Development of B cell epitopes-based enzyme linked immune sorbent assay for detection of bovine anti-Mullerian hormone.
The present study aimed to generate antibodies against predicted B cell epitopic peptides encoding bAMH for developing different ELISA models. Sandwich ELISA was determined to be an excellent technique for assessing bAMH in bovine plasma based on sensitivity tests. The assay's specificity, sensitivity, inter- and intra-assay CV, recovery %, Lower limit of quantification (LLOQ), and Upper limit of quantification (ULOQ) were determined. The test was selective since it did not bind to AMH-related growth and differentiation factors (LH and FSH) or non-related components (BSA, progesterone). The intra-assay CV was 5.67%, 3.12%, 4.94%, 3.61% and 4.27% for 72.44, 183.11, 368.24, 522.24 and 732.25 pg/ml AMH levels, respectively. At the same time, the inter-assay CV was 8.77%, 7.87%, 4.53%, 5.76% and 6.70% for 79.30, 161.27, 356.30, 569.33 and 798.19 pg/ml AMH levels, respectively. The average (Mean ± SEM) recovery percentages were 88-100%. LLOQ was 5 pg/ml and ULOQ at 50 µg/ml (CV < 20%). In conclusion, we developed a new highly sensitive ELISA against bAMH using epitope specific antibodies.


Genome-wide search and comparative genomic analysis of the trypsin inhibitor-like cysteine-rich domain-containing peptides.
It was shown that peptides containing trypsin inhibitor-like cysteine-rich (TIL) domain are able to inhibit proteinase activities, and thus play important roles in various biological processes, such as immune response and anticoagulation. However, only a limited number of the TIL peptides have been identified and characterized so far; and little has been known about the evolutionary relationships of the genes encoding the TIL peptides. BmKAPi is a TIL domain-containing peptide that was identified from Mesobuthus martensii Karsch. Here, we conducted genome-wide searches for new peptides that are homologous to BmKAPi or possess a cysteine pattern similar to that of BmKAPi. As a result, we identified a total of 80 different TIL peptides from 34 species of arthropods. We found that these peptides can be classified into seven evolutionarily distinct groups. Furthermore, we cloned the genomic sequence of BmKAPi; the genomic sequences of the majority of other TIL peptides were also identified from the GenBank database using bioinformatical approaches. Through phylogenetic and comparative genomic analysis, we found 26 cases of intron gain events occurred in the genes of the TIL peptides; however, no instances of intron loss were observed. Moreover, we found that alternative splicing contributes to the diversification of the TIL peptides. It is interesting to see that four genes of the TIL domain-containing peptides overlap in a DNA region located on the chromosome LG B15 of Bombus terretris. These data suggest that the evolution of the TIL peptide genes are dynamic, which was dominated by intron gain.


Persistent bronchography in a newborn with esophageal atresia.
Esophageal atresia (EA) with tracheoesophageal fistula occurs in about 1:2,500 births. We report a case of persistent bronchography in a newborn with EA and distal tracheoesophageal fistula. A large amount of barium sulfate was injected for mistake by a tube directly in the right bronchus to evaluate the patency of the esophagus. The infant showed signs of respiratory distress; he was intubated and transported at children's Hospital Santobono Pausilipon. Here, it was performed a chest X-ray that confirmed the opacification of the right bronchial tree, and it was suspected an EA type 3b. The literature recommends that: evaluation of the patency of the esophagus, with an iodinate contrast medium, should be done in a pediatric specialized center for high risk of lung aspiration.


Aspartate immunoreactivity in the telencephalon of the adult sea lamprey: comparison with GABA immunoreactivity.
The excitatory amino acid l-aspartate (Asp) plays a number of roles in neuronal function. We studied the distribution of Asp-immunoreactive (ir) cells in the telencephalon of young and upstream migrating adult sea lamprey, Petromyzon marinus, and compared it with the distribution of gamma-aminobutyric acid (GABA) immunoreactivity, by using double immunofluorescence methods. Our results reveal for the first time the existence of Asp-ir neuronal populations in the lamprey forebrain. In the olfactory bulbs, Asp-ir neurons were observed in the mitral cell layer and in the inner cellular layer. Many granule-like cells were both Asp-ir and GABA-ir. In the pallium, Asp-ir cells were abundant in the lateral pallium and most of them were also GABA-ir. In the septum/terminal lamina nucleus, some cerebrospinal fluid-contacting type (CSF-c) cells were either Asp-ir or GABA-ir, and a few were double-labeled. Some non-CSF-c septal cells were both Asp-ir and GABA-ir. In the striatum, Asp-ir and/or GABA-ir cells were either subependymal or located in the characteristic arched cell row. In the lateral preoptic region, a few small Asp-ir/GABA-ir neurons were observed. In the caudal preoptic recess nucleus, numerous CSF-c cells were Asp-ir and/or GABA-ir. This study also reveals that colocalization of GABA and Asp immunoreactivities in telencephalic neurons is partial. Further investigation is required to establish whether Asp is a neurotransmitter and/or an intermediate in GABA synthesis in lamprey telencephalon.


Rhabdomyosarcomas developing in association with mediastinal germ cell tumours.
Two mediastinal rhabdomyosarcomas that arose in association with germ cell tumours are reported. One presented as a small component of a mixed germ cell tumour with yolk sac and immature teratomatous elements. The other appeared as a large mass 4 months after diagnosis of a yolk sac carcinoma that had been treated with chemotherapy. The first patient was alive and free of disease 7 years later, whereas the second died of tumour 3 months post-operatively. The proportion of rhabdomyosarcoma within the germ cell tumours appears to have influenced the prognosis of these patients. This observation emphasizes the necessity of performing a thorough search for sarcomatous elements and quantifying their relative proportion in germ cell tumours of the mediastinum.


Incidental Findings on Computerized Tomography Images of Trauma Cases.
This study aimed to evaluate the characteristics of incidental findings (IFs) on computed tomography (CT) scans of trauma admissions, examine associations between IFs and gender and age-groups, and discuss the management strategies. The CT reports were retrospectively reviewed to evaluate IFs. Cases were divided into five age-groups (0-19, 20- 39, 40-59, 60-79,≥80). IFs were classified as "Group 1": congenital anomalies that do not require further investigation, non-degenerative/minor degenerative findings; "Group 2": findings that do not require immediate intervention, require outpatient follow-up/in case of symptoms; and "Group 3": findings that require immediate intervention/further investigation. There were 2385 CT scans and 1802 incidental findings (IFs) in 783 trauma cases. CT scans with IFs constituted 50.2%. The percentage of IFs was 75.6% in males and 24.4% in females, and they occurred in 4.8%, 27.6%, 44.3%, 20.9%, and 2.4% of age groups 1 to 5, respectively. Group 1 had 34.6%, group 2 had 54.6%, and group 3 had 10.8% IFs. There was not any significant association between the classification and gender or age-groups. In terms of organs, IFs of the thyroid and gall bladder & bile ducts were significantly higher among females (P=0.044 and P<0.001, respectively), while IFs in the head & neck region were significantly higher in males (P<0.001). Incidental findings in the kidney, liver, adrenal gland, and vascular structures differed significantly across age-groups (P<0.05). There were no significant relationships between the classification of IFs and gender or age-groups. However, the distribution of IFs was significantly associated with gender and age-groups in terms of organs. Healthcare professionals should consider this relationship when following up and treating patients.


The prognostic role of controlling nutritional status scores in patients with solid tumors.
We conducted a meta-analysis to investigate the association between preoperative controlling nutritional status (CONUT) scores in various solid tumors and clinical outcomes. Relevant studies published up to August 12, 2017 were identified using electronic databases, including PubMed, Embase, and Web of Science. The pooled hazard ratios (HR) and their corresponding 95% confidence intervals (CI) for overall survival (OS) and event-free survival (EFS) were calculated to explore the relationship between preoperative CONUT score and prognosis. In total, 674 patients with solid tumors from four published studies were included in this meta-analysis. The pooled HR for OS was 1.98 (95% CI, 1.34-2.91, p=0.001), indicating that patients with high CONUT scores had worse OS. The pooled HR for EFS was 1.98 (95% CI, 1.34-2.93, p=0.001), revealing that high CONUT scores were significantly associated with short EFS. Our data suggest that high preoperative CONUT scores indicate poor prognosis for patients with solid tumors. Further studies are needed to verify the significance of CONUT scores in clinical practice.


Interaction of bodymass, fat, foraging and stopover period in trans-Sahara migrating passerine birds.
The effect of body mass and fat reserves on the choice of the stopover place and on the stopover period was investigated in 3 species of passerine birds migrating through the Sahara in Egypt. Birds grounded in an oasis with food and water were more than 10% lighter than those from a desert stopover place which offered shade only. Stopover period was in general one day except for the light portion of oasis birds which stopped for up to three weeks during which they regained fat. A calculation of the maximum range which can be covered with the available fat depots revealed that nearly all birds from the desert stopover place should be able to cross the desert whereas about 60% of the oasis birds should not. An intermittant migratory strategy for the desert crossing is proposed with flight during the night and stopover during the day, even without drinking and feeding.


Elastin and collagen in the fetal sheep lung. II. Relationship to mechanical properties of the lung.
The relationship between elastin and collagen concentration and indices of lung maturation was studied in the lungs of fetal sheep. Fetal sheep of 124 days gestation were infused for 84 h with cortisol, triiodothyronine, prolactin, or epidermal growth factor alone or in combination. Pressure-volume curves with air were performed on the lungs and saturated phosphatidylcholine was measured in lung washes. Desmosine and hydroxyproline were determined in lung tissue in seven hormone-treated fetuses that displayed distensible and stable lungs similar to term lungs [volume of air at 40 cm H2O (V40) greater than 1.5 ml/g wet weight and at 5 cm H2O (V5) greater than 0.8 ml/g] and in seven fetuses whose lungs remained nondistensible and unstable (V40 less than 0.6 ml/g and V5 less than 0.4 ml/g). Alveolar saturated phosphatidylcholine was five times higher (p less than 0.001) in distensible than in nondistensible lungs, but attained less than 20% of term values. Desmonsine and hydroxyproline concentrations in parenchyma, pleura, and trachea of nondistensible, unstable lungs were similar to intact controls of 125 days gestation and those in distensible, stable lungs were similar to controls of 137 days gestation. Desmosine (p less than 0.0001) and hydroxyproline (p less than 0.001) concentrations in parenchyma of distensible, stable lungs were higher than those of nondistensible, unstable lungs. We speculate that increased distensibility of the fetal lung in response to treatment with hormones is attributable in part to changes in the composition of connective tissue.


