Is DTPA a good competing chelating agent for Th(IV) in human serum and suitable in targeted alpha therapy?
The interaction between thorium and human serum components was studied using difference ultraviolet spectroscopy (DUS), ultrafiltration and high-pressure-anion exchange chromatography (HPAEC) with external inductively conducted plasma mass spectrometry (ICP-MS) analysis. Experimental data are compared with modelling results based on the law of mass action. Human serum transferrin (HSTF) interacts strongly with Th(IV), forming a ternary complex including two synergistic carbonate anions. This complex governs Th(IV) speciation under blood serum conditions. Considering the generally used Langmuir-type model, values of 10(33.5) and 10(32.5) were obtained for strong and weak sites, respectively. We showed that trace amounts of diethylene triamine pentaacetic acid (DTPA) cannot complex Th(IV) in the blood serum at equilibrium. Unexpectedly this effect is not related to the competition with HSTF but is due to the strong competition with major divalent metal ions for DTPA. However, Th-DTPA complex was shown to be stable for a few hours when it is formed before addition in the biological medium; this is related to the high kinetic stability of the complex. This makes DTPA a potential chelating agent for synthesis of (226)Th-labelled biomolecules for application in targeted alpha therapy.


Possible role of P-glycoprotein in the neuroprotective mechanism of berberine in intracerebroventricular streptozotocin-induced cognitive dysfunction.
The therapeutic potential of berberine has been well documented in various neurological problems. However, the neurological mechanism of berberine remains untapped in the light of its P-glycoprotein (P-gp)-mediated gut efflux properties responsible for reduced bioavailability. Verapamil, a well known L-type calcium channel blocker, has additional inhibitory activity against P-gp efflux pump. Thus, there is a strong scientific rationale to explore the interaction of berberine with verapamil as a possible neuroprotective strategy. The present study was designed to evaluate the effect of berberine, verapamil, and their combination on behavioral alterations, oxidative stress, mitochondrial dysfunction, neuroinflammation, and histopathological modifications in intracerebroventricular streptozocin (ICV-STZ)-induced sporadic dementia of Alzheimer's type in rats. Single bilateral ICV-STZ (3 mg/kg) administration was used as an experimental model of sporadic dementia of Alzheimer's type. Berberine (25, 50, and 100 mg/kg, oral gavage) or verapamil (2.5 and 5 mg/kg, intraperitoneally) were used as treatment drugs, and memantine (5 mg/kg, intraperitoneally) was used as a standard. Berberine and verapamil significantly attenuated behavioral, biochemical, cellular, and histological alterations, suggesting their neuroprotective potential. Further, treatment of berberine (25 and 50 mg/kg) with verapamil (2.5 and 5.0 mg/kg) combinations respectively significantly potentiated their neuroprotective effect which was significant as compared to their effect per se in ICV-STZ-treated animals. The augmentative outcome of verapamil on the neuroprotective effect of berberine can be speculated due to the inhibition of P-gp efflux mechanism and the prevention of calcium homeostasis alteration. Additionally, anti-inflammatory and antioxidant effects of both berberine and verapamil could also contribute in their protective effect.


A specialist service evaluation: a cross-sectional survey approach.
This article presents the findings of a service evaluation of a specialist urogynaecology service and highlights the implications for nursing practice. To evaluate the overall patient experience and the degree to which individual needs were being met, and make improvements to service delivery. A cross-sectional survey questionnaire was sent to a random sample of women (n=350) who were registered on the electronic patient record system from January to June 2020. Two items on the questionnaire related specifically to communication with patients during the first COVID-19 lockdown in March 2020. Routine service data were collected and included in descriptive statistical analysis. Qualitative themes were thematically analysed. The response rate was 39% (n=137). More than 90% of respondents felt listened to during consultations with nursing and medical personnel, and had trust and confidence in their clinical expertise, felt involved with decisions about care and felt comfortable with intimate examinations. Negative responses related to poor communication with administration and rescheduling appointments. Findings resulted in a departmental review of admin processes, which resulted in improvements to administrative systems, staff training, communication and information giving, and directly benefited patients.


Embolic inner ear decompression illness: correlation with a right-to-left shunt.
Inner ear decompression illness is thought to be a rare phenomenon in recreational divers, isolated signs and symptoms of inner ear dysfunction usually being attributed to inner ear barotrauma. We present 11 cases of inner ear dysfunction in nine divers with inner ear decompression illness. All nine divers had significant right-to-left shunt as diagnosed by transcranial Doppler sonography. The authors thought that mechanism of causation in these cases may have been intravascular bubble emboli and that inner ear decompression illness may be more common among recreational divers than currently recognized. Failure to treat inner ear decompression illness with recompression therapy can result in permanent disability. Because the differential diagnosis between inner ear barotrauma and inner ear decompression illness can be impossible, the authors suggested that divers who present with inner ear symptoms following a dive should have recompression immediately after having undergone bilateral paracentesis.


Impact of daily versus weekly hematinic supplementation on anemia in pregnant women.
To compare the effectivity of weekly versus daily iron therapy in reducing maternal anemia and to evaluate the association of maternal hemoglobin and fetal growth. Prospective. Tertiary care teaching hospital in an urban metropolis. 40 pregnant women received daily and 40 pregnant women received weekly oral therapy (335 mg of ferrous sulphate and 500 g folic acid) for a period of 14 weeks. The age of each pregnant woman and their baseline anthropometric data (weight, height and body mass index) were estimated. Hemoglobin and hematocrit estimations were carried out during follow period at 4 wks, 8 wks and 14 weeks. Serum ferritin values as a marker of iron status were also calculated in both the groups initially, at 14 weeks and at the time of delivery. Fetal anthropometric indices of 137 full term neonates delivered to mothers included in either of the supplementation groups or admitted to the hospital were also studied in relation to maternal hemoglobin concentration. Forty subjects each were initially randomized into groups I and II. The age of pregnant women along with their baseline anthropometric data were similar in both groups. A total of 29 pregnant women in group I and 27 pregnant women in group II could be regularly followed up. The increase in hemoglobin and hematocrit values were similar in daily and weekly supplemented mothers. An intention to treat analysis also showed similar results. The ferritin values were similar at the start of supplementation and after 14 wks of weekly or daily iron therapy. Birth weight, crown heel length, head circumference of the neonate and placental weight increased significantly with rise in maternal hemoglobin levels. Weekly iron supplementation is an effective mode of treating anemia among pregnant women and maternal anemia during pregnancy is adversely associated with fetal growth.


Facile preparation of low cytotoxicity fluorescent carbon nanocrystals by electrooxidation of graphite.
A simple and facile method was developed to prepare fluorescent carbon nanocrystals (CNCs) with low cytotoxicity and no photobleaching, by electrooxidation of graphite in aqueous solution.


Adsorption of complement proteins on surfaces with a hydrophobicity gradient.
Activation of the complement system is recognized as one of the major problems with respect to biocompatibility of biomaterials. The binding of C3 (central component of complement) and B (factor B, an activator of C3), and H (factor H, an inhibitor of C3 activation) plays a crucial role in the activation of the alternative pathway of complement on the surfaces of biomaterials during extracorporeal procedures. Here we report on the adsorption of C3, B or H on to the silica surface with a hydrophobicity gradient. The amount of native 125I-C3 bound to both hydrophilic and hydrophobic surfaces was very similar (0.8 and 0.9 micrograms/cm2; 4 x 10(-12) mol/cm2). Neither factor H nor factor B was able to displace already adsorbed 125I-C3 from either of the surfaces. The extent of binding of factors B and H to preadsorbed C3 was a function of the surface hydrophobicity: more 125I-B or 125I-H was bound to C3 adsorbed at the hydrophilic end than at the hydrophobic end of the gradient surface. The binding of 125I-B or 125I-H to preadsorbed C3 appeared to be influenced by the availability of their binding sites on adsorbed C3 molecules rather than by the amount of surface-bound C3. At the hydrophobic end of the gradient surface the molar binding ratio of B/C3 was considerably smaller than the molar binding ratio of H/C3. It can be speculated that the hydrophobicity of the surface determines orientation and/or conformation of adsorbed C3 molecule; when adsorbed at the hydrophobic end of the gradient, C3 molecule predominantly exposes the binding site to which only factor H can bind.(ABSTRACT TRUNCATED AT 250 WORDS)


Implementation effect of institutional policy of EGD observation time on neoplasm detection.
The observation time in EGD is associated with detection rate of premalignant or neoplastic lesions in the upper GI (UGI) tract. The aim of this study was to evaluate an institutional policy of EGD observation time on the detection rate of UGI neoplasms. From July 2017 to March 2019, all endoscopists were requested to comply with our institutional policy of spending more than 3 minutes of observation time in every screening EGD. Observation time was defined as the time from when the endoscope reached the duodenum to when it was withdrawn. We obtained a neoplasm detection rate (NDR) during this period and compared it with that of a baseline period from 2009 to 2015. During the study period, 30,506 EGDs were performed. Mean subject age was 49.9 ± 10.5 years, and 56.5% were men. All endoscopists achieved an average EGD observation time of more than 3 minutes during this period. Mean observation time was 3:35 ± 0:50, which was significantly longer than the baseline (2:38 ± 0:21, P < .001). NDR was .33%, which was higher than the baseline (.23%, P < .001). Even after adjusting for subjects' age and gender, smoking history, and endoscopists' biopsy sampling rate, prolonged EGD observation time of more than 3 minutes increased the NDR of UGI neoplasms (odds ratio, 1.51; 95% confidence interval, 1.21-1.75). This study provides evidence that implementing a protocol of a prolonged observation time could increase NDR. Observation time should be an important quality indicator of the EGD examination.


Visuospatial exploration and art therapy intervention in patients with Parkinson's disease: an exploratory therapeutic protocol.
Though abnormalities of visuospatial function occur in Parkinson's disease, the impact of such deficits on functional independence and psychological wellbeing has been historically under- recognized, and effective treatments for this impairment are unknown. These symptoms can be encountered at any stage of the disease, affecting many activities of daily living, and negatively influencing mood, self-efficacy, independence, and overall quality of life. Furthermore, visuospatial dysfunction has been recently linked to gait impairment and falls, symptoms that are known to be poor prognostic factors. Here, we aim to present an original modality of neurorehabilitation designed to address visuospatial dysfunction and related symptoms in Parkinson's disease, known as "Art Therapy". Art creation relies on sophisticated neurologic mechanisms including shape recognition, motion perception, sensory-motor integration, abstraction, and eye-hand coordination. Furthermore, art therapy may enable subjects with disability to understand their emotions and express them through artistic creation and creative thinking, thus promoting self-awareness, relaxation, confidence and self-efficacy. The potential impact of this intervention on visuospatial dysfunction will be assessed by means of combined clinical, behavioral, gait kinematic, neuroimaging and eye tracking analyses. Potential favorable outcomes may drive further trials validating this novel paradigm of neurorehabilitation.


