Primary prevention of cardiovascular disease by an occupational health service.
Worksites are considered to be a key channel for the delivery of interventions to prevent cardiovascular disease. The aim of this study was to evaluate the effect on the blood cholesterol levels of an intervention program offered by an occupational health service. The intervention group consisted of 95 employees and the reference group consisted of 74 employees, in all, 169 subjects, with a serum cholesterol > or = 5.2 mmol/l. Both groups completed a standardized questionnaire. Occupational health nurses carried out the blood sampling before and after the program. The intervention group was then offered counseling on physical activity and a dietician offered individual counseling on healthy food habits. The reference group was not the subject of the intervention program. The mean cholesterol level decreased by 0.3 mmol/l (5%) in the intervention group and for the men the decrease was 0.5 mmol/l, while the mean level of the reference group was unchanged. Furthermore, there was a nonsignificant decrease of the mean triglyceride level in the intervention group. The results of this controlled trial indicates that risk factors for cardiovascular disease can be reduced by interventions at the worksite. Even modest reductions of cholesterol levels may reduce the risk to a tangible degree.


The role of 'eat-me' signals and autophagy cargo receptors in innate immunity.
Selective autophagy is an important effector mechanism of cell autonomous immunity, in particular against invasive bacterial species. Anti-bacterial autophagy is activated by rupture of bacteria-containing vacuoles and exposure of bacteria to the cytosol. The autophagy cargo receptors p62, NDP52 and Optineurin detect incoming bacteria that have become associated with specific 'eat-me' signals such as Galectin-8 and poly-ubiquitin and feed them into the autophagy pathway via interactions with phagophore-associated ATG8-like proteins. Here we review recent progress in the field regarding the origin of bacteria-associated 'eat-me' signals, the specific roles of individual cargo receptors and how disrupting cargo receptor function may be important for bacterial evasion of autophagy.


Clinical and molecular characteristics of kinase domain duplications across diverse cancer types in the Chinese population.
Kinase domain duplications (KDDs) have recently been recognized as oncogenic mutations and possible association with drug resistance in cancers. Here, targeted sequencing was performed with the tumor tissue and/or plasma from 65 cancer patients with KDDs. Intact KDDs were identified in approximately 0.1% of the total population across multiple cancer types. EGFR KDD was first identified in colorectal cancer and breast cancer, whereas FGFR2 KDD was first identified in gastric cancer. Tumors with EGFR KDD displayed lower concurrent TP53 gene alterations (p = 0.03) and slightly higher chromosome instability (p = 0.27) compared to tumors with non-EGFR-KDDs. Immune pathway analysis further revealed the enrichment of the cytokine receptors pathway (93%) in the KDD carriers. Hyperprogression-related gene mutations were identified in four cases. Collectively, our data revealed the genomic features of KDD alterations in a multi-cancer cohort, providing more information for the potential treatment application in the KDD carriers.


Intravenous catheter aspiration for obtaining basic analytes during intravenous infusion.
The aspiration of blood through a functioning IV line to obtain samples for laboratory analysis was evaluated. Thirty-eight emergency department patients were studied. Each had an 18-gauge IV catheter placed and then received a 100-mL bolus of either normal saline, lactated Ringer's, or 5% dextrose in water. Two samples of blood ("first aspirate" and "second aspirate") were then aspirated from the IV catheter while one sample was obtained by venipuncture from the opposite arm (control). All three samples were then analyzed for CBC, electrolytes, BUN, creatinine, and glucose. Catheter aspiration succeeded in 30 of 38 attempts (79%). Three samples were hemolyzed, and five samples were unable to be fully aspirated. Results of paired t testing showed only occasional statistical significance and except for bicarbonate were not of clinical significance. This study suggests that catheter aspiration is a useful method of obtaining blood for certain laboratory tests in patients receiving IV infusions.


Impact of romosozumab on serum calcium concentration and factors predicting the fluctuations in calcium concentration upon romosozumab administration: A multicenter retrospective study.
As romosozumab has both bone anabolic and antiresorptive effects, it is not clear which patient groups are more likely to have decreased calcium concentrations when treated with romosozumab. The aim of this study was to investigate the impact of romosozumab treatment on serum calcium concentration in patients with osteoporosis with a high risk of fractures and identify factors that might be associated with, or even predict, a fluctuation in calcium concentration upon romosozumab administration. In total, 47 patients were included in this retrospective study. We performed a Wilcoxon signed-rank test to identify differences in the calcium concentration before and 1 month after romosozumab initiation. Associations between baseline variables and changes in serum calcium concentration were investigated with a multiple-linear regression model using a forward-backward stepwise procedure. Romosozumab administration reduced the serum calcium concentration by an average of 3.1 % after 1 month. No patient complained of symptoms of hypocalcemia during the first month after treatment. Univariate regression analysis showed that age and calcium concentration were significantly associated with the decrease in serum calcium concentrations by romosozumab administration. In addition, stepwise regression analysis identified age and calcium concentrations as independent factors associated with the decrease in calcium concentration by romosozumab. Romosozumab administration caused a modest but significant decrease in serum calcium concentration. Older age and higher baseline calcium concentrations were associated with a greater decrease in calcium concentrations by romosozumab administration. Although the likelihood of severe hypocalcemia from romosozumab administration may be low, physicians prescribing romosozumab to patients with osteoporosis should be aware of the symptoms of hypocalcemia and promptly evaluate calcium levels if patients complain of these symptoms.


Insulin-Like Growth Factor 2 (IGF-2) Regulates Neuronal Density and IGF-2 Distribution Following Hippocampal Intracerebral Hemorrhage.
The insulin-like growth factor 2 (IGF-2) is a growth factor and anti-inflammatory cytokine that plays a crucial role in memory consolidation. However, the precise role of this factor in acute brain damage is still unclear. The present study aimed to evaluate the variations in hippocampal IGF-2 distribution on different days and investigate the effect of recombinant IGF-2 on memory cell density, and IGF-2 distribution following acute hippocampal damage resulting from intracerebral hemorrhage (ICH). ICH was induced by injection of 100 μL of autologous blood into the left hippocampus of 72 male Sprague-Dawley rats. Recombinant IGF-2 was injected into the damaged hippocampus 30 min post-induction of ICH in the ICH-IGF-2 group. Then, on postoperative days 1, 3, 7, and 14, samples of brain tissue were collected to perform histopathological and immunohistochemical examinations. The stereological study indicated that the volume of the hippocampus and the number of neurons had a significant reduction, and the infarct volume had a significant increase following ICH. Following the injection of IGF-2, a significant improvement was observed in stereological studies. Immunohistochemical data showed that IGF-2 distribution increased in the hippocampus on different days after ICH, and IGF-2 injection led to a dramatic reduction in this distribution. In summary, the gradual increase of endogenous IGF-2 as growth and anti-inflammatory factor following hemorrhagic stroke reveals a critical role of this factor in brain recovery after injury. Moreover, the injection of IGF-2 can prevent cell death and alleviate the damage caused by the hemorrhagic stroke.


Five-year results of vocal fold augmentation using autologous fat or calcium hydroxylapatite.
To evaluate 5-year voice outcomes of vocal fold augmentation (VFA) using autologous fat (AF) injection via direct microlaryngoscopy versus office-based calcium hydroxylapatite (CaHA) injection. Retrospective study of patients who underwent VFA between 2012 and 2015, with a 5-year follow-up. Patients with a glottic gap of ≤ 3 mm caused by unilateral vocal fold paralysis or vocal fold atrophy were included in the study. VFA was performed using AF injection via direct microlaryngoscopy in 17 patients, and using office-based CaHA injection in 19 patients. Subjective satisfaction with voice, voice handicap index (VHI), and maximal phonation time (MPT) were analyzed pre-injection, and at 12 and 60 months post-VFA. Altogether 36 patients underwent VFA between 2012 and 2015, of whom 5 were excluded within 1 year post-VFA, and 2 were excluded between 1 and 5 years post-VFA. Of the remaining 29 patients, 3 (10.3%) underwent re-intervention at between 1 and 3 years post-VFA. Thus, the 5-year follow-up included 26 patients (72.2%; 11 males and 15 females). At 5 years after surgery, 73.1% of the patients were satisfied with their voice, with no significant between-group difference (P = 0.307). The mean improvement of VHI was 28.8 ± 17.82 in the autologous fat group versus 33 ± 26.24 in the CaHA group (P = 0.458). MPT improvement was also similar between the two groups: 6.2 ± 4.26 for the autologous fat group versus 6.3 ± 4.34 for the CaHA group (P = 0.667). Both AF injection via direct microlaryngoscopy and office-based CaHA injection yielded good and comparable 5-year results.


Marek's disease virus genome separation from feather tip extracts by pulsed field gel electrophoresis.
Marek's disease virus is an oncogenic herpes virus of poultry that is highly cell associated. In the infected tissues and tumors the virus replicates in a low copy number. The propagation and dissemination of the virus takes place at the feather follicle epithelium, where the viral genome is produced in high copy number. As the viral genome is a large circular DNA molecule (200 kbp), pulsed field gel electrophoresis was used for separation of the viral genome directly from the infected chicken. DNA was extracted from tumors or feather tips by the phenol:chloroform technique or by low melting agar technique. It was found that feathers, being the site of virus productive replication, are useful for separation of free Marek's disease virus DNA from in vivo infections.


Correspondence of results from hepatocyte studies with in vivo response.
Isolated hepatocyte systems are being examined in our laboratory for a number of applications, including alternatives to animal testing. This report summarizes findings from studies with chlorinated aliphatics, acetaminophen, nitrotoluenes, and cyanide and its antidotes that relate to in vivo toxicity and validation of these systems for cytotoxicity screening.


Adolescent Immunization Schedule: Need for a Relook.
Adolescent immunization is one of the important yet a neglected field in India. There is no adolescent-specific schedule in the government's Universal Immunization Program. Though a separate adolescent immunization schedule exists for the private sector, there is almost no data on the coverage rates of the adolescent vaccines. With the changing epidemiology of certain vaccine preventable diseases, rapid development in the field of vaccinology and the advent of some new vaccines, there is a need to revisit the adolescent vaccination schedule. Common vaccine preventable diseases like dengue, mumps, hepatitis A and typhoid should be given higher priority whereas an alternate strategy should be adopted on the use of the vaccine against diphtheria, tetanus and pertussis.


