H2S regulates endothelial nitric oxide synthase protein stability by promoting microRNA-455-3p expression.
The aims of the present study are to determine whether hydrogen sulfide (H2S) is involved in the expression of endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) production, and to identify the role of microRNA-455-3p (miR-455-3p) during those processes. In cultured human umbilical vein endothelial cells (HUVECs), the expression of miR-455-3p, eNOS protein and the NO production was detected after administration with 50 μM NaHS. The results indicated that H2S could augment the expression of miR-455-3p and eNOS protein, leading to the increase of NO level. We also found that overexpression of miR-455-3p in HUVECs increased the protein levels of eNOS whereas inhibition of miR-455-3p decreased it. Moreover, H2S and miR-455-3p could no longer increase the protein level of eNOS in the presence of proteasome inhibitor, MG-132. In vivo, miR-455-3p and eNOS expression were considerably increased in C57BL/6 mouse aorta, muscle and heart after administration with 50 μmol/kg/day NaHS for 7 days. We also identified that H2S levels and miR-455-3p expression increased in human atherosclerosis plaque while H2S levels decreased in plasma of atherosclerosis patients. Our data suggest that the stability of eNOS protein and the NO production could be regulated by H2S through miR-455-3p.


Spatial assessment of monitoring network in coastal waters: a case study of Kuwait Bay.
Spatial analyses of water-quality-monitoring networks in coastal waters are important because pollution sources vary temporally and spatially. This study was conducted to evaluate the spatial distribution of the water-quality-monitoring network of Kuwait Bay using both geostatistical and multivariate techniques. Three years of monthly data collected from six existing monitoring stations covering Kuwait Bay between 2009 and 2011 were employed in conjunction with data collected from 20 field sampling sites. Field sampling locations were selected based on a stratified random sampling scheme oriented by an existing classification map of Kuwait Bay. Two water quality datasets obtained from different networks were compared by cluster analysis applied to the Water Quality Index (WQI) and other water quality parameters, after which the Kriging method was used to generate distribution maps of water quality for spatial assessment. Cluster analysis showed that the current monitoring network does not represent water quality patterns in Kuwait Bay. Specifically, the distribution maps revealed that the existing monitoring network is inadequate for heavily polluted areas such as Sulaibikhat Bay and the northern portion of Kuwait Bay. Accordingly, the monitoring system in Kuwait Bay must be revised or redesigned. The geostatistical approach and cluster analysis employed in this study will be useful for evaluating future proposed modifications to the monitoring stations network in Kuwait Bay.


Dynamics of Awake Hippocampal-Prefrontal Replay for Spatial Learning and Memory-Guided Decision Making.
Spatial learning requires remembering and choosing paths to goals. Hippocampal place cells replay spatial paths during immobility in reverse and forward order, offering a potential mechanism. However, how replay supports both goal-directed learning and memory-guided decision making is unclear. We therefore continuously tracked awake replay in the same hippocampal-prefrontal ensembles throughout learning of a spatial alternation task. We found that, during pauses between behavioral trajectories, reverse and forward hippocampal replay supports an internal cognitive search of available past and future possibilities and exhibits opposing learning gradients for prediction of past and future behavioral paths, respectively. Coordinated hippocampal-prefrontal replay distinguished correct past and future paths from alternative choices, suggesting a role in recall of past paths to guide planning of future decisions for spatial working memory. Our findings reveal a learning shift from hippocampal reverse-replay-based retrospective evaluation to forward-replay-based prospective planning, with prefrontal readout of memory-guided paths for learning and decision making.


Co-axial acoustic-based optical coherence vibrometry probe for the quantification of resonance frequency modes in ocular tissue.
We present a co-axial acoustic-based optical coherence vibrometry probe (CoA-OCV) for vibro-acoustic resonance quantification in biological tissues. Sample vibrations were stimulated via a loudspeaker, and pre-compensation was used to calibrate the acoustic spectrum. Sample vibrations were measured via phase-sensitive swept-source optical coherence tomography (OCT). Resonance frequencies of corneal phantoms were measured at varying intraocular pressures (IOP), and dependencies on Young´s Modulus (E), phantom thickness and IOP were observed. Cycling IOP revealed hysteresis. For E = 0.3 MPa, resonance frequencies increased with IOP at a rate of 3.9, 3.7 and 3.5 Hz/mmHg for varied thicknesses and 1.7, 2.5 and 2.8 Hz/mmHg for E = 0.16 MPa. Resonance frequencies increased with thickness at a rate of 0.25 Hz/µm for E = 0.3 MPa, and 0.40 Hz/µm for E = 0.16 MPa. E showed the most predominant impact in the shift of the resonance frequencies. Full width at half maximum (FWHM) of the resonance modes increased with increasing thickness and decreased with increasing E. Only thickness and E contributed to the variance of FWHM. In rabbit corneas, resonance frequencies of 360-460 Hz were observed. The results of the current study demonstrate the feasibility of CoA-OCV for use in future OCT-V studies.


Anti-programmed cell death-1 monoclonal antibody therapy before or after allogeneic hematopoietic cell transplantation for classic Hodgkin lymphoma: a literature review.
Approximately 10-30% of patients with classic Hodgkin lymphoma (cHL) have relapsed or refractory (r/r) disease after standard first-line therapy. Clinical trials have shown an acceptable safety profile and high response rate for anti-programmed cell death-1 monoclonal antibodies (anti-PD-1 mAbs) in patients with r/r cHL. Although anti-PD-1 mAbs have significantly increased treatment options for r/r cHL, most patients eventually relapse. In the current era, allogeneic hematopoietic cell transplantation (allo-HCT) is still a clinical option for r/r cHL. Anti-PD-1 mAbs have been explored as bridging therapy to allo-HCT and salvage therapy for relapse after allo-HCT. Although early reports showed increased risks of severe graft-versus-host disease (GVHD) in patients who received anti-PD-1 mAb before or allo-HCT, survival outcomes were favorable, suggesting the feasibility of PD-1 blockade around the time of allo-HCT. Based on clinical and biological data, posttransplant cyclophosphamide-based GVHD prophylaxis is a promising strategy to reduce GVHD and improve survival after allo-HCT following PD-1 blockade. Close monitoring and early intervention are needed for treatment-emergent GVHD following PD-1 blockade after allo-HCT. Further studies with a larger cohort and extended follow-up will provide insights into better patient selection, optimal dosing, and strategies to manage complications of PD-1 blockade in the context of allo-HCT.


Comparative analysis of the effects of five soil fumigants on the abundance of denitrifying microbes and changes in bacterial community composition.
Soil fumigation is currently the most effective method for controlling soil-borne pests and diseases in high-value crops. To better understand the effect of chloropicrin (CP), dazomet (DZ), dimethyl disulfide (DMDS), allyl isothiocyanate (AITC) and 1,3-dichloropropene (1,3-D) fumigants on soil microorganisms, this study monitored changes in the diversity and community composition of soil bacteria involved in denitrification using real-time PCR and high-throughput gene sequencing techniques. These five fumigants significantly decreased the bacterial population size in some phyla including Proteobacteria, Chloroflexi and Acidobacteria, and increased the bacterial population size in other phyla such as Firmicutes, Gemmatimonadetes, Actinobacteria, Verrucomicrobia, Saccharibacteria and Parcubacteria. Although bacterial diversity declined after CP fumigation, it was briefly stimulated by the other four fumigants. Meanwhile, all five fumigants temporarily decreased populations of denitrifying bacteria containing the napA, narG, nirS or nirK enzyme-encoding genes. Denitrifiers bearing the cnorB, qnorB or nosZ genes were relatively stable following DZ and DMDS fumigation. However, cnorB and nosZ decreased initially following CP, AITC and 1,3-D fumigation. Simultaneously, the abundance of qnorB significantly increased in AITC and 1,3-D fumigated soils. These results showed that soil fumigation significantly shifted the abundance and community structure of denitrifying bacteria. This study will help to predict the response of different phyla of denitrifying bacteria to soil fumigation.


Predictors of Physician Recommendation for Ethically Controversial Medical Procedures: Findings from an Exploratory National Survey of American Muslim Physicians.
Physician religiosity can influence their ethical attitude toward medical procedures and can thereby impact healthcare delivery. Using a national survey of American Muslim physicians, we explored the association between physician recommendation of three controversial medical procedures--tubal ligation, abortion, and porcine-based vaccine--and their (1) religiosity, (2) utilization of bioethics resources, and (3) perception of whether the procedure was a medical necessity and if the scenario represented a life threat. Generally, multivariate models found that physicians who read the Qur'an more often as well as those who perceived medical necessity and/or life threat had a higher odds recommending the procedures, whereas those who sought Islamic bioethical guidance from Islamic jurists (or juridical councils) more often had a lower odds. These associations suggest that the bioethical framework of Muslim physicians is influenced by their reading of scripture, and the opinions of Islamic jurists and that these influences may, paradoxically, be interpreted to be in opposition over some medical procedures.


TP53 supports basal-like differentiation of mammary epithelial cells by preventing translocation of deltaNp63 into nucleoli.
Multiple observations suggest a cell type-specific role for TP53 in mammary epithelia. We developed an in vitro assay, in which primary mouse mammary epithelial cells (mMECs) progressed from lumenal to basal-like phenotypes based on expression of Krt18 or ΔNp63, respectively. Such transition was markedly delayed in Trp53(-/-) mMECs suggesting that Trp53 is required for specification of the basal, but not lumenal cells. Evidence from human basal-like cell lines suggests that TP53 may support the activity of ΔNp63 by preventing its translocation from nucleoplasm into nucleoli. In human lumenal cells, activation of TP53 by inhibiting MDM2 or BRCA1 restored the nucleoplasmic expression of ΔNp63. Trp53(-/-) mMECs eventually lost epithelial features resulting in upregulation of MDM2 and translocation of ΔNp63 into nucleoli. We propose that TP63 may contribute to TP53-mediated oncogenic transformation of epithelial cells and shed light on tissue- and cell type-specific biases observed for TP53-related cancers.


