Miracle-dz/UniFAR-FTUs huggingface dataset:
Gastric Transitional Zones, Areas where Helicobacter Treatment Fails: Results of a Treatment Trial Using the Sydney Strain Mouse Model

ABSTRACT Current combination therapies cure Helicobacter pylori infection in 75 to 85% of cases. However, many treatment failures are not explained by antibiotic resistance. Our goal was to explore treatment failures under in vivo conditions by using the H. pylori Sydney strain (SS1) mouse model. Mice infected with H. pylori (SS1) were treated with monotherapies or combination therapies used in human trials. Bacterial levels and distribution of organisms within the stomach were assessed 24 h after treatment to determine clearance and location of treatment failures and 29 days after treatment to determine cure rates. Except for treatment with metronidazole, mono- and dual therapies did not cure infection but resulted in decreases in bacterial levels and differences in distribution within the stomach. In cases of treatment failure when clarithromycin was used, omeprazole and dual therapy with omeprazole and amoxicillin resulted in organisms being cleared from the antrum, but organisms remained in the antrum-body transitional zone. The triple therapies of OMC and bismuth subcitrate, metronidazole, and tetracycline were successful in eradicating infection. Except for metronidazole monotherapy and triple therapy with OAC, there was good correlation between the Sydney strain mouse model and humans with respect to the success of antimicrobial therapy. The antrum-body transitional zone was identified as a sanctuary site in treatment failure. This could result from antimicrobial agents not functioning effectively at this site or bacteria in this location expressing products that protect them against antimicrobial agents. This is the first demonstration of a possible sanctuary site as a reason for failure of therapy.
The impact of functioning pancreas–kidney transplantation and pancreas alone transplantation on the lipid metabolism of statin‐naïve diabetic patients

Abstract: Objective: To compare the lipid profile (total cholesterol – TC, triglycerides – TG, high density lipoprotein cholesterol – HDL‐c, low density lipoprotein cholesterol – LDL‐c and non‐HDL cholesterol – NHDL‐c) of patients with functioning pancreas–kidney transplantation (PKT) or pancreas transplantation alone (PTA) after one (T1) and two yr (T2) following their pre‐transplantation data (T0).
Antigens of Streptococcus mutans I. Characterization of a Serotype-Specific Determinant from Streptococcus mutans

A membrane-associated glycerol teichoic acid antigen has been isolated from Streptococcus mutans AHT and a similar antigen has been demonstrated to be present in each of the other Bratthall serotype a organisms studied. Trichloroacetic acid-extracted material was resolved into two phosphorus-containing antigenic fractions (B and C) by agarose chromatography. Fraction B was preliminarily identified as a phospholipid moiety with a glycerol-to-phosphorus ratio of 2:1, and fraction C showed a ratio of 1:1 indicative of a glycerol teichoic acid. This latter fraction also was associated with glucose, galactose, alanine, and fatty acids. Diglycerol triphosphate, the compound characteristically released from 1-3 phosphodiester-linked glycerol teichoic acids by alkaline hydrolysis, was isolated and characterized. Alanine was identified as its alkaline-labile, ester-linked D-isomer. A glyceride was isolated containing a disaccharide of glucose and galactose attached to the 2-hydroxyl group of glycerol. Hapten inhibition analysis demonstrated that β-galactosides were the greatest inhibitors of the precipitin reaction (>75%), whereas glucose and its derivatives inhibited to a much lesser extent (<30%). Comparative immunodiffusion and immuno-electrophoresis analyses demonstrated that all six Bratthall serotype a organisms tested contained this antigenic determinant and that it was absent in serotypes b, c, and d. It is suggested that the common antigenic determinant of this serotype within S. mutans may be a β-galactoside associated with a glycerol teichoic acid and possibly other polymers.
Variation in the larval recovery of Toxocara canis from the murine brain: implications for behavioural studies

Abstract The migratory pathway of Toxocara canis larvae was determined by infecting mice with a low, medium or high dose of embryonated T. canis eggs and determining numbers of larvae present in the brain, liver, lungs, kidneys and muscle on days 5, 14 and 26 post infection. Variation was seen in the numbers of larvae recorded in the organs of mice which had received the same number of eggs and were at the same stage of infection. This variation was particularly marked in the brain indicating that, for the purposes of behavioural studies, the actual numbers of larvae found in the brain rather than the number assumed from the dose would have to be taken into account when analysing the behaviour of infected mice.
Decreased interleukin‐10 in tracheal aspirates from preterm infants developing chronic lung disease

