Hyperphagia, mild developmental delay but apparently no structural brain anomalies in a boy without SOX3 expression.
The transcription factor SOX3 is widely expressed in early vertebrate brain development. In humans, duplication of SOX3 and polyalanine expansions at its C-terminus may cause intellectual disability and hypopituitarism. Sox3 knock-out mice show a variable phenotype including structural and functional anomalies affecting the branchial arches and midline cerebral structures such as the optic chiasm and the hypothalamo-pituitary axis. SOX3 is claimed to be required in normal brain development and function in mice and humans, as well as in pituitary and craniofacial development. We report on an 8-year-old boy with a 2.1 Mb deletion in Xq27.1q27.2, which was found to be inherited from his healthy mother. To our knowledge, this is the smallest deletion including the entire SOX3 gene in a male reported to date. He is mildly intellectually disabled with language delay, dysarthria, behavior problems, minor facial anomalies, and hyperphagia. Hormone levels including growth, adrenocorticotropic and thyroid stimulating hormones are normal. Magnetic resonance imaging (MRI) at age 6 years showed no obvious brain anomalies. Genetic redundancy between the three members of the B1 subfamily of SOX proteins during early human brain development likely explains the apparently normal development of brain structures in our patient who is nullisomic for SOX3.


Susceptibility Weighted Imaging and White Matter Abnormality Findings in Service Members With Persistent Cognitive Symptoms Following Mild Traumatic Brain Injury.
Mild traumatic brain injury (mTBI) is a major health concern among active duty service members and Veterans returning from combat operations, and it can result in variable clinical and cognitive outcomes. Identifying biomarkers that can improve diagnosis and prognostication has been at the forefront of recent research efforts. The purpose of this study was to compare the sensitivity and specificity of abnormalities identified using more traditional magnetic resonance imaging (MRI) sequences such as fluid attenuation inversion recovery (FLAIR) to more advanced MRI sequences such as susceptibility weighted imaging (SWI) among a cohort of active duty service members experiencing persistent cognitive symptoms after mTBI. One-hundred and fifty-two active duty service members (77 mTBI, 58 orthopedically injured [OI] only, 17 post-traumatic stress disorder [PTSD] only) underwent MRI and neuropsychological evaluation at a large military treatment facility. Results demonstrated that FLAIR white matter hyperintensities (WMHs) were present in all three groups at statistically similar rates (41% mTBI, 49% OI, and 29% PTSD). With the exception of a single OI participant showing a small discrete SWI lesion, SWI abnormalities were overwhelmingly present in mTBI patients (22% mTBI, 1% OI, and 0% PTSD). Functionally, mTBI participants with and without SWI abnormalities did not differ in demographics, symptom reporting, or cognitive performance. However, mTBI participants with and without WMH did differ for on measures of working memory with the mTBI participants with WMH having worse cognitive performance. No other significant differences were noted for those participants with and without imaging abnormalities for either the OI or PTSD only cohorts. These results appear to illustrate the sensitivity and specificity of SWI findings though these results did not have any significant functional impact in this cohort. In contrast, WMHs noted on FLAIR imaging were not sensitive or specific findings, but functionally relevant among mTBI participants. These findings emphasize the complexity of injury and functional outcome in mTBI patients that requires additional examination.


'The beauty and the less beautiful': exploring the meanings of dying at 'home' among community and practitioner representatives and advocates across Canada.
Significant structural and normative pressures privilege the ideal of dying at home in Canada. At the same time, the social complexities and meanings associated with dying in particular locations remain critically unexamined. The aim of this study is to explore how diverse community members, including health and social care stakeholders, talk about preferences for locations of dying, with a particular focus on meanings of dying at home. Semi-structured virtual interviews were conducted with 24 community and practitioner representatives and advocates across Canada during the Covid-19 pandemic. This included compassionate community advocates, palliative care professionals and volunteers, bereaved carers, and members of queer, rural, and immigrant communities. Participants were asked about their own preferences for location of dying and elaborated on these aspects with regard to their client population or community group. Our analysis illuminates how meanings of dying at home are connected to previous experiences and perceptions of institutional care. As such, participants' perspectives are often framed as a rejection of institutional care. Dying at home also often signals potential for preserving ontological security and relational connection in the face of life-threatening illness. However, participants' expertise simultaneously informs a sense that dying at home is often unattainable. At times, this awareness underpins interpretations of both preferences and choices as contingent on considerations of the nature and type of illness, concerns about impacts on families, and available resources. The ideal of dying at home is nuanced by identity, relational, and structural contexts. Knowledge from this study can inform realistic and practical person-centered planning across care settings. It can also help create more representative public policy and health system quality indicators regarding a 'good death' that do not rely on or perpetuate undeveloped and unrealistic assumptions about dying, home, and family care.


"Hotness" stability of chicken hot-wing products as affected by preparation methods and storage.
Chicken hot-drumettes containing 2% cayenne pepper were prepared using three different cooking methods and stored under two different temperatures for "hotness" evaluation. Results demonstrated that the hotness of the samples were highest when products were cooked in a microwave oven, followed by convection oven, and least hot by deep-fat frying. Regardless of the cooking method, the degree of hotness of the hot-drumette decreased drastically during refrigerated storage. Results also indicated that the loss of hotness was associated with the increase of 2-thiobarbituric acid (TBA) values in the product. The addition of antioxidants such as butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), rosemary, and sodium nitrate during preparation or vacuum packaging retarded lipid oxidation of chicken hot-drumettes and retarded the loss of hotness of the products during refrigerated storage.


Epidemiology of acoustic neuromas.
In Denmark one surgical team, during the last 7 years, has performed about 80 per cent of all acoustic neuroma surgery. Because of this centralization, in such a limited population as that of Denmark, we have attempted to make a epidemiological survey of all diagnosed tumours in the period from 1976 to 1983. Systematic and prospective records were made by the authors of all patients with translabyrinthine operations, and data on patients with suboccipital operations were collected retrospectively from the six neurosurgical departments in Denmark. The average annual incidence was 8 tumours per million inhabitants, with the highest incidence of approximately 13 tumours per million occurring in Copenhagen County. The incidence reported in previously published autopsy series is 800-900 times higher and the following may serve as an explanation for this enormous difference: Autopsy series are in all probability based on highly selected cases; they are predominantly based on elderly people and the incidence is not directly applicable to the population at large. Several of the silent tumours from the autopsy series were located in the cochlea or in the labyrinth and not in the internal ear canal. The conclusion from our study is that both the knowledge and data available at present are insufficient to serve as a basis for an actual calculation of incidence and prevalence of acoustic neuromas.(ABSTRACT TRUNCATED AT 250 WORDS)


A tandem array of minimal U1 small nuclear RNA genes is sufficient to generate a new adenovirus type 12-inducible chromosome fragile site.
Infection of human cells with adenovirus serotype 12 (Ad12) induces metaphase fragility of four, and apparently only four, chromosomal loci. Surprisingly, each of these four loci corresponds to a cluster of genes encoding a small abundant structural RNA: the RNU1 and RNU2 loci contain tandemly repeated genes encoding U1 and U2 small nuclear RNAs (snRNAs), respectively; the PSU1 locus is a cluster of degenerate U1 genes; and the RN5S locus contains the tandemly repeated genes encoding 5S rRNA. These observations suggested that high local levels of transcription, in combination with Ad12 early functions, can interfere with metaphase chromatin packing. In support of this hypothesis, we and others found that an artificial tandem array of transcriptionally active, but not inactive, U2 snRNA genes would generate a novel Ad12-inducible fragile site. Although U1 and U2 snRNA are both transcribed by RNA polymerase II and share similar enhancer, promoter, and terminator signals, the human U1 promoter is clearly more complex than that of U2. In addition, the natural U1 tandem repeat unit exceeds 45 kb, whereas the U2 tandem repeat unit is only 6.1 kb. We therefore asked whether an artificial array of minimal U1 genes would also generate a novel Ad12-inducible fragile site. The exogenous U1 genes were marked by an innocuous U72C point mutation within the U1 coding region so that steady-state levels of U1 snRNA derived from the artificial array could be quantified by a simple primer extension assay. We found that the minimal U1 genes were efficiently expressed and were as effective as minimal U2 genes in generating a novel Ad12-inducible fragile site. Thus, despite significant differences in promoter architecture and overall gene organization, the active U1 transcription units suffice to generate a new virally inducible fragile site.


Biomimetic Strategies To Treat Traumatic Brain Injury by Leveraging Fibrinogen.
There were over 27 million new cases of traumatic brain injuries (TBIs) in 2016 across the globe. TBIs are often part of complicated trauma scenarios and may not be diagnosed initially because the primary clinical focus is on stabilizing the patient. Interventions used to stabilize trauma patients may inadvertently impact the outcomes of TBIs. Recently, there has been a strong interest in the trauma community toward administrating fibrinogen-containing solutions intravenously to help stabilize trauma patients. While this interventional shift may benefit general trauma scenarios, fibrinogen is associated with potentially deleterious effects for TBIs. Here, we deconstruct what components of fibrinogen may be beneficial as well as potentially harmful following TBI and extrapolate this to biomimetic approaches to treat bleeding and trauma that may also lead to better outcomes following TBI.


A Multifunctional Bis-Adduct Fullerene for Efficient Printable Mesoscopic Perovskite Solar Cells.
Printable mesoscopic perovskite solar cells (PMPSCs) have exhibited great attractive prospects in the energy conversion field due to their high stability and potential scalability. However, the thick perovskite film in the mesoporous layers challenges the charge transportation and increase grain boundary defects, limiting the performance of the PMPSCs. It is critical not only to improve the electric property of the perovskite film but also to passivate the charge traps to improve the device performance. Herein we synthesized a bis-adduct 2,5-(dimethyl ester) C60 fulleropyrrolidine (bis-DMEC60) via a rational molecular design and incorporated it into the PMPSCs. The enhanced chemical interactions between perovskite and bis-DMEC60 improve the conductivity of the perovskite film as well as elevate the passivation effect of bis-DMEC60 at the grain boundaries. As a result, the fill factor (FF) and power conversion efficiency (PCE) of the PMPSCs containing bis-DMEC60 reached 0.71 and 15.21%, respectively, significantly superior to the analogous monoadduct derivative (DMEC60)-containing and control devices. This work suggests that fullerene derivatives with multifunctional groups are promising for achieving high-performance PMPSCs.