Oxidative stress mediated apoptotic potential of mefloquine on experimental trichinellosis.
Conventional anthelmintics such as albendazole could not achieve complete cure of trichinellosis till now. The antimalarial mefloquine mediates oxidative stress and disrupts lysosomal functions leading to cell death. Therefore, the aim of this work was to investigate the effect of mefloquine on experimental acute and chronic trichinellosis and to clarify the possible mechanisms of such effects. Mice were divided into four groups; Group I: Uninfected untreated control (20 mice); Group II: Infected untreated control (40 mice); Group III: infected and treated with albendazole (400 mg/kg) (40 mice); Group IV: infected and treated with mefloquine (300 mg/kg) (40 mice). All infected treated groups were equally subdivided into 2 subgroups; (a) treated on the 2nd day post infection (dpi) for 3 days, (b) treated on the 35th dpi for 5 days. Parasitological adults and larvae counting besides immunohistopathological examination of intestines and muscles were done. Biochemical assay of oxidant/antioxidant status, apoptotic, cytoprotective and inflammatory biomarkers in intestinal and muscle homogenates were achieved. Results showed that both albendazole and mefloquine significantly reduced adults and larvae counts with higher efficacy of albendazole in the intestinal phase and superiority of mefloquine in the muscle phase. The superiority of mefloquine was indicated by increased inflammatory immune infiltration and decreased anti-apoptotic immunohistochemical markers expression in both jejunal and muscle tissues. Biochemically, mefloquine treatment showed highly significant oxidative, apoptotic and inflammatory effects. So, our results suggest that mefloquine might be a superior treatment for chronic trichinellosis.


A search for faecal viruses in new-born and other infants.
Faecal specimens were collected at weekly intervals over the winter months from 141 new-born infants without diarrhoea. Contrary to the findings in other studies, no viruses were detected by electron micriscopy or culture in any of these specimens. Over the same period faecal specimens were collected from 84 infants up to four years of age admitted to hospital. Rotaviruses or adenoviruses were found in 48% of infants with gastroenteritis. Enteroviruses and other small round virus-like particles were found in infants both with and without gastroenteritis. No viruses or pathogenic bacteria could be found in 34% of specimens from infants with gastroenteritis.


Molecular basis of neurofibromatosis type 1 (NF1): mutation analysis and polymorphisms in the NF1 gene.
Neurobromatosis type 1 (NF1) is one of the commonest genetic disorders in humans. The gene for NF1 was cloned in 1990. The protein encoded by the gene (neurofibromin) has extensive sequence homology with GTPase-activating protein (GAP). Despite screening the whole coding region of the gene for large and medium size rearrangements and approximately 40% of the coding region of the gene for small alterations, only 45 germ-line mutations have been reported in more than 500 unrelated patients. Of these, 25 mutations involve small changes in the gene, of which 17 (68%) result in the formation of an inappropriate stop codon. A "hot spot" for mutations has not been identified. The high mutation rate at this locus and the general difficulty in identifying mutations are discussed. A complete understanding of the structure and function of the NF1 gene awaits further detailed studies of both naturally occurring and in vitro-generated mutations.


Responses of morphological, physiological, and biochemical characteristics of maize (Zea mays L.) seedlings to atrazine stress.
Atrazine is a synthetic herbicide applied to control broadleaf weeds in different crops. In many parts of the world, atrazine is mainly applied for controlling weeds in maize fields. However, studies on the possible adverse effects of atrazine on maize crop can hardly be found in literature. The present study was therefore conducted to evaluate the effect of atrazine on different characteristics of maize seedlings including germination, growth, chlorophyll contents, soluble sugars, proteins and proline levels, ions accumulation, cell viability, and cell injury. In addition, the effects of atrazine on reactive oxygen species (ROS) accumulation and antioxidant enzymes activities in maize seedlings were estimated. It was found that at high concentration, atrazine slightly but significantly inhibited seed germination and growth of maize seedlings. Light-harvesting pigments (chlorophylls a and b, and total carotenoids) exhibited a higher sensitivity to atrazine and were negatively impacted by atrazine at doses above 50 ppm. Atrazine caused an increase in soluble sugars at all tested doses and decrease in soluble proteins at the highest tested dose. Exposure of maize seedlings to atrazine resulted in an increased cell injury and decreased cell viability. Atrazine did not affect the concentration of Na+, K+, and Ca2+ ions in maize seedlings to any greater extent; however, some minor changes were observed in some cases. An increase in the stress marker, proline, was found upon exposure to atrazine. The observed effects of atrazine in maize seedlings can be attributed to oxidative stress as revealed by an increase in H2O2 content and higher activities of peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT) enzymes in atrazine-treated seedlings. The present investigation concludes that atrazine has the potential to adversely affect germination and growth of maize seedlings by inducing oxidative stress that causes increased cell injury and decreased cell viability as well as impairs the concentration of light-harvesting pigments.


Clinical characterization of a newly described neonatal diabetes syndrome caused by RFX6 mutations.
Mutations in the RFX6 gene were recently described to underlie a distinct autosomal recessive syndrome of neonatal diabetes comprising intestinal atresia and hepatobiliary abnormalities. Until now, only six patients harboring RFX6 mutations have been reported. We report on a new case due to a novel homozygous splice site mutation and update on the clinical outcome of a previously reported patient. In addition we review the clinical and molecular features of all RFX6 mutated cases to better characterize the syndrome. Our results suggest that despite the early postnatal fulminant course, patients who survive may expect a relatively favorable prognosis.


Approaches to studying the role of growth factors in the progression of breast tumours from the steroid sensitive to insensitive state.
Progression from steroid sensitive to autonomous proliferation can be modelled in several cultured mammary tumour cell lines by long-term withdrawal of steroids. A feature of all the four systems studied thus far is that the basal growth in the absence of steroid increases with duration of steroid withdrawal until it reaches that obtained in the presence of steroid. It cannot be assumed that the increased proliferation in the absence of steroid is modulated by the same pathways as those stimulated by steroids in sensitive cells. Therefore, we feel that mechanisms of progression can best be studied via cell behaviour in the absence of steroid. With both the mouse S115 and human T-47-D systems, changes in sensitivity to several growth factors accompany progression; responses to TGF beta 1 are of particular interest in the T-47-D cells where this growth factor becomes stimulatory in the steroid insensitive state. This is accompanied by upregulation of TGF beta 1 mRNA. This upregulation of TGF beta agrees with the finding that ER - PR - primary human breast tumours contain more TGF beta 1 than do ER + PR + tumours; TGF alpha has the opposite pattern. Furthermore, only 40 and 30 kDa TGF beta species have been detected within cultured cells and primary tumours; TGF alpha exists in a 30 kDa form. The functions of these large forms of TGF alpha and TGF beta are unclear. Our conclusions from these experiments is that the increased proliferation in the absence of steroid accompanying progression may not be mediated by the same pathways as those perturbed by steroids in sensitive cells. Furthermore, TGF beta 1 may have different effects in steroid responsive and unresponsive cells.


Advances in Mn-Based Electrode Materials for Aqueous Sodium-Ion Batteries.
Aqueous sodium-ion batteries have attracted extensive attention for large-scale energy storage applications, due to abundant sodium resources, low cost, intrinsic safety of aqueous electrolytes and eco-friendliness. The electrochemical performance of aqueous sodium-ion batteries is affected by the properties of electrode materials and electrolytes. Among various electrode materials, Mn-based electrode materials have attracted tremendous attention because of the abundance of Mn, low cost, nontoxicity, eco-friendliness and interesting electrochemical performance. Aqueous electrolytes having narrow electrochemical window also affect the electrochemical performance of Mn-based electrode materials. In this review, we introduce systematically Mn-based electrode materials for aqueous sodium-ion batteries from cathode and anode materials and offer a comprehensive overview about their recent development. These Mn-based materials include oxides, Prussian blue analogues and polyanion compounds. We summarize and discuss the composition, crystal structure, morphology and electrochemical properties of Mn-based electrode materials. The improvement methods based on electrolyte optimization, element doping or substitution, optimization of morphology and carbon modification are highlighted. The perspectives of Mn-based electrode materials for future studies are also provided. We believe this review is important and helpful to explore and apply Mn-based electrode materials in aqueous sodium-ion batteries.


Effects of anthropogenic light on anuran calling site.
The natural environment can be negatively impacted by a variety of human activities, including the production of artificial light at night. Recent studies suggest that pollution from anthropogenic light alters animal behavior. Despite being highly nocturnal, little attention has been given to anurans and the effects artificial light at night has on their behavior. This study investigated whether artificial light influenced male call site selection in east Texas anurans. Ambient light levels were quantified at five sites that varied in urbanization and artificial light levels. Calling males were located and ambient light was then measured at the male's call location. Light levels at those call locations were compared to the general light environment as measured at random locations in the area. There was a consistent pattern where males at the brightest sites called from locations darker than the general light environment. However, male call locations at the brightest sites were generally brighter than those at the darker sites suggesting that, while male anurans avoid illuminated areas for calling, males in more urbanized populations may be unable to do so. As such, male anurans at sites with higher light pollution may experience a form of habitat loss where preferred darker habitat is not available.


Superior Gluteal Reconstruction Results in Promising Outcomes for Massive Abductor Tendon Tears.
To evaluate the 1-year outcomes of a small patient series following open gluteus medius/minimus repair with human dermal allograft incorporated into the repair construct using a double-row repair. Data from consecutive patients undergoing a superior gluteal reconstruction for massive, irreparable abductor tendon tears with severe tendon loss and atrophy by a single fellowship trained surgeon from January 2018 to May 2019 were collected and analyzed. Baseline demographic data and magnetic resonance imaging were collected preoperatively. Clinical outcomes including Hip Outcome Score-Activities of Daily Living (HOS-ADL), HOS-Sports Subscale (HOS-SS), modified Harris hip score (mHHS), international Hip Outcome Score-12 (iHOT-12), visual analog scale (VAS) pain, and VAS satisfaction were recorded at 1-year postoperatively. A total of 8 patients underwent open superior gluteal reconstruction for severe hip abductor deficiency. The mean age and body mass index were 62.6 ± 7.3 years and 29.6 ± 5.3 kg/m2, respectively. The majority of patients were female (N = 7, 87.5%). Three (37.5%) patients had undergone previous endoscopic gluteus medius repair and presented for revision surgery. All patients had full-thickness tears with gluteus medius and gluteus minimus involvement. Patients were evaluated at an average of 11.5 ± 1.7 months from the initial surgical intervention and reported a mean HOS-ADL of 82.9 ± 24.3, HOS-SS of 73.2 ± 37.3, mHHS of 83.6 ± 17.1, iHOT-12 of 63.9 ± 27.4, VAS Pain of 30.0 ± 23.1, and VAS Satisfaction of 87.1 ± 17.0. There was no evidence of retears in this patient cohort as defined by physical examination findings and/or corroborating magnetic resonance imaging. Superior gluteal reconstruction for massive, irreparable abductor tendon tears with severe tendon loss and atrophy is a technique that demonstrates promising 1-year postoperative outcomes in both primary and revision patients. Level IV, therapeutic case series.


