Pathogenic Yeasts Recovered From Acne Vulgaris: Molecular Characterization and Antifungal Susceptibility Pattern.
Acne vulgaris is a disorder showing persistent inflammation in the pilosebaceous follicles. It is one of the most prevalent dermatoses that millions of people suffer from globally. The aim of this study was to identify Candida species from patients with acne and to determine their drugs susceptibility. A total of 70 cutaneous samples from acne vulgaris patients suspected to have Candida infections were collected. Macroscopic and microscopic morphology were recorded followed by polymerase chain reaction-sequencing of ITS regions, using universal primers. In vitro antifungal susceptibility was performed using Clinical and Laboratory Standards Institute method. Overall, 11 Candida species including Candida parapsilosis 8 (72.73%), Candida krusei 1 (12.5%), Candida lusitaniae 1 (12.5%), Candida kefyr 1 (12.5%), and a Trichosporon asahi out of the collected clinical materials were isolated and identified. C. parapsilosis isolates susceptibility to diverse concentrations of the antifungal agents to isolate Cp1 study indicated that the isolated Cp8 and Cp5 with minimal inhibitory concentration (MIC) 50 = 32, 0.5, 0.25 and MIC 90 of <64, <1, <0.5 μg/ml fluconazole, itraconazole, and ketoconazole were resistant, respectively. Some of the isolates having relative strength, almost all other species of C. parapsilosis isolates were susceptible to these drugs. C. parapsilosis was the most prevalent Candida species in acne vulgaris samples which had higher in vitro susceptibility for antifungals.


Base J originally found in kinetoplastida is also a minor constituent of nuclear DNA of Euglena gracilis.
We have analyzed DNA of EUGLENA: gracilis for the presence of the unusual minor base beta-D-glucosyl-hydroxymethyluracil or J, thus far only found in kinetoplastid flagellates and in DIPLONEMA: Using antibodies specific for J and post-labeling of DNA digests followed by two-dimensional thin-layer chromatography of labeled nucleotides, we show that approximately 0.2 mole percent of EUGLENA: DNA consists of J, an amount similar to that found in DNA of Trypanosoma brucei. By staining permeabilized EUGLENA: cells with anti-J antibodies, we show that J is rather uniformly distributed in the EUGLENA: nucleus, and does not co-localize to a substantial extent with (GGGTTA)(n) repeats, the putative telomeric repeats of EUGLENA: Hence, most of J in EUGLENA: appears to be non-telomeric. Our results add to the existing evidence for a close phylogenetic relation between kinetoplastids and euglenids.


Predictors and treatment outcome of hyperglycemic emergencies at Jimma University Specialized Hospital, southwest Ethiopia.
Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) commonly known as hyperglycemic emergencies are the two most common life-threatening acute metabolic complications of diabetes. The objective of this study is to assess predictors and treatment outcome of hyperglycemic emergencies (HEs) among diabetic patients admitted to Jimma University Specialized Hospital (JUSH). It is a three year retrospective review of medical records of patients admitted with HEs at JUSH. Patient demographics, admission clinical characteristics, precipitants, insulin used and treatment outcomes were extracted. Statistical analysis was done using student's t test, Chi square test, and binary logistic regression with level of α set at 0.05. Statistical significance was considered for variables with p < 0.05. Complete data was available for 163 out of 421 patients admitted with HEs. The majority (62.6 %) were males. Mean age of patients was 36.6 ± 15.9 years. About 64 % of patients had type 1 diabetes. About 93 % of the participants developed DKA. The most common precipitants of HEs were infections 95 (59 %), non-compliance to medications 52 (32.3 %), and newly diagnosed diabetes 38 (23.6 %). Recurrent hyperglycemia, hypoglycemia and ketonuria occurred in 88 (54 %), 34 (20.9 %) and 31 (20.5 %) patients respectively. Mean amount of insulin used and duration of treatment till resolution of DKA were 136.85 ± 152.41 units and 64.38 ± 76.34 h respectively. The median length of hospital stay was 6 days. Mortality from HEs was 16 (9.8 %). Admission serum creatinine >1.2 mg/dL (P = 0.018), co-morbidity (P < 0.001) and sepsis (P = 0.014) were independent predictors of HEs mortality. Infections, non-compliance and new onset diabetes were the most common precipitants of HEs. Length of hospital stay and mortality were high. High use of insulin, recurrent hyperglycemia, hypoglycemia, and ketonuria were common during HEs management. Elevated serum creatinine, sepsis and co-morbidity are independent predictors of HEs mortality.


Sensing substrate rigidity by mechanosensitive ion channels with stress fibers and focal adhesions.
Cell motility, spreading, proliferation and differentiation are critically influenced by substrate rigidity. To sense substrate rigidity, cells apply traction forces to cell-substrate adhesions via actin stress fibers (SFs) and measure mechanical responses of the substrate. Besides mechanosensitive adaptor proteins, mechanosensitive (MS) channels are involved in the substrate rigidity sensing. MS channels located at or near focal adhesions (FAs) convert the rigidity-dependent stress generated in SF/FA system into the level of cytoplasmic Ca(2+) concentration ([Ca(2+)]cyt) by locally altering their Ca(2+) permeability. Besides by external forces, cells spontaneously generate rigidity-dependent localized [Ca(2+)]cyt increases, implicating MS channels as intrinsic force measurement system. This mechanism may contribute to not only substrate rigidity sensing but also regulation of cell migration.


Severe bacterial infections in patients with non-transfusion-dependent thalassemia: prevalence and clinical risk factors.
Bacterial infection is one of the major causes of death in patients with thalassemia. Clinical predictive factors for severe bacterial infection were evaluated in patients with non-transfusion-dependent thalassemia (NTDT). A retrospective study was conducted of patients with NTDT aged ≥ 10 years at Srinagarind Hospital, Khon Kaen University, Thailand. Clinical characteristics and potential clinical risk factors for bacterial infection were collected. Risk factors for bacterial infection were evaluated by multivariate logistic regression analysis. A severe bacterial infection was found in 11 of the total 211 patients with NTDT (5.2%). None of the clinical factors assessed was shown to be statistically associated with severe bacterial infection in patients with NTDT. However, three factors were demonstrated to be potential predictive factors for severe bacterial infection: time after splenectomy >10 years, deferoxamine therapy, and serum ferritin >1000 ng/ml. None of the patients died from infection. The prevalence of bacterial infection in patients with NTDT was found to be moderate. Time after splenectomy >10 years, deferoxamine therapy, and iron overload may be clinical risk factors for severe bacterial infection in patients with NTDT. Bacterial infection should be recognized in splenectomized patients with NTDT, particularly those who have an iron overload.


Microglial and neural differentiation in human teratomas.
Ten human teratomas arising outside the central nervous system (CNS) were studied using a panel of immunohistochemical, and lectin histochemical stains to determine the relationship of the presence of microglia to markers of neural maturity or differentiation. Microglia, identified by silver carbonate, Ricinus communis agglutinin-1 (RCA-1), or both were found in eight out of ten cases. They were common in mature areas which also had S-100, glial fibrillary acidic protein, vimentin, neurofilament, and synaptophysin immunostaining. Microglia were distinguished from macrophages in necrotic foci. Cells which were RCA-1 positive and silver carbonate positive were found in immature neural tissues but these lacked all typical features of microglia. These observations indicate that true microglia are frequent in nonCNS teratomas and that they are found in association with other indicators of neural maturation. The presence of possible precursors in immature areas suggests that microglia undergo maturation concurrent with neural differentiation in these tumors.


Dorsal Wrist Ganglion Associated with Extensor Digitorum Brevis Manus: Case Report and Review of the Literature.
Aberrant accessory muscles are rare entities in the hand. The extensor digitorum brevis manus (EDBM) muscle is amongst them and may be seen in association with dorsal ganglion cysts. Distinguishing an EDBM muscle is relevant in the diagnostic consideration of a dorsal ganglion in order to facilitate and guide its proper treatment. To date, there have been only few reports of an EDBM in association with a dorsal ganglion cyst. We report our experience with an incidental intraoperative finding of an intramuscular EDBM dorsal ganglion cyst and follow with a literature review and guide to management.


Extensive skin bridging with glans epithelium replacement by penile shaft skin following newborn circumcision.
Extensive skin bridging with replacement of glans epithelium by shaft skin is an unusual complication of newborn circumcision not previously described. Patients with extensive skin bridges and replacement of at least 50% of glans epithelium with shaft skin underwent lysis of the bridges and excision of displaced skin. Fibrin glue was used to coat the raw glans surface, and urinary diversion was provided for 1 week. Six boys aged 2-15 years underwent the procedure. In each the glans healed with a smooth, cosmetically normal appearance. There were no complications. Skin bridges after newborn circumcision can be associated with unsightly replacement of normal glans epithelium by shaft skin. Correction involves division of the skin bridges and excision of all abnormal skin with a coating of fibrin glue over the raw surface. Glans epithelium subsequently recovers the glans, restoring a normal appearance.


Long-Term Outcomes of Autologous Hematopoietic Stem Cell Transplant (HSCT) for Multiple Myeloma: While New Horizons Emerge, It Is Still Only a Silver Lining for Resource-Constrained Settings.
Background Significant hurdles impede the optimal implementation of hematopoietic stem cell transplantation (HSCT) in low-middle income countries (LMICs). Herein, we highlight the challenges faced in LMICs while performing HSCT and report the long-term outcomes of patients with newly diagnosed multiple myeloma (MM) who underwent autologous HSCT (AHSCT) at our center. Besides, we provide a comprehensive review of studies reporting long-term outcomes of AHSCT in MM from the Indian subcontinent. Methodology This study was conducted at the State Cancer Institute, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, India. Case records of all patients with MM who received AHSCT from December 2010 to July 2018 were reviewed retrospectively. A non-systematic literature search was performed using PubMed and Google Scholar databases. Data regarding clinicopathological parameters and long-term follow-up were extracted from relevant studies and for patients included in our study. Results At our center, 47 patients (median age 52.0 years) with MM underwent AHSCT. Majority of patients had stage III disease (ISS) and median time to transplant was 11.5 months. The five-year progression free survival (PFS) and overall survival (OS) were 59.1% and 81.2%, respectively. Studies from the Indian subcontinent have observed a five-year OS of ~50% to ~85%. However, a greater variability in the five-year PFS has been reported, ranging from ~20% to ~75%. The median time to transplant has ranged from seven to 17 months (indicating time delays) with median CD34 cell counts of 2.7-6.3×106 cells/kg (lower than developed countries). Conclusions Despite significant resource limitations in LMICs, AHSCT is increasingly been performed in MM with encouraging long-term outcomes.


