High tibial osteotomy for osteoarthritis of the knee with varus deformity utilizing the hemicallotasis method.
A hemicallotasis method has been developed utilizing an external fixator as high tibial osteotomy (HTO), and satisfactory results of this method with the external fixator have been reported. This external fixator has a universal joint that moves in all directions. We have recently designed a hemicallotasis device for this operation. HTO for the knee with varus deformity utilizing the hemicallotasis method was performed on 44 knees. The patients had a mean age at operation of 65 years (range 49-82 years), a mean follow-up period of 68 months (range 36-119 months), and a mean preoperative knee score of 66 points (range 27-90 points). The operated knees had a mean knee score at the final follow-up of 86 points (range 51-98 points), but the mean range of knee motion was not changed as follows. Before surgery, the mean flexion was 129 degrees (range 90-150 degrees) and the mean extension was -5 degrees (range -30 to 0 degrees), whereas at the final follow-up, the corresponding values were 127 degrees (range 85-150 degrees) and -4 degrees (range -25 to 0 degrees), respectively. Radiographically, the femorotibial joint was classified as grade 2 in 9 knees, grade 3 in 21 knees, and grade 4 in 14 knees according to the classification of osteoarthritis (Kellgren and Laurence). The patellofemoral joint was also classified as grade 1 in 39 knees, grade 2 in 2 knees, and grade 3 in 3 knees. The mean femorotibial angle was 184 degrees (4 degrees varus) before surgery, 169 degrees (11 degrees valgus) after pin extraction, and was maintained at the final follow-up. The complications of this method were relatively few and consisted of pin-tract infection (8 knees), deep vein thrombosis (3 knees), and delayed union (2 knees). No peroneal nerve palsy or compartment syndrome was encountered. No knee was converted to total arthroplasty. However, administration of analgesics was necessary in ten knees at the final follow-up. The hemicallotasis method easily determined the angle of correction even in the knees with ligamentous laxity. Nevertheless, one of the major demerits of this method was a longer period of application of the external fixator. The level of evidence was level IV (case series).


Obstructive sleep apnea and dementia: A role to play?
A growing number of studies, in animal models and humans, have highlighted the link between sleep and Alzheimer's disease (AD) pathophysiology. Among sleep disorders, obstructive sleep apnea (OSA) appears to be a potentially interesting comorbidity, as it is highly prevalent in the middle-aged and elderly population, often associated with some cognitive impairment, associated with an increased risk of developing cognitive decline and dementia including AD, and indeed treatable. The association between OSA and cognition varies according to the studies, but OSA is more frequent in older people with AD than those who are cognitively normal. People with OSA suffer from daytime sleepiness, impaired cognitive function and an increased risk of developing mild cognitive impairment, dementia and AD than those without OSA. Finally, the literature suggests a link between OSA and AD biomarkers. Whether screening and treating OSA could have positive impact on the levels of AD biomarkers and slow or even prevent incident dementia remain to be investigated. It therefore seems essential to understand the role of OSA in the pathophysiology of AD, as there is still no effective treatment to slow or halt its progression. At present, treating the risk factors that can promote the development and/or worsening of AD represents a promising strategy for delaying or even thwarting the onset of symptoms.


Two Indian families with Greig cephalopolysyndactyly with non-syndromic phenotype.
The Greig cephalopolysyndactyly syndrome (GCPS) is a rare, autosomal dominant, pleiotropic, multiple congenital anomaly syndrome. The typical findings include hypertelorism, macrocephaly with frontal bossing, and polysyndactyly. We present two families, with GCPS with a non-syndromic phenotype, without the characteristic craniofacial anomalies and with the presence of complex digital anomalies including various types of polydactyly and syndactyly of the fingers and toes. The cases were proven to be GCPS by mutational analysis of GL13 gene. Our patients support the fact that the phenotypic spectrum of GL13 mutations is broader than that encompassed by the usual clinical diagnostic criteria. Individuals with features of familial polysyndactyly should be screened for mutations in GL13 even if they do not fulfill clinical criteria.


The Handicap of Hidradenitis Suppurativa.
Hidradenitis suppurativa (HS) is a chronic skin disease, with painful, foul-smelling, recurring inflammation, leading to a diminished quality of life. Patients with HS also often suffer from depression, have an impaired sexual health, and may have difficulty performing their work duties.


Replacement of a hopeless maxillary central incisor: a technique for the fabrication of an immediate implant-supported interim restoration.
Placement of a dental implant and an interim restoration in the esthetic zone immediately following tooth extraction is now a common procedure. However, in such clinical situations, the fabrication of an appropriate interim restoration may be challenging. The aim of this article is to present a technique for modifying the extracted tooth so it can be used as an implant-supported interim restoration.


In vivo and in vitro analysis in a rat model using zoledronate and alendronate medication: microbiological and scanning electron microscopy findings on peri-implant rat tissue.
The aim of the present study was to assess the development of bacterial deposits and morphological parameters around dental zirconia and titanium implants compared with natural teeth during systemic bisphosphonate medication. Fifty-four rats were randomly allocated into one control group and two experimental groups (drug application of zoledronic and alendronic acid), with 18 animals in each group. After 4 weeks of drug delivery, either a zirconia or a titanium implant was immediately inserted. Microbiological analysis conducted 1 week, 8 weeks, and 12 weeks after surgery included total bacterial count and composition measurements. Samples were analyzed in a scanning electron microscope (SEM) equipped with energy-dispersive X-ray spectroscopy (EDX). Bone cell morphology was analyzed by transmission electron microscopy (TEM). One week after surgery, titanium and zirconia implants of the alendronic acid and control group showed a significantly higher bacterial count when compared to natural teeth in rats with zoledronic acid administration (p < 0.01). Less significant differences were recorded after 3 months, at which time no inter-material differences were evaluated (p > 0.05). I n the control group, TEM analysis showed that the osteoblasts had a strongly developed endoplasmic reticulum. In contrast, the endoplasmic reticulum of the osteoblasts in drug-treated animals was significantly less developed, indicating less activity. Within the limits of this study, neither implant material was superior to the other at 3-month follow-up. With regard to the treatment and complications of patients with bisphosphonates, the implant material should not be an influencing factor. Bisphosphonates can be used in the rat model to reduce not only the activity of osteoclasts but also osteoblasts of the peri-implant bone.


Conversion of medical waste into value-added products using a novel integrated system with tail gas treatment: Process design, optimization, and thermodynamic analysis.
The COVID-19 pandemic has generated substantial medical waste (MW), posing risks to society. Based on widespread MW incineration, this study proposes an integrated system with tail gas treatment to convert MW into value-added products with nearly zero emissions. Herein, steam generators and supercritical CO2 cycles were used to recover energy from MW to produce high-temperature/pressure steam and electricity. A simple power generation cycle achieved a net electricity efficiency of 22.4% through optimization. Thermodynamic analysis revealed that the most energy and exergy loss occurred in incineration. Furthermore, a pressurized reactive distillation column purified the resultant tail gas. The effects of inlet temperature, pressure, liquid/gas ratio, and recycle ratio on the removal and conversion efficiencies of NO2 and SO2 were evaluated. Nearly 100% of the SO2 and 75% of the NO2 generated by the incineration of MW have been converted into their acid forms. Based on the proposed tail gas treatment unit, high-purity CO2 (∼98% purity) was finally obtained.


Dynamic changes in the cytoskeleton during human spermiogenesis.
To investigate the structural changes in the cytoskeleton (microtubules, microfilaments) and examine the expression of centrosomal functional proteins during human spermiogenesis. Immunofluorescent staining of human spermiogenic cells. University hospital and IVF clinic. Human testicular tissues were obtained by testicular sperm aspiration (TESA) under informed consent. Three cases of obstructive azoospermia, with confirmed normal spermatogenesis, were examined. Spermatogenic cells were fixed with microtubule-stabilizing buffer. Immunocytochemical detection of microtubules, microfilaments, and centrosome was performed using monoclonal antibodies against alpha- and beta-tubulin, phalloidin, and functional centrosomal proteins. Samples were examined using epifluorescence and laser scanning confocal microscopes. During the Sb2 period, microtubules formed the manchette structure, which extended from the equator of the nucleus through the cytoplasm. Microfilaments were organized in the periacrosamal region during spermiogenesis (Sa to Sd). Although centrin was observed throughout the spermiogenic period, gamma-tubulin was detected only in the Sb2 period. Dynamic cytoskeletal movement was observed during human spermiogenesis. Cytoskeletal rearrangements in the Sb2 period appear to play important roles in the morphologic changes that occur during human spermiogenesis. Studies of the cytoskeletal system during spermiogenesis may help identify some causes of male infertility (e.g., teratozoospermia, maturation arrest).


Bacillus Calmette-Guerin immunotherapy for bladder cancer.
Bacillus Calmette-Guerin immunotherapy has been found by a number of investigators to be effective in the treatment and prevention of superficial bladder cancer. While the optimal protocol for bacillus Calmette-Guerin remains to be determined, experience with 92 randomized and 30 nonrandomized (high risk) patients followed for up to 5 years provides information that may improve future protocols. Side effects of bacillus Calmette-Guerin are observed to increase with increasing frequency and duration of treatment. The protection from tumor recurrence has persisted: only 6 of 30 patients (20 per cent) treated with bacillus Calmette-Guerin have had recurrent tumor compared to 14 of 27 controls (52 per cent, p equals 0.008, chi-square test), and mean time to recurrence increased from 24 to 48 months (p less than 0.005, Savage). Skin test reactivity to purified protein derivative is particularly useful in predicting response to bacillus Calmette-Guerin immunotherapy. Currently, 60 patients have been randomized to receive bacillus Calmette-Guerin immunotherapy and only 1 of 22 patients (4.5 per cent) in whom the purified protein derivative skin test results converted from negative to positive has had recurrent tumor, compared to 12 recurrences (32 per cent) in patients whose skin tests were positive before treatment or failed to convert following treatment (p equals 0.014, chi-square). Seven recurrences (33 per cent) developed in 21 patients whose skin tests remained negative (p equals 0.015) and 5 recurrences (29 per cent) developed in 17 patients whose tests previously were positive (p equals 0.068, Fisher's test, not significant). The benefit of percutaneous bacillus Calmette-Guerin is suggested by the observations that the recurrence rate in patients treated with intravesical bacillus Calmette-Guerin alone is 40 per cent, and all 7 patients whose purified protein derivative skin tests were negative continued to have negative results when percutaneous bacillus Calmette-Guerin was omitted (p equals 0.003). Among high risk patients a marked decrease in or complete prevention of recurrent tumor was observed in 82 per cent of 22 patients treated previously with chemotherapy and 11 of 14 (78 per cent) with carcinoma in situ have had a complete response.


