgical procedure. This study reports healthcare professionals' private accounts of the strategies adopted to manage the imbalance of demand and resource, using colorectal cancer surgery as a case study. Twenty-seven semistructured interviews were conducted with healthcare professionals between June and November 2020. A key informant sampling approach was used, followed by snowballing to achieve maximum regional variation across the UK. Data were analysed thematically using the constant comparison approach. In the context of considerable resource constraint, surgical teams overcame challenges to continue elective cancer provision. They achieved this by pursuing a combination of strategies: relocating surgical services; prioritizing patients within and across surgical specialties; adapting patient treatment plans; and introducing changes to surgical team working practices. Despite national guidance, prioritization decisions were framed as complex, and the most challenging of the strategies to implement, both practically and emotionally. There is a need to better support surgeons tasked with prioritizing patients when capacity exceeds demand.


Update on the Essure System for Permanent Birth Control.
In 2002, the U.S. Food and Drug Administration approved the Essure system for permanent birth control. Implantation with this device offers a minimally invasive option for permanent female contraception that is placed during a brief office visit. Unlike laparoscopic tubal sterilization, the Essure procedure requires no hospitalization or general anesthesia, resulting in minimal recovery time. After a decade of stability in the report of adverse effects, the U.S. Food and Drug Administration noted a sharp increase in patient-reported adverse events, including chronic pelvic pain, irregular bleeding, allergic reactions, and autoimmune-like reactions. In response to this increase in complaints, the U.S. Food and Drug Administration issued updated guidelines for patient education and counseling. This article discusses those updates, as well as implications for nurses who provide health care to women seeking permanent contraception.


The cervical somatosensory evoked potential in man: far-field, conducted and segmental components.
Somatosensory evoked potentials (SEPs) to median nerve stimulation were recorded from neck and scalp electrodes in 23 normal adults using cephalic and non-cephalic (knee) references simultaneously. With a cephalic reference, the neck SEP consisted of several 'negative' potentials that had the same latency at all recording locations. Simultaneous recordings from neck-scalp, neck-knee and scalp-knee derivations demonstrated that scalp far-field potentials significantly contributed to neck-to-scalp recordings and obscured the cervical SEPs. With a non-cephalic reference, the neck SEP consisted of a prominent positive wave (P9) followed by a large negative component (N13). A small positive potential, P10, seen in the lower neck, gradually increased in latency and amplitude from lower to upper neck and appeared as a P11 potential at upper cervical levels. In lower neck recordings, a negative wave, N11, was also present and in some subjects exhibited a latency shift from lower to upper neck. P9, P11 and N11 had a short refractory period suggesting a presynaptic origin whereas N13 had a longer refractory period indicating a postsynaptic generator. The consensus that P9 originates in the peripheral nervous system is consistent with its rapid recovery cycle. The bipolar characteristics of N11 and P11 as well as their latency shift and their short recovery cycle suggest that they reflect activity in the cervical dorsal columns. N13, that displayed no latency shift and had a longer recovery cycle, may originate in spinal cord dorsal horn interneurons.


Dynamic active-site induced by host-guest interactions boost the Fenton-like reaction for organic wastewater treatment.
In heterogeneous catalysis, uncovering the dynamic evolution of active sites in the working conditions is crucial to realizing increased activity and enhanced stability of catalyst in Fenton-like activation. Herein, we capture the dynamic changes in the unit cell of Co/La-SrTiO3 catalyst during the exemplary peroxymonosulfate activation process using X-ray absorption spectroscopy and in situ Raman spectroscopy, revealing the substrate tuned its structural evolution, which is the reversible stretching vibration of O-Sr-O and Co/Ti-O bonds in different orientations. This process effectively promotes the generation of key SO5* intermediates, which is beneficial to the formation of 1O2 and SO4•- from persulfate on the Co active site. Density functional theory and X-ray absorption spectroscopy show that the optimized structural distortion enhanced the metal-oxygen bond strength by tuning the eg orbitals and increased the number of transferred electrons to peroxymonosulfate by about 3-fold, achieving excellent efficiency and stability in removing organic pollutants.


Phacoemulsification after T-hex keratotomy.
T-hex keratotomy surgically corrects manifest hyperopia. The typical patient presenting for this surgery is a presbyope who develops symptoms from latent hyperopia. These patients are older than typical radial keratotomy patients and are thus likely to develop senile cataracts sooner. The exact surgical approach to cataract surgery in such patients is unknown. We report a patient who had successful cataract extraction by phacoemulsification with implantation of a posterior chamber lens after a previous routine T-hex keratotomy. The preoperative workup and the surgical technique did not require modification.


Noninvasive finger plethysmography for continuous blood pressure monitoring in patients with left ventricular assist device.
Accurate blood pressure (BP) measurement remains challenging in patients with HeartMate 3™ left ventricular assist devices (HM3 LVADs). The Finapres® NOVA is a promising non-invasive continuous BP monitor that uses the volume clamp method via a finger cuff, so here we aimed to validate the instrument in HM3 patients. In a single-center cohort, BP was monitored in 15 patients within 72 h following HM3 implantation. A radial artery catheter quantified arterial blood pressure (ABP), while the NOVA measured finger arterial pressure (fiAP) and reconstructed brachial artery pressure (reBAP). Waveforms were recorded for 10 min, and mean values were calculated in 15-s intervals. fiAP and ABP were moderately correlated during both the first (ICC 0.61, p = 0.04) and final measurements (ICC 0.66, p = 0.03). reBAP and ABP were strongly correlated during both the first (ICC 0.81, p = 0.002) and final measurements (ICC 0.83, p = 0.001). Both NOVA-derived values may underestimate low BP values while overestimating relatively high BP values. The reBAP was within 5 mm Hg of the ABP in 40% of patients (and within 10 mm Hg in 67%). This pilot represents the first evidence in support of the Finapres® NOVA for non-invasive BP measurement in select patients with HM3 LVADs. The instrument may provide useful data during BP medication adjustments or pump titration, but despite the correlation between the non-invasive reBAP and invasive ABP, individual-level inaccuracy may be clinically meaningful. Further investigation is needed to clarify these limitations and optimize accuracy before widespread adoption in this unique patient population.


