Recent approaches to intracellular delivery of drugs and DNA and organelle targeting.
Intracellular delivery of various drugs, including DNA, and drug carriers can sharply increase the efficiency of various treatment protocols. However, the receptor-mediated endocytosis of drugs, drug carriers, and DNA results in their lysosomal delivery and significant degradation. The problem can be solved and therapy efficacy still further increased if the approaches for direct intracytoplasmic delivery that bypass the endocytic pathway are developed. This is especially important for many anticancer drugs (proapoptotic drugs whose primary action site is the mitochondrial membrane) and gene therapy (nuclear or mitochondrial genomes should be targeted). This review considers several current approaches for intracellular drug delivery: the use of pH-sensitive liposomes, the use of cell-penetrating proteins and peptides, and the use of immunoliposomes targeting intracellular antigens. Among intracellular targets, nuclei (gene therapy), mitochondria (proapoptotic cancer therapy and targeting of the mitochondrial genome), and lysosomes (lysosomal targeting of enzymes for the therapy of the lysosomal storage diseases) are considered. Examples of successful intracellular and organelle-specific delivery of biologically active molecules, including DNA, are presented; unanswered questions, challenges, and future trends are also discussed.


Detection of human interchromosomal trans-splicing in sequence databanks.
Trans-splicing is a common phenomenon in nematodes and kinetoplastids, and it has also been reported in other organisms, including humans. Up to now, all in silico strategies to find evidence of trans-splicing in humans have required that the candidate sequences follow the consensus splicing site rules (spliceosome-mediated mechanism). However, this criterion is not supported by the best human experimental evidence, which, except in a single case, do not follow canonical splicing sites. Moreover, recent findings describe a novel alternative tRNA mediated trans-splicing mechanism, which prescinds the spliceosome machinery. In order to answer the question, 'Are there hybrid mRNAs in sequence databanks, whose characteristics resemble those of the best human experimental evidence?', we have developed a methodology that successfully identified 16 hybrid mRNAs which might be instances of interchromosomal trans-splicing. Each hybrid mRNA is formed by a trans-spliced region (TSR), which was successfully mapped either onto known genes or onto a human endogenous retrovirus (HERV-K) transcript which supports their transcription. The existence of these hybrid mRNAs indicates that trans-splicing may be more widespread than believed. Furthermore, non-canonical splice site patterns suggest that infrequent splicing sites may occur under special conditions, or that an alternative trans-splicing mechanism is involved. Finally, our candidates are supposedly from normal tissue, and a recent study has reported that trans-splicing may occur not only in malignant tissues, but in normal tissues as well. Our methodology can be applied to 5'-UTR, coding sequences and 3'-UTR in order to find new candidates for a posteriori experimental confirmation.


Cyst formation and poly-beta-hydroxybutyric acid accumulation in Azotobacter.
Stevenson, L. H. (Louisiana State University, Baton Rouge), and M. D. Socolofsky. Cyst formation and poly-beta-hydroxybutyric acid accumulation in Azotobacter. J. Bacteriol. 91:304-310. 1966.-The relationship between cyst formation and the accumulation of poly-beta-hydroxybutyric acid (PHB) in Azotobacter vinelandii (A. agilis) was investigated. After various periods of growth, the cells were harvested, and the amount of PHB and the extent of encystment were determined. The polymer content of the cells increased sharply and reached a maximum on the 2nd day of growth followed by a gradual decline as the culture aged. At maximal accumulation, the PHB content was 35% of the dry weight, and the PHB-nitrogen ratio was 11:1. Those substrates promoting the highest polymer content (glucose, butanol) also promoted 95 to 100% encystment. Manipulation of the carbon and nitrogen supply in the medium indicated that both the maximal PHB content and the extent of cyst formation could be controlled. A direct correlation was noted between the amount of polymer accumulated and the percentage of cysts formed, indicating a possible role of PHB as a carbon or energy source, or both, for the encystment process.