Age-related Changes in Lateral Entorhinal and CA3 Neuron Allocation Predict Poor Performance on Object Discrimination.
Age-related memory deficits correlate with dysfunction in the CA3 subregion of the hippocampus, which includes both hyperactivity and overly rigid activity patterns. While changes in intrinsic membrane currents and interneuron alterations are involved in this process, it is not known whether alterations in afferent input to CA3 also contribute. Neurons in layer II of the lateral entorhinal cortex (LEC) project directly to CA3 through the perforant path, but no data are available regarding the effects of advanced age on LEC activity and whether these activity patterns update in response to environmental change. Furthermore, it is not known the extent to which age-related deficits in sensory discrimination relate to the inability of aged CA3 neurons to update in response to new environments. Young and aged rats were pre-characterized on a LEGO© object discrimination task, comparable to behavioral tests in humans in which CA3 hyperactivity has been linked to impairments. The cellular compartment analysis of temporal activity with fluorescence in situ hybridization for the immediate-early gene Arc was then used to identify the principal cell populations that were active during two distinct epochs of random foraging in different environments. This approach enabled the extent to which rats could discriminate two similar objects to be related to the ability of CA3 neurons to update across different environments. In both young and aged rats, there were animals that performed poorly on the LEGO object discrimination task. In the aged rats only, however, the poor performers had a higher percent of CA3 neurons that were active during random foraging in a novel environment, but this is not related to the ability of CA3 neurons to remap when the environment changed. Afferent neurons to CA3 in LEC, as identified with the retrograde tracer choleratoxin B (CTB), also showed a higher percentage of cells that were positive for Arc mRNA in aged poor performing rats. This suggests that LEC contributes to the hyperactivity seen in CA3 of aged animals with object discrimination deficits and age-related cognitive decline may be the consequence of dysfunction endemic to the larger network.


Assessment and treatment of mental fatigue after a traumatic brain injury.
Mental fatigue is a frequently occurring symptom after mild, moderate or severe traumatic brain injury (TBI). Such mental fatigue may become a long-lasting problem, irrespective of severity and even after recovery from other neurological or psychiatric symptoms. Two characteristics of this mental fatigue are that patients easily become exhausted and there is generally a long recovery time. There is a need to increase knowledge and awareness of mental fatigue as it interferes considerably with work, studies, and social activities. Assessment is difficult and few treatment studies have been carried out. For the purposes of assessment, the development of the Mental Fatigue Scale is described here, and we also summarise the few treatment studies found for fatigue after TBI. Symptom alleviation is reported through Mindfulness-Based Stress Reduction (MBSR), light therapy and for the psychostimulant methylphenidate and the dopamine stabiliser (-)-OSU6162. However, more knowledge of the origin of mental fatigue and its underlying mechanisms is needed for development of more efficient therapeutic methods. Prospective randomised trials focusing on long-term outcomes are warranted and should include both pharmacological and non-pharmacological treatments.


Helping surgeons work 'smarter'.
Operating theatre technology has developed significantly in recent years, with increasing automation and control of functions like lighting, pendants, cameras, and viewing screens, a growing focus on infection control, the ability to stream footage of live surgery to other locations for training, and the growth of technology designed to enable surgeons to operate laparoscopically, resulting in less invasive procedures, faster recovery times, and enhanced throughput. Against this backdrop, HEJ examines how some of the latest operating theatre systems are benefting users.


Prophage Diversity of 'Candidatus Liberibacter asiaticus' Strains in California.
Huanglongbing (HLB) is a highly destructive citrus disease and is associated with a nonculturable bacterium, 'Candidatus Liberibacter asiaticus'. 'Ca. L. asiaticus' in the United States was first found in Florida in 2005 and is now endemic there. In California, 'Ca. L. asiaticus' was first detected in Hacienda Heights in Los Angeles County in 2012 and has now been detected in multiple urban locations in southern California. Knowledge of 'Ca. L. asiaticus' strain diversity in California is important for HLB management. In this study, genomic diversity among 10 'Ca. L. asiaticus' strains from six California locations were analyzed using a next-generation sequencing (NGS) (Illumina MiSeq and HiSeq) approach. Draft genome sequences of 'Ca. L. asiaticus' strains were assembled. Sequences of the 16S ribosomal RNA gene and nrdB confirmed 'Ca. L. asiaticus' identity. Prophages were detected in all 'Ca. L. asiaticus' strains. The California 'Ca. L. asiaticus' strains formed four prophage typing groups (PTGs): PTG1, with type 1 prophage only (strains from Anaheim, San Gabriel, and Riverside); PTG2, with type 2 prophage only (strains from Hacienda Heights); PTG1-3, with both type 1 and 3 prophages (a strain from Cerritos); and PTG1-2, with both type 1 and type 2 prophages (a strain from La Habra). Analyses of the terL sequence showed that all California 'Ca. L. asiaticus' strains were not introduced from Florida but likely from locations in Asia. Miniature inverted-repeat transposable elements were found in all 'Ca. L. asiaticus' strains, yet, a jumping-out event was detected in the 'Ca. L. asiaticus' strain from Cerritos. Altogether, this study demonstrated that the NGS approach focusing on prophage variation was sensitive and effective in revealing diversity of 'Ca. L. asiaticus' strains in California.


EEDi-5285: An Exceptionally Potent, Efficacious, and Orally Active Small-Molecule Inhibitor of Embryonic Ectoderm Development.
Inhibition of embryonic ectoderm development (EED) is a new cancer therapeutic strategy. Herein, we report our discovery of EEDi-5285 as an exceptionally potent, efficacious, and orally active EED inhibitor. EEDi-5285 binds to the EED protein with an IC50 value of 0.2 nM and inhibits cell growth with IC50 values of 20 pM and 0.5 nM in the Pfeiffer and KARPAS422 lymphoma cell lines, respectively, carrying an EZH2 mutation. EEDi-5285 is approximately 100 times more potent than EED226 in binding to EED and >300 times more potent than EED226 in inhibition of cell growth in the KARPAS422 cell line. EEDi-5285 has excellent pharmacokinetics and achieves complete and durable tumor regression in the KARPAS422 xenograft model in mice with oral administration. The cocrystal structure of EEDi-5285 in a complex with EED defines the precise structural basis for their high binding affinity. EEDi-5285 is the most potent and efficacious EED inhibitor reported to date.


Rosuvastatin-related rhabdomyolysis causing severe proximal paraparesis and acute kidney injury.
We describe the case of a 76-year-old man who presented with bilateral lower limb weakness associated with decreased urine output. His initial blood results showed acute kidney injury (AKI) stage 3 with substantially raised serum creatine kinase concentration of 37 950 IU/L (normal range <171 U/L). He had been on high-dose rosuvastatin for 4 years with a recent brand change occurring 1 week prior to onset of symptoms. There was no history of pre-existing neuromuscular disease. Statin-related rhabdomyolysis was suspected and rosuvastatin was withheld. His muscle strength gradually improved. He required haemodialysis for 10 weeks. He was discharged home after a complicated course of hospitalisation. His renal function improved and he became dialysis-independent; however, he was left with residual chronic kidney disease.


Characterizing the knowledge of educators receiving training in systematic literacy instruction.
Addressing the needs of students with dyslexia requires an in-depth knowledge of various components of a multi-dimensional approach to reading intervention, which is supported by an understanding of the structure of the language being taught. The current study explored the association between teacher knowledge of the English language and different stages of training provided through 2-year courses that meet the objectives of the International Dyslexia Association (IDA) standards of teacher knowledge and practice. It included 347 K-12 licensed teachers who were at various stages of training when they completed a test of knowledge in the areas of Phonological Sensitivity, Phonemic Awareness, Decoding, Spelling, and Morphology. The level of terminal degree (i.e., BA or MA) held by participating teachers and their amount of teaching experience did not predict performance on the test. In contrast, participating teachers differed in their level of knowledge as a function of how much training they had received as part of a 2-year course. Increased training was associated with elevated levels of knowledge. Moreover, teachers who completed the 2-year training program and went on to obtain certification through a national certifying organization had reliably greater knowledge than those who had not. Additionally, the weakest domains of knowledge across all teachers were in spelling and morphology, suggesting a need for improved training in these domains, given that they are identified deficiencies for persistently poor responders to reading intervention and in children presenting with late emerging forms of reading disability.


Ribosomal release without peptidyl tRNA hydrolysis at translation termination in a eukaryotic system.
A 22-codon upstream open reading frame (uORF2) in the human cytomegalovirus UL4 transcript leader inhibits downstream translation in cis. Previous studies revealed that the peptide product of uORF2 mediates this inhibitory effect by interfering with translation termination at its own stop codon. The block at termination results both in accumulation of the nascent uORF2 peptide linked to tRNA(Pro), the tRNA that decodes the final codon of uORF2, and in stalling of ribosomes at the end of uORF2. The stalled ribosomes create a barrier that obstructs ribosomal transit to the downstream cistron. In the current studies, we further investigated the mechanism of uORF2-mediated translational inhibition by assessing the kinetics of uORF2 peptidyl tRNA(Pro) hydrolysis and ribosomal release from the uORF2 termination site. Whereas hydrolysis of a mutant, noninhibitory uORF2 peptidyl tRNA is nearly complete in less than 1 min, hydrolysis of the wild-type peptidyl tRNA is negligible even after 30 min. In spite of this remarkably prolonged block to hydrolysis of the uORF2 peptidyl tRNA(Pro), most ribosomes are released from the uORF2 termination site within 15 min. Thus, peptidyl tRNA hydrolysis is not absolutely required for ribosomal release in this system. These results suggest that a eukaryotic cellular mechanism exists for removing stalled ribosomes from mRNAs in the absence of peptidyl tRNA hydrolysis.


Developmental regulation of translation by the 5' noncoding region of murine c-myc mRNA in Xenopus laevis.
The translational efficiency of chloramphenicol acetyltransferase (CAT) mRNA containing a 5' noncoding sequence derived from exon 1 of the murine c-myc gene (360CAT) has been examined at different stages of Xenopus egg development. In contrast to its reduced translation in the Xenopus oocyte, 360CAT mRNA is translated as efficiently as CAT mRNA when injected into either mature Xenopus eggs or Xenopus embryos. No significant alteration of 360CAT mRNA stability was observed up to 10 h post-fertilization in Xenopus embryos as compared to that of CAT mRNA. The increase in 360CAT mRNA translational efficiency in Xenopus embryos was not observed with CAT mRNAs possessing other inhibitory 5' noncoding sequences. The increase in 360CAT mRNA translational efficiency is attributed to a trans-acting factor synthesized or activated following Xenopus oocyte maturation. The possible significance of the 5' noncoding region of c-myc mRNA in developmental expression of c-myc is discussed.