Impact of Introducing Catheter-based Renal Denervation into Japan for Hypertension Management: Estimation of Number of Target Patients and Clinical Relevance of Ambulatory Blood Pressure Reduction.
New medical approaches to the autonomic nervous system, such as catheterbased renal denervation, have been introduced into clinical practice in the recent years for patients who have resistant hypertension. We estimate the number of subjects in Japan who would benefit from renal denervation when this treatment is introduced into Japan, based on data from the Jichi Medical University clinical trials. We also discuss the logical basis of changing the formerly used primary endpoint, i.e., office BP, to 24-hr ambulatory BP in future clinical trials. Among JAMP registry data, the total number of hypertensives was 5,858 and the patients who were prescribed ≥ 3 drugs including diuretics were 749. The poorly controlled hypertension rate was 32% in the group prescribed ≥ 3 drugs including diuretics and it constitutes 4.1% of the total hypertensive patients. We also analyzed the data of JMS ABPM cohort study wave 1 (811 patients). The hazard ratios (HRs) for each 10-mmHg increase in BP was 1.38 (95%CI 1.17-1.63, p<0.001) for 24-hr BP and 1.18 (95%CI 1.05-1.33, p=0.006) for office BP. However, the significance for office BP was lost once the 24-hr, daytime and nighttime ambulatory BP data were added to the covariates. The prevalence of resistant hypertensive patients among all of the hypertensive patients is 4.1%. Based on this prevalence, the number of resistant hypertensive individuals in Japan would be 1,870,000 patients. In future renal denervation clinical studies in Japan, we should set the primary endpoint as a 24-hr systolic BP reduction measured by ABPM.


Production of a monoclonal antibody against Aeromonas hydrophila and its application to bacterial identification.
to develop a monoclonal antibody (MAb) for the rapid detection of Aeromonas hydrophila in human faeces. A monoclonal antibody with strong specificity against Aer. hydrophila was obtained by the fusion of myeloma cells and splenocytes of a mouse immunized with vegetative cells of Aer. hydrophila ATCC 7966, followed by a two-step selection against other species of the genera. ELISA analyses revealed that MAb 5F3 strongly reacts with all the Aer. hydrophila strains evaluated, showing a just basal reactivity against other species of the genera, especially Aer. sobria and Aer. caviae. MAb 5F3 was characterized as an IgG that recognized a polypeptide of approximately 110 kDa. This MAb could be used to detect Aer. hydrophila in human stool samples.


On the importance of fat reserves for the little auk (Alle alle) chicks.
The pattern of fat deposition and inter-year variation in the amount of deposited fat, lean dry mass (LDM) and water were studied in the chicks of little auk (Alle alle), an arctic alcid, at Spitsbergen in the 1984, 1986 and 1987 breeding seasons. The lipid index (lipid mass/LDM) rose from 0.29 at hatching to about 0.70 at the age of maximum body mass attained in the nest, the highest yet recorded for seabirds except procellariiforms. Just before fledging the index dropped to 0.38. Fat mass in 1984 chicks and also fresh body mass of older 1984 chicks was significantly lower than in the other two seasons, but there were no statistical year-to-year differences in LDM's of chicks. The amount of fat in chicks was significantly correlated with certain weather parameters. Fasting capability (FC) of the chicks (the time that chicks could survive when using only their lipid stores) was calculated from fat mass and previous data on metabolic rates of chicks. The FC's of all 108 chicks collected in three seasons were greater than maximum interval between two consecutive feeds to chicks reported in the study colony. Also the estimated fat reserves of 99.7% of chicks weighed in 1984 were sufficient to support them for longer than the maximum recorded intervals between feeds. In relation to death by starvation, little auk chicks, at least up to the age of maximum body mass, have a substantial surplus of fat. This is contrary to the hypothesis that fat depots in seabird chicks assist survival during the periodic fasts resulting from unpredictable feeding conditions.


Bihemispheric decreases of regional cerebral blood flow in dementia: correlation with age-matched normal controls.
Regional cerebral blood flow (rCBF) was measured by the xenon 133 inhalation method in 20 patients with senile and presenile dementia, and values were compared with flow data obtained in a series of 44 age-matched normal controls. The rCBF was reduced in patients with both presenile and senile dementia, and the degree of decrease exceeded the age-related rCBF decline in normal subjects. Similar rCBF reductions were observed in the left and right cerebral hemispheres and in general were homogeneously distributed in the various areas. The rCBF reductions in normal aging and in dementia may be associated with similar underlying cerebral morphological changes. Our findings suggest that the greater rCBF decreases in dementia compared with the values in age-matched controls may quantitatively reflect more severe pathological alterations in the brains of patients with intellectual deterioration.


Microsequence analysis of peptides and proteins. VI. A continuous flow reactor for sample concentration and sequence analysis.
We have designed and tested a continuous flow reactor (CFR) for microsequence analysis of peptides and proteins. The CFR forms the site for immobilization of the peptide or protein substrate and automated Edman chemistry. The CFR was constructed from 0.125-in.-o.d., 0.0625-in.-i.d. Teflon tubing (length 2-3 cm) containing 5-10 mg of Polybrene-coated, spherical, porous silica (100-200-micron particle size). The silica is retained in the CFR with porous Teflon filters (Zitex) at the bed bottom and optionally at the bed top. The i.d. of the CFR was selected for a tight press fit when 0.0625-in.-o.d. Teflon lines are inserted at the top and bottom of the CFR. This design allows the replacement of the existing cartridge/glass fiber disk found in conventional microsequencers with a CFR with a minimal amount of changes. The advantages of the CFR over the previous design include a lower background or noise level and no need to precycle Polybrene before sample application, and the entire unit is inexpensive and therefore disposable. We believe that the decrease in noise, especially the decrease in the commonly observed diphenylthiourea peak, is due to the more direct flow path and relative absence of unswept area in the CFR. Several standard peptides and proteins were sequenced in the CFR to demonstrate the improved results. A direct comparison to the cartridge/glass fiber disk design demonstrated less background and higher initial and repetitive yields for the CFR. An additional advantage is the ability to directly concentrate samples on CFRs containing reverse-phase packing. We have successfully concentrated 1.0-ml samples (200 pmol) onto 5 mg of octyldecylsilyl-derivatized silica in yields of 95-100%. The resulting samples were microsequenced after addition of Polybrene-coated silica to the CFR with high initial and repetitive yields. This methodology promises to improve sample handling and microsequence analysis of low picomole amounts of peptides and proteins.


Family functioning, peer influence, and media influence as predictors of bulimic behavior.
One hundred and twenty undergraduate women students reported their height and weight and completed the Eating Disorder Questionnaire (EDQ), the Eysenck Personality Inventory (EPI), the Beck Depression Inventory (BDI), the Family Assessment Device (FAD), the Body Shape Questionnaire (BSQ), the Body Image Assessment (BIA), and measures of peer and media influence. Family functioning was shown to be a poor predictor of bulimic behavior, whereas peer influence was a significant predictor. Media influence interacted with body dysphoria to increase the likelihood of bulimic behavior. The BSQ was a better predictor of bulimic behavior than the BIA, suggesting that students' responses to a measure that asks questions about specific areas of the body may reflect their feelings of body dysphoria more accurately than a measure that relies on a generalized silhouette.


