A qualitative quantitative mixed methods study of domestic violence against women.
Violence against women is one of the most widespread, persistent and detrimental violations of human rights in today's world, which has not been reported in most cases due to impunity, silence, stigma and shame, even in the age of social communication. Domestic violence against women harms individuals, families, and society. The objective of this study was to investigate the prevalence and experiences of domestic violence against women in Semnan. This study was conducted as mixed research (cross-sectional descriptive and phenomenological qualitative methods) to investigate domestic violence against women, and some related factors (quantitative) and experiences of such violence (qualitative) simultaneously in Semnan. In quantitative study, cluster sampling was conducted based on the areas covered by health centers from married women living in Semnan since March 2021 to March 2022 using Domestic Violence Questionnaire. Then, the obtained data were analyzed by descriptive and inferential statistics. In qualitative study by phenomenological approach and purposive sampling until data saturation, 9 women were selected who had referred to the counseling units of Semnan health centers due to domestic violence, since March 2021 to March 2022 and in-depth and semi-structured interviews were conducted. The conducted interviews were analyzed using Colaizzi's 7-step method. In qualitative study, seven themes were found including "Facilitators", "Role failure", "Repressors", "Efforts to preserve the family", "Inappropriate solving of family conflicts", "Consequences", and "Inefficient supportive systems". In quantitative study, the variables of age, age difference and number of years of marriage had a positive and significant relationship, and the variable of the number of children had a negative and significant relationship with the total score and all fields of the questionnaire (p < 0.05). Also, increasing the level of female education and income both independently showed a significant relationship with increasing the score of violence. Some of the variables of violence against women are known and the need for prevention and plans to take action before their occurrence is well felt. Also, supportive mechanisms with objective and taboo-breaking results should be implemented to minimize harm to women, and their children and families seriously.


Biomimetic nanoparticles directly remodel immunosuppressive microenvironment for boosting glioblastoma immunotherapy.
Glioblastoma (GBM), as a very aggressive cancer of central nervous system, is very challenging to completely cure by the conventional combination of surgical resection with radiotherapy and chemotherapy. The success of emerging immunotherapy in hot tumors has attracted considerable interest for the treatment of GBM, but the unique tumor immunosuppressive microenvironment (TIME) of GBM leads to the failure of immunotherapy. Here, we show the significant improvement of the immunotherapy efficacy of GBM by modulating the TIME through novel all-in-one biomimetic nanoparticles (i.e. CS-I/J@CM NPs). The nanoparticles consist of utrasmall Cu2-x Se nanoparticles (NPs) with outstanding intrinsic properties (e.g., photo-responsive Fenton-like catalytic property for inducing immunogenic cell death (ICD) and alleviating the hypoxia of tumor), indoximod (IND, an inhibitor of indoleamine-2,3-dioxygenease in tumor), JQ1 (an inhibitor for reducing the expression of PD-L1 by tumor cells), and tumor cell membrane for improving the targeting capability and accumulation of nanoparticles in tumor. We reveal that these smart CS-I/J@CM NPs could drastically activate the immune responses through remodeling TIME of GBM by multiple functions. They could (1) increase M1-phenotype macrophages at tumor site by promoting the polarization of tumor-associated macrophages through the reactive oxygen species (ROS) and oxygen generated from the Fenton-like reaction between nanoparticles and H2O2 within tumor under NIR II irradiation; (2) decrease the infiltration of Tregs cells at tumor site through the release of IND; (3) decrease the expression of PD-L1 on tumor cells through JQ1. The notable increments of anti-tumor CD8+T cells in the tumor and memory T cells (TEM) in the spleen show excellent therapy efficacy and effectively prevent the recurrence of GBM after modulation of the TIME. This work demonstrates the modulation of TIME could be a significant strategy to improve the immunotherapy of GBM and other cold tumors.


Mutational landscape of intestinal crypt cells after long-term in vivo exposure to high fat diet.
Obesity is a modifiable risk factor in cancer development, especially for gastrointestinal cancer. While the etiology of colorectal cancer is well characterized by the adenoma-carcinoma sequence, it remains unclear how obesity influences colorectal cancer development. Dietary components of a high fat diet along with obesity have been shown to modulate the cancer risk by perturbing the homeostasis of intestinal stem cells, yet how adiposity impacts the development of genomic instability has not been studied. Mutational signatures are a powerful way to understand how a complex biological response impacts genomic stability. We utilized a mouse model of diet-induced obesity to study the mutational landscape of intestinal crypt cells after a 48-week exposure to an experimental high fat diet in vivo. By clonally enriching single crypt derived cells in organoid culture and obtaining whole genome sequences, we analyzed and compared the mutational landscape of intestinal epithelial cells from normal diet and high fat diet mice. Single nucleotide substitution signatures and indel signatures present in our cohort are found equally active in both diet groups and reflect biological processes of normal aging, cellular replication, and oxidative stress induced during organoid culturing. Thus, we demonstrate that in the absence of activating mutations or chemical exposure, high fat diet alone is not sufficient to increase genomic instability.


Establishment of a new pull-out strength testing method to quantify early osseointegration-An experimental pilot study.
The animal study aims to evaluate a new experimental model for measuring sole the influence of the surface characteristics independent from implant macro-design on the level of osseointegration by registering the pull-out strength needed for removal of experimental devices with different surfaces from artificial defects. Seventy-two test bodies (36 with the FRIADENT(®) plus surface, 36 with the P15/HAp biofunctionalized surface) were inserted in six adult domestic pigs with artificial calvarial defects. The experimental devices were designed to fit in the defects leaving a gap between the test body and the local bone. After 21 days of healing, the animals were sacrificed and the test bodies were pulled out with a standardised reproducible pull-out device measuring the pull-out strength. The pull-out strength for both groups was compared. Twenty-one days after insertion a mean force of 412 ± 142 N for the P15/HAp group and 183 ± 105 N for the FRIADENT(®) plus group was measured for the removal of the specimens from the calvarial bone. The difference between the groups was statistically significant (p < 0.0001). The experimental set-up seems to be a suitable method when measuring the impact of implant surfaces on the early stage of osseointegration.


Overexpression of granulocyte-macrophage colony-stimulating factor in mouse liver enhances the susceptibility of lipopolysaccharide leading to massive apoptosis of hepatocytes.
We examined whether antigen-nonspecific accumulation of dendritic cells (DCs) and macrophages in the liver by the overexpression of granulocyte macrophage-colony stimulating factor (GM-CSF) could prime severe liver injury after LPS injection. We injected a recombinant adenovirus encoding GM-CSF intravenously (AdGM), and LPS was administered 7 days later. Liver histology, serum alanine aminotransferase (ALT) levels and apoptosis of hepatocytes were examined. Liver histology of the AdGM-primed mice showed marked infiltrates of mononuclear cells (DCs and macrophages) without granuloma formation on day 7. Expression of toll-like receptor-4 on intrahepatic mononuclear cells isolated from AdGM-primed mice was up-regulated. After LPS injection, serum ALT levels in AdGM-primed mice reached about 6000 IU/l at 12 h, and all those mice died within 24 h. Hemorrhagic liver injury with massive apoptosis of hepatocytes was histologically recognized. When AdGM and LPS were injected in FasL-deficient C57BL/6J-gld/gld mice, serum ALT levels were not elevated by the pretreatment with a neutralizing anti-TNF-alpha antibody. Our present study provides a new model of severe liver injury, in which antigen-nonspecific accumulation of DCs and macrophages in the liver by overexpressing GM-CSF enhances the susceptibility to LPS, leading to hemorrhagic liver injury with massive hepatocyte apoptosis after LPS injection.


Pharmacogenetics of clozapine treatment response and side-effects in schizophrenia: an update.
Clozapine (CLZ) is the most effective treatment for treatment-resistant schizophrenia (SCZ) patients, with potential added benefits of reduction in suicide risk and aggression. However, CLZ is also mainly underused due to its high risk for the potentially lethal side-effect of agranulocytosis as well as weight gain and related metabolic dysregulation. Pharmacogenetics promises to enable the prediction of patient treatment response and risk of adverse effects based on patients' genetics, paving the way toward individualized treatment. This article reviews pharmacogenetics studies of CLZ response and side-effects with a focus on articles from January 2012 to February 2015, as an update to the previous reviews. Pharmacokinetic genes explored primarily include CYP1A2, while pharmacodynamic genes consisted of traditional pharmacogenetic targets such as brain-derived neurotrophic factor as well novel mitochondrial genes, NDUFS-1 and translocator protein. Pharmacogenetics is a promising avenue for individualized medication of CLZ in SCZ, with several consistently replicated gene variants predicting CLZ response and side-effects. However, a large proportion of studies have yielded mixed results. Large-scale Genome-wide association studies (e.g., CRESTAR) and targeted gene studies with standardized designs (response measurements, treatment durations, plasma level monitoring) are required for further progress toward clinical translation. Additionally, in order to improve study quality, we recommend accounting for important confounders, including polypharmacy, baseline measurements, treatment duration, gender, and age at onset.


Effects of clinoptilolite on growth performance and antioxidant status in broilers.
The objective of this study was to compare the effects of natural clinoptilolite and modified clinoptilolite on growth performance and antioxidant capacity in broiler chicks. Two hundred forty 1-day-old commercial Arbor Acres broilers were randomly distributed into three treatments, each of which had eight replicates. Each replicate contains 10 chicks. Control (CON) group fed with the basal diets, natural clinoptilolite (NCLI) group fed basal diets with 2 % natural clinoptilolite, and modified clinoptilolite (MCLI) group fed basal diets with 2 % modified clinoptilolite for 42 days. The results showed that the 2 % supplementation of natural clinoptilolite and modified clinoptilolite had no adverse effect on growth performance of broilers at 42 days of age. Relative weights of organs were not influenced by dietary treatments at 21 and 42 days. The activity of total nitric oxide synthase was significantly (P < 0.05) decreased in MCLI group than CON group at 21 days of age. At 21 and 42 days, the activities of glutathione peroxidase, catalase, total superoxide dismutase, total antioxidant capacity (T-AOC) were significantly (P < 0.05) increased in NCLI and MCLI groups than the CON group while there was no difference in T-AOC between CON and NCLI groups. The malondialdehyde content was significantly (P < 0.05) decreased in NCLI and MCLI groups than the CON group. It was concluded that the addition of 2 % natural clinoptilolite and modified clinoptilolite to diet can improve antioxidant capacity in broilers, although their effects on growth performance was negligible.


