Comparison of pituitary-adrenocortical response to hypoglycaemia and surgery.
The hypothalamic-pituitary-adrenocortical (HPA) responses to the hypoglycaemic stimulus and to operation (laparotomy) are compared. The studies were carried out in eight patients who were subjected to insulin-induced hypoglycaemia on the day before elective abdominal surgery. Plasma corticotrophin (ACTH) and plasma cortisol concentration increases were virtually indentical during the two procedures, which suggests that hypoglycaemia and surgical trauma are comparable stress factors and that the hypoglycaemia test is reliable in predicting the HPA responses to major surgical trauma.


Experiences of critically ill patients in the ICU.
Experiences of critically ill patients are an important aspect of the quality of care in the intensive care (ICU). The aims of the study were firstly, to evaluate the perceptions of patients regarding nursing care in the ICU, and secondly, to explore patients' perceptions and experiences of ICU stay. A qualitative approach using a semi-structured focused interview in 11 patients was used (phase 1), followed by a quantitative approach using a self-reported questionnaire in 100 patients, 62 were returned and 50 could be evaluated (phase 2). A number of themes emerged from the interviews (phase 1), although support dominated as an important key theme. This was experienced as a continuum from the feeling being supported by the nurse to not being supported. This key theme was central to each of the three categories emerging from the data pertaining to: (1) providing the seriously ill patient with information and explanation, (2) placing the patient in a central position and (3) personal approach by the nurse. The responders to the subsequent questionnaire (phase 2) predominantly experienced sleeping disorders (48%), mostly related to the presence of noise (54%). Psychological problems after ICU stay were reported by 11% of the patients, i.e. fear, inability to concentrate, complaints of depression and hallucinations. Although the nurses' expertise and technical skills are considered important, caring behaviour, relieving the patient of fear and worries were experienced as most valuable in bedside critical care.


Transient neutropenia of childhood.
Patient characteristics and clinical course are described in 21 children with newly discovered neutropenia (absolute neutrophil count less than 1500/microliter). Only children over age 3 months are included; 19 of 21 were less than age 2 years. The majority had respiratory tract infections and 11 had been on various medications at the time neutropenia was discovered. Bacteria were isolated from the blood of three patients (S. pneumoniae in two, H. influenzae in one) and from urine in one (E. coli). Respiratory syncytial virus was cultured from the nasopharynx of two patients. Opportunistic, gram-negative and staphylococcal infections did not occur. Neutrophil counts in all but one child returned to normal within 6 weeks of onset; half recovered within 7 days. Bone marrow examination was performed in 13 patients: maturation arrest at various stages in the myeloid series was noted in six, and seven had normal myeloid maturation. Bone marrow findings did not correlate with degree or duration of neutropenia. These observations indicate that previously well infants with isolated neutropenia generally have a benign clinical course, although three patients were ultimately proven to have significant chronic illness. Recommendations are made as to management.


Circumferential dynamic stabilization of the lumbar spine: a biomechanical analysis.
To assess segmental angulation and mobility following implantation of the Charité artificial disc in combination with the posterior dynamic fixation device dynamic stabilization system (DSS) and the interspinous spacer Coflex at the L4-L5 segment, respectively. Six human L4-L5 specimens were loaded with pure moments of ±7.5 Nm in flexion/extension, lateral bending, and axial rotation in a custom-made spine tester. The testing protocol was as follows: (a) intact condition, (b) destabilization by resection of the anterior longitudinal ligament (ALL), (c) implantation of the Charité with retained posterior longitudinal ligament (PLL), (d) supplemental DSS implantation, (e) removal of DSS rods and PLL resection, (f) DSS rod re-implantation, (g) enlargement of rod length, and (h) removal of DSS and implantation of Coflex. Range of motion (ROM), neutral zone, and segmental angulation were determined. ALL resection did not influence significantly ROM. TDR increased lateral bending and axial rotation only after resection of the PLL, whereas flexion/extension remained unchanged. DSS limited all degrees of freedom prior to and after PLL resection. Rod length enlargement had no significant effect. Coflex limited significantly flexion/extension compared to the intact state and TDR, whereas lateral bending and axial rotation remained unchanged. TDR increased lordosis, whereas Coflex had a substantial kyphosing effect. This study demonstrates that posterior dynamic stabilization in combination with TDR reduces flexion/extension ROM and segmental lordosis in a monosegmental biomechanical model.


Antimicrobial activities of crude leaf extracts of Acalypha wilkesiana.
Water, ethanol, chloroform and hexane extracts of Acalypha wilkesiana leaves were investigated for in vitro antimicrobial activities by agar-diffusion and tube-dilution techniques. The water and ethanol extracts inhibited the growth of standard and local strains of bacteria and fungi including Staphylococcus aureus, Trichophyton rubrum, Trichophyton mentagrophytes, Candida albicans and Aspergillus flavus. The aqueous extract did not exert any inhibitory action on Klebsiella pneumoniae and Proteus mirabilis while the ethanol extract was active. The minimum inhibitory concentrations of the extracts ranged between 0.25 and 32 mg/ml, while the minimum cidal concentrations were between 1.0 and 64 mg/ml. The aqueous extract was found to be static in action while the ethanolic extract was uniformly cidal in effect.


[Interdisciplinary cooperation in the diagnosis and therapy of diseases of the adrenal glands and the parathyroid glands].
It is reported on the interdisciplinary cooperation between internists, radiologists and surgeons in the diagnostics and therapy of endocrinological diseases (suprarenal gland, parathyroid gland). On the basis of instances diagnostic step programmes are represented and first experiences of the cooperation are reported.


Expression of human ferredoxin in Saccharomyces cerevisiae: mitochondrial import of the protein and assembly of the [2Fe-2S] center.
Vertebrate ferredoxins function in the transfer of reducing equivalents from NADPH:ferredoxin oxidoreductase to cytochrome P450 enzymes involved in steroid metabolism. We report here the expression of human mitochondrial ferredoxin in the yeast Saccharomyces cerevisiae. The full-length ferredoxin protein containing the ferredoxin mitochondrial leader sequence could not be stably expressed in S. cerevisiae, but a fusion protein consisting of the mature portion of ferredoxin linked to the mitochondrial leader sequence of the S. cerevisiae cytochrome c oxidase subunit Va protein (COX5a) could be stably expressed. The COX5a:ferredoxin fusion protein was targeted to the mitochondria as a preprotein and was cleaved at the normal processing site of the COX5a presequence during import into the matrix. Absorption spectra and electron transfer activity of the isolated fusion protein established that the [2Fe-2S] center was correctly assembled and incorporated into the recombinant ferredoxin in this heterologous system.


[Clinical study of the auxiliary action of bleomycin in surgery and radiotherapy of cervical cancer and evaluation of modes of administration for the enhancement of the effects and alleviation of the adverse effects].
A total of 54 cases of carcinoma of the uterine cervix were treated with bleomycin adjuvant to surgery and radiation. Bleomycin was injected intravenously or continuously intraarterially or, using oleaginous bleomycin, locally into the infravaginal portion of the cervix, and its significance in administration routes was evaluated in terms of a five-year survival rate. Furthermore, how bleomycin concentrates in the blood, cancerous lesions and regional lymphnodes was examined after administration using following various methods: an aqueous bleomycin, intravenously, continuously intraarterially, and through dispersion to intrapelvic dead space or injected as an oleaginous bleomycin locally to infravaginal portion or applied as vaginal suppository and cervical pellet. Most appropriate routes with increased focal concentrations and reduced blood concentrations proved to enhance anti-neoplastic effects and alleviate side effects. Among them, results with local injection of oleaginous bleomycin to infravaginal portion and continuous intraarterial injection of aqueous bleomycin were most satisfactory. Complete relief from cervical carcinoma by single administration of bleomycin alone is hardly attainable; however, the efficacy of bleomycin as an adjuvant therapy, using a several types of the bleomycins, is highly appreciated in combination with pre- and post-operative treatment and radiotherapy.


Potential lipase inhibitors from Chinese medicinal herbs.
Obesity has become a major health concern, and it places both personal and economic burdens on the world's population. Traditional Chinese medicinal herbs are rich source of lead compounds and are possible drug candidates, which may be used to treat this condition. This study screened potent pancreatic lipase inhibitors found in traditional Chinese medicinal herbs for ability to treat obesity. A porcine pancreatic lipase inhibition assay was established, and the inhibitory activity of 35 traditional Chinese medicinal herbs was evaluated at a concentration of 200 μg/mL. Two elutions of herbal extracts with strong lipase inhibitory activity were further fractionated by preparative high-performance liquid chromatography into 22 sub-fractions each, and these sub-fractions were tested for anti-lipase activity. Sub-fractions, which exhibited strong lipase inhibitory activity, were continuously fractionated into individual compounds. Two active compounds with potent anti-lipase activity were finally isolated and identified from two traditional Chinese medicinal herbs, respectively. Among 35 traditional Chinese medicinal herbs, the 95% ethanol elutions of Panax notoginseng (Burk.) F.H. Chen (Araliaceae) and Magnolia officinalis Rehd. et Wils (Magnoliaceae) showed strong anti-lipase activity. Two compounds, including 20(S)-ginsenoside Rg3 and honokiol were identified using bioactivity-guided isolation with IC50 = 33.7 and 59.4 μg/mL, respectively. 20(S)-ginsenoside Rg3 and honokiol might be suitable candidates for the treatment of obesity.


Roles for leptin receptor/STAT3-dependent and -independent signals in the regulation of glucose homeostasis.
Leptin activates the long form of the leptin receptor (LRb) to control feeding and neuroendocrine function and thus regulate adiposity. While adiposity influences insulin sensitivity, leptin also regulates glucose homeostasis independently of energy balance. Disruption of the LRb/STAT3 signal in s/s mice results in hyperphagia, neuroendocrine dysfunction, and obesity similar to LRb null db/db mice. Insulin resistance and glucose intolerance are improved in s/s compared to db/db animals, however, suggesting that LRb/STAT3-independent signals may contribute to the regulation of glucose homeostasis by leptin. Indeed, caloric restriction normalized glycemic control in s/s animals, but db/db mice of similar weight and adiposity remained hyperglycemic. These differences in glucose homeostasis were not attributable to differences in insulin production between s/s and db/db animals but rather to decreased insulin resistance in s/s mice. Thus, in addition to LRb/STAT3-mediated adiposity signals, non-LRb/STAT3 leptin signals mediate an important adiposity-independent role in promoting glycemic control.