Genome-enabled discovery of anthraquinone biosynthesis in Senna tora.
Senna tora is a widely used medicinal plant. Its health benefits have been attributed to the large quantity of anthraquinones, but how they are made in plants remains a mystery. To identify the genes responsible for plant anthraquinone biosynthesis, we reveal the genome sequence of S. tora at the chromosome level with 526 Mb (96%) assembled into 13 chromosomes. Comparison among related plant species shows that a chalcone synthase-like (CHS-L) gene family has lineage-specifically and rapidly expanded in S. tora. Combining genomics, transcriptomics, metabolomics, and biochemistry, we identify a CHS-L gene contributing to the biosynthesis of anthraquinones. The S. tora reference genome will accelerate the discovery of biologically active anthraquinone biosynthesis pathways in medicinal plants.


Are major laparoscopic pancreatic resections worthwhile? A prospective study of 32 patients in a single institution.
Laparoscopic surgery has been used increasingly as a less invasive alternative to conventional open surgery. Recently, laparoscopic therapy for pancreatic diseases has made significant strides. The current investigation studied pancreatic resection by laparoscopy. The objective of this study was to assess the feasibility, safety, and outcome of laparoscopic pancreatic major resection for benign and malignant lesions of the pancreas. A prospective study of laparoscopic pancreatic resections was undertaken in patients with benign and malignant lesions of the pancreas. Over an 8-year period, 32 patients underwent laparoscopic pancreatic major resection: 21 left pancreatectomies (1 performed using a retroperitoneal approach), and 11 pancreatoduodenectomies (10 Whipple procedures and 1 total pancreatectomy). All the operations were performed in a single institution. The operations were performed without serious complications. Only one left pancreatectomy was converted to laparotomy because of massive splenic bleeding, and one Whipple procedure was converted because of adhesion to the portal vein. In four of the Whipple operations, the resection was performed completely laparoscopically, and the reconstruction was done via a small midline incision. There was no operative mortality. In 16 patients of the left pancreatectomy group, the spleen was preserved. The mean blood loss was 150 and 162 ml; and the mean operating time was 154 and 284 min, respectively, for the left pancreatectomy and the Whipple procedure. Postoperative complications occurred for five patients after left pancreatectomy and for three patients after the Whipple procedure. Two patients needed surgical reexploration after left pancreatectomy because of intraperitoneal haemorrhage and eventration of the extraction site. Two patients underwent reoperation after the Whipple procedure: one because of intraabdominal bleeding and the other because of small bowel obstruction. The mean hospital stay was 10.8 days after left the pancreatectomy and 13.6 days after the whipple procedure. Laparoscopic left pancreatectomy for benign and malignant lesions is feasible, safe, and beneficial. We believe that pancreatoduodenectomy should be performed only in selected cases and by a highly skilled laparoscopic surgeon. If there is any doubt, an open resection should be performed.


Designing an effective statewide tobacco control program--Massachusetts.
Smoking-related illnesses kill > 10,000 Massachusetts residents each year and cost hundreds of millions of dollars of public and private expenditures for health care. To combat this public health problem, in 1992 Massachusetts voters approved a referendum question calling for an increased excise tax on tobacco products, with the revenue supporting a Health Protection Fund. Approximately 40% of the fund is used to finance the Massachusetts Tobacco Control Program (MTCP), administered by the Massachusetts Department of Public Health. During the first 3 fiscal years (FY), the MTCP budget has averaged just over $40 million annually, declining during that period from approximately $43 million in FY 1995 to < $37 million in FY 1997.


Vulvar Aphthous Ulcer in an Adolescent After Pfizer-BioNTech (BNT162b2) COVID-19 Vaccination.
Vulvar aphthous ulcers are a rare type of genital lesion most common in non-sexually active adolescents. Vulvar aphthous ulcers are typically associated with viral infections. To date, there have been several cases reported in patients infected with COVID-19. Vulvar aphthous ulcers following vaccination have not been previously reported in the literature. We present the case of a 16-year-old adolescent who developed vulvar aphthous ulceration following Pfizer-BioNTech (BNT162b2) vaccination. Through an extensive literature search, we found no previous reports of vulvar aphthous ulcer following vaccination. Our case highlights a potential novel side effect of Pfizer-BioNTech COVID-19 vaccination and a new etiology for vulvar aphthous ulcers. This case suggests that vulvar aphthous ulcers might be associated with COVID-19 vaccination through a yet undetermined mechanism that requires further investigation.


Gene duplication and the evolution of plant MADS-box transcription factors.
Since the first MADS-box transcription factor genes were implicated in the establishment of floral organ identity in a couple of model plants, the size and scope of this gene family has begun to be appreciated in a much wider range of species. Over the course of millions of years the number of MADS-box genes in plants has increased to the point that the Arabidopsis genome contains more than 100. The understanding gained from studying the evolution, regulation and function of multiple MADS-box genes in an increasing set of species, makes this large plant transcription factor gene family an ideal subject to study the processes that lead to an increase in gene number and the selective birth, death and repurposing of its component members. Here we will use examples taken from the MADS-box gene family to review what is known about the factors that influence the loss and retention of genes duplicated in different ways and examine the varied fates of the retained genes and their associated biological outcomes.


Calcific tendinitis of the shoulder.
Calcific tendinitis of the shoulder is a process involving calcium deposition commonly in the rotator cuff tendons. It is a cell-mediated process that is often chronic in nature, but it is usually self-limiting with regard to its acute pain states. Nonoperative management is still the treatment of choice and is successful in up to 90% of patients. When conservative measures fail, a needling technique or surgical removal may be indicated; the trend is toward arthroscopic management. Acromioplasty should not be performed without radiographic signs of impingement. If a resulting large rotator cuff defect is found after removal of the calcific deposit, it may be worthwhile to close the defect arthroscopically with suture to prevent cuff tear progression and to promote healing.


Excision products of immunoglobulin gene rearrangements.
We have isolated circular DNAs from splenocytes of euthymic and athymic mice, and prepared the DNA libraries of 1.5 X 10(6) clones. Hundreds of clones homologous to immunoglobulin (Ig) heavy chain segments (DSP2 and DQ52-JH) or light chain segments (J kappa and J lambda) have been identified. Southern hybridization predicted that three of 12 euthymic mouse clones homologous to DQ52-JH and four of 10 athymic mouse clones homologous to DSP2 contained reciprocal recombination products of D-J joining. Some of these clones were characterized by sequencing: two clones contained the precise excision product of the recombination of a DSP2 segment with either JH2 or JH3 segment; two clones showed imprecise ligation of the DSP2-JH2 coding joint and precise ligation of the DFL16.1-JH3 reciprocal joint in the same molecule. They seem to represent a replacement of the pre-existing DSP2-JH2 rearrangement by joining an upstream DFL16 segment to a downstream JH3 segment. The presence in extrachromosomal DNA of a reciprocal recombination product of DH-JH joining is consistent with the view that immunoglobulin genes, like T cell receptor (TCR) genes, can be rearranged in B cell lineage by the looping-out and excision of chromosomal DNA.


Foods and beverages associated with higher intake of sugar-sweetened beverages.
Although consumption of sugar-sweetened beverages (SSBs) is associated with higher caloric intakes, the amount SSBs contribute to higher intakes has not been addressed. To estimate the amount SSBs contribute to higher caloric intakes and determine how the diets of SSB consumers and nonconsumers differ. The What We Eat In America, NHANES 2003-2010 surveys were combined into a sample of 13,421 children; analyses were conducted in December 2012. To determine the contribution of SSBs to higher caloric intakes, total non-SSB intake (food + non-SSB beverages) of SSB consumers and nonconsumers were compared using linear regression models controlling for demographic and socioeconomic factors. Analyses also compared intakes between nonconsumers and SSB consumers with different amounts of SSB consumption. For children aged 2-5 years and 6-11 years, total non-SSB intakes did not differ between nonconsumers and SSB consumers at any level of SSB consumption, indicating that SSBs were primarily responsible for the higher caloric intakes among SSB consumers. A similar finding was observed among children aged 12-18 years; however, both food and SSB contributed to higher caloric intakes of adolescents consuming ≥500 kcal of SSBs. Among those aged 12-18 years, higher intakes of foods (e.g., pizza, burgers, fried potatoes, and savory snacks) and lower intakes of non-SSB beverages (e.g., fluid milk and fruit juice) were associated with increased SSB intake. Sugar-sweetened beverages are primarily responsible for the higher caloric intakes of SSB consumers, and SSB consumption is associated with intake of a select number of food and beverage groups, some of which are often unhealthy (e.g., pizza and grain-based desserts).


Survey of Italian neurological output in the three years 1989-1991.
On the wave of the furore over the haphazard approach to academic promotion in Italy and the role of published work in it, our analysis clears the role of the neurological publications in the three years 1989-1991. The data analysis, carried out by consulting on-line data bank and comparing the Italian production with that one of two sampled countries (France and Germany), shows that in the field of clinical neuroscience, this criticism is not in order.


[Experience of organization of flushing and disinfection of centralized system of hot water supply in town Verkhnyaya Pyshma after its colonization by Legionella].
Causes of outbreak incidence of pneumonia due to Legionella infection in population of Verkhnyaya Pyshma as well as factors promoting colonization of town's hot water supply system by Legionella were discussed. Experience of organization of flushing and disinfection of hot water supply system was described, effectiveness of different methods of disinfection was evaluated.


Protective effects of different concentrations of selenium nanoparticles on rainbow trout (Oncorhynchus mykiss) primary hepatocytes under heat stress.
Heat stress leads to altered expression of associated heat shock proteins (HSPs), which are critical molecular chaperones related to cellular function in living organisms. Selenium nanoparticles (SeNPs), a nanocomposite form of Se, have a protective effect against heat stress-induced cellular damage. In this study, primary rainbow trout hepatocytes were isolated to identify the protective function of SeNPs in rainbow trout hepatocytes. Experiments were divided into five groups and SeNPs were added at concentrations of 0, 2.0, 3.0, 5.0 and 8.0 μg/mL and incubated at 18 ℃ for 4, 8, 12, 24 and 48 h respectively. Hepatocyte viability, GSH-Px and SOD activity were enhanced and MDA content was reduced following the addition of SeNPs. Expression of GSH-P1 and genes related to HSPs (including HSP70a, HSP60, HSP90β, HSP10 and HSP47) were significantly increased and the optimal concentration of SeNPs for adding to hepatocytes was identified as 5.0 µg/mL. Adding 5.0 µg/mL SeNPs following heat stress (24 ℃) increased hepatocyte viability, GSH-Px and SOD activity, while MDA levels first decreased and then increased. Expression of GSH-P1 and genes related to HSPs (including HSP70a, HSP60, HSP90β, HSP10 and HSP47) were significantly higher than controls. In summary, SeNPs and slight heat stress synergistically enhanced the expression of GSH-P1 and HSPs and protected hepatocytes from heat stress damage, suggesting that SeNPs is a potential hepatocyte protective therapeutic agent.