Promotion of BACE1 mRNA alternative splicing reduces amyloid beta-peptide production.
Production of the amyloid beta-peptide (Abeta) via sequential proteolytic cleavage of the amyloid precursor protein by beta- and gamma-secretases is strongly implicated in the pathogenesis of Alzheimer disease. The beta-secretase that executes the first cleavage event is a transmembrane aspartyl protease known as beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1). BACE1 pre-mRNA is alternatively spliced through the use of alternative splice sites in exons 3 and 4, although the significance of these splicing events is unclear. Here, we quantitatively measured relative levels of BACE1 transcripts and identified a novel splice variant of BACE1. We found a subtle but significant difference in BACE1 splicing between brain and pancreas, indicating the cellular environment can affect BACE1 alternative splicing. Furthermore, we have shown that BACE1 proteins translated from alternatively spliced transcripts have dramatically reduced beta-secretase activity and promotion of BACE1 alternative splicing reduces Abeta production. These findings illustrate the importance of BACE1 alternative splicing in affecting the level of Abeta produced in cells and suggest that targeting regulation of BACE1 alternative splicing is a potential therapeutic strategy for lowering beta-secretase activity.


Fibrous dysplasia of the mandible: Surgical treatment with platelet-rich plasma and a corticocancellous iliac crest graft-report of a case.
This paper reports on an alternative treatment method for mandibular reconstruction in a very rare symptomatic adult form of fibrous dysplasia. The treatment included excision of all the dysplastic tissue excluding the inner cortex and the lower border of the mandible, where cryosurgery was applied. Platelet-rich plasma was added to the autogenous bone and used to fill dead spaces and interfaces. Three months after reconstruction, implants were inserted in the hard dense bone that showed no resorption. Seven years after surgery, the patient was completely asymptomatic and had an excellent cosmetic outcome. A very simple method, based on a new paradigm approach, provided excellent functional and cosmetic results avoiding complex reconstruction procedures and delayed hospitalization in a patient with fibrous dysplasia.


[The significance of intestinal decompression and lavage in the treatment of ileus and peritonitis].
The results of treatment of 67 patients, admitted to the hospital clinic for the spread peritonitis and ileus were studied. In 37 of them (main group) the intestinal decompression and hypothermic lavage was performed, in 30 (control group)--intestinal decompression only. The operation character and intensive therapy volume in patients of both groups were similar. In conduction of hypothermic intestinal lavage the accelerated restoration of intestinal peristalsis was noted, as well as the peritonitis and intoxication symptoms elimination. Duration of treatment of patients in stationary in the main and control groups had constituted, accordingly (11.6 +/- 0.73) and (16.8 +/- 1.03) days, lethality--8.1 and 13.8, frequency of complications--10.8 and 30%.


Influencing adolescent life style: the role of mass media.
Since 1981, the Alberta Alcohol and Drug Abuse Commission has been conducting a primary prevention program intended to alter the development of intoxicant use patterns in adolescents. The program uses an integrated set of approaches involving mass communications, face-to-face program elements, community action and small-scale education activities. Mass media have a unique and powerful role as one element of such a program. Able to introduce broad concepts and convey basic, general information, they can also aid in establishing an atmosphere of acceptance of critical issues. Mass media alone probably cannot alter behavior. However, they can reinforce essential arguments and legitimize the community-based, face-to-face program elements that may be able to achieve lasting behavior change.


Usefulness of 99mTc-methylene diphosphonate scintigraphy in nephrocalcinosis.
Abnormally increased uptake of 99mTc-methylene diphosphonate in the kidney parenchyma was found in a patient with acutely exacerbated sarcoidosis. The findings could be related to active sites of nephrocalcinosis.


A recognisable short stature syndrome with premature aging and pigmented naevi.
We report the progress up to the age of seven years of a small for dates baby whose face and neck are strikingly devoid of subcutaneous tissue and who has, in addition, multiple pigmented naevi.


RAS: Circuitry and therapeutic targeting.
Cancer has affected the lives of millions worldwide and is truly regarded as a devastating disease process. Despite advanced understanding of the genomic underpinning of cancer development and progression, therapeutic challenges are still persistent. Among all the human cancers, around 33% are attributed to mutations in RAS oncogene, a crucial component of the signaling pathways. With time, our understanding of RAS circuitry has improved and now the fact that it activates several downstream effectors, depending on the type and grades of cancer has been established. The circuitry is controlled via post-transcriptional mechanisms and frequent distortions in these mechanisms lead to important metabolic as well as immunological states that favor cancer cells' growth, survival, plasticity and metastasis. Therefore, understanding RAS circuitry can help researchers/clinicians to develop novel and potent therapeutics that, in turn, can save the lives of patients suffering from RAS-mutant cancers. There are many challenges presented by resistance and the potential strategies with a particular focus on novel combinations for overcoming these, that could move beyond transitory responses in the direction of treatment. Here in this review, we will look at how understanding the circuitry of RAS can be put to use in making strategies for developing therapeutics against RAS- driven malignancies.


Blood arginine vasopressin, adrenocorticotropin hormone, and cortisol concentrations at admission in septic and critically ill foals and their association with survival.
Sepsis is an important cause for neonatal foal mortality. The hypothalamic-pituitary-adrenal axis (HPAA) responses to sepsis are well documented in critically ill humans, but limited data exist in foals. The purpose of this study was to evaluate the HPAA response to sepsis in foals, and to associate these endocrine changes with survival. Blood concentrations of arginine vasopressin (AVP), adrenocorticotropin hormone (ACTH), and cortisol will be higher in septic foals as compared with sick nonseptic and healthy foals. The magnitude of increase in hormone concentration will be negatively associated with survival. Fifty-one septic, 29 sick nonseptic, and 31 healthy foals of < or =7 days of age were included. Blood was collected at admission for analysis. Foals with positive blood culture or sepsis score > or =14 were considered septic. Foals admitted with disease other than sepsis and healthy foals were used as controls. AVP, ACTH, and cortisol concentrations were measured using validated immunoassays. AVP, ACTH, and cortisol concentrations were increased in septic foals. Septic nonsurvivor foals (n = 26/51) had higher plasma ACTH and AVP concentrations than did survivors (n = 25/51). Some septic foals had normal or low cortisol concentrations despite increased ACTH, suggesting relative adrenal insufficiency. AVP, ACTH, and cortisol concentrations were higher in sick nonseptic foals compared with healthy foals. Increased plasma AVP and ACTH concentrations in septic foals were associated with mortality. Several septic foals had increased AVP : ACTH and ACTH : cortisol ratios, which indicates relative adenohypophyseal and adrenal insufficiency.


Dorsal Cochlear Nucleus Fusiform-cell Plasticity is Altered in Salicylate-induced Tinnitus.
Following noise overexposure and tinnitus-induction, fusiform cells of the dorsal cochlear nucleus (DCN) show increased spontaneous firing rates (SFR), increased spontaneous synchrony and altered stimulus-timing-dependent plasticity (StDP), which correlate with behavioral measures of tinnitus. Sodium salicylate, the active ingredient in aspirin, which is commonly used to induce tinnitus, increases SFR and activates NMDA receptors in the ascending auditory pathway. NMDA receptor activation is required for StDP in many brain regions, including the DCN. Blocking NMDA receptors can alter StDP timing rules and decrease synchrony in DCN fusiform cells. Thus, systemic activation of NMDA receptors with sodium salicylate should elicit pathological changes to StDP, thereby increasing SFR and synchrony and induce tinnitus. Herein, we examined the action of salicylate in tinnitus generation in guinea pigs in vivo by measuring tinnitus using two behavioral measures and recording single-unit responses from DCN fusiform cells pre- and post-salicylate administration in the same animals. First, we show that animals administered salicylate show evidence of tinnitus using both behavioral paradigms, cross-validating the tests. Second, fusiform cells in animals with tinnitus showed increased SFR, synchrony and altered StDP timing rules, like animals with noise-induced tinnitus. These findings suggest that alterations to fusiform-cell plasticity are an essential component of tinnitus, regardless of induction technique.


Auditory-Perceptual Evaluation of Voice Quality of Cochlear-implanted and Normal-hearing Individuals: A Reliability Study.
This study aimed to present an experience in rating voices of adults with normal hearing and adults with cochlear implants and critically examine the outcomes, discussing pros and cons of the methodology used. This is a cross-sectional, prospective study. One hundred and fifty voice samples, consisting of 50 sustained vowels, 50 samples of connected speech, and 50 samples of conversational speech, belonging to 25 adults with hearing impairment with cochlear implants and 25 adults with normal hearing, were perceptually analyzed for inter-rater agreement and intra-rater reliability. Three experienced judges rated the voice samples using visual analog scales of parameters considered relevant for cochlear-implanted population such as articulation, intonation, and resonance. The raters participated in three training sessions for calibration and had 1 month to complete the ratings individually. Twenty percent of the samples were repeated randomly to verify intra-rater reliability. The levels of agreement and reliability were verified using the interclass correlation coefficient. The inter-rater agreement varied widely across the parameters and speech tasks, from poor to excellent agreement. The only parameter for which the raters maintained consistently good or excellent agreement for all groups and emissions was the pitch. For intra-rater reliability, two of the raters presented excellent reliability for most parameters across all of the speech tasks, whereas one rater presented more inconsistencies. In this reliability study, factors such as extensive deadline for the auditory perceptual evaluation, lack of periodic recalibration, speech tasks, and familiarity with the population studied were identified as factors that contributed to inconsistent reliability results.


Metagenomics-metabolomics analysis of microbial function and metabolism in petroleum-contaminated soil.
Contamination of soil by petroleum is becoming increasingly serious in the world today. However, the research on gene functional characteristics, metabolites and distribution of microbial genomes in oil-contaminated soil is limited. Considering that, metagenomic and metabonomic were used to detect microbes and metabolites in oil-contaminated soil, and the changes of functional pathways were analyzed. We found that oil pollution significantly changed the composition of soil microorganisms and metabolites, and promoted the relative abundance of Pseudoxanthomonas, Pseudomonas, Mycobacterium, Immundisolibacter, etc. The degradation of toluene, xylene, polycyclic aromatic hydrocarbon and fluorobenzoate increased in Xenobiotics biodegradation and metabolism. Key monooxygenases and dioxygenase systems were regulated to promote ring opening and degradation of aromatic hydrocarbons. Metabolite contents of polycyclic aromatic hydrocarbons (PAHs) such as 9-fluoronone and gentisic acid increased significantly. The soil microbiome degraded petroleum pollutants into small molecular substances and promoted the bioremediation of petroleum-contaminated soil. Besides, we discovered the complete degradation pathway of petroleum-contaminated soil microorganisms to generate gentisic acid from the hydroxylation of naphthalene in PAHs by salicylic acid. This study offers important insights into bioremediation of oil-contaminated soil from the aspect of molecular regulation mechanism and provides a theoretical basis for the screening of new oil degrading bacteria.