Augmentation of catecholamine-stimulated [3H]GDP release in adipocyte membranes from exercise-trained rats.
The effects of exercise training on the catecholamine-stimulated [3H]GDP release in rat adipocyte membranes prelabeled with [3H]GTP and the adenylate cyclase activity were investigated. Exercise training significantly increased the release of [3H]GDP in response to (-)isoproterenol. The adenylate cyclase activity induced by a nonhydrolyzable guanine nucleotide analogue, Gpp(NH)p, was significantly greater in exercise-trained rats.


Primary Empty Sella Syndrome Presenting With Severe Hyponatremia And Minimal Salt Wasting.
A 41 year old Jordanian gentleman known case of osteogenesis imperfecta presented with vomiting, decreased oral intake followed by confusion. At presentation he was found to have signs of hypogonadism with severe hyponatremia. The hyponatremia responded to intravenous steroid replacement .This alerted the physicians to search for other pituitary hormone deficiencies. Our patient had pneumonia with respiratory failure. He was intubated and mechanically ventilated. Subsequent tracheostomy was done because of failure of weaning. His GCS remained very low despite treatment of infection and correction of electrolyte imbalance. He had multiple hormone deficiencies. He was found to be severely hypothyroid, replacement of thyroxine caused gradual improvement of GCS over a period of six to eight weeks. In the absence of history pituitary adenoma, pituitary, irradiation or surgery, a diagnosis of primary empty Sella syndrome with anterior pituitary dysfunction was made.


Solubilizing water involved in protein extraction using reversed micelles.
The extraction of protein using reversed micelles was investigated in relation to the amount of solubilizing water in the reversed micellar organic phase. The minimal concentration of amphiphilic molecule di-2-ethylhexyl sodium sulfosuccinate (C(20)H(37)O(7)Na) (AOT) required for 100% cytochrome c extraction was recognized. This critical AOT concentration increased with protein concentration in the aqueous phase. On this minimal AOT condition, the molar ratio of solubilizing water to extracted protein was found to be a constant of 3500 under C(KCI) = 1.0 x 10(2) mol . m(-3) in this system. This ratio means the hydrophillic surroundings required for extracting one protein molecule into the micellar organic phase under the suitable pH and salt concentration for the forward extraction. In this regard, AOT molecules seemed to take the part of water solubilizing agent in the reversed micellar extraction. This role of AOT is important to extract protein under the suitable pH and salt concentration. The amount of solubilizing water in the protein-containing system was larger than in the protein-free system. This difference shows that the water molecules accompany the extracted protein into the reversed micellar organic phase at constant ratio 2200 under C(KCI) = 1.0 x 10(2) mol . m(-3), i.e., accompanying water molecules per one extracted protein. The minimal AOT concentration increased with ionic strength. On this minimal AOT condition, the molar ratio of solubilizing water to extracted protein also increased with ionic strength, so that in higher ionic strength, more solubilizing water was required. Then more AOT was required to provide the hydrophillic surroundings for protein. The pH affected the minimal AOT concentration required for 100% protein extraction.


Serum tumor marker half-life during chemotherapy allows early prediction of complete response and survival in nonseminomatous germ cell tumors.
The prognostic value and therapeutic utility of monitoring the decay of alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) after chemotherapy for nonseminomatous germ cell tumors was assessed. Patients treated on successive front line chemotherapy protocols at Memorial Hospital between 1979 and 1988 were studied. Marker values taken within the first 90 days of treatment were reviewed for the 198 patients who had initially abnormal values and serial measurements at Memorial Hospital. Since markers frequently increased in an unpredictable fashion in the first week after chemotherapy, prechemotherapy values would be inaccurate for assessment of subsequent half-life. Therefore, the first two values measured greater than 7 days after the start of treatment were used for all calculations of half-life. Among 38 patients who had the two successive AFP measurements elevated, those who later achieved a complete response (CR) had a median AFP half-life of 6.1 days (n = 20), whereas those not achieving CR had a median AFP half-life of 13.3 days (P = 0.02). Among 37 patients with the two successive HCG values elevated, those who later achieved CR had a median HCG half-life of 4.2 days (n = 10), whereas those not achieving CR had a median HCG half-life of 18.4 days (P = 0.04). Forty-two patients who had an AFP half-life greater than 7 days or an HCG half-life greater than 3 days had significantly shorter overall survival (median, 8 months) than the other 156 patients (median not reached) (P less than 0.0001). These 42 patients also achieved CR in lower proportion (29%) than the other 156 patients (89%) (P less than 0.0001). Cox regression identified prolonged marker half-life as the most significant independent predictor of survival. Lack of appropriate decay of serum tumor markers can identify patients unlikely to achieve CR or prolonged survival and thus can be used to select patients during treatment who may benefit from an early change to more aggressive therapy.


Dapagliflozin therapy in type-2 diabetes: current knowledge and future perspectives.
Dapagliflozin is a new antidiabetic agent that belongs to the class of sodium glucose transporter 2 (SGLT-2) inhibitors. By decreasing renal glucose absorption, these agents target hyperglycemia independent of insulin secretion or insulin sensitivity. This unique mechanism of action differentiates them from existing antidiabetic agents currently on the market. It has been hypothesized that SGLT-2 inhibitors can be effectively and safely combined with other agents, including insulin, and incretin-based therapies. They can be used either as monotherapy, or in dual- or triple-agent combinations. Dapagliflozin has been shown to be effective and safe in patients with type-2 diabetes, with modest but significant reductions in HbA1c and a number of potentially beneficial and sustained non-glycemic effects, including those on body weight, plasma lipids and systolic blood pressure. In addition, dapagliflozin has been shown to have a generally favorable safety profile and is well tolerated. Ongoing studies may provide definitive answers on the cardiovascular safety and efficacy of SGLT-2 inhibitors in patients with type-2 diabetes.


Original disorder-order transition related to electronic and magnetic properties in the thermoelectric misfit phase [Ca2CoO3][CoO2]1.62.
A structural phase transition is shown around 400 K for the thermoelectric lamellar misfit cobalt oxide [Ca2CoO3][CoO2]1.62. This transition is related to a rearrangement of the central [CoO] layer of the [Ca2CoO3] slab of this structure, characterized by a commensurate intrinsic modulation q2 = 2/3a*-1/3c*. The partial residual disorder related to split Co and O atomic sites along the misfit b direction disappears and one can describe this layer with its triple chains as a modulated configuration with a regular and not distorted periodicity along b. This phase transition is associated with small changes observed in the transport and magnetic properties as a function of temperature.


Inhibition of melanogenesis by Aster yomena callus pellet extract in melanoma cells and patients with skin pigmentation.
Plant tissue culture holds immense potential for the production of secondary metabolites with various physiological functions. We recently established a plant tissue culture system capable of producing secondary metabolites from Aster yomena. This study aimed to uncover the mechanisms underlying the potential therapeutic effects of Aster yomena callus pellet extract (AYC-P-E) on photoaging-induced skin pigmentation. Excessive melanogenesis was induced in B16F10 melanoma cells using α-melanocyte stimulating hormone (α-MSH). The effects of AYC-P-E treatment on melanin biosynthesis inducers and melanin synthesis inhibition were assessed. Based on the results, a clinical study was conducted in subjects with skin pigmentation. AYC-P-E inhibited melanogenesis in α-MSH-treated B16F10 cells, accompanied by decreased mRNA and protein expression of melanin biosynthesis inducers, including cyclic AMP response element-binding protein (CREB), tyrosinase, microphthalmia-associated transcription factor (MITF), tyrosinase related protein-1 (TRP-1), and TRP-2. This anti-melanogenic effect was mediated by mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) phosphorylation. Treatment of subjects with skin pigmentation with AYC-P-E-containing cream formulations resulted in 3.33%, 7.06%, and 8.68% improvement in the melanin levels at 2, 4, and 8 weeks, respectively. Our findings suggest that AYC-P-E inhibits excessive melanogenesis by activating MEK/ERK and AKT signaling, potentiating its cosmetic applications in hyperpigmentation treatment.


[Effects of exogenous Ca2+ on the growth and Zn accumulation of two Sedum alfredii Hance ecotypes].
A hydroponic study was conducted to investigate the biomass, root morphology, and zinc (Zn), calcium (Ca) and sulfur (S) contents of two Sedum alfredii ecotypes under effects of different concentration calcium (Ca2+) addition. The results showed that with increasing exogenous Ca2+ concentration, the dry mass of the two S. alfredii ecotypes increased, and the shoot dry mass of hyperaccumulation ecotype increased significantly (P <0.05). The root length and root surface area of hyperaccumulation ecotype increased with increasing exogenous Ca2+ concentration, while those of non-hyperaccumulation ecotype were in adverse. The Zn accumulation in the root, stem and leaf of hyperaccumulation ecotype was increased with increasing exogenous Ca2+ concentration though the differences among Ca2+ treatments were not significant (P >0.05), while the Zn accumulation in the shoot of non-hyperaccumulation ecotype was significantly low (P <0.05). The Ca accumulation in the root, stem and leaf of non-hyperaccumulation ecotype had a significant positive correlation with the concentration of exogenous Ca2+ (P <0.05), so as the S accumulation in the root of hyperaccumulation ecotype (P <0.01). Exogenous Ca2+ promoted the Zn absorption and accumulation of hyperaccumulation ecotype, while inhibited the Zn accumulation of non-hyperaccumulation ecotype. Appropriate concentration of exogenous Ca2+ could promote the growth of hyperaccumulation ecotype S. alfredii, and improve its ability of accumulating more zinc.


Indolizy Carbene Ligand. Evaluation of Electronic Properties and Applications in Asymmetric Gold(I) Catalysis.
We report herein a new family of carbene ligands based on an indolizine-ylidene (Indolizy) moiety. The corresponding gold(I) complexes are easily obtained from the gold(I)-promoted cyclization of allenylpyridine precursors. Evaluation of the electronic properties by experimental methods and also by DFT calculations confirms strong σ-donating and π-accepting properties of these ligands. Cationization of the gold(I) complexes generates catalytic species that trigger diverse reactions of (poly)unsaturated precursors. When armed with a methylene phosphine oxide moiety on the stereogenic center adjacent to the nitrogen atom, the corresponding bifunctional carbene ligands give rise to highly enantioselective heterocyclizations. DFT calculations brought some rationalization and highlighted the critical roles played by the phosphine oxide group and the tosylate anion in the asymmetric cyclization of γ-allenols.


