Should Surgeons Evaluate the Anatomy of Drummond Marginal Artery and Riolan's Arch Preoperatively?
The Drummond marginal artery and the Riolan's arch are important links between the superior mesenteric artery (SMA) and inferior mesenteric artery (IMA), which provide collateral flow in case of arterial occlusion or significant stenosis. The Riolan's arch is important in colorectal surgery since it allows for vascularization of the descending colon by the SMA after ligation of the IMA at its origin, especially in cancer patients. In this study, we aimed to evaluate the presence of the Drummond marginal artery and the Riolan's arch. In addition, we assessed anatomic variants of the middle colic artery (MCA) and classified the anatomic relationships between SMA and SMV. Following screening, 115 abdominal CT scans were included in the study. For all cases, the presence of the Drummond marginal artery and the Riolan's arch, the first diameter of these arterial structures at their origins, the first emerging diameter and anatomic variants of the MCA, and the anatomic relationships between SMA and SMV were evaluated. Drummond marginal artery was present in all participants (100%). The Riolan's arch was observed in 27.8% of all cases and was higher than in other studies. This can be related to the focus of this arch. In addition, we did not find any similar study in the literature that evaluated MCA origin types, SMA-SMV variants with the presence of the Drummond artery and the Riolan's arch, and the first emerging diameters of vascular structures, such as the Drummond marginal artery, the Riolan's arch, and MCA. Evaluating and stating whether the Drummond marginal artery and the Riolan's arch are seen in thin section abdominal computed tomography (CT) and CT angiographies preoperatively may help in planning appropriate resections and can reduce unwanted postoperative morbidity.


Experiences from the harmonization of Finnish national population-based health survey data.
Aims: There are several advantages to pooling survey data from individual studies over time or across different countries. Our aim is to share our experiences on harmonizing data from 13 Finnish health examination surveys covering the years 1972-2017 and to describe the challenges related to harmonizing different variable types using two questionnaire variables - blood pressure measurement and total cholesterol assessment - as examples. Methods: Data from Finnish national population-based health surveys were harmonized as part of the research project 'Projections of the Burden of Disease and Disability in Finland - Health Policy Prospects', including variables from questionnaires, objective health measurements and results from the laboratory analysis of biological samples. The process presented in the Maelstrom Research guidelines for data harmonization was followed with minor adjustments. Results: The harmonization of data from objective measurements and biomarkers was reasonably straightforward, but questionnaire items proved more challenging. Some questions and response options had changed during the covered time period. This concerned, for example, questionnaire items on the availability and use of medication and diet. Conclusions: The long time period - 45 years - made harmonization more complicated. The survey questions or response options had changed for some topics due to changes in society. However, common core variables for topics that were especially relevant for the project, such as lifestyle factors and certain diseases or conditions, could be harmonized with sufficient comparability. For future surveys, the use of standardized survey methods and the proper documentation of data collection are recommended to facilitate harmonization.


Maximizing Tumor Control and Limiting Complications With Stereotactic Body Radiation Therapy for Pancreatic Cancer.
Stereotactic body radiation therapy (SBRT) and stereotactic ablative body radiation therapy is being increasingly used for pancreatic cancer (PCa), particularly in patients with locally advanced and borderline resectable disease. A wide variety of dose fractionation schemes have been reported in the literature. This HyTEC review uses tumor control probability models to evaluate the comparative effectiveness of the various SBRT treatment regimens used in the treatment of patients with localized PCa. A PubMed search was performed to review the published literature on the use of hypofractionated SBRT (usually in 1-5 fractions) for PCa in various clinical scenarios (eg, preoperative [neoadjuvant], borderline resectable, and locally advanced PCa). The linear quadratic model with α/β= 10 Gy was used to address differences in fractionation. Logistic tumor control probability models were generated using maximum likelihood parameter fitting. After converting to 3-fraction equivalent doses, the pooled reported data and associated models suggests that 1-year local control (LC) without surgery is ≈79% to 86% after the equivalent of 30 to 36 Gy in 3 fractions, showing a dose response in the range of 25 to 36 Gy, and decreasing to less than 70% 1-year LC at doses below 24 Gy in 3 fractions. The 33 Gy in 5 fraction regimen (Alliance A021501) corresponds to 28.2 Gy in 3 fractions, for which the HyTEC pooled model had 77% 1-year LC without surgery. Above an equivalent dose of 28 Gy in 3 fractions, with margin-negative resection the 1-year LC exceeded 90%. Pooled analyses of reported tumor control probabilities for commonly used SBRT dose-fractionation schedules for PCa suggests a dose response. These findings should be viewed with caution given the challenges and limitations of this review. Additional data are needed to better understand the dose or fractionation-response of SBRT for PCa.


Closed shoulder reduction by glenohumeral joint distraction. A technical note.
We describe a shoulder reduction technique by direct distraction at the glenohumeral joint in supine position. The technique can be performed by one or two providers and has an easy learning curve, and the use of anesthesia is not mandatory. It is anatomically based and combines traction-counter-traction technique along with scapula manipulation.


Phosphate stresses affect ionome and metabolome in tea plants.
In order to study the response of tea plants to P stress, we conducted the ionomic and metabolomic analysis by ICP-OES, GC-MS and LC-MS. The results demonstrated that P was antagonistic with S, and was cooperative with Cu, Zn, Mn and Fe under P-deficiency. However, P was antagonistic with Mn, Fe and S, and was cooperative with Cu and Zn under P-excess. Moreover, P-deficiency or excess reduced the syntheses of flavonoids and phosphorylated metabolites. P-deficiency decreased the amount of glutamate and increased the content of glutamine, while P-excess decreased the content of glutamine. Besides, P-deficiency increased three organic acids and decreased three organic acids. P-excess increased the contents of malic acid, oxalic acid, ribonic acid and etc. involved in primary metabolism, but decreased the contents of p-coumaric acid, indoleacrylic acid, related to secondary metabolism. Furthermore, the contents of Mn and Zn were found to be positively related to the amounts of myricetin and quercetin, and the content of Mn to be positively related to the amount of arabinose. The results implied that the P stresses severely disturbed the metabolism of minerals and metabolites in tea plants, which influenced the yield and quality of tea.


Pseudo-set framing.
Pseudo-set framing-arbitrarily grouping items or tasks together as part of an apparent "set"-motivates people to reach perceived completion points. Pseudo-set framing changes gambling choices (Study 1), effort (Studies 2 and 3), giving behavior (Field Data and Study 4), and purchase decisions (Study 5). These effects persist in the absence of any reward, when a cost must be incurred, and after participants are explicitly informed of the arbitrariness of the set. Drawing on Gestalt psychology, we develop a conceptual account that predicts what will-and will not-act as a pseudo-set, and defines the psychological process through which these pseudo-sets affect behavior: over and above typical reference points, pseudo-set framing alters perceptions of (in)completeness, making intermediate progress seem less complete. In turn, these feelings of incompleteness motivate people to persist until the pseudo-set has been fulfilled. (PsycINFO Database Record


Efficacy and Safety of Fluoroscopy-Guided Self-Expandable Metal Stent Placement for Treatment of Malignant Colorectal Obstruction.
To investigate long-term outcomes after SEMS insertion in patients with malignant colorectal obstruction and to identify the risk factors for complications. The data of 119 patients with malignant colorectal obstruction who received SEMS insertion between March 2014 and February 2020 were retrospectively analyzed. Patients were divided into two groups according to the intent of treatment, i.e., stenting as "bridge to surgery" (surgical group) and stenting for palliation (palliative group). Technical and clinical success rates and incidence of complications were compared between the two groups. The overall technical and clinical success rates were 97.5% and 96.6%, respectively. The technical and clinical success rates and complication rate were comparable between the two groups. In the palliative group, the mean stent patency time was 230 days. Patency rates were not significantly different between primary CRC and recurrent CRC. Incidence of complications was higher in the palliative group than in the surgical group. In multivariate analysis, chemotherapy before stent implantation may increase the risk of stent-related complications, whereas chemotherapy after stent implantation did not. Additionally, the factors independently associated with complications were female sex and preoperative chemotherapy. SEMS under fluoroscopic guidance is a safe and effective treatment for malignant colorectal obstruction. For patients with resectable CRC, stent placement can serve as a bridge to elective surgery. It is worth noting that adjuvant chemotherapy between SEMS and surgery did not increase the complications. For patients with recurrent CRC, stent placement can relieve symptoms, alleviate pain, and improve quality of life.


Histamine secretion from mast cells treated with chlortetracycline (aureomycin): a novel calcium ionophore.
The novel calcium ionophore chlortetracycline (CTC) induced histamine secretion (less than or equal to 90%) from isolated rat peritoneal mast cells in a pH and dose-dependent fashion. The process was dependent on exogenous calcium ions and was inhibited by extremes of temperature and metabolic blockers. The release was rapid, being essentially complete within 1 min, but the half-life of the process varied inversely with the concentration of the ionophore. In contrast to receptor-mediated ligands, but in keeping with other ionophores, the activated state induced by CTC did not decay with time. The secretion was effectively inhibited, according to the concentration of the ionophore, by disodium cromoglycate and other anti-allergic or cyclic AMP-active drugs. These results confirm our previous contention that these agents do not act on receptor-mediated calcium-channels. CTC induced a significant (less than or equal to 50%) release of histamine from enzymically dispersed rat mesenteric mast cells but was essentially inactive against isolated mast cells from the mesentery or lung of the guinea-pig. These results extend our former observations on the functional heterogeneity of mast cells and show that, in common with other secretagogues, ionophores may exhibit selectivity in their mode of action.


Kinetics study and recycling strategies in different stages of full-component pyrolysis of spent LiNixCoyMnzO2 lithium-ion batteries.
Full-component pyrolysis has been proven to be a prospective method for the disposal of organic matters and the cathode material reduction of spent LiNixCoyMnzO2 (NCM) lithium-ion batteries (LIBs). However, the kinetics of the full-component pyrolysis of spent NCM LIBs is still unclear. This work represents the first attempt to study the kinetics of different stages of full-component pyrolysis of NCM LIBs based on isoconversional method to guide the recycling of spent LIBs. Pyrolysis process was divided into four stages in accordance to the main weight loss temperature ranges and the classical Kissinger-Akahira-Sunose and Flynn-Wall-Ozawa kinetics models were employed to calculate the activation energy (E) in each stage. The main physicochemical reactions were clarified though in situ analysis, and the average E in the four stages was determined: (I) The volatilization of electrolytes occurred in the temperature range of 100-200 °C with the E of 98.6 kJ/mol. (II) The decomposition of organic matters and the preliminary reduction of cathode material transpired in the temperature range of 400-500 °C with the E of 227.2 kJ/mol. (III) The further reduction of NiO and CoO occurred from 650 to 800 °C with the E of 258.8 kJ/mol. (Ⅳ) The reduction of MnO took place from 850 to 1000 °C with the E of 334.9 kJ/mol. The recycling strategies based on full-component pyrolysis of spent NCM LIBs was accordingly proposed. During pyrolysis, the cathode material was gradually reduced and the pyrolytic products can be controlled through temperature regulation.