Functional outcomes of all-inside arthroscopic anterior talofibular ligament repair with loop suture versus free-edge suture.
Anatomic repair of anterior talofibular ligament (ATFL) is used to manage chronic lateral ankle instability (CLAI). However, the optimal suture configuration used to repair the ATFL is not yet determined. It remains unclear whether suture configuration affects clinical outcomes in such patients. To compare the functional outcomes of all-inside arthroscopic ATFL repair using either a loop suture and or a free-edge suture configuration in CLAI patients. Cohort study; Level of evidence, 3. This retrospective cohort study included 71 patients with CLAI who had undergone an all-inside arthroscopic ATFL repair procedure with either loop suture (n = 36) or free-edge suture (n = 35) from February 2016 to July 2018. Comparable pre-operatively, the Visual analogy score (VAS), American Orthopedic Foot and Ankle Society scoring system (AOFAS), Karlsson Ankle Functional Score (KAFS) scoring system, Anterior Talar Translation (ATT) and Active Joint Position Sense (AJPS) were used to evaluate postoperative ankle function. There were no postoperative wound complications, implant reactions, or neurological or vascular injuries. Postoperative hospitalization, VAS, AOFAS, KAFS, AJPS and the time of return to sport were similar between the loop suture group and free-edge suture group. Requiring a longer procedure time, patients with loop suture configuration achieved better ATT. All-inside arthroscopic ATFL repair procedure for CLAI treatment provides better ATT and comparable functional outcomes when a loop suture configuration is used instead of a free-edge suture configuration. A statistical difference in ATT was observed. Given the relatively short follow-up, it is questionable whether this will have any clinical relevance.


A comparison of time delay and decreasing prompt hierarchy strategies in teaching banking skills to students with moderate handicaps.
Four students with moderate handicaps were taught to cash checks and to use an automatic teller through either a decreasing prompt hierarchy or time delay procedure. The strategies were compared within a multielement design. Results indicated that both strategies led to the acquisition of the target tasks; however, the decreasing prompt hierarchy was more efficient. Four and 8-week follow-up probes indicated that the strategies were equally effective in producing maintenance of performance.


High-dose chemotherapy plus peripheral blood stem cell transplantation for patients with relapsed germ cell tumors and active brain metastases.
The optimal management of progressive brain metastases in patients with germ cell tumors (GCTs) remains unsettled. This study reports the management of 25 consecutive patients with relapsed GCTs and progressive brain metastases undergoing high-dose chemotherapy (HDCT) with peripheral blood stem cell transplantation (PBSCT) at Indiana University from 2006 to 2016. All patients were planned to undergo HDCT, which consisted of carboplatin at 700 mg/m2 on days 1 to 3 plus etoposide at 750 mg/m2 on days 1 to 3, followed by PBSCT on day 5 for 2 cycles. Patients were treated with brain metastectomy, stereotactic radiotherapy or whole-brain radiotherapy, HDCT alone, or a combination thereof. All 25 patients had progressive brain metastases at the time of initiating HDCT. Patient and disease characteristics, management of brain metastases, and outcomes were measured. Platelet transfusions were given to maintain platelet counts > 30,000/µL; the goal was >50,000/µL when there were signs of prior or active hemorrhaging. Twenty-two of 25 patients completed both courses of HDCT. The median α-fetoprotein level was 7.5 ng/mL (range, 1.6-1130 ng/mL), and the human chorionic gonadotropin level was 31.3 IU/mL (range, 0.5-25,601 IU/mL). At a median follow-up of 24.5 months (range, 0.4-117 months), 11 patients (44%) were alive with no evidence of disease, 2 patients were alive with relapsed disease, and 12 patients had died of disease progression or complications from HDCT. Fifteen patients developed progressive brain metastases despite radiation and/or craniotomy before HDCT, and 8 of these patients were alive without evidence of disease. There were no intracranial hemorrhagic events leading to death. Patients with relapsed GCTs and progressive brain metastases are curable with multimodality therapy that includes HDCT and peripheral blood stem cell transplantation.


Absorption, translocation, and metabolism of florpyrauxifen-benzyl and cyhalofop-butyl in cyhalofop-butyl-resistant barnyardgrass [Echinochloa crus-galli (L.) P. Beauv.].
Dose-response experiments were conducted to assess the sensitivity of one susceptible and three putative resistant (R1, R2, and R3) barnyardgrass [Echinochloa crus-galli (L.) P. Beauv.] biotypes to florpyrauxifen-benzyl and cyhalofop-butyl alone and as a formulated premix. Subsequently, potential resistance mechanisms of the barnyardgrass were evaluated. Based on biomass reduction results, resistant/susceptible ratios were calculated for R1 (7.0-50), R2 (7.0-150), and R3 (18-214) biotypes. Absorption and translocation of [14C]-florpyrauxifen-benzyl decreased in R1 and R3 biotypes, but not for [14C]-cyhalofop-butyl. The metabolism of [14C]-florpyrauxifen-benzyl to [14C]-florpyrauxifen-acid was >2-fold less in resistant biotypes (9-11%) than in the susceptible biotype (23%). Moreover, the production of [14C]-florpyrauxifen-acid in susceptible barnyardgrass (not in the R biotypes) increased 3-fold when florpyrauxifen-benzyl and cyhalofop-butyl were applied in mixture compared to florpyrauxifen-benzyl applied alone. The tested barnyardgrass biotypes had no mutation in the Transport Inhibitor Response1, auxin-signaling F-box, and acetyl coenzyme A carboxylase genes. Although further studies on cyhalofop-butyl resistance with respect to analysis of specific metabolites are needed, our findings in this study demonstrates that the evolution of florpyrauxifen-benzyl resistance in multiple resistant barnyardgrass can be related to non-target-site resistance mechanisms reducing absorption and translocation of the herbicide and causing reduced conversion or rapid degradation of florpyrauxifen-acid.


Acute rapamycin rescues the hyperexcitable phenotype of accumbal medium spiny neurons in the valproic acid rat model of autism spectrum disorder.
We previously demonstrated that prenatal exposure to valproic acid (VPA), an environmental model of autism spectrum disorder (ASD), leads to a hyperexcitable phenotype associated with downregulation of inward-rectifying potassium currents in nucleus accumbens (NAc) medium spiny neurons (MSNs) of adolescent rats. Aberrant mTOR pathway function has been associated with autistic-like phenotypes in multiple animal models, including gestational exposure to VPA. The purpose of this work was to probe the involvement of the mTOR pathway in VPA-induced alterations of striatal excitability. Adolescent male Wistar rats prenatally exposed to VPA were treated acutely with the mTOR inhibitor rapamycin and used for behavioral tests, ex vivo brain slice electrophysiology, single-neuron morphometric analysis, synaptic protein quantification and gene expression analysis in the NAc. We report that postnatal rapamycin ameliorates the social deficit and reverts the abnormal excitability, but not the inward-rectifying potassium current defect, of accumbal MSNs. Synaptic transmission and neuronal morphology were largely unaffected by prenatal VPA exposure or postnatal rapamycin treatment. Transcriptome analysis revealed extensive deregulation of genes implied in neurodevelopmental disorders and ionic mechanisms exerted by prenatal VPA, which was partially reverted by postnatal rapamycin. The results of this work support the existence of antagonistic interaction between mTOR and VPA-induced pathways on social behavior, neurophysiological phenotype and gene expression profile, thus prompting further investigation of the mTOR pathway in the quest for specific therapeutic targets in ASD.


Stability ofAlternaria toxins in fruit juices and wine.
Alternaria alternata is a common fungal parasite on fruits and other plants and produces a number of mycotoxins, including alternariol (3,7,9-trihydroxy-1-methyl-6H-dibenzo [b,d]pyran-6-one), alternariol monomethyl ether (3,7-dihydroxy-9-methoxy-1-methyl-6H-dibenzo[b,d]pyran-6-one), and the mutagen altertoxin I {[1S-(1α,12aβ,12bα)] 1,2,11,12,12a, 12b-hexahydro-1,4,9,12a-tetrahydroxy-3,10-perylenedione}. Alternariol and alternariol monomethyl ether have previously been detected in some samples of fruit beverages. Stability studies of these toxins as well as altertoxin I added to fruit juices and wine (10-100 ng/mL) were carried out. To include altertoxin I in the analysis, cleanup with a polymer-based Varian Abselut solid phase extraction column was used, as recoveries from C-18 columns were low. The stabilities of alternariol and alternariol monomethyl ether in a low acid apple juice containing no declared vitamin C were compared with those in the same juice containing added vitamin C (60 mg/175 ml); there were no apparent losses at room temperature over 20 days or at 80°C after 20 min. in either juice. Altertoxin I was moderately stable in pH 3 buffer (75% remaining after a two week period). Furthermore, altertoxin I was stable or moderately stable in three brands of apple juice tested over 1-27 day periods and in a sample of red grape juice over 7 days. It is concluded that altertoxin I is sufficiently stable to be found in fruit juices and should be included in methods for alternariol and alternariol monomethyl ether.


The rate of port-site metastases after 2251 laparoscopic procedures in women with underlying malignant disease.
The aim was to describe the rate of laparoscopic trocar-related subcutaneous tumor implants in women with underlying malignant disease. An analysis of a prospective database of all patients undergoing transperitoneal laparoscopic procedures for malignant conditions performed by the gynecologic oncology service. Between July 1991 and April 2007, laparoscopic procedures were performed in 1694 patients with a malignant intraabdominal condition and in 505 breast cancer patients undergoing risk-reducing, diagnostic or therapeutic laparoscopic procedures without intraabdominal disease. Port-site metastases were documented in 20 of 1694 patients (1.18%) who underwent laparoscopic procedures for a malignant intraabdominal condition. Of these, 15 patients had a diagnosis of epithelial ovarian or fallopian tube carcinoma, 2 had breast cancer, 2 had cervical cancer, and 1 had uterine cancer. Nineteen of 20 patients (95%) had simultaneous carcinomatosis or metastases to other sites at the time of port-site metastasis. Patients who developed port-site metastases within 7 months from the laparoscopic procedure had a median survival of 12 months whereas patients who developed port-site metastasis >7 months had a median survival of 37 months (P=0.004). No port-site recurrence was documented in patients undergoing risk-reducing, diagnostic or therapeutic laparoscopic procedures for breast cancer without intraabdominal disease. The rate of port-site tumor implantation after laparoscopic procedures in women with malignant disease is low and almost always occurs in the setting of synchronous, advanced intraabdominal or distant metastatic disease. The presence of port-site implantation is a surrogate for advanced disease and should not be used as an argument against laparoscopic surgery in gynecologic malignancies.


Fatal fulminant HSV-2 myocarditis: A complicated presentation.
Herpes simplex virus type 2 (HSV-2) infection is the leading cause of genital lesions. Infrequently HSV-2 primary infection can spread and involve other tissue and organs, however in immunocompetent individuals extra-genital complications are rare findings. In this report we present a fatal case of fulminant myocarditis and terminal liver involvement, caused by HSV-2 infection, with a unique presentation. Diagnosis was made only post-mortem.