The effect of cGMP in rabbit auricle as studied by a cut-end method.
Cyclic GMP was applied to the rabbit right auricle by a cut-end method. The nucleotide decreased the spontaneous rate, hyperpolarized the cell membrane and reduced the amplitude and the slow component of the action potential. It also decreased the force of contraction. These results suggest that cGMP may be the mediator of the action of acetylcholine in the rabbit auricle.


Epileptogenicity of white matter lesions in cerebral small vessel disease: a systematic review and meta-analysis.
The epileptogenic properties of white matter lesions (WML) in cerebral small vessel disease (CSVD) are not yet understood. The aim of our systematic review and meta-analysis was to estimate the association between the extent of WML in CSVD and epilepsy, analyze whether these WML are associated with an increased risk of seizure recurrence, and evaluate if treatment with anti-seizure medication (ASM) is justified in first-seizure patients with WML and no cortical lesions. Following a pre-registered study protocol (PROSPERO-ID CRD42023390665), we systematically searched Pubmed and Embase for relevant literature comparing WML load between patients with epilepsy and controls as well as studies on seizure recurrence risk and ASM therapy in the presence vs. absence of WML. We calculated pooled estimates using a random effects model. Eleven studies comprising 2983 patients were included in our study. Presence of WML (OR 2.14, 95% CI 1.38-3.33) and presence of relevant WML as assessed by visual rating scales (OR 3.96, 95% CI 2.55-6.16) but not WML volume (OR 1.30, 95% CI 0.91-1.85) were significantly associated with seizures. These results stayed robust in sensitivity analyses restricted to studies on patients with late-onset seizures/epilepsy. Only two studies assessed the association between WML and risk of seizure recurrence with conflicting results. Currently, there are no studies on the efficacy of ASM therapy in the presence of WML in CSVD. This meta-analysis suggests an association between presence of WML in CSVD and seizures. More research is needed addressing the association between WML and risk of seizure recurrence and ASM therapy focusing on a population of patients with a first unprovoked seizure.


Sofosbuvir and Ribavirin for 24 Weeks Is An Effective Treatment Option for Recurrent Hepatitis C Infection After Living Donor Liver Transplantation.
Recurrent hepatitis C virus (HCV) has been a serious problem after liver transplantation (LT). We report our experience of 24-week therapy with sofosbuvir (SOF) and ribavirin (RBV) in post-LT recurrent HCV in living donor liver transplantation (LDLT) setting in South Asia. Data from all patients treated for post-transplantation HCV recurrence in a single center were analyzed. Treatment regimen was 24 weeks of SOF 400 mg daily and RBV (starting at 800 mg daily, increased as tolerated). Sustained virological response (SVR) was assessed 12 weeks and 24 weeks after completion of treatment. 63 patients (median age 52 [range 30-69] years; 80% males) were treated. Most (76.2%) were treatment experienced and predominant HCV genotype was 3 (77.7%) followed by 1 (20.6%). Median transient elastography (Fibroscan) score was 7 (range 3-11) kPa and none of the patients had cirrhosis. SVR12 was achieved in 60 of 63 patients (95.2%) while SVR24 was noted in 59 (93.7%). SVR12 rates were as good in genotype-3 as in genotype-1. Older age, longer period after transplantation, higher Fibroscan value and higher need for erythropoietin were likely to be associated with relapse. Adverse effects were noted in 34 patients and weakness and fatigue were the commonest side effects. Significant drop in hemoglobin (<8 g/dL) was seen in 6 patients. SOF + RBV combination therapy for 24 weeks was safe and effective in treatment of for post-LT recurrent HCV in a single LT center and remains relevant due to its low cost and lack of drug interactions.


Efficiency of blood utilization in elective surgical patients.
Requesting blood prior to a surgical procedure for perioperative transfusion is a common practice in surgical patients. More unit of blood is requested than used by anticipating the patient will be transfused to provide a safety margin in an event of unexpected haemorrhage. Over requesting with minimal utilization results in significant wastage of blood, reagents and human resource. This study was conducted to assess blood utilization practice of the largest tertiary hospital in Ethiopia. A cross-sectional prospective study method was used. Data was collected using a Proforma questionnaire by perusal of each individual patient's records from December 1, 2017 to February 28, 2018.patient age, sex, department requesting the blood, level of operating surgeon, hemodynamic status, number of unit requested, number of unit crossed matched and number of unit transfused were collected. Efficiency of blood utilization was calculated with three indices: Crossmatch to transfusion ratio, transfusion probability, and transfusion index indices. Blood was requested for 406 patients and a total of 898 units were crossmatched for this patients. Overall Crossmatch to transfusion ration, transfusion probability and transfusion index were 7.6, 15.3% and 0.29 respectively. Results showed insignificant blood usage. Among different departments and units, better blood utilization was seen in neurosurgical unit with C/T ratio, TP and TI of 4.9, 24.4 and 0.6% respectively, while worst indices were from obstetrics unit with C/T ratio, TP and TI of 31.0, 6.5% and 0.06. Using all the three parameters for evaluation of efficiency of blood utilization, the practice in our hospital shows ineffective blood utilization in elective surgical procedure. Blood requesting physician should order the minimum blood anticipated to be used as much as possible.


Before and During the First COVID-19 Surge: Work Conditions, Burnout, and Mental Health Among Resident Physicians in a Department of Psychiatry in the USA.
Resident physicians are critical frontline workers during pandemics, and little is known about their health. The study examined occupational and mental health risks among US psychiatry residents before and during the first COVID-19 surge. Longitudinal data were collected from a cohort of US psychiatry residents at one academic medical center in October 2019, before the pandemic, and April 2020 after the initiation of a state-level stay-at-home order. Primary outcome measures were psychological work empowerment, defined as one's self-efficacy towards their work role, and occupational burnout. A secondary outcome was mental health. In May and June 2020, resident engagement sessions were conducted to disseminate study findings and consider their implications. Fifty-seven out of 59 eligible residents participated in the study (97%). Half the study sample reported high burnout. From before to during the first COVID-19 surge, psychological work empowerment increased in the total sample (p = 0.03); and mental health worsened among junior residents (p = 0.004), not senior residents (p = 0.12). High emotional exhaustion and depersonalization were associated with worse mental health (p < 0.001). In engagement sessions, themes related to residents' work conditions, COVID-19, and racism emerged as potential explanations for survey findings. The study is exploratory and novel. During early COVID, psychiatry residents' well-being was impacted by occupational and societal factors. Postpandemic, there is a growing psychiatrist shortage and high demand for mental health services. The findings highlight the potential importance of physician wellness interventions focused on early career psychiatrists who were first responders during COVID.


The frequency of sarcopenia has increased in patients with glomerulonephritis.
Sarcopenia is defined as the loss of muscle mass and muscle strength, and its frequency increases in kidney patients. However, sarcopenia frequency in patients with glomerulonephritis is unknown. The present study aimed to investigate the frequency of sarcopenia in patients with glomerulonephritis and compare the results with the healthy population for the first time in the literature. A total of 110 participants, including 70 patients previously diagnosed with glomerulonephritis and 40 healthy individuals, were included in the study. The diagnosis of sarcopenia was made based on the EWSGOP 2 Criteria. The mean age of the glomerulonephritis patients group was 39.3 ± 1.5. In the anthropometric measurements of the patients, walking speed was low in 50 patients (71.4%), muscle strength was decreased in 44 patients (62.9%), and sarcopenia was detected in 10 patients (14.3%) according to the EWGSOP 2 Criteria. Considering the anthropometric measurements of the control group, sarcopenia was not detected in any of the subjects according to the EWGSOP 2 Criteria. The result of the present study revealed that the rate of sarcopenia was significantly higher in glomerulonephritis patients compared to the healthy population and that sarcopenia can also be observed even in middle age in this population. We think it would be beneficial for clinicians treating glomerulonephritis to be more careful regarding sarcopenia and keep these parameters in mind during treatment.


Silk fiber for in-tube solid-phase microextraction to detect aldehydes by chemical derivatization.
Aldehydes are the potentially damaging pollutants in the environment, but it is difficult to be determined due to the low concentration level. Therefore, to accurate analysis of aldehydes, it is important for efficient sample preparation with selective enrichment and rapid separation. Environmentally friendly silk fiber as adsorbent material was directly applied to develop in-tube solid-phase microextraction for analyzing aqueous samples combined with high performance liquid chromatography. 2,4-Dinitrophenylhydrazine as a derivative reagent was used for chemical derivatization of aldehydes before extraction. Under optimum conditions, an online analysis method was built with the limits of detection in the range of 0.005-0.01μgL-1 and the linearity in the range of 0.03-10μgL-1. Three aldehydes were determined in two real samples, and the relative recoveries were in the range of 95-102%.


Inspiratory muscle training with threshold or incentive spirometry: Which is the most effective?
Inspiratory muscular training (IMT) increases the respiratory muscle strength, however, there is no data demonstrating its superiority over the incentive spirometry (IS) in doing so. Values of muscle strength after IMT (Threshold IMT(®)) and by the IS (Voldyne(®)) in healthy females was compared. Subjects (n=40) were randomly divided into control group (CG, n=14), IS group (ISG, n=13) and threshold group (TG, n=13). PImax was measured before (pre-IMT), at 15 and 30 days of IMT. There was an increase in PImax of the TG at 15 days (p<0.001) and 30 days of IMT (p<0.001). The same occurred with the ISG, which increased the PImax at 15 days (p<0.001) and 30 days of training (p<0.001). After 30 days of IMT, the TG presented a PImax which was significantly higher than ISG and the CG (p=0.045 and p<0.001, respectively). It can be concluded that IMT by threshold was more effective in increasing muscle strength than the Voldyne.


Fatal gas embolism as a complication of Nd-YAG laser surgery during treatment of bilateral choanal stenosis.
A 40-day-old infant boy underwent Nd-YAG laser surgery because of congenital bilateral choanal stenosis. Cyanosis and cardiovascular collapse occurred during the operation. Resuscitation was initiated, but in vain; the patient died. The evolution of clinical events was consistent with a diagnosis of gas embolism. In the investigation of causes, the use of a sapphire tip with the Nd-YAG laser and the cooling of the tip with N2 gas were thought to have contributed to the fatal outcome. The authors warn of the potential risk of gas embolism with the Nd-YAG laser and a coaxial gas cooling system, and they emphasize the importance of monitoring for gas embolism in high-risk patients.