The costs of back pain in industry.
The overall costs of back pain, including the costs of medical care, compensation for lost wages, and indirect costs, are reviewed and their magnitude emphasized.


A randomized trial of very early decompressive craniectomy in children with traumatic brain injury and sustained intracranial hypertension.
The object of our study was to determine, in children with traumatic brain injury and sustained intracranial hypertension, whether very early decompressive craniectomy improves control of intracranial hypertension and longterm function and quality of life. All children were managed from admission onward according to a standardized protocol for head injury management. Children with raised intracranial pressure (ICP) were randomized to standardized management alone or standardized management plus cerebral decompression. A decompressive bitemporal craniectomy was performed at a median of 19.2 h (range 7.3-29.3 h) from the time of injury. ICP was recorded hourly via an intraventricular catheter. Compared with the ICP before randomization, the mean ICP was 3.69 mmHg lower in the 48 h after randomization in the control group, and 8.98 mmHg lower in the 48 hours after craniectomy in the decompression group (P=0.057). Outcome was assessed 6 months after injury using a modification of the Glasgow Outcome Score (GOS) and the Health State Utility Index (Mark 1). Two (14%) of the 14 children in the control group were normal or had a mild disability after 6 months, compared with 7 (54%) of the 13 children in the decompression group. Our conclusion was that when children with traumatic brain injury and sustained intracranial hypertension are treated with a combination of very early decompressive craniectomy and conventional medical management, it is more likely that ICP will be reduced, fewer episodes of intracranial hypertension will occur, and functional outcome and quality of life may be better than in children treated with medical management alone (P=0.046; owing to multiple significance testing P <0.0221 is required for statistical significance). This pilot study suggests that very early decompressive craniectomy may be indicated in the treatment of traumatic brain injury.


Reactive oxidants and myeloperoxidase and their involvement in neutrophil extracellular traps.
Neutrophils release extracellular traps (NETs) in response to a variety of inflammatory stimuli. These structures are composed of a network of chromatin strands associated with a variety of neutrophil-derived proteins including the enzyme myeloperoxidase (MPO). Studies into the mechanisms leading to the formation of NETs indicate a complex process that differs according to the stimulus. With some stimuli an active nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is required. However, assigning specific reactive oxygen species involved downstream of the oxidase is a difficult task and definitive proof for any single oxidant is still lacking. Pharmacological inhibition of MPO and the use of MPO-deficient neutrophils indicate active MPO is required with phorbol myristate acetate as a stimulus but not necessarily with bacteria. Reactive oxidants and MPO may also play a role in NET-mediated microbial killing. MPO is present on NETs and maintains activity at this site. Therefore, MPO has the potential to generate reactive oxidants in close proximity to trapped microorganisms and thus effect microbial killing. This brief review discusses current evidence for the involvement of reactive oxidants and MPO in NET formation and their potential contribution to NET antimicrobial activity.


Generation of azimuthally polarized beams in fast axial flow CO2 laser with hybrid circular subwavelength grating mirror.
A hybrid circular subwavelength grating mirror is proposed and fabricated as a rear mirror in a fast axial flow CO2 laser system to generate azimuthally polarized beams (APBs). This grating mirror, with particular gold-covered ridges and nanopillar-stuffed grooves, performs wideband TE wave reflectivity and high polarization selectivity. It shows that the polarization selectivity mechanism lies in the gold ridge's high reflectivity to the TE wave and the lower TM wave reflectivity, which are the result of the mode leaking into substrate through the dielectric-like nanopillar layer. Finally, a high-quality 550 W APB is obtained in subsequent experiments, which provides potential applications in drilling and welding.