Doppler blood flow velocity waveforms in the fetal renal artery.
In 19 out of 20 human fetuses we recorded blood velocity waveforms in the renal artery by means of a duplex Doppler sector scanner. One fetus was at 22 weeks gestation, 7 fetuses were between 32 and 35 weeks, and 12 fetuses between 36 and 40 weeks. There was no evidence of intrauterine growth retardation and there was a normal quantity of amniotic fluid in all pregnancies. We also recorded waveforms in the umbilical artery, the descending aorta, and the internal carotid artery. The RI in these vessels showed normal values in all cases. There was no end-diastolic flow in four of the seven fetuses studied at 32 to 35 weeks gestation. The mean RI of fetuses with end-diastolic flow was 0.86 (SD 0.03). The interpretations of these results, and ideas for future studies are discussed.


Effect of remifentanil on postoperative nausea and vomiting: a randomized pilot study.
Opioid-related postoperative nausea and vomiting should not occur following remifentanil administration because of its relatively short time to elimination. However, studies have indicated that the incidence of postoperative nausea and vomiting associated with remifentanil is similar to that with other opioids. Hence, we aimed to determine whether intraoperative remifentanil itself is associated with postoperative nausea and vomiting when postoperative pain is managed without opioid use. In this prospective pilot study, 150 patients who underwent unilateral upper limb surgery under general anesthesia with brachial plexus block were included. Patients in the remifentanil and control groups received 0.5 µg/kg/min remifentanil and saline, respectively. Postoperative pain was managed using a brachial plexus block, non-steroidal anti-inflammatory drugs, and acetaminophen. The presence of postoperative nausea and vomiting within the first 24 h after anesthesia was assessed by an evaluator blinded to patient allocation. Eight patients were excluded from the final analysis, resulting in 72 and 70 patients in the remifentanil and control groups, respectively. Postoperative nausea and vomiting within 24 h after surgery occurred in 11 and 9 patients in the remifentanil and control groups, respectively. These data suggest that remifentanil use only minimally affects the incidence of postoperative nausea and vomiting under sevoflurane anesthesia. UMIN Clinical Trials Registry identification number: UMIN000016110.


Ulceration occurring after ALA-PDT combined with plum-blossom needle percussion for the treatment of pretibial Bowen's disease: A case report.
We used 5-aminolevulinic acid-photodynamic therapy (ALA-PDT) combined with plum-blossom needle (PBN) on a 3.5 cm × 3.0 cm pretibial region to treat an elderly woman suffering from Bowen's disease (BD). Before the application of ALA, the PBN was inserted 3-4 times vertically starting at 5 cm above the lesion. Then, 20 % 5-ALA cream was applied with an incubation time of 3.5 h. A semiconductor laser at a wavelength of 635 nm was used to illuminate the lesion at 100 J/cm2 using 60 mW/cm2. A total of three sessions of ALA-PDT were performed at 2-3-week intervals, thus removing the lesion of BD. However, a 1.5 cm × 1.0 cm ulceration occurred 2 weeks after the third session when the PBN was used. Therefore, PBN percussion or other methods for promoting ALA penetration should be carefully applied to avoid ulceration, especially on the sites with less subcutaneous tissue.


HIV-associated neurocognitive disorders and the impact of combination antiretroviral therapies.
HIV-associated neurocognitive disorders (HAND) are the most common preventable and treatable cause of dementia. While the incidence of the most severe form of HAND, HIV-associated dementia, has decreased since the introduction of combination antiretroviral therapy (cART), the prevalence of less severe forms of HAND has continued to rise. HAND leads to a subcortical dementia consisting of a triad of cognitive, behavior, and motor dysfunction. No single laboratory test can establish HAND, but ancillary studies including neuropsychological testing, neuroimaging studies, and cerebrospinal fluid (CSF) analysis are useful for supporting or refuting the diagnosis. More recent evidence has suggested that higher central nervous system-penetrating cART may lead to greater suppression of CSF HIV viral loads and improved cognition. Because viral control generally has been successful without eliminating cognitive dysfunction, further clinical studies that assess adjunctive neuroprotective drugs are likely to be required.


Safety and efficacy of brilliant blue g250 (BBG) for lens capsular staining: a phase III physician-initiated multicenter clinical trial.
To evaluate the safety and efficacy of BBG (Brilliant Blue G250) for lens capsular staining during cataract surgery with continuous curvilinear capsulorhexis. Prospective clinical study. This clinical trial enrolled 30 eyes of 30 patients who underwent cataract surgery with BBG (0.25 mg/mL Brilliant Blue G250) for capsular staining. Visualization of the lens capsule and the ease of capsulorhexis with BBG staining were evaluated in five grades (grade 0 to 4) by the Independent Data Monitoring Committee and the surgeons. The safety of BBG was also evaluated in terms of ocular and systemic tolerance for 7 days after surgery. The use of BBG improved visualization of the lens capsule and complete capsulorhexis was performed in all patients. The major endpoint (Independent Data Monitoring Committee evaluation) showed that use of BBG improved visualization of the lens capsule and the ease of capsulorhexis (grades 2 to 4); the committee's grading results were similar to those of the surgeons. Frequent complications observed in more than two eyes were conjunctival injection, corneal edema and intraocular pressure elevation. No severe complications were observed in ocular and systemic evaluations. BBG staining contributed to improved visualization of the lens capsule and aided in the completion of capsulorhexis during cataract surgery. The use of BBG for capsular staining also exhibited favorable safety results.


Equivalence of two screens of cognitive functioning: the Short Portable Mental Status Questionnaire and the Orientation-Memory-Concentration test.
To determine the equivalence of two screens of cognitive functioning: the Short Portable Mental Status Questionnaire (SPMSQ) and the Orientation-Memory-Concentration (OMC) test. The design was cross-sectional and longitudinal. Four rural and one urban county in the Piedmont region of North Carolina (n = 3210). A stratified random cluster sample (n = 3210) of people 68 years of age and older. SPMSQ and OMC at the fourth wave of the Duke Established Populations for Epidemiologic Studies of the Elderly (EPESE); disability, depression, and death measurements from the fourth through seventh waves of EPESE; demographic characteristics. On the SPMSQ and the OMC (r = .80), 15.3% and 38.4%, respectively, of those tested were rated cognitively impaired. Poorer scores were associated with older age, black race, and less education. These associations were attenuated on the dichotomized SPMSQ but not on the OMC. Both measures predicted disability and depressive symptomatology currently and 3 years hence and death. The SPMSQ and OMC, although highly correlated, are not equivalent. Association with race and education are greater for the OMC, whereas an association with age exists for both measures. The milder level of impairment identified by the OMC increases predictive capacity.


Opinions of dentists and directors of nursing concerning dental care provision for Adelaide nursing homes.
The complex oral health problems of nursing home residents have been well documented. However, the influences on residents' oral health status, including opinions and experiences of dental professionals and nursing home staff, have not yet been adequately investigated. The baseline questionnaire component of this longitudinal study was mailed to all registered dentists practising in Adelaide and Adelaide nursing home directors of nursing (DONs). 413 dentists and 97 DONs indicated that Adelaide dentists' interest and training in nursing home dentistry was low. Dental service provision for nursing home residents was very low and dentists preferred to provide treatment at their dental practices. Few dental hygienists were working in nursing homes and dental professionals provided little educational assistance for nursing home staff. Dentists and DONs held several common and many varying perceptions of the problems associated with dental care provision in nursing homes. Both identified a group of nursing home environmental constraints and a lack of portable dental equipment. DONs further identified a group of resident related problems, and dentists a group of dental practice-related problems. These study results provide important information concerning problems with nursing home dentistry for dental service providers, educators, policy-makers, administrators and nursing home staff.


Catalytic asymmetric construction of chiral hydropyridazines via conjugate addition of N-monosubstituted hydrazones to enones.
The first example of a highly enantioselective and scalable formal diaza-ene reaction between N-monosubstituted hydrazones and enones catalyzed by a simple chiral primary-second diamine salt has been developed. The catalytic process provides a highly practical and stereoselective synthetic method for chiral hydropyridazines.


[Mechanism and Research Progress of Microbiome in the Development of Lung Cancer].
Lung cancer is one of the most common malignant tumors with poor prognosis in China, and most patients are diagnosed as advanced patients. Studies have shown that the microecological characteristics of lung cancer patients are different from healthy people, and the microorganisms of the respiratory tract can affect the occurrence and development of lung cancer through various mechanisms. In recent years, the study of the correlation between microbiome and disease has become another research hotspot following the Human Genome Project. However, at present, there are relatively few studies on the characteristics of lung cancer and respiratory microbiome. Therefore, it is necessary to further explore the potential relationship between lung cancer and microbial flora. By studying the mechanism of action of respiratory microorganisms in the development of lung cancer, it is expected to provide a clearer scientific basis in the clinical diagnosis, treatment and prognosis assessment of lung cancer. This article reviews the current researches on microbial flora and lung cancer, and provides new ideas for clinical diagnosis and treatment of lung cancer. .


Synthesis and immobilization of ceramide analogs on silica particles.
Ceramides are the major lipid components of the stratum corneum, the major permeability barrier of the skin. Here we report a chemical synthesis of ceramide analogs covalently bonded on the silica particles, that can be used to predict the skin permeability of chemicals via HPLC methods.


Oxidative stress in multiple sclerosis: Central and peripheral mode of action.
Accumulating evidence suggests that oxidative stress plays a major role in the pathogenesis of multiple sclerosis (MS). Reactive oxygen species (ROS), which if produced in excess lead to oxidative stress, have been implicated as mediators of demyelination and axonal damage in both MS and its animal models. One of the most studied cell populations in the context of ROS-mediated tissue damage in MS are macrophages and their CNS companion, microglia cells. However, and this aspect is less well appreciated, the extracellular and intracellular redox milieu is integral to many processes underlying T cell activation, proliferation and apoptosis. In this review article we discuss how oxidative stress affects central as well as peripheral aspects of MS and how manipulation of ROS pathways can potentially affect the course of the disease. It is our strong belief that the well-directed shaping of ROS pathways has the potential to ameliorate disease progression in MS.