Serum level of prostatic acid phosphatase after diagnostic rectal examination. Comparison between spectrophotometric and a radioimmunological assay.
The serum level of prostatic acid phosphatase was measured before and after diagnostic rectal palpation in 24 patients with a clinically normal prostate and in 32 patients with benign hyperplasia of the prostate. There was a significant rise in the 32 patients with benign prostatic hyperplasia. All of the values had returned to the original level after 24 h. Similar results were obtained with either a spectrophotometric method or a radioimmunoassay.


The interpretation of multi-exponential water proton transverse relaxation in the human and porcine eye lens.
We report results of 1H NMR transverse relaxation experiments on human and porcine eye lenses. Several authors have reported that transverse relaxation is not mono-exponential when observed by the Carr-Purcell-Meiboom-Gill (CPMG) sequence and have interpreted the results by postulating the presence of "pools" of water molecules in different binding environments that do not exchange rapidly on the NMR timescale. We have compared CPMG data for intact lenses with results for lens homogenates and have combined a CPMG spectroscopic pulse train with NMR micro-imaging to study the nature of the transverse relaxation process in human and porcine lenses. Fast exchange of water protons with the lens proteins (crystallins) leads to an enhanced transverse relaxation rate that varies linearly with protein concentration. At the resolution of NMR micro-imaging the transverse relaxation process is mono-exponential. The results show that the multi-exponential CPMG data observed spectroscopically for whole lenses reflect spatial variations in crystallin content through the lens rather than the presence of distinct "bound" and "free" water pools.


Structural features, temperature adaptation and industrial applications of microbial lipases from psychrophilic, mesophilic and thermophilic origins.
Microbial lipases are very prominent biocatalysts because of their ability to catalyze a wide variety of reactions in aqueous and non-aqueous media. Here microbial lipases from different origins (psychrophiles, mesophiles, and thermophiles) have been reviewed. This review emphasizes an update of structural diversity in temperature adaptation and industrial applications, of psychrophilic, mesophilic, and thermophilic lipases. The microbial origins of lipases are logically dynamic, proficient, and also have an extensive range of industrial uses with the manufacturing of altered molecules. It is therefore of interest to understand the molecular mechanisms of adaptation to temperature in occurring lipases. However, lipases from extremophiles (psychrophiles, and thermophiles) are widely used to design biotransformation reactions with higher yields, fewer byproducts, or useful side products and have been predicted to catalyze those reactions also, which otherwise are not possible with the mesophilic lipases. Lipases as a multipurpose biological catalyst have given a favorable vision in meeting the needs of several industries such as biodiesel, foods, and drinks, leather, textile, detergents, pharmaceuticals, and medicals.


Is back pain a diagnostic problem in clinical practices? A rare case report.
Multiple thoracic disc herniations are rare, and few reports exist in the literature. Diagnosis of these herniations is often missed because of their lack of specific clinical presentation. They may be treated conservatively or surgically. We presented a 35-year-old woman with five contiguous level thoracic disc herniations. She was admitted with upper back pain. Magnetic resonance imaging showed disc herniations at levels T6-7, T7-8, T8-9, T9-10 and T10-11. All were left sided and on the same line in the sagittal plane. The patient underwent conservative treatment. This report presented an unusual case and discussed its mechanisms.


Morphology and laminar distribution of neuropeptide Y immunoreactive neurons in the human striate cortex.
The morphology, laminar distribution, and distribution relative to cytochrome oxidase patches of neuropeptide-Y immunoreactive (NPY-ir) neurons were studied in the human striate cortex. The density of NPY-ir cells was highest in the white matter. NPY-ir neurons were sparsely distributed within the cortical layers. NPY-ir neurons were located in both cytochrome oxidase dense patch and interpatch regions. However, the paucity of NPY-ir neurons in layer III, where cytochrome oxidase patches are most clearly demonstrated, precluded establishing a clear relationship of NPY-ir neurons to cytochrome oxidase patches. NPY-ir neurons exhibited a variety of nonpyramidal morphologies, and many of them had axons with recurrent or looped trajectories. A dense plexus of NPY-ir axons was located just beneath the pia, and these axons were concentrated at the entry points of pial blood vessels. Other NPY-ir neurons had cell bodies or processes in close proximity to cerebral capillaries. These results suggest a role of NPY in cortical metabolism, control of cerebral circulation, or activity-related changes in local blood flow.


Isolated phrenic nerve injury after apparently atraumatic puncture of the internal jugular vein.
Vascular lesions due to subclavian and internal jugular vein puncture may result in hematomas, which are usually clinically evident. While mostly benign, some of these hematomas can cause compression of the surrounding structures. When the hematoma is obvious, straightforward correlation can be made between the symptoms, for instance nerve compression, and the clinical signs. We present a case where we missed the diagnosis of phrenic nerve paralysis, which occurred after an unsuccessful, but apparently atraumatic attempt to puncture the internal jugular vein, prior to cardiac surgery. At the time the diagnosis was made (8 days post-op), the radiographic appearance of the neck was normal, and further investigation (i.e., CT-scan) had become pointless. A retrospective study of serial chest X-rays disclosed a space occupying lesion in the right lateral neck that displaced the nasogastric tube. This abnormality could only be seen on the first film and disappeared on the following. Since phrenic nerve paralysis is extremely rare in our institution, even after cardiac surgery, and as there was no clinical evidence of hematoma, our attention was not been drawn to the only definite sign that could have led to an early diagnosis.


[Benzylbis(dimethylamino)methylsilyl-kappa2C,N](N,N,N',N'-tetramethylethylenediamine-kappa2N,N)lithium(I).
The title compound, [Li(C12H21NSi)(C6H16N2)], is an intermediate in the synthesis of the corresponding organometallic compounds. The molecule has an unusual C-Si-N-Li four-membered heterocycle which adopts a folded conformation, with the coordination around the Li, N, C and Si atoms being distorted tetrahedral. Its structure is strongly supported by 1H NMR, 13C NMR and 13C-1H correlation spectra. The compound has potential for application in the synthesis of other novel organometallic compounds.


Central nervous system tumors.
Central nervous system tumors are the most frequent malignant tumor in children and the main cause of death in this age group after traffic accidents. The current estimates are that one adult in 2500 is a survivor of a brain tumor that occurred during childhood. These tumors are particularly heterogeneous in terms of histology/biology, treatment, and outcome. They share, however, a high risk of neurological and cognitive morbidity due to the disease itself and the treatment modalities (radiotherapy, surgery, and chemotherapy). Diagnosis is frequently delayed because symptoms are usually nonspecific at the beginning of the evolution. Posterior fossa is the most frequent site and the tumors present most frequently with signs of intracranial hypertension. Supratentorial tumors are more frequent in infants and in adolescents; seizures are not uncommon, especially for benign tumors. When adjuvant treatment is needed, radiotherapy is usually the mainstay apart from some histologies where chemotherapy may be sufficient: low-grade gliomas, desmoplastic medulloblastomas, malignant glial tumors in infants. Multidisciplinary care is best performed in tertiary care centers and should include early rehabilitation programs soon after surgery.


Metabolic changes in a conidia-induced Claviceps paspali strain during submerged fermentation.
Chemical changes in the mycelium of the conidial Claviceps paspali mutant strain, isolated after gamma irradiation, were followed during the course of submerged fermentation and compared with the mycelial parent strain; both strains are capable of producing simple lysergic acid derivatives. The syntheses of lipids, carbohydrates, phosphates, nucleic acids, proteins, and alkaloids, as well as nutrient uptake, were determined. It was found that conidiation induced by mutagenic treatment was accompanied by a set of changes in the metabolic pattern. In the conidial mutant, the primary and secondary metabolic activities were repressed and the protein to nonprotein compound ratio of the cells was changed in favour of protein compounds.


Generation of a large-scale vascular bed for the in vitro creation of three-dimensional cardiac tissue.
The definitive treatment for severe heart failure is transplantation. However, only a small number of heart transplants are performed each year due to donor shortages. Therefore, novel treatment approaches based on artificial organs or regenerative therapy are being developed as alternatives. We have developed a technology known as cell sheet-based tissue engineering that enables the fabrication of functional three-dimensional (3D) tissue. Here, we report a new technique for engineering human cardiac tissue with perfusable blood vessels. Our method involved the layering of cardiac cell sheets derived from human induced pluripotent stem cells (hiPSCs) on a vascular bed derived from porcine small intestinal tissue. For the vascular bed, a segment of porcine small intestine was harvested together with a branch of the superior mesenteric artery and a branch of the superior mesenteric vein. The small intestinal tissue was incised longitudinally, and the mucosa was resected. Human cardiomyocytes derived from hiPSCs were co-cultured with endothelial cells and fibroblasts on a temperature-responsive dish and harvested as a cardiac cell sheet. A triple-layer of cardiac cell sheets was placed onto the vascular bed, and the resulting construct was subjected to perfusion culture in a bioreactor system. The cardiac tissue on the vascular bed pulsated spontaneously and synchronously after one day of perfusion culture. Electrophysiological recordings revealed regular action potentials and a beating rate of 105 ± 13/min (n = 8). Furthermore, immunostaining experiments detected partial connection of the blood vessels between the vascular bed and cardiac cell sheets. We succeeded in engineering spontaneously beating 3D cardiac tissue in vitro using human cardiac cell sheets and a vascular bed derived from porcine small intestine. Further development of this method might allow the fabrication of functional cardiac tissue that could be used in the treatment of severe heart failure.


The impact of the timely birth dose vaccine on the global elimination of hepatitis B.
In 2016 the World Health Organization set the goal of eliminating hepatitis B globally by 2030. Horizontal transmission has been greatly reduced in most countries by scaling up coverage of the infant HBV vaccine series, and vertical transmission is therefore becoming increasingly dominant. Here we show that scaling up timely hepatitis B birth dose vaccination to 90% of new-borns in 110 low- and middle-income countries by 2030 could prevent 710,000 (580,000 to 890,000) deaths in the 2020 to 2030 birth cohorts compared to status quo, with the greatest benefits in Africa. Maintaining this could lead to elimination by 2030 in the Americas, but not before 2059 in Africa. Drops in coverage due to disruptions in 2020 may lead to 15,000 additional deaths, mostly in South-East Asia and the Western Pacific. Delays in planned scale-up could lead to an additional 580,000 deaths globally in the 2020 to 2030 birth cohorts.


