Binding sites of mu receptor increased when acupuncture analgesia was enhanced by droperidol: an autoradiographic study.
To study if mu receptor participates in the process of potentiation of droperidol (Dro) on acupuncture analgesia (AA). Autoradiographic technic was used. Ohmefentanyl, a highly selective ligand of mu receptors, was used in radio-receptor binding assay in Sprague-Dawley rat brain sections. The binding sites of [beta-3H, p-benzoyl-3H]ohmefentanyl were increased greatly in many nuclei of rat brain after AA, and were further increased when AA was enhanced by Dro. Higher increase was seen in caudate nucleus, accumbens, periaqueductal gray (PAG), interpeduncular nucleus, amygdala (P < 0.01 vs rats treated with electroacupuncture alone); moderate increase was noted in thalamus, lateral area of hypothalamus, spinal dorsal horn (P < 0.01 or 0.05); slight increase appeared in septum, preoptic area, hippocampus, substantia nigra (P < 0.05). Mu opioid receptors mediated the Dro-induced enhancement of AA.


Invariant NKT cells require autophagy to coordinate proliferation and survival signals during differentiation.
Autophagy regulates cell differentiation, proliferation, and survival in multiple cell types, including cells of the immune system. In this study, we examined the effects of a disruption of autophagy on the differentiation of invariant NKT (iNKT) cells. Using mice with a T lymphocyte-specific deletion of Atg5 or Atg7, two members of the macroautophagic pathway, we observed a profound decrease in the iNKT cell population. The deficit is cell-autonomous, and it acts predominantly to reduce the number of mature cells, as well as the function of peripheral iNKT cells. In the absence of autophagy, there is reduced progression of iNKT cells in the thymus through the cell cycle, as well as increased apoptosis of these cells. Importantly, the reduction in Th1-biased iNKT cells is most pronounced, leading to a selective reduction in iNKT cell-derived IFN-γ. Our findings highlight the unique metabolic and genetic requirements for the differentiation of iNKT cells.


Barriers and enablers to emergency obstetric and newborn care services use in Wolaita Zone, Southern Ethiopia: a qualitative case study.
Globally, 11.4 million untreated obstetric complications did not receive Emergency Obstetric and Newborn Care (EmONC) services yearly, with the highest burden in low and middle-income countries. Half of the Ethiopian women with obstetric complications did not receive EmONC services. However, essential aspects of the problem have not been assessed in depth. This study, therefore, explored the various aspects of barriers and enablers to women's EmONC services utilization in southern Ethiopia. A qualitative case study research design was used in nine districts of the Wolaita Zone. A total of 37 study participants were selected using a purposive stratified sampling technique and interviewed till data saturation. Twenty-two key informant interviews were conducted among front-line EmONC service providers, managers, community leaders, and traditional birth attendants (TBAs). Individual in-depth interviews were conducted among 15 women with obstetric complications. The trustworthiness of the research was assured by establishing credibility, transferability, conformability, and dependability. NVivo 12 was used to assist with the thematic data analysis. Five themes emerged from the analysis: service users' perception and experience (knowledge, perceived quality, reputation, respectful care, and gender); community-related factors (misconceptions, traditional practices, family and peer influence, and traditional birth attendants' role); access and availability of services (infrastructure and transportation); healthcare financing (drugs and supplies, out-of-pocket expenses, and fee exemption); and health facility-related factors (competency, referral system, waiting time, and leadership). Many women and their newborns in the study area suffered severe and life-threatening complications because of the non-utilization or delayed utilization of EmONC services. A key policy priority should be given to enhancing women's awareness, eliminating misconceptions, improving women's autonomy, and ensuring traditional practices' role in EmONC service utilization. Community awareness interventions are required to enhance service uptake. Furthermore, the health systems must emphasize improving the quality of care, inequitable distribution of EmONC facilities, and essential drugs. The financial constraints need to be addressed to motivate women from low socioeconomic status. Furthermore, intersectoral collaboration is required to maintain a legal framework to control and prohibit home deliveries and empower women.


Assessment of cytotoxicity and DNA damage exhibited by siloranes and oxiranes in cultured mammalian cells.
The potential reactivity and structural properties of oxiranes (epoxides) are advantageous when considering polymers for medical devices. However, epoxy compounds are widely known to have genotoxic properties. The objective of the study was to evaluate the cytotoxicity and primary DNA damage effects induced by oxiranes and siloranes, silicon containing oxiranes. The siloranes, Ph-Sil, Tet-Sil, and Sil-Mix and the oxiranes Cyracure UVR-6105 and 1,3-bis[2-(2-oxiranylmethyl) phenoxy]pentane (OMP-5) were dissolved in organic solvents and dilutions containing less than 0.5% solvent were used in biological assays. The concentration that reduced the viability of 50% (TC(50)) of L929 cells was measured using the MTT assay and guided the selection of subtoxic doses for evaluation of DNA damage. Ph-Sil was more cytotoxic than OMP-5, Cyracure UVR-6105 and Sil-Mix. However, the TC(50) value of Tet-Sil could not be determined due to its poor solubility. DNA damage was evaluated in the sister chromatid exchange (SCE) assay with CHO cells, and the alkaline comet assay with L929 cells. In contrast to the siloranes, the oxiranes exhibited significant increases (p>0.05) in SCE frequencies and DNA migration relative to their solvent controls. Our findings support previous reports that siloranes have low genotoxic potential and can be suitable components for development of biomaterials.


[Portal hypertension and pregnancy].
Pregnancy in patients with portal hypertension is rare but worrying for the clinician. Although the effects of portal hypertension during pregnancy have not been fully elucidated, there is an evident increase in morbidity, especially associated with cirrhosis, which justifies the idea of at-risk pregnancy and requires management by a multidisciplinary team. The prevention and treatment of gastrointestinal haemorrhage is quite similar to that in nonpregnant patients. Investigation and management of portal hypertension before and at the beginning of pregnancy can reduce the risks of foetal loss, restricted intra-uterine growth, premature birth and maternal mortality, which are closely related to gastrointestinal haemorrhage. The risks related to the underlying disease, such as liver failure with cirrhosis and thromboembolic risk with vascular diseases associated with thrombophilia must be taken into consideration. Generally, vaginal delivery with early analgesics for the mother assisted by an extraction device should be preferred to caesarean section, which must be reserved for obstetrical indications.


The Effect of Transurethral Resection of the Prostate on Erectile and Ejaculatory Functions in Patients with Benign Prostatic Hyperplasia.
The aim of this study was to investigate the effect of TURP on erectile function (EF) and ejaculatory function (EJF). A total of 91 patients who underwent TURP were retrospectively assessed. Patients were divided into two groups based on International Index of Erectile Function (IIEF-5): group A included 41 patients with normal EF, and group B included 50 patients with erectile dysfunction (ED). All patients were evaluated for EF and EJF at baseline, 1, 3, and 6 months after TURP by using IIEF-5, Ejaculatory Domain-Male Sexual-Health Inventory (Ej-MSHQ). In group A, there were no significant statistical differences in mean IIEF-5 at baseline and after TURP 22.88 ± 0.81 versus 22.63 ± 2.63 (p = 0.065). However, in group B, there was significant improvement in IIEF-5 after TURP all over the follow-up time points in comparison to the baseline (p = <0.001). The loss of EJF was significant among patients in group A. There was significant improvement of IPSS and Qmax in group A after surgery compared to group B. The results confirmed that TURP has no significant negative influence on EF, and patients with preexisting ED were improved after TURP. On the contrary, the loss of EJF was significant.


A role for herpesvirus entry mediator as the receptor for herpes simplex virus 1 entry into primary human trabecular meshwork cells.
The human eye is an important target for infection with herpes simplex virus 1 (HSV-1). Damage to cells forming the trabeculum of the eye by HSV-1 infection could contribute to the development of glaucoma, a major blinding disease. Primary cultures of human trabecular meshwork cells were used as an in vitro model to demonstrate the ability of HSV-1 to enter into and establish a productive infection of the trabeculum. Blocking of entry by anti-herpesvirus entry mediator (HVEM) antibody implicated HVEM as the major receptor for HSV-1 infection.


Defining hydrops and indications for open fetal surgery for fetuses with lung masses and vascular tumors.
The aim of this study was to identify the most accurate prenatal predictors of outcomes and need for fetal surgery for fetuses with high-risk lung masses and vascular tumors. The records of all fetuses with high-risk lung mass (congenital cystic adenomatoid malformation-volume ratio > 1.6 or findings of hydrops) and vascular tumor evaluated between July 2001 and March 2011 were reviewed retrospectively. Hydrops was defined as accumulation of fluid in 2 or more compartments. Of fetuses with high-risk lung mass, hydrops was identified in 46% (11/24). Fetuses with hydrops and an abnormal echocardiogram (n = 8) demonstrated poor survival without fetal surgery (13%) compared with 100% survival in fetuses with hydrops and a normal echocardiogram (n = 3; P = .02). Of 21 fetuses with vascular tumor (11 sacrococcygeal and 8 cervical teratomas; 2 hemangioendotheliomas), hydrops was identified in 29% and an abnormal echocardiogram in 57%. All fetuses with hydrops had an abnormal echocardiogram and either died (n = 5) or required fetal surgery (n = 1). However, all fetuses with abnormal echocardiograms alone (n = 7) survived without fetal intervention. For fetuses with lung mass, an abnormal echocardiogram in the setting of hydrops is the best predictor of mortality and need for fetal surgery. For fetuses with vascular tumor, hydrops in the setting of high-output physiology best predicts demise and need for fetal surgery.


Sex difference in responsiveness to Aztreonam of monooxygenase system in liver microsomes from rats.
Effect of successive administration of Aztreonam on microsomal monooxygenase system was investigated in male and female Sprague-Dawley rats. The activities of benzphetamine N-demethylase, aminopyrine N-demethylase, p-nitroanisole O-demethylase and aniline hydroxylase in liver microsomes from male rats were decreased dose-dependently by Aztreonam. On the contrary, the activities in liver microsomes from female rats were slightly increased rather than decreased by the administration of Aztreonam. In addition, Aztreonam was found to decrease the specific content of microsomal cytochrome P-450 in male rats but not in female rats. The decreases in the activities observed in male rats were accompanied by a parallel decrease in the specific content of cytochrome P-450. Furthermore, the results of quantitation of P-450 (M-1), one of the male specific forms of cytochrome P-450, indicated that the administration of Aztreonam resulted in a dose-dependent decrease in the content of P-450 (M-1) in liver microsomes from male rats.