Hyperoncotic ultrahigh molecular weight dextran solutions reduce trypsinogen activation, prevent acinar necrosis, and lower mortality in rodent pancreatitis.
Acinar necrosis in patients with acute pancreatitis can be due to enzymatic injury, ischemia, or both. We hypothesized that novel therapy aimed at an improvement of pancreatic microcirculation early in the course of pancreatitis may reduce the lethality and acinar damage. Forty-six dextran-resistant rats received controlled intraductal infusion of glycodeoxycholic acid (10 mmol/L), followed by intravenous cerulein (5 micrograms/kg/h) for 6 hours. Beginning 30 minutes after the induction of pancreatitis, all animals were resuscitated with Ringer's lactate (RL) (8 mL/kg/h intravenously for 9 hours). In addition, they were given intra-aortic bolus infusions (2 mL/kg at 30, 60, 90, and 150 minutes) of either RL, sodium chloride (NaCl) (7.5%) and dextran 60,000 (10%) (HHS-60), NaCl (7.5%) and dextran 500,000 (10%) (HHS-500), or NaCl (0.9%) and dextran 500,000 (10%) (DEX-500). Despite high-volume fluid resuscitation in the groups that received RL and HHS-60, 70% of the animals in each of these groups died within 24 hours. In contrast, the mortality rates in the groups of animals that received HHS-500 and DEX-500 were dramatically reduced to 0% and 10%, respectively (p = 0.005, p = 0.02). Histopathologic scores for acinar necrosis were significantly lower in the group of animals that received DEX-500 (p < 0.009) compared with those that received RL and HHS-60. Finally, total amounts of trypsinogen activation peptides in ascites were significantly lower in the animals that received HHS-500 (p < 0.004) and DEX-500 (p < 0.02) compared with those that received RL and HHS-60. Rapid bolus infusion of hyperoncotic ultrahigh molecular weight dextran solution with or without hypertonic saline but not RL or hypertonic-hyperoncotic saline-dextran significantly reduced pathologic trypsinogen activation, prevented acinar necrosis, and improved survival in acute experimental pancreatitis. We speculate that a sustained improvement of pancreatic microcirculation by ultrahigh molecular weight dextran is the mechanism of action.


Timing of initiation of dialysis: time for a new direction?
The past 15 years have seen tremendous growth in the initiation of dialysis at higher levels of kidney function in the setting of mixed evidence and at great societal economic cost. We review recent data on the early dialysis initiation trend, the clinical and economic impact of early dialysis initiation and the future implications for the management of advanced chronic kidney disease (CKD). The percentage of patients who initiate dialysis with an estimated glomerular filtration rate (eGFR) above 10 ml/min/1.73m(2) is now greater than 50%, including 20% who initiate with an eGFR above 15 ml/min/1.73m(2). The drivers behind these findings are probably diverse but recent literature does not seem to support a higher symptom burden among the ageing CKD population as the major cause. The Initiating Dialysis Early And Late (IDEAL) trial provides guidance on the safety of waiting for symptoms or lower levels of estimated glomerular filtration rate prior to beginning dialysis. In addition, economic analyses based on the IDEAL and US Renal Data System findings suggest that significant cost savings could be achieved by reversing the early initiation trend. These findings should help clinicians and policy makers looking to rein in costs while maintaining the quality of CKD care.


An outbreak of Q fever affecting postal workers in Oxfordshire.
Twenty-five people in Oxfordshire were found to have had clinical illness due to Q fever in the 3 months from April to June 1983. Twelve cases were diagnosed through the routine laboratory diagnostic service. Five of these were postmen, four of whom worked in a sorting office where an outbreak of illness similar to influenza had been noted by the Occupational Health Nurse. Thirteen cases were diagnosed by active case-finding in this sorting office but investigation failed to define the source of the outbreak. Nine of the 18 postal workers were found to have antibodies to phase I Coxiella burnetii antigen. The significance of these antibodies is discussed. Surveillance for over 2 years has not revealed anyone with symptoms or signs suggestive of chronic Q fever. An outbreak of Q fever among postal workers has not previously been described. We recommend continued surveillance for this enigmatic condition.


Complete genome sequence of a novel capillovirus infecting Hevea brasiliensis in China.
Tapping panel dryness (TPD) is a complex disorder that causes partial or complete cessation of latex drainage upon tapping of rubber trees (Hevea brasiliensis). In this work, we determined the complete genome sequences of a novel virus identified in a rubber tree with TPD syndrome in China. The genome of the virus consists of 6811 nt and possesses two overlapping open reading frames (ORF1 and ORF2), encoding a polyprotein and a movement protein, respectively. The polyprotein shares 37% amino acid sequence identity with cherry virus A (CVA, ARQ83874.1) over 99% coverage. The genome architecture is similar to that of members of the genus Capillovirus (family Betaflexiviridae). Phylogenetic analysis of the replicase proteins showed that the virus clustered together with members of the genus Capillovirus. The new virus is tentatively called "rubber tree virus 1" (RTV1). RTV1 is the first virus reported to infect rubber trees. This work lays a foundation for research into finding the potential causal agent of TPD in Hevea brasiliensis.


'Slicing' glioblastoma drivers with the Swiss cheese model.
The Swiss cheese model is used to assess risks and explain accidents in a variety of industries. This model can be applied to dissect the homeostatic mechanisms whose cumulative dysregulation contributes to disease states, including cancer. Using glioblastoma (GBM) as an exemplar, we discuss how specific protumorigenic mechanisms collectively drive disease by affecting genomic integrity, epigenetic regulation, metabolic homeostasis, and antitumor immunity. We further highlight how host factors, such as hormonal differences and aging, impact this process, and the interplay between these 'system failures' that enable tumor progression and foster therapeutic resistance. Finally, we examine therapies that consider the interactions between these elements, which may comprise more effective approaches given the multifaceted protumorigenic mechanisms that drive GBM.


Optimization of a membrane oxygenation system for cell culture in stirred tank reactors.
Bubble free aeration of animal cell cultures in conventional stirred tank reactors is performed with a silicone tubing oxygenation system. This system is characterized for the laboratory fermenter BIOSTAT M with 1.5 l working volume in respect to oxygen transfer and mixing performance.


MS/MS of protonated polyproline peptides: the influence of N-terminal protonation on dissociation.
A unique collision-induced dissociation pattern was observed for protonated polyproline peptides of length n in which y(n-2) and/or y(n-4) ions were formed in much higher abundance than any other product ions. Cleavage occurs only at every other amide bond, such that product ions are formed only from the losses of even numbers of proline residues. Exclusive losses of even numbers of proline residues were not observed from sodiated peptides. Further study of the tandem mass spectrometry (MS/MS) patterns of protonated proline-rich peptides showed that the substitution of alanine in the second position of polyproline peptides did not prevent the dominant formation of y(n-2) and y(n-4) ions. The loss of ProAla to form the y(8) ion from (ProAlaPro(8)NH(2)+H)(+) was as abundant as the loss of ProPro from (Pro(10)NH(2)+H)(+). However, modification of the peptides that presumably affected the location of the proton on the peptide did alter the MS/MS spectra. Pro(10) and Pro(5) with blocked N-termini or with arginine substituted for the first proline residue did not form abundant y(n-2) or y(n-4) ions. MS(3) and double resonance experiments showed that dissociation of intermediate y(n) product ions can produce y(n-2) ions, but are not necessary dissociation pathway intermediates. This analysis suggests that the ionizing proton must be located at the N-terminus for the peptide ion to dissociate in this manner.


Interference of intradermal tuberculin tests on the serodiagnosis of paratuberculosis in cattle.
In this experiment 63 animals from a paratuberculosis (PTB) and tuberculosis-free herd were tested by Intradermal Tuberculin Tests (ITT) and blood samples were collected before PPD inoculation and on days 3, 15, 30, 60 and 90 post-inoculation (p.i.). Sera were tested for PTB-specific antibodies by ELISA-PPA and confirmed by a commercial ELISA. Three (4.76%) animals were positive by ELISA-PPA and five (7.93%) in the commercial ELISA, between days 30 and 90 p.i. These results suggest that ITT can interfere in the reliability of ELISAs and that serological testing for PTB should be avoided for 90d after PPD inoculation.


Ontogeny of relationship of middle ear and temporomandibular (squamomandibular) joint in mammals. II. Morphology and ontogeny in insectivores.
The ontogeny of the mandibular joint and the middle ear region was studied in Erinaceus europaeus, Sorex araneus, Talpa europaea and Elephantulus rozeti. During development, a passage connection was found between the mandibular condyle and Meckel's cartilage that is produced by the primordium of the lateral pterygoid muscle. The articular disk is formed apart and it appears later in development.


Correlation between Pituitary Stalk Interruption Syndrome and Prokineticin Receptor 2 and Prokineticin 2 Mutations.
To analyze the correlation between pituitary stalk interruption syndrome (PSIS) and prokineticin receptor 2 (PROKR2) and prokineticin 2 (RROK2) mutations. PROKR2 and RROK2 genotypes were identified by multiplex polymerase chain reaction analysis with exon-flanking primers and by automated sequencing techniques with peripheral blood DNA samples from 59 patients with PSIS. Of these 59 PSIS patients, 6 showed intragenic deletions at the PROKR2 locus. Of them, 5 patients exhibited intragenic subsititution of exon 2 (c.991G>A), and the remaining one patient exhibited intragenic subsititution of exon 2 (c.1057C>T). No PROK2 mutation was found in these PSIS patients. PROKR2 may be the susceptibility gene of PSIS.


