The use of biological selenium nanoparticles to suppress Triticum aestivum L. crown and root rot diseases induced by Fusarium species and improve yield under drought and heat stress.
Fusarium species threaten wheat crops around the world and cause global losses. The global trend is toward using biological materials such as selenium (Se) in nano form to control these fungi. Bulk selenium is toxic and harmful at high doses; however, selenium nanoparticles are safe; therefore, the aim of this study to employ the biological selenium nanoparticles (BioSeNPs) synthesized by Lactobacillus acidophilus ML14 in controlling wheat crown and root rot diseases (CRDs) induced by Fusarium spp., especially Fusarium culmorum and Fusarium graminearum, and their reflection on the growth and productivity of wheat. The ability of BioSeNPs to suppress the development and propagation of F. culmorum and F. graminearum and the CRDs incidence were also investigated. The obtained BioSeNPs were spherical with a size of 46 nm and a net charge of -23.48. The BioSeNPs significantly scavenged 88 and 92% of DPPḢ and ABTṠ radicals and successfully inhibited the fungal growth in the range of 20-40 µg/mL; these biological activities were related to the small size of BioSeNPs and the phenolic content in their suspension. Under greenhouse conditions, the wheat supplemented with BioSeNPs (100 µg/mL) was significantly reduced the incidence of CRDs by 75% and considerably enhanced plant growth, grain quantity and quality by 5-40%. Also, photosynthetic pigments and gas exchange parameters were significantly increased as compared to chemical selenium nanoparticles (Che-SeNPs) and control. This study results could be recommended the use of BioSeNPs (100 µg/mL) in reducing CRDs incidence and severity in wheat plants, enhancing their tolerance with drought and heat stress, and increasing their growth and productivity as compared to control and Che-SeNPs.


Comparison of the serial dilution indicator and intragastric titration methods for measurement of meal-stimulated gastric acid secretion in man.
Two in vivo methods that permit quantitation of gastric acid secretion immediately after the meal are currently in use: intragastric titration and the serial dilution indicator method. During intragastric titration, intragastric pH is artificially maintained at 5.5 to 7 by the continuous addition of alkali to the gastric contents, while during serial dilution the intragastric pH is permitted to seek its natural pH. This study compared gastric acid secretion and serum gastrin in response to a liquid protein meal measured by both techniques in 10 subjects. Mean (+/- SE) 3-hr acid outputs were almost identical (53.6 +/- 6.0 mmol/3 hr with intragastric titration and 52.0 +/- 8.5 mmol/3 hr with serial dilution indicator). Furthermore, 30 min secretory responses in individual subjects were highly correlated (r = 0.98 +/- 0.01, P less than 0.001). Also, in spite of intragastric pH being less than 1.5 by 90 min after the meal during the serial dilution method, total integrated serum gastrin concentrations after the meal were similar (intragastric titration = 20.6 +/- 7.3 ng min/ml versus serial dilution indicator = 23.5 +/- 9.8 ng min/ml) and individual 30-min gastrins during the two separate tests were highly correlated (r = 0.80 +/- 0.06, P less than 0.01). It is concluded that both meal-stimulated gastric acid secretion and serum gastrin concentrations as measured by intragastric titration and by the serial dilution indicator method produced similar results.


Overcoming Barriers to Accessing Surgery and Rehabilitation in Low and Middle-Income Countries: An Innovative Model of Patient Navigation in Nepal.
Injury and disability are prominent public health concerns, globally and in the country of Nepal. Lack of locally available medical infrastructure, socioeconomic barriers, social marginalization, poor health literacy, and cultural barriers prevent patients from accessing surgical and rehabilitative care. Overcoming these barriers is an insurmountable challenge for the most vulnerable and marginalized, resulting in absence of treatment or even death. Sundar Dhoka Saathi Sewa (SDSS), a non-government organization, provides a patient navigation service which facilitates referrals to tertiary centers from Nepal's most remote areas. Specific criteria ensure that patient referrals are appropriate in regard to clinical and socioeconomic need, while comprehensive counselling helps guide the patient and family. The SDSS staff meet patients upon arrival in Kathmandu and facilitate admission to the appropriate tertiary hospital. They advocate for the patient, provide medicine, supply food and cover all treatment costs. This project has enabled access to treatment for more than 1200 children for conditions leading to long-term disability and/or congenital heart disease. Interventions include a wide range of surgical and rehabilitative procedures such as complex orthopedics, cleft lip and palate, congenital talipes equinovarus, burn contractures, neurological cases, and cardiac surgery for valvular disease, septal defects and other congenital malformations. The SDSS model of patient navigation is effective in overcoming the barriers to access surgical care and rehabilitation in Nepal. The success is owed to committed international donors, capacity building, effective counselling, advocacy, compassion, and community. We believe that this model could be replicated in other LMICs.


Use of microvascular flaps including free osteocutaneous flaps in reconstruction after composite resection for radiation-recurrent oral cancer.
Fourteen patients underwent microsurgical free flap procedures for reconstruction after composite resection of radiation-recurrent oral cancer. The use of attached metatarsal bone in nine patients for mandibular reconstruction is in our view a significant advance in this field. Two failures occurred, one due to sepsis and one to delayed thrombosis. Our experience indicates that this procedure deserves a place in the surgical treatment of patients afflicted with oral malignancy.


Synthesis, characterization, and monkey positron emission tomography (PET) studies of [18F]Y1-973, a PET tracer for the neuropeptide Y Y1 receptor.
Neuropeptide Y receptor subtype 1 (NPY Y1) has been implicated in appetite regulation, and antagonists of NPY Y1 are being explored as potential therapeutics for obesity. An NPY Y1 PET tracer is useful for determining the level of target engagement by NPY Y1 antagonists in preclinical and clinical studies. Here we report the synthesis and evaluation of [(18)F]Y1-973, a novel PET tracer for NPY Y1. [(18)F]Y1-973 was radiolabeled by reaction of a primary chloride with [(18)F]KF/K2.2.2 followed by deprotection with HCl. [(18)F]Y1-973 was produced with high radiochemical purity (>98%) and high specific activity (>1000 Ci/mmol). PET studies in rhesus monkey brain showed that the distribution of [(18)F]Y1-973 was consistent with the known NPY Y1 distribution; uptake was highest in the striatum and cortical regions and lowest in the pons, cerebellum nuclei, and brain stem. Blockade of [(18)F]Y1-973 uptake with NPY Y1 antagonist Y1-718 revealed a specific signal that was dose-dependently reduced in all regions of grey matter to a similarly low level of tracer uptake, indicative of an NPY Y1 specific signal. In vitro autoradiographic studies with [(18)F]Y1-973 in rhesus monkey and human brain tissue slices revealed an uptake distribution consistent with the in vivo PET studies. Highest binding density was observed in the dentate gyrus, caudate-putamen, and cortical regions; moderate binding density in the hypothalamus and thalamus; and lowest binding density in the globus pallidus and cerebellum. In vitro saturation binding studies in rhesus monkey and human caudate-putamen homogenates confirmed a similarly high B(max)/K(d) ratio for [(18)F]Y1-973, suggesting the tracer may provide a specific signal in human brain of similar magnitude to that observed in rhesus monkey. [(18)F]Y1-973 is a suitable PET tracer for imaging NPY Y1 in rhesus monkey with potential for translation to human PET studies.


Quality of life of ALS and LIS patients with and without invasive mechanical ventilation.
There are very few studies where quality of life (QOL) is assessed in patients with complete physical and functional disability and dependence to invasive mechanical ventilation (IV). We compared QOL of amyotrophic lateral sclerosis (ALS) and locked-in-syndrome (LIS) patients with invasive mechanical ventilation to ALS and LIS patients without mechanical invasive ventilation. Thirty-four patients, 27 with ALS and seven with LIS (vascular or tumoral aetiology) were included in the study. Twelve had invasive ventilation, 22 had non-invasive ventilation, and in the non-invasive ventilation group, five of them had ventilation via mask. The following scales were used for patients: ALS Functional Rating Scale (ALSFRS), McGILL, Short-Form 36 (SF36), Beck Depression Inventory-II, the Toronto Alexithymia Scale and the anxiety inventory of Spielberger. Mean ALSFRS scores were significantly lower in the invasive ventilation group (IV) than in the non-invasive ventilation group. McGILL and SF36 were not significantly different between the IV group and the non-invasive ventilation group; there were no significant differences between the two groups for others scales either. Comparison between IV group and LIS without invasive mechanical ventilation revealed no significant difference for SF36 and McGILL QOL scores. QOL was not significantly different between the IV and not invasively ventilated patients, but ALSFRS was significantly lower in the IV group, and comparison of QOL scores between non-ventilated LIS patients who had the same score of dependence that invasively ventilated patients did not show any difference. Invasive mechanical ventilation for patients who accept tracheotomy allows life prolongation and their QOL is not affected; medical teams should be aware of that.


Cardiopulmonary arrest secondary to compression of the heart owing to esophageal hiatal hernia: a case report.
Esophageal hiatal hernia is commonly encountered in clinical practice. We describe a case of cardiac compression caused by an esophageal hiatal hernia that resulted in circulatory failure and cardiac arrest. An 82-year-old woman presented to our hospital with vomiting, which progressed to cardiac arrest in the emergency room after computed tomography (CT) imaging. CT revealed gastric herniation into the mediastinum, with marked cardiac compression. Cardiopulmonary resuscitation was performed, and a nasogastric tube was inserted for gastric decompression, which resulted in the return of spontaneous circulation and subsequent hemodynamic stabilization. However, the patient died of aspiration pneumonia 4 days later. Gastric decompression can lead to rapid improvements in respiration and circulation in patients with an esophageal hiatal hernia. Nonetheless, to prevent complications, such as those observed in our patient, definitive surgical treatment is warranted.


[Computed Tomography in the Evaluation of Coronary Atherosclerotic Plaques: Comparison With Intravascular Ultrasound].
Determination of computed tomography angiography (CTA) informativeness in assessment of state of atherosclerotic coronary plaque (ACP) and identification of signs of its instability compared with intravascular ultrasound (IVUS). Coronary CTA was carried out in 52 patients with clinical presentation of non-ST elevation (NSTE) acute coronary syndrome on the first day of hospitalization. ACPs were identified in 32 of 52 patients (61.5%). IVUS was performed in 32 patients (mean age 58+/-11.4 years, 27 men, 5 women, 22 with unstable angina, 10 with NSTE myocardial infarction) and 50 plaques in 45 coronary arteries were characterized (39 with spectral analysis of IVUS data). All data were compared with the results of coronary CTA. Sensitivity and specificity of CTA in the detection of stenosis >50% were 97.67 and 71.40%, respectively. Correlation analysis showed a high comparability of methods in determining plaque burden (r=0.80, 95% confidence interval [CI] 0.67 - 0.88, p<0.0001), plaque length (r=0.75, 95%CI 0.60 - 0.85, p<0.0001), and remodeling index (r=0.62, 95%CI 0.40 - 0.77, p<0.0001). Threshold value for "low-density areas" of plaques typical for thin cap fibroatheroma was less or equal 41 Hounsfield units (sensitivity 82%; specificity 86%; area under the curve 0.824; 95% CI 0.615 - 0.947, p<0.0005). Coronary CT is a non-invasive method for rapid characterization of ACP. CT results correlate well with IVUS data, including identification of such important signs of plaque instability as presence of "low-density zone" and positive remodeling at the plague level.