Dopamine D4 receptor gene and the -521C>T polymorphism of the upstream region of the dopamine D4 receptor gene in schizophrenia.
The dopamine D4 receptor (DRD4) is a candidate gene for increasing genetic susceptibility to schizophrenia. A recent study found that a -521C>T promoter base pair change affects transcriptional regulation of the DRD4 gene. The present study was designed to investigate the role of both the -521C>T single nucleotide polymorphism and the DRD4 variable number tandem repeat (VNTR) polymorphism. A case-control study of 630 Chinese schizophrenic patients and 428 Chinese controls was conducted to test for allelic association with schizophrenia. The number of DRD4 VNTR fragments was associated with schizophrenia. Long DRD4 VNTR fragments as opposed to short fragments were commoner in schizophrenia. No evidence was found for allelic association between the -521C>T DRD4 polymorphism and schizophrenia. This study provides preliminary and unconfirmed evidence for the involvement of the DRD4 repeat VNTR in the pathogenesis of schizophrenia.


Effect of tilt of 2 acrylic intraocular lenses on high-order aberrations.
To investigate the high-order aberrations (HoAs) in pseudophakia between 2 foldable acrylic intraocular lenses (IOL) with differences in the tilt of IOL. Department of Ophthalmology, Nara Medical University, Nara, Japan. Sixty-four eyes that had uncomplicated phacoemulsification and IOL implantation were assigned to 1 of 2 groups: Acryfold 60BB (HOYA [n=30 eyes]) and AcrySof MA60AC (Alcon [n=34 eyes]). All patients had best corrected visual acuity better than 20/25. High-order aberrations were measured using the Hartmann-Shack aberrometer at 4.0 mm and 6.0 mm wavefront aperture diameters, and the IOL tilt and decentration were measured using Scheimpflug videophotography. There was a significant difference in the IOL tilt (60BB=2.22 degrees +/- 1.44 (SD), 60AC=3.18 +/- 1.84 degrees; P=.041, Mann-Whitney U test), but no difference in IOL decentration (P>.05). In the cornea, there were no differences between the 2 groups in HoAs at 4.0 mm and 6.0 mm aperture diameters (P>.05, Mann-Whitney U test). In the whole eye, there was no difference between the 2 groups in spherical-like aberrations, coma-like aberrations, and total aberrations at the 4.0 mm and 6.0 mm aperture diameters (P>.05). The compensation of the internal optics with the 60BB group was better than with the 60AC group for coma-like (P=.037) and total aberrations (P=.010) at 6.0 mm aperture diameter. The smaller tilt of the IOL induced more compensation for the coma-like and total aberrations at the 6.0 mm aperture diameter. The IOL tilt should be small, especially in a large pupil, with regard to HoAs.


The structure of kaliophilite KAlSiO4, a long-lasting crystallographic problem.
Kaliophilite is a feldspathoid mineral found in two Italian magmatic provinces and represents one of the 12 known phases with composition close to KAlSiO4. Despite its apparently simple formula, the structure of this mineral revealed extremely complex and resisted structure solution for more than a century. Samples from the Vesuvius-Monte Somma and Alban Hills volcanic areas were analyzed through a multi-technique approach, and finally the crystal structure of kaliophilite was solved using 3D electron diffraction and refined against X-ray diffraction data of a twinned crystal. Results were also ascertained by the Rietveld method using synchrotron powder intensities. It was found that kaliophilite crystallizes in space group P3 with unit-cell parameters a = 27.0597 (16), c = 8.5587 (6) Å, V = 5427.3 (7) Å3 and Z = 54. The kaliophilite framework is a variant of the tridymite topology, with alternating SiO4 and AlO4 tetrahedra forming sheets of six-membered rings (63 nets), which are connected along [001] by sharing the apical oxygen atoms. Considering the up (U) and down (D) orientations of the linking vertex, kaliophilite is the first framework that contains three different ring topologies: nine (1-3-5) (UDUDUD) rings, six (1-2-3) (UUUDDD) rings and twelve (1-2-4) (UUDUDD) rings. This results in a relatively open (19.9 tetrahedra nm-3) channel system with multiple connections between the double six-ring cavities. Such a framework requires a surprisingly large unit cell, 27 times larger than the cell of kalsilite, the simplest phase with the same composition. The occurrence of some Na for K substitution (3-10%) may be related to the characteristic structural features of kaliophilite. Micro-twinning, pseudo-symmetries and anisotropic hkl-dependent peak broadening were also detected, and they may account for the elusive character of the kaliophilite crystal structure.


Association between achalasia and nitric oxide synthase gene polymorphisms.
Our group previously reported the absence of nitric oxide synthase (NOS) in the gastroesophageal junction of patients with achalasia. NOS exists in three distinct isoforms: neuronal NOS (nNOS), endothelial NOS (eNOS), and inducible isoform (iNOS). Some studies have shown that NO production is regulated by NOS polymorphisms. To assess whether some functional polymorphisms in the nNOS, iNOS, or eNOS genes are involved in susceptibility to suffer from achalasia. Genomic DNA from 80 unrelated Spanish Caucasian patients with sporadic achalasia and 144 healthy subjects matched for age (+/-5 yr) and gender was typed by PCR and RFLP methods for the 27-bp variable number of tandem repeat (VNTR) polymorphism in intron 4 of the eNOS gene, a CA microsatellite repeat and a Nla III (C-->T) restriction fragment length polymorphism (RFLP) in exon 29 of the nNOS gene, and two nucleotide substitutions located in exon 16 (C-->T) and exon 22 (G-->A) of the iNOS gene. No significant differences in carriage, genotype, and allele frequencies of the nNOS, iNOS, or eNOS gene polymorphisms were found between patients with achalasia and controls. Individuals homozygous for genotype iNOS22*A/A tended to be more frequent in achalasia (20%vs 11%, odds ratio [OR] 1.79, 95% confidence interval [CI] 0.89-3.59, p= 0.09) as were those homozygous for the rare eNOS*4a allele (6.2%vs 1.4%, OR 4.5, 95% CI 0.89-22.67, p= 0.1) although the difference did not reach statistical significance. No differences in genotype and allele distribution were found with respect to epidemiological and clinical characteristics of patients with achalasia. Our data suggest that NOS gene polymorphisms are not involved in the susceptibility to and nature of the clinical course of sporadic achalasia. However, studies in a greater number of patients are required to analyze the tendency toward a higher prevalence of genotypes iNOS22*A/A and eNOS*4a4a.


Postpartum IUD contraception--a review of an international experience.
Postpartum insertion of intrauterine contraceptive devices (IUDs) performed while women are still in hospital has a number of advantages. Earlier reports, however, generally associated this procedure with high expulsion rates. Recent studies, on the other hand, have shown that if IUDs are inserted immediately (within 10 minutes) after placental delivery, it is safe and effective. In some experienced centers, fairly low expulsion rates are reported. In this paper the experiences with postplacental IUD insertions from international studies are reviewed, the lessons we have learned from these experiences summarized, and future research directions suggested.


Factors Influencing CAM-ICU Documentation and Inappropriate "Unable to Assess" Responses.
Detecting delirium with standardized assessment tools such as the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) is important, but such detection is frequently hampered by poor documentation and inappropriate "unable to assess" responses (in noncomatose patients). To identify patient, clinical, and workplace factors that may impede or facilitate appropriate delirium assessment through use of the CAM-ICU, specifically documentation and inappropriate "unable to assess" responses. An electronic health record-based data set was used to quantify CAM-ICU documentation and inappropriate "unable to assess" responses during 24 months. Associated patient (eg, age), clinical (eg, diagnosis), and workplace (eg, geographic location within the ICU, shift) factors were evaluated with multivariable regression. Of 28 586 CAM-ICU documentation opportunities, 66% were documented; 16% of documentations in alert or lightly sedated patients had inappropriate "unable to assess" responses. Night shift was associated with lower CAM-ICU documentation rates (P = .001), whereas physical restraints and location on side B (rather than side A) of the ICU were associated with higher documentation rates (P < .05 for both). Age older than 80 years, non-White race, intubation, and physical restraints were associated with more inappropriate "unable to assess" responses (all P < .05), as was infusion of propofol, midazolam, dexmedetomidine, or fentanyl (all P < .05). Data from electronic health records can identify patient, clinical, and workplace factors associated with CAM-ICU documentation and inappropriate "unable to assess" responses, which can help target quality improvement efforts related to delirium assessment.


Influence of aminophylline and cyclic AMP on glycogen metabolism in fetal rat lung in organ culture.
The glycogen content of fetal rat lung declines coincident with increased pulmonary phospholipid synthesis. Aminophylline, a methylxanthine cyclic adenosine 3',5' monophosphate (AMP) phosphodiesterase inhibitor, and cyclic AMP augment fetal lung phospholipid synthesis. Because lung glycogen breakdown may contribute to pulmonary phospholipid synthesis, the effects of aminophylline and cyclic AMP on glycogen metabolism were studied in explants of 19 day fetal rat lung in organ culture. Treatment with aminophylline or dibutyryl cyclic AMP for 24 hr, resulted in a 25% (P less than 0.025) and 75% (P less than 0.001) decrease, respectively, in the glycogen content of the explants. Glycogen synthase I activity was reduced by 32% in aminophylline treated cultures (P less than 0.025) and 25% in cyclic AMP treated cultures (P less than 0.025). The percent of total synthase in the active form was significantly reduced in all treated cultures. Neither aminophylline nor cyclic AMP treatment resulted in significant changes in glycogen phosphorylase a or total phosphorylase activity.


Bilateral coronal and sagittal synostosis in X-linked hypophosphatemic rickets: a case report.
Craniosynostosis can be gene-linked, or caused by metabolic diseases, such as rickets, which results from a deficiency or impaired metabolism of vitamin D, magnesium, phosphorus or calcium leading to hypomineralization of the bone. X-linked dominant hypophosphatemic rickets (XLHR) is the most prevalent genetic type of hypophosphatemic rickets and is caused by germ line mutations in the PHEX-gene. In XLHR, only few case reports of craniosynostosis were described. Here, we present a clinical report of an 18 months old child with XLHR and bilateral coronal and sagittal synostosis who was treated by subtotal cranial vault remodelling with fronto-orbital advancement and right-angled Z-osteotomies. As a consequence of the child's diminished bone regeneration capacity, surgery that is performed after the age of 1 year requires more extensive craniectomy, multiple osteotomies and rigid fixation for calvarial vault remodelling to prevent extensive bone defects.


Pancreatic acinar heterogeneity hijacks carcinogenesis and homeostasis.
In this issue, Jiang and colleagues employ multiple lineage-tracing approaches to elaborate on the role of Tff2+ transit-amplifying progenitor cells in the pancreatic acinar compartment of mice. This work provides insights into the steady-state homeostasis and tumor-suppressive features of certain progenitor cells and presents findings on acinar cell heterogeneity.