The inability to balance pulmonary injury with healing may predispose preterm infants to chronic lung disease (CLD). It is postulated that the production of interleukin (IL)‐10, an anti‐inflammatory cytokine, is gestationally influenced and that CLD‐prone infants may have a reduced ability to produce IL‐10. Methods: Tracheal fluid (TF) was collected at least twice weekly from 48 mechanically ventilated infants within the first 7 d of life while intubated. Results: A total of 87 TF specimens were obtained. None of the 11 CLD infants (24‐31 wk of gestation) had TF IL‐10 levels above 4 pg/ml (0/20 TF specimens), while 14 (70%) of the 20 non‐CLD preterm infants (27–36 wk of gestation) had IL‐10 levels above 5 pg/ml in one or more of their TF specimens (18/48 TF specimens, p < 0.001). Only the 5 term infants who were ventilated for severe lung disease had raised IL‐10 levels (17 infants, 5/19 TF specimens). IL‐10 levels, if detected, (range 6‐938 pg/ml) tended to be higher with increasing gestation (Spearman's rho coefficient = 0.43; p= 0.003). TF IL‐10 detection was not associated with hyaline membrane disease, antenatal steroids or influenced by TF sample volume. Overall IL‐8 levels were wide ranging but towards the end of week 1 the levels were significantly higher in CLD infants (CLD: median 34 184 ng/ml, preterm non‐CLD: median 699 ng/ml, p < 0.001, term: 2961 ng/ml, p= 0.028).
Immunization coverage in three districts of North West Frontier Province (NWFP).

AIM This community-based study was conducted to assess the progress of Expanded Programme on Immunization (EPI) in North West Frontier Province (NWFP) of Pakistan. METHOD In this cross sectional survey, 120 randomly selected clusters in 03 districts of NWFP were included, 2673 children in the age group 12-35 months of 2583 randomly selected families were visited. RESULTS The results showed that 65% of children were fully immunized, but out of them only half could be verified by immunization, need of 2nd and 3rd dose and no faith in immunization were the major causes of failure of immunization programme. Moreover, mother too busy, absence of vaccinator and inconvenient place of immunization were the obstacles pointed out by the parents. CONCLUSION This study suggests the areas where improvement can be made to achieve the real target of immunization coverage. It is concluded that despite of more than 20 years of efforts by EPI, the ultimate objectives have not been achieved.
Limited utility of ICD‐10 and DSM‐IV classification of dissociative and conversion disorders in India

Studies of psychiatric out‐patients from India have found that diagnosis of some of the subcategories of the dissociative and conversion disorders of the ICD and DSM classificatory systems are rarely made in this setting. Moreover, it was found that a significant percentage of patients seen in psychiatric practice may not fit into the defined subcategories of dissociative (conversion) disorders of these systems of classification. We studied the prevalence of various ICD‐10 and DSM‐IV categories of dissociative (conversion) disorders and our own proposed category of ‘brief dissociative stupor’(BDS), among all the in‐patients of a psychiatric unit in a general teaching hospital, over a 2‐year period. There were 18 patients who fulfilled our criteria for BDS and 18 patients in the second group which included all of the remaining subjects with a diagnosis of any other subcategory of dissociative disorder according to ICD‐10. Our analysis revealed that there were no patients with a diagnosis of dissociative amnesia, fugue, stupor, trance and possession disorders or identity disorders. There were significantly more female patients in the BDS group, and they also had significantly more comorbid Axis‐I diagnoses and panic attacks. Since 50% of our patients fulfilled the criteria for BDS, there is clearly a need for further studies to establish the prevalence of this subcategory in patients from other centres. The classification of these patients with this phenomenology is problematic. Inclusion of a subcategory of dissociative non‐epileptic seizures, instead of dissociative convulsions, should improve the classification of dissociative (conversion) disorders.
Autophagy downstream of endosomal Toll-like receptor signaling in macrophages is a key mechanism for resistance to Leishmania major infection