Using kinetic Monte Carlo simulations to design efficient magnetic nanoparticles for clinical hyperthermia.
The purpose of this study was to identify the properties of magnetite nanoparticles that deliver optimal heating efficiency, predict the geometrical characteristics to get these target properties, and determine the concentrations of nanoparticles required to optimize thermotherapy. Kinetic Monte Carlo simulations were employed to identify the properties of magnetic nanoparticles that deliver high Specific Absorption Rate (SAR) values. Optimal volumes were determined for anisotropies ranging between 11 and 40 kJ/m3 under clinically relevant magnetic field conditions. Atomistic spin simulations were employed to determine the aspect ratios of ellipsoidal magnetite nanoparticles that deliver the target properties. A numerical model was developed using the extended cardiac-torso (XCAT) phantom to simulate low-field (4 kA/m) and high-field (18 kA/m) prostate cancer thermotherapy. A stationary optimization study exploiting the Method of Moving Asymptotes (MMA) was carried out to calculate the concentration fields that deliver homogenous temperature distributions within target thermotherapy range constrained by the optimization objective function. A time-dependent study was used to compute the thermal dose of a 30-min session. Prolate ellipsoidal magnetite nanoparticles with a volume of 3922 ± 35 nm3 and aspect ratio of 1.56, which yields an effective anisotropy of 20 kJ/m3 , constituted the optimal design at current maximum clinical field properties (H0 = 18 kA/m, f = 100 kHz), with SAR = 342.0 ± 2.7 W/g, while nanoparticles with a volume of 4147 ± 36 nm3 , aspect ratio of 1.29, and effective anisotropy 11 kJ/m3 were optimal for low-field applications (H0 = 4 kA/m, f = 100 kHz), with SAR = 50.2 ± 0.5 W/g. The average concentration of 3.86 ± 0.10 and 0.57 ± 0.01 mg/cm3 at 4 and 18 kA/m, respectively, were sufficient to reach therapeutic temperatures of 42-44°C throughout the prostate volume. The thermal dose delivered during a 30-min session exceeded 5.8 Cumulative Equivalent Minutes at 43°C within 90% of the prostate volume (CEM43T90 ). The optimal properties and design specifications of magnetite nanoparticles vary with magnetic field properties. Application-specific magnetic nanoparticles or nanoparticles that are optimized at low fields are indicated for optimal thermal dose delivery at low concentrations.


Selective catalysis of A.T base pair proton exchange in DNA complexes: imino proton NMR analysis.
Polyaromatic molecules with amino chain substituents, upon binding with DNA, selectively catalyze exchange of the A.T base pair protons with bulk water protons. The amine-catalyzed exchange is mediated by compounds which are A.T and G.C base sequence specific, intercalators, and outside binders. A mechanism for the selective exchange, involving transient opening and closing of individual A.T base pairs in the duplex, is discussed.


Association between Interleukin-6 (G174C and G572C) promoter gene polymorphisms and risk of ischaemic stroke: A meta-analysis.
Interleukin-6 (IL-6), as one of the most typical pro-inflammatory and immunoregulatory cytokines, is believed to be associated with the genesis and maintenance of inflammatory response. Genetic association studies (GAS) that have investigated the association between Interleukin 6 (G174C and G572C) promoter gene polymorphisms and susceptibility to ischemic stroke (IS) which have produced contradictory and unconvincing results. The aim of this meta-analysis is to provide a relatively comprehensive account of the association of IL-6 (G174C and G572C) polymorphisms with susceptibility to IS. A literature search was conducted using electronic database PubMed, Medline, and Trip database for all case-control studies investigating for association of IL-6 genetic polymorphisms with ischemic stroke published till August 30, 2014. The following combinations of main keywords were used: ('Interleukin-6' or 'IL-6') and ('ischaemic stroke or 'cerebral infarction' or 'IS') and ('genetic polymorphism' or 'single nucleotide polymorphisms' or 'SNP'). Pooled Odds ratios (ORs) and 95% confidence intervals (CIs) were determined for IL-6 gene-disease association. Meta-analysis was carried out using Revman 5.3 software. 16 case-control studies involving a total of 3,317 IS patients and 3,432 healthy controls for G174C polymorphism and 3 case-control studies with a total of 2,001 IS patients and 2,027 healthy controls for G572C IL-6 gene polymorphisms were included in a meta-analysis. For IL-6 G174C gene polymorphisms, no significant association was observed under dominant [GC + CC vs. GG: OR = 1.01, 95% CI: 0.77-1.34, P = 0. 92], recessive [CC vs. GG + GC: OR = 0.82, 95% CI: 0.40-1.70, P = 0. 59] and allelic model [C vs. G Allele: OR = 0.99, 95% CI: 0.74-1.31, P = 0. 93]. For IL-6 G572C, no significant association was observed under dominant [CC vs. GG + GC: OR = 0.99, 95% CI: 0.57-1.71, P = 0. 97], recessive [CC vs. GG + GC: OR = 0.93, 95% CI: 0.60-1.45, P = 0. 75] and allelic model [C vs. G Allele: OR = 0.95, 95% CI: 0.66-1.36, P = 0. 76]. This meta-analysis shows that IL-6 (G174C) and IL-6 (G572C) gene polymorphisms may not be associated with an increased susceptibility to IS. Further studies are required for confirmatory results.


Infantile fibrosarcoma with TPM3-NTRK1 fusion in a boy with Bloom syndrome.
Bloom syndrome (BS) is a genomic and chromosomal instability disorder with prodigious cancer predisposition caused by pathogenic variants in BLM. We report the clinical and genetic details of a boy who first presented with infantile fibrosarcoma (IFS) at the age of 6 months and subsequently was diagnosed with BS at the age of 9 years. Molecular analysis identified the pathogenic germline BLM sequence variants (c.1642C>T and c.2207_2212delinsTAGATTC). This is the first report of IFS related to BS, for which we show that both BLM alleles are maintained in the tumor and demonstrate a TPM3-NTKR1 fusion transcript in the IFS. Our communication emphasizes the importance of long-term follow up after treatment for pediatric neoplastic conditions, as clues to important genetic entities might manifest later, and the identification of a heritable tumor predisposition often leads to changes in patient surveillance and management.


Investigation on dung beetle's (Heliocopris Hope, 1838) chitosan valorisation for hydrogel 3D printing.
Biopolymers and their derivatives are materials with increasing interest for industry and especially for sustainable engineering development. Among such kind of materials, carbohydrate polymer like highly deacetylated chitin (chitosan) is widely used for a wide range of applications, including material and biomedical developments. The majority of industrially produced chitosan is based on chitin extracted from crustacean exoskeleton. However, with increase of interest on this material, chitosan's production will rapidly become insufficient and other species should be investigated as new sources of chitosan. In the present work, we focus on the preparation of chitosan from giant dung beetles (Genus Heliocopris, Hope, 1838). This genus was chosen to show the possibility to take animals that develop and leave near dejection and valuate them for material applications. This work includes all the chitosan extraction procedures, chitosan characterisation IR, SEM, NMR, ash content, and deacetylation degree. Finally, the prepared carbohydrate polymer is used to form hydrogel. The prepared gel has been characterised and used for 3D printing, to show the compatibility of extracted chitosan with biomaterial application.


Dopamine biosensor based on surface functionalized nanostructured nickel oxide platform.
A dopamine biosensor has been developed using nickel oxide nanoparticles (NPs) and tyrosinase enzyme conjugate. Nickel oxide (NiO) NPs were synthesized by sol-gel method using anionic surfactant, sodium dodecyl sulphate (SDS), as template to control the size of synthesized nanoparticles. The structural and morphological studies of the prepared NPs were carried out using X-ray diffraction (XRD), transmission electron microscopy (TEM) and dynamic light scattering (DLS) techniques. Afterwards, tyrosinase enzyme molecules were adsorbed on NiO NPs surface and enzyme coated NPs were deposited on indium tin oxide (ITO) coated flexible polyethylene terephthalate (PET) substrate by solution casting method. The formation of enzyme-NPs conjugate was investigated by atomic force microscopy (AFM) and Fourier transform infrared spectroscopy (FTIR) techniques and used in selective detection and estimation of neurochemical dopamine by electrochemical method. The fabricated Tyrosinase/NiO/ITO electrode exhibits high sensitivity of 60.2nA/µM in linear detection range (2-100μM) with a detection limit of 1.038μM. The proposed sensor had a response time of 45s, long shelf life (45 days) with good reproducibility and selectivity in presence of interfering substances and was validated with real samples. The tyrosinase enzyme functionalized NiO platform has good bio-sensing efficacy and can be used in detection of other catecholamines and phenolic neurochemicals.


The story of the internal carotid artery of mammals: from Galen to sudden infant death syndrome.
Some anatomical aspects of the blood supply of the brains of mammals have been examined to illuminate their functions. A fundamental explanation of sudden infant death syndrome (cot death) is suggested following experimental observations. Speculative contributions have been made to comparative physiological ideas concerning mammals of pronograde and erect habitus, their vascular pressure adaptations and temperature management. Neuro- and interventional radiologists may make some significant future applications of these ideas. Of immediate practical interest is the possibility of influencing the well-being of human embryos' neural tube development in utero by a comprehensive study of their temperature environment.


Structure and magnetic properties of RE₄CoCd and RE₄RhCd (RE = Tb, Dy, Ho).
New rare earth metal rich cadmium compounds RE₄CoCd and RE₄RhCd (RE = Tb, Dy, Ho) were prepared by high-frequency melting of the elements in sealed tantalum tubes. The samples were studied by x-ray powder and single-crystal diffraction. All the compounds crystallize with Gd₄RhIn-type structure, with space group [Formula: see text]. The structures are built up from rigid three-dimensional networks of condensed, cobalt (rhodium) centred trigonal RE₆ prisms. The voids left by these networks are filled by Cd₄ cluster units and the coordination number 14 polyhedra of the RE1 atoms. The terbium and dysprosium compounds in both series undergo antiferromagnetic ordering, whereas the holmium compounds exhibit ferromagnetic ordering. The magnetic ordering in these compounds is characterized by broad peaks around the transition temperatures. The results of detailed crystallographic investigations and preliminary magnetic and specific heat studies are presented and discussed in this work.


Association of high sensitive C-reactive protein with coronary heart disease: a Mendelian randomization study.
Whether high sensitivity C-reactive protein (hs-CRP) has a causal effect on coronary heart disease (CHD) is unclear. This study investigated the causal effect of hs-CRP on CHD risk using Mendelian Randomization (MR) analysis. A total of 3802 subjects were recruited in the follow-up study. Linear regression model was used to evaluate the relationship between CRP polymorphisms and hs-CRP. Survival receiver operator characteristic curve method was used to explore the cut-off of hs-CRP on CHD incidence. Cox regression model was applied to detect the association of hs-CRP with CHD by calculating the hazard ratio (HR) and 95% confidence interval (CI). Rs1205 and rs876537 in CRP were selected as instrumental variables in MR analysis. During a median follow-up time of 5.01 years, 98 CHD incidence was identified (47.03/104 person-years). Hs-CRP was significantly increased among rs1205 and rs876537 genotypes with r values of 0.064 and 0.066, respectively. Hs-CRP 1.08 mg/L was identified as the cut-off value with a maximum value of sensitivity and specificity on prediction of CHD. Participants with ≥1.08 mg/L of hs-CRP has a higher risk of CHD incidence than that of participants with < 1.08 mg/L, the adjusted HR (95% CI) was 1.69 (1.11-2.60) with a P value of 0.016. No significant casual association was observed between hs-CRP and CHD with a P value of 0.777. The association between hs-CRP and CHD is unlikely to be causal, hs-CRP might be a predictor for incidence of CHD in general population.