Homocysteinemia due to folate deficiency.
We examined the relationship between serum folate and total homocyst(e)ine levels by determining protein-bound homocyst(e)ine in stored serum from 19 subjects with subnormal serum folate (less than 2 ng/mL), 137 subjects with low normal serum folate (between 2.0 and 3.9 ng/mL), 44 subjects with normal serum folate (between 4.0 and 17.9 ng/mL), and 38 subjects with high serum folate (above 18 ng/mL). Eighty-four percent of the subjects with subnormal serum folate and 56% of the subjects with low normal serum folate had more than 7.05 nmol/mL serum total homocyst(e)ine (ie, more than two standard deviations above the normal mean). Thirty-two percent of these subjects had more than a three-fold increase in serum total homocyst(e)ine. These observations support the hypothesis that depletion of tissue folate causes homocysteinemia in nonhomocystinuric subjects. Subnormal as well as low normal concentrations of serum folate appear to produce an accumulation of homocyst(e)ine. In addition, relatively normal levels of serum total homocyst(e)ine were observed in four pregnant women with low serum folate, supporting previous suggestions of an influence of female sex hormone(s) in homocysteine metabolism.


[Skeletotopy of the kidneys of American mink Mustela vison (Brisson, 1756)].
A radiological and anatomical analysis of the position of 120 kidneys of 60 minks of both sexes in relation to the vertebral column was carried out. It was found that they are situated at the height of Th13 to L5, the right kidney is situated more cranially than the left one and most often across the fourteenth rib (female 51.5%, male 59.3%).


Expression of Leptin and Sirtuin-1 is associated with poor prognosis in patients with osteosarcoma.
Sirtuin-1 (SIRT1) is a downstream target of Leptin, and its inhibition promotes p53-mediated apoptosis. This study aimed to evaluate the expression and prognostic significance of Leptin and SIRT1 in osteosarcoma. Leptin and SIRT1 levels in osteosarcoma samples from 89 patients were evaluated by immunohistochemical staining. The correlations between Leptin and SIRT1 expression with clinical parameters were analyzed by Spearman's test and Pearson's chi-squared test. Prognostic factors were identified by Univariate and multivariate Cox regression analysis. We found that Leptin and SIRT1 expression was low in 23.6% and 20.2%; moderate in 25.8% and 24.7%; and high in 50.5% and 55.1% of patients with osteosarcoma, respectively. Both Leptin and SIRT1 expression were significantly associated with the Enneking stage, distant metastasis and neo-adjuvant chemotherapy. Leptin expression and SIRT1 expression were significantly correlated and they were significantly associated with shorter overall survival. Among osteosarcoma patients who received neo-adjuvant chemotherapy, both Leptin and SIRT1 expression were significantly associated with overall survival of osteosarcoma patients in univariate analysis, but only SIRT1 expression was significantly associated with overall survival of osteosarcoma patients in multivariate analysis. In conclusion, Leptin and SIRT1 expressions are significantly associated with shorter overall survival of osteosarcoma patients, and SIRT1 expression is a significant independent prognostic indicator in patients with osteosarcoma.


Effect of serum content and diluent selection on assay sensitivity and signal intensity in multiplex bead-based immunoassays.
In the Luminex multiplexed immunoassay system, complex samples such as human serum are diluted to minimize disturbing matrix effects with a specific diluent. This diluent has to imitate the sample matrix to allow interpolation and has to provide optimal cytokine-antibody binding for all cytokines. Because diluents influence multiplex immunoassay results, this paper explores several methods to determine the quality of a chosen diluent. Two commercially available diluents, DY997 and RD6 from R&D Systems, were compared in a 19-plex immunoassay setup from Luminex. Using diluent DY997, multiplex signal intensity was reduced by 55% when spiked samples (chemokines and cytokines at 100 pg/mL) contained 50% v/v human serum, compared to samples containing 25% v/v. When using diluent RD6, signal intensity was reduced by 20% when samples contained 50% v/v human serum, compared to 25% v/v human serum. Diluent DY997 showed decreasing multiplex assay sensitivity with increasing protein concentrations, but not as low as in the presence of 50% v/v human serum. In a 19-plex setup, this paper describes signal intensity, assay sensitivity and background signal levels in relation to the total volume-fraction of serum and protein concentration. For the determination of cytokines in serum samples with the multiplexed system Luminex the diluent RD6 seems more appropriate than the diluent DY997.


Fluoropyrimidine chemotherapy: recommendations for DPYD genotyping and therapeutic drug monitoring of the Swiss Group of Pharmacogenomics and Personalised Therapy.
Fluoropyrimidines (FPs), mainly 5-fluorouracil (5-FU) and its oral prodrug capecitabine (Cap), remain the backbone of the treatment of many different solid tumors. Despite their broad use in clinical routine, 10–40% of patients experience severe, and in rare cases (0.2–0.5%) even lethal, FP-related toxicity in early chemotherapy cycles. Today, there is a plethora of evidence that genetic variants in the gene encoding for the 5-FU catabolising enzyme dihydropyrimidine dehydrogenase (DPD, encoded by DPYD) are predictive of severe FP-related toxicities, and international clinical practice recommendations for DPYD genotype-guided FP dosing and therapeutic drug monitoring (TDM) are available. In spite of this strong evidence and DPYD genotyping becoming standard practice in other countries, it is has not been widely adopted in Switzerland to date. Here, we discuss current guidelines on genotype-guided FP dosing and TDM, and propose recommendations tailored to the situation in Switzerland to facilitate their clinical uptake for the further individualisation of FP chemotherapy. We recommend preemptive testing of four DPYD variants (c.1905+1G>A (rs3918290), c.1679T>G (rs55886062), c.2846A>T (rs67376798) and c.1129-5923C>G (rs75017182, c.1236G>A/HapB3)) in patients with an indication for FP-based chemotherapy, with the costs reimbursed through the compulsory health insurance in Switzerland. Carriers of these variants (6.5% in the Swiss population) have a 40–50% risk of developing severe early-onset toxicity when treated with standard FP doses. In these patients, we therefore recommend the use of a reduced starting dose, based on a dose adjustment scheme provided herein. Furthermore, we recommend the use of infusional 5-FU in patients with a DPYD risk genotype in order to enable TDM-based dose escalation. Only if the use of an infusional 5-FU regimen is not feasible should a slow titration of Cap, starting with the recommended reduced dose and basing further doses on monitoring of toxicity, be considered. Given that several studies have shown that TDM in 5-FU treatment improves not only the therapy's safety, but potentially also its efficacy, we also include detailed TDM-based dosing guidelines and discuss the pre-analytical aspects of 5-FU TDM.


Towards an insight on photodamage in hair fibre by UV-light: An experimental and theoretical study.
In this research, an experimental and theoretical study was conducted to design a photodegradation mechanism of the amino acid tryptophan (Trp) in hair fibres. For the experimental research, Caucasian hair fibres were exposed to several different solar radiation simulation periods. Then, Trp and its photoproducts (N-formylkynurenine and kynurenine) were assayed by excitation and emission spectroscopic analysis. For the theoretical study, reactions involved in the photodegradation of Trp were evaluated by high-level quantum mechanical calculations in a density functional theory (DFT) framework which indicate a probable Trp degradation mechanism with a minimum expended energy pathway. The biochemistry concerning these reactions is essentially important for a biological system where the degradation of Trp occurs.


Emotions at work.
Health-care organizations are just beginning to recognize the importance of developing a manager's emotional quotient, or interpersonal skills.


Regulatory T cells in pregnancy.
Tolerance mechanisms are responsible for the survival of the fetus within the maternal uterus without being attacked by the cells of the maternal immune system despite their direct contact. Regulatory T cells (Treg) were claimed to be important players in the tolerance towards the fetus bearing alloantigens. Recent evidence confirmed an augmentation in the number of Treg during pregnancy and, most importantly, diminished numbers of Treg were associated with immunological rejection of the fetus. This could be prevented by adoptively transferring CD4(+)/CD25(+) Treg cells from normal pregnant mice into abortion-prone animals. Treg prevented abortion while creating a transient tolerant microenvironment characterized by high levels of TGF-beta, LIF, and HO-1. Downregulated levels of Treg were accordingly also reported during human miscarriage. Furthermore, we have evidence suggesting that, to be protective, Treg need to be activated by male antigens during pregnancy.


Are Gait Parameters for Through-knee Amputees Different From Matched Transfemoral Amputees?
Through-knee amputation is a common amputation level after battlefield injuries during the medical evacuation process. However, there are limited data comparing through-knee amputation with transfemoral amputation as a definitive amputation level in terms of gait parameters. (1) Does through-knee amputation result in improved gait velocity when compared with matched transfemoral amputees? (2) Do through-knee amputees have a faster gait cadence than matched transfemoral amputees? (3) Do through-knee amputees have a different stride length or stride width than matched transfemoral amputees? (4) Does through-knee amputation result in decreased work of ambulation when compared with matched transfemoral amputees? Between January 2008 and December 2012, six male active-duty military patients who had undergone unilateral through-knee amputations as a result of trauma underwent gait studies at our institution. Of those, four of six underwent gait analysis after being able to walk for at least 3 months without assistive devices, and this group was studied here. Most through-knee amputees who were not included had elective revisions of their amputations from through-knee to a transfemoral amputation before completing 3-month gait data. Each of the amputees studied was matched to a transfemoral amputee based on height, body mass index, and contralateral amputation level resulting in a case-control study of active-duty military male amputee patients. Inclusion required complete gait data collected while walking at a self-selected pace wearing custom prosthetic devices. The through-knee amputees had a median (range) age of 32 years (23-41 years) and the transfemoral amputees had a median age of 24 years (22-27 years). Three-dimensional gait data were collected and analyzed. A power analysis found that to detect a clinically important difference (set at a change in work of ambulation of 1 J/kgm) with a p value of 0.05 and a β set to 0.2, a study population of 56 patients per group would be required; that being said, our results on a much smaller population must be considered exploratory. With the numbers available, we found no differences in gait velocity when comparing through-knee (1.18 m/sec) and matched transfemoral amputees (1.20 m/sec, difference of medians = 0.02 m/sec; p = 0.964). Likewise, we found no differences in gait cadence when comparing through-knee with transfemoral amputees (104 versus 106 steps/min, respectively, difference of means 2 steps/min, p = 0.971). There was no difference in stride length or stride width when comparing through-knee (70 cm and 18 cm, respectively) with transfemoral amputees (70 cm and 19 cm, respectively; p = 0.948 and p = 0.440). With the numbers available, we did not identify a difference in the work of ambulation for through-knee amputees when compared with matched transfemoral amputees (8.3 versus 7.5 J/kg, respectively; p = 0.396). Based on our findings, we are unable to demonstrate any functional advantages of knee disarticulation over transfemoral amputation. Although there are theoretical advantages for maintaining an intact femur during the medical evacuation and serial débridement process, we question the utility of knee disarticulation as a definitive amputation level; however, larger numbers of patients are needed to confirm these results. Level III, therapeutic study.