Parietal connectivity mediates multisensory facilitation.
Our senses interact in daily life through multisensory integration, facilitating perceptual processes and behavioral responses. The neural mechanisms proposed to underlie this multisensory facilitation include anatomical connections directly linking early sensory areas, indirect connections to higher-order multisensory regions, as well as thalamic connections. Here we examine the relationship between white matter connectivity, as assessed with diffusion tensor imaging, and individual differences in multisensory facilitation and provide the first demonstration of a relationship between anatomical connectivity and multisensory processing in typically developed individuals. Using a whole-brain analysis and contrasting anatomical models of multisensory processing we found that increased connectivity between parietal regions and early sensory areas was associated with the facilitation of reaction times to multisensory (auditory-visual) stimuli. Furthermore, building on prior animal work suggesting the involvement of the superior colliculus in this process, using probabilistic tractography we determined that the strongest cortical projection area connected with the superior colliculus includes the region of connectivity implicated in our independent whole-brain analysis.


Gamma-ray energies in the decay of 38Cl.
In order to resolve a long-standing discrepancy of some 30 standard deviations between the two most precise previously reported values of the γ-ray energies in the (38)Cl decays, we have undertaken a new precision measurement of the decay energies using a variety of different sources for energy calibration. The deduced energies from the present work are 1642.668 ± 0.010 and 2167.395 ± 0.010 keV. These results agree very well with one of the previous reports and disagree with the other.


Distribution of bacteria in the rumen contents of dairy cows given a diet supplemented with soya-bean oil.
1. Liquid-associated bacteria (LAB) were harvested from the liquid phase (LAB1) and from the solid phase of rumen contents after washing and manual shaking (LAB2). Solid-adherent bacteria (SAB) were recovered after washing and pummelling the total particles (SAB1). The distribution and the chemical composition of these three bacterial compartments were investigated in four dairy cows fitted with rumen fistulas. The animals received successively a diet consisting of one part hay and one part barley-based concentrate (diet C) and the same diet containing free soya-bean oil (79 g/kg dry matter (DM); diet So). 2. The efficiency of removal of SAB1 from total particles of rumen digesta collected 1 h after feeding, was calculated from the diaminopimelic acid content in particles and of the corresponding detached bacteria. It was 24% on diet C and 18% on diet So (P less than 0.05), using a combination of homogenizing and 'stomaching' treatments in saline (9 g sodium choloride/1) (reference treatment). For diets C and So respectively it was lowered by Tween in saline solution (1 g/l; 22.7 and 17.8%, not significant), but was increased when using a previous chilling (6 h at 4 degrees) of homogenized particles before stomaching in saline (28.8 and 24.7%, P less than 0.05) and in Tween 80 in saline (1 g/l; 26.6 and 20.8%, P less than 0.05). 3. The extent of removal of SAB1 from the solid fraction of rumen digesta by the reference treatment decreased with decreasing particle size; it was at the highest for particles retained on 4 and 2 mm sieves (62.1-82.1%) and still elevated for particles retained on 0.8, 0.4 and 0.1 mm sieves (41.3-57.9%). It was very much reduced for particles smaller than 0.1 mm (11.7-14.5%), suggesting the occurrence of favourable conditions for the adhesion of SAB firmly resistant to removal (SAB2). 4. The concentration of total SAB (SAB1 + SAB2) in particles collected 1 h after feeding was lower (P less than 0.05) in diet C (190 g/kg DM) than in diet So (234 g/kg DM). Values averaged 595-645 g/kg DM for particles smaller than 0.1 mm, but only 61 and 81-98 g/kg DM for particles retained on 4 and 0.4 mm sieves, and on a 0.1 mm sieve respectively.(ABSTRACT TRUNCATED AT 400 WORDS)


Updates on targeting human epidermal growth factor receptor 2-positive breast cancer: what's to know in 2021.
To highlight recent practice changing clinical trials, focusing on those leading to new drug approvals, in human epidermal growth factor receptor 2-positive (HER2+) breast cancer. The improved disease-free survival of adjuvant trastuzumab emtansine (T-DM1) over trastuzumab in patients with residual disease has made neoadjuvant sequencing of therapy standard for most patients with early stage disease. In patients with metastatic HER2+ breast cancer, trastuzumab deruxtecan has recently shown dramatically improved efficacy over T-DM1. Tucatinib is an oral tyrosine kinase inhibitor with best in class blood-brain barrier penetration. Margetuximab, a novel HER2-targeted chimeric monoclonal antibody with an engineered Fc receptor designed to activate local immune response, was recently approved in heavily pretreated patients based on modest but significant improvement in progression-free survival. Patients with HER2+ breast cancer have a variety of therapeutic options in the early stage and metastatic setting. Optimal sequencing of therapy will depend on patient-specific factors such as site of tumor progression and underlying comorbidities. De-escalation of the first-line metastatic regimen may be considered in select patients with hormone positive/HER2+ breast cancer, by using endocrine therapy instead of chemotherapy in combination with HER2-targeted therapy, which may improve side effects without sacrificing efficacy.


Mycophenolic acid reverses TGF beta-induced cell motility, collagen matrix contraction and cell morphology in vitro.
The aim of this study was to elucidate functional and molecular effects of mycophenolic acid (MPA) on non-lymphatic, kidney epithelial cells treated with transforming growth factor (TGF). MPA effects were studied using HK2 cells incubated with EGF and TGF. The reversibility of these effects was verified using guanosine and 8-aminoguanosine. The following assays were applied: cell proliferation, viability, collagen matrix contraction, scratch wound closure, spindle index, FACS with anti-CD29 and anti-CD326, promoter demethylation of RAS protein activator like 1 (RASAL1), as well as gene expression of RASAL1, integrin 1ß (ITGB1) (CD29) and epithelial cell adhesion molecule (EpCam) (CD326). Cell proliferation was inhibited by increasing concentrations of MPA, whereas neither apoptosis nor cytotoxicity was detected. Stimulation with EGF and/or TGF led to a significant collagen matrix contraction that was successfully inhibited by MPA. In addition, scratch wound closure was inhibited by incubation with TGF alone or with EGF. Under the same conditions, cell morphology (spindle shape) and molecular phenotype (ITGB1(High)EpCam(Low)/ITGB1(Low)EpCam(High)) were both significantly changed, suggesting an epithelial to mesenchymal transformation. Cell morphology and motility, as well as molecular phenotype, were reversible after MPA treatment with TGF transformation in both presence/absence of EGF, thereby suggesting a correlation with the previously described antifibrotic effects of MPA. Dysregulation of TGF signal transduction appears to be related to progression of fibrosis. A TGF-transformed kidney epithelial cell line derived from human proximal tubules was used to study whether the immunosuppressive drug: MPA possesses any functional or molecular antifibrotic effects. Functional and morphological in vitro changes induced by both the TGF and epithelial-growth-factor were reversible by treatment with MPA. An inhibitory effect of MPA on the TGF pathway appears to be responsible for the previously described antifibrotic effects of the MPA in the COL4A3-deficient mouse model of renal fibrosis.


Transforaminal Endoscopic Approach for Lumbar Extraforaminal Synovial Cysts: Technical Note.
Lumbar facet cysts are commonly seen in degenerative lumbar conditions causing stenosis and radiculopathy. Extraforaminal lumbar facet cysts are a rare entity and present a surgical challenge because of their location. Transforaminal endoscopic spine surgery is an emerging technique in spine surgery but has never been described as a treatment option for lumbar radiculopathy in the setting of extraforaminal lumbar facet cyst. A technique for the transforaminal endoscopic treatment of an extraforaminal lumbar facet cyst is presented in 2 patients. We retrospectively reviewed 321 cases of patients who underwent transforaminal endoscopic surgery in a 4-year period with a minimum follow-up of 2 years. A series of 2 patients who underwent transforaminal endoscopic foraminotomy and cyst resection procedures for extraforaminal lumbar facet cysts between 2014 and 2017 is presented: A 51-year-old woman with a right L4-5 extraforaminal cyst improved from a preoperative visual analog scale (VAS) of 7 and Oswestry disability index (ODI) of 26 to a 1-year postoperative VAS score of 2 and ODI of 4; and a 71-year-old woman with a left L5-S1 extraforaminal cyst improved from a preoperative VAS of 7 and ODI of 30 to a 1-year postoperative VAS score of 2 and ODI of 6. Transforaminal endoscopic surgery for a lumbar radiculopathy in the setting of an extraforaminal lumbar facet cyst is presented as a unique minimally invasive approach for the treatment of extraforaminal lumbar facet cyst that avoids facet resection and fusion.


Diabetes mellitus induced by somatostatin analogue therapy is not permanent in acromegalic patients.
Therapy with somatostatin analogues (SSAs) may have deleterious effects on glucose metabolism in patients with acromegaly, often leading to the development of diabetes mellitus (DM). The aim of the study was to evaluate whether DM, developed during therapy with SSAs, may revert after drug withdrawal and cure of acromegaly with pituitary adenomectomy. Retrospective cohort study, in a tertiary referral centre. Eighteen acromegalic patients without DM at the diagnosis of acromegaly treated with SSAs as a primary therapy, and then cured by pituitary adenomectomy. Endocrine status and glucose homeostasis were evaluated at diagnosis of acromegaly and at least every 6 months during SSA therapy. At each visit, patients were classified into one of the following classes: normal glucose tolerance, prediabetes, overt diabetes. Median follow-up after starting SSAs therapy was 69 months (IQR 54.75-132.25). During SSA therapy, all patients had controlled acromegaly defined by normal serum IGF1 concentrations for the age. Of the 13 euglycaemic patients at diagnosis, three developed prediabetes and three diabetes, whereas, of the five prediabetic patients at diagnosis, two worsened to overt diabetes and three remained in the prediabetic range (P = 0.04). After curing acromegaly with pituitary adenomectomy and subsequent SSA withdrawal, prediabetes reverted in five of six patients, and diabetes in all five patients (three reverted to euglycaemia, while two reverted to prediabetes) (P = 0.01). In acromegalic patients with controlled disease, changes in glycaemic status induced by SSAs are not permanent.


The percutaneous treatment of angioaccess graft complications.
In the last decade, percutaneous techniques have been used with increasing frequency to treat angioaccess graft complications. The role of these procedures and their outcomes in patients on hemodialysis remains unclear. The records of all patients receiving percutaneous treatment of failed or failing angioaccess grafts were reviewed. Patient demographics, site and type of percutaneous intervention, and results of treatment were recorded. Survival curves were plotted using the Kaplan-Meier method, and differences in times to first failure between types of intervention were tested using the log rank method. Grafts not requiring thrombolysis had significantly higher patency rates than those that did (P < 0.0001). Patency of grafts undergoing angioplasty of sites remote from the venous anastomosis were significantly higher than those of grafts undergoing venous anastomotic dilatation (P = 0.0004). Percutaneous techniques are most effective in treating failing but patent angioaccess grafts, especially those with stenoses remote from the venous anastomosis. The efficacy of percutaneous techniques diminishes significantly when used to treat grafts that have progressed to occlusion.


