Carbon dioxide water-bath treatment augments peripheral blood flow through the development of angiogenesis.
In this study, we investigated the effects of CO2 water-bath therapy on blood flow and angiogenesis in the ischemic hind limb, as well as some plasma angiogenic factors in peripheral ischemic model. The hind limb ischemia was induced by occluding the femoral artery for 2 weeks in rats and treated with or without CO2 water-bath therapy at 37 °C for 4 weeks (20 min treatment every day for 5 days per week). The peak blood flow and minimal and mean blood flow in the ischemic skeletal muscle were markedly increased by the CO2 water-bath therapy. This increase in blood flow was associated with development of angiogenesis in the muscle, as well as reduction in the ischemia-induced increase in plasma malondialdehyde levels. Although plasma vascular endothelial growth factor and nitric oxide levels were increased in animals with peripheral ischemia, the changes in these biomarkers were not affected by CO2 water-bath therapy. These results suggest that augmentation of blood flow in the ischemic hind limb by CO2 water-bath therapy may be due to the development of angiogenesis and reduction in oxidative stress.


Thermal benefit of sibling presence in the newborn rabbit.
Newborn rabbits compete vigorously for the mother's milk, and survivors benefit from littermate deaths. Here we report that rabbit pups also may benefit from littermate presence in terms of increased thermal efficiency. Pups nursed normally once a day by their mother but otherwise raised alone had a lower probability of survival, lower body temperature, and lower efficiency of converting milk into body mass than their siblings raised with littermates. The contribution of a more favorable thermal environment to the better growth and survival of group-raised pups was supported by the finding that single pups raised at higher ambient temperatures grew more rapidly than single pups raised at lower temperatures. These effects were most clearly seen across Days 2 to 5, after which time differences between treatment groups were no longer significant. Thus, the results of this study suggest that the benefits as well as costs of having siblings must be weighed against each other when considering the manner in which sibling presence influences individual development and survival.


Use of supercharged cover screw as static magnetic field generator for bone healing, 2nd part: in vivo enhancement of bone regeneration in rabbits.
In 1979, Pulsed electromagnetic fields (PEMFs) were approved by the Food and Drug Administration as an effective method in the treatment of non-unions. As well as PEMFs, also static magnetic fields (SMFs) have been widely investigated in orthopaedic studies. Even if the exact mechanism of action is not well understood, a large number of studies showed specific effects both at cellular and tissue levels. As bone fracture healing and osseointegration share the same biological events, the application of magnetic field stimulation in order to facilitate the osseointegration process has been suggested. In this study we investigated BIC and newly formed bone volume around dental implants inserted in the tibia of New Zealand rabbits after SMF stimulation, generated by a small-customized cover-screw-shaped neodymium-iron-bore magnet placed in the inner cavity of dental implants. As a result, we found that the SMF field generated around dental implants enhanced bone healing in the animal model. Our findings represent, to our knowledge, the first ready clinical technique for dental implants showing the ability of SMF to promote the osteogenesis process in vivo.


Ground and valence-excited states of SF: a multireference configuration interaction with single and double excitations+Q study.
Ab initio calculations on the ground and valence-excited states of the sulfur monofluoride radical have been performed using entirely uncontracted all-electron augmented correlation consistent polarized valence quintuple zeta basis sets and the internally contracted multireference configuration interaction with single and double excitations method and Davidson correction (+Q). Potential-energy curves of all valence electronic states and the spectroscopic constants of several bound states are fitted. It is the first time that the entire 27-omega states generated from the 12 valence lambda-S states which come from the S(3P(g)) and F(2P(u)) atomic states of SF radical have been studied theoretically. The effects of spin-orbit coupling and the avoided crossing rule between omega states of the same symmetry are analyzed. The calculated results reproduce well the available experimental values and predict the properties of several bound excited states that have never been observed in experiment. The transition properties of the dipole-allowed transitions from bound excited states to the ground state are predicted for the first time, including the transition dipole moments, the Franck-Condon factors, and the radiative lifetimes.


Clinical guidelines of depression: a qualitative study of GPs' views.
Clinical guidelines have become an increasingly familiar component of health care, although their passive dissemination does not ensure implementation. This study is concerned with general practitioners' (GPs) views of guideline implementation in general practice. It focuses specifically on their views about guidelines for the management of patients with depression. To elicit and explore GPs' views about clinical guidelines for the management of depression, their use in practice, barriers to their use, and how best to implement guidelines. Qualitative study using in-depth interviews with a purposive sample of GPs. General Practices across the Scottish Grampian region, and Northeast England. Eleven GPs who had participated in a previous questionnaire based depression study were interviewed. Interviews were transcribed and analyzed using the "framework technique." Several participating GPs did not agree with recommendations of the current depression guidelines; some thought they were insufficiently flexible to use with the variety of patients they see. The volume of guidelines received, lack of time and resources (particularly mental health professionals for referrals) were seen as the main barriers to guideline use. A range of factors contributes to variability in compliance with guidelines for the management of depression. For guideline use to increase, GPs in this study said they would like to see more resources put in place; a reduction in the number of guidelines they receive; incorporation of guideline recommendations onto computer decision support systems; and regular audit and feedback to allow them to monitor their practice.


A construction of pooling designs with some happy surprises.
The screening of data sets for "positive data objects" is essential to modern technology. A (group) test that indicates whether a positive data object is in a specific subset or pool of the dataset can greatly facilitate the identification of all the positive data objects. A collection of tested pools is called a pooling design. Pooling designs are standard experimental tools in many biotechnical applications. In this paper, we use the (linear) subspace relation coupled with the general concept of a "containment matrix" to construct pooling designs with surprisingly high degrees of error correction (detection.) Error-correcting pooling designs are important to biotechnical applications where error rates often are as high as 15%. What is also surprising is that the rank of the pooling design containment matrix is independent of the number of positive data objects in the dataset.


Analysis of the structural and dynamic properties of human N-terminal domain of apolipoprotein E by molecular dynamics simulations.
Whereas the lipid-free N-terminal domain of apolipoprotein E (apoE-NT) adopts a four-helix bundle, the lipid-bound form is believed to undergo a large conformational change likely to be characterized by the opening of the bundle. ApoE-NT in a water/alcohol mixture was also shown to experience conformational changes exhibiting similarities with those induced upon lipid binding. The structure and dynamics of apoE-NT have been here investigated by analyzing 40 ns and 60 ns molecular dynamics simulations performed in water and in a water/propanol mixture, respectively. The overall structural properties show alterations of the tertiary structure of apoE-NT in the water/alcohol system in agreement with those observed experimentally. In contrast, in the water simulation, the sampled conformations remain closer to the crystal structure that served as a starting point for both simulations. Interestingly, several propanol molecules are seen to penetrate two hydrophobic regions of the bundle interior. One of these regions is enclosed in part by the short helix (H1') connecting helices 1 and 2 of the bundle which has been experimentally shown to be important for modulating lipid binding activity of apoE-NT. Principal component analysis of the water/propanol trajectory confirms that the region including H1' is the locus of the largest motion. Another region involves the loop connecting helix 2 and helix 3 which has been hypothesized to play the role of a hinge in the opening of the bundle.


Antiviral chemotherapy.
Specific antiviral chemotherapy now has an established role in the treatment of many virus infections, particularly those caused by herpesviruses. This change is one of the major medical developments of the last decade. There is reason to believe that further advances will occur, and we can look forward to a range of antiviral drugs comparable to those available for bacterial infections.


Chemically Accurate Simulation of a Polyatomic Molecule-Metal Surface Reaction.
Although important to heterogeneous catalysis, the ability to accurately model reactions of polyatomic molecules with metal surfaces has not kept pace with developments in gas phase dynamics. Partnering the specific reaction parameter (SRP) approach to density functional theory with ab initio molecular dynamics (AIMD) extends our ability to model reactions with metals with quantitative accuracy from only the lightest reactant, H2, to essentially all molecules. This is demonstrated with AIMD calculations on CHD3 + Ni(111) in which the SRP functional is fitted to supersonic beam experiments, and validated by showing that AIMD with the resulting functional reproduces initial-state selected sticking measurements with chemical accuracy (4.2 kJ/mol ≈ 1 kcal/mol). The need for only semilocal exchange makes our scheme computationally tractable for dissociation on transition metals.


Clinical Study of an Online Tool for Standardizing Hospital Care.
We assessed if use of an online clinical decision support tool improved standardization and quality of care in hospitalized patients with lower extremity cellulitis (LEC). This was a 14-month preintervention and postintervention study of 85 LEC admissions. There was significantly higher usage of the online LEC care process model (CPM) in the postintervention phase (p < .001). There was a trend toward higher rates of appropriate antibiotic regimen in the postintervention group both initially and at discharge (p = .063 for both). A sensitivity analysis of CPM users versus nonusers demonstrated a significantly higher rate of appropriate initial antibiotics prescribed when the CPM was used (p < .001). Use of this online CPM was associated with improved standardization, as demonstrated by increased ordering of an appropriate initial antibiotic regimen for hospitalized patients with LEC.


[Food insecurity in households with adolescents in the Brazilian Amazon: prevalence and associated factors].
This cross-sectional population-based study in 2007 focused on prevalence of food insecurity and associated factors in households with adolescents in four towns in the Legal Amazonia located along highway BR-163, from Cuiabá, Mato Grosso State, to Santarém, Pará State, Brazil. The study applied the Brazilian Food Insecurity Scale to a sample of 363 households. Anthropometric assessment was performed on 534 adolescents from 10 to 19 years of age. A Poisson model was used in the multiple regression analysis. The results showed 23.1% prevalence of moderate to severe food insecurity, suggesting association with the following: low income, poor sanitation, head of household born in Mato Grosso State, and the adolescent's race (black). The results emphasize the need for improved access to basic sanitation, training of human resources to generate employment/income, and educational activities to improve understanding of food insecurity and its determinants.


