[Follow-up and ultrasound-controlled early treatment of hip dysplasia].
The reliability of ultrasound of the hip is examined by the courses of mature and physiologically immature hips. The results of sonographically controlled therapy of the congenital dysplasia of the hip are investigated. 470 children out of a hip-screening program could be controlled at least one more time clinically and by ultrasound. X-rays were taken at the end of treatment in children who were treated by an abduction device. The sonographical and radiological results were compared and grafically presented. None of 570 matured hips deteriorated. 88% of the physiologically immature hips matured spontaneously while 12% got a cast because of unsatisfactory development. 68 pathological hips improved soon under therapy in an abduction device applied a few days after birth; they reached the borderline of 60 degrees at the maximum age of 80 days. X-ray examinations at the end of therapy showed normal acetabular indices in all cases. Six of 22 girls showed deterioration of the acetabular indices in further x-ray controls at the age of one year. Even in successful therapy of the congenital dysplasia in the newborn hip x-ray examinations are highly recommended to recognize deteriorations and to initiate another therapy if neccessary.


Psychotropic drugs for the management of cancer-related fatigue: a systematic review and meta-analysis.
Cancer-related fatigue (CRF) is a common symptom affecting 60-90% of cancer survivors, and effective management for CRF is not yet available. Recently, an increasing number of trials examining the use of psychotropic drugs for the treatment of CRF have been performed, but these trials have yielded inconsistent results. Therefore, we conducted a meta-analysis aimed at assessing the effect and safety of psychotropic drugs for the management of CRF. Ten eligible trials of the psychotropic drugs methylphenidate and modafinil in a total of 1582 participants treated for CRF were subjected to statistical analyses. A meta-analysis of seven of these studies indicated that methylphenidate was superior to placebo for the treatment of CRF. Another meta-analysis of three studies evaluating modafinil found that this drug was no better than placebo. Adverse events were similar between both methylphenidate and modafinil and the placebo groups. Our meta-analysis indicated that the treatment of CRF with methylphenidate appears to be effective, whereas modafinil provides no benefit. These results of this analysis warrant further trials to confirm the efficacy and safety of psychotropic drugs for the treatment of CRF.


Experimental renal transplantation in rats improves cardiac dysfunction caused by chronic kidney disease while LVH persists.
Chronic kidney disease (CKD) causes congestive heart failure (CHF) with systolic dysfunction and left ventricular hypertrophy (LVH), which is a major contributor to increased mortality in CKD patients. It remains unclear whether cardiovascular changes that occur during the course of CKD can be reversed when renal function is restored by transplantation. To investigate this, chronic kidney disease was established in F344 rats by subtotal nephrectomy (SNx) for 8 weeks, followed by transplantation of a functional kidney from an isogenic F344 donor. SNx rats without transplantation and sham-operated animals served as controls. Renal function was assessed before and throughout the experiment. In addition, cardiac ultrasound was performed at weeks 0, 8, 12 and 16. At the end of the experiment, intra-arterial blood pressure was measured and kidneys and hearts were histologically and molecularly examined. Eight weeks after SNx, rats developed marked renal dysfunction associated with significant glomerulosclerosis and tubulointerstitial fibrosis, but also an increase in left ventricular mass. After transplantation, renal function normalized but relative heart weight and ventricular mass as assessed by ultrasound scans showed no reduction compared with SNx controls. However, left ventricular wall thickness, fractional shortening and ejection fraction was normalized by renal transplantation. At 8 weeks after kidney transplantation, cardiac expression of BNP and FGF23 was also at levels comparable to healthy controls, whereas these factors were significantly increased in SNx rats. Cardiac fibrosis, as measured by fibronectin mRNA expression, was completely normalized, whereas cardiac fibronectin protein was still slightly but not significantly increased in transplanted animals compared to controls. In addition, the myofibroblast marker collagen 1, as assessed by immunohistochemistry, was significantly increased in SNx rats and also normalized by renal transplantation. Interestingly, CD68+ macrophages were significantly reduced in the hearts of SNx rats and in transplanted animals at slightly higher levels compared to controls. Restoration of renal function by kidney transplantation normalized early cardiac changes at most functional and molecular levels, but did not completely reverse LVH. However, further studies are needed to determine whether restoration of renal function can also reverse LVH at a later time point.


Hormone therapy after uterine cervical cancer treatment: a Swedish population-based study.
This study aims to assess use of hormone therapy (HT) after cervical cancer treatment in women of premenopause age. We identified 837 women aged 45 years or younger at diagnosis of cervical cancer in the Swedish Cancer Register from January 1, 2005 to September 30, 2009 with a minimal follow-up of 1.5 years. Information on cancer treatment (surgical operation, radiotherapy, and/or chemotherapy) was obtained through the National Patient Register. Use of HT was estimated through HT dispensing during follow-up as recorded in the Prescribed Drug Register. Percentage of recommended dose was assessed by frequency of HT dispensing at half-year intervals up to April 1, 2011 or a maximal age of 50 years. A total of 257 women (31%) received acute estrogen deprivation due to bilateral salpingo-oophorectomy and/or radiotherapy. Among these women, 171 (67%) of 257 had at least one dispensing of HT during the period 0.5 to 1 year after diagnosis, and 118 (46%) of 257 were dispensed 75% or more of the recommended dose. Proportion users decreased to 39% at 4.5 to 5 years after diagnosis (21% with ≥ 75% of the recommended dose). Women younger than 40 years had a higher prevalence of HT use at 0.5 to 1 year (79%), decreasing to 45% after 4.5 to 5 years. The results did not vary by cancer histology. Fewer than half of cervical cancer survivors with therapy-induced early menopause used HT at or close to the recommended dose, and the use decreased during follow-up. Increased awareness of the health benefits of HT for this patient group is needed among professionals and women.


Periodontal management of gingival enlargement associated with Sturge-Weber syndrome.
The Sturge-Weber syndrome is a rare uncommon neurocutaneous disorders with angiomas involving the leptomeninges (Leptomeningeal Angiomas) and skin of the face, typically in the ophthalmic (V1) and maxillary (V2) distributions of the trigeminal nerve. The cutaneous angioma is called a Port-Wine Stain. It is commonly referred to as "Sturge-Weber syndrome after Sturge and Weber who first described this affliction in 1879. This article present a case of Sturge-Weber syndrome associated with gingival enlargement, its management and follow-up results.


[Long-term results of revisional hip alloplasty using the X-change technique].
In this paper the authors evaluate the long-term results of revisional hip alloplasty using the X-change technique with an Exeter endoprosthesis. This evaluation is performed using clinical material consisting of 52 operated patients, namely 41 female patients (78.8%) and 11 male patients (21.2%). In order to evaluate achieved results the authors propose such time criteria that performed remodelling of implanted bone grafts allows for full weight-bearing on the operated limb. They emphasize the importance of well-performed operation according to the rules of X-change technique, the way of implanting homogenous frozen bone and the way of cementing the implant, which all are indispensable to the success of the operation. Following those steps, the authors have achieved full remodelling of bone grafts between 12 and 16 month since the day of the operation.


Mass Spectrometry Identification of N-Chlorinated Dipeptides in Drinking Water.
We report the identification of N-chlorinated dipeptides as chlorination products in drinking water using complementary high-resolution quadrupole time-of-flight (QTOF) and quadrupole ion-trap mass spectrometry techniques. First, three model dipeptides, tyrosylglycine (Tyr-Gly), tyrosylalanine (Tyr-Ala), and phenylalanylglycine (Phe-Gly), reacted with sodium hypochlorite, and these reaction solutions were analyzed by QTOF. N-Cl-Tyr-Gly, N,N-di-Cl-Tyr-Gly, N-Cl-Phe-Gly, N,N-di-Cl-Phe-Gly, N-Cl-Tyr-Ala, and N,N-di-Cl-Tyr-Ala were identified as the major products based on accurate masses, 35Cl/37Cl isotopic patterns, and MS/MS spectra. These identified N-chlorinated dipeptides were synthesized and found to be stable in water over 10 days except N,N-di-Cl-Phe-Gly. To enable sensitive detection of N-chlorinated dipeptides in authentic water, we developed a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method with multiple reaction monitoring (MRM) mode. N-Cl-Tyr-Gly, N,N-di-Cl-Tyr-Gly, N-Cl-Phe-Gly, N-Cl-Tyr-Ala, and N,N-di-Cl-Tyr-Ala along with their corresponding dipeptides were detected in authentic tap water samples. The dipeptides were clearly detected in the raw water, but the N-chlorinated dipeptides were at background levels. These results suggest that the N-chlorinated dipeptides are produced by chlorination. This study has identified N-chlorinated dipeptides as new disinfection byproducts in drinking water. The strategy developed in this study can be used to identify chlorination products of other peptides in drinking water.


Infrapatellar contracture syndrome. Diagnosis, treatment, and long-term followup.
Infrapatellar contracture syndrome is an uncommon but recalcitrant cause of reduced range of motion after knee surgery or injury. The results and conclusions presented here are based on a retrospective clinical study evaluating the long-term outcome in 75 patients who developed infrapatellar contracture syndrome. These 75 patients (76 knees) were evaluated at an average followup of 53 months after the index (inciting) procedure or injury. Comparing subgroups within the study population, factors that correlated with poorer results or more severe infrapatellar contracture syndrome were found to be acute anterior cruciate ligament repair or reconstruction, the use of patellar tendon autograft for anterior cruciate ligament reconstruction, nonisometric graft placement, multiple surgical procedures, use of closed manipulation, and the development of patella infera. We concluded that appropriate procedures can substantially increase the range of motion in patients with infrapatellar contracture syndrome. However, residual functional morbidity persists in many patients, and the outcome, as determined by subjective knee function scores, is only fair. The natural history of an anterior cruciate ligament-deficient knee appears to be more benign than the natural history of a knee that develops infrapatellar contracture syndrome.


CT interpretation of craniofacial anomalies: a comparative analysis by undergraduate dental students.
The aim of this study was to evaluate the accuracy and reproducibility of computed tomography (CT) image interpretation made in axial slices (2D-CT) and 3D reconstructed images (3D-CT) of patients with craniofacial anomalies. The analyses were made by undergraduate dental students, and compared with the diagnoses considered upon surgical intervention. Computed tomography of 43 patients were analyzed independently by three calibrated examiners (undergraduate students) with, respectively, one, two, and three semesters of experience in craniofacial CT training and interpretation. The analysis of 2D-CT and 3D-CT images were performed at distinct times using an independent workstation associated with a specific computer graphics software for volumetric images. The analysis of inter-examiner agreement and of the agreement between observers and the gold standard was performed using the Kappa test. The accuracy evaluation presented a progressively higher value for examiners with progressively broader experience in 2D-CT and 3D-CT image interpretation. 3D-CT analyses allowed a higher inter-examiner agreement (1 - 0.896) than 2D-CT analyses (1 - 0.614). 3D-CT was considered more precise and accurate than 2D-CT for all students' evaluations. The reproducibility and accuracy varied according to the experience in CT interpretation, and the most experienced student achieved results closer to the gold standard.