Cadmium affects autophagy in the human intestinal cells Caco-2 through ROS-mediated ERK activation.
Cadmium is a toxic metal that enters the food chain. Following oral ingestion, the intestinal epithelium has the capacity to accumulate high levels of this metal. We have previously shown that Cd induces ERK1/2 activation in differentiated but not proliferative human enterocytic-like Caco-2 cells. As autophagy is a dynamic process that plays a critical role in intestinal mucosa, we aimed the present study 1) to investigate the role of p-ERK1/2 in constitutive autophagy in proliferative Caco-2 cells and 2) to investigate whether Cd-induced activation of ERK1/2 modifies autophagic activity in postconfluent Caco-2 cell monolayers. Western blot analyses of ERK1/2 and autophagic markers (LC3, SQSTM1), and cellular staining with acridine orange showed that ERK1/2 and autophagic activities both decreased with time in culture. GFP-LC3 fluorescence was also associated with proliferative cells and the presence of a constitutive ERK1/2-dependent autophagic flux was demonstrated in proliferative but not in postconfluent cells. In the latter condition, serum and glucose deprivation triggered autophagy via a transient phosphorylation of ERK1/2, whereas Cd-modified autophagy via a ROS-dependent sustained activation of ERK1/2. Basal autophagy flux in proliferative cells and Cd-induced increases in autophagic markers in postconfluent cells both involved p-ERK1/2. Whether Cd blocks autophagic flux in older cell cultures remains to be clarified but our data suggest dual effects. Our results prompt further studies investigating the consequences that Cd-induced ERK1/2 activation and the related effect on autophagy may have on the intestinal cells, which may accumulate and trap high levels of Cd under some nutritional conditions.


Psychometric performance of the PAncreatic CAncer disease impact (PACADI) score.
Pancreatic Cancer Disease Impact (PACADI) score measures the impact of pancreatic cancer (PC) on important health dimensions, selected by patients. The aim of this single center study was to test the psychometric performance of the Pancreatic Cancer Disease Impact (PACADI) score. Patients with suspected pancreatic cancer (PC) completed PACADI, the EuroQol-5D (EQ-5D index) and Edmonton Symptom Assessment System (ESAS) in this longitudinal observational study. Measures were compared across patients with PC (n = 210), other malignant lesions (OML) (n = 109) and non-malignant lesions (NML) (n = 41). Associations, test-retest and internal consistency reliability, longitudinal changes, sensitivity to change and prediction of mortality during the first year were examined in patients with PC. The three measures discriminated between PC and OML. The PACADI score correlated strongly at baseline (n = 199)/after three months (n = 85) with the EQ-5D index and ESAS "sense of well-being" (0.64 and 0.66/0.73 and 0.69, p < 0.001, respectively), showed high test-retest reliability (ICC 0.84) and very good internal consistency reliability (Cronbach's alpha 0.81-0.85) across all visits. Scores improved over time at 3, 6, 9 and 12 months for survivors, and standardized response mean (SRM) for improvement between 2 and 3 months (n = 44) was 0.80 (PACADI), -0.59 (EQ-5D index) and 0.69 (ESAS "sense of well-being"). The PACADI score significantly predicted mortality within the first year (p = 0.02) in contrast to the EQ-5D index and ESAS "sense of well-being". This study showed satisfactory psychometric performance of the PACADI score. The results support its use in clinical practice and intervention trials.


Intravitreal injections: past trends and future projections within a UK tertiary hospital.
To describe past trends and future projections for the number of intravitreal injections being administered at a large tertiary hospital in London, United Kingdom. Retrospective data from Moorfields Eye Hospital were collected using the electronic medical record system. Descriptive statistics were used to visualise overall trends. Time series forecasting was used to predict the number of injections that will be administered up to and including the year 2029. The number of injections has increased nearly 11-fold from 2009 to 2019, with a total of 44,924 injections delivered in 2019. The majority of injections were given for the treatment of neovascular age-related macular degeneration. Aflibercept formed 87% of injections administered in 2019. The number of injections is predicted to continue to increase every year, with nearly 83,000 injections forecasted in the year 2029. The demand for intravitreal injections has increased substantially over the last decade and is predicted to further increase. Healthcare systems will need to adapt to accommodate the high demand. Other solutions may include longer-acting therapies to reduce the treatment burden.


Significance of inducibility of atrial fibrillation after pulmonary vein isolation in patients with healthy left atrium substrate.
The significance of the inducibility of atrial fibrillation (AF) after pulmonary vein isolation (PVI) in patients with AF remains disputable and polarizing. Therefore, we investigated the prognostic value of the inducibility of AF on long-term outcome after PVI in patients without low-voltage left atrial (LA) substrate. Two hundred forty-five patients (mean age 59+/-9years, 72% male) without LA low-voltage areas (defined as electrogram amplitudes <0.5 mV) undergoing first PVI procedure were included in the study. Following successful PVI, inducibility was assessed by burst pacing from coronary sinus with a cycle length (CL) of 300, 250, and 200 ms or the shortest CL resulting in 1:1 atrial capture. During the follow-up period of up to 3 years, the rhythm outcome was monitored by serial 7-days Holter electrocardiogram. AF was induced in 38 patients (16%). Atypical atrial flutter was observed in six patients (2%), while typical flutter in three cases (1%). Within the first 3 months, early recurrence was diagnosed in 39 patients (16%), while late recurrence was detected in 58 patients (24%) after a mean AF free survival of 28 ± 1 months. While there was no impact on early recurrence, AF inducibility affected long-term recurrence (31 ± 1 vs 23 ± 3 months; P = .001). In multivariate analysis, AF inducibility (hazard ratio [HR] 2.14; 95% confidence interval [CI], 1.03-4.45; P = .041) and persistent type of AF (HR 2.17; 95%CI, 1.06-4.47; P = .034) were associated with late AF recurrence. In patients without low-voltage substrate undergoing PVI, AF inducibility is a significant predictor of long-term outcome. The pathomechanisms of this phenomenon must be further studied to be addressed by additional treatment.


Diagnostic morphologic and urodynamic antegrade pyelography.
Diagnostic antegrade pyelography, with a thin needle, is basically a simple procedure that can be performed relatively rapidly under local anesthesia with few complications of significance. Its role, however, is frequently crucial to subsequent patient management. During morphologic antegrade examination, aspirated urine can be analyzed for tumor cells (cytologic examination), infection (smear, culture), or other biochemical alterations. The use of antegrade pyelography in the demonstration of internal diversion, ureteral fistula, and the site and cause of obstruction is well established. Dynamic antegrade study is crucial in the assessment of many pyeloureteral units in which the issue of current obstruction is equivocal or uncertain. Absolute renal and bladder pressures are obtained simultaneously; these and the calculated differential pressure provide objective data relative to ureteral resistance to urine flow and renal nephron preservation.


Effects of Thai native chicken breast meat consumption on serum uric acid level, biochemical parameters, and antioxidant activities in rats.
This study aimed to evaluate the effect of a high protein diet comprising breast meat from commercial broiler (BR), Thai native (PD), and commercial broiler × Thai native crossbred (KKU-ONE) chicken on serum uric acid, biochemical parameters, and antioxidant activities in rats. Male Sprague-Dawley rats were divided into four groups. The control group received a standard chow diet, and the other three groups were fed a high protein diet (70% standard diet + 30% BR, PD, or KKU-ONE chicken breast) for five weeks. The PD- and KKU-ONE-fed rats had lower plasma total cholesterol and triglyceride levels than the control rats. A decrease in HDL-c was also observed in rats fed a diet containing BR. Liver weight, liver enzyme, plasma ALP, xanthine oxidase activity, serum uric acid, creatinine, superoxide production, and plasma malondialdehyde levels increased in BR-fed rats. The findings of this study might provide evidence to support the use of Thai native and Thai native crossbred chicken breast meat as functional foods.


Subcompartments of the endoplasmic reticulum.
The endoplasmic reticulum (ER) is the largest continuous endomembrane structure in the cytoplasm. It may be viewed as a series of unique subcompartments. In this review, we examine the rough ER, nuclear envelope and several smooth ER subcompartments. Consideration is given to the characteristic properties and functions of the ER and its domains, and to the formation and maintenance of subcompartments. Associations within the ER membrane bilayer, and with constituents of the cytoplasm and the ER lumen, contribute to the formation of domains and lead to the establishment of subcompartments that reflect specialized functions and vary according to the physiologic state and phenotype of the individual cell. Although the structural complexity of some ER subcompartments (such as the sarcoplasmic reticulum) is highly elaborate, the ER remains a dynamic organelle, subject to assembly and disassembly, capable of extensive remodelling and active in exchange with other organelles through mechanisms of membrane transport.


Superconductivity in nickel-based 112 systems.
Superconductivity has been discovered recently in infinite-layer nickel-based 112 thin films R 1-x A xNiO2 (R = La, Nd, Pr and A = Sr, Ca). They are isostructural to the infinite-layer cuprate (Ca,Sr)CuO2 and are supposed to have a formal Ni 3d 9 valence, thus providing a new platform to study the unconventional pairing mechanism of high-temperature superconductors. This important discovery immediately triggers a huge amount of innovative scientific curiosity in the field. In this paper, we try to give an overview of the recent research progress on the newly found superconducting nickelate systems, both from experimental and theoretical aspects. We mainly focus on the electronic structures, magnetic excitations, phase diagrams and superconducting gaps, and finally make some open discussions for possible pairing symmetries in Ni-based 112 systems.