Anakinra in hospitalized patients with severe COVID-19 pneumonia requiring oxygen therapy: Results of a prospective, open-label, interventional study.
The aim of this study was to evaluate the efficacy of anakinra in patients who were admitted to hospital for severe COVID-19 pneumonia requiring oxygen therapy. A prospective, open-label, interventional study in adults hospitalized with severe COVID-19 pneumonia was conducted. Patients in the interventional arm received subcutaneous anakinra (100 mg twice daily for 3 days, followed by 100 mg daily for 7 days) in addition to standard treatment. Main outcomes were the need for mechanical ventilation and in-hospital death. Secondary outcomes included successful weaning from supplemental oxygen and change in inflammatory biomarkers. Outcomes were compared with those of historical controls who had received standard treatment and supportive care. A total of 69 patients were included: 45 treated with anakinra and 24 historical controls. A need for mechanical ventilation occurred in 14 (31%) of the anakinra-treated group and 18 (75%) of the historical cohort (p < 0.001). In-hospital death occurred in 13 (29%) of the anakinra-treated group and 11 (46%) of the historical cohort (p = 0.082). Successful weaning from supplemental oxygen to ambient air was attained in 25 (63%) of the anakinra-treated group compared with 6 (27%) of the historical cohort (p = 0.008). Patients who received anakinra showed a significant reduction in inflammatory biomarkers. In patients with severe COVID-19 pneumonia and high oxygen requirement, anakinra could represent an effective treatment option and may confer clinical benefit. ISRCTN74727214.


Enhanced speech perception in noise and cortical auditory evoked potentials in professional musicians.
The current research investigated whether professional musicians outperformed non-musicians on auditory processing and speech-in-noise perception as assessed using behavioural and electrophysiological tasks. Spectro-temporal processing skills were assessed using a psychoacoustic test battery. Speech-in-noise perception was measured using the Listening in Spatialised Noise - Sentences (LiSN-S) test and Cortical Auditory Evoked Potentials (CAEPs) recorded to the speech syllable/da/presented in quiet and in 8-talker babble noise at 0, 5, and 10 dB signal-to-noise ratios (SNRs). Ten professional musicians and 10 non-musicians participated in this study. Musicians significantly outperformed non-musicians in the frequency discrimination task and low-cue condition of the LiSN-S test. Musicians' N1 amplitude showed no difference between 5 dB and 0 dB SNR conditions while non-musicians showed significantly lower N1 amplitude at 0 dB SNR compared to 5 dB SNR. Brain-behaviour correlation for musicians showed a significant association between CAEPs at 5 dB SNR and the low-cue condition of the LiSN-S test at 30-70 ms. Time-frequency analysis indicated musicians had significantly higher alpha power desynchronisation in the 0 dB SNR condition indicating involvement of attention. Through the use of behavioural and electrophysiological data, the results provide converging evidence for improved speech recognition in noise in musicians.


Fast (40-150Hz) oscillations are associated with positive slow waves in the ictal EEGs of epileptic spasms in West syndrome.
To elucidate the generative mechanisms of epileptic spasms (ESs) in West syndrome, we investigated the temporal relationship between scalp fast (40-150Hz) oscillations (FOs) and slow waves in the ictal electroencephalograms (EEGs) of ESs. In 11 infants with WS, ictal FOs were detected in a bipolar montage based on spectral and waveform criteria. Their temporal distribution was analyzed in terms of the positive peaks (trough point, TT) of identical EEG data in a referential montage. Among six EEG data sections defined according to TT, the number of FOs, peak power values, and peak frequencies were compared. We identified a total of 1014 FOs (946 gamma and 68 ripple oscillations), which clustered closely at TT. The number of gamma oscillations in the 1s epoch including TT was significantly higher than those in the prior and subsequent phases. Peak power values and frequencies tended to be higher in these positive phase sections. The temporal association of FO clustering and positive slow waves in the ictal EEGs of ES indicated that active neuronal firing related to FOs underlies the generation of ESs and their ictal slow waves.


A novel in vivo mouse intervertebral disc degeneration model induced by compressive suture.
Intervertebral disc degeneration (IDD) is the root cause of many musculoskeletal disorders of the spine. However, the etiology of IDD is complex and still not well understood. Animal models of IDD would be useful in deciphering the underlying mechanisms. But the existing animal models have their limitations. Therefore, to establish a novel mouse model that can simulate the human IDD process in vivo, we proposed to carefully circumcise the 2 mm-wide tail skin and then compressively sutured the defect with a simple end-to-end suture to exert excessive pressure on the disc. After 1-week, 2-week, and 4-week compression, the mice were sacrificed and the intervertebral discs were harvested for tissue analysis. The radiological, morphological, and molecular modifications of intervertebral discs were measured to characterize this model. Radiologically, the water content of the intervertebral disc decreased significantly after 2-week compression. Morphologically, the nucleus pulposus showed a decrease in volume and the number of notochordal cells. The compressive suture also broke the balance between anabolic and catabolic enzymes in nucleus pulposus, which led to the remodeling of the extracellular matrix in nucleus pulposus as the content of aggrecan and collagen II decreased. The compressive suture could induce intervertebral discs degeneration in a more reasonable way, which was solely influenced by mechanical loading, as the mice caudal vertebrae still moved freely after the operation. This kind of animal model could be adapted as a reliable in vivo mouse IDD model for the research regarding the etiology and treatments of IDD.


Pseudoisodicentric bisatellited extra marker chromosome (tetrasomy 22pter----q11, trisomy Yqh), derived from a maternal Y/22 translocation. Association between this tetrasomy and "cat eye" phenotypical features.
A patient with multiple congenital anomalies suggestive of the "Cat eye" syndrome was found to have an extra marker bisatellited chromosome 22 derived from a maternal Y/22 translocation, identified by multiple banding patterns in cultures treated with DA. The proband's karyotype is 47,XX, + psu idic(22)(Yqter----Yq12::22p13----22q11::++ +22q11----22p13::Yq12----Yqter), t(22;Y)(p13;q12)mat., being tetrasomic for 22pter----q11, and trisomic for Yqh. Similarity between his clinical features and reported "Cat eye" cases, confirms that this region is responsible for the phenotypical expression of the syndrome.


Growth and Biochemical Composition Characteristics of Arthrospira platensis Induced by Simultaneous Nitrogen Deficiency and Seawater-Supplemented Medium in an Outdoor Raceway Pond in Winter.
Arthrospira platensis, a well-known cyanobacterium, is widely applied not only in human and animal nutrition but also in cosmetics for its high amounts of active products. The biochemical composition plays a key role in the application performance of the Arthrospira biomass. The present study aimed to evaluate the growth and biochemical composition characteristics of A. platensis, cultured with a nitrogen-free and seawater-supplemented medium in an outdoor raceway pond in winter. The results showed that the biomass yield could achieve 222.42 g m-2, and the carbohydrate content increased by 247% at the end of the culture period (26 d), compared with that of the starter culture. The daily and annual areal productivities were 3.96 g m-2 d-1 and 14.44 ton ha-1 yr-1 for biomass and 2.88 g m-2 d-1 and 10.53 ton ha-1 yr-1 for carbohydrates, respectively. On the contrary, a profound reduction was observed in protein, lipid, and pigment contents. Glucose, the main monosaccharide in the A. platensis biomass, increased from 77.81% to 93.75% of total monosaccharides. Based on these results, large-scale production of carbohydrate-rich A. platensis biomass was achieved via a low-cost culture, involving simultaneous nitrogen deficiency and supplementary seawater in winter.


Rapid genotyping of single nucleotide polymorphisms using novel minor groove binding DNA oligonucleotides (MGB probes).
Novel fluorescent oligonucleotides that contain a 3' minor groove binding group (MGB) hybridize to single-stranded targets with increased sequence-specificity compared to ordinary DNA probes. This reduces non-specific probe hybridization and results in low background fluorescence during the 5' nuclease PCR assay (TaqMan, Applied Biosystems, Foster City, CA). We developed a method for closed-tube genotyping using two allele-specific MGB probes labeled with different fluorophores in one reaction. After PCR, tubes were transported to a fluorescence plate-reader for analysis of fluorescence. Common spreadsheet software was used for automated genotype assignment. As an example, DNA samples from 172 hemochromatosis patients were selected and tested for molecular defects in the HFE gene, i.e., mutations in codon 63 and 282. Tight genotype clusters were observed for both codons and results with MGB probes were identical to conventional genotyping (PCR + restriction-fragment-length-polymorphism). We show that this fast and easy method can be used for large-scale (high-throughput) genetic studies but also for routine molecular diagnostics without post-PCR manipulation of amplicons or the need for real-time quantitative PCR machines. Hum Mutat 19:554-559, 2002.


Regulation of axial elongation by Cdx.
The primordia of the post-otic mouse embryo forms largely from a bipotential cell population containing neuromesodermal progenitors (NMP) which reside in the tail bud and contribute to the elaboration of the major body axis after gastrulation. The mechanisms by which the NMP population is both maintained and subsequently directed down mesodermal and neural lineages is incompletely understood. The vertebrate transcription factor Cdx2, is essential for axial elongation and has been implicated in maintaining the NMP niche and in specification of NMP derivatives. To better understand the role of the Cdx family in axial elongation, we employed a conditional mutant allele which evokes total loss of Cdx function, and enriched for tail bud progenitors through the use of a Pax2-GFP transgenic reporter. Using this approach, we identified 349 Cdx-dependent genes by RNA sequencing (RNA-seq). From these, Gene Ontology and chromatin immunoprecipitation analysis further revealed a number of putative direct Cdx candidate target genes implicated in axial elongation, including Sp8, Isl1, Evx1, Zic3 and Nr2f1. Additional analysis of available single-cell RNA-seq data from mouse tail buds revealed the co-expression of Sp8, Isl1, Evx1 and Zic3 with Cdx2 in putative NMP cells, while Nr2f1 was excluded from this population. These findings identify a number of novel Cdx targets and provide further insight into the critical roles for Cdx in elaborating the post-otic embryo.


Lysophospholipase of Escherichia coli.
A lysophospholipase from Escherichia coli cells was purified about 1,500-fold to near homogeneity by extraction with Tris-HCl buffer, streptomycin treatment, (NH4)2SO4 fractionation, column chromatographies on Sephadex G-200, DEAE-cellulose and hydroxylapatite-cellulose, and polyacrylamide gel electrophoresis. The final preparation had a molecular weight of 39,500 plus or minus 500. The enzyme hydrolyzes 1-acylglycerylphosphorylethanolamine, 2-acylglycerylphosphorylethanoiamine, and 1-acylglycerylphosphorylglycerol, but does not attack diacylphospholipids with long chain fatty acids, such as phosphatidylethanolamine and phosphatidylglycerol. The enzyme does not show any esterase activity against p-nitrophenyl acetate or palmitate. Although it does not hydrolyze triacylglycerol or diacylglycerol, it hydrolyzes 1-acylglycerol at almost the same rate as 1-acyl-sn-glycerol-3-phosphorylethanolamine. Results indicated that the acyl-hydrolyzing activities toward monoacyl-glycerylphosphorylethanolamine and monoacylglycerol belong to the same enzyme. In general, acidic and nonionic detergents inhibited the reaction. This lysophospholipase preparation hydrolyzes the monomolecular and micellar forms of lysophospholipids as well as of monoacylglycerol. The monomolecular and micellar forms of Triton X-100 both inhibited the hydrolyses of lysophospholipids and monoacylglycerol.