Levels of DNA damage in blood leukocyte samples from non-diabetic and diabetic female rats and their fetuses exposed to air or cigarette smoke.
The objective of the present study was to evaluate DNA damage level in blood leukocytes from diabetic and non-diabetic female Wistar rats exposed to air or to cigarette smoke, and to correlate the findings with levels of DNA damage detected in blood leukocyte samples from their fetuses. A total of 20 rats were distributed into four experimental groups: non-diabetic (control; G1) and diabetic exposed to filtered air (G2); non-diabetic (G3) and diabetic (G4) exposed to cigarette smoke. Rats placed into whole-body exposure chambers were exposed for 30min to filtered air (control) or to tobacco smoke generated from 10 cigarettes, twice a day, for 2 months. Diabetes was induced by a pancreatic beta-cytotoxic agent, streptozotocin (40mg/kgb.w.). At day 21 of pregnancy, each rat was anesthetized and humanely killed to obtain maternal and fetal blood samples for genotoxicity analysis using the alkaline comet assay. G2, G3 and G4 dams presented higher DNA damage values in tail moment and tail length as compared to G1 group. There was a significant positive correlation between DNA damage levels in blood leukocyte samples from G2 and G3 groups (tail moment); G3 and G4 groups (tail length) and G3 group (tail intensity) and their fetuses. Thus, this study showed the association of severe diabetes and tobacco cigarette smoke exposure did not exacerbate levels of maternal and fetal DNA damages related with only diabetes or cigarette smoke exposure. Based on the results obtained and taking into account other published data, maternal diabetes requires rigid clinical control and public health and education campaigns should be increased to encourage individuals, especially pregnant women, to stop smoking.


Influence of social dominance on production, welfare and the quality of meat from beef bulls.
The aim of this study was to assess the effect of social dominance on some indicators of welfare, production and meat quality of young bulls. A total of 60 bulls of the Gasconne breed, 9 months old, housed indoors were used. Indices of success order were calculated to reflect social dominance of each bull into three ranking categories (low, middle and high). Blood samples were taken to measure cortisol, lactate, glucose, creatine kinase, non-esterified fatty acid and neutrophil/lymphocyte ratio (N/L). M. longissimus samples were analysed in terms of pH, water holding capacity (WHC), texture, colour and sensorial attributes. Social rank influenced cattle stress response, which had an effect on productive performance but not on meat quality traits, with the exception of the sensory traits. These results emphasize the importance of implementing best management practices during pre-harvest handling of cattle in order to modulate any possible risk factor for social stress.


Common needs in uncommon conditions: a qualitative study to explore the need for care in pediatric patients with rare diseases.
Challenges faced by children diagnosed with a rare disease or complex condition and their family members are often characterized by disease-specific complexities, such as a prolonged diagnostic process, an uncertain prognosis, and the absence of curative treatment. The psychological burden of living with a rare disease or complex condition is often understudied and may present overarching concepts that shape the general experience of having been diagnosed with a rare condition. The present study examines common needs from a comprehensive perspective combining relevant aspects from the rare disease literature in a theoretical perspective from pediatric psychology, such as a family-centred, developmental and interdisciplinary approach. An exploratory study was designed among parents from children with a rare disease or complex condition in an Integrated University Children's Hospital in the Netherlands. Semi-structured interviews were conducted with open-ended questions based around the experience of having a child diagnosed with a rare condition, such as the psychosocial impact on the child and it's development, the impact on the family, and how provided care was experienced. Twelve interviews were analysed with a thematic content analysis to identify common needs. Eight themes followed from the analysis and uncovered the need for (1) family-focused care, (2) coping with uncertainty, (3) empathic communication, (4) practical support, (5) information, (6) psychological support, (7) interdisciplinary care, and (8) social support. The results from our study provide directions for research and health care to support young patients with a rare disease or complex condition and their families. Moreover, our results demonstrated that there are overarching concepts across different rare diseases that may be optimally supported with interdisciplinary care.


Repeated ethanol exposure influences key enzymes in cholesterol and lipid homeostasis via the AMPK pathway in the rat prefrontal cortex.
Cholesterol homeostasis has been proposed to be implicated in the development of addiction. However, the effects of ethanol on cholesterol homeostasis within the brain are not well understood. One of the most important regulators of cholesterol homeostasis is HMG-CoA reductase (HMG-CoAR), the rate-limiting enzyme of cholesterol biosynthesis. We examined the phosphorylation of HMG-CoAR and the other key regulator of lipid synthesis, acetyl-CoA carboxylase (ACC), following acute or chronic treatment with ethanol (0.5, 1, or 2 g/kg) in the rat prefrontal cortex. The phosphorylation of AMP-activated protein kinase (AMPK), which regulates the HMG-CoAR activity, and its well-known upstream regulators, was also studied. The phosphorylation of HMG-CoAR and ACC were transiently increased by ethanol treatment only in animals previously treated chronically with ethanol. Acute administration to naïve animals did not induce the phosphorylation, regardless of dosage. Similarly, the phosphorylation of AMPK and the upstream regulators, LKB1 and CaMK4, were transiently increased only in chronically ethanol-treated animals. In naïve animals, a high dose (2 g/kg) of ethanol decreased phosphorylation. The phosphorylation of TAK1, another upstream kinase of AMPK, was increased only from 30 min to 24 h after the chronic treatment with ethanol. Together, these results indicate that repeated exposure is required for the activating effect of ethanol on HMG-CoAR and ACC. This effect seems to be mediated by the AMPK system, and may contribute to the long-lasting neuroadaptation involved in the development of alcohol dependence.


Effects of posture on gastric emptying and satiety ratings after a nutritive liquid and solid meal.
To study the effects of posture and meal structure on gastric emptying and satiety, nine women ingested tomato soup and then immediately or 20 min later an egg sandwich, when seated and when supine. The lag time was not different, but the half-emptying time of the sandwich was 32% longer (P < 0.01) and the emptying rate after the lag phase was 39% slower (P < 0.01) when the subjects were supine than when they were seated. The half-emptying time of the soup was 50% longer (P < 0.01) when the subjects were supine and ingested the soup immediately before the sandwich than in the other three conditions. Postprandial hunger ratings recovered more slowly (P < 0.01) when the subjects ingested the soup 20 min before the sandwich than when they ingested the soup immediately before the sandwich. These results suggest that posture did not affect the intragastric distribution of the sandwich but affected propulsion of the meal into the intestine and that postprandial satiety was enhanced by the cumulative effect over time of a 20-min "head start" in stimulation of intestinal receptors by emptying of the soup.


Antioxidants attenuate atherosclerotic plaque development in a balloon-denuded and -radiated hypercholesterolemic rabbit.
Oxidation of lipoproteins is considered to be a key contributor to atherogenesis. Antioxidants are potential antiatherogenic agents because they can inhibit lipoprotein oxidation. Radiation has been shown to increase oxidative stress leading to increased atherogenesis. This study is designed to test the potential of antioxidants to inhibit atherosclerotic plaque progression in balloon-denuded and -radiated rabbits. Two groups of New Zealand white rabbits (n=36) were fed with 1% cholesterol diet (control diet) or with 1% cholesterol diet containing a mixture of various antioxidants for 1 week. Iliac arteries in all the animals were balloon denuded and continued to fed with 0.15% cholesterol diet or 0.15% cholesterol diet containing antioxidants (antioxidant diet). Four weeks after balloon denudation one iliac artery in 12 animals from each group was radiated and all the animals were continued to be fed with the same diet. Four weeks after radiation animals were sacrificed and morphometric analysis of iliac arteries (n=12) in nonradiated and radiated animals were performed. Plaque area (PA) in the rabbits that were fed with cholesterol diet is 0.2+/-0.12 mm2, and it is increased by 2.75-fold (P<.05) in the radiated arteries of animals fed with cholesterol diet. Plaque area in the animals fed with antioxidant diet is 50% less then the one in the animals fed with cholesterol diet. Similarly, plaque area in radiated arteries of the animals fed with antioxidant diet is 50% less then the animals fed with cholesterol diet. Antioxidants significantly attenuate atherosclerotic plaque progression in balloon-injured and -radiated hypercholesterolemic rabbits.


Ocular manifestations of adult T-cell leukemia/lymphoma. A clinicopathologic study.
Adult T-cell leukemia/lymphoma (ATLL) is a recently described distinct clinicopathologic entity characterized by an extremely aggressive clinical course, a leukemic or lymphomatous proliferation of hyperlobulated peripheral T cells, and an association with infection by a retrovirus, human T-lymphotropic virus type I (HTLV-I). The authors present a patient with ATLL who initially had clinical features of severe uniocular intraocular inflammation, simulating acute retinal necrosis or herpetic retinitis, but results of histopathologic examination of the globe showed ATLL. A 38-year-old man had severe unilateral intraocular inflammation associated with widespread diffuse retinitis. Two weeks later, a focal retinitis with vasculitis developed nasal to the optic disc in the opposite eye. Shortly thereafter, mental disturbance developed, and the patient died less than 3 months after onset of the ocular symptoms. Results of postmortem examination showed atypical lymphocytic infiltration in the eyes, brain, and other systemic organs. Results of histopathologic and immunohistochemical studies showed that the atypical cells infiltrating the ocular tissues were ATLL cells. Patients infected with HTLV-I initially can have intraocular T-cell lymphoma that simulates acute retinal necrosis or herpetic retinitis.


Programmable auditory stimulus generator and electro-acoustic transducers--measurements of sound pressure in an artificial ear and human ear canal.
The measurement of sound pressure wave forms of different headphones resulted in considerable differences in an artificial ear and in the external auditory canal in man. This concerns, in particular, the pattern of stimuli used to elicit the auditory nerve and brain-stem auditory evoked potentials. By varying the electrical input to the headphones by means of a programmable stimulus generator, it can be shown that the sound pressure wave form can be influenced considerably.