The effects of fuel reduction treatments on runoff, infiltration and erosion in two shrubland areas in the north of Spain.
The immediate effects of prescribed burning, shrub clearing and shrub mastication on runoff, infiltration and erosion were evaluated in two contrasting shrubland areas in northern Spain. Rainfall simulations (67 mm h(-1) for 30 min) were conducted immediately after fuel reduction treatments in each runoff plot. Compared to shrub mastication and shrub clearing, prescribed burning generated the lowest infiltration rate and highest runoff and erosion rates at both study sites. However, sediment yields measured immediately after treatments were low in all cases, from 0.31 to 2.22 g m(-2) after shrub clearing, 0.40-1.63 g m(-2) after shrub mastication and 2.30-8.11 g m(-2) after prescribed burning. Slope, type of fuel reduction treatment and the depth and cover of the soil organic layer remaining after treatment were the most important variables determining runoff and erosion during the first rainfall event following treatment. In the rainfall simulation plots subjected to prescribed burning, the maximum temperatures reached at the organic layer/mineral soil interface during burning also had a significant effect on soil loss. The findings show that good fuel management prescriptions make fire hazard reduction and soil conservation compatible in cases where the remaining soil cover is about 70%.


Evaluation on persistence and mobility of metsulfuron-methyl at oil palm plantation: residue field trial experiment versus VARLEACH model.
The present paper discussed the comparison of the persistence and mobility of metsulfuron-methyl from a residue field trial experiment and simulation using a VARLEACH model. The residue field trial experiment was performed at Sungai Buloh Oil Palm Estate, Selangor. The plots were treated with metsulfuron-methyl at two treatment rates of 15 g a.i ha-1 (T1) and 30 g a.i ha-1 (T2). Soil samples were collected at 0, 1, 3, 7, 14, 21, 30, 60 and 90 days after treatment (DAT) and analysed subsequently by HPLC-UV. The results show that metsulfuron-methyl degraded rapidly in the soil with the half-life (t½) of 6.3 days in T1 and 7.9 days in T2. The simulation of VARLEACH model gave similar pattern of persistence and mobility of metsulfuron-methyl in the soil profile. However, total residues and the mobility of the metsulfuron-methyl were poorly simulated by the VARLEACH model due to consistent overestimation of the quantified residues. Results indicated that the metsulfuron-methyl lost more rapidly than the prediction values from VARLEACH model. In this case, simulation models which use transformation routines similar and which include additional degraded processes such as leaching, volatilisation, plant uptake or runoff could be considered. Albeit, overestimated values on the concentrations of metsulfuron-methyl are reported using VARLEACH model, the model still can be used as rapid and fast approach to predict the behaviour of pesticide at minimum cost.


Polymorphisms in the vitamin D receptor gene and type 1 diabetes mellitus risk: an update by meta-analysis.
Four well known polymorphisms (BsmI, FokI, ApaI, TaqI) in the VDR gene have been implicated in susceptibility to type 1 diabetes mellitus (T1DM), but the results to date have been inconclusive. The aim of this study was to investigate the association between polymorphisms in the VDR gene and T1DM risk by meta-analysis. A total of 57 case-control studies in 26 published studies were included. The results indicated that the BsmI polymorphism is associated with increased risk of T1DM (BB+Bb vs. bb: OR=1.30, 95% CI=1.03-1.63), while the FokI, ApaI and TaqI polymorphisms were not. In the subgroup analysis by ethnicity, the increased risk of T1DM remained in the Asian subgroup for the BsmI polymorphism; whereas no significant association was found in other populations for other polymorphisms. Results from the current study suggest that the BsmI polymorphism is associated with increased risk of T1DM, especially in Asians. Further studies are needed to confirm our results.


Hypocalcemia secondary to hypomagnesemia in a patient on liraglutide.
A 73-year-old man with type 2 diabetes on Liraglutide with a history of coronary artery disease. Admitted to emergency for abdominal pain, severe diarrhea and episodes of tetany attacks. Laboratory workup reveals hypomagnesemia, hypocalcemia and normal parathormone (PTH). After intravenous administration of magnesium and calcium, the blood ionogram quickly normalized. In addition, plasma levels of intact parathyroid hormone increased immediately after magnesium administration. Strongly suggests that hypocalcemia resulted from a disruption of adequate parathyroid hormone secretion caused by hypomagnesemia which in turn was caused by severe diarrhea under treatment with Liraglutide.


Tourette syndrome and other tic disorders of childhood.
Tourettte syndrome (TS) is a common, childhood onset neuropsychiatric disorder consisting of multiple motor and one or more vocal tics which persist for more than 1 year. Comorbid psychiatric diagnoses are frequent in this patient population, including attention-deficit/hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). Tics can be simple or complex, and have a tendency to change over time. Tics are preceded by a premonitory sensation, wax and wane in frequency, and are often exacerbated by stress or excitement. Tic severity usually peaks in childhood, and improves in early adulthood. TS is a highly heritable disorder with a polygenic inheritance. The fundamental pathophysiology of TS is not known, although existing evidence suggests that it involves dysfunction of the basal ganglia and frontal cortical circuits, as well as dopaminergic neurotransmission. Treatment of TS involves consideration of symptom severity and comorbidity. In general, comorbid ADHD and OCD lead to greater disability in these patients, and therefore are the initial treatment priority. As treatment for tics does not alter the natural history of the disorder, it is only recommended if the tics are causing disability. Effective treatments to suppress tics include α-adrenergic agonists and antipsychotic medications.


The effect of dermally applied levamisole against the parasitic nematodes of cattle.
A series of trials to establish the anthelmintic efficiency of levamisole, when applied dermally to calves, is described. The levamisole base was formulated in a suitable solvent system at 100 g/l and applied dermally at a dose rate of 8 mg base/kg. This gave efficiencies of 97.1-100%, 88.5-100%, 100%, 98.7-100% and 89.2-100% against adult Haemonchus placei, Ostertagia spp, Cooperia spp, Oesophagostomum radiatum and Trichostrongylus axei, respectively. Activity against the immature stages of H. placei was recorded at 100%, and against immature Cooperia spp the range was 96.3-100%. Extremely variable results were obtained against immature Ostertagia spp, efficiency ranging from 0% to 100%. Efficiency against adult Dictyocaulus viviparus was in the range of 84-100%. The potential advantage of a dermally applied anthelmintic is discussed.


Rhomboid excision and Limberg flap for managing pilonidal sinus: long-term results in 411 patients.
To investigate the results of rhomboid excision and the Limberg flap procedure to treat pilonidal sinus disease. The records of 411 patients with pilonidal sinus disease, who underwent rhomboid excision and Limberg flap procedure, were analysed. All sinus tracks were resected en bloc, and a Limberg flap was prepared from left or right gluteal region. A suction drain was routinely used. The mean follow-up period was 109.2 +/- 4.5 months (range: 12-183 months). Recurrence occurred in 12 (2.91%) patients who were all male. In 42 (10.21%) patients, anaesthesia or hypoaesthesia of the upper portion of the flap occurred; this was temporary in 25 patients. Twelve (2.91%) patients developed a seroma and 15 (3.64%) a wound infection. The average hospital stay was 3.2 days (range: 1-10 days), and the average time of return to work was 12.4 days (range: 7-18 days). The average time to walk without pain was 13.4 days (range: 10-28 days) and the average time to sitting on the toilet without pain was 16.1 days (range: 12-28 days). The Limberg flap procedure is effective and has a low complication rate, short time for returning to normal activity and short hospitalization.


Comparison of three different methods used in the preparation of leukocyte-poor platelet concentrates.
We compared three methods for preparing leukocyte-poor platelet concentrates from random donors: the centrifugation procedure 400 g/6 min, the filtration by Immugard TFIG 500 Y and the Cutter Leukotrap platelet pooling system. The most efficient method with regard to removal of leukocytes and platelet yield could be obtained by filtration through the Immugard filter. Platelet loss was less than 10% and the residual leukocyte count was lower than 10 X 10(6).


Advances in genotoxicity of titanium dioxide nanoparticles in vivo and in vitro.
Titanium dioxide nanoparticles (TiO2 NPs) are currently one of the most widely used nanomaterials. Due to an increasing scope of applications, the exposure of humans to TiO2 NP is inevitable, such as entering the body through the mouth with food additives or drugs, invading the damaged skin with cosmetics, and entering the body through the respiratory tract during the process of production and handling. Compared with TiO2 coarse particles, TiO2 NPs have stronger conductivity, reaction activity, photocatalysis, and permeability, which may lead to greater toxicity to organisms. Given that TiO2 was classified as a category 2B carcinogen (possibly carcinogenic to humans), the genotoxicity of TiO2 NPs has become the focus of attention. There have been a series of previous studies investigating the potential genotoxicity of TiO2 NPs, but the existing research results are still controversial and difficult to conclude. More than half of studies have shown that TiO2 NPs can cause genotoxicity, suggesting that TiO2 NPs are likely to be genotoxic to humans. And the genotoxicity of TiO2 NPs is closely related to the exposure concentration, mode and time, and experimental cells/animals as well as its physicochemical properties (crystal type, size, and shape). This review summarized the latest research progress of related genotoxic effects through in vivo studies and in vitro cell tests, hoping to provide ideas for the evaluation of TiO2 NPs genotoxicity.


Increased amyloidogenic processing of transgenic human APP in X11-like deficient mouse brain.
X11-family proteins, including X11, X11-like (X11L) and X11-like 2 (X11L2), bind to the cytoplasmic domain of amyloid β-protein precursor (APP) and regulate APP metabolism. Both X11 and X11L are expressed specifically in brain, while X11L2 is expressed ubiquitously. X11L is predominantly expressed in excitatory neurons, in contrast to X11, which is strongly expressed in inhibitory neurons. In vivo gene-knockout studies targeting X11, X11L, or both, and studies of X11 or X11L transgenic mice have reported that X11-family proteins suppress the amyloidogenic processing of endogenous mouse APP and ectopic human APP with one exception: knockout of X11, X11L or X11L2 has been found to suppress amyloidogenic metabolism in transgenic mice overexpressing the human Swedish mutant APP (APPswe) and the mutant human PS1, which lacks exon 9 (PS1dE9). Therefore, the data on X11-family protein function in transgenic human APP metabolism in vivo are inconsistent. To confirm the interaction of X11L with human APP ectopically expressed in mouse brain, we examined the amyloidogenic metabolism of human APP in two lines of human APP transgenic mice generated to also lack X11L. In agreement with previous reports from our lab and others, we found that the amyloidogenic metabolism of human APP increased in the absence of X11L. X11L appears to aid in the suppression of amyloidogenic processing of human APP in brain in vivo, as has been demonstrated by previous studies using several human APP transgenic lines with various genetic backgrounds. X11L appears to regulate human APP in a manner similar to that seen in endogenous mouse APP metabolism.


New bronchodilators selected by molecular topology.
Molecular topology has been applied to find new lead compounds with bronchodilator activity. Among the selected compounds stands out 3-(1H-tetrazol-5yl)-9H-thioxanthene-9 -one-10,10-dioxide, anthrarobin, 9-oxo-9H-thioxantene-3-carboxylic-10,10-dioxide acid, acenocoumarol and griseofulvin, with a percentage of relaxation, at 0.1 mM, of 91, 92, 85, 69, and 74%, respectively. Theophylline shows a correspondent value of 77% (Emax = 100% at 1 mM).