Freehand S2-Alar-Iliac Screw Placement Technique in Lumbosacral Spinal Tumors: A Preliminary Study.
S2-alar-iliac (S2AI) screw technique is widely used in spinal surgery, but it is rarely seen in the field of spinal tumors. The aim of the study is to report the preliminary outcomes of the freehand S2AI screw fixation after lumbosaral tumor resection. The records of patients with lumbosacral tumor who underwent S2AI screw fixation between November 2016 to November 2020 at our center were reviewed retrospectively. Outcome measures included operative time, blood loss, complications, accuracy of screws, screw breach, and overall survival. Mean ± standard deviation or range was used to present continuous variables. Kaplan-Meier curve was used to present postoperative survival. A total of 23 patients were identified in this study, including 12 males and 11 females, with an average age of 47.3 ± 14.5 (range,15-73). The mean operation time was 224.6 ± 54.1 (range, 155-370 min). The average estimated blood loss was 1560.9 ± 887.0 (600-4000 ml). A total of 46 S2AI screws were implanted by freehand technique. CT scans showed three (6.5%) screws had penetrated the iliac cortex, indicating 93.5% implantation accuracy rate. No complications of iatrogenic neurovascular or visceral structure were observed. The average follow-up time was 31.6 ± 15.3 months (range, 13-60 months). Two patients' postoperative plain radiography showed lucent zone around the screw. One patient underwent reoperation for wound delayed infection. At the latest follow-up, eight patients had tumor-free survival, 11 had survival with tumor, and four died of disease. The freehand S2AI screw technique is reproducible, safe, and reliable in the management of lumbosacral spinal tumors.


Symptomatic skeletal-related events in patients receiving longer term bone-modifying agents for bone metastases from breast and castration resistant prostate cancers.
The effect of longer-term use of bone-modifying agent (BMA) on symptomatic skeletal event (SSE) rates in patients with bone metastases remains unclear. This retrospective study of a cohort of patients in a randomized controlled trial evaluated SSEs in patients receiving BMAs at a single cancer center. Data from patients with metastatic breast and castration-resistant prostate cancer (CRPC) were interrogated to evaluate the effects of longer-term use of BMAs on incidence, type, and risk factors for SSEs. Of 162 patients, 109 (67%) had breast cancer (BC) and 53 (33%) CRPC. Median age at diagnosis of bone metastases was 61.9 years (range 27.5-97.2) for BC patients and 72.1 (range 37.0-92.2) for CRPC patients. Median duration of BMA use was 2.3 years (range 0.1-9.9 years) for BC and 3.8 years (range 1.5-9.4) for CRPC patients. The initial BMAs in BC patients were pamidronate (46.8%), denosumab (31.2%), and zoledronate (22%). All CRPC patients received denosumab. During follow-up, 59% of BC and 75% of CRPC patients had at least one SSE. The number of patients experiencing ≥ 1 SSE per year was higher in the first year after bone metastasis diagnosis (63/162; 38.9%) compared with that in the second (26/149; 17.5%) and third years (30/123; 24.4%). Neither age, visceral disease, multiple bone metastases, nor biological markers for BC had a significant impact on time to first SSE. The risk for SSEs was greatest in the first year after diagnosis of bone metastasis. Studies evaluating de-escalation and even stopping of BMAs with longer-term use may therefore be warranted.


On the derivation of coefficient of Morse potential function for the silicene: a DFT investigation.
In this paper, the structural and mechanical properties of silicene are investigated by the density functional theory calculations. To calculate Young's, bulk, and shear moduli and Poisson's ratio of the silicene, the optimized unit cells containing two atoms are proposed and the effect of chirality on the elastic properties of silicene is examined. It is shown that the silicene has an isotropic behavior, while graphene has an anisotropic behavior. The results showed that calculated moduli for the silicene are significantly lower than those of graphene in zigzag and armchair directions, while Poisson's ratio of silicene is higher than that of graphene. The paper describes one common type of inharmonic interatomic potentials used for constructing nonlinear models of the material using the modified Morse potential function. Using this concept, the effects of chirality on dissociation energy, inflection point, and coefficients of the modified Morse potential function are studied. Comparison of the cutoff distance value in the modified Morse potential showed that inflection point values for the armchair and zigzag graphene are highly direction-dependent, whereas these values have negligible difference for silicene.


Pros of priming in the diagnosis of growth hormone deficiency.
Priming with sex steroids in stimulation tests for the diagnosis of GHD is still under debate. Most of the data on utility of priming during GH stimulation so far seem to support its use in the diagnosis of GHD in childhood. There is a propensity to treat growth retarded children who test subnormally to stimulation tests with GH. However, some studies analyzing the final height or height gain during GH treatment in such children failed to show any improvement in height. This paper summarizes previous studies on priming to analyze the utility of priming as a valid method to better the diagnostic capacity of the test.


Preparation, characterization, and bioavailability evaluation of antioxidant phosvitin peptide-ferrous complex.
Iron deficiency anemia (IDA) is one of the commonest global nutritional deficiency diseases, and the low bioavailability of iron is a key contributing factor. The peptide-iron complex could be used as a novel iron supplement to improve iron bioavailability. In this study, antioxidant low molecular weight (<3 kDa) phosvitin peptide (named PP-4) was separated to prepare a phosvitin peptide-ferrous complex (named PP-4-Fe); then the structural conformation of PP-4-Fe was characterized and its bioavailability by in vitro digestion was evaluated. The results showed that PP-4 had good ferrous-binding activity with 96.14 ± 2.86 μg Fe2+ mg-1 , and had a strong antioxidant effect with 995.61 ± 79.75 μmol TE mg-1 in 2,2'-azinobis'3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 62.3 ± 3.95 μmol FeSO4 mg-1 in ferric ion reducing antioxidant power (FRAP). After ferrous binding, the FRAP activity of PP-4-Fe, enhanced by 1.8 times, formed a more ordered structure with an increase in α-helix and decrease in γ-random coil. The ferrous binding sites of PP-4 involved were the amino, carboxyl, imidazole, and phosphate groups. The PP-4-Fe complex displayed excellent gastrointestinal stability and antioxidant effects during digestion. The iron dialysis percentage of PP-4-Fe was 74.59% ± 0.68%, and increased to 81.10% ± 0.89% with the addition of 0.25 times vitamin C (VC). This indicated that PP-4-Fe displayed excellent bioavailability and VC in sufficient quantities had a synergistic effect on improving bioavailability. This study demonstrated that antioxidant phosvitin peptide was an efficient delivery system to protect ferrous ions and suggested that the phosvitin peptide-ferrous complex has strong potential as a ferrous supplement. © 2023 Society of Chemical Industry.


Psychometric properties of the EQ-5D-3L in South Australia: a multi-method non-preference-based validation study.
Although HRQoL tools such as the EQ-5D-3L are significant in determining health status, these measures have not been validated in general populations in Australia. This study aims to psychometrically validate the EQ-5D-3L in a large population sample in Australia for the first time. The EQ-5D-3L was included in the Dental Care and Oral Health study (DCOHS), conducted in a South Australian population sample. The participants were 23-91 years old, and 44.1% were male. The EQ-5D-3L was responded to on a three-point rating scale ("none"/"no", "some" and "extremely"/"unable"/"confined"). We employed the area under the receiver operating characteristic curve (AUROC) to evaluate whether the EQ-5D-3L total score could identify participants with diagnosed diseases and mental health disorders. Psychometric validation of the EQ-5D-3L investigated dimensionality with Exploratory Graph Analysis, model fit, floor/ceiling effects and criterion validity. The EQ-5D-3L comprised two dimensions, Activities and Symptoms. According to Root Mean Squared Error of Approximation (RMSEA) (<.05) and Comparative Fit Index (CFI) (>.950), the 2-dimensional structure showed excellent model fit with good reliability for the Activities subscale (Ωc = 0.80-95% CI [0.77, 0.83]), and poor reliability for the Symptom subscale (Ωc = 0.56-95% CI [0.53, 0.58]). The EQ-5D-3L showed adequate reliability (Ωc = 0.70-95% CI [0.67, 0.72]). The EQ-5D-3L showed good discrimination for diagnosed diseases (ranging from 64.3% to 86.3%). Floor/ceiling effects were observed across all items. The EQ-5D-3L total score discriminated between respondents who were experiencing health conditions (e.g. cancer, cardiovascular disease, stroke) from healthy individuals. Despite the ceiling effects, the EQ-5D-3L displayed good psychometric properties as an HRQoL measure and discriminated between health states in the general South Australian population. Further research should investigate the psychometric properties of the EQ-5D-5L in South Australia and whether an increased number of response categories can mitigate the observed ceiling effects.


Dog Tales: Mindful Dog Interactions Evoke Similar Experiences to Dog Assisted Mindfulness Meditations.
Stay-at-home regulations in response to COVID-19 have put humans at increased risk of loneliness. Some studies support dog ownership as a protection against loneliness, while other studies have suggested the lockdowns can be used to reflect upon the similar restrictions owners impose on their pets on a daily basis. This study evaluated two novel ways to enrich the lives of pet dogs in the home, while also providing benefits to owners. It was hypothesized that a six-week Dog Assisted Mindfulness (DAM) intervention and a Dog Interactions (DI) intervention would positively impact owner-rated loneliness, mindfulness, and owner-dog emotional attachment, compared to a control group. Seventy-three participants were randomly assigned to each group. Mixed methods ANOVAs found no significant main effects of group, nor any group × time interaction effects. Qualitative analyses revealed common experiences among participants in the two active interventions, including enhanced owner-dog connection, and feelings of relaxation, happiness and engagement both during and after participating in the weekly activities. There was also an added benefit of 'dog happiness' in the interactions group. Future studies should investigate this in a more objective manner and in the meantime, regular owner-dog interactions should be encouraged, especially during times of extended lockdown.


Changes in the organization of actin filaments in the stereocilia of noise-damaged lizard cochleae.
Alligator lizards exposed to 105 dB broadband noise for 24 h showed a 33 dB loss in hearing which was almost completely recovered 11 days after removal from the noise. Two lesions were found in the actin filament organization which could affect the rigidity of the stereocilia and thus could account for this hearing loss. These lesions preferentially affect the tallest stereocilia. The more common one is a depolymerization of the actin filaments at the base of the stereocilium where it makes contact with the cuticular plate. This results in a displacement and detachment of the stereocilium from its rootlet, thereby affecting the orientation of the tallest stereocilium. The other lesion involves a loss in crossbridges between adjacent actin filaments in the stereocilium. We demonstrate that such a loss will dramatically affect the rigidity of the stereocilia.