A data-driven approach to evaluate factors affecting resident performance in cataract surgery.
To evaluate the operative duration and clinical performance of ophthalmology residents performing standard phacoemulsification cataract surgeries using information available from electronic health records (EHR). This is a retrospective cohort study. De-identified surgical records of all standard phacoemulsifications performed in a tertiary institution between 1st January 2015 and 8th August 2018 were retrieved from the hospital EHR. The main outcome measures were improvement in operative duration with case experience, corrected distance visual acuity (CDVA) improvement, and intra-operative complication rates. Twelve ophthalmology residents performed a total of 1427 standard phacoemulsifications. The median operative duration was 27 min (interquartile range, 22-34 min), which improved from 31 to 24 min (before the 101st case [Group 1] versus 101st case onwards [Group 2], p < 0.001). Gradient change analysis (non-linear regression) showed significant reduction until the 100th case (p = 0.043). Older patients (0.019), worse pre-operative CDVA (0.343), and surgery performed by Group 1 (1.115) were significantly associated with operative duration above 30 min. LogMAR CDVA improved from a mean of 0.57 ± 0.52 pre-operatively to 0.10 ± 0.18 post-operatively (p < 0.001). Posterior capsule rupture (PCR) rate decreased from 4.0% [Group 1] to 2.1% [Group 2] (p = 0.096), while overall complication rate decreased from 8.9% to 3.1% (p < 0.001). The median operative duration reduced consistently with surgical experience for the first 100 cases. Older patients, poorer pre-operative VA, and surgical experience of less than 100 cases were significantly associated with an operative duration above 30 min. There was a statistically significant decrease in complication rate between Group 1 and 2.


Stability of the saccadic oculomotor system.
A variety of different types of instability has been found in the saccadic system of humans. Some of the instabilities correspond to clinical conditions, whereas others are inherent in the normal saccadic system. How can these instabilities arise within the mechanism of normal saccadic eye movements? A physiologically-based model of the saccadic system predicts that horizontal saccadic oscillations will occur with excessive mutual inhibition between the left and right burst cells and with underaction of the pause cells. The amplitudes and frequencies of the oscillations had ranges of 0-6 degrees and 6-20 cycles per second, respectively. Application of stability analysis techniques to the model reveals that development of the oscillations can be explained by the Hopf bifurcation mechanism. Future development of this approach will involve classifying pathological instabilities of the saccadic system according to the bifurcation involved in their generation.


Immune checkpoint inhibitors in hepatocellular carcinoma: emerging challenges in clinical practice.
Systemic therapy for advanced hepatocellular carcinoma has expanded at an unprecedented pace over the past 5 years. After tyrosine kinase inhibitors dominated the field for more than a decade, immune checkpoint inhibitor (ICI)-based therapies have become the main component in systemic first-line treatment of this cancer. Delivery of immunotherapy in routine clinical practice recognises several challenges. In this Viewpoint, we discuss the major gaps in knowledge around the role of ICI-based therapies in patients with Child-Pugh class B. We discuss the challenges in individuals with rare histological subtypes of primary liver cancer, including combined hepatocellular-cholangiocarcinoma, fibrolamellar hepatocellular carcinoma, and sarcomatoid hepatocellular carcinoma. We also review data on ICI rechallenge in patients previously treated with ICIs, and discuss atypical patterns of progression related to immunotherapy (ie, hyperprogressive disease and pseudoprogression).


The importance of voltage-dependent sodium channels in cerebral ischaemia.
Strategies for the treatment of thromboembolic stroke are based on restoring the blood flow as soon as possible and protecting the neurons from the deleterious consequences of cerebral ischaemia. Interest has focused on blockers of voltage-dependent Na+ channels as potential neuroprotective agents because they prevent neuronal death in various experimental models of cerebral ischaemia and act cytoprotectively in models of white matter damage. Although several Na+ blockers are currently being tested in various phases of clinical development, most of these agents are relatively weak and unspecific. I therefore consider it worthwhile to search for molecules which specifically block voltage-dependent Na+ channels for the treatment of cerebral ischaemia.


Cardiopulmonary bypass after prolonged cardiac arrest in dogs.
Ventricular fibrillation (VF) cardiac arrest of more than ten minutes can be survived by cerebral neurons, but restoration of spontaneous circulation (ROSC) by external CPR is unreliable. Cardiopulmonary bypass (CPB) permits control of pressure, flow, oxygenation, temperature, and composition of blood. After 12 1/2 minutes of normothermic VF cardiac arrest, CPB was used as a research tool for reperfusion and assisted circulation for two hours in ten dogs without thoracotomy, with plasma substitute priming, and without preceding CPR (a deliberately nonclinical scenario). Recovery was compared with that in ten control dogs in which standard CPR with advanced life support (ALS) for up to 30 minutes was used to achieve ROSC. Both groups subsequently had blood pressure, blood gases, ventilation, and other parameters controlled for 20 hours, and intensive therapy to 72 hours. CPB achieved ROSC more successfully (ten of ten vs six of ten controls) (P less than .05), and more rapidly, with fewer defibrillation attempts and with less epinephrine (P less than .05). CPB improved 72-hour survival (seven of ten vs two of ten controls) (P = .025). Between two and 24 hours, of those with ROSC, intractable cardiogenic shock killed four of six control dogs (NS). CPB was followed by fewer arrhythmias. CPB increased recovery of consciousness (five of ten CPB vs zero of six controls with ROSC) (P = .037), but achieved neurologic normality in only one of ten. Cardiac arrest and CPB (without CPR) resulted in less myocardial morphologic damage than did standard CPR (P less than .025).(ABSTRACT TRUNCATED AT 250 WORDS)


Analysis of 203 patients with penetrating neck injuries.
Selective nonoperative management (SNOM) of penetrating neck injuries (PNI) has steadily gained favor, but indications for surgery and adjunctive diagnostic studies remain debated. The purpose of the present study is to validate a protocol of SNOM of PNI based on physical examination, which further dictates complementary investigations and management. A prospective observational study was conducted in a South African tertiary urban trauma center with a high prevalence of penetrating trauma. All consecutive patients admitted with penetrating neck injuries over a 13-month period were included. A total of 203 patients were included in the study: 159 with stab wounds and 42 with gunshot wounds. A vascular injury was identified in 27 (13.3%) patients, pharyngoesophageal injury in 18 (8.9%) patients, and an upper airway injury in 8 (3.9%) patients. Only 25 (12.3%) patients required surgical intervention. A further 8 (3.9%) patients had therapeutic endovascular procedures. The remaining 158 (77.8%) patients, either asymptomatic or with negative work-up, were managed expectantly. There were no clinically relevant missed injuries. Selective nonoperative management of neck injuries based on clinical examination and selective use of adjunctive investigational studies is safe in a high-volume trauma center.


Analytical toxicology: guidelines for sample collection postmortem.
The reliability and relevance of any analytical toxicology result is determined in the first instance by the nature and integrity of the specimen(s) submitted for analysis. This article provides guidelines for sample collection, labelling, transport and storage, especially regarding specimens obtained during a postmortem examination. Blood (5 mL) should be taken from two distinct peripheral sites, preferably left and right femoral veins, taking care not to draw blood from more central vessels. Urine (if available), vitreous humour (separate samples from each eye), a representative portion of stomach contents, and liver (10-20 g, right lobe) are amongst other important specimens. A preservative (sodium fluoride, 0.5-2% weight by volume (w/v) should be added to a portion of the blood sample/the sample from one vein, and to urine. Leave a small (10-20% headspace) in tubes containing liquids if they are likely to be frozen. Precautions to minimise the possibility of cross-contamination of biological specimens must be taken, especially if volatile poison(s) may be involved. If death occurred in hospital, any residual antemortem samples should be sought as a matter of urgency. Hair/nail collection should be considered if chronic exposure is suspected, for example, in deaths possibly related to drug abuse. A lock of hair the width of a pen tied at the root end is required for a comprehensive drug screen. The value of providing as full a clinical/occupational/circumstantial history as possible together with a copy of the postmortem report (when available) and of implementing chain-of-custody procedures when submitting samples for analysis cannot be over-emphasised.


Total synthesis of (+/-)-lysergic acid, lysergol, and isolysergol by palladium-catalyzed domino cyclization of amino allenes bearing a bromoindolyl group.
Ergot alkaloids and their synthetic analogs have been reported to exhibit broad biological activity. We investigated direct construction of the C/D ring system of ergot alkaloids based on palladium-catalyzed domino cyclization of amino allenes. With this biscyclization as the key step, total synthesis of (+/-)-lysergic acid, (+/-)-lysergol, and (+/-)-isolysergol was achieved.


Striatal dopaminergic pathways as a target for the insecticides permethrin and chlorpyrifos.
Because insecticide exposure has been linked to both Parkinsons disease and Gulf War illness, the neurotoxic actions of pyrethroid and organophosphate insecticides on behavior and striatal dopaminergic pathways were investigated in C57BL/6 mice treated with permethrin (three i.p. doses at 0.2-200 mg/kg) or chlorpyrifos (three s.c. doses at 25-100 mg/kg) over a 2-week period. Permethrin altered maximal [3H]dopamine uptake in striatal synaptosomes from treated mice, with changes in Vmax displaying a bell-shaped curve. Uptake was increased to 134% of control at a dose of 1.5 mg/kg. At higher doses of PM (25 mg/kg), dopamine uptake declined to a level significantly below that of control (50% of control at 200 mg/kg, P < 0.01). We also observed a small, but statistically significant decrease in [3H]dopamine uptake by chlorpyrifos, when given at a dose of 100 mg/kg. There was no significant effect on the Km for dopamine transport. Evidence of cell stress was observed in measures of mitochondrialfunction, which were reduced in mice given high-end doses of chlorpyrifos and permethrin. Although cytotoxicity was not reflected in decreased levels of striatal dopamine in either 200 mg/kg PM or 100 mg/kg CPF treatment groups, an increase in dopamine turnover at 100 mg/kg CPF was indicated by a significant increase in titers of the dopamine metabolite, 3,4-dihydroxyphenylacetic acid. Both permethrin and chlorpyrifos caused a decrease in open field behavior at the highest doses tested. Although frank Parkinsonism was not observed, these findings confirm that dopaminergic neurotransmission is affected by exposure to pyrethroid and organophosphorus insecticides, and may contribute to the overall spectrum of neurotoxicity caused by these compounds.