Metastatic basal cell carcinoma to the lungs: Case report and review of literature.
Basal cell carcinoma is the most common form of skin cancer and it rarely metastasizes. The prevalence of metastatic basal cell carcinoma (MBCC) varies between 0.0028% and 0.55% of all cases. Over 250 MBCC have been reported in the literature. We present a case with large recurrent basal cell carcinoma of the face with radiological and histopathological findings indicating the presence of metastasis to the lungs.


[Long term experience with the IUD copper-T-200 (author's transl)].
During a period of seven years pregnancy-, expulsion- and extraction-rates of the copper-T-200 were determined for two different groups of patients in a university hospital. The first group were patients of the ambulatory care service representing an heterogenous composition. The other group were patients from a private practice representing a more homogenous population. In the first group insertions and controls were done by different physicians at various stages of their training, in the second group they were performed by an experienced clinician. In the first group there were 1397 primary IUD-insertions and 22,203 months of use, in the second group the corresponding data were 272 primary insertions an 5127 months of use. The pregnancy rates calculated according to the Pearl-index were 1.0 and 0.24, respectively. The expulsion rates were calculated as 0.8 and 0.2, respectively. The extraction rates because of unwanted side-effects were 4.4 in the first and 1.6 in the second group of patients. There seems to be an advantage in having the care of the IUD-patient being taken by an experienced physician, especially regarding the extraction rates because of unwanted side effects.


Proteomic approach to breast cancer.
Breast cancer is the most common cancer affecting women worldwide. Despite tremendous advances in screening, diagnosis, and treatment, the causes of this disease remain elusive and complex. Proteomics is a rapidly developing field that can explore the heterogeneity of breast cancer and supplement the wealth of information gained from genomics. This article serves as an overview of the application of matrix-assisted laser desorption/ionization source with a time-of-flight (MALDI-TOF) proteomic techniques as applied to breast cancer. Examples of the clinical applicability of MALDI-TOF mass spectrometry are provided but represent only a fraction of the potential uses yet to be discovered. In addition, a brief summary of the bioinformatics issues that surround proteomics is included. Mass spectrometry has provided new proteomic approaches to unravel the complexities of clinical specimens relevant to breast cancer diagnostics. In particular, MALDI-TOF mass spectrometry analysis has been used to differentiate cancer profiles from benign profiles in samples from sera, plasma, tissue, nipple fluid, and ductal lavage. Some discriminating proteins have subsequently been identified. Mass spectrometry applications to breast cancer diagnostics continue to be developed but are evolving faster than bioinformatics/statistical analysis can adapt. The future of these techniques in terms of clinical investigation is limitless, but in terms of general applicability, these applications are currently cost-prohibitive.


Inhibition of the mitochondrial permeability transition improves bone fracture repair.
Bone fracture is accompanied by trauma, mechanical stresses, and inflammation - conditions known to induce the mitochondrial permeability transition. This phenomenon occurs due to opening of the mitochondrial permeability transition pore (MPTP) promoted by cyclophilin D (CypD). MPTP opening leads to more inflammation, cell death and potentially to disruption of fracture repair. Here we performed a proof-of-concept study and tested a hypothesis that protecting mitochondria from MPTP opening via inhibition of CypD improves fracture repair. First, our in vitro experiments indicated pro-osteogenic and anti-inflammatory effects in osteoprogenitors upon CypD knock-out or pharmacological inhibition. Using a bone fracture model in mice, we observed that bone formation and biomechanical properties of repaired bones were significantly increased in CypD knock-out mice or wild type mice treated with a CypD inhibitor, NIM811, when compared to controls. These effects were evident in young male but not female mice, however in older (13 month-old) female mice bone formation was also increased during fracture repair. In contrast to global CypD knock-out, mesenchymal lineage-specific (Prx1-Cre driven) CypD deletion did not result in improved fracture repair. Our findings implicate MPTP in bone fracture and suggest systemic CypD inhibition as a modality to promote fracture repair.


Turkish adolescents' attitudes toward physical education.
1,163 middle school students (586 girls, 577 boys; Grades 6-8) were selected through a stratified random sampling method to examine their attitudes toward physical education (PE) by grade, student's sex, sports participation characteristics, and teacher's sex. They were administered the Attitude Toward Physical Education Scale for Children. Factorial analysis of variance indicated that Grade 8 students' mean attitude scores were less positive than those of Grade 6 students, but the attitudes of boys and of sports participants were more positive than of girls and nonsports participants. Findings were similar regardless of the teacher's sex.


Engineered polymeric amphiphiles self-assembling into nanostructures and acting as efficient gene and drug carriers.
Nonviral gene delivery systems are finding widespread use due to their safety, rapid and economical production, and ease of modification. In this work, series of N-alkyl-substituted linear polyethylenimine (CP) polymers have been synthesized, characterized, and investigated about how degree of substitution (hydrophobic-hydrophilic balance) (i.e. N-alkylation) influenced the transfection efficiency. Mobility shift assay demonstrated efficient binding of plasmid DNA (pDNA). Transfection efficiency and cytotoxicity of CP polymers were assessed in vitro, which revealed that all the formulations exhibited higher transfection activity than linear polyethylenimine (lPEI) and commercial transfection reagents, Lipofectamine and Superfect, with negligible toxicity (MTT assay). In the projected series, one of the formulations, CP-3-pDNA complex, displayed the highest transfection efficiency (∼1.6-12 folds vs. lPEI and commercial transfection reagents) and effectively carried GFP-specific siRNA inside the cells as monitored by measuring the suppression in the gene expression of the target gene. Further, flow cytometry experiments confirmed that CP-3-pDNA complex transfected the highest number of cells. Besides, CP-3 was also evaluated in terms of its capability to entrap hydrophobic drug molecules. The results showed that it efficiently encapsulated an anti-cancer drug, etoposide, and released it in a controlled fashion over a period of time. Altogether, the data support that CP-3 is a promising vector for nucleic acid as well as hydrophobic drug delivery.


An Efficient Strategy for the Synthesis of 1-(Trifluoromethylsulfonamido)propan-2-yl Esters and the Evaluation of Their Cytotoxic Activity.
An efficient method for the synthesis of 1-(trifluoromethylsulfonamido)propan-2-yl benzoates is described, the products of the reaction were characterized by heteronuclear single quantum coherence spectroscopy (HSQC), heteronuclear multiple bond correlation (HMBC) and NMR experiments. The overall process began with the activation of the oxazoline ring by triflic anhydride, followed by the opening of the five-membered ring in the 5-methyl-2-phenyl-4,5-dihydrooxazole system. The cytotoxic activity of the new trifluoromethyl sulfonamides was evaluated with six cancer cell lines and human gingival fibroblasts, posteriorly analyzing the influence on cytotoxicity exerted by the withdrawing and donor substituents at the para-position of the phenyl ring. Compounds 3b-e showed cytotoxic activity, with IC50 values ranging from 17-17.44 µM for the cell lines tested, finding the highest effect for compound 3e.


Krüppel-Like Factor 4 Enhances Sensitivity of Cisplatin to Esophageal Squamous Cell Carcinoma (ESCC) Cells.
BACKGROUND The aim of this study was to elucidate the role of Krüppel-Like factor 4 (KLF4) in cisplatin resistance in esophageal squamous cell carcinoma (ESCC) cells, which may eventually help to improve the treatment efficacy. MATERIAL AND METHODS Human esophageal squamous cell carcinoma (ESCC) cell line CaEs-17, TE-1, EC109, KYSE510, KYSE140, KYSE70, and KYSE30 were selected to detect their sensitivity to cisplatin. 5-Azacytidine-2'-deoxycytidine (5'-Aza-CdR) treatment and methylation-specific PCR (MS-PCR) were used to detect the methylation status for KLF4. Cell viability, apoptosis, and cell cycle were measured using methyl thiazolyl tetrazolium (MTT) assay, Annexin V affinity assay, and flow cytometry, respectively. RESULTS The sensitivity to cisplatin was different in the seven ESCC cell lines, with TE-1 having the lowest sensitivity and KYSE140 having the highest sensitivity. Interestingly, the level of KLF4 was relatively low in TE-1 cells; while it was high in KYSE140 cells. These results suggested that KLF4 may be involved in cisplatin resistance. The promoter region was mostly unmethylated in KYSE140 cells; while it was hypermethylated in TE-1 cells. After treatment with demethylation reagent 5-Aza-CdR, cisplatin sensitivities were significantly increased after upregulation of KLF4, as the IC50 values were significantly decreased in the TE-1 cell treated with 5-Aza-CdR. Furthermore, upregulation of KLF4 induced cell apoptosis and cell cycle arrest at S phase. CONCLUSIONS KLF4 enhances the sensitivity of cisplatin to ESCC cells through apoptosis induction and cell cycle arrest. Our data provided a novel insight to the mechanism of cisplatin resistance; overexpression of KLF4 may be a potential therapeutic strategy for cisplatin resistance in human ESCC.


Pathology of dendrites in subacute spongiform virus encephalopathies.
The spongiform changes in the cerebral cortex of scrapie mice and of chimpanzees afflicted with experimental kuru and Creutzfeldt-Jakob disease were examined by electron microscopy. The pathognomonic findings consisted of swelling and vacuolation of neurons, particularly of dendrites. Fusion of swollen cells and processes occurred. The changes were associated with alterations of plasma membranes. Curled fragments of membranes accumulated at points of cell fusion and at the margin of vacuoles within dendrites. The abnormal membranes were wider and more osmiophilic than normal plasma membranes. These findings as well as other data on the nature of the atypical viruses of scrapies, kuru, and Creutzfeldt-Jakob disease indicate that the infectious agents are closely associated with membranes and that alterations of neuronal membranes initiate the spongiform degeneration of neurons.


Biotypes of Central Nervous System Complications in People Living With Human Immunodeficiency Virus (HIV): National Institute of Mental Health Perspectives on Advancing the Future of HIV Healthcare.
Despite effective suppressive antiretroviral therapy, central nervous system (CNS) complications related to human immunodeficiency virus (HIV) remain a significant problem for people with HIV (PWH). Numerous studies have contributed data to define the mechanisms underlying HIV-associated CNS pathophysiology, but causality remains elusive, with no effective therapies to prevent, reduce, or reverse HIV-associated CNS complications. Multiple physiological, clinical, cognitive, behavioral, social, and environmental factors contribute to the observed heterogeneity of adverse CNS outcomes among PWH. The National Institute of Mental Health in collaboration with investigators engaged in research related to HIV associated CNS complications organized a series of meetings to review the state of the science and facilitate the development of biologically based measures to identify the phenotypic heterogeneity of CNS outcomes linked to pathophysiology (biotypes). In this article, we summarize the proceedings of these meetings and explore the precision medicine framework to identify critical factors linked to the etiopathogenesis of CNS outcomes in PWH.