Snowboarding trauma.
Injuries sustained by 487 snowboarders over 1991-1993 winter seasons and 565 injury cases compiled nationally were reviewed. Over 80% of patients in both series are between 5 and 24 years old. Distal radius (wrist) fractures and upper extremity soft tissue trauma were common injuries. None of the Vermont snowboarders wore protective equipment. Snowboarding is a sport with the potential for disabling injuries in a young segment of the population. To reduce the number of injuries, all participants should wear protective wrist and upper extremity pads. The mechanism of injury in most injured snowboarders was loss of control of the equipment. More injuries are expected in this popular sport without mandated protective equipment and training.


Anesthetic management of patients with pheochromocytomas: a report of three cases.
The perioperative management of patients with pheochromocytoma is a challenge to even the most seasoned practitioner. Preoperative preparation, close monitoring, and anticipation of hemodynamic changes is critical for a successful outcome.


Ataxia telangiectasia mutated (Atm) knockout mice as a model of osteopenia due to impaired bone formation.
ATM is a member of the PI-3 kinase protein family, encoded by the gene, ATM, responsible for ataxia telangiectasia (AT). AT is recognized as a genomic instability syndrome, sharing accelerated senescence symptoms in human and mouse. Here, we present evidence that the bone phenotype of Atm knockout (AtmKO) mice is similar to that observed in disuse and/or aging syndromes. A significant decrease in 3-dimensional bone volume fraction (BV/TV) of the fifth lumbar vertebra was observed in AtmKO mice by microCT, compared with heterozygous control mice at 10 weeks of age. Bone histomorphometry revealed that both BFR/BS and Oc.S/BS were significantly decreased in KO mice. To determine the cellular basis of this bone phenotype, we employed in vitro osteoclastogenesis and colony formation assays using bone marrow cells derived from KO and control mice. There was no difference in osteoclast formation in ex vivo cultures. CFU-F was markedly reduced in AtmKO-derived cultures compared with control mice, whereas differentiation of calvaria-derived osteoblasts did not differ between the genotypes. Furthermore, expression levels of IGF1R were significantly decreased, and p38 was aberrantly phosphorylated in marrow stromal cells from AtmKO mice. These results indicate that the pathogenesis of the osteopenic phenotype in AtmKO mice is similar to that of disuse and/or aging syndromes and is caused, at least in part, by a stem cell defect due to lack of IGF signaling.


Determination of the structure of the Escherichia coli K100 capsular polysaccharide, cross-reactive with the capsule from type b Haemophilus influenzae.
The structure of the Escherichia coli K100 capsular polysaccharide, cross-reactive with that from type b Haemophilus influenzae, was determined by using a combination of chemical and spectroscopic techniques. The structure of the K100 repeating unit was found to be----3)-beta-D-Ribf-(1----2)-D-ribitol-5-(PO4----. The K100 polysaccharide is thus identical in composition to, but different in linkage from, the H. influenzae type b capsular polysaccharide, which has beta-D-Ribf-(1----1)-D-ribitol linkages.


Rapid amplification of 5' complementary DNA ends (5' RACE).
This method is used to extend partial cDNA clones by amplifying the 5' sequences of the corresponding mRNAs 1-3. The technique requires knowledge of only a small region of sequence within the partial cDNA clone. During PCR, the thermostable DNA polymerase is directed to the appropriate target RNA by a single primer derived from the region of known sequence; the second primer required for PCR is complementary to a general feature of the target-in the case of 5' RACE, to a homopolymeric tail added (via terminal transferase) to the 3' termini of cDNAs transcribed from a preparation of mRNA. This synthetic tail provides a primer-binding site upstream of the unknown 5' sequence of the target mRNA. The products of the amplification reaction are cloned into a plasmid vector for sequencing and subsequent manipulation.


Endoscopic management of renal lymphangioma: a case report.
A 46-year-old woman presented with total painless gross hematuria, an 8-mm polypoid mass that proved to be a lymphangioma was found in the upper pole collecting system of the left kidney. The mass was resected ureteroscopically with holmium laser fulguration of the base. The few reported cases of this rare lesion suggest that rigorous postoperative surveillance is not necessary for this benign condition.


Success of day-case treatment of zygomatic and orbital fractures.
Traditionally, surgical management of zygomaticomaxillary complex (ZMC) and orbital fractures occurs within two to three weeks of the injury, followed by an overnight admission to allow for extended eye observations. This is due to the risk of postoperative retrobulbar haemorrhage (RBH) or orbital compartment syndrome (OCS), a rapidly progressive and sight threatening emergency that requires immediate intervention. In September 2016 the oral and maxillofacial surgery (OMFS) department at Leeds Teaching Hospitals redesigned their trauma service with a full-time trauma consultant, a dedicated clinic, and a weekly morning elective trauma theatre list. This allowed for standardisation of the management of patients with OMFS injuries. Furthermore, a formal day-case ZMC and orbital fracture pathway was developed to allow patients to undergo surgical management of such fractures with a same-day discharge. This has since been identified as an area of excellence by the Getting It Right First Time (GIRFT) programme, and is in line with the addition of ZMC and orbital fractures to the procedural list written by the British Association of Day Case Surgery (BADS). Unbeknown to the unit, the volume of day-case procedures was the highest within the UK, demonstrating the importance of GIRFT in highlighting areas of good or unique practice. The aim of this study was to determine the impact of our day-case pathway and designated OMFS trauma service on compliance with recent recommendations by GIRFT and BADS. Secondly, it was to determine the safety of same-day discharge with regards to postoperative complications.


Oral health knowledge and practice of 12 to 14-year-old Almajaris in Nigeria: A problem of definition and a call to action.
We studied oral health knowledge and practices of 12 to 14-year-old Almajiri boys in northern Nigeria because we found few studies on their health, and none on their oral health. We present our study after explaining the desperate life circumstances and context of Nigeria's approximately 10 million Almajiri youth. Our results, when compared with those of previously studied populations (those most similar in terms of environment, age range, and oral health characteristics) show that the Almajiris fare poorly. Although the international community has paid some attention to the Nigerian Almajiri children's educational needs, there has been little support for health, and none for oral health. We argue that the World Health Organization could better assist Nigeria and these children by assuring that the Almajiris are not excluded from programs targeting children classified as 'street children', and make specific recommendations.


NLRP3 inflammasome inhibitor CY-09 reduces hepatic steatosis in experimental NAFLD mice.
Non-alcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases. The NOD-like receptor protein 3 (NLRP3) inflammasome was suggested to be involved in the pathogenesis of NAFLD. A small-molecule named CY-09 is a new selective and direct inhibitor of the NLRP3 inflammasome. We aimed to investigate whether CY-09 is effective for the treatment of NAFLD in a high-fat diet (HFD)-induced mouse model. Twenty mice were fed by HFD for 14 weeks, and then were randomly assigned into two groups: (1) control group receiving dimethylsulfoxide (DMSO) solution; (2) CY-09 group receiving CY-09 injection. In an 8-week follow-up, oral glucose tolerance test (OGTT) and homeostasis model assessment of insulin resistance (HOMA-IR) were used to measure glucose metabolism. Liver steatosis was evaluated by the NAFLD activity score (NAS) and deemed as the primary outcome. The body weight in CY-09 group was significantly lower than the DMSO control group on 27 weeks (41.0 ± 3.5 g vs. 49.7 ± 5.2 g, P = 0.014). The area under the curve (AUC) of OGTT was less in CY-09 group than that in DMSO group (35.81 ± 6.79 vs. 22.91 ± 2.58 mmol/L·hr, P = 0.004), as well as HOMA-IR (14.36 ± 3.89 vs. 8.82 ± 2.04 mmol.mIU.L-2, P = 0.023). Microscopically, liver lipid droplets dramatically improved and significantly lower NAS was observed in CY-09 group (8.25 ± 1.26 vs. 3.20 ± 0.45, P < 0.001). CY-09 reduces hepatic steatosis in experimental NAFLD mice and CY-09 may be a potential therapeutic drug of NAFLD in clinical practice.


Inhibitory effect of sesaminol glucosides on lipopolysaccharide-induced NF-kappaB activation and target gene expression in cultured rat astrocytes.
The inflammatory reaction plays an important role in the pathogenesis of the neurodegenerative disorder including Alzheimer's disease (AD). Sesame lignan compounds such as sesaminol glucosides (SG) exhibit a range of pharmacological activities including anti-oxidative and anti-inflammatory action. In this study, we tried to elucidate possible effects of SG on lipopolysaccharide (LPS)-induced inflammatory reaction and its underlying mechanism in cultured astrocytes. SG (10-100 microg/ml) inhibited LPS-induced generation of nitric oxide (NO) and reactive oxygen species (ROS), as well as inhibited LPS-induced cytosolic phospholipase A2 (cPLA2), cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) expression dose-dependently. This inhibitory effect of SG on NO and ROS generation was enforced by addition of glutathione (GSH) in culture. In addition, SG prevented LPS-induced DNA binding and transcriptional activity of nuclear factor KappaB (NF)-kappaB. Consistent with the inhibitory effect on NF-kappaB activity, SG inhibits phosphorylation and degradation of inhibitory KappaB (IkappaB), thereby translocation of p50 of NF-kappaB. These data show that SG has an anti-inflammatory effect through inhibition of NF-kappaB, and may be a useful agent for prevention of inflammatory disease like AD.


Requirement of norD for Brucella suis virulence in a murine model of in vitro and in vivo infection.
A mutant of Brucella suis bearing a Tn5 insertion in norD, the last gene of the operon norEFCBQD, encoding nitric oxide reductase, was unable to survive under anaerobic denitrifying conditions. The norD strain exhibited attenuated multiplication within nitric oxide-producing murine macrophages and rapid elimination in mice, hence demonstrating that norD is essential for Brucella virulence.