Low-fat pork liver pâtés enriched with n-3 PUFA/konjac gel: dynamic rheological properties and technological behaviour during chill storage.
Low-fat pork liver pâtés enriched with n-3 PUFA/konjac gel were formulated by replacing (total or partially) pork backfat by a combination of healthier oils (olive, linseed and fish oils) and konjac gel. Dynamic rheological properties and technological behaviour of pâtés during chill storage (2 °C, 85 days) were analysed. Cooking yields were affected (P<0.05) by formulation, with percentages ranging between 88 and 98%. According to the frequency sweep test, pâtés presented a gel/emulsion-like pattern with a loosely-structured network and the consistency of a viscoelastic gel. Thermal processing caused the formation of a protein gel network with a considerable element of emulsion-like characteristics. Pâtés became lighter and less red (P<0.05) during chill storage. Purge losses of around 1% were observed at the end of the storage period, irrespective of formulation. Textural parameters of pâtés were affected by formulation and storage time. The results suggest that the replacement of pork back fat by oil-in-water emulsion and the incorporation of konjac gel could provide a mixture of ingredients that effectively mimics the normal animal fat content in pâtés.


Investigating employees' deviant work behavior in the hotel industry during COVID-19: Empirical evidence from an emerging country.
Employees in the hotel industry are among the most vulnerable groups that have been severely affected by the COVID-19 pandemic. Anchored on the general strain theory, transactional theory of stress and coping, and theory of justice, this study investigates the mechanism through which hotel employees' perceived job insecurity affects their deviant work behavior during the COVID-19 pandemic. A survey method was used to collect three-wave sample data from 988 hotel employees in popular tourist destinations in Vietnam. Multivariate data analysis reveals a positive relationship between perceived job insecurity and deviant work behavior, and this relationship is mediated by psychological distress. Furthermore, abusive supervision positively moderates the association between psychological distress-deviant work behavior and the indirect influence of perceived job insecurity on deviant work behavior through psychological distress. These findings are useful for hotel managers seeking to manage and develop employees in a global health crisis such as COVID-19.


Right ventricular perforation during femoral venous cannulation--lessons learned.
Peripheral cannulation for cardiopulmonary bypass is increasingly used for minimally invasive and re-operative cardiac surgery. Transoesophageal echo (TOE) is used routinely to guide placement of the peripheral venous cannula in the right atrium/superior vena cava (SVC). We here present a case where despite use of TOE, placement of the venous cannula led to perforation of the right ventricular apex. We describe the surgical management of the problem and highlight strategies to avoid this complication.


Reinforced fascia patch limits cyclic gapping of rotator cuff repairs in a human cadaveric model.
Scaffolds continue to be developed and used for rotator cuff repair augmentation, but clinical or biomechanical data to inform their use are limited. We have developed a reinforced fascia lata patch with mechanical properties to meet the needs of musculoskeletal applications. The objective of this study was to assess the extent to which augmentation of a primary human rotator cuff repair with the reinforced fascia patch can reduce gap formation during in vitro cyclic loading. Nine paired human cadaveric shoulders were used to investigate the cyclic gap formation and failure properties of augmented and non-augmented rotator cuff repairs with loading of 5 to 180 N for 1000 cycles. Augmentation significantly decreased the amount of gap formation at cycles 1, 10, 100, and 1000 compared with non-augmented repairs (P < .01). The mean gap formation of the augmented repairs was 1.8 mm after the first cycle of pull (vs 3.6 mm for non-augmented repairs) and remained less than 5 mm after 1000 cycles of loading (4.7 mm for augmented repairs vs 7.3 mm for non-augmented repairs). Furthermore, all augmented repairs were able to complete the 1000-cycle loading protocol, whereas 3 of 9 non-augmented repairs failed before completing 1000 loading cycles. This study supports further investigation of reinforced fascia patches to provide mechanical augmentation, minimize tendon retraction, and possibly reduce the incidence of rotator cuff repair failure. Future investigation in animal and human studies will be necessary to fully define the efficacy of the reinforced fascia device in a biologic healing environment.


Ascending fiber projections from the midbrain central gray to the ventromedial hypothalamus in the rat.
In 18 urethane-anesthetized ovariectomized female rats, 54 neurons in and around the hypothalamic ventromedial nucleus were transynaptically activated by electrical stimulation of the mesencephalic central gray matter. Ventromedial nucleus afferents from either the dorsal longitudinal fascicle (N = 10) or the medial forebrain bundle (N = 8) were disrupted by a small knife cut. In animals which lacked inputs from the dorsal longitudinal fascicle by a cut posterior to the ventromedial nucleus, transynaptic activation followed central gray stimulation in 20 cells; 26 cells were driven from the central gray in animals deprived of afferents through the medial forebrain bundle by a cut placed laterally to the ventromedial nucleus. Two patterns of synaptic activation followed electrical stimulation at 0.5 Hz: one type of response occurred during a latency range of 4 to 20 ms with fluctuation of each response less than 5 ms, the other type was characterized by diffuse activation for 50 ms following central gray stimulation. It was noted that the former time-locked response occurred in 19 among 20 cells in the posterior-cut animals, and the latter diffuse response was seen in 20 of 26 cells in the lateral-cut animals. Electrical stimulation of the ventromedial nucleus in another group of seven animals with the posterior cut caused antidromic activation of 19 central gray cells at latencies of 4.8 to 21.0 ms. Thus, central gray axons in the medial forebrain bundle were shown to have direct access to the ventromedial nucleus and multisynaptic pathways intervened for those in the dorsal longitudinal fascicle.


Delicate conformational balance of the redox enzyme cytochrome P450cam.
The energy landscapes of proteins are highly complex and can be influenced by changes in physical and chemical conditions under which the protein is studied. The redox enzyme cytochrome P450cam undergoes a multistep catalytic cycle wherein two electrons are transferred to the heme group and the enzyme visits several conformational states. Using paramagnetic NMR spectroscopy with a lanthanoid tag, we show that the enzyme bound to its redox partner, putidaredoxin, is in a closed state at ambient temperature in solution. This result contrasts with recent crystal structures of the complex, which suggest that the enzyme opens up when bound to its partner. The closed state supports a model of catalysis in which the substrate is locked in the active site pocket and the enzyme acts as an insulator for the reactive intermediates of the reaction.


Effects of cytosine arabinoside on in vivo and in vitro mouse limb development.
When pregnant mice were exposed to 40 mg per kg of cytosine arabinoside (ara-C) on days 10 to 12 of gestation, adactylous limbs with large, distally located blisters were found when the fetuses were examined on day 18. Embryonic limbs exposed transplacentally under identical conditions and explanted to culture exhibited the same morphological abnormality as did limbs exposed directly in culture to 0.1 to 1 microgram per ml of ara-C. Two noncytotoxic analogues of ara-C, uridine arabinoside (ara-U) and hypoxanthine arabinose (ara-HX), had no influence on morphological differentiation of limbs in vitro. Ara-C alone caused a dose-related decrease in uptake of 3H-thymidine and 35SO4 in cultured limb buds. Production of this morphologically distinct malformation in vitro will allow detailed biochemical investigations on the effect of ara-C limb ectodermal-mesenchymal interactions.


CYPRUS TURKISH FAIRY TALES: GLIMPSE OF A HARMONIOUS PAST.
On the island of Cyprus, believed to be the birthplace of Aphrodite, the Muslim minority (settled there following the Ottoman conquest of the island in 1571) and Orthodox Christians (the native majority) lived together in peace for hundreds of years. However, as a result of ethnic conflict in the late 1950s, the Muslim Cypriot Turks established their own political state in the north of the island in 1974, and Cyprus was divided into northern Turkish and southern Greek sections. This paper attempts to examine historical, religious, cultural and psychological aspects of the relationship between these two large groups, prior to recent conflicts, by studying fairy tales told by Turkish Cypriots about a hundred years ago. It is hoped that this paper will encourage similar studies of other communities where different large-group identities live side by side, and that such studies may support their peaceful co-existence.


Pre-hospital lung ultrasound for cardiac heart failure and COPD: is it worthwhile?
Pre-hospital ultrasound is a new challenge and lung ultrasound could be an interesting opportunity in the pre-hospital medical service. The aim of our study was to evaluate the efficacy of lung ultrasound in out-of-hospital non-traumatic respiratory insufficiency. We planned a case-controlled study in the ULSS 5 ovest vicentino area (Vicenza-Italy) enrolling subjects with severe dyspnea caused by cardiac heart failure or acute exacerbation of chronic obstructive pulmonary disease. We compared drugs administration, oxygen delivery, and laboratory tests between those patients with ultrasound integrated management and those without ultrasound. Pre-hospital lung ultrasound had a high specificity (94.4%) and sensitivity (100%) for the correct identification of alveolar interstitial syndrome using B lines, whereas the percentages obtained with pleural effusion were lower (83.3, 53.3%, respectively). The patients with ultrasound integrated management received a more appropriate pharmacological therapy (p 0.01), as well as non-invasive ventilation (CPAP) was used more frequently in those with an acute exacerbation of chronic obstructive pulmonary disease (p 0.011). Laboratory tests and blood gases analysis were not significant different between the two study groups. In a sub-analysis of the patients with an A profile, we observed a significant lower concentration of PCO2 in those with an ultrasound integrated management (PCO2: 42.62 vs 52.23 p 0.049). According with physicians' opinion, pre-hospital lung ultrasound gave important information or changed the therapy in the 42.3% of cases, whereas it just confirmed physical examination in the 67.7% of cases. Pre-hospital lung ultrasound is easy and feasible, and learning curve is rapid. Our study suggests that cardiac heart failure and acute exacerbation of chronic obstructive pulmonary disease can be considered two indications for pre-hospital ultrasound, and can improve the management of patient with acute respiratory insufficiency.