Reflecting on the Synergy Between Computer-Mediated Intercultural Communication and the Coronavirus Memory Archive: An Intrinsic Case Study.
The coursebook-centered approach adopted by the Hellenic Open University's Master's program in TEIL/TEFL has lost momentum during the coronavirus lockdown periods. This study addresses synergies between institutional policy and involved participants through the experience of an EFL teacher with a Computer-Mediated Intercultural Communication-based assignment about the online archivability of teaching and learning reflections. Relying on her study journal, the EFL teacher proposed a reflection-based inquiry into the compilation of a student-generated coronavirus memory archive on the e-me digital platform. Three journaling spaces emerged in the context of teacher development: the physical, the digital and the academic archive. The results indicated the transformative effects that archival procedures have on the dominant training practices of a graduate-level TEFL program. This study holds implications for flipping a switch on the educator-educatee relationship, while examining how reflective teaching pedagogy assimilates the learners' creative response to remoteness.


Phase I study of induction chemotherapy with afatinib, ribavirin, and weekly carboplatin and paclitaxel for stage IVA/IVB human papillomavirus-associated oropharyngeal squamous cell cancer.
The human papillomavirus (HPV) E6 oncoprotein enhances the oncogenic potential of ErbB proteins in HPV-related malignancies. This phase I study evaluates the addition of afatinib, an ErbB family inhibitor, and ribavirin to paclitaxel and carboplatin induction chemotherapy in HPV-associated, locally advanced oropharyngeal squamous cell carcinoma (SCC). This dose escalation study included 2 doses of oral afatinib: 30 and 40 mg daily. Ribavirin dosing was weight based. Paclitaxel (80 mg/m2 ) and carboplatin (area under the curve [AUC] 1.5) were administered on days 1 and 8 of each 21-day cycle. After 3 cycles, patients were removed from protocol to receive definitive treatment. Among 10 patients, there were no dose-limiting toxicities. Six patients (67%) had unconfirmed objective partial responses. The 2-year progression-free survival rate was 75%. Afatinib, ribavirin, paclitaxel, and carboplatin induction chemotherapy is safe and well tolerated. The phase II recommended dose of afatinib is 40 mg oral daily in this combination regimen.


Beta-catenin mutations in liver tumors induced by 2-amino-3,4-dimethylimidazo[4,5-f]quinoline in CDF1 mice.
Heterocyclic amines are potent mutagens and carcinogens formed in cooked protein rich foods. In this study, we screened liver tumors induced by 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) in CDF1 mice for beta-catenin and APC mutations and other genetic alterations shown to occur in human hepatocellular carcinomas (HCC), including mutations in the p53 and H-ras genes, c-myc amplification and E-cadherin promoter methylation. SSCP followed by direct DNA sequencing revealed mutations in exon 2 of the beta-catenin gene in 2 of 16 liver tumors (12.5%). Promoter methylation of the E-cadherin gene was detected in one liver tumor induced by MeIQ. There were no mutations in the mutation cluster region of the APC gene, in exons 5-8 of the p53 gene, or in codons 12, 13 and 61 of the H-ras gene, nor c-myc amplification in any of liver tumors induced by MeIQ. These data indicate that except for the occasional disruption of the Wnt pathway through beta-catenin mutations, the genetic pathways involved in the development of HCC differ significantly between human liver cancer and tumors induced in mice by MeIQ, but do not rule out the possibility that heterocyclic amines constitute a carcinogenic risk factor in humans.


Triplet pregnancy with acardius acranius after preimplantation diagnosis.
To report the first case of fetal malformation after preimplantation diagnosis for Duchenne muscular dystrophy (DMD). Case report. Perinatal center in a university hospital. A conductor for DMD in her third pregnancy. Preimplantation diagnosis was performed in an outside hospital. In our center, a dichorionic triplet pregnancy with acardius acranius was diagnosed. The anastomosis between the "pump"-twin and the fetus with acardius was embolized with histoacryl to prevent worsening cardiac insufficiency of the "pump"-twin. Pregnancy outcome. The anastomosis between the "pump"-twin and the fetus with acardius was occluded successfully. Premature preterm rupture of membranes led to rapid labor and delivery at 24 + 5 weeks' gestation. The smaller girl died of severe hyaline membrane disease, whereas the other infant had no major clinical problems and has developed well. There might be an association between embryo biopsy and fetal malformations. The setting up of a birth register after embryo biopsy is strongly recommended.


A six-year follow up study for evaluation of the 85 dBA safe criterion for noise exposure.
This study included 114 workers who have been exposed to noise levels of 78 to 91.4 dBA and followed over a six year period. Workers exposed to nose levels up to 85 dBA eight hours daily for six days per week and for twelve years showed a slightly higher (1%) hearing impairment than the corresponding control subjects. Impairment of hearing among workers exposed to higher noise levels was 9.6%.


Novel inhibitors targeting PPM1D phosphatase potently suppress cancer cell proliferation.
Protein phosphatase magnesium-dependent 1δ (PPM1D, Wip1) is a p53 inducible serine/threonine phosphatase. PPM1D is a promising target protein in cancer therapy since overexpression, missense mutations, truncating mutations, and gene amplification of PPM1D are reported in many tumors, including breast cancer and neuroblastoma. Herein, we report that a specific inhibitor, SL-176 that can be readily synthesized in 10 steps, significantly inhibits proliferation of a breast cancer cell line overexpressing PPM1D and induces G2/M arrest and apoptosis. SL-176 decreases PPM1D enzyme activity potently and specifically in vitro. These results demonstrate that SL-176 could be a useful lead compound in the development of effective anti-cancer agents.


[Experimental study and clinical evaluation of rapid maxillary expansion (RME) with a fixed orthodontic appliance].
The purpose of this study was to observe the histologic changes of midpalatal suture, periodontal and pulp tissues after RME. The results of this study showed that RME is a rapid, effective and safe treatment method in certain indications.


Fistulae of the internal thoracic vessels: report of two cases.
Arteriovenous fistulae involving the internal thoracic vessels are extremely rare. The multiple causes, variable clinical presentation, and inconsistent delay of onset of clinical symptoms in addition to their rarity make their diagnosis difficult. However, the complications of untreated internal thoracic fistulae are potentially fatal, emphasizing the need to make a prompt and correct diagnosis. Once the diagnosis is made and the investigational workup complete, treatment consists of either surgical ligation and excision or percutaneous transcatheter embolization. We report two cases of patients with internal thoracic fistulae: one arising as a complication of a tube thoracostomy and the other following an anterior thoracotomy. The second case report describes a rupture of the internal thoracic fistulae, a complication not reported earlier.


Electrode-heart interface: definition of the ideal electrode.
In dual-chamber pacing in order to maintain the advantages of small pulse generator size and volume, and increased longevity, it becomes necessary to reduce pulse generator output. This may be accomplished by optimizing the electrode-heart interface. New electrode designs may reduce polarization losses; perhaps even newer materials should be considered. The results of accumulated data must be applicable to long-term pacing.


A multi-channel EEG mini-cap can improve reliability for recording auditory brainstem responses in chinchillas.
Disabling hearing loss affects nearly 466 million people worldwide (World Health Organization). The auditory brainstem response (ABR) is the most common non-invasive clinical measure of evoked potentials, e.g., as an objective measure for universal newborn hearing screening. In research, the ABR is widely used for estimating hearing thresholds and cochlear synaptopathy in animal models of hearing loss. The ABR contains multiple waves representing neural activity across different peripheral auditory pathway stages, which arise within the first 10 ms after stimulus onset. Multi-channel (e.g., 32 or higher) caps provide robust measures for a wide variety of EEG applications for the study of human hearing. However, translational studies using preclinical animal models typically rely on only a few subdermal electrodes. We evaluated the feasibility of a 32-channel rodent EEG mini-cap for improving the reliability of ABR measures in chinchillas, a common model of human hearing. After confirming initial feasibility, a systematic experimental design tested five potential sources of variability inherent to the mini-cap methodology. We found each source of variance minimally affected mini-cap ABR waveform morphology, thresholds, and wave-1 amplitudes. The mini-cap methodology was statistically more robust and less variable than the conventional subdermal-needle methodology, most notably when analyzing ABR thresholds. Additionally, fewer repetitions were required to produce a robust ABR response when using the mini-cap. These results suggest the EEG mini-cap can improve translational studies of peripheral auditory evoked responses. Future work will evaluate the potential of the mini-cap to improve the reliability of more centrally evoked (e.g., cortical) EEG responses.


[Study of the molecular structure and mechanisms of pond snail neuron cholinoreceptor function by means of in vivo chemical modification].
The molecular structure of acetylcholine receptors (AChR) of Lymnaea stagnalis neurons has been studied using specific agents to definite chemical groups. The disulphide bond important for AChR function was discovered, the reduction of which by dithiotreitol (DTT) inactivates AChR. The drugs exciting AChR protect the disulphide bond against modification with DTT likely due to the conformational changes of an active site and its environment. Desensitized AChR can also be modified by DDT (if it is not occupied by agonist). It is suggested that the system transmitting the conformational change from the AChR active site to its ionophore is responsible for desensitization.


Suppression of Membranous LRP5 Recycling, Wnt/β-Catenin Signaling, and Colon Carcinogenesis by 15-LOX-1 Peroxidation of Linoleic Acid in PI3P.
APC mutation activation of Wnt/β-catenin drives initiation of colorectal carcinogenesis (CRC). Additional factors potentiate β-catenin activation to promote CRC. Western diets are enriched in linoleic acid (LA); LA-enriched diets promote chemically induced CRC in rodents. 15-Lipoxygenase-1 (15-LOX-1), the main LA-metabolizing enzyme, is transcriptionally silenced during CRC. Whether LA and 15-LOX-1 affect Wnt/β-catenin signaling is unclear. We report that high dietary LA promotes CRC in mice treated with azoxymethane or with an intestinally targeted Apc mutation (ApcΔ580) by upregulating Wnt receptor LRP5 protein expression and β-catenin activation. 15-LOX-1 transgenic expression in mouse intestinal epithelial cells suppresses LRP5 protein expression, β-catenin activation, and CRC. 15-LOX-1 peroxidation of LA in phosphatidylinositol-3-phosphates (PI3P_LA) leads to PI3P_13-HODE formation, which decreases PI3P binding to SNX17 and LRP5 and inhibits LRP5 recycling from endosomes to the plasma membrane, thereby increasing LRP5 lysosomal degradation. This regulatory mechanism of LRP5/Wnt/β-catenin signaling could be therapeutically targeted to suppress CRC.