Photooxidation of atrazine and its influence on disinfection byproducts formation during post-chlorination: effect of solution pH and mechanism.
Partial photooxidation of micropollutants may lead to various degradation intermediates, obviously affecting disinfection byproducts (DBPs) formation during the post-chlorination process. The photooxidation of atrazine (ATZ) in aqueous solutions with low-pressure mercury UV lamps in UV, UV/H2O2 and UV/TiO2 treatment system and the formation of chlorinated disinfection byproducts (DBPs) during subsequent chlorination processes including dichloroacetic acid (DCAA), trichloroacetic acid (TCAA), 1,1,1-trichloro-2-propanone (TCP), trichloromethane (TCM) and chloropicrin (CHP) were investigated in this study. The effect of solution pH on the oxidation pathway of ATZ in three UV photooxidation treatment process and the impact of photooxidation on the DBPs formations were assessed. Based on UPLC-ESI-MS/MS analyses, identification of main oxidation intermediates was performed and the plausible degradation pathways of ATZ in photooxidation system were proposed, indicating that photooxidation of ATZ in UV/H2O2 and UV/TiO2 process system was significantly pH-dependent processes. Dichloroacetic acid (DCAA), trichloroacetic acid (TCAA), 1,1,1-trichloro-2-propanone (TCP), trichloromethane (TCM) and chloropicrin (CHP) were detected in photooxidized ATZ solutions. Compared to the other three DBPs, TCM and TCP were the main DBPs formed. The DBPs formations were greatly promoted in oxidized ATZ solutions. Solution pH and UV irradiation time exhibited obvious impact on the DBPs formation on the basis of DBP species. The variation tendency of DBPs observed relates to the combustion of ATZ in photooxidation system and the production oxidation intermediates.


LRRK2 phosphorylates Snapin and inhibits interaction of Snapin with SNAP-25.
Leucine-rich repeat kinase 2 (LRRK2) is a gene that, upon mutation, causes autosomal-dominant familial Parkinson's disease (PD). Yeast two-hybrid screening revealed that Snapin, a SNAP-25 (synaptosomal-associated protein-25) interacting protein, interacts with LRRK2. An in vitro kinase assay exhibited that Snapin is phosphorylated by LRRK2. A glutathione-S-transferase (GST) pull-down assay showed that LRRK2 may interact with Snapin via its Ras-of-complex (ROC) and N-terminal domains, with no significant difference on interaction of Snapin with LRRK2 wild type (WT) or its pathogenic mutants. Further analysis by mutation study revealed that Threonine 117 of Snapin is one of the sites phosphorylated by LRRK2. Furthermore, a Snapin T117D phosphomimetic mutant decreased its interaction with SNAP-25 in the GST pull-down assay. SNAP-25 is a component of the SNARE (Soluble NSF Attachment protein REceptor) complex and is critical for the exocytosis of synaptic vesicles. Incubation of rat brain lysate with recombinant Snapin T117D, but not WT, protein caused decreased interaction of synaptotagmin with the SNARE complex based on a co-immunoprecipitation assay. We further found that LRRK2-dependent phosphorylation of Snapin in the hippocampal neurons resulted in a decrease in the number of readily releasable vesicles and the extent of exocytotic release. Combined, these data suggest that LRRK2 may regulate neurotransmitter release via control of Snapin function by inhibitory phosphorylation.


A large animal model to evaluate the effects of Hsp90 inhibitors for the treatment of lung adenocarcinoma.
Ovine pulmonary adenocarcinoma (OPA) is a naturally occurring lung cancer of sheep caused by Jaagsiekte sheep retrovirus (JSRV). The JSRV envelope glycoprotein (Env) functions as a dominant oncoprotein in vitro and in vivo. In order to develop the basis for the use of OPA as a lung cancer model, we screened a variety of signal transduction inhibitors for their ability to block transformation by the JSRV Env. Most inhibitors were not effective in blocking JSRV Env-induced transformation. On the contrary, various Hsp90 inhibitors efficiently blocked JSRV transformation. This phenomenon was at least partly due to Akt degradation, which is activated in JSRV-transformed cells. Hsp90 was found expressed in tumor cells of sheep with naturally occurring OPA. In addition, Hsp90 inhibitors specifically inhibited proliferation of immortalized and moreover primary cells derived from OPA tumors. Thus, OPA could be used as a large animal model for comprehensive studies investigating the effects of Hsp90 inhibitors in lung adenocarcinoma.


Occurrence of fungal metabolites--fumonisins at the ng/L level in aqueous environmental samples.
The B-series fumonisins (FBs) are some of the most prevalent mycotoxins produced as a secondary metabolite by Fusarium species growing on cereals. For decades they have been studied extensively in food and feed products, but there is no information about their occurrence in the aquatic environment or about how these mycotoxins are transported to the surface water and the groundwater. The aim of this study was to clarify the causes of fumonisin occurrence in aquatic ecosystems by examining the relation between mycotoxin contamination of crops and their levels in the aquatic environment. Water samples were collected from drainage ditches and wells or watercourses located in agricultural areas in the Wielkopolska region, Poland. Our research conducted on an annual basis showed the seasonal variability of fumonisin B1 concentration in the analyzed water samples, with the highest concentration in the post-harvest season (September to October) at 48.2 ng L(-1), and the lowest in winter and spring at 21.9 ng L(-1). Fumonisins B2 and B3 in water samples were not detected. Cereal samples were collected in the harvest season from each agricultural area close to tested water bodies. Mycotoxins were present in all cereal samples at concentrations from 43.3 to 1055.9 ng g(-1). Our results confirm that fumonisins are transported to aquatic systems by rainwater through soil. On the basis of available literature, this is the first report concerning the presence of fumonisin B1 in different aquatic environments. To date their ecotoxicological effects are largely unknown and require further investigation.


Neurologic Complications After Kidney Transplantation.
The clinical focus after kidney transplantation often is centered on graft function. However, neurologic complications are a common, significant, and under-recognized contributor to patient morbidity and mortality. Neurologic syndromes can arise through exacerbation of pre-existing conditions or can be newly acquired in the setting of increased risk of infection and drug toxicity after transplantation. We present a comprehensive review of neurologic complications after kidney transplantation.


The surgical intensive care unit of The Mount Sinai Hospital: a brief history focusing on contributions to academic critical care medicine and excellence in patient care.
The Mount Sinai Hospital Surgical Intensive Care Unit (SICU) was founded in 1969. Drs. William Shoemaker and Christopher Bryan-Brown were the first directors. Since it was founded, the SICU has been an integral part of the Mount Sinai Medical Center, providing a wide variety of clinical services including critical care, central line placement, and nutritional consultation. As one of the largest training programs in the United States and a frequent contributor to the medical literature, the SICU has also played a vital role in academic critical care medicine.


Bioresorbable Vascular Scaffold for the Treatment of Coronary Bifurcation Lesions: Immediate Results and 1-year Follow-up.
The treatment of coronary lesions with a bioresorbable vascular scaffold has been shown to be effective. However there is little information about its use in bifurcations. The aim of this study was to analyze the safety and efficacy of the bioresorbable scaffold in the treatment of coronary bifurcation lesions. From January 2012 to January 2015, we used a bioresorbable vascular scaffold to treat 194 patients with 230 bifurcation lesions. The scaffold geometry was examined by intracoronary imaging techniques in 145 bifurcations (65%). In all, 78% of the bifurcations were evaluated angiographically during follow-up (computed tomography angiography in 138 and coronary angiography in 41). The most common clinical presentation was acute coronary syndrome (81%). The most frequent type of bifurcation was 1,1,1 (34%). A simple approach was the chosen strategy in 221 bifurcations (96%). In 90 of these lesions, the side branch was postdilated through the cells of the platform and, in 3 cases, strut fractures were observed in optical coherence tomography. Procedural success was achieved in all patients. There was 1 case of subacute thrombosis and 1 sudden cardiac death during the first month. The duration of angiographic follow-up was 7.3±1.6 months and that of clinical follow-up, 14±6 months. Twelve (5%) restenoses were documented and revascularized. During follow-up, 2 patients (1%) had an infarction in another territory and another 2 patients (1%) died; the remaining patients had a symptom-free follow-up. The incidence of thrombosis was 1.3%. Treatment of bifurcation coronary lesions using a provisional approach is feasible and safe, with a low rate of adverse events.


LRRC31 is induced by IL-13 and regulates kallikrein expression and barrier function in the esophageal epithelium.
Eosinophilic esophagitis (EoE) is an allergic inflammatory disease of the esophagus featuring increased esophageal interleukin-13 (IL-13) levels and impaired barrier function. Herein, we investigated leucine-rich repeat-containing protein 31 (LRRC31) in human EoE esophageal tissue and IL-13-treated esophageal epithelial cells. LRRC31 had basal mRNA expression in colonic and airway mucosal epithelium. Esophageal LRRC31 mRNA and protein increased in active EoE and strongly correlated with esophageal eosinophilia and IL13 and CCL26 (chemokine (C-C motif) ligand 26) mRNA expression. IL-13 treatment increased LRRC31 mRNA and protein in air-liquid interface-differentiated esophageal epithelial cells (EPC2s). At baseline, differentiated LRRC31-overexpressing EPC2s had increased barrier function (1.9-fold increase in transepithelial electrical resistance (P<0.05) and 2.8-fold decrease in paracellular flux (P<0.05)). RNA sequencing analysis of differentiated LRRC31-overexpressing EPC2s identified 38 dysregulated genes (P<0.05), including five kallikrein (KLK) serine proteases. Notably, differentiated LRRC31-overexpressing EPC2s had decreased KLK expression and activity, whereas IL-13-treated, differentiated LRRC31 gene-silenced EPC2s had increased KLK expression and suprabasal epithelial detachment. We identified similarly dysregulated KLK expression in the esophagus of patients with active EoE and in IL-13-treated esophageal epithelial cells. We propose that LRRC31 is induced by IL-13 and modulates epithelial barrier function, potentially through KLK regulation.


Surgical reconstruction for penile fracture: a systematic review.
Penile fracture is a rare condition that describes the rupture of the corpus cavernosum following direct, high-pressure trauma to the erect penis. There is no standardized management algorithm for these patients. We performed a systematic review of the past 10 years regarding management of penile fractures. A complete PRISMA-P 2015 checklist was performed where we reviewed English articles published over the past 10 years to identify 105 articles, where 63 articles were of relevance and subsequently narrowed to a total of 28 articles into the final review for this study. We determined that immediate penile exploration and tunica repair is considered the most common and current management of penile fractures with experts demonstrating that it leads to the fastest in recovery in erectile function and positive cosmetic outcomes. However, we also determined that the specific algorithm can be variable-down to the suture material, use of catheterization, urethroplasty when involved, and length of recovery/follow-up. In the last several decades, men with penile fracture have been treated, in most cases, with immediate surgical intervention. This review highlights the varying practices regarding surgical exploration, injury repair, and postoperative management in men with a penile fracture. Immediate penile exploration and tunica repair have been the mainstay approach of management.