Metabolic effects of bunaftine, a new antiarrhythmic agent: comparison with quinidine, ajmaline, procainamide, xylocaine and propranolol.
The effects of bunaftine (Meregon), quinidine, ajmaline, procainamide, xylocaine and propranolol have been investigated on glycolysis and oxygen consumption of rabbit heart and on the metabolic rate of trained rats. Quinidine, bunaftine and ajmaline stimulated glycolysis, procainamide was inactive while xylocaine and propranolol inhibited it. Myocardial oxygen consumption was reduced by quinidine and bunaftine only at high concentrations. However quinidine at 1-10(5) g/ml showed stimulating effect. Ajmaline and procainamide were inactive; xylocaine had a weak stimulating effect at 1-10(-6), propranolol had a stimulating effect at 3-10(-5) and 1-10(6) while it had an inhibiting effect at 1-10(-4) and 5-10(-3). With the exception of xylocaine and propranolol, which inhibited metabolic rate of trained animals, all the other drugs were inactive. In view of these findings, the mechanism of action of anti-arrhythmic drugs is discussed and it is suggested that the metabolic changes they induce are to be considered as secondary or toxic effects, the main site of action being the myocardial cell membrane.


Micronutrients and vertical transmission of HIV-1.
ABSTRACT Vertical transmission of HIV from mother to infant can occur during pregnancy, at the time of delivery, or post-natally through breast-feeding and is a major factor in the continuing spread of HIV infection. Inadequate nutritional status may increase the risk of vertical HIV transmission by influencing mater-nal and child factors for transmission. The potential effects on these factors include impaired systemic immune function in pregnant women, fetuses, and children; an increased rate of clinical, immunologic, and virologic disease progression; impaired epithelial integrity of the placenta and genital tract; increased viral shedding in breast milk from inflammation of breast tissue; increased risk of low birth weight and preterm birth; and impaired gastrointestinal immune function and integrity in fetuses and children. Micronutrient deficiencies are prevalent in many HIV-infected populations, and numerous studies have reported that these deficiencies impair immune responses, weaken epithelial integrity, and are associated with accelerated HIV disease progression. Although low serum vitamin A concentrations were shown to be associated with an increased risk of vertical HIV transmission in prospective cohort studies, randomized, placebo-controlled trials have reported that vitamin A and other vitamin supplements do not appear to have an effect on HIV transmission during pregnancy or the intrapartum period. However, the ability of prenatal and postpartum micronutrient supplements to reduce transmission during the breast-feeding period is still unknown.


Laser removal of tattoos.
In Western countries the phenomenon of "tattooing" is expanding and tattoos are considered a new fashion among young people. In this paper we briefly trace the history of tattooing, the techniques used, the analysis of pigments used, and their possible adverse reactions. We also carried out a review of the international literature on the use of Q-switched laser in tattoo removal and its complications, and we describe our experience in the use of this technique.


Electronic effects and the stereochemistries in rearrangement-displacement reactions of triaryl(halomethyl)silanes with fluoride and with alkoxide ions.
Tetrabutylammonium fluoride (TBAF) reacts with (halomethyl)diphenyl(para-substituted-phenyl)silanes (13, X = Cl), 14 (X = Br), and 15 (X = I) in ether solvents to give fluorodiphenyl(para-substituted-phenylmethyl)silanes (17a) and fluorophenyl(phenylmethyl)(para-substituted-phenyl)silanes (20a) by attack on silicon and migrations of the phenyl or the para-substituted-phenyl groups to C-1 with displacement of chloride ion. Sodium methoxide in dioxane effects rearrangement-displacements of 14 (X = Br) to yield methoxydiphenyl(para-substituted-phenylmethyl)silanes (17b) and methoxyphenyl(phenylmethyl)(para-substituted-phenyl)silanes (20b). The migratory aptitudes of the varied phenyl groups in rearrangement-displacements of 13 with F(-) at 25 degrees C are p-CF(3)-Ph, 2.72 > p-Cl-Ph, 1.67 > Ph, 1.00 > p-CH(3)-Ph, 0.91 > p-CH(3)O-Ph, 0.58 > p-(CH(3))(2)N-Ph, 0.55. For reactions of 14 with sodium methoxide in dioxane, the migratory aptitudes at 23 degrees C are p-CF(3)-Ph, 2.53 > p-Cl-Ph, 1.64 > Ph, 1.00 > p-CH(3)O-Ph, 0.84 > p-CH(5)-Ph, 0.79 > p-(CH(3))(2)N-Ph, 0.68. The migratory aptitudes in the above rearrangement-displacements are increased by electron-withdrawing substituents, and logarithms of the migratory aptitudes give satisfactory linear correlations with sigma and/or sigma-zero values of the phenyl substituents. Hammett correlations however of the migratory aptitudes from reactions of F(-) with 13 (X = Cl) at 0 and -20 degrees C, 14 (X = Br) at 23, 0, and -20 degrees C, and 15 (X = I) at 23 degrees C are not linear. (+)-(Bromomethyl)methyl-1-naphthylphenylsilane (23, +8.29 degrees, cyclohexane) reacts with CsF and with TBAF in THF to give benzylfluoromethyl-1-naphthylsilane (51, = 0.00 degrees, cyclohexane) and fluoromethyl-(1-naphthylmethyl)phenylsilane (52, impure) in 10.4:1 ratio along with unchanged 23 ( 8.29 degrees, cyclohexane). Sodium methoxide and (+)-23 in dioxane at 25 degrees C and at 0 degrees C yield (+)-benzylmethoxymethyl-1-naphthylsilane (64) and (+)-methoxymethyl(1-naphthylmethyl)phenylsilane (65) in approximately 9:1 ratio. The conversions of (+)-23 to (+)-64 occur with >93% inversion about silicon. Reaction of (+)-23 with sodium methoxide at 25 degrees C to give (+)-65 also occurs with inversion. Further, sodium ethoxide and sodium 2-propoxide react with (+)-23 at 20-25 degrees C by rearrangement-displacements on silicon with phenyl migrations to yield (+)-benzylethoxymethyl-1-naphthylsilane (69) and (+)-benzylmethyl-1-naphthyl-2-propoxysilane (70), respectively, each with >95% inversion about silicon. The mechanisms of rearrangement-displacements of 13-15 and (+)-23 by fluoride and by alkoxide ions are discussed.


Risk factors for disease progression in Japanese patients with COVID-19 with no or mild symptoms on admission.
Although the risk factors for coronavirus disease 2019 (COVID-19) mortality have been identified, there is limited information about the risk factors for disease progression after hospitalization among Japanese patients with COVID-19 exhibiting no or mild symptoms. All 302 consecutive patients who were admitted to our institutions and diagnosed with COVID-19 between March and December 2020 were retrospectively assessed. Ultimately, 210 adult patients exhibiting no or mild symptoms on admission were included in the analysis. They were categorized into the stable (no oxygen needed) and worsened (oxygen needed) groups, and their characteristics and laboratory data were compared. Among 210 patients, 49 progressed to a severe disease stage, whereas 161 did not. The mean patient age was 52.14 years, and 126 (60.0%) patients were male. The mean body mass index (BMI) was 23.0 kg/m2, and 71 patients were overweight (BMI ≥ 25 kg/m2). Multivariate logistic analysis showed that old age, overweight, diabetes mellitus (DM), and high serum ferritin levels were independent risk factors for disease progression. Clinicians should closely observe patients with COVID-19, especially those with risk factors such as old age, overweight, DM, and high serum ferritin levels, regardless of whether they have no or mild symptoms.


Craniofacial morphology in the velo-cardio-facial syndrome.
The velo -cardio-facial syndrome is a recently delineated congenital malformation syndrome, probably of autosomal dominant inheritance. Previous reports have concentrated on facial, oropharyngeal, cardiac, speech, language, and psychological features of this fairly common syndrome. To date, no radiographic data have been presented which might help to further delineate the syndrome, nor has there been an explanation of the characteristic facial appearance seen in this syndrome. This current study reports on cephalometric evidence of platybasia (obtuse angulation of the cranial base) in the velo -cardio-facial syndrome. The finding of platybasia adds one more phenotypic feature to the syndrome and also may help to explain the facial features of retrognathia, malar flatness, and prominence of the nasal root.


The Arkansas River Valley Rural Health Cooperative: building a three-pronged approach to improved health and health care.
This paper describes the Arkansas River Valley Rural Health Cooperative (ARVRHC), one of the Arkansas networks jump-started with support from the Southern Rural Access Program (SRAP). The initial goal of the network was to develop a subsidized health insurance program to provide affordable medical services for the uninsured population (23%) in the 3-county service area. When planning efforts called for the network to address broader needs, the ARVRHC crafted a more comprehensive 3-pronged program model consisting of 3 interrelated programs: (1) the Health Care Access Program (HCAP), (2) the Health Education and Disease Management Program (HE&DMP), and 3) the Information and Assistance Program (I&AP). The HCAP is designed to address the financial barriers to access through a community-based health plan. The HE&DMP focuses on improving the health of individuals through education, counseling, and preventive care. The I&AP links low-income families to existing public assistance programs (e.g., Medicaid) and social support services. The Prescription Drug Assistance Program is one of the I&AP programs that helps individuals without prescription coverage obtain drugs at no cost. A key lesson learned is the importance of combining technical assistance with funding. The ARVRHC has been successful in leveraging funding, having received over $1.7 million in grant funds since 1999. A critical challenge facing the network today is the need for ongoing subsidy funding. Proposed legislation for a federal demonstration of the HCAP and similar programs would enable full implementation and evaluation of this model.