Leishmaniasis is caused by protozoan parasites of the genus Leishmania. In mammalians, these parasites survive and replicate in macrophages and parasite elimination by macrophages is critical for host resistance. Endosomal Toll-like receptors (TLRs) have been shown to be crucial for resistance to Leishmania major in vivo. For example, mice in the resistant C57BL/6 genetic background that are triple-deficient for TLR3, -7, and -9 (Tlr3/7/9−/−) are highly susceptible to L. major infection. Tlr3/7/9−/− mice are as susceptible as mice deficient in MyD88 or UNC93B1, a chaperone required for appropriate localization of endosomal TLRs, but the mechanisms are unknown. Here we found that macrophages infected with L. major undergo autophagy, which effectively accounted for restriction of parasite replication. Signaling via endosomal TLRs was required for autophagy because macrophages deficient for TLR3, -7, and 9, UNC93B1, or MyD88 failed to undergo L. major-induced autophagy. We also confirmed that Myd88−/−, Tlr3/7/9−/−, and Unc93b1−/− cells were highly permissive to L. major replication. Accordingly, shRNA-mediated suppression of Atg5, an E3 ubiquitin ligase essential for autophagosome elongation, in macrophages impaired the restriction of L. major replication in C57BL/6, but did not affect parasite replication in Myd88−/− or Unc93b1−/− macrophages. Rapamycin treatment reduced inflammatory lesions formed in the ears of Leishmania-infected C57BL/6 and Tlr3/7/9−/− mice, indicating that autophagy operates downstream of TLR signaling and is relevant for disease development in vivo. Collectively, our results indicate that autophagy contributes to macrophage resistance to L. major replication, and mechanistically explain the previously described endosomal TLR-mediated resistance to L. major infection.
Role of obstructive sleep apnea in cardiovascular disease

Purpose of review To provide an update on the connection between obstructive sleep apnea (OSA) and cardiovascular disease. Recent findings Large prospective studies have established that OSA is associated with an increased incidence of hypertension and, in men, of coronary disease, stroke, and heart failure. Advances in understanding the pathophysiologic basis for these associations include identification of a role for OSA in inducing abnormalities in hepatic lipid-metabolizing enzymes, endothelial dysfunction, and upregulation of pro-inflammatory and pro-thrombotic mediators. A large body of data implicates OSA as playing a significant role in the occurrence and resistance to treatment of atrial fibrillation. Clinical trials have shown small-to-modest improvements in blood pressure associated with continuous positive airway pressure (CPAP) use, with smaller or uncontrolled studies suggesting that CPAP may improve cardiovascular outcomes or intermediate markers. Summary OSA and cardiovascular disease commonly co-aggregate. Multiple studies indicate that OSA contributes to or exacerbates cardiovascular disease, and thus may be a novel target for cardiovascular risk reduction. Although the evidence supports screening and treatment of OSA in patients at risk for cardiovascular disease, it also underscores a need for well powered clinical trials to examine the role of CPAP and other therapies in these populations.
Augmentation of Tissue Transglutaminase Expression and Activation by Epidermal Growth Factor Inhibit Doxorubicin-induced Apoptosis in Human Breast Cancer Cells*

Tissue transglutaminase (TGase) exhibits both a GTP binding/hydrolytic capability and an enzymatic transamidation activity. Increases in TGase expression and activation often occur in response to stimuli that promote cellular differentiation and apoptosis, yet the signaling mechanisms used by these stimuli to regulate TGase expression and activation and the role of TGase in these cellular processes are not well understood. Retinoic acid (RA) consistently induces TGase expression and activation, and it was shown recently that RA-induced TGase expression was inhibited in NIH3T3 mouse fibroblasts co-stimulated with epidermal growth factor (EGF). Here we investigate whether EGF also antagonized RA-induced TGase expression in breast cancer cells. We found that EGF stimulation affected TGase expression and activation very differently in these cancer cells. Not only did EGF fail to block RA-induced TGase expression, but also EGF alone was sufficient to potently up-regulate TGase expression and activation in SKBR3 cells, as well as MDAMB468 and BT-20 cells. Inhibiting phosphoinositide 3-kinase activity severely diminished the ability of EGF and RA to increase TGase protein levels, whereas a constitutively active form of phosphoinositide 3-kinase potentiated the induction of TGase expression by EGF in SKBR3 cells. Because EGF is an established antiapoptotic factor, we examined whether the protection afforded by EGF was dependent on its ability to up-regulate TGase activity in SKBR3 and BT-20 cells. Exposure of cells to a TGase inhibitor or expression of a dominant-negative form of TGase potently inhibited EGF-mediated protection from doxorubicin-induced apoptosis. Moreover, expression of exogenous TGase in SKBR3 cells mimicked the survival advantage of EGF, suggesting that TGase activation is necessary and sufficient for the antiapoptotic properties of EGF. These findings indicate for the first time that EGF can induce TGase expression and activation in human breast cancer cells and that this contributes to their oncogenic potential by promoting chemoresistance.
Medullary respiratory neurones and control of laryngeal motoneurones during fictive eupnoea and cough in the cat