Suppression of allene oxide synthase 3 in potato increases degree of arbuscular mycorrhizal fungal colonization.
Arbuscular mycorrhizal (AM) is a mutually beneficial interaction among higher plants and soil fungi of the phylum Glomeromycota. Numerous studies have pointed that jasmonic acid plays an important role in the development of the intraradical fungus. This compound belongs to a group of biologically active compounds known as oxylipins which are derived from the oxidative metabolism of polyunsaturated fatty acids. Studies of the regulatory role played by oxylipins in AM colonization have generally focused on jasmonates, while few studies exist on the 9-LOX pathway of oxylipins during AM formation. Here, the cDNA of Allene oxide synthase 3 (AOS3), a key enzyme in the 9-LOX pathway, was used in the RNA interference (RNAi) system to transform potato plants in order to suppress its expression. Results show increases in AOS3 gene expression and 9-LOX products in roots of wild type potato mycorrhizal plants. The suppression of AOS3 gene expression increases the percentage of root with mycorrhizal colonization at early stages of AM formation. AOS3 RNA interference lead to an induction of LOXA and 13-LOX genes, a reduction in AOS3 derived 9-LOX oxylipin compounds and an increase in jasmonic acid content, suggesting compensation between 9 and 13-LOX pathways. The results in a whole support the hypothesis of a regulatory role for the 9-LOX oxylipin pathway during mycorrhization.


Gene expression and function study of fusion immunotoxin anti-Her-2-scFv-SEC2 in Escherichia coli.
The whole sec2 DNA fragment was obtained by polymerase chain reaction with total genomic DNA extracted from Staphylococcus aureus. The newly discovered gene contains 717 bp (GenBank Accession number AY450554) and encodes 239 amino acids in accordance with the protein sequence reported in GenBank. The sec2 gene was fused to anti-Her-2 scFv gene with a DNA linker at the upstream to construct the fusion gene of immunotoxin which was subcloned to expression vector pET-32a(+) and expressed efficiently in Escherichia coli. The purified fusion immunotoxin could target the HER-2 overexpressed by breast tumor cell SK-Br-3 in vitro and demonstrate tumor-inhibition effect on SK-Br-3.


Synthetic approach toward alpha-aminomethyl-gamma-butyrolactones from beta-lactam synthons elaborated by SmI2-mediated reductive coupling reactions.
A simple and straightforward synthetic approach was developed to access a biologically important class of alpha-aminomethyl-gamma-butyrolactones via a beta-lactam synthon strategy involving successive ring-opening and lactonization processes from alpha-hydroxyethyl-substituted beta-lactams that were elaborated by SmI2-mediated reductive coupling reaction.


Primitive neuroectodermal tumors of the abdominal wall and vulva in children: Report of two cases and review of the literature.
Primitive neuroectodermal tumors are rare, highly malignant small round cell tumors belonging to the Ewing sarcoma family. The purpose of this article is to present clinical manifestation, histology, treatment, and prognosis of two primitive neuroectodermal tumors (PNETs) in extremely rare anatomic locations, the abdominal wall and vulva. Case 1 was a 66-month-old girl with lesions on the abdominal wall; tumor size was about 3.4 cm × 6.1 cm × 2 cm. The patient underwent radical resection of the tumor. After the operation, an alternating vincristine, doxorubicin, and cyclophosphamide/ifosfamide and etoposide (IE) regimen was given for eight cycles, and the patient survived for 66 mo without progression. Case 2 was a 40-month-old girl, with a vulvar lesion; tumor size was about 3.3 cm × 5 cm × 2.5 cm. The tumor was partially resected by surgery. The family left treatment after two cycles of vincristine, pirarubicin, and cyclophosphamide/IE chemotherapy, and the patient died at home six months after surgery. PNET is a rare, fast-growing, highly malignant tumor that requires histologic and molecular analyses for exact diagnosis, and multimodal treatment is required to achieve a good prognosis.


Colonic ameboma: its appearance on CT: report of a case.
Ameboma is an uncommon manifestation of amebiasis, occurring in 1.5 percent of cases. It can mimic both carcinoma and inflammatory bowel disease. The first known report of the CT appearance of ameboma is presented. This entity should be considered in any patient with a colon mass, history of travel to an endemic area, and symptoms of amebiasis.


Investigation of the factors influencing spinal manipulative therapy force transmission through the thorax: a cadaveric study.
Spinal manipulative therapy (SMT) clinical effects are believed to be linked to its force-time profile characteristics. Previous studies have revealed that the force measured at the patient-table interface is most commonly greater than the one applied at the clinician-patient interface. The factors explaining this force amplification remains unclear. To determine the difference between the force applied to a cadaveric specimen's thoracic spine and the resulting force measured by a force-sensing table, as well as to evaluate the relationship between this difference and both the SMT force-time characteristics and the specimens' characteristics. Twenty-five SMTs with different force-time profiles were delivered by an apparatus at the T7 vertebra of nine human cadaveric specimens lying prone on a treatment table equipped with a force plate. The difference between the force applied by the apparatus and the resulting force measured by the force plate was calculated in absolute force (Fdiff) and as the percentage of the applied force (Fdiff%). Kinematics markers were inserted into T6 to T8 spinous and transverse processes to evaluate vertebral displacements during the SMT thrusts. Mixed-effects linear models were run to evaluate the variance in Fdiff and Fdiff% explained by SMT characteristics (peak force, thrust duration and force application rate), T6 to T8 relative and total displacements, and specimens' characteristics (BMI, height, weight, kyphosis angle, thoracic thickness). Sixty percent of the trials showed lower force measured at the force plate than the one applied at T7. Fdiff¸ was significantly predicted (R2marginal = 0.54) by peak force, thrust duration, thoracic thickness and T6-T7 relative displacement in the z-axis (postero-anterior). Fdiff% was significantly predicted (R2marginal = 0.56) by force application rate, thoracic thickness and total T6 displacements. For both dependant variables, thoracic thickness showed the highest R2marginal out of all predictors. Difference in force between the clinician-patient and the patient-table interfaces is influenced by SMT force-time characteristics and by thoracic thickness. How these differences in force are associated with vertebral displacements remains unclear. Although further studies are needed, clinicians should consider thorax thickness as a possible modulator of forces being transmitted through it during prone SMT procedures.


Reference Standards for Cardiorespiratory Fitness in Brazil: A POOLED ANALYSIS AND OVERVIEW OF HETEROGENEITY IN NATIONAL AND INTERNATIONAL STUDIES.
This study aimed to propose reference standards for cardiorespiratory fitness (CRF) for Brazil from a pooled analysis and to compare peak oxygen uptake (V˙ o2peak ) in Brazilian, United States (US), and Norwegian samples, exploring possible national and international differences. Reference values for treadmill V˙ o2peak in three different Brazilian regions were assessed from previous publications. We analyzed available samples to assess possible differences, generate weighted average data for Brazil, and compared them with US and Norwegian data. Brazilian reference values had a lower V˙ o2peak value for the Northeast region and a higher V˙ o2peak value for the Southeast region for all sex and age groups. International comparisons with the Brazilian pooled data (n = 26661) revealed higher values for the Norwegian sample (n = 3810) and lower values for the US sample (n = 16278). The observed heterogeneity in CRF is possibly related to differences in anthropometric (weight, height) and socioeconomic factors, which differed among the samples. Also, Brazilian data showed a curvilinear V˙ o2peak age reduction trend rather than the linear characteristic commonly utilized, and the regression curves were different from those for US and Norwegian data. This study provides new CRF reference standards for Brazil. After pooling data from three Brazilian regions, a comparison revealed notable differences between regions, evidencing a negative gradient from Southern to Northern regions. Similarly, the international comparisons between Brazil, US, and Norway data revealed CRF heterogeneity, with differences in the V˙ o2peak values and in the age relationship patterns. These findings reinforce the importance of using national- or regional-specific V˙ o2peak reference values, ensuring proper CRF evaluation.


Determination of m-hydroxymandelic acid, m-hydroxyphenylglycol and their conjugates in human plasma using liquid chromatography with electrochemical detection.
An LC method for the analysis of m-hydroxymandelic acid (MHMA) and m-hydroxyphenylglycol (MHPG) and their conjugates in human plasma was developed and validated. The method for the quantitation involved extraction of acidified plasma (subject to hydrolysis with beta-glucuronidase for 120 min with 500 units of enzyme/0.25 ml of plasma at 37 degrees C for the conjugates) with an organic phase (methyl-tert-butyl ether). Analysis of MHMA, MHPG and the internal standard (3-hydroxy-4-methoxymandelic acid) was carried out on an ODS stationary phase: 100 x 4.6 mm, 5 mu followed by a 75 x 4.6 mm, 3 mu using 1% acetonitrile in 0.1 M acetic acid as the mobile phase. An electrochemical detector operated at +1.15 V vs Ag/AgCl was employed for the detection. The standard curves were linear in the range of 10.0-250.0 ng ml-1 for MHMA and 5.0-125.0 ng ml-1 for MHPG. The limit of quantitation was 10.0 ng ml-1 for MHMA and MHPG. Acceptable accuracy and precision were obtained during the intra-batch and inter-batch analysis for both the assays.


Radionuclide imaging of the spleen with heat denatured technetium-99m RBC when the splenic reticuloendothelial system seems impaired.
Imaging of the spleen of 10 patients who had been hematologically diagnosed with sickle-cell anemia (SCA) was studied with [99mTc]tin colloid and heat denatured [99mTc]RBCs. In all ten patients, there was faint or nonvisualization of the spleen with [99mTc]tin colloid. However, with heat denatured [99mTc]RBCs, nine spleens were well visualized, and the uptake was homogenous. One spleen had two patchy areas of uptake. The results indicate that when splenic phagocytic function is impaired as reflected by nonvisualization of the spleen with [99mTc]tin colloid, it is still possible to image such a spleen with heat denatured [99mTc]RBCs.


Validation of Ultrasound Dating Protocols Using Data From Twins Conceived Through In Vitro Fertilization in Nova Scotia: A Retrospective Cohort Study.
Clinical practice guidelines recommend determining gestational age (GA) for twin pregnancies using the fetal crown rump length (CRL) of the larger fetus. This study investigated whether the CRL of the larger or smaller fetus at 11-14 weeks best predicted in vitro fertilization (IVF) assigned GA. A retrospective cohort study of twin pregnancies conceived by IVF ± intracytoplasmic sperm injection, 2004-2022, generated GA estimations for each co-twin CRL at the 11-14 week ultrasound, to determine which fetus (smaller or larger) more consistently predicted IVF-assigned GA. Monoamniotic twins and twins with known structural or vascular abnormalities were excluded. Paired t tests evaluated the ability of CRL to predict GA, and logistic regression evaluated the predictive ability of each of the co-twin groups with increasing size differences. Statistical significance was set at P < 0.05. Viewpoint 6 identified 359 eligible twin pairs. CRL was closest with the smaller fetus (0.38 days); CRL for both the smaller (95% CI 0.16-0.61) and the larger (2.25 days, 95% CI 2.04-2.46) fetus showed deviation from IVF-assigned GA. As the absolute difference between the small and large fetus increased, the ultrasound-estimated GA of the smaller fetus was still consistently closer to IVF-assigned GA. In this selected population of twins with known GA, the CRL of the smaller fetus more accurately predicted IVF-assigned GA even with increasing differences in fetal size. These findings provide important information for appropriately dating pregnancies to facilitate adherence to national guidelines to monitor for pregnancy complications, and plan frequency and type of fetal surveillance, as well as timing of delivery.


