Quality of life, self-care ability, and sense of coherence in hemodialysis patients: a comparative study.
The number of patients treated for end-stage renal disease has increased in Sweden as in the rest of the world. During the last 6 years, more than 1000 people per year started renal replacement therapy in Sweden. Today hemodialysis (HD) patients have the opportunity to choose from different treatment modalities, home HD, self-care dialysis or conventional dialysis. The aim of the study was to investigate whether there are differences in the way HD patients view their quality of life, self-care ability and sense of coherence if they dialyze themselves at home, dialyze themselves in center (self-care), or if they are dialyzed by nurses in an outpatient dialysis unit. The instruments consisted of the Short Form 36 (SF-36) health survey, the Appraisal of Self-Care Agency questionnaire and the Sense of Coherence questionnaire. Nineteen patients participated in the study (5 patients on home HD, 6 self-care patients and 8 patients on conventional in center dialysis). There was a tendency for those who dialyzed at home to score higher on quality of life, self-care ability and sense of coherence than those who dialyzed themselves in center. Since the number of participants in this study was low, it is necessary for future studies to include more patients to verify the results.


The instructional effectiveness of a web-based audiometry simulator.
With distance learning becoming more of a reality than a novelty in many undergraduate and graduate training programs, web-based clinical simulations can be identified as an instructional option in distance education that has both a sound pedagogical foundation and clinical relevance. The purpose of this article is to report on the instructional effectiveness of a web-based pure-tone audiometry simulator by undergraduate and graduate students in speech-language pathology. Graduate and undergraduate majors in communication sciences and disorders practiced giving basic hearing tests on either a virtual web-based audiometer or a portable audiometer. Competencies in basic testing skills were evaluated for each group. Results of our analyses of the data indicate that both undergraduate and graduate students learned basic audiometric testing skills using the virtual audiometer. These skills were generalized to basic audiometric testing skills required of a speech language pathologist using a portable audiometer.


Involvement of Neuroactive Steroids in Pain, Depression and Anxiety.
Comorbidity between major depressive disorder (MDD), anxiety (generalized anxiety, panic disorder, social anxiety disorder) and pain is a major complicating factor in the diagnosis and treatment of psychiatric and neurological disorders. Although numerous neurotransmitters and/or neuromodulators may be involved, abnormalities in the GABAergic and glutamatergic systems seem to be a common factor in all these disorders. Neuroactive steroids (NASs) have been the object of considerable interest in this area in recent years since they appear to act predominantly on GABA-A and glutamate NMDA receptors. An overview of the possible involvement of NASs in MDD, anxiety and pain is provided in this chapter.


GLS as a diagnostic biomarker in breast cancer: in-silico, in-situ, and in-vitro insights.
Recently, a novel programmed cell death mechanism, Cuproptosis, has been discovered and found to play an important role in the development and progression of diverse tumors. In the present study, we comprehensively investigated the core gene of this mechanism, GLS, in breast cancer. Bulk RNA sequencing data were curated from the TCGA repository to investigate the aberrant expression of GLS over diverse cancer types. Then, we examined its efficacy as a diagnostic biomarker in breast cancer by Area Under Curve (AUC) of the Receiver Operative Characteristic (ROC) curve. Furthermore, by applying siRNA technique, we knocked down the GLS expression level in cancerous cell lines, measuring the corresponding effects on cell proliferation and metastasis. Afterward, we explored the potential implications of GLS expression in the tumor immune microenvironment quantitatively by using several R packages and algorithms, including ESTIMATE, CIBERSORT, etc. Pan-cancer analysis suggested that GLS was aberrantly over-expressed in many cancer types, with breast cancer being typical. More in-depth analyses revealed the expression of GLS exerted a high ROC-AUC value in breast cancer diagnosis. Through the knock-down of GLS expression, it was found that GLS expression was strongly relevant to the growth and metastasis of tumor. Furthermore, it was also found to be correlated with the immune tumor microenvironment. We highlighted that GLS expression might be applicable as a diagnostic biomarker in breast cancer and possess significant implications in the growth and metastasis of tumor and the immune tumor microenvironment, sharing new insights into ontological and personalized medicine.


Laser Doppler flowmetry in the diagnosis of chronic compartment syndrome.
Chronic compartment syndrome (CCS) is usually considered to be due to ischaemia of muscle. We have attempted to use the direct measurement of muscle blood flow for diagnosis since the assessment of intracompartmental pressure does not provide accurate knowledge of the vascular state. We recorded simultaneously continuous measurements of the laser Doppler flow (LDF) in muscle and the intracompartment pressure (ICP) after exercise in seven patients with CCS, and in seven control subjects. The mean ICP was 74.1 +/- 4.4 mmHg in CCS patients and 24.2 +/- 3.4 mmHg in control subjects one minute after exercise, decreasing to 34.6 +/- 2.3 mmHg and 15.0 +/- 1.6 mmHg at 20 min, respectively. The LDF was 0.80 +/- 0.11 arbitrary units (AU) in control subjects and 1.09 +/- 0.14 AU in CCS patients one minute after exercise, and 0.41 +/- 0.11 AU and 0.27 +/- 0.04 AU, respectively, at the end of the recovery period. The ICP showed a progressive decrease over time in both groups. The LDF decreased sharply during the first minutes of recovery in control subjects, but in patients with CCS there was a delayed hyperaemic peak with blood flow reaching 0.84 +/- 0.10 AU at nine minutes as against 0.33 +/- 0.06 AU for control subjects (p < 0.01). The ICP increased in both control subjects and CCS patients after exercise with no clear cut-off point between the groups. By contrast, changes in muscle blood flow over time were clearly different between control subjects and patients with CCS. For this reason, LDF should be investigated further as a technique for the diagnosis of CCS.


Clinical and angiographic outcomes of diabetic patients after coronary stenting: a comparison of native vessel stent restenosis rates in different diabetic subgroups.
The main objectives of this study were to analyze the relationship between stent restenosis and microalbuminuria, which may express not only the glomerular vessels damage but also widespread microvascular dysfunction including coronary arterial disease, and to determine the angiographic and clinical outcomes of different diabetic subgroups after coronary stenting. Identification of the factors that may predict the outcome after coronary stent placement in diabetic patients could assist in deciding different stenting strategies in different diabetic subgroups. Control coronary angiographies were performed in 136 diabetic patients 6 months after coronary stent implantation. Patients were divided into 3 subgroups according to their microalbuminuria status. Clinical and angiographic outcomes and distribution of various risk factors were determined for these subgroups. Blood pressure and serum cholesterol concentrations were higher in the overt diabetic nephropathy group. The mean diseased vessel segment rate was lower in patients without microalbuminuria. Although the mean stent length and size were similar, patients without microalbuminuria had lower restenosis rates (23.9% vs 53.2% [microalbuminuria] and 46.2% [overt diabetic nephropathy] p<0.01). Insulin therapy or gender caused no difference in restenosis rate. Although stent lengths and diameters were not different, patients with microalbuminuria had higher restenosis rates. The authors suggest that microalbuminuria may be an independent risk factor for restenosis in patients with diabetes.


Analysis of hemorrhagic fever with renal syndrome and its pathogenic gene sequence based on geographic information system.
This study analyzed the temporal-spatial distribution characteristics, epidemiological characteristics and gene sequences of hemorrhagic fever with renal syndrome (HFRS) in Guangxi, with the intention of providing a theoretical and technical support for the prevention of HFRS. A map of the incidence of HFRS of different cities in Guangxi was drawn up using the Geographic Information System (GIS) to investigate the epidemiological characteristics and infection source of HFRS between 2013 and 2016. Guangxi has a low incidence of HFRS, and autumn and winter are the main high-incidence seasons. Cases of HFRS were reported in all regions in Guangxi except Laibin city between 2013 and 2016. The distribution of cases in the four years suggested that Guilin, Nanning, Hechi and Wuzhou were the main infected regions, especially the local areas in the north of Guilin. The nucleotide and amino acid of S fragment and M fragment of Hantaviruses (HV) detected were highly homologous, and no obvious variation was found. Through analyzing the space-time characteristics, epidemiological characteristics and gene sequence of HFRS in Guangxi, it was found that areas rich in water, grass and moisture, such as paddy fields, are the main active areas for the host of HFRS.


Neuroimaging findings in newborns with congenital heart disease prior to surgery: an observational study.
Neurodevelopmental impairment has become the most important comorbidity in infants with congenital heart disease (CHD). We aimed to (1) investigate the burden of brain lesions in infants with CHD prior to surgery and (2) explore clinical factors associated with injury. Prospective observational study. Single centre UK tertiary neonatal intensive care unit. 70 newborn infants with critical or serious CHD underwent brain MRI prior to surgery. Prevalence of cerebral injury including arterial ischaemic strokes (AIS), white matter injury (WMI) and intracranial haemorrhage. Brain lesions were observed in 39% of subjects (95% CI 28% to 50%). WMI was identified in 33% (95% CI 23% to 45%), subdural haemorrhage without mass effect in 33% (95% CI 23% to 45%), cerebellar haemorrhage in 9% (95% CI 4% to 18%) and AIS in 4% (95% CI 1.5% to 12%). WMI was distributed widely throughout the brain, particularly involving the frontal white matter, optic radiations and corona radiata. WMI exhibited restricted diffusion in 48% of cases. AIS was only observed in infants with transposition of the great arteries (TGA) who had previously undergone balloon atrial septostomy (BAS). AIS was identified in 23% (95% CI 8% to 50%) of infants with TGA who underwent BAS, compared with 0% (95% CI 0% to 20%) who did not. Cerebral injury in newborns with CHD prior to surgery is common.


Biochemistry of amyloid β-protein and amyloid deposits in Alzheimer disease.
Progressive cerebral deposition of the amyloid β-protein (Aβ) in brain regions serving memory and cognition is an invariant and defining feature of Alzheimer disease. A highly similar but less robust process accompanies brain aging in many nondemented humans, lower primates, and some other mammals. The discovery of Aβ as the subunit of the amyloid fibrils in meningocerebral blood vessels and parenchymal plaques has led to innumerable studies of its biochemistry and potential cytotoxic properties. Here we will review the discovery of Aβ, numerous aspects of its complex biochemistry, and current attempts to understand how a range of Aβ assemblies, including soluble oligomers and insoluble fibrils, may precipitate and promote neuronal and glial alterations that underlie the development of dementia. Although the role of Aβ as a key molecular factor in the etiology of Alzheimer disease remains controversial, clinical trials of amyloid-lowering agents, reviewed elsewhere in this book, are poised to resolve the question of its pathogenic primacy.