Time course of blood nerve barrier reconstitution after sectioning: implications for xenograft studies.
The time course of blood-nerve barrier recovery in mouse nerves was studied after proximal and distal segmental sciatic sections. Transfer constants for uptake of isotopically labeled sucrose and urea were determined. Sectioned segments were examined ultrastructurally. Marked alterations in isotope uptake for 2 months with gradual restoration of blood-nerve barrier by 6 months was found. Ultrastructure of sectioned segments showed increased numbers of perineurial compartments. Human nerve xenografts to immunosuppressed animals remain hypomyelinated for 6 months which may be related to damage to the blood-nerve barrier.


Prior chronic stress induces persistent polyI:C-induced allodynia and depressive-like behavior in rats: Possible involvement of glucocorticoids and microglia.
When animals suffer from viral infections, they develop a set of symptoms known as the "sickness response." Recent studies suggest that psychological stress can modulate the sickness response. However, it remains uncertain whether acute and chronic psychosocial stresses have the same effect on viral infection-induced sickness responses. To address this question, we compared changes in polyI:C-induced sickness responses, such as fever, change of body weight and food intake, mechanical allodynia, and depressive-like behavior, in rats that had been pre-exposed to single and repeated social defeat stresses. Intraperitoneal injection of polyI:C induced a maximal fever of 38.0°C 3h after injection. Rats exposed to prior social defeat stress exhibited blunted febrile responses, which were more pronounced in the repeated stress group. Furthermore, only the repeated stress group showed late-onset and prolonged mechanical allodynia lasting until 8days after injection in the von Frey test and prolonged immobility time in the forced swim test 9days post-injection. To assess the role of glucocorticoids and microglia in the delayed and persistent development of these sickness responses in rats exposed to repeated stress, we investigated the effect of pretreatment with RU486, a glucocorticoid receptor antagonist, and minocycline, an inhibitor of microglial activation, on polyI:C-induced allodynia and depressive-like behavior. Pretreatment with either drug inhibited both the delayed allodynia and depressive-like behavior. The present study demonstrates that repeated, but not single, social defeat stress followed by systemic polyI:C administration induced prolonged allodynia and depressive-like behavior in rats. Our results show that even though a single-event psychosocial stress does not have any effect by itself, animals may develop persistent allodynia and depressive-like behavior when they suffer from an infectious disease if they are pre-exposed to repeated or chronic psychosocial stress. Furthermore, this study suggests that stress-induced corticosterone and microglial activation play a pivotal role in this phenomenon.


Post-COVID-19 conditions in children and adolescents diagnosed with COVID-19.
This study aimed to investigate the prevalence of and the factors associated with post-COVID-2019 condition in COVID-19 children and adolescents in Germany. The present retrospective cohort study used data from the Disease Analyzer database (IQVIA), and included patients aged <18 years who were diagnosed with COVID-19 in one of 524 general and 81 pediatric practices in Germany between October 2020 and August 2021 (index date: first COVID-19 diagnosis). Post-COVID-19 condition was assessed between the index date and November 2021. Covariates included age, sex, type of practice, and chronic conditions documented in at least 1% of the population. There were 6568 children and adolescents included in this study (mean [SD] age 10.1 [4.9] years; 49.2% girls). The prevalence of post-COVID-19 condition was 1.7% in the population. Patients aged 13-17 years were more likely to be diagnosed with post-COVID-19 condition compared with those being aged ≤5 years (RR = 3.14). Anxiety disorders (RR = 2.53), somatoform disorders (RR = 2.11), and allergic rhinitis (RR = 2.02) were also significantly associated with post-COVID-19 condition. Post-COVID-19 condition was rare in COVID-19 children and adolescents in Germany. Data from other settings are warranted to confirm these findings. The prevalence of post-COVID-19 condition was 1.7% in this population of children and adolescents. Older children and adolescents were more likely to be diagnosed with post-COVID-19 condition than their younger counterparts. Anxiety disorders, somatoform disorders, and allergic rhinitis were significantly associated with post-COVID-19 condition. More data from other settings and countries are warranted to corroborate or refute these findings.


Ultrasound-Guided Chest Compressions in Out-of-Hospital Cardiac Arrests.
There is a significant variability in survival rates for cardiopulmonary resuscitation (CPR) in out of-hospital cardiac arrest (OHCA), and some data indicate that ultrasound improves CPR. We evaluated the feasibility of ultrasound for monitoring chest compressions in OHCA. We planned a prospective study in patients with an ultrasound-integrated CPR for OHCA. Chest compressions were performed on the intermammillary line (IML), but the position was changed according to the quality of the heart squeezing, evaluated by ultrasound. End-tidal carbon dioxide (ETCO2) was used as the control parameter. Then we compared the area with the highest squeezing with the position of the heart in the chest computed tomography (CT) scans of 20 hospitalized patients. Chest compressions were good, partial, and inadequate on the IML in 58.4%, 48.9%, and 2.8% of cases, respectively. These percentages were 75%, 25%, and 0% after these modifications: none (47.2%), increased depth (8.3%), hands moved on the lower third of the sternum (27.8%), on left parasternal line of the lower part of the sternum (13.9%), and on the center of the sternum (1 case). Accordingly, ETCO2 improved significantly (20.37 vs. 37.10, p < 0.0001). The CT scans showed that the larger biventricular area (BVA) was under the parasternal line of the lower third of the sternum, and the mean distance IML-BVA was 5.7 cm. Our study has demonstrated that CPR in OHCA can be improved using ultrasound and changing the position of the hands. This finding was connected with the ETCO2 and confirmed by chest CT scans.


Enzymatic radioimmunoassay for detecting Leptospira interrogans serovar pomona in the urine of experimentally-infected pigs.
An enzymatic radioimmunoassay (ERIA) has been developed for detecting Leptospira interrogans serovar pomona in porcine urine. Four grower pigs were experimentally infected with serovar pomona. A total of 39 urine samples was collected, and ERIA was compared with dark ground microscopy (DGM) and culture for demonstrating leptospiruria. Of 20 samples positive by at least one technique, leptospires were detected by ERIA in 14, by culture in 16 and by DGM in 13. ERIA, unlike the other 2 methods, was suitable for use with urine which had been stored frozen for several months.


Temperature leads to annual changes of plant community composition in alpine grasslands on the Qinghai-Tibetan Plateau.
In most grassland ecosystems, the effects of mean temperature increase on plant communities have been investigated; however, the effects of climate fluctuations on local plant community metrics are much less well understood. We conducted a nine-year survey in alpine meadow and alpine steppe to investigate the effects of inter-annual temperature and precipitation variation on plant community composition, species richness, and species diversity on the central Qinghai-Tibetan Plateau, China. We unexpectedly found that annual variability of growing season temperature, and not precipitation, is a driver of plant composition and species diversity in both habitats. Generally, increasing temperature had a negative effect on species diversity in meadow (r2 = 0.94) and steppe (r2 = 0.95). In the meadow habitat, the proportion of grass decreased with increasing temperature and ultimately had positive impacts on the proportion of sedges. In steppe habitat, legumes increased and forbs decreased with the increase of growing season temperature; both legumes and forbs negatively affected proportion of grass and resulted in grass remaining stable under temperature change. Our results provide evidence that responses of functional group composition and species richness to temporal change of temperature are very different from those responses to mean temperature increase on the central Qinghai-Tibetan Plateau. In our results, temperature is a main regulator for annual variation of functional group composition and species richness, while soil water content is a dominant regulator for community responses in other experimental warming studies.


Dolichoectasia Presenting as Renal Artery Aneurysm in a Deceased Donor Kidney: A Case Report and Review of the Literature.
We describe a case of fusiform aneurysm of the renal artery on a background of dolichoectasia in a kidney recovered from a deceased donor. The donor, a 57-year-old female, had died of an extensive nonsurvivable subarachnoid hemorrhage. Fusiform aneurysms involving the main renal artery and its superior branch had extended into the hilum with insufficient accessible stump for safe reconstruction. Placement of a stent through an intraoperative radiologic intervention was not possible without compromising renal perfusion. Consequently, renal transplant did not proceed. Dolichoectasia is a condition associated with generalized weakness of the arterial vascular wall and may result in aneurysm formation. When the renal artery is involved, a safe reconstruction excising the aneurysmal segment may be considered before transplant of the kidney.


Increased intestinal P-glycoprotein expression and activity with progression of diabetes and its modulation by epigallocatechin-3-gallate: Evidence from pharmacokinetic studies.
The aim of this study was to evaluate the change in the expression and the activity of intestinal P-glycoprotein (efflux transporter) with progression of diabetes in rats. Diabetes was induced in Wistar rats using a combination of low dose streptozotocin along with high fat diet. The expression of intestinal P-glycoprotein significantly increased (P≤0.05) with the progression of diabetes which was inferred from the mRNA analysis of mdr1a and mdr1b genes in the ileum segment of rat intestine. Furthermore, a significant increase (P≤0.05) in Na(+)-K(+) ATPase activity was observed in the ileum segment of rat intestine with the progression of diabetes. As a result of this, a significant decrease in the intestinal uptake and peroral bioavailability of the P-glycoprotein substrates (verapamil and atorvastatin) was observed along with the progression of diabetes as compared to normal animals. To address this problem of impaired drug uptake and bioavailability, a reported P-glycoprotein inhibitor, epigallocatechin-3-gallate, was experimentally evaluated. The treatment with epigallocatechin-3-gallate resulted in significant reduction in the expression and activity of P-glycoprotein and subsequent improvement in the intestinal uptake and peroral bioavailability of both verapamil and atorvastatin in normal as well as in diabetic animals. The findings of this study rationalised the use and established the mechanism of action of epigallocatechin-3-gallate to overcome P-glycoprotein mediated drug efflux and will also be helpful in therapeutic drug monitoring in diabetes.


Microplastics existence affected heavy metal affinity to ferrihydrite as a representative sediment mineral.
The coexistence of minerals, heavy metals and microplastics in sediment has been widely reported, while the interactions between minerals and heavy metals may be affected by the presence of microplastics. Therefore, to elucidate the effect of microplastics on the interactions between heavy metals and sediment minerals, this study conducted a series of experiments using polystyrene (PS) microplastics, Pb/Cr/Cd and ferrihydrite (Fh). The presence of PS microplastics with ferrihydrite (Fh-MPs200, mass ratio of ferrihydrite to PS of 200:1) improved the adsorption capacity of ferrihydrite, especially with an increase of 36 % for Pb. Morphological characterization demonstrated that the nano-ferrihydrite particles were dispersed on the surface of the PS microplastics, increasing the available reaction sites of the ferrihydrite particles. Furthermore, the results of zeta potential and pH effect showed that the reduction in electrostatic repulsion after adding PS was another critical reason for the increase in Pb adsorption by Fh-MP200. As a result, the presence of PS microplastics enhanced the complexation of Pb ions and the hydroxyl groups on the ferrihydrite surface. This study demonstrated that the presence of microplastics in the sedimentary environment can alter the dispersion and surface properties of minerals, thereby affecting the accumulation and transportation of heavy metals at the water-sediment interface.