Combined effects of mechanical and ischemic injury to cortical cells: secondary ischemia increases damage and decreases effects of neuroprotective agents.
Traumatic brain injury (TBI) involves direct mechanical damage, which may be aggravated by secondary insults such as ischemia. We utilized an in vitro model of stretch-induced injury to investigate the effects of mechanical and combined mechanical/ischemic insults to cultured mouse cortical cells. Stretch injury alone caused significant neuronal loss and increased uptake of the dye, propidium iodide, suggesting cellular membrane damage to both glia and neurons. Exposure of cultures to ischemic conditions for 24h, or a combination of stretch and 24h of ischemia, caused greater neuronal loss compared to stretch injury alone. Next, we tested the neuroprotective effects of superoxide dismutase (SOD), and the nitric oxide (NO) synthase inhibitors 7-nitroindazole (7-NINA) and lubeluzole. In general, these agents decreased neuronal loss following stretch injury alone, but were relatively ineffective against the combined injury paradigm. A combination of SOD with 7-NINA or lubeluzole offered no additional protection than single drug treatment against stretch alone or combined injury. These results suggest that the effects of primary mechanical damage and secondary ischemia to cortical neurons are cumulative, and drugs that scavenge superoxide or reduce NO production may not be effective for treating the secondary ischemia that often accompanies TBI.


Prognostic impact of completion of initial high-dose methotrexate therapy on primary central nervous system lymphoma: a single institution experience.
This retrospective single-center study assessed the feasibility, outcomes, and side-effects of high-dose methotrexate (HD-MTX) plus procarbazine in the treatment of immunocompetent patients with primary central nervous system lymphoma (PCNSL). Ninety-one patients diagnosed with PCNSL between January 2001 and December 2011 were treated with HD-MTX plus procarbazine. To reduce neurotoxicity in patients aged ≥60 years, only those not responding to chemotherapy and patients with relapse underwent whole-brain irradiation. All 91 consecutive patients were scheduled to receive HD-MTX. Their median age was 66 years (range 32-88 years) and their median Karnofsky performance score was 40 (range 20-100). While 56 patients (61.5 %) completed 3 cycles of HD-MTX chemotherapy and 48 (52.7 %) showed a complete response, treatment was stopped in 11 patients (12.1 %) due to toxicity. The median overall survival and progression-free survival were 40.6 and 11.7 months, respectively. Overall survival was significantly improved in patients who completed 3 cycles of chemotherapy compared with those did not (56.4 vs 24.0 months; p = 0.013 by univariate and p = 0.022 by multivariate analysis). Initial treatment with HD-MTX plus procarbazine was effective in patients with PCNSL. Completion of 3 cycles of HD-MTX chemotherapy was a significant independent prognostic factor for patient survival.


Assessment of remote ischemic conditioning delivery with optical sensor in acute ischemic stroke: Randomised clinical trial protocol.
Remote ischemic conditioning (RIC) is delivered by a blood pressure cuff over the limb, raising pressure 50 mmHg above the systolic blood pressure, to a maximum of 200 mmHg. The cuff is inflated for five minutes and then deflated for five minutes in a sequential ischemia-reperfusion cycle 4-5 times per session. Elevated pressure in the limb may be associated with discomfort and consequently reduced compliance. Continuous assessment of relative blood concentration and oxygenation with a tissue reflectance spectroscopy (a type of optical sensor device) placed over the forearm during the RIC sessions of the arm will allow us to observe the effect of inflation and deflation of the pressure cuff. We hypothesize, in patients with acute ischemic stroke (AIS) and small vessel disease, RIC delivered together with a tissue reflectance sensor will be feasible. The study is a prospective, single-center, randomized control trial testing the feasibility of the device. Patients with AIS within 7 days from symptoms onset; who also have small vessel disease will be randomized 2:1 to intervention or sham control arms. All patients randomized to the intervention arm will receive 5 cycles of ischemia/reperfusion in the non-paralyzed upper limb with a tissue reflectance sensor and patients in the sham control arm will receive pressure by keeping the cuff pressure at 30 mmHg for 5 minutes. A total of 51 patients will be randomized, 17 in the sham control arm and 34 in the intervention arm. The primary outcome measure will be the feasibility of RIC delivered for 7 days or at the time of discharge. The secondary device-related outcome measures are fidelity of RIC delivery and the completion rate of intervention. The secondary clinical outcome includes a modified Rankin scale, recurrent stroke and cognitive assessment at 90 days. RIC delivery together with a tissue reflectance sensor will allow insight into the blood concentration and blood oxygenation changes in the skin. This will allow individualized delivery of the RIC and improve compliance. ClinicalTrials.gov Identifier: NCT05408130, June 7, 2022.


Effect of rapid cycle deliberate practice in peripheral intravenous catheters insertion training: A simulation experimental study.
to compare the effect of rapid cycle deliberate practice simulation training with skill-training simulation on peripheral intravenous catheter insertion for Licensed Practical Nurses. The use of peripheral intravenous catheters is associated with high rates of complications, although it is widely used in clinical practice. Training strategies to ensure good performance can minimize the risks inherent to this procedure. A randomized simulation experimental pre-post interventional study. Sixty participants were allocated to intervention (n = 30) or control (n = 30) groups. Participants allocated to the intervention group were trained through the Rapid cycle deliberate practice simulation strategy, while participants in the control group were trained through the skill-training simulation strategy. A pre-test was applied before any intervention and a post-test after intervention. The primary outcome was the performance in the peripheral intravenous catheter insertion skill. The comparison of correct performance in the tests was analyzed intergroup and intragroup. The effect size of the interventions was also analyzed. The t-Student and Mann-Whitney tests compared the difference between the groups. The training effect was calculated by Cohen's dm and Glass's Δ measures. Performance between the pre-post-test increased from 59.4% to 96% (p < 0.001) in the intervention group and from 57.8% to 93.5% in the control group (p < 0001). There was no statistical difference between the groups after intervention (p = 0225). Cohen's dm measurement was 2.95 and 3.59 in the control and intervention groups, respectively. The rapid cycle deliberate practice simulation strategy resulted in Licensed Practical Nurses' performance improvements in peripheral intravenous catheter insertion, evidenced by the increase of correct performance actions in the post-test compared to the pre-test. However, with no statistical difference compared to the skill-training simulation strategy.


What is the 'voltage drop' when an effective health promoting intervention for older adults-Choose to Move (Phase 3)-Is implemented at broad scale?
Choose to Move (CTM), an effective health-promoting intervention for older adults, was scaled-up across British Columbia, Canada. Adaptations that enable implementation at scale may lead to 'voltage drop'-diminished positive effects of the intervention. For CTM Phase 3 we assessed: i. implementation; ii. impact on physical activity, mobility, social isolation, loneliness and health-related quality of life (impact outcomes); iii. whether intervention effects were maintained; iv) voltage drop, compared with previous CTM phases. We conducted a type 2 hybrid effectiveness-implementation pre-post study of CTM; older adult participants (n = 1012; mean age 72.9, SD = 6.3 years; 80.6% female) were recruited by community delivery partners. We assessed CTM implementation indicators and impact outcomes via survey at 0 (baseline), 3 (mid-intervention), 6 (end-intervention) and 18 (12-month follow-up) months. We fitted mixed-effects models to describe change in impact outcomes in younger (60-74 years) and older (≥ 75 years) participants. We quantified voltage drop as percent of effect size (change from baseline to 3- and 6-months) retained in Phase 3 compared with Phases 1-2. Adaptation did not compromise fidelity of CTM Phase 3 as program components were delivered as intended. PA increased during the first 3 months in younger (+1 days/week) and older (+0.9 days/week) participants (p<0.001), and was maintained at 6- and 18-months. In all participants, social isolation and loneliness decreased during the intervention, but increased during follow-up. Mobility improved during the intervention in younger participants only. Health-related quality of life according to EQ-5D-5L score did not change significantly in younger or older participants. However, EQ-5D-5L visual analog scale score increased during the intervention in younger participants (p<0.001), and this increase was maintained during follow-up. Across all outcomes, the median difference in effect size, or voltage drop, between Phase 3 and Phases 1-2 was 52.6%. However, declines in social isolation were almost two times greater in Phase 3, compared with Phases 1-2. Benefits of health-promoting interventions-like CTM-can be retained when implemented at broad scale. Diminished social isolation in Phase 3 reflects how CTM was adapted to enhance opportunities for older adults to socially connect. Thus, although intervention effects may be reduced at scale-up, voltage drop is not inevitable.


The acute effects of temperature variability on heart rate variability: A repeated-measure study.
The impacts of temperature variability on cardiac autonomic function remain unclear. To explore the short-term associations between daily temperature variability and parameters of heart rate variability (HRV). This is a repeated-measure study among 78 eligible participants in Shanghai, China. We defined temperature variability as diurnal temperature range (DTR), the standard-deviation of temperature (SDT) and temperature variability (TV). We evaluated 3 frequency-domain HRV parameters (VLF, LF and HF) and 4 time-domain parameters (SDNN, SDANN, rMSSD and pNN50). We used linear mixed-effect models to analyze the data after controlling for environmental and individual confounders. Temperature variability was significantly associated with decreased HRV, especially on the concurrent day. The exposure-response relationships were almost inversely linear for most parameters. Every one interquartile range (IQR) increase of DTR was associated with a decrease of 3.92% for VLF, 6.99% for LF, 5.88% for HF, 3.94% for rMSSD and 1.30% for pNN50. Each IQR increase of SDT was associated with a decline of 6.48% for LF, 5.91% for HF, 4.26% for rMSSD and 1.87% for pNN50. Every IQR increase of SDT was associated with a decrease of 4.39% for VLF, 7.67% for LF, 6.52% for HF, 3.22% for SDNN, 2.98% for SDANN, 4.05% for rMSSD, and 1.41% for pNN50. The decrements in HRV associated with temperature variability were more prominent in females. Temperature variability on the concurrent day could significantly decrease cardiac autonomic function, especially in females.