Secondary aneurysmal bone cyst in Langerhans cell histiocytosis: Case report, literature review.
Langerhans cell histiocytosis (LCH) is a rare disease of the myeloid precursor cells, it predominantly occurs in the skull and long bones as unifocal bone lesions. Aneurysmal bone cysts (ABC) are benign, expansive and lytic bone. Reports of secondary ABC occurring in LCH are rare, having only been reported twice in the skull. Here, we report the first case of LCH masquerading as ABC in a 14-month-old female child who presented with a rapidly growing mass in her left femur. The lesion had typical radiological features of ABC, and only histological examination revealed the presence of cells suggestive of LCH.


Antigenic content of an in vitro cellular immunity reactive cell surface extract of Raji cells.
Antigenic content of a Raji cell surface extract (TS) was studied by sequential abosrption of rabbit antiserum to this extract with different cells. Anti-TS was first allowed to react exhaustively with human blood cells followed by HeLa cells and human diploid fibroblasts. The residual reactivity was studied by stepwise absorption with an EBV-negative B lymphoblastoid cell line, BJAB, and then with B1--19, a clone derived from EBV transformed BJAB cells. These processes delineated three kinds of reactivities in anti-TS having specificities for antigens on B blasts, EBV-determined cell surface antigen(s) and antigens that are exclusive to Raji cells, respectively. These results are compatible with the heterogeneous protein content of TS and with the results of our earlier in vitro cell-mediated immunity studies using a similar preparation of Raji cell TS.


Early steps of follicular lymphoma pathogenesis.
Follicular lymphoma (FL) pathogenesis is a complex and fascinating multi-hit process, escalating along successive derailments of the distinctive molecular and cellular mechanisms paving B-cell differentiation and activation. This progressive subversion of B-cell receptor diversification mechanisms and B-cell homeostasis likely occurs during a protracted preclinical phase of asymptomatic growth, in which premalignant clones already disseminate and establish "niches" in secondary lymphoid organs. Following FL diagnosis, a parallel indolent behavior is observed in most patients, slowly progressing over a period of many years, to eventually generate a highly refractory (and in some case transform into an aggressive subtype of) lymphoma. Novel insights in human germinal center B-cell biology recently allowed a more comprehensive understanding of the various illegitimate events sequentially involved in the premalignant progression phases. In this review, we will discuss how these new data have modified our perception of early FL pathogenesis, the new questions and challenges it opened up, and how this knowledge could impact on innovative programs of early detection, follow-up, and patient management.


Potential economic impact of applying DRG-based prospective payment categories to inflammatory bowel disease patients.
New incentives regarding delivery of inpatient care by physicians and administrators have resulted from Medicare's DRG-based prospective reimbursement system. As these payment systems become widely adopted by other third-party payors, implications for adequate hospital reimbursement and quality inpatient care will intensify. This study of inflammatory bowel disease inpatients examines discharge data for 300 patients comprising 507 admissions from 1983 to 1987 at a large tertiary center hospital. While only 10.8% of these discharges were Medicare patients, all discharges were assigned a diagnosis-related-group reimbursement to derive a theoretical monetary loss or gain for the hospital. Overall hospital losses averaged $127.24 per case for this patient population, in which the medical and pediatric cases were adequately reimbursed, and the surgical admissions represented greater losses. The average length of stay for all patients decreased from 11.9 to 7.4 days over the study period, mostly a result of reductions in surgical hospital stays. We conclude that reimbursement for medical and pediatric discharges under DRG 179 appear adequate for this hospital, while surgical inflammatory bowel disease reimbursement is not. These data will be useful for comparison of future trends of inpatient utilization for inflammatory bowel disease patients as prospective reimbursement practices become more widespread.


Antibiotic therapy of the newborn.
The bacteria infecting newborn babies have changed over the last few decades and vary from place to place. Each neonatal unit must therefore make its own choice of antibiotics to attack the local pathogens. This choice must be reconsidered regularly because of the continuing change in pathogens, such as the recent problems encountered with Staphylococcus epidermidis. The newer beta-lactam antibiotics, especially the third-generation cephalosporins, are proving useful in the treatment of neonatal infections.


Rectal tear causing prolapsed ileum after closed abdominal injury.
A case of prolapsed ileum through a tear in the rectal wall, passing through a tear in the rectal wall, passing through the anal canal, after a blunt injury to the abdomen in a child is presented. The cause and management of the condition are discussed.


A unified mitochondria mechanistic target of rapamycin acyl-coenzyme A dehydrogenase 10 signal relay modulation for metformin growth inhibition in human immortalized keratinocytes cells.
Metformin exhibits antiproliferative and proapoptotic effects in a variety of diseases, characterized by malignant and nonmalignant hyperplastic cells; however, the underlying molecular mechanism of metformin in psoriasis has not been elucidated. In the current study, we found that after metformin treatment the proliferation of human immortalized keratinocytes (HaCaT) was significantly inhibited, while cell apoptosis was increased in a dose-dependent manner, accompanied with enhanced protein expression of acyl-coenzyme A dehydrogenase 10 (ACAD10). Furthermore, mechanism analysis revealed that ACAD10 expression is induced by downregulated activities of mechanistic target of rapamycin 1 (mTORC1) signaling rather than AMP-activated protein kinase signaling. The inactivation of mTORC1 by rapamycin pretreatment or rotenone-induced mitochondrial complex inhibition showed a similar effect because of the metformin treatment on the proliferation and apoptosis of HaCaT keratinocytes. Overexpression of mTORC1 almost reversed the antiproliferation and proapoptosis effects induced by metformin. This study showed that the metformin treatment inhibited HaCaT cells proliferation and promoted apoptosis by affecting the mitochondrial-mTORC1 signaling and elevated the ACAD10 expression. Hence, metformin can be used as a potential therapeutic agent for psoriasis.


Preoperative staging of non-small cell lung cancer: transesophageal US-guided fine-needle aspiration biopsy of mediastinal lymph nodes.
To evaluate the usefulness of transesophageal real-time ultrasound (US)-guided fine-needle aspiration biopsy (FNAB) in staging non-small cell lung carcinoma. Two patients (a 64-year-old man and a 48-year-old woman) with non-small cell lung carcinoma and mediastinal lymphadenopathy detected at computed tomography underwent preoperative evaluation with transesophageal real-time US-guided FNAB. Two aspirates were obtained from each patient. Diagnostic tissue from a contralateral posterior mediastinal lymph node was obtained from the first aspirate in each case. Neither patient experienced a complication as a result of this technique, and both were subsequently referred for palliative therapy in light of these findings. Real-time US-guided FNAB is useful in the preoperative staging of disease in selected patients with non-small cell lung cancer.


[A primary clinical analysis of artificial bone implantation of cleft palate].
To observe whether repairing the hard palate can improve velopharyngeal function. 40 patients with hard palate cleft were randomly divided into two groups: the control group and the implantation group. Each group had 20 patients. The patients in the implantation group were implanted with compound artificial bone of HA--Bone cement. All patients hag been followed up for three months postoperatively. The patients in the repaired group were examined using computer tomography. All patients were examined using NPF. The implanted artificial bone had no rejection. The computer tomography showed that the implanted artificial bone in hard palate had no shifting, subsidence or breakage. The movement of soft palate of the implantation group was greater than the control group. The velopharyngeal function of the implantation group was much better than the control group. Repairing the hard palate cleft with artificial bone can improve velopharyngeal function.


Leishmania donovani infection induce Extracellular signal-regulated kinase ½ (ERK½) mediated lipid droplet generation in macrophages.
Recently unfolded mechanisms showed lipid droplet helps in pathogen survival and paralyzes host immune response. In the present study, we showed the extent of lipid droplet(LD) generation in Leishmania donovani infection, the signaling involved, and their function concerning pathogenicity. RAW 264.7 and J774A.1 cells were used to infect with L. donovani and then flow cytometry and confocal microscopy were used to detect lipid droplet generation and subsequent assays. In this study, we showed that L. donovani AG83 (AG83/MHOM/1983) triggers lipid droplet formation in macrophages in a time-dependent manner. We provide novel insight into the signaling molecules which is responsible for LD accumulation. Interestingly, LPG deficient attenuated Leishmania strain UR6 (UR6/MHOM/1978) failed to fuel LD generation. But inhibition of phagosome maturation drastically stimulates LD accumulation in UR6 infected MΦs. Aspirin treatment in AG83 infected MΦs does not only lower LD load but also favors phagolysosome biogenesis and corrects cytokine balance. Employing strategies to circumvent halt in phagosome maturation using drugs that manipulate lipid droplet generation could be used as a therapeutic tool to resist parasite growth in the early hour of infection.


Pathway-based meta-analysis for partially paired transcriptomics analysis.
Pathway-based differential expression analysis allows the incorporation of biological domain knowledge into transcriptomics analysis to enhance our understanding of disease mechanisms. To integrate information among multiple studies at the pathway level, pathway-based meta-analysis can be performed. Paired or partially paired samples are common in biomedical research. However, there are currently no existing pathway-based meta-analysis methods appropriate for paired or partially paired study designs. In this study, we developed a pathway-based meta-analysis approach for paired or partially paired samples. Meta-analysis on the transcriptomics profiles were conducted using p-value-based, rank-based, and effect size-based algorithms. The application of our approach was demonstrated using partially paired data from psoriasis transcriptomics studies. Upon combining six transcriptomics studies, genes related to the cell cycle and DNA replication pathways are found to be highly perturbed in psoriatic lesional skin samples. Results were validated externally with independent RNA-Seq data. Comparison with existing pathway meta-analysis methods revealed consistent results, with our method showing higher detection power. This study demonstrated the utility of our newly developed pathway-based meta-analysis that allows the incorporation of partially paired or paired samples. The proposed framework can be applied to omics data including but not limited to transcriptomics data.


Diagnosis of hemochromatosis.
If untreated, hemochromatosis can cause serious illness and early death, but the disease is still substantially under-diagnosed. The cornerstone of screening and case detection is the measurement of serum transferrin saturation and the serum ferritin level. Once the diagnosis is suspected, physicians must use serum ferritin levels and hepatic iron stores on liver biopsy specimens to assess patients for the presence of iron overload. Liver biopsy is also used to establish the presence or absence of cirrhosis, which can affect prognosis and management. A DNA-based test for the HFE gene is commercially available, but its place in the diagnosis of hemochromatosis is still being evaluated. Currently, the most useful role for this test is in the detection of hemochromatosis in the family members of patients with a proven case of the disease. It is crucial to diagnose hemochromatosis before hepatic cirrhosis develops because phlebotomy therapy can avert serious chronic disease and can even lead to normal life expectancy.