Exploring the perceptions of radiographers pertaining to the provision of quality radiological services in Zimbabwe.
Radiology is part of the service industry; therefore, there is a need to understand quality and its associated factors. The cost of poor service quality is a loss of competitive advantage, increased litigation, misdiagnosis, unnecessary radiation exposure, and patient mortality. There has been little research into the factors influencing the quality of radiological services in Zimbabwe. This work, therefore, aimed to explore the radiographer's perceptions of the factors that affect the quality of radiological services at central hospitals in the Harare Metropolitan Province. A qualitative, explorative study applying the SERVQUAL model was carried out. One-on-one interviews with 10 purposively sampled radiographers employed at central hospitals in the Harare Metropolitan Province were conducted. The data were managed by Nvivo 12 (QSR International) and analyzed by framework analysis. Radiographer's perceptions of the factors that affect the quality of radiological services were categorized by five themes namely; i. Tangibles - the physical appearance of the radiology department and facilities, ii. Reliability and dependability - the ability to perform the promised service dependably and accurately, iii. Responsiveness - the willingness to help patients and provide prompt service, iv. Assurance - the knowledge and courtesy of radiology staff and their ability to inspire trust and confidence, and v. Empathy - caring, the individualized attention the radiology department provides to its patients. Economically viable, well-designed national strategies are needed to prioritize and fund radiology in Zimbabwe and other resource-constrained settings. Recognition of acquired specialist skills by radiographers to halt the exodus and training of radiologists, radiology nurses, medical physicists, and biomedical engineers by local institutions will go a long way in improving the quality of radiological services.


Restoration of conduction in the spinal roots correlates with clinical recovery from experimental autoimmune encephalomyelitis.
In the Lewis rat, acute experimental autoimmune encephalomyelitis (EAE) induced by inoculation with myelin basic protein (MBP) and adjuvants is characterized by tail and hindlimb weakness that resolves spontaneously after several days. In rats with neurological signs of this form of EAE (MBP-EAE) we have previously demonstrated demyelination and nerve conduction block in the proximal peripheral nervous system (PNS) and in the central nervous system (CNS). The present study was performed to assess conduction in the PNS and CNS, after recovery from acute MBP-EAE, using direct recordings from surgically exposed spinal roots and spinal cord dorsal columns. The study revealed that 1-2 weeks after clinical recovery from tail paralysis there was almost complete restoration of conduction in the sacral spinal roots but persistent severe conduction abnormalities in the dorsal columns. Significant restoration of conduction through the dorsal columns occurred over the following 2 weeks. These findings indicate that PNS conduction block due to a demyelinating polyradiculitis is a major cause of the neurological signs of acute MBP-EAE in the Lewis rat.


Enhanced biennial variability in the Pacific due to Atlantic capacitor effect.
The El Niño-Southern Oscillation (ENSO) and the variability in the Pacific subtropical highs (PSHs) have major impacts on social and ecological systems. Here we present an Atlantic capacitor effect mechanism to suggest that the Atlantic is a key pacemaker of the biennial variability in the Pacific including that in ENSO and the PSHs during recent decades. The 'charging' (that is, ENSO imprinting the North Tropical Atlantic (NTA) sea surface temperature (SST) via an atmospheric bridge mechanism) and 'discharging' (that is, the NTA SST triggering the following ENSO via a subtropical teleconnection mechanism) processes alternate, generating the biennial rhythmic changes in the Pacific. Since the early 1990s, a warmer Atlantic due to the positive phase of Atlantic multidecadal oscillation and global warming trend has provided more favourable background state for the Atlantic capacitor effect, giving rise to enhanced biennial variability in the Pacific that may increase the occurrence frequency of severe natural hazard events.


Influence of follicle stage on artificial ovary outcome using fibrin as a matrix.
Do primordial-primary versus secondary follicles embedded inside a fibrin matrix have different capabilities to survive and grow after isolation and transplantation? Mouse primordial-primary follicles showed a lower recovery rate than secondary follicles, but both were able to grow. Fresh isolated mouse follicles and ovarian stromal cells embedded in a fibrin matrix are capable of surviving and developing after short-term autografting. In vivo experimental model using 11 donor Naval Medical Research Institute (NMRI) mice and 11 recipient severe combined immunodeficiency (SCID) mice. Both ovaries from all NMRI mice were mechanically disrupted and primordial-primary and secondary follicles were isolated with ovarian stromal cells. They were then encapsulated in a fibrin matrix composed of 12.5 mg/ml of fibrinogen (F12.5) and 1 IU/ml of thrombin (T1) (F12.5/T1), and grafted to the inner part of the peritoneum of SCID mice for 2 and 7 days. This study was conducted at the Gynecology Research Unit, Université Catholique de Louvain. All materials were used to conduct histological (H-E staining) and immunohistochemical (Ki67, TUNEL) analyses. Although all grafted fibrin clots were recovered, the follicle recovery rate on day 2 was 16 and 40% for primordial-primary and secondary follicles respectively, while on day 7, it was 6 and 28%. The secondary group showed a significantly higher recovery rate than the primordial-primary group (23%, P-value <0.001). Follicles found in both groups were viable, as demonstrated by live/dead assays, and no difference was observed in the apoptosis rate between groups, as evidenced by TUNEL. Their growth to further stages was confirmed by Ki67 immunostaining. As demonstrated by our results, secondary follicles appear to be more likely to survive and develop than primordial-primary follicles in a fibrin matrix after both periods of grafting. These findings may also be attributed to the specific features of the fibrin matrix, which could benefit larger follicles, but not smaller follicles. This study is essential to understanding possible impairment caused by factors such as the isolation procedure or fibrin matrix composition to the survival and development of different follicle stages. It therefore provides the basis for further investigations with longer periods of grafting. This study was supported by grants from the Fonds National de la Recherche Scientifique de Belgique (grant Télévie No. 7.4578.14 and 7.4627.13, grant 5/4/150/5 awarded to Marie-Madeleine Dolmans), Fonds Spéciaux de Recherche, Fondation St Luc, the Foundation Against Cancer, and the Region Wallone (Convention N°6519-OVART) and donations from Mr Pietro Ferrero, Baron Frère and Viscount Philippe de Spoelberch. None of the authors have any competing interests to declare.


Positional cloning and comprehensive mutation analysis of a Japanese family with lithium-responsive bipolar disorder identifies a novel DOCK5 mutation.
Bipolar disorder (BD) is a severe psychiatric disorder characterized by the recurrence of depressive and manic episodes. Its heritability is high, and many linkage and association studies have been performed. Although various linkage regions and candidate genes have been reported, few have shown sufficient reproducibility, and none have identified the pathogenic genes based on the results of the linkage analysis. To find functional variants that are expected to be rare and have strong genetic effects, we recruited ten healthy individuals, two individuals with unknown status, and six patients with BD or recurrent major depressive disorder (MDD) from a Japanese family consisting of 21 members. We performed a genome-wide linkage analysis using a 100K single-nucleotide polymorphism (SNP) array and microsatellite markers to narrow linkage regions within this family. Subsequently, we performed whole-exome sequencing for two patients with BD to identify genetic mutations in the narrowed linkage regions. Then, we performed co-segregation analysis for DNA variants obtained from the results of the exome sequencing. Finally, we identified a rare heterozygous mutation in exon 31 of DOCK5 (c.3170A>G, p.E1057G). Convergent functional genomics analysis revealed that DOCK5 was listed as one of the biomarkers for mood state and suicidality. Although DOCK5 is still a functionally unknown gene, our findings highlight the possibility of a pathological relationship between BD and DOCK5.


Performance of the Matsumiya scoring system in cervical cancer patients with bone metastasis: an external validation study.
Accurate prognostic prediction of survival in cervical cancer patients with bone metastasis is important for treatment planning. We aimed to externally validate the Matsumiya scoring system using external patient data. We collected a retrospective cohort of patients with cervical cancer diagnosed with bone metastasis at Chiang Mai University Hospital from 1st January 2007 to 31st December 2016. The Matsumiya score was composed of 5 predictors, including the presence of extraskeletal metastasis, ECOG performance status, history of previous chemo- or radiotherapy, the presence of multiple bone metastasis, and bone metastasis-free interval < 12 months. Harrell's C-statistics and score calibration plots were used to evaluate the score performance. We also reconstructed the development study to estimate apparent performance values for comparison during external validation. A total of 124 cervical cancer patients with bone metastasis were included in this study. The 13-, 26-, and 52-week survival probabilities in the validation study were 70.1%, 50.5%, and 25.7%, respectively. Several differences were identified between development and validation studies regarding clinical characteristics, case-mix, and predictor-outcome associations. Harrell's C-statistics in the development and validation study were 0.714 and 0.567. The score showed poor agreement between the observed and the predicted survival probabilities in the validation study. Score reweighting and refitting showed only modest improvement in performance. A prognostic scoring system by Matsumiya et al. performed poorly in our cohort of Thai cervical cancer patients with bone metastasis. We suggested that the score should be sufficiently updated before being used.


Alkylation of DNA and hemoglobin in the mouse following exposure to ethene and ethene oxide.
Exposure of mice to 14C-labelled ethene or ethene oxide gave rise to hydroxyethylations of nucleophilic sites in hemoglobin and DNA. The relative amounts of alkylation products of different amino acids in hemoglobin were the same for the two compounds. Furthermore, the ratio between the degree of alkylation of DNA in various organs and of hemoglobin was approximately the same, supporting a previous conclusion that ethene oxide is the reactive intermediate formed in vivo from ethene. A comparison of the degrees of alkylation obtained per unit exposure dose (ppm X h) of ethene oxide and of ethene, respectively, showed that at low levels of ethene about 8% of the inhaled amount is metabolized to ethene oxide. It was estimated that the maximal rate of metabolism (Vmax) of ethene corresponds to exposure to an air level of 4 ppm of ethene oxide.


Poliovirus 2Apro expression inhibits growth of yeast cells.
Poliovirus encodes two proteases, 2Apro and 3Cpro that participate in the processing of the viral polyprotein and cleave a number of host proteins. Both proteases have been cloned and expressed in an inducible manner in Saccharomyces cerevisiae cells. The expression of 2Apro, but not 3Cpro, was highly toxic for yeast cells such that growth was arrested after 5 h of induction and cell survival sharply declined. Cellular morphology was profoundly modified by expression of poliovirus 2Apro, in such a way that electron dense granules and autophagosomic bodies arise in the cytoplasm. Experiments aimed at defining the yeast function affected by 2Apro suggested that translation was not the target of protease toxicity, but showed that RNA synthesis was profoundly blocked.