Learning MRI-based classification models for MGMT methylation status prediction in glioblastoma.
The O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation has been shown to be associated with improved outcomes in patients with glioblastoma (GBM) and may be a predictive marker of sensitivity to chemotherapy. However, determination of the MGMT promoter methylation status requires tissue obtained via surgical resection or biopsy. The aim of this study was to assess the ability of quantitative and qualitative imaging variables in predicting MGMT methylation status noninvasively. A retrospective analysis of MR images from GBM patients was conducted. Multivariate prediction models were obtained by machine-learning methods and tested on data from The Cancer Genome Atlas (TCGA) database. The status of MGMT promoter methylation was predicted with an accuracy of up to 73.6%. Experimental analysis showed that the edema/necrosis volume ratio, tumor/necrosis volume ratio, edema volume, and tumor location and enhancement characteristics were the most significant variables in respect to the status of MGMT promoter methylation in GBM. The obtained results provide further evidence of an association between standard preoperative MRI variables and MGMT methylation status in GBM.


A common nuclear factor that binds to the transcriptional control regions of ribosomal protein L5 and 5S rRNA genes.
We have examined the binding of chicken nuclear protein to the promoter regions of chicken ribosomal protein L5 and 5S rRNA genes. A nuclear protein was shown to bind to similar sequences in both promoter regions of the L5 gene (-36 to -21) and the internal control region of 5S rRNA gene (56 to 71). Its molecular mass was estimated to be 34 kDa. Competition gel mobility assay showed that the protein is different from the TATA-box binding protein (TBP). The protein may play a role in a transcriptional coordination of the two genes transcribed by different polymerases, RNA polymerase II and III.


Inhibition of bacterial growth by lignocaine in propofol emulsion.
Contamination of propofol, in an emulsion formulation, has been associated with infective complications. Local anaesthetics,some of which are known to have antibacterial properties, are frequently added to the solution to reduce pain on injection. We examined the growth rates of E. coli, S. aureus, S. epidermidis and P. aeruginosa in propofol with and without lignocaine 0.1%-2% after incubation for 2, 5 and 24 hours at 37 degrees C. Growth of microorganisms in each solution was compared by counting the number of colony forming units (CFU). Propofol supported the growth of all microorganisms. An increase in the number of CFUs was observed in all drug combinations 2, 5 and 24 hours after inoculation except for S. aureus (P<0.05). No difference was found in CFU numbers between 2 and 5 hours for this microorganism. With E. coli, a significant decline in colony counts was observed in mixtures of 1% and 2% lignocaine (P<0.05). With the other microorganisms only 2% lignocaine showed a significant reduction in the number of CFUs (P<0.05). We conclude that lignocaine in recommended clinical doses (0.05%-0.1%) did not exhibit adequate antibacterial activity to prevent infective complications.


Artificial membrane excitability revisited and implications for the gating of voltage-dependent ion channels.
Excitability phenomena in planar lipid bilayers doped with alamethicin and protamines have been first described by Mueller and Rudin (Nature 217, 713-719, 1968). These properties are reinvestigated here with virtually solvent-free bilayers made of synthetic phospholipids doped with alamethicin charged component (Glu18) and protamine or other synthetic basic polypeptides. After retrieving the narrow set of experimental requisites allowing negative resistance and action potentials to develop, the potencies of different basic polypeptides were compared. Poly-arginines were found to be by far the most efficient. We also describe a transient increase of current amplitude upon addition of calcium that may reflect a lateral phase separation and conversely a gradual decrease of negative resistance due to tetrodotoxin, a potent sodium channel blocker. Functional modulations are correlated with conformational changes assayed in circular dichroism: alamethicin ellipticity in small unilamellar vesicles is markedly reduced upon protamine addition, only if the ionic strength is in the same low range that is compatible with regenerative conductance properties. These results are discussed in the framework of current models of ion channels gating.


[Early Efficacy Observation of Pomalidomide-based Regimen in the Treatment of High-risk Multiple Myeloma].
To investigate the efficacy and safety of pomalidomide based regimen in the treatment of high-risk multiple myeloma (MM). Clinical data of 27 high-risk MM patients treated in Shanxi Bethune Hospital from January 2021 to December 2022 were retrospectively analyzed. All patients were treated with pomadomide based regimen for at least 2 consecutive cycles, and the early therapeutic effect and safety were observed. Overall remission rate (ORR) was 63.0%(17/27 cases) and deep remission rate was 22.2%(6/27 cases) after 2 cycles of treatment; ORR was 90.5%(19/21 cases) and deep remission rate was 66.7%(14/21 cases) after 4 cycles of treatment. Both ORR and deep remission rate were significantly higher after 4 cycles of treatment than 2 cycles (P=0.044, P=0.003). Beyond that, in the newly diagnosed and relapsed refractory MM groups, ORR after 2 cycles of treatment were 75%(9/12 cases) and 60%(9/15 cases), and deep remission rates were 25%(3/12 cases) and 20%(3/15 cases), respectively; ORR after 4 cycles of treatment were 100%(9/9 cases) and 83.3%(10/12 cases), and deep remission rates were 77.8%(7/9 cases) and 58.3%(7/12 cases), respectively, while there was no significant difference in remission rates between the two groups (P>0.05). In the group of creatinine ≥177 μmol/L, the serum creatinine level was significantly decreased after 2 cycles of treatment compared with that pre-treatment (P=0.001). The 1q21 amplified subgroup accounted for the largest proportion (21/27 cases), ORR was 66.7%(14/21 cases) and deep remission rate was 23.8%(5/21 cases) after 2 cycles of treatment, ORR was 88.9%(16/18 cases) and deep remission rate was 66.7%(12/18 cases) after 4 cycles of treatment. In all the symptoms, the most common adverse reactions were pulmonary infection in 9 cases and hematological adverse reactions of grade 1-2 in 8 cases. The pomalidomide-based treatment regimen has good early curative effect on the newly diagnosed and relapsed refractory high-risk MM, and also benefits to the high-risk cytogenetic MM, or MM with renal impairment. Therefore, this treatment regimen showed a good safety, and the long-term curative effect needs to be further assessed by more clinical data.


Induction of stress- and immune-associated genes in the Indian meal moth Plodia interpunctella against envenomation by the ectoparasitoid Bracon hebetor.
Envenomation is an important process in parasitism by parasitic wasps; it suppresses the immune and development of host insects. However, the molecular mechanisms of host responses to envenomation are not yet clear. This study aimed to determine the transcription-level responses of the Indian meal moth Plodia interpunctella against envenomation of the ectoparasitoid Bracon hebetor. Quantitative real-time reverse-transcription PCR was used to determine the transcriptional changes of 13 selected genes, which are associated with development, metabolism, stress, or immunity, in the feeding and wandering fifth instar larvae over a 4-day period after envenomation. The effects of envenomation on the feeding-stage larvae were compared with those of starvation in the transcriptional levels of the 13 genes. Most selected genes were altered in their expression by either envenomation or starvation. In particular, a heat shock protein, hsp70, was highly upregulated in envenomated larvae in both the feeding and wandering stages as well as in starved larvae. Further, some genes were upregulated by envenomation in a stage-specific manner. For example, hsp25 was upregulated after envenomation in the feeding larvae, but hsp90 and an immune-associated gene, hemolin, were upregulated in the wandering larvae. However, both envenomation and starvation resulted in the downregulation of genes associated with development and metabolism. Taken together, P. interpunctella upregulated stress- and immune-responsive genes, but downregulated genes associated with development and metabolism after envenomation. This study provides important information for understanding the molecular mechanisms of host responses to parasitism.


Surface characterization and cytotoxicity analysis of plasma sprayed coatings on titanium alloys.
In the realm of biomaterials, metallic materials are widely used for load bearing joints due to their superior mechanical properties. Despite the necessity for long term metallic implants, there are limitations to their prolonged use. Naturally, oxides of titanium have low solubilities and form passive oxide film spontaneously. However, some inclusion and discontinuity spots in oxide film make implant to adopt the decisive nature. These defects heighten the dissolution of metal ions from the implant surface, which results in diminishing bio-integration of titanium implant. To increase the long-term metallic implant stability, surface modifications of titanium alloys are being carried out. In the present study, biomimetic coatings of plasma sprayed hydroxyapatite and titanium were applied to the surface of commercially pure titanium and Ti6Al4V. Surface morphology and surface chemistry were studied using scanning electron microscopy and X-ray photoelectron spectroscopy, respectively. Cyclic potentiodynamic polarization and electrochemical impedance spectroscopy were carried out in order to study their electrochemical behavior. Moreover, cytotoxicity analysis was conducted for osteoblast cells by performing MTS assay. It is concluded that both hydroxyapatite and titanium coatings enhance corrosion resistance and improve cytocompatibility.


A new diarylheptanoid from Alpinia officinarum promotes the differentiation of 3T3-L1 preadipocytes.
A new diarylheptanoid, namely trans-(4R,5S)-epoxy-1,7-diphenyl-3-heptanone (1), and a new natural product, 7-(4″-hydroxy-3″-methoxyphenyl)-1-phenyl-hepta-4E,6E-dien-3-one (2), were obtained from the aqueous extract of Alpinia officinarum Hance, together with three other diarylheptanoids, 5-hydroxy-1,7-diphenyl-3-heptanone (3), 1,7-diphenyl-4E-en-3-heptanone (4) and 5-methoxy-1,7-diphenyl-3-heptanone (5). The structures were characterised mainly by analysing their physical data including IR, NMR and HRMS. This study highlights that the 4,5-epoxy moiety in 1 is rarely seen in diarylheptanoids. In addition, the five isolates were tested for their differentiation activity of 3T3-L1 preadipocytes. The results showed that these compounds could dose-dependently promote adipocyte differentiation without cytotoxicity (IC50 > 100 μM).