GABA-A Receptors Mediate Tonic Inhibition and Neurosteroid Sensitivity in the Brain.
Neurosteroids like allopregnanolone (AP) are positive allosteric modulators of synaptic and extrasynaptic GABA-A receptors. AP and related neurosteroids exhibit a greater potency for δ-containing extrasynaptic receptors. The δGABA-A receptors, which are expressed extrasynaptically in the dentate gyrus and other regions, contribute to tonic inhibition, promoting network shunting as well as reducing seizure susceptibility. Levels of endogenous neurosteroids fluctuate with ovarian cycle. Natural and synthetic neurosteroids maximally potentiate tonic inhibition in the hippocampus and provide robust protection against a variety of limbic seizures and status epilepticus. Recently, a consensus neurosteroid pharmacophore model has been proposed at extrasynaptic δGABA-A receptors based on structure-activity relationship for functional activation of tonic currents and seizure protection. Aside from anticonvulsant actions, neurosteroids have been found to be powerful anxiolytic and anesthetic agents. Neurosteroids and Zn2+ have preferential affinity for δ-containing receptors. Thus, Zn2+ can prevent neurosteroid activation of extrasynaptic δGABA-A receptor-mediated tonic inhibition. Recently, we demonstrated that Zn2+ selectively inhibits extrasynaptic δGABA-A receptors and thereby fully prevents AP activation of tonic inhibition and seizure protection. We confirmed that neurosteroids exhibit greater sensitivity at extrasynaptic δGABA-A receptors. Overall, extrasynaptic GABA-A receptors are primary mediators of tonic inhibition in the brain and play a key role in the pathophysiology of epilepsy and other neurological disorders.


Consequence of body packing of illicit drugs.
During the last decade, increased rates of drug traffic have led the smugglers to use various methods. One of these methods of illicit drug smuggling is body packing. Smuggling by intra-abdominal concealment is called "body packing". In this research, mortality rate was investigated due to body packing in Tehran. A descriptive study (case series) was designed on all corpses referred to the Forensic Medicine Organization of Tehran between April 1999 - December 2000. Demographic data such as sex, age, marital status, addiction, job, education level, type of opioid and the weight, number of packets, and results of blood and urine morphine tests by thin-layer chromatographic method were investigated. Continental system of law is used in Iran and 0.06% of the referred corpses to Forensic Medicine Organization of Tehran were body packers. There were 12 cases, all of them were men. The mean age of body packers was 43 years (range 20 - 62). The minimum weight of the packets was 20 g and the maximum weight was 1400 g (mean = 501 g). The minimum number of the packets was one and the maximum number of the packets was 48. Twenty five percent of the corps were putrefied and one corpse was mummified. None of the body packers had academic education nor were employed. Nine of them lived in cities. Twenty five percent of them were intravenous addicts. The corpses were found mostly in terminals (17%), roads (58%), and cities (25%). Hospital physicians may neglect this type of gastrointestinal foreign body if they are not aware of the body packer syndrome. Body packing should be suspected in anyone with signs of drug-induced toxic effects after a recent arrival on city terminals or when there is no history of recreational drug use.


Interrater Reliability of AM-PAC "6-Clicks" Basic Mobility and Daily Activity Short Forms.
The interrater reliability of 2 new inpatient functional short-form measures, Activity Measure for Post-Acute Care (AM-PAC) "6-Clicks" basic mobility and daily activity scores, has yet to be established. The purpose of this study was to examine the interrater reliability of AM-PAC "6-Clicks" measures. A prospective observational study was conducted. Four pairs of physical therapists rated basic mobility and 4 pairs of occupational therapists rated daily activity of patients in 1 of 4 hospital services. One therapist in a pair was the primary therapist directing the assessment while the other therapist observed. Each therapist was unaware of the other's AM-PAC "6-Clicks" scores. Reliability was assessed with intraclass correlation coefficients (ICCs), Bland-Altman plots, and weighted kappa. The ICCs for the overall reliability of basic mobility and daily activity were .849 (95% confidence interval [CI]=.784, .895) and .783 (95% CI=.696, .847), respectively. The ICCs for the reliability of each pair of raters ranged from .581 (95% CI=.260, .789) to .960 (95% CI=.897, .983) for basic mobility and .316 (95% CI=-.061, .611) to .907 (95% CI=.801, .958) for daily activity. The weighted kappa values for item agreement ranged from .492 (95% CI=.382, .601) to .712 (95% CI=.607, .816) for basic mobility and .251 (95% CI=.057, .445) to .751 (95% CI=.653, .848) for daily activity. Mean differences between raters' scores were near zero. Raters were from one health system. Each pair of raters assessed different patients in different services. The ICCs for AM-PAC "6-Clicks" total scores were very high. Levels of agreement varied across pairs of raters, from large to nearly perfect for physical therapists and from moderate to nearly perfect for occupational therapists. Levels of agreement for individual item scores ranged from small to very large.


Will genetic testing alter the management of disease caused by infectious agents? A cost-effectiveness analysis of gene-testing strategies for prevention of rheumatic Fever.
Cost-effectiveness analysis was done to evaluate the potential health and economic effects of a genetic screening program to identify individuals at risk for rheumatic fever (RF). The current RF prevention strategy was compared with a new, primary prevention strategy involving early genetic testing and intensive prophylaxis to prevent a first attack among individuals at high risk for RF. When analysis of a hypothetical 2000 birth cohort was done from a societal perspective, the prevention strategy involving genetic screening and prophylaxis for high-risk persons reduced the number of RF cases and increased life span at an estimated discounted cost of $7900 per quality-adjusted life-year gained. Genetic screening became the preferred (least expensive) strategy if the test specificity was >/=98%, the annual cost of prophylaxis was <$550, or the annual cost of caring for an individual with severe rheumatic heart disease increased to >$32,000. When used with available antibiotic prophylaxis, genetic testing has the potential to provide a cost-effective strategy for the primary prevention of RF and its sequelae.


Relationship of retinoid and carotenoid metabolism with caecotrophy in rabbits.
The relationship of retinoid and carotenoid metabolism with caecotrophy was studied in adult female New Zealand White rabbits kept in individual metabolic cages. Caecotrophy was prevented by the use of plastic collars. The dry matter, crude protein, fibre, fat and ash contents of hard and soft faecal samples were determined. The retinoid (retinol and retinyl palmitate) and carotenoid (canthaxanthin, beta-carotene, beta-cryptoxanthin, lutein and zeaxanthin) levels of the blood, liver, kidney, caecal content and faeces were also measured by high-performance liquid chromatography (HPLC). The prevention of caecotrophy resulted in a significant decrease of blood retinol (P < 0.001) and retinyl palmitate (P < 0.01) concentration but it did not cause any significant change in the retinol and retinyl palmitate contents of the liver and kidney. The caecal content (25.78 +/- 6.87 microg/g) and the soft faeces (34.52 +/- 10.48 microg/g) contained the retinoids in similar amounts. Various carotenoids were found in considerable amounts in different types of faeces, while in the tissues (blood, liver and kidney) these pigments did not occur in substantial amounts. Total carotenoid concentration was similar in the caecal content (11.23 microg/g) and in the caecotroph (13.85 microg/g). On the basis of the results it can be assumed that the retinoid content of rabbit feed could be lowered in the presence of adequate caecal function and caecotrophy.


Linear EBUS in staging non-small cell lung cancer and diagnosing benign diseases.
As an evolving technique, linear endobronchial ultrasound is becoming the first choice and standard of care not only to diagnose the malignant and benign mediastinal lesions but also to stage non-small cell lung cancer. Lung cancer is the leading cause of cancer-related mortality in both men and women. The disease causes more death compared with colorectal, breast, and prostate cancers combined in the United States. Staging of lung cancer determines the prognosis. The type of lung cancer has changed in the past few decades. The frequency of adenocarcinoma has increased, whereas squamous cell carcinoma now is less frequent. Determining the cell type and its molecular characteristics allow targeted treatments in adenocarcinoma. The diagnosis of indeterminate mediastinal lymph nodes or masses and staging lung cancer might be challenging. This article will review the principles and clinical utility of endobronchial ultrasound in mediastinal lesions.


A case of Fanconi syndrome whose origin was suspected to be cystinosis.
We report a case of 6 year old girl with Fanconi syndrome the origin of which was suspected to be cystinosis. Pathological findings of a renal biopsy showed needle-like materials in the epithelial cells but the cystine content of the white blood cells was normal. Although excessive urinary loss of growth hormone was detected, the height and weight of the patient was normal. Urinary loss of growth hormone did not cause growth retardation in this case.


Psychoneuroimmunology and its relationship to the differential diagnosis of temporomandibular disorders.
Psychoneuroimmunology (PNI) is a field of medicine which joins immunology and neurobiology. It focuses on the relationship of stress upon the hypothalamic-adrenal-pituitary (HPA) axis. Depletion of hormones and neurotransmitters within the HPA-axis, as a result of stress, can lead to a multitude of diseases and disorders. Therefore, it is necessary for the dentist to be familiar with PNI and the HPA-axis in order to make an accurate diagnosis of TMD.


Rates of peripheral arterial occlusive disease in patients with chronic myeloid leukemia in the chronic phase treated with imatinib, nilotinib, or non-tyrosine kinase therapy: a retrospective cohort analysis.
Peripheral arterial occlusive disease (PAOD) occurs in patients with chronic phase chronic myeloid leukemia (CML-CP) treated with tyrosine kinase inhibitors (TKIs). The risk of developing PAOD on TKI therapy is unknown and causality has not been established. Patients with CML-CP from three randomized phase III studies (IRIS, TOPS and ENESTnd) were divided into three cohorts: no TKI (cohort 1; n=533), nilotinib (cohort 2; n=556) and imatinib (cohort 3; n=1301). Patients with atherosclerotic risk factors were not excluded. Data were queried for terms indicative of PAOD. Overall, 3, 7 and 2 patients in cohorts 1, 2 and 3, respectively, had PAOD; 11/12 patients had baseline PAOD risk factors. Compared with that of cohort 1, exposure-adjusted risks of PAOD for cohorts 2 and 3 were 0.9 (95% CI, 0.2-3.3) and 0.1 (95% CI, 0.0-0.5), respectively. Multivariate logistic regression revealed that nilotinib had no impact on PAOD rates compared with no TKI, whereas imatinib had decreased rates of PAOD compared with no TKI. Nilotinib was associated with higher rates of PAOD versus imatinib. Baseline assessments, preferably within clinical studies, of PAOD and associated risk factors should occur when initiating TKI therapy in CML; patients should receive monitoring and treatment according to the standard of care for these comorbidities.