A study on managerial leadership in education: A systematic literature review.
Articles on managerial leadership (ML) have been published from year to year, since 1950s. The use of ML theory in previous research is common, but some inconsistencies are found regarding the terms commonly used. In other words, there is a mismatch between the use of the term ML in article paper and structures. This will certainly have an impact on bias and ambiguity for future research literatures. Theoretical review on this topic is rarely carried out, specifically in ML theory. The novelty of this research lies in the classification results of articles that used the term ML in accordance with the theory. This theoretical review was conducted to examine the classification of accuracy of articles which were using the term ML in title with four consistency and accuracy indicators on the article structures starting from the problem, aim, literature, results and discussion, as well as conclusion sections. This review as a qualitative literature research used a language and historical approach, as well as a ML theory. This study Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The technique and instrument used was bibliographic instruments, comprehensive list of keywords and mixed search terms to search the articles online with the help of Google Chrome and Mozilla Firefox browsers. A total of 68 articles published from 1959 to 2022 as a final reviewed. They were obtained from several well-known digital journal content such as Jstor, Proquest, Oxford University Press, Google Scholar, and National Library, as well as various journals under major publishers such as Elsevier, Taylor & Francis, SAGE, Emerald, Brill, and Wiley. The data collected were analyzed using content analysis with 4 indicators of consistent (accurate & additional) and inconsistent (difference & additional), and 4 accuracy category of accuracy, appropriate, bias, and error for determaining the articles classification, and validated them by using triangulation and grounded theory. The results showed that in 1959 the first article appeared using the word ML, in 2012 the first and only article appeared that only used ML, and the last is in 2022. Then, the consistency of the title with other article sections is 17 articles (25% of 68) according to the accurate term indicator. Last, the accuracy of articles was divided into four categories: 10 articles (15% of 68) in the accuracy category. This systematic review contributes the article classification that can become a more established scientific roadmap of references and reasoning of studying ML.


Purification of the antibacterial fragments of guinea-pig major basic protein.
In this study, we tried to purify the antibacterial fragments of guinea-pig major basic protein (MBP) using Staphylococcus aureus. The antibacterial activity of MBP was not affected by the pyridylethylation, suggesting that the disulfide bonds were not necessary for the antibacterial activity. When pyridylethylated-MBP was digested with alpha-chymotrypsin, the four potent antibacterial fragments (fragment V (Arg105-Tyr119), fragment IX (Thr1-Phe67), fragment X (Ile54-Leu97) and fragment XIII (Arg25-Phe67)) were isolated by reverse-phase high-performance liquid chromatography. Anti-MBP monoclonal antibody, BMK-13 neutralized the antibacterial activity of PE-MBP and fragments IX, X and XIII, but not the activity of fragment V, suggesting that Ile54-Phe67, the common amino-acid sequence of fragments IX, X and XIII, might be involved in the antibacterial activity of MBP. In fact, the synthetic peptide, Ile54-Phe67 exerted the antibacterial activity, and the activity was neutralized with BMK-13. The antibacterial activity of Ile54-Phe67 was lost by the modification with peptidylarginine deiminase which converted arginine residue to citrulline residue, suggesting that the arginine residues may be important for the antibacterial activity.


Tuberculosis and COVID-19: A combined global threat to human civilization.
A new era has begun with the discovery of SARS-CoV-2 in a seafood market in Wuhan, China. The SARS-CoV-2 outbreak has wreaked havoc on health systems and generated worldwide attention. The world's attention was diverted from the treatment of the leading chronic infectious illness, Mycobacterium tuberculosis. The similarities in the performance of the two infectious species had obvious repercussions. Administrative efforts to combat SARS-CoV-2 have weakened the tuberculosis control chain. As a result, progress against tuberculosis has slowed. Thus, the goal of this review is to examine the impact of SARS- CoV-2 on a chronic public health issue: tuberculosis.


The relationship of coping strategies, social support, and attachment style with posttraumatic growth in cancer survivors.
This cross-sectional study investigated attachment style, coping strategies, social support, and posttraumatic growth (PTG) in 54 cancer survivors. Secure attachment was significantly associated with active coping, positive reframing, and religion, and these were all associated with PTG. Insecure types of attachment and social support variables were unrelated to PTG. Regression analysis suggests that positive reframing and religion as coping strategies may mediate the relationship between secure attachment and PTG.


Bioaccessibility of lead in urban soil of Broken Hill, Australia: A study based on in vitro digestion and the IEUBK model.
This study was conducted to investigate lead (Pb) bioaccessibility in urban soil and to assess health risk to children in the city of Broken Hill, Australia, which was established around one of the world's largest lead-zinc-silver mines. Fifty-three topsoil (0-0.1m) and 50 subsoil (0.3-0.5m) samples were collected from earthen footpaths, nature strips, parks or vacant land throughout the urban area. The soil samples were analysed for total Pb concentration, Pb bioaccessibility and Pb mineral phases, together with important soil physicochemical properties known to influence Pb bioaccessibility. Lead bioaccessibility ranged from 24% to 89% in topsoil and from 16% to 100% in subsoil, exhibiting a generally decreasing pattern with increasing distance from the orebody. Lead bioaccessibility was strongly positively related to total Pb concentration in both the topsoil and subsoil. In subsoil, a moderate negative correlation existed between Pb bioaccessibility and soil pH, while a moderate positive correlation existed between Pb bioaccessibility and soil organic matter (OM) content. In contrast, only a weak positive correlation existed between Pb bioaccessibility and OM content in topsoil. The presence of different Pb mineral phases also appeared to have caused variation in soil Pb bioaccessibility, with galena (PbS)-rich samples tending to exhibit lower Pb bioaccessibility. The prediction of blood lead (PbB) levels in Broken Hill children aged 1-4years using the IEUBK model well matched the measured data from a recent PbB screening, suggesting a high risk of childhood chronic low-level Pb exposure (PbB levels >5μg/dL) in Broken Hill, especially in the vicinity of the orebody. Future Pb abatement programs in Broken Hill should utilise the IEUBK model to establish target soil Pb values in an effort to achieve particular child PbB outcomes.


Serum concentration and dose-response relationships for carprofen in rheumatoid arthritis.
Thirty-eight patients with active, definite, or classical rheumatoid arthritis were tested in a double-blind, 3-week-per-arm, multiple-crossover, randomized, block-design comparison of 100, 300, 600, and 800 mg/day carprofen given b.i.d. A linear dose-response relationship was demonstrated for six of nine efficacy measures (p less than 0.052). A plasma concentration to therapeutic response relationship was shown just before or 1 to 2 hours after a dose (p less than 0.05) for seven efficacy parameters for the patients with at least three serum carprofen concentrations. By nonparametric analysis, with the patients divided into three equal groups, the percent of responders rose from 38.1% to 50% to 59.1%. Sixty-nine percent of patients responded when carprofen concentrations were greater than 10 micrograms/ml, whereas only 9% responded when they were below 1.9 micrograms/ml. Although only seven patients had limiting side effects, there was a tendency toward a dose-toxicity relationship through 600 mg daily carprofen.


First reproductive signs of inbreeding depression in Southern California male mountain lions (Puma concolor).
Long-term studies of mountain lions (Puma concolor) in Southern California have documented persistent small population sizes and the lowest genetic variation of any mountain lion population, except for the Federally endangered mountain lion subspecies, the Florida panther (Puma concolor coryi). There is overwhelming molecular evidence supporting inbreeding and low genetic diversity in these Southern California populations but there is a lack of phenotypical evidence of inbreeding depression. The primary goal of this study was to assess male mountain lions, in Southern California, for teratospermia (>60% abnormal sperm production), one of the first signs of inbreeding depression in mountain lions that are associated with decreased reproduction and population decline. From December 2019 to December 2020, we surveyed mountain lions during live captures, after mortality events, and in images collected from camera traps in the following populations: Santa Monica Mountains, Santa Susana Mountains, Santa Ana Mountains, and the Eastern Peninsular Range. Mountain lions were sampled for known physical abnormalities associated with inbreeding depression such as teratospermia, cryptorchidism, and distal tail kinks. For teratospermia, we extracted testes from five males post-mortem to assess sperm morphology. Epididymal sperm evaluations revealed all males were teratospermic. Across all samples, on average, 93% of observed spermatozoa were abnormal. We physically examined 32 mountain lions (males and females) for distal tail kinks, and we observed one individual affected. We examined 15 male mountain lions for cryptorchidism, and we observed one unilaterally cryptorchid male and one male with testes that differed significantly in size, likely reflecting asynchronous migration of the testes during puberty. Further, we identified three other animals in camera-trap images that had distal tail kinks, for a total of four. In conclusion, from December 2019 to December 2020, we identified nine individuals exhibiting physical signs of inbreeding depression. These reproductive and physical signs of inbreeding depression in Southern California mountain lions increase the urgency of conservation efforts in the region.


Schistosoma mansoni: sterol and phospholipid composition of cercariae, schistosomula, and adults.
The sterol and phospholipid composition of cercariae, schistosomula, and adult Schistosoma mansoni was analyzed by gas-liquid chromatography and high-performance liquid chromatography (HPLC). Cercariae and schistosomula contained cholesterol, desmosterol, campesterol, stigmasterol, and beta-sitosterol while adults contained only cholesterol. In all stages cholesterol comprised greater than 50% of the total sterols, and in cercariae and schistosomula desmosterol comprised 38 and 21% of the total sterols, respectively. The other three sterols, campesterol, stigmasterol, and beta-sitosterol, made up approximately 10% of the total. The same five sterols found in cercariae and schistosomula were present in the hepatopancreas of uninfected snails but with a much higher desmosterol concentration in the parasite, 38%, than in the snail, 2%. As in cercariae and schistosomula the three minor sterols comprised approximately 10%. Thus, the sterol composition of cercariae and schistosomula was similar but not identical to that of the snail host. Phosphatidylcholine was the major phospholipid of all three stages (50%) as determined by two HPLC procedures. The remaining phospholipids consisted of phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol. In addition, in adults there were small quantities of sphingomyelin and lysophosphatidylcholine. The percentage of each phospholipid was similar among stages with the exception of a slight increase in phosphatidylserine in adults compared to cercariae and schistosomula. These results show that a characteristic lipid composition is found in cercariae, schistosomula, and adults.


Analyses of Mlc-IIBGlc interaction and a plausible molecular mechanism of Mlc inactivation by membrane sequestration.
In Escherichia coli, glucose-dependent transcriptional induction of genes encoding a variety of sugar-metabolizing enzymes and transport systems is mediated by the phosphorylation state-dependent interaction of membrane-bound enzyme IICB(Glc) (EIICB(Glc)) with the global repressor Mlc. Here we report the crystal structure of a tetrameric Mlc in a complex with four molecules of enzyme IIB(Glc) (EIIB), the cytoplasmic domain of EIICB(Glc). Each monomer of Mlc has one bound EIIB molecule, indicating the 1:1 stoichiometry. The detailed view of the interface, along with the high-resolution structure of EIIB containing a sulfate ion at the phosphorylation site, suggests that the phosphorylation-induced steric hindrance and disturbance of polar intermolecular interactions impede complex formation. Furthermore, we reveal that Mlc possesses a built-in flexibility for the structural adaptation to its target DNA and that interaction of Mlc with EIIB fused only to dimeric proteins resulted in the loss of its DNA binding ability, suggesting that flexibility of the Mlc structure is indispensable for its DNA binding.