A comparative study of intravenous paracetamol and intravenous tramadol for postoperative analgesia in laparotomies.
Pain in the perioperative setting or thereafter plays a significant role in delaying an otherwise successful recovery. Hence, mitigation of such postoperative pain assumes importance. Among the various agents employed for such mitigation, opioids and non-steroidal anti-inflammatory drugs have for some time taken center stage. However, alas they are not without their share of adverse effects. This study was undertaken with the purpose of elucidating the efficacy of intravenous (IV) paracetamol as compared to IV tramadol in mitigating postoperative pain while observing its effect on hemodynamic stability and the presence of adverse drug reactions, if any. A total of 60 randomized cases aged ranges from 20 to 60 years of both sexes divided into two groups (each for paracetamol and tramadol) scheduled for laparotomies were administered IV paracetamol and tramadol for postoperative pain relief and assessed with visual analog scale (VAS) score and variations in vital parameters to ascertain extent of pain relief and post-operative nausea vomiting (PONV). Data so collected was statistically interpreted, and observations extrapolated. Save for a perceptible decline in PONV with paracetamol group compared with tramadol group with a statistically significant P < 0.001, nothing statistically significant was observed in any other parameter, including VAS scores between either group. IV paracetamol is a safer alternative to tramadol with lesser PONV in the postoperative period translates into the lesser duration of hospitalization and hence earlier discharge.


Prenatal diagnosis of bowel malposition using T2-weighted fetal MRI sequences.
The goal of this study was to investigate the capability of T2-weighted magnetic resonance imaging (MRI) in revealing fetal bowel malposition. All fetal MRI examinations (excluding central nervous system MRI examinations) performed in our department from January 2005 to January 2014 were retrospectively studied by 2 independent observers for situs, stomach and jejunum location on T2-weighted images. Patients data were also reviewed for results of ultrasound examinations, MRI indication, and gestational age. Abnormally positioned jejunums were classified into 3 groups: intrathoracic (A), extra-fetal (B) and abnormal intra-fetal (C). Prenatal data were compared to postnatal imaging, surgery or autopsy findings that served as standard of reference. A total of 709 fetal MRI examinations were analyzed. In 64 fetus (9%), the jejunum was not present in the left subgastric area on T2-weighted MR images. In these 64 fetuses, proximal jejunum was intrathoracic (41/64, 64%, group A), extra-fetal (11/64, 17%, group B), or intra-abdominal but abnormally positioned (12/64, 19%, group C). Interobserver agreement was 100%. All diagnoses for fetuses in groups A and B (52 cases) were confirmed postnatally (41 cases) or at autopsy (11 cases). In group C, bowel malposition was suspected after ultrasound in only 2/12 fetuses (16.6%); it was confirmed postnatally in 1 fetus but not confirmed in the remaining one. In the 10 remaining fetuses (83%), malposition was confirmed postnatally although not initially suspected. T2-weighted fetal MR images are useful for the prenatal diagnosis of bowel malposition, even when they are unsuspected on ultrasound examination.


Safe sedation in modern cardiological practice.
Safe sedation is fundamental to many modern cardiological procedures, and following the publication of the report on safe sedation by the Academy of Medical Royal Colleges, this report discusses sedation specifically in cardiological practice. The major areas within cardiology that use sedation are cardioversion, catheter ablation particularly of atrial fibrillation, transoesophageal echocardiography, implantable device (cardiovascular implantable electronic device) procedures and other procedures such as transcatheter aortic valve replacement. There is increasing demand for cardiological sedation but there is wide geographical variation in its use and there are also growing data to support non-anaesthetists giving sedation. The use of benzodiazepines, particularly for short procedures, is common, but even here good record-keeping and audit together with an understanding of the continuum of sedation and having appropriately trained staff and the necessary facilities are vital. Nurse administration of propofol may be appropriate for some procedures in cardiology that require at least moderate sedation. Appropriate training is essential and the use of capnography and target controlled infusion pumps for propofol administration is recommended.