Effects of interleukin-2 and interleukin-2-activated cells on in vitro myelopoiesis.
Lymphokine-activated killer (LAK) cells from human peripheral blood mononuclear cells cultured with recombinant interleukin-2 (IL-2) have been used clinically in adoptive immunotherapy for cancer patients. To study the influence of LAK cells and IL-2 on haematopoiesis, an in vitro assay system for colony formation of granulocyte-macrophage progenitor cells (GM-CFC) was used. LAK cells from cultures of either human peripheral blood (PB) or human bone marrow (BM) mononuclear cells were both inhibitory to allogeneic BM-derived GM-CFC. Inhibitory activity could be transferred with supernatants from co-cultures of LAK cells and BM targets, but also from the IL-2 activated PB- or BM-derived cells alone. The inhibitory activity from the initially non-cytotoxic/non-inhibitory BM population was rapidly induced by IL-2 activation, and preceded the generation of cytotoxic LAK cells in the culture. These experiments show that inhibition of haematopoietic progenitor cells by IL-2 is not dependent on generation of cytotoxic LAK cells, but rather the result of IL-2-induced cytokine production. We conclude that the synergistic action of interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) may contribute to inhibition, but that also other cytokines are responsible for the observed inhibition of BM-derived GM-CFC.


What do patients think about minimally invasive total hip arthroplasty?
The introduction of minimally invasive techniques for hip replacement into clinical practice has been driven by the perceived benefits of smaller incisions, shorter in-patient stays and faster rehabilitation. This may be at the cost of higher complication rates. The purpose of this study was to explore the opinions and priorities of patients in relation to these techniques. A cross-sectional survey was performed in an elective out-patient setting. Of 44 patients approached, 36 agreed to participate. From most important to least important, patients rated the following items in order: 'rate of complications'; 'implant survival'; 'length of rehabilitation'; 'time in hospital' and 'length of scar'. Despite this, 21 of 35 (60%) responders stated they would accept the offer of minimally invasive techniques if made. Patients appear to prioritise long-term outcomes and low complication rates over the shorter scars, reduced in-patient stay and reduced rehabilitation times potentially offered by minimally invasive hip arthroplasty. Despite this, the technique remains popular among patients.


Changes in muscle, fat and bone mass after 36 weeks of maximal androgen blockade for prostate cancer.
To assess the effects of androgen deprivation therapy (ADT) on whole-body and regional muscle, fat and bone mass in men with prostate cancer without metastatic bone disease. Seventy-two men aged 44-88 years underwent spine, hip and whole-body dual-energy X-ray absorptiometry scans at baseline and after 36 weeks of ADT. The change in whole-body and regional lean mass (LM), fat mass (FM), and bone mineral content and density (BMD) were determined. In addition, the prostate specific antigen (PSA), serum testosterone and haemoglobin levels were measured, and the level of physical activity and fatigue assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-30. The upper limb, lower limb, trunk and whole-body LM decreased by a mean (sem) of 5.6 (0.6)%, 3.7 (0.5)%, 1.4 (0.5)% and 2.4 (0.4)% (P < 0.01), respectively, while FM increased by 20.7 (3.3)%, 18.7 (2.7)%, 12.0 (2.5)% and 13.8 (2.3)% (P < 0.001). Hip, spine, whole-body and upper limb BMD decreased by 1.9 [corrected] (0.3)% [corrected], 3.3 [corrected] (0.4)%, 1.6 [corrected] (0.3)% and 1.3 (0.3%) (P < 0.001), but not lower limb BMD. Serum testosterone, PSA and haemoglobin levels decreased by 93.3 (0.4)%, 98.2 (0.5)%, and 8.8 (0.9)% (P < 0.001), respectively. In addition, physical activity levels decreased and levels of fatigue increased. After 36 weeks of ADT there was a significant decrease in whole-body and regional LM and bone mass, while whole-body and regional FM increased in older men with prostate cancer. Strategies to counteract changes in soft tissue and bone mass during ADT should be formulated to minimize the risk of sarcopenia, osteoporosis and obesity.


Evaluation of nutritional characteristics and bioactive compounds of soursop-yoghurt and soursop-frozen dessert.
The nutritional quality, sensory attributes, polyphenols and acetogenins content in yoghurt and frozen dessert formulated with soursop pulp were investigated. The addition of soursop pulp to yoghurt and frozen dessert improved the sensory attributes and the nutritional quality of soursop dairy products resulting in a composition of 0.92 and 2.17% of dietary fiber, 11.25 and 9.84 mg/100 g of vitamin C as well as 243.02 and 490.98 mg/100 g of total polyphenols, respectively. Acetogenins were extracted from both dairy products using maceration, sonication, microwave and Soxhlet. Sonication showed to be faster and safer than the other methods for acetogenins extraction. Higher annonacin (an acetogenin) content was found in yoghurt (38 ng/g) than in frozen dessert (15 ng/g). The quantification of bioactive compounds implied the nutraceutical properties to yoghurt and ice cream when they are added with soursop pulp. The results are useful for the consumers seeking healthier foods.


Long-term instability of fasting plasma glucose predicts mortality in elderly NIDDM patients: the Verona Diabetes Study.
The aim of this study was to evaluate whether long-term glucose control, as assessed by fasting plasma glucose determinations during 3 years, is a predictor of all-cause mortality in elderly NIDDM patients. Five hundred and sixty-six NIDDM patients attending the Verona Diabetes Clinic, aged 75 years and over, were followed-up from 1 January 1987 to 31 December 1991 to assess all-cause mortality. From their clinical records all fasting plasma glucose determinations available for the years 1984 to 1986 were collected and analysed. Patients were grouped in tertiles according to mean (M-FPG), coefficient of variation (CV-FPG) and trend over time (slope, S-FPG) of fasting plasma glucose during the period of retrospective evaluation. Mortality was assessed by observed/expected ratios, univariate Kaplan-Meier survival analysis and multivariate Poisson regression model. By 31 December 1991, 61 men and 127 women had died. Increased observed/expected ratios were found in women from the top M-FPG tertile, in patients (men and women) from the top CV-FPG tertile and in patients with a S-FPG less than -0.30 mmol/l per year (lowest tertile). Patients in the lowest tertile of CV-FPG and in the middle tertile of S-FPG had a reduced mortality risk. Kaplan-Meier survival analysis indicated that patients with high CV-FPG as well as those in tertiles I and III of S-FPG (i.e., those with a definitely negative or definitely positive slope) had an increased probability of dying, without any significant differences between the three tertiles of M-FPG.(ABSTRACT TRUNCATED AT 250 WORDS)


Manipulating midbrain stem cell self-renewal.
In this issue of Cell Stem Cell, Falk and colleagues (Falk et al., 2008) demonstrate that differential responsiveness to TGF-beta signaling selectively modulates self-renewal of dorsal midbrain stem cells. This observation may lead to strategies for expanding specific neural stem cell subtypes.


Robust and adhesive lignin hybrid hydrogel as an ultrasensitive sensor.
The fabrication of hydrogel for sensing purposes remains to be a challenge since the hydrogel needs to have both good mechanical strength and adhesiveness. This work reports a robust and adhesive hydrogel mainly constructed with AgNPs@lignin, polyacrylamide (PAM) and sodium alginate (SA). The silver nanoparticles (AgNPs) were in-situ generated via the reaction between lignin and silver ammonia ([Ag(NH3)2]+). The resultant lignin hybrid hydrogel exhibited a stress, strain and tearing energy up to 0.055 MPa, 1000% and 250 J·m-2, respectively. Furthermore, the hydrogel adhered to different materials with an adhesion energy of higher than 230 J·m-2. This hydrogel was demonstrated to be an ideal sensing material since it could detect both large-scale motions and tiny physiological signals including breathing and pulse. The hydrogel also exhibited good antibacterial performance and biocompatibility. This work provides a good example to design a lignin-based high-performance hydrogel material for sensing purposes.


Efficacy of ultrasound-guided parasternal block in adult cardiac surgery: a meta-analysis of randomized controlled trials.
Pain after cardiac surgery is a common and severe postoperative complication. As a new regional nerve block method, ultrasound-guided parasternal block (PSB) has been increasingly used to supplement the analgesic effects of opioids in order to eliminate opioid-related adverse drug events, but its efficacy still remains controversial. In the present meta-analysis, we aim to screen all eligible randomized controlled trials (RCTs) and give a comprehensive summary of the clinical value of PSB after adult cardiac surgery. We searched all RCTs about PSB after cardiac surgery in the database of PubMed, Embase, Cochrane, CNKI and Wanfang with no limitation of language from inception to September 2021. Two reviewers were independently involved in the process of data extraction. Meta-analysis was performed by using Review Manager software. The quality of included RCTs were assessed by using Cochrane's risk of bias assessment tool, and funnel plots were drawn to assess publication bias. A total of 12 RCTs with 366 patients in PSB group and 364 patients in control group were included in the present meta-analysis. Pooled analysis revealed that intraoperative and postoperative consumption of sufentanil were significantly decreased with the addition of PSB (P<0.05). Numerical rating scale (NRS) scores in PSB group were found to be significantly lower than that of control group at extubation, postoperative 4 h and 8 h (P<0.05) instead of postoperative 24 h or longer. PSB could reduce the incidence of postoperative nausea and vomiting (PONV) (P<0.05). In addition, we demonstrated that PSB was significantly related to decreased mechanical ventilation time, total length of ICU stay and hospital days (P<0.05). Through decreasing the consumption of opioids, ultrasound-guided PSB could relieve pain and limit opioid-related complications. Clinical outcomes, such as mechanical ventilation time, total length of ICU stay and hospital days, will also be improved. Our findings prove that ultrasound-guided PSB is an effective regional analgesic method after adult cardiac surgery.


Transanal total mesorectal excision achieves equivalent oncologic resection compared to laparoscopic approach, but with functional consequences.
This study compared transanal total mesorectal excision (taTME) to laparoscopic total mesorectal excision (laTME) for the treatment of low rectal cancer. Adequacy of oncologic resection as well as postoperative outcomes were analyzed. We retrospectively reviewed all proctectomy for low rectal cancer by a single surgeon at our institution from January 2014 to September 2019. There were 20 taTME and 30 laTME patients. TaTME patients had more distal tumors with no difference in pathologic resection margins or frequency of positive distal margin. Operative times were longer for taTME, but there were no differences in short-term outcomes or complications. TaTME patients had a higher rate of postoperative fecal incontinence. TaTME may be a good option for the most distal tumors, when distal margins may be compromised. TaTME provides equivalent oncologic resection, but there is a higher incidence of postoperative fecal incontinence.