[CT-based classification aid for acetabular fractures: evaluation and clinical testing].
The basis for the classification of acetabular fractures depends on accurate radiological diagnostics. The use of conventional X-rays alone implicates a low intrapersonal reproducibility and interpersonal reliability. By applying computed tomography (CT) at an early stage in the emergency room, the typical diagonal X-rays of ala and obturator, on which the classification is based, are no longer recommended. The aim of this study was to develop a new reliable classification system based on standardized CT slices according to the system of Judet and Letournel without using diagonal X-rays. In this study 12 select cases with acetabular fractures were peer reviewed. In each case eight characteristic CT slices (five axial, two coronal and one sagittal) were selected as well as the conventional anteroposterior X-ray of the pelvis. All cases were peer reviewed by 14 members of the "AG Becken" (working group pelvis). The classification of the acetabular fractures was based on Judet and Letournel and the results were compared with the reference classification. The results were scaled according to differences to the original classification and the relevance to the approach as well as the medical qualification of the member. A total of 167 out of 168 possible classifications were conducted, 90 cases (54 %) were in accordance with the reference classification. In 69 cases (41 %) the outcome was different, which would have had no influence on the choice of the surgical approach. A wrong classification was present eight times (5 %). According to the medical qualification status the senior physicians were right in 54%, the residents in 53 %. Within the group of senior physicians 7.5 % of the classifications were completely wrong and 93 % of the participating members would have preferred to have more CT slices. The CT-based classification developed represents an adaption to the current standard of diagnostics of acetabular fractures and represents a step towards simplification of the classification. It is suitable to estimate the correct surgical approach and the behavior of the fracture. For an accurate classification and the association to one of the fracture types in the system of Judet and Letournel more slices and 3D reconstructions (MPR) are necessary.


Association between c135G/A genotype and RET proto-oncogene germline mutations and phenotype of Hirschsprung's disease.
Several genes, including the major susceptibility gene RET, have roles in development of Hirschsprung's disease. Results of genetic-linkage analysis of patients with familial disease with both long-segment and short-segment phenotypes have shown close linkage with the RET locus. We aimed to investigate whether both RET mutations and polymorphisms contribute to phenotype of Hirschsprung's disease. We looked at the coding region of all 21 exons of the RET proto-oncogene, including the flanking intronic sequences, by direct DNA sequencing in 76 caucasians from Germany with Hirschsprung's disease. 20 different mutations were detected in 18 patients. Mutations were under-represented in patients with a homozygous RET c135A/A genotype in association with short-segment phenotype. Short-segment phenotype also arose if the RET mutation was on the c135A allele; conversely, a RET germline mutation on the c135G allele resulted in long-segment phenotype, particularly in heterozygous c135G/A patients. These observations lend support to the idea that both RET alleles have a role in pathogenesis of Hirschsprung's disease, in a dose-dependent fashion. We also showed that the c135G/A polymorphism modifies the phenotype by a within-gene interaction between the c135A variant and a mutation.


Heavy metal accumulation in leaves of selected plant species in urban areas of Delhi.
Heavy metals beyond their permissible limits are major contaminants and causes of concern due to their persistent nature and health hazards. Several studies validated the utilization of plants as biomonitors and bioaccumulators for heavy metal pollution. Therefore, this study was conducted to examine the proficiency for heavy metal monitoring and mitigation by commonly found plant species in urban areas of Delhi. For this objective, four sites (viz., control, residential, commercial, and industrial) and sixteen usually growing plant species were selected. Four heavy metals, i.e., lead (Pb), cadmium (Cd), copper (Cu), and zinc (Zn), were analysed for soil and dust from each site, and leaf samples from each plant, at all sites, and various other parameters were calculated. Among the four elements, Pb and Cd showed maximum geoaccumulation and contamination at all sites. Pollution load index (PLI) values for both soil and dust indicated that industrial sites (1.78, 2.15) were most contaminated followed by commercial (1.52, 1,87), residential (1.41, 1.67), and control (1.22, 1.37) sites. Concentrations of Pb, Cu, and Zn were found to be highest in Morus alba, while Cd concentrations were found to be highest in Millettia pinnata (L.) Panigrahi. From various analyses, we concluded that commonly found plant species such as Ficus religiosa L., Terminalia arjuna (Roxb. Ex DC.) Wight &Arn., Morus alba L., Prosopis juliflora (Sw.) DC., and M. pinnata proved to be exceptional biomonitors and bioaccumulators for heavy metals in urban areas. Therefore, these plant species are highly recommended for plantation in urban areas for decontamination of the air and soil by mitigating heavy metal pollution.


Novel intraoperative use of the "Tensipresser" to assess factors predictive of pancreatic fistula after pancreaticoduodenectomy.
Pancreatic fistula (PF) is a challenging complication of pancreaticoduodenectomy (PD). 'Soft pancreas' is reported as a risk factor for PF; however, palpation by the surgeon is not an objective method of evaluating pancreatic texture. We conducted this study to investigate whether a texture analyzer called a "Tensipresser" can be used to quantify pancreatic tissue hardness and predict the development of postoperative PF. We assessed pancreatic texture in 85 patients who underwent PD. After surgeons assessed the texture of the pancreas subjectively, the physical properties were measured on the pancreatic margin intraoperatively, by the two-bite method using the "Tensipresser". The incidence and severity of PF were based on the definitions of the International Study Group on Pancreatic Fistula. Symptomatic PF (grade B and C) developed in 16% of the patients. Patients were divided into two groups based on the Tensipresser measurement: those with a soft and fragile pancreas with hardness < 2070 gw/cm2 and cohesiveness < 0.65 (SF group); and all other patients (non-SF group). In the univariate and multivariate analysis, a small pancreatic duct diameter (<4 mm), no conduction of preoperative chemoradiation therapy, and inclusion in the SF group were significant predictors of PF. The Tensipresser can evaluate pancreatic texture objectively, helping to define intraoperatively, those at risk of the development of PF.


Nicotinic cholinergic intercellular communication: implications for the developing auditory system.
In this paper, research on the temporal and spatial distribution of cholinergic-related molecules in the lower auditory brainstem, with an emphasis on nicotinic acetylcholine receptors (nAChRs), is reviewed. The possible functions of acetylcholine (ACh) in driving selective auditory neurons before the onset of hearing, inducing glutamate receptor gene expression, synaptogenesis, differentiation, and cell survival are discussed. Experiments conducted in other neuronal and non-neuronal systems are drawn on extensively to discuss putative functions of ACh and nAChRs. Data from other systems may provide insight into the functions of ACh and nAChRs in auditory processing. The mismatch of presynaptic and postsynaptic markers and novel endogenous agonists of nAChRs are discussed in the context of non-classical interneuronal communication. The molecular mechanism that may underlie the many functions of ACh and its agonists is the regulation of intracellular calcium through nAChRs. The possible reorganization that may take place in the auditory system by the exposure to nicotine during critical developmental periods is also briefly considered.


Operative results in 143 patients with hepatocellular carcinoma.
A total of 143 patients who underwent hepatic resection for hepatocellular carcinoma in our department were reviewed. The review was conducted for two periods: 1970-1982 (early period) and 1983-1990 (late period), that is, the periods before and after introduction of the hepatic surgical technique involving the use of a microwave tissue coagulator and ultrasonic dissector. One patient underwent extended lobectomy, 12 lobectomy, 9 segmentectomy, and 26 partial hepatectomy during the early period. Two patients underwent extended lobectomy, 7 lobectomy, 9 segmentectomy, 36 subsegmentectomy, and 41 partial hepatectomy during the late period. Operative mortality and hospital mortality were 16.7% and 22.9% during the early period and 1.1% and 8.4% during the late period, respectively. The overall mortality rate was significantly lower during the late period than during the early period. Postoperative complications developed in 62.5% of the patients with hepatic resection during the early period and in 48.4% of the patients during the late period. The size of tumors during the early period was significantly greater than that during the late period. Intraoperative blood loss during the late period was significantly lower than that during the early period. The survival curve was better among patients who underwent hepatic resection during the late period than among those during the early period. The satisfactory results during the late period are due to the introduction of intraoperative ultrasonography, microwave tissue coagulation, and ultrasonic dissection for hepatic surgery.


Magnetic resonance imaging in orbital diagnosis.
Today, computed tomography is the primary diagnostic imaging test in orbital disease. Magnetic resonance in some instances is complementary and in a few conditions superior to CT. The relationship between these two imaging modalities is evolving.


Employing Dictyostelium as an Advantageous 3Rs Model for Pharmacogenetic Research.
Increasing concern regarding the use of animals in research has triggered a growing need for non-animal research models in a range of fields. The development of 3Rs (replacement, refinement, and reduction) approaches in research, to reduce the reliance on the use of animal tissue and whole-animal experiments, has recently included the use of Dictyostelium. In addition to not feeling pain and thus being relatively free of ethical constraints, Dictyostelium provides a range of distinct methodological advantages for researchers that has led to a number of breakthroughs. These methodologies include using cell behavior (cell movement and shape) as a rapid indicator of sensitivity to poorly characterized medicines, natural products, and other chemicals to help understand the molecular mechanism of action of compounds. Here, we outline a general approach to employing Dictyostelium as a 3Rs research model, using cell behavior as a readout to better understand how compounds, such as the active ingredient in chilli peppers, capsaicin, function at a cellular level. This chapter helps scientists unfamiliar with Dictyostelium to rapidly employ it as an advantageous model system for research, to reduce the use of animals in research, and to make paradigm shift advances in our understanding of biological chemistry.


Development and assessment of a home care tracheotomy manual.
As home care tracheotomy has become a viable option for children with long-term canulation, medical personnel are challenged to provide as safe an environment as possible out of the hospital for these children. The tools used in the training of the families and other caregivers have received little attention in the literature. This study describes the development of a home-care tracheotomy manual for parents. The use of appropriate content presented in an organized, informative and pleasing fashion at the appropriate reading level is stressed. The evaluation of the manual by parents with children who have a child with a tracheotomy is also described.


Towards an anthropological psychiatry.
The situation of present day psychiatry is described as being dominated by an empiricist perspective. The limitations of this perspective are analyzed and a rough sketch of the hermeneutical approach in psychiatry is offered. It is argued that a fully developed hermeneutical psychiatry implies a reference towards anthropological themes. Three of them, time, historicity and corporality, are investigated.