Gas flaring and resultant air pollution: A review focusing on black carbon.
Gas flaring is a prominent source of VOCs, CO, CO2, SO2, PAH, NOX and soot (black carbon), all of which are important pollutants which interact, directly and indirectly, in the Earth's climatic processes. Globally, over 130 billion cubic metres of gas are flared annually. We review the contribution of gas flaring to air pollution on local, regional and global scales, with special emphasis on black carbon (BC, "soot"). The temporal and spatial characteristics of gas flaring distinguishes it from mobile combustion sources (transport), while the open-flame nature of gas flaring distinguishes it from industrial point-sources; the high temperature, flame control, and spatial compactness distinguishes gas flaring from both biomass burning and domestic fuel-use. All of these distinguishing factors influence the quantity and characteristics of BC production from gas flaring, so that it is important to consider this source separately in emissions inventories and environmental field studies. Estimate of the yield of pollutants from gas flaring have, to date, paid little or no attention to the emission of BC with the assumption often being made that flaring produces a smokeless flame. In gas flares, soot yield is known to depend on a number of factors, and there is a need to develop emission estimates and modelling frameworks that take these factors into consideration. Hence, emission inventories, especially of the soot yield from gas flaring should give adequate consideration to the variation of fuel gas composition, and to combustion characteristics, which are strong determinants of the nature and quantity of pollutants emitted. The buoyant nature of gas flaring plume, often at temperatures in the range of 2000 K, coupled with the height of the stack enables some of the pollutants to escape further into the free troposphere aiding their long-range transport, which is often not well-captured by model studies.


Renal synthesis of arginine in chronic renal failure: in vivo and in vitro studies in rats with 5/6 nephrectomy.
Synthesis of arginine (Arg) from citrulline (Cit) by the kidney is a major source of Arg for the body. The high level of plasma Cit in chronic renal failure is often thought to result from the impairment of the renal conversion of Cit to Arg. To verify this assumption, we performed two studies in Sprague-Dawley rats with 5/6 nephrectomy (CRF rats) and in sham-operated rats (CONT rats). In study I synthesis of Arg by isolated proximal convoluted tubules (PCT; the nephron segment exhibiting the highest Arg synthesis) was measured in vitro with two concentrations of Cit (200 or 50 microM) corresponding to those observed in plasma of rats with or without renal failure. In study II the net renal uptake of Cit and release of Arg were determined in vivo by measuring PAH clearance and arterial and renal venous Arg, and Cit concentrations in anesthetized rats. The in vitro results showed that Arg synthesis increased only in proportion to the hypertrophy of remnant PCT (+50%), and was highly and similarly dependent on Cit concentration in PCT of remnant and normal kidneys (Arg production with 200 microM Cit was 3 times higher than with 50 microM Cit for both CONT and CRF). The in vivo results showed that renal Cit uptake and Arg release were not altered in CRF: -286 +/- 28 versus -326 +/- 16 nmol Cit.min-1 (NS), and + 390 +/- 47 versus + 399 +/- 22 nmol Arg.min-1 (NS) in CONT and CRF rats, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


The hepatitis B virus X protein induces paracrine activation of human hepatic stellate cells.
Chronic hepatitis B virus (HBV) infection is a major cause of liver fibrosis, eventually leading to cirrhosis and hepatocellular carcinoma. Although the involvement of the X protein of HBV (HBx) in viral replication and tumor development has been extensively studied, little is known about its possible role in the development of fibrosis. In this work we show that expression of HBx in hepatocytes results in paracrine activation and proliferation of hepatic stellate cells (HSCs), the main producers of extracellular matrix proteins in the fibrotic liver. Both human primary HSCs and rat HSCs exposed to conditioned medium from HBx-expressing hepatocytes showed increased expression of collagen I, connective tissue growth factor, alpha smooth muscle actin, matrix metalloproteinase-2, and transforming growth factor-beta (TGF-beta), together with an enhanced proliferation rate. We found that HBx induced TGF-beta secretion in hepatocytes and that the activation of HSCs by conditioned medium from HBx-expressing hepatocytes was prevented by a neutralizing anti-TGF-beta antibody, indicating the involvement of this profibrotic factor in the process. Our results propose a direct role for HBx in the development of liver fibrosis by the paracrine activation of stellate cells and reinforce the indication of antiviral treatment in patients with advanced HBV-related chronic liver disease and persistent liver replication.


Lusutrombopag increases hematocytes in a compensated liver cirrhosis patient.
A 56-year-old Japanese man with liver cirrhosis (LC) due to hepatitis C virus was admitted to our hospital for radiofrequency ablation of residual tumor following lusutrombopag administration. Laboratory tests revealed thrombocytopenia and leukopenia. The patient's LC was managed, and he was classified as Child-Pugh A. After admission, lusutrombopag was administered for 7 days. The platelet count increased to over 50,000/mm3 after 7-14 days and returned to previous levels 50 days after administration. Leukocyte and erythrocyte counts also increased in response to the treatment and stayed elevated for over 120 days. Lusutrombopag acts selectively on human thrombopoietin (TPO) receptors and activates signaling pathways that promote the proliferation and differentiation of bone marrow progenitor cells into megakaryocytes, consequently increasing the blood platelet count. However, the patient treated with lusutrombopag in our case study showed increased blood leukocyte and erythrocyte counts as well. Given that TPO receptors are reportedly expressed in not only megakaryocyte progenitor cells but also hematopoietic progenitors, lusutrombopag may potentially improve pancytopenia caused by LC and can be used for the recovery of blood counts before other treatments.


Imbalanced nucleocytoskeletal connections create common polarity defects in progeria and physiological aging.
Studies of the accelerated aging disorder Hutchinson-Gilford progeria syndrome (HGPS) can potentially reveal cellular defects associated with physiological aging. HGPS results from expression and abnormal nuclear envelope association of a farnesylated, truncated variant of prelamin A called "progerin." We surveyed the diffusional mobilities of nuclear membrane proteins to identify proximal effects of progerin expression. The mobilities of three proteins-SUN2, nesprin-2G, and emerin-were reduced in fibroblasts from children with HGPS compared with those in normal fibroblasts. These proteins function together in nuclear movement and centrosome orientation in fibroblasts polarizing for migration. Both processes were impaired in fibroblasts from children with HGPS and in NIH 3T3 fibroblasts expressing progerin, but were restored by inhibiting protein farnesylation. Progerin affected both the coupling of the nucleus to actin cables and the oriented flow of the cables necessary for nuclear movement and centrosome orientation. Progerin overexpression increased levels of SUN1, which couples the nucleus to microtubules through nesprin-2G and dynein, and microtubule association with the nucleus. Reducing microtubule-nuclear connections through SUN1 depletion or dynein inhibition rescued the polarity defects. Nuclear movement and centrosome orientation were also defective in fibroblasts from normal individuals over 60 y, and both defects were rescued by reducing the increased level of SUN1 in these cells or inhibiting dynein. Our results identify imbalanced nuclear engagement of the cytoskeleton (microtubules: high; actin filaments: low) as the basis for intrinsic cell polarity defects in HGPS and physiological aging and suggest that rebalancing the connections can ameliorate the defects.