A kinetic study on carboxylic acids production using bovine slaughterhouse wastewater: a promising substrate for resource recovery in biotechnological processes.
Carboxylic acids (CA) are considered high added-value compounds, and their production from wastes has gained economic and environmental notoriety. However, the CA production and kinetic modeling using some agro-industrial wastewaters, such as bovine slaughterhouse wastewater (SHW), are not well reported in the literature. Therefore, the objective of this work was to evaluate the CA production potential using SHW as a substrate under acidogenic conditions and to apply mathematical models to estimate the kinetic parameters of particulate organic matter hydrolysis, soluble organic matter consumption, and CA production. Tests were carried out in quadruplicate batch reactors with a 250-mL reaction volume, with brewery sludge as inoculum and using chloroform (0.05%, v/v) for methanogenesis inhibition. The obtained yield was 0.55 g acids gCODA-1, corresponding to 0.76 gCOD gCODA-1. The production of caproic acid without the addition of electron donors was achieved. Mathematical models that describe exponential growth, such as the first-order exponential model, cone model, and Fitzhugh model, were the most suitable to describe the production kinetics of CA. Finally, SHW seems to be a promising substrate to be investigated in the carboxylic platform.


Macrophage migration inhibitory factor is associated with positive cultures in patients with sepsis after cardiac surgery.
This prospective consecutive observational study describes the blood levels of macrophage migration inhibitory factor (MIF), other cytokines, and markers of acute-phase response in 49 consecutive patients who developed the clinical syndrome of sepsis after cardiac surgery. Before starting antimicrobial treatment, all patients underwent microbiologic screening, and blood samples were collected. These samples subsequently were assayed for MIF, macrophage chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6 and -10, procalcitonin (PCT), and C-reactive protein (CRP). Patients with positive cultures (n = 25) had a higher mortality (P = 0.046) and higher levels of MIF (P < 0.001) than those with negative cultures (n = 24). We could not detect significant difference between the groups concerning the levels of CRP, PCT, IL6, IL10, MCP-1, or TNF-alpha. MIF levels showed an area under receiver operator curve of 0.823 for the prediction of culture-proven bacterial infection, with the best cut-off value at 988.5 pg/mL. In conclusion, circulating levels of MIF could be indicated as a valuable marker of microbiologically documented sepsis in patients after cardiac surgery, which suggests that MIF may be prospectively explored as a useful diagnostic tool in this setting.


Rapid affinity measurement of protein-protein interactions in a microfluidic platform.
A rapid screening method has been developed to determine binding affinities for protein-ligand interactions using the Gyrolab workstation, a commercial microfluidic platform developed to accurately and precisely quantify proteins in solution. This method was particularly suited for assessing the high-affinity interactions that have become typical of therapeutic antibody-antigen systems. Five different commercially available antibodies that bind digoxin and a digoxin-bovine serum albumin (BSA) conjugate with high affinity were rigorously evaluated by this method and by the more conventional kinetic exclusion assay (KinExA) method. Binding parameter values obtained using Gyrolab were similar to those recovered from KinExA. However, the total experimental time for 20 binding affinity titrations, with each titration covering 12 data points in duplicate, took approximately 4h by the Gyrolab method, which reduced the experimental duration by more than 10-fold when compared with the KinExA method. This rapid binding analysis method has significant applications in the screening and affinity ranking selection of antibodies from a very large pool of candidates spanning a wide range of binding affinities from the low pM to μM range.


IFI27 Integrates Succinate and Fatty Acid Oxidation to Promote Adipocyte Thermogenic Adaption.
Mitochondria are the pivot organelles to control metabolism and energy homeostasis. The capacity of mitochondrial metabolic adaptions to cold stress is essential for adipocyte thermogenesis. How brown adipocytes keep mitochondrial fitness upon a challenge of cold-induced oxidative stress has not been well characterized. This manuscript shows that IFI27 plays an important role in cristae morphogenesis, keeping intact succinate dehydrogenase (SDH) function and active fatty acid oxidation to sustain thermogenesis in brown adipocytes. IFI27 protein interaction map identifies SDHB and HADHA as its binding partners. IFI27 physically links SDHB to chaperone TNF receptor associated protein 1 (TRAP1), which shields SDHB from oxidative damage-triggered degradation. Moreover, IFI27 increases hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha (HADHA) catalytic activity in β-oxidation pathway. The reduced SDH level and fatty acid oxidation in Ifi27-knockout brown fat results in impaired oxygen consumption and defective thermogenesis. Thus, IFI27 is a novel regulator of mitochondrial metabolism and thermogenesis.


Electrocardiographic markers of structural heart disease and predictors of death in 2332 unselected patients undergoing outpatient Holter recording.
To test the hypothesis that the QS interval of ventricular ectopic beats (VEBs) (ventricular ectopic QS interval, VEQSI) would provide a marker for the presence of structural heart disease and a predictor of mortality. We interviewed and examined 2332 patients undergoing Holter ECG monitoring for clinical indications. In persons with VEBs, the morphologies were counted and the QS interval was measured for each of these morphologies. The duration of the broadest VEB, measured from the QRS onset in the derivation showing the earliest onset to its end in the derivation showing the latest termination, was taken as that patient's VEQSI. Survival was ascertained from public health records. Of 15 electrocardiographic variables pre-selected as potential prognostic indicators, VEQSI demonstrated the strongest association with the presence of structural heart disease (P = 0.013). Thirty-four persons died in 16 +/- 4 months follow-up. Univariate predictors of mortality are age, history of myocardial infarction, maximum heart rate, QS interval, the number of VEB morphologies, and the VEQSI. On multivariate analysis, only age (P < 0.001) and the number of VEB morphologies (P = 0.02) predicted mortality. VEQSI predicts the presence of structural heart disease. The number of VEB morphologies in a Holter recording predicts all-cause mortality.


Lateral Epicondylitis and Physical Exposure at Work? A Review of Prospective Studies and Meta-Analysis.
In view of recent published studies, a meta-analysis was undertaken on prospective studies in order to assess any association between lateral epicondylitis and physical exposure at work. Using the key words "lateral epicondylitis" AND "occupational" AND ("cohort" OR "longitudinal," OR "incidence") without limitations on the language or year of publication, original prospective studies were selected from 4 databases (PubMed, Scopus, Web of Science, and Base de Données de Santé Publique) after 2 rounds (valid design, valid association reported, and valid work exposure). Relevant associations between physical exposure at work and incident lateral epicondylitis were extracted from the articles, and a meta-risk was calculated using the generic variance approach (meta-odds ratios [meta-ORs]). From 2001 to 2014, 5 prospective studies were included. Among 6,922 included subjects (and 3,449 who were followed), 256 cases of incident lateral epicondylitis were diagnosed 2.5-6 years after baseline. All the published studies found a significant estimation of relative risk for a positive association between combined biomechanic exposure involving the wrist and/or elbow and incidence of lateral epicondylitis. The overall meta-OR was 2.6 (95% confidence interval 1.9-3.5), with a low heterogeneity (Q = 1.4, P > 0.05). Funnel plots and Egger's test did not suggest major publication bias. The results of this meta-analysis strongly support the hypothesis of an association between biomechanic exposure involving the wrist and/or elbow at work and incidence of lateral epicondylitis.


In vitro microbicidal, anti-biofilm and cytotoxic effects of different commercial antiseptics.
Topical antiseptics are widely used for wound treatment, with the goal of disrupting biofilm capacity. We analysed the effectiveness of a variety of antiseptics to inhibit various stages of biofilm formation and to remove biofilms in vitro as well as the agents' cytotoxic effects on fibroblasts. We found that the chlorine-releasing agents exhibited immediate anti-biofilm effects in the short term, with lesser cytotoxicity than agents prepared from more stable compounds, such as biguanide or modified diallyl disulfide-oxide, which, conversely, have better long-term effectiveness. Among the examined organisms, Gram-positive bacteria and Candida albicans were the most sensitive to the antiseptics, whereas Pseudomonas aeruginosa and Acinetobacter baumannii were relatively resistant to them. Formulations whose mechanisms of action involve the release of chemically active chlorine were more effective when administered in solution than the gel form, likely because of the stability of the active ingredients during or after preparation of the formula. Interestingly, hypochlorous acid and some superoxidation solutions were effective in preventing biofilm formation within a short time period and showed virtually no toxicity. Our study indicates that most antiseptics remain effective long enough to prevent biofilm formation; thus, even brief application of an antiseptic agent during initial wound treatment can lead to better wound management outcomes.


Cephalosporins as key lead generation beta-lactam antibiotics.
Antibiotics are antibacterial compounds that interfere with bacterial growth, without harming the infected eukaryotic host. Among the clinical agents, beta-lactams play a major role in treating infected humans and animals. However, the ever-increasing antibiotic resistance crisis is forcing the pharmaceutical industry to search for new antibacterial drugs to combat a range of current and potential multi-resistant bacterial pathogens. In this review, we provide an overview of the development, innovation, and current status of therapeutic applications for beta-lactams with a focus on semi-synthetic cephalosporins. Cephalosporin C (CPC), which is a natural secondary metabolite from the filamentous fungus Acremonium chrysogenum, plays a major and demanding role in both producing modern antibiotics and developing new ones. CPC serves as a core compound for producing semi-synthetic cephalosporins that can control infections with different resistance mechanisms. We therefore summarize our latest knowledge about the CPC biosynthetic pathway and its regulation in the fungal host. Finally, we describe how CPC serves as a key lead generation source for the in vitro and better, in vivo synthesis of 7-aminocephalosporanic acid (7-ACA), the major core compound for the pharmaceutical synthesis of current and future semi-synthetic cephalosporins. KEY POINTS: • Latest literature on cephalosporin generations • Biotechnical production of cephalosporins • In vivo production of 7-ACA.