Multicenter study on the effectiveness of the pre-epiglottic baton plate for airway obstruction and feeding problems in Robin sequence.
Treatment of Robin sequence is often either invasive or of unproven effectiveness. The pre-epiglottic baton plate (PEBP) is a well-studied alternative, yet is not widely applied internationally. We report on a prospective 3-center cohort study investigating this treatment. Based on an agreed protocol, parents of infants with Robin sequence referred to participating centers were offered enrollment, which involved taking a maxillary cast followed by endoscopy to fit the plate and sleep studies to monitor its effectiveness. Recordings were centrally analyzed by sleep specialists blinded to timing and center. Primary outcome was the mixed-obstructive apnea index, defined as the number of such apneas/h of sleep; secondary outcomes included the desaturation index to <80% pulse oximeter saturation and weight gain. Of 75 infants referred, 49 could be included; 1 center failed to perform appropriate sleep studies. Within a mean hospitalization of 3 weeks, the mixed-obstructive apnea index decreased (median; interquartile range) from 15.9 (6.3-31.5) to 2.3 (1.2-5.4); it decreased further to 0.7 (0.1-2.4) in the 32 infants who had a successful 3-month follow-up sleep study performed. The desaturation index normalized (from 0.38 (0-2.7) to 0.0 (0-0.1)). Mean standard deviation score for weight remained unchanged between admission and follow-up, while the proportion of tube-fed infants decreased from 74 to 14%. This prospective multi-center cohort study confirms retrospective audits on the effectiveness of PEBP treatment in improving upper airway obstruction and feeding problems, the main clinical problems of infants with Robin sequence. International collaboration is required to compare this with other treatment approaches. Number NCT02266043 , Registered 30/09/2014; registered partially retrospectively.


Highly open chalcogenide frameworks built from unusual defective supertetrahedral clusters.
Enlarging the openess of chalcogenide frameworks is of significance for functionalizing semiconducting open frameworks, which are usually limited by their own interpenetration due to the rigid clusters and monotonous linkers. Herein, we report two zeolite-like chalcogenide open frameworks constructed from unusual defective supertetrahedral clusters and various kinds of linkers. Both the structures exhibit impressive architecture and high extra-framework volume ratios.


ALCAR promote adult hippocampal neurogenesis by regulating cell-survival and cell death-related signals in rat model of Parkinson's disease like-phenotypes.
Parkinson's disease (PD) is characterized by the degeneration of dopaminergic neurons in the nigrostriatal pathway that leading to progressive motor and nonmotor symptoms. The formation of newborn neurons in the adult hippocampus is affected by many factors such as anxiety, depression and impairment in learning and memory that are commonly observed nonmotor symptoms in PD, indicating the role of adult neurogenesis in PD pathophysiology. Acetyl-l-carnitine (ALCAR), regulate mitochondrial metabolism and has been reported to improve cognitive functions in different neurodegenerative disorders through an unknown mechanism. For the first time, we investigated the effect of ALCAR on adult neurogenesis in the 6-hydroxydopamine (6-OHDA) induced rat model of PD-like phenotypes and also explored the possible underlying mechanism of action. A single unilateral administration of 6-OHDA into the medial forebrain bundle reduced neural progenitor cell (NPC) proliferation, long-term survival and neuronal differentiation in the hippocampus. Interestingly, chronic treatment with ALCAR (100 mg/kg/day, i.p) potentially enhanced proliferation, long term survival and neuronal differentiation of NPCs in rat model of PD-like phenotypes. ALCAR treatment stimulates cell survival related signals (AKT and BCL-2) by inhibiting cell death related cues (GSK-3β and BAX) which might be responsible for a neuroprotective effect of ALCAR in rat model of PD-like phenotypes. We conclude that ALCAR exerts neuroprotective effects against 6-OHDA-induced impairment in hippocampal neurogenesis by regulating cell survival and cell death-related signals.


Middle cranial fossa approach for acoustic neuroma.
The middle fossa approach for the resection of small acoustic neuromas is a viable, but underutilized treatment modality with the goal of hearing preservation. The authors aim to demonstrate this approach and its nuances through this video presentation. A 38-year-old man presented with an incidentally discovered small, intracanalicular acoustic neuroma that was initially observed, but growth was noted. The patient had good hearing, and therefore a hearing preservation approach was offered. A gross-total resection was achieved, and the patient maintained good hearing postoperatively. This video demonstrates relevant anatomy, surgical indications, technical aspects of resection, including reconstruction, and postoperative outcomes. The video can be found here: https://stream.cadmore.media/r10.3171/2021.7.FOCVID21124.


Mg2+- or Mn2+-dependent endonuclease activities of human myeloid leukemia cells capable of producing nucleosomal-size DNA fragmentation.
The presence of at least two distinct Mg2+- or Mn2+-dependent, Ca2+-independent endonuclease activities was shown in the myeloid leukemia cell line P39. One of them was recovered from nuclear extracts and the other from a cytoplasmic fraction. The molecular size of the former was 30 kDa in both gel filtration and activity gel and that of the latter approximately 130-140 kDa in gel filtration and 65-70 kDa in activity gel. These two activities were almost completely inhibited by 0.1 mM ZnCl2 or 0.1 mM aurintricarboxylic acid, common inhibitors of apoptosis. Both could produce nucleosomal-size DNA fragmentation when incubated with diethyl-pyrocarbonate-treated nuclei as substrates, and the pattern of cleavage was 3'-OH and 5'-P. Taken together, either or both of these activities may be associated with apoptosis of myeloid leukemia cells.


Effect of microtubule inhibitors on malignant invasion in vitro.
The malignant C3H/3T3 mouse cells MO4 invaded embryonic chick heart fragments in an organotypic coculture system on semisolid medium, which mimicked malignant invasion. In this system, at a dose of 1 microgram/ml, the microtubule inhibitors colchicine, demecolcine, vincristine sulfate, vinblastine sulfate, or methyl[5-(2-thienylcarbonyl)-1H-benzimidazol-1-yl]-carbamate (Nocodazole) totally inhibited malignant invasion. At the same dose the drugs were also mitostatic, which was apparent from C-mitoses and from the absence of postmetaphase figures. At a mitostatic dose of 10 microgram/ml, 5-fluorouracil (FUra), cytosine arabinoside, or bleomycin did not interfere with malignant invasion. Combined treatment of the cocultures with the antimetabolite FUra (10 microgram/ml) plus the microtubule inhibitor Nocodazole (1 microgram/ml) completely inhibited invasion. These cocultures also showed the effective inhibition of mitosis by FUra, because Nocodazole-induced C-mitoses were absent. The reversibility of the anti-invasive effect of 4-day treatment with Nocodazole (1 microgram/ml) was demonstrated in shaker cocultures with the use of fluid medium. Our in vitro experiments indicated that cytoplasmic microtubules were involved in malignant invasion and that cell division and invasion constituted separate characteristics of malignant cells.


One-Pot Aminoethylation of Indoles/Pyrroles with Alkynes and Sulfonyl Azides.
A general and efficient one-pot aminoethylation of substituted indoles/pyrroles was accomplished for the synthesis of various tryptamine derivatives employing a combination of alkynes and sulfonyl azides as readily accessible aminoethylating agents. The reaction features a successful integration of copper-catalyzed alkyne and azide cycloaddition to N-sulfonyl-1,2,3-triazole, rhodium-catalyzed selective insertion of α-iminocarbenes onto the C3-H bond of indoles, and reduction of the resultant enamides to tryptamine derivatives employing either NaCNBH3 or palladium catalyst, in one-pot. The reaction also showed excellent functional-group tolerance and allowed the synthesis of various substituted tryptamines in good to excellent yield. This transformation constitutes a one-pot formal regioselective functionalization of terminal alkynes. Utility of the synthesized tryptamine was further demonstrated in the synthesis of dihydro-β-carboline and tryptoline.


Thoracoscopic vagotomy as a safe adjunct to remedial gastric surgery.
Patients who have had prior subdiaphragmatic dissection with an incomplete vagotomy or Nissen fundoplication present added challenges when they require vagotomy and gastric resection. In this setting, thoracoscopic vagotomy offers significant advantages. A second attempt at vagotomy in a previously dissected field can be prolonged and frustrating. In addition to these concerns, repeat dissection can also lead to failure to find the vagal trunks, perforation of the esophagus, hemorrhage, and/or splenic injury. In our experience, three patients requiring gastrectomy or resection of a marginal ulcer have undergone thoracoscopic vagotomy at the time of transabdominal gastric surgery. The thoracoscopic approach avoided either a thoracoabdominal incision or combined thoracic and abdominal incisions while allowing dissection of the vagal trunks to be performed in normal tissue planes. The minimally invasive approach afforded decreased postoperative pain and excellent clinical results. Thoracoscopic vagotomy offers a welcome alternative to re-exploration of a previously dissected distal esophagus in search of vagal trunks, especially when they have been missed at the time of the first operation. Further application of this approach is recommended.


Contrast-enhanced US Evaluation of Hepatocellular Carcinoma Response to Chemoembolization: A Prospective Multicenter Trial.
Background Contrast-enhanced (CE) US has been studied for use in the detection of residual viable hepatocellular carcinoma (HCC) after locoregional therapy, but multicenter data are lacking. Purpose To compare two-dimensional (2D) and three-dimensional (3D) CE US diagnostic performance with that of CE MRI or CT, the current clinical standard, in the detection of residual viable HCC after transarterial chemoembolization (TACE) in a prospective multicenter trial. Materials and Methods Participants aged at least 21 years with US-visible HCC scheduled for TACE were consecutively enrolled at one of three participating academic medical centers from May 2016 to March 2022. Each underwent baseline 2D and 3D CE US before TACE, 2D and 3D CE US 1-2 weeks and/or 4-6 weeks after TACE, and CE MRI or CT 4-6 weeks after TACE. CE US and CE MRI or CT were evaluated by three fellowship-trained radiologists for the presence or absence of viable tumors and were compared with reference standards of pathology (18%), angiography on re-treatment after identification of residual disease at 1-2-month follow-up imaging (31%), 4-8-month CE MRI or CT (42%), or short-term (approximately 1-2 months) CE MRI or CT if clinically decompensated and estimated viability was greater than 50% at imaging (9%). Diagnostic performance criteria, including sensitivity and specificity, were obtained for each modality and time point with generalized estimating equation analysis. Results A total of 132 participants were included (mean age, 64 years ± 7 [SD], 87 male). Sensitivity of 2D CE US 4-6 weeks after TACE was 91% (95% CI: 84, 95), which was higher than that of CE MRI or CT (68%; 95% CI: 58, 76; P < .001). Sensitivity of 3D CE US 4-6 weeks after TACE was 89% (95% CI: 81, 94), which was higher than that of CE MRI or CT (P < .001), with no evidence of a difference from 2D CE US (P = .22). CE MRI or CT had 85% (95% CI: 76, 91) specificity, higher than that of 4-6-week 2D and 3D CE US (70% [95% CI: 56, 80] and 67% [95% CI: 53, 78], respectively; P = .046 and P = .023, respectively). No evidence of differences in any diagnostic criteria were observed between 1-2-week and 4-6-week 2D CE US (P > .21). Conclusion The 2D and 3D CE US examinations 4-6 weeks after TACE revealed higher sensitivity in the detection of residual HCC than CE MRI or CT, albeit with lower specificity. Importantly, CE US performance was independent of follow-up time. Clinical trial registration no. NCT02764801 © RSNA, 2023 Supplemental material is available for this article.