Vitamin D deficiency in pregnancy and the risk of preterm birth: a nested case-control study.
Each year, an estimated 15 million babies are born preterm. Micronutrient deficiencies, including vitamin D deficiency (VDD), are common in many low- and middle-income countries (LMICs), and these conditions are often associated with adverse pregnancy outcomes. Bangladesh experiences a high prevalence of VDD. The country also has a high preterm birth (PTB) rate. Using data from a population-based pregnancy cohort, we estimated the burden of VDD during pregnancy and its association with PTB. Pregnant women (N = 3,000) were enrolled after ultrasound confirmation of gestational age at 8-19 weeks of gestation. Trained health workers prospectively collected phenotypic and epidemiological data at scheduled home visits. Trained phlebotomists collected maternal blood samples at enrollment and 24 -28 weeks of gestation. Aliquots of serum were stored at -800 C. We conducted a nested case-control study with all PTB (n = 262) and a random sample of term births (n = 668). The outcome, PTB, was defined as live births < 37 weeks of gestation, based on ultrasound. The main exposure was vitamin D concentrations of 24-28 weeks maternal blood samples. The analysis was adjusted for other PTB risk factors. Women were categorized as VDD (lowest quartile of 25(OH)D; < = 30.25 nmol/L) or not deficient (upper-three quartiles of 25(OH)D; > 30.25 nmol/L). We used logistic regression to determine the association of VDD with PTB, adjusting for potential confounders. The median and interquartile range of serum 25(OH)D was 38.0 nmol/L; 30.18 to 48.52 (nmol/L). After adjusting for co-variates, VDD was significantly associated with PTB [adjusted odds ratio (aOR) = 1.53, 95% confidence interval (CI) = 1.10 - 2.12]. The risk of PTB was also higher among women who were shorter (aOR = 1.81, 95% CI: 1.27-2.57), primiparous (aOR = 1.55, 95% CI = 1.12 - 2.12), passive smokers (aOR = 1.60, 95% CI = 1.09 - 2.34), and those who received iron supplementation during pregnancy (aOR = 1.66, 95% CI: 1.17, 2.37). VDD is common in Bangladeshi pregnant women and is associated with an increased risk of PTB.


Hydrogen sulphide ameliorates hexavalent chromium toxicity in two cereal crops: Role of antioxidant enzymes and proline metabolism.
Chromium pollution in soils is a major threat as it reduces crop yields. Hence, researchers seek methods/strategies which could curtail such losses. We report the role of H2 S in alleviating hexavalent chromium [Cr(VI)] stress in two cereals crops, i.e. wheat and rice seedlings, by estimating various physiological attributes. Cr(VI) reduced shoot and root length in both cereals through increased accumulation of Cr(VI) in root tips and increased in oxidative stress markers, i.e. superoxide radicals (SOR), H2 O2 and lipid peroxidation (as MDA equivalent). Supplementation with H2 S alleviated Cr(VI) toxicity in both cereal crops. Application of H2 S increased tolerance to Cr(VI) stress by protecting photosynthesis and enhancing activity of antioxidant enzymes, particularly glutathione-S-transferase and content of proline. Rice was more resistant to Cr(VI) than wheat seedlings.


Implementing a community-based shared care breast cancer survivorship model in Singapore: a qualitative study among primary care practitioners.
The adaptability of existing recommendations on shared care implementation to Asian settings is unknown. This qualitative study aims to elicit public- and private-sectors primary care practitioners' (PCPs) perspectives on the sustainable implementation of a shared care model among breast cancer survivors in Singapore. Purposive sampling was employed to engage 70 PCPs from SingHealth Polyclinics, National University Polyclinics, National Healthcare Group Polyclinics, and private practice. Eleven focus groups and six in-depth interviews were conducted between June to November 2018. All sessions were audio-recorded and transcribed verbatim. Guided by the RE-AIM framework, we performed deductive thematic analysis in QSR NVivo 12. PCPs identified low-risk breast cancer survivors who demonstrated clear acceptability of PCPs' involvement in follow-up as suitable candidates for shared care. Engagement with institution stakeholders as early adopters is crucial with adequate support through PCP training, return pathways to oncologists, and survivorship care plans as communication tools. Implementation considerations differed across practices. Selection of participating PCPs could consider seniority and interest for public and private practice, respectively. Proposed adoption incentives included increased renumeration for private PCPs and work recognition for public PCPs. Public PCPs further proposed integrating shared care elements to their existing family medicine clinics. PCPs perceived shared care favorably as it echoed principles of primary care to provide holistic and well-coordinated care. Contextual factors should be considered when adapting implementation recommendations to Asian settings like Singapore. With limited competitive pressure, the government is then pivotal in empowering primary care participation in survivorship shared care delivery.


Does depression increase the risk of dementia? Updated meta-analysis of prospective studies.
Our primary aim was to conduct an update meta-analysis of prospective studies investigating the association between depression and dementia risk. We searched Pubmed database to identify all relevant papers published from January 2014 to March 2019. Prospective studies with a minimum follow-up period of 1 year, baseline depression assessment, absence of dementia or mild cognitive impairment at baseline were selected. We calculated pooled relative risks (RR), with a random effect model, as well as compute population attributable fraction (PAF) of dementia due to depression. Eight cohorts were included. A statistically significant association between depression and dementia risk, with a pooled RR of 1.63 (95% CI: 1.30-2.04), and a PAF of 9.0% (95% CI: 4.5%-14.1%), were found. Depression is associated with an increased risk of dementia in this meta-analysis.


Fifteen- to twenty-year results after the Hill antireflux operation.
Antireflux surgery, specifically the Hill procedure, has been shown to be effective management of refractory reflux when assessed in the relatively short term. This study follows 441 patients from the time of their initial operation and reports on assessments conducted after 5 to 10 years and 15 to 20 years. The late study group comprises 167 patients (mean age 71 years) with an average follow-up of 17.8 years; 15.6% of patients had undergone a previous antireflux operation. Overall subjective good and excellent results, as determined by the patients themselves, were seen to improve significantly (p less than 0.02) between the two follow-up periods, 82% and 88%, respectively. No serious late complications such as fistula, bleeding, or obstruction were observed in this series. The Hill antireflux operation, properly performed, provides durable long-term results.


Carbon-carbon bond formation in the reaction of hydrated carbon dioxide radical anions with 3-butyn-1-ol.
Electrochemical activation of carbon dioxide in aqueous solution is a promising way to use carbon dioxide as a C1 building block. Mechanistic studies in the gas phase play an important role to understand the inherent chemical reactivity of the carbon dioxide radical anion. Here, the reactivity of CO2 •-(H2O)n with 3-butyn-1-ol is investigated by Fourier transform ion cyclotron (FT-ICR) mass spectrometry and quantum chemical calculations. Carbon-carbon bond formation takes places, but is associated with a barrier. Therefore, bond formation may require uptake of several butynol molecules. The water molecules slowly evaporate from the cluster due to the absorption of room temperature black-body radiation. When all water molecules are lost, butynol evaporation sets in. In this late stage of the reaction, side reactions occur including H• atom transfer and elimination of HOCO•.


Advanced pharmacy practice of a doctor of pharmacy student at an allied surgical ward in a hospital in Africa.
The pharmacy profession is undergoing transformational change in Ghana. The role of pharmacists has become more patient-focused with increased accountability and responsibility. This study is aimed at reporting the experiential learning on the clinical interventions made and documented at the Allied Surgical Wards of Korle-Bu Teaching Hospital (KBTH).This involves a review of patient's medical records during the Advanced Pharmacy Practice Experience (APPE) learning. One case each from Eye, Ear, Nose, Throat, (ENT) and Dental units' subspecialty were reviewed from October 7, 2019 to November 15, 2019 b y a Pharm D student. The student was able to make prompt clinical interventions that contributed to patient care in clinical wards assigned during her clinical clerkship.


Analysis of the He-, Ar- and Kr-broadening coefficients of water vapor transitions in a wide spectral region.
An analysis of the measured He-, Ar- and Kr- broadening coefficients γ for 1575 water vapor transitions of 27 vibrational bands belonging to the 0.6-11,200 cm-1 spectral region is performed using an empirical function that contains adjustable parameters. A universal function is detected during the analysis. This function depends on the parameters that are common for all perturbers A = (He, Ar or Kr). A universal function multiplied by one additional parameter x20(A) determines the broadening coefficients γ(A) for each perturber A = (He, Ar or Kr).Two fitting procedures are used. The first considers the fit of measured γ(exp) for individual rotational branches while the other considers the global fit of all 1575 measured γ(exp). In the second procedure, ratios of γ(Kr)/γ(He) = 2.543 ± 0.040 and γ(Kr)/γ(Ar) = 1.252 ± 0.036 are found. The coefficients derived from the fitted parameters are compared statistically to measured coefficients.


Protein synthesis in resting and stimulated human lymphocytes.
The ribosomal profiles in lysates from resting and phytohemagglutinin stimulated human lymphocytes have been analyzed by sucrose gradient centrifugation. The percentage of polyribosomes increased during lymphocyte transformation reaching a maximal value of 60 to 70% of the total ribosomes after 72 hours of mitogen addition. This time period coincides with maximal in vivo protein synthesis. On the other hand, in nonstimulated lymphocytes, about 25% of the ribosomal particles appeared as aggregates, independently of the incubation period. Experiments performed with homologous cell free systems containing ribosomes and supernatant fluids prepared from unstimulated or activated lymphocytes demonstrate that the mixtures containing both components from stimulated lymphocytes are several fold more active in polypeptide synthesis than the systems which contain ribosomal particles and cell sap from resting cells. Assays carried out with mixtures combining the components from both sources indicate that the increased activity depends on ribosomes as well as on the supernatant fractions.


Impact of the COVID-19 pandemic on the quality of diabetes care: Insights from longitudinal data in Switzerland.
In this population-based cohort study on diabetes care, self-reported quality indicators measured just before (2019) and during (2021) the COVID-19 pandemic were comparable, apart from a modest increase in seasonal influenza immunization and a small decline in patient-centeredness of care in 2021.


Idiopathic combined retinal vessels occlusion in a pregnant woman: a case report.
Ocular vascular occlusion is an extremely rare event, especially in the young population. This diagnosis is always associated with active systemic diseases in young adults and needs thrombophilia workup. Nevertheless, we present the case of a pregnant woman suffering from idiopathic combined central retinal vein and cilioretinal artery occlusion. A 36-year-old pregnant Iranian woman at the 36th week of her second pregnancy complained of subacute unilateral painless decreased vision of her left eye. She had experienced a transient vision loss that lasted several minutes, but attacks gradually became more frequent and finally persistent over a several-day period. Finally combined central retinal vein and cilioretinal artery occlusion was established. Her visual acuity improved to 4/10 in a month without any ocular intervention except for a short duration of prophylactic dose enoxaparin, and the acuity reached 8/10 without any complications in the third month follow-up visit. At 1 year follow-up, the visual acuity had not changed and no macular edema was seen. Ocular vascular occlusion is extremely rare among young adults, and even rarer among pregnant women. According to this, any suspected retinal vascular event in this population should raise suspicion for underlying diseases such as hypertension, diabetes, autoimmune diseases, migraine, preeclampsia syndrome, and thrombophilia. However, as seen in this presented case, idiopathic ocular vascular occlusion events can occur also.