Nootkatone Improves Chronic Unpredictable Mild Stress-Induced Depressive-Like Behaviors by Repressing NF-κB/NLRP3-Mediated Neuroinflammation.
To explore the effect of nootkatone (NKT) on chronic unpredictable mild stress (CUMS)-induced depressive-like behaviors and the mechanism underlying NKT improving the depressive-like behaviors. The CUMS-induced depression model was established in mice. Fifty mice were randomized into 5 groups (n=10) in accordance with a random number table: control group, CUMS group, CUMS + NKT (6 mg/kg) group, CUMS + NKT (12 mg/kg) group, and CUMS + ketamine group. From the 22th day, NKT (6 or 12 mg/kg) or ketamine (0.5 mg/kg) was given with intragastric administration every day for 21 days. Behavioral tests including forced swimming test (FST), tail suspension test (TST), sucrose preference test (SPT) and open-field test (OFT) were carried out. The mRNA and protein expressions of interleukin (IL)-1β, IL-18, IL-6, and tumor necrosis factor (TNF)-α in hippocampus were assessed using quantitative realtime polymerase chain reaction (PCR), Western blot analysis, and enzyme linked immunosorbent assay. The nuclear factor-κB (NF-κB)/NOD-like receptor 3 (NLRP3) inflammasome pathway was analyzed using Western blot and immunofluorescence analysis. NKT treatment improved CUMS-induced depressive-like behaviors in mice (P<0.05 or P<0.01). NKT significantly decreased the mRNA and protein levels of IL-1β, IL-18, IL-6, and TNF-α in hippocampus of CUMS mice (P<0.05 or P<0.01). Furthermore, NKT repressed CUMS-induced activation of NF-κB signaling and NLRP3 inflammasome (P<0.01). More important, Nigericin, a NLRP3 activator, destroyed the effect of NKT on repressing neuroinflammation and improving depressive-like behaviors (P<0.05 or P<0.01). NKT ameliorates the depressive-like symptoms, in part by repressing NF-κB/NLRP3-mediated neuroinflammation.


Oxidized low density lipoprotein (LDL) affects hyaluronan synthesis in human aortic smooth muscle cells.
Thickening of the vessel in response to high low density lipoprotein(s) (LDL) levels is a hallmark of atherosclerosis, characterized by increased hyaluronan (HA) deposition in the neointima. Human native LDL trapped within the arterial wall undergoes modifications such as oxidation (oxLDL). The aim of our study is to elucidate the link between internalization of oxLDL and HA production in vitro, using human aortic smooth muscle cells. LDL were used at an effective protein concentration of 20-50 μg/ml, which allowed 80% cell viability. HA content in the medium of untreated cells was 28.9 ± 3.7 nmol HA-disaccharide/cell and increased after oxLDL treatment to 53.9 ± 5.6. OxLDL treatments doubled the transcripts of HA synthase HAS2 and HAS3. Accumulated HA stimulated migration of aortic smooth muscle cells and monocyte adhesiveness to extracellular matrix. The effects induced by oxLDL were inhibited by blocking LOX-1 scavenger receptor with a specific antibody (10 μg/ml). The cholesterol moiety of LDL has an important role in HA accumulation because cholesterol-free oxLDL failed to induce HA synthesis. Nevertheless, cholesterol-free oxLDL and unmodified cholesterol (20 μg/ml) induce only HAS3 transcription, whereas 22,oxysterol affects both HAS2 and HAS3. Moreover, HA deposition was associated with higher expression of endoplasmic reticulum stress markers (CHOP and GRP78). Our data suggest that HA synthesis can be induced in response to specific oxidized sterol-related species delivered through oxLDL.


Water relations and photosynthesis of a barrel cactus, Ferocactus acanthodes, in the Colorado desert.
The structural characteristics, water relations, and photosynthesis of Ferocactus acanthodes (Lemaire) Britton and Rose, a barrel cactus exhibiting Crassulacean acid metabolism (CAM), were examined in its native habitat in the western Colorado desert. Water storage in its succulent stem permitted nighttime stomatal opening ot continue for about 40 days after the soil water potential became less than that of the stem, a period whe the plant would be unable to extract water from the soil. After 7 months of drought and consequent unreplenished water loss from a plant, diurnal stomatal activity was not observed and the stem osmotic pressure was 6.4 bars, more than double the value measured during wet periods with nighttime stomatal opening. F. acanthodes had a shallow root system (mean depth of 8 cm) which responded within 24 h to rainfall.When the nocturnal stem surface temperature was raised from 8.0° C to 35.0° C, the stomatal resistance increased 4-fold, indicating that cool nighttime temperatures are advantageous for gas exchange by F. acanthodes. Moreover, the optimal temperature for CO2 uptake in the dark was only 12.6° C. CO2 uptake at night became maximal for 3.0 mEinsteins cm-2 of photosynthetically active radiation incident during the preceding day, and the minimum number of incident quanta absorbed per CO2 fixed was 68. The transpiration ratio (mass of water transpired/mass of CO2 fixed) had the relatively low value of 70 for an entire year, consistent with values obtained for other CAM plants. The total amount of water annually diverted to the floral structures was about 6% of the stem wet weight. The annual growth increment estimated from the net CO2 assimilation corresponded to about 10% of the stem mass for barrel cacti 34 cm tall, in agreement with measured dimension changes, and indicated that such plants were about 26 years old.


Synthesis of transparent aqueous sols of colloidal layered niobate nanocrystals at room temperature.
Transparent aqueous sols of colloidal tetramethylammonium niobate nanocrystals were synthesized by mixing tetramethylammonium hydroxide (TMAOH), niobium ethoxide, and water at TMAOH/Nb≥0.7 at room temperature. The X-ray diffraction patterns of the thin films prepared by evaporating the colloidal solutions on a glass substrate indicated that the colloidal niobate had a layered crystalline structure. Two types of layered structures are known as a layered niobate, i.e. M(4)Nb(6)O(17)·nH(2)O and MNb(3)O(8) (M=H, H(3)O, or alkaline metal). Raman spectra and electron diffraction suggested that the niobate nanocrystals were similar in crystal structure to M(4)Nb(6)O(17)·nH(2)O compounds. Moreover, when niobium oxide thin films were fabricated from the niobate colloidal solutions by the sol-gel method, oriented T-Nb(2)O(5) thin films, whose c-axis was parallel to the substrate surface, were obtained. The orientation of the thin films was probably attributed to the layered structure of the colloidal niobate nanocrystals.


Four thermostatic steps: A novel CRISPR-Cas12-based system for the rapid at-home detection of respiratory pathogens.
The outbreak of coronavirus disease 2019 (COVID-19) in 2019 has severely damaged the world's economy and public health and made people pay more attention to respiratory infectious diseases. However, traditional quantitative real-time polymerase chain reaction (qRT-PCR) nucleic acid detection kits require RNA extraction, reverse transcription, and amplification, as well as the support of large-scale equipment to enrich and purify nucleic acids and precise temperature control. Therefore, novel, fast, convenient, sensitive and specific detection methods are urgently being developed and moving to proof of concept test. In this study, we developed a new nucleic acid detection system, referred to as 4 Thermostatic steps (4TS), which innovatively allows all the detection processes to be completed in a constant temperature device, which performs extraction, amplification, cutting of targets, and detection within 40 min. The assay can specifically and sensitively detect five respiratory pathogens, namely SARS-CoV-2, Mycoplasma felis (MF), Chlamydia felis (CF), Feline calicivirus (FCV), and Feline herpes virus (FHV). In addition, a cost-effective and practical small-scale reaction device was designed and developed to maintain stable reaction conditions. The results of the detection of the five viruses show that the sensitivity of the system is greater than 94%, and specificity is 100%. The 4TS system does not require complex equipment, which makes it convenient and fast to operate, and allows immediate testing for suspected infectious agents at home or in small clinics. Therefore, the assay system has diagnostic value and significant potential for further reducing the cost of early screening of infectious diseases and expanding its application. KEY POINTS: • The 4TS system enables the accurate and specific detection of nucleic acid of pathogens at 37 °C in four simple steps, and the whole process only takes 40 min. •A simple alkali solution can be used to extract nucleic acid. • A small portable device simple to operate is developed for home diagnosis and detection of respiratory pathogens.


Neurocalcin-immunoreactive receptor cells in the rat olfactory epithelium and vomeronasal organ.
Occurrence of neurocalcin, a calcium-binding protein with three EF hand motifs, was examined immunohistochemically in the rat olfactory epithelium and vomeronasal organ epithelium. Immunoreactivity was detected in receptor cells in these epithelia. Immunoreactions were distributed in cytoplasm associated with outer mitochondrial membrane, endoplasmic reticulum and microtubules. Olfactory and vomeronasal nerve fibers in the lamina propria exhibited immunoreactivity. Neurocalcin may participate in calcium signalling and cytoskeletal arrangement in receptor cells.


The transport of electrolytes in the gut and the use of oral rehydration solutions.
This presentation summarizes the recent advances in knowledge of the physiologic and pathophysiologic process underlying the transport of electrolytes across the small intestine and formulate a rationale for the use of oral electrolyte solutions in diarrheal diseases.


A radioenzymatic method to measure picogram amounts of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) in small samples of brain tissue.
A radioenzymatic method for simultaneous determination of dopamine and DOPAC in small brain areas is described. By using this assay, 250 pg of dopamine and 150 pg of DOPAC can be estimated. The present method has been applied to compare the effect of different psychotropic drugs on the dopamine and DOPAC levels in the caudate nucleus, substantia nigra and medial basal hypothalamus.


Surface-plasmon-coupled optical force sensors based on metal-insulator-metal metamaterials with movable air gap.
We proposed surface-plasmon-coupled optical force sensors based on metal-insulator-metal (MIM) metamaterials with a movable air gap as an insulator layer. The MIM metamaterial was composed of an air gap sandwiched by a metal nanodot array and a metal diaphragm, the resonant wavelength of which was red-shifted when the air gap was narrowed by applying a normal force. We designed and fabricated a prototype of the proposed sensor and confirmed that the MIM metamaterial could be used as a force sensor with larger sensitivity than a force sensor based on Fabry-Pérot interferometer (FPI).


Glucagon-like peptide-1 therapy in people with obesity restores natural killer cell metabolism and effector function.
People with obesity (PWO) have functionally defective natural killer (NK) cells, with a decreased capacity to produce cytokines and kill target cells, underpinned by defective cellular metabolism. It is plausible that the changes in peripheral NK cell activity are contributing to the multimorbidity in PWO, which includes an increased risk of cancer. This study investigated whether therapy with long-acting glucagon-like peptide-1 (GLP-1) analogues, which are an effective treatment for obesity, could restore NK cell functionality in PWO. In a cohort of 20 PWO, this study investigated whether 6 months of once weekly GLP-1 therapy (semaglutide) could restore human NK cell function and metabolism using multicolor flow cytometry, enzyme-linked immunosorbent assays, and cytotoxicity assays. These data demonstrate that PWO who received GLP-1 therapy have improved NK cell function, as measured by cytotoxicity and interferon-γ/granzyme B production. In addition, the study demonstrates increases in a CD98-mTOR-glycolysis metabolic axis, which is critical for NK cell cytokine production. Finally, it shows that the reported improvements in NK cell function appear to be independent of weight loss. The restoration, by GLP-1 therapy, of NK cell functionality in PWO may be contributing to the overall benefits being seen with this class of medication.