Effects of Red Blood Cell Transfusion on Long-Term Disability of Patients with Traumatic Brain Injury.
This 3-year prospective study examined the association between red blood cell transfusion (RBCT) and 1-year neurocognitive and disability levels in 309 patients with traumatic brain injury (TBI) admitted to the neurological intensive care unit (NICU). Using a telephone interview-based survey, functional outcomes were assessed by the Glasgow Outcome Scale (GOS), Rancho Los Amigos Levels of Cognitive Functioning Scale (RLCFS), and Disability Rating Scale (DRS) and dichotomized as favorable and unfavorable (dependent variable). The adjusted influence of RBCT on unfavorable results was assessed by conventional logistic regression, controlling for illness severity and propensity score (introduced as a continuous variable and by propensity score-matched patients). Overall, 164 (53 %) patients received ≥1 unit of RBCT during their NICU stay. One year postinjury, transfused patients exhibited significantly higher unfavorable GOS (46.0 vs. 22.0 %), RLCFS (37.4 vs. 15.4 %), and DRS (39.6 vs. 18.7 %) scores than nontransfused patients. Although transfused patients were more severely ill upon admission, their adjusted odds ratios (95 % confidence intervals) for unfavorable GOS, RLCFS, and DRS scores were 2.5 (1.2-5.1), 3.0 (1.4-6.3), and 2.3 (1.1-4.8), respectively. These odds ratios remained largely unmodified when the calculated propensity score was incorporated as an independent continuous variable into the multivariate analysis. Furthermore, in 76 pairs of propensity score-matched patients, the rate of an unfavorable RLCFS score at the 1-year (but not 6-month) follow-up was significantly higher in transfused than nontransfused patients [3.0 (1.1-8.2)]. Our results strongly suggest an independent association between RBCT and unfavorable long-term functional outcomes of patients with TBI.


Specificity of passive serum protection against Nippostrongylus brasiliensis and Nematospiroides dubius in mice.
Fewer and smaller worms were recovered from, and significantly fewer parasite eggs were voided by, mice injected with mouse antiserum raised against Nippostrongylus brasiliensis or Nematospiroides dubius after infection with the homologous nematode species compared with the control mice. The passive transfer of protective immunity was specific for the species which induced the antibody response in the donor mice. Passively immunized mice infected with the heterologous nematode species harboured the same number of worms, with the same epg output, as parasites in the control mice, but were stunted. Serological cross-reactions were observed between the two donor antiserum pools and N. dubius and N. brasiliensis antigens.


Flexible Superhydrophobic and Superoleophilic MoS2 Sponge for Highly Efficient Oil-Water Separation.
Removal of oils and organic solvents from water is an important global challenge for energy conservation and environmental protection. Advanced sorbent materials with excellent sorption capacity need to be developed. Here we report on a superhydrophobic and superoleophilic MoS2 nanosheet sponge (SMS) for highly efficient separation and absorption of oils or organic solvents from water. This novel sponge exhibits excellent absorption performance through a combination of superhydrophobicity, high porosity, robust stability in harsh conditions (including flame retardance and inertness to corrosive and different temperature environments) and excellent mechanical properties. The dip-coating strategy proposed for the fabrication of the SMS, which does not require a complicated process or sophisticated equipment, is very straightforward and easy to scale up. This finding shows promise for water remediation and oil recovery.


[Transplantation and explantation from a psychosomatic perspective].
At first glance, transplantation medicine and psychosomatic medicine seem little related. This survey points out the possible contributions of psychosomatics to transplantation medicine. Special attention is given to organ donors, who in articles on transplantation medicine hardly receive the consideration they deserve.


Dopamine D2 receptor signaling dynamics of dopamine D2-neurotensin 1 receptor heteromers.
Biochemical, histochemical and coimmunoprecipitation experiments have indicated the existence of antagonistic dopamine D2 (D2R) and neurotensin 1 (NTS1R) receptor-receptor interactions in the dorsal and ventral striatum indicating a potential role of these receptor-receptor interactions in Parkinson's disease and schizophrenia. By means of Bioluminiscence Resonance energy transfer (BRET(2)) evidence has for the first time been obtained in the current study for the existence of both D2LR/NTS1R and D2SR/NTS1R heteromers in living HEK293T cells. Through confocal laser microscopy the NTS1R(GFP2) and D2R(YFP) were also shown to be colocated in the plasma membrane of these cells. A bioinformatic analysis suggests the existence of a basic set of three homology protriplets (TVM, DLL and/or LRA) in the two participating receptors which may contribute to the formation of the D2R/NTS1R heteromers by participating in guide-clasp interactions in the receptor interface. The CREB reporter gene assay indicated that the neurotensin receptor agonist JMV 449 markedly reduced the potency of the D2R like agonist quinpirole to inhibit the forskolin induced increase of the CREB signal. In contrast, the neurotensin agonist was found to markedly increase the quinpirole potency to activate the MAPK pathway as also studied with luciferase reporter gene assay measuring the degree of SRE activity as well as with ERK1/2 phosphorylation assays. These dynamic changes in D2R signaling produced by the neurotensin receptor agonist may involve antagonistic allosteric receptor-receptor interactions in the D2LR-NTS1R heteromers at the plasma membrane level (CREB pathway) and synergistic interactions in PKC activation at the cytoplasmatic level (MAPK pathway).


Pronator teres is an appropriate donor muscle for restoration of wrist and thumb extension.
To compare the detailed architectural properties of the pronator teres (PT), extensor carpi radialis brevis (ECRB), and extensor pollicis longus (EPL) muscles to evaluate the suitability of PT-to-ECRB and PT-to-EPL surgical procedures. Muscle physiologic cross-sectional areas and region-specific muscle fiber lengths were measured in cadaveric PT, ECRB, and EPL muscles (n = 10 muscles of each type). One-way repeated-analyses of variance measures and post hoc t tests with Bonferroni corrections were used for statistical comparisons. The ulnar head of the PT was present in 8 of 10 specimens. The average PT fiber length was similar to that of the ECRB (7.02 +/- 0.49 cm vs 6.17 +/- 0.27 cm) but was significantly longer than that of the EPL (5.44 +/- 0.25 mm). Fiber length in the humeral head of the PT was longer compared with the ulnar head (7.19 +/- 0.52 cm vs 4.14 +/- 0.25 cm). The average physiologic cross-sectional area of the PT was similar to that of the ECRB (3.5 +/- 0.4 cm2 vs 3.3 +/- 0.3 cm2) but was significantly larger than that of the EPL (3.5 +/- 0.4 cm2 vs 1.1 +/- 0.1 cm2). From an architectural point of view the PT is an excellent donor choice for transfer to the ECRB for restoration of wrist extension or to the EPL for restoration of thumb extension. Because there is fiber length heterogeneity within the PT, however, when the ulnar head is present it may limit the total excursion of the donor muscle. These data suggest that releasing the ulnar head of the PT before transfer may result in larger excursions of this important motor in tendon transfer surgery.


Diagnostic value of platelet indices in infected nonunion: a retrospective study.
The diagnostic value of platelet indices has been evaluated in various infectious diseases but not in infected nonunion. The purpose of this study was to assess the usefulness of platelet indices for diagnosis of infected nonunion after open reduction and internal fixation. This retrospective study was performed in patients who underwent primary fracture nonunion revision surgeries from January 2016 to December 2021. A total of 297 patients were included in the study: 96 with infected nonunion (group A) and 201 with aseptic nonunion (group B). Receiver operator characteristic (ROC) curve analysis was performed to evaluate diagnostic value of each index. Area under the curve (AUC), sensitivity, specificity, and positive and negative predictive values were calculated and compared. Demographic characteristics were comparable between the two groups. White blood cell (WBC) count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), plasma fibrinogen, plasma D-dimer, platelet count (PC), plateletcrit, and ratio of platelet count to mean platelet volume (PC/MPV) were significantly higher, and MPV and platelet distribution width (PDW) significantly lower, in group A than in group B (P < 0.05). ROC analysis showed PC/MPV and plasma fibrinogen to have better diagnostic value than the other coagulation indicators (AUC of 0.801 and 0.807, respectively). The combination of ESR, plasma fibrinogen, and PC/MPV had good sensitivity and specificity for diagnosis of infected nonunion. PC/MPV had better diagnostic value than ESR and plasma fibrinogen in the subgroup of patients with coagulation-related comorbidities. Plasma fibrinogen and PC/MPV ratio might be useful parameters for early diagnosis of infected nonunion.


The dopamine D(3) receptor Ser9Gly polymorphism modulates prepulse inhibition of the acoustic startle reflex.
The dopamine D(3) receptor (DRD(3)) is suspected to modulate prepulse inhibition (PPI) in animals and humans, but definite conclusions cannot be drawn due to lack of selective DRD(3) ligands. The Ser9Gly polymorphism is a common variant of the DRD(3) gene and determines the gain of function of the D(3) receptor. This is the first study to examine the influence of the DRD(3) Ser9Gly polymorphism on human PPI. Prepulse inhibition was measured in 101 healthy male subjects presented with 75-dB and 85-dB prepulses at 30-, 60-, and 120-msec prepulse-pulse intervals. Subjects were grouped according to their DRD(3) status into a Gly/Gly, a Ser/Gly, and a Ser/Ser group. Analyses of variance showed that at all prepulse and interval conditions, Gly/Gly individuals had the lowest PPI and the greatest onset latency facilitation and Ser/Ser individuals had the highest PPI and the lowest onset latency facilitation, while Ser/Gly individuals were intermediate. These results suggest that PPI is modulated by the D(3) receptor and its levels depend on the Ser9Gly polymorphism.