Myelinogenesis in the optic nerve of (C57BL x CBA) F1 hybrid mice: a morphometric analysis.
Myelinogenesis in the optic nerve of the mouse begins by the end of the first week of postnatal life and proceeds well into adulthood. The optic nerve from different postnatal age groups of (C57BL x CBA) F1 hybrid mice was analysed ultrastructurally and morphometrically. Features examined were the myelinated and unmyelinated nerve fibres, mean myelinated nerve fibre diameter, myelinated nerve fibre diameter spectrum, number of myelin sheath lamellae in relation to fibre diameter and age. Results obtained showed that the optic nerve of the mouse is populated entirely by unmyelinated nerve fibres at birth. Myelinogenesis begins at about the fifth postnatal day (pnd), with clearer evidence by the 6th pnd. It starts selectively with the largest fibres and then progresses to involve other fibres of decreasing diameter. After the onset, myelinogenesis progresses with increasing rapidity, becoming most intense from the second week up to the fifth week, so that by the end of the fifth week about 73% of fibres have become myelinated. From then onward, the process proceeds at a progressively diminishing rate until, by the 16th week, virtually all the remaining 27% fibres are myelinated. At onset, the myelin sheath is loosely wrapped around the axons, but with increasing age the myelin lamellae become more compact around the axons. The population of unmyelinated fibres continued to diminish so that at the completion of the process (16th week), they were only very rarely encountered. Myelinogenesis in the optic nerve of the mouse appears to follow a similar course to that seen in other central tracts having a similar fibre diameter spectrum.


Increased sclerostin associated with stress fracture of the third metacarpal bone in the Thoroughbred racehorse.
The exact aetiology and pathogenesis of microdamage-induced long bone fractures remain unknown. These fractures are likely to be the result of inadequate bone remodelling in response to damage. This study aims to identify an association of osteocyte apoptosis, the presence of osteocytic osteolysis, and any alterations in sclerostin expression with a fracture of the third metacarpal (Mc-III) bone of Thoroughbred racehorses. A total of 30 Mc-III bones were obtained; ten bones were fractured during racing, ten were from the contralateral limb, and ten were from control horses. Each Mc-III bone was divided into a fracture site, condyle, condylar groove, and sagittal ridge. Microcracks and diffuse microdamage were quantified. Apoptotic osteocytes were measured using TUNEL staining. Cathepsin K, matrix metalloproteinase-13 (MMP-13), HtrA1, and sclerostin expression were analyzed. In the fracture group, microdamage was elevated 38.9% (sd 2.6) compared with controls. There was no difference in the osteocyte number and the percentage of apoptotic cells between contralateral limb and unraced control; however, there were significantly fewer apoptotic cells in fractured samples (p < 0.02). Immunohistochemistry showed that in deep zones of the fractured samples, sclerostin expression was significantly higher (p < 0.03) than the total number of osteocytes. No increase in cathepsin K, MMP-13, or HtrA1 was present. There is increased microdamage in Mc-III bones that have fractured during racing. In this study, this is not associated with osteocyte apoptosis or osteocytic osteolysis. The finding of increased sclerostin in the region of the fracture suggests that this protein may be playing a key role in the regulation of bone microdamage during stress adaptation.Cite this article:Bone Joint Res 2018;7:94-102.


Automatic pedicle screw planning using atlas-based registration of anatomy and reference trajectories.
An algorithm for automatic spinal pedicle screw planning is reported and evaluated in simulation and first clinical studies. A statistical atlas of the lumbar spine (N = 40 members) was constructed for active shape model (ASM) registration of target vertebrae to an unsegmented patient CT. The atlas was augmented to include 'reference' trajectories through the pedicles as defined by a spinal neurosurgeon. Following ASM registration, the trajectories are transformed to the patient CT and accumulated to define a patient-specific screw trajectory, diameter, and length. The algorithm was evaluated in leave-one-out analysis (N = 40 members) and for the first time in a clinical study (N = 5 patients undergoing cone-beam CT (CBCT) guided spine surgery), and in simulated low-dose CBCT images. ASM registration achieved (2.0 ± 0.5) mm root-mean-square-error (RMSE) in surface registration in 96% of cases, with outliers owing to limitations in CT image quality (high noise/slice thickness). Trajectory centerlines were conformant to the pedicle in 95% of cases. For all non-breaching trajectories, automatically defined screw diameter and length were similarly conformant to the pedicle and vertebral body (98.7%, Grade A/B). The algorithm performed similarly in CBCT clinical studies (93% centerline and screw conformance) and was consistent at the lowest dose levels tested. Average runtime in planning five-level (lumbar) bilateral screws (ten trajectories) was (312.1 ± 104.0) s. The runtime per level for ASM registration was (41.2 ± 39.9) s, and the runtime per trajectory was (4.1 ± 0.8) s, suggesting a runtime of ~(45.3 ± 39.9) s with a more fully parallelized implementation. The algorithm demonstrated accurate, automatic definition of pedicle screw trajectories, diameter, and length in CT images of the spine without segmentation. The studies support translation to clinical studies in free-hand or robot-assisted spine surgery, quality assurance, and data analytics in which fast trajectory definition is a benefit to workflow.


Determination of small-field output factors for beam-matched linear accelerators using various detectors and comparison of detector-specific output correction factors using IAEA Technical Report Series 483 protocol.
Beam matching is widely used to ensure that linear accelerators used in radiotherapy have equal dosimetry characteristics. Small-field output factors (OF) were measured using different detectors infour beam-matched linear accelerators and the measured OFs were compared with existing treatment planning system (TPS) Monte Carlo algorithm calculated OFs. Three Elekta Versa HDTM and one Elekta InfinityTMlinear accelerators with photon energies of 6 MV flattening filter (FF), 10 MVFF, 6 MV flattening filter free (FFF) and 10 MVFFF were used in this study. All the Linac'swere beam-matched, Dosimetry beam data were ± 1% compare with Reference Linac. Ten different type of detectors (four ionizationchambers and six diode detectors) were used for small-field OF measurements. The OFs were measured for field sizes of 1 × 1 to 10 × 10 cm2, and normalized to 10 × 10 cm2 field size. The uncorrected and corrected OFs were calculated from these measurements. The corrected OF was compare with existing treatment planning system (TPS) Monte Carlo algorithm calculated OFs. The small-field corrected and Uncorrected OF variations among the linear accelerators was within 1% for all energies and detectors. An increase in field size led to a reduction in the difference between OFs among the detectors, which was the case for all energies. The RSD values decreased with increasing field size. The TRS 483 provided Detector-specificoutput-correction factor (OCF) reduced uncertainty in small-field measurements. It is necessary to implement the OF-correction of small fields in a TPS. Special care must be taken to incorporate the corrected small-field OF in a TPS.


Developing a xylanase XYNZG from Plectosphaerella cucumerina for baking by heterologously expressed in Kluyveromyces lactis.
Xylanase can replace chemical additives to improve the volume and sensory properties of bread in the baking. Suitable baking xylanase with improved yield will promote the application of xylanase in baking industry. The xylanase XYNZG from the Plectosphaerella cucumerina has been previously characterized by heterologous expression in Pichia pastoris. However, P. pastoris is not a suitable host for xylanase to be used in the baking process since P. pastoris does not have GRAS (Generally Regarded As Safe) status and requires large methanol supplement during the fermentation in most conditions, which is not allowed to be used in the food industry. Kluyveromyces lactis, as another yeast expression host, has a GRAS status, which has been successfully used in food and feed applications. No previous work has been reported concerning the heterologous expression of xylanase gene xynZG in K. lactis with an aim for application in baking. The xylanase gene xynZG from the P. cucumerina was heterologously expressed in K. lactis. The recombinant protein XYNZG in K. lactis presented an approximately 19 kDa band on SDS-PAGE and zymograms analysis. Transformant with the highest halo on the plate containing the RBB-xylan (Remazol Brilliant Blue-xylan) was selected for the flask fermentation in different media. The results indicated that the highest activity of 115 U/ml at 72 h was obtained with the YLPU medium. The mass spectrometry analysis suggested that the hydrolytic products of xylan by XYNZG were mainly xylobiose and xylotriose. The results of baking trials indicated that the addition of XYNZG could reduce the kneading time of dough, increase the volume of bread, improve the texture, and have more positive effects on the sensory properties of bread. Xylanase XYNZG is successfully expressed in K. lactis, which exhibits the highest activity among the published reports of the xylanase expression in K. lactis. The recombinant XYNZG can be used to improve the volume and sensory properties of bread. Therefore, the expression yield of recombinant XYNZG can be further improved through engineered strain containing high copy numbers of the XYNZG, and optimized fermentation condition, making bread-baking application possible.


Genetic tools in the study of drug self-administration.
Recent studies have shown that large genetic differences exist in the extent to which orally delivered ethanol will come to serve as a positive reinforcer under operantly defined conditions. In addition, these studies suggest that a significant correlation exists between results from two-bottle choice studies of ethanol drinking and operant self-administration studies of ethanol functioning as a reinforcer. The present paper reports further genetic influences on ethanol self-administration which were found using Long Sleep and Short Sleep mice, bred selectively for high and low duration of loss of the righting reflex in responses to ethanol, respectively. It was possible to establish ethanol as a reinforcer in Long Sleep mice but not in Short Sleep mice. These results indicate that neurosensitivity to ethanol may determine the absolute amount of ethanol consumption but is not highly related to the ability of ethanol to serve as a positive reinforcer. In addition, this paper presents genetic correlations which indicate that (a) ethanol preference and self-administration are highly correlated across genotype; (b) sensitivity to ethanol and self-administration of this drug are not highly genetically correlated; (c) ethanol is not self-administered in operant studies solely for its caloric value; and (d) there exist important genetic determinants of drug reinforced behavior.


A phantom study: Should 124 I-mIBG PET/CT replace 123 I-mIBG SPECT/CT?
The isotope 123 I is commonly labeled with meta-iodobenzylguanidine (mIBG) for imaging of neuroendocrine tumors, such as pheochromocytomas and neuroblastomas. 123 I-mIBG SPECT/CT imaging is performed for staging, follow-up and selection of patients for treatment with 131 I mIBG. As an alternative to 123 I, 124 I-mIBG PET/CT may be used, potentially taking advantage of the superior PET image quality. The purpose of this study was to investigate whether 124 I PET/CT improves image quality as compared with 123 I SPECT/CT for equal patient effective radiation dose (in mSv). Phantom measurements were performed using the NEMA-2007 image quality phantom. SPECT and PET reconstruction settings were used with and without time-of-flight (TOF) and point-spread-function (PSF) modeling. As a measure of image quality, the contrast-to-noise ratio (CNR) was calculated. The ratio of the 123 I to 124 I activity concentration was determined at which the contrast-to-noise ratio was equal for both modalities. This metric was defined as the contrast equivalent activity ratio (CEAR). CEARs of 47.7, 25.6, 23.1, 14.6, 10.0, and 9.1 were obtained for a TOF and PSF modeled 124 I reconstruction method and an attenuation and scatter-corrected 123 I reconstruction method for sphere sizes of 10 to 37 mm, respectively. As the effective radiation dose of 124 I-mIBG is higher than of 123 I-mIBG (in mSv/MBq), an equal effective dose corresponds to a CEAR of 5 to 10. Therefore, CEARs higher than 5 to 10 indicate that 124 I PET/CT outperforms 123 I SPECT/CT in the sense of image quality for equal patient effective radiation dose. The CEAR is much larger than a factor of 5 to 10 (needed for equal patient effective radiation dose) for most of the reconstruction methods and sphere sizes. Therefore, 124 I-mIBG PET/CT is expected to improve image quality and/or may be used to reduce effective patient dose as compared with 123 I-mIBG SPECT/CT.