Crystallizing the function of the magnetosome membrane mineralization protein Mms6.
The literature on the magnetosome membrane (MM) protein, magnetosome membrane specific6 (Mms6), is reviewed. Mms6 is native to magnetotactic bacteria (MTB). These bacteria take up iron from solution and biomineralize magnetite nanoparticles within organelles called magnetosomes. Mms6 is a small protein embedded on the interior of the MM and was discovered tightly associated with the formed mineral. It has been the subject of intensive research as it is seen to control the formation of particles both in vivo and in vitro Here, we compile, review and discuss the research detailing Mms6's activity within the cell and in a range of chemical in vitro methods where Mms6 has a marked effect on the composition, size and distribution of synthetic particles, with approximately 21 nm in size for solution precipitations and approximately 90 nm for those formed on surfaces. Furthermore, we review and discuss recent work detailing the structure and function of Mms6. From the evidence, we propose a mechanism for its function as a specific magnetite nucleation protein and summaries the key features for this action: namely, self-assembly to display a charged surface for specific iron binding, with the curvature of the surfaces determining the particle size. We suggest these may aid design of biomimetic additives for future green nanoparticle production.


Surgical Treatment of Portal Vein Thrombosis With the Use of Cadaveric Venous Patch After Donor Hepatectomy: A Case Report.
Live donors should be the priority of transplant professionals to prevent surgery-related morbidity and mortality during living-donor liver transplantation. Portal vein thrombosis after donor hepatectomy is an important complication which can be prevented by careful preoperative as well as perioperative evaluation. If portal vein thrombus occurs after donor hepatectomy, anticoagulation and surgical thrombectomy and even portal vein reconstruction should be kept in mind. Cadaveric venous patches can be used for the reconstruction of narrowed and angulated portal veins. Here we report the surgical treatment of a donor with a cadaveric venous patch who developed portal vein thrombosis after donor hepatectomy.


Prediction of mental status in carriers of the fragile X mutation using CGG repeat length.
For genetic counseling in fragile X (fra(X)) families, it is important to know the diagnostic impact of the CGG repeat length in carriers of the fragile X mutation. We have analyzed the CGG repeat length in 106 males and 73 females who had inherited the maternal fra(X) mutation. The sensitivity, specificity, and predictive value of the CGG repeat analyses, as measured on Southern blots of PstI/EcoRI digests, were calculated. In males the sensitivity, specificity and negative predictive value were 99%, 100% and 94%; respectively. In females the specificity (60%) and, consequently, the positive predictive value (82%) was reduced. Therefore, it remains impossible to predict accurately whether a female fetus demonstrating a full mutation will be affected. On the other hand, the negative predictive value of the CGG test in females was 100%. We have no evidence, as yet, that for female carriers with the full mutation, cytogenetic analysis is of additional value to predict the mental status. However, we have observed one mentally retarded fra(X) case with extreme mosaicism in which a typical premutation fragment was the predominant DNA species. Therefore, until more data and better DNA tests are available, we would like to advocate additional cytogenetic investigation if in a fetus a CGG repeat length in the premutation range is found.


Acute GI bleeding in the setting of supratherapeutic international normalized ratio in patients taking warfarin: endoscopic diagnosis, clinical management, and outcomes.
Acute GI bleeding is a life-threatening complication of warfarin therapy. Acute GI bleeding in patients with an international normalized ratio of 4.0 or greater (supratherapeutic) is often attributed to trivial mucosal lesions. The aim of the study was to determine the frequency of potentially significant lesions that would warrant endoscopy in this setting. A retrospective review was conducted of patients treated with warfarin who were admitted to a single Veterans Affairs hospital from 1996 to 2000 with acute GI bleeding. Endoscopic findings, clinical management, and outcomes are reviewed for patients with a supratherapeutic international normalized ratio (>or=4.0) and compared with patients with an international normalized ratio in the therapeutic range (2.0-3.9). Fifty-five patients with an international normalized ratio of 4.0 or greater (mean 8.4 [3.9]) and 43 patients with an international normalized ratio between 2.0 and 3.9 (mean 2.9 [0.6]) were hospitalized with acute GI bleeding. Thirty-seven patients (67%) with a supratherapeutic international normalized ratio and GI bleeding underwent upper endoscopy. Of these, 81.1% had positive findings, 18.9% had peptic ulcer disease, and 7.2% required endoscopic treatment. Thirty-eight percent of the patients with a supratherapeutic international normalized ratio underwent lower endoscopy; of these, 57.1% had abnormal findings and 9.5% required endoscopic treatment. Four patients (7.3%) in the supratherapeutic international normalized ratio group died during the index hospitalization. When patients with GI bleeding and a therapeutic international normalized ratio were compared with those with a supratherapeutic international normalized ratio, there were no significant differences between the two groups with regard to days of hospitalization, units of blood transfused, frequency of recurrent bleeding, need for surgery, or in-hospital deaths. The high frequency of clinically significant lesions in patients taking warfarin with an international normalized ratio in the supratherapeutic range and acute GI bleeding supports a role for endoscopic evaluation.


Numerical investigation of angulation effects in stenosed renal arteries.
Numerical study of angulation effects of renal arteries on blood flow has been of great interest for many researchers. Objective : This paper aims at numerically determining the angulation effects of stenosed renal arteries on blood flow velocity and renal mass flow. An anatomically realistic model of abdominal aorta and renal arteries is reconstructed from CT-scan images and used to conduct numerical simulation of pulsatile non-Newtonian blood flow incorporating fluid-structure interaction. The renal arteries in the realistic model have left and right branch angles of 53˚ and 45˚, respectively. Atrapezium shape stenosis is considered in the entrance of right renal artery. Two other branch angles, i.e. 90 and 135˚, are also considered for right renal artery to study the angulation effects. Comparison between models with right renal branch angles of 45˚, 90˚ and 135˚ reveals that high curvature of streamlines in the entrance of the renal artery with the angle of 135˚ causes the flow velocity and renal mass flow to be less than those of 45˚and 90˚. It is concluded that large renal branch angles cause the arteries to be unable to deliver blood in the requisite amounts to kidney. Kidney responds to counteract low blood flow by activating the renin-angiotension system which leads to severe hypertension.


[Surgical treatment of lung cancer in patients with concurrent cardiovascular system diseases].
The data are reported on 1000 patients operated upon for lung cancer, in 290 of them concomitant cardiovascular lesions have been revealed. The postoperative mortality was found to be higher in patients with postinfarction cardiosclerosis, hypertension of stage II--III at the age under 59, while in chronic coronary insufficiency, arrhythmia and impaired conductivity the mortality rate was not increased. In patients over 60 the postoperative mortality was higher than in young patients, however, a concomitant cardiovascular pathology rendered no appreciable effect. A 5-year survival in concomitant cardiovascular pathology was 25% versus 33.3% in control patients, that is attributed by the authors to a large number of "compromise" saving operations in patients with concomitant cardiovascular lesions.


Helical catena-poly[[tris(1H-benzimidazole-kappaN(3))cobalt(II)]-micro-maleato-kappa(3)O,O':O"].
The crystal structure of the title compound, [Co(C(4)H(2)O(4))(C(7)H(6)N(2))(3)](n), consists of polymeric chains of the Co(II) complex. Two maleate dianions and three benzimidazole ligands coordinate to the Co(II) atom with a distorted octahedral geometry. The maleate dianions bridge neighbouring Co(II) atoms via both terminal carboxylic acid groups, one of which is monodentate and the other bidentate, to form a helical structure of alternating maleate dianions and Co(II) atoms, with a pitch height of 9.2667 (17) A. The absolute structure has been determined, and the crystal contains only right-handed helices. Intrahelical N-H...O hydrogen bonds stabilize the helical structure, while interhelical N-H...O hydrogen bonds link neighbouring helices to form the supramolecular structure.


siRNA Delivery by Stimuli-Sensitive Nanocarriers.
Since its discovery in the late 1990, small interfering RNA (siRNA) have quickly crept into the biopharmaceutical research as a new and powerful tool for the treatment of different human diseases based on altered gene-expression. Despite promising data from many pre-clinical studies, concrete hurdles still need to be overcome to bring therapeutic siRNAs in clinic. The design of stimuli-sensitive nanopreparations for gene therapy is a lively area of the current research. Compared to conventional systems for siRNA delivery, this type of platform can respond to local stimuli that are characteristics of the pathological area of interest, allowing the release of nucleic acids at the desired site. Acidic pH, de-regulated levels of enzymes, altered redox potential and magnetic field are examples of stimuli exploit to design stimuli-sensitive nanoparticles. In this review, we discuss on recent stimulisensitive strategies for siRNA delivery and we highlight on the potential of combining multiple stimuli-sensitive strategies in the same nano-platform for a better therapeutic outcome.


Replicational organization of three weakly expressed loci in Physarum polycephalum.
We previously mapped early-activated replication origins in the promoter regions of five abundantly transcribed genes in the slime mold Physarum polycephalum. This physical linkage between origins and genes is congruent with the preferential early replication of the active genes in mammalian cells. To determine how general this replicational organization is in the synchronous plasmodium of Physarum, we analyzed the replication of three weakly expressed genes. Bromodeoxyuridine (BrdUrd) density-shift and gene dosage experiments indicated that the redB (regulated in development) and redE genes replicate early, whereas redA replicates in mid-S phase. Bi-dimensional gel electrophoresis revealed that redA coincides with an origin that appears to be activated within a large temporal window in S phase so that the replication of the gene is not well defined temporally. The early replication of the redB and redE genes is due to the simultaneous activation of flanking origins at the onset of S phase. As a result, these two genes correspond to termination sites of DNA replication. Our data demonstrate that not all the Physarum promoters are preferred sites of initiation but, so far, all the expressed genes analyzed in detail either coincide with a replication origin or are embedded into a cluster of early firing replicons.