Clear cell carcinoma of the endometrium.
In a clinical-pathologic review of 825 cases of endometrial carcinoma diagnosed between 1955 and 1984, 735 cases were confirmed as endometrial carcinoma. From this group 29 cases of clear cell carcinoma of the endometrium were found representing a 4% frequency. Clear cell carcinoma of the endometrium was found in an older group of women, all postmenopausal. No relationship to the use of estrogen could be demonstrated. The frequency of clear cell carcinoma of the endometrium dropped from 6% in the group diagnosed between 1955 and 1969 to 3% in the group diagnosed between 1970 and 1984, although the numbers of cases of endometrial cancer rose from 194 to 525 in the comparative time span. Clear cell carcinoma of the endometrium has a poorer prognosis, with a 64% 5-year survival rate compared with an 80% 5-year survival rate for adenocarcinoma, not otherwise stated. Three patients died after 5 years of disease. Treatment is still not satisfactory, but the proved therapy remains total abdominal hysterectomy plus salpingo-oophorectomy. The role of adjunctive therapy has not been established.


Avoidance of Pile-Driving Noise by Hudson River Sturgeon During Construction of the New NY Bridge at Tappan Zee.
Sturgeon movements were monitored during a pile-driving operation. Fewer sturgeon were detected during pile driving and remained for a shorter time than during silent control periods. Moreover, the short time spent by sturgeon near pile driving suggests that they were unlikely to have reached the criterion of 187 dB re 1 μPa(2)·s cumulative sound exposure level. These results suggest that sturgeon are likely to avoid impact pile driving and not remain long enough to experience physiological effects, thus providing empirical evidence that the 206 dB re 1 μPa peak sound pressure level is the appropriate criterion for assessing the impacts of pile-driving noise on sturgeon.


Structural and bio-mineralization features of alumina zirconia composite influenced by the combined Ca2+ and PO43- additions.
The structural and bioactivity features of alumina zirconia composite (AZC) due to Ca2+ and PO43- additions are demonstrated. An in situ synthetic approach, starting from the solution precursors is devised for the powder synthesis in which the assorted range of Ca2+ and PO43- additions were done to the equimolar concentrations of Al3+ and Zr4+ precursors. The results witnessed the unique crystallization of tetragonal zirconia (t-ZrO2) at 1100 °C while Ca2+, PO43- and Al2O3 remained in their amorphous state in the system. On further heat treatment, α-Al2O3 crystallized at 1200 °C, which enforced t- → m-ZrO2 transformation while Ca2+ and PO43- still retained their amorphous state. The immersion tests in simulated body fluid (SBF) solution validated the enhanced bio-mineralization activity of AZC due to Ca2+ and PO43- additions. The results from the indentation tests demonstrated good uniformity in the elastic modulus and hardness data of the investigated specimens. Further, in vitro cell culture tests ascertained the bioactivity of all the AZC compositions.


Characterization of high capacitance electrodes for the application of direct current electrical nerve block.
Direct current (DC) can briefly produce a reversible nerve conduction block in acute experiments. However, irreversible reactions at the electrode-tissue interface have prevented its use in both acute and chronic settings. A high capacitance material (platinum black) using a charge-balanced waveform was evaluated to determine whether brief DC block (13 s) could be achieved repeatedly (>100 cycles) without causing acute irreversible reduction in nerve conduction. Electrochemical techniques were used to characterize the electrodes to determine appropriate waveform parameters. In vivo experiments on DC motor conduction block of the rat sciatic nerve were performed to characterize the acute neural response to this novel nerve block system. Complete nerve motor conduction block of the rat sciatic nerve was possible in all experiments, with the block threshold ranging from -0.15 to -3.0 mA. DC pulses were applied for 100 cycles with no nerve conduction reduction in four of the six platinum black electrodes tested. However, two of the six electrodes exhibited irreversible conduction degradation despite charge delivery that was within the initial Q (capacitance) value of the electrode. Degradation of material properties occurred in all experiments, pointing to a possible cause of the reduction in nerve conduction in some platinum black experiments .


Methaemoglobinaemia in young infants with diarrhoea.
Seventeen infants under 2 months of age are described who presented with methaemoglobinaemia and acute diarrhoea during a period of 2 years. No infants beyond this age presented with such characteristics. In none of them was one of the known mechanisms of methaemoglobin formation found. All infants recovered with conventional therapy. Methaemoglobin associated with diarrhoea relapsed in three infants before they were 2 months old. Twenty-six similar cases have been reported in the literature. The mechanism of methaemoglobinaemia in these infants is unclear.


[Technique and biomechanics of Kirschner wire osteosynthesis in children].
Safe and stable fixation of metaphyseal and epiphyseal fractures by Kirschner (K-)wire osteosynthesis. Use of various K‑wire configurations depending on the fracture morphology. In accordance with the AO Pediatric Comprehensive Classification of Long-Bone Fractures (PCCF), all Salter-Harris (SH) and metaphyseal fractures as well as fractures of the foot and hand independent of the reduction technique, closed or open, provided that adaptation osteosynthesis allows sufficient stability. Fixation/immobilization in a plaster cast is mandatory after K‑wire osteosynthesis. All diaphyseal fractures, if a K-wire is not used as an intramedullary nail. Fractures that can not be correctly reduced or are nonreducible fractures. After closed or open, as anatomical reduction as possible, one, two, occasionally three K‑wires per fragment are inserted under fluoroscopic control. Care must be taken that the K‑wires optimally capture the fragment to be fixed as well as the main fragment (metaphysis). It must therefore be possible to make a strictly lateral and correct anteroposterior x‑ray by image intensifier. It is important that the C‑arm can be positioned at the appropriate level. Rotating the limb should be minimized, as prior to fixation the previously reduced fragments may shift again, resulting in poor K‑wire fixation. Depending on the morphology of the fracture, size of the fragments and location of the fracture (humerus, forearm, femur or tibia, hand or foot), the K‑wiring technique must be adapted, e.g., mono-laterally crossed, mono-laterally divergent, in an ascending or descending direction, or the most commonly used ascending crossed technique. In most cases, the K‑wires protrude through the sin and the exposed ends are bent. This allows removal without renewed anesthesia in the outpatient setting. K‑wire osteosynthesis is neither a compression osteosynthesis (OS) nor a neutralization OS, but is always an adaptation and fixation of the fragments. Therefore, K‑wire OS always needs additional immobilization using a plaster or prefabricated splint. Immobilization in plaster cast for 4-5 weeks, depending on the age; care must be taken to avoid interference between the cast and the skin/K-wires. With technically and optimally performed fixation and correct indication for K‑wire OS, as well as adequate posttreatment, very good to good results are achieved.


High success rate and low incidence of headache and neurological symptoms with two spinal needle designs in children.
In children, only a few trials have evaluated the use of spinal needles with special tip designs. In this study, we compared the success rate and incidence of post-dural puncture complaints of two small-gauge spinal needle designs used in children undergoing spinal anaesthesia (SA). Three hundred and three children aged 9 months to 17 years presenting for subumbilical surgery were randomly assigned to have a 26G Atraucan (n = 156) or 27G Whitacre (n = 147) spinal needle for SA. The number of attempts to obtain successful cerebrospinal fluid (CSF) return and the success rate of SA were recorded. The first week of recovery was recorded by a diary. Both groups had a similar one-attempt success rate: 80% in the Atraucan group and 81% in the Whitacre group. Failure to obtain CSF occurred in one patient in the Atraucan group and in two patients in the Whitacre group. Paraesthesia was observed more commonly in the Whitacre group (10%) than in the Atraucan group (2%) (P = 0.004). The success rate of SA was 96%, with no differences between the two needles; one child was given general anaesthesia and 11 children (3%) a single dose of supplemental analgesia for the skin incision. Forty-one children (15%) developed a headache, 13 of which were classified as post-dural puncture headache (PDPH), seven cases (5%) in the Atraucan group and six (4%) in the Whitacre group; none of the children required a blood patch. Fifteen children (10%) in the Atraucan group and nine (7%) in the Whitacre group developed low back pain. Two children (1%) in the Atraucan group and four (3%) in the Whitacre group developed transient neurological symptoms (TNSs). Both needles were associated with a high success rate and a low incidence of complaints.


Is indoor and outdoor greenery associated with fewer depressive symptoms during COVID-19 lockdowns? A mechanistic study in Shanghai, China.
Increasing numbers of studies have observed that indoor and outdoor greenery are associated with fewer depressive symptoms during COVID-19 lockdowns. However, most of these studies examined direct associations without sufficient attention to underlying pathways. Furthermore, few studies have combined different types of indoor and outdoor greenery to examine their effects on the alleviation of depressive symptoms. The present study hypothesized that indoor and outdoor exposure to greenery increased the perceived restorativeness of home environments, which, in turn, reduced loneliness, COVID-related fears, and, ultimately, depressive symptoms. To test our hypotheses, we conducted an online survey with 386 respondents in Shanghai, China, from April to May 2022, which corresponded to strict citywide lockdowns that resulted from the outbreak of the Omicron variant. Indoor greenery measures included the number of house plants, gardening activities, and digital nature exposure as well as semantic image segmentation applied to photographs from the most viewed windows to quantify indoor exposure to outdoor trees and grass. Outdoor greenery measures included total vegetative cover (normalized difference vegetation index [NDVI]) within a 300 m radius from the home and perceived quality of the community's greenery. Associations between greenery and depressive symptoms/clinical levels of depression, as measured by the Patient Health Questionnaire-9 (PHQ-9), were examined using generalized linear and logistic regression models. Structural equation modeling (SEM) was used to test pathways between greenery exposure, restorativeness, loneliness, fear of COVID-19, and depressive symptoms. The results showed that: 1) indoor and outdoor greenery were associated with fewer depressive symptoms; 2) greenery could increase the restorativeness of the home environment, which, in turn, was associated with fewer COVID-related mental stressors (i.e., loneliness and fear of COVID-19), and ultimately depressive symptoms; and 3) gender, education, and income did not modify associations between greenery and depressive symptoms. These findings are among the first to combine objective and subjective measures of greenery within and outside of the home and document their effects on mental health during lockdowns. Comprehensive enhancements of greenery in living environments could be nature-based solutions for mitigating COVID-19 related mental stressors.