Solvent-free synthesis of nitrone-containing template as a chemosensor for selective detection of Cu(II) in water.
A state-of-the-art method was developed for repurposing nitrone-containing compounds in the chemosensory field, the ability of the designed molecules to chelate metal cations was evaluated, and their unprecedented solubility in water was confirmed. A facile, rapid, and solvent-free method of synthesizing small molecular mass chemosensors was developed by using a modulative α-aryl-N-aryl nitrone template. α-(Z)-Imidazol-4-ylmethylen-N-phenyl nitrone (Nit1) and α-(Z)-2-pyridyl-N-phenyl nitrone (Nit2) were prepared in 15 min, isolated in less than 60 min with ca. 90% yield, and screened against nine metal cations. Nit1 is a small-molecular-mass compound (188 g mol-1) that is water-soluble and has specificity for sensing Cu2+ with an association constant of K = 1.53 × 1010 and a limit of detection (LOD) of 0.06 ppm. These properties make Nit1 a competitive chemosensor for the detection of Cu2+ in aqueous solution. The nitrone-containing template used in this study is a step forward for new and small chemosensory entities.


A study of HIV seropositivity with various clinical manifestation of herpes zoster among patients from Karnataka, India.
To study the various clinical presentations of herpes zoster and to find out the proportion of HIV positivity in these patients. A time bound study was conducted from November 2004 to October 2005. All clinically diagnosed cases of herpes zoster were tested for HIV infection with ELISA and confirmed by Tridot and Coomb AID. Total numbers of 90 zoster cases were recorded. Mean duration of pre herpetic neuralgia was 2.134 (standard deviation=1.424, F=8.951, P<0.001). The thoracic dermatome (46.66%) was most commonly involved, followed by the cranial nerves (18.88%), lumbar (14.44%), cervical (13.33%) and sacral (6.66%) nerves. A substantial proportion, 34 (37.77%) out of 90 cases, were found to be HIV positive. Of these, 64.7 percent of the HIV seropositive herpes zoster patients belonged to the age group of 21-40 years. Out of 39 who had a risk of exposure to STDs and whose ages were less than 50 years, 31 (79.48%) tested positive for HIV infection. The occurrence of zoster in the young age group in patients who report a history of risk factors for HIV, may need testing. Herpes zoster serves as a clinical indicator of HIV seropositivity and one of the earliest manifestations.


Multifunctional targeted solid lipid nanoparticles for combined photothermal therapy and chemotherapy of breast cancer.
Photothermal therapy has emerged as a new promising strategy for the management of cancer, either alone or combined with other therapeutics, such as chemotherapy. The use of nanoparticles for multimodal therapy can improve treatment performance and reduce drug doses and associated side effects. Here we propose the development of a novel multifunctional nanosystem based on solid lipid nanoparticles co-loaded with gold nanorods and mitoxantrone and functionalized with folic acid for dual photothermal therapy and chemotherapy of breast cancer. Nanoparticles were produced using an economically affordable method and presented suitable physicochemical properties for tumor passive accumulation. Upon Near-Infrared irradiation (808 nm, 1.7 W cm-2, 5 min), nanoparticles could effectively mediate a temperature increase of >20 °C. Moreover, exposure to light resulted in an enhanced release of Mitoxantrone. Furthermore, nanoparticles were non-hemolytic and well tolerated by healthy cells even at high concentrations. The active targeting strategy was found to be successful, as shown by the greater accumulation of the functionalized nanoparticles in MCF-7 cells. Finally, the combined effects of chemotherapy, light-induced drug release and photothermal therapy significantly enhanced breast cancer cell death. Overall, these results demonstrate that the developed lipid nanosystem is an efficient vehicle for breast cancer multimodal therapy.


Idiopathic hypersomnia: a study of 77 cases.
To review the clinical and polysomnographic characteristics of idiopathic hypersomnia as well as the long-term response to treatment. The Respiratory Support and Sleep Centre at Papworth Hospital, Cambridge, UK. A large database of more than 6000 patients with sleep disorders was reviewed. A retrospective study of the clinical and polysomnographic characteristics of 77 patients with idiopathic hypersomnia was performed. Comparison with a similar group of patients with narcolepsy was performed. The response to drug treatment was assessed in 61 patients over a mean follow-up of 3.8 years. Idiopathic hypersomnia was 60% as prevalent as narcolepsy. Comparison with a similar group of patients with narcolepsy showed that those with idiopathic hypersomnia were more likely to have prolonged unrefreshing daytime naps, a positive family history, increased slow-wave sleep, and a longer sleep latency on the Multiple Sleep Latency Test. The results of the Multiple Sleep Latency Test were not helpful in predicting disease severity or treatment response. The clinical features were heterogeneous and of variable severity. The majority of patients with idiopathic hypersomnia had symptoms that remained stable over many years, but 11% had spontaneous remission, which was never seen in narcolepsy. Two thirds of patients with idiopathic hypersomnolence had a sustained improvement in daytime somnolence with medication, although a third needed high doses or combinations of drugs. Idiopathic hypersomnolence has characteristic clinical and polysomnographic features but the prolonged latency on the Multiple Sleep Latency Test raises doubt about the validity of this test within the current diagnostic criteria. The disease often responds well to treatment and a substantial minority of patients appear to spontaneously improve.


Nucleotide sequence of a carboxyphosphonoenolpyruvate phosphonomutase gene isolated from a bialaphos-producing organism, Streptomyces hygroscopicus, and its expression in Streptomyces lividans.
The carboxyphosphonoenolpyruvate (CPEP) phosphonomutase gene of bialaphos-producing Streptomyces hygroscopicus, which encodes a C-P bond forming enzyme was cloned into Streptomyces lividans and sequenced. The amino acid composition of the protein coded in an open reading frame of 295 codons and its calculated molecular mass, 32,800 Da, coincided well with those of the purified enzyme. Introduction of the CPEP phosphonomutase gene, the expression of which is controlled by the promoter of the aph gene, into S. lividans resulted in the production of this enzyme at a level almost equivalent to that in the parent strain.