Systemic treatments for resectable carcinoma of the esophagus.
One of the most prevalent malignancies in the world is esophageal cancer (EC). The 5-year survival rate of EC remains pitiful despite treatment advancements. Neoadjuvant chemoradiotherapy in conjunction with esophagectomy is the standard of care for patients with resectable disease. The pathological complete response rate, however, is not acceptable. A distant metastasis or a locoregional recurrence will occur in about half of the patients. To increase the clinical effectiveness of therapy, it is consequently vital to investigate cutting-edge and potent therapeutic modalities. The approach to the management of resectable EC using immunotherapy has been considerably altered by immune checkpoint inhibitors. Systemic immunotherapy has recently been shown to have the potential to increase the survival of patients with resectable EC, according to growing clinical data. A combination of chemotherapy, radiation, and immunotherapy may have a synergistic antitumor impact because, according to mounting evidence, these treatments can stimulate the immune system via a number of different pathways. In light of this, it makes sense to consider the value of neoadjuvant immunotherapy for patients with surgically treatable EC. In this review, we clarify the rationale for neoadjuvant immunotherapy in resectable EC patients, recap the clinical outcomes of these approaches, go through the upcoming and ongoing investigations, and emphasize the difficulties and unmet research requirements.


Dengue Fever: A Rare Cause Of Immune Thrombocytopenia.
Immune thrombocytopenia (ITP) is a rare autoimmune disorder characterized by low platelet count and skin-mucosal bleeding. In adults it is usually idiopathic and may have a chronic onset, while in children it is usually acute following a viral illness. Dengue has been rarely reported as a cause of ITP. We report a case of a young adult woman that presented with acute ITP following a dengue virus infection.


A study of estrogen metabolic clearance rates and transfer factors.
We have attempted to measure the metabolic clearance rates (MCR) and the transfer factors of estradiol (E(2)) and estrone (E(1)) during 2-hr and 12-hr infusions. When estradiol-(3)H was infused for 2 hr, apparent equilibrium was reached at 70 min; the 12-hr infusions showed that plasma estradiol-(3)H levels increased slowly throughout the infusion. When estrone-(3)H was infused, constancy of estrone-(3)H levels was not attained in either the 2-hr infusions or in the two 12-hr infusions. The tritium level in the metabolite of the infused estrogen did not become constant in 50% of the short infusions and increased during all the long infusions. Thus, the conversion ratios C(E1E2) and C(E2E1) continually changed and transfer factors could not be calculated. The apparent "MCR'S" calculated on the basis of the 2-hr studies expressed as liters/24 hr per m(2) +/-SD were: "MCR(E1)" (women) 980 +/-94, (men) 1170 +/-95; "MCR(E2)" (women) 615 +/-17, (men) 830 +/-30. The estradiol "MCR's" differed significantly between men and women. "MCR(E2)" was the same using either estradiol-(14)C or -(3)H and was unchanged by the infusion of 170 mug of estradiol daily. Postmenopausal women had estrogen "MCR's" in the same range as premenopausal women. Excess glucocorticoids increased the "MCR(E2)."


Update on MRI Pulse Sequences for the Knee: Imaging of Cartilage, Meniscus, Tendon, and Hardware.
Magnetic resonance imaging (MRI) is widely used in the clinical setting as well as for research applications. Since its inception, technical development has broadly progressed as a response to challenges in both the clinical and research settings. Higher magnetic field strength and advances in hardware and software have revolutionized the diagnostic potential of MRI and moved well beyond diagnosis to characterization of tissue metabolism, biochemistry, disease pathogenesis, and material property, to name a few. This article focuses on state-of-the-art clinical and cutting-edge novel pulse sequences applied to knee MRI.


Network Pharmacology Prediction and Experimental Validation of Trichosanthes-Fritillaria thunbergii Action Mechanism Against Lung Adenocarcinoma.
We aimed to study the mechanism of Trichosanthes-Fritillaria thunbergii in treating lung adenocarcinoma (LUAD) based on network pharmacology and experimental verification. The effective components and potential targets of Trichosanthis and Fritillaria thunbergii were collected by high-throughput experiment and reference-guided (HERB) database of traditional Chinese medicine and a similarity ensemble approach (SEA) database, and the LUAD-related targets were queried by the GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. A drug-component-disease-target network was constructed by Cytoscape software. Protein-protein interaction (PPI) network, gene ontology (GO) function, and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were conducted to obtain core targets and key pathways. An aqueous extract of Trichosanthes-Fritillaria thunbergii and A549 cells were used for the subsequent experimental validation. Through the HERB database and literature search, 31 effective compounds and 157 potential target genes of Trichosanthes-Fritillaria thunbergii were screened, of which 144 were regulatory targets of Trichosanthes-Fritillaria thunbergii in the treatment of lung adenocarcinoma. The GO functional enrichment analysis showed that the mechanism of action of Trichosanthes-Fritillaria thunbergii against lung adenocarcinoma is mainly protein phosphorylation. The KEGG pathway enrichment analysis suggested that the treatment of lung adenocarcinoma by Trichosanthes-Fritillaria thunbergii mainly involves the PI3K/AKT signaling pathway. The experimental validation showed that an aqueous extract of Trichosanthes-Fritillaria thunbergii could inhibit the proliferation of A549 cells and the phosphorylation of AKT. Through network pharmacology and experimental validation, it was verified that the PI3K/AKT signaling pathway plays a vital role in the action of Trichosanthes-Fritillaria thunbergii in treating lung adenocarcinoma.


On the Design of an Efficient Cardiac Health Monitoring System Through Combined Analysis of ECG and SCG Signals.
Cardiovascular disease (CVD) is a major public concern and socioeconomic problem across the globe. The popular high-end cardiac health monitoring systems such as magnetic resonance imaging (MRI), computerized tomography scan (CT scan), and echocardiography (Echo) are highly expensive and do not support long-term continuous monitoring of patients without disrupting their activities of daily living (ADL). In this paper, the continuous and non-invasive cardiac health monitoring using unobtrusive sensors is explored aiming to provide a feasible and low-cost alternative to foresee possible cardiac anomalies in an early stage. It is learned that cardiac health monitoring based on sole usage of electrocardiogram (ECG) signals may not provide powerful insights as ECG provides shallow information on various cardiac activities in the form of electrical impulses only. Hence, a novel low-cost, non-invasive seismocardiogram (SCG) signal along with ECG signals are jointly investigated for the robust cardiac health monitoring. For this purpose, the in-laboratory data collection model is designed for simultaneous acquisition of ECG and SCG signals followed by mechanisms for the automatic delineation of relevant feature points in acquired ECG and SCG signals. In addition, separate feature points based novel approach is adopted to distinguish between normal and abnormal morphology in each ECG and SCG cardiac cycle. Finally, a combined analysis of ECG and SCG is carried out by designing a Naïve Bayes conditional probability model. Experiments on Institutional Review Board (IRB) approved licensed ECG/SCG signals acquired from real subjects containing 12,000 cardiac cycles show that the proposed feature point delineation mechanisms and abnormal morphology detection methods consistently perform well and give promising results. In addition, experimental results show that the combined analysis of ECG and SCG signals provide more reliable cardiac health monitoring compared to the standalone use of ECG and SCG.


Expression of a 50 kDa putative receptor for bovine viral diarrhea virus in bovine fetal tissues.
The expression of a 50 kDa bovine viral diarrhea virus putative receptor in different bovine fetal tissues from 3-month old fetuses was studied. The receptor expression was examined by immunocytochemical staining and by immunoblotting using antiidiotypic probe (anti-D89). Intense specific staining in enterocytes of the small and large intestines, cortical tubular epithelial cells of kidneys, respiratory epithelial cells of the trachea and esophageal mucosal epithelial cells was observed, demonstrating the strong expression of bovine viral diarrhea virus receptor in the tissues. Weak staining was found in cerebellum, thymus, spleen, liver, cerebrum, and lung tissues; however, heart tissues were negative. Immunoblotting results correlated with the immunoperoxidase staining assays. Thus, the expression levels of the receptor are variable in different tissues. This pattern of expression may provide clues to the pathogenic potential of bovine viral diarrhea virus in the bovine fetus.


The effect of note-taking skills training on the achievement motivation in learning on B.A students in Shahid Bahonar University of Kerman and Kerman University of Medical Sciences (Iran).
To evaluate the effect of note-taking skills training on the achievement motivation in learning. The experimental study comprised graduate students of the 2010-11 batch at Kerman's Bahonar University and Kerman's Medical Sciences University, Iran. The study sample included 110 people; 55 in the test group, and 55 in the control group. They were randomly selected and replaced through the single-stage cluster sampling. To collect the data, a questionnaire was used. Pre-test was performed before the training session in two groups. After training course, a post-test was taken. For data analysis, the independent t-test, was used. The average pre-test score of the test group was 182 +/- 34.15, while for the control group it was 191 +/- 30.37 (p < 0.089). After the training, the post-test showed statistically significant change. The test group scored 220 +/- 20.94 against the controls who scored 195 +/- 27.26 (p < 0.001). The findings showed that achievement motivation in learning increased significantly after imparting training in note-taking skills. Authorities in the educational system should invest more for promotion of such skills.


Human (semisynthetic) insulin and porcine insulin in the treatment of non-insulin-dependent diabetes. A double-blind, comparative clinical trial.
Twenty-one patients with non-insulin-dependent diabetes, who had not previously received insulin therapy, participated in a double-blind comparative trial of six months' duration to evaluate the efficacy of human (semisynthetic) insulin. Patients were allocated at random to treatment either with human (semisynthetic) insulin (10 patients) or with an equivalent porcine insulin regimen (11 patients). Sex ratio, age, body mass index, duration of diabetes, C-peptide concentrations, baseline metabolic control and initial insulin requirements were similar in both groups. After six months, no significant differences between the treatment effects of human (semisynthetic) insulin and porcine insulin, as assessed by measurements of fasting and postprandial plasma glucose levels, the concentration of glycosylated haemoglobin, serum lipid levels, insulin dose, and body weight, were found. No adverse reactions, injection-site anomalies, or drug-related biochemical abnormalities were noted in either group. It was concluded that human (semisynthetic) insulin is as effective as porcine insulin in initiating the treatment of patients with non-insulin-dependent diabetes who require insulin therapy.


The effects of McDonalds, Kentucky Fried Chicken and Pizza Hut meals on recommended diets.
The objective was to study the effect of three common takeaway meals on recommended healthy diets. New South Wales Department of Health recommended diets of 5020, 6275, 9205 and 12,540 kilojoules were used. An evening meal from each of these diets was substituted with one of three common fast food chain takeaway meals 1, 2, 3 and 5 times per week. The 3 takeaway meals were from McDonalds, Pizza Hut and Kentucky Fried Chicken. The effects of each of these meals on average daily kilojoule, fibre, fat, P/S ratio, protein and carbohydrate intakes were assessed. The takeaway meals were high in fat and kilojoules and low in fibre and therefore contravened the Dietary Guidelines for Australians. Addition of these meals increased average kilojoule consumption and the percentage energy contribution of fat and decreased the P/S ratio and fibre intake. The magnitude of these deleterious effects was directly proportional to the number of times the meals were included each week and inversely proportional to the energy content of the diet. The adverse effects were greatest with the McDonalds and Kentucky Fried Chicken meals. Takeaway meals may be convenient but the meals which were tested were too high in fat and kilojoules and too low in fibre to be a regular part of a balanced diet. Even one takeaway meal per week adversely affects the lower kilojoule recommended healthy diets.