Analysis of a major rat idiotype associated with Anti-GAT antibodies.
An anti-idiotypic antiserum was raised in a rabbit against a pool of purified F.344 rat anti-GAT antibodies. GAT-13, the idiotype defined by this serum, is present in all F.344 anti-GAT sera from primary and secondary anti-GAT responses. Anti-GAT sera of 13 inbred rat strains, with different RT1 haplotypes and with different heavy- and light-chain allotypes, all express idiotypic determinants cross-reacting with GAT-13. Thus, like in mice anti-GAT antibodies from rats express public idiotypic determinants. The anti-idiotypic serum also recognizes a highly conserved idiotypic specificity present on mouse and guinea-pig anti-GAT antibodies. The mouse, rat and guinea-pig express a similar highly conserved idiotypic specificity after immunization with GAT. All anti-GAT antibodies from the mouse and guinea-pig bear this idiotypic specificity. These results confirm the existence in the anti-GAT response of interspecies cross-reactive idiotypic determinants.


Development and characterization of a continuous macrophage cell line, LRTM, derived from thymus of Labeo rohita (Hamilton 1822).
A long-term thymic macrophage cell line from the thymus explants of Labeo rohita designated as LRTM (L. rohita thymic macrophages) was established, which has been maintained in culture for more than 1 yr. This cell line designated LRTM cells have been subcultured for 70 passages. The cells shape was initially long and elongated; with subsequent passages, the cells became short and epithelial like. The cells exhibited optimum growth in L-15 containing 10% fetal bovine serum and also in Dulbecco's modified Eagle's medium at 37°C with 5% CO2 and showed 85+-% viability after 12 mo storage in liquid nitrogen. In addition, cells showed nonspecific esterase and surface expression of Fc receptors for immunoglobulin G and classes I and II major histocompatibility complex antigens. These observations confirmed that this cell line had the morphologic and functional features as a macrophage. The cells exhibited phagocytic activity by engulfing yeast cells as well as fluorescent latex beads, which was demonstrated by scanning electron microscopy and Giemsa staining. The long-term cultured cells show rapid production of reactive oxygen and nitrogen intermediates following stimulation with lipopolysaccharides and phorbol miristate acetate (PMA). Mostly, all the cells were alpha napthyl esterase acetate positive. After stimulation with PMA and lipopolysaccharide, cultured fish macrophages produced reactive oxygen and nitrogen intermediates. The karyotype analysis showed that these cells have a tetraploid karyotype with 100 chromosomes in each cell, indicating that they are normal L. rohita cells. Amplification, sequencing, and alignment of fragments of two mitochondrial genes 12S rRNA from rohu confirmed that the cell line originated from L. rohita. This cell line should be useful for studying the role of thymic macrophages in differentiation and maturation of thymocytes and can be source of macrophage-specific enzymes and cytokines. The macrophage cell line will be invaluable in studies of pathogen/macrophage interactions, the mechanisms of macrophage antimicrobial effector functions and the contribution of macrophages to the specific immune responses of teleosts.


The survey on cellular and tissue-engineered therapies in Europe and neighboring Eurasian countries in 2014 and 2015.
With the support of five established scientific organizations, this report, the seventh of its kind, describes activity in Europe for the years 2014 and 2015 in the area of cellular and tissue-engineered therapies, excluding hematopoietic stem cell (HSC) treatments for the reconstitution of hematopoiesis. In 2015 [respectively 2014], 205 [276] teams from 32 countries responded to the cellular and tissue-engineered therapy survey; 178 [126] teams reported treating 3686 [2665] patients. Indications were musculoskeletal/rheumatological disorders (32% [33%]), cardiovascular disorders (12% [21%]), hematology/oncology (predominantly prevention or treatment of graft versus host disease and HSC graft enhancement; 20% [20%]), neurological disorders (4% [6%]), gastrointestinal disorders (<1% [1%]) and other indications (31% [20%]). The majority of autologous cells (60% [73%]) were used to treat musculoskeletal/rheumatological (44% [36%]) disorders, whereas allogeneic cells were used mainly for hematology/oncology (61% [68%]). The reported cell types were mesenchymal stromal cells (40% [49%]), chondrocytes (13% [6%]), hematopoietic stem cells (12% [23%]), dermal fibroblasts (8% [3%]), dendritic cells (2% [2%]), keratinocytes (1% [2%]) and others (24% [15%]). Cells were expanded in vitro in 63% [40%] of the treatments, sorted in 16% [6%] of the cases and rarely transduced (<1%). Cells were delivered predominantly as suspension 43% [51%], intravenously or intra-arterially (30% [30%]), or using a membrane/scaffold (25% [19%]). The data are compared with those from previous years to identify trends in a still unpredictably evolving field. Perspectives of representatives from plastic surgery practitioners, Iran and ISCT are presented (contributing authors D.A. Barbara, B. Hossein and W.L. Mark, respectively).


The post-injury changes that occur in transected foetal nerves; an experimental study in the rat.
The findings of this experimental foetal rat study have shown that transection of the peripheral branches of the maxillary and facial nerves on the 18th day of gestation is followed by axonal degeneration and regeneration. Although these processes are similar to those which occur in the adult animal, they occur more rapidly in the foetus. In this study the regenerating axons had crossed the wound and entered the neural tubes of the distal nerve segments by 24 hours after injury.


Mechanisms of SARS-CoV-2-associated anosmia.
Anosmia, the loss of the sense of smell, is one of the main neurological manifestations of COVID-19. Although the SARS-CoV-2 virus targets the nasal olfactory epithelium, current evidence suggests that neuronal infection is extremely rare in both the olfactory periphery and the brain, prompting the need for mechanistic models that can explain the widespread anosmia in COVID-19 patients. Starting from work identifying the non-neuronal cell types that are infected by SARS-CoV-2 in the olfactory system, we review the effects of infection of these supportive cells in the olfactory epithelium and in the brain and posit the downstream mechanisms through which sense of smell is impaired in COVID-19 patients. We propose that indirect mechanisms contribute to altered olfactory system function in COVID-19-associated anosmia, as opposed to neuronal infection or neuroinvasion into the brain. Such indirect mechanisms include tissue damage, inflammatory responses through immune cell infiltration or systemic circulation of cytokines, and downregulation of odorant receptor genes in olfactory sensory neurons in response to local and systemic signals. We also highlight key unresolved questions raised by recent findings.


Study of the Changes of Acrosomal Enzyme, Nitric Oxide Synthase, and Superoxide Dismutase of Infertile Patients with Positive Antisperm Antibody in Seminal Plasma.
The purpose of this article is to study the effect of positive antisperm antibody (AsAb) in seminal plasma on acrosomal enzyme activity, nitric oxide synthase (NOS) activity, and superxide dismutase (SOD) activity of spermatozoa. A total of 40 infertility patients with positive AsAb in seminal plasma were selected as experimental group, and 40 fertile males were selected as control group. Based on the changes in absorbance, the acrosomal enzyme activity was detected by the BAEE/ADH method, the NOS activity was detected by the redoxreaction assay, and SOD level was measured with xanthine oxidase method. Compared with the control group, acrosomal enzyme activity of spermatozoa of the experimental group was significantly decreased (P < 0.01), NOS activity was apparently increased (P < 0.01), and the SOD level in seminal plasma was significantly decreased (P < 0.01). The infertility caused by positive AsAb in seminal plasma may be related to the changes in the acrosomal enzyme of spermatozoa and the SOD and NOS activities in seminal plasma.


Contribution of UVB and UVA to UV-dependent stimulation of cyclooxygenase-2 expression in artificial epidermis.
Both UVB (280-320 nm) and UVA (320-400 nm) radiation lead to an enhanced expression of cyclooxygenase-2 (COX-2) in epidermal cells in various in-vitro and in-vivo models. It is demonstrated here that the expression of COX-2 is induced in artificial human epidermis exposed to simulated solar light (>290 nm). Employing filters eliminating specified regions from the simulated solar spectrum, the UVB and UVA-2 (320-350 nm) regions are shown to fully account for induction of COX-2 mRNA and protein as well as the enhanced production of prostaglandin E(2) after irradiation. At the protein level, approximately 70% of the total induction by solar light is due to light in the UVA-2 region. UVA-1 (350-400 nm), visible light and IR radiation are practically ineffective. COX-2 induction by simulated solar light is attenuated in the presence of inhibitors of p38(MAPK) or of c-Jun-N-terminal kinases (JNK), whereas COX-2 induction by UVA is blocked only by inhibition of JNK. UV-induced COX-2 expression is not affected by inhibition of the MEK 1,2/ERK 1,2 pathways.


GAP1(IP4BP)/RASA3 mediates Galphai-induced inhibition of mitogen-activated protein kinase.
The dopamine D2S receptor (short isoform) couples to inhibitory Galphai/o proteins to inhibit thyrotropin-releasing hormone (TRH)-stimulated p42/p44 mitogen-activated protein kinase (ERK1/2) phosphorylation in GH4ZR7 rat pituitary cells, consistent with its actions to inhibit prolactin gene transcription and cell proliferation. However, the underlying mechanism is unclear. To identify novel Galphai effectors, yeast two-hybrid screening of a GH4ZR7 cDNA library was done using constitutively active Galphai3-Q204L, and multiple clones of the RasGAP cDNA GAP1(IP4BP)/RASA3 were identified. In yeast mating assay, RASA3 preferentially interacted with activated forms of Galphai/o/z proteins, but not with Galphas. A direct interaction was indicated by in vitro pull-down assay, in which S-His-RASA3 preferentially bound guanosine 5'-O-(gamma-thio)triphosphate-activated Galphai3 and Galphai2 compared with guanosine 5'-O-(beta-thio)diphosphate-inactivated proteins. Similarly, in co-immunoprecipitation studies in HEK-293 cells, FLAG-tagged RASA3 preferentially interacted with activated mutants of Galphai3 and Galphai2 compared with wild type proteins. In GH4ZR7 cells, co-immunoprecipitation studies of endogenous proteins demonstrated a Galphai3-RASA3 complex that was induced upon TRH/D2S receptor co-activation. To address RASA3 function in dopamine D2S receptor-induced inhibition of ERK1/2 activity, endogenous RASA3 protein expression was suppressed (70% knockdown) in GH4ZR7 cells stably transfected with full-length antisense cDNA of RASA3. The selected antisense clones had similar levels of dopamine D2S receptor binding and D2S-induced inhibition of cAMP formation compared with parental GH4ZR7 cells. In these clones, D2S-mediated inhibition of TRH-induced phospho-ERK1/2 was reversed by 70-80% compared with parental GH4ZR7 cells. Our results provide a novel mechanism for dopamine D2S-induced inhibition of ERK1/2 and indicate that RASA3 links Galphai proteins to inhibit Gq-induced Ras/ERK1/2 activation.