Brain micro glutamic acid-rich protein is the C-terminal endpiece of the neurofilament 68-kDa protein as determined by the primary sequence.
The amino acid sequence of bovine brain micro glutamic acid-rich protein was determined by analysis of tryptic and Trimeresurus flavoviridis protease peptides of the molecule. The protein comprised 82 amino acid residues and has an Mr of 8992. The established sequence was highly homologous (90% identity) to the sequence of C-terminal 82 residues of the neurofilament 68-kDa protein from porcine spinal cord; there are differences of 8 residues which could be species-specific amino acid substitutions. This indicates that the micro glutamic acid-rich protein may arise by a restricted proteolysis of the neurofilament 68-kDa protein, with the break occuring toward the C-terminus.


Preliminary researches on the characterization of the glycoconjugates in the oviduct of Rana esculenta complex during its reproductive cycle.
Biochemical investigations were carried out on the oviduct of Rana esculenta. It was demonstrated that in the oviduct of Rana esculenta there is a heteropolysaccharide formed by sulphated acid glycoconjugates and neutral glycoproteins. The presence and the functional role of glucidic components are discussed and compared to previous histochemical data.


Safety and effectiveness of fluorescence laparoscopy in precise hepatectomy: A meta-analysis.
To perform a systematic review of the safety and effectiveness of fluorescence laparoscopy-guided precise hepatectomy. We searched the PubMed, Embase, Web of Science, and Cochrane Library databases from inception to December 1, 2022, using the search terms "indocyanine green," "ICG," "infracyanine green," "laparoscopy," "liver resection," and "hepatectomy." After performing a methodological quality assessment of the included studies, the overall results were subjected to meta-analysis using Review Manager 5.3. After screening, the meta-analysis included a total of 13 articles. The studies included 1,115 patients who were grouped into the fluorescence laparoscopy (490 patients) and conventional laparoscopy (625 patients) groups. All articles included in the meta-analysis were of high quality. The results of the meta-analysis revealed that compared to the conventional laparoscopy group, the fluorescence laparoscopy group had a higher R0 resection rate (odds ratio=4.03, 95% confidence interval [1.50, 10.83], P = 0.006), lower blood transfusion rate (odds ratio=0.46, 95% confidence interval [0.21, 0.97], P = 0.04) and lower blood loss (mean difference=-36.58; 95% confidence interval [-59.75, -13.41], P = 0.002). However, the length of hospital stay, operative time, and incidence of postoperative complications did not differ significantly between both groups (P>0.05). Compared to conventional laparoscopy, fluorescence laparoscopy provides better application effects in hepatectomy. The surgical procedure has demonstrated good safety and feasibility, which make it worthy of popularization.


Serum proteins of mice with splenomegaly.
Our earlier serum electrophoretic study in 'lethargic' mutant mice showed that the quantity of protein in 1 band is inversely related to the size of the spleen. In this study, we demonstrate that this protein band almost entirely disappears in mice with splenomegaly following spontaneous skin infection. The results suggest that this serum protein may play a role in regulating growth of lymphoid tissue.


Prenatal DEHP exposure predicts neurological disorders via transgenerational epigenetics.
Recent experimental and observational research has suggested that childhood allergic asthma and other conditions may be the result of prenatal exposure to environmental contaminants, such as di-(2-ethylhexyl) phthalate (DEHP). In a previous epidemiological study, we found that ancestral exposure (F0 generation) to endocrine disruptors or the common plasticizer DEHP promoted allergic airway inflammation via transgenerational transmission in mice from generation F1 to F4. In the current study, we employed a MethylationEPIC Beadchip microarray to examine global DNA methylation in the human placenta as a function of maternal exposure to DEHP during pregnancy. Interestingly, global DNA hypomethylation was observed in placental DNA following exposure to DEHP at high concentrations. Bioinformatic analysis confirmed that DNA methylation affected genes related to neurological disorders, such as autism and dementia. These results suggest that maternal exposure to DEHP may predispose offspring to neurological diseases. Given the small sample size in this study, the potential role of DNA methylation as a biomarker to assess the risk of these diseases deserves further investigation.


Effect of Pramlintide on Postprandial Glucose Fluxes in Type 1 Diabetes.
Early postprandial hyperglycemia and delayed hypoglycemia remain major problems in current management of type 1 diabetes (T1D). Our objective was to investigate the effects of pramlintide, known to suppress glucagon and delay gastric emptying, on postprandial glucose fluxes in T1D. This was a single-center, inpatient, randomized, crossover study. Twelve patients with T1D who completed the study were analyzed. Subjects were studied on two occasions with or without pramlintide. Triple tracer mixed-meal method and oral minimal model were used to estimate postprandial glucose turnover and insulin sensitivity (SI). Integrated liver insulin sensitivity was calculated based on glucose turnover. Plasma glucagon and insulin were measured. Glucose turnover and SI were the main outcome measures. With pramlintide, 2-hour postprandial glucose, insulin, glucagon, glucose turnover, and SI indices showed: plasma glucose excursions were reduced (difference in incremental area under the curve [iAUC], 444.0 mMmin, P = .0003); plasma insulin concentrations were lower (difference in iAUC, 7642.0 pMmin; P = .0099); plasma glucagon excursions were lower (difference in iAUC, 1730.6 pg/mlmin; P = .0147); meal rate of glucose appearance was lower (difference in iAUC: 1196.2 μM/kg fat free mass [FFM]; P = .0316), endogenous glucose production was not different (difference in iAUC: -105.5 μM/kg FFM; P = .5842), rate of glucose disappearance was lower (difference in iAUC: 1494.2 μM/kg FFM; P = .0083). SI and liver insulin sensitivity were not different between study visits (P > .05). Inhibition of glucagon and gastric emptying delaying reduced 2-hour prandial glucose excursions in T1D by delaying meal rate of glucose appearance.


Kinematic differences between gender specific and traditional knee implants.
In the ongoing debate about gender-specific (GS) vs. traditional knee implants, there is limited information about patella-specific outcomes. GS femoral component features should provide better patellar tracking, but techniques have not existed previously to test this accurately. Using novel computed tomography and radiography imaging protocols, 15 GS knees were compared to 10 traditional knees, for the 6 degrees of freedom of the patellofemoral and tibiofemoral joints throughout the range of motion, plus other geometric measures and quality of life (QOL). Significant differences were found for patellar medial/lateral shift, where the patella was shifted more laterally for the GS femoral component. Neither group demonstrated patellar maltracking. There were no other significant differences in this well-functioning group.