Six-minute walk distance in healthy subjects: reference standards from a general population sample.
The 6-min walking distance (6MWD) test is a useful tool to obtain a measure of functional exercise capacity. However, reference equations have been mainly based on selected populations or small samples. The purpose of this study was to determine the reference equations to predict the 6MWD in a large Italian population sample of healthy adults of a wide age range. In the frame of the multi case-control population-based study Gene Environment Interaction in Respiratory Diseases (GEIRD), we studied 530 healthy subjects: 287 females ranging 21-76 and 243 males ranging 21-78 years of age. We measured 6MWD, demographic and anthropometric data and collected the reported physical activity. A multiple linear regression model for the 6MWD included age, age2, height, weight and physical activity for both sex equations. The two-way interaction age-height and age-weight and the quadratic terms of weight and height were also tested for inclusion separately in each model. The mean ± SD for 6MWD was 581.4 ± 66.5 m (range 383-800 m) for females and 608.7 ± 80.1 m (range 410-875 m) for males. The reference equations were 6MWD = 8.10*age + 1.61*heightcm-0.99*weightkg + 22.58*active-0.10*age2 + 222.55 for females (R squared = 0.238) and 6MWD = 26.80*age + 8.46*heightcm-0.45*weightkg-2.54*active-0.06*age2-0.13*age*heightcm-890.18 for males (R squared = 0.159), where "active" is 1 when the subject is physically active, 0 otherwise. This study is the first to describe the 6MWD in a large population sample of young, middle aged and elderly healthy Caucasian subjects, and to determine reference equations. These findings will help to improve the evaluation of Italian and European patients with diseases influencing their functional capacity.


Respiratory failure due to infliximab induced interstitial lung disease.
Although poorly understood, interstitial lung disease has been reported as a possible complication of tumor necrosis factor alpha inhibitors. We report a case of interstitial lung disease in a 64-year-old man with psoriasis 3 weeks after the initiation of infliximab treatment. The patient had received two fortnightly infusions of infliximab following a short course of methotrexate. Thoracic computed tomography showed bilateral ground glass and interstitial infiltrates, while the results of microbiology and immunologic workup were negative. Likewise, bronchoalveolar lavage detected neither typical nor atypical pathogens. Infliximab-induced interstitial lung injury was suspected and corticosteroid therapy was administered which resulted in rapid clinical and radiological improvement. This is one of the few reported cases of interstitial lung disease due to infliximab in the psoriasis population. The patient had no pre-existing lung pathology, while his previous exposure to methotrexate was minimal and was not temporally associated with the induction of interstitial lung disease.


Ubiquitination is a major modulator for the activation of inflammasomes and pyroptosis.
Inflammasomes are a central node of the innate immune defense system against the threat of homeostatic perturbance caused by pathogenic organisms or host-derived molecules. Inflammasomes are generally composed of multimeric protein complexes that assemble in the cytosol after sensing danger signals. Activated inflammasomes promote downstream proteolytic activation, which triggers the release of pro-inflammatory cytokines therefore inducing pyroptotic cell death. The inflammasome pathway is finely tuned by various mechanisms. Recent studies found that protein post-translational modifications such as ubiquitination also modulate inflammasome activation. Targeting the ubiquitination modification of the inflammasome pathway might be a promising strategy for related diseases. In this review, we extensively discuss the advances in inflammasome activation and pyroptosis modulated by ubiquitination which help in-depth understanding and controlling the inflammasome and pyroptosis in various diseases.


Refractory chylothorax in a patient with Waldenström Macroglobulinemia: A case report.
A refractory chylothorax secondary to Waldenström Macroglobulinemia (WM) has rarely been reported in literature, but often responds to chemotherapy and conservative measures. Few reports have been published reporting the use of surgical intervention when standard medical therapies fail. We present a 76-year-old male who developed a large right sided chylothorax with a soft tissue mass encasing the descending thoracic aorta. Pleural fluid flow cytometry and biopsy of the mass demonstrated findings diagnostic of WM. Despite chemoimmunotherapy and conservative measures, he required frequent, high-volume, therapeutic thoracentesis for relief of dyspnea. Thoracic duct embolization (TDE) was performed which resolved the patient's chylothorax, however he subsequently developed lower volume serosanguinous pleural effusions. Patient continued requiring therapeutic thoracentesis bimonthly and ultimately proceeded with pleurectomy of the right lung to achieve resolution of symptoms. To our knowledge, this is the first reported case where pleurectomy has successfully treated refractory pleural effusions in a patient with WM.


Organochalcogen peroxidase mimetics as potential drugs: a long story of a promise still unfulfilled.
Organochalcogen compounds have attracted the interest of a multitude of studies to design potential therapeutic agents mimicking the peroxidase activity of selenium-based glutathione peroxidases (GPx's). Starting from the pioneering ebselen, various compounds have been synthesized over the years, which may be traced in three major classes of molecules: cyclic selenenyl amides, diaryl diselenides, and aromatic or aliphatic monoselenides. These compounds share common features and determinants needed to exert an efficient GPx-like activity, such as polarizing groups in close proximity to selenium and steric effects. Nonetheless, the reactivity of selenium, and tellurium as well, poses serious problems for the predictability of the biological effects of these compounds in vivo when used as potential drugs. These molecules, indeed, interfere with thiols of redox-regulated proteins and enzymes, leading to unexpected biological effects. The various chemical aspects of the reaction mechanism of peroxidase mimetics are surveyed here, focusing on experimental evidence and quantum mechanics calculations of organochalcogen representatives of the various classes.


[The utilization of small repeated doses of iodine 131 in the treatment of Graves' disease. Results (author's transl)].
In graves' disease small amounts of radioactive iodine administered repeatedly on a monthly basis depending on the progress of the disease is a method whose effectiveness we have studied on 192 cases over a period of 3 to 7 years. Relapses (4 %), failures (11 %) permanent hypothyroidism (24 % after 7 years) and the duration of the active stage have been collated with different clinical or biological parameters in order better to define the main factors that determine the course and prognosis. The size of the goitre and the presence of antithyroglobulin antibodies are among the most significant.


AIDS as a cause of dementia in the elderly.
It has been recognized that AIDS can present initially as dementia without other neurological or clinical manifestations. In addition, HIV-contaminated blood transfusions in the elderly seem to be underreported. Because of these findings, dementia in the elderly may be misdiagnosed as Alzheimer's disease or other causes of senile dementia. This paper reports on one patient who presented with a diagnosis of Alzheimer's disease and was later found to have AIDS.


Effect of Asparagus racemosus (Shatavari) on gastric emptying time in normal healthy volunteers.
Asparagus racemosus (Shatavari) is used in Ayurveda for dyspepsia (amlapitta) and as a galactogogue. It was hence compared with a modern drug, metoclopramide, which is used in dyspepsia to reduce gastric emptying time. Gastric emptying half- time (GE t1/2) was studied in 8 healthy male volunteers using a cross-over design. The basal GE t1/2 in volunteers was 159.9 +/- 45.9 min (mean +/- SD) which was reduced to 101 +/- 40.8 min by Shatavari (p less than 0.001) and to 85.3 +/- 21.9 by metoclopramide (p less than 0.001). Metoclopramide and Shatavari did not differ significantly in their effects.


Emerging Patient-Centered Concepts in Pain Among Adults With Chronic Kidney Disease, Maintenance Dialysis, and Kidney Transplant.
Patient reports of moderate to severe pain are common across the spectrum of chronic kidney disease. The synergistic effects of comorbid depression and anxiety can lead to maladaptive coping responses to pain, namely pain catastrophizing and illness-related post-traumatic stress disorder. If underlying depression and anxiety and associated maladaptive coping responses are not treated, patients can experience an increased perception of pain, worsened disability, decreased quality of life, withdrawal from social activities, and increased morbidity and mortality. Meanwhile, interest in nonpharmacologic treatments for pain that targets coping as well as comorbid anxiety and depression has been increasing, particularly given the significant societal damage that has resulted from the opioid epidemic. Evidence-based, nonpharmacologic treatments have shown promise in treating pain in areas outside of nephrology. Currently, little is known about the effects of these treatments among adults with CKD, and particularly end-stage kidney disease, when chronic pain can become debilitating. In this review, we examine patient-centered concepts related to pain that have received little attention in the nephrology literature. We also describe emerging areas of research, including omics technologies for biomarker discovery and advanced symptom clustering methods for symptom phenotyping, which may be useful to future kidney disease research and treatment.


The ART of Electronic Prescribing.
Medication errors are common. Electronic Health Records (EHR) reduce some of the roots with some while they create others. EHR need to evolve. A suggestion is made to deal with prescriptions that are new. being titrated, to support the process of prescribing and hopefully correcting errors linked to it.


Dual porphyria in double heterozygotes with porphobilinogen deaminase and uroporphyrinogen decarboxylase deficiencies.
A coexistent dual deficiency of porphobilinogen deaminase (PBG-D; EC 184.108.40.206) and uroporphyrinogen decarboxylase (EC 22.214.171.124) in erythrocytes was recognized in five individuals, four males and one female. Clinically, the female and one male were diagnosed as suffering from acute intermittent porphyria (AIP), and the other two males were diagnosed as having porphyria cutanea tarda (PCT). Biochemically, the excretion pattern of urinary and fecal heme precursors exhibited a complex constellation with signs characteristic for both AIP and PCT. A coexistent dual enzyme deficiency of PBG-D and URO-D could be confirmed by repeated studies over 10 years. Clinical courses of both disease manifestations were observed. Family investigations have shown that the two disorders do not consistently segregate together. The findings suggest that the dual porphyria reflects a double heterozygous condition of coexistent AIP and PCT genes in the same individual.


Protein quality control: chaperones culling corrupt conformations.
Achieving the correct balance between folding and degradation of misfolded proteins is critical for cell viability. The importance of defining the mechanisms and factors that mediate cytoplasmic quality control is underscored by the growing list of diseases associated with protein misfolding and aggregation. Molecular chaperones assist protein folding and also facilitate degradation of misfolded polypeptides by the ubiquitin-proteasome system. Here we discuss emerging links between folding and degradation machineries and highlight challenges for future research.