The ghrelin gene products and exendin-4 promote survival of human pancreatic islet endothelial cells in hyperglycaemic conditions, through phosphoinositide 3-kinase/Akt, extracellular signal-related kinase (ERK)1/2 and cAMP/protein kinase A (PKA) signalling pathways.
Pancreatic islet microendothelium exhibits unique features in interdependent relationship with beta cells. Gastrointestinal products of the ghrelin gene, acylated ghrelin (AG), unacylated ghrelin (UAG) and obestatin (Ob), and the incretin, glucagon-like peptide-1 (GLP-1), prevent apoptosis of pancreatic beta cells. We investigated whether the ghrelin gene products and the GLP-1 receptor agonist exendin-4 (Ex-4) display survival effects in human pancreatic islet microendothelial cells (MECs) exposed to chronic hyperglycaemia. Islet MECs were cultured in high glucose concentration and treated with AG, UAG, Ob or Ex-4. Apoptosis was assessed by DNA fragmentation, Hoechst staining of the nuclei and caspase-3 activity. Western blot analyses and pharmacological inhibition of protein kinase B (Akt) and extracellular signal-related kinase (ERK)1/2 pathways, detection of intracellular cAMP levels and blockade of adenylyl cyclase (AC)/cAMP/protein kinase A (PKA) signalling were performed. Levels of NO, IL-1β and vascular endothelial growth factor (VEGF)-A in cell culture supernatant fractions were measured. Islet MECs express the ghrelin receptor GHS-R1A as well as GLP-1R. Treatment with AG, UAG, Ob and Ex-4 promoted cell survival and significantly inhibited glucose-induced apoptosis, through activation of PI3K/Akt, ERK1/2 phosphorylation and intracellular cAMP increase. Moreover, peptides upregulated B cell lymphoma 2 (BCL-2) and downregulated BCL-2-associated X protein (BAX) and CD40 ligand (CD40L) production, and significantly reduced the secretion of NO, IL-1β and VEGF-A. The ghrelin gene-derived peptides and Ex-4 exert cytoprotective effects in islet MECs. The anti-apoptotic effects involve phosphoinositide 3-kinase (PI3K)/Akt, ERK1/2 and cAMP/PKA pathways. These peptides could therefore represent a potential tool to improve islet vascularisation and, indirectly, islet cell function.


Cellular and humoral observations in a patient with allergic bronchopulmonary aspergillosis during a nonasthmatic exacerbation.
A patient is described with an asymptomatic exacerbation of allergic bronchopulmonary aspergillosis (ABPA), clinically characterized by pulmonary infiltrates, with absence of obstructive reactions and a short period of hemoptysis 2 weeks before hospitalization. Cell counts and antibody concentrations were measured in serum, and bronchoalveolar fluid (BAF) samples and values were compared with data from previous periods of symptomatic exacerbations. During the asymptomatic exacerbation, concentrations of antibody to Aspergillus fumigatus, total IgE, and precipitating antibodies were elevated in peripheral blood. No quantitative differences in specific antibody concentrations (IgE, IgG, IgA, and IgM) against A. fumigatus were found between sera from symptomatic and asymptomatic periods of ABPA. In contrast to observations in the serum, protein concentrations in BAL fluid were normal during the asymptomatic period, whereas high concentrations were found during the symptomatic phases. Local antibody concentrations (in BAF) were characterized by high levels of IgA antibodies against A. fumigatus. During asymptomatic and symptomatic phases, eosinophils were elevated in peripheral blood, in sputum, in BAF, and highly elevated in tissue biopsy specimens. Activated eosinophils were found, as indicated by the presence of light-density cells in the circulation and monoclonal antieosinophil cationic protein binding to bronchoalveolar lavage eosinophils. In contrast to the symptomatic phase of ABPA in 1980, demonstrating aspecific airway reactivity to several pharmacologically active substances, no such hyperreactivity was found during the asymptomatic phase of ABPA in 1986. It is proposed that the asymptomatic infiltrative phase of ABPA is an intermediate stage that can develop into a symptomatic phase after prolonged and intensified infiltration of eosinophils. Mediators from the inflammatory cells may be involved in the induction of bronchial hyperresponsiveness. After induction of this hyperreactive stage of the airways, additional liberation of mediators from either eosinophils and/or mast cells will lead to a symptomatic (obstructive) phase of ABPA.


Inhibition of erosive dissolution by sodium fluoride: evidence for a dose-response.
The aim of this study was to investigate the protective effects of sodium fluoride solutions and commercial mouthrinses on hydroxyapatite (HA) dissolution in citric acid in vitro, with and without a salivary pellicle. A rapid-throughput HA solubility-reduction model was employed in which HA dissolution was quantified using ion chromatography. Two HA substrates were selected, a high-resolution powder and 80 μm diameter beads, and studied in the presence and absence of a salivary pellicle (pooled human saliva, 2 h). Immediately prior to acid exposure, substrates were exposed to one of a number of pre-treatments that included aqueous fluoride (F(-)) solutions and commercially available mouthrinses with F(-) concentrations of 0-450 μg/g (as NaF). Dissolution reduction was calculated relative to a deionised water negative control. For aqueous solutions and mouthrinses, a fluoride dose-response was observed with a plateau around 100 μg/g F(-) for both HA substrates, with or without pellicle. Concentrations as low as 10 μg/g F(-) significantly reduced HA dissolution. The HA substrate had little impact on the fluoride dose-response, and the fluoride was equally effective in the presence of a pellicle as in its absence. Fluoride significantly reduced HA dissolution at concentrations of 10 μg/g and higher. A fluoride dose-response was seen at low concentrations. This study illustrates the use of a powerful rapid-throughput HA solubility-reduction model for investigating HA dissolution in citric acid in the presence of dissolution inhibitors. A single exposure to fluoride solutions with fluoride concentrations and exposure time representative of brushing or rinsing with mainstream oral care products was shown to significantly inhibit HA dissolution under conditions relevant to dental erosion. A similar efficacy was observed in the presence and absence of salivary pellicle.


Microbial surveillance of Hajj tents: Bioaerosol sampling coupled with real-time multiplex PCR.
Respiratory tract infections are common among pilgrims attending annual Hajj in Mecca, Saudi Arabia. Pilgrims typically spend most of the Hajj period inside ventilated tents, where microorganisms may be transmitted through bioaerosols and droplets. To perform microorganism surveillance inside Hajj tents and assess the similarities between microorganisms isolated from tent bioaerosol samples and nasopharyngeal swabs (NP) of tent occupants. Respiratory microorganisms in bioaerosols collected from Hajj tents over a 4-day period were compared with NP of tent occupants using real-time multiplex polymerase chain reaction analysis. A total of 152 samples were collected: 120 tent bioaerosol samples collected on days 9, 10, 11, and 12 of Dhu al-Hijjah, and 32 NP collected on day 12 of Dhu al-Hijjah (corresponding to 23/08/2018). Eighty-three (69.2%) bioaerosol samples tested positive for at least 1 microorganism, with the number of pathogens increasing over the 4 days of sampling. Twenty-seven (84.38%) NP swabs from tent occupants also tested positive. Microorganisms identified in pilgrim nasal carriage and tent bioaerosol samples were similar, and included K. pneumonia, S. aureus, S. pneumonia, human adenovirus, Moraxella, influenza A, and H. influenza. The data suggest that the Hajj tent environment may contribute to the spread of airborne infections during Hajj. This can have important ramifications for novel pathogens with pandemic potential.


A critical synopsis of the diagnostic and screening radiology outcomes literature.
In summary, the radiology outcomes research literature is both extensive and broad. The methodologic quality, however, is quite variable. Overall, this quality could be improved by intervention in two areas: methodologic dissemination and development. The number of researchers investigating radiology-related outcomes is high, and presently there are over 20 journals devoted exclusively to radiology research. Even with a relatively narrow definition of "outcomes," we identified over 200 radiology outcomes studies, most from the past few years. However, the methodologic quality of most of these articles was relatively low, with important design flaws and biases. Nonetheless, a substantial number of radiology publications do employ state-of-the-art research methods and innovative approaches to methodologic challenges. The quality of radiology outcomes research overall would benefit tremendously from dissemination of such research methods. Instruction in outcomes research methods is accessible to radiologists. For example, there have been several recent articles and series of articles on outcomes research methods in JAMA, including guidelines for the performance and reporting of cost-effectiveness analyses (38-40) and for developing clinical prediction rules (57). Within radiology, several recent articles have appeared on, among other things, cost-effectiveness analysis (34,59,60), assessing quality of life (43), screening for disease (53), and defining the study population (61). The research compendium compiled for the GERRAF (General Electric-Association of University Radiologists Radiology Research Academic Fellowships) program remains a comprehensive methodologic source for many of the issues in radiology outcomes research, and outcomes research methods courses are offered every year at the Society for Health Services Research in Radiology and Society for Medical Decision Making meetings, as well as at the meeting of the Radiological Society of North America. Even so, awareness of the need for such research techniques remains limited. Dissemination of sound research methods is limited at least in part by the current incentives in radiology research. At many institutions, the number of research publications produced, rather than their quality, determines promotion or academic success. Unfortunately, more rigorous study designs often require more time and resources. Further, because peer reviewers are often as uninformed about research methods as the bulk of those who are submitting manuscripts, it may actually be more difficult to publish articles with more advanced methodologic designs. The standard in radiology is the uncontrolled case series, and deviation from the standard may make acceptance for publication more difficult. On a more optimistic note, recent publication of a number of methodology articles suggests that at least some journals are promoting improved research in methodology (43,53,59-61). We hope that time will be available for manuscript reviewers to learn to understand the strengths and weaknesses of various research approaches. If more rigorous study designs were required for publication, radiology outcomes research would probably improve drastically. Nevertheless, the current peer-review system does not effectively promote sound research design. The other great incentive in research is funding. Clearly, if advanced research design is required for funding, then there is incentive for improvement in research quality. Traditionally, National Cancer Institute and other National Institutes of Health and public sector funding has been predicated on a high level of research sophistication. Undoubtedly, availability of grants for diagnostic and screening imaging clinical trials and other research will go far to improve radiology research methods. The other traditional source of research funding is industry.


Unchanged plasma levels of dimethylarginines and nitric oxide in chronic hepatitis C.
Previous studies have shown that asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA) and nitric oxide (NO) play a prominent role in liver dysfunction. The objective of this study was to determine whether plasma levels of ADMA, SDMA and NO are altered in patients with chronic hepatitis C. Plasma levels of ADMA, SDMA and NO (nitrite plus nitrate) were measured in 22 patients with chronic hepatitis C and 24 patients with sustained virologic response after treatment with peginterferon plus ribavirin. Seven healthy volunteers served as controls. Plasma levels of ADMA, SDMA and NO were not significantly different between groups: chronic hepatitis C, ADMA 0.55+/-0.06, SDMA 0.22+/-0.03, NO 36.3+/-5.9 micromol/l; treated patients, ADMA 0.60+/-0.15, SDMA 0.31+/-0.05, NO 36.1+/-5.5 micromol/l; controls, ADMA 0.65+/-0.08, SDMA 0.28+/-0.05, NO 40.7+/-8.9 micromol/l). Our results show that plasma NO, ADMA and SDMA concentrations are not changed in patients with chronic hepatitis C without superimposed signs of acute inflammatory activity. Furthermore, no significant differences in plasma values of NO and dimethylarginines were observed between the group of untreated patients and the group of patients treated with interferon plus ribavirin.