Docetaxel Rechallenge Improves Survival in Patients With Metastatic Castration-resistant Prostate Cancer: A Retrospective Study.
Docetaxel has been widely used in metastatic Castration-resistant Prostate Cancer (mCRPC) patients for decades. The purpose of the study was to evaluate the efficacy of docetaxel rechallenge in patients with mCRPC. We retrospectively compared patients who had received either first-line docetaxel and rechallenge after Androgen Receptor-axis Targeted therapies (ARAT), to those without rechallenge docetaxel. Multivariate cox-regression analysis was used to evaluate survival. Out of the 204 patients with mCRPC enrolled in the study, 24 patients received docetaxel rechallenge and 180 did not. The median overall survival was 50.11 months in the rechallenge group, as compared to 26.36 months in the non-rechallenge group (p of log rank=0.044). In the multivariate model, doxetaxel rechallenge was an independent risk factor for overall survival [hazard ratio (HR)=0.59, 95% confidence interval (CI)=0.32-0.99], together with the performance status score 2 (HR=2.46, 95%CI=1.32-4.58), hormone-sensitive state duration (HR=0.99, 95%CI=0.99-0.999), liver (HR=1.90, 95%CI=1.04-3.47) and brain metastases (HR=2.23, 95%CI=1.26-5.46). The advantage of rechallenge was addressed in the androgen receptor-axis-targeted (ARAT) non-responsive patients (HR=0.36, 95%CI=0.17-0.78). Adverse events were at 29.17% with Grade 3/4 neutropenia and at 20.83% with Grade 1/2 neutropenia in the docetaxel rechallenge group. The docetaxel rechallenge improved survival in patients with mCRPC failure of first-line docetaxel and subsequent abiraterone acetate or enzalutamide. Independent predictive factors for overall survival included i) the performance status, ii) hormone-sensitive state duration, iii) liver and iv) brain metastases. Patients non-responsive to ARATs will benefit from docetaxel rechallenge with regards to overall survival.


Efficacy of RetroNectin-activated cytokine-induced killer cell therapy in metastatic brain tumor patients.
The aim of this study was to investigate the clinical efficacy of RetroNectin-activated cytokine-induced killer cell (R-CIK) therapy following conventional therapies in patients with metastatic brain tumors. This study included 20 patients with metastatic brain tumors. Patients received R-CIK therapy following conventional therapies (including chemotherapy and target therapy). Progression-free survival (PFS), overall survival (OS), and prognostic factors were evaluated. Of the 4 breast cancer patients in our cohort, 2 remained alive and 2 died. Of the 14 non-small cell lung cancer (all adenocarcinoma) patients, 3 had a partial response, 8 had stable disease, and 3 had progressive disease after receiving R-CIKs. The overall response rate was 21.4% (3/14), and the disease control rate was 78.6% (11/14). The median PFS and OS were 7.7 months (95% confidence interval (CI) 3-16.5 months) and 12.6 months (95% CI 6-21 months), respectively. R-CIKs combined with conventional therapies could improve the prognosis of metastatic brain tumor patients, especially of those with adenocarcinoma of the lung.


Previous flight facilitates partner finding in female crickets.
In the cricket Gryllus bimaculatus, flying occurs soon after the last imaginal molt and precedes the mating behavior in natural conditions. Here, we tested the hypothesis that flying may improve subsequent behavioral performance in a novel environment in female crickets. We developed a behavioral set-up to test female cricket responsiveness to male calling song as well as their ability to locate and find the source of the song. The male song was produced by a loudspeaker hidden behind the fabric wall of a spacious square arena. Forced flight prior to the test promoted female sexual searching behavior in the novel environment. After the flight, more females reached the hidden source zone, spent more time near the source and finally more of them climbed over the wall section immediately in front of the hidden loudspeaker. At the same time, their behavior in the arena did not differ from the control group when the calling song was not delivered, suggesting that flight exerts its behavioral effects by influencing sexual motivation. Our results support the suggestion that preceding intense locomotion facilitates sexual searching behavior of females in a novel environment.


Bilateral Painful Hand Seizures: An Atypical Somatotopic Syndrome.
Painful Hand Seizures are a rarely reported form of secondary sensory seizures (SSS) characterized by painful, bilateral sensorimotor hand involvement and preserved consciousness. We report our case to aid neurologists in recognizing SSS as an atypical presentation of seizures.


Biological treatment in adult-onset Still's disease.
Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder that is characterised by high spiking fever, arthritis or arthralgia, and evanescent rash. Many other systemic manifestations may occur. Pathogenesis of AOSD remains partially unknown but a major role has been recently attributed to pro-inflammatory Th1 cytokines, including tumour necrosis factor-α (TNF-α), interleukin (IL)-1, IL-6 and IL-18. Despite limited evidence, mainly based on observational studies and the extrapolation to AOSD of the results of a few controlled studies that have been conducted in children with systemic juvenile idiopathic arthritis, biological agents represent a major therapeutic advances for patients with AOSD refractory to conventional treatment or presenting life-threatening manifestations. Both IL-1 and IL-6 blockade may be more effective than TNF-α blockers. Although debatable, therapeutic strategies are proposed.


Prevalence of glucose 6-phosphate dehydrogenase deficiency in highly malaria-endemic municipalities in the Brazilian Amazon: A region-wide screening study.
Difficulties associated with the assessment of glucose-6-phosphate dehydrogenase deficiency (G6PDd), particularly in remote areas, hinders the safe use of 8-aminoquinolines such as primaquine (PQ) and tafenoquine against Plasmodium vivax malaria due to the risk of haemolysis. This cross-sectional study was conducted in 41 malaria-endemic municipalities of six states in the Brazilian Amazon, between 2014 and 2018. Male individuals were screened for G6PDd using the qualitative Fluorescent Spot Test using fingerpick-collected whole blood samples. Point and interval estimates of the G6PDd prevalence were calculated for each state. Deficient samples were genotyped for the most prevalent variants in the Amazon. Frequencies of P. vivax malaria recurrences were estimated for G6PDd and non-G6PDd patients. This is one of the largest surveys ever conducted in Latin America, covering the entire malaria endemic area in the Brazilian Amazon. These results indicate that an important proportion of the population is at risk of hemolysis if exposed to PQ and its congener drug tafenoquine. The adoption of G6PDd screening protocols is essential to ensure the safety of individuals treated with those drugs and should also be considered when implementing malaria elimination strategies. A total of 14,847 individuals were included, of which 5.6% presented G6PDd. The state of Acre had the highest G6PDd prevalence (8.3%), followed by Amapá (5.8%), Pará (5.7%), Rondônia (5.4%), Roraima (4.2%) and Amazonas (4.0%). From 828 genotyped samples, African A+ (6.2%), African A- (39.3%) and wild-type (non-African non-Mediterranean; 54.2%) variants were found. A greater proportion of malaria recurrences was found among G6PD deficient individuals [16.7% vs 4.1%, Risk ratio 3.52 (2.16-5.74) p < 0.01]. Brazilian Ministry of Health; Fundação de Amparo à Pesquisa do Estado do Amazonas (FAPEAM).


Reversal operations after brain damage.
The ability to perform reversals--that is, the appreciation of the relationship between original and transformed states of knowledge--is critical to human thought processes. In order to assess whether a number of "special-purpose processors" are responsible for reversal operations, depending on the particular context in which the reversal is couched, or whether a single "core processing mechanism" subserves a critical aspect of reversal operations regardless of the specific context, patients with localized brain damage were asked to solve eight reversal problems. Visual and auditory reversals mediated by linguistic and non-linguistic symbol systems were presented. The findings demonstrate that patients with insult to the anterior portion of the right hemisphere encounter more difficulty performing reversals than patients with right posterior insult, Broca's aphasics, and fluent aphasics. This is regardless of the symbol system mediating the reversal, regardless of the modality of presentation, and regardless of the amount of available processing time. Subjects with insult to the posterior region of the left hemisphere or the right hemisphere also exhibit some difficulty solving reversal problems, although their difficulties appear modality specific. These data lend support to the claim that a core processing mechanism may play a critical role in the performance of reversal operations.


NMR structure of an intracellular loop peptide derived from prostaglandin EP3alpha receptor.
We found that a peptide (EP3a: TIKALVSRCRAKAAV) corresponding to the N-terminal site of the intracellular third loop of human prostaglandin EP3alpha receptor could activate G protein alpha-subunit directly. The activity was almost same as Mastoparan-X, a G protein activating peptide from wasp venom. The three-dimensional molecular structure of the peptide in SDS-d(25) micelles was determined by 2D (1)H NMR spectroscopy. The structure of EP3a consists of a positive charge cluster on the C-terminal helical site. The cluster was also found in several corresponding receptor peptides. Therefore, the positive charge cluster on the helical structure might play a crucial role in activation of G protein.


Prediction of drug solubility from structure.
The aqueous solubility of a drug is an important factor affecting its bioavailability. Numerous computational methods have been developed for the prediction of aqueous solubility from a compound's structure. A review is provided of the methodology and quality of results for the most useful procedures including the model implemented in the QikProp program. Viable methods now exist for predictions with less than 1 log unit uncertainty, which is adequate for prescreening synthetic candidates or design of combinatorial libraries. Further progress with predictive methods would require an experimental database of highly accurate solubilities for a large, diverse collection of drug-like molecules.


Conventional and Alternative Mesenchymal Stem Cell Therapies for the Treatment of Diabetes.
Diabetes is a public health problem affecting millions of people around the world. Despite the availability of many antidiabetic medications, the adequate level of control of the disease and management of diabetic patients remain a huge challenge. Because of the limitations of current therapies and the tremendous potential of non-conventional treatments such as stem cell therapy, herein, we review the applications of mesenchymal stem cells (MSCs) in treating diabetes. Owing to their unique regenerative and immunomodulatory properties, MSCs have been widely utilized in numerous applications both in animal models and human clinical trials for the treatment of diabetes. This review will summarize the latest experimental and clinical studies that have provided evidence of the beneficial role of MSCs in diabetes treatment.


Systemic reactions to subcutaneous allergen immunotherapy.
Subcutaneous allergen immunotherapy (SCIT) has been practiced for 100 years. Many trials have established the efficacy of SCIT in reducing symptoms of both seasonal allergic rhinitis and asthma due to aeroallergens. However, clinical benefits of SCIT are tempered by risks of injection-related systemic reactions and life-threatening anaphylaxis. This article reviews data derived from retrospective surveys conducted to define the incidence, prevalence, and factors contributing to injection-related fatal anaphylactic and near-fatal systemic reactions, as well as recently initiated longitudinal surveillance studies of SCIT reactions.


Regionalization of perinatal care for the United States.
A scheme of regionalization is proposed in which a regional perinatal system within a defined geographic area permits access of the high risk mother-fetus and infant to the appropriate level of technology for improved perinatal outcome.