Application of elemental bioimaging using laser ablation ICP-MS in forest pathology: distribution of elements in the bark of Picea sitchensis following wounding.
Element distribution in the bark of two 20-year-old clones of Picea sitchensis following wounding was studied using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). Bark was sampled at 0, 3, and 43 days after wounding and analysed using a focused Nd:YAG laser (266 nm). Intensities of (13)C, (25)Mg, (27)Al, (31)P, (32)S, (39)K, (48)Ca, (55)Mn, (57)Fe, (63)Cu and (64)Zn were measured by ICP-MS to study elemental distribution across the bark samples during the wound repair process. A clear accumulation of Mg, P and K at the boundary zone between the lesion and healthy tissue was detected in the wounded samples and was more distinctive at 43 than at 3 days after treatment. This zone of accumulation mapped onto the position of formation of the ligno-suberised boundary zone and differentiation of the wound periderm. These accumulations suggest major roles for Mg, P and K in the non-specific response of Sitka spruce both to wounding, possibly as co-factors to enzymes and energy utilisation. The LA-ICP-MS method developed in this work proved useful to study spatial element distribution across bark samples and has great potential for applications in other areas of plant pathology research.


Pseudogenes: pseudo or real functional elements?
Pseudogenes are genomic remnants of ancient protein-coding genes which have lost their coding potentials through evolution. Although broadly existed, pseudogenes used to be considered as junk or relics of genomes which have not drawn enough attentions of biologists until recent years. With the broad applications of high-throughput experimental techniques, growing lines of evidence have strongly suggested that some pseudogenes possess special functions, including regulating parental gene expression and participating in the regulation of many biological processes. In this review, we summarize some basic features of pseudogenes and their functions in regulating development and diseases. All of these observations indicate that pseudogenes are not purely dead fossils of genomes, but warrant further exploration in their distribution, expression regulation and functions. A new nomenclature is desirable for the currently called 'pseudogenes' to better describe their functions.


Meeting the challenge of interpreting high-resolution single nucleotide polymorphism array data in prenatal diagnosis: does increased diagnostic power outweigh the dilemma of rare variants?
Several studies have already shown the superiority of chromosomal microarray analysis (CMA) compared with conventional karyotyping for prenatal investigation of fetal ultrasound abnormality. This study used very high-resolution single nucleotide polymorphism (SNP) arrays to determine the impact on detection rates of all clinical categories of copy number variations (CNVs), and address the issue of interpreting and communicating findings of uncertain or unknown clinical significance, which are to be expected at higher frequency when using very high-resolution CMA. Prospective validation study. Tertiary clinical genetics centre. Women referred for further investigation of fetal ultrasound anomaly. We prospectively tested 104 prenatal samples using both conventional karyotyping and high-resolution arrays. The detection rates for each clinical category of CNV. Unequivocal pathogenic CNVs were found in six cases, including one with uniparental disomy (paternal UPD 14). A further four cases had a 'likely pathogenic' finding. Overall, CMA improved the detection of 'pathogenic' and 'likely pathogenic' abnormalities from 2.9% (3/104) to 9.6% (10/104). CNVs of 'unknown' clinical significance that presented interpretational difficulties beyond results from parental investigations were detected in 6.7% (7/104) of samples. Increased detection sensitivity appears to be the main benefit of high-resolution CMA. Despite this, in this cohort there was no significant benefit in terms of improving detection of small pathogenic CNVs. A potential disadvantage is the high detection rate of CNVs of 'unknown' clinical significance. These findings emphasise the importance of establishing an evidence-based policy for the interpretation and reporting of CNVs, and the need to provide appropriate pre- and post-test counselling.


Wave separation analysis-derived indexes obtained from radial and carotid tonometry in healthy pregnancy and pregnancy-associated hypertension: Comparison with pulse wave analysis-derived indexes.
Increased wave reflections assessed by pulse wave analysis (PWA) was proposed as one of the potential culprits of hypertension seen in women with pregnancy-associated hypertension (PAH). However, this statement has never been confirmed with "Wave Separation Analysis" (WSA), a more sophisticated mathematical approach that analyzes the amplitude and interaction between forward and backward aortic pressure waveform components. To characterize potential changes in pressure wave components of PAH compared to healthy non-pregnant (NP) women and women with normal pregnancies (HP) by using WSA and compared these findings with PWA-derived indexes; secondarily, to evaluate differences in WSA-derived indexes between subgroups of PAH (i.e., preeclampsia [PE] and gestational hypertension [GH]). Using radial and carotid applanation tonometry, we quantified in HP (n = 10), PAH (n = 16), and NP (n = 401): (i) PWA-derived indexes; (ii) WSA-derived indexes: forward (Pf) and backward (Pb) waveform components, backward component arrival time (PbAT), reflection magnitude (RM = Pb/Pf) and index [RIx = Pb/(Pf + Pb)]. While PAH was associated with a higher Pf compared to HP and NP, Pb and PbAT were similar between the groups. Both GH and PE showed a higher Pf compared to HP, but only PE had a trend of presenting with higher Pb and lower PbAT compared to the other groups. Finally, PAH showed a trend of having lower RM and RIx compared to NP and HP, with no differences between GH and PE. PAH was associated with higher Pf, but not higher Pb, compared to NP and HP, although PE also demonstrated a trend of higher Pb.


Prepregnancy Polycystic Ovary Syndrome as a Risk Factor of Subsequent Preterm Labor: A National Population-Based Cohort Study.
Background: Preterm labor and the following preterm births, which account for most of the perinatal deaths, are an important issue in public health. The study aims to assess the risk of subsequent preterm labor in pregnant females who have prepregnancy polycystic ovary syndrome (PCOS). Methods: This study has enrolled 1,000,000 randomly sampled females retrieved from the Taiwan National Health Insurance Research Database (NHIRD) during 1998−2012. The study excluded prepregnancy PCOS females who were initially diagnosed at age <15 or >45, and those who had inconsistent diagnoses. Moreover, the medical records of blood hormone tests, gynecologic ultrasonography, pelvic examinations, and tocometers were verified to confirm the accuracy of both diagnoses of PCOS and preterm labor. Among the prepregnancy PCOS females who became pregnant (the case group), each was age-matched to four females without prepregnancy PCOS (the control group). Results: Pregnant females in the case group (n = 1959) had a higher incidence of preterm labor than those in the control group (n = 7836) (42.98% vs. 21.99%, p < 0.0001). Analyzed by using logistic regression, the risk of preterm labor was significantly higher in the case group compared with the control group (crude OR: 2.674; 95% CI: 2.410−2.968, p < 0.0001). After adjustment with covariates, further analysis revealed a similar trend (adjusted OR: 2.405; 95% CI: 2.158−2.680, p < 0.0001). Among 1959 PCOS females in the case group, 196 had undergone metformin treatment. Compared with females without metformin treatment (the non-metformin subgroup), the metformin users (metformin subgroup) presented a reduced risk for preterm labor (adjusted OR: 2.238; 95% CI: 1.657−3.023). The risk of subsequent preterm labor was reduced by about 10% for the metformin subgroup compared with the non-metformin subgroup. Conclusions: Prepregnancy PCOS is an independent and significant risk factor of subsequent preterm labor. Among prepregnancy PCOS females, the risk of preterm labor is lowered by about 10% in metformin users compared with non-metformin females.


An explanation for the recent increase in the fall death rate among older Americans: a subgroup analysis.
We sought to explain the recent increase in the death rate from falls among Americans aged 65 years and older. Using the CDC WONDER online database, a longitudinal analysis of subgroups of fall mortality based on the International Classification of Diseases, 10th Revision (ICD-10) was conducted in older adults and in younger people. We used linear regression to examine the statistical significance of trends in mortality rates during 1999-2007. The overall mortality rate from falls increased by 55% among older Americans (≥65 years of age) during 1999-2007, from 29 per 100,000 population to 45 per 100,000 population. For those aged ≥65 years, the largest increase by far (698%) occurred in the subgroup "other falls on the same level," followed by a moderate increase in falls involving wheelchairs or furniture (48%). The steepest increases at all ages occurred from 1999 to 2000, after ICD-10 took effect. State-level analysis confirmed the findings for the entire United States. From 1999 to 2007, total mortality from falls decreased by 5% in people younger than 45 years of age and increased by 44% for those aged 45-64 years; mortality from "other falls on the same level" increased by 202% and 431%, respectively, in these age groups. Because the reported minor increases in emergency department and hospitalization rates for falls were insignificant, the almost sevenfold increase in death rates from "other falls on the same level" strongly suggests an effect of improved reporting quality.


Surgical treatment of lesions of the long head of the biceps brachii tendon with rotator cuff tear: a prospective randomized clinical trial comparing the clinical results of tenotomy and tenodesis.
Tenotomy and tenodesis are common treatments for lesions in the long head of biceps tendon (LHBT); however, which treatment is superior is still controversial. This study compared the outcomes of tenotomy with outcomes of tenodesis for treatment of LHBT lesions with rotator cuff tears. The study enrolled 128 patients with LHBT lesions and small- to medium-sized rotator cuff tear. Arthroscopic LHBT tenotomy was done in 56 patients (group I), and LHBT tenodesis was done for 72 patients (group II) with rotator cuff repair. American Shoulder and Elbow Surgeons Score, simple shoulder test, pain visual analog scale, range of motion, and cosmetic changes were assessed initially, at 3, 6, and 12 months postoperatively, and the last visit. The elbow motor power and magnetic resonance imaging were evaluated at 12 months. Both groups showed improvement in functional scores after treatments, but no significant difference was found between the 2 groups at each assessment. The rate of Popeye deformity was 3 times higher in group I (P = .04). Group II showed greater forearm supination power than group I (P = .02). On magnetic resonance imaging, 45 patients (80.4%) in group I showed maintenance of the LHBT cut end within the bicipital groove, whereas 65 patients (90.3%) in group II showed maintenance of fixated LHBT. For the treatment of LHBT lesions with rotator cuff tear, patients with tenotomy and tenodesis both showed significant improvements in functional scores. The incidence of Popeye deformity was about 3-times higher in tenotomy group. No significant differences in elbow motor power were observed except greater forearm supination power in the tenodesis group.