1 This study addressed the hypothesis that ventrolateral medullary respiratory neurones participate in the control of laryngeal motoneurones during both eupnoea and coughing. 2 Data were obtained from 28 mid‐collicular decerebrated, artificially ventilated cats. Cough‐like motor patterns (fictive cough) in phrenic, lumbar and recurrent laryngeal nerves were elicited by mechanical stimulation of the intrathoracic trachea. Microelectrode arrays were used to monitor simultaneously several neurones in the ventral respiratory group, including the Bötzinger and pre‐Bötzinger complexes. Spike trains were evaluated for responses during fictive cough and evidence of functional connectivity with spike‐triggered averages of efferent recurrent laryngeal nerve activity. 3 Primary features were observed in averages triggered by 94 of 332 (28 %) neurones. An offset biphasic wave with a positive time lag was present in the unrectified average for 10 inspiratory and 13 expiratory neurones. These trigger neurones were respectively identified as inspiratory laryngeal motoneurones with augmenting, decrementing, plateau and ‘other’ discharge patterns, and expiratory laryngeal motoneurones with decrementing firing patterns. 4 Rectified averages triggered by inspiratory neurones included 37 offset peaks, 11 central peaks and one offset trough. Averages triggered by expiratory neurones had 12 offset peaks, six central peaks and four offset troughs. Relationships inferred from these features included premotor actions of inspiratory neurones with augmenting, decrementing, plateau and ‘other’ patterns on inspiratory laryngeal motoneurones, and premotor actions of decrementing and ‘other’ expiratory neurones on expiratory laryngeal motoneurones. Corresponding changes in neuronal firing patterns during fictive cough supported these inferences. 5 The data confirm and extend previous results on the control of laryngeal motoneurones during eupnoea and support the hypothesis that the same premotor neurones help to shape motoneurone firing patterns during both eupnoea and coughing.
Intrathecal baclofen after traumatic brain injury: early treatment using a new technique to prevent spasticity.

BACKGROUND In the early course of severe head trauma, the clinical value of intrathecal administration of baclofen to reduce autonomic disorders and spasticity has not been established. METHODS We studied four patients (Glasgow Coma Scale score 3 or 4) with autonomic disorders and spasticity who failed to respond to conventional treatment during the early course of head injury. Baclofen (25 microg/mL) was infused continuously through an intrathecal catheter inserted at patient bedside and subcutaneously tunneled. When this treatment was successful, the spinal catheter was removed and surgically replaced by another catheter connected to a subcutaneous pump. Clinical follow-up was obtained at 6 months after the head injury. RESULTS Mean delay for the initiation of intrathecal baclofen was 25 days (range, 21 to 31 days), and optimal dose was 385 +/- 185 microg/day. In all patients, the Ashworth score was consistently reduced (3.5 +/- 0.5 vs. 4.5 +/- 0.5 for upper limbs and 2 +/- 0.5 vs. 4.5 +/- 0.5 for lower limbs), as were both the frequency and intensity of autonomic disorders. The spinal catheters were used during a mean period of 9.5 +/- 1.7 days without complications. All three survivors were equipped with a programmable pump and had a lower Ashworth score at 6 months. Autonomic disorders had disappeared in two patients and remained modest in the remaining patient. CONCLUSION Continuous administration of baclofen via the intrathecal route using this new technique seems to reduce autonomic disorders and spasticity during the early course of severe traumatic head injury.
Standard laparoscopic trocars for the treatment of tension pneumothorax: A superior alternative to needle decompression