Expression of a recombinant derivative of human aromatase P450 in insect cells utilizing the baculovirus vector system.
Aromatase P450 (P450arom) is the enzyme responsible for estrogen biosynthesis. Studies of the relationship of the function of this enzyme to its structure have been hampered by lack of a suitable preparation. In the present report we describe the expression of a recombinant derivative of P450arom in insect cells by means of the baculovirus vector system. This protein, which lacks the first 41 amino acids from the N-terminus, and hence the membrane-spanning region, has spectral properties and activity similar to that of the wildtype protein. Moreover, the presence of a hexameric histidine tag at the C-terminus permits its facile purification by means of nickel-agarose affinity chromatography. This system permits the synthesis of quantities of a biologically active derivative of P450arom suitable for studies designed to explore the relationship of function to structure.


Evidence of carrier mediated transport of ascorbic acid through mammalian cornea.
The purpose of the present study was to evaluate the transport of ascorbic acid, a water soluble molecule, through a predominantly lipophilic cornea. Thus in-vitro permeation of ascorbic acid from aqueous drops through freshly excised mammalian cornea was studied. Aqueous isotonic ophthalmic solutions of ascorbic acid of different concentrations (0.125% w/v to 2% w/v) (pH 5.4) were made. Further 1.0% w/v or 0.5% w/v ascorbic acid solution containing NaCl or dextrose as tonicity modifiers or Na(+)K(+)-ATPase inhibitors were also made. Permeation characteristics of drug were evaluated by putting 1 ml formulation on freshly excised cornea fixed between donor and receptor compartments of an all-glass modified Franz diffusion cell and measuring the drug permeated in the receptor by spectrophotometry at 265 nm, after 120 min. Statistical analysis was done by one-way analysis of variance (ANOVA) followed by Dunnett's test or paired t-test. Increase in drug concentration in the formulation resulted in an increase in the quantity permeated but after a certain level increase in permeation with increase in concentration was minimal. Aqueous drops made isotonic with dextrose showed decreased permeation through paired cornea compared with aqueous drops made isotonic with NaCl from 1% w/v ascorbic acid solution suggesting likely involvement of Na(+) co-transporter but there was decreased permeation through 0.5% w/v ascorbic acid solution made isotonic with NaCl as compared to solution made isotonic with dextrose. Further aqueous drops containing Na(+)K(+)-ATPase inhibitor {MAG-Mono Ammonium Glycyrrhizinate (25 μmol)} showed decreased corneal permeation from 0.5% w/v ascorbic acid solution but there was not significant decrease from 1% ascorbic acid solution since MAG is a competitive inhibitor of ascorbic acid. Aqueous drops containing Na(+)K(+)-ATPase inhibitor {MAG (50 μmol) or Ouabain (1 mmol)} showed decreased corneal permeation of ascorbic acid compared with control from 1% ascorbic acid solution confirming the involvement of Na(+) co-transporter.


Characterization of vaginal lactobacilli in women after kidney transplantation.
Limited number of publications described vaginal microflora after kidney transplantation. Our PubMed search revealed only 18 publications including words "vaginal bacteria & kidney transplant" in the period of 1978-2011. The aim of this study was to characterize lactobacilli isolated from vaginal swabs of women after kidney transplantation, compared with healthy women. Eighteen renal transplant recipients (mean age 36.1) and 20 healthy women (mean age 36.0) were evaluated. Lactobacilli were cultured on MRS and Columbia blood agars. Biochemical identification with API 50 CHL (bioMerieux, Marcy L'Etoile, France) and multiplex PCR according to Song et al. was performed. Lactobacilli were tested for production of H(2)O(2). Minimal inhibitory concentrations (MICs) of selected antimicrobial agents were determined with E-tests (bioMerieux, Marcy L'Etoile, France) and interpreted with CLSI and EUCAST criteria. No bacterial vaginosis was found among studied women. Two strains of group I were identified as Lactobacillus delbrueckii; 18 strains as Lactobacillus gasseri and 15 strains as Lactobacillus crispatus. Only 3 strains from group II were not identified by species-specific mPCR. Group IV was represented with 2 unidentified strains. Vaginal lactobacilli isolated from healthy women represented more homogenous group compared with heterogenous renal transplant recipients. Biochemical identification of lactobacilli by API 50 CHL kits was concordant with mPCR results only in 7 cases (17.5%), all 7 strains were identified as L. crispatus. Majority (93%) of lactobacilli were H(2)O(2) producers. All isolated lactobacilli (100%) demonstrated high resistance to metronidazole (MIC > 256 μg/ml). Only 2 strains resistant to vancomycin (MICs: 32 and 256 μg/ml respectively), in the study and control group, and one to moxifloxacin (MIC = 32 μg/ml), were found. Resistance to metronidazole and vancomycin was concordant in CLSI and EUCAST (2010) criteria. Although significant differences between lactobacilli isolated from vaginas of kidney transplant and healthy women were not demonstrated, we demonstrated strains resistant to metronidazole, vancomycin and moxifloxacin in groups of examined women. Our study was performed on a small group of kidney transplant recipients and further more detailed molecular studies on a larger group of patients are required to confirm our results.


Capsaicin and menthol in the treatment of itch and pain: recently cloned receptors provide the key.
Topical capsaicin is reported to be an effective treatment for idiopathic intractable pruritus ani. While both capsaicin and menthol application produce a transient perianal burning sensation, only capsaicin relieves itching. Classical observations on functional desensitisation of nociceptors by capsaicin may explain the beneficial effects but the recent discovery of a range of receptors which respond to capsaicin, menthol, and temperature, and their expression in subsets of sensory nerve fibres, provides an exciting prospect towards advancing our understanding and treatment of sensory dysfunction.


Effects of body mass index on IVF outcomes in different age groups.
Herein, we aimed to analyse the effects of body mass index (BMI) on the treatment outcomes of in vitro fertilisation (IVF) in a cohort of women undergoing their first IVF cycle. A total of 2311 cycles from 986 women undergoing their first IVF/intracytoplasmic sperm injection cycle with fresh/frozen embryo transfer between January 2018 and December 2021 at the Center of Reproductive Medicine, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, were considered in this retrospective cohort study. First, the included patients were classified into four groups based on their BMI: underweight (BMI < 18.5 kg/m2, 78 patients), normal weight (18.5 ≤ BMI < 24 kg/m2, 721patients), overweight (24 ≤ BMI < 28 kg/m2, 147 patients), and obese (BMI ≥ 28 kg/m2, 40 patients). The IVF outcomes included the Gn medication days; Gn dosage; number of retrieved oocytes, mature oocytes, fertilized oocytes, cleavages, and available embryos and high-quality embryos; implantation rate; clinical pregnancy rate and live birth rate. Next, all the obtained data were segregated into three different subgroups according to the patient age: < 30 years, 30-38 years and > 38 years; the IVF pregnancy outcomes were compared among the groups. Compared with the other three groups, the underweight group had a higher number of fertilized oocytes, cleavage and available embryos and a smaller Gn medication days and required a lower Gn dosage. There was no difference in the number of retrieved oocytes and mature oocytes among the groups. Moreover, compared with the women aged 30-38 years in the overweight group, those in the normal weight group had a significantly higher implantation rate, clinical pregnancy rate and live birth rate (p = 0.013 OR 1.75, p = 0.033 OR 1.735, p = 0.020 OR 1.252 respectively). The clinical pregnancy rate was also significantly higher in those aged 30-38 years in the normal weight group than in the obese group (p = 0.036 OR 4.236). Although the BMI can greatly affect the pregnancy outcomes of women aged 30-38 years, it has almost no effects on the outcomes of younger or older women.


Early and long-term results of arthroscopic treatment for shoulder stiffness.
We evaluated the efficacy of arthroscopic treatment in 42 patients with shoulder stiffness. Of 44 stiff shoulders, 30 were classified as primary idiopathic, 7 were classified as traumatic, 4 occurred after prolonged immobilization, and 3 occurred in diabetic patients. Similar intraarticular findings were made in all cases. Bursoscopy suggested subacromial impingement in one third of the patients; they underwent not only capsular release but also subacromial decompression. Gains in motion and the Japanese Orthopaedic Association score were statistically significant at 4 weeks after operation and at a mean follow-up of 7.5 years. The results at the latest follow-up were excellent in 37 shoulders (84%), good in 3 (7%), and poor in 4 (9%). Of the 4 poor results, 2 were in patients with traumatic injury, 1 in a diabetic patient, and 1 in a primary idiopathic patient. There were no complications related to the arthroscopic procedure. Our treatment combines fast recovery with long-term efficacy.


Comparative effectiveness of Ginkgo injections for treating vertebrobasilar insufficiency: A systematic review and network meta-analysis.
This study sought to assess the clinical effectiveness of Ginkgo injections (GIs) combined with conventional drugs for vertebrobasilar insufficiency (VBI). Randomized controlled trials (RCTs) that assessed the adjunctive effects of GIs for patients with VBI were retrieved from several English and Chinese databases from inception to December 2018. The Cochrane risk of bias method was used to evaluate the methodological quality of the eligible trials. The data were analysed by Stata 13.0 and WinBUGS 1.4.3 software. A total of 20 RCTs that included 1710 patients were included. All RCTs had an unclear risk of bias or a high risk of bias. The network meta-analysis (NMA) showed that the use of four kinds of GIs, especially Ginkgo leaf extract and dipyridamole injections (GDs), as adjunctive therapies with drugs for VBI increased the total effectiveness rate. Ginkgo biloba leaf extract injections (EGbs) combined with conventional drugs were more effective than only conventional drugs for improving the results of transcranial Doppler ultrasonography (TCD). Shuxuening injections (SXNs) seemed superior for improving blood viscosity-related indicators. Adverse events were mentioned in nine trials, and there was no difference between the GI group and the control group for the incidence rate of adverse events. GIs showed significant benefits as an add-on therapy for VBI, as GIs increased the total effectiveness rate and improved the results of TCD examinations. Due to the limited sample size and quality of the included trials, the results of this review still need to be tested in larger, rigorous studies in the future.