Comparing ultrasonographically assessed carotid and abdominal aorta plaques in cardiovascular disease risk estimation.
Individual risk estimation is an essential part of cardiovascular (CV) disease prevention. Several imaging parameters have been studied for this purpose. Based on mounting evidence, international guidelines recommend the ultrasound assessment of carotid artery plaques to refine individual risk estimation. Previous studies have not compared carotid artery and abdominal aorta plaques in CV risk estimation. Our aim was to explore this matter in a prospective study setting. Participants were part of the Oulu Project Elucidating Risk of Atherosclerosis (OPERA) project. All participants (n = 1007, 50% males, aged 51.3 ± 6.0 years) were clinically examined in the beginning of 1990's and followed until the end 2014 for fatal and non-fatal CV events. During a median follow-up of 22.5 (17.5-23.2) years, 246 (24%) participants suffered a CV event and 79 (32%) of those CV events were fatal. When compared to those without plaques, both carotid (hazard ratio, HR 2.854 [95% confidence interval, CI, 2.188-3.721, p < 0.001) and abdominal aorta plaques (HR 2.534 [1.503-4.274], p < 0.001) were major risk factors for CV events as an aggregate endpoint. These associations remained even after adjusting the multivariable models with age, sex, systolic blood pressure, smoking, diabetes, LDL cholesterol, and with previous CV events (coronary artery disease and stroke/transient ischemic attack). However, only carotid plaques were significant risk factors for fatal CV events: multivariable adjusted HR 2.563 (1.452-4.524), p = 0.001. Furthermore, reclassification and discrimination parameters were improved only when carotid plaques were added to a baseline risk model. Adding abdominal aorta plaques to the baseline risk model improved C-statistic from 0.718 (0.684-0.751) to 0.721 (0.688-0.754) whereas carotid plaques improved it to 0.743 (0.710-0.776). Both carotid and abdominal aorta plaques are significant risk factors for CV events, but only carotid plaques provide prognostic information beyond traditional CV risk factors on fatal CV events. If one ultrasound parameter for plaque detection and CV risk estimation had to be chosen, carotid plaques may be preferred over abdominal aorta.


Synthesis and structure-activity relationship of coumarins as potent Mcl-1 inhibitors for cancer treatment.
Myeloid cell leukemia-1 (Mcl-1) is a validated and attractive target for cancer therapy. Over-expression of Mcl-1 in many cancers allows cancer cells to evade apoptosis and contributes to their resistance to current chemotherapeutics. In this study, more than thirty coumarin derivatives with different substituents were designed and synthesized, and their Mcl-1 inhibitory activities evaluated using a fluorescence polarization-based binding assay. The results showed that the catechol group was a key constituent for Mcl-1 inhibitory activity of the coumarins, and methylation of the catechol group led to decreased inhibitory activity. The introduction of a hydrophobic electron-withdrawing group at the C-4 position of 6,7-dihydroxycoumarin, enhanced Mcl-1 inhibitory capacity, and a hydrophilic group in this position was unbeneficial to the inhibitory potency. In addition, the introduction of a nitrogen-containing group to the C-5 or C-8 position, which allowed an intramolecular hydrogen bond, was also unfavorable for Mcl-1 inhibition. Among all coumarins tested, 4-trifluoromethyl-6,7-dihydroxycoumarin (Cpd 4) displayed the most potent inhibitory activity towards Mcl-1 (Ki = 0.21 ± 0.02 μM, IC50 = 1.21 ± 0.56 μM, respectively), for which the beneficial effect on taxol resistance was also validated in A549 cells. A strong interaction between Cpd 4 and Mcl-1 in docking simulations further supported the observed potent Mcl-1 inhibition ability of Cpd 4. 3D-QSAR analysis of all tested coumarin derivatives further provides new insights into the relationships linking the inhibitory effects on Mcl-1 and the steric-electrostatic properties of coumarins. These findings could be of great value for medicinal chemists for the design and development of more potent Mcl-1 inhibitors for biomedical applications.


Effects of Low-Dose Bisphenol A on DNA Damage and Proliferation of Breast Cells: The Role of c-Myc.
Humans are exposed to low-dose bisphenol A (BPA) through plastic consumer products and dental sealants containing BPA. Although a number of studies have investigated the mammary gland effects after high-dose BPA exposure, the study findings differ. Furthermore, there has been a lack of mechanistic studies. The objective of this study was to investigate the effect and the mechanism of low-dose BPA in mammary gland cells. We evaluated DNA damage following BPA exposure using the comet assay and immunofluorescence staining, and used cell counting and three-dimensional cultures to evaluate effects on proliferation. We examined the expressions of markers of DNA damage and cell-cycle regulators by immunoblotting and performed siRNA-mediated gene silencing to determine the role of c-Myc in regulating BPA's effects. Low-dose BPA significantly promoted DNA damage, up-regulated c-Myc and other cell-cycle regulatory proteins, and induced proliferation in parallel in estrogen receptor-α (ERα)-negative mammary cells. Silencing c-Myc diminished these BPA-induced cellular events, suggesting that c-Myc is essential for regulating effects of BPA on DNA damage and proliferation in mammary cells. Low-dose BPA exerted c-Myc-dependent genotoxic and mitogenic effects on ERα-negative mammary cells. These findings provide significant evidence of adverse effects of low-dose BPA on mammary cells.


Familial meningioma. Case report with cytogenetic study.
A family is presented of which two members were shown to have an intracranial meningioma. We performed a chromosome study in the affected living individual and several other relatives, with special attention for chromosome 22 anomalies. In neither of them a chromosomal abnormality could be detected. However, in view of the recent cytogenetic findings reported in meningioma, it is suggested that karyotyping should be performed in every family with two or more members affected by meningioma.


Syndromic management of common illnesses in hospitalized children and neonates: a cost identification study.
To find out drug treatment cost per illness per patient admitted to pediatric ward. Patients admitted to pediatric ward over a period of 1 year were studied without exclusions. Following presentations were studied: fever, rapid breathing, diarrhea, severe malnutrition and neurological problems such as altered conscious level or convulsion. In this prospective observational study, patients with other problems were excluded. The subjects were also categorized as critically sick, sick and stable. Expenditure on medicines was calculated individually for each patient. Total expenditure, average cost and illness-wise cost were subsequently derived. Management of illnesses was on the lines of existing guidelines of our center. Sick newborns or newborns referred for special care were separately studied. Following outcome variables were studied: death or discharge, length of hospital stay and the day on which symptomatic relief was noted. 774 children and 141 newborns were studied. 25(3.2%) died. Presenting features were as follows: fever-568 (73.4%), rapid breathing-175 (22.6%), diarrhea-145 (18.7%), mild-moderate malnutrition-278 (35.8%), severe malnutrition-111 (14.3%) and neurological problems-41 (5.3%). Category-wise distribution was as follows: critically sick-89 (11.3%), sick-188 (24.3%) and stable-497 (46.2%). Average hospital stay was 7.1 days and symptomatic relief was experienced by day three in 77.7% cases. Average cost of medicines per patient was INR-167.8 (USD-4.2), 173 patients required oxygen and mean expenditure on oxygen was INR-310 (USD-8) and 68 patients required inotropes with a mean expenditure of INR-198 (USD-5). Of the 141 newborns admitted, 20(14.1%) died. Mean hospital stay was 9.8 days and average cost of drug treatment was INR-790 (USD-20) in newborns. This cost analysis study presents drug treatment costs for common illnesses at a referral centre in a developing country. It gives an option to choose drugs for an optimum mix of cost and effectiveness.


Transfer of Maternal Immune Cells by Breastfeeding: Maternal Cytotoxic T Lymphocytes Present in Breast Milk Localize in the Peyer's Patches of the Nursed Infant.
Despite our knowledge of the protective role of antibodies passed to infants through breast milk, our understanding of immunity transfer via maternal leukocytes is still limited. To emulate the immunological interface between the mother and her infant while breast-feeding, we used murine pups fostered after birth onto MHC-matched and MHC-mismatched dams. Overall, data revealed that: 1) Survival of breast milk leukocytes in suckling infants is possible, but not significant after the foster-nursing ceases; 2) Most breast milk lymphocytes establish themselves in specific areas of the intestine termed Peyer's patches (PPs); 3) While most leukocytes in the milk bolus were myeloid cells, the majority of breast milk leukocytes localized to PPs were T lymphocytes, and cytotoxic T cells (CTLs) in particular; 4) These CTLs exhibit high levels of the gut-homing molecules α4β7 and CCR9, but a reduced expression of the systemic homing marker CD62L; 5) Under the same activation conditions, transferred CD8 T cells through breast milk have a superior capacity to produce potent cytolytic and inflammatory mediators when compared to those generated by the breastfed infant. It is therefore possible that maternal CTLs found in breast milk are directed to the PPs to compensate for the immature adaptive immune system of the infant in order to protect it against constant oral infectious risks during the postnatal phase.


Emergency department length of stay following discontinuation of routine oral contrast material.
To determine the effect of discontinuing routine oral contrast material on emergency department (ED) length of stay (LOS), time from order to CT completion, and preliminary report turnaround time (TAT). A HIPAA-compliant, IRB-waived, single-institution, retrospective cohort study was conducted on adult patients presenting with abdominal pain to the ED from October 2015 to April 2019. Routine oral contrast material was administered prior to July 2018 and discontinued thereafter. CT workflow (ED LOS, exam completion time, report TAT) data were analyzed in a univariate analysis before and after discontinuation of oral contrast. Pre- versus post-policy data were compared with 2-sided t tests. The primary outcome was ED LOS. Data were analyzed on a process control chart and confidence limits were adjusted using established criteria. There were 5020 included abdominopelvic CTs. After routine oral contrast material was discontinued, ED LOS (13.4 h vs 10.7 h, p < 0.001) and time from CT order to CT completion (2.7 h vs 2.1 h, p < 0.001) declined. However, control chart analysis revealed improvement in overall LOS preceded the policy change by 9 months, while improvement in time to CT completion coincided with the policy change. Preliminary report TAT increased by 4 min after the policy change (29 min vs. 33 min, p < 0.001). Discontinuation of routine oral contrast material in the ED accelerated time to CT completion but had a minor non-significant effect on overall ED LOS. Much of the reduction in overall LOS likely was due to unrelated process improvements.