Pocket gophers (Geomys bursarius), vegetation, and soil nitrogen along a successional sere in east central Minnesota.
Pocket gophers (Geomys bursarius: Geomyidae Rodentia) are shown to affect soil resources and thus, indirectly, vegetation. Gophers reduce average soil nitrogen near the surface and increase point-to-point heterogeneity of soil nitrogen by moving nitrogen-poor subsurface soil to the soil surface. Data from 22 old fields at Cedar Creek Natural History Area, Minnesota, USA show correlations of soil nitrogen, vegetation, and gopher mounds that are consistent with this indirect mechanism by which gophers affect local species composition and old field succession.


Poly(2-oxazoline)s as materials for biomedical applications.
The conjunction of polymers and medicine enables the development of new materials that display novel features, opening new ways to administrate drugs, design implants and biosensors, to deliver pharmaceuticals impacting cancer treatment, regenerative medicine or gene therapy. Poly(2-oxazoline)s (POx) constitute a polymer class with exceptional properties for their use in a plethora of different biomedical applications and are proposed as a versatile platform for the development of new medicine. Herein, a global vision of POx as a platform for novel biomaterials is offered, by highlighting the recent advances and breakthroughs in this fascinating field.


Further characterization of ATP-initiated calcification by matrix vesicles isolated from rachitic rat cartilage. Membrane perturbation by detergents and deposition of calcium pyrophosphate by rachitic matrix vesicles.
Although membrane associated enzymes such as ATPase, alkaline phosphatase, and NTP pyrophosphohydrolase in matrix vesicles (MVs) may underlie the mechanisms of ATP-promoted calcification, prior to the current investigation, the role of the MV membrane in calcification had not been addressed. In this study, various perturbations were introduced to the MV membrane in in vitro calcification systems to determine ideal conditions for ATP-initiated calcification by MVs isolated from rachitic rat epiphyseal cartilage. Membrane integrity appears to be required, since the rupture of the vesicular membrane by vigorously mixing with 10% butanol abolished calcification. In contrast, a mild treatment of MVs with low concentrations (e.g., 0.01%, which is much below the critical concentration for micelle formation) of either neutral Triton X-100 or anionic deoxycholate stimulated calcification by >2-fold, without inducing obvious changes in vesicular appearance. Fourier transform infrared spectroscopic studies were done to identify the mineral phase formed in these experiments. For the first time, rachitic MVs were shown to induce the formation of a calcium pyrophosphate dihydrate-like phase after their exposure to calcifying medium with 1 mM ATP. The integration of spectral areas indicated that calcification was enhanced by Triton X-100. The detergent effect was reversible and appeared to be not mediated through activation of ATPase, alkaline phosphatase, or ATP pyrophosphohydrolase. In contrast to neutral Triton X-100 and anionic deoxycholate, cationic cetyltrimethylammonium bromide inhibited both ATPase activity (I50=10 microM) and ATP-initiated calcification. These observations suggest that membrane perturbations can affect calcification and that the presence of NTP-pyrophosphohydrolase in MVs may play a role in the deposition of CaPPi in rachitic cartilage.


Factors Affecting Intraoperative Gastro-Oesophageal Reflux in Dogs and Cats.
In animals, gastro-oesophageal reflux (GOR) may occur during anaesthesia, and it can lead to severe consequences such as oesophagitis and oesophageal stricture. This systematic review investigates the effect of fasting duration and anaesthetic and nonanaesthetic drugs on GOR in dogs and cats during general anaesthesia. Fifteen clinical studies met the inclusion criteria in this systematic review. In thirteen studies the population was dogs, while in two studies the population was cats. In the meta-analysis, seven studies were included. Four studies on the effect of fasting duration on GOR in dogs were included in the meta-analysis. In total, 191 dogs had a fasting duration less than 5 h, while 311 dogs had a fasting duration more than 5 h. The heterogeneity of the studies was high and statistically significant (p = 0.0002, I2 = 85%), but the overall effect was statistically nonsignificant (p = 0.82, odds ratio = 0.81, 95% CI 0.15, 4.26), in favour of the low fasting duration (<5 h). Concerning the effect of antacids on GOR, three studies were included in the meta-analysis. The heterogeneity of the studies was low and nonsignificant (p = 0.13, I2 = 52%) and the overall effect was statistically nonsignificant (p = 0.24). The low number of studies and the diverse factors affecting the incidence of reflux prevented us from reaching valuable conclusions on the risk factors for GOR.


Novel paradigm enables accurate monthly gestational screening to prevent congenital toxoplasmosis and more.
Congenital toxoplasmosis is a treatable, preventable disease, but untreated causes death, prematurity, loss of sight, cognition and motor function, and substantial costs worldwide. In our ongoing USA feasibility/efficacy clinical trial, data collated with other ongoing and earlier published results proved high performance of an Immunochromatographic-test(ICT) that enables accurate, rapid diagnosis/treatment, establishing new paradigms for care. Overall results from patient blood and/or serum samples tested with ICT compared with gold-standard-predicate-test results found ICT performance for 4606 sera/1876 blood, 99.3%/97.5% sensitive and 98.9%/99.7% specific. However, in the clinical trial the FDA-cleared-predicate test initially caused practical, costly problems due to false-positive-IgM results. For 58 persons, 3/43 seronegative and 2/15 chronically infected persons had false positive IgM predicate tests. This caused substantial anxiety, concerns, and required costly, delayed confirmation in reference centers. Absence of false positive ICT results contributes to solutions: Lyon and Paris France and USA Reference laboratories frequently receive sera with erroneously positive local laboratory IgM results impeding patient care. Therefore, thirty-two such sera referred to Lyon's Reference laboratory were ICT-tested. We collated these with other earlier/ongoing results: 132 of 137 USA or French persons had false positive local laboratory IgM results identified correctly as negative by ICT. Five false positive ICT results in Tunisia and Marseille, France, emphasize need to confirm positive ICT results with Sabin-Feldman-Dye-test or western blot. Separate studies demonstrated high performance in detecting acute infections, meeting FDA, CLIA, WHO ASSURED, CEMark criteria and patient and physician satisfaction with monthly-gestational-ICT-screening. This novel paradigm using ICT identifies likely false positives or raises suspicion that a result is truly positive, rapidly needing prompt follow up and treatment. Thus, ICT enables well-accepted gestational screening programs that facilitate rapid treatment saving lives, sight, cognition and motor function. This reduces anxiety, delays, work, and cost at point-of-care and clinical laboratories. Toxoplasmosis is a major health burden for developed and developing countries, causing damage to eyes and brain, loss of life and substantial societal costs. Prompt diagnosis in gestational screening programs enables treatment, thereby relieving suffering, and leading to > 14-fold cost savings for care. Herein, we demonstrate that using an ICT that meets WHO ASSURED-criteria identifying persons with/without antibody to Toxoplasma gondii in sera and whole blood with high sensitivity and specificity, is feasible to use in USA clinical practice. We find this new approach can help to obviate the problem of detection of false positive anti- T.gondii IgM results for those without IgG antibodies to T.gondii when this occurs in present, standard of care, predicate USA FDA cleared available assays. Thus, this accurate test facilitates gestational screening programs and a global initiative to diagnose and thereby prevent and treat T.gondii infection. This minimizes likelihood of false positives (IgG and/or IgM) while maintaining maximum sensitivity. When isolated IgM antibodies are detected, it is necessary to confirm and when indicated continue follow up testing in ∼2 weeks to establish seroconversion. Presence of a positive ICT makes it likely that IgM is truly positive and a negative ICT makes it likely that IgM will be a false positive without infection. These results create a new, enthusiastically-accepted, precise paradigm for rapid diagnosis and validation of results with a second-line test. This helps eliminate alarm and anxiety about false-positive results, while expediting needed treatment for true positive results and providing back up distinguishing false positive tests.