Host sex and transplanted human induced pluripotent stem cell phenotype interact to influence sensorimotor recovery in a mouse model of cortical contusion injury.
Traumatic brain injury (TBI) is a substantial cause of disability and death worldwide. Primary head trauma triggers chronic secondary injury mechanisms in the brain that are a focus of therapeutic efforts to treat TBI. Currently, there is no successful clinical strategy to repair brain injury. Cell transplantation therapies have demonstrated promise in attenuating secondary injury mechanisms of neuronal death and dysfunction in animal models of brain injury. In this study, we used a unilateral cortical contusion injury (CCI) model of sensorimotor brain injury to examine the effects of human induced pluripotent stem cell (hiPSC) transplantation on pathology in male and female adult mice. We determined transplanted hiPSC-derived neural stem cells (NSCs) and neuroblasts but not astrocytes best tolerate the injured host environment. Surviving NSC and neuroblast cells were clustered at the site of injection within the deep layers of the cortex and underlying corpus callosum. Cell grafts extended neuritic processes that crossed the midline into the contralateral corpus callosum or continued laterally within the external capsule to enter the ipsilateral entorhinal cortex. To determine the effect of transplantation on neuropathology, we performed sensorimotor behavior testing and stereological estimation of host neurons, astrocytes, and microglia within the contused cortex. These measures did not reveal a consistent effect of transplantation on recovery post-injury. Rather the positive and negative effects of cell transplantation were dependent on the host sex, highlighting the importance of developing patient-specific approaches to treat TBI. Our study underscores the complex interactions of sex, neuroimmune responses and cell therapy in a common experimental model of TBI.


LncRNA CASC2 targets CAV1 by competitively binding with microRNA-194-5p to inhibit neonatal lung injury.
Long non-coding RNAs (lncRNAs) are vital regulators of different biological processes during bronchopulmonary dysplasia (BPD). This study was conducted to probe the biological roles of lncRNA CASC2 in the pathogenesis of BPD and neonatal lung injury. Firstly, a hyperoxia-induced mouse model with BPD was established. LncRNAs with differential expression in lung tissues of normal and BPD mice were analyzed by microarray. An adenovirus vector overexpressing CASC2 was constructed and its functions on BPD symptoms in model mice were analyzed. Gain- and loss-of function studies of CASC2 were performed in a bronchial epithelial cell line BEAS-2B to determine its role in cell apoptosis and proliferation under normoxic and hyperoxic conditions. The downstream mechanical molecules of lncRNA CASC2 were predicted on bioinformatics systems and confirmed by luciferase assays. The functional interactions among lncRNA CASC2, miR-194-5p, and CAV1 in BPD were determined by rescue experiments. Consequently, lncRNA CASC2 was found to be poorly expressed in BPD mice. Besides, overexpressed CASC2 was found to relieve the symptoms of BPD in neonatal mice and suppress apoptosis as well as promote proliferation in hyperoxia-induced BEAS-2B cells. Importantly, CASC2 was found to regulate CAV1 expression by competitively binding to miR-194-5p and downregulate the activity of the TGF-β1 signaling pathway, thereby suppressing lung injury. Either miR-194-5p upregulation or CAV1 downregulation blocked the roles of CASC2. To sum up, this study evidenced that CASC2 alleviates hyperoxia-induced lung injury in mouse and cell models with the involvement of a miR-194-5p-CAV1 crosstalk and the TGF-β1 inactivation.


Ethanol exposure during either adolescence or adulthood alters the rewarding effects of cocaine in adult rats.
The present studies assessed the effects of adolescent and adult ethanol exposure on the rewarding effects of cocaine as measured with the conditioned place preference procedure. Male rats were exposed to intraperitoneal (IP) injections of ethanol or vehicle for 10 days [postnatal days (PNDs) 30-39 or PNDs 70-79; 2 mg/kg]. Place preference conditioning began on PND 65 or PND 105, respectively, and consisted of a baseline test followed by four conditioning cycles with either 0, 5, 10 or 20 mg/kg cocaine. Following the fourth conditioning cycle a final preference test was performed. Changes in time on the drug-paired side between the baseline and final test were analyzed. Animals exposed to vehicle (during adolescence or adulthood) showed a significant place preference at 20 mg/kg cocaine. Animals exposed to ethanol (during adolescence or adulthood) showed a significant place preference at 10mg/kg cocaine. Exposure to ethanol (adolescents or adults) sensitized the rewarding effects of cocaine. This may indicate an increase in the abuse liability of cocaine following a history of ethanol exposure.


Synthesis and biological activities of phenyl piperazine-based peptidomimetic growth hormone secretagogues.
A new class of potent, orally active phenyl piperazine-based GH secretagogues have been discovered from attempts to mimic the arrangement of the phenyl substituent in the spiroindanyl piperidine and spiroindoline sulfonamide privileged structures of 4 and 1, respectively. The best of these compounds, 18 (EC50 = 2.8 nM) is nearly as potent as MK-0677 for releasing GH from rat pituitary cells.


The role of add-back therapy in the United States.
Gonadotropin-releasing hormone (GnRH) agonists are effective in reducing pelvic pain due to endometriosis, but they are associated with a number of hypoestrogenic side effects, such as vasomotor symptoms and loss of bone mineral density. Add-back therapy with a progestin or a progestin plus low-dose estrogen helps to reduce the side effects associated with GnRH agonist administration without compromising efficacy. Add-back therapy should be initiated at the same time as the treatment with a GnRH agonist and longer-term therapy beyond 6 months can be considered in patients meeting the appropriate criteria.


Relationship between margin of stability and deviations in spatiotemporal gait features in healthy young adults.
Increased variability of spatio-temporal features while walking is related to increased risk of falls. It is thought that variability in foot placement and timing reflects responses to mechanical instability while walking. The purpose of this study was to determine whether 'extreme' values of step length, width and time follow transient periods of low mechanical stability during the single support phase of gait in healthy young adults. We conducted secondary analysis of a portion of an existing dataset. Eleven healthy adults walked on an instrumented treadmill. Participants were outfitted with reflective markers and completed two 1-min periods of walking at each of 3 speeds (0.8m/s, 1.2m/s, and 1.6m/s). Margins of stability were calculated relative to the anterior, posterior, lateral, and medial boundaries of the base of support, and the value at heel strike and the minimum value during the first half of each single-support phase were extracted. Step length, swing time, and step width were calculated from motion capture and ground reaction force data. Extreme values for consecutive steps were identified using Poincaré plots, and margins of stability in each direction were compared between 'normal' and 'extreme' steps. Margins of stability in both the anterior and medial direction were lower prior to long and wide steps, respectively. Margins of stability in the anterior and medial directions were lower prior to quick steps, and margins of stability in the posterior and lateral directions were lower prior to slow steps. There were either no significant differences in margin of stability between 'normal' and 'extreme' steps at heel strike, or the direction of the relationship was reversed to that observed during single support. These data suggest that spatio-temporal variability may reflect adjustments in step placement and timing to compensate for transient periods of low mechanical stability when walking.


Ultrastructural localization of gustducin immunoreactivity in microvilli of type II taste cells in the rat.
Gustducin is a transducin-like G protein (guanine nucleotide-binding protein) that is expressed in taste bud cells. Gustducin is believed to be involved in bitter and possibly sweet taste transduction. In the present study, we demonstrate that a subset of type II cells displays immunoreactivity to antisera directed against gustducin in taste buds of rat circumvallate papilla. Immunogold particles are present both in the microvilli and cytoplasm of the immunoreactive cells. Quantitative analysis of the data suggests that the number of colloidal gold particles (P<0.001) and nanogold particles (P<0.01) in the immunoreactive type II cells are much greater than in type I cells. There are also approximately 2.5 times (P<0.05) as many colloidal gold particles associated with the microvilli versus the cytoplasm in the immunoreactive type II cells. The ultrastructural distribution of gustducin immunoreactivity is consistent with its proposed role in the initial events of sensory transduction by gustatory receptor cells.


Pancreatitis in childhood.
Thirty cases of pancreatitis in children are reviewed. Diagnosis is based on the clinical findings of pancreatic inflammation, laboratory confirmation with elevated serum and/or urinary amylase values, and in some cases surgical or postmortem tissue substantiation. Four major classes of pancreatitis are defined in children: (1) traumatic; (2) systemic-disease associated; (3) drug-induced, caused by drug therapy for various life-threatening diseases, and (4) chronic pancreatitis, with or without an anatomic abnormality. If cases of traumatic pancreatitis are excluded, females outnumber males 5 to 1. A high index of suspicion is necessary to make the diagnosis, and this is very important if the mortality for pancreatitis in children is to be lowered. Awareness and consistent early aggressive intervention should increase the salvage rate.


The master growth regulator DELLA binding to histone H2A is essential for DELLA-mediated global transcription regulation.
The DELLA genes, also known as 'Green Revolution' genes, encode conserved master growth regulators that control plant development in response to internal and environmental cues. Functioning as nuclear-localized transcription regulators, DELLAs modulate expression of target genes via direct protein-protein interaction of their carboxy-terminal GRAS domain with hundreds of transcription factors (TFs) and epigenetic regulators. However, the molecular mechanism of DELLA-mediated transcription reprogramming remains unclear. Here by characterizing new missense alleles of an Arabidopsis DELLA, repressor of ga1-3 (RGA), and co-immunoprecipitation assays, we show that RGA binds histone H2A via the PFYRE subdomain within its GRAS domain to form a TF-RGA-H2A complex at the target chromatin. Chromatin immunoprecipitation followed by sequencing analysis further shows that this activity is essential for RGA association with its target chromatin globally. Our results indicate that, although DELLAs are recruited to target promoters by binding to TFs via the LHR1 subdomain, DELLA-H2A interaction via the PFYRE subdomain is necessary to stabilize the TF-DELLA-H2A complex at the target chromatin. This study provides insights into the two distinct key modular functions in DELLA for its genome-wide transcription regulation in plants.


Development of a versatile computer integrated control system for bioprocess controls.
A general approach is described for the implementation of a networked multi-unit computer integrated control system. The use of data acquisition hardware and graphical programming tools alleviates tedious programming and maintains potency and flexibility. One application of the control system, the control of a mammalian cell perfusion culture based on a key nutrient glucose concentration, was demonstrated. The control system offers customized user interface for all process control parameters and allows the flexibility for continued improvement and implementation of new tailored functions. The temperature, pH, dissolved oxygen and glucose level were accurately controlled.