Immunohistochemical demonstration of Leu-7 (HNK-1), Neurone-specific Enolase (NSE) and Protein-Gene Peptide (PGP) 9.5 in the developing camel (Camelus dromedarius) heart.
The development of the heart-conducting system has been controversially discussed. The common opinion that these specialized myocytes originate from mesodermal precursors has been challenged when nerve-specific antigens (Leu-7, NF, GIN2) were demonstrated in embryonic hearts of various species, suggesting a neural crest contribution to the embryonic conducting tissue. Anti-Leu-7 (HNK-1) antibodies were reported to reliably mark the conducting system in developing rat, chicken and human hearts. The present investigation was carried out on the hearts of 15 camel fetuses at 35, 45, 60, 75 and 100 cm crown-rump length (three specimens for each stage), in addition to three adult hearts. We investigated the antigenicity of cardiac structures for Leu-7, NSE (Neurone specific Enolase) and PGP (Protein Gene Peptide) 9.5. In all specimens investigated, both NSE and PGP 9.5 were expressed by cardiac nerves and conducting system components. The sinuatrial and atrioventricular nodes, the atrioventricular bundle as well as subendocardial and intramyocardial Purkinje fibers were stained. In contrast, the developing conducting system did not react with anti-Leu-7 antibody, although Leu-7 antigenicity was strongly expressed by the developing cardiac nerves. In adult camel hearts, the same pattern of immunoreactivity for the markers studied was still retained. Our results show that the expression of marker proteins for the developing conducting system is species-specific. Therefore, these markers are of little significance in discussions on the possible neurogenic nature of the heart conducting tissue.


Assessing psychological distress in patients with facial paralysis using the Hospital Anxiety and Depression Scale.
Anxiety and depression are seen among patients with facial paralysis (FP), but less is known about the exact prevalence. The aim of the current study is to assess the prevalence of anxiety and depressive disorders in the FP population and to investigate possible differences between patients with left- and right-sided FP. Fifty-nine patients with FP and 59 healthy individuals were included in this study between March and December of 2014. The Hospital Anxiety and Depression Scale was used to assess the prevalence of anxiety and depression among these groups. The mean age of the patients and controls was 56 ± 15 and 40 ± 16 years, respectively. Twenty-eight patients had left-sided FP, 30 patients had right-sided FP, and one patient had bilateral FP. In the patient group, approximately 30% had anxiety and 25% had a depressive disorder. Compared with the control group, significantly more patients presented with mild anxiety (p = 0.031), mild depression (p = 0.047), and moderate depression (p = 0.006). No significant differences were found in terms of the prevalence of anxiety between left- and right-sided FP. However, significantly more patients with left-sided FP had mild depression (p = 0.018) than those with right-sided FP. This study found a significant difference in anxiety and depression between patients with FP and healthy controls. No clinically significant difference was noted in the prevalence of anxiety or depression between patients with left- and right-sided FP.


Effects of acute administration or chronic ethanol ingestion on sexual organs monoamine levels in male rats.
1. Acute or chronic treatment with ethanol modify the monoamine levels in epididymis (body, tail) and prostate, without changes in head epididymis and seminal vesicle of male rats. 2. The prostate seems to be the most affected in acute treatment while the epididymis body is altered after prolonged exposure to ethanol.


Real time PCR using TaqMan and SYBR Green for detection of Enterobacter sakazakii in infant formula.
Enterobacter sakazakii is an emerging pathogen that causes meningitis, bacteremia, sepsis, and necrotizing enterocolitis in neonates and children. Powdered milk-based infant formulas have been associated with the E. sakazakii-related outbreaks in premature or other immunocompromised infants. In this study, we developed two real time PCR assays using TaqMan and SYBR Green to identify the pathogen after selective enrichment in mLST and BHI. The accuracy of two detections was tested by 35 strains of E. sakazakii and 88 non-E. sakazakii bacterial strains. The results showed that all of these E. sakazakii strains were positive reaction to the detections and all of the non-E. sakazakii strains were negative. The newly developed assays enable us to detect 1.1 CFU/100 g infant formula. And both of the assays can be accomplished within 2 business days. Compared to the traditional detection, the real time PCR procedures are quicker and simpler. In this study, we also developed a new method to design the primers, which can support multiple real time PCR with one pair of primers in SYBR Green detection. The detection methods are more sensitive and effective based on Two-Tm-Value of PCR.


[Temporality in nursing research: a metronome for the benefit of quality?]
Time is a key element of the nursing research process, notably because it is lacking in daily life and is subject to strict regulations. Engage in a nursing research project thereby forces the researcher to review the time available, to rethink nursing practice. It can therefore prove to be a useful tool in the organisation of are and the improvement of practices.


Can pepsin immunohistochemical staining of laryngeal lesions accurately diagnose non-acid laryngeal reflux?
Non-acid reflux is the most common form of laryngopharyngeal reflux (LPR). However, the damage caused by non-acid reflux to the laryngeal mucosa is weaker than that caused by acid reflux. To evaluate whether pepsin immunohistochemical (IHC) staining of laryngeal lesions can accurately diagnose acidic and non-acidic LPR. Hypopharyngeal-esophageal multichannel intraluminal impedance-pH monitoring was performed, and the patients were divided into acid reflux and non-acid reflux groups. Pathological sections of laryngeal lesions were examined using pepsin IHC staining, which was positive when pepsin was detected in the cytoplasm. The study included 136 patients, with 58 in the acid reflux group, 43 in the non-acid reflux group, and 35 in the without reflux group. There were no significant differences in the positive rate of pepsin IHC staining between the non-acid and acid reflux groups (p = .421). The sensitivity of pepsin IHC staining for the diagnosis of acid and non-acid reflux was 94.8% and 90.7%, respectively. The sensitivity of pepsin IHC staining for laryngeal lesions in the diagnosis of non-acidic LPR is satisfactory. Pepsin IHC staining is suitable for LPR screening of patients with laryngeal lesions as it is economical, non-invasive, and highly sensitive.


The dynamics of social support and affective well-being before and during COVID: An experience sampling study.
Based on the dynamic motivational activation (DMA) theoretical framework, this study examines the dynamic, reciprocal relationship between social support and affective well-being in both face-to-face (F2F) and online channels before and during the COVID-19 pandemic. Using experience sampling method, 2002 surveys on F2F and online interactions were collected from 64 participants. Dynamic panel modeling results showed that emotional support was associated with lower emotional discomfort toward F2F and online social interactions. Then, the emotional discomfort toward the F2F interactions drove the subsequent pursuit of emotional support, practical support, and informational support on the online channels. Additionally, findings suggested that individuals were more likely to obtain informational support via F2F communication after experiencing stronger emotional discomfort online during the pandemic.


Bacterial induction of proinflammatory cytokines in inflammatory bowel disease.
It has become increasingly clear that inflammatory bowel disease (IBD) develops on the background of genetic defects in the host, conveying an increased susceptibility to an environmental antigen or antigens. The environmental factor implicated in the pathophysiology of gut inflammation, which is undergoing increased scrutiny, is the intestinal flora. The intestinal flora as a whole and specific bacteria and their products have been found to trigger cytokine expression in various cell types. Consistently, multiple bacterial strains were found to induce tumor necrosis factor alpha (TNF-α) and interleukin-8 (IL-8) in macrophage and epithelial cell systems, respectively, in particular in Crohn's disease. Interestingly, various cell types from patients with IBD display an increased susceptibility to specific bacterial products, including flagellin, pili, and lipopolysaccharides. It remains to be determined whether additional effector proteins regulate cytokine expression and the aberrant mucosal immune response in IBD.


Schwannoma of external auditory canal.
Schwannomas of the external auditory canal are extremely rare and only a few cases have been reported in the literature. Herein, we report a case of schwannoma of the external ear canal in a 41-year male. Clinicians should consider the possibility that the schwannoma may originate in the external auditory canal mimicking other more frequently observed lesions.


Laparoscopic Promontohysteropexy During Pregnancy.
To present a case of uterine prolapse in a pregnant patient at 10 weeks of gestation who was successfully treated by laparoscopic promontohysteropexy. To our knowledge, this is the first case of laparoscopic promontopexy during pregnancy to be reported in the literature. Step-by-step description of the surgery using videos (Canadian Task Force classification 3). Uterine prolapse is a rare condition in young patients and is extremely rare in pregnant women. The reported incidence of uterine prolapse during pregnancy is 1/10,000 to 15,000 deliveries [1]. To date, only a few cases of prolapse during pregnancy have reported in the literature, most of which were treated with pessary insertion. A case involving laparoscopic surgery for uterine prolapse during pregnancy was reported by Matsumoto et al 1999 [2], but the authors did not perform the promontohysteropexy technique. A 27-year-old patient with uterine prolapse at 10 weeks of gestation was referred to our clinic for severe pelvic pain. Conservative treatment with pessary insertion was attempted but failed. Consequently, the patient was scheduled for laparoscopic promontohysteropexy. The surgery was made difficult by the increased size and softness of the uterus. To create an adequate surgical field, the sigmoid colon and right adnexa were suspended at the abdominal wall. The peritoneum above the promontorium was incised, and the longitudinal ligament was dissected. The paravesical spaces were opened, and the vesicovaginal space was dissected. A polypropylene mesh in the shape of an inverted "T" was introduced. The small arm was sutured to the anterior vaginal wall, and the posterior arms were passed through the posterior leaves of the broad ligament and fixed to the cervix at the level of the uterosacral ligaments. Both posterior arms were fixed at the level of the promontory using the Protack device (Medtronic, Minneapolis, MN). The mesh was completely covered with peritoneum. The patient was discharged 3 days after surgery, with no pain and with normal pelvic floor status. The pregnancy proceeded uneventfully, and she delivered a 3500-g healthy baby by scheduled cesarean section at 39 weeks of gestation. During surgery, the position of the mesh around the uterus was assessed. The mesh was completely covered with peritoneum, and there were no adhesions due to mesh insertion. At 6 months after delivery, pelvic floor status was reassessed and found to be normal. Written informed consent for reporting this case was obtained from the patient before the procedure. The procedure was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. The Institutional Review Board and Ethical Committee of Victor Babeş University of Medicine and Pharmacy ruled that approval was not required for this study. Laparoscopic promontohysteropxy can be performed during pregnancy if conservative treatment, such as pessary insertion, fails to restore the normal pelvic floor status.


[Preparation of hyperimmune horse serum against Ebola virus].
Immunization of horses with Ebola virus resulted in production of specific virus-neutralizing antibodies with their maximal level attained on days 28 to 42 postimmunization. Repeated cycles of immunization lead to increase of antibodies titer to 1:4096.


Reversal by glucocorticoid hormones of the loss of a fibronectin and probollagen matrix around transformed human cells.
Confluent cultured human skin fibroblasts had an extracellular fibrillar matrix of fibronectin and procollagen. Human skin fibroblasts transformed by SV40 did not have such a matrix. Treatment of transformed fibroblasts with 10(-5) to 10(-8) M dexamethasone and 10(-5) to 10(-7) M cortisol, but not testosterone or progesterone, caused partial restoration of the matrix. Glucocorticoid-treated transformed human fibroblasts can serve as a model for partial reversion toward normal or differentiation of transformed human fibroblasts.