Suprachoroidal hemorrhage: outcome of surgical management according to hemorrhage severity.
To report the visual and anatomic outcome after surgical drainage of suprachoroidal hemorrhage according to hemorrhage severity. A retrospective chart review. Forty-eight consecutive eyes undergoing surgical drainage of a suprachoroidal hemorrhage at The Medical College of Wisconsin were examined. Demographic and clinical data were abstracted from patients' medical records. Eyes were classified into four categories of increasing hemorrhage complexity: (1) nonappositional choroidal hemorrhage without vitreous or retinal incarceration in the wound (12 eyes); (2) centrally appositional choroidal hemorrhage without vitreous or retinal incarceration in the wound (17 eyes); (3) choroidal hemorrhage with associated vitreous incarceration in the wound (11 eyes); and (4) choroidal hemorrhage with associated retinal incarceration in the wound (8 eyes). Visual acuity, rate of persistent hypotony, and incidence of irreparable retinal detachment after surgical drainage for four classes of suprachoroidal hemorrhage were defined. Overall, 11 (23%) of 48 eyes had no light perception (NLP) vision develop, 9 (19%) of 48 eyes had persistent postsurgical hypotony (intraocular pressure < 6), and 21 (64%) of 33 eyes with retinal detachment enjoyed successful retinal reattachment surgery. A definite trend toward an increased rate of NLP vision (P < 0.02), persistent hypotony (P < 0.05), and irreparable retinal detachment (P = 0.11) was observed with increasing suprachoroidal hemorrhage complexity. Eyes with retinal incarceration, compared to eyes without retinal incarceration, had an increased rate of NLP vision (63% vs. 15%; P < 0.01), persistent postsurgical hypotony (50% vs. 13%; P < 0.05), and irreparable retinal detachment (50% vs. 20%; P = 0.07). Eyes requiring surgical drainage of a suprachoroidal hemorrhage have a guarded prognosis, with a poorer outcome associated with increasing hemorrhage complexity. A classification system incorporating choroidal apposition, and vitreous and retinal incarceration in the wound, provides a format for reporting and assessing the efficacy of management strategies in this condition.


Programmed Ribosomal Frameshifting Mediates Expression of the α-Carboxysome.
Many bacteria employ a protein organelle, the carboxysome, to catalyze carbon dioxide fixation in the Calvin Cycle. Only 10 genes from Halothiobacillus neapolitanus are sufficient for heterologous expression of carboxysomes in Escherichia coli, opening the door to detailed mechanistic analysis of the assembly process of this complex (more than 200MDa). One of these genes, csoS2, has been implicated in assembly but ascribing a molecular function is confounded by the observation that the single csoS2 gene yields expression of two gene products and both display an apparent molecular weight incongruent with the predicted amino acid sequence. Here, we elucidate the co-translational mechanism responsible for the expression of the two protein isoforms. Specifically, csoS2 was found to possess -1 frameshifting elements that lead to the production of the full-length protein, CsoS2B, and a truncated protein, CsoS2A, which possesses a C-terminus translated from the alternate frame. The frameshifting elements comprise both a ribosomal slippery sequence and a 3' secondary structure, and ablation of either sequence is sufficient to eliminate the slip. Using these mutants, we investigated the individual roles of CsoS2B and CsoS2A on carboxysome formation. In this in vivo formation assay, cells expressing only the CsoS2B isoform were capable of producing intact carboxysomes, while those with only CsoS2A were not. Thus, we have answered a long-standing question about the nature of CsoS2 in this model microcompartment and demonstrate that CsoS2B is functionally distinct from CsoS2A in the assembly of α-carboxysomes.


Functional comparison of recombinant interleukin 2 (IL-2) with IL-2-containing preparations derived from cultured cells.
Due to its purity and potential availability in large amounts, human recombinant interleukin 2 (IL-2) expressed in Escherichia coli is an important source of IL-2 for experimentation and possible therapy. To date, very few comparisons between the activity of recombinant IL-2 and conventional cell-derived preparations of IL-2 have been made. This is particularly important since the use of recombinant IL-2 may have some specific limitations. For example, recombinant IL-2 is not post-translationally modified as are cell-derived preparations. Lack of modifications such as glycosylation of threonine 3 may alter efficacy or stability. Comparative studies are necessary to demonstrate the efficacy, species specificity, and stability of recombinant IL-2. By comparing IL-2 activity of recombinant IL-2 to that of cell-derived IL-2, we have demonstrated that each of the preparations are equally active in several murine and human IL-2 proliferation assays and that IL-2 is the active moiety in these assays. In contrast to previous reports, we also show that recombinant IL-2 is sufficient to establish and maintain long-term cell lines. Additionally, by using "synthetic" recombinant IL-2 of defined protein sequence, we have demonstrated that this amino acid-defined structure is indeed responsible for the functions attributed to IL-2.


Parental exposure to waterborne selenite induces transgenerational development toxicity in zebrafish offspring.
Excessive selenium (Se), especially selenite form exerts great toxicity to fish. Most studies have attached considerable attention to the adverse effects of Se on parental fish. However, the transgenerational toxicity of Se on fish has been rarely reported. In the present study, zebrafish embryos were exposed to environmentally relevant concentrations of Na₂SeO₃ (0, 12.5, 25, 50, and 100 μg/L) for 120 days. And the exposed zebrafish (F0) were allowed to spawn with normal zebrafish after sexual maturity. Subsequently, the offspring (F1) were cultured in clean water for 5 days. In the F0 generation, exposure to 100 μg/L Na₂SeO₃ significantly increased the Se content in the tissues (liver, brain and gonad) and decreased the body length and weight. After parental exposure to 100 μg/L Na₂SeO₃, the increased mortality, elevated malformation rate and reduced body length were measured in F1 zebrafish. The Se content was only significantly increased in F1 larvae derived from exposed females in the 100 μg/L exposure group. The contents of thyroid hormones (THs), growth hormone (GH) and insulin-like growth factor (IGF) significantly decreased in F0 and F1 zebrafish. The transcriptional levels of genes along the hypothalamic-pituitary-thyroid (HPT) axis and growth hormone/insulin-like growth factor (GH/IGF) axis were detected to further explore the possible mechanisms of Se-induced thyroid and growth hormone disruption. The results suggest that the toxicity of Se in zebrafish can be markedly transmitted to offspring. And the transgenerational development toxicity might be different due to the differences in gender of exposed parents.


Aging in Africa: a critical review.
My goal in this article is to analyze gerontological discourses in Africa using articles in this collection as a spring board. The broad intention is to explore the possible areas of intersection between research in African aging and other social science disciplines such as history, politics and linguistics as a way of demonstrating how gerontology may contribute to scholarship in other disciplines.


Ocular changes during pregnancy.
To summarize available literature on physiologic and pathologic ocular changes during pregnancy. Narrative review of literature. Ocular changes occur commonly during pregnancy. Although most of these are benign physiologic responses to the metabolic, hormonal, and immunologic modifications to adopt the gestational product, there is some serious pathology that may develop, exacerbate, or even resolve over the course of pregnancy which requires prompt diagnosis and management. The pathological eye conditions can be classified into preexisting pathologies and emerging ocular diseases. Regardless of the different mechanisms by which these ocular changes occur, the key point is the establishment of an effective perinatal screening program to monitor the new development or successive progression of these ocular abnormalities. Irrespective of the visual health status of the pregnant women, regular perinatal eye examination should be scheduled in order to assure continuous surveillance of healthy eyes. Treatment of pathologic ocular conditions or functionally disturbing benign changes relies on an appropriate patient selection. Discriminating pathological eye disease from physiologic ocular changes is important in order to establish an individualized treatment or preventive plan and constitutes the mainstay of obstetric ophthalmology. This individualized approach should always weigh the ocular benefits of treatment to the mother against the potential harms to the fetus.


Protease Inhibition: Design, Technology & Opportunities--First RSC/SCI Symposium on Protease Inhibition.18-19 May 1998, London, UK.
This symposium, organized jointly by the Royal Society of Chemistry and the Society of Chemical Industry, aimed to distil current knowledge on the classification, structure and mechanism of proteolytic enzymes whilst focusing on the approaches and methodology being used to identify potent and selective inhibitors. A wide range of therapeutic targets covering all proteinase classes was presented to a largely medicinal chemical audience of around 130 participants from the UK and mainland Europe. There were no poster sessions.


Postoperative pyothorax a risk factor for acute exacerbation of idiopathic interstitial pneumonia following lung cancer resection.
Acute exacerbation (AE) of idiopathic interstitial pneumonia (IP) is a potentially fatal postoperative complication following lung cancer resection. Postoperative pyothorax (PP) following development of a bronchopleural fistula (BPF) after lung surgery induces continuous inflammation and may affect the occurrence of AE. We investigated the relationship between AE and PP in patients who underwent pulmonary resection for lung cancer. A total of 941 patients who underwent lung resection due to primary lung cancer from 2006 to 2015 at our hospital were investigated. Of the 941 enrolled patients, 137 (14.6 %) had idiopathic IP and were predominantly male (p < 0.01). Pathological stage Ia and adenocarcinoma were observed at significantly high rates in the non-IP group (p < 0.01). Patients with IP showed a tendency for a higher percentage of PP (p = 0.054). Of the 137 patients with IP, 17 (12.4 %) showed postoperative AE. Furthermore, PP was observed in three cases in the AE(+) group and two in the AE(-) group. PP had a correlation with a significantly higher incidence of AE (p = 0.007). PP was found to be a significant risk factor for postoperative AE in lung cancer patients undergoing a pulmonary resection. Since IP itself is likely a risk factor for PP, prevention of BPF is important for patients with IP, as it can lead to PP.


Adsorption of folic acid molecule on diphenylalanine peptide nanohole as a drug delivery in cancer treatment: a molecular dynamics simulation study.
Using the molecular dynamics simulation method, the adsorption of folic acid as a drug with diphenylalanine peptide nanohole as an efficient nanodrug delivery system was investigated computationally. It focuses on the structural properties, drug loading capacity in the carrier, intermolecular interactions, and drug encapsulation behaviors. The results show that the average number of hydrogen bonds between diphenylalanine and folic acid will increase when the system reaches equilibrium. In addition, by increasing the weight concentration of folic acid from 0.3 to 0.9%, the number of hydrogen bond between them increases about 18%. In other words, hydrogen bonding can play an effective role in the binding of folic acid to the drug carrier. The results of the radial distribution function of water molecules around the carrier mass center show that its effective radius is around 1.2 nm (or 12 Å), which is in a good agreement with the results obtained from the hydrodynamic radius. The initial structures were optimized in Amber molecular mechanics using Gaussian 09 software in aqueous medium in DFT/B3LYP/6-31 g(d). The molecular structure of folic acid was obtained from the PubChem database. The initial parameters are embedded in AmberTools. To calculate partial charges, restrained electrostatic potential (RESP) method was used. Gromacs 2021 software, modified water model (SPC/E), and Amber 03 force field have been used in all simulations. VMD software was used to view simulation photos.