The whole is indeed more than the sum of its parts: perceptual averaging in the absence of individual item representation.
We tested Ariely's (2001) proposal that the visual system represents the overall statistical properties of sets of objects against alternative accounts of rapid averaging involving sub-sampling strategies. In four experiments, observers could rapidly extract the mean size of a set of circles presented in an RSVP sequence, but could not reliably identify individual members. Experiment 1 contrasted performance on a member identification task with performance on a mean judgment task, and showed that the tasks could be dissociated based on whether the test probe was presented before or after the sequence, suggesting that member identification and mean judgment are subserved by different mechanisms. In Experiment 2, we confirmed that when given a choice between a probe corresponding to the mean size of the set and a foil corresponding to the mean of the smallest and largest items only, the former is preferred to the latter, even when observers are explicitly instructed to average only the smallest and largest items. Experiment 3 showed that a test item corresponding to the mean size of the set could be reliably discriminated from a foil but the largest item in the set, differing by an equivalent amount, could not. In Experiment 4, observers rejected test items dissimilar to the mean size of the set in a member identification task, favoring test items that corresponded to the mean of the set over items that were actually shown. These findings suggest that mean representation is accomplished without explicitly encoding individual items.


Expression of natural killer (NK) cell-specific alloantigens on a mouse NK-like cell line.
As part of the strategy for screening for natural killer (NK) cell-specific monoclonal antibodies (MoAb) we have raised a number of murine NK-like cell lines in media containing interleukin-2 (IL-2). The detection of specific NK cell alloantigens on a C57BL/6 cell line in long-term culture in IL-2 is the subject of this paper. The C57BL/6 cell line has the morphology of large granular lymphocytes (LGL) and exhibits strong cytolytic activity against the archetype NK cell target, YAC-1. Absorption of three anti-NK antiserum, NZB anti-BALB/c (anti-NK-2.1), BALB/c anti-DBA/2 (anti-NK-3.1) and CE anti-CBA (anti-NK-4.1), with the C57BL/6 cell line removed the anti-NK activity from these antisera. Flow cytometric studies of the C57BL/6 cell line demonstrated significant binding of the anti-NK-1.1 MoAb produced by hybridoma PK136. Our results suggest that the C57BL/6 NK-like cell line exhibits some of the properties of naive NK cells and expresses all the known NK cell-specific alloantigens, NK-1.1, NK-2.1, NK-3.1 and NK-4.1 and therefore is potentially useful in selecting NK specific hybridomas and in studying the biology of NK cells.


Unsteady non-Newtonian blood flow through a tapered overlapping stenosed catheterized vessel.
The unsteady flow characteristics of blood in a catheterized overlapping stenosed artery are analyzed in presence of body acceleration and magnetic field. The stenosed arterial segment is modeled as a rigid constricted tube. An improved shape of stenosis in the realm of the formulation of the arterial narrowing caused by atheroma is integrated in the present study. The catheter inside the artery is approximated by a thin rigid tube of small radius while the streaming blood in the artery is characterized by the Carreau model. Employing mild stenosis condition, the governing equation of the flow is derived which is then solving numerically using finite difference scheme. The variation of axial velocity, flow rate, resistance impendence and wall shear stress is shown graphically for various parameters of interest. The flow patterns illustrating the global behavior of blood are also presented.


Heart rate variability biofeedback improves cardiorespiratory resting function during sleep.
The present study was designed to examine the effect of heart rate variability (HRV) biofeedback on the cardiorespiratory resting function during sleep in daily life. Forty-five healthy young adults were randomly assigned to one of three groups: HRV biofeedback, Autogenic Training(AT), and no-treatment control. Participants in the HRV biofeedback were instructed to use a handheld HRV biofeedback device before their habitual bedtime, those in the AT were asked to listen to an audiotaped instruction before bedtime,and those in the control were asked to engage in their habitual activity before bedtime. Pulse wave signal during sleep at their own residences was measured continuously with a wrist watch-type transdermal photoelectric sensor for three time points. Baseline data were collected on the first night of measurements, followed by two successive nights for HRV biofeedback, AT, or control. Cardiorespiratory resting function was assessed quantitatively as the amplitude of high frequency(HF) component of pulse rate variability, a surrogate measure of respiratory sinus arrhythmia. HF component increased during sleep in the HRV biofeedback group,although it remained unchanged in the AT and control groups. These results suggest that HRV biofeedback before sleep may improve cardiorespiratory resting function during sleep.


Arthroscopic meniscal repair.
Arthroscopic meniscal repair is a promising new technique for treating peripheral meniscal tears. With proper attention to surgical technique, the repair can be safely performed by any surgeon with moderate arthroscopic skills. We recommend that in all cases the capsule be exposed through a small incision to identify and protect the neurovascular structures. When an associated ACL tear is present, ligamentous reconstruction is also recommended. Although we currently limit our repairs to peripheral tears, newer techniques may expand indications for this procedure.


Capnocytophaga (Capnocytophaga ochracea group) bacteremia in hematological patients with profound granulocytopenia.
The clinical and microbiological features of 7 cases of bacteremia due to Capnocytophaga (Capnocytophaga ochracea group) are reported. They were diagnosed during 1991-93 at three hospital clinics. Five patients were < 10 years old and all had hematological disorders, 4 acute lymphoblastic leukemia and 1 each had aplastic anemia, non-Hodgkin lymphoma, and myelodysplastic syndrome. All were profoundly granulocytopenic with an absolute granulocyte count < 0.13 x 10(9)/l, and all but 1 had oral lesions as a possible portal of entry. A favourable response to antibiotic therapy was recorded in all patients but one who, being profoundly granulocytopenic, rapidly succumbed to Pseudomonas aeruginosa septicemia. None of the isolates were beta-lactamase producers. In addition to penicillin the isolates were susceptible to broad-spectrum cephalosporins and ciprofloxacin, but resistant to aminoglycosides.