Commentary: why do research on spirituality and health, and what do the results mean?
I address two related questions in this article. First, why conduct research on religion/spirituality (R/S) and health? Second, what are the dangers of misinterpreting or misapplying the results from such research? If relationships are found, so what? What is the practical value or clinical relevance of such information? Why should investigators spend time and scarce financial resources to explore such connections? What might health care professionals do differently as a result? How would people live their lives differently in light of such information? Questions like these need solid answers for the field to continue to move forward. Related to the "So what?" question is the issue of how results from research in this area are translated into popular understanding and application. After discussing why conducting research on religion and health is important, I identify a recently published research report that focuses on the relationship between R/S and self-control, an article that received considerable media press coverage. I present the results reported by the authors of this study and then examine a column written about the study that appeared in the New York Times. Finally, I explore what the findings mean, how the media portrayed the findings, and problems that might result depending on how people applied those findings.


Expression, purification and function of cysteine desulfurase from Sulfobacillus acidophilus TPY isolated from deep-sea hydrothermal vent.
The cysteine desulfurase (SufS) gene of Sulfobacillus acidophilus TPY, a Gram-positive bacterium isolated from deep-sea hydrothermal vent, was cloned and over-expressed in E. coli BL21. The recombinant SufS protein was purified by one-step affinity chromatography. The TPY SufS contained a well conserved motif RXGHHCA as found in that of other microorganisms, suggesting that it belonged to group II of cysteine desulfurase family. The recombinant TPY SufS could catalyze the conversion of l-cysteine to l-alanine and produce persulfide, and the enzyme activity was 95 μ/μL of sulfur ion per minute. The growth of E. coli BL21 was promoted by over-expressing TPY SufS in vivo or by directly adding recombinant TPY SufS in the medium (4.3-4.5 × 108 cells/mL vs. 3.2-3.5 × 108 cells/mL). Furthermore, the highest cell density of E. coli BL21 when the TPY SufS was over-expressed was about 3.5 times that of the control groups in the presence of sodium thiosulfate. These results indicate that the SUF system as the only assembly system of iron-sulfur clusters not only has significant roles in survival of S. acidophilus TPY, but also might be important for combating with high content of sulfide.


Paroxysmal Nonkinesigenic Dyskinesias Responsive to Carbamazepine in Fahr Syndrome: A Case Report.
This study aimed to report the case of a patient with paroxysmal nonkinesigenic dyskinesias and Fahr syndrome who had a marked response to carbamazepine. We present the case of a 57-year-old female patient with episodes of paroxysmal choreoathetoid dyskinesias in the oromandibular region and distal region of upper and lower extremities, with fluctuating dystonic postures in the same distribution; duration was variable ranging from 30 minutes to 3 hours. Laboratory studies were consistent with primary hyperparathyroidism with bilateral brain calcifications. Treatment with low doses of carbamazepine was successful.


A combination of the modified Mallampati score, thyromental distance, anatomical abnormality, and cervical mobility (M-TAC) predicts difficult laryngoscopy better than Mallampati classification.
Unanticipated difficult tracheal intubation is a significant source of morbidity and mortality in anesthetized patients. A number of modules have been developed to predict difficult airways, but they are often complex in nature. We combined the modified Mallampati score (M), thyromental distance (T), anatomical abnormality (A), and cervical mobility (C) into a single scoring system with the acronym M-TAC, and evaluated it against Mallampati scoring. We prospectively analyzed 500 adult patients of the American Society of Anesthesiologists (ASA) class I or II, scheduled for elective surgery under general anesthesia. Preoperative airway assessments using M-TAC were performed, all of which were given a score. Anesthesiologists, blinded to the pre-anesthetic airway assessment, performed laryngoscopy and graded the laryngoscopic view as per Cormack and Lehane's classification. For the study purpose, difficult laryngoscopy was defined as Cormack and Lehane Grade 3 or 4 of laryngoscopic view. An M-TAC score ≥ 4 had a significantly higher sensitivity (96% vs. 72%) and specificity (86% vs. 78%) with a high positive predictive value (44% vs. 28%) and a very low false negative value (2% vs. 15%) in comparison with Mallampati scoring (p < 0.05). Analysis of the receiver operating characteristic (ROC) curve for predicting difficult laryngoscopy revealed an area under the curve of 0.83 (95% CI = 0.78-0.88) for Mallampati scoring and 0.94 (95% CI = 0.92-0.96) for M-TAC scoring system. The M-TAC scoring system has provided a higher sensitivity and specificity in predicting difficult laryngoscopy in comparison with Mallampati classification.


Gamma knife radiosurgery for brain metastases: do patients benefit from adjuvant external-beam radiotherapy? An 18-month comparative analysis.
To analyze 18 months of results of gamma knife stereotactic radiosurgery in the treatment of brain metastases and determine factors affecting outcome by examining the effectiveness of additional external-beam radiotherapy (XRT). Between January 2000 and September 2001, 61 patients with 103 tumors diagnosed as cerebral metastases were treated with gamma knife. Mean patient age was 57 years (range = 36-81). Lung carcinoma (55.7%) was the most common primary cancer, followed by melanoma (14.8%) and breast carcinoma (11.5%). Mean KPS of the patients was 70 (range = 50-90). Twenty-seven patients had solitary metastases while 34 had multiple tumors. Forty-three patients (59 tumors in total) received only radiosurgery, while 18 patients (44 tumors in total) had prior XRT. Tumor volume ranged from 0.5 to 33 cm(3) (mean = 9.74 cm(3)). Mean marginal dose prescription to the tumor was 15 Gy (range = 11-21 Gy). Median follow-up was 11 months. Twenty-one patients (34.4%) were alive at last follow-up and 40 (65.6%) had died. Seventeen deaths (42.5%) were reported to be due to progressive brain disease, while 23 deaths (57.5%) were due to uncontrolled primary. Control of the treated lesions was achieved in 45 patients (73.8%) and 84 tumors (81.6%). Mean overall survival of the patients is 8 months (range = 1-19 months). The actuarial 12-month tumor control rate using the Kaplan-Meier method for this series is 68.2 +/- 0.06%. Results of the log-rank test revealed that younger age (<55 years), small tumor volume (<10 cm(3)), and increasing tumor dose (>15 Gy) correlated with improved brain disease-free survival (p < 0.05). Overall survival, local tumor control rate and the freedom from brain disease period (based on the appearance of new brain tumors after radiosurgery) were analyzed separately for the groups receiving radiosurgery alone and those with prior XRT to detect any additional benefit of XRT. No statistically significant difference was found between the two groups for any of the considered outcomes. Gamma knife stereotactic radiosurgery is a safe and effective treatment option for patients with cerebral metastases. It provides survival benefits and improves quality of life by achieving excellent control of the brain disease, irrespective of patients' age or number of brain tumors. The addition of XRT in younger patients with small brain metastases does not improve survival and/or control of the brain disease.


A Systematic Review of Population-Based Studies of Chronic Bowel Symptoms in Cancer Survivors following Pelvic Radiotherapy.
Pelvic radiotherapy can damage surrounding tissue and organs, causing chronic conditions including bowel symptoms. We systematically identified quantitative, population-based studies of patient-reported bowel symptoms following pelvic radiotherapy to synthesize evidence of symptom type, prevalence, and severity. Medline, CINAHL, EMBASE, and PsychINFO were searched from inception to September 2022. Following independent screening of titles, abstracts, and full-texts, population and study characteristics and symptom findings were extracted, and narrative synthesis was conducted. In total, 45 papers (prostate, n = 39; gynecological, n = 6) reporting 19 datasets were included. Studies were methodologically heterogeneous. Most frequently assessed was bowel function ('score', 26 papers, 'bother', 19 papers). Also assessed was urgency, diarrhea, bleeding, incontinence, abdominal pain, painful hemorrhoids, rectal wetness, constipation, mucous discharge, frequency, and gas. Prevalence ranged from 1% (bleeding) to 59% (anal bleeding for >12 months at any time since start of treatment). In total, 10 papers compared radiotherapy with non-cancer comparators and 24 with non-radiotherapy cancer patient groups. Symptom prevalence/severity was greater/worse in radiotherapy groups and symptoms more common/worse post-radiotherapy than pre-diagnosis/treatment. Symptom prevalence varied between studies and symptoms. This review confirms that many people experience chronic bowel symptoms following pelvic radiotherapy. Greater methodological consistency, and investigation of less-well-studied survivor populations, could better inform the provision of services and support.


Natural history of mild and of moderate aortic stenosis-new insights from a large prospective European study.
Increased life expectancy has led to a higher prevalence of calcific aortic valve disease. Both ends of the disease spectrum-sclerosis of the aortic valve without hemodynamic obstruction and the late stage of aortic valve stenosis (AS)-have been associated with increased morbidity and mortality. This raises the question of the prognostic contribution of atherosclerotic diseases and other comorbidities as opposed to the hemodynamic effect of obstructive AS. Hence, the evaluation of asymptomatic patients with mild or moderate AS without comorbidities is of major interest. In the Simvastatin and Ezetimibe in Aortic Stenosis study, with the exception of hypertension, comorbidities were excluded, thus allowing an analysis of the effect of pure AS as well as the effect of hypertension on the progression and outcome of AS. We discuss the results that emerged from this large European prospective study and relate these to the published literature.


Nucleotide sequence of the gene encoding the 35-kDa protein of Mycobacterium tuberculosis.
A 35-kilodalton (kDa) protein of Mycobacterium tuberculosis is expressed by recombinant Escherichia coli which possess a plasmid that contains a 2.4-kilobase fragment of M. tuberculosis chromosomal DNA. The nucleotide sequence of this fragment was determined by the dideoxynucleotide chain-termination method. Analysis of the sequence revealed four open reading frames that could encode proteins greater than 250 amino acids in length. The reading frame for the 35-kDa protein was identified by subcloning DNA fragments into expression vectors pTTQ18 and pTTQ19, and assaying for production of the 35-kDa protein by Western blotting. A protein with a primary structure of 270 amino acids and a predicted molecular weight of 29,260 daltons was deduced from the nucleotide sequence. A computer-aided search of nucleic and amino acid sequence databases did not identify any proteins with significant sequence similarity to this protein. The organization of the gene encoding this protein was compared with other mycobacterial genes that have been sequenced. Information obtained from the investigation of this protein may aid in the development of reagents to diagnose and control mycobacterial disease.