Current management of mediastinal tumors.
The incidence of mediastinal tumors is increasing throughout North America. The benign variants are usually managed by relatively simple surgical procedures. Malignant mediastinal tumors can be among the most challenging of medical and surgical conditions and may require the expertise of medical, radiation, and surgical oncologists. Thymomas, germ-cell tumors, and lymphomas comprise the majority of the malignant mediastinal neoplasms. Some variants are managed entirely medically while others are extirpated initially. Many require multimodality therapies, either according to an accepted protocol or, more challengingly, off protocol.


Inhibitory Effects of Ellagic Acid on Glucosyltransferases from Mutans Streptococci.
Ellagic acid and its derivatives were found to abrogate the enzymatic activity of the glucosyltransferases (GTases) of mutans streptococci. These compounds preferentially inhibited the water-soluble glucan synthesis by GTase of Streptococcus mutans MT8148 and inhibited the water-insoluble glucan synthesis by GTase of Streptococcus sobrinus 6715. This inhibition resulted in a reduction of cellular adherence of mutans streptococci to a glass surface.


Rare Variants in Tissue Inhibitor of Metalloproteinase 2 as a Risk Factor for Schizophrenia: Evidence From Familial and Cohort Analysis.
Candidate gene and genome-wide association study based common risk variant identification is being complemented by whole exome sequencing (WES)/whole genome sequencing based rare variant discovery in elucidation of genetic landscape of schizophrenia (SZ), a common neuropsychiatric disorder. WES findings of de novo mutations in case-parent trios have further implied genetic etiology, but do not explain the high genetic risk in general populations. Conversely, WES in multiplex families may be an insightful strategy for the identification of highly penetrant rare variants in SZ and possibly enhance our understanding of disease biology. In this study, we analyzed a 5-generation Indian family with multiple members affected with SZ by WES. We identified a rare heterozygous missense variant (NM_003255: c.506C>T; p.Pro169Leu; MAF = 0.0001) in Tissue Inhibitor of Metalloproteinase 2 (TIMP2, 17q25.3) segregating with all 6 affected individuals but not with unaffected members. Linkage analysis indicated a maximum logarithm of the odds score of 1.8, θ = 0 at this locus. The variant was predicted to be damaging by various in silico tools and also disrupt the structural integrity by molecular dynamics simulations. WES based screening of an independent SZ cohort (n = 370) identified 4 additional rare missense variants (p.Leu20Met, p.Ala26Ser, p.Lys48Arg and p. Ile217Leu) and a splice variant rs540397728 (NM_003255:c.232-5T>C), also predicted to be damaging, increasing the likelihood of contribution of this gene to SZ risk. Extensive biochemical and knockout mouse studies suggesting involvement of TIMP2 in neurodevelopmental and behavioral deficits, together with genetic evidence for TIMP2 conferring SZ risk from this study may have possible implications for new therapeutics.


Ramosissimin, a new flavonol from Tararix ramosissima, induces apoptosis in rheumatoid arthritis fibroblast-like synoviocytes.
Tamarix ramosissima is a traditional Chinese herbal medicine used for rheumatoid arthritis (RA) treatment in Northwest China. Chemical investigation of EtOH/H2O extracts of T. ramosissima led to the discovery of a new flavonol, ramosissimin (1), together with the known flavonoids compounds quercetin (2), quercetin-3'4'-dimethylether (3) and kaempferol (4). By means of high resolution electrospray ionization mass spectroscopy (HRESIMS) and 1D and 2D-NMR experiments, and after comparison with literature data, the structures of the compounds were determined. The effect of compound 1 on the viability of RA fibroblast-like synoviocytes (RA-FLS) was evaluated by MTT assay. Apoptosis-inducing effect of compound 1 in RA-FLS was further investigated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay and activated caspase-3/7 level assessment using luminescent assay. The results revealed that ramosissimin displayed remarkable proliferation inhibitory effect in RA-FLS. Furthermore, compound 1 could significantly induce cellular apoptosis of RA-FLS and increase activated caspase-3/7 levels. It is suggested that ramosissimin may inhibit the proliferation of RA-FLS by inducing apoptosis.


Inhibitory effect of 2,3-dibenzylbutane-1,4-diol; a mammalian lignan, on the CA2+ channel in rabbit femoral artery.
2,3-Dibenzylbutane-1,4-diol (DBB) is a mammalian lignan derived from human urine. To investigate the pharmacological actions of mammalian lignans, the effects of DBB on high K(+)-induced contraction in rabbit femoral artery were studied. High K+ induced a transient contraction followed by sustained contraction, and both depended on extracellular Ca2+. DBB inhibited transient contraction as well as sustained contraction. Verapamil or nifedipine inhibited sustained contraction more effectively than transient contraction. DBB inhibited the transient contraction remaining in the verapamil- or the nifedipine-pretreated preparation in a concentration-dependent manner. Moreover, DBB inhibited sustained contraction elicited by Bay K 8644 (Ca2+ channel activator). These results indicate that DBB effects not only the sensitive Ca2+ channels but also the insensitive channels.


Modelling of the charge carrier mobility in disordered linear polymer materials.
We introduced a molecular-scale description of disordered on-chain charge carrier states into a theoretical model of the charge carrier transport in polymer semiconductors. The presented model combines the quantum mechanical approach with a semi-classical solution of the inter-chain charge hopping. Our model takes into account the significant local anisotropy of the charge carrier mobility present in linear conjugated polymers. Contrary to the models based on the effective medium approximation, our approach allowed avoiding artefacts in the calculated concentration dependence of the mobility originated in its problematic configurational averaging. Monte Carlo numerical calculations show that, depending on the degree of the energetic and structural disorder, the charge carrier mobility increases significantly with increasing charge concentration due to trap filling. At high charge carrier concentrations, the effect of the energetic disorder disappears and the mobility decreases slightly due to the lower density of unoccupied states available for the hopping transport. It could explain the experimentally observed mobility degradation in organic field-effect transistors at high gate voltage.


Isolation of etiological agent of hydropericardium syndrome in chicken embryo liver cell culture and its serological characterization.
The virus causing hydropericardium syndrome was isolated in chicken embryo liver (CEL) cell culture from livers obtained from naturally infected broilers. The cytopathic effects characterized by rounding and degeneration of cells were visible 36 hr post infection in first passage. At 4th passage level, the infectivity titre was 5.24 log10 TCID50/ml. In May-Grunwald and Giemsa stained cells, basophilic intranuclear inclusions ('bird eye' inclusion), typical of aviadenovirus infection, were observed. The specificity of inclusion was confirmed by indirect immunofluorescence. Various serological tests, such as agar gel precipitation test, counter immuno electrophoresis, micro serum neutralization test and enzyme linked immunosorbent assay were also standardized to confirm the isolation of etiological agent of hydropericardium syndrome in CEL cell culture and to diagnose the disease in poultry.


Evaluation of udder cisterns and effects on milk yield of dairy ewes.
Nine Manchega (0.94 L/d) and 10 Lacaune (2.07 L/d) ewes at the same stage of lactation (90 d in milk) were used to study the interbreed differences in milk yield, mammary morphological traits, and machine-milking ability. Udder traits were measured after 6 h of udder filling before the start of the experiment. Cisternal area (by ultrasonography), cisternal milk (by teat cannula drainage), and alveolar milk (by machine milking after an intravenous oxytocin injection) were randomly measured 8 h after milking for 2 wk consecutively either with an intravenous injection of an oxytocin receptor blocking agent (atosiban, AT) or without (control, C) to avoid the occurrence of milk letdown before milking. Lacaune ewes had greater udder depth (22.5 +/- 0.9 vs. 19.6 +/- 0.9 cm) and cistern height (27.1 +/- 3.8 vs. 15.6 +/- 3.5 mm), whereas Manchega ewes had longer (42.7 +/- 1.5 vs. 32.7 +/- 1.5 mm) and wider teats (17.4 +/- 0.5 vs. 13.9 +/- 0.5 mm). Values per half udder for Manchega and Lacaune ewes differed in cisternal area (12.8 +/- 0.7 and 23.7 +/- 0.6 cm(2)) and cisternal milk (120 +/- 0.6 and 269 +/- 0.5 mL), but not in alveolar milk (95 +/- 0.5 and 102 +/- 0.4 mL), respectively. Cisternal area and cisternal milk were positively correlated (r = 0.79). Ratios between cisternal and alveolar milk were 56:44 and 73:27 for Manchega and Lacaune ewes, respectively. Cisternal milk volumes obtained with the AT or C treatment were similar in Manchega (111 +/- 10 vs. 122 +/- 8 mL) but differed in Lacaune ewes (239 +/- 8 vs. 299 +/- 8 mL), respectively. Consequently, alveolar milk with AT vs. C was similar in Manchega (104 +/- 8 vs. 86 +/- 7 mL) but different in Lacaune ewes (115 +/- 7 vs. 89 +/- 7 mL). Results of this experiment confirm the need for the use of an oxytocin-blocking agent for accurate evaluation of milk contained in the udder of dairy ewes. Moreover, despite the differences in daily milk yield, alveolar milk did not vary between breeds, emphasizing the role of the cisternal more than the alveolar compartment for maximizing daily milk secretion in dairy sheep.