Lumbar Disc Herniation Presented with Contralateral Symptoms.
This study aimed to unravel the putative mechanism underlying the neurologic deficits contralateral to the side with lumbar disc herniation (LDH) and to elucidate the treatment for this condition. From January 2009 to June 2015, 8 patients with LDH with predominantly contralateral neurologic deficits underwent surgical treatment on the side with LDH with or without decompressing the symptomatic side. A retrospective review of charts and radiological records of these 8 patients was performed. The putative mechanisms underlying the associated contralateral neurological deficits, magnetic resonance imaging (MRI), electromyography (EMG), and the adequate surgical approach are discussed here. MRI revealed a similar laterally skewed paramedian disc herniation, with the apex deviated from the symptomatic side rather than directly compressing the nerve root; this condition may generate a contralateral traction force. EMG revealed radiculopathies in both sides of 6 patients and in the herniated side of 2 patients. Based on EMG findings and the existence of suspicious lateral recess stenosis of the symptomatic side, 6 patients underwent bilateral decompression of nerve roots and 2 were subjected to a microscopic discectomy to treat the asymptomatic disc herniation. No specific conditions such as venous congestion, nerve root anomaly or epidural lipomatosis were observed, which may be considered the putative pathomechanism causing the contralateral neurological deficits. The symptoms resolved significantly after surgery. The traction force generated on the contralateral side and lateral recess stenosis, rather than direct compression, may cause the contralateral neurologic deficits observed in LDH.


Effects of brief glucocorticoid exposure on growth of vascular smooth muscle cells in culture.
While prolonged exposure of vascular smooth muscle cells (VSMC) to glucocorticoid has been shown to inhibit cell proliferation, the effect of a brief pulse exposure is not known. We studied the short-term effects of pulse exposure to dexamethasone (DEX) on DNA synthesis in cultured VSMC. VSMC were pulsed with DEx for varying time intervals and [3H]thymidine incorporation into cells after 24 h was measured. Exposure to DEX for 24 h decreased [3H]thymidine incorporation, while pulse treatments with DEX from 2 min to 6 h significantly increased [3H]thymidine incorporation. Maximal proliferative effect was observed with a 20-min exposure. The effect of a 20-min pulse was dose-dependent, with the half-maximal dose of DEX being approximately 10(-7) M. A selective glucocorticoid receptor antagonist, RU486, inhibited the proliferative effect of DEx. Concentrated conditioned medium from cells exposed to 10(-6) M DEX increased [3H]thymidine incorporation by other VSMC in a dose-dependent manner. These results suggest that short-term pulse DEX exposure is capable of producing one or more autocrine growth factors in VSMC via a glucocorticoid receptor action. This effect of glucocorticoid pulses may contribute to the pathogenesis of arteriosclerosis and hypertension.


delGA (rs67491583) variant and colorectal cancer risk in an indigenous African population.
A recent study showed a higher frequency of GA deletion at rs67491583 in African American colorectal cancer (CRC) patients compared to controls, suggesting a likely contribution of this allele to racial disparity in CRC risk predisposition. We conducted a pilot study in an indigenous African population to evaluate this potential CRC risk variant. We collected epidemiological data and biological specimen from consenting consecutive CRC cases and controls presenting at the Oncology Clinic of University College Hospital, Ibadan from 2001 to 2007. We examined germline DNA for delGA by PCR-amplification of two overlapping fragments using standard primers. The products were directly sequenced using Applied Biosystems BigDye v3.1 sequencing chemistry and AB 13730 automatic DNA sequencer. There were 45 cases and 45 controls of which genotyping was successful in 39 cases and 38 controls. There were 5 heterozygous and 2 homozygous GA deletions with frequency of 11.54% (9/78) among cases whereas there were 8 heterozygous and 1 homozygous GA deletions among controls with frequency of 13.15% (10/76). (p= 0.79, OR 0.88, 95% CI 0.34-2.28). This study suggests that there is no association between the delGA (rs67491583) variant and CRC risk in this indigenous African population. However our sample size was small and the participants were not ethnically homogenous. Further studies are required to evaluate this marker in African CRC.


Iron and copper release in drinking-water distribution systems.
A large-scale pilot study was carried out to evaluate the impacts of changes in water source and treatment process on iron and copper release in water distribution systems. Finished surface waters, groundwaters, and desalinated waters were produced with seven different treatment systems and supplied to 18 pipe distribution systems (PDSs). The major water treatment processes included lime softening, ferric sulfate coagulation, reverse osmosis, nanofiltration, and integrated membrane systems. PDSs were constructed from PVC, lined cast iron, unlined cast iron, and galvanized pipes. Copper pipe loops were set up for corrosion monitoring. Results showed that surface water after ferric sulfate coagulation had low alkalinity and high sulfates, and consequently caused the highest iron release. Finished groundwater treated by conventional method produced the lowest iron release but the highest copper release. The iron release of desalinated water was relatively high because of the water's high chloride level and low alkalinity. Both iron and copper release behaviors were influenced by temperature.


Crystal structure of the human fatty acid synthase enoyl-acyl carrier protein-reductase domain complexed with triclosan reveals allosteric protein-protein interface inhibition.
Human fatty acid synthase (FAS) is a large, multidomain protein that synthesizes long chain fatty acids. Because these fatty acids are primarily provided by diet, FAS is normally expressed at low levels; however, it is highly up-regulated in many cancers. Human enoyl-acyl carrier protein-reductase (hER) is one of the FAS catalytic domains, and its inhibition by drugs like triclosan (TCL) can increase cytotoxicity and decrease drug resistance in cancer cells. We have determined the structure of hER in the presence and absence of TCL. TCL was not bound in the active site, as predicted, but rather at the protein-protein interface (PPI). TCL binding induces a dimer orientation change that causes downstream structural rearrangement in critical active site residues. Kinetics studies indicate that TCL is capable of inhibiting the isolated hER domain with an IC50 of ∼ 55 μM. Given the hER-TCL structure and the inhibition observed in the hER domain, it seems likely that TCL is observed in the physiologically relevant binding site and that it acts as an allosteric PPI inhibitor. TCL may be a viable scaffold for the development of anti-cancer PPI FAS inhibitors.


Different activation patterns in the visual cortex of late and congenitally blind subjects.
A key issue in developmental neuroscience is the role of activity-dependent mechanisms in the epigenetic induction of functional organization in visual cortex. Ocular blindness and ensuing visual deprivation is one of the rare models available for the investigation of experience-dependent cortical reorganization in man. In a PET study we demonstrate that congenitally blind subjects show task-specific activation of extrastriate visual areas and parietal association areas during Braille reading, compared with auditory word processing. In contrast, blind subjects who lost their sight after puberty show additional activation in the primary visual cortex with the same tasks. Studies in blind-raised monkeys show that crossmodal responses in extrastriate areas can be elicited by somatosensory stimulation. This is consistent with the crossmodal extrastriate activations elicited by tactile processing in our congenitally blind subjects. Since primary visual cortex does not show crossmodal responses in primate studies, the differential activation in late and congenitally blind subjects highlights the possibility of reciprocal activation by visual imagery in subjects with early visual experience.


The autoimmune infiltrate of Basedow's disease: analysis of clonal level and comparison with Hashimoto's thyroiditis.
The availability of high efficiency T-cell cloning techniques recently allowed the identification and characterization of clones derived from the thyroid infiltrate of patients with autoimmune thyroid diseases. Phenotypical and functional analysis of T-cell clones obtained from thyroid infiltrates of patients with Hashimoto's thyroiditis show that most of them are progenies of CD8+ cytolytic T cells with natural killer activity. This phenomenon, of potential importance in tissue damage, is markedly less pronounced in Basedow's disease glands. In both Hashimoto's thyroiditis and Basedow's disease only a minority of clones appear to be specific for autologous thyroid cells and most of them are potent interferon-gamma producers, while increased secretion of tumor necrosis factor-alpha is observed only in Hashimoto's thyroiditis. In contrast with normal lymphoid tissue, only very few T cell clones derived from both BD and HT infiltrates were able to produce detectable amounts of IL-4, suggesting that most of the thyroid-infiltrating T cells represent quite homogeneous populations of Th1-type "inflammatory" T cells. This peculiar potential of lymphokine secretion could play a role in the expression and/or maintenance of thyroid autoimmunity and thyroid functional damage.


HGF/Met-Signaling Contributes to Immune Regulation by Modulating Tolerogenic and Motogenic Properties of Dendritic Cells.
Hepatocyte growth factor (HGF)-signaling via Met can induce mitogenic, morphogenic, and motogenic activity in various cell types. Met expression in the immune system is limited to cells with antigen-presenting capacities, including dendritic cells (DCs). Thus, it appears highly conceivable that Met-signaling impacts on adaptive immune responses. However, the mechanisms by which HGF imparts its effects on immunological responses are not yet fully understood. DCs possess unique functionalities that are critically involved in controlling both tolerance and immunity. HGF conveys immunoregulatory functions, which strongly correlate with that of DCs orchestrating the apt immune response in inflammation. Therefore, this review focuses on the current knowledge of Met-signaling in DCs with specific emphasis on the morphogenic and motogenic activities. HGF has been identified to play a role in peripheral immune tolerance by directing DC differentiation towards a tolerogenic phenotype. In skin immunity, Met-signaling was shown to drive mobilization of DCs by regulating matrix metalloproteinase activities. This is strikingly reminiscent of the role of Met for regulating a cell fate program during embryonic development, wound healing, and in tumor invasion known as epithelial-mesenchymal transition (EMT). Thus, the concept emerges that an EMT program is executed by Met-signaling in DCs, which will be also discussed.