First record of Cnemidochroma phyllopus (Coleoptera: Cerambycidae) in the province of Corrientes, Argentina and potential distribution in the southern part of South America.
Cnemidochroma Schmidt, 1924, a small genus of the tribe Callichromatini endemic in South America, comprises six species of which the only one recorded in Paraguay, Uruguay, Argentina and Brazil is C. phyllopus (Gurin-Mneville, 1844). The aim of this study was to estimate potential suitable areas for C. phyllopus to provide further knowledge on its current distribution. A dataset of 43 records was compiled and species distribution modelling was employed linking these occurrences with bioclimatic variables. Results indicate higher suitability conditions along the Atlantic coast of Brazil, reaching north Uruguay and extending inland to Paraguay and northern parts of Argentina. In addition, we report a new distributional record from Corrientes, Argentina.


Subtle hyperproinsulinaemia characterises the defective insulin secretory capacity in offspring of glutamic acid decarboxylase antibody-positive patients with latent autoimmune diabetes mellitus in adults.
We set out to assess whether hyperproinsulinaemia is an early finding in latent autoimmune diabetes in adults (LADA). We measured plasma proinsulin and C-peptide responses during a 2-h oral glucose tolerance test (OGTT) and in the hyperglycaemic clamp in 21 normoglycaemic offspring of LADA patients testing positive for glutamic acid decarboxylase antibodies (GADA) or islet cell antibodies (ICA), and in 17 healthy control subjects without a family history of diabetes. The study groups had comparable areas under the curves of blood glucose, plasma proinsulin, C-peptide and proinsulin/C-peptide in the OGTT. However, the offspring of LADA patients had higher proinsulin/C-peptide in the hyperglycaemic clamp (P < 0.01 versus the control group). The offspring of GADA-positive LADA patients (n = 9) had higher proinsulin and proinsulin/C-peptide than did the control group in the OGTT (P < 0.05 for both comparisons) and in the hyperglycaemic clamp (P < 0.001 and P < 0.05 respectively). They also had higher proinsulin than the offspring of ICA-positive LADA patients (n = 12) (P < 0.001) in the hyperglycaemic clamp. The offspring of ICA-positive LADA patients did not clearly show hyperproinsulinaemia during the tests, but they had lower maximal glucose-stimulated insulin secretory capacity than the control group (P < 0.05) and the offspring of GADA-positive LADA patients (P < 0.05) in the hyperglycaemic clamp. These results suggested that insulin secretion in the offspring of GADA-positive LADA patients is characterised by subtle defects in the processing of insulin precursors. Furthermore, various proinsulin responses among the offspring of LADA patients with different autoimmune markers provided further evidence that LADA is a heterogeneous disorder.


Clinical syndromes, natural history, and pathophysiology of vascular lesions of the spinal cord.
With superselective angiography and careful clinical evaluation, dural fistulas were found to be the most important and most frequent origin of spinal arteriovenous malformations. Diagnosis may not be made for months or years, however, because dural fistulas never bleed and clinical deterioration is slow. Therapy with interventional techniques or microsurgery is relatively safe. Perimedullary fistulas and intramedullary angiomas mostly deteriorate quickly because of hemodynamic or hemorrhagic problems. Close teamwork of interventionalists and neurosurgeons is mandatory.


Digital image analysis of mean AgNOR area objectively discriminates between reactive plasmacytosis and multiple myeloma in cytologic smears from bone marrow aspirates.
To differentiate between reactive plasmacytosis (RP) and multiple myeloma (MM) in bone marrow aspirates by assessment of silver-stainable nucleolar organizer regions (AgNORs). Archival cytologic smears (n = 69) from bone marrow aspirates were retrospectively investigated. Twenty cases had RP and 49 cases MM (24 low-grade, 22 intermediate-grade and 3 high-grade MM). Diagnoses were confirmed by evaluation of the corresponding bone marrow trephine biopsies. Cytologic smears were subjected to AgNOR staining using a standardized silver-staining protocol and assessed by two independent clinical histopathologists using digital image analysis. AgNOR count and area were analyzed in 100 plasma cell nuclei per sample. The mean AgNOR area was found to be significantly (p < 0.001) higher in low-grade MM (mean: 23.4 microm(2); range: 19.2-26.7 microm(2)) than in RP cases (mean: 6.2 microm(2); range: 3.8-8.4 microm(2)). In contrast, mean AgNOR count failed to disclose significant differences between low-grade MM (mean: 5.36; range: 1-7) and RP (mean: 3.68; range: 1-6). Digital image analysis of the mean AgNOR area might be used as a diagnostically useful adjunct to aid objectively in the challenging differentiation between RP and MM in bone marrow aspirates.


Real-time quaking-induced conversion assay using a small-scale substrate production workflow for the diagnosis of Creutzfeldt-Jakob disease.
The lack of a dedicated surveillance program for prion disease, particularly in low- and middle-income countries (LMICs), has hindered the global effort to address this public health threat. Although cerebrospinal fluid (CSF) Real-time quaking-induced conversion (RT-QuIC) is considered the most reliable test for sporadic Creutzfeldt-Jakob disease (sCJD), its availability in LMICs is limited because of its cost and technical difficulty in generating the recombinant prion protein substrate (recPrP). This study aimed to evaluate the performance of RT-QuIC with recPrP produced in-house through a small-scale method-that is, the application of reusable prepacked chromatography columns and subsequent dialysis. Here, CSF specimens from patients suspected of having prion disease were consecutively collected and stored between October 2015 and January 2023. Electronic medical record data were reviewed to clinically classify participants as probable sCJD or non-sCJD. CSF RT-QuIC was performed using in-house recPrP. Its specificity and sensitivity for diagnosing probable sCJD were reported, along with details of other clinical data and investigations. We found that among 39 eligible participants, with a median (interquartile range) age of 64 (56-70) years and 16 (41%) female, 13 had probable sCJD and the remaining 26 unequivocally suffered from nonprion disorders. Magnetic resonance imaging and electroencephalogram were suggestive of sCJD in 100% (13/13) and 46.2% (6/13) of sCJD participants, respectively. RT-QuIC was positive in 12/13 sCJD participants (sensitivity 0.92, 95% confidence interval [CI] 0.67-0.99) and negative in all non-sCJD participants (specificity 1.00, 95% CI 0.87-1.00). CSF tau/p-tau ratio showed sensitivity and specificity of 0.62-1.0 and 0.85-1.0, respectively. In summary, RT-QuIC using recPrP generated through a small-scale workflow demonstrated great performance in detecting sCJD. Given its performance results along with its low cost, this technique could feasibly be implemented in LMICs and potentially be the first step toward establishing local prion disease surveillance programs.