In vitro and in vivo actions of zinc ion affecting cellular substances which influence host metabolic responses to inflammation.
Glycogen-stimulated rabbit peritoneal exudate cells (polymorphonuclear leukocytes, PMN) produce prostaglandins (PG) and substances which induce alterations (mediators) in experimental animals characteristic of host metabolic responses to infection and other acute inflammatory stresses. The effect of Zn2+ on mediator production and PG synthesis was examined because: Zn homeostasis is perturbed during infection, Zn is known to regulate some cellular functions, and there appears to be an interrelationship between PG synthesis and mediator production. Using exudate cells, 2 mM Zn2+ caused complete inhibition of in vitro PG synthesis as assessed by conversion of [1-14C] arachidonic acid into PG. This concentration of Zn2+ also inhibited production of substances mediating plasma Zn depression, hepatic amino acid "uptake", fever, and neutrophil release from bone marrow. Conversely, Zn2+ did not inhibit in vivo metabolic responses to these mediators. Zn-pretreatment of rabbits or simultaneous injection of Zn2+ and crude PMN-derived pyrogenic activity resulted in prolongation of fever. It is suggested that this action of Zn2+ may be attributed to either stabilization of cyclic AMP through inhibition of phosphodiesterase or a Zn-mediator interaction which stabilizes crude endogenous pyrogen. The potential physiological significance of these results includes: possible potentiation of the host's defense mechanisms by Zn2+ and its utilization for prolongation of fever to determine its effect on potentially temperature-dependent host defense mechanisms.


Effect of novel 1-phenyl-3-methyl-4-acylpyrazolones on iron chelation and Fenton reaction.
Iron is an essential element in many physiological processes due to its ability to easily convert between two oxidation states Fe(III)/Fe(II). However, at a pathological state, unbound iron may promote the production of highly toxic hydroxyl radicals via Fenton reaction, particularly when it is present in the excess.Iron chelators forming tight complexes with iron may prevent this reaction. In this study, novel synthetic 1-phenyl-3-methyl-4-acyl-pyrazol-5-ones were analyzed for their iron-chelating properties at four pathophysiologically relevant pH conditions (4.5-7.5) as well as for their effects on iron-based Fenton reaction. For the former competitive ferrozine spectrophotometric assay and for the latter HPLC method using salicylic acid as the indicator of hydroxyl radical production were used. All of the tested acylpyrazolones were efficient ferric chelators, however, their ferrous-chelating properties were clearly dependent on an acyl substitution. Interestingly, several acylpyrazolones had ferrous-chelating properties superior to those of the standard iron chelator - deferoxamine. Of particular interest is H2QpyQ, i.e. 2,6-bis[4(1-phenyl-3-methylpyrazol-5-one)carbonyl]pyridine, whose ferrous-chelating properties were increasing while pH was decreasing. In spite of large differences in ferrous chelation, a majority of the tested acylpyrazolones were powerful inhibitors of Fenton reaction as deferoxamine. In conclusion, the novel 1-phenyl-3-methyl-4-acyl-pyrazol-5-ones are efficient iron chelators and H2QpyQ may represent a prototype of specific iron chelators designed for chelation at acidic conditions in particular.


The Standard Membrane Feeding Assay: Advances Using Bioluminescence.
In preclinical development, the efficacy of agents with putative effects on Plasmodium transmission is determined using the standard membrane feeding assay (SMFA). Because the end-point of the SMFA is normally the enumeration of oocysts on the mosquito midgut, the assays reliance on mosquito dissections and microscopy makes it slow, labor-intensive, and subjective. Below, we describe a novel method of assessing the transmission of a Plasmodium falciparum strain expressing the firefly luciferase protein in the SMFA. The use of a transgenic parasite strain allows for the elimination of mosquito dissections in favor of a simple approach where whole mosquitoes are homogenized and examined directly for luciferase activity. Measuring the mean luminescence intensity of groups of individual or pooled mosquitoes provides comparable estimates of transmission reducing activity at 5-10-fold the throughput capacity of the standard microscopy based SMFA. This high efficiency protocol may be of interest to groups screening novel drug compounds, vaccine candidates, or sera from malaria exposed individuals for transmission reducing activity (TRA).


Immediate versus delayed medical treatment for first-trimester miscarriage: a randomized trial.
To compare immediate vs delayed medical treatment for first-trimester miscarriage. Randomized open-label trial in a university hospital gynecologic emergency department. Between April 2003 and April 2006, 182 women diagnosed with spontaneous abortion before 14 weeks' gestation were assigned to immediate medical treatment (oral mifepristone, followed 48 hours later by vaginal misoprostol, n = 91) or sequential management (1 week of watchful waiting followed, if necessary, by the above-described medical treatment, n = 91). Vacuum aspiration was performed in case of treatment failure, hemorrhage, pain, infection, or patient request. Compared with immediate medical treatment, sequential management resulted in twice as many vacuum aspirations overall (43.5% vs 19.1%; P < .001), 4 times as many emergent vacuum aspirations (20% vs 4.5%; P = .001), and twice as many unplanned visits to the emergency department (34.1% vs 16.9%; P = .009). Delaying medical treatment of first-trimester miscarriage increases the rate of unplanned surgical uterine evacuation.


[Screening for Y chromosome microdeletions in assisted reproductive techniques].
In case of infertility due to azoospermia, clinical, sonographical and biological examinations suggest obstructive or non obstructive causes. In cases of non obstructive azoospermia, genomic microdeletions must be determined particularly in the Y chromosome long arm, as well as autosomal abnormality. A constitutional karyotype must also be done. The so-called Y AZFa, AZFb and AZFc zones could be partially or totally absent. Genotype is mostly correlated with histology. Thus, when large AZFa and AZFb microdeletions are detected there is theoretically no chance to find testicular spermatozoa. If only AZFc microdeletions are present, testicular biopsy is possible with a good chance of mature spermatozoa retrieval before microinjection, and AZFc microdeletions are also often present (10%) in cases of severe oligospermia. Couples must be informed of genomic deletions and a genetic counseling is essential to explain the potential childhood risks after assisted reproductive techniques. This problem has been discussed by the French "High Authority of Health". It recommends determination of these Y microdeletions when oligozoospermia is severe (lower than one million spermatozoa per milliliter).


Effectiveness and safety of rabbit anti-thymocyte globulin in Japanese patients with aplastic anemia.
Immunosuppressive therapy (IST) with antithymocyte globulin (ATG) and cyclosporine A is the standard treatment for aplastic anemia (AA). The ATG formulation in Japan was changed from horse ATG [Lymphoglobulin(®) (LG)] to rabbit ATG [Thymoglobulin(®) (TG)] in 2009. Since then, 12 patients with AA have been treated with TG. Here, we summarize the effectiveness and safety of TG in comparison with data from 14 AA patients treated with LG before April 2009. One subject treated with LG but none treated with TG terminated the treatment due to a grade III adverse effect. The overall 6-month response rate after IST was similar for LG and TG (67 and 75 %). Infection was noted in five (38 %) and four (33 %) subjects treated with LG and TG, respectively. The initial response rate was significantly higher in the early-treatment group treated within a year of diagnosis than in the late-treatment group, who were treated more than a year after diagnosis (85 vs. 29 %, respectively), as reported previously, without apparent differences between the LG and TG groups. We conclude that TG at a dose of 2.5 mg/kg/day for 5 days is effective and safe in Japanese patients with AA.


Incorporating feminist theory and insights into a restorative justice response to sex offenses.
Sex offenses, particularly nonpenetration sex offenses and acquaintance sexual assault, are all too common. Because these crimes reinforce women's fear of crime and restrict spatial and social freedom, it is paramount for the justice system to act affirmatively; however, it does not. This article identifies several failures in the current response to these sex offenses. We describe the research demonstration project, RESTORE, operating in Pima County, Arizona, which uses a restorative justice response as a way of remedying some of those failures. Identifying central feminist insights that guided the development of that project, the article addresses concerns raised by feminists about the use of restorative justice for gendered violence. We conclude that most if not all of these concerns apply to cases of on going domestic violence--cases specifically excluded from the RESTORE program--rather than to cases of acquaintance sexual assault or nonpenetration sex offenses.


Tumours in Iceland. 10. Malignant tumours of the female breast. A histological classification, laterality, survival and epidemiological considerations.
The Icelandic Cancer Registry has records of 1,720 cases of malignant tumours of the female breast diagnosed in 1,659 patients in the 30-year period 1955-1984. Of these, 1,658 tumours were invasive. Sufficient histological material existed for 1,666 malignant tumours to make it possible to classify them according to the criteria published by the WHO. The most frequent histological type was Ductal carcinoma: 1,064 neoplasms, or 64%. Second in frequency was Lobular carcinoma: 175 neoplasms, or 10%; third was Mucinous carcinoma: 115 neoplasms, or 7%; and fourth in frequency was Medullary carcinoma: 69 neoplasms, or 4%. The incidence of carcinoma of the breast increased by 74% from 37.0 per 100,000 per annum in 1955-59 to 64.4 per 100,000 in 1980-84. This increase in incidence affected all morphological types, but Lobular and Mucinous more than Ductal and Medullary. The survival times have improved with time. Unilateral tumours were 710 in the right and 837 in the left breast. Both breasts were involved 167 times (106 patients), and in 6 patients the side was not recorded. A second primary was more likely to develop when the first one was in the right breast. This study of malignant tumours of the breast is the tenth in a series of investigations into histological classification of tumours occurring in Iceland.


Competition between freshwater fish and goldeneyes Bucephala clangula (L.) for common prey.
Results of a descriptive field study showed that goldeneyes preferred lakes without fish to those with fish. Field experiments were carried out in order to investigate whether or not this preference could be ascribed to a higher food supply in the lakes devoid of fish, as goldeneyes and some freshwater fish (perch and roach in the studied lakes) to some extent feed on the same kinds of prey. Changes in the abundance of prey common to fish and goldeneyes and the use by goldeneyes of lakes after experimentally changed predation pressure from fish were studied. Some aquatic insect groups, Cloeon larvae, Odonata larvae, water bugs, dytiscids, and Chaoborus larvae, proved sensitive to predation from fish. Goldeneyes increased their use of an experimental lake after fish were removed, and they used this lake more than an adjacent control lake. It is suggested that fish are able to reduce the availability of foods common to the goldeneyes to such an extent that the selection by the ducks of feeding localities is affected, and that exploitation competition between freshwater fish and goldeneyes may occur.