First report of 'Candidatus Phytoplasma asteris' associated with yellowing, scorching and decline of almond trees in India.
The almond, a commercially important tree nut crop worldwide, is native to the Mediterranean region. Stone fruit trees are affected by at least 14 'Candidatus Phytoplasma' species globally, among which 'Candidatus Phytoplasma asteris' is one of the most widespread phytoplasma infecting Prunus dulcis, causing aster yellows disease. Recently, almond plantations of Nauni region were consistently affected by phytoplasma, as evidenced by visible symptoms, fluorescent microscopic studies and molecular characterization. During several surveys from May to September 2020-2022, almond aster yellows phytoplasma disease showing symptoms such as chlorosis, inward rolling, reddening, scorching and decline with an incidence as high as 40%. Leaf samples were collected from symptomatic almond trees and the presence of phytoplasma was confirmed through fluorescent microscopic studies by employing DAPI (4, 6-diamino-2-phenylindole) that showed distinctive light blue flourescent phytoplasma bodies in phloem sieve tube elements. The presence of phytoplasma in symptomatic almond trees was further confirmed using nested PCR with specific primer pairs followed by amplification of 16S rDNA and 16S-23S rDNA intergenic spacer (IS) fragments. Sequencing and BLAST analysis of expected amplicon of the 16S rDNA gene confirmed that the almond phytoplasma in Himachal Pradesh was identical to the aster yellows group phytoplasma. Phylogenetic analysis of 16S rDNA almond phytoplasma also grouped 'Prunus dulcis' aster yellows phytoplasma within 16SrI-B subgroup showed 94% nucleotide identity with 'Prunus dulcis' phytoplasma PAEs3 and 'Prunus dulcis' phytoplasma PAE28 from Iran. This research presents the first host report of 'Candidatus Phytoplasma asteris' infecting almonds in India, expanding the knowledge of the diversity and distribution of phytoplasma strains affecting almond trees globally.


Inflammatory and Metabolic Syndrome Biomarker Analysis of Vascular Outcomes in End-stage Renal Disease.
End-stage renal disease (ESRD) presents a complex syndrome in which inflammatory and metabolic processes contribute to disease progression and development of comorbid conditions. Over $1 trillion is spent globally on ESRD care. Plasma samples collected from 83 ESRD patients prior to hemodialysis were profiled for metabolic and inflammatory biomarker concentrations. Concentrations were compared between groups with and without history of stroke, acute coronary syndrome (ACS), congestive heart failure (CHF), and coronary artery disease (CAD). The 25 patients (30.1%) with history of stroke demonstrated decreased plasma interferon-γ levels (p = 0.042) and elevated plasma resistin, interleukin (IL)-1α, and leptin levels (p = 0.008, 0.021, 0.026, respectively) when compared with ESRD patients without history of stroke. The 14 patients (16.9%) with history of ACS demonstrated elevated plasma IL-6 levels (p = 0.040) when compared with ESRD patients without history of ACS. The 30 patients (36.1%) with history of CHF demonstrated decreased plasma leptin levels (p = 0.031) and elevated plasma IL-1β levels (p = 0.042) when compared with ESRD patients without history of CHF. Finally, the 39 patients (47.0%) with history of CAD demonstrated elevated plasma IL-1α levels (p = 0.049) when compared with ESRD patients without history of CAD. Plasma biomarker concentration disturbances were observed in ESRD patients with history of stroke, ACS, CHF, and CAD when compared with ESRD patients without such history. Proinflammatory biomarker elevations were seen in stroke, ACS, CHF and CAD, while adipocytokine aberrations were observed in both stroke and CHF. These studies demonstrate that biomarker profiling of vascular comorbidities in ESRD may provide useful diagnostic and prognostic information in the management of ESRD patients.


Psychiatric consultation to geriatric medically ill inpatients in a university hospital.
Using hospital admissions data, medical records, and the Consultation-Liaison Outcome Evaluation System, we studied psychiatric consultation to hospitalized medical-surgical patients who were aged 60 years or older. In comparison with younger patients, the geriatric population was less often referred for psychiatric consultation. Those referred had less prior psychiatric history than the group aged less than 60 years. They received a different distribution of psychiatric diagnoses. Consultants recommended psychotropic medication and diagnostic actions more often for the elderly; the former was related to the presence of organic mental disorder. Concordance with consultants' recommendations and diagnoses did not vary with patients' age. Certain aspects of the consultation process are thus modified when geriatric patients are involved, and specific features of "geriatric consultation" are unique.


Evaluation of ultrafine particle emissions from laser printers using emission test chambers.
It has now been recognized that some hardcopy devices emit ultrafine particles (d(p) < 100 nm) during their operation. As a consequence, the time-dependent characterization of particle release from laser printers is of high interest in order to evaluate the exposure of office workers to such emissions. The emission profiles of different printers can be compared in test chambers using a standardized test protocol and measuring devices with high time resolution. The extraction of meaningful and comparable data from the obtained data set is a complex procedure due to the different emission behavior patterns of the printers. The calculation of the unit specific emission rate (SERu) is of limited use because the emission profiles during the printing process ranged between short-term bursts and constant particle release. Therefore, other parameters such as the particle loss-rate coefficient, beta, which provides information about the testing conditions, and the area belowthe time vs concentration curve, F, which characterizes the particle release, allow for a comparison of the different printer tests. Variations in the emission behavior could not be associated with specific manufacturers or product lines. In addition, when performing several print jobs on the same device, with only short pauses between jobs, the emission rate was reduced in some cases. This further complicates the ability to determine the influence of printer construction and consumables, such as toner and paper, on the concentration of particles emitted.


Effect of meal frequency and timing on physical performance.
Two areas of sports nutrition in which the periodicity of eating has been studied relate to: (1) the habitually high energy intakes of many athletes, and (2) the optimization of carbohydrate (CHO) availability to enhance performance. The present paper examines how the timing and frequency of food and fluid intake can assist the athlete and physically-active person to improve their exercise performance in these areas. Frequent eating occasions provide a practical strategy allowing athletes to increase energy intake while concomitantly reducing the gastric discomfort of infrequent large meals. The optimization of CHO stores is a special challenge for athletes undertaking prolonged training or competition sessions. This is a cyclical process with post-exercise CHO ingestion promoting muscle and liver glycogen re-synthesis; pre-exercise feedings being practised to optimize substrate availability and feedings during exercise providing a readily-available source of exogenous fuel as endogenous stores become depleted. The timing and frequency of CHO intake at these various stages are crucial determinants for optimizing fuel availability to enhance exercise capacity.


Exercise capacity as a predictor of post-thoracotomy morbidity.
Although severe impairment on routine pulmonary function tests will identify patients with a high post-thoracotomy morbidity, cardiopulmonary complications often develop in patients with only a mild-to-moderate impairment in pulmonary function. To determine whether the preoperative exercise capacity can prospectively identify those at risk of developing complications, 22 patients scheduled for thoracotomy (mean age, 55.7 +/- 2 yr) underwent an incremental exercise test on a cycle ergometer to determine their maximal O2 uptake (VO2max) prior to thoracotomy. Routine pulmonary function tests were performed and postoperative forced expiratory volume in one second (FEV1) was predicted from split function perfusion lung scan in all subjects. Eleven of the 22 patients had no cardiopulmonary complications postoperatively. The age, history of prior cardiovascular disease, degree of impairment on routine pulmonary function tests, and predicted postoperative FEV1 were similar in those who did and those who did not experience complications. However, those without complications had a significantly higher VO2max than did those who experienced complications (22.4 +/- 1.4 versus 14.9 +/- 0.9 ml/kg/min, p less than 0.001). Only 1 of 10 patients with a VO2max greater than 20 ml/kg/min had a complication, whereas all 6 patients with a VO2max less than 15 ml/kg/min had a complication. We conclude that exercise testing is a useful adjunct in the evaluation of operative risk for thoracotomy.


Exploring the Molecular Mechanism of Niuxi-Mugua Formula in Treating Coronavirus Disease 2019 via Network Pharmacology, Computational Biology, and Surface Plasmon Resonance Verification.
In China, Niuxi-Mugua formula (NMF) has been widely used to prevent and treat coronavirus disease 2019 (COVID-19). However, the mechanism of NMF for treating COVID-19 is not yet fully understood. This study aimed to explore the potential mechanism of NMF for treating COVID-19 by network pharmacology, computational biology, and surface plasmon resonance (SPR) verification. The NMF-compound-target network was constructed to screen the key compounds, and the Molecular Complex Detection (MCODE) tool was used to screen the preliminary key genes. The overlapped genes (OGEs) and the preliminary key genes were further analyzed by enrichment analysis. Then, the correlation analysis of immune signatures and the preliminary key genes was performed. Molecular docking and molecular dynamic (MD) simulation assays were applied to clarify the interactions between key compounds and key genes. Moreover, the SPR interaction experiment was used for further affinity kinetic verification. Lipid and atherosclerosis, TNF, IL-17, and NF-kappa B signaling pathways were the main pathways of NMF in the treatment of COVID-19. There was a positive correlation between almost the majority of immune signatures and all preliminary key genes. The key compounds and the key genes were screened out, and they were involved in the main pathways of NMF for treating COVID-19. Moreover, the binding affinities of most key compounds binding to key genes were good, and IL1B-Quercetin had the best binding stability. SPR analysis further demonstrated that IL1B-Quercetin showed good binding affinity. Our findings provided theoretical grounds for NMF in the treatment of COVID19.


Dielectrophoretically controlled fabrication of single-crystal nickel silicide nanowire interconnects.
We report here on applying electric fields and dielectric media to achieve controlled alignment of single-crystal nickel silicide nanowires between two electrodes. Depending on the concentration of nanowire suspension and the distribution of electrical field, various configurations of nanowire interconnects, such as single, chained, and branched nanowires were aligned between the electrodes. Several alignment mechanisms, including the induced charge layer on the electrode surface, nanowire dipole-dipole interactions, and an enhanced local electrical field surrounding the aligned nanowires are proposed to explain these novel dielectrophoretic phenomena of one-dimensional nanostructures. This study demonstrates the promising potential of dielectrophoresis for constructing nanoscale interconnects using metallic nanowires as building blocks.


Community-Based Caregiver and Family Interventions to Support the Mental Health of Orphans and Vulnerable Children: Review and Future Directions.
The goal of this paper was to conduct a review of studies from 2008 to 2019 that evaluated community-based caregiver or family interventions to support the mental health of orphans and vulnerable children (OVC) in sub-Saharan Africa, across four domains: (a) study methodology, (b) cultural adaptation and community participation, (c) intervention strategies, and (d) effects on child mental health. Ten interventions were identified. Findings revealed that the majority of studies used a randomized controlled trial or quasi-experimental design, but few conducted long-term follow-up; that all programs undertook cultural adaptation of the intervention using community participatory methods, or were locally developed; that the majority of interventions targeted caregiving behavior and/or caregiver-child relationships using behavioral and cognitive-behavioral strategies, or were home visiting interventions; and that interventions had mixed effects on OVC mental health. Progress and gaps revealed by these findings are discussed, as are suggestions for possible new directions in this area of intervention science.