Dual-responding circularly polarized luminescence based on mechanically and thermally induced assemblies of cyano-distyrylbenzene hydrogen bonding liquid crystals.
Circularly polarized luminescence controlled by both mechanics and temperature was observed for the first time. The cyano-distyrylbenzene-cholesterol liquid crystals exhibited not only mechanochromism and thermochromism but also mechanically induced and thermally induced circularly polarized.


Falsely raised plasma theophylline concentrations in renal failure.
We studied the validity of plasma theophylline measurements in renal failure. Patients with increased serum creatinine receiving theophylline had drug measurements by four methods: high pressure liquid chromatography (HPLC) fluorescence polarization immunoassay (FPIA), enzyme immunoassay (EIA) and dipstick immunoassay (DI). The mean +/- SD (mumol/l) for plasma theophylline in the 18 patients with renal impairment was: HPLC 63.4 +/- 36.7; EIA 64.4 +/- 35.9; FPIA 70 +/- 3.43; DI 122 +/- 65.9. A significant correlation (r = 0.94, p less than 0.01) was obtained between serum creatinine and the difference in theophylline concentrations between HPLC and DI. Plasma theophylline results should be interpreted with caution in patients with renal failure.


Rapid identification of Candida albicans and its related species Candida stellatoidea and Candida dubliniensis by a single PCR amplification using primers specific for the repetitive sequence (RPS) of Candida albicans.
Candidiasis is caused by several Candida species, of which Candida stellatoidea and C. dubliniensis are phenotypically close to C. albicans. Although current molecular biology-based techniques can distinguish between C. albicans and C. dubliniensis, a convenient tool that can distinguish C. stellatoidea from C. albicans has not yet been developed. To develop a system that can simply, rapidly and specifically distinguish C. albicans from the related Candida species C. stellatoidea and C. dubliniensis. Genomic DNAs were purified from various yeast species and amplified by primers specific for the repetitive sequence (RPS) of C. albicans. The PCR products were purified and sequenced in order to test the specificity of the PCR amplification. The PCR primers only amplified several products from C. albicans, C. stellatoidea and C. dubliniensis. Sequence analysis of the products revealed that C. stellatoidea and C. dubliniensis both had RPSs including alt repeats, similar to C. albicans. After the PCR amplification, each of the three Candida species showed a unique amplification profile. Furthermore, RFLP analysis of the PCR products using EcoRI and ClaI produced species-specific restriction profiles. This PCR-based technique targeting the alt repeats in the RPS is useful as a tool for the rapid identification and distinction of C. albicans, C. stellatoidea and C. dubliniensis.


Adapting to Multiple Sclerosis Stigma Across the Life Span.
Most people with multiple sclerosis (MS) experience social stigma at mild-to-moderate levels, with potential implications for their health. However, little is known about how adults adapt to social stigma across their lives, or with respect to MS stigma in particular. Using a large national database and controlling for confounding demographic and health-related variables, this study examined whether longer MS duration was associated with reports of stigma in people with MS. Data were available from 6771 participants enrolled in the semiannual survey conducted by the North American Research Committee on Multiple Sclerosis (NARCOMS). Participants completed measures of MS stigma and reported on demographic and health-related covariates. With disability level, age, and other demographic and health-related covariates taken into account, the longer respondents had lived with MS, the less stigma they felt. Results were similar for people's anticipation of stigma and their feelings of isolation because of stigma. As people gain experience living with MS, their adaptations to the social aspects of their illness may allow them to structure their lives so that they can mitigate the impact of stigma. Doctors, therapists, and other health care personnel should consider that patients with MS might be especially concerned and distressed by stigma earlier in the course of their illness.


White Matter Lesions as Brain Frailty and Age are Risk Factors for Surgical Clipping of Unruptured Intracranial Aneurysms in the Elderly.
We aimed to identify the risk factors for surgical treatment of unruptured intracranial aneurysms (UIAs) in individuals aged >60 years, particularly focusing on white matter lesions (WMLs). We investigated a total of 214 patients with UIAs. The patient group comprised 53 males and 151 females with an average age of 68.2 years. UIA size ranged from 2.7 to 26 (mean: 7.3) mm. The primary endpoint of the study was patient prognosis evaluated at the time of discharge using the modified Rankin Scale. We examined the risk factors for poor outcome and WMLs using magnetic resonance imaging. Poor outcome was observed in 23 (10.7%) patients. Significant correlations were observed between poor outcome and UIA size (P < 0.0001), UIAs located posteriorly (P = 0.0204), UIA thrombosis (P = 0.0002), and presence of WMLs (P < 0.0001) in univariate regression analysis. However, no significant correlations were noted between poor outcome and age (P = 0.1438). Multivariate logistic regression analyses showed significant correlations between poor outcome and UIA size (P < 0.0001), presence of WMLs (P = 0.001). Severe WMLs based on the Fazekas classification was correlated to age (P < 0.0001) and atherosclerosis (P = 0.0001). Severe WMLs were associated with ischemia (P < 0.001) and epilepsy (P = 0.0502) as well as length of hospitalization (P < 0.0001). Severe WMLs are risk factors for surgical treatment of UIAs in the elderly. Surgical indications must be considered and caution should be taken when managing patients with severe WMLs.


Haploidentical Hematopoietic Cell Transplantation with Post-Transplant Cyclophosphamide in a Patient with Chronic Granulomatous Disease and Active Infection: A First Report.
We describe haploidentical hematopoietic cell transplantation (HCT) with high-dose post-transplant cyclophosphamide (PTCy) in a boy with x-linked chronic granulomatous disease (CGD). A persistent and life-threatening fungal infection was the indication for HSCT. Non-myeloablative conditioning with PTCy (50 mg/kg days 3 and 4) was used in the absence of fully matched donors. Engraftment occurred on day 24. The patient experienced Grade 2 graft-versus-host disease of the skin and gastrointestinal tract and CMV infection, both of which were controlled. Chimerism was 100 % at days 30 and 6 months. Cessation of antifungal therapy was consistent with cure of the infection. Haploidentical HCT with high-dose PTCy for CGD is feasible and succeeded even in the context of active infection.


Vestibular schwannoma microsurgery with special reference to facial nerve preservation.
To retrospectively study the outcomes of vestibular schwannoma (VS) resection. Between January 2003 and December 2006, 103 consecutive patients who had undergone VS resection were included in this study. Medical records, operation summaries, follow-up data, and neuroradiological findings were analyzed. The relationship between tumor size, location, and topography relative to the facial nerve bundles was studied for a mean duration of 16 months (range: 3-39 months). Complete tumor resection in combination with anatomic preservation of the facial nerve was achieved in 101 (98.1%) cases. The facial nerve was fully preserved in 100% of cases with small or medium tumors and in 37/39 patients with large tumors. Overall, 83.5% of patients had normal or near-normal facial nerve function 3-12 months post-surgically. The mortality rate was 0%. Even in large VS, preservation of facial nerve function (H-B Grade I or II) should be prioritized over total resection. For tumors >3cm, the goal of low morbidity and maintenance of normal facial nerve function can be attained with the retrosigmoid transmeatal approach, refined microsurgical technique, and intraoperative facial nerve monitoring.


Correlation of event-related potentials N170 with dysfunctional attitudes in patients with major depressive disorder.
Cognitive impairment frequently accompanies first-episode major depressive disorder (MDD) in patients. Early detection and intervention for cognitive impairment can enhance the quality of life for individuals with depressive disorders. Impaired emotion recognition may serve as an initial manifestation of cognitive impairment in these patients. This study examines the characteristics of event-related potentials N170 and dysfunctional attitudinal questionnaire total scores, as well as each factor and their correlation, revealing characteristic electroencephalogram (EEG) changes associated with cognitive impairment in first-episode MDD patients. A total of 88 patients experiencing first-episode MDD and 29 healthy volunteers from the same period participated in the study. They underwent event-related potential N170 measures to assess mood recognition function, the 17-item Hamilton depression scale (HAMD-17) to evaluate the severity of depressive disorder, and the Dysfunctional Attitudes Scales(DAS) to appraise cognitive function. The dysfunctional attitude questionnaire's total score and each factor score were higher in the MDD group compared to the healthy control (HC) group. The MDD group exhibited lower amplitudes than the HC group at CZ, PZ, POZ, P7, PO7, P8, and PO8 electrode points. A correlation was identified between the P7 and PO7 electrode points of the event-related potential N170 and cognitive function. This study solely considered neutral face emotional stimuli and did not account for depressive disorder subtypes. Differences were observed between the MDD and HC groups in cognitive function and N170 amplitude in the central brain region (CZ, PZ, POZ), left posterior temporal region (P7), left occipitotemporal region (PO7), right posterior temporal region (P8), and right occipitotemporal region (PO8). Additionally, a correlation was found between N170 latency in the left posterior temporal region of the brain (P7) and the left occipitotemporal region (PO7) with cognitive function.


Genotyping of blood groups in alloimmunized patients with β-thalassemia major by T-ARMS-PCR and multiplex-aso-pcr.
Beta-thalassemia major is a severe hemolytic anemia requiring life-long blood transfusion. Planned random donor blood transfusion is associated with alloimmunization against incompatible antigens. Determination of the minor blood group systems phenotype or genotype, and administration of the compatible blood components can significantly reduce the rate of alloimmunization. The present study aimed to determine the prevalence of alloimmunization, and genotype/phenotype characteristics of the minor blood groups systems in patients with β-thalassemia major. This study was conducted on 1147 β-thalassemia major patients. Initially, antibody screening and antibody identification were performed. Then, phenotyping and genotyping for the Rh, Kell, Kidd, and Duffy blood groups were done in alloimmunized patients using monoclonal antibodies and Multiplex-Allele Specific Oligonucleotide-Polymerase Chain Reaction (Multiplex-ASO-PCR) and Tetra-primer amplification refractory mutation system-PCR (T-ARMS-PCR), respectively. Any phenotype/genotype discrepancy was assessed by direct sequencing. Ninety-seven (8.5 %) out of 1147 patients had alloantibodies against the minor blood group antigens (44 males, 45.4 %, and 53 female, 54.6 %). The most common alloantibodies were against the RH (n: 47, 48.5 %), and the Kell (n: 23, 23.7 %) blood groups systems. Twenty-three (2.1 %) genotype/phenotype discrepancies out of 1067 tests, including 9 in the Rh (9.3 %), 8 in Duffy (34.8 %), and 6 in Kidd (26.1 %) blood groups were detected. No discrepancy was found in the Kell blood group system. Direct sequencing revealed that the results of molecular methods were correct. Multiplex-ASO-PCR and T-ARMS-PCR molecular methods are fast, reliable and cost-benefit molecular methods for the minor blood group genotyping in multi-transfused β-thalassemia major patients.