Estimation of blood and urine levels of eight metals and essential trace elements collected from living Subjects compared to urine, cardiac and femoral postmortem blood, and other postmortem samples: A forensic toxicology study.
Along with the regular toxicology testing, different samples collected during the autopsy might be subjected to metal level estimation to investigate the cause of death in some cases. Utilizing a scientific procedure on postmortem specimens is crucial for interpreting forensic toxicological analytical results. Even modest procedural errors made by incompetent forensic toxicologists and chemists who lack proper specialized training and knowledge can alter the scientific conclusions and hence the legal verdict. The current work studies an overview of eight metals and element levels in living and deceased human bodies. It could be a substantial contribution to establishing normal or so-called "reference" metal levels under antemortem and postmortem situations, hence aiding in identifying reliable future interpretations of results produced by numerous researchers in the same field. The current work aimed to study the concentration of eight metals in the blood samples (cardiac and femoral), urine, and other samples (Spleen, liver, and renal tissues) collected from human cadavers at different postmortem intervals in addition to blood and urine samples collected from the living population as a contribution to establishing normal or so-called "reference" metal levels under antemortem and postmortem situations. Postmortem autopsy blood samples (cardiac and femoral), urine, and other samples (Spleen, liver, and renal tissues) were collected from 400 deceased subjects. These samples were analyzed for the estimation of the eight metals under research, namely, Arsenic (As), Selenium (Se), Silver (Ag), Cadmium (Cd), Antimony (Sb), Mercury (Hg), Zinc (Zn) and Lead (Pb). In addition, blood and urine samples from 400 living volunteer subjects were analyzed for the same eight elements under study. In the postmortem group, the mean metal levels in cases with absent, early, and advanced putrefaction simultaneously in μg/L were 2.45 ± 3.30, 3.25 ± 5.18, and 3.81 ± 1.95 for As. For Se, the results were 10.74 ± 4.21, 10.54 ± 5.28, and 9.96 ± 4.14. 4.04 ± 1.74, 3.48 ± 1.32, and 3.74 ± 0.91 were the results for Ag. For Cd, they were 8.35 ± 3.91, 12.15 ± 3.05, and 24.51 ± 31.25 with P < 0.0001**. 1.48 ± 1.85, 1.61 ± 1.85, and 1.62 ± 1.74 were the same results for Sb; 6.07 ± 2.44, 5.22 ± 2.17, and 5.39 ± 1.82 for Hg. 395 ± 79.8, 553 ± 51.7, and 704 ± 97.2 for Zn with a P-value <0.005*. As for lead, the results were 15.61 ± 24.19, 14.76 ± 23.05, and 24.61 ± 52.72. As the postmortem interval increased, Cd and Zn levels increased (p < 0.0001, <0.005* simultaneously).


Cytomegalovirus viral load and mortality after haemopoietic stem cell transplantation in the era of pre-emptive therapy: a retrospective cohort study.
Although cytomegalovirus viral load is commonly used to guide pre-emptive therapy in the post-transplantation setting, few data are available correlating viraemia with clinical endpoints. We therefore investigated the association between cytomegalovirus viral load and mortality in the first year after haemopoietic stem cell transplantation. In this retrospective cohort study, we included patients from the Fred Hutchinson Cancer Research Center, WA, USA, who received an allogeneic haemopoietic stem cell transplantation between Jan 1, 2007, and Feb 28, 2013, were cytomegalovirus seropositive or had a seropositive donor, and underwent weekly plasma cytomegalovirus monitoring by PCR through to day 100 post-transplantation. Cox proportional hazards models were used to estimate the association of cytomegalovirus viral load at different thresholds with overall mortality by 1 year post-transplantation, adjusting for the use of pre-emptive therapy and other factors such as neutropenia, and graft-versus-host disease. Of the 1037 patients initially selected for inclusion in this cohort, 87 (8%) patients were excluded because of missing cytomegalovirus testing and 24 (2%) were excluded because of their participation in cytomegalovirus prophylaxis trials. In the remaining 926 patients included in this study, the cumulative overall mortality was 30·0% (95% CI 26·9-33·0) 1 year after haemopoietic stem cell transplantation. 95 patients developed cytomegalovirus disease; death was directly attributable to cytomegalovirus disease in three (1%) of 263 patients who died in the first year after transplantation. A cytomegalovirus viral load of 250 IU/mL or greater was associated with increased risk of early (day 0-60 post-transplantation) death (adjusted hazard ratio [HR] 19·8, 95% CI 9·6-41·1). The risk was attenuated after day 60 (adjusted HR 1·8, 95% CI 1·3-2·3). Similar associations were noted for higher cytomegalovirus viral load thresholds. Cytomegalovirus viraemia is associated with an increased risk of overall mortality in the first year after haemopoietic stem cell transplantation, independent of the use of pre-emptive therapy, and with evidence of a positive dose-response relationship. These data indicate the suitability of viral load as a surrogate clinical endpoint for clinical trials for cytomegalovirus vaccines, biologics, and drugs. Merck and Co, National Institutes of Health.


The Risk of Mortality Associated With Opioid Use in Patients With Acute Heart Failure: Systematic Review and Meta-analysis.
The impact of opioids in acute heart failure (AHF) is unclear. This systematic review with meta-analysis aimed to evaluate the mortality risk associated with opioid use in AHF. An electronic search was performed in MEDLINE, CENTRAL, Web of Science Core Collection, and SCIELO (December 2019) for randomized controlled trials and observational studies evaluating the impact of opioids in in-hospital and 30-day mortality in patients with AHF. Data were screened, extracted, and appraised by 2 independent reviewers. A random-effects meta-analysis to estimate the pooled odds ratios (OR) with 95% confidence intervals (CI) was performed and heterogeneity was evaluated using the I2 statistics. Six observational retrospective studies with 151,735 participants were included. Pooled results showed a statistical significant association between morphine and in-hospital mortality (OR 1.78; 95% CI 1.01-3.13; I2 = 92%; 6 studies) and 30-day mortality (OR 1.56; 95% CI 1.14-2.15; I2 = 0; 2 studies). Both outcomes were rated as having a serious risk of bias and had a very low Grading of Recommendation, Assessment, Development, and Evaluation evidence. Opioids seem to be associated with an increased risk of short-term mortality in AHF patients; however, the confidence in the estimated effect is very low, which highlights the need of further research to evaluate this question.


Rapid magnetic isolation of extracellular vesicles via lipid-based nanoprobes.
Extracellular vesicles (EVs) can mediate intercellular communication by transferring cargo proteins and nucleic acids between cells. The pathophysiological roles and clinical value of EVs are under intense investigation, yet most studies are limited by technical challenges in the isolation of nanoscale EVs (nEVs). Here, we report a lipid nanoprobe that enables spontaneous labelling and magnetic enrichment of nEVs in 15 minutes, with isolation efficiency and cargo composition similar to what can be achieved by the much slower and bulkier method of ultracentrifugation. We also show that the lipid nanoprobes, which allow for downstream analyses of nucleic acids and proteins, enabled the identification of EGFR and KRAS mutations following nEV isolation from blood plasma from non-small-cell lung-cancer patients. The efficiency and versatility of the lipid nanoprobe opens up opportunities in point-of-care cancer diagnostics.


Mycobacterium avium infection of the skin resembling lepromatous leprosy.
A patient on systemic steroid therapy developed a cutaneous papule while histologically resembled lepromatous leprosy. Cultures of this lesion grew Mycobacterium avium. Since there was no evidence of disseminated infection the lesion was excised and the patient continues to do well.


A randomized trial of saline solution-moistened misoprostol versus dry misoprostol for first-trimester pregnancy failure.
The purpose of this study was to estimate whether the efficacy of treatment with intravaginal misoprostol for first-trimester pregnancy failure is enhanced by the addition of saline solution. Eighty women with embryonic/fetal death or anembryonic pregnancy were assigned randomly to receive either 800 microg of misoprostol with saline solution (group I, 41 women) or without (group II, 39 women). Treatment was repeated on day 3 if the gestational sac remained. Curettage was performed if the gestational sac remained on day 8 or as necessary during at least 30 days of follow-up. Data were analyzed with the Student t test and the chi(2) or Fisher exact test. By the first follow-up visit, 73% (group I) and 64% (group II) of women passed the gestational sac (P=.38). By the second follow-up visit, expulsion rates were 83% and 87%, respectively (P=.59). Five subjects in each group underwent curettage. Misoprostol is effective for the treatment of failed first-trimester pregnancy. The expulsion rate is not improved by adding saline solution.


Natural enrichment of Cd and Tl in the bark of trees from a rural watershed devoid of point sources of metal contamination.
To help understand the bioaccumulation of Cd and Tl in beaver tissue, we examined the enrichment of these metals in vegetation available to the animals. Bark was collected from 40 species of trees and shrubs, along with a complete soil weathering profile, within a small watershed devoid of trace metal contamination. Weathering resulted in a 5x enrichment of Cd in the soils relative to the underlying sediments, and a 6x Tl depletion: while Cd was lost from calcite and accumulates in the organic matter and oxyhydroxide fractions, Tl occurred only in the residual fraction. Soil processes alone, however, cannot explain the anomalous concentrations and enrichments of Cd in willow and poplar which contain up to 8.5 mg/kg Cd. The concentrations of Cd and Tl in the dissolved fraction (<0.45 μm) of the Wye River are similar (1.2 ± 0.4 and 1.6 ± 0.1 ng/L, respectively), and are taken to estimate their bioavailability in soil solutions. Normalizing the Cd/metal ratios in bark to the corresponding ratios in water yields the Stream Enrichment Factor: this novel approach shows that all plant species are enriched in Cd relative to Ni; 33 relative to Cu, 13 relative to Zn, and 7 relative to Mn. Thus, many plants preferentially accumulate Cd, especially willow and poplar, over these essential micronutrients. Clearly, the enrichment of Cd over Tl in bark is not a reflection of differences in bioavailability, but rather on the preferential uptake of Cd by the plants. The profound natural bioaccumulation of Cd in the bark of willow and poplar, the two favourite foods of the beaver, has ramifications for the use of these aquatic mammals as biomonitors of environmental contamination, as well as for the direct and indirect consumption of bark for traditional food and medicine.


Sexual Well-Being After Nipple-Sparing Mastectomy: Does Preservation of the Nipple Matter?
The primary aim of this study was to evaluate patient-reported outcome measures in patients undergoing mastectomy with and without breast reconstruction (immediate or delayed) with and without nipple preservation. All female patients undergoing mastectomy between 2011 and 2015 at Mayo Clinic Rochester were identified and were mailed the BREAST-Q survey. Breast satisfaction, psychosocial well-being, and sexual well-being were evaluated and compared by surgery type using Wilcoxon rank-sum tests for univariate analysis and linear regression for multivariable analysis adjusting for potential confounders. Of 1547 patients, 771 completed the BREAST-Q survey (response rate 50%). Of these 771 respondents, 237 (31%) did not have reconstruction, 198 (26%) had nipple-sparing mastectomy with reconstruction (NSM), and 336 (44%) had skin-sparing mastectomy with reconstruction (SSM) ± nipple-areolar complex (NAC) reconstruction (via surgery ± tattoo). Patients with breast reconstruction had consistently higher BREAST-Q scores versus those without. Comparing NSM with all SSMs, there was no difference in satisfaction with breasts (mean 71.8 vs. 70.2, p = 0.21) or psychosocial well-being (mean 81.9 vs. 81.3, p = 0.47); however, sexual well-being was significantly higher in the NSM group on univariate (mean 64.5 vs. 58.0, p = 0.002) and multivariable (β = -4.69, p = 0.03) analysis. Sexual well-being scores were similar for NSM and the SSM subgroups with any type of NAC reconstruction. This study demonstrates that NSM positively impacts patient sexual well-being after breast reconstruction compared with SSM, particularly SSM without nipple reconstruction or tattoo. SSM with any type of NAC reconstruction achieved similar satisfaction and sexual well-being to those undergoing NSM.