A preliminary investigation of laparoscopic fundoplication treatment on gastroesophageal reflux disease-related respiratory symptoms.
Extraesophageal syndromes are more difficult to identify and treat than the usual esophageal symptoms. The current study explores the efficacy of laparoscopic Nissen fundoplication (LNF) on gastroesophageal reflux disease (GERD)-related respiratory symptoms (RSs) during a 12-month follow-up observation. From April 2008 to September 2009, LNF was performed on 198 patients (107 men and 91 women) with GERD-related RSs according to underlying esophageal motility. A questionnaire form ranging from 0 to 5 was the basic requirement for recording pretreatment and posttreatment and for making detailed evaluation of the symptoms. All scores of GERD-related RSs, such as heartburn, regurgitation, coughing, breathe holding, wheezing, shortness of breath, and choking, significantly decreased at the 12th month. All the patients who participated in the current study were adults and elders aged 22 to 84 years with a mean age of 49 ± 12.89. The median length of stay was 4.3 days with a range of 2 to 8 days. The median score of heartburn, regurgitation, coughing, wheezing, shortness of breath, choking, and chest pain decreased from 4.92 ± 1.99, 4.98 ± 1.81, 7.23 ± 1.87, 7.50 ± 1.88, 5.83 ± 2.13, 5.94 ± 2.22, and 4.92 ± 1.88 to 1.62 ± 2.33, 0.64 ± 1.43, 2.79 ± 2.82, 2.53 ± 2.96, 1.37 ± 2.10, 1.28 ± 2.09, and 1.57 ± 2.55 (P<0.01), respectively. A total of 173 patients had various relieved symptom scores, 16 patients (8.1%) had different scale recurrence of symptoms after laparoscopic fundoplication treatment, and 13 patients had to retreat to omeprazole as an auxiliary medical therapy. Three other patients rejected any therapy, and no deaths occurred. A single patient converted from laparoscopic surgery to open surgery. Several short-term symptoms included retrosternal uneasiness or pain (n = 63; 31.8%), dysphagia (n = 45; 22.7%), abdominal distension (n = 87; 43.9%), and diarrhea (n = 23; 11.6%). Early dysphagia lasting <6 weeks was common, and 45 patients (22.7%) underwent an early esophagogastroduodenoscopy or contrast swallow. Five patients (2.5%) who had prolonged dysphagia during the 6-month clinical review required esophageal dilatation, and the outcomes were successful. LNF can be an effective means for treating RSs in patients with GERD.


Metabolic profiling of Garcinia mangostana (mangosteen) based on ripening stages.
Metabolomics is an emerging research field based on exhaustive metabolite profiling that have been proven useful to facilitate the study of postharvest fruit development and ripening. Specifically, tracking changes to the metabolome as fruit ripens should provide important clues for understanding ripening mechanisms and identify bio-markers to improve post-harvest technology of fruits. This study conducted a time-course metabolome analysis in mangosteen, an economically important tropical fruit valued for its flavor. Mangosteen is a climacteric fruit that requires an important plant hormone ethylene to regulate ripening processes and rate. We first categorized mangosteen samples in different ripening stages based on color changes, an established indicator of ripening. Using gas chromatography/mass spectrometry, small hydrophilic metabolites were profiled from non-ripened to fully ripened (ripening stages 0-6). These metabolites were then correlated with color changes to verify their involvement mangosteen ripening. Our results suggest that the increase of 2-aminoisobutyric acid, psicose, and several amino acids (phenylalanine, valine, isoleucine, serine, and tyrosine) showed a correlation with the progression of mangosteen ripening. This is the first report of the application of non-targeted metabolomics in mangosteen.


Molecular basis of cystic fibrosis disease: an Indian perspective.
Cystic fibrosis is a common autosomal recessive disorder usually found in population of white Caucasian descent. Now it is well documented the presence of CF disease in India with the advancement of laboratory testing. As once it was thought non existence of this disease in our population. Most of the phenotype of CF disease was in accordance of western population. Genetic analysis of CFTR gene in Indian CF patients revealed that most common mutation was delta F508 mutation. However, it was less than Caucasian population. CFTR mutations are also a causative factor in the pathogenesis of male infertility due to obstructive azoospermia. There are two most common mutation viz. IVS8-T5 and delta F508 which are responsible for congenital absence of vas deferens in male infertility patients. Elevated levels of sweat chloride at two occasions along with the presence of two mutations in CFTR gene was gold standard method for diagnosis of CF disease. It is noteworthy here that due to magnitude of Indian population, the total CF disease load would be more than many European countries. Clinical data demonstrate the prevalence of both classical and genetic form of CF in India.


Coexistent naïve phenotype and higher cycling rate of cord blood T cells as compared to adult peripheral blood.
Umbilical cord blood (UCB) T cells are predominantly CD45RA(+), secrete less cytokines, and have diminished cytotoxicity compared to adult peripheral blood (PB). We hypothesized that the functional impairment of bulk UCB cells results from the relative dominance of immature lymphocyte subsets. In this study we established the physiologic ranges of lymphocyte subsets in UCB, and contrasted those with adult PB. Four-color FACS was utilized to characterize surface and intracellular protein expression on lymphocyte subsets from fresh unmanipulated UCB and adult PB. We found that UCB contain significantly higher absolute numbers of T cells, NK cells, and B cells than adult PB (p<0.0001). UCB also contains more "naïve" cells not only among CD4(+) and CD8(+) T cells but also among B lymphocytes (p=0.003). Most UCB T cells are CD45RA(+)/CD62L(+) "recent thymic emigrants" with smaller TCRgammadelta (p<0.0001) and CD25(+) subsets (p=0.0068). Fewer UCB T cells display HLA-DR and CCR-5 activation markers (p<0.0001) while the CD8(+)/CD57(+)/CD28(-) "suppressor," CD8(+)/CD45RA(+)/CD27(-) "cytotoxic," and skin homing CLA(+) T-cell subsets are absent altogether. Compared with adult PB, more cord blood T cells progress through cell cycle (p<0.0001) and enter apoptosis (p=0.0003). Unlike in adult PB, the majority of proliferating Ki-67(+) T cells in UCB retain a CD45RA(+)/RO(-), CD69(-), CD25(-), HLA-DR(-) "resting" phenotype (p=0.0002). Most T and B lymphocytes express a nai;ve phenotype in cord blood while "suppressor" and "cytotoxic" T-cell subsets are absent. Cycling UCB T cells retain a nai;ve immunophenotype that may represent homeostatic expansion rather than antigen-driven proliferation.


Evaluation of the combination of endothelin receptor antagonists (ERA) and phosphodiesterase-5 inhibitors for the treatment of pulmonary arterial hypertension (PAH) in pathologic human pulmonary arteries in an ex-vivo organ bath model.
Medical combination therapy of pulmonary arterial hypertension (PAH) may alleviate the drawbacks of monotherapy by avoiding drug tolerance and by increasing effectiveness, as shown by the combination of ambrisentan and tadalafil (AMBITION trial). The present ex-vivo study evaluated the combination of the endothelin receptor antagonists (ERA) macitentan and bosentan with the phosphodiesterase-5 (PDE-5) inhibitor vardenafil in pulmonary arteries from patients suffering from terminal lung disease as a model of PAH. Segments of the pulmonary vessels were excised from resected lungs of patients requiring lung transplantation (LTX). Contraction of pulmonary arteries (PA) was elicited by consecutive dose-response curves of endothelin-1 (ET-1) followed by norepinephrine (NE) to allow inhibition by different pathways. Forces were measured isometrically in an organ bath in the presence and absence of ERA and PDE-5 inhibitors and their combination. PA of 38 patients were examined between October 2016 and November 2019. Bosentan (1E-7 M) and macitentan (1E-8 M, 3E-8 M, 1E-7 M) inhibited ET-1 induced contractions, whereas vardenafil (1E-6 M, 3E-6 M, 1E-5 M) inhibited only the NE induced part of the contractions. Vardenafil enhanced bosentan-induced inhibition of vasoconstriction in a dose-dependent fashion. Combination effects exceeded single bosentan at 3E-6 M and 1E-5 M vardenafil, and they exceeded single vardenafil at the lower vardenafil concentrations. Macitentan showed a more pronounced inhibition than bosentan regardless of the lower concentrations. Accordingly, combination effects with vardenafil resembled those of macitentan alone. Macitentan and bosentan were potent antagonists of vasoconstriction in PA of LTX patients. The benefit of drug combinations was demonstrated at selected concentrations only owing to a narrow therapeutic range of vardenafil in this ex-vivo model. These results suggest the utility of drug combinations other than the established pair of ambrisentan and tadalafil in PAH treatment but also make a case for a further assessment of vasodilator properties of drugs complementing ERA.


A device for transplantation of single cells.
A device with a high degree of precision is described for the transplantation of single identified cells in specified regions of the host brain. It consists of two co-centric micropipettes where the inner pipette, functioning as a plunger, is used to drive the cells contained near the tip of the outer pipette into the host. The use of a pre-calibrated micrometer to control the movement of the inner pipette obviates the need of visual monitoring for successful transplantation.


Significance of H1 and H2 receptors in the human nose: rationale for topical use of combined antihistamine preparations.
The aim of this experiment was to study the importance of histamine H1 and H2 receptors in the human nose. We therefore provoked 25 healthy human subjects with histamine after local pretreatment with the H1 receptor antagonist, chlorpheniramine maleate, the H2 receptor antagonist, ranitidine hydrochloride, and a combination of these two antihistamines. The histamine-induced increase in nasal airway resistance was 52% inhibited by combined use of the two antihistamine sprays (p less than 0.05), 22% by chlorpheniramine alone (p less than 0.05), and 29% by ranitidine. The two sprays together were significantly better than the H1 antagonists alone (p less than 0.05). These results suggest an equal importance of H1 and H2 receptors in nasal blood vessels, and an additive effect of H1 and H2 antihistamines. Although chlorpheniramine effectively blocked tickling and the reflex-mediated symptoms, sneezing and hypersecretion, ranitidine had no effect, which suggests an H1 and not an H2 effect on sensory nerve endings in the airway epithelium.