Attack rate of dengue-like illness among teachers in Kaohsiung City, 1988.
The present study is based on a questionnaire evaluating 2,770 school teachers, including those from elementary, junior-high, senior-high, and occupational schools, in Kaohsiung city. The response rate was 91.1% (2,626/2,770). The self-reported cumulative incidence of dengue-like illness was 7.9% (207/2,626) and the physician-diagnosed cumulative incidence was 5.6% (148/2,626). There is no significant difference between distribution of infections among subjects' gender, educational background, and the associated school regardless of self-reported cases or diagnosed cases. Among those self-reported dengue infected teachers, 60.1% (119/207) required sick leaves. The difference of sick leaves among subjects by either education background or associated school was not significant. However, more females stayed home because of the illness than males did.


Regeneration of carbon nanotube and nanofibre composite film electrode for electrical removal of cupric ions.
Low cost and large scale carbon nanotube and nanofibre (CNT-CNF) composite films have been fabricated and employed as electrodes for electrosorption of cupric ions. The regeneration of the saturated CNT-CNF film electrode has been investigated. Three methods (short-circuiting, short-circuiting and then reversing voltage, reversing voltage and then short-circuiting) are used for regeneration. The results show that low regeneration efficiency of CNT-CNF film electrode due to electrodeposition of Cu on the electrode surface can be highly improved by regeneration applying reverse voltage combined with short circuit. 93% regeneration efficiency can be achieved when 0.8 V reverse voltage is applied before short-circuiting during regeneration of CNT-CNF film electrode.


Gravity-capillary lumps generated by a moving pressure source.
The nonlinear wave pattern generated by a localized pressure source moving over a liquid free surface at speeds below the minimum phase speed (c{min}) of linear gravity-capillary waves is investigated experimentally and theoretically. At these speeds, freely propagating fully localized solitary waves, or "lumps," are known theoretically to be possible. For pressure-source speeds far below c{min}, the surface response is a local depression similar to the case with no forward speed. As the speed is increased, a critical value is reached c{c} approximately 0.9c{min} where there is an abrupt transition to a wavelike state that features a steady disturbance similar to a steep lump behind the pressure forcing. As the speed approaches c{min}, a second transition is found; the new state is unsteady and is characterized by continuous shedding of lumps from the tips of a V-shaped pattern.


Coagulation abnormalities in 22 cats with naturally occurring liver disease.
Twenty-two cats with liver disease were evaluated for coagulation abnormalities including alterations in prothrombin time, activated partial thromboplastin time, thrombin time, factor VII activity, and platelet count. The purpose of the study was to determine the prevalence of coagulation abnormalities in this population of cats, classify abnormalities according to underlying pathogenesis, and determine if serum biochemical parameters typically used as indicators of liver disease showed any correlation with the coagulation abnormalities present. Study results indicated that at least 1 coagulation abnormality was present in 82% of the cats. Prolongation of prothrombin time was most common (16/22 cats) and factor VII activity was below reference range (< 60%) in 15 cats. When classified according to underlying pathogenesis, vitamin K deficiency was the most common abnormality found (11/22). Other abnormalities were less common and included hepatic synthetic failure (3/22), indeterminate (3/22), and disseminated intravascular coagulation (1/22). Increase in alkaline phosphatase (ALP) activity was the only biochemical abnormality that showed statistically significant correlation with coagulation abnormalities (P = .023). Cats with marked increases in ALP activity were more likely to have coagulation abnormalities than those with only mild increases in ALP activity.


Reliability of prisoners' attitudes to their drinking behaviour.
A sample of male prisoners was examined by means of a questionnaire and subsequently by a structured interview. Control subjects who denied heavy drinking were used to study test-retest reliability of a group who admitted that drinking was a problem and a third group who admitted heavy drinking but denied problem drinking. Non-heavy drinkers and the heaviest drinkers are shown to be the most reliable and the intermediate group least reliable.


Feasibility of a large area x-ray sensitive vidicon for medical fluoroscopy: signal and noise factors.
A large area x-ray sensitive vidicon is being investigated as an alternative to the x-ray image intensifier and television camera combination for medical fluoroscopy. Signal generation in an x-ray vidicon involves an x-ray photoconductive layer whose surface is scanned by an electron beam. The single x-ray to electron conversion stage of the x-ray vidicon offers a greatly improved modulation transfer function (MTF) over the x-ray image intensifier. This superior MTF allows signal and x-ray quantum noise at high spatial frequencies to be passed to the preamplifier with less attenuation. In cardiac cine applications this would allow quantum noise limited operation at higher spatial frequencies than is possible with the x-ray image intensifier system.


A miR-155-Peli1-c-Rel pathway controls the generation and function of T follicular helper cells.
MicroRNA (miRNA) deficiency impairs the generation of T follicular helper (Tfh) cells, but the contribution of individual miRNAs to this phenotype remains poorly understood. In this study, we performed deep sequencing analysis of miRNAs expressed in Tfh cells and identified a five-miRNA signature. Analyses of mutant mice deficient of these miRNAs revealed that miR-22 and miR-183/96/182 are dispensable, but miR-155 is essential for the generation and function of Tfh cells. miR-155 deficiency led to decreased proliferation specifically at the late stage of Tfh cell differentiation and reduced CD40 ligand (CD40L) expression on antigen-specific CD4(+) T cells. Mechanistically, miR-155 repressed the expression of Peli1, a ubiquitin ligase that promotes the degradation of the NF-κB family transcription factor c-Rel, which controls cellular proliferation and CD40L expression. Therefore, our study identifies a novel miR-155-Peli1-c-Rel pathway that specifically regulates Tfh cell generation and function.


Epstein-Barr virus-encoded poly(A)- RNA confers resistance to apoptosis mediated through Fas by blocking the PKR pathway in human epithelial intestine 407 cells.
Our recent findings demonstrated that the Epstein-Barr virus-encoding small nonpolyadenylated RNA (EBER) confers resistance to various apoptotic stimuli and contributes to the maintenance of malignant phenotypes in Burkitt's lymphoma. In this study we investigated the role of EBER in the human epithelial Intestine 407 cell line, which is known to be susceptible to Fas (Apo1/CD95)-mediated apoptosis. Fas, a member of the tumor necrosis factor receptor family, transduces extracellular signals to the apoptotic cellular machinery, leading to cell death. Transfection of the EBER gene into Intestine 407 cells significantly protected the cells from Fas-mediated apoptosis, whereas EBER-negative cell lines underwent apoptosis after Fas treatment. EBER bound double-stranded RNA-dependent protein kinase R (PKR), an interferon-inducible serine/threonine kinase, and abrogated its kinase activity. Moreover, expression of the catalytically inactive dominant-negative PKR provided resistance to Fas-induced apoptosis. Expression of EBER or dominant-negative PKR also inhibited the cleavage of poly(ADP-ribose) polymerase, a mediator of the cellular response to DNA damage, downstream of the Fas-mediated apoptotic pathway. These results in combination indicate that EBER confers resistance to Fas-mediated apoptosis by blocking PKR activity in Intestine 407 cells, consistent with the idea that EBER contributes to the maintenance of epithelioid malignancies.


Pretreatment of lipopolysaccharide (LPS) ameliorates D-GalN/LPS induced acute liver failure through TLR4 signaling pathway.
Endotoxin tolerance (ET) is an important phenomenon, which affects inflammation and phagocytosis. Pretreatment with low dose of lipopolysaccharide (LPS) can protect liver injury from various hepatotoxicants such as acetaminophen and pseudomonas aeruginosa exotoxin A. The current study aimed to investigate the protecting mechanisms of endotoxin tolerance in acute liver failure induced by D-galactosamine (D-GalN)/LPS and possible role of toll-like receptors 4 (TLR4) signaling pathway in this phenomenon. Acute liver failure was induced by Injection of D-GalN/LPS. To mimic endotoxin tolerance, male Sprague-Dawley rats were treated with low dose of LPS (0.1 mg/kg once a day intraperitoneally for consecutive five days) before subsequent injection of D-GalN/LPS. Rat survival was determined by survival rate. Liver injury was confirmed by serum biochemical and liver histopathological examination. Inflammatory cytokines were determined by ELISA and nuclear factor-kappa B (NF-κB) (P65), toll-like receptors 4 (TLR4) and Interleukin-1 receptor-associated kinase-1 (IRAK-1) were measured by reverse transcriptase polymerase chain reaction and western blot respectively. Pretreatment of LPS significantly improved rat survival. Moreover, rats pretreated with LPS exhibited lower serum enzyme (ALT, AST and TBiL) level, lower production of inflammatory cytokines and more minor liver histopathological damage than rats without pretreatment of LPS. LPS pretreatment suppressed production of TLR4 and IRAK-1. LPS pretreatment also inhibited activation of hepatic NF-κB. These results indicated that endotoxin tolerance contributed to liver protection against D-GalN/LPS induced acute liver failure through down-regulation of TLR4 and NF-κB pathway.


On Callistocypris thailandensis sp. nov. (Ostracoda, Crustacea) from Thailand.
Callistocypris thailandensis sp. nov. is here described from terrestrial habitat in Khao Yai National Park, Nakhon Ratchasima province, Thailand. The new species differs from the other three Callistocypris species in the shape of carapace, the presence of strong longitudinal ridges on the ventral part of the valves and the chaetotaxy of several limbs. Zoogeography and ecology of the genus are briefly discussed.


Loculated empyema due to tuberculosis in a child.
A 9-year-old girl from black ethnic origin presented with a history of fever, cough, loss of weight and right-sided chest wall pain for 2 weeks. Chest X-ray demonstrated an effusion, which was shown to be loculated on chest CT scan. She was not responding to medical treatment and at thoracotomy loculated pus was drained. Mycobacterium tuberculosis (TB) was cultured from the pus. TB is a rare cause of loculated empyema with an overlapping clinical and radiological picture with pyogenic infections.