Mercury contamination in spotted seatrout, Cynoscion nebulosus: an assessment of liver, kidney, blood, and nervous system health.
Marine fishes in South Florida (Florida Keys-Florida Bay-Everglades region) accumulate higher concentrations of mercury (Hg) in their tissues than similar fishes from other areas of the southeastern U.S., though it is not known whether these elevated levels affect fish health. In this study, we used quantifiable pathological and biochemical indicators to explore Hg-associated differences in marine fish from South Florida, where Hg contamination is high, and from Indian River Lagoon, Florida, which served as a reference area. Hg concentrations in all tissues of mature spotted seatrout (Cynoscion nebulosus) from South Florida were significantly higher than those from Indian River Lagoon and were within the threshold range of those in studies where effects of Hg exposure have been observed. The distribution of Hg among tissues followed the same trend in both areas, with the greatest concentration in kidney tissue, followed by liver, muscle, brain, gonad, and red blood cells. Blood-plasma biochemistry showed that concentrations of iron, inorganic phosphate, lactate dehydrogenase, and aspartate aminotransferase were significantly less in South Florida. Also, fructosamine and alkaline phosphatase were significantly less in South Florida. Liver histology revealed that pyknosis/necrosis, interstitial inflammation, and bile duct hyperplasia were found only in seatrout from South Florida, and steatosis/glycogen was more frequently found in Indian River Lagoon specimens. In renal tissue, interstitial inflammation, glomerular dilatation and thickening, and tubular degeneration and necrosis were more frequently found in South Florida specimens. Changes in the liver cytoskeleton and morphology may explain some of the differences in blood parameters between study areas. Neurochemical analyses showed that brain N-methyl-d-aspartic acid (NMDA) receptors (but not those of muscarinic cholinergic receptors, monoamine oxidase, or acetylcholinesterase) were significantly less in fish from South Florida than from Indian River Lagoon. These findings provide compelling evidence that elevated Hg could cause quantifiable pathological and biochemical changes that might influence the health of spotted seatrout and could also affect other marine fish species.


Generator based approach to analyze mutations in genomic datasets.
In contrast to the conventional approach of directly comparing genomic sequences using sequence alignment tools, we propose a computational approach that performs comparisons between sequence generators. These sequence generators are learned via a data-driven approach that empirically computes the state machine generating the genomic sequence of interest. As the state machine based generator of the sequence is independent of the sequence length, it provides us with an efficient method to compute the statistical distance between large sets of genomic sequences. Moreover, our technique provides a fast and efficient method to cluster large datasets of genomic sequences, characterize their temporal and spatial evolution in a continuous manner, get insights into the locality sensitive information about the sequences without any need for alignment. Furthermore, we show that the technique can be used to detect local regions with mutation activity, which can then be applied to aid alignment techniques for the fast discovery of mutations. To demonstrate the efficacy of our technique on real genomic data, we cluster different strains of SARS-CoV-2 viral sequences, characterize their evolution and identify regions of the viral sequence with mutations.


Trophic magnification of polybrominated diphenyl ethers in the marine food web from coastal area of Bohai Bay, North China.
Trophic transfer of polybrominated diphenyl ethers (PBDEs) in aquatic ecosystems is an important criterion for assessing their environmental risk. This study analyzed 13 PBDEs in marine organisms collected from coastal area of Bohai Bay, China. The concentrations of total PBDEs (Σ13PBDEs) ranged from 12 ± 1.1 ng/g wet weight (ww) to 230 ± 54 ng/g ww depending on species. BDE-47 was the predominant compound, with a mean abundance of 20.21 ± 12.97% of total PBDEs. Stable isotopic ratios of carbon (δ(13)C) and nitrogen (δ(15)N) were analyzed to determine the food web structure and trophic level respectively. Trophic magnification factors (TMFs) of PBDEs were assessed as the slope of lipid equivalent concentrations regressed against trophic levels. Significant positive relationships were found for Σ13PBDEs and eight PBDE congeners (BDE-28, BDE-47, BDE-49, BDE-66, BDE-85, BDE-99, BDE-100 and BDE-154). Monte-Carlo simulations showed that the probabilities of TMF >1 were 100% for Σ13PBDEs, BDE-47, BDE-85, BDE-99 and BDE-100, 99% for DE-28, BDE-49, BDE-66 and BDE-154, 94% for BDE-153, and 35% for BDE-17.


Ethanol toxic effect on the newborn rat liver.--Histochemical and electronmicroscopical investigations.
The object of the study was the liver of newborn rats. Specimens were taken from the 2nd to the 8th hour after birth. Tissue material was obtained from control animals and the newborns whose mothers had been ethanol fed throughout gestation period. 40% ethanol was administered in doses of 8.0 g/kg weight, by gastric tube. In the newborn liver ethanol ingestion had led to significant accumulation of lipids, a strong acid phosphatase reaction and to a drop in succinic dehydrogenase activity. Histochemically, the intensity of alcohol dehydrogenase activity did not show any difference when the ethanol treated newborn liver was compared with controls. Ultrastructurally, the changes in the liver cells were expressed by a disappearance of the rough endoplasmic reticulum elements. Mitochondria were often swollen and distorted.


Studies on the outbreak of hepatitis A in an institute for mentally retarded children.
The authors encountered an outbreak of acute hepatitis in a public institute for mentally retarded children in Aomori Prefecture, Japan. Studies revealed that the probable vehicles of transmission of infection were contaminated water, contaminated meals, and close contact. From the clinical manifestations and epidemiological investigations of 41 affected children and staff members, an outbreak of hepatitis A was strongly suspected. Immune electron microscopy disclosed hepatitis A virus antigen particles in the stool specimens collected during the few days before and after peak transaminase elevation. Hepatitis A antigen was further extracted and purified. The antigen was the first reported recovery of the virus from a natural outbreak of hapatitis A in Asia. Subsequently, with the immune adherence hemagglutination test, using this extracted antigen, an increase in titer of antibody to hepatitis A antigen was demonstrated. Thus, this epidemic was serologically established as an outbreak of hepatitis A. Human immune serum globulin for the protection against hepatitis A was administrated to the 80 individuals concerned, and it was effective in preventing the clinical manifestation of hepatitis.


Effects of the Diet Inclusion of Common Vetch Hay Versus Alfalfa Hay on the Body Weight Gain, Nitrogen Utilization Efficiency, Energy Balance, and Enteric Methane Emissions of Crossbred Simmental Cattle.
A low nitrogen utilization efficiency (NUE, the ratio of retained N to N intake) and high methane (CH4) emissions of ruminants can lead to potentially high diet protein wastage and directly contribute to global warming. Diet manipulation is the most effective way to improve NUE or reduce CH4 emissions. This study investigated how replacing oat hay with alfalfa hay (AH) or common vetch hay (CVH) with different proportions (20% (20) and 40% (40) of the total dry matter (DM) allowance) affects the body weight gain (BWG), NUE, and CH4 emissions of crossbred Simmental cattle. The forage dry matter intake (DMI) and the total DMI of cattle fed on a CVH40 diet were significantly higher than the values for those fed on AH20 or AH40 diets (p < 0.05). There were no differences in the BWG for the four treatments observed, however, nutrient digestibility significantly decreased in the AH40 diet as compared with the AH20 diet (p < 0.05). The NUE was significantly lower in AH40 than in CVH20. The CH4 emissions were significantly lower for the CVH40 diet than with the AH20 diet (p < 0.05). Our findings suggest that a 20% AH and 40% CVH substitution for oat hay are the optimal proportions to maintain the BWG, NUE, nutrient digestibility, and reduce the CH4 emissions of crossbred Simmental cattle. Overall, CVH has a greater potential to reduce CH4 emissions than AH.


Antimüllerian hormone levels are independently related to ovarian hyperandrogenism and polycystic ovaries.
To determine the relationship of antimüllerian hormone (AMH) levels to polycystic ovaries and ovarian androgenic function. Prospective case-control study. General clinical research center. Eumenorrheic asymptomatic volunteers without (V-NO; n = 19; reference population) or with (V-PCO; n = 28) a polycystic ovary and hyperandrogenemic anovulatory subjects grouped according to ovarian function into typical PCOS (PCOS-T; n = 37) and atypical PCOS (PCOS-A; n = 18). Pelvic ultrasonography, short dexamethasone androgen-suppression test (SDAST), and GnRH agonist (GnRHag) test. Baseline AMH levels were related to polycystic ovary status, testosterone response to SDAST, and 17-hydroxyprogesterone response to GnRHag test. AMH levels correlated with SDAST and GnRHag test outcomes. AMH was elevated (>6.2 ng/mL) in 32% of V-PCO versus 5% V-NO. The 21% of V-PCO who met Rotterdam PCOS criteria all had functional ovarian hyperandrogenism, but AMH levels were similar to nonhyperandrogenic V-PCO. AMH >10.7 ng/mL discriminated V-PCO from PCOS with 96% specificity and 41% sensitivity for PCOS-T, and insignificantly for PCOS-A. AMH levels are independently related to ovarian androgenic function and polycystic ovaries. Very high AMH levels are specific but insensitive for PCOS. In the absence of hyperandrogenism, moderate AMH elevation in women with normal-variant polycystic ovaries seems to indicate an enlarged oocyte pool.


Investigation of the Annexin A5 M2 haplotype in 500 white European couples who have experienced recurrent spontaneous abortion.
Annexin A5 is a placental anti-coagulant protein that contains four nucleotide substitutions (M2 haplotype) in its promoter. This haplotype is a risk factor for recurrent spontaneous abortion (RSA). The influence of the M2 haplotype in the gestational timing of spontaneous abortions, paternal risk and relationships with known risk factors were investigated. European couples (n = 500) who had experienced three or more consecutive spontaneous abortions, and two fertile control groups, were selected for this study. The allele frequency of M2 was significantly higher among patients who had experienced early RSA than among controls (P = 0.002). No difference was found between controls and patients who had undergone late spontaneous abortions. No difference was found between patients who had experienced RSA who had a live birth or no live births, or between patients who were positive or negative for known risk factors. Male and female partners in each group had similar allele frequencies of M2. The M2 haplotype is a risk factor for early spontaneous abortions, before the 12th week of gestation, and confers about the same relative risk to carriers of both sexes. Having one or more M2 allele(s) in combination with other risk factors further increases the RSA risk.


International pharmacy survey of peripheral vasopressor infusions in critical care (INFUSE).
The primary objective was to determine the proportion of hospitals that administered norepinephrine peripheral vasopressor infusions (PVIs) in critically ill adult patients. Secondary objectives were to describe how norepinephrine is used such as the maximum duration, infusion rate and concentration, and to determine the most common first-line PVI used by country. An international multi-centre cross-sectional survey study was conducted in adult intensive care units in Australia, US, UK, Canada, and Saudi Arabia. Critical care pharmacists from 132 institutions responded to the survey. Norepinephrine PVIs were utilised in 86% of institutions (n = 113/132). The median maximum duration of norepinephrine PVIs was 24 h (IQR 24-24) (n = 57/113). The most common maximum norepinephrine PVI rate was between 11 and 20 μg/min (n = 16/113). The most common maximum norepinephrine PVI concentration was 16 μg/mL (n = 60/113). Half of the institutions had a preference to administer another PVI over norepinephrine as a first-line agent (n = 66/132). The most common alternative PVI used by country was: US (phenylephrine 41%, n = 37/90), Canada (dopamine 31%, n = 5/16), UK (metaraminol 82%, n = 9/11), and Australia (metaraminol 89%, n = 8/9). There is variability in clinical practice regarding PVI administration in critically ill adult patients dependent on drug availability and local institutional recommendations.