Body Composition, Relative Dose Intensity, and Adverse Events among Patients with Colon Cancer.
Despite evidence that low muscle increases the risk of chemotoxicity, most chemotherapies are dosed on body surface area without considering body composition. Among 178 patients with colon cancer, we assessed muscle and adipose tissue with multiple techniques and examined their associations with relative dose intensity (RDI) and adverse events. We estimated (i) cross-sectional skeletal muscle area (SMA) and total adipose tissue (TAT) area at L3 from computed tomography (CT); (ii) appendicular lean mass (ALM) and total body fat (TBF) mass from dual-energy X-ray absorptiometry (DXA); and (iii) total body skeletal muscle mass using D3-creatine (D3Cr) dilution. We standardized each measurement by its sex-specific standard deviation (SD). The primary outcome was reduced RDI (RDI <85%). The secondary outcome was the number of moderate and severe adverse events during each cycle of chemotherapy. We estimated the associations of muscle and adipose tissue measurements (per SD increase) with reduced RDI using logistic regression and adverse events using generalized estimating equations for repeated measures. Higher CT SMA and DXA ALM were significantly associated with a lower risk of reduced RDI [odds ratios: 0.56 (0.38-0.81) for CT SMA; 0.56 (0.37-0.84) for DXA ALM]. No measurements of muscle or adipose tissue were associated with adverse events. More muscle was associated with improved chemotherapy completion among patients with colon cancer, whereas muscle and adipose tissue were not associated with adverse events. Considering body composition may help personalize dosing for colon cancer chemotherapy by identifying patients at risk for poor chemotherapy outcomes.


Characterization of highly virulent Escherichia coli strains by ribosomal DNA restriction fragment length polymorphism.
Patterns of ribosomal DNA polymorphism were examined to compare carboxylesterase B type B1 strains and B2 strains of Escherichia coli isolated from extra-intestinal infections. DNA from 14 type B2 strains showing the presence of alpha-haemolysin and mannose-resistant haemagglutinin and lethality to mice and 14 type B1 strains lacking these characteristics, was digested with HindIII, EcoRI, BamHI or BglII restriction enzymes and analysed by Southern blotting. The obtained ribotypes clearly differentiated the B2 strains from the B1 strains. These results indicate that genotypes of the highly virulent B2 strains are different from that of the less virulent B1 strains.


Role of citalopram in the treatment of agitation in Alzheimer's disease.
Neuropsychiatric symptoms (NPS) are common among individuals with Alzheimer's disease (AD), associated with excess morbidity and mortality, greater healthcare use, earlier institutionalization, and caregiver burden. Agitation presents as emotional distress, excessive psychomotor activity, aggressive behaviors, disruptive irritability and dishibition. There is an unmet need to find pharmacologic treatment for agitation in patients with AD that can be safely and effectively used as a concurrent treatment alongside psychosocial interventions. A recent, multicenter, randomized, placebo-controlled trial explored the efficacy of a 30-mg daily dose of citalopram for agitation in patients with AD and showed a significant decrease in agitation for citalopram compared with placebo. Both QTc prolongation and cognitive worsening, as measured by the Mini Mental State Examination, were observed in the citalopram group and present a concern to clinicians. Citalopram at a 20-mg daily dose should be considered as a possible first-line treatment in addition to psychosocial intervention.


[Differential diagnosing of hypercalcemias].
Primary hyperparathyreosis and tumour diseases are the two most frequent causes of hypercalcaemia. Surgical removal of parathyroid adenoma is the permanent solution for hypercalcaemia. Hypercalcaemia may occur in 20-30% of patients with cancer in the course of the disease. It causes progressive deterioration of the overall condition of the patient which culminates in a coma-like state with renal failure and means a bad prognosis for the affected person. Evaluation of clinical condition and obtaining the immunoreactive parathormone level data are of extreme importance for correct diagnosis. Normal or even low parathormone levels almost surely exclude primary hyperparathyreosis as the source of hypercalcaemia. Additional, less frequent causes of hypercalcaemia should also be taken into consideration, such as diseases caused by the granulomatose tissue, familial benign hypocalciuric hypercalcaemia, drug provoked hypercalcaemia, high thyroid hormone doses and patient dehydration. Fast replenishment of liquids and administration of bisphosphonates are the cornerstones of hypercalcaemia therapy.


Informationist education.
The National Institutes of Health (NIH) funds biomedical research and conducts its own research. One way the NIH Library supports this work is by providing librarians with biomedical training and encouraging them to become embedded with researchers and administrators. Some of these "informationists" have degrees in scientific or health fields, and all engage in ongoing training, mostly through coursework at local institutions and at NIH itself. This article elaborates on the training of NIH informationists. Past research has indicated that patrons welcome librarians with biomedical training, which may in turn lead to greater communication between librarians and researchers.


Adult type beta-galactosidase and neuraminidase deficiency in three siblings.
In recent years, there have been described a number of patients with beta-galactosidase and neuraminidase deficiency of juvenile onset. The clinical features in these patients are myoclonus, cherry-red spots, insidious visual loss, corneal clouding, gargoyle like appearance and ataxia. The condition appears to be transmitted as an autosomal recessive trait. Pathologically it has been characterized that there are vacuolation of lymphocytes, and inclusion bodies such as concentric membranous bodies in the ganglion cells of the rectum. Here we report a patient with beta-galactosidase and neuraminidase deficiency of juvenile onset in whom unusual "fingerprint" profiles were obtained in the submucosal ganglion cells in the rectum and will discuss the clinical significance of the inclusion bodies.


Dual role of oestrogens as hormones and pro-carcinogens: tumour initiation by metabolic activation of oestrogens.
Epidemiological evidence increasingly points to exogenous or endogenous oestrogens as a risk factor for breast cancer. However, it is unlikely that induction of oestrogen-dependent tumour growth is the sole contribution of oestrogens to tumour development in the mammary gland, because oestrogen receptors are barely detectable in normal mammary epithelial cells. In this review, I examine a mechanism for mammary carcinogenesis, which emphasizes tumour initiation by metabolic activation of oestrogens in combination with cell transformation and growth stimulation by oestrogen receptor-mediated processes. Catecholestrogen metabolites are capable of metabolic redox cycling between quinone and hydroquinone forms, a mechanism of free radical generation. Several types of direct and indirect free radical-mediated DNA damage are induced by oestrogens in vitro and in vivo, such as DNA single strand breaks, 8-hydroxylation of guanine bases, and DNA adduct formation by malondialdehyde, a decomposition product of free radical-induced lipid peroxides. The substrate for redox cycling and free radical generation may be 4-hydroxoestradiol, because this metabolite is formed from oestradiol by a specific oestrogen 4-hydroxylase detected in several human organs including mammary tissue. It has also been formed in organs of rodents where oestrogens induce tumours, with the exception of the liver. 4-Hydroxyoestradiol is a potent, long-acting oestrogen and may complete the carcinogenic process by stimulating receptor-mediated proliferation. An understanding of a possible mechanism of mammary carcinogenesis as a result of oestrogen-mediated initiation means that several prevention strategies, based on inhibiting metabolic activation of oestrogens or free radical action, can be developed.


Deaf: A Concept Analysis From a Cultural Perspective Using the Wilson Method of Concept Analysis Development.
The purpose of this article is to provide an analysis of the concept Deaf to increase health care provider (HCP) understanding from a cultural perspective. Deaf signers, people with hearing loss who communicate primarily in American Sign Language (ASL), generally define the term Deaf as a cultural heritage. In the health care setting, the term deaf is most often defined as a pathological condition requiring medical intervention. When HCPs are unaware that there are both cultural and pathological views of hearing loss, significant barriers may exist between the HCP and the Deaf individual. The concept of Deaf is analyzed using the Wilsonian method. Essential elements of the concept "Deaf" from a cultural perspective include a personal choice to communicate primarily in ASL and identify with the Deaf community. Resources for HCPs are needed to quickly identify Deaf signers and provide appropriate communication.


The changing relationship between unemployment and total fertility.
The aim of this paper is to investigate whether there has been a fundamental change in the relationship between economic conditions and fertility. We use panel data methods to study the short-term changes in total fertility and the unemployment rate in a range of Organisation for Economic Co-operation and Development (OECD) countries from 1957 to 2014. We find that although fertility was counter-cyclical before 1970, with good economic times being associated with lower fertility, since then it has become pro-cyclical, with good economic times being associated with higher fertility.


Comparison of antibiotic activities by using serum bactericidal activity over time.
In evaluating antimicrobial agents with similar spectra of activity, it is difficult to determine equivalent dosage regimens. In vitro potency, pharmacokinetic disposition, and other factors determine the usual dosing regimen. Knowledge of the serum bactericidal activity over time may assist in defining the potency of comparative antimicrobial agents. Cefoxitin and ceftizoxime, cephalosporins with gram-negative aerobic and anaerobic activity, have been promoted as monotherapy in the treatment of intra-abdominal infection. In a randomized, crossover study, six healthy volunteers received single 30-mg/kg doses of cefoxitin and ceftizoxime. Greater serum activity against Escherichia coli and Bacteroides fragilis was observed with ceftizoxime than with cefoxitin. The results suggest that ceftizoxime can be administered in a lower daily dosage than cefoxitin. We propose that the present study may serve as a prototype for future studies attempting to assess equivalent dosing regimens for antibiotics with similar spectra of activity.


A new, powerful glycosylation method: activation of thioglycosides with dimethyl disulfide-triflic anhydride.
Dimethyl disulfide reacts with triflic anhydride to provide a highly reactive electrophile. Various thioglycosides, differing in their thio aglycons, carbohydrate units, and protecting group pattern, were activated with Me2S2-Tf2O in the presence of different glycosyl acceptors. The reactions proceeded at low temperatures within a short time, affording oligosaccharides in high yields both on primary and secondary hydroxyls. Armed and disarmed glycosyl donors were activated equally efficiently.


[The early stages of schizophrenia].
A total of 385 schizophrenic patients were studied (including 96 cases of an intially erroneous diagnosis of schizophrenia). It was possible to reveal early signs of schizophrenia in 84.3% of the patients, and in 50% -- to establish factors predisposing to exposure or which expose initial manifestations of the disease. Schizophrenia can be rightly diagnosed in the early periods if character peculiarities and the course of the initial period of the disease are taken into account, as well as the influence of such factors as heredity, age and periods which provoke the disease. It is stressed that the early forms of schizophrenia are often atypical, incomplete in their clinical picture where neurotic-like and psychopathic-like phenomena often predominate.


Many potential pathways to future pandemic influenza.
Although influenza A viruses have caused pandemics for centuries, future pandemics cannot be predicted with our current understanding and resources. Concern about an H5N1 avian influenza pandemic has caused alarm since 1997, but there are many other possible routes to pandemic influenza.