Change of growth pattern, metabolism, and quality and quantity of maize plants after irrigation with magnetically treated water.
Water molecules can be affected by magnetic fields (MF) due to their bipolar characteristics. In the present study maize plants, from sowing to the end period of generative stage, were irrigated with magnetically treated water (MTW).Tap water was treated with MF by passing through a locally designed alternative magnetic field generating apparatus (110 mT). Irrigation with MTW increased the ear length and fresh weight, 100-grain fresh and dry weights, and water productivity (119.5%, 119.1%, 114.2%, 116.6% and 122.3%, respectively), compared with the control groups. Levels of photosynthetic pigments i.e. chlorophyll a and b, and the contents of anthocyanin and flavonoids of the leaves were increased compared to those of non-treated ones. Increase of the activity of superoxide dismutase (SOD) and ascorbate peroxidase (APX) in leaves of the treated plants efficiently scavenged active oxygen species and resulted in the maintenance of photosynthetic membranes and reduction of malondealdehyde. Total ferritin, sugar, iron and calcium contents of kernels of MTW-irrigated plants were respectively 122.9%, 167.4%, 235% and 185% of the control ones. From the results presented here it can be concluded that the influence of MF on living plant cells, at least in part, is mediated by water. The results also suggest that irrigation of maize plant with MTW can be applied as a useful method for improvement of quantity and quality of it.


An international study of middle school students' preferences about digital interactive education activities for promoting psychological well-being and mental health.
The present study investigated students' preferences about technology tools and digital education activities to be used in classroom to facilitate the implementation of a mental health promotion program. Students' preferences have been elicited during one session focus group lasting 60 minutes. Overall, 26 focus groups, facilitated by 33 teachers, were organized in 9 schools of five European countries. Overall, 283 students who attended the first, second and third year of middle school (aged 10-15 years) volunteered to participate in the focus groups. The majority of preferences indicated smartphone to communicate or to get information and tablet for a better use in classroom. Collaborative games have been considered as more useful and beneficial compared to the other digital educational activities proposed. Teachers require further insight into the pedagogical role of ICT and training. There is a need to encourage them to provide opportunities to allow students to use technology to solve problems or develop abilities for a better socio-emotional functioning and, ultimately, mental health.


Diagnostic and classification value of metalloproteinases in squamous human laryngeal carcinoma.
Metalloproteinases (MMPs) are a class of enzymes largely involved in tumour progression and metastasis. At least twenty different enzymes are recognized that are also present under normal state of tissues. Their activity is regulated by their presence as proenzymes and by the concomitant presence of the respective tissue inhibitors (TIMPs). The present study describes the alterations of MMPs observed in human laryngeal carcinoma with respect to tumour classification and compares their activity in normal and cancerous tissues and biopsy specimens. Samples from five patients who underwent laryngectomy, from five biopsies and three from autopsies were used. The MMPs of normal and malignant human laryngeal cartilage and of biopsy specimens were identified immunochemically and by zymography using gelatin or casein as substrates. Healthy cartilage from autopsies was found to contain almost exclusively MMP-1, proMMP-2 and proMMP-9. Normal parts from laryngectomies contained, in addition, significant amounts of active MMP-2. The respective malignant parts contained both MMP-2 and -9 in increased amounts in their latent and active forms. Similar profile of MMPs was also identified in tissues surrounding affected cartilage. These alterations were found to be in good accordance with tumour stage and were also observed in biopsy samples. Thus, analysis of MMPs in biopsies can be used together with the clinicopathological parameters for the classification or early diagnosis of laryngeal tumours.


Use of computers in dysmorphology.
As a consequence of the increasing power and decreasing cost of digital computers, dysmorphologists have begun to explore a wide variety of computerised applications in clinical genetics. Of considerable interest are developments in the areas of syndrome databases, expert systems, literature searches, image processing, and pattern recognition. Each of these areas is reviewed from the perspective of the underlying computer principles, existing applications, and the potential for future developments. Particular emphasis is placed on the analysis of the tasks performed by the dysmorphologist and the design of appropriate tools to facilitate these tasks. In this context the computer and associated software are considered paradigmatically as tools for the dysmorphologist and should be designed accordingly. Continuing improvements in the ability of computers to manipulate vast amounts of data rapidly makes the development of increasingly powerful tools for the dysmorphologist highly probable.


Hymenoptera Venom Immunotherapy: Tolerance and Efficacy of an Ultrarush Protocol versus a Rush and a Slow Conventional Protocol.
Background and Objective. Various venom immunotherapy (VIT) protocols are available for Hymenoptera allergy. Although adverse reactions (ADRs) to VIT are widely reported, controlled trials are still needed. We conducted a randomized prospective study to evaluate ADRs and the efficacy of three VIT regimens. Methods. 76 patients with Hymenoptera allergy, aged 16-76 years, were randomized to receive an ultrarush protocol (group A: 27 patients), a rush protocol (group B: 25), or a slow protocol (group C: 24). Aqueous venom extract was used in incremental phase and an adsorbed depot in maintenance phase. ADRs and accidental Hymenoptera stings during VIT were used to evaluate efficacy. Results. During incremental treatment, ADRs occurred in 1.99%, 3.7%, and 3.9% of patients in groups A, B, and C, and in 0.99%, 1.46%, and 2.7%, respectively, during maintenance. ADRs were significantly fewer in group A (incremental + maintenance phase) than in group C (1.29% versus 3.2%; P = 0.013). Reactions to accidental Hymenoptera stings did not differ among groups (1.1%, 1.2%, and 1.1%). Conclusion. Ultrarush was as effective as the rush and slow protocols and was associated with a low incidence of reactions to stings. This study indicates that ultrarush VIT is a valid therapeutic option for Hymenoptera allergy.


A coupled-channel model of the 3Pi(u) states of N2: structure and interactions of the 3ssigma(g)F3 3Pi(u) and 3ppi(u)G3 3Pi(u) Rydberg states.
New and existing spectroscopic data on N(2), obtained using a wide variety of experimental techniques, are interpreted using a coupled-channel Schrodinger-equation (CSE) model of the structure and predissociation dynamics for the interacting Rydberg and valence states of (3)Pi(u) symmetry. As a result, v>0 levels of the 3ppi(u)G(3) (3)Pi(u) Rydberg state are assigned correctly for the first time, leading to the identification of very strong perturbations in the G(3)-state vibrational structure. A four-channel CSE model, which includes the 3ssigma(g)F(3) (3)Pi(u) and 3ppi(u)G(3) (3)Pi(u) Rydberg states and the C(') (3)Pi(u) and C (3)Pi(u) valence states, indicates strong Rydberg-Rydberg coupling between the F(3) and G(3) states, strong Rydberg-valence coupling between the G(3) and C(') states, and weaker coupling between the F(3) and C(') states.


Ethanol Extract of Pinus koraiensis Leaf Ameliorates Alcoholic Fatty Liver via the Activation of LKB1-AMPK Signaling In Vitro and In Vivo.
Although Pinus koraiensis leaf (PKL) was reported for its anti-diabetes, anti-obesity and anticancer effects as a folk remedy, the inhibitory effect of PKL on alcoholic fatty liver has never been elucidated yet. This study investigated the molecular mechanisms of PKL on alcoholic fatty liver in HepG2 cells, Sprague Dawley (SD) rats and Imprinting Control Region (ICR) mice. Pinus koraiensis leaf increased phosphorylation of liver kinase B1 (LKB1)/AMP-activated protein kinase signaling, low-density lipoprotein receptor and decreased fatty acid biosynthesis-related proteins such as sterol regulatory element-binding protein 1c, fatty acid synthase, 3-hydroxy-3-methylglutaryl-CoA reductase in HepG2 cells. In SD rats with 25% alcohol-induced fatty liver, PKL suppressed the levels of aspartate aminotransferase and triglyceride and also enhanced the activities of antioxidant enzymes including superoxide dismutase, glutathione peroxidase and glutathione s-transferase compared with untreated control. Furthermore, PKL increased serum alcohol dehydrogenase and serum aldehyde dehydrogenase, but decreased serum alcohol concentration in ICR mice after alcohol administration. Consistently, histochemical analysis revealed that PKL attenuated alcohol-induced fatty liver in SD rats. Overall, these findings suggest that PKL ameliorates alcohol-induced fatty liver via activation of LKB1-AMP-activated protein kinase and modulation of proteins related to lipogenesis synthesis, cholesterol synthesis and fatty acid oxidation. Copyright © 2017 John Wiley & Sons, Ltd.


Dementia-free life expectancy among elderly Japanese.
A 3-year prospective cohort study was conducted to estimate the life expectancy free of dementia (dementia-free life expectancy) in a representative sample of older persons living in an urban Japanese community. For the persons aged 65 years and older, who were not demented at the baseline survey in 1988, mortality and incidence rates of dementia were calculated. At the age of 65 years, males showed a total life expectancy of 18 years, including 16 years free of dementia, and females showed a total life expectancy of 23 years, including 18 years without dementia. At 65 years, the dementia-free life expectancy represented 89% of the total life expectancy for males and 79% for females. Total life expectancy and dementia-free life expectancy were longer among females than among males. However, the life-years with dementia were longer among females. This result would be attributable to a higher incidence of dementia and a lower mortality among females.


A cross-sectional survey of Saudi gastroenterologists: Transition strategies for adolescents with inflammatory bowel disease.
The transition of adolescents with inflammatory bowel disease (IBD) from pediatric to adult care requires a well-structured standardized protocol to ensure the delivery of optimal healthcare and decrease the risk of nonadherence, hospitalizations, and complications. The aims of this survey are to evaluate current IBD transition practices adopted by gastroenterology services across the Kingdom of Saudi Arabia (KSA) and to identify the major challenges standing in the way of implementing effective transition strategies from the perspectives of pediatric and adult gastroenterologists. An online survey was distributed to KSA pediatric and adult gastroenterologists through the Kingdom's national gastroenterology association. The questionnaire included closed-ended questions regarding existing institutional transition strategies and perspectives regarding the impact of different factors on their ability to effectively transition adolescents from pediatric to adult care. A total of 80 adult and pediatric gastroenterologists responded to the survey invitation. Most of the participating gastroenterologists worked at a tertiary care center (82.5%). The majority of gastroenterologist (73.8%) reported that they do not follow a defined protocol for transitioning in their current practices. However, a structured transition program was noted to be "very important" by 78.8% of gastroenterologists. The most favored method of transitioning was joint outpatient clinic attended by patient, caregiver, pediatric gastroenterologist, and adult gastroenterologist (35.9%) and the most commonly reported barrier to transitioning was "lack of proper preparation" for transitioning (53.2%). Although acknowledged by the majority of participants as being "very important," no standardized IBD transition protocol is followed in the majority of practices across KSA. A well-structured national protocol for transitioning adolescents with IBD is needed.