Construction of a rapid electrochemical biosensor consisting of a nanozyme/aptamer conjugate for waterborne microcystin detection.
Microcystin-LR (MC-LR) is a hepatotoxin generated by the excessive proliferation of cyanobacteria, which is a threat to humans and wildlife. Therefore, rapid detection of MC-LR is an important challenge. This study describes a rapid electrochemical biosensor comprising nanozymes and aptamers. Alternating current electrothermal flow (ACEF) significantly reduced the MC-LR detection period to 10 min. We also used MnO2/MC-LR aptamer conjugates to improve the sensitivity to MC-LR detection. Here, MnO2 amplified the electrochemical signal and the aptamer showed high selectivity for MC-LR. Under the optimal conditions, the limit of detection (LOD) and selectivity in freshwater were detected using cyclic voltammetry and differential pulse voltammetry. As a result, an LOD of 3.36 pg mL-1 was observed in the linear concentration range of 10 pg mL-1 to 1 μg mL-1. This study quickly and sensitively detected MC-LR in a situation where it causes serious damage worldwide. In addition, the ACEF technology introduction is the first example of MC-LR detection, suggesting a wide range of possibilities for MC-LR biosensors.


Successful Hemodialysis Treatment of Severe Hypercalcemia Following COVID-19 in Multiple Myeloma: A Case Report.
BACKGROUND Hypercalcemia, a serum calcium exceeding 10.5 mg/dL, is a multi-factorial metabolic disorder that results from an imbalance in calcium homeostasis. CASE REPORT We report a case of a 67-year-old male with recently diagnosed multiple myeloma who presented to our emergency department 3 weeks after COVID-19 infection with altered mental status and a fall. On admission he was found to have severe hypercalcemia with a level over 18.0 mg/dL. Despite IV fluids, calcitonin, steroids, and zoledronic acid, he had persistent, critically elevated calcium levels. The decision to initiate hemodialysis was made, which successfully treated his hypercalcemia. CONCLUSIONS This report presents a case of malignant hypercalcemia in an individual with COVID-19 and multiple myeloma and highlights the importance of considering dialysis as a viable treatment for hypercalcemia when other modalities have failed.


Learning protein secondary structure from sequential and relational data.
We propose a method for sequential supervised learning that exploits explicit knowledge of short- and long-range dependencies. The architecture consists of a recursive and bi-directional neural network that takes as input a sequence along with an associated interaction graph. The interaction graph models (partial) knowledge about long-range dependency relations. We tested the method on the prediction of protein secondary structure, a task in which relations due to beta-strand pairings and other spatial proximities are known to have a significant effect on the prediction accuracy. In this particular task, interactions can be derived from knowledge of protein contact maps at the residue level. Our results show that prediction accuracy can be significantly boosted by the integration of interaction graphs.


The effect of lutein and Zeaxanthine on dyslipidemia: A meta-analysis study.
The relationship between circulating Lutein and zeaxanthin (L/Z) concentrations, and plasma lipoproteins has been indicated by observational studies. However, the beneficial impact of L/Z administration on dyslipidemia are unclear. This meta-analysis aimed to investigate the effect of oral intake of L/Z on circulating total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), as well as high-density lipoprotein-cholesterol (HDL-C) levels. We electronically assessed all eligible interventional studies through different electronic databases, including PubMed, Scopus, ISI -Web of Science, and Cochrane library until Jun 2021. After identifying the quality of each included randomized controlled trials, they were evaluated by assessing the risk-difference between treatment and control groups by pooling available data on net change of serum LDL-C, HDL-C, and Cholesterol. L/Z supplementation has null effect on circulating levels of TC (WMD: -3.82 95% CI: -13.83, 6.18; I-square: 85.2%), and LDL-C (WMD: -4.54; 95% CI: -11.5, 2.48; I-square: 83.9%). In contrast, L/Z treatment could significantly increase HDL-C levels in older adults (WMD: 4.06; 95% CI: 0.64, 7.48; I-square: 50.7%). L/Z administration could be an effective treatment for improving circulating HDL-C concentration in elderly adults.


Dietary Squalene Induces Cytochromes Cyp2b10 and Cyp2c55 Independently of Sex, Dose, and Diet in Several Mouse Models.
To investigate the effects of squalene, the main hydrocarbon present in extra virgin olive oil, on liver transcriptome in different animal models and to test the influence of sex on this action and its relationship with hepatic lipids. To this purpose, male C57BL/6J Apoe-deficient mice are fed a purified Western diet with or without squalene during 11 weeks and hepatic squalene content is assessed, so are hepatic lipids and lipid droplets. Hepatic transcriptomic changes are studied and confirmed by RT-qPCR. Dietary characteristics and influence of squalene doses are tested in Apoe-deficient on purified chow diets with or without squalene. These diets are also given to Apoa1 and wild-type mice on C57BL/6J background and to C57BL/6J xOla129 Apoe-deficient mice. Squalene supplementation increases its hepatic content without differences among sexes and hormonal status. The Cyp2b10 and Cyp2c55 gene expressions are significantly up-regulated by the squalene intake in all models, with independence of sex, sexual hormones, dietary fat content, genetic background and dose, and in Apoe-deficient mice consuming extra-virgin olive oil. Hepatic squalene increases the expression of these cytochromes and their changes in virgin olive oil diets may be due to their squalene content.


Selective matrix metalloproteinase inhibition reduces left ventricular remodeling but does not inhibit angiogenesis after myocardial infarction.
Broad inhibition of matrix metalloproteinases (MMPs) attenuates left ventricular remodeling after myocardial infarction (MI). However, it is not clear if selective MMP inhibition strategies will be effective or if MMP inhibition will impair angiogenesis after MI. We used a selective MMP inhibitor (MMPi) that does not inhibit MMP-1 in rabbits, which, like humans but unlike rodents, express MMP-1 as a major collagenase. On day 1 after MI, rabbits were randomized to receive either inhibitor (n=10) or vehicle (n=8). At 4 weeks after MI, there were no differences in infarct size or collagen fractional area. However, MMPi reduced ventricular dilation. The increase in end-diastolic dimension from day 1 to week 4 was 3.1+/-0.5 mm for vehicle versus 1.3+/-0.3 mm for MMPi (P<0.01). The increase in end-systolic dimension was 2.8+/-0.5 mm for vehicle and 1.3+/-0.4 mm for MMPi (P<0.05). Furthermore, MMPi reduced infarct wall thinning; the minimal infarct thickness was 0.8+/-0.1 mm for vehicle and 1.6+/-0.3 mm for MMPi (P<0.05). Interestingly, the MMPi group had increased numbers of vessels in the subendocardial layer of the infarct; the number of capillaries was increased in the subendocardial layer (46+/-4 vessels/field versus 17+/-3 vessels/field for vehicle; P<0.001), and the number of arterioles was also increased (4.0+/-0.8 vessels/field versus 2.0+/-0.4 vessels/field for vehicle; P<0.05). MMP inhibition attenuates left ventricular remodeling even when the dominant collagenase MMP-1 is not inhibited; furthermore, this selective MMP inhibition appears to increase rather than decrease neovascularization in the subendocardium.


[Rapid palatal expansion. Monitoring of orthopedic effects with C.A.T].
It has been made a check with TAC on 10 subjects, submitted to Rapid Expansion Palatal. The technique provided a direct and careful vision of the disiuntion, allowing to prove with scientific exactitude for the first time the diastase of ptherigoideis processes.


The pictorial context dependency of savant artists: a research note.
The relative immunity of the concept of size constancy in the face of changes to the retinal image as well as the pictorial device of linear perspective were investigated with 9 savant artists and 9 controls. For drawing use of pictorial rules seemed independent of levels of intelligence; however, when a construction instead of a drawing task had to be carried out, diagnosis rather than the presence or absence of talent was the decisive factor.


Human immunodeficiency virus-associated motor axonal polyradiculoneuropathy.
To report two cases of an axonal motor polyradiculoneuropathy associated with human immunodeficiency virus infection in otherwise asymptomatic subjects. Case series. Tertiary care hospital neurology inpatient service. Electrophysiologic testing showed acute denervation with almost normal sensory potentials and no evidence of demyelination. These cases present an example of an acute axonal polyradiculoneuropathy in persons infected with human immunodeficiency virus without acquired immunodeficiency syndrome.


Destruction of isolates from the Pittsburgh Veterans Affairs Laboratory.
The Pittsburgh Veterans Affairs hospital administration closed the research laboratory directed by Victor Yu and Janet Stout and destroyed isolates collected as part of a series of clinical studies over 25 years. This article discusses the implications and protests such destruction as an affront to science and scientific study. A petition signed by 243 individuals accompanies this article.


Generalized likelihood ratio tests for change detection in diffusion tensor images: application to multiple sclerosis.
The automatic analysis of subtle changes between MRI scans is an important tool for monitoring disease evolution. Several methods have been proposed to detect changes in serial conventional MRI but few works have considered Diffusion Tensor Imaging (DTI), which is a promising modality for monitoring neurodegenerative disease and particularly Multiple Sclerosis (MS). In this paper, we introduce a comprehensive framework for detecting changes between two DTI acquisitions by considering different levels of representation of diffusion imaging, namely the Apparent Diffusion Coefficient (ADC) images, the diffusion tensor fields, and scalar images characterizing diffusion properties such as the fractional anisotropy and the mean diffusivity. The proposed statistical method for change detection is based on the Generalized Likelihood Ratio Test (GLRT) that has been derived for the different diffusion imaging representations, based on the core assumption of a Gaussian diffusion model and of an additive Gaussian noise on the ADCs. Results on synthetic and real images demonstrate the ability of the different tests to bring useful and complementary information in the context of the follow-up of MS patients.


The Efficacy of Negative Pressure Wound Therapy and Antibiotic Beads in Lower Extremity Salvage.
Antibiotic beads and negative pressure wound therapy (NPWT) represent two methods of wound management used during staged debridement in the post-trauma limb salvage pathway. The efficacy of NPWT and antibiotic beads in preventing infection remains unclear. This study is a retrospective review of patients with traumatic lower extremity open fractures who received NPWT and/or antibiotic beads before soft tissue reconstruction at an urban level 1 trauma center between August 2007 and December 2015. Patients with wound infections before application of NPWT and/or antibiotic beads were excluded. In 73 lower extremities requiring soft tissue coverage, 46 received antibiotic beads and 48 received NPWT. Overall infection rate was 15.1%. Use of antibiotic beads was associated with a decreased risk of infection (6.4% versus 30.7%; P = 0.01). Use of NPWT was associated with an increased risk of one or more complications (45.7% versus 4.2%; P = 0.001). The development of infection was associated with a greater period of time between application of antibiotic beads (22 ± 13 versus 12 ± 6 d, P = 0.01) or NPWT (23 ± 15 versus 10 ± 11 d, P = 0.004) and soft tissue coverage. Overall limb salvage rate was 95.9%; secondary amputation was associated with development of infection (P = 0.001) but not with use of NPWT or antibiotic beads. Antibiotic beads may prevent infections in patients awaiting soft tissue coverage of wounds. NPWT may contribute to a greater rate of complication. Limb salvage was successful in most cases regardless of method of wound management.