The use of three-dimensional biometric Foot and Ankle Offset to predict additional realignment procedures in total ankle replacement.
Decision to perform associated corrective alignment procedures in patients undergoing total ankle replacement (TAR) is commonly made intraoperatively. The Foot and Ankle Offset (FAO) can evaluate multiplanar deformity and be an effective instrument in surgical planning. This study objective was to assess the ability of this tool to predict the need for additional realignment procedures at the time of TAR. In this retrospective study, we enrolled 21 patients who underwent TAR and had preoperative WBCT studies. Two independent and blinded observers calculated the preoperative FAO using dedicated software. FAO measurements were compared between the different alignment groups (physiological alignment, valgus and varus). A multivariate regression analysis was used to assess the correlation between performed realignment procedures and FAO values. Mean preoperative FAO was 4.4% (95%CI = 1.4-7.5). The number of osseous realignment procedures needed was found to correlate positively and significantly with FAO (p = .001). The number of osseus procedures needed was significantly higher in patients with valgus malalignment (p = .009). Patients with valgus malalignment needing a medial column procedure had a relative risk of 6.3 when compared to varus malalignment patients (p = .02). The number of additional bony realignment procedures performed at the time of TAR significantly correlated with preoperative FAO and that the number of osseus procedures needed was significantly higher in patients with valgus malalignment. Such biometric tools may enhance the preoperative assessment and surgical planning for patients undergoing TAR, with the potential to optimize surgical outcomes.


A fully diarylmethylene-bridged triphenylamine derivative as novel host for highly efficient green phosphorescent OLEDs.
A fully diarylmethylene-bridged triphenylamine derivative is efficiently synthesized. It has an almost planar triphenylamine (TPA) skeleton and exhibits excellent thermal and morphological stability. Devices with the novel TPA derivative as host material and Ir(ppy)(3) as triplet emitter show a maximum current efficiency of 83.5 cd/A and a maximum power efficiency of 71.4 lm/W for green electrophosphorescence.


Analysis of patient dose in full field digital mammography.
Now, full field digital mammography (FFDM) is widely used in diagnosis of breast cancer. With the development of FFDM, the radiation dose delivered to the patients involved in an imaging protocol is of utmost concern. Here, we analyzed the average glandular dose (AGD) and entrance surface exposure (ESE) of 1397 patients (6008 images) who underwent mammographic examinations by FFDM in three modes with automatic optimization of parameters (AOP), namely STD for standard mode, CNT for contrast mode and DOSE for dose mode. In addition, exposure factors including kVp, tube loading (mAs), and target/filter combination were evaluated. As a result, the patient dose was sorted as CNT>STD>DOSE. The dose difference among the three AOP modes was mainly attributed to the selection of mAs. The AGD and breast compressed thickness were well correlated in STD and DOSE modes. However, the correlation between CNT-delivered AGD and breast compressed thickness was dependent on the range of the breast thickness and patient age. The findings on dose and exposure characteristics of the three AOP modes get useful message of patient dose in the acquisition of FFDM.


Energy-converting hydrogenases: the link between H2 metabolism and energy conservation.
The reversible interconversion of molecular hydrogen and protons is one of the most ancient microbial metabolic reactions and catalyzed by hydrogenases. A widespread yet largely enigmatic group comprises multisubunit [NiFe] hydrogenases, that directly couple H2 metabolism to the electrochemical ion gradient across the membranes of bacteria and of archaea. These complexes are collectively referred to as energy-converting hydrogenases (Ech), as they reversibly transform redox energy into physicochemical energy. Redox energy is typically provided by a low potential electron donor such as reduced ferredoxin to fuel H2 evolution and the establishment of a transmembrane electrochemical ion gradient ([Formula: see text]). The [Formula: see text] is then utilized by an ATP synthase for energy conservation by generating ATP. This review describes the modular structure/function of Ech complexes, focuses on insights into the energy-converting mechanisms, describes the evolutionary context and delves into the implications of relying on an Ech complex as respiratory enzyme for microbial metabolism.


Extensive radiation-induced heart disease in an adult patient treated for lymphoma as a child.
Cardiovascular complications are the second leading cause of late mortality in survivors of Hodgkin's lymphoma (HL) exposed to mediastinal radiotherapy. Symptomatic cardiac disease following classic thoracic irradiation for HL is reported in 10%-30% of patients at 5-10 years of follow-up. We present the case of a 44-year-old man with a history of left cervical nodular lymphocyte predominant HL treated at childhood with 40 Gy extended field thoracic irradiation (Mantle) who presented with mixed aortic and mitral valve disease, coronary artery stenosis, myocardial and aortic calcifications, and mediastinal fibrosis. Despite extensive cardiac surgery, the postoperative course was complicated and resulted in the patient's death. We review herein the typical cardiac involvement related to mediastinal radiotherapy and the controversies surrounding its surgical approach.


The cellular prion protein: biochemistry, topology, and physiologic functions.
Studies on the transmission from man to animals of Creutzfeld-Jacob disease (CJD) led Prusiner to identify a proteinaceous infectious particle lacking nucleic acid, which was called prion. The identification of the infectious prion (PrPsc) then led to the discovery of the normal cellular counterpart (PrPc). One of the still enigmatic aspects regarding prion diseases is actually how, where, and when the transformation PrPc/PrPsc is occurring, this being due to the result of a large extent to the fact that so far most studies have been dedicated to the formation and transmission of PrPsc, whereas the understanding of physiologic roles of PrPc are in their infancy. In this review, we hope to identify the most reliable hypotheses for future experiments on PrPc. This is relevant not only for the understanding of PrPc functions but also to unravel the enigmatic nature of PrPc/PrPsc conversion.


Counting plaques and tangles in Alzheimer's disease: concordance of technicians and pathologists.
Our primary aim is to provide a descriptive approach to the analysis of counts of plaques and tangles by different readers. We wanted to find out whether subjects with minimal training can count plaques and tangles in histological specimens of patients with Alzheimer's disease and controls. Two experienced neuropathologists trained three student helpers to recognize plaques and tangles in slides obtained from autopsy material. After training, the students and pathologists examined coded slides from patients with Alzheimer's disease and controls. Some of the slides were repeated to provide an estimate of reliability. Each reader read four fields which were averaged to obtain estimates of plaque and tangle counts. Raters are compared on four aspects of concordance: location, scale, precision and accuracy. Precision and accuracy are combined to provide an estimate of concordance. We conclude that subjects with minimal training can be taught to count plaques and tangles. Concordance with the neuropathologists was somewhat greater for tangles. This paper also provides a methodology for comparing raters.


Characterization, source identification, risk assessment of potentially toxic elements (PTEs) in the surface water and sediment of the Beibu Gulf, China.
The concentrations, distribution, and risk of seven potentially toxic elements (PTEs), including As, Cd, Cr, Cu, Hg, Pb, and Zn, in seawater and sediment from the eastern Beibu Gulf of China were studied using national standard methods. Results showed that the concentrations of PTEs in seawater exhibited significant spatial and seasonal variations, resulting in tolerable non-carcinogenic and carcinogenic health risks for both adults and children. The sediment concentrations of PTEs were generally lower than historical values, indicating an acceptable pollution level and ecological risk, except for Hg. Granularity was found to be an important factor in regulating the distribution. Furthermore, principal component analysis (PCA) and positive matrix factorization (PMF) model simulation revealed that the sources of PTEs in sediment were primarily of natural origin, with the exception of Hg, which was predominantly of anthropogenic origin. The parent rock of As was different from that of other PTEs.


Diurnal secretion profiles of growth hormone, thyrotrophin and prolactin in Parkinson's disease.
Recently, a massive loss of both hypocretin and melanin-concentrating hormone (MCH) neurones was found in the hypothalamus of Parkinson's disease (PD) patients. Because both hypocretin and MCH play a key role in the regulation of sleep, energy homeostasis and autonomic function, partly by modulation of the somatotrophic, thyrotrophic and lactotrophic axes, neuroendocrine dysregulation may contribute to some of the non-motor features of PD. In eight de novo, medication-free PD patients and eight age-, sex- and body mass index-matched controls, we measured serum levels of growth hormone (GH), thyroid-stimulating hormone (TSH) and prolactin every 10 min for 24 h. Auto-deconvolution, cosinor and approximate entropy analysis were applied to quantify GH, TSH and prolactin secretion rates, diurnal rhythmicity, as well as regularity of hormone release. Sleep was polygraphically-recorded throughout the night. Total 24-h secretion of GH (191 ± 31 versus 130 ± 39 mU/l/24 h), TSH (38 ± 9 versus 36 ± 2 mU/l/24 h) and prolactin (102 ± 14 versus 116 ± 17 μg/l/24 h), as well as their diurnal rhythmicity and regularity of release, were not significantly different between PD patients and controls (all P ≥ 0.12). Fasting levels of insulin-like growth factor-1 were also unaltered in PD patients. However, free thyroxine (T(4) ) levels were significantly higher in PD patients compared to controls (16.19 ± 0.80 versus 13.88 ± 0.40 pmol/l; P = 0.031). In PD patients, prolactin levels were related to disease duration (r = 0.76, P = 0.028), whereas both GH (r = -0.91, P = 0.002) and free T(4) (r = -0.71, P = 0.050) levels correlated inversely with body fat content. Apart from a mild increase in free T(4) levels, we found no indications for altered somatotrophic, thyrotrophic and lactotrophic axes activity in early-stage PD patients.


Bacterial contamination of cystic fibrosis clinics.
Respiratory pathogens from CF patients can contaminate inpatient settings, which may be associated with increased risk of patient-to-patient transmission. Few data are available that assess the rate of bacterial contamination of outpatient settings. We determined the frequency of contamination of CF clinics and the effectiveness of alcohol-based disinfectants in reducing hand carriage of bacterial pathogens. We conducted a point prevalence survey and before-after trial in outpatient clinics at 7 CF centers. The study examined CF patients with positive respiratory cultures for Pseudomonas, Staphylococcus, Stenotrophomonas or Burkholderia species. Hand carriage and environmental contamination with respiratory pathogens were assessed during clinic visits (Part I) and the effectiveness of hand hygiene performed by CF patients (Part II) was determined using molecular typing of recovered isolates. In Part I (n=97), the contamination rate was 13.6%. Pseudomonas and S. aureus, including methicillin-resistant strains, were cultured from patients' hands (7%), the exam room air (8%), and less commonly, environmental surfaces (1%). In Part II (n=100), the hand carriage rate of pathogens was 13.5% and 4 participants without initial detection of pathogens had hand contamination when recultured at the end of the clinic visit. Respiratory pathogens from CF patients can contaminate their hands and the clinic environment, but the actual risk of patient-to-patient transmission in the outpatient setting remains difficult to quantify. These findings support several recommendations CF infection control recommendations including hand hygiene for staff and patients, contact precautions for certain pathogens, and disinfecting equipment and surfaces touched by patients and staff.