[Germline mutations of tetranucleotide DNA repeats in families with normal children and reproductive pathology].
We have previously reported a high rate of tetranucleotide DNA repeat mutations, including mutations of both germline and somatic origin, in spontaneous human abortuses. To analyze in more detail mutational microsatellite (MS) variability in meiosis and its possible association with disturbed embryonic development, we have conducted a comparative study of mutation rates of a complex of 15 autosomal tetranucleotide MSs in 55 families with healthy children and in 103 families that have had spontaneous abortuses with normal karyotypes. In the families with miscarriage, the gametic MS mutation rate was higher than in the families with normal reproductive function (4.36 x 10(-3) versus 2.32 x 10(-3) per locus per gamete per generation), but this difference was statistically nonsignificant (P = 0.25). No association of MS mutations with familiar miscarriage was found. Mutations at the MS loci studied were recorded almost 3 times as often in spermatogenesis as in oogenesis, which is likely to result from a greater number of DNA replication cycles in male germline cell precursors than in female ones. Mutations increasing and reducing the MS sequence length appeared at virtually the same rate. Changes in MS DNA sequence length per one repeated element, i.e., single-step mutations (93% of cases) exceeded all other events of allele length change. The highest number of mutations (81.2%) was found in longer alleles. This distribution of mutations by size, direction, and parental origin corresponds to the multistep mutation model of their emergence via mechanism of DNA strand slippage during replication.


Estimating epidemiological data of Multiple sclerosis using hospitalized data in Shandong Province, China.
Multiple sclerosis (MS) is a rare chronically debilitating disease. There are few reports on the burden of disease of MS and prevalence in China. The authors intended to estimate disease burden and prevalence of MS in Shandong Province using available epidemiologic data. Prevalence was calculated using DISMOD II software based on incidence extrapolated from hospitalization data, case fatality and remission rate from literature as input indexes. Disability-adjusted life year (DALY) was computed with epidemiologic indexes estimated by DISMOD II program. The prevalence of MS was estimated to be 3.7(95 % CI: 1.65-5.8) and 6.7(95 % CI: 2.7-9.56) cases per 100,000 people for males and for females, respectively. The mean age at onset of MS was 36.0(43.0 ± 30.0 years in males and 33.7(43.4 ± 29.7) years in females. Duration of the disease was estimated to be 34.0 (31.6 ± 21.0) years for males and 39.5(34.9 ± 21.8) years for females. The disease burden in disability-adjusted life years was 3316, comprised of 903 (27.2 %) years of life lost (YLL) and 2413 (72.8 %) years lived with disability (YLD). Our study highlighted that population in Shandong Province had a high prevalence of MS and the patients had a heavy disease burden. It also revealed that the results obtained in this paper would be useful to provide a reference for establishing specific healthcare policies for this rare disease in Shandong Province.


Correction: Wdr62 is involved in female meiotic initiation via activating JNK signaling and associated with POI in humans.
[This corrects the article DOI: 10.1371/journal.pgen.1007463.].


[14 C]2-Deoxyglucose uptake marks systems activated by rewarding brain stimulation.
Autoradiography of sections from the brains of anesthetized rats injected with [14C] 2-doexyglucose revealed neural systems unilaterally activated by rewarding electrical stimulation of the medial forebrain bundle. Since this new technique marks neural systems on the basis of their activity, it has great potential in functional neuroanatomy. The potential is easily realized in brain-stimulation studies, where systems may be driven to exceptionally high levels of activity.


Degradation of several polycyclic aromatic hydrocarbons by laccase in reverse micelle system.
Remediation of polycyclic aromatic hydrocarbons (PAHs) in oily sludge has become the focus of attention. UV spectrophotometer analysis showed that four types of PAHs were found in sample, which including phenanthrene, anthracene, benzo(a)anthracene and benzo(b)fluoranthene. In order to degrade PAH effectively, the laccase reverse micelles system was proposed. The system protects laccase from being affected by organic phase. Reverse micelles were prepared by using isooctane to simulate oil. The optimum water content W0 was 10 by measuring the electrical conductivity of the system. Under this condition, the effects of pH, temperature and ionic strength on the degradation rate of PAHs were investigated. Also, compared with that of non-immobilized laccase, the ratio between the secondary structures of laccase under different conditions was studied. The results showed that the highest laccase activity was obtained at pH 4.2 and 30 °C with 60 mmol/L KCl. Meanwhile, the structure of α-helix accounts for the largest proportion, and the ratio of α-helix in the laccase secondary structure in the laccase-reverse micelle system was higher than that of the non-immobilized one under this condition. Finally, predicting the reactive site of the degradation of polycyclic aromatic hydrocarbons was simulated by ORCA (Version 4.2.0). The application in oily sludge was further conducted. This study provides an effective method and basis for the degradation of PAHs in oily sludge.


Determination of flavin contents in neutrophils by a sensitive chemiluminescence assay: evidence for no translocation of flavoproteins from the cytosol to the membrane upon cell stimulation.
A sensitive and specific chemiluminescence (CL) method with bacterial luciferase was adapted for accurate measurement of the flavins FAD and FMN in the membrane and cytosolic fractions of neutrophils prepared from pig and human blood. The FAD and FMN contents (FAD/FMN = 100:2) in the membranes were essentially the same in resting (R) and myristate-stimulated (S) cells, although O2(-)-generation was markedly enhanced exclusively in S membranes. The O2(-)-forming activity of S samples remained unchanged or even increased after washing the membranes with buffer, although one-third of the FAD was lost during washing (a decrease from 140 to 95 pmol/10(8) cell-equivalent (CE) during washing). The cytosol is known to contain at least three components that are essential for O2- production (p47-phox, p67-phox, and a G-protein), and that are translocated to membranes upon activation, but its flavin content was one tenth of that of the membranes. The cytosol was treated with fatty acids in the absence of membranes to induce substantial precipitation of p47-phox, p67-phox and a protein of 32 kDa. No difference relative to a solvent-control was noted in the low flavin content of the precipitate indicating that these cytosolic components are not flavoproteins. These results do not support the possibility of translocation of a cytosolic flavoprotein to the membrane upon activation of the respiratory burst.


Research on psychological attributions and intervention strategies of new energy hybrid vehicle purchase behavior.
Based on the questionnaire survey, this paper developed a theoretical model of the factors influencing consumers' purchase behavior for new energy hybrid vehicles using the theory of planned behavior and structural equation modeling techniques. It then used SPSS and AMOS to perform factor analysis, model fitness, and path analysis to reach the following conclusions: perceived behavioral control, behavioral attitude, and subjective norm have a significant positive influence on behavioral intention, and behavioral intention has a significant influence on actual behavior. However, there is no significant effect of perceived behavioral control on actual purchase behavior, but rather an indirect effect on actual behavior through the mediating variable of behavioral intention. The analysis of the multi-group model based on the individual characteristics of consumers showed that the coefficient of subjective norm on behavioral intention was higher for extroverted consumers than for introverted consumers; the influence of behavioral attitude on behavioral intention was significantly higher for introverted consumers than for subjective norm on behavioral intention.


Thrombosis, cancer, and COVID-19.
Cancer and coronavirus disease 2019 (COVID-19) have unusual similarities: they both result in a markedly elevated risk of thrombosis, exceptionally high D-dimer levels, and the failure of anticoagulation therapy in some cases. Cancer patients are more vulnerable to COVID-19 infection and have a higher mortality rate. Science has uncovered much about SARS-CoV-2, and made extraordinary and unprecedented progress on the development of various treatment strategies and COVID-19 vaccines. In this review, we discuss known data on cancer-associated thrombosis (CAT), SARS-CoV-2 infection, and COVID-19 vaccines and discuss considerations for managing CAT in patients with COVID-19. Cancer patients should be given priority for COVID-19 vaccination; however, they may demonstrate a weaker immune response to COVID-19 vaccines than the general population. Currently, the Centers for Disease Control and Prevention recommends an additional dose and booster shot of the COVID-19 vaccine after the primary series in patients undergoing active cancer treatment for solid tumors or hematological cancers, recipients of stem cell transplant within the last 2 years, those taking immunosuppressive medications, and those undergoing active treatment with high-dose corticosteroids or other drugs that suppress the immune response. The mainstay of thrombosis treatment in patients with cancer and COVID-19 is anticoagulation therapy.


Complications of hysteroscopy and how to avoid them.
The advances in surgical technology such as bipolar electrosurgery, endometrial ablation devices, hysteroscopic sterilization, and morcellators have revolutionized this surgical modality. This article reviews the potential complications in hysteroscopic surgery and the means by which they may be minimized or avoided.


[Bacillus Calmette-Guérin osteomyelitis. A case report in a former preterm baby].
Postvaccination osteo-articular mycobacterial infectious disease is a rare and potentially serious complication after Bacillus Calmette-Guérin (BCG) vaccine. We report on a case of a former preterm baby born at 30 weeks of gestation who was vaccinated with BCG Copenhagen strain at 2 months of age. He presented 6 months later with a painful limp, which was found to be a mono-articular osteitis of the right ankle. Histology of the biopsy showed signs of mycobacterial infection and molecular analysis confirmed a BCG infection. Blood tests did not reveal any immunodeficiency associated with the disease (IFN-gamma levels were normal). The course of the disease was favorable with 9 months of antibiotic therapy against mycobacteria. BCG complications should lead to screening for immunodeficiency. The prognosis of BCG osteitis is excellent if the disease is localized. No link between prematurity and BCG complications has been found to date. BCG vaccination of premature infant should be the same as for the general population.


Sustainability in the global value chain-a scientometric analysis.
For its promise in enhancing sustainability, the global value chain (GVC) has grown in relevance and sparked many studies. Due to different value activities in multiple countries and industry clusters, the competition and cooperation among value chains have attracted the considerable attention of business leaders and academicians worldwide. GVC-related sustainability research is a niche area despite its widespread presence in the literature. To bridge the gap, we use scientometric analysis in this paper, examining the corpus of 753 articles published in Web of Science journals from 2001 till 2021. This review illuminates the research performance constituents (e.g., most prolific authors, nations, institutions, and journals), the themes and issues that underpin the fields' intellectual structure, and transforming discoveries. GVC depends on nine basic clusters for sustainability research (i.e., global value chain participation, gendered global production network, repositioning organisational dynamics, labour stands, learning opportunities, Internet era). Future studies can be conducted to generate new knowledge across ten thematic (based on keywords) clusters (i.e., market liberalisation, trade pollution nexus, value chain dynamics, global value chain reconfiguration, non-governmental organisation, multipolar governance). A model that encompasses current knowledge of the global value chain for sustainability is developed, and avenues for future research are provided.


Simulation of quantitative characters by genes with biochemically definable action. VI. Modifications of a simple model.
Investigations on metric characters of defined genotypes of Matthiola incana, and application of different linear models for the estimation of genetic parameters, indicate that the use of midparental value as a reference point results in parameter estimates that do not correspond to the actual biological situation. Use of the most recessive genotype as a reference point causes all of the contributions of single loci to be undirectional and positive, and all the allelic and nonallelic interactions to be unidirectional and negative, in accord with our Model 2.2. The results indicate that the phenotypic response to allelic substitutions follows the characteristics of a saturation curve. The possibility is discussed that the saturation character results from regulating processes, whereas deviations of single measurements from the response curve, or response surface, reflect real interactions between allelic and nonallelic genes.