Fasciola hepatica: lithogenic capacity in experimentally infested rats and chemical determination of the main stone components.
A study was done of the possible association between the development of common bile-duct stones and the presence of worms in rats experimentally infected with Fasciola hepatica. A total of 157 rats were individually infected with 20 metacercariae, and another 40 animals served as controls. The rats were dissected at 100, 200, 300, and 400 days postinfection (p.i.). A significant association was observed between the observation of stones and the presence of F. hepatica adults. The global frequency of bile-duct lithiasis in the parasitized rats was 22%, with a significantly lower incidence being observed in the younger group (100 days p.i.). Different analytical techniques were used to determine the main stone components. Energy-dispersive X-ray microanalysis showed calcium to be the main component in all cases (82-94%). Scanning electron microscopy, nuclear magnetic resonance ([1H]- and [13C]-NMR), and mass spectrometry revealed the predominance of palmitic (C-16) and stearic (C-18) acid.


Impaired myocardial 123I-metaiodobenzylguanidine uptake in Lewy body disease: comparison between dementia with Lewy bodies and Parkinson's disease.
Iodine-123-labeled metaiodobenzylguanidine (123I-MIBG) myocardial scintigraphy has been used to evaluate cardiac sympathetic denervation in Lewy body disease (LBD) including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Patients with LBD had marked reductions in cardiac MIBG accumulation, indicative of severe impairment of the cardiac sympathetic nervous systems. However, the differences in scintigraphy between DLB and PD have not been determined. To compare cardiac sympathetic function in early disease stage measured with 123I-MIBG scintigraphy between DLB and PD. 123I-MIBG myocardial scintigraphy was performed in 22 patients with early-stage DLB, 41 patients with early idiopathic PD and 15 normal control subjects who were matched for age and disease duration. The heart-to-mediastinum (H/M) ratio was calculated. 123I-MIBG uptake of the myocardium was significantly lower in patients with early DLB than in controls. The mean value of H/M ratio in patients with DLB was significantly lower than those in patients with PD, independent of the Hoehn and Yahr stage. Our findings suggest that cardiac sympathetic function in DLB is severely impaired even in the early disease stage.


Antifibrillatory actions of d,l-nadolol in a conscious canine model of sudden coronary death.
The role of beta-adrenergic receptor blockade in preventing ventricular fibrillation in a conscious canine model of sudden coronary death was examined using d,l-nadolol and the non-beta-adrenergic receptor blocking isomer, d-nadolol. On day 4, after a temporary 90-min occlusion of the left anterior descending coronary artery, an anodal current of 150 microA was applied to the intimal surface of the left circumflex coronary artery. Occlusive or nonocclusive thrombosis of the artery was accompanied by ST-segment changes. In saline-treated animals (n = 15), ST-segment changes were followed by sinus tachycardia and QT-segment prolongation, with development of ventricular premature beats. Ventricular fibrillation developed in 14 animals (93%). Pretreatment with 1 (n = 9) or 8 mg/kg d,l-nadolol (n = 13) did not alter the development of left circumflex coronary artery thrombosis and ischemic ST-segment changes, but decreased the incidence of ventricular fibrillation and increased survival at 24 h (56% and 63%, respectively) (p less than 0.01 versus saline). d,l-Nadolol also attenuated the sinus tachycardia and QT-interval prolongation accompanying acute ischemia. d-Nadolol (1 mg/kg), the non-beta-adrenergic receptor blocking isomer, failed to prevent development of ST-segment changes. Sinus tachycardia and QT-interval prolongation were not prevented, and ventricular fibrillation developed in all eight animals (100%). In animals without previously induced anterior myocardial ischemic injury (n = 10), left circumflex coronary artery thrombosis failed to produce sinus tachycardia and QT-interval prolongation and was associated with a lower incidence of ventricular fibrillation (20%, p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)


Role of Armadillo repeat 2 and kinesin-II motor subunit Klp64D for wingless signaling in Drosophila.
Armadillo (Arm) is crucial for transducing Wingless (Wg) signaling. Previously, we have shown that Klp64D, a motor subunit of Drosophila kinesin-II, interacts with Arm for Wg signaling. Molecular basis for this interaction has remained unknown. Here we identify a critical Arm repeat (AR) required for binding Klp64D and Wg signaling. Arm/[Formula: see text]-catenin family proteins contain a conserved domain of 12 Arm repeats (ARs). Five of these ARs can interact with Klp64D, but only the second AR (AR2) binds to the cargo/tail domain of Klp64D. Overexpression of AR2 in wing imaginal disc is sufficient to cause notched wing margin. This phenotype by AR2 is enhanced or suppressed by reducing or increasing Klp64D expression, respectively. AR2 overexpression inhibits Wg signaling activity in TopFlash assay, consistent with its dominant-negative effects on Klp64D-dependent Wg signaling. Overexpression of the Klp64D cargo domain also results in dominant-negative wing notching. Genetic rescue data indicate that both AR2 and Klp64D cargo regions are required for the function of Arm and Klp64D, respectively. AR2 overexpression leads to an accumulation of Arm with GM130 Golgi marker in Klp64D knockdown. This study suggests that Wg signaling for wing development is regulated by specific interaction between AR2 and the cargo domain of Klp64D.


Laparoscopic versus open preperitoneal prosthetic herniorrhaphy for recurrent inguinal hernia.
Laparoscopic herniorrhaphy (LH) shares the same repair principle as open preperitoneal prosthetic herniorrhaphy (PPH). Theoretically, the recurrence rate of LH for recurrent inguinal hernia will match the low recurrence rate of PPH (1.2-3%). One-hundred forty-five cases of recurrent inguinal hernia were retrospectively studied between 1990 and 1994. Forty-two cases receiving LH were compared to 103 cases receiving PPH. There were no differences in operative time, hospital stay, morbidity rate, satisfaction scale and recurrence rate between the LH group and the PPH group. The LH group showed significantly less postoperative pain and 2 times shorter convalescence (p<0.01). Unsuspected asymptomatic contralateral hernia was found in 4.8% of patients receiving LH. 11.9% of patients had bilateral hernia repairing at the same time in the LH group. LH is suitable for recurrent inguinal hernia, but further investigation of this technique is required before its wide application.


Modified natural cycle in in vitro fertilization.
The first live birth after IVF was achieved in a purely natural cycle. Because early attempts at IVF were associated with low efficiency, ovarian stimulation was added to achieve a greater margin for error in oocyte retrieval, fertilization, and thus, overall pregnancy success. As technology improved, the intuitive appeal of the natural cycle led investigators to once again attempt IVF without antecedent gonadotropin stimulation. Triggering of ovulation with hCG was added to allow for accurate scheduling of oocyte retrieval and thus increased oocyte yield. When GnRH antagonists became available, premature ovulations could be prevented, albeit at the cost of adding some form of ovarian stimulation to continue follicle development until ovulation triggering. This type of cycle came to be known as the "modified natural cycle." These modified natural IVF cycles are associated with decreased medication costs, they produce acceptable pregnancy rates, and they may be particularly appropriate for patients at increased risk of ovarian hyperstimulation syndrome, poor responders, and those wishing to avoid supernumerary embryo production.


Carbon dioxide exchange of Antarctic crustose lichens in situ measured with a CO2/H2O porometer.
Photosynthesis and respiration of crustose lichens in their natural situation were measured by means of a Walz porometer with a modified cuvette and a plexiglass ring. Habitat influence and the specific performance of three maritime Antarctic species were demonstrated by diurnal courses of microclimate and CO2 exchange during rainy days. In further field experiments the photosynthetic response to soaking with water was tested. Haematomma erythromma is rain-exposed at its natural habitat on coastal rocks but tends to dry out quickly. The photosynthetic efficiency of the chlorophyll of this photophilous species was high. Lecidea sciatrapha appears to be chionophilous and had a low light compensation point of its net photosynthesis. The photosynthetic rates per surface area of these two species were low compared with those of Caloplaca sublobulata. According to its habitat selection C. sublobulata is typified as an ombrophobous lichen. This characterization was confirmed experimentally by our gas exchange measurements.


Chemical properties and biological activity of a polysaccharide from Melocactus depressus.
An arabinogalactan with mean Mr of 6.85 x 10(4), was isolated from the pulps of Melocactus depressus Hook by fractionation on Sephacryl S-300 HR. Chemical and spectroscopic studies indicated that it has a branched arabinogalactan type structure composed of beta-(1-->4) linked D-galactopyranose residues with beta-(1-->3) and beta-(1-->6) branching points. Its structural features include also alpha-(1-->2), alpha-(1-->3) and alpha-(1-->5) linked L-arabinofuranose residues. The polysaccharide demonstrated a phagocytosis stimulating property.


A rapid scoping review of fear of infertility in Africa.
Fear of infertility (FOI) is often reported in studies about reproductive health but this literature not yet mapped. The aim of this rapid scoping review of qualitative studies was to describe the nature of FOI in Africa. Eligibility criteria were qualitative data from Africa reporting views of women and men of any age. MEDLINE and CINAHL databases were searched for English language citations to February 2019 using keywords related to fear, infertility and Africa. Two independent reviewers screened texts for inclusion. Of 248 citations identified, 38 qualitative and six review papers were included. FOI was reported in diverse groups (e.g., men, women, fertile, infertile, married, unmarried, teachers, religious leaders). Two types of fears were identified: (1) fear of triggering infertility due to specific reproductive choices and (2) fear of the dire future consequences of infertility. Choices were perceived to affect fertility via internal accumulation and blockage (e.g., of menstrual blood), structural damage (e.g., burnt eggs), internal movement of contraceptive material, deliberate toxicity preventing population growth and behavioral effects impeding sexual activity. Diverse feared consequences of infertility were reported (e.g., polygamy, economic hardships). Fears were reported to affect reproductive behaviour (e.g., stopping contraception), help-seeking and social behaviour. FOI is a phenomenon that should be studied in its own right. Fears could originate from genuine threats, incorrect knowledge, distortions of truths, or dissemination of false information. Rigorous studies are needed to better understand FOI and integrate it in health education, client counselling and family planning service provision.