Long-term treatment with corticosteroids/ACTH in asthmatic children. IV. Skeletal maturation.
Skeletal maturation in severe bronchial asthma was studied in 15 children during and after treatment with depot tetracosactrin and in 6 children during treatment with prednisolone. Attained skeletal maturity before treatment was below the reference mean in the majority of children. Skeletal maturation was enhanced during treatment with depot tetracosactrin, which led to more advanced attained skeletal maturity at withdrawal than at start of treatment. There was a tendency towards larger increases of skeletal maturity than of height. The influence of adrenal androgens, released by ACTH-stimulation and good control of the disease are probably relevant factors for the acceleration of skeletal maturation. After withdrawal of depot tetracosactrin the rate of skeletal maturation normalized. During prednisolone treatment there was a delay of skeletal maturation leading to a progressive relative decrease of attained skeletal maturity, and closely related to a delay in linear growth. Treatment with depot tetracosactrin may thus induce enhancement of skeletal maturation, but with the treatment regimen found to be efficacious in bronchial asthma, the effect is not very pronounced and does not perceptibly affect the ultimate outcome of growth.


How to account for early overly small risk sets in the analysis of pregnancy outcome data?-Comparison of different methods for stabilizing the Aalen-Johansen estimator.
In analyzing pregnancy data concerning drug exposure in the first trimester, the risk of spontaneous abortions is of primary interest. For estimating the cumulative incidence function, the Aalen-Johansen estimator is typically used, and competing risks such as induced abortion and livebirth are considered. However, the delayed study entry can lead to overly small risk sets for the first events. This results in large jumps in the estimated cumulative incidence function of spontaneous abortions or induced abortions using the Aalen-Johansen estimator, and consequently in an overestimation of the probability. Several approaches account for early overly small risk sets. The first approach is conditioning on the event time being greater than the event time causing the large jump. Second, the events can be ignored by censoring them. Third, the events can be postponed until a large enough number is at risk. These three approaches are compared. All approaches are applied using data of 54 lacosamide-exposed pregnancies. The Aalen-Johansen estimate of the probability of spontaneous abortion is 22.64%, which is relatively large for only three spontaneous abortions in the dataset. The conditional approach and the ignore approach have an estimated probability of 7.17%. In contrast, the estimate of the postpone approach is 16.45%. In this small sample, bootstrapped confidence intervals seem more accurate. In the analyses of pregnancy data with rare events, the postpone approach is favorable as no events are excluded. However, the approach that ignores early events has the narrowest confidence interval.


Surface plasmon resonance phase-shift interferometry: real-time DNA microarray hybridization analysis.
Surface plasmon resonance (SPR) phase-shift interferometry (PSI) is a novel technique which combines SPR and modified Mach-Zehnder PSI to measure the spatial phase variation caused by biomolecular interactions upon a sensing chip. The SPR-PSI imaging system offers high resolution and high-throughout screening capabilities for microarray DNA hybridization without the need for additional labeling, and provides valuable quantitative information. The SPR-PSI imaging system has an enhanced detection limit of 2.5 x 10(-7) refraction index change, a long-term phase stability of pi/100 in 30 min, and a spatial phase resolution of pi/300 with 100 x 100 microm2 detection area. This study successfully demonstrates the label-free observation of 15-mer DNA microarray.


Site-directed mutagenesis of arginine-114 and tryptophan-129 in the cytochrome b subunit of the bc1 complex of Rhodobacter sphaeroides: two highly conserved residues predicted to be near the cytoplasmic surface of putative transmembrane helices B and C.
The cytochrome b subunit of the ubiquinol:cytochrome c oxidoreductase (the bc1 complex) contains two heme prosthetic groups, cytochrome bL and cytochrome bH. In addition, this subunit also provides major elements of the quinol oxidation site (Qo) and a separate quinone reductase site (Qi), which are thought to be located on opposite sides of the membrane. Site-directed mutagenesis has been used to explore the role(s) of specific amino acid residues in this subunit from the photosynthetic bacterium Rhodobacter sphaeroides. Previous work identified five residues, Gly48 (Gly33), Ala52 (Gly37), His217 (His202), Lys251 (Lys228), and Asp252 (Asp229), as being either at or near the quinone reductase site (the residue numbers in parentheses designate the equivalent positions in the yeast mitochondrial enzyme). These residues are predicted to be near the cytoplasmic boundaries of transmembrane helices: helix A (G48, A52), helix D (H217), or helix E (K251, D252). In the current work, the importance of two additional highly conserved residues, which are also predicted to be near the cytoplasmic boundaries of transmembrane helices, is explored by site-directed mutagenesis. R114 (helix B) has been substituted with K, Q, and A, and W129 (helix C) has been changed to A and F. The results suggest that a positively charged residue at position 114 is important. The R114K mutation causes only subtle effects, which appear to be localized to cytochrome bH and the quinone reductase site. In contrast, R114Q is not assembled, and R114A, although partially assembled, is nonfunctional and appears to have a very low amount of cytochrome b associated with the complex. Both mutants at position 129 (W129A and W129F) are able to support the photosynthetic growth of the organism, but show abnormal characteristics. The defects associated with the W129A mutation appear to be primarily associated with the quinone reductase site and cytochrome bH, whereas the W129F mutation appears to result in more global defects that also perturb the cytochrome bL locus. The results are consistent with the placement of residues R114 and W129 near the cytoplasmic side of the membrane, but suggest that these residues are important for the assembly and overall stability of the complex.


[The effectiveness of short-segment posterior instrumentation of thoracolumbar burst fractures].
We evaluated the results of short-segment posterior instrumentation of thoracolumbar burst fractures and investigated correlations between radiographic and functional results as well as factors that affected correction losses. We reviewed 48 patients (30 males, 18 females; mean age 40+/-14 years; range 18 to 67 years) who underwent short-segment posterior instrumentation with pedicle screws and fusion. The most common involvement was at L1 in 18 patients (37.5%), followed by T12 in 11 patients (22.9%). According to the Frankel grading system, six patients had complete, 14 patients had incomplete neurologic deficits. The Cobb angles were measured, and canal remodeling was assessed by computed tomography. Modified functional results were derived using the Denis pain and work scales. The mean follow-up was 21.7+/-9.1 months (range 12 to 48 months). The mean correction in the Cobb angle was 18.2+/-8.6 degrees (p<0.01), the mean correction loss was 7.4+/-5.7 degrees (p<0.01), and the mean canal remodeling was 51.3+/-9.3% (p<0.001). There was a significant correlation between Cobb angle correction and correction loss (r=0.38, p<0.01). An intraoperative correction of greater than 15 degrees was significantly associated with a greater correction loss (p<0.05). Patients with a correction loss of more than 10 degrees had a significantly poorer Denis pain score and modified functional result (p<0.05). Modified functional results were excellent in 16 patients (33.3%), good in 23 patients (47.9%), fair in seven patients (14.6%), and poor in two patients (4.2%). At final follow-ups, the Cobb angle was not correlated with functional results (p>0.05). All the patients having incomplete neurologic deficits improved by at least 1 Frankel grade. An intraoperative correction exceeding 15 degrees is significantly associated with a greater correction loss, which in turn has a significantly adverse effect on functional results.


The protein antigens of peripheral nerve myelin.
Peripheral nervous system (PNS) tissue contains a variety of proteins, lipids, and carbohydrates that may serve as immunogens in proving immune responses, as antigens participating in immunological reactions, or as both types of agents. Three proteins P0, P1, and P2, account for approximately 70% of PNS myelin proteins. P0 is the major PNS myelin protein and is restricted to the PNS. P1 is similar to, if not identical with, myelin basic protein, the component of central nervous system myelin which induces experimental allergic encephalomyelitis. P2 has neuritogenic properties for inducing experimental allergic neuritis and may be involved in immune-mediated PNS myelin injury in humans. The complete amino acid sequence for P2 has recently been delineated, and its neuritogenic, immunogenic, and antigenic features can now be further characterized.


Do the Concentration and Volume of Local Anesthetics Affect the Onset and Success of Infraclavicular Anesthesia?
Although local anesthesia is a suitable method for upper limb surgeries, there is debate regarding the effects of appropriate dosing. In the current study, we investigated the effects of the concentration and volume of a local anesthetic on the beginning and quality of anesthesia during upper limb orthopedic surgeries. This double-blinded, randomized, clinical trial was conducted on 60 patients aged between 18 and 85 years candidated for upper limb orthopedic operations. The patients were equally and randomly distributed into two groups (n = 30). Under ultrasound imaging guidance, the first group received 7 mL of 2% lidocaine and the second group 10 mL of 1.3% lidocaine into the brachial plexus cords. The onset of block and the level of sensory and motor block were documented for each nerve territory. The onset of sensory and motor block was significantly shorter in the 1.3% lidocaine group than in the 2% lidocaine group (P ≤ 0.05). The success rate of sensory and motor block was not different. The quality (completeness) of sensory block for the musculocutaneous nerve and that of motor block for the radial nerve were significantly better in the 1.3% lidocaine group than in the 2% lidocaine group. The volume of the injected anesthetic accelerated the onset of sensory and motor block without affecting the rate of success in our patients.


Non-Linear Characterisation of Cerebral Pressure-Flow Dynamics in Humans.
Cerebral metabolism is critically dependent on the regulation of cerebral blood flow (CBF), so it would be expected that vascular mechanisms that play a critical role in CBF regulation would be tightly conserved across individuals. However, the relationships between blood pressure (BP) and cerebral blood velocity fluctuations exhibit inter-individual variations consistent with heterogeneity in the integrity of CBF regulating systems. Here we sought to determine the nature and consistency of dynamic cerebral autoregulation (dCA) during the application of oscillatory lower body negative pressure (OLBNP). In 18 volunteers we recorded BP and middle cerebral artery blood flow velocity (MCAv) and examined the relationships between BP and MCAv fluctuations during 0.03, 0.05 and 0.07Hz OLBNP. dCA was characterised using project pursuit regression (PPR) and locally weighted scatterplot smoother (LOWESS) plots. Additionally, we proposed a piecewise regression method to statistically determine the presence of a dCA curve, which was defined as the presence of a restricted autoregulatory plateau shouldered by pressure-passive regions. Results show that LOWESS has similar explanatory power to that of PPR. However, we observed heterogeneous patterns of dynamic BP-MCAv relations with few individuals demonstrating clear evidence of a dCA central plateau. Thus, although BP explains a significant proportion of variance, dCA does not manifest as any single characteristic BP-MCAv function.