Effect of 1.5 tesla nuclear magnetic resonance imaging scanner on implanted permanent pacemakers.
Patients with a permanent pacemaker are currently restricted from diagnostic nuclear magnetic resonance (NMR) imaging because of potential adverse effects on the pacemaker by the magnet. Previous work has shown that NMR imaging will result in asynchronous pacing of the pulse generator within a given distance of the magnet. The radiofrequency signal generated by the system may also result in rapid cardiac pacing, which may have deleterious effects. This study utilized a 1.5 tesla unit in an in vivo laboratory animal to evaluate the unit's effects on eight different pulse generators from two manufacturers. All pacemakers functioned in an asynchronous mode when placed within a certain distance of the magnet. In addition, transient reed switch inhibition was observed. Seven of the eight pulse generators paced rapidly when exposed to the radiofrequency signal and there was a dramatic decrease in arterial blood pressure. Whether effective rapid cardiac pacing would occur could not be predicted before exposure to the magnetic resonance unit. Nuclear magnetic resonance imaging with high magnetic fields in patients with a pacemaker should continue to be avoided until the mechanism of the rapid cardiac pacing can be further delineated and either predicted or prevented.


Investigation of wavy microchannel ability on electronic devices cooling with the case study of choosing the most efficient microchannel pattern.
A numerical study was conducted to investigate the ability of wavy microchannels to damp the temperature fluctuations generates in electronic devices. Five wavy patterns are considered with the amplitude and wavelength in the ranges of 62.5 to 250 μm and 1250 to 5000 μm, respectively to study the effect of governing phenomena of flow within wavy patterns on thermal-hydraulic performance. The flow regime is laminar and the Reynolds number is in the range of 300 to 900, and a relatively high heat flux of 80 W/cm2 is applied to the microchannels substrate. Also, variable flux condition is studied for heat fluxes of 80, 120, 160, 200, and 240 W/cm2 and for the most efficient wavy and straight microchannels. Results showed that the geometries with larger amplitude to wavelength ratio have a lower radius of curvature and larger Dean number, and as a result of transverse flow (secondary flow) amplification, they have enhanced heat transfer. Also, by comparing the ratio of the transverse velocity components to the axial component, it was found that by decreasing the radius of curvature and increasing the Dean number, transverse velocity increases, which intensifies the heat transfer between the wall and the fluid. The appraisement of the performance evaluation criterion (PEC) illustrates that the wavy case with an amplitude of 250 μm and wavelength of 2500 μm is the best geometry from the thermal-hydraulic point of view in the studied range. Finally, with variable flux condition, the wavy microchannel has responded well to the temperature increase and has created a much more uniform surface temperature compared to straight pattern. The proposed wavy pattern ensures that there are no hotspots which could damage the electronic chip. Presented wavy patterns can be used in heat sinks heat transfer enhancement to allow the chip to run in higher heat fluxes.


Vago-vagal activation of naloxone-sensitive non-adrenergic, non-cholinergic jejunal contractions in the anaesthetized cat.
Experiments were performed on chloralose-anaesthetized cats, pretreated with guanethidine and with ligated adrenals and sectioned splanchnic nerves. The animals were paralysed and artificially ventilated. Jejunal motility was recorded by an intraluminal balloon, as volume changes at a constant pressure. Cervical or abdominal vagal afferent stimulation was performed before and after the administration of atropine. In both circumstances jejunal contractions were elicited. The latency of onset and the duration of the responses were significantly shorter before than after atropine. Strength-duration and frequency-response relationships, respectively, did not differ significantly prior and subsequent to atropine. Naloxone (0.05-0.5 mg kg-1 i.v.) blocked these reflexly induced atropine-resistant jejunal contractions, as did section of the contralateral vagus. Possible mechanisms of action of these putative opioid receptor-mediated neurogenic effects are discussed. The present study demonstrates that non-adrenergic, non-cholinergic, naloxone-sensitive jejunal contractions can be elicited as a vago-vagal reflex, where the receptive field seems to be located within the abdominal cavity.


[Haplotype Analysis of Oculopharyngeal Muscular Dystrophy (OPMD) Locus in Yakutia].
Oculopharyngeal muscular dystrophy (OPMD) is a hereditary neuromuscular disease with autosomal dominant and rarely with autosomal recessive inheritance types. This study included 50 patients with a clinical diagnosis of OPMD, 23 asymptomatic carriers of the mutation from 45 unrelated families, and 56 healthy relatives, as well as population samples of four ethnic groups of Yakutia: Yakuts, Evens, Evenks, Yukaghirs. It was found that the cause of OPMD development in all investigated families is the same increase in.GCN repeats to 14 copies in the PABPN1 gene. The molecular structure ofthe (GCN)₁₄ mutant allele is (GCG)₁₀(GCA)₃GCG. The genetic variability of ten SNPs at the OPMD locus was studied in patient families and population samples. The haplotypes of OPMD were determined by a segregation analysis technique using the EM algorithm in the groups of patients, mutation carriers, and population samples. Only one haplotype of four SNPs (ATCG) linked with the (GCN)₁₄ mutant allele was found in Yakuts and Russian patients and OPMD mutation carriers. Probably, this indicates the accumulation of mutations as a result of the founder effect.


The patient involvement in nursing education: A mixed-methods systematic review.
To evaluate the effects patient involvement in nursing education has on students, patients and academic staff using a specific theoretical framework. Mixed-methods systematic review based on Joanna Briggs Institute methodology (Prospero no. CRD42022327158). Seven databases (PubMed, Cochrane Library, Cinahl, PsychINFO, Scopus, ERIC, Embase), Google Scholar and reference lists were searched. Qualitative, quantitative and mixed-method studies published from 2012 to 2022 were included. Two reviewers independently assessed the studies for eligibility and quality; any disagreement was discussed with a third reviewer. Data were extracted and analysed according to the Joanna Briggs Institute converged integrated approach. Twenty-one qualitative, one quantitative and five mixed-methods studies met the inclusion criteria. Data were provided from three points of view: students, patients and academic staff. Student integrated findings included: (i) students' reactions towards patient involvement in education; (ii) students' views on the learning process and (iii) on ethical issue. From the patient point of view, the integrated findings addressed (i) patients' goals and effects on students' learning; (ii) how patients teach and get involved with students; (iii) how patients perceived their role; the patients' views on facilitators (iv) and barriers (v) in education; (vi) the perceived effects of being involved in education. Four integrated findings were derived from the academic staff's point of view: (i) academics' perceptions on patient vulnerability; (ii) perceived barriers to the efficacy of patient involvement in education; (iii) effects of patient involvement in nursing education; and (iv) methodological aspects of patient involvement in university curriculum. This systematic review provides useful information from all stakeholders' perspectives on the effects of patient involvement in nursing education. It offers a broader view of the implications for implementation and for developing theoretical frameworks and hypotheses for future research.


A systematic review of underlying genetic factors associated with ureteropelvic junction obstruction in stenotic human tissue.
Genetic factors are implicated in the development of ureteropelvic junction obstruction (UPJO). The aims of this study were: 1) condense and examine the existing data in studies containing information regarding differential gene expression in tissues from patients with UPJO and 2) investigate associations between genetic markers and their related pathways. A systematic review of studies published between January 2000 and September 2021 was conducted using the following databases: Ovid/Medline, PubMed, Wiley Cochrane Central Register of Controlled Trials, Web of Science, and Scopus. Of 249 studies, 10 were included in the final analysis. The search was performed using the terms "ureteropelvic junction obstruction", "genetic", "gene", and "gene expression". Literature pertaining to differential gene expression in UPJO patients as compared to healthy controls was identified. Studies containing gene expression and quantification of molecular data carried out directly on stenotic tissue samples were selected for analysis. Gene network connections and functional analyses were then determined using MetaScape software. From the ten studies identified for analysis, fifteen genes were noted as differentially expressed. In UPJO patients, nine genes were upregulated (ET1, ACTA2, MCP-1, TGFB1, NFKB1, IL-6, HIF1A, S100A1, SYP) and six were downregulated (ADM, NOS2, EGF, PDGFRA, UCHL1, NGFR). These genes were principally involved in HIF-1 signaling pathway, blood vessel development, positive regulation of signaling receptor activity, and Ras signaling pathway. A potential link exists between genes related to hypoxia, excessive fibrous tissue formation, and inflammation in the development of UPJO, and these connections merit more detailed, tissue level investigations in UPJO patients. The outcomes of this systematic review may lay the groundwork for the development of future targeted therapies and novel biomarker detection for treatments, early detection, and possible prediction and prevention of development of UPJO.


The diameter response of retinal arterioles in diabetic maculopathy is reduced during hypoxia and is unaffected by the inhibition of cyclo-oxygenase and nitric oxide synthesis.
Diabetic retinopathy is accompanied with changes in the diameter regulation and oxygenation of retinal vessels. Previous studies have shown that in normal persons and in diabetic patients without retinopathy hypoxia-induced vasodilatation is mediated by cyclo-oxygenase (COX) products and nitric oxide (NO). The purpose of the present study was to study whether these effects can be reproduced in patients with diabetic maculopathy. Eighteen patients with diabetic maculopathy aged 29-57 years were examined using the Dynamic Vessel Analyzer. The resting diameter and the diameter changes of retinal arterioles during isometric exercise and flicker stimulation were studied before and during breathing a hypoxic gas mixture. The examinations were also performed before and during intravenous infusion of the NOS inhibitor L-NMMA, and were repeated on a second day after topical administration of the COX-inhibitor diclofenac. The diameter of retinal arterioles showed no significant change during hypoxia or L-NMMA infusion, or after topical application of diclofenac (p > 0.25 for all comparisons). The resting diameter of the venules was significantly increased during hypoxia (p = 0.003) and decreased during L-NMMA infusion (p < 0.0001). The diameter of retinal venules during isometric exercise increased significantly during hypoxia (p = 0.01). Flicker stimulation induced significant dilatation of the venules, which was significantly reduced during hypoxia and increased during L-NMMA infusion (p < 0.0001 for all comparisons). Hypoxia-induced dilatation of retinal arterioles is severely reduced in patients with diabetic maculopathy. Future intervention studies aimed at normalizing the diameter regulation of retinal arterioles in diabetic patients should preferentially be conducted in the early stages of the disease where the potential for changing the vessel diameter is preserved. ClinicalTrials.gov identifier: NCT01689090.