Effects of endotoxin on the pancreatic ultrastructure.
Intravenous administration of Escherichia coli endotoxin caused a state of shock with increased serum cationic trypsin-like immunoreactivity (CTLI) in a porcine model. The pancreatic acinar cells revealed focal changes, including intracellular oedema, appearance of membrane-bound vacuoles and breaks in the plasma membrane. In the micro circulatory vessels, there was swelling of endothelial cells. Similar changes have been observed in hemorrhagic and cardiogenic shock. This study demonstrates severe ultrastructural changes in the pancreas during E. coli endotoxin shock.


Etiologic agents and diseases found associated with clinical aspergillosis in falcons.
The aim of this study was to describe parasitological, microbiological, and pathological findings associated with the isolation of Aspergillus species in 94 clinically diseased captive falcons from Dubai. Concomitant agents and/or diseases were identified in 64 cases, causing either single (n = 36) or multiple coinfections (n = 28). Diagnoses found more often in association with aspergillosis were chronic fatigue and immune dysfunction syndrome (CFIDS) (n = 29), Caryospora sp. (n = 16), Serratospiculum seurati infestation (n = 14), cestodiasis (n = 6), bumblefoot (n = 5), trematodosis due to Strigea falconispalumbi (n = 5), trichomoniasis (n = 4), Babesia shortti (n = 4), Mannheimia (Pastorella) haemolytica (n = 4), interstitial hepatitis (n = 4), Escherichia coli (n = 3), and Clostridium perfringens enterotoxemia (n = 2). Compared with a control group of 2000 diseased falcons without evidence of aspergillosis, the prevalence of Babesia shortti, CFIDS, Mannheimia (Pastorella) haemolytica, Escherichia coli, and falcon herpes virus infection was conspicuously higher in association with aspergillosis. These entities may be considered suitable candidates as predisposing factors for the mycosis.


Can markers injected into a single-loop anterior cruciate ligament graft define the axes of the tibial and femoral tunnels? A cadaveric study using roentgen stereophotogrammetric analysis.
Lengthening of a soft-tissue anterior cruciate ligament (ACL) graft construct over time, which leads to an increase in anterior laxity following ACL reconstruction, can result from relative motions between the graft and fixation devices and between the fixation devices and bone. To determine these relative motions using Roentgen stereophotogrammetry (RSA), it is first necessary to identify the axes of the tibial and femoral tunnels. The purpose of this in vitro study was to determine the error in using markers injected into the portions of a soft-tissue tendon graft enclosed within the tibial and femoral tunnels to define the axes of these tunnels. Markers were injected into the tibia, femur, and graft in six cadaveric legs the knees of which were reconstructed with single-loop tibialis grafts. The axes of the tunnels were defined by marker pairs that were injected into the bones on lines parallel to the walls of the tibial and femoral tunnels (i.e., standard). By using marker pairs injected into the portions of the graft enclosed within the tibial and femoral tunnels and the marker pairs aligned with the tunnel axes, the directions of vectors were determined by using RSA, while a 150 N anterior force was transmitted at the knee. The average and standard deviations of the angle between the two vectors were 5.5+/-3.3 deg. This angle translates into an average error and standard deviation of the error in lengthening quantities (i.e., relative motions along the tunnel axes) at the sites of fixation of (0.6+/-0.8)%. Identifying the axes of the tunnels by using marker pairs in the graft rather than marker pairs in the walls of the tunnels will shorten the surgical procedure by eliminating the specialized tools and time required to insert marker pairs in the tunnel walls and will simplify the data analysis in in vivo studies.


Pulmonary complications of methotrexate therapy.
Diffuse interstitial pulmonary infiltration was first reported in 1969, occurring during intermittent methotrexate therapy and it is suggested that it represents an adverse reaction to this drug. Despite the severity of the clinical and radiological changes, the disease is usually self-limiting. An additional case is presented and the previous 28 reported cases of this syndrome are summarized. Since intermittent methotrexate therapy is becoming more widely used, the importance of recognizing this respiratory illness as a possible complicating reaction to the drug is stressed.


Suboptimal use of statin therapy in elderly patients with atherosclerosis: a population-based study.
Current evidence suggests that statin use plays an important role in improving adverse cardiovascular outcomes in patients with atherosclerosis. However, limited population-based data are available on use of statin therapy in these patients in Canada. We sought to study trends in statin use to treat these patients in Ontario during a 10-year period. We conducted a population-based cross-sectional time series analysis between April 1, 1995, and March 31, 2004, using health care data from Ontario, Canada. During the study period, 343,154 elderly patients with atherosclerosis were identified. Of these, 235,615 (68.7%) had coronary artery diseases (CAD), 115,012 (33.5%) had cerebrovascular disease (CVD), and 23,886 (7.0%) had peripheral arterial disease (PAD). About 46% were women, and mean patient age was 77.1 (SD, 7.5) years. During the study period, the percentage of patients treated with a statin in each group increased considerably, from 9.8% to 55.3% in all atherosclerotic patients (P < .01), from 11.8% to 61.2% in CAD patients (P < .01), from 5.3% to 41.2% in CVD patients (P < .01), and from 6.8% to 43.3% in PAD patients (P < .01). During the entire study period, the percentage of statin users was lowest among PAD and CVD patients, followed by patients with both a history of PAD and CVD. The use of statin therapy in elderly patients with symptomatic atherosclerosis has increased substantially during the past decade, but many patients remain untreated. The suboptimal use is greatest among patients with PAD or CVD, or both, and lowest in patients with CAD. Given the heightened risk of cardiovascular adverse outcomes in patients with atherosclerosis, these data have important and immediate implications.


Pancreatic islet defects in NIDDM.
While circulating insulin levels may at times appear to be normal or even elevated in patients with NIDDM, depending on the control group for comparison and the glucose level at which subjects are studied, a profound impairment of pancreatic B-cell function is characteristic of NIDDM and contributes to the hyperglycemia in this condition (Halter, et al., 1985). Table I lists some of the defects of pancreatic islet function that have been observed in NIDDM.


Biomechanical comparison of four triangular osteosynthesis fixations for unilateral vertical sacral fractures.
To compare the stability and biomechanical characteristics of four commonly used triangular osteosynthesis techniques to treat unilateral vertical sacral fractures and provide a clinical application reference. Finite element models of Tile C-type pelvic ring injury (unilateral Denis II sacral fracture) were produced. In four models, sacral fractures were fixed with a combination of unilateral L5, unilateral L4, and L5 iliac lumbar fixation with lengthened or normal sacroiliac screws. The biomechanical properties of the four fixation models were measured and compared under bipedal stance and lumbar rotation. The fixation stability of the model with the lengthened sacroiliac screw was excellent, and the fracture end was stable. The stability of fixation using unilateral L4 and L5 segments was close to that of unilateral L5 segment fixation. Triangular osteosynthesis transverse stabilization devices using lengthened sacroiliac screws can increase the vertical stability of the sacrum after internal fixation and increase the stability of the fracture. When triangular osteosynthesis lumbar fixation segments were selected, simultaneous fixation of L4 and L5 segments versus only L5 segments did not significantly enhance the vertical stability of the sacrum or the stability of the fracture end.


Outcome of prophylactic endoscopic vacuum therapy for high-risk anastomosis after esophagectomy.
Background: Endoscopic vacuum therapy (EVT) has become an established procedure for the treatment of anastomotic leaks (AL) in upper gastrointestinal surgery. A novel approach is the use of EVT for preventing leaks in high-risk anastomosis. The aim of this study was to analyze the outcome of prophylactic EVT (pEVT) in patients receiving surgical revision of the anastomosis after oncological Ivor-Lewis esophagectomy (ILE) due to AL.Material and methods: Between June 2016 and February 2019, all patients who underwent anastomotic revision after ILE due to a confirmed AL were included. The primary outcome was the success rate of pEVT, which was defined as absence of an AL after revision. Secondary outcome parameters were duration of treatment, inflammatory levels, and ICU/hospital stay.Results: Twenty-one patients underwent anastomotic revision due to an AL. The cause of the AL was ischemia in nine patients (42.9%) and non-ischemia (other) in 12 patients (57.1%). PEVT was performed in 14 patients (66.6%). The overall success rate of pEVT was five out of 14 patients (35.7%).Conclusions: Prophylactic EVT cannot prevent a re-leak in patients with high-risk anastomosis due to surgical revision of an AL after oncological ILE. However, pEVT might help to control the clinical condition of these patients.


Artificial Human Sweat as a Novel Growth Condition for Clinically Relevant Pathogens on Hospital Surfaces.
The emergence of biofilms on dry hospital surfaces has led to the development of numerous models designed to challenge the efficacious properties of common antimicrobial agents used in cleaning. This is in spite of limited research defining how dry surfaces are able to facilitate biofilm growth and formation in such desiccating and nutrient-deprived environments. While it is well established that the phenotypical response of biofilms is dependent on the conditions in which they are formed, most models incorporate a nutrient-enriched, hydrated environment dissimilar to the clinical setting. In this study, we piloted a novel culture medium, artificial human sweat (AHS), which is perceived to be more indicative of the nutrient sources available on hospital surfaces, particularly those in close proximity to patients. AHS was capable of sustaining the proliferation of four clinically relevant multidrug-resistant pathogens (Acinetobacter baumannii, Staphylococcus aureus, Enterococcus faecalis, and Pseudomonas aeruginosa) and achieved biofilm formation at concentration levels equivalent to those found in situ (average, 6.00 log10 CFU/cm2) with similar visual characteristics upon microscopy. The AHS model presented here could be used for downstream applications, including efficacy testing of hospital cleaning products, due to its resemblance to clinical biofilms on dry surfaces. This may contribute to a better understanding of the true impact these products have on surface hygiene. IMPORTANCE Precise modeling of dry surface biofilms in hospitals is critical for understanding their role in hospital-acquired infection transmission and surface contamination. Using a representative culture condition which includes a nutrient source is key to developing a phenotypically accurate biofilm community. This will enable accurate laboratory testing of cleaning products and their efficacy against dry surface biofilms.


Increased ductal responsiveness to PGE2 after maternal treatment with aspirin and ibuprofen.
This work was conducted to determine whether aspirin and ibuprofen, when administered prenatally may potentiate a reopening of the neonatal ductus arteriosus (DA) induced by PGE2 after postnatal closure. In the first experiment, a subcutaneous injection of PGE2 (4 microgram(s)) was administered to newborn rats 3 hr after a Cesarean delivery from pregnant females which had been orally given 100 or 300 mg/kg/day of aspirin and 10 or 30 mg/kg/day of ibuprofen on days 18, 19 and 20 of gestation. The ratio of the DA to the pulmonary artery (PA) was determined at intervals after the injection. The DA/PA ratio was significantly higher in newborn rats from mothers who were transplacentally administered these agents than the control. We also examined the hypothesis that maternal treatment with nonsteroidal anti-inflammatory drugs (NSAID), such as aspirin and ibuprofen, inhibits the catabolism of PGE2 and that the increased reopening of the DA was partly due to this inhibition. 15-hydroxy prostaglandin dehydrogenase (15-PGDH) in neonatal lungs, the key enzyme involved in catalyzing PGE2 to convert it to its inactive metabolite 15-keto-PGE2, was not affected by maternal treatment with aspirin and ibuprofen. These results suggest that the increased ductal responsiveness to PGE2 in newborn rats was a common response after maternal NSAID treatment, but the catabolism of PGE2 in the lungs did not always contribute to this response.