Liposomal amphotericin B for the treatment of severe fungal infection.
Amphotericin B is commonly used in the intensive care unit to treat invasive fungal infection. This medication is associated with a number of adverse events during infusion, such as fever, rigors, chills, electrolyte disorders and renal insufficiency. Liposomal amphotericin B can be used as an alternative to conventional amphotericin B to treat fungal infection. Patients receiving liposomal amphotericin B experience fewer adverse events than recipients of the conventional formulation; moreover, the liposomal formulation has been found to be as effective as the conventional amphotericin B to treat specific fungal infections. Unfortunately, the pharmacoeconomics of the liposomal formulation has limited the use of this medication. The purpose of this article is to present a brief summary of conventional amphotericin B with an emphasis on the narrow therapeutic index of this antibiotic. The liposomal amphotericin B solution is compared to conventional amphotericin B regarding the pharmacokinetics and pharmacodynamics. Therapeutic use, tolerability, and pharmacoeconomic implications of liposomal amphotericin B are discussed.


[Autoimmune encephalitis associated to antibodies against the N-methyl-D-aspartate receptor: Report of two cases].
Anti-N-methyl-D-aspartate receptor encephalitis is a neurological syndrome that is more common in young women and is often associated with ovarian teratoma. It is characterized by acute general unspecific symptoms that evolve to neurological deterioration, psychosis and seizures. In its more advanced stage it is associated with abnormal movements and dysautonomia.We report two cases in women of 23 and 12 years of age. Given its low incidence, we present the clinical exercise that led to their diagnoses and the treatment options employed.


Visualization of distal splenorenal shunt by isotopic splenovenography.
Radioisotopic angiography of the splenic vein was performed in six patients following a distal splenorenal shunt (Warren procedure). Under echographic guidance, the spleen was punctured with a 22-gauge needle, and Tc-99m pertechnetate was injected into the splenic pulp. In five patients whose esophageal varices had remained atrophic, the splenic vein, the left renal vein, the inferior vena cava, and the heart were clearly visualized within 8 seconds. In one patient, in whom recurrence of esophageal varices had been recognized, the splenic vein was not imaged. The injected material coursed mainly upwards through collaterals.


Photosensitivity and anti-Ro (SS-A) antibodies in black patients with systemic lupus erythematosus (SLE).
Ninety-two patients with SLE, 36 black and 56 white, were studied prospectively for photosensitivity and anti-Ro (SS-A) and anti-La (SS-B) antibodies. Photosensitivity was found in 19% of black patients, compared to 71% of white patients (p = 0.001). Anti-Ro antibodies were found in 69% of black and 54% of white patients (p = 0.013). Photosensitivity was present in 87% of Ro-positive white patients and in 54% of Ro-negative white patients (p = 0.007). However, in black patients with SLE there was a strong negative association: 4% of Ro-positive patients were photosensitive while 55% of Ro-negatives were photosensitive (p = 0.001). This suggests that black SLE patients may possess a factor which 'blocks' photosensitivity, perhaps by preventing local tissue damage caused by the interaction of Ro antibodies and ultraviolet light.


Synthesis and beta-adrenergic antagonist activity of novel (3-cyanodihydropyridyl)propanolamines.
The synthesis and beta-adrenergic antagonist activities of 1-(1-dihydropyridyl)-3-alkylamino-2-propanols (9-16) in which the aryloxy group of aryloxypropanolamines (1) is replaced by a 1-[2-t-(n-)butyl-3-cyano-1,2-dihydropyridyl] (9-12) or 1-[6-t-(n-)butyl-3-cyano-1,6-dihydropyridyl] (13-16) moiety is described. These replacements resulted in a substantial reduction in beta 1 (atria) and beta 2 (trachea) adrenergic antagonist activities relative to the reference drug metoprolol. Structure-activity correlations indicate the relative potency order is 1,2-dihydropyridyl greater than 1,6-dihydropyridyl, n-Bu greater than t-Bu for dihydropyridyl substituents, and that this class of compounds are non-selective beta-antagonists with a beta 1/beta 2 selectivity ratio close to unity.


Examination of the role of serine phosphorylation in phospholipase C-gamma and its related P47 in cAMP-mediated depression of epidermal growth factor signal transduction.
Forskolin-pretreatment of A431 cells reduced both intrinsic and epidermal growth factor (EGF)-induced EGF receptor phosphorylation, however, phosphorylation of phospholipase C-gamma (PLC-gamma) was stimulated under the same conditions. No significant difference was detected in the amount of phosphotyrosine of PLC-gamma between two cultures with or without forskolin treatment followed by EGF. On the other hand, phosphorylation of a 47 kDa protein (P47) which cross-reacted with an anti-PLC-gamma monoclonal antibody, was stimulated by both forskolin and EGF. Phosphorylation was exclusively on serine residues in this case. These results indicate that both PLC-gamma and P47 are phosphorylated by a cAMP-dependent protein kinase and the EGF-stimulated serine kinase, and suggest that serine phosphorylation of PLC-gamma has no effect on ligand-dependent coupling with the EGF receptor.


Improvements of the lipoprotein profile after coronary bypass surgery: additional effects of an exercise training program.
We have followed physical working capacity and the plasma lipoprotein pattern in 37 males who underwent coronary artery surgery for severe disabling angina pectoris. In order to evaluate the effect of exercise training, 18 patients were randomized to a supervised bicycle training programme three times a week for 12 weeks starting 6 weeks after surgery. Before surgery, working capacity was severely reduced in all subjects. The mean HDL cholesterol level was low (0.8 +/- 0.2 mmol l-1) and the mean plasma LDL concentration moderately elevated (4.6 +/- 0.9 mmol l-1). In the non-training group, physical working capacity increased significantly, and 18 weeks after surgery reached a plateau about 45% above the preoperative values. In the training group, a further improvement to about 60% above preoperative levels was registered at the end of the training program. In the non-training group, HDL cholesterol concentrations rose rapidly to levels between 10 and 15% above the preoperative values. One year after surgery, HDL cholesterol levels were 20% higher than before surgery. There was a parallel rise in apolipoprotein A1 concentrations by about 10% which indicates that the increase in HDL occurred mainly in the lipid rich HDL2 subfraction. There were no changes in plasma lipids or in LDL cholesterol concentrations. In the training group, the increase in HDL was about 20% during the first 26 weeks. One year after surgery, HDL levels were 23% above preoperative values. In this group, we also registered a significant decrease in plasma triglyceride levels by about 25% after two months of exercise.(ABSTRACT TRUNCATED AT 250 WORDS)


Oncocytic glomus tumour: a new variant.
A new variant of glomus tumour characterized by oncocytic change is reported. The light and electron microscopy and immunohistological findings are described. This is the first reported case of an oncocytoma of non-epithelial origin.


Game-Theoretical Model of the Voluntary Use of Insect Repellents to Prevent Zika Fever.
Zika fever is an emerging mosquito-borne disease. While it often causes no or only mild symptoms that are similar to dengue fever, Zika virus can spread from a pregnant woman to her baby and cause severe birth defects. There is no specific treatment or vaccine, but the disease can be mitigated by using several control strategies, generally focusing on the reduction in mosquitoes or mosquito bites. In this paper, we model Zika virus transmission and incorporate a game-theoretical approach to study a repeated population game of DEET usage to prevent insect bites. We show that the optimal use effectively leads to disease elimination. This result is robust and not significantly dependent on the cost of the insect repellents.


Design of a decentralized reusable research database architecture to support data acquisition in large research projects.
The diagnostic and therapeutic processes, as well as the development of new treatments, are hindered by the fragmentation of information which underlies them. In a multi-institutional research study database, the clinical information system (CIS) contains the primary data input. An important part of the money of large scale clinical studies is often paid for data creation and maintenance. The objective of this work is to design a decentralized, scalable, reusable database architecture with lower maintenance costs for managing and integrating distributed heterogeneous data required as basis for a large-scale research project. Technical and legal aspects are taken into account based on various use case scenarios. The architecture contains 4 layers: data storage and access are decentralized at their production source, a connector as a proxy between the CIS and the external world, an information mediator as a data access point and the client side. The proposed design will be implemented inside six clinical centers participating in the @neurIST project as part of a larger system on data integration and reuse for aneurism treatment.


Regional anesthesia in diabetic peripheral neuropathy.
The aim of this review is to summarize recent relevant literature regarding regional anesthesia in the diabetic neuropathic patient and formulate recommendations for clinical practice. Diabetic neuropathic nerves, but not nerves of diabetic patients per se, exhibit complex functional changes. As a result, they seem more sensitive to local anesthetics, and are more difficult to stimulate. When catheters are used postoperatively, diabetes is an independent risk factor for infection. The pathophysiologic mechanisms underlying diabetic polyneuropathy are complex. Several pathways are thought to contribute to the development of diabetic neuropathy, triggered most importantly by chronic hyperglycemia. The latter induces inflammation and oxidative stress, causing microvascular changes, local ischemia and decreased axonal conduction velocity. Regional anesthesia is different in patients with diabetic neuropathy in several regards. First, the electric stimulation threshold of the nerve is markedly increased whereby the risk for needle trauma in stimulator-guided nerve blocks is theoretically elevated. Second, the diabetic nerve is more sensitive to local anesthetics, which results in longer block duration. Third, local anesthetics have been conjectured to be more toxic in diabetic neuropathy but the evidence is equivocal and should not be a cause to deny regional anesthesia to patients with a valid indication. Lastly, when peripheral nerve catheters are used, diabetes is an independent predisposing factor for infection.