SARS-CoV-2 droplet deposition path and its effects on the human upper airway in the oral inhalation.
It is crucial to study the uptake of viral droplets in the human respiratory system to control, prevent, and treat diseases. In this study, a well-verified real anatomical model was used; the passage of air in the human upper respiratory system computed using high-quality Computer Tomography (CT) images. Then, the airflow field, along with the coronavirus micro-droplets injection, was examined in this realistic model using the Fluid-Structure Interaction (FSI) method. The Discrete Phase Model (DPM) was used to solve the field, and with the help of it, the accurate assessment of the temporal and spatial motion of the deposition in the virus-impregnated droplets was obtained in vitro in the upper respiratory system. The results show that the amount of deposited micro-droplets in the nasal cavity area is meager at the inhalation only through the oral. However, it has the most residence time in this area. The most and least droplet absorption occurred in the oral cavity and larynx-trachea, respectively. Deposition efficiency is about 100% in 30 L/min flow rate and 10 μm diameter; in other words, no droplet enters the lungs. This study's other achievements include the relatively inverse relationship between droplets deposition efficiency in some parts of the upper airway, which have the most deformation in the tract. Utilization of a realistic model with accurate and precise computational analysis can end speculation about the deposition zone, accumulation, and the effects of the COVID-19 virus on the upper respiratory tract. On the other hand, recognizing the virus-containing droplet location can ease understanding the areas where the virus can first infect in the upper respiratory tract.


Effect of Concentration of Flaxseed (Linum usitatissimum) and Duration of Administration on Fatty Acid Profile, and Oxidative Stability of Pork Meat.
Flaxseed is a common ingredient used for livestock feed. The aim of this work was to study the effect of a diet supplemented with flaxseed at 5% and 10% concentrations in the intervals of 3 and 6 weeks prior slaughter on fatty acid profile and oxidative stability of pork meat. Meat samples were collected after slaughter from each animal (five groups, n = 6). Samples of the musculus longissimus dorsi (MLD) and the musculus gluteobiceps (MGB) were selected. Chemical composition, fatty acid profile and oxidative stability during the storage of meat under chilling conditions (4 °C, 7 days) was analyzed. The addition of flaxseed significantly affected the composition of fatty acid profile and the shelf life of the produced meat. The fat content was changed in the experimental groups with 10% flaxseed supplementation (10.84% in MGB and 9.56% MLD) versus the control group. Despite the different concentrations of flaxseed, the best EPA/AA ratio was observed in the experimental groups fed with flaxseed supplementation for 3 weeks. The worst oxidative stability of meat samples (p < 0.05) was recorded in the experimental groups with the addition of flaxseed for 6 weeks, which was related to higher PUFA content in samples of the experimental groups and higher susceptibility of PUFAs to lipid oxidation. The oxidative stability of meat in the experimental group fed 5% flaxseed supplementation for 3 weeks was not affected.


Efferent projections from the mammillary complex of the guinea pig: an autoradiographic study.
The efferent projections from the medial and lateral mammillary nuclei of the guinea pig were traced after injecting tritiated amino acid. The major efferent started as the principal mammillary tract, but soon divided into mammillothalamic and mammillotegmental tracts. The mammillothalamic tract projected anterodorsally and terminated in the anterior dorsal, anterior ventral and anterior medial thalamic nuclei. The mammillotegmental tract projected caudally and terminated in the dorsal tegmental nucleus and central gray. The mammillary efferents in the mammillary peduncle ran via the tegmentum of the midbrain and pons. It terminated in the dorsal and ventral tegmental nuclei, basal pontine nucleus and pontine tegmental reticular nucleus. A diffuse mammillary projection had fibers directed dorsally which distributed in the midline thalamic nuclei and in central gray. Rostral projections via the medial forebrain bundle from the medial mammillary nucleus were found in the septal area and diagonal band of Broca. The lateral mammillary nucleus sent fibers which also joined the mammillothalamic and mammillotegmental tracts. These terminated bilaterally mainly in the anterior dorsal and anterior ventral nuclei of the thalamus, and caudally in the dorsal and ventral tegmental nuclei and basal pontine nucleus.


Determination of key events in mouse hepatocyte maturation at the single-cell level.
Hepatocytes, the liver's predominant cells, perform numerous essential biological functions. However, crucial events and regulators during hepatocyte maturation require in-depth investigation. In this study, we performed single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq) to explore the precise hepatocyte development process in mice. We defined three maturation stages of postnatal hepatocytes, each of which establishes specific metabolic functions and exhibits distinct proliferation rates. Hepatic zonation is gradually formed during hepatocyte maturation. Hepatocytes or their nuclei with distinct ploidies exhibit zonation preferences in distribution and asynchrony in maturation. Moreover, by combining gene regulatory network analysis with in vivo genetic manipulation, we identified critical maturation- and zonation-related transcription factors. This study not only delineates the comprehensive transcriptomic profiles of hepatocyte maturation but also presents a paradigm to identify genes that function in the development of hepatocyte maturation and zonation by combining genetic manipulation and measurement of coordinates in a single-cell developmental trajectory.


Location of deuterium oxide solvent isotope effects in the glutamate dehydrogenase reaction.
Stopped flow studies of D2O kinetic solvent isotope effects on the reaction catalyzed by L-glutamate dehydrogenase reveal, in addition to several effects apparently attributable simply to pKa shifts, a 2-fold pH-independent effect on the velocity of the steady state oxidative deamination of L-glutamate by enzyme and NADP. Comparable pH-independent D2O kinetic solvent isotope effects are seen both in a transient phase of the reaction in which alpha-ketoglutarate is displaced by L-glutamate from an enzyme-NADPH-alpha-ketoglutarate (product) complex and in an analogous model reaction in which alpha-ketoglutarate is displaced by D-glutamate. These results suggest that alpha-ketoglutarate dissociation from an enzyme-NADPH-alpha-ketoglutarate complex is rate-limiting in the steady state.


[Trabeculetomy-iridencleisis with marginal cyclodialysis in the treatment of selected cases of childhood- and juvenile glaucoma].
This surgery method is thought for cases, where previous operations have not been successful or for such, in which severe scaring tissue reactions must be expected. The diaphanoscopy of the anterior chamber angle is considered helpfull for the choice of the surgery way. Between 1975 and february 1978 trabeculectomy combined with radical lobelike iridencleisis and marginal cyclodialyse was performed in 4 cases and the i.o. pressure could be normalised. Complications did not occure.


High circulating frequencies of tumor necrosis factor alpha- and interleukin-2-secreting human T-lymphotropic virus type 1 (HTLV-1)-specific CD4+ T cells in patients with HTLV-1-associated neurological disease.
Significantly higher frequencies of tumor necrosis factor alpha- and interleukin-2-secreting human T-lymphotropic virus type 1 (HTLV-1)-specific CD4(+) T cells were present in the peripheral blood mononuclear cells of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients than in those of asymptomatic carriers with similar provirus loads. The data suggest that HTLV-1-specific CD4(+) T cells play a role in the pathogenesis of HAM/TSP.


[Duties of institutions and heads of health care centers in the area of infection control, information, assessment, registration and financing of benefits provided to TB patients].
The Act on preventing and counteracting infections and infectious diseases in humans effective in Poland provides for the duty of the heads of health care outlets and institutions to counteract spreading of TB in units under their management. They are, by all means, responsible for monitoring infections in their respective units, involving development, implementation and monitoring of practical implementation of procedures aiming at limiting dissemination of TB in hospitals and outpatient clinics. Medical service unit managers are also responsible for providing members of their staffs with means of individual protection against infection with Mycobacterium tuberculosis bacillus. Their duties also include notification of all recognized TB cases in their respective units. TB is an infectious diseases included in the occupational disease list. Assessment of TB as occupational disease is the responsibility of provincial TB prevention clinics. The Act also provides for principles of financing of individual benefits available for the insured TB patients and those not insured.


Generation of an iPSC line (AKOSi004-A) from fibroblasts of a female adult NPC1 patient, carrying the compound heterozygous mutation p.Val1023Serfs*15/p.Gly992Arg and of an iPSC line (AKOSi005-A) from a female adult control individual.
Niemann-Pick disease Type C (NPC) is a rare progressive neurodegenerative disorder with an incidence of 1:120,000 caused by mutations in the NPC1 or NPC2 gene leading to a massive cholesterol accumulation. Here, we describe the generation of induced pluripotent stem cells (iPSCs) of an affected female adult individual carrying the NPC1 mutation p.Val1023Serfs*15/p.Gly992Arg and an iPSC line from an unrelated healthy female adult control individual. Human iPSCs were derived from fibroblasts using retroviruses carrying the four reprogramming factors OCT4, SOX2, KLF4 and C-MYC. These lines provide a valuable resource for studying the pathophysiology of NPC and for pharmacological intervention.


The comparative effects of early-life undernutrition and subsequent differential environments on the dendritic branching of pyramidal cells in rat visual cortex.
Male rats were either undernourished or fed normally from birth to day 21, after which time food was made freely available. At 1 month of age littermate pairs from both nutritional groups were housed in either enriched or impoverished conditions for 30 days and then killed for brain measurements. Significant deficits due to undernutrition were observed in the weight and size of the cerebrum, but not in the thickness or area of the visual cortex. Although there were large differences of between 21 and 39% in the number of higher-order basal dendrites of layers II and III pyramidal cells, and of about 19% in the distal ring intersections, none except the fourth-order branches and intersections at 100 micron from the cell body approached statistical significance. Changes in cerebral weight and size also occurred as a result of differential housing, with the enriched rats showing increased values relative to their impoverished littermates. In contrast to the nutritional treatment, differential housing significantly affected cortical thickness and area, as well as basal dendritic branching of the pyramidal cells. Enriched rats had relative increases of 26% in the number of fifth-order branches and 45-80% in the number of distal ring intersections.


Potential hazard associated with scraping preparative thin layer chromatography plates.
Scraping TLC plates in a hood leads to contamination of the hood, equipment, worker, and the environment. The magnitude of contamination is presented as a fraction of the chemical delivered, and the effects of plate thickness, dryness, and adsorbent material are examined. Frequent clean-up and decontamination are recommended.