Implementing Lean Quality Improvement in Primary Care: Impact on Efficiency in Performing Common Clinical Tasks.
Many primary care practices have adopted Lean techniques to reduce the amount of time spent completing routine tasks. Few studies have evaluated both immediate and sustained impacts of Lean to improve this aspect of primary care work efficiency. To examine 3-year impacts of Lean implementation on the amount of time taken for physicians to complete common clinical tasks. Non-randomized stepped wedge with segmented regression and interrupted time series analysis (January 2011-December 2016). A total of 317 physician-led teams in 46 primary care departments in a large ambulatory care delivery system. Lean redesign was initiated in one pilot site followed by system-wide spread across all primary care departments. Redesigns included standardization of exam room equipment and supplies, streamlining of call management processes, care team co-location, and team management of the electronic inbox. Time-stamped EHR tracking of physicians' completion time for 4 common tasks: (1) office visit documentation and closure of patient charts; (2) telephone call resolution; (3) prescription refill renewal; and (4) response to electronic patient messages. After Lean implementation, we found decreases in the amount of time to complete: office visit documentation (- 29.2% [95% CI: - 44.2, - 10.1]), telephone resolution (- 22.2% [95% CI: - 38.1, - 2.27]), and renewal of prescription refills (- 2.96% per month [95% CI: - 4.21, - 1.78]). These decreases were sustained over several years. Response time to electronic patient messages did not change significantly. Lean redesigns led to improvements in timely completion of 3 out of 4 common clinical tasks. Our findings support the use of Lean techniques to engage teams in routine aspects of patient care. More research is warranted to understand the mechanisms by which Lean promotes quality improvement and effectiveness of care team workflows.


The influence of total hip replacement on hip pain and the use of analgesics.
The influence of total hip replacement (THR) on pain and use of analgesics was evaluated in 511 patients with McKee-Farrar and Brunswik prostheses. The mean age of the patients was 63.8 years and the mean follow-up time 4.2 years. The average grade of pain decreased from 1.8 to 4.9 as evaluated according to Charnley. The proportion of regular users of all analgesics decreased from 75% to 17% (P less than 0.001). Indomethacin was the most common preoperative drug and the proportion of its regular use decreased from 47 to 12% (P less than 0.001). The preoperative association which existed between the grade of pain and the regular drug users in each pain grade decreased more than expected by the preoperative figures. Postoperatively those with previous hip operations, McKee-Farrar prosthesis, one hip replaced, reapplications and removal of the prosthesis gave inferior results with respect to pain than those without previous surgery, with Brunswik prosthesis, both hips replaced and with the original prosthesis in situ. In addition to previous THR operations, type of the hip prosthesis, bilateral or unilateral surgery, primary or secondary coxarthrosis and reapplication of the prosthesis influenced the use of drugs. THR, however, brought a marked drop in the use of analgesics and this effect should be taken into account when assessing the costs and benefits of THR.


The failed attribution of the Nobel Prize for Medicine or Physiology to Viktor Hamburger for the discovery of Nerve Growth Factor.
The announcement in October 1986 that the Nobel Prize for Physiology or Medicine was to awarded to Rita Levi Montalcini and Stanley Cohen for the discovery of nerve growth factor (NGF) and epidermal growth factor, respectively, caused many to wonder why Viktor Hamburger in whose laboratory the initial work was done had not been included in the award. This article try to reconstruct the history of the discovery of NGF with the aim to re-establish a correct dynamic of the events.


Aldehyde dehydrogenase 2 and arrhythmogenesis.
Cardiac arrhythmia is a common cardiovascular disease that leads to considerable economic burdens and significant global public health challenges. Despite the remarkable progress made in recent decades, antiarrhythmic therapy remains suboptimal. Aldehyde dehydrogenase 2 (ALDH2), a critical detoxifying enzyme, catalyzes toxic aldehydes and protects individuals from damage caused by oxidative stress. Accumulating evidence has demonstrated that ALDH2 activation has potential antiarrhythmic benefits. The correlation between ALDH2 deficiency and arrhythmogenesis has been widely recognized. In this review, we summarize recent research on the potential role of ALDH2 activation and antiarrhythmic protection, as well as the role played by the ALDH2∗2 polymorphism (rs671) in promoting arrhythmic risk. Additionally, we discuss important new findings illustrating the use of ALDH2 activators, which may prove to be promising antiarrhythmic therapy agents.


Cavovarus deformity in Charcot-Marie-Tooth disease: is there a hindfoot equinus deformity that needs treatment?
Charcot-Marie-Tooth disease (CMT), one of the most common hereditary neurologic disorders, often results in debilitating cavovarus foot deformities. The deformities are still not fully understood, and the treatment recommendations are consequently heterogeneous, often including calf muscle or Achilles tendon lengthening. We examined 40 patients (80 feet) with CMT and bilateral cavovarus deformities (19 men and 21 women, mean age 33.6 ± 14.6 years) and the feet of a healthy control population of 13 individuals (7 men and 6 women, mean age 43.9 ± 10.8 years). In all cases 3D instrumented gait analysis results with both conventional Plug-in-Gait analysis and the Heidelberg Foot Measurement Method (HFMM) were used to determine the sagittal plane kinematics, dorsi-plantar flexion (DPF), tibio-talar dorsiflexion (TTDF), and medial arch angle (MAA), and the results of patients and the control group were compared using the 2 methods. Decreased and increased dorsiflexion using TTDF was defined as 1 standard deviation below or above the mean of the control. Comparisons were done using descriptive statistics, the Pearson correlation coefficient and ANOVA. The TTDF was found to be decreased in 18 of the 80 feet examined (22.5 %), normal in 31 feet (38.75 %), and increased in 31 feet (38.75 %). The Pearson coefficient showed a positive correlation with R = 0.765, p < 0.001 between decreased TTDF values found by HFMM and decreased DPF values found with conventional Plug-in-Gait analysis, but a very weak correlation in patients with normal TTDF (R = -0.118) and increased TTDF (R = 0.078). Also, in patients with decreased TTDF values, there was a weak to moderate correlation with the MAA (R = 0.335), but no correlation between the MAA and DPF (R = 0.023). The HFMM, unlike the conventional Plug-in-Gait analysis, distinguishes between the segments of the foot in foot deformities and facilitates evaluation of the hindfoot equinus component in patients with CMT and cavovarus deformity. Although there is a significant correlation between decreased TTDF with HFMM and decreased DPF with conventional Plug-in-Gait analysis, this correlation was not seen in patients with normal or increased TTDF values. Conventional Plug-in-Gait analysis alone does not indicate if an increased plantar flexion deformity is the result of either a cavus deformity or hindfoot equinus deformity, which limits its usefulness in assisting in treatment decision making.


Overweight patients are more susceptible for acute liver failure.
To determine a potential correlation of gender, age, and/or body mass index (BMI) with the development of acute-on-chronic liver failure (AOC). A retrospective 2.5-year study employed 34 patients (65% females and 35% males, aged 37.9 +/- 12.6 years) fulfilling established criteria for acute liver failure (ALF). Patients were subdivided into ALF (n = 18) and AOC (n = 16) groups, according to a history of prior chronic liver disease. Causes of liver failure included drug toxicity (52.9%), viral hepatitis (26.5%), and acute excessive ethanol abuse (11.8%). all anamneses were thoroughly reviewed. Throughout the course of the study, the patients were monitored for established clinical signs and laboratory parameters indicating acute liver injury. Gender, age, and BMI were correlated with the clinical outcome. Twelve patients (35.3%) received an orthotopic liver allograft, with one re-transplantation. Six patients (17.6%), including two transplanted individuals, died in the course of the study. Of all parameters evaluated, BMIs were significantly higher in AOC vs. ALF (p < 0.002), revealing values of > 25 in 62.5% of the AOC patients. When subjected to acute risk factors, elevated BMI clearly coincided with a higher rate of AOC. Importantly, half of all patients initially classified as ALF by employing current criteria thus suffered from AOC coinciding with increased mortality. Generally, these results call for a reduction of the BMI. Specifically, our findings argue for a closer BMI monitoring of patients at risk of developing chronic liver disease.


Manganese peroxidase h4 isozyme mediated degradation and detoxification of triarylmethane dye malachite green: optimization of decolorization by response surface methodology.
A cDNA encoding for manganese peroxidase isozyme H4 (MnPH4), isolated from Phanerochaete chrysosporium, was expressed in Pichia pastoris, under the control of alcohol oxidase I promoter. The recombinant MnPH4 was efficiently secreted onto media supplemented with hemin at a maximum concentration of 500 U/L, after which purified rMnPH4 was used to decolorize the triarylmethane dye malachite green (MG). Response surface methodology (RSM) was employed to optimize three different operational parameters for the decolorization of MG. RSM showed that the optimized variables of enzyme (0.662 U), MnSO4 (448 μM), and hydrogen peroxide (159 μM) decolorized 100 mg/L of MG completely at 3 h. Additionally, UV-VIS spectra, high-performance liquid chromatography, gas chromatography-mass spectrometry, and liquid chromatography-electrospray ionization/mass spectrometry analysis confirmed the degradation of MG by the formation of main metabolites 4-dimethylamino-benzophenone hydrate, N, N-dimethylaniline (N,N-dimethyl-benzenamine), and methylbenzaldehyde. Interestingly, it was found that rMnPH4 mediates hydroxyl radical attack on the central carbon of MG. Finally, rMnPH4 degraded MG resulted in the complete removal of its toxicity, which was checked under in vitro conditions.


Human Recombinant Arginase I [HuArgI(Co)-PEG5000]-Induced Arginine Depletion Inhibits Pancreatic Cancer Cell Migration and Invasion Through Autophagy.
Pancreatic cancer is one of the most aggressive solid cancers and the fourth leading cause of cancer death in men and women. We previously showed that arginine depletion, using arginase I [HuArgI(Co)-PEG5000], selectively triggers cell death by autophagy in PANC-1 pancreatic cancer cells. The mechanism of action of [HuArgI(Co)-PEG5000], however, has remained poorly understood. In this study, we investigated the effects of arginine depletion on PANC-1 cell migration, adhesion, and invasion and determined the main molecular targets, which mediate PANC-1 cell response to treatment with HuArgI(Co)-PEG5000. This was done through examining 2-dimensional (2D) cell motility assays (wound healing and time lapse), cell adhesion, and cell invasion assays, as well as immunostaining for focal adhesions and invadopodia in cells without or with the treatment with arginase. We demonstrate that arginine depletion decreases PANC-1 2D cell migration, adhesion, and 3D invasion. Moreover, our data suggest that these effects are mediated by autophagy and subsequent decrease in the activation of members of Ras homolog gene family (Rho) GTPase family. Altogether, these findings uncover the mechanism of action of [HuArgI(Co)-PEG5000] and highlight the promising and selective anticancer potential for arginine depletion in the treatment of pancreatic cancer cells.