Stenting of the proximal colon in patients with malignant large bowel obstruction: techniques and outcomes.
Self-expandable metal stents are used throughout the GI tract to relieve malignant obstructions. Our purpose was to determine the outcome after colonic stent placement into the proximal colon. Medical records of patients from 3 institutions who underwent attempts at placement of self-expandable metal stents for malignant obstructions of the proximal colon were retrospectively reviewed. Extracted data included patient characteristics, obstruction location, and goal of procedure (palliation vs bridge to surgery). Academic medial centers. Those with right-sided malignant colonic obstruction. Placement of colonic stent. Initial technical success, relief of obstruction, and early and long-term complications. Twenty-one patients (15 men, 6 women; mean age 67 years) were included. Tumor type was colonic adenocarcinoma in 19 patients. Obstruction was complete in 8 patients and subtotal in 13 patients. Stenting was attempted as a bridge to surgery in 8 patients and as palliation in 13 patients. Initial technical success was achieved in 20 of 21 patients (95%). Complete relief of obstruction was achieved in 17 of 20 patients who had technical success (85%), unachieved in 2 patients (No. 14 and 17), and unknown in 1 patient (No. 6). There were no procedure-related complications (bleeding, perforation, etc). The only long-term complication was stent reocclusion from tumor ingrowth. Retrospective, single-arm analysis. Self-expandable metal stents appear to be safe and effective in the treatment of malignant obstruction of the proximal colon. Technical and clinical success rates are comparable to those seen with distal colonic stenting.


Data from the European registry for patients with McArdle disease and other muscle glycogenoses (EUROMAC).
The European registry for patients with McArdle disease and other muscle glycogenoses (EUROMAC) was launched to register rare muscle glycogenoses in Europe, to facilitate recruitment for research trials and to learn about the phenotypes and disseminate knowledge about the diseases through workshops and websites. A network of twenty full and collaborating partners from eight European countries and the US contributed data on rare muscle glycogenosis in the EUROMAC registry. After approximately 3 years of data collection, the data in the registry was analysed. Of 282 patients with confirmed diagnoses of muscle glycogenosis, 269 had McArdle disease. New phenotypic features of McArdle disease were suggested, including a higher frequency (51.4%) of fixed weakness than reported before, normal CK values in a minority of patients (6.8%), ptosis in 8 patients, body mass index above background population and number of comorbidities with a higher frequency than in the background population (hypothyroidism, coronary heart disease). The EUROMAC project and registry have provided insight into new phenotypic features of McArdle disease and the variety of co-comorbidities affecting people with McArdle disease. This should lead to better management of these disorders in the future, including controlling weight, and preventive screening for thyroid and coronary artery diseases, as well as physical examination with attention on occurrence of ptosis and fixed muscle weakness. Normal serum creatine kinase in a minority of patients stresses the need to not discard a diagnosis of McArdle disease even though creatine kinase is normal and episodes of myoglobinuria are absent.


Cosmological tests of general relativity.
General relativity theory could be tested on a cosmological scale by measuring the Hubble constant and the deceleration parameter, if, in addition, everything could be known about the matter filling the universe. If, on the other hand, nothing could be presupposed about the matter content of the universe, general relativity could not be tested by measuring any number of time derivatives of the scale factor. But upon making the assumption of a universe filled with a non-interacting mixture of non-relativistic matter and radiation we can in principle test general relativity by measuring the first five derivatives of the scale factor. In the following, some general relations are presented using this assumption.


Propranolol toxicity presenting with early repolarization, ST segment elevation, and peaked T waves on the ECG.
A 58-year-old man presented stating that he had voluntarily ingested eight 80-mg propranolol tablets in approximately 24 hours. He was asymptomatic at the time of presentation. Subsequently, the patient developed only mild bradycardia. The ECG showed sinus bradycardia with striking early repolarization, ST segment elevation, and peaked T waves. These ECG abnormalities represent an unusual pattern for beta-adrenergic blocking agent toxicity.


Artificial intelligence in clinical and genomic diagnostics.
Artificial intelligence (AI) is the development of computer systems that are able to perform tasks that normally require human intelligence. Advances in AI software and hardware, especially deep learning algorithms and the graphics processing units (GPUs) that power their training, have led to a recent and rapidly increasing interest in medical AI applications. In clinical diagnostics, AI-based computer vision approaches are poised to revolutionize image-based diagnostics, while other AI subtypes have begun to show similar promise in various diagnostic modalities. In some areas, such as clinical genomics, a specific type of AI algorithm known as deep learning is used to process large and complex genomic datasets. In this review, we first summarize the main classes of problems that AI systems are well suited to solve and describe the clinical diagnostic tasks that benefit from these solutions. Next, we focus on emerging methods for specific tasks in clinical genomics, including variant calling, genome annotation and variant classification, and phenotype-to-genotype correspondence. Finally, we end with a discussion on the future potential of AI in individualized medicine applications, especially for risk prediction in common complex diseases, and the challenges, limitations, and biases that must be carefully addressed for the successful deployment of AI in medical applications, particularly those utilizing human genetics and genomics data.


Biomechanical performance of short and long cephalomedullary nail constructs for stabilizing different levels of subtrochanteric fracture.
The aim of this study was to assess biomechanical performance of short and long Cephalomedullary nail constructs consisting of different number of distal screw for stabilizing different levels of subtrochanteric fracture. The femur obtained from computed tomography scanner was used to create a transverse fracture at 15 mm (level A), 35 mm (level B), and 55 mm (level C) below the lesser trochanter. Short and long Cephalomedullary nails were virtually inserted to the fractured femur. Four-node tetrahedral element was used to build up finite element (FE) models for biomechanical analysis. The analysis focused on post-operative stage of partial weight-bearing. Stress on the implant localized at the surface between lag screw/nail and distal screw/nail. Short Cephalomedullary nail exhibited higher stress than long Cephalomedullary nail. The stress in short Cephalomedullary nail could be reduced by using two distal screws fixation and the fracture at level A produced less stress than that of level B and C. Either short or long nail with two distal screws is sufficient to withstand the stress magnitude produced from the physiologic load. When single dynamic distal screw was used, stress on implant, elastic strain at fracture gap, and bone stress reached the high values. Elastic strain of the fracture gap at level C were less than that of level A and B, but no statistically significant difference. There was no proximal cancellous bone damage observed from the FE analysis. Long Cephalomedullary nail with at least two distal locking screws remains a proper implant for subtrochanteric fracture fixation in overall locations. However, short Cephalomedullary nail with two distal screws may be a candidate for a high subtrochanteric fracture. Single dynamic screw insertion is strongly not recommended with either short or long nail regarding implant failure.


Apple peel deformity of the small bowel without atresia in a congenital mesenteric defect.
Congenital mesenteric defects are rare causes of bowel obstruction. Even rarer are mesenteric defects with an apple peel type of deformity, probably described definitively only once previously. We present a case of a 3 year old boy who presented with a septic-like picture of severe metabolic acidosis and lethargy from a bowel obstruction with bowel ischemia. At laparotomy he was found to have bowel infarction due to herniation through a congenital mesenteric defect with an apple peel type of deformity of the bowel without bowel atresia.


Accuracy of KinectOne to quantify kinematics of the upper body.
Motion analysis systems deliver quantitative information, e.g. on the progress of rehabilitation programs aimed at improving range of motion. Markerless systems are of interest for clinical application because they are low-cost and easy to use. The first generation of the Kinect™ sensor showed promising results in validity assessment compared to an established marker-based system. However, no literature is available on the validity of the new 'Kinect™ for Xbox one' (KinectOne) in tracking upper body motion. Consequently, this study was conducted to analyze the accuracy and reliability of the KinectOne in tracking upper body motion. Twenty subjects performed shoulder abduction in frontal and scapula plane, flexion, external rotation and horizontal flexion in two conditions (sitting and standing). Arm and trunk motion were analyzed using the KinectOne and compared to a marker-based system. Comparisons were made using Bland Altman statistics and Coefficient of Multiple Correlation. On average, differences between systems of 3.9±4.0° and 0.1±3.8° were found for arm and trunk motion, respectively. Correlation was higher for the arm than for the trunk motion. Based on the observed bias, the accuracy of the KinectOne was found to be adequate to measure arm motion in a clinical setting. Although trunk motion showed a very low absolute bias between the two systems, the KinectOne was not able to track small changes over time. Before the KinectOne can find clinical application, further research is required analyzing whether validity can be improved using a customized tracking algorithm or other sensor placement, and to analyze test-retest reliability.


Prevalence of outsourcing and perception of clinical nutrition managers on performance of health care dietetics services.
A nationwide survey of clinical dietitians and clinical nutrition managers was conducted to assess the prevalence of outsourcing in health care dietetics services and to evaluate perceived performance of dietetics services. A questionnaire was developed, validated by an expert panel, and pilot tested prior to data collection. Members of the Clinical Nutrition Management Dietetic Practice Group (N=1,668) were selected as the study sample. Of 431 respondents, 152 (35.3%) indicated that management of both patient and cafeteria foodservices was outsourced. When mean scores of perceived performance ratings were compared using t test, respondents from self-operated facilities rated several items related to patient and cafeteria food quality and material and human resource utilization higher than respondents at contract-managed facilities. No significant differences were found in performance related to decision-making process, buying power, or training programs. Results suggest that careful weighing of advantages and disadvantages of outsourcing is needed before making decisions regarding outsourcing dietetics services.


The evolving role of immune cells in prostate cancer.
Prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer-related death among men in western countries. Androgen deprivation therapy (ADT) is considered the standard therapy for recurrent prostate cancer; however, this therapy may lead to ADT resistance and tumor progression, which seems to be regulated by epithelial-mesenchymal transition (EMT) and/or neuroendocrine differentiation (NED). In addition, recent data suggested the involvement of either adaptive or innate infiltrated immune cells in the initiation, progression, metastasis, and treatment of prostate cancer. In this review, we outlined the characteristics and roles of these immune cells in the initiation, progression, metastasis, and treatments of prostate cancer. We also summarized the current therapeutic strategies in targeting immune cells of the prostate tumor microenvironment.