Medium-Chain fatty acids and long-chain alcohols production from waste activated sludge via two-stage anaerobic fermentation.
Traditional bioenergy recovery in the form of short chain fatty acids (SCFAs) from waste activated sludge (WAS) is generally limited by economic unattractiveness and complexity of products separation. Herein, a novel biotechnology process of two-stage anaerobic fermentation for converting the WAS into high energy density, easy-separated medium chain fatty acids (MCFAs) and long-chain alcohols (LCAs) was evaluated. In this process, the WAS was first converted to WAS alkaline fermentation liquid (WASAFL), serving as electron acceptors (EAs) and inoculum, then adding ethanol as electron donor (ED) for chain elongation (CE). The co-production of MCFAs and LCAs during CE were studied under three different ED to EA ratios, i.e., 3:1, 4:1 and 5:1. Experimental results demonstrated that when the ratio of ED to EA increased from 3:1 to 5:1, the production of MCFA and LCAs respectively increased from 5.57 ± 0.17 and 2.58 ± 0.18 to7.67 ± 0.48 and 4.21 ± 0.19 g COD/L. A similar observation was made in the total product electron efficiency, increasing from 59.9% to 72.1%. However, the highest total product selectivity (i.e., 68.0%) and highest products production yield (i.e., 59.77%) were not achieved at the ED to EA ratio of 5:1 due to toxicity caused by higher accumulation of n-caproate. The kinetic analysis further confirmed that high ratio of ED to EA induced improvement in product maximum yield, production rate for both MCFAs and LCAs. Microbial community analysis indicated that Clostridium, Caproiciproducens, Acinetobacter, Exilispira, and Oscillibacter were clearly enriched in the CE reactor and had positive correlation with MCFAs and LCAs production.


A comparative evaluation of cardiac and neurological safety status of two commonly used oral hypoglycaemic agents in T2-DM Swiss albino mice model.
Diabetes mellitus (DM), along with its associated complications, including diabetic neuropathy and hyperlipidemia, has become a global concern in the last few decades. The main objective of our study is to evaluate the comparative neuro-safety status, serum plasma glucose, and lipid-lowering potential of two widely recognized antidiabetic drugs named metformin and glimepiride. The neurological evaluation was done by open field test, hole board test, forced swimming test, dark and lighthouse test, and elevated plus maze test by employing diazepam as standard. Serum blood glucose level of streptozotocin (STZ)-induced diabetic mice was determined by glucose oxidizing method using a glucometer. Total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and very-low-density lipoprotein cholesterol (VLDL-C) levels were estimated by using the reference method where atorvastatin was used as standard. In neurological evaluation, both drugs produce almost the same anxiolytic activity in the open field test, hole board test, light and dark house test, and elevated plus maze test. However, in the forced swimming test, glimepiride produced more antidepressant activity than metformin. Glimepiride was found to remarkably reduce serum glucose and VLDL-C levels more than metformin, whereas, for other parameters, metformin takes over glimepiride sometimes took over the standard atorvastatin. The results of our study indicate that both oral hypoglycaemic drugs alter the lipid index while producing some anxiolytic effects on the central nervous system. Thus, recommended to be carefully administered to patients with low BMI and might be beneficial to patients suffering from peripheral nerve function and anxiety.


Ceramide Kinase Inhibition Drives Ferroptosis and Sensitivity to Cisplatin in Mutant KRAS Lung Cancer by Dysregulating VDAC-Mediated Mitochondria Function.
Ceramide kinase (CERK) is the mammalian lipid kinase from which the bioactive sphingolipid, ceramide-1-phosphate (C1P), is derived. CERK has been implicated in several promalignant phenotypes with little known as to mechanistic underpinnings. In this study, the mechanism of how CERK inhibition decreases cell survival in mutant (Mut) KRAS non-small cell lung cancer (NSCLC), a major lung cancer subtype, was revealed. Specifically, NSCLC cells possessing a KRAS mutation were more responsive to inhibition, downregulation, and genetic ablation of CERK compared with those with wild-type (WT) KRAS regarding a reduction in cell survival. Inhibition of CERK induced ferroptosis in Mut KRAS NSCLC cells, which required elevating VDAC-regulated mitochondria membrane potential (MMP) and the generation of cellular reactive oxygen species (ROS). Importantly, through modulation of VDAC, CERK inhibition synergized with the first-line NSCLC treatment, cisplatin, in reducing cell survival and in vivo tumor growth. Further mechanistic studies indicated that CERK inhibition affected MMP and cell survival by limiting AKT activation and translocation to mitochondria, and thus, blocking VDAC phosphorylation and tubulin recruitment. Our findings depict how CERK inhibition may serve as a new key point in combination therapeutic strategy for NSCLC, specifically precision therapeutics targeting NSCLC possessing a KRAS mutation.


The single instrument port laparoscopic (SIMPL) nephrectomy.
To describe a novel modification of the posterior prone retroperitoneoscopic nephrectomy/nephroureterectomy which allows the entire procedure to be performed through a single instrument port. With the patient in a prone position, a retroperitoneal working space is created with the aid of a homemade balloon. A single instrument port is then placed at the tip of the 11th/12th rib under direct vision. Gerota's fascia is incised, the kidney is reflected anteriorly, and the hilar vessels are identified and divided. The ureter is mobilized as far distally as possible before division. The specimen is removed directly via the camera port or in an endobag. We have employed this technique in 26 children with a high success rate. The median operating time was 58 (range 45-90) min. Blood loss was minimal in all cases and there were no complications. There have been no conversions and the cosmetic outcome has been excellent. Most of the children (24 of 26) were discharged home the day after surgery. The single instrument port laparoscopic (SIMPL) nephrectomy is a feasible and safe technique for the experienced paediatric laparoscopic urologist.


Innovation in resident education - Description of the Neurology International Residents Videoconference and Exchange (NIRVE) program.
There is considerable heterogeneity in residency education around the world. The Neurology International Residents Videoconference and Exchange (NIRVE) program aims to deliver neurology educational content to residents across different resource settings and countries through a monthly videoconferencing platform. Its purpose is to fill gaps in didactic teaching, increase exposure to a variety of cases including various practices and delivery of neurology in multiple countries, as well as integrate global health content into neurology education. NIRVE also facilitates resident exchanges among participating sites. In this descriptive article, we report NIRVE's structure and its cumulative productivity. Since its creation, NIRVE has held more than 90 videoconference rounds and has connected 16 sites in North America, South America, Europe, Asia and Africa. We describe challenges encountered since the inception of the program eleven years ago. NIRVE also fosters a culture of long-term international connection and collaboration. During global disease outbreaks, such as the current COVID-19 pandemic, videoconference rounds serve as a sustainable alternative means to deliver education. Future goals include increasing the number of sites involved, including a focus on Africa and Asia, and fostering resident-led advocacy projects.


Impact of non-driving related tasks while operating automated driving systems (ADS): A systematic review.
Automated Driving Systems (ADS) (SAE, 2021), promise improved safety and comfort for drivers. Current technological advances have resulted in increased automation capabilities. However, with the increase in automation capabilities, there is a shift in how drivers interact with their vehicles. Drivers can now temporarily hand over the control of the driving task to ADS under certain conditions. However, with ADS in temporary control of the vehicle, drivers may choose to engage in non-driving related tasks (NDRT). The current capabilities of ADS do not allow drivers to hand over control of the driving task indefinitely. Drivers must remain aware and be ready to take back control if necessary. There is a need to better understand drivers' performance and behaviors when driving with ADS, especially when engaged in NDRTs. This literature review, therefore, aims to understand the state of knowledge on automated vehicle systems and driver distraction. This review was conducted as per PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Studies found a significant increase in takeover times while engaging in NDRTs and driving with automation active. Studies also discuss a change in driver's visual attention, with more focus given to NDRTs as compared to the front roadway. The concerning effects of increasing reaction times and decreases in visual attention can be mitigated by using interventions and studies have had success in redirecting drivers attention and reorient them to the task of driving. The review, therefore, includes a discussion of ADS and NDRT engagement and its impact on driving behaviors such as take-over times, visual attention, trust, and workload. Implications on driver safety and performance are discussed in light of this synthesis.


Structural studies of the doublecortin family of MAPs.
Doublecortin (DCX) is a microtubule (MT)-stabilizing protein essential for neuronal migration during human brain development. Missense mutations in DCX cause severe brain defects. This implies that the many other MT-stabilizing proteins in neurons cannot compensate for DCX function. To understand the unusual properties of DCX, we expressed the recombinant human DCX in Sf9 cells and undertook structural characterization of its interaction with MTs using cryo-electron microscopy. DCX specifically nucleates 13-protofilament (13-pf) MTs, the architecture of human MTs in vivo. Cryo-electron tomography (cryo-ET) of DCX-nucleated MTs showed that they are primarily built from B-lattice contacts interrupted by a single discontinuity, the seam. Because of this asymmetry, we used single-particle reconstruction and determined the 8Å structure of DCX-stabilized 13-pf MTs in the absence of a stabilizing drug. The DCX-binding site, at the corner of four tubulin dimers, is ideally suited to stabilize both lateral and longitudinal tubulin lattice contacts. Its precise geometry suggests that DCX is sensitive to the angle between pfs, and thereby provides insight into the specificity of DCX for 13-pf MT architecture. DCX's precise interaction at the corner of four tubulin dimers also means that DCX does not bind the MT seam. Our work has provided mechanistic insight into the evolutionarily conserved DCX family of MT-stabilizing proteins and also into more general regulatory mechanisms of the MT cytoskeleton.


Prolactin receptor on dissociated mammary epithelial cells at different stages of development.
Properties of prolactin receptors were measured by monitoring [125I]prolactin binding to specific receptor sites on collagenase-dissociated mammary epithelial cells of virgin, pregnant and lactating mice. On a Scatchard plot the data generated a straight line and the estimated dissociation constant (Kd) and number of receptor sites on lactating cells were 0.9 x 10(-9) and 1540 per cell. The [125I]prolactin binding was inhibited in presence of unlabeled prolactin and other lactogenic polypeptide hormones, but not by nonlactogenic polypeptide hormones. The [125I]prolactin binding was sensitive to pronase and trypsin but not to DNAase, RNAase and hyaluronidase. Scatchard plot analysis further showed that while the number of receptors on mammary cells was variable at different stages of endocrine regulated developmental changes of the gland, Kd of the hormone--receptor complex generally remained similar. The high level of prolactin receptors on mammary cells of virgins was reduced during pregnancy and the lactating mammary cells showed a highly elevated level of prolactin receptors. The results demonstrate that specific prolactin receptors can be measured on collagenase dissociated mammary epithelial cells and this method permits a direct assessment of the number of receptors on a per cell basis rather than indirect estimates, based on average DNA or protein content of the tissue, composed of heterogeneous cell types.