Aromatase modulation alters gonadal differentiation in developing zebrafish (Danio rerio).
This study investigated whether gonadal sex differentiation of zebrafish (Danio rerio) is susceptible to compounds that interfere with cytochrome P450 aromatase (P450arom). Treatment of zebrafish during the period of gonadal differentiation with either the non-steroidal aromatase inhibitor fadrozole or 17alpha-methyltestosterone (MT) changed gonad morphological differentiation and altered the pattern of P450arom gene (CYP19) expression. Application of fadrozole (500 microg/g of food) between days 35 and 71 post-fertilisation (pf) resulted in 100% masculinisation, i.e. the gonads of all individuals examined ( n = 40) showed testicular morphology. At the same time, fadrozole treatment suppressed gonadal CYP19A (gonad-derived CYP19 gene) mRNA expression, as assessed by means of semi-quantitative RT-PCR. After termination of fadrozole treatment at day 71 pf and subsequent rearing of zebrafish under control conditions until 161 days pf, the gonads of all individuals still displayed testicular morphology. Gonadal CYP19A expression, however, showed a dimorphic pattern, with 14 out of 22 individuals having low CYP19A mRNA levels similar to those found in testes of control fish, while eight fish showed high, ovary-like levels of gonadal CYP19A mRNA. MT treatment (10 microg/l) during the period of gonadal differentiation (days 35 to 71 pf) resulted in phenological feminisation, i.e., all fish examined (n = 28) showed an ovarian gonadal morphology. While gonadal CYP19A expression was suppressed compared to control fish, cerebral CYP19B (brain-derived CYP19 gene) mRNA expression was increased in 71-day-old MT-treated fish. The results from this study provide evidence that exogenous compounds interfering with the P450arom system are able to disrupt, even persistently, gonadal sex differentiation of the protogynic zebrafish.


Secondhand smoke exposure among never-smoking adolescents in Wuhan, China.
Without smoke-free legislation in Wuhan, China, we investigated secondhand smoke (SHS) exposure at home, school, and public places for never-smoking school-going adolescents in 2019. A cross-sectional study was carried out within the Global Youth Tobacco Survey (GYTS) framework. Weighted univariate, bivariate and multivariable analyses were conducted. The prevalence of SHS exposure among never-smoking adolescents at home, school and public places was 25.7%, 31.9% and 48.9%, respectively. Multivariable logistic regression analysis showed that parents smoking, peers smoking and observing teachers smoking in school were all significantly related to a higher probability of SHS exposure at home, school, and public places. Never-smoking adolescents who had smoking parents had 14 times (adjusted odds ratio [aOR], 14.00; 95% confidence interval [CI], 11.37-17.24) higher odds of SHS exposure at home; Never-smoking adolescents who observed teachers smoking in school had about 10 (aOR = 9.76; 95% CI = 7.13-13.36) and four times (aOR = 3.55; 95% CI = 2.77-4.55) higher odds of SHS exposure in school and public places, respectively. Adopting comprehensive smoke-free legislation in public places and smoke-free home rules and implementing and supervising smoke-free school policies may further reduce SHS exposure among adolescents.


Know your risks, help mitigate them.
With multimillion dollar penalties threatening health organizations, risk management policies are scaling the list of daily priorities.


The impact of low mineral content water on cardiac function in diabetic rats: focus on oxidative stress.
The aim of this study was to estimate the effects of natural low mineral water from the source "Sneznik-1/79" in Serbia on glycemia as well as heart function in rats with diabetes mellitus type 2 (T2DM), with the special emphasis on the role of the oxidative stress. Twenty Wistar albino rats (males, 4 weeks old at the beginning of the study, body weight 180 ± 20 g) were included in the study. Rats were divided randomly into 2 groups (10 animals per group): T2DM: rats with diabetes mellitus type 2 with free access to tap water; T2DM + SW: rats with diabetes mellitus type with free access to natural mineral water from "Sneznik-1/79". Glucose level, ex vivo cardiac function as well as systemic and cardiac redox state were assessed. At the end of the study protocol, glucose level was lower in diabetic rats who consumed mineral water. Moreover cardiac function wasn't affected by mineral water intake, however, significant antioxidant effects were observed. Our study suggests that 4-week consumption of low mineral water from the spring "Sneznik-1/79" has important role in regulation of glycemia and altering redox state in favor of elevated antioxidant capacity without affecting heart function. Based on our findings we may assume that low mineral water from the spring "Sneznik-1/79" has the potential to be used either as preventive strategy or as additional therapeutic strategy in management of T2DM.


Simulation-based investigation of partially parallel imaging with a linear array at high accelerations.
Partially parallel imaging strategies such as SMASH, SENSE, and PILS rely on the sensitivity distribution of phased array RF coils to reduce MRI imaging time. Using an N-element phased array, these techniques allow maximum accelerations, L, such that L < or = N, with acceleration defined as the factor by which scan time is reduced in comparison to traditional, fully gradient encoded acquisitions. As N increases in modern MRI facilities or using special hardware extensions, its role as the primary limitation in partially parallel imaging will be reduced and other limiting factors will become dominant. Two such factors include available SNR and the variation of sensitivity distributions with imaging depth. Simulations have been conducted to evaluate the impact of slice depth and noise on partially parallel reconstructions for the case of a square linear array of overlapped elements that are parallel to the imaging plane. Results indicate that even when sensitivity distributions are exactly known, the linear surface array can only provide high accelerations over a limited imaging depth due to changing suitability of the sensitivity distributions for partially parallel reconstruction. This work emphasizes the importance of simulations for target-based partially parallel array design.


Clonal tracking of haematopoietic cells: insights and clinical implications.
Recent advances in high-throughput genomics have enabled the direct tracking of outputs from many cell types, greatly accelerating the study of developmental processes and tissue regeneration. The capacity for long-term self-renewal with multilineage differentiation potential characterises the cellular dynamics of a special set of developmental states that are critical for maintaining homeostasis. In haematopoiesis, the archetypal model for development, lineage-tracing experiments have elucidated the roles of haematopoietic stem cells to ongoing blood production and the importance of long-lived immune cells to immunological memory. An understanding of the biology and clonal dynamics of these cellular fates and states can provide clues to the response of haematopoiesis to ageing, the process of malignant transformation, and are key to designing more efficacious and durable clinical gene and cellular therapies.


spa Types and Staphylococcal Enterotoxin Production of Staphylococcus aureus Isolated from Wild Boar.
Little is known about the structure of S. aureus population and the enterotoxin gene content in wild boar. In 1025 nasal swabs from wild boars, 121 S. aureus isolates were identified. Staphylococcal enterotoxin (SE) genes were identified in 18 isolates (14.9%). The seb gene was found in 2 S. aureus isolates, sec in 2 isolates, the see and seh genes were found in 4 and 11 isolates, respectively. The production of SEs was evaluated in bacteria grown in microbial broth. Concentration of SEB reached 2.70 µg/ml after 24 h and 4.46 µg/ml at 48 h. SEC was produced at 952.6 ng/ml after 24 h and 7.2 µg/ml at 48 h. SEE reached 124.1 ng/ml after 24 h and 191.6 ng/ml at 48 h of culture. SEH production reached 4.36 µg/ml at 24 h and 5.42 µg/ml at 48 h of culture. Thirty-nine spa types were identified among S. aureus isolates. The most prevalent spa types were t091 and t1181, followed by t4735 and t742, t3380 and t127. Twelve new spa types, i.e., t20572‒t20583 were identified. The wild boar S. aureus population was shown to contain previously identified animal/human-associated spa types and spa types not identified in humans or animals. We also indicate that wildlife animals can be a significant reservoir of see-positive S. aureus.


Differential deficits in spatial and temporal interlimb coordination during walking in persons with incomplete spinal cord injury.
Returning to community walking remains a major challenge for persons with incomplete spinal cord injury (iSCI) due, in part, to impaired interlimb coordination. Here, we examined spatial and temporal features of interlimb coordination during walking and their associations to gait deficits in persons with chronic iSCI. Do deficits in spatial and temporal interlimb coordination correspond differentially to clinical indicators of walking performance in persons with iSCI? Sixteen persons with chronic iSCI and eleven able-bodied individuals participated in this study. Participants walked at self-selected gait speeds along an instrumented walkway that recorded left and right step lengths and times. We quantified interlimb coordination in terms of normalized differences between left and right step lengths (spatial asymmetry index) and step times (temporal asymmetry index), as well as, gap and phase coordination indices. We then assessed the extent to which these indices independently associated with clinical measures of walking performance. Participants with iSCI demonstrated greater spatial and temporal asymmetry, as well as, reduced gap and phase interlimb coordination as compared to age-matched controls (p < 0.001). We found no linear relationships between spatial and temporal asymmetry indices (p > 0.05) or between gap and phase coordination indices (p > 0.05). Spatial and temporal asymmetry indices weakly correlated with SCI-FAI composite scores (r2 = 0.26; p = 0.04). However, only spatial asymmetry indices strongly correlated with slower walking speed (r2 = 0.51; p < 0.002). We also found participants who used a hand-held assistive device (walker) demonstrated great spatial asymmetry as compared to those who did not (p < 0.03). Differential impairments in spatial and temporal interlimb coordination correspond to overground walking deficits in persons with chronic iSCI. Spatial asymmetry associated with decreased walking speed and increased reliance on hand-held assistive devices. Gait training methods that target well-defined space and time domains of interlimb coordination may enhance overground gait training in persons with iSCI.


Access to primary healthcare services and associated factors in urban slums in Nairobi-Kenya.
Access to primary healthcare is crucial for the delivery of Kenya's universal health coverage policy. However, disparities in healthcare have proved to be the biggest challenge for implementing primary care in poor-urban resource settings. In this study, we assessed the level of access to primary healthcare services and associated factors in urban slums in Nairobi-Kenya. The data were drawn from the Lown scholars' study of 300 randomly selected households in Viwandani slums (Nairobi, Kenya), between June and July 2018. Access to primary care was measured using Penchansky and Thomas' model. Access index was constructed using principal component analysis and recorded into tertiles with categories labeled as poor, moderate, and highest. Generalized ordinal logistic regression analysis was used to determine the factors associated with access to primary care. The adjusted odds ratios (AOR) and 95% confidence intervals were used to interpret the strength of associations. The odds of being in the highest access tertile versus the combined categories of lowest and moderate access tertile were three times higher for males than female-headed households (AOR 3.05 [95% CI 1.47-6.37]; p < .05). Households with an average quarterly out-of-pocket healthcare expenditure of ≥USD 30 had significantly lower odds of being in the highest versus combined categories of lowest and moderate access tertile compared to those spending ≤ USD 5 (AOR 0.36 [95% CI 0.18-0.74]; p < .05). Households that sought primary care from private facilities had significantly higher odds of being in the highest versus combined categories of lowest and moderate access tertiles compared to those who sought care from public facilities (AOR 6.64 [95% CI 3.67-12.01]; p < .001). In Nairobi slums in Kenya, living in a female-headed household, seeking care from a public facility, and paying out-of-pocket for healthcare are significantly associated with low access to primary care. Therefore, the design of the UHC program in this setting should prioritize quality improvement in public health facilities and focus on policies that encourage economic empowerment of female-headed households to improve access to primary healthcare.