Pleiotropic regulatory locus 2 exhibits unequal genetic redundancy with its homolog PRL1.
In plants, signaling leading to resistance against biotrophic pathogens is complex. Perception of pathogenic microbes by resistance (R) proteins is relayed though successive activities of downstream components, in a network that is not well understood. PLEIOTROPIC REGULATORY LOCUS 1 (PRL1) and >20 other proteins are members of the MOS4-associated complex (MAC), a regulatory node in defense signaling. Of all characterized MAC members, mutations in PRL1 cause the most severe susceptibility towards both virulent and avirulent microbial pathogens. Genetic suppressors of prl1 represent new signaling elements and may aid in further unraveling of defense mechanisms. Our identification and characterization of a dominant suppressor of prl1 revealed a regulatory, gain-of-function mutation in PLEIOTROPIC REGULATORY LOCUS 2 (PRL2), a close homolog of PRL1. Loss-of-function mutants of PRL2 do not exhibit altered phenotypes; however, prl1 prl2 double mutants exhibit enhanced morphological defects consistent with unequal genetic redundancy between the homologs. Up-regulated gene expression mediated by the dominant prl2-1D allele completely suppresses disease susceptibility in the prl1 mutant background and also restores wild-type appearance, further supporting functional equivalence between the two PRL proteins.


Complete recovery after glucocorticoid replacement therapy in a case of primary adrenal insufficiency caused by adrenal tuberculosis infection.
Symptoms of primary adrenal insufficiency (PAI) are commonly nonspecific, causing the disease to be misdiagnosed or often delayed, and patients may present to the hospital with a life-threatening crisis. Previous case reports have documented that patients in this condition often require lifelong glucocorticoid replacement therapy. This study aimed to present a noteworthy outcome of PAI caused by adrenal tuberculosis infection, demonstrating complete recovery after six months of glucocorticoid replacement therapy. A 38-year-old Indonesian man presented to the endocrinology clinic in a tertiary hospital with a chief complaint of epigastric pain. The patient experienced nausea, vomiting, loss of consciousness, weight loss, excessive sweat, decreased appetite, weakness, and dizziness in the past 2 weeks. Laboratory examinations revealed hyponatremia, elevated adrenocorticotropic hormone, and suppressed morning plasma cortisol level. A non-contrast-enhanced abdominal MRI showed unilateral right-side adrenal enlargement and calcification. The patient's Mantoux test was positive. Corticosteroids and anti-tuberculosis therapy were administered. After 6 months, hydrocortisone was discontinued due to the patient's good clinical condition and normal morning plasma cortisol levels. After a 1-year follow-up, the patient remained asymptomatic with normal cortisol levels. We hypothesized several reasons for this unique outcome: (i) the patient was relatively young compared to previous cases, suggesting an adequate immune system may play a role; (ii) despite a 1-month delay in diagnosis and treatment, the absence of skin hyperpigmentation suggested an acute presentation, potentially contributing to the favorable outcome; and (iii) the absence of comorbidities potentially positively impacted the patient's outcome. Symptoms of adrenal insufficiency are often nonspecific and may only become apparent once significant damage has occurred to the adrenal gland. Clinical adjustments and a comprehensive understanding of epidemiological knowledge are necessary for diagnosing patients with endocrine diseases in limited-resource settings. Complete recovery in primary adrenal insufficiency caused by tuberculosis infection might be due to younger age, acute presentation, and absence of comorbidities.


Imaging of Ocular Angle Structures with Fourier Domain Optical Coherence Tomography.
Imaging of the Schlemm's Canal is complicated by the small physiological size and the location several hundred microns beneath the sclera. Noninvasive imaging of Schlemm's canal and Trabecular Meshwork (TM) in vivo with Fourier Domain Optical Coherence Tomography (FD OCT) can provide clinicians with a powerful tool to visualize ocular angular structures crucial for glaucoma management. To investigate the appearance of Schlemm's canal and TM on FD OCT images. FD OCT images of the Schlemm's canal and TM were obtained with three different wavelengths using prototype FD OCT systems in a normal volunteer. FD OCT images using the 1310 nm wavelength prototype were obtained in three representative cases of glaucoma surgery performed on angle structures. The longer imaging depth and deeper tissue penetration of the 1310 nm system provided the clearest image of the TM and Schlemm's canal in the normal patient. In case 1, images pre- and post-trabectome surgery clearly showed the location and appearance of TM. In case 2, images post-canaloplasty surgery showed the location and appearance of Schlemm's canal. In case 3, images pre- and post-trabeculotomy surgery further confirms the appearance and location of the Schlemm's canal and TM. Operating wavelength of the FD OCT system and exact location of the scan across different meridians minimally affects the appearance of the ocular anatomy. The postoperative images of three angle glaucoma surgeries confirmed the location of Schlemm's canal and TM. How to cite this article: Asrani S, Young M, Xu J, Sarunic MV. Imaging of Ocular Angle Structures with Fourier Domain Optical Coherence Tomography. J Current Glau Prac 2013;7(2):85-87.