New measurements of the European Muon Collaboration effect in very light nuclei.
New Jefferson Lab data are presented on the nuclear dependence of the inclusive cross section from (2)H, (3)He, (4)He, (9)Be and (12)C for 0.3 < x < 0.9, Q(2) approximately 3-6 GeV(2). These data represent the first measurement of the EMC effect for (3)He at large x and a significant improvement for (4)He. The data do not support previous A-dependent or density-dependent fits to the EMC effect and suggest that the nuclear dependence of the quark distributions may depend on the local nuclear environment.


Algorithm for coding DNA sequences into "spectrum-like" and "zigzag" representations.
An algorithm for encoding long strings of building blocks, like 4 DNA bases (adenine-A, cytosine-C, thymine-T, and guanidine-G), 20 natural amino acids (from Alanine Ala to Valine-Val, plus the stop triplet), or all 64 possible base triplets (from AAA to TTT), into "zigzag" or "spectrum-like" representations is suggested. The new encoding scheme can be derived in the 3-, 2-, or 1-dimensional form depending on the user's wishes. The only information, besides the string for which the "spectrum-like" representation is sought, is the initial positioning of the complete set of units from which the string is composed, i.e., four positions for A, C, G, and T, or 20 positions for natural amino acids plus stop, etc. This initial positioning can be initialized in either the 3-, 2-, or 1-D form. As an illustration of the suggested encoding scheme of the visual and chemometric comparison of the first 10 exon strings of the beta globin gene of 10 different species, each string consisting of about 100 basic amino acids long is shown.


Prevalence of acanthosis nigricans in newly-diagnosed type 2 diabetes.
To determine the prevalence of acanthosis nigricans in a population of patients with newly-diagnosed type 2 diabetes mellitus. Chart review of men and women treated for newly diagnosed type 2 diabetes at the University Diabetes Treatment Center at Parkland Health and Hospital System in Dallas, Texas between January 1998 and December 1999. The presence of acanthosis nigricans was evaluated on the posterior neck of each individual. Of 216 patients identified with newly diagnosed type 2 diabetes, 78 individuals (36.1%) presented with acanthosis nigricans involving the back of the neck. Most subjects were obese, with the mean BMI of the subject population at 32.7 +/- 5.8 kg/m2 (mean +/- SD). Prevalence of acanthosis nigricans increased with degree of obesity, with fully 54.1% of the population with a BMI of > or = 30 kg/m2 manifesting the skin lesion. The prevalence of acanthosis nigricans differed notably among ethnic groups, as the lesion occurred in 50 (52.6%) of 95 African-American subjects and 28 (35.9%) of 78 Latin-American subjects. Patients with acanthosis nigricans required markedly higher insulin doses (82.3 +/- 7.2 units/day) to achieve euglycemia compared to those without the disorder (50.2 +/- 5.7 units/day). These results suggest that acanthosis nigricans is a readily visible marker of hyperinsulinemia and is frequently encountered in patients with type 2 diabetes. Prevalence of acanthosis nigricans is influenced by ethnicity and BMI in this patient population.


The role of protein kinase C in histamine secretion from mast cells.
Receptor activation on the cell surface is coupled through a guanine nucleotide regulatory protein to polyphosphoinositide phosphodiesterase. The activation of this enzyme catalyses the hydrolysis of phosphatidylinositol biphosphate. One of the products of this hydrolysis is diacylglycerol, which activates protein kinase C. It can also be activated by tumour-promoting phorbol esters. The synthetic diacylglycerol, 1-oleoyl-2-acetyl-rac-glycerol (OAG) and the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) have been used to stimulate protein kinase C in a pure population of rat peritoneal mast cells. Both of them caused histamine release, but the rate of release with TPA or OAG alone was slow. The release was inhibited by blocking the oxidative energy metabolism with antimycin A, and was associated with progressive exocytosis, showing that it is a secretory process. Studies on the interaction between the stimulation of protein kinase C by OAG/TPA and the secretagogues showed a dual effect, both potentiation and inhibition. Antigen (in sensitized cells) and compound 48/80 showed this pattern of response. With the calcium ionophore, A23187, potentiation was the dominant effect, although some inhibition could be shown with TPA. This is possibly related to the large calcium influx which causes translocation of protein kinase C to the membranes and enhances its activity. The potentiation suggests that protein kinase C is involved in the secretion process by the secretagogues, while the inhibition reflects a regulatory function, which is apparently exerted through an inhibition of phosphatidylinositol breakdown. Calcium uptake was enhanced by both TPA and OAG. Protein kinase C may thus contribute to the replenishment of the intracellular calcium stores after the secretory response.


Multicenter Adoption and Outcomes of Nodal Observation for Patients with Melanoma and Sentinel Lymph Node Metastases.
Following publication of the MSLT-II trial showing no survival benefit of completion lymphadenectomy (CLND) in patients with melanoma sentinel lymph node (SLN) metastases, it is expected that practice patterns have changed. The purpose of this study is to understand real-world practices and outcomes after publication of this landmark trial. Patients with truncal/extremity melanoma SLN metastases diagnosed between 2013 and 2019 at four academic cancer centers were included in this retrospective cohort study. Descriptive statistics, Cox proportional hazards model, and multivariable regression were used to characterize the cohort and identify predictors of CLND, harboring non-SLN (NSLN) metastases, and survival. Results of 1176 patients undergoing SLN biopsy, 183 had SLN metastases. The number of patients who underwent CLND before versus after trial publication was 75.7.% versus 20.5% (HR 0.16, 95% CI 0.09-0.28). Of those undergoing nodal observation (NO), 92% had a first nodal-basin ultrasound, while 63% of patients had a fourth. In exploratory multivariable analyses, age ≥ 50 years was associated with lower rate of CLND (HR 0.58, 95% CI 0.36-0.92) and larger SLN deposit (> 1.0 mm) with increased rate of CLND (HR 1.87, 95% CI 1.17-3.00) in the complete cohort. Extracapsular extension was associated with increased risk of NSLN metastases (HR 12.43, 95% CI 2.48-62.31). Adjusted survival analysis demonstrated no difference in recurrence or mortality between patients treated with CLND versus NO at median 2.2-year follow-up. Nodal observation was rapidly adopted into practice in patients with melanoma SLN metastases at four centers in Canada. Younger age and higher nodal burden were associated with increased use of CLND after trial publication. Ultrasound (US) surveillance decreased with time from SLNB. In our study, CLND was not associated with a decreased risk of recurrence or mortality.


Current status of functional lower extremity surgery in adult spastic patients.
Ten percent of upper motor neuron spastic patients are candidates for functional surgery. If the main cause of the disability is abnormal muscle tone and not sensation, balance, cognition, or perceptual problems, good results from tendon lengthening or transfers are to be expected. The preoperative work-up should consist of examination, trial orthoses, nerve blocks, and most importantly dynamic electromyography. Releases or neurectomies are generally done in nonfunctional patients. Phenol blocks are a temporizing procedure during the phase of neurologic recovery. The patients all tolerated the anesthesia well, and the surgical risks are the same as in other lower extremity procedures.


Modeling osteosarcoma progression by measuring the connectivity dynamics using an inference of multiple differential modules algorithm.
Understanding the dynamic changes in connectivity of molecular pathways is important for determining disease prognosis. Thus, the current study used an inference of multiple differential modules (iMDM) algorithm to identify the connectivity changes of sub‑network to predict the progression of osteosarcoma (OS) based on the microarray data of OS at four Huvos grades. Initially, multiple differential co‑expression networks (M‑DCNs) were constructed, and weight values were assigned for each edge, followed by detection of seed genes in M‑DCNs according to the topological properties. Using these seed gene as a start, an iMDM algorithm was utilized to identify the multiple candidate modules. The statistical significance was determined to select multiple differential modules (M‑DMs) based on the null score distribution of candidate modules generated using randomized networks. Additionally, the significance of Module Connectivity Dynamic Score (MCDS) to quantify the dynamic change of M‑DMs connectivity. Further, DAVID was employed for KEGG pathway enrichment analysis of genes in dynamic modules. In addition to the basal condition, four conditions, OS grade 1‑4, were also included (M=4). In total, 4 DCNs were constructed, and each of them included 2,138 edges and 272 nodes. A total of 13 genes were identified and termed 'seed genes' based on the z‑score distribution of 272 nodes in DCNs. Following the module search, module refinement and statistical significance analysis, a total of four 4‑DMs (modules 1, 2, 3 and 4) were identified. Only one significant 4‑DM (module 3 in the DCNs of grade 1, 2, 3 and 4 OS) with dynamic changes was detected when the MCDS of real 4‑DMs were compared to a null distribution of MCDS of random 4‑DMs. Notably, the genes of the dynamic module (module 3) were enriched in two significant pathway terms, ubiquitin‑mediated proteolysis and ribosome. The seed genes with the highest degrees included protein phosphatase 1 regulatory subunit 12A (PPP1R12A), UTP3, small subunit processome component homolog (UTP3), prostaglandin E synthase 3 (PTGES3). Thus, pathway functions (ubiquitin‑mediated proteolysis and ribosome) and several seed genes (PPP1R12A, UTP3, and PTGES3) in the dynamic module 3 may be associated with the progression of OS and may serve as potential therapeutic targets in OS.


Parotid or carotid? Misled by site.
We present an interesting scenario where a 64 years old male presented with a long standing painless, infra-auricular swelling, which had progressively increased in size. Based on the site, the clinical impression was of a salivary gland lesion and FNAC was performed. The smears were unusually cellular and had necrotic background. The cytological diagnosis was a cystic neoplasm of salivary gland, possibly mucoepidermoid carcinoma. Warthin's tumor was also kept in differential. However, the radiological investigations, which were made available after the FNAC report were conflicting with cytological diagnosis of a malignancy and were characteristic of a carotid body tumor, generally a benign neoplasm. Surgical excision of the tumor with regional lymph node sampling was done and histopathological examination solved the puzzle by revealing metastasis of paraganglioma to right posterior triangle lymph nodes. This case is unique because of the unusual presentation of a malignant paraganglioma as an infra-auricular swelling, which was clinically considered as a parotid tumor. The clinician as well as the pathologist need to be aware of such diagnostic pitfall. Diagn. Cytopathol. 2017;45:569-573. © 2017 Wiley Periodicals, Inc.