Early diagnosis of cutaneous T-cell lymphoma by DNA flow cytometry on skin biopsies.
Seven patients with mycosis fungoides early plaque stage with nondiagnostic histology had single-cell DNA content measured by flow cytometry for estimation of clonal ploidy. A total of 63 skin specimens were examined by histology and DNA measurements concurrently during the course of the disease. In addition, six patients had blood samples studied. All seven patients demonstrated aneuploid DNA histograms when the specimens were obtained from skin lesions. In 36 specimens the aneuploid peaks were hyperdiploid. By sequential studies one patient demonstrated two different aneuploid cell clones, one located in the hyperdiploid region and one located in the hypotetraploid region. All patients developed mycosis fungoides which were histologically confirmed, and the time from first aneuploid DNA histogram until diagnostic histology varied from 5 to 21 months (median, 12 months). In six of the patients a normal diploid DNA histogram was found of peripheral blood lymphocytes. The finding of aneuploidy in patients with early mycosis fungoides who still have a nondiagnostic histology emphasizes the value of flow cytometry as a complementary diagnostic aid which facilitates an early diagnosis.


The comparative fine structure and surface glycoconjugate expression of three life stages of Leishmania major.
The cellular ultrastructure and surface glycoconjugate expression of three life stages of Leishmania major were compared. Noninfective logarithmic phase promastigotes (LP) are immature cells bearing a thin cell coat, short flagellum, small and empty flagellar pocket, and a loose cytoplasm filled with profiles of ER and large Golgi complex. LP also contain subpopulations of maturing cells containing less ER and Golgi and synthesizing cytoplasmic granules of different size, number, and electron-density. Infective or metacyclic promastigotes (MP) are fully differentiated nondividing forms with a thickened, prominent cell coat, long flagellum, distended flagellar pocket filled with secretory material, and few cytoplasmic organelles other than abundant electron-dense granules. Tissue amastigotes also contain electron-dense cytoplasmic granules, their flagellar pockets are also enlarged and contain secretory material, but they lack a discernable cell coat. Immunogold labeling of GP63 on the cell surface was extensive only on amastigotes. Promastigote GP63 appeared to be masked by the presence of a densely packed lipophosphoglycan (LPG) coat which was extensively labeled on the entire surface of MP and LP. An elongated, developmentally modified form of LPG was abundantly labeled only on MP. LPG was poorly labeled on amastigotes, arguing that the promastigote cell coat is a stage-specific structure which is lost during intracellular transformation.


Interaction patterns of adolescents with depression and the important adults in their lives.
The purpose of this study is to describe common interaction patterns between adolescents who are depressed and the important adults in their lives, with special attention given to interactions that influence the course of the teens' depression. Data are drawn from an ongoing grounded theory study of the management strategies and service usage patterns of adolescents who are depressed. The sample includes 52 young adults between the ages of 18 and 21 who experienced depressive symptoms as adolescents, 4 of their parents, and 8 professionals who work with youths. All participants discussed how both adolescents and adults ignore, hide, or minimize the adolescents'distress by putting up a façade. The three common interaction patterns that were identified (maintaining the façade, poking holes in the façade, breaking down the façade) are responses to the façade. The author discusses interaction patterns and their influence on the course of the adolescents' depression.


Phytochemistry and pharmacological activity of the genus artemisia.
Artemisia and its allied species have been employed for conventional medicine in the Northern temperate regions of North America, Europe, and Asia for the treatments of digestive problems, morning sickness, irregular menstrual cycle, typhoid, epilepsy, renal problems, bronchitis malaria, etc. The multidisciplinary use of artemisia species has various other health benefits that are related to its traditional and modern pharmaceutical perspectives. The main objective of this review is to evaluate the traditional, modern, biological as well as pharmacological use of the essential oil and herbal extracts of Artemisia nilagirica, Artemisia parviflora, and other allied species of Artemisia. It also discusses the botanical circulation and its phytochemical constituents viz disaccharides, polysaccharides, glycosides, saponins, terpenoids, flavonoids, and carotenoids. The plants have different biological importance like antiparasitic, antimalarial, antihyperlipidemic, antiasthmatic, antiepileptic, antitubercular, antihypertensive, antidiabetic, anxiolytic, antiemetic, antidepressant, anticancer, hepatoprotective, gastroprotective, insecticidal, antiviral activities, and also against COVID-19. Toxicological studies showed that the plants at a low dose and short duration are non or low-toxic. In contrast, a high dose at 3 g/kg and for a longer duration can cause toxicity like rapid respiration, neurotoxicity, reproductive toxicity, etc. However, further in-depth studies are needed to determine the medicinal uses, clinical efficacy and safety are crucial next steps.


Disease-free survival difference between African Americans and whites after radical prostatectomy for local prostate cancer: a multivariable analysis.
Age-adjusted mortality rates (per 100,000) for men with prostate cancer from 1991 through 1997 reported by the Surveillance, Epidemiology, and End Results national registry have consistently demonstrated that African-American men (AAM) have twice the death rate of white men (WM). However, there has been considerable controversy as to how this relates to progression-free survival among these men. In an attempt to address this controversy of localized prostate cancer, we report on a multivariable analysis of survival data of a large number of AAM and WM who underwent radical prostatectomy. The study cohort was composed of 791 men whose only prostate cancer treatment was radical prostatectomy performed between July 1990 and December 1999. The variables analyzed were age, preoperative prostate-specific antigen level, pathologic grade and stage, and race/ethnicity. Pathologic examination of all specimens was performed in a uniform manner according to an established protocol. Multivariable analysis based on Cox's proportional hazards regression model was performed to assess whether a significant difference in progression-free survival time between AAM and WM persisted after controlling for the main effects of other prognostic factors. The study cohort consisted of 229 AAM and 562 WM. Our results indicated that all variables, except age, had highly significant effects on progression-free survival, even in the presence of other predictors. The effects of age, preoperative serum prostate-specific antigen level, and pathologic grade and stage did not account for the racial disparity in progression-free survival among men diagnosed with clinically localized prostate cancer and treated with radical prostatectomy.


House fly (Musca domestica) larvae meal as an ingredient with high nutritional value: Microencapsulation and improvement of organoleptic characteristics.
Insects have potential to become food ingredients, but it is necessary to improve the sensory properties of insects to help them to be better accepted by the population. The purpose of this study was to produce and characterize house fly larval meal (FLM) converted to a micro-encapsulated powder to improve appearance and other organoleptic characteristics. FLM showed high protein (54%) and lipid (22%) content, with a microbiological activity compatible for food purposes. Moreover, the high content of essentials amino acids (lysine, cysteine and leucine) and unsaturated fatty acids (oleic, linoleic and palmitoleic) make FLM a valuable nutritional source. Spray drying was selected to encapsulate FLM (0.5-2% w/v) using maltodextrin (20% w/v) and alginate (0.5% w/v). Encapsulation improved the appearance of FLM, creating a white-beige, monodispersed micro-powder (9 µm in size). Micro-powder with 2% FLM is considered a good source of protein (5.1%). Microencapsulation also dramatically reduced the volatile emissions of FLM. In conclusion, novel FLM micro-powders were developed using a simple and scalable encapsulation technique. The micro-powder with 2% FLM is a good source of protein, has a pleasant appearance similar to vegetable meals and has improved odor compared to typical insect meals. Thus, insect-based food ingredients in micro-powders could become more accepted by the general population.


The limitations of environmental management systems in Australian agriculture.
The efficacy of government-supported programs to encourage improved management of land and water systems associated with agricultural land in Australia has been mixed. The broad approach of Australian governments is reviewed briefly. Evidence is presented from case assessments of a program to promote adoption of environmental management systems (EMSs) to improve environmental outcomes from agricultural practices. EMSs are systems implemented to manage the environmental impacts and ameliorate environmental risk associated with business activity. Data are presented on reported EMS activity and experience of four selected groups of farmers in Victoria, south-eastern Australia, representing broad-acre cropping, beef and dairy farming. The pro-environmental behaviours of farmers were mediated through voluntary adoption of government and industry sponsored EMSs, often with financial incentives and other support. Findings from the study were that adoption of EMS practices with sufficient public benefits is unlikely to occur at sufficient scale for significant environmental impact. Farmers more readily adopted practices which were financially beneficial than those which had a positive environmental impact. Although the focus on voluntary market-based instrument (MBI) type programs is popular in western countries, enforcing regulation is an important, but usually politically unpopular, component of land use policy. The comparative advantage of EMSs differed for the industries studied, but overall there were insufficient market drivers for widespread EMS adoption in Australia. Environmental outcomes could be more effectively achieved by directly funding land management practices which have highest public net benefits. Having a clear and unambiguous management objective for a particular land management policy is more likely to achieve outcomes than having multiple objectives as occurs in a number of international programs currently.


Antidepressant efficacy of Agomelatine: Meta-analysis of placebo controlled and active comparator studies.
Agomelatine is a novel antidepressant that was developed to counter the adverse effects associated with the standard SSRIs and SNRIs that limited their usage. Publication bias was identified in antidepressant trials which can potentially overestimate the treatment efficacy. This meta-analysis was designed to assess the overall antidepressant effect of Agomelatine by pooling all the published and unpublished studies available till date. Studies conducted on adult patients who met with the criteria for MDD that evaluated efficacy of Agomelatine at acute phase (6-12weeks) and at long term phase (24weeks) were included. The primary efficacy measured with SMD of final mean scores of HAM-D and MADRS. Secondary efficacy measures of Response, remission and safety parameters were evaluated with relative risks. RevMan version 5.4 was used for analysis of both continuous (Standardized mean difference) and dichotomous outcomes (response, remission and all cause of discontinuation). Efficacy parameters were presented with 99% confidence intervals while safety parameters were presented with 95% CI. A total of 9233 patients were included from 27 studies. In acute phase placebo controlled studies, Agomelatine had a statistically significant SMD of - 0.24 (-0.39 to -0.09) and response rate of (1.25, 1.07-1.47). In comparison (RR 0.99, 0.92-1.07) Agomelatine is an effective antidepressant having similar efficacy with the currently used antidepressants.