Up-regulated astroglial TWIK-related acid-sensitive K+ channel-1 (TASK-1) in the hippocampus of seizure-sensitive gerbils: a target of anti-epileptic drugs.
In order to identify the modulation of TASK (TWIK-related Acid-Sensitive K(+)) channel expressions in epilepsy, we conducted a comparative analysis of TASK channel immunoreactivities in the hippocampus of seizure-resistant (SR) and seizure-sensitive (SS) gerbils. There was no difference of the TASK-1 and TASK-2 channel expressions in the hippocampi of young SR and SS gerbils (1-2 months old). In adult SS gerbil hippocampus, TASK-1 immunoreactivity in astrocytes was higher than that in adult SR gerbil hippocampus. After seizures, TASK-1 immunoreactivity was significantly down-regulated in astrocytes of the SS gerbil hippocampus. In addition, various anti-epileptic drugs selectively affect TASK-1 immunoreactivity in astrocytes of the SS gerbil hippocampus. Gabapentin, lamotrigine, topiramate and valproic acid reduced the number of TASK-1(+) astrocytes in the hippocampus to 10-25% of that in saline-treated SS adult gerbils, whereas carbamazepine and vigabatrin decreased to approximately 50%. Therefore, the present study demonstrates that up-regulated TASK-1 immunoreactivity in astrocytes may be involved in the seizure activity of SS adult gerbils and suggests that the astroglial TASK-1 channel may be a target for epilepsy therapeutics.


Prevention of experimental autoimmune myocarditis by hydrodynamics-based naked plasmid DNA encoding CTLA4-Ig gene delivery.
Rat experimental autoimmune myocarditis (EAM) is a T cell-mediated disease that resembled the giant cell myocarditis seen in humans. Soluble CTLA4 improves some autoimmune diseases by blocking costimulatory signals on T cell. We investigated the effect of hydrodynamics-based naked plasmid DNA encoding CTLA4-immunoglobulin (Ig) gene delivery. Lewis rats were immunized with cardiac myosin and treated with hydrodynamic-based transfection, namely a rapid tail vein injection of a large volume of pCAGGS encoding CTLA4-Ig chimera solution on Day 0. The vector-derived CTLA4-Ig mRNA expressions were mainly detected in the liver and plasma CTLA4-Ig protein levels were maintained at about 2 mug/mL during the experiment period. On Day 17, the ratio of heart to body weight, the amount of mRNA of atrial natriuretic peptide, and the inflammatory areas in CTLA4 group were significantly lower than in the control group treated with empty plasmid. Maximum rate of intraventricular pressure rise and decline (dP/dT), minimum dP/dT, left ventricular end-diastolic pressure, and central venous pressure improved significantly after treatment with CTLA4-Ig. On Day 14, expressions of IL-2 in popliteal lymph nodes in the CTLA4-Ig group were significantly lower than in the control group. Hydrodynamics-based transfection of plasmid encoding CTLA4-Ig chimera dramatically prevented EAM.


A relationship between dynamic and static assessments of knee joint load. Gait analysis and radiography before and after knee replacement in 45 patients.
In a prospective study of 45 gonarthrosis patients treated with total knee arthroplasty, we performed gait analysis with the Vifor system preoperatively and 6 months and 2 years postoperatively. An evaluation was made of the relationship between dynamic measurements of knee joint load and static, radiographic measurements of alignment. Correlations were found between the knee joint moments in the frontal plane and the Hip-Knee-Ankle (HKA) angles on all measurement occasions, likewise between changes of moments and changes in HKA by the operation. Thus, static alignment reflects the loading conditions during gait.


Pharmacological blockage of ICAM-1 improves angiotensin II-induced cardiac remodeling by inhibiting adhesion of LFA-1+ monocytes.
Intercellular adhesion molecule-1 (ICAM-1) is a member of an immunoglobulin-like superfamily of adhesion molecules that mediate leukocyte adhesion to vascular endothelium and are involved in several cardiovascular diseases, including ischemia-reperfusion injury, myocardial infarction, and atherosclerosis. However, the role of ICAM-1 in angiotensin II (ANG II)-induced cardiac remodeling in mice remains unclear. Wild-type mice were administered an IgG control or ICAM-1 neutralizing antibody (1 and 2 mg/mouse, respectively) and ANG II (1,000 ng·kg-1·min-1) for up to 14 days. Cardiac contractile function and structure were detected by echocardiography. Hypertrophy, fibrosis, and inflammation were assessed by histological examination. The infiltration of lymphocyte function-associated antigen-1 (LFA-1+) monocytes/macrophages was assessed by immunostaining. The mRNA expression of genes was evaluated by quantitative RT-PCR analysis. Protein levels were tested by immunoblotting. We found that ICAM-1 expression in ANG II-infused hearts and ICAM-1 levels in serum from human patients with heart failure were significantly increased. Moreover, ANG II infusion markedly enhanced ANG II-induced hypertension, caused cardiac contractile dysfunction, and promoted cardiac hypertrophy, fibrosis, and LFA-1+ macrophage infiltration. Conversely, blockage of ICAM-1 with a neutralizing antibody dose-dependently attenuated these effects. Moreover, our in vitro data further demonstrated that blocking ICAM-1 inhibited ANG II-induced LFA-1+ macrophage adhesion to endothelial cells and migration. In conclusion, these results provide novel evidence that blocking ICAM-1 exerts a protective effect in ANG II-induced cardiac remodeling at least in part through the modulation of adhesion and infiltration of LFA-1+ macrophages in the heart. Inhibition of ICAM-1 may represent a new therapeutic approach for hypertrophic heart diseases.NEW & NOTEWORTHY Leukocyte adhesion to vascular endothelium is a critical step in cardiovascular diseases. ICAM-1 is a member of immunoglobulin-like superfamily of adhesion molecules that binds LFA-1 to mediate leukocytes adhesion and migration. However, the significance of ICAM-1 in ANG II-induced cardiac remodeling remains unclear. This study reveals that blocking of ICAM-1 prevents ANG II-induced cardiac remodeling via modulating adhesion and migration of LFA-1+ monocytes, may serve as a novel therapeutic target for hypertensive cardiac diseases.


Evaluation of the role of protein kinase Czeta in insulin-induced heart 6-phosphofructo-2-kinase activation.
A wortmannin-sensitive and insulin-stimulated protein kinase (WISK) that phosphorylates and activates heart 6-phosphofructo-2-kinase (PFK-2) was purified from serum-fed HeLa cells and found to contain protein kinase Czeta (PKCzeta). Both WISK and recombinant PKCzeta were inhibited by a pseudo-substrate peptide inhibitor of PKCzeta. WISK and PKCzeta phosphorylated and activated recombinant heart PFK-2 by increasing its Vmax. The phosphorylation sites in heart PFK-2 for WISK were Ser466 and Thr475, whereas PKCzeta phosphorylated only Thr475. In perfused rat hearts, insulin activated protein kinase B (PKB) 16-fold compared with the untreated controls. However in the same experiments, no change in phosphorylation state of the activation loop Thr410 residue of PKCzeta was observed. By contrast, in incubations of isolated rat epididymal adipocytes, where insulin activated PKB 30-fold compared with the untreated controls, a 50% increase in PKCzeta Thr410 phosphorylation was detected. Lastly in HEK 293T cells transfected with heart PFK-2, co-transfection with a kinase-inactive PKCzeta construct failed to prevent insulin-induced PFK-2 activation. Therefore, it is unlikely that PKCzeta is required for PFK-2 activation by insulin in heart.


First results from the selective chopper radiometer on Nimbus 4.
This article describes the temperature profiles through the atmosphere that are being obtained from the radiometer on Nimbus 4.


Triethylene melamine-induced sister-chromatid exchange in murine lymphocytes exposed in vivo.
The induction of sister-chromatid exchange (SCE) by triethylene melamine (TEM), a known animal carcinogen, was investigated in an in vivo exposure/in vitro culture murine lymphocyte assay. Dose-related increases in SCE were observed in B6D2F1 mice following a single i.p. injection of 0.5, 1 or 2 mg/kg TEM. SCE frequencies remained elevated over baseline levels at 24 h post exposure. It is hoped that studies of this nature can determine whether the in vivo/in vitro murine lymphocyte SCE assay is useful for predicting the carcinogenic potential of an agent.


Osteogenic potential of human umbilical cord-derived mesenchymal stromal cells cultured with umbilical cord blood-derived fibrin: a preliminary study.
This study examined the potential for osteogenesis via regenerative medicine using autologous tissues (umbilical cord (UC) and umbilical cord blood (UCB)) in nude mice. The study was designed to provide the three elements required for regenerative medicine (cell, scaffold, and growth factor) and autoserum for culture by means of autologous tissues. Mesenchymal stromal cells were obtained from UC (UC-MSCs). Fibrin, platelet-rich-plasma, and autoserum were obtained from UCB as scaffold, growth factor and serum for culture respectively. UC-MSCs were obtained from Wharton jelly and cultured with UCB-derived fibrin (UCB-fibrin) for 3-4 weeks to induce their differentiation into osteoblasts. They were implanted subcutaneously into the dorsum of male nude mice for 6 weeks prior to undergoing assessment. The assessments performed were haematoxylin and eosin, and alizarin red staining, immunohistochemical staining of human mitochondria, scanning electron microscopy, scanning electron microscopy with energy dispersive X-ray spectrometry and real-time reverse transcriptase-polymerase chain reaction to assess the expressions of osteoblast markers. Consequently, the differentiation of UC-MSCs into osteoblasts and the production of hydroxyapatite were verified. This study suggested the possible formation of bone tissue using biomedical materials obtained from UC and UCB.


Purification and partial characterization of a lysine-specific protease of Porphyromonas gingivalis.
A lysine-specific protease hydrolysing peptide bonds at the carboxyl side of lysine residues in Porphyromonas gingivalis was purified from culture supernatant by a combination of ion-exchange chromatography, gel filtration, and affinity chromatography. The molecular mass was 48 kDa and the pI value was 7.3. The enzyme hydrolysed the peptide bonds at the carboxyl side of lysine residues in synthetic substrates and natural proteins.