Single-Cell RNA Sequencing of Urinary Cells Reveals Distinct Cellular Diversity in COVID-19-Associated AKI.
AKI is a common sequela of infection with SARS-CoV-2 and contributes to the severity and mortality from COVID-19. Here, we tested the hypothesis that kidney alterations induced by COVID-19-associated AKI could be detected in cells collected from urine. We performed single-cell RNA sequencing (scRNAseq) on cells recovered from the urine of eight hospitalized patients with COVID-19 with (n=5) or without AKI (n=3) as well as four patients with non-COVID-19 AKI (n=4) to assess differences in cellular composition and gene expression during AKI. Analysis of 30,076 cells revealed a diverse array of cell types, most of which were kidney, urothelial, and immune cells. Pathway analysis of tubular cells from patients with AKI showed enrichment of transcripts associated with damage-related pathways compared with those without AKI. ACE2 and TMPRSS2 expression was highest in urothelial cells among cell types recovered. Notably, in one patient, we detected SARS-CoV-2 viral RNA in urothelial cells. These same cells were enriched for transcripts associated with antiviral and anti-inflammatory pathways. We successfully performed scRNAseq on urinary sediment from hospitalized patients with COVID-19 to noninvasively study cellular alterations associated with AKI and established a dataset that includes both injured and uninjured kidney cells. Additionally, we provide preliminary evidence of direct infection of urinary bladder cells by SARS-CoV-2. The urinary sediment contains a wealth of information and is a useful resource for studying the pathophysiology and cellular alterations that occur in kidney diseases.


Multiple paternity in a viviparous toad with internal fertilisation.
Anurans are renowned for a high diversity of reproductive modes, but less than 1 % of species exhibit internal fertilisation followed by viviparity. In the live-bearing West African Nimba toad (Nimbaphrynoides occidentalis), females produce yolk-poor eggs and internally nourish their young after fertilisation. Birth of fully developed juveniles takes place after 9 months. In the present study, we used genetic markers (eight microsatellite loci) to assign the paternity of litters of 12 females comprising on average 9.7 juveniles. In 9 out of 12 families (75 %), a single sire was sufficient; in three families (25 %), more than one sire was necessary to explain the observed genotypes in each family. These findings are backed up with field observations of male resource defence (underground cavities in which mating takes place) as well as coercive mating attempts, suggesting that the observed moderate level of multiple paternity in a species without distinct sperm storage organs is governed by a balance of female mate choice and male reproductive strategies.


[Chemical constituents of Changium smyrnioides].
To study chemical constituents of Changium smyrnioides Wolff. The chemical components were isolated and purified by silica gel column and recrystallization. The chemical structures were elucidated on the basis of physico-chemical properties and spectral data. Ten compounds were isolated and identified as lignoceric acid (1), beta-sitosterol (2), stigmasterol (3), 5-hydroxy-8-methoxypsoralen (4), glycerylmonopalmitate (5), L-pyroglutamic acid (6), succinic acid (7), vanillic acid-4-O-beta-D-glucopyranoside (8 ), vanillic acid (9), daucosterol (10). Compounds 1, 4, 5, 6, 8 and 9 are obtained from the plant for the first time.


The role of oral health in gastrointestinal malignancies.
Many studies have shown a connection between poor oral health and a number of systemic diseases. Recent studies have demonstrated an association between poor oral health and the oral microbiota to carcinogenesis. This review article will focus on studies that link oral dysbiosis, periodontal disease, and specific oral microorganisms to gastrointestinal malignancies. These studies provide some insight and understanding of the role of the oral microbiome in carcinogenesis. Understanding how the oral microbiota is related to carcinogenesis and gastrointestinal malignancies could lead to identifying biomarkers and provides future treatment modalities. More research in this area would be beneficial to the diagnosis and treatment of patients with gastrointestinal malignancies.


Advances in the Prediction of Protein Aggregation Propensity.
Protein aggregation into β-sheet-enriched insoluble assemblies is being found to be associated with an increasing number of debilitating human pathologies, such as Alzheimer's disease or type 2 diabetes, but also with premature aging. Furthermore, protein aggregation represents a major bottleneck in the production and marketing of proteinbased therapeutics. Thus, the development of methods to accurately forecast the aggregation propensity of a certain protein is of much value. A myriad of in vitro and in vivo aggregation studies have shown that the aggregation propensity of a certain polypeptide sequence is highly dependent on its intrinsic properties and, in most cases, driven by specific short regions of high aggregation propensity. These observations have fostered the development of a first generation of algorithms aimed to predict protein aggregation propensities from the protein sequence. A second generation of programs able to map protein aggregation on protein structures is emerging. Herein, we review the most representative online accessible predictive tools, emphasizing their main distinctive features and the range of applications. In this review, we describe representative biocomputational approaches to evaluate the aggregation properties of protein sequences and structures, while illustrating how they can become very useful tools to target protein aggregation in biomedicine and biotechnology.


Vitamin D metabolism and function during pregnancy and the neonatal period.
Recent evidence suggests that vitamin D plays an important role in calcium homeostasis during pregnancy and early extrauterine life. Vitamin D is metabolized by successive hydroxylations to 25-hydroxyvitamin D and then to 1,25-dihydroxyvitamin D, the most potent known metabolite of the vitamin. During pregnancy, the concentrations of this metabolite in maternal serum increase in parallel with the increased need to absorb dietary calcium. 1,25-Dihydroxyvitamin D is produced in the fetoplacental unit as well as in the maternal kidneys. Receptors for 1,25-dihydroxyvitamin D appear to be present in the placenta suggesting that the placenta may be a target for vitamin D action. Developmental changes in vitamin D metabolism and action have been documented in the neonate as well as in the mother and fetus. Clinical studies indicate that adequate vitamin D intake is important during pregnancy. Administration of vitamin D or its metabolites appears to be useful in the treatment of neonatal disorders.


Novel in-situ decoration of single-walled carbon nanotube transistors with metal nanoparticles.
The carbon nanotube-metal nanoparticle complex has attracted a lot of research interest because of their potential applications in catalysis and gas sensing. Here we introduce a novel electrochemical method to realize in-situ decoration of single-walled carbon nanotube field effect transistors (CNT-FET) with metal nanoparticles using a sacrificial electrode. In this process, metal atoms are first ionized into an electrolyte solution by applying a potential difference between the sacrificial electrode and the grounded source/drain electrodes connecting the nanotube of the CNT-FET. The positive metal ions migrate under the influence of the electric field, and deposit on the grounded nanotube as metal nanoparticles. This method provides for better control over the quantity and size of the deposited nanoparticles compared to other decoration methods. We demonstrate successful deposition of Au and Ag nanoparticles on carbon nanotube field effect devices, with the quantity and size of the nanoparticles varying as a function of the applied potential. We show that the metal nanoparticle size can vary from 10 nm to over 300 nm, and the spatial distribution can change from very scarce decoration to a near continuous coating. Such metal nanoparticles have potential applications in chemical sensors, as they interact with gas molecules and generate an electrical signal in the nanotube, which can be detected. They can also be explored as biological anchoring sites for bio-functionalization of the nanotube, which is critical to developing highly sensitive and selective bio-sensors.


Ion-specific interactions between halides and basic amino acids in water.
Ion specific behavior of halides at surfaces of aqueous basic amino acids is unraveled by means of molecular dynamics simulations employing both nonpolarizable and polarizable force fields. Analysis in terms of density plots, cumulative sums, and residence times provides a clear, robust, and quantitative picture of specific ion effects. Small anions like fluoride, but not heavier halides, exhibits strong affinity for positively charged groups in the order guanidinium > imidazolium > ammonium. In contrast, large soft anions such as iodide are weakly attracted to nonpolar regions of the amino acids. Because interactions of halides with positively charged groups exhibit a local character and are not overwhelmingly strong, similar behavior will be observed (in an additive sense) as well at surfaces of hydrated proteins.


Free cholesterol and cholesterol esters in bovine oocytes: Implications in survival and membrane raft organization after cryopreservation.
Part of the damage caused by cryopreservation of mammalian oocytes occurs at the plasma membrane. The addition of cholesterol to cell membranes as a strategy to make it more tolerant to cryopreservation has been little addressed in oocytes. In order to increase the survival of bovine oocytes after cryopreservation, we proposed not only to increase cholesterol level of oocyte membranes before vitrification but also to remove the added cholesterol after warming, thus recovering its original level. Results from our study showed that modulation of membrane cholesterol by methyl-β-cyclodextrin (MβCD) did not affect the apoptotic status of oocytes and improved viability after vitrification yielding levels of apoptosis closer to those of fresh oocytes. Fluorometric measurements based on an enzyme-coupled reaction that detects both free cholesterol (membrane) and cholesteryl esters (stored in lipid droplets), revealed that oocytes and cumulus cells present different levels of cholesterol depending on the seasonal period. Variations at membrane cholesterol level of oocytes were enough to account for the differences found in total cholesterol. Differences found in total cholesterol of cumulus cells were explained by the differences found in both the content of membrane cholesterol and of cholesterol esters. Cholesterol was incorporated into the oocyte plasma membrane as evidenced by comparative labeling of a fluorescent cholesterol. Oocytes and cumulus cells increased membrane cholesterol after incubation with MβCD/cholesterol and recovered their original level after cholesterol removal, regardless of the season. Finally, we evaluated the effect of vitrification on the putative raft molecule GM1. Cholesterol modulation also preserved membrane organization by maintaining ganglioside level at the plasma membrane. Results suggest a distinctive cholesterol metabolic status of cumulus-oocyte complexes (COCs) among seasons and a dynamic organizational structure of cholesterol homeostasis within the COC. Modulation of membrane cholesterol by MβCD improved survival of bovine oocytes and preserved integrity of GM1-related rafts after vitrification.