Establishing a physician's office laboratory.
Practical approaches to setting up or expanding a physician's office laboratory, either independently or with the assistance of a laboratory consultant, are provided. Ways to assess the issues that may determine the success of an office laboratory are reviewed, including physical features, personnel training, methods or instruments, and the importance of documentation.


Clinical utility of a Web-enabled risk-assessment and clinical decision support program.
Risk-stratified guidelines can improve quality of care and cost-effectiveness, but their uptake in primary care has been limited. MeTree, a Web-based, patient-facing risk-assessment and clinical decision support tool, is designed to facilitate uptake of risk-stratified guidelines. A hybrid implementation-effectiveness trial of three clinics (two intervention, one control). consentable nonadopted adults with upcoming appointments. agreement between patient risk level and risk management for those meeting evidence-based criteria for increased-risk risk-management strategies (increased risk) and those who do not (average risk) before MeTree and after. chart abstraction was used to identify risk management related to colon, breast, and ovarian cancer, hereditary cancer, and thrombosis. Participants = 488, female = 284 (58.2%), white = 411 (85.7%), mean age = 58.7 (SD = 12.3). Agreement between risk management and risk level for all conditions for each participant, except for colon cancer, which was limited to those <50 years of age, was (i) 1.1% (N = 2/174) for the increased-risk group before MeTree and 16.1% (N = 28/174) after and (ii) 99.2% (N = 2,125/2,142) for the average-risk group before MeTree and 99.5% (N = 2,131/2,142) after. Of those receiving increased-risk risk-management strategies at baseline, 10.5% (N = 2/19) met criteria for increased risk. After MeTree, 80.7% (N = 46/57) met criteria. MeTree integration into primary care can improve uptake of risk-stratified guidelines and potentially reduce "overuse" and "underuse" of increased-risk services.Genet Med 18 10, 1020-1028.


The antitumor effect of oncolytic respiratory syncytial virus via the tumor necrosis factor-alpha induction and ROS-bax-mediated mechanisms.
Cervical cancer represents one of the most prevalent cancers among women worldwide, particularly in low- and middle-income nations. Oncolytic viruses (OVs) can infect cancer cells selectively and lethally without harming normal cells. Respiratory syncytial virus (RSV) is an oncolytic virus for anticancer therapy because of its propensity to multiply within tumor cells. This research aimed to assess the in vitro antitumor activities and molecular basis processes of the oncolytic RSV-A2 on the TC-1 cancer cells as a model for HPV‑related cervical cancers. Cellular proliferation (MTT) and lactate dehydrogenase (LDH) release assays were used to investigate the catalytic impacts of RSV-A2 by the ELISA method. Real-time PCR and flow cytometry assays were utilized to assess apoptosis, autophagy, intracellular concentrations of reactive oxygen species (ROS), and cell cycle inhibition. Our MTT and LDH results demonstrated that TC-1 cell viability after oncolytic RSV-A2 treatment was MOI-dependently and altered significantly with increasing RSV-A2 virus multiplicity of infection (MOI). Other findings showed that the RSV-A2 potentially resulted in apoptosis and autophagy induction, caspase-3 activation, ROS generation, and cell cycle inhibition in the TC-1 cell line. Real-time PCR assay revealed that RSV-A2 infection significantly elevated the Bax and decreased the Bcl2 expression. The results indicated that oncolytic RSV-A2 has cytotoxic and inhibiting effects on HPV-associated cervical cancer cells. Our findings revealed that RSV-A2 is a promising treatment candidate for cervical cancer.


Types and outcomes of pharmacist-managed travel health services: A systematic review.
Pharmacists have an important role in providing travel health services and medications to travelers. However, given the limited literature on this topic, the aim of this study is to systematically review the types and outcomes of pharmacist-managed travel health services. A comprehensive literature search was performed in four electronic databases, namely Scopus, Web of Science, PubMed and ProQuest to identify studies published in English from 1999 to July 2022. The inclusion criteria included the studies that reported an experience of providing dedicated travel health services by pharmacists and reported the outcomes and/or evaluation of these travel health services. Nine studies were identified from the literature and included in the review. The pharmacists have provided a wide range of general and specialized travel health services including pre-travel risk assessment, routine and travel-related vaccination service, prescribing or recommending medications for travel-related illnesses, counseling and travel health advice. Overall, 94-100% of the patients were satisfied or very satisfied with pharmacist-managed travel health services. In addition, a good acceptance rate of pharmacist recommendations for vaccines and travel-related mediations was reported with most studies reporting an overall acceptance rate of ≥75% (acceptance rate range: 48%-94.2%). In addition, high rates of acceptance of other nonpharmacological advices were noted. Pharmacists with training in travel medicine have successfully provided a wide range of general and specialized travel health services. Most travelers were highly satisfied with the pharmacy-based travel health services and accepted the pharmacist recommendations.


Interdependent nuclear accumulation of budding yeast Cdt1 and Mcm2-7 during G1 phase.
Cdt1 is essential for loading Mcm2-7 proteins into prereplicative complexes (pre-RCs) during replication licensing and has been found in organisms as diverse as fission yeast and humans. We have identified a homologue of Cdt1 in Saccharomyces cerevisiae, which is required for pre-RC assembly. We show that, like Mcm2-7p, Cdt1p accumulates in the nucleus during G1 phase and is excluded from the nucleus later in the cell cycle by cyclin dependent kinases (cdks). Cdt1p interacts with the Mcm2--7p complex, and the nuclear accumulation of these proteins during G1 is interdependent. This coregulation of Cdt1p and Mcm2-7p represents a novel level of pre-RC control.


Identification of allergens in a selected group of asthmatics in Lebanon.
Anti-allergen antibodies were searched for by an Enzyme Immunoassay in the sera obtained from 60 patients with a clinical diagnosis of asthma. Allergic rhinitis was also present in 28 patients. The diagnosis of asthma was based on clinical criteria that include history and clinical evidence of airflow obstruction. Ten potential allergens (Bermuda grass, Olive tree, Parietaria, Alternaria, Cat hair dander, Dog hair dander, Mite DPT, Mugwort, Birch tree and Timothy grass) common to the Mediterranean area, were utilized. Twenty-five of 60 specimens were seropositive. Mite DPT was the allergen identified in 16 of the 25 seropositive specimens. Six of the 25 seropositive specimens reacted with more than one allergen. This may be due to the existence of similar antigenic determinant groups in the allergens used. There was no correlation between the occurrence of rhinitis in addition to asthma on one hand and the identified allergen on the other. Sixteen of the 25 seropositive patients were female. This observation is believed to be related to their occupation. Dog hair dander was identified as the allergen in 1 of the 25 seropositive patients. The low figure obtained was expected because keeping house pets is not a common practice in Lebanon. The 35 seronegative patients may belong to the intrinsic asthma group or the causative allergen in each case was not one of the 10 allergens used in this study. These results indicate that the house dust mite appears to be the most common allergen in the Lebanese asthmatic group studied.


Effects of acute noise traumata on whole-nerve and single-unit activity.
This paper gives some preliminary results of a research program on the effects of noise traumata on cochlear functioning. Measurements reported here include: the latency of the whole-nerve (compound) action potential (AP), the selectivity of frequency-tuning curves (e.g., the Q10-values) measured for the AP (with a forward-masking technique) and for single units in the antero-ventral cochlear nucleus (AVCN), the degree of phase-locking of the action potentials of these units to the stimulus waveform, and the phase of the stimulus waveform to which these potentials are locking. The noise traumata were induced during the experiments. After inducement of the traumata we found: an increase of AP latency, if a sinusoidal stimulas was presented at the same sound pressure level as before the trauma; no effect on AP latency (for most stimulus frequencies), if the latency values measured at the pre- and post-trauma thresholds were compared; a decrease of Q10-values of the AP frequency-tuning curves, (the pre-trauma Q10-values were small in comparison with single nerve fiber data); a decrease of the Q10-values of the single-unit frequency-tuning curves; no effect on the degree of phase-locking of the single-unit potentials to the stimulus waveform; an increase of cochlear response time calculated from the phase of the stimulus waveform to which the single-unit potentials are locking as a function of stimulus frequency.


Cloning and sequencing of the PHO80 gene and CEN15 of Saccharomyces cerevisiae.
The PHO80 gene, which is one of the regulatory genes exerting negative control in the pho system of Saccharomyces cerevisiae, was cloned. The 1.8 kb DNA fragment carrying the PHO80 gene was sequenced and one open reading frame large enough to encode 293 amino acids was found in the sequence. Northern blot analysis of poly(A)+-RNA isolated from cells grown under repressed and derepressed conditions revealed that (i) the size of the PHO80 message was around 1.4 kb, (ii) the expression of the PHO80 gene was not affected by the presence or absence of inorganic phosphate in the medium, and (iii) the expression of the PHO80 gene was not affected by pho2, pho4, pho81, or by pho80 itself. A centromere sequence was found downstream of the PHO80 coding region.


[Immunohistochemical study of inflammatory infiltrates in minor salivary glands in Sjögren's syndrome and other autoimmune diseases].
A study of the phenotype, activation and adhesive cells factors and cytokines in minor salivary glands in patients with primary Sjögren's syndrome (pSS), secondary Sjögren's syndrome (sSS) and autoimmune diseases (AD) without Sjögren's syndrome. We have studied the minor salivary glands in 30 patients with pSS, 30 patients with sSS, 19 patients with AD without SS and 18 controls, using immunohistochemical techniques to analyze the molecular expression of CD3, CD4, CD8, CD20, CD25, CD14, CD56, CD11a, CDw50 (ICAM-3), HLA-DR, IL-1, TNF-alpha and IFN-gamma in lymphocytic infiltration and epithelial cells. Phenotype features were similar in patients with pSS and sSS, except that CD20+ lymphocyte expression was significantly higher in the sSS group (p = 0.023). The patients affected by AD without SS had activated lymphocytes in minor salivary glands in a similar manner to patients affected by pSS and sSS. No significant differences were found in HLA-DR expression in epithelial cells. We found unusual CD25 expression in epithelial cells in patients with SS but not in patients with AD without SS. The differences between pSS and sSS are related to SS theoretical time development and to immunosuppressive treatments. The immunohistochemical pattern of minor salivary glands is similar in patients with pSS and sSS. Patients with AD are likely to develop immunological changes in minor salivary glands attributable to activated lymphocytes.