Viability of dental implants in head and neck irradiated patients: A systematic review.
The purpose of this systematic review was to evaluate the safety of dental implants placed in irradiated bone and to discuss their viability when placed post-radiotherapy (RT). A systematic review was performed to answer the questions: "Are dental implants in irradiated bone viable?" and "What are the main factors that influence the loss of implants in irradiated patients?" The search strategy resulted in 8 publications. A total of 331 patients received 1237 implants, with an overall failure rate of 9.53%. The osseointegration success rates ranged between 62.5% and 100%. The optimal time interval between irradiation and dental implantation varied from 6 to 15 months. The interval time between RT and implant placement and the radiation doses are not associated with significant implant failure rates. The placement of implants in irradiated bone is viable, and head and neck RT should not be considered as a contraindication for dental rehabilitation with implants. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2229-E2240, 2016.


Computer-assisted method for intracavitary radiotherapy of cancer of the uterine cervix.
This paper describes a simple computer system for calculating the radiation dose rate to selected points in the pelvis of a patient treated by gynaecological insertion of applicators loaded with radioactive sources. The calculations are performed on the basis of radiographs made before the sources are placed in the applicators. The system consists of a minicomputer, a teletype and a digitizer. The method allows an optimum loading distribution to be determined within a few minutes once the radiographic images are available.


YouTube® in Spanish as an information source for patients with autoimmune hepatitis.
A large number of patients with autoimmune hepatitis (AH) seek information about their disease on the Internet. The reliability, comprehensiveness, and quality of said information in Spanish has not been studied. Our aim was to describe the characteristics of the information about AH on YouTube®. An analytic observational study evaluated videos in Spanish about AH available on YouTube®, describing their general characteristics, viewer engagement, and information sources. Standardized tools were utilized to analyze reliability (DISCERN), comprehensiveness, and overall quality (Global Quality Score [GQS]). One hundred videos were included, 93% of which provided information from healthcare professionals (group 1), and 7% of which reflected patient opinions (group 2). There were differences in the median reliability (DISCERN 4 vs 2, p ≤ 0.05) and comprehensiveness (4 vs 2, p ≤ 0.05) scores between groups, but equal overall quality (GQS 3 vs 2, p = 0.2). Reliability (DISCERN 4; RIC 3-4) and comprehensiveness (4.5; IQR 3-5) were higher in videos by professional organizations, compared with those by independent users, healthcare information websites, and for-profit organizations (DISCERN 3; IQR 2.5-3.5) (p < 0.001). Reliability (DISCERN 2; IQR 1.5-3), comprehensiveness (2; IQR 1.5-2.5), and quality (GQS 2.5; IQR 1.5-3.5) were lower for videos made by for-profit organizations. The majority of videos about AH in Spanish on YouTube® have good reliability, comprehensiveness, and quality. Videos created by academic organizations had higher scores, thus their collaboration, with respect to patient opinion videos, is suggested.


Multiple origins of BBCC allopolyploid species in the rice genus (Oryza).
In the rice genus (Oryza), about one half of the species are allopolyploids. These species are not only important resources for rice breeding but also provide a unique opportunity for studying evolution of polyploid species. In the present study, we sequenced four biparentally inherited nuclear loci and three maternally inherited chloroplast fragments from all diploid and tetraploid species with the B- and C-genome types in this genus. We detected at least three independent origins of three BC-genome tetraploid species. Specifically, the diploid O. punctata (B-genome) and O. officinalis (C-genome) were the parental progenitors of O. minuta and O. malampuzhaensis with O. punctata being the maternal donors, whereas the diploid O. punctata and O. eichingeri (C-genome) were the progenitors of tetraploid O. punctata with O. punctata being the paternal donor. Our relaxed clock analyses suggest that all the BBCC species originated within the last one million years, which is coincident with the severe climate oscillations occurred during the last ice age, implying the potential impact of climate change on their formations and dispersals. In addition, our results support previous taxonomic arguments that the tetraploid O. punctata might be better treated as a separate species (O. schweinfurthiana).


Bladder instillation of Escherichia coli lipopolysaccharide alters the muscle contractions in rat urinary bladder via a protein kinase C-related pathway.
Uropathogenic Escherichia coli is a common cause of urinary tract infection. We determined the effects of intravesical instillation of E. coli lipopolysaccharide (LPS, endotoxin) on muscle contractions, protein kinase C (PKC) translocation, and inducible nitric oxide synthase (iNOS) expression in rat urinary bladder. The contractions of the isolated rat detrusor muscle evoked by electrical field stimulations were measured short-term (1 h) or long-term (24 h) after intravesical instillation of LPS. One hour after LPS intravesical instillation, bladder PKC-alpha translocation from cytosolic fraction to membrane fraction and endothelial (e)NOS protein was elevated, and detrusor muscle contractions were significantly increased. PKC inhibitors chelerythrine and Ro32-0432 inhibited this LPS-enhanced contractile response. Application of PKC activator beta-phorbol-12,13-dibutyrate enhanced the muscle contractions. Three hours after intravesical instillation of LPS, iNOS mRNA was detected in the bladder. Immunoblotting study also demonstrated that the induction of iNOS proteins is detected in bladder in which LPS was instilled. 24 h after intravesical instillation of LPS, PKC-alpha translocation was impaired in the bladder; LPS did not affect PKC-delta translocation. Muscle contractions were also decreased 24 h after LPS intravesical instillation. Aminoguanidine, a selective iNOS inhibitor, blocked the decrease in PKC-alpha translocation and detrusor contractions induced by LPS. These results indicate that there are different mechanisms involved in the alteration of urinary bladder contractions after short-term and long-term treatment of LPS; an iNOS-regulated PKC signaling may participate in causing the inhibition of muscle contractions in urinary bladder induced by long-term LPS treatment.


Knowledge, Attitudes, and Practices towards Food Poisoning among Parents in Aseer Region, Southwestern Saudi Arabia.
Background: Food poisoning is caused by eating contaminated food. Improper food safety knowledge, poor food handling, and inadequate personal hygiene may allow microbes to grow in sufficient numbers to cause a food-borne illness. The aim of this paper was to assess the knowledge, attitudes, and practices regarding food poisoning and its determinants of parents in the Aseer region of Saudi Arabia. Methodology: This is a descriptive cross-sectional study conducted on 3011 parents in the Aseer region in the southwest region of Saudi Arabia. An online questionnaire was used to collect the data. The level of knowledge of the participants was scored as a percentage and further classified as "good" or "poor". Attitudes were classified as "positive", "neutral", or "negative" based on a calculated composite mean score. The participants were asked about standard food hygiene practices, and the practices were recorded based on how often they were performed, with the results recorded as "usually", "sometimes", or "never". Results: The age range of the parents was between 18 and 65 years old, with a mean age of 28.9 ± 10.4 years. Among the participants, 96.2% were Saudi, and 81.8% were female. Almost 53% of the fathers and 41% of the mothers were university graduates. About 55% of the mothers were housewives. Almost equal proportions of the parents had "good" and "poor" levels of knowledge on food poisoning. Around 41% of the parents had positive attitudes towards safe food consumption. Older parents (defined as above 30 years of age), males, university graduates, and urban residents had significantly higher levels of knowledge regarding food poisoning. Conclusions: This study provided much needed information on the knowledge, attitudes, and practices related to food poisoning among parents in the Aseer region of Saudi Arabia. Although most respondents reported satisfactory practices, gaps were identified in knowledge and attitudes. This suggests a need for further investigation focused on the observed practices and strengthening health education activities for the community.


High Salt Diet Impairs Male Fertility in Mice via Modulating the Skeletal Homeostasis.
Male reproductive functions and bone health are both adversely affected by the high salt diet (HSD). Nevertheless, the underlying mechanism via which it alters the sperm function remains largely unknown. This study examines the mechanism by which HSD affects male fertility by impairing bone health. For investigating the same, male BALB/c mice were categorized into three groups-HSD group (fed with 4% NaCl), a low salt diet (LSD) group (fed with 0.4% NaCl), and a control group (fed with a normal diet) for 6 weeks and thereafter assessed for various sperm parameters, bone turnover markers, and testosterone levels. Furthermore, the quantitative assessment of testosterone biosynthesis enzymes was performed. Interestingly, we observed that mice fed with HSD showed significant alterations in sperm parameters-motility, count, and vitality, including morphological changes compared to both the LSD and the control groups. In addition, serum analysis showed an increase in bone resorption markers and a decrease in bone formation markers in the HSD group (p < 0.05). Further, HSD caused a decrease in the testosterone level and mRNA expression of testosterone biosynthesis enzymes. Importantly, a significant decrease in bone formation marker osteocalcin (OC) was observed to coincide with the dip in testosterone level in the HSD group. Given that OC plays a key role in maintaining male fertility, the above findings suggest that a decrease in OC levels may affect the testosterone biosynthesis pathway, reducing testosterone hormone secretion and thereby resulting in decreased spermatogenesis. The study for the first time delineates and bridges the mechanism of HSD-mediated bone loss (results in a deficiency of OC) with decreased testosterone biosynthesis and thus impaired male fertility.


Distal interphalangeal joint arthrodesis for degenerative osteoarthritis with compression screw: results in 102 digits.
To assess objective and subjective outcomes of distal interphalangeal joint arthrodesis with a headless compression screw for degenerative osteoarthritis. We retrospectively analyzed 102 cases of distal interphalangeal joint arthrodesis performed with headless compression screws on 59 patients. We included only primary cases of degenerative osteoarthritis with a minimum follow-up of 7 months. We identified appropriate bone coaptation and hardware positioning on postoperative radiographs in all digits. The mean follow-up period was 26 months (range, 7-67 mo). In 89 of 102 cases, patients were fully satisfied; in 9 cases, they were satisfied. Four complications occurred: 2 cases of prominent hardware, 1 complex regional pain syndrome type 1, and 1 symptomatic bony callus on the fused joint. Secondary surgery was required in each of these 4 cases. No nonunion, malunion, nail dystrophy, pseudarthrosis, or infection occurred. All arthrodeses healed. Distal interphalangeal joint arthrodesis with headless compression screws was shown to be safe and effective in cases of degenerative osteoarthritis, with a low complication rate.