Assessment of rapid wastewater surveillance for determination of communicable disease spread in municipalities.
Wastewater surveillance (WS) helps to improve the understanding of the spread of communicable diseases in communities. WS can assist public health decision-makers in the design and implementation of timely mitigation measures. There is an increased need to use reliable, cost-effective, simple, and rapid WS systems, given traditional analytical (or 'gold-standard') programs are instrument/time-intensive, and dependent on highly skilled personnel. This study investigated the application of the portable GeneXpert platform for WS of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A virus (IAV), influenza B virus (IBV), and respiratory syncytial virus (RSV). The GeneXpert system with the Xpert Xpress-SARS-CoV-2/Flu/RSV test kit uses reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to analyze wastewater samples. From September 2022 through January 2023, wastewater samples were collected from the influents of municipal wastewater treatment plants (MWTPs) of Saskatoon, Prince Albert, and North Battleford in the province of Saskatchewan, Canada. Both raw and concentrated wastewater samples were subjected to the GeneXpert analysis. Results showed that the Saskatoon wastewater viral loads were significantly correlated to Saskatchewan's influenza and COVID-19 clinical cases, with a lead time of 10 days for IAV and a lag time of 4 days for SARS-CoV-2. Additionally, the GeneXpert analysis of the three cities' wastewater samples showed that the raw WS could capture the dynamics of SARS-CoV-2 and IAV due to their correlation with concentrated WS. Interestingly, IBV loads were not detected in any wastewater samples, while the Saskatoon and Prince Albert wastewater samples collected following the 2023 holiday season (end of December and beginning of January) were positive for RSV. This study indicates that the GeneXpert has excellent potential for use in the development of an early warning system for transmissible disease in municipalities and limited-resource communities while simultaneously providing stakeholders with an efficient WS methodology.


Rab and rho GTPases are involved in specific response of periodontal ligament fibroblasts to mechanical stretching.
To investigate the contribution of ras-related signalling molecules to the mechanotransduction process, stretch-sensing human periodontal ligament (PDL) fibroblasts were isolated and cultured in dishes with a flexible bottom. The cells were stimulated by stretching the bottom of the dishes and membrane fractions were prepared and analysed at the level of mapping small GTP-binding proteins by high resolution two-dimensional gel electrophoresis followed by renaturing transfer and an [alpha-32P]GTP-overlay procedure. This analysis revealed that mechanically-stretched PDL fibroblasts exhibit complete down-regulation of rhoA and induction of rab6, rab17 and a putative member of the rab3 subfamily in a cell type-specific manner.


High frequency of erythromycin A resistance and distribution of mefE and ermB genes in clinical isolates of Streptococcus pneumoniae in Japan.
The ermB and mefE genes are important in terms of their responsibility for macrolide resistance in Streptococcus pneumoniae. We investigated the distribution of the ermB and mefE genes in erythromycin A-resistant S. pneumoniae isolated in our hospital during the period 1995-1998. All amoxicillin-low-susceptible isolates were considered to be resistant to erythromycin A. All isolates with resistance to erythromycin A (minimum inhibitory concentrations [MICs], > or =0.5 microg/ml) possessed ermB or mefE genes. The MICs of erythromycin A for most mefE-positive isolates ranged from 0.5 to 2 microg/ml. On the other hand, approximately 85% of ermB-positive isolates demonstrated high-level resistance to erythromycin A (MICs, > or =4 microg/ml) while the others showed low-level resistance (MICs, 0.5 to 2 microg/ml). In ermB-positive isolates with low-level resistance, high-level resistant mutants were selected with a frequency of 3.1 x 10(-6)-1.8 x 10(-3) on agar containing 4-32 MIC of erythromycin A, whereas in mefE-positive isolates, no high-level resistant mutants were detected. Mutants from ermB-positive isolates with low-level resistance showed reversibility and heterogeneity. Our data indicated a wide distribution of erythromycin A-resistant isolates with mefE or ermB genes among amoxicillin-low-susceptible S. pneumoniae in Japan. In addition, it is likely that ermB-positive isolates with low-level resistance show heterogeneous high-level resistance.


Correlation between standing height, sitting height, and arm span as an index of pulmonary function in 6-10-year-old children.
The present study evaluates the relationships of pulmonary volumes and flows and the anthropometric variables of standing height, sitting height, and arm span in 100 6-10-year-old children. To be included in the study, all children were required to be healthy and above the 3rd percentile of the curve of Tanner et al. (Arch Dis Child 1966;41:454-471; Arch Dis Child 1966;41:613-635) for height and weight. Standing height, sitting height, and arm span were measured according to standard protocol. The pulmonary function measurements were: tidal volume, minute respiratory volume, respiratory rate, expiratory reserve volume, inspiratory capacity, vital capacity, residual volume (RV), functional residual capacity, total lung capacity (TLC), forced vital capacity (FVC), forced expiratory volume in 1 sec of FVC (FEV(1)), forced expiratory flow measured between 25-75% of FVC, and FEV(1)/FVC and RV/TLC ratios. Simple linear regression best expressed the correlation between pulmonary function and the anthropometric variables. Significant correlations between anthropometric and pulmonary function measurements were observed, with FVC and FEV(1) showing the highest and RV the lowest r(2) values. There was a significant positive correlation between standing height and arm span according to linear regression and Bland-Altman comparison (Bland and Altman, Lancet 1968;8:307-310). Our results suggest that when an accurate determination of standing height cannot be obtained, arm span could be used interchangeably, using the same regression equation. However, for patients with limb deformities, regression equations of pulmonary function measurements in relation to sitting height may be a better choice for estimating pulmonary function.


Sleep and mortality: a population-based 22-year follow-up study.
Long and short sleep have been associated with increased mortality. We assessed mortality and 3 aspects of sleep behavior in a large cohort with 22-year follow-up. Prospective, population-based cohort study. 21,268 twins aged > or =18 years responding to questionnaires administered to the Finnish Twin Cohort in 1975 (response rate 89%), and 1981 (84%). N/A. Subjects were categorized as short (<7 h), average, or long (>8 h) sleepers; sleeping well, fairly well, or fairly poorly/poorly; no, infrequent, or frequent users of hypnotics and/or tranquilizers. Cox proportional hazard models were used to obtain hazard ratios (HR) for mortality during 1982-2003 by sleep variable categories and their combinations. Adjustments were done for 10 sociodemographic and lifestyle covariates known to affect risk of death. Significantly increased risk of mortality was observed both for short sleep in men (+26%) and in women (+21%), and for long sleep (+24% and +17%), respectively, and also frequent use of hypnotics/tranquilizers (+31% in men and +39% in women). Snoring as a covariate did not change the results. The effect of sleep on mortality varied between age groups, with strongest effects in young men. Between 1975 and 1981, sleep length and sleep quality changed in one-third of subjects. In men there was a significant increase for stable short (1.34) and stable long (1.29) sleep for natural deaths, and for external causes in stable short sleepers (1.62). Our results show complicated associations between sleep and mortality, with increased risk in short and long sleep.


Postmortem changes in ancient Egyptian child mummies: Possible pitfalls on CT images.
To identify and interpret computed tomography (CT) findings of postmortem changes in ancient Egyptian child mummies. Whole-body CT examinations of 21 ancient Egyptian child mummies from German (n = 18), Italian (n = 1), and Swiss museums (n = 2). Conspicuous CT findings from prior evaluations with various research questions that were assessed as postmortem changes were classified, and special cases were illustrated and discussed. Postmortem changes were classified into several categories. From these, individuals with evidence of invasion of resin/oil/tar into bone, dried fluid-levels within bone most likely due to natron, probable interaction of natron with soft tissues and bone, as well as insect infestation were demonstrated. One challenge of paleoradiology is to differentiate between intravital and postmortem changes, which can be multifarious. These changes can be obvious, but also subtle, and can mimic diseases. The provided classification of postmortem changes, as well as the demonstrated cases, may serve as models for further paleoradiological investigations. The dried intraosseous fluid levels in two mummies, most likely due to natron, suggests that these children were immersed in a liquid natron bath, in contrast to the current scientific view that natron for mummification was routinely applied in the solid form. CT was used as the only examination method, as sampling of the mummies was not possible. The awareness that postmortem changes on CT images of ancient Egyptian mummies might mimic pathology should be raised to reduce or avoid incorrect interpretation.


Trapping of polycyclic aromatic hydrocarbons in vehicle exhaust using an in-tube extraction device for analysis by gas chromatography-barrier ionization discharge detection.
This work presents a methodology for polycyclic aromatic hydrocarbons (PAHs) trapping from vehicular emissions using an in-tube extraction device (IT-FEx). Trapping selectivity studies were conducted, evaluating the interaction profile between the aromatic compounds and the polymeric phase (composed of polydimethylsiloxane and internal to the IT-FEx devices), as in an aqueous equilibrium system (25 min of sampling), and as in gaseous dynamic phase (30 s of sampling), regarding a qualitative evaluation. The adsorption profiles were similar, with greater affinity for medium-sized PAHs (four aromatic rings) than for the smaller (one to three rings) and larger (five to six rings). The device was attached to a vehicle emission sampler to evaluate the qualitative emission of diesel-powered vehicles. Certain PAHs, such as phenanthrene, fluoranthene, benz[a]anthracene, chrysene, benzo[b]fluoranthene, and benzo[k]fluoranthene, were effectively trapped by the IT-FEx device and detected by the GC-BID analysis. Finally, it was possible to develop a process that combined the steps of sample preparation and instrumental analysis, using the IT-FEx device and applying it to the gaseous matrix in the dynamic phase; until then, little was elucidated regarding the use of this apparatus. This sampling device, combined with analysis by gas chromatography with a barrier ionization discharge detector (GC-BID), is a powerful tool for identifying many compounds from vehicular emissions and does not require solvents in sample preparation.