Complement-dependent killing of Nippostrongylus brasiliensis infective larvae by rat alveolar macrophages.
Histopathological studies have provided circumstantial evidence that helminth parasite destruction occurs in the lung; however controlled in vitro studies on the helminthocidal activity of lung cells have not been reported. This study presents evidence that Nippostrongylus brasiliensis infection in the rat induces alterations in broncho-alveolar lavage (BAL) cell numbers, differential counts, and in vitro helminthocidal activity. Normal, uninfected rats yielded 3.3 +/- 0.6 X 10(6) BAL cells/rat, consisting predominantly of alveolar macrophages (greater than 90%). However on days 2-8 post-infection there was a 1.5-2.4-fold increase in BAL cell numbers with a significant neutrophilia on day 2 and a significant increase in the absolute number of all cell types on day 8. On day 32 post-infection, BAL cell numbers had returned to control levels. Normal BAL cells neither adhered to nor killed N. brasiliensis infective larvae (L3) in the presence of rat complement. By contrast BAL cells recovered from infected rats on days, 2, 8 or 32 post-infection (D2, D8 and D32 BAL cells, respectively) adhered under similar conditions. However, only D8 and D32 BAL cells killed L3. This complement-dependent killing correlated with significantly increased numbers of C3 receptor bearing alveolar macrophages in D8 and D32 BAL cells. Complement-dependent alveolar macrophage helminthocidal activity may therefore play an important role in lung resistance against resident or migrating helminths.


Antioxidant activity, reducing power and total phenolic content of some lichen species.
The total antioxidant activity, total phenolic content and reducing power of methanol and water extracts of four lichen species, Bryoria fuscescens, Dermatocarpon intestiniformis, Peltigera rufescens and Pseudevernia furfuracea, were determined in vitro. Water and methanol extracts of P. rufescens showed the highest antioxidant activity. However, there was no correlation between antioxidant activity and total phenolic content of the extracts. Although the methanol extract of P. furfuracea had the highest total phenolic contents, it exhibited low antioxidant activity. In contrast, there was a strong correlation between reducing power and total antioxidant activity of the extracts. The highest reducing power was determined for the methanol extract of P. rufescens.


Terminal patient care: advantages on the applicability of anticipated will directives in the hospital context.
To know the advantages related to the applicability of the advance directives of will in the hospital context from the perspective of nurses, doctors and family members. Qualitative, descriptive and exploratory study with semi structured interviews carried out from October to November 2014, with nurses, doctors and family members of patients in the final stage. Afterwards, a discursive textual analysis was carried out. Four categories emerged: respect for patient's autonomy; support in confrontation of conflicts with and from family members; reduction of conflicts in the team about treatments and conducts; disclosure and instrumentation for application of the Advance Directives of Will. The respect for personal autonomy permeates the advantages when relating the conduct of treatments at the end of life with the Advance Directives of Will. Thus, disagreements involving the processes at the end of life would be supported by the patient's desire, besides implying in the reduction of the fear of professionals in facing lawsuits and in the support of the family.


Risk assessment for fetal toxicity.
This paper reviews the problem of performing risk assessments using data on fetal toxic effects. It briefly discusses the usual dose-response models and their inappropriateness for application to such data. The paper then considers tests for determining whether the fetal toxic effect is increased over that of the control group. Assuming an increase has been shown, the use of a fetal toxicity, dose-response model for risk assessment is discussed. The paper then applies these methods to data from an experiment using female mice mated with irradiated males. Finally, the paper discusses the need for further statistical research in this important area.