Self-assembled extracellular macromolecular matrices and their different osteogenic potential with preosteoblasts and rat bone marrow mesenchymal stromal cells.
Extracellular environment is a physical support that is critical to cell adhesion, migration, and differentiation. In this work, cell-derived matrices (CDMs) were obtained by separately culturing fibroblasts, preosteoblasts, and chondrocytes. The cells were grown on a coverslip and subjected to decellularization using detergents and enzymes. The resulting matrices were named fibroblast-derived matrix (FDM), preosteoblast-derived matrix (PDM), and chondrocyte-derived matrix (CHDM). We hypothesize that the unique compositional and structural feature of each CDM provides cells with a distinct microenvironment capable of functioning as a different signaling cue in the regulation of preosteoblast and rat bone marrow mesenchymal stromal cell (BMSC) osteogenic differentiation. SEM images show that each cell type creates its unique surface texture in a fibrillar structure. Three major macromolecules, fibronectin, type I collagen, and laminin, were clearly identified using both immunofluorescence and Western blot, in which FDM exhibited a much stronger signal of each ECM component than that of PDM or CHDM. For early cell morphology, BMSCs on the CDMs were highly elongated in a spindle-like shape. Both preosteoblasts and BMSCs proliferated well on CDMs comparable to the control. Once preosteoblasts were cultured for 2 weeks, their osteogenic activity was significantly different depending on the type of CDM. Using Alizarin red and von Kossa staining, we found that the cells on the FDM were much more osteogenic than the other groups. Furthermore, FDM was the most effective in upregulating the osteogenic markers, such as alkaline phosphatase (ALP), osteopontin, osteocalcin, and type I collagen. In particular, we observed a 2.5-fold increase in ALP activity with FDM compared to that of control and CHDM. In stark contrast, CHDM was very poor in stimulating osteogenic differentiation of preosteoblasts. Interestingly, these results were reproducible with the use of BMSCs, which are much more heterogeneous in cell populations than preosteoblasts. CHDM was still very weak in triggering the osteogenesis of BMSCs, whereas both FDM and PDM were equally competitive. This study demonstrates that a combination of factors (surface texture and composition) shape a unique cellular microenvironment, which serves as a physical cue toward the osteogenic differentiation of preosteoblasts and BMSCs.


D-dimer trends predict COVID-19 patient's prognosis: A retrospective chart review study.
This is a retrospective study of patients admitted to Jackson Hospital, Montgomery, Alabama, with a diagnosis of COVID-19 from January 1, 2021, to February 15, 2022. The independent variables used in the models were patient sex, age, race, BMI category, daily D-dimer categories, categories of anticoagulation doses, bleeding episodes, and vaccination status. The three different categories of anticoagulation doses were considered for the purpose of the study which were Enoxaparin 40 mg daily vs Enoxaparin 80 mg daily vs Enoxaparin 1 mg/kg or equivalent daily. The study reviewed a total of 100 hospitalized patients. Intermediate-dose anticoagulation was found to be the optimal dose as only 14% patients died compared to a 36 and 50% death rate among those treated with low-dose and high-dose anticoagulation, respectively. The multivariate linear regression model predicting patient oxygen requirements revealed D-dimer and bleeding status to be statistically significant predictors with a p value of <0.01. For the patients who had a D-dimer value ≥2 µg/mL, the oxygenation requirement was predicted to be 31 L higher than those with a D-dimer <2 µg/mL (99% CI; p < 0.01). When mean D-dimer and corresponding oxygen requirements were calculated per hospitalization days category, the D-dimer levels and oxygen requirements were noted to follow the same trends indicating that both values tended to increase and decrease simultaneously. The study concludes daily D-dimer trends can predict COVID-19 patient survival or daily oxygen requirements indicating that D-dimer can be the miracle molecule for COVID-19 prognosis.


Perioperative problems in patients with brainstem tumors and their influence on patient outcome.
Patients with brainstem tumors have many associated systemic abnormalities and are prone to develop perioperative complications. We studied the problems associated with brainstem tumors and their influence on the postoperative neurological outcome. Retrospective review of records of patients who underwent surgery for brainstem tumors over a period of 8 years was done. Preoperative variables, perioperative complications and neurological outcome as assessed by Glasgow Outcome Scale at the time of hospital discharge were noted. Association between perioperative factors and the unfavorable neurological outcome was evaluated. Data of 70 patients were retrieved, 7 patients were excluded from the study because of incomplete data and data analysis was carried out for 63 patients. We found that lower cranial nerve palsies (32%) and hydrocephalus (43%) were common preoperatively. Various intraoperative problems encountered were hemodynamic instability (56%), major blood loss requiring blood transfusion (40%) and venous air embolism (11%), and postoperative problems were meningitis (51%), hypokalemia (38%), chest infection (21%), seizure (11%), deterioration of Glasgow Coma Scale (GCS, 11%), hyponatremia (8%), hydrocephalus (6%), respiratory distress (3%) and operatives site hematoma (3%). Fifty-six (89%) patients had favorable outcome at hospital discharge whereas, 7 (11%) had an unfavorable outcome. There was no association between pre- and intra-operative factors and the neurological outcome. Deterioration of GCS, chest infection, and the need for reintubation and tracheostomy were associated with unfavorable neurological outcome. Patients of brainstem tumors are at increased risk of perioperative complications. Some of the postoperative complications were associated with unfavorable neurological outcome.


[Determinants of diphemanil methylsulfate (Prantal) utilization: a survey of practice in the French neonatal and intensive care units].
Diphemanil methylsulfate (Prantal) is a quaternary ammonium with parasympathicolytic properties. It is used in premature and term neonates with bradycardias related to vagal hyper reflectivity (HRV). To assess the use of Prantal in the French neonatal and intensive care units: its indications, its modalities of use, its side effects and the number of patients treated during 1 year (2004) in France. A questionnaire was electronically sent to all neonatology units and all neonatal intensive care units in France. Among 202 units, 121 (60%) answered the questionnaire. Prantal was reported to be used in 51 (42.1%) units. Among them, 38 (31.4%) actually treated 169 patients in 2004 with a mean number of patients treated by unit of 4. The diagnostic of HRV was supported by: a history of malaise (84.3%), bradycardia (94.1%), oculocardiac reflex (74.5%), cardiac Holter (76.4%), cardiorespirographic recording (19.6%), esophageal pHmetry (35.2%) and esophageal fibroscopy (21.5%). The mean starting dosing was 4.7 mg/kg/d, the mean maximal dosing was 9 mg/kg/d and the mean daily intakes were initially 2.3 and secondary 2.9. Prantal dosing was adjusted to weight in 54.9%, every month in 85.7%. Treatment was stopped at the mean post-natal age of 6 months, mostly in a progressive manner and without monitoring help. Prantal was seldom used in 2004 in France for different reasons: HRV is an uncertain entity, the efficacy of Prantal has not been validated and atropinic side effects can be encountered.


Purification of lactate dehydrogenase isoenzymes one, two, and three from human erythrocytes.
Lactate dehydrogenase (LD) isoenzymes 1, 2, and 3 were prepared from human erythrocytes by sequential ion-exchange chromatography followed by general-ligand (AMP analog) affinity chromatography. Respective yields, purification factors, and specific activities (kU per gram of protein) were 25%, 4394-fold, and 209.7; 40% 4385-fold, and 199.1; and 18%, 7565-fold, and 192.9. The respective preparations contained less than 0.5% of contaminating LD isoenzyme activity as judged from electrophoresis on thin-layer agarose, were homogeneous as judged by electrophoresis on polyacrylamide gel (both in the presence and absence of sodium lauryl sulfate), and showed minor contamination by other LD isoenzymes as judged by analytical isoelectric focusing. We think that these preparations would be useful as human-based calibrating or reference materials. Their purity is such that these preparations could also be used as antigens for the development of suitable antisera.


The influence of apical periodontitis on circulatory inflammatory mediators in peripheral blood: A prospective case-control study.
To explore the influence of apical periodontitis (AP) on inflammatory markers in blood of otherwise healthy individuals and to depict the inflammatory profile of the healing after dental extraction. This is a prospective case-control intervention study, during which, individuals with a diagnosis of AP of one affected tooth were included, along with a control group matched for age and gender. A broad panel of blood inflammatory mediators was examined longitudinally in all subjects during six visits. In the case of the AP subjects, the tooth with AP was extracted at the third visit. Results were analysed by linear regression analyses and linear mixed-model analyses. A total of 53 subjects were included in the study, 27 with AP and 26 without. Fifteen females and 12 males were included in the AP group, and 14 females and 12 males in the control group. At baseline, granulocyte colony-stimulating factor (p < .001), interleukin (IL)-1β (p = .03) and IL-4 (p = .01) were significantly lower in AP subjects than in controls. Comparison of the differences between baseline and the last visit, i.e. 3 months after the tooth extraction, showed a significant reduction in IL-10 (p = .03) and IL-12p70 (p = .01). The immunologic profile of chronic AP in one tooth and its healing profile reveals a systemic low-grade inflammation through compensatory immunosuppression. A larger lesion or multiple lesions could disrupt the balance that the system is trying to maintain, resulting in loss of homeostasis.


The use of xenogenic dermal matrices in the context of open extremity wounds: where and when to consider?
Optimal treatment of orthopaedic extremity trauma includes meticulous care of both bony and soft tissue injuries. Historically, clinical scenarios involving soft tissue defects necessitated the assistance of a plastic surgeon. While their expertise in coverage options and microvascular repair is invaluable, barriers preventing collaboration are common. Acellular dermal matrices represent a promising and versatile tool for orthopaedic trauma surgeons to keep in their toolbox. These biological scaffolds are each unique in how they are used and promote healing. This review explores some commercial products and offers guidance for selection in different clinical scenarios involving traumatic wounds.


An insight into nanocellulose as soft condensed matter: Challenge and future prospective toward environmental sustainability.
Nanocellulose, a structural polysaccharide that has caught tremendous interests nowadays due to its renewability, inherent biocompatibility and biodegradability, abundance in resource, and environmental friendly nature. They are promising green nanomaterials derived from cellulosic biomass that can be disintegrated into cellulose nanofibrils (CNF) or cellulose nanocrystals (CNC), relying on their sensitivity to hydrolysis at the axial spacing of disordered domains. Owing to their unique mesoscopic characteristics at nanoscale, nanocellulose has been widely researched and incorporated as a reinforcement material in composite materials. The world has been consuming the natural resources at a much higher speed than the environment could regenerate. Today, as an uprising candidate in soft condensed matter physics, a growing interest was received owing to its unique self-assembly behaviour and quantum size effect in the formation of three-dimensional nanostructured material, could be utilised to address an increasing concern over global warming and environmental conservation. In spite of an emerging pool of knowledge on the nanocellulose downstream application, that was lacking of cross-disciplinary study of its role as a soft condensed matter for food, water and energy applications toward environmental sustainability. Here we aim to provide an insight for the latest development of cellulose nanotechnology arises from its fascinating physical and chemical characteristic for the interest of different technology holders.