Health impact of hepatic-venous-occlusive disease in a small town in Ethiopia-Case study from Tahtay koraro district in Tigray region, 2017.
Hepatic venous-occlusive disease is blockage of microscopic veins in the liver causing 20-50% mortality. Ingestion of pyrrolizidine alkaloid plant, radiation therapy, and post-bone-marrow-transplant reactions are the commonest causes. In Ethiopia, a venous-occlusive disease outbreak was identified in 2002 in Tahtay Koraro district, Tigray. Suspected due to ingestion of the toxic pyrrolizidine alkaloid plant Ageratum conyzoids, found throughout the district. We aimed to describe the surveillance data of venous-occlusive disease from September 2006 to August 2016 in Tahtay koraro district, Ethiopia, 2017. We defined a possible Hepatic venous-occlusive disease case as any patient with abdominal pain for at least 2 weeks, abdominal distention, and hepato-splenomegaly during September 2006-August 2016. We reviewed previous district line lists, weekly reports, and clinical records to identify and describe cases. Agricultural interventions were obtained from the agricultural offices of the district. We identified 179 possible cases with 83 deaths with a case-fatality rate of 46.3%. Among cases, 110 (61.5%) were males and 113 (63%) were >15 years. In total, 164 (91.6%) cases were from one village (Kelakil). The pick number of cases of VOD in this village was during 2008/09 which was 1076. The highest incidence (86/100,000) occurred in 2008. During the study period, 2,746 years of potential life were lost due to Hepatic venous-occlusive disease. Mechanical removal of the Ageratum started in 2011. Hepatic venous-occlusive disease was an ongoing problem in Tahtay Koraro; However, the problem has largely been alleviated by displacing people from the affected area and removing the causative weed. More research is needed to understand why Kelakil village was more affected despite the widespread presence of the weed. Chemical and mechanical removal of the Ageratum could strengthen intervention activities.


Use of high-flow nasal cannula oxygen therapy for patients with terminal cancer at the end of life.
Few studies have focused on high-flow nasal cannula (HFNC) usage in the last few weeks of life. The aim of this study was to identify the status of HFNC use in patients with cancer at the end of life and the relevant clinical factors. We performed a retrospective cohort study in a tertiary hospital in the Republic of Korea. Among patients with cancer who died between 2018 and 2020, those who initiated HFNC within 14 days before death were included. Patients were categorized based on the time from HFNC initiation to death as imminent (<4 days) and non-imminent (≥4 days). Among the 2191 deceased patients with terminal cancer, 329 (15.0%) were analyzed. The median age of the patients was 66 years, and 62.9% were male. The leading cause of respiratory failure was pneumonia (70.2%), followed by pleural effusion (30.7%) and aggravation of lung neoplasms (18.8%). Most patients were conscious (79.3%) and had resting dyspnea (76.3%) at HFNC initiation. Patients received HFNC therapy for a mean of 3.4 days in the last 2 weeks of life, and 62.6% initiated it within 4 days before death. Furthermore, female sex, no palliative care consultation, no advance statements in person on life-sustaining treatment, and no resting dyspnea were independently associated with the imminent use of HFNC. Many patients with cancer started HFNC therapy at the point of imminent death. However, efforts toward goal-directed use of HFNC at the end-of-life stage are required.


Performance of 11C-Pittsburgh Compound B PET Binding Potential Images in the Detection of Amyloid Deposits on Equivocal Static Images.
The goal of this study was to clarify whether binding potential (BP) images using (11)C-Pittsburgh compound B ((11)C-PiB) and dynamic PET can reliably detect cortical amyloid deposits for patients whose (11)C-PiB PET static images are ambiguous and whether visual ratings are affected by white matter retention. Static and BP images were constructed for 85 consecutive patients with cognitive impairment after (11)C-PiB dynamic PET. Cortical uptake was visually assessed as positive, negative, or equivocal for both types of images. Quantitatively, the standardized uptake value ratio (SUVR) from the static image, the nondisplaceable BP from the dynamic image for mean gray matter uptake, and the ratio of gray matter uptake to white matter retention were compared among (11)C-PiB-positive, (11)C-PiB-equivocal, and (11)C-PiB-negative groups. Forty-three scans were visually assessed as (11)C-PiB-positive in both the static and the BP images. Ten scans were (11)C-PiB-equivocal in the static images. In 8 of them, the BP images were (11)C-PiB-positive, whereas the other 2 were (11)C-PiB-equivocal. Thirty-two scans were assessed as (11)C-PiB-negative in the static images. In the BP images, 4 were (11)C-PiB-positive and 2 were (11)C-PiB-equivocal. The mean gray matter uptake of (11)C-PiB in SUVR and nondisplaceable BP, respectively, showed statistically significant differences among the (11)C-PiB-positive, (11)C-PiB-equivocal, and (11)C-PiB-negative groups. The ratio of gray matter uptake to white matter retention was lower in the BP images than static images from the (11)C-PiB-negative and (11)C-PiB-equivocal groups, whereas it was higher in the (11)C-PiB-positive group. (11)C-PiB PET BP images can clarify visual interpretation of clinical static (11)C-PiB-equivocal images by reducing the interference of nonspecific white matter retention. We conclude that (11)C-PiB-equivocal PET findings on static images reflect cortical amyloid deposits, which can be verified using BP images. Furthermore, quantitative assessments, such as SUVR and nondisplaceable BP, are of no use for correctly rating equivocal visual findings.


Long-Term Survival After Off-Pump Coronary Artery Bypass Grafting.
The aim of this study was to compare the long-term survival rates of patients undergoing isolated first-time coronary artery bypass grafting (CABG) by off-pump CABG with the long-term survival rates in patients undergoing CABG using cardioplegic cardiopulmonary bypass techniques. All patients undergoing isolated CABG at a single center (Manchester Heart Centre, Manchester, United Kingdom) between 2000 and 2014 were included. Propensity score matching was performed on the basis of on demographic variables. The in-hospital morbidity and long-term all-cause mortality rates for matched patients were compared. A total of 8,055 patients were identified, with a median follow-up of 7.0 years. With patients matched for preoperative patient characteristics, there was no significant difference in long-term survival between cardiopulmonary bypass and off-pump CABG (n = 2,082 each; 11.5 years vs 11.3 years; p = 0.178). In the off-pump CABG group, there were significantly fewer in-hospital cerebrovascular complications (0.5% vs 1.1%; p = 0.017), and mean length of stay was shorter (7.6 days vs 8.1 days; p < 0.0001). Arterial conduit use was significantly higher in the off-pump group, with more right mammary artery grafts (16.3% vs 4.3%; p < 0.0001) and sequential grafts (27.1% vs 13.5%; p < 0.0001). The mean number of grafts was higher in the on-pump group (3.28 ± 0.94 vs 3.10 ± 1.10; p < 0.0001). Long-term survival after off-pump CABG is not inferior to long-term survival after on-pump CABG despite a lower mean number of grafts. A statistically significant difference in cerebrovascular complications may be related to conduit choice and reduced aortic manipulation.


Severe penetrating trauma in Switzerland: first analysis of the Swiss Trauma Registry (STR).
The purpose of this study was to examine the epidemiology, demographics, injury characteristics and outcomes of patients who presented to Swiss trauma centers following severe penetrating trauma. Swiss Trauma Registry (STR)-cohort analysis including patients with severe (ISS ≥ 16 or AIS head ≥ 3) penetrating trauma between 2017 and 2019. Primary outcome was mortality. Secondary outcomes were hospital and intensive care unit (ICU) length of stay (LOS), and prehospital times. During the 3-year study period, 134 (1.6% of entire STR) patients with severe penetrating trauma were identified [64 (48%) gunshot wounds (GSW), 70 (52%) stab wounds (SW)]. Median age was 40.5 (IQR 29.0-59.0) and 82.8% were male. Mortality rate was 50% for GSW; 9% for SW. Overall, prehospital time [incident to arrival emergency department (ED)] was 65 (IQR 45-94) minutes. The median number of patients admitted for a severe GSW/SW per center and year was 2 (range 0-14). Of 64 patients who sustained a GSW, 42 (65.6%) were self-inflicted. Mortality in self-inflicted GSW reached 66.7%, with the head being severely injured in 78.6%. The 67 patients with severe isolated torso GSW/SW had an ISS of 20 (IQR 16-26) and a mortality of 15%. Multivariable analysis identified severe chest trauma, ED Glasgow Coma Scale ≤ 8, age, self-infliction, massive blood transfusion and ISS as independent predictors for mortality. Severe penetrating trauma is very rare in Switzerland. Mortality ranges from 9% in SW to 67% in self-inflicted GSW. Particularly in the setting of GSW/SW to the torso, reduction in prehospital time may further improve patient outcomes.


A multicenter study of the morbidity of radical cystectomy in select elderly patients with bladder cancer.
We evaluated the morbidity of radical cystectomy for invasive bladder cancer in select patients older than 75 years using recent data from 2 academic hospitals. We analyzed 73 radical cystectomies performed from January 1995 to June 2000 in patients 75 to 89 years old (median age 79.3). Cases were categorized according to the American Society of Anesthesiologists classification with a score of 2 in 41, 3 in 30 and 4 in 2. External urinary diversion was performed in 51 cases and an ileal neobladder was constructed in 22. We evaluated the incidence and type of complications, clinical outcome, and postoperative care unit and hospital stay. Statistical analysis was done using the chi-square and Student t tests. Median operative time was 263 minutes (range 95 to 451). The perioperative mortality rate was 2.7%. The intraoperative, early and late postoperative complication rates were 38.4%, 46.5% and 16.4%, respectively. Three reoperations (4.1%) were necessary. The most common early complications were pyelonephritis in 12.3% of cases, disorientation in 10.9%, pneumonia in 8.2% and prolonged ileus in 12.3%. The most common late complications were ureteroileal anastomotic stenosis in 5 cases and hernia in 3. Median postoperative care unit and hospital stays were 12 and 34 days, respectively. At a median followup of 14.4 months (range 6 to 74) the overall mortality rate was 31.5%. Hospital stay was significantly higher in patients with complications. The incidence of complications was similar in the 2 groups. These data support the aggressive surgical management of bladder cancer in select elderly patients. A rigorous multidisciplinary team approach can provide acceptable perioperative morbidity.


Posterior mediastinal hemangioma.
We report posterior mediastinal hemangiomas in a 4-month-old and a 6-month-old girl. The masses were identified on radiographs of the chest followed by contrast-enhanced CT. Histological evaluation of the surgical specimens established the final diagnosis. Although mediastinal hemangiomas have been described, they remain a rare entity. A diagnosis can be suggested by relatively high attenuating masses on contrast-enhanced CT. Posterior mediastinal hemangiomas sometimes mimic neuroblastomas, which is the most common posterior mediastinal in this age group.


Ficus retusa-stabilized gold and silver nanoparticles: Controlled synthesis, spectroscopic characterization, and sensing properties.
Ficus retusa was used as reducing and stabilizing agent in the green synthesis of silver and gold nanoparticles with high dispersion stability and controllable size and shape. The controlling of reaction conditions i.e. contact time, extract quantity, metal concentration, and pH value enables the tuning of the particle size and size distribution of the metal nanoparticles. UV-visible spectroscopy was used to follow the spectral profile changes of the surface plasmon resonance of the metal nanoparticles due to different treatments. The surface plasmon resonance varies between 400 and 432 nm and between 522 and 554 nm for silver and gold nanoparticles, respectively, depending on the different reaction parameters. Atomic force and transmission electron microscopy results confirmed the success of preparation of spherical silver (15 nm) and gold (10-25 nm) nanoparticles with narrow size-distribution. Fourier transform infrared spectroscopy suggested the phenolic compounds play the key role in the reduction and stabilizing of metal ions. The colorimetric sensitivity of silver and gold nanoparticles to detect the presence of heavy metals in water was studied.