Vitamin D Deficiency Is Prevalent in Morbidly Obese Adolescents Prior to Bariatric Surgery.
Obese adults are frequently vitamin D deficient before bariatric surgery; whether similar abnormalities exist in morbidly obese adolescents is unknown. To determine the prevalence of vitamin D deficiency in morbidly obese adolescents. Cross-sectional study of preoperative laboratory measures from 236 adolescents evaluated for bariatric surgery. The group (N = 219 with 25-hydroxyvitamin D (25OHD) and parathyroid hormone (PTH) levels; 76 boys, 143 girls; 15.9 ± 1.2 years; 43% Caucasian, 35% Hispanic, and 15% African American) had mean BMI of 47.6 ± 8.1 kg/m2. 25OHD levels were deficient (<20 ng/mL) in 53%; 8% had severe deficiency (<10 ng/mL); only 18% of patients were replete (>30 ng/mL). 25OHD levels were inversely associated with BMI (r = -0.28, < 0.0001) and PTH levels (r = -0.24, P = 0.0003). Race was the strongest predictor of 25OHD (P < 0.002); 82% of African Americans, 59% of Hispanics, and 37% of Caucasians were deficient. African American race, BMI, and PTH explained 21% of the variance in 25OHD (P < 0.0001). Most adolescents presenting for bariatric surgery have suboptimal vitamin D levels, with African Americans and those with higher BMIs at greatest risk for vitamin D deficiency. All morbidly obese adolescents should be screened for vitamin D deficiency before bariatric procedures.


Emergence of multi-drug resistant organisms (MDROs) causing Fournier's gangrene.
Fournier's gangrene is an uncommon but often devastating infection. There are few contemporary data on the risk factors and evolving microbiologic trends including drug-resistant organisms implicated in these life-threatening infections. A retrospective study of Fournier's gangrene from 2006 to 2015 at a large academic hospital was conducted. Cases were identified using ICD codes (ICD-9: 608.83, V13.89; ICD-10: N49.3, Z87.438), and a review of medical, radiographic, and pathology records was performed to confirm each case. Data collected included socio-demographics, medical conditions, bacterial pathogens and their resistance patterns, treatments, and outcome. Descriptive and univariate statistics were performed. A total of 59 cases were evaluated with an overall incidence of 31.8 cases per 100,000 admissions which remained stable over the study period. Mean age was 56 years (range 18-91), 71% were male, and 44% white. Risk factors included overweight/obesity (61%), diabetes (44%, with a mean A1c of 9.6%), immunocompromised state (34%), and illicit use (20%). A causative organism was identified in all except 2 cases; 12 patients (21%) had a multidrug-resistant organism (MDRO) with MRSA being the most common pathogen (n = 8, 14% of all cases), followed by ESBL E. coli (n = 3) and MDRO Acinetobacter (n = 1). MRSA was the sole pathogen isolated in five (63%) of the eight cases involving this organism. Among those with an aerobic Gram-negative rod (GNR) isolated, 32% were fluoroquinolone-resistant. Overall, 30% of cases had a poor outcome (15% died and an additional 15% had loss of an organ/body part). Those with an MDRO were more likely to experience a poor outcome (42% vs. 28%), although this was not statistically significant (p = 0.48); of note, most (83%) MDRO cases were initially treated with an antibiotic that the organism was susceptible. This report highlights the emergence of MDROs as an important cause of Fournier's gangrene including MRSA and drug-resistant GNRs. Antibiotics should be chosen with broad-spectrum, anti-MDRO activity given the high morbidity and mortality associated with these infections.


An alternative Avrami equation to evaluate kinetic parameters of the interaction of Hg(II) with thin chitosan membranes.
In this work, thin chitosan membranes were utilized as an adsorbent for the removal of Hg(II) from aqueous solutions. A rise of temperature accelerates the mass transfer of Hg(II) to the membranes, surfaces. The kinetic data did not present a good fitting to the traditional Lagergren adsorption kinetic equations. An alternative Avrami kinetic equation was employed and successfully fitted to the kinetic adsorption quantities. From this new equation, two regions presenting distinct kinectic parameters were found, and the use of the parameter n was also relationed to the determination of the kinetic order. Variations of the adsorption kinetic rate in relation to the time, the initial Hg(II) concentration, and the temperature were also calculated and are discussed.


Human bertiellosis from north India.
A 4-y-old boy presented with a history of episodes of gripping abdominal pain and intermittent shedding of segments of a worm in stool, which used to actively change in size and shape. On the basis of measurements of the segments and characteristic features of the eggs, the worm was identified as Bertiella studeri. The characteristic morphological details of the worm, the pitfalls in its identification and the zoonotic potential of this rare cestodal infection are discussed here.


Automated parallel solid-phase synthesis of non-peptide CCR1 receptor antagonists.
An automated, parallel, solid-phase synthesis and screening strategy using commercially available aryl acetic acids as starting materials has discovered novel, non-peptide CCR1 antagonists (K(i) < 100 nM).


Anterior cingulate cortex orexin signaling mediates early-life stress-induced social impairment in females.
Early-life stress has long-term impacts on the structure and function of the anterior cingulate cortex (ACC), and raises the risk of adult neuropsychiatric disorders including social dysfunction. The underlying neural mechanisms, however, are still uncertain. Here, we show that, in female mice, maternal separation (MS) during the first three postnatal weeks results in social impairment accompanied with hypoactivity in pyramidal neurons (PNs) of the ACC. Activation of ACC PNs ameliorates MS-induced social impairment. Neuropeptide Hcrt, which encodes hypocretin (orexin), is the top down-regulated gene in the ACC of MS females. Activating ACC orexin terminals enhances the activity of ACC PNs and rescues the diminished sociability observed in MS females via an orexin receptor 2 (OxR2)-dependent mechanism. Our results suggest orexin signaling in the ACC is critical in mediating early-life stress-induced social impairment in females.


Immunogenicity of two recombinant hepatitis B vaccines in older individuals.
Currently available hepatitis B vaccines are recombinant, yeast-derived preparations given in 10-micrograms or 20-micrograms doses. The optimum dose remains controversial. We sought to assess the relative immunogenicity of two hepatitis B vaccines, given in different doses, in older individuals. In a multicenter, double-blind, randomized clinical trial, a total of 460 healthy subjects between 39 and 70 years of age were screened and immunized with either Engerix-B 20 micrograms or Recombivax HB 10 micrograms in standard, intramuscular, 3-dose regimens. Of these, 397 subjects were eligible to continue vaccination. Immunogenicity was measured by determination of antibody to hepatitis B surface antigen (anti-HBs). Seroconversion and seroprotection rates, and geometric mean titers of anti-HBs were calculated at 1, 3, 6, and 8 months after the initial dose of vaccine. Seroprotection rates for subjects receiving the 20-micrograms dose of vaccine were slightly, but not significantly, greater than for subjects receiving the 10-micrograms dose, at each time point. However, at 3 months, males receiving the higher dose had significantly higher seroprotection rates than males receiving the lower dose: 63% versus 37% (p < 0.001). At 8 months, geometric mean titers for the group receiving Engerix-B 20 micrograms were significantly greater than that for the group receiving Recombivax HB 10 micrograms: 840 mIU/mL versus 340 mIU/mL (p = 0.001). Immunization with the 20-micrograms dose of recombinant hepatitis B virus vaccine appeared to result in more rapid development of seroprotective anti-HBs titers in older men and in higher titers of anti-HBs at the completion of vaccination when compared to the 10-micrograms dose. The latter data suggest that the 20-micrograms dose may result in a longer duration of seroprotective anti-HBs titers.


Identification and validation of shared genes and key pathways in endometriosis and endometriosis-associated ovarian cancer by weighted gene co-expression network analysis and machine learning algorithms.
Epidemiological studies reported that patients with endometriosis had an increased risk of developing endometriosis-associated ovarian cancer (EAOC). The present study aimed to identify shared genes and key pathways that commonly interacted between EAOC and endometriosis. The expression matrix of ovarian cancer and endometriosis were collected from the Gene Expression Omnibus database. The weighted gene co-expression network analysis (WGCNA) was used to construct co-expression gene network. Machine learning algorithms were applied to identify characteristic genes. CIBERSORT deconvolution algorithm was used to explore the difference in tumor immune microenvironment. Furthermore, diagnostic nomogram was constructed and evaluated for supporting clinical practicality. We identified 262 shared genes between EAOC and endometriosis via WGCNA analysis. They were mainly enriched in cytokine-cytokine receptor interaction. After protein-protein interaction network and machine learning algorithms, we recognized two characteristic genes (EDNRA, OCLN) and established a nomogram that presented an outstanding predictive performance. The hub genes demonstrated remarkable associations with immunological functions. Survival analysis indicated that dysregulated expressions of EDNRA and OCLN were closely correlated with prognosis of ovarian cancer patients. gene set enrichment analyses revealed that the two characteristic genes were mainly enriched in the cancer- and immune-related pathways. Our findings pave the way for further investigation of potential candidate genes and will aid in improving the diagnosis and treatment of EAOC in endometriosis patients. More research is required to determine the exact mechanisms by which these two hub genes affecting the development and progression of EAOC from endometriosis.


Effects of aerosol administration of a thromboxane receptor antagonist (S-1452) on experimental asthma in guinea pigs.
The importance of thromboxane A2 (TXA2), one of the arachidonate metabolites, in the pathogenesis of bronchial asthma has been emphasized recently. Because aerosolized administration of antiasthmatic drugs is effective and safe, this study examined the effect of aerosolized TXA2 receptor antagonist (S-1452) on allergic bronchoconstriction in passively sensitized and mechanically ventilated guinea pigs. Under the cover of antihistamine, antigen-induced bronchoconstriction was markedly inhibited by pretreatment with aerosolized S-1452 inhalation in a dose-dependent manner. Although aerosolized S-1452 itself provoked weak bronchoconstriction for its partial agonist effect, bronchial responsiveness to inhaled histamine did not change 10 min after S-1452 inhalation. These results indicate that aerosolized S-1452 may be useful in treating bronchial asthma.


Daily inhibition of postprandial hyperglycaemia with JTT-608, a novel oral antidiabetic agent, ameliorates pancreatic function in neonatally streptozotocin-treated rats.
Chronic glycaemic control, in particular, the control of postprandial hyperglycaemia, is essential for preventing the development of diabetic complications. We therefore evaluated the chronic treatment effect of a new antidiabetic agent, JTT-608 [trans-4-(methylcyclohexyl)-4-oxobutyric acid], in neonatally streptozotocin-treated rats. The rats were maintained with liquid meal three times a day and treated orally with JTT-608 10 min before each meal for 12 weeks. Haemoglobin A1C (HbA1C) and fasting blood glucose levels were measured at 4-week intervals, and effects of JTT-608 on pancreatic function and diabetic complications were examined after dosing period. The postprandial hyperglycaemia was suppressed by JTT-608 administration, and both HbA1C levels and fasting blood glucose levels were reduced during the experimental period. After the treatment period of 12 weeks, JTT-608 further improved the early insulin secretion and the impaired glucose tolerance after meal loading in the diabetic rats. Also, pathological examination revealed that JTT-608 reduced the incidence of the decrease in immunoreactivity of insulin. In examination of other diabetic complications, JTT-608 ameliorated the reduced motor nerve conduction velocities observed in diabetic rats and inhibited the incidence of cataracts with diabetes. We conclude that a newly developed antidiabetic agent, JTT-608, improves the pancreatic function and prevents the development of diabetic complications by inhibition of daily postprandial hyperglycaemia and could be useful for the treatment of diabetic subjects with impaired insulin secretion.