High-resolution single nucleotide polymorphism arrays identified an atypical microdeletion of the Williams-Beuren syndrome interval in a patient presenting with a different phenotype.
The present study aimed to identify the mutation causing an atypical syndrome. High-resolution single nucleotide polymorphism (SNP) arrays are considered to be a major detection method for submicroscopic chromosomal rearrangements smaller than 5 Mb in size. Genomic DNA samples of the patient and his parents were converted to a final concentration of 50 ng/ml. The Illumina BeadScan genotyping system and the HumanOmni1‑Quad Chip were employed to obtain the signal intensities of SNP probes. The patient presented with congenital heart disease, autism, mental retardation, growth retardation, hypercalcemia, nephroliths and cleft palate. The karyotypes of the patient and his parents were normal. The present study employed high‑resolution SNP arrays to analyze the whole genome for copy number variations (CNVs). A total of 309 CNVs were discovered. A de novo 1.5 Mb gain of chromosome 7q11.23 (Chr7: 72,357,322‑73,856,472) was identified following exclusion of CNVs presented in the Database of Genomic Variants. In conclusion, to the best of our knowledge, the current study describes the first case of a patient presenting with Williams‑Beuren syndrome alongside supravalvular aortic stenosis, autism and cleft palate, and identifies an atypical deletion at 7q11.23.


Cases of violence against people with disabilities notified by Brazilian health services, 2011-2017.
To describe cases of violence against people with disabilities notified by Brazilian health services between 2011 and 2017. This was a descriptive study of secondary data on notifications of violence against people with disabilities recorded on the Notifiable Health Conditions Information System (Sinan). 116,219 cases of violence against people with disabilities were recorded in the period. Most of the victims were female (67%), White (50.7%), between 20 and 59 years old (61.6%) and mentally disabled (58.1%), with multiple disabilities occurring frequently (15.9%), especially mental and intellectual disabilities. Self-inflicted violence accounted for 44.5% of notifications. Physical violence was the most reported (51.6%), and in 36.5% of notifications the probable aggressor was a family member. The description of cases of violence against people with disabilities notified by Brazilian health services can contribute to the formulation and improvement of public policies to address this important problem.


Systematic review of the role of calprotectin in cirrhosis.
Calprotectin is a calcium-binding-S100-protein synthetized mainly in neutrophils which has been demonstrated to be an accurate biomarker of the presence of these cells. Gut barrier dysfunction in patients with advanced chronic liver disease (ACLD), in addition to the lack of noninvasive tools for diagnosis and prognosis of cirrhosis decompensations, has raised interest in this biomarker. Our aim is to summarize the current evidence regarding the role of calprotectin in terms of its diagnostic and prognostic utility in ACLD. We performed a systematic search (PROSPERO registration no. CRD42023389069) of original articles published without any restrictions on the publication date until January 2023 providing information about calprotectin for the prognosis or diagnosis of ACLD and its decompensations in adult patients. A total 227 articles were identified, and 26 observational studies finally met the inclusion criteria. In 14 studies, calprotectin was measured in ascitic fluid, all of which reported higher calprotectin values in spontaneous bacterial peritonitis, while cut-off points for its diagnosis were proposed in nine studies. Three studies reported higher faecal calprotectin levels in patients with hepatic encephalopathy and portal hypertension. Four studies evaluated faecal calprotectin and one plasma calprotectin as biomarkers for gut barrier integrity and bacterial translocation. Calprotectin is emerging as a promising biomarker in ACLD, particularly for the management of bacterial infections and alcohol-related liver disease. Further research with better study designs should help to determine the feasibility of calprotectin measurement in routine clinical practice.


[Sentinel node biopsy in our department].
The author presents a group of two female patients with breast cancer and a male patient with malignant melanoma where mainly due to a borrowed scintillation tube combined with preoperative administration of methylene blue a sentinel node was successfully extirpated. The author analyzes the technical aspect of the biopsy. He is convinced that by combining the two methods its is within the powers of a district department to implement the method successfully.


[Treatment of paroxysmal supraventricular tachycardia and tachyarrhythmia with verapamil].
The antiarrhythmic effect of isoptin was verified in 47 patients--30 with paroxysmal supraventricular tachycardia and 17--with paroxysmal ventricular fibrillation: in case of paroxysmal supraventricular tachycardia with 5--10 mg isoptin i.v. for the restoration of sinus rhythm and with 240--320 mg orally for maintaining the effect and in case of ventricular fibrillation--i. v. for the slowing down the heart rate. Isoptin, i. v. applied, restores the sinus rhythm in 93,3 per cent of the patients with paroxysmal supraventricular tachycardia and in 17,6 per cent--with ventricular fibrillation and slowsdown the heart rate in 94,6 per cent among those with ventricular fibrillation. The oral isoptin reduces the paroxysms of the supraventricular tachycardia in 86 per cent and slowsdown the sinus rate and lengthens PQ.


Diurnal profile of pancreatic polypeptide, pancreatic glucagon, gut glucagon and insulin in human morbid obesity.
The diurnal profiles of pancreatic glucagon, insulin, pancreatic polypeptide (PP), and enteroglucagon were studied in five obese non-diabetic subjects (195 +/- 11 per cent of ideal body weight) and in six age matched controls. All the subjects were served with ordinary mixed meals five times during the day. The obese subjects were normoglycemic but hyperinsulinemic. Both groups showed rapid increases in PP to all meals, but the PP-response was significantly impaired in the obese group during the first part of the day. Normal subjects showed significant enteroglucagon responses to all meals, and had elevated levels throughout the day. In obese subjects, levels and responses were much lower at all times. Pancreatic glucagon profiles were similar. It is concluded that the possible role of abnormalities of PP and enteroglucagon secretion in the pathogenesis of human obesity deserves further study.


Placebo-controlled trial of riluzole in multiple system atrophy.
We performed a placebo-controlled cross-over trial of riluzole (100 mg b.i.d.) in 10 patients with probable multiple system atrophy (MSA) administering riluzole and placebo for 4 weeks each with a 4-week washout period. Outcome measures evaluated short-term anti-Parkinsonian effects using the Unified Parkinson's Disease Rating Scale (UPDRS) subscales (UPDRS-II, activities of daily living; UPDRS-III, motor examination; sum of UPDRS-II and -III) before and at the end of each treatment phase. Delta values were calculated by subtracting the UPDRS scores measured at the end of each treatment arm from those before onset of each medication phase. Riluzole was generally well tolerated. There were no significant anti-Parkinsonian effects of riluzole comparing the UPDRS delta values for both treatment arms using the Wilcoxon signed-rank test. It is unlikely that riluzole treatment could have clinically meaningful anti-Parkinsonian effects in MSA. A trial assessing the disease-modifying potential of riluzole in MSA is underway.


[The repair of the membrane lipid bilayer in oxidative stress: phosphatidylethanolamine reacylation in synaptosome, photoreceptor and erythrocyte membranes].
The participation of unsaturated (linoleic and arachidonic) and saturated (palmitic) fatty acids in reacylation of phosphatidylethanolamine (PE) in synaptosomes, photoreceptor membranes and erythrocytes at oxidative stress was studied. Induction of lipid peroxidation (LPO) was found to result in a significant decrease in the content of PE polyenoic fatty acids due to their oxidative destruction. It might be related to both an activation of phospholipase A2 and a decrease in PE reacylation rate. On contrary, under the same conditions an increase in incorporation of palmitic acid into PE was observed. The results of this study suggest that phospholipid deacylation-reacylation reactions comprise an important mechanism of both protection and adaptation of organisms to oxidative stress.


Can managed care and competition control Medicare costs?
Medicare+Choice (M+C) was conceived to bring managed care and competitive forces to bear on Medicare. Ultimately, M+C could not thrive under the conditions of the marketplace and the Balanced Budget Act of 1997. Here I review what went wrong and the lessons from the experience, concluding that M+C is a tool, not a strategy. While managed care in a multiple-choice environment may have the potential to generate limited savings, promoting managed care and competition alone will not preempt the need for a debate on Medicare's obligations and how to finance them.


Prevention strategies for gastric cancer: a global perspective.
Despite the substantial burden of gastric cancer worldwide, population strategies for primary prevention have not been introduced in any country. Recognizing the causal role of Helicobacter pylori infection, there is increasing interest in population-based programs to eradicate the infection to prevent gastric cancer. Nonetheless, the paucity of available evidence on feasibility and effectiveness has prevented implementation of this approach. There are very few secondary prevention programs based on screening with endoscopy or radiography, notably in the Republic of Korea and Japan, two of the countries with the highest incidence rates of gastric cancer. In Korea, where the organized screening program is in place, survival rate of gastric cancer is as high as 67%. More research is needed to quantify the specific contribution of the screening program to observed declines in mortality rates. Gastric cancer screening is unlikely to be feasible in many Low-Middle Income Countries where the gastric cancer burden is high. Prevention strategies are still under development and the optimal approach may differ depending on local conditions and societal values. The present review gives an overview of the etiology and burden of the disease, and possible prevention strategies for countries and regions confronted with a significant burden of disease.


Cardiorenal syndrome type 2: from diagnosis to optimal management.
The deterioration of renal function, which is linked to chronic heart failure by a chronological and causal relationship (ie, the so-called cardiorenal syndrome [CRS] type 2), has recently become a matter of growing debate. This debate has concerned the efficacy, safety, and cost effectiveness of the therapies that have been implemented thus far for this syndrome (for example, the intravenous [IV] loop diuretics, such as repeated IV boluses or slow IV infusions, as well as mechanical fluid removal, particularly by means of isolated ultrafiltration [IUF]). Further controversies have also emerged concerning the optimal dosage and timing of some evidence-based drugs, such as angiotensin-converting-enzyme inhibitors. The present review summarizes the currently used diagnostic tools for detecting renal damage in CRS type 2. Subsequently, the meaning of worsening renal function is outlined, as well as the sometimes inconsistent therapeutic schemes that have been implemented in order to prevent or counteract worsening renal function. The need to elaborate upon more detailed and comprehensive scientific recommendations for targeted prevention and/or therapy of CRS type 2 is also underlined. The measures usually adopted (such as the more accurate modulation of loop diuretic dose, combined with the exploitation of other diuretics that are able to achieve a sequential blockade of the nephron, as well as the use of IV administration for loop diuretics) are briefly presented. The concept of diuretic resistance is illustrated, along with the paramount operational principles of IUF in diuretic-resistant patients. Some controversies regarding the comparison of IUF with stepped diuretic therapy in patients with CRS type 2 are also addressed.