Induced tolerance of neonate Heliothis zea to host plant allelochemicals and carbaryl following incubation of eggs on foliage of Lycopersicon hirsutum f. glabratum.
Incubation of Heliothis zea (Boddie) eggs on foliage of Lycopersicon hirsutum f. glabratum C.H. Mull (accession PI 134417) results in neonates with elevated levels of tolerance to the toxic effects of PI 134417 foliage attributable to 2-tridecanone found in the glandular trichomes which abound on that foliage. The neonates from such eggs are also shown to have elevated levels of tolerance to the carbamate insecticide carbaryl. Incubation of eggs in an atmosphere containing 2-tridecanone similarly produced elevated levels of tolerance to 2-tridecanone among resulting neonates, indicating that 2-tridecanone is the likely inducing agent and that exposure to 2-tridecanone vapor, which is known to emanate from PI 134417 foliage, is sufficient for induction. Analysis of the cytochrome P-450 content in gut microsomes of fifth instar larvae indicated that exposure of larvae to 2-tridecanone in artificial diet or to PI 134417 foliage resulted in significantly elevated levels of cytochrome P-450 relative to larvae fed diet without 2-tridecanone or foliage of L. esculentum which contains no 2-tridecanone. In addition, removal of the glandular trichomes from PI 134417 foliage eliminated the ability of that foliage to induce elevated levels of cytochrome P-450. These results provide circumstantial evidence that cytochrome P-450 may be involved in the induced tolerance to xenobiotics among neonates from eggs exposed to 2-tridecanone or PI 134417 foliage.


Genetically modified seeds and plant propagating material in Europe: potential routes of entrance and current status.
Genetically modified organisms (GMO), mainly crop plants, are increasingly grown worldwide leading to large trade volumes of living seeds and other plant material both for cultivation and for food and animal feed. Even though all the traded GMOs have been assessed for their safety with regards to human and animal health and the environment, there still are some concerns regarding the potential uncontrolled release in the environment of authorized or unauthorized GM plants. In this review, we identify the possible entrance routes of GM seeds and other propagating plant material in the EU which could be linked to unauthorized release of GMOs in the environment. In addition, we discuss the situation with GM plant cultivation in some non-EU countries in terms of potential risks for GM seed imports. The available body of information suggests that GM seeds and plant propagating material can enter the EU due to problems with labeling/traceability of GM seed lots, contamination of conventional seed lots and accidental release into the environment of grains imported for food and animal feed. Even though cases of uncontrolled release of authorized GMOs, as well as, release of unauthorized GMOs have been reported, they can be generally attributed to adventitious and technically unavoidable presence with little environmental impact. In conclusion, the probability of GM seeds and plant propagating material illegally entering the cultivation in EU is unlikely. However, specific monitoring programs need to be established and maintained to facilitate the compliance of European farmers with the current GMO legislation.


The Morel-Lavallée lesion: pathophysiology, clinical presentation, imaging features, and treatment options.
Morel-Lavallée lesions are posttraumatic hemolymphatic collections related to shearing injury and disruption of interfascial planes between subcutaneous soft tissue and muscle. We review the pathophysiology of Morel-Lavallée lesions, clinical presentation, and potential sites of involvement. Magnetic resonance imaging (MRI) is the modality of choice for characterization. We present the MRI classification and highlight the key imaging features that distinguish the different types, focusing on the three most common: seroma, subacute hematoma, and chronic organizing hematoma. Potential mimics of Morel-Lavallée lesions, such as soft tissue sarcoma and hemorrhagic prepatellar bursitis, are compared and contrasted. Treatment options and a management algorithm are also briefly discussed.


Ubiquitin-binding domains.
Ubiquitin-binding domains (UBDs) are a collection of modular protein domains that non-covalently bind to ubiquitin. These recently discovered motifs interpret and transmit information conferred by protein ubiquitylation to control various cellular events. Detailed molecular structures are known for a number of UBDs, but to understand their mechanism of action, we also need to know how binding specificity is determined, how ubiquitin binding is regulated, and the function of UBDs in the context of full-length proteins. Such knowledge will be key to our understanding of how ubiquitin regulates cellular proteins and processes.


Making a sPLAsh: The expanding repertoire of EV signaling.
Extracellular vesicles (EVs) and their cargo act as signaling moieties by transferring their cargo to recipient cells, thereby mediating intercellular communication in complex tissue environments such as the tumor microenvironment. In the accompanying paper, Kudo et al. describe the interaction between tumor EVs and soluble phospholipase released by macrophages, leading to the remodeling of EV membranes and the release of lipid mediators that facilitate tumor growth by inducing an immune-tolerant phenotype.


Effect of iron supplementation during pregnancy on the behaviour of children at early school age: long-term follow-up of a randomised controlled trial.
Although routine Fe supplementation in pregnancy is a common practice, its clinical benefits or risks are uncertain. Children born to mothers in the Fe group in a trial of Fe supplementation in pregnancy have been found to have a significantly higher risk of abnormal behaviour at 4 years of age than those born to mothers in the placebo group. The objective of the present study therefore was to determine whether Fe supplementation in pregnancy influences child behaviour at early school age. The study was a follow-up of children at 6-8 years of age after women (n 430) were randomly allocated to receive a daily Fe supplement (20 mg) or placebo from 20 weeks gestation until delivery. The supplement reduced the incidence of Fe-deficiency anaemia at delivery from 9 % to 1 %. Child behaviour and temperament were assessed using the Strengths and Difficulties Questionnaire and the Short Temperament Scale for Children. Of the children, 264 (61 %) participated in the follow-up. Mean behaviour and temperament scores and the proportion of parent-rated and teacher-rated abnormal total difficulties scores did not differ between the Fe and placebo groups. However, the incidence of children with an abnormal teacher-rated peer problems subscale score was higher in the Fe group (eleven of 112 subjects; 8 %) than in the placebo group (three of 113 subjects; 2 %); the relative risk was 3.70 (95 % CI 1.06, 12.91; P = 0.026). We conclude that prenatal Fe supplementation had no consistent effect on child behaviour at early school age in this study population. Further investigation regarding the long-term effects of this common practice is warranted.


A high cholecystectomy rate in a cohort of Mexican American women who are postpartum at the time of oral contraceptive pill initiation.
Opinions regarding the association between gallbladder disease and oral contraceptive (OCs) differ. The objective of this article is to quantify cholecystectomy rate among women initiating OCs. Women under the age of 25 years were enrolled at four sites in a randomized trial evaluating initiation of OCs. Hospitalizations while enrolled were elicited during follow-up interviews, and medical records of women who underwent cholecystectomy were reviewed. Of 757 women enrolled at University of Texas Southwestern Medical Center (UTSW), 8 underwent cholecystectomy, a rate of 25.3/1000 woman-years (95% CI=8.1, 42.5). All eight were Mexican American and postpartum when they initiated OCs. The expected rate is 4.2/1000 woman-years for U.S. women aged 15-44. Women enrolled at the UTSW site had an increased rate of cholecystectomy and were more likely to be postpartum and Mexican American than women enrolled at the other sites.


Biomimetic poly(γ-glutamic acid) hydrogels based on iron (III) ligand coordination for cartilage tissue engineering.
For the problems in the research on differentiation of mesenchymal stem cells (BMSCs), such as poor differentiation tendency and low differentiation efficiency, a novel photo-crosslinked extracellular matrix (ECM) inspired double network hydrogel that composed of poly(γ-glutamic acid) (γ-PGA) hydrogel and Fe3+ ligand coordination was designed and manufactured. Compared with those traditional γ-PGA based hydrogels, the introduction of Fe3+ significantly enhanced the mechanical properties of the hydrogel and accelerated the chondrogenesis efficiency of BMSCs chondrogenesis. The experimental results confirmed that the mechanical properties of hydrogel enhanced by the introduction of metal ions Fe3+ could promote BMSCs proliferation, induce cartilage-specific gene expression, and increase secretion of hydroxyproline (HYP) and glycosaminoglycan (GAG). As a result, this method could promote chondrogenic differentiation of BMSCs, accelerate the regeneration of cartilage, and was prospective to be conducive to the research work of cartilage defect repair. Thus, the mechanically enhanced γ-PGA hydrogel scaffold by Fe3+ could mediate BMSCs differentiation and provide a scientific and theoretical basis for research and development of biomedical materials on cartilage tissue engineering field.


Does the Bicoid gradient matter?
The generation and interpretation of positional information are key processes in developmental systems. In this issue, Chen et al. report discoveries made in the Drosophila embryo that give new insights into how positional information can be produced by patterning gradients.


Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopy on Intact Dried Leaves of Sage (Salvia officinalis L.): Accelerated Chemotaxonomic Discrimination and Analysis of Essential Oil Composition.
Sage (Salvia officinalis L.) is cultivated worldwide for its aromatic leaves, which are used as herbal spice, and for phytopharmaceutical applications. Fast analytical strategies for essential oil analysis, performed directly on plant material, would reduce the delay between sampling and analytical results. This would enhance product quality by improving technical control of cultivation. The attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) method described here provides a reliable calibration model for quantification of essential oil components [EOCs; R(2) = 0.96; root-mean-square error of cross-validation (RMSECV) = 0.249 mL 100 g(-1) of dry matter (DM); and range = 1.115-5.280 mL 100 g(-1) of DM] and main constituents [e.g., α-thujone/β-thujone; R(2) = 0.97/0.86; RMSECV = 0.0581/0.0856 mL 100 g(-1) of DM; and range = 0.010-1.252/0.005-0.893 mL 100 g(-1) of DM] directly on dried intact leaves of sage. Except for drying, no further sample preparation is required for ATR-FTIR, and the measurement time of less than 5 min per sample contrasts with the most common alternative of hydrodistillation followed by gas chromatography analysis, which can take several hours per sample.


New therapeutic perspectives for demyelinating retrobulbar optic neuritis.
In patients with demyelinating retrobulbar optic neuritis (RON), a spontaneous or corticosteroid-induced improvement is generally observed within the first month, but this is clinically insignificant in 5%-7% of patients. We report the case histories of four patients who were considered to be "non-responders" to corticosteroids because their visus remained unchanged or had improved by only 1/10 after one month from intravenous corticoid therapy begun 2-7 days after disease onset, and who were therefore subsequently administered high intravenous doses of immunoglobulin. Three of these patients completely recovered in a period of 3-9 months; the fourth showed only a partial improvement, but this was consolidated after long-term continuation of the same therapy. These cases suggest the possible efficacy of early administration of intravenous immunoglobulin in RON patients who fail to respond to cortisone therapy. As recently demonstrated in animal models, it can be hypothesised that the result is due to immuno-mediated mechanisms of action that reduce autoimmune responses in the short- and medium-term, and in the long-term favour remyelination.