[Reconstruction with the anterolateral thigh flap interposition for defect after tumor resection of hypopharyngeal and cervical esophageal cancer].
To evaluate the effectiveness of the anterolateral thigh flap in reconstruction for the tissue defects of hypopharyngeal and cervical esophageal tumor resection. Retrospective review of two clinical cases who underwent pharyngoesophageal reconstruction with the anterolateral thigh flap after tumor ablation. No flap failure, fistula and stricture occurred in two patients. Two patients tolerated a regular diet. An esophageal voice was progressively acquired with the help of speech therapy. With followup for 16 and 41 months two patients were alive without tumor evolution. The higher success rate,lower complication, quick recovery, made the anterolateral thigh flap interposition is the ideal choice for pharyngoesophageal reconstruction.


Visible-light-driven C(sp2)-H arylation of phenols with arylbromides enabled by electron donor-acceptor excitation.
We have developed a catalyst-free visible-light-driven C(sp2)-H arylation of unprotected phenols with arylbromides to give 2-arylated phenols. This reaction proceeds through the excitation of an electron donor-acceptor complex between a phenolate and an arylbromide, electron transfer, and debrominative C(sp2)-C(sp2) coupling.


Exosomal circRNA as a novel potential therapeutic target for multiple myeloma-related myocardial damage.
Myocardial damage is a mostly incurable complication of multiple myeloma (MM) that seriously affects the treatment outcome and quality of life of patients. Exosomal circular RNAs (exo-circRNAs) play an important role in tumor occurrence and development and are considered key factors in MM pathogenesis. However, the role and mechanism of action of exo-circRNAs in MM-related myocardial damage are still unclear. This study aimed to investigate correlations between exo-circRNAs and MM and to preliminarily explore the role of exo-circRNAs in MM-related myocardial damage. Six MM patients and five healthy controls (HCs) were included in the study. High-throughput sequencing and qRT-PCR verification were used to obtain a profile of abnormally expressed exo-circRNAs. GO, KEGG, miRanda, TargetScan and Metascape were used for bioinformatics analyses. H9C2 cells treated with exosomes from U266 cells were used in cell experiments. CCK-8, PCR, immunofluorescence and western blotting assays were used to detect cell proliferation and expression of autophagy-related indicators. Electron microscopy was used to observe the number of autophagic vesicles. Bioinformatics analysis showed that circRNAs with upregulated expression had the potential to promote MM-related myocardial damage. In addition, PCR results confirmed that circ-G042080 was abundantly expressed in the serum exosomes of 20 MM patients. Correlation analysis showed that the expression level of circ-G042080 was positively correlated with the clinical level of MM and MM-related myocardial damage and that circ-G042080 might interfere with MM-related myocardial damage through a downstream miRNA/TLR4 axis. Cell experiments demonstrated that the circ-G042080/hsa-miR-4268/TLR4 axis might exist in H9C2 cells incubated with exosomes and cause abnormal autophagy. Abnormal expression of serum exo-circRNAs was found to be associated with MM-related myocardial damage, suggesting that exo-circRNAs might become a new diagnostic marker of MM-related myocardial damage and a therapeutic target.


Molecular analysis of antimicrobial agent translocation through the membrane porin BpsOmp38 from an ultraresistant Burkholderia pseudomallei strain.
Burkholderia pseudomallei (Bps) is a Gram-negative bacterium that causes melioidosis, an infectious disease of animals and humans common in northern and north-eastern parts of Thailand. Successful treatment of melioidosis is difficult due to intrinsic resistance of Bps to various antibacterial agents. It has been suggested that the antimicrobial resistance of this organism may result from poor permeability of the active compounds through porin channels located in the outer membrane (OM) of the bacterium. In previous work, a 38-kDa protein, named "BpsOmp38", was isolated from the OM of Bps. A topology prediction and liposome-swelling assay suggested that BpsOmp38 comprises a β-barrel structure and acts as a general diffusion porin. The present study employed black lipid membrane (BLM) reconstitution to demonstrate the single-channel conductance of the trimeric BpsOmp38 to be 2.7±0.3 nS in 1M KCl. High-time resolution BLM measurements displayed ion current blockages of seven antimicrobial agents in a concentration-dependent manner with the translocation on-rate (kon) following the order: norfloxacin≫ertapenem>ceftazidime>cefepime>imipenem>meropenem>penicillin G. The dwell time of a selected antimicrobial agent (ertapenem) decayed exponentially with increasing temperature. The energy barrier for the ertapenem binding to the affinity site inside the BpsOmp38 channel was estimated from the Arrhenius plot to be 12 kT and for the ertapenem release to be 13 kT at +100 mV. The BLM data obtained from this study provide the first insight into antimicrobial agent translocation through the BpsOmp38 channel.


Plowing the atrium and growing thrombi: two cases of large atrial thrombi following ablative and surgical procedure for atrial fibrillation.
We present two patients with a large left atrial (LA) thrombus following invasive treatment for atrial fibrillation and inadequate anticoagulation. Case 1: A 30-year-old woman, with a one-year history of symptomatic paroxysmal atrial fibrillation resistant to medical therapy, underwent catheter ablation for atrial fibrillation. Three days after the procedure the patient presented with dizziness, fatigue, rapid atrial fibrillation with a sub-therapeutic INR. Transesophageal echocardiography (TEE) revealed a large LA thrombus. Case 2: A 59-year-old male, with severe mitral regurgitation and chronic atrial fibrillation, underwent mitral valve repair and Cox-Maze procedure. Three months later, while asymptomatic, a follow-up transthoracic echocardiography a large posterior LA thrombus was imaged. His INR was also sub-therapeutic. Both patients were treated by enhancing anticoagulation and close echocardiographic follow-up. So far both patients have remained asymptomatic two months following discharge. Large LA thrombi detected by transthoracic echocardiography are a rare complication of the Cox-Maze procedure and radio-frequency ablation for atrial fibrillation, which may occur even in patients with restored normal sinus rhythm receiving inadequate anticoagulation therapy.


The disulphide bond pattern of bitistatin, a disintegrin isolated from the venom of the viper Bitis arietans.
The disulphide bond pattern of the long disintegrin bitistatin (83 amino acids, 14 cysteines) was established using structural information gathered by amino acid analysis, N-terminal sequencing, and molecular mass determination of fragments isolated by reversed-phase HPLC after polypeptide degradation with trypsin and oxalic acid. A computer program was used to calculate all possible combinations of disulphide-bonded peptides matching the mass spectrometric data, and the output was filtered using compositional and sequence data. Disulphide bonds between cysteines 16-34, 18-29, 28-51, 42-48, 47-72, and 60-79 are conserved in medium-long disintegrins flavoridin and kistrin (70 amino acids, 12 cysteines), and the two cysteine residues at positions 5 and 24 found in bitistatin but not in other disintegrin molecules are disulphide-bridged. This linkage creates an extra, large loop, which, depending on whether the NMR structure of flavoridin or kistrin is used for modelling the structure of bitistatin, lies opposite or nearly parallel, respectively, to the biologically active RGD-containing loop.


Pain characteristics in Italian people with spinal cord injury: a multicentre study.
Multicentre cross-sectional study. The objective of this study is to evaluate prevalence, location and characteristics of pain in hospital inpatients people with spinal cord injury (SCI). Ten Italian rehabilitation centres specialized in spinal injury care, where inpatients are admitted both after the acute lesion and for late complications (time since injury, median [IQR]: 0.8 [0.2-8.2] years). All the persons were submitted to AIS scale assessment [1] and modified Ashworth scale [2]; personal data and anamnesis were recorded; any pain within 1 week was investigated and the International Spinal Cord Injury Pain Basic Data Set (ISCIPBDS) Italian version [3] was administered by physicians expert in type of pain definition. Of 385 included persons, 275 (72%) suffered pain, with the score value median [IQR]: 6 [4-8]. The worst pain of the person was nociceptive in 52% and neuropathic in 48% of the cases; 46% of nociceptive pain was located in the neck-shoulder region, whereas 67% of neuropathic pain was located in the sublesional part of the body. In 48% of the whole population, spasticity was observed but only 74% of them had pain. Being old and female are associated with high pain development, OR (95% CI): 1.24 (1.01-1.04) and 1.83 (1.05-3.20), respectively. A high prevalence of pain is confirmed in persons with SCI, with both nociceptive and neuropathic pain characteristics. Only old age and female sex resulted as variables highly associated with pain.


High Prevalence of Mansonella ozzardi Infection in the Amazon Region, Ecuador.
We reviewed Giemsa-stained thick blood smears, obtained through the national malaria surveillance program in the Amazon region of Ecuador, by light microscopy for Mansonella spp. microfilariae. Of 2,756 slides examined, 566 (20.5%) were positive. Nested PCR confirmed that the microfilariae were those of M. ozzardi nematodes, indicating that this parasite is endemic to this region.


Free sequestered disc herniation at the S2 level misdiagnosed as neuroma.
The case of a 38 year-old-man with a mass at the S2 level similar to a benign nerve root tumor (neuroma) is reported. The CT scan examination revealed the mass close underneath but not in connection with a disc herniation at the L5/S1 level. During operation the mass was not encountered as tumor but as free sequestered disc herniation, which was confirmed by histological examination. The reasons for considering the mass a tumor are discussed.


Laboratory production of 100 base pair DNA molecular weight markers.
DNA molecular weight markers are routinely used in agarose gel electrophoresis. Here we report a method called PCR-synthesized marker (PSM) to generate DNA molecular rulers by PCR in the laboratory. This strategy can also be used to produce 100 bp RNA molecular weight markers by run-off transcription.


Substrate specificity of endoglucanases: what determines xyloglucanase activity?
Endoglucanases from Trichoderma viride differ in their activity and mode of action towards xyloglucans. In order to explain the basis for their different behavior, the number of substrate-binding sites of three endoglucanases (endoI, endoIV, and endoV) were determined using bond cleavage frequencies of both normal and reduced cellodextrins and Ko/K(m). EndoIV differed from other endoglucanases described so far, in having at least nine putative binding sites. The specificities of the three endoglucanases towards various xyloglucans derived from apple fruit and potato were determined. Also, the release of oligosaccharides from these substrates in time was monitored. It was concluded that the endoglucanases prefer to bind unbranched glucosyl residues. Because most xyloglucans are composed of XXXG-type of building units, distant subsites are needed to bind xyloglucan. Having at least nine substrate-binding sites, endoIV seems to be well equipped to degrade xyloglucans which was confirmed by its high xyloglucanase activity.


Short-course treatment of typhoid fever with ciprofloxacin in south India.
This study assessed the performance of short-course ciprofloxacin for the treatment of 34 adult patients with culture-positive typhoid fever. Patients received ciprofloxacin, 750 mg orally twice daily for 7 d. Measurement of response was based upon time from initial treatment to fever lysis, to afebrile state, and to symptom resolution. Ciprofloxacin-treated patients defervesced in a mean of 3.21 d (+/- 0.56), with stabilization of temperature in 4.0 +/- 0.73 d. After 90 d follow-up, no relapse or carrier was identified. Side effects during therapy were minimal.