Acetylcholine-related proteins in non-neoplastic appearing colonic mucosa from patients with colorectal neoplasia.
The pathogenesis of colorectal neoplasia (CRN) has been associated with altered non-neuronal acetylcholine (ACh) metabolism. The aim of this study was to characterize expression, function, and cellular location of ACh-related proteins in biopsies obtained from endoscopic normal-appearing sigmoid colon in patients with and without CRN. Messenger-RNA (mRNA) levels of 17 ACh-related proteins were quantified by rt-qPCR. Functional responses to ACh, measured as electrogenic transepithelial short circuit current (SCC), were recorded using the Ussing chamber technique. Finally, cellular localization of choline transporter-like proteins (CTLs) and butyryl-cholinesterase enzyme (BChE) was determined by immunohistochemistry. mRNA expression of CTL1 and CTL4 was increased in patients with CRN (P = 0.002 and P = 0.04, respectively). In functional experiments, baseline SCC was increased in CRN patients. ACh induced rapid biphasic changes in SCC. An initial decreasing phase was observed in the minority of CRN patients versus the majority of controls (25% vs 69%, respectively, P = 0.031). For the second increasing phase of SCC, data indicated ACh-activation of two receptors. For both parts of the biphasic response, the half maximal effective concentration and maximal responses showed no difference between patient groups. Immunohistochemistry demonstrated CTL1, 3 and 4 and BChE to be localized to colonic crypt cells. We conclude that CRN is associated with increased expression of CTL1 and CTL4, augmented basal prostaglandin-dependent secretion, and altered functional channel response to ACh in human endoscopic normal-appearing colonic mucosa. The immunohistochemical findings support CTL1, CTL3, CTL4, and BChE to be involved in non-neuronal mucosal ACh metabolism.


Meta-Analysis of the Relationship between Deep Brain Stimulation in Patients with Parkinson's Disease and Performance in Evaluation Tests for Executive Brain Functions.
Parkinson's disease (PD) is a neurodegenerative condition, which compromises the motor functions and causes the alteration of some executive brain functions. The presence of changes in cognitive symptoms in PD could be due to the procedure of deep brain stimulation (DBS). We searched in several databases for studies that compared performance in executive function tests before and after the DBS procedure in PE and then performed a meta-analysis. After the initial search, there were 15 articles that specifically evaluated the functions of verbal fluency, working memory, cognitive flexibility, abstract thinking, and inhibition. It was found that there were differences in the evaluation of the cognitive functions in terms of the protocols, which generated heterogeneity in the results of the meta-analysis. Likewise, a tendency to diminish functions like verbal fluency and inhibition was found, being this consistent with similar studies. In the other functions evaluated, no difference was found between pre- and postsurgery scores. Monitoring of this type of function is recommended after the procedure.


Topology of binding sites for carbamyl phosphate in aspartate transcarbamylase from Escherichia coli. The use of pyridoxal phosphate as covalent probe.
Pyridoxal phosphate, a competitive inhibitor of aspartate transcarbamylase, binds to six sites in the catalytic and to twelve sites in the regulatory subunits of this hexameric protein. The properties of its association to the active sites of the enzyme are very similar to those observed with one of its substrates, carbamyl phosphate. It tightly binds to one half of the sites in the absence of succinate, an analogue of the second substrate. Since pyridoxal phosphate can be linked covalently to the protein by reduction, the distribution of the high affinity binding sites on catalytic trimers was studied after dissociation of modified holoenzyme. Electrophoresis of isolated subunits under non-denaturing conditions revealed four distinct bands, corresponding to trimers containing 0 to 3 pyridoxal phosphate derivatives. The distribution among the four species as a function of ligand concentration in the absence of succinate indicates that in the native oligomer, pyridoxal phosphate (and by extrapolation, carbamyl phosphate) binds to both catalytic trimers, rather than to three sites on a single subunit.


Polydextrose and activities of brush-border membrane enzymes of small intestine in rats and glucose absorption in humans.
We investigated the effect of polydextrose, one of the water-soluble non-digestible polysaccharides, on the activities of brush-border membrane enzymes of small intestine in rats and on glucose absorption with relation to the thickness of the unstirred water layer in humans. Rats were fed a 5% polydextrose-supplemented elemental diet for 2 or 4 wk. The mucosal alkaline phosphatase, maltase, and sucrase activities were measured in the upper, middle, and lower intestine. There was no significant difference between control and polydextrose groups. The potentiometric tube was inserted orally in the jejunum. Glucose absorption was measured by perfusion with the solutions with or without 5% polydextrose. There was no significant difference in the glucose absorption rate or the thickness of the unstirred water layer between control and polydextrose solutions. The increase in viscosity of the polydextrose solution was negligible. This study indicated that polydextrose had no effect on the thickness of the unstirred water layer and did not inhibit glucose absorption in humans.


Anisotropic thermal transport in Weyl semimetal TaAs: a first principles calculation.
A fundamental understanding of the phonon transport property is crucial to predict the thermal management performance in micro/nano-electronic devices. By combining first principle calculations and Boltzmann phonon transport equation, we investigate thermal transport in TaAs-a typical Weyl semimetal. The lattice thermal conductivity of TaAs at room temperature was found to be 39.26 W mK(-1) and 24.78 W mK(-1) along the a(b) and c crystal axis, respectively, showing obvious anisotropy. Detailed analyses of the mode level phonon properties further revealed that the three acoustic phonon modes dominate the overall thermal transport and the major phonon scattering channels in this typical Weyl semimetal were TA1/TA2/LA + O ↔ O and A + A ↔ O. The representative phonon mean free path of TaAs was also calculated in this paper, which provide helpful guidance for the thermal management of TaAs-based electronic devices.


Measuring quality of life in care homes when self-report is challenging: the construct validity, structural characteristics and internal consistency of the mixed-methods adult social care outcomes toolkit.
The adult social care outcomes toolkit (ASCOT) measures social care-related quality of life (SCRQoL) using self-completion questionnaires and interviews. Many care home residents find such methods inaccessible, leading to a reliance on proxy-reporting. This study aimed to establish the psychometric properties of the mixed-methods toolkit [ASCOT-Care Homes, 4 outcome (CH4)] for measuring SCRQoL when residents cannot self-report. Two cross-sectional, mixed-methods studies were undertaken in care homes for older people in England between 2015 and 2020. We used the ASCOT-CH4 (observation, and interviews with residents and proxies) to collect information about SCRQoL and collected additional data on residents' needs and characteristics, and variables hypothesised to be related to SCRQoL.Hypothesis testing was applied to establish construct validity, Cronbach's alpha for internal consistency and exploratory factor analysis for structural validity. The combined dataset included 475 residents from 54 care homes (34 nursing, 20 residential). Half had a diagnosis of dementia. Less than a third of residents were able to complete an ASCOT interview. Observations and proxy interviews informed researcher ratings, meaning there were no missing ASCOT-CH4 scores. ASCOT-CH4 was found to be a weak unidimensional scale, consistent with other ASCOT measures, with acceptable internal consistency (α = 0.77, 8 items). Construct validity was supported by the findings. The ASCOT-CH4 is an alternative to conventional proxy-questionnaires for measuring the SCRQoL of care home residents, with good psychometric properties. A limitation is that users need a range of data collection skills. Future research should explore whether findings are replicable when data are collected by other researchers.


[History of Clinical Psychiatry of Sapienza University of Rome in Policlinico Umberto I].
The present article intends to go over the history of the Psychiatric Clinic of the Sapienza University of Rome, starting from the beginning of the teaching of Psychiatry at Santa Maria della Pietà mental hospital, back in 1871, to the eventual founding, at the University "La Sapienza" and the Umberto I general hospital, of the Institute of Psychiatric Clinic and next of the Nervous and Mental Diseases' Clinic with the enclosed specialization school in Psychiatry. A detailed overview is supplied on the characters of the eminent scientists who have succeeded over time at the head of the Clinic and on the description of its different organization, conceived by each of them because of their educational and cultural roots. In this humus is born, in 1966, the journal Rivista di Psichiatria, still alive. To follow, a brief description of what the academic Psychiatry of the Umberto I nowadays represents, and indeed point of contact of different psychiatric thinking roots, with an organic, pharmacological, phenomenological, and psychotherapeutic orientation, this latter in the psychodynamic, cognitive-behavioral, and family-related approaches.


The patient's role in rheumatology care.
This article reviews narrative and empiric studies in rheumatology and related literature to explicate the patient's role in rheumatology care. In contrast to early conceptualizations, such as Parsons' sick role that emphasized compliance, current literature describes chronic disease patients as active participants in their care, rather than passive recipients of care. Active patients roles include participant in shared decision making, self-manager, and help and information seeker. All of these roles are colored by the individual's need to preserve a personally defined acceptable lifestyle. Suggestions for strategies that physicians and health professionals can use to engage and support these essential patient roles are also reviewed.


Socio-ethical analysis of equity in access to nutrigenomics interventions for obesity prevention: a focus group study.
The goal of nutrigenomics is to develop nutritional interventions targeted to individual genetic make-up. Obesity is a prime candidate for nutrigenomics research. Personalized approaches to prevention of diseases associated with obesity may be available in the near future. Nevertheless, in the context of limited resources, access to a nutrigenomics personalized health service raises questions around equity. Using focus groups, the present qualitative research study provides empirical data on ethical concerns and values surrounding the nutrigenomics-guided personalized nutrition for obesity prevention. Eight focus groups were convened including 27 healthy individuals and 21 individuals who self-identified as obese or at risk of obesity. The transcripts of the focus group were analyzed according to the qualitative method of grounded theory. Responsibility, reciprocity, and solidarity emerged as the key ethical criteria perceived by the respondents to be significant in terms of how health professionals should determine access to personalized nutrition services. Still, exclusion of individuals from specific nutrigenomic services is likely to conflict with the imperatives of medical deontology and contemporary social consensus. The representation of equity in this paper is novel: it considers the intersection of nutrigenomics and personalized nutritional interventions specifically in the context of limited public resources for health services.