Sarcoma botryoides in an infant.
A 17-month-old girl with no medical history presented at our emergency room with abnormal vaginal bleeding and vaginal tissue loss with a "grape bunch" appearance. Physical examination showed no abnormalities, but gynaecological examination showed abnormal vaginal tissue protruding through the vagina introitus. Given the typical clinical presentation, the age of the girl and the location and aspect of the lesion, there was a high suspicion of the botryoid variant of embryonal rhabdomyosarcoma of the vagina. Histology of a biopsy of the lesion was consistent with embryonal rhabdomyosarcoma. As no metastases were detected, the girl received chemotherapy. This case report describes the importance of early recognition of the typical clinical symptoms of sarcoma botryoides, since a rapid diagnosis followed by treatment is necessary to prevent death.


Optimum parameters in a model for tumour control probability including interpatient heterogeneity.
A model for computing tumour control probability (TCP) is studied which embodies a dependence on the size of the irradiated volume, the density of clonogenic cells and the dose received, together with the alpha and beta parameters of the linear quadratic model of cell kill. The model can be used to describe situations where both the dose and the clonogenic cell densities are inhomogeneously distributed; however there is still uncertainty about its radiobiological parameters and the author aims to establish parameters for four types of tumour. In its simplest form, when the volumes are spherical, the clonogenic cell density is considered constant throughout the volume and the dose is uniform, the model has been used (by D.J. Brenner, 1993) to predict the radiobiological parameter alpha which allows the model to best fit the observed clinical data for four types of tumour. Here a new set of fits to the data presented by Brenner is constructed using a model which includes the distribution of radiosensitivity across a heterogeneous patient population. It is shown that this leads to a different set of optimum radiobiological parameters when the clonogenic cell density is of the order of 107 cells cm-3.


Regulation of Mammalian Mitochondrial Gene Expression: Recent Advances.
Perturbation of mitochondrial DNA (mtDNA) gene expression can lead to human pathologies. Therefore, a greater appreciation of the basic mechanisms of mitochondrial gene expression is desirable to understand the pathophysiology of associated disorders. Although the purpose of the mitochondrial gene expression machinery is to provide only 13 proteins of the oxidative phosphorylation (OxPhos) system, recent studies have revealed its remarkable and unexpected complexity. We review here the latest breakthroughs in our understanding of the post-transcriptional processes of mitochondrial gene expression, focusing on advances in analyzing the mitochondrial epitranscriptome, the role of mitochondrial RNA granules (MRGs), the benefits of recently obtained structures of the mitochondrial ribosome, and the coordination of mitochondrial and cytosolic translation to orchestrate the biogenesis of OxPhos complexes.


Celebrating 75 years of oestradiol.
Oestrogens exert important effects on the reproductive as well as many other organ systems in both men and women. The history of the discovery of oestrogens, the mechanisms of their synthesis, and their therapeutic applications are very important components of the fabric of endocrinology. These aspects provide the rationale for highlighting several key components of this story. Two investigators, Edward Doisy and Alfred Butenandt, purified and crystalized oestrone nearly simultaneously in 1929, and Doisy later discovered oestriol and oestradiol. Butenandt won the Nobel Prize for this work and Doisy's had to await his purification of vitamin K. Early investigators quickly recognized that oestrogens must be synthesized from androgens and later investigators called this process aromatization. The aromatase enzyme was then characterized, its mechanism determined, and its structure identified after successful crystallization. With the development of knock-out methodology, the precise effects of oestrogen in males and females were defined and clinical syndromes of deficiency and excess described. Their discovery ultimately led to the development of oral contraceptives, treatment of menopausal symptoms, therapies for breast cancer, and induction of fertility, among others. The history of the use of oestrogens for postmenopausal women to relieve symptoms has been characterized by cyclic periods of enthusiasm and concern. The individuals involved in these studies, the innovative thinking required, and the detailed understanding made possible by evolving biologic and molecular techniques provide many lessons for current endocrinologists.


Patient- and Nurse-Controlled Analgesia: 22-Year Experience in a Pediatric Hospital.
Pediatric pain management has rapidly changed over the last 2 decades. In this study, we describe the changing practices and adverse events (AEs) related to patient-controlled analgesia (PCA) and/or nurse-controlled analgesia (NCA) over a 22-year period. After institutional review board approval, retrospective data from a single tertiary-care pediatric hospital were collected between 1994 and 2016. Subgroup analyses were done for surgical and medical case patients. We reported the number of times that PCA and/or NCA was ordered annually, the median and interquartile ranges for age, PCA and/or NCA duration and length of stay, and AE frequencies. Over 22 years, 32 338 PCAs and/or NCAs were ordered in this institution. Morphine and hydromorphone were used most commonly. Between 1994 and 2006, initial orders for PCA and/or NCA increased 2.5-fold. After 2007, initial orders for PCA and/or NCA rapidly decreased; after 2013, the decrease continued at a slower rate, with a total of 1007 orders in 2016. This decrease occurred despite increased hospital admissions and surgeries. Between 2007 and 2012, peripheral nerve blocks rapidly increased (10-fold). After 2002, 146 AEs were reported (1.0%). Of those, 50.5% were nonintercepted, and 20.6% were intercepted AEs; 5.5% and 6.2% were preventable and nonpreventable AEs, respectively. PCA and/or NCA usage continues to be common in pediatric patients, although usage has declined and stabilized in the setting of other emerging methods of analgesia and increases in the number of minimally invasive surgical procedures. The overall rate of AEs was extremely low. However, improvements to eliminate all errors are needed, especially with medications with a great risk of harm (such as opioids).


Anthocyanin biosynthetic pathway switched by metalloregulator PbrR to enable a biosensor for the detection of lead toxicity.
Environmental lead pollution mainly caused by previous anthropogenic activities continuously threatens human health. The determination of bioavailable lead is of great significance to predict its ecological risk. Bacterial biosensors using visual pigments as output signals have been demonstrated to have great potential in developing minimal-equipment biosensors for environmental pollutant detection. In this study, the biosynthesis pathway of anthocyanin was heterogeneously reconstructed under the control of the PbrR-based Pb(II) sensory element in Escherichia coli. The resultant metabolic engineered biosensor with colored anthocyanin derivatives as the visual signal selectively responded to concentrations as low as 0.012 μM Pb(II), which is lower than the detection limit of traditional fluorescent protein-based biosensors. A good linear dose-response pattern in a wide Pb(II) concentration range (0.012-3.125 μM) was observed. The color deepening of culture was recognized to the naked eye in Pb(II) concentrations ranging from 0 to 200 μM. Importantly, the response of metabolic engineered biosensors toward Pb(II) was not significantly interfered with by organic and inorganic ingredients in environmental water samples. Our findings show that the metabolic engineering of natural colorants has great potential in developing visual, sensitive, and low-cost bacterial biosensors for the detection and determination of pollutant heavy metals.


Multidimensional Timbre Spaces of Cochlear Implant Vocoded and Non-vocoded Synthetic Female Singing Voices.
Many post-lingually deafened cochlear implant (CI) users report that they no longer enjoy listening to music, which could possibly contribute to a perceived reduction in quality of life. One aspect of music perception, vocal timbre perception, may be difficult for CI users because they may not be able to use the same timbral cues available to normal hearing listeners. Vocal tract resonance frequencies have been shown to provide perceptual cues to voice categories such as baritone, tenor, mezzo-soprano, and soprano, while changes in glottal source spectral slope are believed to be related to perception of vocal quality dimensions such as fluty vs. brassy. As a first step toward understanding vocal timbre perception in CI users, we employed an 8-channel noise-band vocoder to test how vocoding can alter the timbral perception of female synthetic sung vowels across pitches. Non-vocoded and vocoded stimuli were synthesized with vibrato using 3 excitation source spectral slopes and 3 vocal tract transfer functions (mezzo-soprano, intermediate, soprano) at the pitches C4, B4, and F5. Six multi-dimensional scaling experiments were conducted: C4 not vocoded, C4 vocoded, B4 not vocoded, B4 vocoded, F5 not vocoded, and F5 vocoded. At the pitch C4, for both non-vocoded and vocoded conditions, dimension 1 grouped stimuli according to voice category and was most strongly predicted by spectral centroid from 0 to 2 kHz. While dimension 2 grouped stimuli according to excitation source spectral slope, it was organized slightly differently and predicted by different acoustic parameters in the non-vocoded and vocoded conditions. For pitches B4 and F5 spectral centroid from 0 to 2 kHz most strongly predicted dimension 1. However, while dimension 1 separated all 3 voice categories in the vocoded condition, dimension 1 only separated the soprano stimuli from the intermediate and mezzo-soprano stimuli in the non-vocoded condition. While it is unclear how these results predict timbre perception in CI listeners, in general, these results suggest that perhaps some aspects of vocal timbre may remain.


Loose Panicle1 encoding a novel WRKY transcription factor, regulates panicle development, stem elongation, and seed size in foxtail millet [Setaria italica (L.) P. Beauv.].
Panicle development is an important agronomic trait that aids in determining crop productivity. Foxtail millet and its wild ancestor green foxtail have recently been used as model systems to dissect gene functions. Here, we characterized a recessive mutant of foxtail millet, loose-panicle 1 (lp1), which showed pleiotropic phenotypes, such as a lax primary branching pattern, aberrant branch morphology, semi-dwarfism, and enlarged seed size. The loose panicle phenotype was attributed to increased panicle lengths and decreased primary branch numbers. Map-based cloning, combined with high-throughput sequencing, revealed that LP1, which encodes a novel WRKY transcription factor, is responsible for the mutant phenotype. A phylogenetic analysis revealed that LP1 belongs to the Group I WRKY subfamily, which possesses two WRKY domains (WRKY I and II). A single G-to-A transition in the fifth intron of LP1 resulted in three disorganized splicing events in mutant plants. For each of these aberrant splice variants, the normal C2H2 motif in the WRKY II domain was completely disrupted, resulting in a loss-of-function mutation. LP1 mRNA was expressed in all of the tissues examined, with higher expression levels observed in inflorescences, roots, and seeds at the grain-filling stage. A subcellular localization analysis showed that LP1 predominantly accumulated in the nucleus, which confirmed its role as a transcriptional regulator. This study provides novel insights into the roles of WRKY proteins in regulating reproductive organ development in plants and may help to develop molecular markers associated with crop yields.