BACKGROUND Needle thoracostomy (NT) is a commonly taught intervention for tension pneumothorax (tPTX) but has a high failure rate. We hypothesize that standard 5-mm laparoscopic trocars may be a safe and more effective alternative. METHODS Thirty episodes of tPTX and 27 episodes of tension-induced pulseless electrical activity (PEA) were induced in five adult swine using thoracic CO2 insufflation via balloon trocar. Tension was defined as a 50% decrease in cardiac output. Chest decompression was performed with 5-mm laparoscopic trocars for the treatment of both tPTX with hemodynamic compromise and tension-induced PEA. The lungs and heart were inspected and graded at necropsy for trocar-related injury. Results were also compared with success rates with NT in the same model. RESULTS The placement of a 5-mm trocar rapidly and immediately relieved tension physiology in 100% of the cases. Mean arterial pressure, cardiac output, central venous pressure, and pulmonary capillary wedge pressure all returned to baseline within 1 minute of trocar placement. Adequate perfusion was restored in 100% of tension-induced PEA cases within 30 seconds of trocar placement. There was no evidence of trocar-related heart or lung damage in any of the experimental animals at necropsy (mean injury scores, 0 for both). Five-millimeter trocars significantly outperformed standard NT for both tPTX and tension-induced PEA arrest. CONCLUSION tPTX and tension-induced PEA can be safely and effectively treated with chest decompression using 5-mm laparoscopic trocars. This technique may serve as a more rapid and reliable alternative to needle decompression.
In situ gelling properties of anionic thiomers

The aim of this study was to investigate in situ crosslinking systems of anionic thiolated polymers. In order to accelerate the increase in dynamic viscosity of thiolated polymers (thiomers), they were combined with hydrogen peroxide, carbamide peroxide and ammonium persulfate. Thiomers (pectin–cysteine (Pec–Cys), sodium carboxymethylcellulose–cysteine (NaCMC–Cys) and poly(acrylic acid)–cysteine (PAA–Cys)) were synthesized via amide bond formation between the carboxylic acid group of polymers and the primary amino group of l-cysteine. The rheological properties of 1% (m/v) thiomer solutions with oxidizing agents were compared by oscillatory measurements over time (120 min). Pec–Cys and NaCMC–Cys with hydrogen and carbamide peroxide showed a sol-gel phase transition within a few minutes and scored up to 13,000-fold increase in dynamic viscosity. Furthermore, only thiomers exhibiting a polysaccharide backbone (Pec–Cys and NaCMC–Cys) showed a significant increase in viscosity (p < 0.05). In contrast, measurements of carbohydrate thiomers in combination with ammonium persulfate showed an initial increase in viscosity. Afterwards, a decrease in viscosity was observed likely caused by chain scission. According to these results, carbohydrate thiomer/oxidizing agent systems might be useful for various pharmaceutical applications such as for in situ gelling liquid/semisolid formulations or in tissue engineering.
Change in Expression of Heart Carnitine Palmitoyltransferase I Isoforms with Electrical Stimulation of Cultured Rat Neonatal Cardiac Myocytes (*)

Electrical stimulation of neonatal rat cardiac myocytes in culture produces increases in myocyte size (hypertrophy) and organization of actin into myofibrillar arrays. The maturation of the cells is associated with enhanced contractile parameters and cellular calcium content. The numbers and intensity of cellular mitochondrial profiles increase, as measured by scanning laser confocal microscopy. Consistent with the hypertrophic response is increased cellular content of β-myosin heavy chain and cytochrome oxidase subunit Va messages, as well as increases in cytochrome oxidase activity in the stimulated cardiac myocytes. Myocyte contractile capacity is associated with increased expression of the muscle carnitine palmitoyltransferase (CPT-I) isoform as measured by Northern analysis, immunoblotting, and altered sensitivity of CPT-I activity to malonyl-CoA in the stimulated cells. The data suggest that a switch from the liver isoform of CPT-I, prominent in the neonatal rat heart, to the muscle CPT-I which predominates in adult rat heart, takes place in the neonatal cardiac myocytes over the same time period as the hypertrophic-mediated changes in myofibrillar assembly and increased contractile activity.