Multimodal Data Integration Advances Longitudinal Prediction of the Naturalistic Course of Depression and Reveals a Multimodal Signature of Remission During 2-Year Follow-up.
The ability to predict the disease course of individuals with major depressive disorder (MDD) is essential for optimal treatment planning. Here, we used a data-driven machine learning approach to assess the predictive value of different sets of biological data (whole-blood proteomics, lipid metabolomics, transcriptomics, genetics), both separately and added to clinical baseline variables, for the longitudinal prediction of 2-year remission status in MDD at the individual-subject level. Prediction models were trained and cross-validated in a sample of 643 patients with current MDD (2-year remission n = 325) and subsequently tested for performance in 161 individuals with MDD (2-year remission n = 82). Proteomics data showed the best unimodal data predictions (area under the receiver operating characteristic curve = 0.68). Adding proteomic to clinical data at baseline significantly improved 2-year MDD remission predictions (area under the receiver operating characteristic curve = 0.63 vs. 0.78, p = .013), while the addition of other omics data to clinical data did not yield significantly improved model performance. Feature importance and enrichment analysis revealed that proteomic analytes were involved in inflammatory response and lipid metabolism, with fibrinogen levels showing the highest variable importance, followed by symptom severity. Machine learning models outperformed psychiatrists' ability to predict 2-year remission status (balanced accuracy = 71% vs. 55%). This study showed the added predictive value of combining proteomic data, but not other omics data, with clinical data for the prediction of 2-year remission status in MDD. Our results reveal a novel multimodal signature of 2-year MDD remission status that shows clinical potential for individual MDD disease course predictions from baseline measurements.


[Morphometric studies of the human placenta under the influence of sex steroids].
Placentas of different gestational age from women with oral contraception in the early phase of gravidity were studied morphometrically. An elevated risk for a placental insufficiency could not be found.


Noninvasive Imaging of CCR2+ Cells in Ischemia-Reperfusion Injury After Lung Transplantation.
Ischemia-reperfusion injury-mediated primary graft dysfunction substantially hampers short- and long-term outcomes after lung transplantation. This condition continues to be diagnosed based on oxygen exchange parameters as well as radiological appearance, and therapeutic strategies are mostly supportive in nature. Identifying patients who may benefit from targeted therapy would therefore be highly desirable. Here, we show that C-C chemokine receptor type 2 (CCR2) expression in murine lung transplant recipients promotes monocyte infiltration into pulmonary grafts and mediates graft dysfunction. We have developed new positron emission tomography imaging agents using a CCR2 binding peptide, ECLi1, that can be used to monitor inflammatory responses after organ transplantation. Both 64 Cu-radiolabeled ECL1i peptide radiotracer (64 Cu-DOTA-ECL1i) and ECL1i-conjugated gold nanoclusters doped with 64 Cu (64 CuAuNCs-ECL1i) showed specific detection of CCR2, which is upregulated during ischemia-reperfusion injury after lung transplantation. Due to its fast pharmacokinetics, 64 Cu-DOTA-ECL1i functioned efficiently for rapid and serial imaging of CCR2. The multivalent 64 CuAuNCs-ECL1i with extended pharmacokinetics is favored for long-term CCR2 detection and potential targeted theranostics. This imaging may be applicable for diagnostic and therapeutic purposes for many immune-mediated diseases.


Plasma levels of secretory IgA in patients with gastric cancer.
The levels of plasma secretory IgA were measured in patients with gastric cancer and found to be slightly higher (9.6 +/- 6.2 micrograms/ml) than those in healthy controls (7.0 +/- 2.6 micrograms/ml, 0.05 less than P less than 0.1). Secretory IgA levels in those with hepatic metastases (19.7 +/- 12.2 micrograms/ml) were significantly higher than those in patients without hepatic metastases (P less than 0.001). In the latter, there was no significant relationship between plasma secretory IgA levels and the deepest layer of cancerous invasion or lymph node metastases. The secretory IgA levels in cases of well differentiated tubular adenocarcinoma were significantly higher than those with poorly differentiated adenocarcinoma (P less than 0.05). Although there is small diagnostic value in the detection of gastric cancer by measuring the levels of secretory IgA, high levels of secretory IgA in gastric cancer patients may be indicative of the presence of hepatic metastases.


Analgesics in the management of chronic pain. Part two: Step I analgesic drug therapy.
This, the second in a series of five articles, reviews the role of simple analgesics and co-analgesia in the treatment of chronic pain. It should be read in conjunction with Part one which covers general principles of pain management.


Prevalence of Streptococcus mutans and dental decay in school children from Siena (Italy).
Epidemiological indexes of dental decay and prevalence of Streptococcus mutans in dental plaque were studied in a group of 255 schoolchildren aged 6-11 from a suburban area near Siena (Italy). Mutans streptococci were isolated from 17.4% of subjects: a significant correlation with dental decay indexes and with the presence of active caries was observed.


Subthreshold Change in Glycated Hemoglobin and Body Mass Index After the Initiation of Second-Generation Antipsychotics Among Patients With Schizophrenia or Bipolar Disorder: A Nationwide Prospective Cohort Study in Japan.
Objective: The risk of diabetes development has been reported to differ among second-generation antipsychotics (SGAs). However, few studies have focused on the subthreshold change in glycated hemoglobin (HbA1c). Therefore, this study examined the subthreshold change in HbA1c and change in body mass index (BMI) 3 months after patients initiated one of 6 SGAs widely prescribed in Japan. Methods: This is a prospective cohort study of patients followed up based on the Japanese blood glucose monitoring guidelines for patients with schizophrenia. We collected eligible patients' demographic data, medication history, blood tests, and weight measurements both at baseline and 3 months after recruitment, between April 2013 and March 2015. In the 378 patients with schizophrenia, schizoaffective disorder, and bipolar disorder based on ICD-10, we compared the subthreshold change in HbA1c and the change in BMI 3 months after antipsychotic initiation by using multivariate regression analysis. Results: The subthreshold change in HbA1c 3 months after initiating blonanserin was significantly lower compared with olanzapine (B = -0.17, 95% CI = -0.31 to -0.04). In addition, the change in BMI 3 months after initiating blonanserin and aripiprazole was significantly lower compared with olanzapine (B = -0.93, 95% CI = -1.74 to -0.12; B = -0.71, 95% CI = -1.30 to -0.12, respectively). Conclusions: This is the first study to clarify the differences in the subthreshold change in HbA1c among SGAs. Our results suggest that blonanserin is likely to be a favorable treatment for patients with high risk of diabetes. Trial Registration: UMIN Clinical Trial Registry identifier: UMIN000009868.


Binding of synthetic sulfated ligands by human splenic galectin 1, a beta-galactoside-binding lectin.
The carbohydrate-binding site of galectin 1, a vertebrate beta-galactoside-binding lectin, has a pronounced specificity for the betaGal(1-->3)- and betaGal(1-->4)GlcNAc sequences. The binding inhibition study reported herein was carried out to determine whether sulfation of saccharides would influence their binding by galectin 1. The presence of 6'-OSO3- on LacNAc greatly reduces the inhibitory potency relative to LacNAc. 3'-OSO3-LacNAc, 3'-OSO3-Galbeta(1-->3)GlcNAc(beta)1-OBzl and 3-OSO3-Galbeta1-OMe are more potent inhibitors than the non-sulfated parent compounds. Surprisingly, 2'-OSO3-LacNAc showed over 40 fold less inhibitory potency relative to LacNAc. Ovarian carcinoma A121 cells were shown to synthesize sulfated macromolecules that bind to galectin 1. Modulation in vivo of saccharide sulfation may lead to modulation of galectin 1 interaction with glycoconjugates; hence, sulfation could play a role in modulating lectin functions.


A classification algorithm based on dynamic ensemble selection to predict mutational patterns of the envelope protein in HIV-infected patients.
Therapeutics against the envelope (Env) proteins of human immunodeficiency virus type 1 (HIV-1) effectively reduce viral loads in patients. However, due to mutations, new therapy-resistant Env variants frequently emerge. The sites of mutations on Env that appear in each patient are considered random and unpredictable. Here we developed an algorithm to estimate for each patient the mutational state of each position based on the mutational state of adjacent positions on the three-dimensional structure of the protein. We developed a dynamic ensemble selection algorithm designated k-best classifiers. It identifies the best classifiers within the neighborhood of a new observation and applies them to predict the variability state of each observation. To evaluate the algorithm, we applied amino acid sequences of Envs from 300 HIV-1-infected individuals (at least six sequences per patient). For each patient, amino acid variability values at all Env positions were mapped onto the three-dimensional structure of the protein. Then, the variability state of each position was estimated by the variability at adjacent positions of the protein. The proposed algorithm showed higher performance than the base learner and a panel of classification algorithms. The mutational state of positions in the high-mannose patch and CD4-binding site of Env, which are targeted by multiple therapeutics, was predicted well. Importantly, the algorithm outperformed other classification techniques for predicting the variability state at multi-position footprints of therapeutics on Env. The proposed algorithm applies a dynamic classifier-scoring approach that increases its performance relative to other classification methods. Better understanding of the spatiotemporal patterns of variability across Env may lead to new treatment strategies that are tailored to the unique mutational patterns of each patient. More generally, we propose the algorithm as a new high-performance dynamic ensemble selection technique.


Primary cardiac lymphoma diagnosed by endomyocardial biopsy using transthoracic echocardiography in the substernal window.
We report a case of a 56-year-old man with a cardiac tumor, which grew and spread rapidly in the right heart. Using transthoracic echocardiography (TTE) in the substernal window, a transvenous biopsy of the tumor was performed safely. The tissue diagnosis revealed a diffuse large B cell lymphoma. After undergoing chemotherapy, the tumor was completely cured and the patient continues to be in good health. A biopsy using TTE in the substernal window may be a useful method to diagnose right-sided extensive tumors.


The primary optic system in a microphthalmic snake (Calabaria reinhardti).
The retinal projections in the microphthalmic snake Calabaria reinhardti were investigated by means of the radioautographic method following intraocular injections of [3H]proline. The results demonstrated the existence of a general pattern of organization of the primary visual system comparable to that observed in macrophthalmic snakes. However, most of the primary optic centers appeared reduced and showed varying signs of atrophy, whereas others were completely absent. Elsewhere, the ipsilateral visual component appeared as well developed as that found in macrophthalmic snakes. The evolutionary significance of the differential microphthalmic pattern of organization of the primary visual system is discussed.