Mode Specific Electronic Friction in Dissociative Chemisorption on Metal Surfaces: H_{2} on Ag(111).
Electronic friction and the ensuing nonadiabatic energy loss play an important role in chemical reaction dynamics at metal surfaces. Using molecular dynamics with electronic friction evaluated on the fly from density functional theory, we find strong mode dependence and a dominance of nonadiabatic energy loss along the bond stretch coordinate for scattering and dissociative chemisorption of H_{2} on the Ag(111) surface. Exemplary trajectories with varying initial conditions indicate that this mode specificity translates into modulated energy loss during a dissociative chemisorption event. Despite minor nonadiabatic energy loss of about 5%, the directionality of friction forces induces dynamical steering that affects individual reaction outcomes, specifically for low-incidence energies and vibrationally excited molecules. Mode-specific friction induces enhanced loss of rovibrational rather than translational energy and will be most visible in its effect on final energy distributions in molecular scattering experiments.


Indigenous uses of ethnomedicinal plants among forest-dependent communities of Northern Bengal, India.
Traditional knowledge on ethnomedicinal plant is slowly eroding. The exploration, identification and documentation on utilization of ethnobotanic resources are essential for restoration and preservation of ethnomedicinal knowledge about the plants and conservation of these species for greater interest of human society. The study was conducted at fringe areas of Chilapatta Reserve Forest in the foothills of the eastern sub-Himalayan mountain belts of West Bengal, India, from December 2014 to May 2016. Purposive sampling method was used for selection of area. From this area which is inhabited by aboriginal community of Indo-Mongoloid origin, 400 respondents including traditional medicinal practitioners were selected randomly for personal interview schedule through open-ended questionnaire. The questionnaire covered aspects like plant species used as ethnomedicines, plant parts used, procedure for dosage and therapy. A total number of 140 ethnomedicinal species was documented, in which the tree species (55) dominated the lists followed by herbs (39) and shrubs (30). Among these total planted species used for ethnomedicinal purposes, 52 species were planted, 62 species growing wild or collected from the forest for use and 26 species were both wild and planted. The present study documented 61 more planted species as compared to 17 planted species documented in an ethnomedicinal study a decade ago. The documented species were used to treat 58 human diseases/ailments including nine species used to eight diseases/ailments of domestic animals. Stomach-related problems were treated by maximum number of plants (40 species) followed by cuts and wounds with 27 plant species and least with one species each for 17 diseases or ailments. Maximum number of 12 diseases/ailments was cured by Melia azedarach followed by Centella asiatica and Rauvolfia serpentina which were used to cure 11 diseases/ailments each. The list of 140 plant species indicates that the Chilapatta Reserve Forest and its fringe areas are rich in biodiversity of ethnobotanical plant species. Rauvolfia serpentina were the most valuable species in terms of its maximal use with higher use value. The documentation of 78 species maintained in the home gardens indicates the community consciousness on the conservation values of these ethnobotanical species. The communities should be encouraged with improved cultivation techniques of commercially viable ethnobotanical species through capacity building, timely policy intervention along with strong market linkage. This will ensure income generation and livelihood improvement and ultimate conservation of these species.


Dispensabilities of carbonic anhydrase in proteobacteria.
Carbonic anhydrase (CA) (E.C. 22.214.171.124) is a ubiquitous enzyme catalysing interconversion between CO(2) and bicarbonate. The irregular distribution of the phylogenetically distinct classes of CA in procaryotic genome suggests its complex evolutionary history in procaryotes. Genetic evidence regarding the dispensability of CA under high-CO(2) air in some model organisms indicates that CA-deficient microorganisms can persist in the natural environment by choosing high-CO(2) niches. In this study, we studied the distribution of CA in the genome of Proteobacteria. While a large majority of the genome-sequenced Proteobacteria retained a CA gene(s), intracellular bacterial genera such as Buchnera and Rickettsia contained CA-defective strains. Comparison between CA-retaining and CA- deficient genomes showed the absence of whole coding sequence in some strains and the presence of frameshifted coding sequence in other strains. The evidence suggests that CA is inactivated and lost in some proteobacteria during the course of evolution based on its dispensability.


Pathogenic mitochondrial DNA 3243A>G mutation: From genetics to phenotype.
The mitochondrial DNA (mtDNA) m.3243A>G mutation is one of the most common pathogenic mtDNA variants, showing complex genetics, pathogenic molecular mechanisms, and phenotypes. In recent years, the prevention of mtDNA-related diseases has trended toward precision medicine strategies, such as preimplantation genetic diagnosis (PGD) and mitochondrial replacement therapy (MRT). These techniques are set to allow the birth of healthy children, but clinical implementation relies on thorough insights into mtDNA genetics. The genotype and phenotype of m.3243A>G vary greatly from mother to offspring, which compromises genetic counseling for the disease. This review is the first to systematically elaborate on the characteristics of the m.3243A>G mutation, from genetics to phenotype and the relationship between them, as well as the related influencing factors and potential strategies for preventing disease. These perceptions will provide clarity for clinicians providing genetic counseling to m.3243A>G patients.


Evaluation of connectivity map-discovered celastrol as a radiosensitizing agent in a murine lung carcinoma model: Feasibility study of diffusion-weighted magnetic resonance imaging.
This study was designed to identify potential radiosensitizing (RS) agents for combined radio- and chemotherapy in a murine model of human lung carcinoma, and to evaluate the in vivo effect of the RS agents using diffusion-weighted magnetic resonance imaging (DW-MRI). Radioresistance-associated genes in A549 and H460 cells were isolated on the basis of their gene expression profiles. Celastrol was selected as a candidate RS by using connectivity mapping, and its efficacy in lung cancer radiotherapy was tested. Mice inoculated with A549 carcinoma cells were treated with single ionizing radiation (SIR), single celastrol (SC), or celastrol-combined ionizing radiation (CCIR). Changes in radiosensitization over time were assessed using DW-MRI before and at 3, 6, and 12 days after therapy initiation. The tumors were stained with hematoxylin and eosin at 6 and 12 days after therapy. The percentage change in the apparent diffusion coefficient (ADC) value in the CCIR group was significantly higher than that in the SC and SIR group on the 12th day (Mann-Whitney U-test, p = 0.05; Kruskal-Wallis test, p < 0.05). A significant correlation (Spearman's rho correlation coefficient of 0.713, p = 0.001) was observed between the mean percentage tumor necrotic area and the mean ADC values after therapy initiation. These results suggest that the novel radiosensitizing agent celastrol has therapeutic effects when combined with ionizing radiation (IR), thereby maximizing the therapeutic effect of radiation in non-small cell lung carcinoma. In addition, DW-MRI is a useful noninvasive tool to monitor the effects of RS agents by assessing cellularity changes and sequential therapeutic responses.


B (MHC) antigen dependent modulation of GvH reactivity by neonatal thymectomy and alloimmunization.
Using Prague recombinant congenic lines of chickens, we found that neonatal thymectomy led either to a marked suppression (CC donors) or to a transient increase (CB donors) of GvH response against the B-F/L + B-G and B-F/L disparate congenic embryos. Similarly, preimmunization with the B (MHC) different blood led either to the suppression or increase of GvH reactivity of the CC and CB line donors depending on the antigenic difference (B-F/L + B-G, B-F/L, B-G) between the blood used for preimmunization, the immunized donor for GvH splenomegaly assay and the recipient embryos. In all cases, the suppression of GvH response of the CC line donors is accompanied with a marked increase in GvH reactivity against syngeneic and B-G 12 disparate embryos, suggesting an autoimmune state. Furthermore, the CC line chickens suffering from GvHD had lower GvH reactivity against the B (MHC) different embryos and a significantly raised reactivity against syngeneic embryos in comparison with controls. Chickens of the same group recovering from GvHD had an extremely high alloreactivity and only slightly or no increased GvH reactivity against syngeneic embryos.


Cellular and subcellular events of bone resorption in human and experimental cholesteatoma: the role of osteoclasts.
An ultrastructural study of the interface between aural cholesteatoma and adjacent bone was performed on specimens obtained from human and experimental gerbilline cholesteatoma. When an enlarging cholesteatoma contacted bone, a large number of monocytes and macrophages accumulated in the area of contact. The intervening middle ear mucosa degenerated and bone erosion occurred. Anatomic evidence is provided which indicates that bone erosion in both human and experimental cholesteatoma occurred as a result of the action of multinucleated osteoclasts. These osteoclasts had the ultrastructural appearance of normal osteoclasts with a well developed ruffled border and large numbers of mitochondria. These cells stained readily with acid phosphatase stains. Although many other mononuclear cells were seen in the vicinity of the eroded bone, only the multi-nucleated osteoclasts were associated with disappearance of the bone surface. Osteoclasts were commonly found in experimental cholesteatoma, but were infrequent in human cholesteatoma biopsies, presumable because patients undergoing cholesteatoma surgery ara often treated with topical installations of corticosteroids which inhibit osteoclasts.


Purification of guinea pig tumor necrosis factor (TNF): comparison of its antiproliferative and differentiative activities for myeloid leukemic cell lines with those of recombinant human TNF.
Recently, we suggested that the effect of differentiation inducing factor (D-factor) which is found in the supernatant of macrophages, and induced the differentiation of a mouse myeloid leukemic cell line, M1, into macrophage-like cells, may be a result of the cooperative effects of tumor necrosis factor (TNF) and interleukin 1 (IL-1). In this study, we purified guinea pig (G.P.) TNF secreted from peritoneal macrophages and compared the antiproliferative and differentiative effects of the G.P. TNF with those of recombinant human TNF (rHuTNF). The purification scheme consisted of ultrafiltration, gel filtration-high performance liquid chromatography (HPLC), DEAE-HPLC, and reverse-phase HPLC. The cytotoxic activity of the purified substance was approximately 1.5 x 10(8) U/mg. The isoelectric point was 5.2. The molecular weight was 40 to 45 kDa as estimated by gel filtration and 18 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The NH2-terminal amino acid sequence was determined to be Ser-Ala-Ser-Gln-Asn-Asp . . . . Approximately 76 or 71% homology between G.P. TNF and mouse or human TNF exists in the NH2-terminal 21 residues. The purified G.P. TNF and rHuTNF demonstrated D-factor activity only in the presence of recombinant human IL-1 alpha in M1 cells. We also determined the effect of TNF on two human myeloid leukemic cell lines (THP-1 and U937). The purified G.P. TNF and rHuTNF inhibited the growth of U937 cells, but did not induce their differentiation. In THP-1 cells, TNF slightly inhibited the growth and induced differentiation. In mouse cell lines G.P. TNF was more effective than rHuTNF for differentiation.(ABSTRACT TRUNCATED AT 250 WORDS)