Proliferating cell nuclear antigen (PCNA) immunolabeling as a prognostic factor in invasive ductal carcinoma of the breast in Taiwan.
To evaluate the prognostic significance of proliferating cell nuclear antigen (PCNA) in breast cancer, an immunohistochemical assay was performed in 150 patients with invasive ductal carcinomas. The PCNA labeling index (PCNA-LI) was classified into two subgroups at a cut-off point of 45% that gave the best prognostic estimates for PCNA in survival analyses. Seventy-eight tumors had a low PCNA-LI of < or =45% and 72 tumors had a high PCNA-LI of >45%. A high PCNA-LI correlated significantly with p53 overexpression (P<0.03), positive axillary node (P<0.04), short disease-free survival (P<0.001) and overall survival (P<0.0002), but not with other factors. In multivariate analysis, the PCNA-LI predicted the disease-free (P<0.008) and overall survival (P = 0.0007) independently. Our study indicates that the PCNA-LI has independent prognostic value.


Agomelatine affects rat suprachiasmatic nucleus neurons via melatonin and serotonin receptors.
The hypothalamic suprachiasmatic nucleus (SCN), which functions as a circadian pacemaker in mammals, is influenced by melatonin and serotonin. Agomelatine, which acts as an antidepressant and can synchronize disturbed circadian rhythms, displays a unique mechanism of action involving both melatonergic agonist and 5-HT2C antagonist properties. This study investigated the dose-dependent effects of agomelatine, melatonin and a selective 5-HT2C receptor antagonist, S32006, on SCN neurons in an in vitro slice preparation. Brain slices containing the SCN were prepared from male Wistar rats and maintained in a recording chamber. Changes in firing rates of SCN neurons were recorded after perfusion of drugs. SCN firing rates were dose-dependently suppressed by 19.2-80.9% following perfusion of 0.04-0.32mM agomelatine (p<0.001, IC50=0.14mM). Perfusion with melatonin (0.4-3.2mM) resulted in 16.6-62.5% dose-dependent reductions in firing rates (at least p<0.01, IC50=1.59mM) and of the duration of suppression. A selective melatonin receptor antagonist (S22153 at 0.32mM) and a 5-HT2c receptor agonist (Ro60-0175) reduced the suppressive effects of 0.16mM agomelatine by 35% and 50.2%, respectively. A 5-HT2C receptor antagonist (S32006; 0.03-0.12mM) significantly decreased SCN firing rates (19.6-91.8%; at least p<0.05, IC50=0.05mM). Co-perfusion of S32006 (0.06mM) with a 5-HT2C agonist (Ro60-0175; 0.003mM) reduced suppressions evoked by S32006 alone by ~72.1%. These results are consistent with the hypothesis that agomelatine acts directly on the SCN via both agonist effects at melatonergic receptors and antagonist effects at 5-HT2C receptors, which parallel its mechanisms of action as an antidepressant.


Treatment of dopaminomimetic psychosis in Parkinson's disease with electroconvulsive therapy.
Two Parkinsonian patients with chronic nonconfusional dopaminomimetic psychosis were treated with a course of electroconvulsive therapy. In both cases sustained remission of psychosis was obtained in the face of ongoing administration of dopaminomimetics.


Identifying features of quality in rural placements for health students: scoping review.
To explore and synthesise the evidence relating to features of quality in rural health student placements. Scoping review. MEDLINE, CINAHL, Embase, ProQuest, Informit, Scopus, ERIC and several grey literature data sources (1 January 2005 to 13 October 2020). The review included peer-reviewed and grey literature from Organisation for Economic Co-operation and Development listed countries that focused on quality of health student placements in regional, rural and remote areas. Data were extracted regarding the methodological and design characteristics of each data source, and the features suggested to contribute to student placement quality under five categories based on a work-integrated learning framework. Of 2866 resulting papers, 101 were included for data charting and content analysis. The literature was dominated by medicine and nursing student placement research. No literature explicitly defined quality in rural health student placements, although proxy indicators for quality such as satisfaction, positive experiences, overall effectiveness and perceived value were identified. Content analysis resulted in four overarching domains pertaining to features of rural health student placement quality: (1) learning and teaching in a rural context, (2) rural student placement characteristics, (3) key relationships and (4) required infrastructure. The findings suggest that quality in rural health student placements hinges on contextually specific features. Further research is required to explore these findings and ways in which these features can be measured during rural health student placements.


Possible role of Coxsackie-B virus infection in pancreatitis.
Coxsackie-B antibodies were examined in a study of 118 patients with acute and relapsing chronic pancreatitis. The rise in antibody titers was significant in 40 cases. Fourteen had acute, five relapsing acute, and 21 chronic pancreatitis. Among patients with acute pancreatitis, we detected infectious hepatitis in six cases. Two patients with persisting acute pancreatitis received levamisole as an immune adjuvant, which promoted their recovery. It seems that Coxsackie-B virus can cause acute pancreatitis, and it can also worsen chronic pancreatitis.


Small non-coding RNAs govern mammary gland tumorigenesis.
Small non-coding RNAs include siRNA, miRNA, piRNA and snoRNA. The involvement of miRNAs in the regulation of mammary gland tumorigenesis has been widely studied while the role for other small non-coding RNAs remains unclear. Here we summarize the involvement of miRNA in breast cancer onset and progression through regulating the cell cycle and cellular proliferation. The regulation of breast cancer stem cells and tumor regeneration by miRNA is reviewed. In addition, the emerging evidence demonstrating the involvement of piRNA and snoRNA in breast cancer is briefly described.


Systematic characterization of Escherichia coli genes/ORFs affecting biofilm formation.
To understand the nature and function of bacterial biofilm and the process of its formation, we have performed systematic screening of a complete set of Escherichia coli genes/open reading frames (ORFs) to identify those that affect biofilm development upon over-expression. In contrast to the biofilm of strain AG1 used as a control, some of the genes/ORFs when over-expressed led to the formation of an abnormal biofilm such as thin, mat-like, filamentous or one easily detaching from various surfaces. Disruptants of selected genes were constructed in order to clarify their roles in the different stages of biofilm formation. Our results suggest that diverse metabolic pathways contribute to the development of biofilm.


Controllable Phosphorylation of Thioesters: Selective Synthesis of Aryl and Benzyl Phosphoryl Compounds.
The controllable phosphorylations of thioesters were developed. When the reaction was catalyzed by a palladium catalyst, aryl or alkenyl phosphoryl compounds were generated through decarbonylative coupling, while the benzyl phosphoryl compounds were produced through deoxygenative coupling when the reaction was carried out in the presence of only a base.


Efficacy of anti-CD47 antibody-mediated phagocytosis with macrophages against primary effusion lymphoma.
Recently, the critical role of CD47 on the surface of resistant cancer cells has been proposed in their evasion of immunosurveillance. Primary effusion lymphoma (PEL) is a subtype of aggressive non-Hodgkin lymphoma that shows serous lymphomatous effusion in body cavities, especially in advanced acquired immunodeficiency syndrome (AIDS). PEL is resistant to conventional chemotherapy and has a poor prognosis. In this study, we evaluated the effect of anti-CD47 antibody (Ab) on PEL in vitro and in vivo. Surface CD47 of PEL cell lines was examined by flow cytometry. Efficacy of knocking down CD47 or anti-CD47 Ab-mediated phagocytosis against PEL was evaluated using mouse peritoneal macrophages and human macrophages in vitro. Primary PEL cells were injected intraperitoneally into NOD/Rag-2/Jak3 double-deficient (NRJ) mice to establish a direct xenograft mouse model. Surface CD47 of PEL cell lines was highly expressed. Knocking down CD47 and anti-CD47 Ab promoted phagocytic activities of macrophages in a CD47 expression-dependent manner in vitro. Treatment with anti-CD47 Ab inhibited ascite formation and organ invasion completely in vivo compared with control IgG-treated mice. CD47 plays the pivotal role in the immune evasion of PEL cells in body cavities. Therapeutic antibody targeting of CD47 could be an effective therapy for PEL.


Monolithic zirconia as a valid alternative to metal-ceramic for implant-supported single crowns in the posterior region: A systematic review and meta-analysis of randomized controlled trials.
Technical complication rates of standard metal-ceramic implant-supported posterior restorations are relatively high. Whether monolithic zirconia crowns represent a more successful alternative is unclear. The purpose of this systematic review and meta-analysis was to compare the clinical outcomes of posterior monolithic zirconia and metal-ceramic implant-supported single crowns. A search was conducted in MEDLINE, Scopus, Embase, Web of Science, and CENTRAL databases for randomized controlled trials up to April 2023 with a follow-up time of at least 1 year. Restoration and implant survival and failure rates, marginal bone loss (MBL), bleeding on probing (BOP), and technical complications were analyzed by 2 reviewers. Statistical analyses were conducted using the R-statistics software program. The risk of bias was assessed by the Cochrane Risk of Bias Tool 2 (RoB 2), and the certainty of evidence by the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. A total of 11 out of 2030 records were identified by title and abstract, and 4 records were included after full-text analysis. The statistical analysis revealed no significant difference in MBL (MD -0.11, 95% CI: [-0.25; 0.03]), BOP (OR 0.66, 95% CI: [0.25; 1.77]), or implant failure (OR 1.30, 95% CI: [0.24; 7.08]). Monolithic zirconia presented significantly less chipping over 1 year (OR 0.17, 95% CI: [0.03; 0.99]). The chipping rate was 0% for monolithic zirconia and 7.61% for metal-ceramic. Based on a narrative review, the restoration survival rate was 97.5% in the monolithic zirconia group and 99.1% in the metal-ceramic group. Monolithic zirconia showed favorable short-term survival rates and had significantly less chipping over 1 year. Regarding MBL, BOP, and failure rates, both restoration types presented similar results at the 1-year follow-up.


When will laparoscopy totally replace laparotomy?
This clinical opinion explores the current "zeitgeist" of minimally invasive gynaecological surgery (MIGS) as reflected in opinions expressed at the 40th AAGL conference held in Hollywood, Florida. It addresses concerns relating to the introduction of MIGS globally and the current position of robotic surgery in relation to conventional minimally invasive techniques like vaginal hysterectomy and minilaparotomy. It also explores challenges relating to MIGS in the healthcare environment of the 21st century.