Investigating the relationship between serum uric acid to high-density lipoprotein ratio and metabolic syndrome.
This study aimed to determine a parameter to more easily diagnose metabolic syndrome and predict its probability of occurrence in high-risk individuals. In this cross-sectional study, data related to the study population in the Kerman Coronary Artery Disease Risk Factor Study (KERCADRS) were examined. Subjects were divided into two groups with and without metabolic syndrome, and the relevant factors such as the ratios of uric acid to high-density lipoprotein (HDL) (UHR) in these two groups were compared, and the best cut-off point was determined. Data related to 817 people including 96 people with metabolic syndrome and 721 people without metabolic syndrome were analysed. The mean UHR was significantly higher in patients with metabolic syndrome (14.76 ± 6.33%) compared with those without metabolic syndrome (10.0 ± 3.10%) (p < .001). People with high UHR are 2.9 times more at risk of metabolic syndrome and the best cut-off point was 9.50% with 86% sensitivity and 55% specificity. According to our study, UHR is also helpful in diagnosing metabolic syndrome and can also be used to screen people at risk for metabolic syndrome.


Enhancing quality of heart failure care in managed Medicare and Medicaid in North Carolina: results of the North Carolina Achieving Cardiac Excellence (NC ACE) Project.
To evaluate an intervention to improve the quality of care of patients with heart failure in managed Medicare and Medicaid plans in North Carolina. Utilization of angiotensin-converting enzyme inhibitors (ACE-I) and beta-adrenergic receptor blockers (BB) in heart failure (HF) patients remains suboptimal despite evidence-based guidelines supporting their use. Managed care plans identified adult patients with HF during 2000 (preintervention) and from July 1, 2001, through June 30, 2002 (postintervention). Outpatient medical records were reviewed to obtain data regarding type of heart failure, demographics, comorbidities, and therapies. The intervention consisted of guideline summary dissemination, performance audit with feedback, patient-specific chart reminders, and patient activation mailings. We sampled 1613 patients from 5 plans during the preintervention period and 1528 patients during the postintervention period. Assessment of left ventricular function (LVF) increased from 88.2% to 92.5% of patients (P < .0001). Among patients with moderate to severe left ventricular systolic dysfunction, there was no substantive change in treatment with ACE-I or vasodilators, whereas, appropriate treatment with BB increased from 48.3% (with another 11.9% with documented contraindications) to 67.9% (with another 7.5% with documented contraindications). The quality gap decreased from 39.8% to 24.6% (P < .0001). LVF assessment improved despite high preintervention rates. Treatment rates with ACE-I and vasodilators remained high, but did not improve. Treatment rates with BB improved substantially translating into a significant public health benefit. Health-care payers should consider development of financial incentives to encourage collaborative quality improvement programs.


Efficient human-like antibody repertoire and hybridoma production in trans-chromosomic mice carrying megabase-sized human immunoglobulin loci.
Trans-chromosomic (Tc) mice carrying mini-chromosomes with megabase-sized human immunoglobulin (Ig) loci have contributed to the development of fully human therapeutic monoclonal antibodies, but mitotic instability of human mini-chromosomes in mice may limit the efficiency of hybridoma production. Here, we establish human antibody-producing Tc mice (TC-mAb mice) that stably maintain a mouse-derived, engineered chromosome containing the entire human Ig heavy and kappa chain loci in a mouse Ig-knockout background. Comprehensive, high-throughput DNA sequencing shows that the human Ig repertoire, including variable gene usage, is well recapitulated in TC-mAb mice. Despite slightly altered B cell development and a delayed immune response, TC-mAb mice have more subsets of antigen-specific plasmablast and plasma cells than wild-type mice, leading to efficient hybridoma production. Our results thus suggest that TC-mAb mice offer a valuable platform for obtaining fully human therapeutic antibodies, and a useful model for elucidating the regulation of human Ig repertoire formation.


[Treatment of healthy salmonella carriers with lactulose beta-galactosido-fructose (author's transl)].
Oral administration of lactulose (beta-galactosido-fructose) of 25 healthy Salmonella carriers cured 21, but failed in four.


Syntheses and kinetic evaluation of hydroxamate-based peptide inhibitors of glyoxalase I.
Hydroxamate-containing tripeptide analogs resembling a reactive intermediate in glyoxalase I catalysis were prepared by solution methods and were found to be competitive inhibitors of the enzyme from Saccharomyces cerevisiae. Electronic properties of the hydroxamate functionality as well as those of the expected intermediates in the enzyme-catalyzed reaction were compared.


Anesthetics and automaticity of dominant and latent pacemakers in chronically instrumented dogs. I. Methodology, conscious state, and halothane anesthesia: comparison with and without muscarinic blockade during exposure to epinephrine.
Supraventricular dysrhythmias are common during anesthesia, but have been incompletely investigated. Mechanisms may involve altered automaticity of subsidiary pacemakers and participation of vagal reflexes. The following hypotheses were tested: (1) shifts from the sinoatrial (SA) node to subsidiary pacemakers require intact vagal reflexes and (2) halothane sensitizes the heart to epinephrine-induced atrial pacemaker shifts. Epicardial electrodes were implanted in eight dogs on both atrial appendages, the right ventricle, along the sulcus terminalis, and at the His bundle. Weekly testing awake (control), awake with atropine methylnitrate, with 1 and 2 micrograms epinephrine.kg-1.min-1 (3 min-infusions), and under 1.25 and 2 MAC halothane was performed. Electrograms were analyzed for the site of earliest activation (SEA), which was scored 1-6 depending on the distance from the SA node, and expressed as the SEA value. In conscious dogs (control) and at 1.25 MAC halothane, epinephrine increased the SEA values (shifted activation from SA node) and blood pressure, and decreased heart rate; however, with atropine, SEA values were unaffected by epinephrine, although blood pressure and heart rate were elevated. At 2 MAC, atropine did not affect the epinephrine-induced increase in SEA values. Halothane increased SEA values when combined with 1 micrograms epinephrine.kg-1.min-1. Pacemaker shifts account for atrial dysrhythmias in the conscious state and during 1.25 MAC halothane with epinephrine, and require vagal participation. Halothane sensitizes the heart to epinephrine-induced atrial dysrhythmias. Atropine and halothane facilitate His bundle beats during exposure to epinephrine.


Bridging the pharmacokinetics and pharmacodynamics of UK-279,276 across healthy volunteers and stroke patients using a mechanistically based model for target-mediated disposition.
UK-279,276 is a recombinant glycoprotein and is a selective antagonist of CD11b, which in preclinical models of acute stroke blocks the infiltration of activated neutrophils into the site of infarction. Binding of UK-279,276 to the CD11b receptors is hypothesized to facilitate its elimination. The event of an acute stroke leads to proliferation of neutrophils and an up-regulation of CD11b, which results in different pharmacokinetics/pharmacodynamics (PK/PD) in patients than in healthy volunteers. The aim of this current analysis was to develop a mechanistically based model to bridge the differences between healthy volunteers and patients. PK samples, neutrophil counts, and total number and number of free CD11b receptors per neutrophils from three healthy volunteer studies (n=98) and one patient study (n=169) were modeled using the mixed effects modeling software NONMEM version VI (beta). Three mechanistic submodels were developed based on underlying physiology and pharmacology: (1) neutrophil maturation and proliferation, (2) CD11b up-regulation, and (3) three clearance pathways for UK-279-276 including CD11b-mediated elimination. The model accurately described the time course of CD11b expression, CD11b binding, and the measured PK of UK-279,276 and accounted for the PK/PD differences between healthy volunteers and patients. A complex mechanistic model that closely resembled the "true" underlying system provided an effective bridge between healthy volunteers and patients by appropriately accounting for the underlying disease-dependent target mediated disposition.


Physiology based simulation model of triangle shape recognition.
The present paper considers the relation between the shape of a triangle and probability of its recognition. An effect of triangle size on perception of its shape is examined in the first experiment. In the second the loci of eye fixations during triangle recognition task are recorded and analysed. A simulation model of the recognition process is proposed. The model is based on two main assumptions: 1. an accuracy of shape processing is related to the cortical magnification factor, 2. a subject's response depends on actual position of eye fixation. The validity of the model is verified by comparing the theoretical and experimental response distributions. Some psycho-physiological implications are then discussed.


AUF1 protects against ferroptosis to alleviate sepsis-induced acute lung injury by regulating NRF2 and ATF3.
The AU-rich element (ARE)-binding factor 1 (AUF1) acts as a switch for septic shock, although its underlying mechanisms remain largely unknown. In this study, we examined the biological significance and potential molecular mechanism of AUF1 in regulating ferroptosis in sepsis-induced acute lung injury (ALI). Alveolar epithelial cells (AECs) challenged with ferroptosis-inducing compounds and cecum ligation and puncture (CLP)-induced ALI were used as the in vitro and in vivo model, respectively. The stability of AUF1 and its degradation by ubiquitin-proteasome pathway were examined by cycloheximide chase analysis and co-immunoprecipitation assay. The regulation of AUF1 on nuclear factor E2-related factor 2 (NRF2) and activation transcription factor 3 (ATF3) was explored by RNA immunoprecipitation (RIP), RNA pull-down, and mRNA stability assays. Functionally, the effects of altering AUF1, NRF2 or ATF3 on ferroptosis in AECs or ALI mice were evaluated by measuring cell viability, lipid peroxidation, iron accumulation, and total glutathione level. AUF1 was down-regulated in AECs challenged with ferroptosis-inducing compounds, both on mRNA and protein levels. The E3 ubiquitin ligase FBXW7 was responsible for protein degradation of AUF1 during ferroptosis. By up-regulating NRF2 and down-regulating ATF3, AUF1 antagonized ferroptosis in AECs in vitro. In the CLP-induced ALI model, the survival rate of AUF1 knockout mice was significantly reduced and the lung injuries were aggravated, which were related to the enhancement of lung ferroptosis. FBXW7 mediates the ubiquitination and degradation of AUF1 in ferroptosis. AUF1 antagonizes ferroptosis by regulating NRF2 and ATF3 oppositely. Activating AUF1 pathway may be beneficial to the treatment of sepsis-induced ALI.