Functional and phylogenetic diversity of root-associated bacteria of Ajuga bracteosa in Kangra valley.
Present study investigates the cultivable diversity of root-associated bacteria from a medicinal plant Ajuga bracteosa in the Kangra valley, in order to determine their plant growth promoting (PGP) and biotechnological potential. The plant was found to exhibit a positive rhizosphere effect of 1.3-1.5. A total of 123 morphologically different bacteria were isolated from the rhizospheric soil and roots of the plant. Medium composition was found to have significant effect on the composition of isolated bacterial populations. Majority of the rhizospheric soil isolates belonged to α- and γ-Proteobacteria, with Pseudomonas constituting the most dominant species. Endophytic bacterial community, on other hand, consisted almost exclusively of Firmicutes. Majority of the isolates showed PGP activity by producing siderophores and indole acetic acid. Several isolates were found to exhibit very high antioxidant activity in the culture medium. A significant proportion of isolates also demonstrated other ecologically important activities like phosphate solubilization, nitrogen fixation, and production of hydrolytic enzymes including amylase, protease, lipase, chitinase, cellulase, pectinase and phosphatase. Firmicutes were found to be metabolically the most versatile group and performed multiple enzyme activities. This is the first systematic study of culturable bacterial community from the rhizosphere of A. bracteosa, particularly in the Kangra valley region.


Curvature correction in patients with tunical rupture: a necessary adjunct to repair.
We review our experience with traumatic tunical rupture repair with and without simultaneous penile curvature correction. Since November 1987, 11 men 23 to 39 years old have presented to us with tunical rupture, of whom 10 underwent surgical repair. All except 1 of the 8 men injured during sexual activity reported a curved penile appearance during erection. After patient 3 in our series sustained repeat rupture 5 months postoperatively due to penile curvature the next 7 underwent simultaneous curvature correction, which since 1996 has been done using 6-zero nylon. Recovery was uneventful in 2 of the 3 men who underwent simple tunical repair with 4-zero polyglactin or polyglycolic acid. All 7 of subsequent patients in whom curvature correction was performed simultaneously recovered satisfactorily with resumed erectile capability. Although coital position may be an important factor in tunical rupture during sexual activity, penile curvature may be contributory and should be corrected simultaneously with tunical repair.


External and internal effects of tetraethylammonium on voltage-dependent and Ca-dependent K+ currents components in molluscan pacemaker neurons.
Ca-dependent and voltage-dependent K+ currents in Aplysia pacemaker neurons were studied separately by electrophoretic injections of Ca2+ ions into the cells to induce the Ca-dependent component and by step depolarizations in the absence of external Ca2+ ions to induce the voltage-dependent component. Intracellular tetraethylammonium (TEA) blocks the voltage-dependent but not the Ca-dependent K+ current. Extracellular TEA blocks both components reversibly but is more effective in inhibiting the Ca-dependent K+ currents. Our results suggest that there are TEA receptor sites for the voltage-dependent K+ current on each side of the membrane, but only an external receptor site for the Ca-dependent K+ current.


Improvements in Montreal Cognitive Assessment scores after neurobehavioral therapy in adults with functional (nonepileptic) seizures and traumatic brain injury.
Cognitive functioning impacts clinical symptoms, treatment response, and quality of life in adults with functional/nonepileptic seizures (FS/NES), but no study to date examines effects of behavioral FS/NES treatment on cognition in these patients. We hypothesized that there would be a reduction in cognitive symptoms in participants with FS/NES and traumatic brain injury (TBI) following neurobehavioral therapy (NBT). We also hypothesized that select seizure-related, medication, subjective cognitive, and mental health symptoms would be negatively correlated with improvements in cognitive performance after NBT. Participants were 37 adults with TBI + FS/NES and 35 adults with TBI only, recruited from medical centers in the northeastern or southeastern U.S. TBI + FS/NES participants completed a 12 session NBT intervention, and TBI without seizures participants were not treated. All participants completed pre-post assessments of cognition (Montreal Cognitive Assessment [MoCA]) and baseline sociodemographic factors and mental health symptoms. Pre-post MoCA scores increased significantly in TBI + FS/NES participants (28/37 [75.7%] improved) but not in TBI comparisons (10/35 [28.6%] improved). Language, memory, and visuospatial/executive functions, but not attention, improved over time in the TBI + FS/NES group. Gains in cognition were concentrated in those TBI + FS/NES participants with likely baseline cognitive impairments (MoCA total score <26), and 9/17 of these participants moved from the "impaired" range at baseline (<26) to the "intact" range at endpoint (≥26). Lastly, participants taking fewer medications and reporting lower subjective cognitive difficulties at baseline showed larger pre-post MoCA total score improvements. Overall, results from this study suggest the potential for positive change in cognition in FS/NES and co-occurring TBI using evidence-based psychotherapy.


miR-378-3p alleviates contusion spinal cord injury by negatively regulating ATG12.
MicroRNAs (miRNAs or miRs) serve essential roles in the pathogenic process of spinal cord injury (SCI). The present study investigated the role of miR-378-3p and autophagy-related 12 (ATG12) in SCI. RT-qPCR was used to detect the mRNA expression levels of miR-378-3p and ATG12. Cell viability and membrane integrity were evaluated using CCK-8 and LDH assays. For the analysis of the interaction between miR-378-3p and ATG12, a dual-luciferase reporter assay was conducted. The hindlimb function of rats was detected with the Basso, Beattie and Bresnahan score, and the motor deficit index score was used to evaluate nerve function. Using these approaches, it was identified that miR-378-3p expression was downregulated, while that of ATG12 was upregulated in SCI tissues and in cells exposed to hypoxia. Hypoxia repressed the expression of miR-378-3p via hypoxia-inducible factor 1-α. The overexpression of miR-378-3p exerted anti-apoptotic effects on nerve cells by directly repressing ATG12. The infusion of miR-378-3p improved hindlimb motor function and the neurological functions of rats with contusion SCI, which contributed to amelioration of functional deficits and the relief of contusion SCI. Therefore, it was concluded that upregulated expression of miR-378-3p in PC12 or N2A cells repressed the apoptosis of nerve cells, and the administration of miR-378-3p in model rats with contusion SCI improved neurological and motor functions.


Deciphering the molecular details of interactions between anti-COVID drugs and functional human proteins: in silico approach.
The molecular docking calculations have been employed to investigate the interactions a set of proteins with the repurposed anti-COVID drugs. The position of the therapeutic agents within the protein structure was dependent on a particular drug-protein system and varied from the binding cleft to the periphery of the polypeptide chain. Interactions involved in the drug-protein complexation includes predominantly hydrogen bonding and hydrophobic contacts. The obtained results may be of particular importance while developing the anti-COVID strategies as well as for deeper understanding of the drug pharmacodynamics and pharmacokinetics.


ACR Appropriateness Criteria on suspected spine trauma.
The evaluation of patients with suspected spine trauma is controversial. This document addresses several pertinent issues: (1) which patients need imaging, (2) how much imaging is necessary, and (3) exactly what sort of imaging is to be performed. This subject is important, because conservative estimates indicate that more than 1 million blunt trauma patients, who have the potential for sustaining spine injuries, are seen annually in emergency departments in the United States. Adult patients who satisfy any of several "low-risk" criteria for cervical spine injury need no imaging. Patients who do not fall into this category should undergo thin-section computed tomographic examinations that includes sagittal and coronal multiplanar reconstructed images. For those patients who cannot be examined using computed tomography, 3-view radiographic examinations of the cervical vertebrae may be performed to provide preliminary assessments of the likelihood of injury until computed tomography can be performed. Thoracic and lumbar computed tomographic images may be obtained from data collected for thorax-abdomen-pelvis studies. Radiography is recommended for children under 14 years of age. Reconstructed computed tomographic images may be used from thorax-abdomen-pelvis studies of children, if they have been obtained. Magnetic resonance imaging should be the primary modality for evaluating possible spinal cord injury or compression as well as ligamentous injuries in acute cervical spine trauma. Flexion and extension radiography is best reserved for follow-up of symptomatic patients, after neck pain has subsided.


Metabolic and nutritional aspects in continuous renal replacement therapy.
Nutrition is one of the foundations for supporting and treating critically ill patients. Nutritional support provides calories, protein, electrolytes, vitamins, and trace elements via the enteral or parenteral route. Acute kidney injury (AKI) is a common and devastating problem in critically ill patients and has significant metabolic and nutritional consequences. Moreover, renal replacement therapy (RRT), whatever the modality used, also profoundly impacts metabolism. RRT and of the extracorporeal circuit impede 'effect the evaluation of a patient's energy requirements by clinicians. Substrates added and removed within the extracorporeal treatment are not always taken into consideration, making treatment even more challenging. Furthermore, evidence on nutritional support during continuous renal replacement therapy (CRRT) is scarce, and there are no clinical guidelines for nutrition adaptations during CRRT in critically ill patients. Most recommendations are based on expert opinions. This review discusses the complex interaction between nutritional support and CRRT and presents some milestones for nutritional support in critically ill patients on CRRT.


Incidence and predictors of remission and relapse of type 2 diabetes mellitus in Japan: Analysis of a nationwide patient registry (JDDM73).
To determine the incidence of remission and 1-year relapse from remission and associated factors in patients with type 2 diabetes. A total of 48 320 Japanese patients with type 2 diabetes aged ≥18 years, with glycated haemoglobin (HbA1c) levels ≥48 mmol/mol (6.5%) and/or glucose-lowering drug prescription, were identified from databases of specialist clinics from 1989 and followed until September 2022. Remission was defined as HbA1c <48 mmol/mol at least 3 months after cessation of a glucose-lowering drug. Relapse was defined as failure to maintain remission for 1 year. Factors associated with remission and relapse were evaluated by logistic regression analysis. The overall incidence of remissions per 1000 person-years was 10.5, and for those with HbA1c levels of 48 to 53 mmol/mol (6.5% to 6.9%), those taking no glucose-lowering drugs at baseline, and those with a ≥10% body mass index (BMI) reduction in 1 year, it was 27.8, 21.7 and 48.2, respectively. Shorter duration, lower baseline HbA1c, higher baseline BMI, higher BMI reduction at 1 year, and no glucose-lowering drugs at baseline were significantly associated with remission. Among 3677 persons with remission, approximately two-thirds (2490) relapsed within 1 year. Longer duration, lower BMI at baseline, and lower BMI reduction at 1 year were significantly associated with relapse. The results showed that the incidence of remission and predictors of relapse, especially baseline BMI, might differ greatly between East Asian and Western populations. Furthermore, the relationships of BMI reduction with remission and relapse may be greater in East Asian than in Western populations, implying ethnic differences in returning from overt hyperglycaemia to nearly normal glucose levels.