Multiscale real time and high sensitivity ion detection with complementary organic electrochemical transistors amplifier.
Ions are ubiquitous biological regulators playing a key role for vital processes in animals and plants. The combined detection of ion concentration and real-time monitoring of small variations with respect to the resting conditions is a multiscale functionality providing important information on health states. This multiscale functionality is still an open challenge for current ion sensing approaches. Here we show multiscale real-time and high-sensitivity ion detection with complementary organic electrochemical transistors amplifiers. The ion-sensing amplifier integrates in the same device both selective ion-to-electron transduction and local signal amplification demonstrating a sensitivity larger than 2300 mV V-1 dec-1, which overcomes the fundamental limit. It provides both ion detection over a range of five orders of magnitude and real-time monitoring of variations two orders of magnitude lower than the detected concentration, viz. multiscale ion detection. The approach is generally applicable to several transistor technologies and opens opportunities for multifunctional enhanced bioelectronics.


Identification of carotenoids biosynthesis pathway in Schizochytrium sp. and utilization in astaxanthin biosynthesis.
Carotenoids, an important kind of natural pigments with great potential commercial value, have been widely used in nutrition and health care, cosmetics and aquaculture industries. Schizochytrium sp. is a potential cell factory for lipid nutrition chemicals production including docosahexaenoic acid and carotenoids. The purpose of this study is to mine and identify the carotenoid biosynthesis genes in Schizochytrium sp. Firstly, based on the genomic information of Schizochytrium sp., we obtained the gene sequences of a trifunctional enzyme (CrtIBY), carotene hydroxylase (CrtZ) and carotene ketolase (CrtO) in carotenoids biosynthesis pathway by bioinformatics analysis. Subsequently, using the lycopene-producing E. coli as the host, 22.77 ug/L of β-carotene and 44.31 ug/L of zeaxanthin were synthesized by overexpression of CrtIBY and further co-expression with CrtZ from Schizochytrium sp. After that, 54.78 ug/L of astaxanthin was synthesized using hydroxylase and ketonase from Haematococcus pluvialis. The key enzymes for carotenoids biosynthesis identified in this study is of great significance for further understanding the metabolic mechanism in Schizochytrium sp, which could also provide the functional elements and theoretical support for astaxanthin production.


Evolutionary Dynamics and Molecular Mechanisms of HORMA Domain Protein Signaling.
Controlled assembly and disassembly of multi-protein complexes is central to cellular signaling. Proteins of the widespread and functionally diverse HORMA family nucleate assembly of signaling complexes by binding short peptide motifs through a distinctive safety-belt mechanism. HORMA proteins are now understood as key signaling proteins across kingdoms, serving as infection sensors in a bacterial immune system and playing central roles in eukaryotic cell cycle, genome stability, sexual reproduction, and cellular homeostasis pathways. Here, we describe how HORMA proteins' unique ability to adopt multiple conformational states underlies their functions in these diverse contexts. We also outline how a dedicated AAA+ ATPase regulator, Pch2/TRIP13, manipulates HORMA proteins' conformational states to activate or inactivate signaling in different cellular contexts. The emergence of Pch2/TRIP13 as a lynchpin for HORMA protein action in multiple genome-maintenance pathways accounts for its frequent misregulation in human cancers and highlights TRIP13 as a novel therapeutic target.


Complex I-complex II ratio strongly differs in various organs of Arabidopsis thaliana.
In most studies, amounts of protein complexes of the oxidative phosphorylation (OXPHOS) system in different organs or tissues are quantified on the basis of isolated mitochondrial fractions. However, yield of mitochondrial isolations might differ with respect to tissue type due to varying efficiencies of cell disruption during organelle isolation procedures or due to tissue-specific properties of organelles. Here we report an immunological investigation on the ratio of the OXPHOS complexes in different tissues of Arabidopsis thaliana which is based on total protein fractions isolated from five Arabidopsis organs (leaves, stems, flowers, roots and seeds) and from callus. Antibodies were generated against one surface exposed subunit of each of the five OXPHOS complexes and used for systematic immunoblotting experiments. Amounts of all complexes are highest in flowers (likewise with respect to organ fresh weight or total protein content of the flower fraction). Relative amounts of protein complexes in all other fractions were determined with respect to their amounts in flowers. Our investigation reveals high relative amounts of complex I in green organs (leaves and stems) but much lower amounts in non-green organs (roots, callus tissue). In contrast, complex II only is represented by low relative amounts in green organs but by significantly higher amounts in non-green organs, especially in seeds. In fact, the complex I-complex II ratio differs by factor 37 between callus and leaf, indicating drastic differences in electron entry into the respiratory chain in these two fractions. Variation in amounts concerning complexes III, IV and V was less pronounced in different Arabidopsis tissues (quantification of complex V in leaves was not meaningful due to a cross-reaction of the antibody with the chloroplast form of this enzyme). Analyses were complemented by in gel activity measurements for the protein complexes of the OXPHOS system and comparative 2D blue native/SDS PAGE analyses using isolated mitochondria. We suggest that complex I has an especially important role in the context of photosynthesis which might be due to its indirect involvement in photorespiration and its numerous enzymatic side activities in plants.


The coexistence of type 1 diabetes, MODY2 and metabolic syndrome in a young girl.
Even though autoantibodies to pancreatic islet cells are normally found in type 1 diabetes and insulin-resistance due to overweight is more reminiscent of type 2 diabetes, some studies have described β-cell antibodies also in maturity-onset diabetes of the young (MODY) and in type 2 diabetes. A 7-year-old girl was referred to our Unit for incidental hyperglycemia and family history of MODY2 and type 2 diabetes. Genetic evaluation confirmed mutation L134P in exon 4 of the glucokinase gene and a high HLA-risk of type 1 diabetes. During follow-up, she developed type 1 diabetes and overweight-induced metabolic syndrome. The coexistence of MODY, type 1 diabetes and overweight-induced metabolic syndrome confirms that diabetes subtype probably represents a continuum of immune and metabolic dysfunction modified by genetic factors.


Arthroscopic rotator cuff repair: patients with physically demanding work have significantly worse time to return to work, level of employment, and job loss.
The purpose of this study was to determine the results of arthroscopic rotator cuff repair (ARCR) in terms of return to work (RTW). Inclusion criteria were working patients who underwent ARCR for rotator cuff rupture at the study site between 2008 and 2020 and minimum 12 months of follow-up. Patients were stratified based on the physical demand of their work according to the Canadian Classification and Dictionary of Occupations. The primary outcomes were time to RTW, level of employment (LoE), change of tasks, and work loss. Secondary outcomes included the return to sports activities, EQ-VAS, EQ-5D-5L, DASH, and Oxford Shoulder Score. Three-hundred and eighty-three patients were enrolled; at the follow-up evaluation, fifty-three patients (13.8%) lost their job, with a percentage of 34.4% (eleven patients) in the heavy-work category, and five patients (1.3%) chose early retirement. Other twenty-six patients (6.8%) had to lower their level of employment, and twenty patients (5.2%) changing their tasks, with 279 patients (72.9%) returning to their previous work activity. RTW was obtained at a mean time of 4.7 ± 4.6 months, ranging from 3.8 ± 3.1 months in the sedentary work vs 5.8 ± 2.8 months in the very heavy-work category (p = 0.015). The mean EQ-VAS score was 77.3 ± 18 points, the mean Oxford Shoulder Score was 43.4 ± 7.2 points, and the mean DASH score was 9.9 ± 14.5 points; 75.3% returned to their previous level of sport activity. The success of ARCR in terms of RTW is not always complete and varies significantly based on the physical demand of the patient's job. Patients with physically demanding work have a significantly higher time to RTW, reduction of the LoE, and job loss rate, thus affecting the possibility to have a satisfactory return to their previous life. The findings are of clinical relevance since they can help the surgeons to give their patients reliable expectations and to correctly plan the post-operative management. IV.


Synthetic, site-specific biotinylated analogs of human MCP-1.
Human monocyte chemoattractant protein 1 (MCP-1, CCL2) is a 8.6-kDa protein that has been implicated in a number of diseases including atherosclerosis, rheumatoid arthritis, chronic obstructive pulmonary disease and cancer. As part of a program to identify antibodies against MCP-1, we synthesized site-specific, biotinylated human MCP-1 analogs to be used for panning of an antibody phage display library. In contrast to material obtained from random biotinylation, the site-specific biotinylated analogs were homogeneous and retained full activity.


Fate and behaviour of phenanthrene in the natural and artificial soils.
OECD artificial soil has been used routinely as a standardized substrate for soil toxicity tests. However, can be the fate, behaviour and effects of contaminants in artificial soil extrapolated to natural soils? The aim of our study was to verify this hypothesis by comparing the loss, extraction, and bioavailability of phenanthrene in three artificial and three natural soils of comparable organic carbon content. Soils were spiked with 14C-phenanthrene and total 14C-activity change, the fractions extracted by dichloromethane, 70% ethanol, and hydroxypropyl-beta-cyclodextrin, the fraction mineralized by Pseudomonas sp., and taken up by Enchytraeus albidus were measured after 1, 14, 42, and 84 d aging. The loss, extraction, biodegradation and uptake were several times lower in the artificial than natural soils and these differences increased with increasing soil-phenanthrene contact time. These results imply that artificial soil should be used cautiously for the prediction of fate and behaviour in natural soils.


Mitochondrial respiratory activity in porcine longissimus muscle fibers of different pig genetics in relation to their meat quality.
The pig genetics of Duroc, Pietrain (MHS homozygote negative, PiNN), Pietrain (MHS homozygote positive, PiPP) and a F2-Duroc-Pietrain cross-breed were analyzed. The animals had comparable (P>0.05) carcass weights, but the PiPP pigs had higher carcass yield and lean meat values (P<0.05). Considering the meat quality characteristics, the PiPP showed a faster pH drop and higher electrical conductivity, drip loss, shear force as well as lightness and redness values (P<0.05). The PiPP animals had less slow-twitch-oxidative (STO) and more fast-twitch-glycolytic (FTG) muscle fibers, whereas the results of the Duroc animals were converse (P<0.05). The STO and FTG fibers of the PiPP animals were larger than those of the other genetics (P<0.05). The analysis of the mitochondrial respiratory activity (MRA) using permeabilized longissimus muscle fibers resulted in no differences between the pig genetics before and immediately after slaughter. During chilling the MRA decreased in all pigs but to a higher extent in the PiPP pigs (P<0.05).