Endothelial function and endothelial progenitor cells in systemic lupus erythematosus.
The observations that traditional cardiovascular disease (CVD) risk factors fail to fully account for the excessive cardiovascular mortality in patients with systemic lupus erythematosus (SLE) compared with the general population have prompted in-depth investigations of non-traditional, SLE-related risk factors that contribute to cardiovascular complications in patients with SLE. Of the various perturbations of vascular physiology, endothelial dysfunction, which is believed to occur in the earliest step of atherosclerosis, has been extensively investigated for its contribution to CVD risk in SLE. Endothelial progenitor cells (EPCs), which play a crucial part in vascular repair, neovascularization and maintenance of endothelial function, are quantitatively and functionally reduced in patients with SLE. Yet, the lack of a unified definition of EPCs, standardization of the quantity and functional assessment of EPCs as well as endothelial function measurement pose challenges to the translation of endothelial function measurements and EPC levels into prognostic markers for CVD in patients with SLE. This Review discusses factors that contribute to CVD in SLE, with particular focus on how endothelial function and EPCs are evaluated currently, and how EPCs are quantitatively and functionally altered in patients with SLE. Potential strategies for the use of endothelial function measurements and EPC quantification as prognostic markers of CVD in patients with SLE, and the limitations of their prognostication potential, are also discussed.


Histologic comparison of formocresol, platelet-rich fibrin, and hesperidin in pulpotomy: A randomized trial in dogs.
To histologically assess and compare formocresol (FC), platelet-rich fibrin (PRF), and hesperidin (HPN) as pulpotomy agents in dogs. Pulpotomy was attempted from the buccal surface (class V) of 48 teeth in three mongrel dogs (Canis Lupus). Cavities were randomly allocated for three groups (n = 16) according to the pulpotomy agent used; (group I: FC (control), group II: PRF, and group III: HPN). All cavities were then sealed with zinc oxide eugenol followed by resin-modified glass ionomer restoration. Two months later, dogs were euthanized; the specimens were obtained and prepared for histological assessment followed by statistical analysis. HPN specimens showed the best dentin bridge formation and the least inflammatory signs and pulp disorganization. Followed without statistically significant difference by PRF (P ≥ 0.05). Both of HPN and PRF, however, showed a significant difference statistically (P ≤ 0.05) to FC that showed no dentin bridging with more pronounced inflammation, necrosis, and pulp disorganization. For pulpotomy, HPN and PRF seemed histologically to be good substitutes for FC in the dog model.


Cerebrospinal fluid leak after anterior cervical disc fusion: an unusual cause of dysphagia and neck mass.
Dysphagia after anterior cervical disc fusion (ACDF) is a common complaint. We present two cases of dysphagia caused by a rare complication after ACDF: cerebrospinal fluid (CSF) leak into the neck. A case series of two patients. Both patients underwent a chart review, comprehensive history, physical examination, flexible nasolaryngoscopy, and radiographic imaging. A literature review of the MEDLINE database (1966-2006), using key words "dysphagia" and "anterior discectomy," was performed. We present two patients with persistent dysphagia after ACDF surgery caused by CSF leak into the neck. Their clinical presentation, physical and radiographic examination findings, and hospital course will be discussed. CSF collection presenting as dysphagia and neck mass after ACDF must be included in the differential diagnosis because incision and drainage is contraindicated, and fine needle aspiration (FNA) must be performed under sterile conditions. Treatment including lumbar drain or re-exploration is appropriate.


Mycotoxin production by Fusarium oxysporum and Fusarium sporotrichioides isolated from Baccharis spp. from Brazil.
Fusarium oxysporum isolated from roots of and soil around Baccharis species from Brazil produced the trichothecenes T-2 toxin, HT-2 toxin, diacetoxyscirpenol, and 3'-OH T-2 (TC-1), whereas Fusarium sporotrichioides from the same source produced T-2 toxin, HT-2 toxin, acetyl T-2, neosolaniol, TC-1, 3'-OH HT-2 (TC-3), iso-T-2, T-2 triol, T-2 tetraol, and the nontrichothecenes moniliformin and fusarin C. Several unknown toxins were found but not identified. Not found were macrocyclic trichothecenes, zearalenone, wortmannin, and fusarochromanone (TDP-1).


[Non-pharmacological interventions in dementia: an overview with special consideration of digital offerings].
Non-pharmacological interventions such as cognitive therapy, physical activity, and creative art approaches are important components of appropriate care for persons with dementia and their relatives. Although relationships and interpersonal interactions undoubtedly play an important role in all these activities, digital technologies have increasingly established themselves in this area in recent years. The following article describes non-pharmacological interventions for people with dementia (based on the German AWMF S3 dementia guideline), and additionally provides examples of selected digital approaches for this particular target group. As the aim of the interventions is to support persons with dementia in living autonomously and maintaining societal and cultural participation, all the interventions share a consideration for individual resources and the promotion of available potential. Empirical evidence on digital activities remains scarce, so it is not yet possible to make clear recommendations. When using them, it should therefore be borne in mind that although they may represent a valuable supplement, they can never replace human attention. Furthermore, limitations in their practical application, such as unfamiliarity when using digital technologies or excessive demands of cognitively limited users, as well as important ethical aspects (e. g., data protections, personality rights, dignity and self-determination in old age) should not be ignored.


Temporal association between leg movements and respiratory events in patients with obstructive sleep apnea: description and differences between the AASM and WASM scoring criteria.
To describe the temporal association between leg movements (LMs) and respiratory events in patients with obstructive sleep apnea (OSA), and to quantify the difference in scoring respiratory-related leg movement (RRLM) between the American Academy of Sleep Medicine (AASM) criterion and the criterion recommended by the World Association of Sleep Medicine (WASM). Patients with OSA who presented with > 10 LMs of any type per hour of sleep were included in this study. For each participant, RRLMs were scored using both the AASM criterion and the recommended WASM criterion. The occurrence of LMs in relation to respiratory events and the difference in scoring RRLM between the AASM criterion and the criterion recommended by the WASM were quantified. In 32 patients enrolled, mean age was 48.1 ± 11.0 years and 78% were men. LMs were significantly more frequent after respiratory events, followed by before respiratory events, and were rare during respiratory events (P < 0.01). Compared with the AASM criterion, more LMs were classified as RRLMs based on the recommended WASM criterion (P = 0.01). LMs are more frequent after respiratory events than before and during respiratory events, and more LMs are scored as RRLMs based on the recommended WASM criterion than based on the AASM criterion.


Modern rectal cancer multidisciplinary treatment: the role of radiation and surgery.
Treatment of rectal cancer has evolved during the last few decades due to more in-depth knowledge of rectal cancer biology and major advances in the field of preoperative staging, medical management and surgical techniques. Consequently, treatment strategies are shifting moving towards a more personalized approach based on the response to treatment. Currently topics of controversy are centered around the indication for neoadjuvant radiation therapy in locally advanced rectal cancer and the role of surgery in patients with complete clinical response after neoadjuvant combined modality therapy. This manuscript aims to critically evaluate the evolution of treatment of rectal cancer during the last three decades and future directions. A review of the literature has been performed in PubMed/Medline electronic databases. Treatment modalities are moving towards a tailored approach to rectal cancer patients based on the response to chemoradiation. A "wait-and-see" approach and local excision by Transanal Endoscopic Microsurgery (TEM) are strategies recently proposed in case of complete clinical response. The standard of care still requires that locally advanced rectal cancer should be treated by neoadjuvant chemoradiation therapy followed by total mesorectal excision, including patients with a clinical complete response. Further evidence is needed to endorse a "wait-and-see" strategy and to define the role of TEM.


Why does a natural myringostapediopexy cause minimal hearing loss?
Natural myringostapediopexy is a result of tympanic membrane retraction with automastoidectomy that causes the tympanic membrane to plaster onto the stapes directly. It causes minimal conductive hearing impairment.


Impact of intermittently scanned continuous glucose monitoring with alarms on sleep and metabolic outcomes in children and adolescents with type 1 diabetes.
Data about sleep quality and quantity are not available in patients with type 1 diabetes (T1D) using intermittently scanned continuous glucose monitoring (isCGM). We questioned whether the isCGM with alarms could fragment sleep in patients and parents, compared to isCGM without alarms. A prospective, observational study including 47 child-adolescents with T1D who had experience with isCGM without alarms (Freestyle Libre 1-FSL1). They were asked to wear the isCGM with alarms (Freestyle Libre 2-FSL2) for 14 days. Patients enrolled and their caregiver (s), during a 14 day period with FSL1 and the following 14 days with FSL2, completed psychosocial and sleep-related questionnaires. Furthermore they wore an actigraph that was downloaded to a web platform and processed by the validated and certified algorithm "Dormi®." By the switch to the alarmed FSL2 we found about a 5% increase in Time In Range (from 62.5 to 67.8%), a reduction in time spent in hypoglycemia, number of weekly hypoglycemic events, and coefficient of variation. We did not find significant differences in sleep parameters in patients and their parents; therefore, alarms did not worsen the duration and quality of sleep. A significant improvement in the Quality of Life was perceived by parents using FSL2. Introduction of alarms in isCGM systems gives, in the short term, an improvement in metabolic control in terms of time in range and reduction in hypoglycemia, without worsening duration and quality of sleep, measured by actigraphy, in children-adolescent and their parents.


Popliteal vessel trauma: Surgical approaches and the vessel-first strategy.
In this study, we analyzed long-term outcomes following treatment of traumatic popliteal vascular injuries in an urban level I trauma center, using a vessel-first approach in the case of combined vascular and bony/ligamentous injuries and discussing the relative merits of the medial and posterior approach to popliteal vessels. Data including patient demographics, mechanism and type of injury, severity of limb ischemia, Injury Severity Score (ISS), limb ischemia time, time to revascularization from admission, treatment strategy, type of vascular reconstruction, limb salvage and mortality were retrospectively collected in patients treated for traumatic popliteal vessel lesions. All patients in this study were operatively treated using medial and posterior approaches. A vessel-first approach was used where possible. Twenty-four patients (13 male) with a median age of 45 years (range 21-88) and popliteal vessel injury after traumatic knee dislocation (n = 10, 42%), proximal tibia fracture (n = 5, 21%), distal femur fracture (n = 4, 17%), blunt popliteal injury (n = 3, 12%) and penetrating trauma (n = 2, 8%) were identified. Twelve (50%) patients were treated via a medial approach and 12 (50%) via a posterior approach. All had injury of the popliteal artery (15 complete transection, eight local intimal disruption and one pseudoaneurysm) with seven having additional popliteal vein and five with nerve injury. Nineteen patients (88%) presented with limb ischemia Rutherford category ≥II. Vessel reconstruction (four direct sutures, four patch plasties, 16 venous interposition/bypasses) was performed prior to bone/joint stabilization in 22 patients (92%). Thirty-day mortality was zero. Two above-knee amputations were performed within 30 days due to severe infection. During a median follow-up of 59 (range 12-143) months, there were no deaths and no amputations. At the end of follow-up, all patients denied claudication. The vessel-first strategy promises an excellent outcome, independent of the surgical approach needed to repair traumatic popliteal vessel injuries.