[Causality in objective world: Directed Acyclic Graphs-based structural parsing].
The overall details of causality frames in the objective world remain obscure, which poses difficulty for causality research. Based on the temporality of cause and effect, the objective world is divided into three time zones and two time points, in which the causal relationships of the variables are parsed by using Directed Acyclic Graphs (DAGs). Causal DAGs of the world (or causal web) is composed of two parts. One is basic or core to the whole DAGs, formed by the combination of any one variable originating from each time unit mentioned above. Cause effect is affected by the confounding only. The other is an internal DAGs within each time unit representing a parent-child or ancestor-descendant relationship, which exhibits a structure similar to the confounding. This paper summarizes the construction of causality frames for objective world research (causal DAGs), and clarify a structural basis for the control of the confounding in effect estimate.


[Corticosteroids as adjuvants in the treatment of tuberculosis].
The anti-inflammatory effect of corticosteroids has been known for a long time, as have their use in treating diseases with an inflammatory component. Corticosteroids have also been used as an adjunct in treating tuberculosis. We have reviewed the literature to evaluate the rationale for our present treatment strategy. We find no reason for the use of Isoniazide in routine prophylaxis of Mantoux positive or former tuberculosis patients who are treated with corticosteroids. Corticosteroids could be added when treating severe pulmonary tuberculosis. When treating tuberculous pericarditis and severe tuberculous pleurisy, corticosteroids should be used as an adjunct to the antituberculous chemotherapy. No controlled studies have been carried out in patients with tuberculous meningitis, but retrospective reports have shown a lower mortality in patients treated with steroids. In children with stenosis and atelectasis because of endobronchial obstruction due to tuberculosis in mediastinal lymphnodes, corticosteroids should be added to the usual antituberculous regimen.


Release of plasma pancreatic polypeptide in achlorhydric patients after intravenous infusion of gastric inhibitory polypeptide.
In order to evaluate whether gastric inhibitory polypeptide (GIP) could be responsible for the postprandial fall in serum gastrin previously observed in patients with achlorhydria, 7 achlorhydric patients were given 100 ml Lipomul (66 g triglycerides) on one occasion, and 5 of these patients were later given a 30-min intravenous infusion of porcine GIP in a dose of 1 microgram/kg. Following the Lipomul ingestion, serum gastrin fell significantly, whereas no effect on serum gastrin was seen during the intravenous GIP infusion. A small, but significant release of serum insulin was seen shortly after starting the GIP infusion, together with a significant and more sustained release of plasma pancreatic polypeptide (PP). It is concluded that GIP does not lower the serum gastrin levels in achlorhydric patients, but that GIP might participate in the intestinal phase of the PP release.


Pattern of prescribing practices in the Madhya Pradesh, India.
To find out the current status of the 'prescribing practices' in the Primary Health Care facilities of Madhya Pradesh. The cross-sectional survey was conducted in 26 Primary Health Care facilities of the Madhya Pradesh. Consecutive random sampling method was applied for collection of prescriptions from the health facilities. Overall the average number of drugs prescribed per prescription was 2.8; most commonly prescribed drugs were NSAIDs, antibiotics, multivitamins and antihistaminics. Drugs prescribed by generic name were 48.5% (1409/2906), prescription with antibiotics and injections were 60.9% (641/1052) and 13.6% (143/1052) respectively. Drugs prescribed from Essential Drug List were 66.9% (1944/2906). The prescribing practices of the Madhya Pradesh is more of an irrational types like polypharmacy, overuse of antibiotics and injection, less number in generic names and prescribed from Essential Drug List. There is an urgent need for some interventions to improve the situation.


Patient safety considerations regarding dermal filler injections.
Today's population is seeking procedures that enhance or improve its appearance, that require little or no downtime, and that provide immediate results. Dermal filler injections are among the top five procedures performed for this purpose. Patient safety must remain the ultimate goal of any practitioner delivering such procedures. This column will examine pertinent safety considerations in relation to the delivery of dermal filler injections.


Sustained Reduction of Cerebellar Activity in Experimental Epilepsy.
Clinical and experimental evidence suggests a role for the cerebellum in seizure control, while no data are available on cerebellar activity between seizures. We hypothesized that interictal regional activity of the deep cerebellar nuclei is reduced in epilepsy and tested this in an animal model by using ΔFosB and cytochrome oxidase (COX) (immuno)histochemistry. The expression of these two markers of neuronal activity was analysed in the dentate nucleus (DN), interpositus nucleus (IN), and fastigial nucleus (FN) of the cerebellum of fully amygdala kindled rats that were sacrificed 48 hours after their last seizure. The DN and FN of kindled rats exhibited 25 to 29% less ΔFosB immunopositive cells than their respective counterpart in sham controls (P < 0.05). COX expression in the DN and FN of kindled animals was reduced by 32 to 33% compared to respective control values (P < 0.05). These results indicate that an epileptogenic state is characterized by decreased activity of deep cerebellar nuclei, especially the DN and FN. Possible consequences may include a decreased activation of the thalamus, contributing to further seizure spread. Restoration of FN activity by low frequency electrical stimulation is suggested as a possible treatment option in chronic epilepsy.


[Detection of lorazepam and lormetazepam metabolites in urine using thin-layer chromatography].
The determination of benzodiazepine derivatives lorazepam and lormetazepam in urine is based on detection of their metabolites 2-amino-2',5-dichlorobenzophenone and 2-methylamino-2'5-dichlorbenzophenone in hydrolyzed urine. Both substances are structurally very similar to the metabolites of diazepam 2-amino-5-chlorbenzophenone and 2-methylamino-5-chlorbenzophenone and their mobility on thin layer chromatograms is similar as well. This could cause their confusion and misinterpretation of the results. Therefore suitable combination of mobile phases and thin layer plates was sought in this study for the unambiguous identification of respective benzophenones by thin layer chromatography.


A pathogenetic hypothesis of Unverricht-Lundborg disease onset and progression.
Unverricht-Lundborg disease (EPM1), the most common progressive myoclonic epilepsy, is associated with a defect of cystatin B (CSTB), a protease inhibitor. We used CSTB knockout mice to test the hypothesis that EPM1 onset is related to a latent hyperexcitability and that progression depends on higher susceptibility to seizure-induced cell damage. Hippocampal slices prepared from CSTB-deficient mice were hyperexcitable, as they responded to afferent stimuli in CA1 with multiple population spikes and kainate perfusion provoked the appearance of epileptic-like activity earlier than in WT mice. This hyperexcitability may depend on loss of inhibition, because the density of GABA-immunoreactive cells was reduced in the hippocampus of CSTB knockouts. In vivo, CSTB-deficient mice treated with kainate displayed increased susceptibility to seizures, with shorter latency to seizure onset and increased seizure severity compared with WT littermates. Furthermore, a greater degree of neuronal damage was observed in CSTB-deficient than in WT mice after seizures of identical grade, indicating increased susceptibility to seizure-induced cell death.


Drooling in oro-motor dyspraxia: is there a role for surgery?
To report the successful use of a surgical approach for the treatment of drooling in a case of oro-motor dyspraxia. A seven-year-old girl with a diagnosis of oro-motor dyspraxia was referred for management of drooling; this was her only symptom. There were no focal neurological abnormalities. Conservative measures had not helped, and her parents were keen for definitive treatment. Bilateral submandibular duct transposition was performed with no complications. The patient's drooling improved immediately. There are currently no reports in the literature of surgery for persistent drooling in children with oro-motor dyspraxia who are otherwise neurologically and developmentally normal. The mainstay of treatment is speech and language therapy. We report the successful use of surgical techniques, usually reserved for children with cerebral palsy or severe neurological disorders, to treat drooling in an otherwise normal seven-year-old child with oro-motor dyspraxia.


Perception of risk in relation to ultrasound screening for Down's syndrome during pregnancy.
to explore how information about being at risk of carrying a fetus with Down's syndrome was understood, and whether the actual risk and the woman's perception of risk was associated with worry or depressive symptoms during and after pregnancy. observational study. The sample was drawn from the intervention group of a Swedish randomised controlled trial of ultrasound screening for Down's syndrome by nuchal translucency measurement. data were collected by three questionnaires. Questions were asked about recall of the risk score and perception of risk. The Cambridge Worry Scale and the Edinburgh Postnatal Depression Scale measured worry and depressive symptoms, respectively, on all three occasions. of the 796 women who provided data for this study, one in five was unaware that the risk score was noted in her case record. In total, 620 women stated that they had received a risk score, but only 64% of them recalled the figure exactly or approximately. The actual risk was associated with the perceived risk, but of the 31 women who perceived the risk to be high, only 14 were actually at high risk. A high-risk score was not associated with worry or depressive symptoms in mid-pregnancy, in contrast to a woman's own perception of being at high risk. Two months postpartum, no associations were found between maternal emotional well-being and actual or perceived risk. information about fetal risk is complicated and women's perception of risk does not always reflect the actual risk, at least not when presented as a numerical risk score. The possibility that the information may cause unnecessary emotional problems cannot be excluded. caregivers should ascertain that information about fetal risk is interpreted correctly by pregnant women.


A multiphase contrast-enhanced CT radiomics model for prediction of human epidermal growth factor receptor 2 status in advanced gastric cancer.
Background: Accurate evaluation of human epidermal growth factor receptor 2 (HER2) status is of great importance for appropriate management of advanced gastric cancer (AGC) patients. This study aims to develop and validate a CT-based radiomics model for prediction of HER2 overexpression in AGC. Materials and Methods: Seven hundred and forty-five consecutive AGC patients (median age, 59 years; interquartile range, 52-66 years; 515 male and 230 female) were enrolled and separated into training set (n = 521) and testing set (n = 224) in this retrospective study. Radiomics features were extracted from three phases images of contrast-enhanced CT scans. A radiomics signature was built based on highly reproducible features using the least absolute shrinkage and selection operator method. Univariable and multivariable logistical regression analysis were used to establish predictive model with independent risk factors of HER2 overexpression. The predictive performance of radiomics model was assessed in the training and testing sets. Results: The positive rate of HER2 was 15.9% and 13.8% in the training set and testing set, respectively. The positive rate of HER2 in intestinal-type GC was significantly higher than that in diffuse-type GC. The radiomics signature comprised eight robust features demonstrated good discrimination ability for HER2 overexpression in the training set (AUC = 0.84) and the testing set (AUC = 0.78). A radiomics-based model that incorporated radiomics signature and pathological type showed good discrimination and calibration in the training (AUC = 0.85) and testing (AUC = 0.84) sets. Conclusion: The proposed radiomics model showed favorable accuracy for prediction of HER2 overexpression in AGC.