A Hierarchical System for Evaluating the Biogenicity of Metavolcanic- and Ultramafic-Hosted Microalteration Textures in the Search for Extraterrestrial Life.
The low-temperature alteration of submarine volcanic glasses has been argued to involve the activity of microorganisms, and analogous fluid-rock-microbial-mediated alteration has also been postulated on Mars. However, establishing the extent to which microbes are involved in volcanic glass alteration has proven to be difficult, and the reliability of resulting textural biosignatures is debated, particularly in the early rock record. We therefore propose a hierarchical scheme to evaluate the biogenicity of candidate textural biosignatures found in altered terrestrial and extraterrestrial basaltic glasses and serpentinized ultramafic rocks. The hierarchical scheme is formulated to give increasing confidence of a biogenic origin and involves (i) investigation of the textural context and syngenicity of the candidate biosignature; (ii) characterization of the morphology and size range of the microtextures; (iii) mapping of the geological and physicochemical variables controlling the occurrence and preservation of the microtextures; (iv) in situ investigation of chemical signatures that are syngenetic to the microtexture; and (v) identification of growth patterns suggestive of biological behavior and redox variations in the host minerals. The scheme results in five categories of candidate biosignature as follows: Category 1 indicates preservation of very weak evidence for biogenicity, Categories 2 through 4 indicate evidence for increasing confidence of a biogenic origin, and Category 5 indicates that biogenic origin is most likely. We apply this hierarchical approach to examine the evidence for a biogenic origin of several examples, including candidate bacterial encrustations in altered pillow lavas, granular and tubular microtextures in volcanic glass from the subseafloor and a Phanerozoic ophiolite, mineralized microtextures in Archean metavolcanic glass, and alteration textures in olivines of the martian meteorite Yamato 000593. The aim of this hierarchical approach is to provide a framework for identifying robust biosignatures of microbial life in the altered oceanic crust on Earth, and in extraterrestrial altered mafic-ultramafic rocks, particularly on Mars.


Azygos vein aneurysm resection concomitant with heart valve repair via right thoracotomy.
Azygos vein aneurysm is very rare and is usually found incidentally because of its clinical silence. We report a case of recurrent pleural effusion caused by an azygos vein aneurysm in a patient with moderate mitral valve regurgitation (MR) and tricuspid valve regurgitation (TR). Since valve disease is considered a significant precipitating factor for both dyspnoea and pleural effusion, we decided to study the aetiologies of these conditions concomitantly. Azygos vein aneurysm resection in combination with tricuspid and mitral valve repair using cardiopulmonary bypass was performed successfully through a right anterior thoracotomy. The postoperative course was uneventful, and the patient reported improved exercise capacity.


Cognitive dysfunction in patients with renal failure requiring hemodialysis.
Renal failure patients show significant impairment on measures of attention and memory, and consistently perform significantly better on neuropsychological measures of memory and attention, approximately 24 hours after hemodialysis treatment. The objectives are to determine the cognitive dysfunction in patients with renal failure requiring hemodialysis. A total of 60 subjects comprising of 30 renal failure patients and 30 controls were recruited. The sample was matched for age, sex, and socioeconomic status. The tools used were the Standardized Mini-Mental State Examination and the Brief Cognitive Rating Scale. The patients showed high cognitive dysfunction in the pre-dialysis group, in all the five dimensions (concentration, recent memory, past memory, orientation and functioning, and self-care), and the least in the 24-hour post dialysis group. This difference was found to be statistically significant (P=0.001). Patients with renal failure exhibited pronounced cognitive impairment and these functions significantly improved after the introduction of hemodialysis.


The effect of choice interventions on retention-related, behavioural and mood outcomes: a systematic review with meta-analysis.
The provision of choice within interventions has been associated with increased motivation, engagement and interest, as well as improved clinical outcomes. Existing reviews are limited by their wide inclusion criteria or by not assessing behaviour change and mood outcomes. This review examines whether participant-driven choice-based interventions specifically are more likely to be enjoyed and accepted by participants compared to no-choice interventions, and whether this impacts on intervention outcomes in terms of behaviour change or mood. Forty-four randomised controlled trials were identified for inclusion. Random effects meta-analyses were performed for retention-related outcomes (drop-out, adherence and satisfaction), and aggregate behaviour change and mood outcomes. Choice-based interventions resulted in significantly less participant drop-out and increased adherence compared to interventions not offering choice. Results for the behaviour change and mood analyses were mixed. This meta-analytic review demonstrates that choice-based interventions may enhance participant retention and adherence, thus researchers and clinicians alike should consider the provision of choice when designing research and interventions. The evidence for the role of choice in behaviour change and mood is less convincing, and there is a need for more, higher quality research in this area.


Clinical and radiological comparison of femur and fibular allografts for the treatment of cervical degenerative disc diseases.
This consecutive retrospective study was designed to analyze and to compare the efficacy and outcomes of anterior cervical discectomy and fusion (ACDF) using a fibular and femur allograft with anterior cervical plating. A total of 88 consecutive patients suffering from cervical degenerative disc disease (DDD) who were treated with ACDF from September 2007 to August 2010 were enrolled in this study. Thirty-seven patients (58 segments) underwent anterior interbody fusion with a femur allograft, and 51 patients (64 segments) were treated with a fibular allograft. The mean follow-up period was 16.0 (range, 12-25) months in the femur group and 19.5 (range, 14-39) months in the fibular group. Cage fracture and breakage, subsidence rate, fusion rate, segmental angle and height and disc height were assessed by using radiography. Clinical outcomes were assessed using a visual analog scale and neck disability index. At 12 months postoperatively, cage fracture and breakage had occurred in 3.4% (2/58) and 7.4% (4/58) of the patients in the femur group, respectively, and 21.9% (14/64) and 31.3% (20/64) of the patients in the fibular group, respectively (p<0.05). Subsidence was noted in 43.1% (25/58) of the femur group and in 50.5% (32/64) of the fibular group. No difference in improvements in the clinical outcome between the two groups was observed. The femur allograft showed good results in subsidence and radiologic parameters, and sustained the original cage shape more effectively than the fibular allograft. The present study suggests that the femur allograft may be a good choice as a fusion substitute for the treatment of cervical DDD.


Older Adult Caregiving in an Amish Community.
Amish older adults represent a growing and understudied population whose current health practices, interactions with health care systems outside of their community, and care needs are unknown. Limited research exists on why, when, and how Amish older adults and their caregivers experience health care services outside of their family and community. The purpose of the current study was to describe and explore the perspectives of Amish caregivers caring for older adults and their experiences with health care services outside of their community. A qualitative phenomenological research design was used in combination with a community-based participatory framework with caregivers in a small, rural Amish settlement. Amish caregiving of older adults is a complex phenomenon that is influenced by cultural characteristics. Caregivers place significant cultural value on home caregiving, emphasize the experience as a blessing, and relate misunderstandings between themselves and outside health care providers as significant concerns. [Res Gerontol Nurs. 2018; 11(1):29-38.].


A 77-year-old female with a giant hepatic cyst.
A 77-year-old female presented with high blood pressure noted at home. She was having abdominal pain and distension for several years but attributed it to old age and ignored the symptoms. CT scan revealed a giant hepatic liver cyst. The cyst was subsequently excised via laparoscopic unroofing. The patient did well post op and her symptoms were alleviated.


Early sudden unexpected death in infancy (ESUDI)--three case reports and review of the literature.
Early sudden unexpected death in infancy (ESUDI) is a rare cause of death occurring in newborns during the first hours of life. Our aim was to find additional data for the identification of risk factors and establishment of prevention strategies. We describe three cases of ESUDI and give an overview of the literature. ESUDI was observed in term babies with normal birth weight after good postnatal adaptation within the first four hours of life. Maternal age was between 29 and 36 years, mothers were primiparous and of normal weight. All three events occurred during unobserved early skin-to-skin contact. Autopsy and post-mortem metabolic screening revealed no cause of death. A search of the MEDLINE and Web of Science (Thomson Reuters) databases brought to light 132 cases of ESUDI reported in the literature from 1985 to 2012. Concurrent with our observations, first parity and unobserved early skin-to-skin contact seem to be prime predictors of ESUDI. Other pre-described risk factors such as mode of delivery, birth weight, mother's age and body mass index were not seen in our patients. Close observation during the first hours of life is essential and can be life-saving, especially during early skin-to-skin contact.


Quality of Patient-Centered Care Provided to Patients Attending Hematological Cancer Treatment Centers.
The Institute of Medicine has recommended that improvements are needed in patient-centered care. This study examined hematological cancer patients' perceptions of which aspects of cancer care were being delivered well and areas that required improvement, and whether patient characteristics, or the treatment center they attended, were associated with quality of patient-centered care. Participants were recruited via three Australian hematological cancer treatment centers and completed a paper-and-pen survey assessing sociodemographic, disease, and psychological and treatment characteristics at recruitment. A second survey that contained the Quality of Patient-Centered Cancer Care measure was completed one month after recruitment (n = 215). The most frequently delivered feature of patient-centered cancer care was hospital staff showing respect for patients (91.0%). The area of care reported most commonly as not being delivered was hospital staff helping the patient find other cancer patients to talk to (29.8%). Patients without depression reported higher perceived quality of treatment decision-making, co-ordinated and integrated care, emotional support, follow-up care, respectful communication, and cancer information than patients with depression. The treatment center that was attended was associated only with the quality of cancer information patients received. Privacy issues may hinder staff connecting patients directly but this could be overcome via referrals to cancer organizations that offer peer support services.


A neural link between feeling and hearing.
Hearing and feeling both rely upon the transduction of physical events into frequency-based neural codes, suggesting that the auditory system may be intimately related to the somatosensory system. Here, we provide evidence that the neural substrates for audition and somatosensation are anatomically linked. Using diffusion tensor imaging with both deterministic and probabilistic tractography to measure white matter connectivity, we show that there are extensive ipsilateral connections between the primary auditory cortex and the primary and secondary somatosensory regions in the human cerebral cortex. We further show that these cross-modal connections are exaggerated between the auditory and secondary somatosensory cortex in the lesioned hemisphere of a patient (SR) with acquired auditory-tactile synesthesia, in whom sounds alone produce bodily sensations. These results provide an anatomical basis for multisensory interactions between audition and somatosensation and suggest that cross-talk between these regions may explain why some sounds, such as nails screeching down a chalkboard or an audible mosquito, can induce feelings of touch, especially on the contralesional body surface of patient SR.