Economic probes of mental function and the extraction of computational phenotypes.
Economic games are now routinely used to characterize human cognition across multiple dimensions. These games allow for effective computational modeling of mental function because they typically come equipped with notions of optimal play, which provide quantitatively prescribed target functions that can be tracked throughout an experiment. The combination of these games, computational models, and neuroimaging tools open up the possibility for new ways to characterize normal cognition and associated brain function. We propose that these tools may also be used to characterize mental dysfunction, such as that found in a range of psychiatric illnesses. We describe early efforts using a multi-round trust game to probe brain responses associated with healthy social exchange and review how this game has provided a novel and useful characterization of autism spectrum disorder. Lastly, we use the multi-round trust game as an example to discuss how these kinds of games could produce novel bases for representing healthy behavior and brain function and thus provide objectively identifiable subtypes within a broad spectrum of mental function.


A Spatial-Temporal Graph Attention Network for Automated Detection and Width Estimation of Cortical Spreading Depression Using Scalp EEG.
We present an end-to-end Spatial-Temporal Graph Attention Network (STGAT) for non-invasive detection and width estimation of Cortical Spreading Depressions (CSDs) on scalp electroencephalography (EEG). Our algorithm, that we refer to as CSD Spatial-temporal graph attention network or CSD-STGAT, is trained and tested on simulated CSDs with varying width and speed ranges. Using high-density EEG, CSD-STGAT achieves less than 10.96% normalized width estimation error for narrow CSDs, with an average normalized error of 6.35%±3.08% across all widths, enabling non-invasive and automated estimation of the width of CSDs for the first time. In addition, CSD-STGAT learns the temporal and spatial features of CSDs simultaneously, which improves the "spatio-temporal tracking accuracy" (i.e., the defined detection performance metric at each electrode) of the narrow CSDs by up to 14%, compared to the state-of-the-art CSD-SpArC algorithm, with only one-tenth of the network size. CSD-STGAT achieves the best spatio-temporal tracking accuracy of 86.27%±0.53% for wide CSDs using high-density EEG, which is comparable to the performance of CSD-SpArC with less than 0.38% performance reduction. We further stitch the detections across all electrodes and over time to evaluate the "temporal accuracy". Our algorithm achieves less than 0.7% false positive rate in the simulated dataset with inter-CSD intervals ranging from 5 to 60 minutes. The lightweight architecture of CSD-STGAT paves the way towards real-time detection and parameter estimation of these waves in the brain, with significant clinical impact.


[Anti-VEGF therapy resistance in neovascular age-related macular degeneration].
With account to the increase in the elderly population in most of the developed countries, the WHO defines age-related macular degeneration (AMD) as one of the main causes of blindness in the world. A large percentage of disability is accounted for by exudative, or neovascular, form of AMD. Today, a total of 5 anti-VEGF drugs exist that are recommended for treatment of exudative AMD: pegaptanib, ranibizumab, bevacizumab, aflibercept, and conbercept. Despite significant progress in the treatment of neovascular AMD yielded by the introduction into clinical practice of anti-VEGF drugs, some patients report a lack (down to complete lack) of response with standard treatment patterns and even a decrease in treatment efficacy after repeated intravitreal injections.


[Smoking and blood pressure: A complex relationship].
Hypertension and tobacco smoking are two major modifiable risk factors for atheromatous disease and its cardiovascular complications. If systolic hypertension (SBP≥140mmHg and DBP<90mmHg) is the leading risk factor for stroke, smoking (nicotine) has a more powerful impact on coronary events, aortic aneurysms, and peripheral artery disease. Smoking can transiently modify the regulation of blood pressure (BP) by a swift effect on the autonomic nervous system. It also accelerates arterial aging, which plays a role in chronic hypertension. Chronic sympathetic activation induced by tobacco smoking also has some involvement in lipid metabolism and insulin resistance, both implicated in atheromatous disease. Thus, smoking can contribute to the development of atheromatous renal artery stenosis, which is an aggravating cause of hypertension. It may also reduce the effectiveness of most antihypertensive drugs. Finally, it is often associated with increased alcohol consumption. All these factors may contribute to poor blood pressure control in these high-risk CV patients. Smoking cessation is effective regardless of patient age and length of consumption. Every effort should thus be made to support smoking cessation. This is the objective of the French "Plan Sans Tabac" (No Tobacco Plan) and the related actions conducted by the French Federation of Cardiology.