Paternal prevalence and risk factors for comorbid depression and anxiety across the first 2 years postpartum: A nationwide Canadian cohort study.
To determine the prevalence of comorbid depression and anxiety symptoms in fathers and investigate the predictors for comorbidity during the first- and second-year following birth. In a longitudinal Canadian study, couples were recruited within 3 weeks of childbirth. Fathers completed a survey after the birth of their child followed by questionnaires at 3, 6, 9, 12, 18, and 24 months postpartum on paternal depression and anxiety symptoms and potential risk factors. Sequential logistic regression was used for analysis. Of the 3217 enrolled fathers, 2544 (79.08%) provided data for at least one time point during the first year postpartum and 2442 (75.29%) in the second year. Overall, 569 fathers (22.4%) had comorbid depression and anxiety symptoms at some point during the first year postpartum (2.2% at baseline to 8.9% at 6 months), and 323 fathers (13.2%) had comorbidity at some point during their second year postpartum (8.1% at 18 months and 8.6% at 24 months). Strongest risk factors associated with paternal comorbidity were poor or fair perceived health at 4 weeks postpartum, depression before pregnancy, anxiety in the current pregnancy, significant adverse childhood experiences, positive ADHD screen, and victim of intimate partner violence. High rates of comorbidity among fathers in the first 2 years postpartum demonstrate the importance of perinatal mental health management at a family level. The identification of important modifiable comorbidity risk factors highlights areas for further research and the development of interventions to support paternal mental health to optimize child and family outcomes.


Improvement by application of three nanomaterials on flavor quality and physiological and antioxidant properties of tomato and their comparison.
In recent years, it has been found that the flavor quality of tomato is continuously reduced compared with the original tomato varieties. Studies have found that nanomaterials can improve crop quality, but the differences and related mechanisms among different nanomaterials were not reported. In this study, nano-Se, nano-TiO2 and nano-CeO2 were spraying on tomato, and the effects of the three nanomaterials on the flavor quality and physiological and antioxidant properties of fruits were analyzed and compared. The results showed compared with nano-TiO2 and nano-CeO2, nano-Se showed more obvious positive effects. Nano-Se increased the size and weight of tomato fruits and the levels of soluble sugar, promoted the accumulation of photosynthetic pigment, decreased the content of titratable acid, and also changed the expression of related genes, finally making the fruit sweeter; it also promoted the accumulation of antioxidant substances and nutrients such as lycopene, ascorbic acid, salicylic acid, GSH, SOD and CAT and decreased the content of MDA, H2O2 and OFR thus improving the antioxidant performance of fruits; the contents of volatiles were also increased and the olfactory experience of tomato was improved. Nano-TiO2 and nano-CeO2 also improved the flavor quality and antioxidant properties of tomato, but the degree was lower than nano-Se. This experiment provided references for selecting more appropriate nanomaterials to improve tomato quality, and revealed the effects and mechanisms of different nanomaterials on tomato quality.


Further analysis of c-Ha-ras mutations in papillomas initiated by several polycyclic aromatic hydrocarbons and papillomas from uninitiated, promoter-treated skin in SENCAR mice.
In this study we analyzed the mutations in c-Ha-ras from skin papillomas initiated with benzo[a]pyrene (B[a]P), 7-methylbenz[a]anthracene (7-MBA), and 10-fluoro-7-methylbenz[a]anthracene (10-F-7-MBA) and from papillomas induced by treatment with tumor promoter alone. Among the papillomas induced by treatment with tumor promoter alone, 56% (nine of 16) had mutations in c-Ha-ras. These mutations were found primarily in codon 61 and included both A182-->T and A182-->G mutations. In addition, one promoter-induced tumor had a G35-->A mutation in codon 12, and one had a G37-->C mutation in codon 13. The other promoter-induced papillomas did not have detectable mutations in codons 12, 13, or 61. Most of the B[a]P-initiated papillomas (77%; 10 of 13) did not have detectable mutations in c-Ha-ras codons 12, 13, or 61. However, three of these B[a]P-initiated papillomas had c-Ha-ras codon 13 mutations; one had a G37-->C transversion and two had G38-->T transversions. Most of the 7-MBA-initiated tumors and all of the 10-F-7-MBA-initiated tumors had an activated c-Ha-ras gene [nine of 10 (90%) and 11 of 11 (100%), respectively]. These mutations were almost exclusively A182-->T transversions in codon 61 except for two 7-MBA-initiated papillomas that had G37-->C transversions in codon 13. The results suggest that more than one mechanism may contribute to activation of c-Ha-ras by polycyclic aromatic hydrocarbons (PAHs) in mouse skin. Furthermore, the absence of c-Ha-ras mutations in most B[a]P-initiated papillomas, as well as in a significant fraction of those induced by tumor promoter alone, suggests that there may be other molecular targets involved in tumor initiation by PAHs in mouse skin.


Quantitative Proteomic Analysis Reveals Important Roles of the Acetylation of ER-Resident Molecular Chaperones for Conidiation in Fusarium oxysporum.
Fusarium oxysporum is one of the most abundant and diverse fungal species found in soils and includes nonpathogenic, endophytic, and pathogenic strains affecting a broad range of plant and animal hosts. Conidiation is the major mode of reproduction in many filamentous fungi, but the regulation of this process is largely unknown. Lysine acetylation (Kac) is an evolutionarily conserved and widespread posttranslational modification implicated in regulation of multiple metabolic processes. A total of 62 upregulated and 49 downregulated Kac proteins were identified in sporulating mycelia versus nonsporulating mycelia of F. oxysporum. Diverse cellular proteins, including glycolytic enzymes, ribosomal proteins, and endoplasmic reticulum-resident molecular chaperones, were differentially acetylated in the sporulation process. Altered Kac levels of three endoplasmic reticulum-resident molecular chaperones, PDIK70, HSP70K604, and HSP40K32 were identified that with important roles in F. oxysporum conidiation. Specifically, K70 acetylation (K70ac) was found to be crucial for maintaining stability and activity of protein disulphide isomerase and the K604ac of HSP70 and K32ac of HSP40 suppressed the detoxification ability of these heat shock proteins, resulting in higher levels of protein aggregation. During conidial formation, an increased level of PDIK70ac and decreased levels of HSP70K604ac and HSP40K32ac contributed to the proper processing of unfolded proteins and eliminated protein aggregation, which is beneficial for dramatic cell biological remodeling during conidiation in F. oxysporum.


Methotrexate polyglutamates in cultured human cells.
Cultured human fibroblasts accumulated methotrexate polyglutamates to levels far in excess of the dihydrofolate reductase binding capacity. After four days in methotrexate-free medium the intracellular drug level dropped by 70% but nearly 80% of the remaining methotrexate was in the form of polyglutamates. Reduced folates prevented the accumulation of polyglutamates and the effects of methotrexate on deoxyuridine incorporation into DNA and cell growth if present along with methotrexate from the beginning of the incubation. However, the reduced folates were less effective if added to cells after a long exposure to methotrexate alone. Thymidine, glycine, and adenosine (GAT) prevent methotrexate toxicity only if maintained in the incubation medium. However, preincubation with methotrexate and GAT permits continued synthesis and accumulation of polyglutamates so that when the GAT and methotrexate were removed, toxicity from the retained methotrexate polyglutamates could be expressed. (2,4-diamino-5-(3'4'-dichlorophenyl)-6 methyl pyrimidine (DDMP), an antifol that does not form polyglutamate derivatives, inhibited deoxyuridine incorporation into DNA as long as the DDMP remained in the culture medium. Compared to what was seen with longer exposures to methotrexate, removal of DDMP resulted in a greater reversal of the inhibition of deoxyuridine incorporation.


The Estes operation (transposition of one ovary to the uterine cavity): its results in the rabbit model.
Pregnancies have been reported after the Estes procedure (EP). These results have not been duplicated in modern attempts. The recent report of intrauterine fertilization in humans gives support to the feasibility of this procedure as a possible alternative to in vitro fertilization. An animal model is needed to evaluate the outcome of this operation. Consequently, 14 mature New Zealand white rabbits had one ovary placed in the uterine cavity after contralateral oophorectomy and bilateral salpingectomy. One month later, the animals were mated with a fertile buck. Fourteen to 16 days after that, the outcome was evaluated. Twenty-five to 75% of the ovarian surface was exposed to the uterine lumen, and no evidence of ovulation or implantation was found. The lack of pregnancies was attributed to an ovulatory dysfunction. Anovulation after the EP may also occur in the clinical situation, as suggested by one histologic study. The ovulatory function of these patients has not been characterized in the literature. Documentation of a successful intrauterine fertilization with delivery of a term baby supports the theoretical feasibility of the EP; however, anovulation incurred by our procedure appears to be the major drawback.


Possibilities for flight in the carabid beetle Nebria brevicollis (F.) : The importance of food during larval growth.
The carabid beetle Nebria brevicollis (F.), despite being macropterous, has a very low flight potential. Only a few percent of the beetles has functional flight muscles, flight motivation is low, and the period favourable for flight is short. The inability to fly is caused mainly by arrested development of the flight muscles. Dispersers are formed only under favourable conditions in the larval stages as shown by laboratory experiments (much food, short daylength). In N. brevicollis dispersal by flight cannot be considered as a reaction to deteriorating conditions but just the other way round. Because of the usually low numbers of potential dispersers conditions during larval development are apparently suboptimal. However, N. brevicollis is widespread and abundant in our area. The "choice" of using energy for the metabolic costs of larval growth, and only secondarily for the building up of flight muscles does not prevent the species from fully exploiting the habitat.


Intermittent Wolff-Parkinson-White syndrome due to phase 3 and phase 4 block: disappearance of rapid ventricular response during atrial fibrillation.
A 65-year-old man with Wolff-Parkinson-White syndrome type A had a rapid ventricular response over an accessory pathway during atrial fibrillation. Four months later, electrophysiological study revealed the following properties: 1) The antegrade accessory pathway conduction showed phase 3 and phase 4 block. 2) The retrograde concealed accessory pathway conduction eliminated phase 4 block in the antegrade accessory pathway conduction. 3) Premature ventricular excitation arose from the accessory pathway or from the ventricular muscle close to its distal end. 4) Atrial fibrillation during isoproterenol infusion did not show rapid ventricular response. Spontaneous impairment of accessory pathway conduction due to phase 3 and phase 4 block was suspected.


Skeletal muscle fibroblasts in health and disease.
As the primary producer of extracellular matrix (ECM) proteins in skeletal muscle, fibroblasts play an important role providing structural support to muscle. Skeletal muscle ECM is vital for force transduction from muscle cells to tendons and bones to create movement. It is these ECM connections that allow the movement created in muscle to be transmitted to our skeleton. This review discusses how fibroblasts participate in maintaining this healthy ECM within skeletal muscle. Additionally, from a basic science perspective, we discuss current methods to identify and study skeletal muscle fibroblasts, as this is critical to bettering our understanding of these important cells. Finally, skeletal muscle fibrosis is discussed, which is a devastating clinical condition characterized by an overproduction of ECM within skeletal muscle. We discuss the role that fibroblasts and other cells play in muscle fibrosis as well as the implications of this work.