Improved computer-aided detection of small polyps in CT colonography using interpolation for curvature estimation.
Surface curvatures are important geometric features for the computer-aided analysis and detection of polyps in CT colonography (CTC). However, the general kernel approach for curvature computation can yield erroneous results for small polyps and for polyps that lie on haustral folds. Those erroneous curvatures will reduce the performance of polyp detection. This paper presents an analysis of interpolation's effect on curvature estimation for thin structures and its application on computer-aided detection of small polyps in CTC. The authors demonstrated that a simple technique, image interpolation, can improve the accuracy of curvature estimation for thin structures and thus significantly improve the sensitivity of small polyp detection in CTC. Our experiments showed that the merits of interpolating included more accurate curvature values for simulated data, and isolation of polyps near folds for clinical data. After testing on a large clinical data set, it was observed that sensitivities with linear, quadratic B-spline and cubic B-spline interpolations significantly improved the sensitivity for small polyp detection. The image interpolation can improve the accuracy of curvature estimation for thin structures and thus improve the computer-aided detection of small polyps in CTC.


Fate, occurrence and potential adverse effects of antimicrobials used for treatment of tuberculosis in the aquatic environment in South Africa.
The consumption of tonnes of anti-tubercular and other anti-microbial compounds for the control of the tuberculosis epidemic and other opportunistic diseases associated with human immunodeficiency virus presents tuberculosis-endemic countries such as South Africa, with a problem regarding the occurrence and fate of these compounds in the aquatic environment. The majority of these compounds are not readily degradable and could persist in the aquatic environment with potential detrimental effect on the aquatic microbiota ecosystem, development and dissemination of anti-microbial resistance as well as chronic toxicity in humans due to long-term exposure. This review summarises and discusses the occurrence, fate and potential adverse effects of the commonly administered anti-tubercular compounds in the aquatic environment in tuberculosis-endemic countries and South Africa in particular. It further attempts to identify information gaps in the literature regarding anti-tubercular compounds in the environment that needs further investigation so that their risk can be comprehensively assessed and impact mitigated.


[Food habits and consumption of French adolescents. Synthesis of recent surveys].
Studies concerning French adolescents' eating habits have been published during the past four years. The review of such studies shows that nutrient intakes and food consumption are close to those of the adult population. Only the amount of nutrients especially with respect to lipids seems to be more satisfactory than in adults. This observation emphasizes the importance of familial environmental as the main factor of eating habits. French adolescents eat as the preceding generation even if some behaviors (snacks, fastfood) may appear very different from those in adults. However, this similitude does not imply that such habits are satisfactory.


Synthesis, inhibition properties against xanthine oxidase and molecular docking studies of dimethyl N-benzyl-1H-1,2,3-triazole-4,5-dicarboxylate and (N-benzyl-1H-1,2,3-triazole-4,5-diyl)dimethanol derivatives.
This study focused on synthesis various dimethyl N-benzyl-1H-1,2,3-triazole-4,5-dicarboxylate and (N-benzyl-1H-1,2,3-triazole-4,5-diyl)dimethanol derivatives under the conditions of green chemistry without the use of solvent and catalysts. Their inhibition properties were also investigated on xanthine oxidase (XO) activity. All dimethanol and dicarboxylate derivatives exhibited significant inhibition activities with IC50 values ranging from 0.71 to 2.25 μM. Especially, (1-(3-bromobenzyl)-1H-1,2,3-triazole-4,5-diyl)dimethanol (5c) and dimethyl 1-(4-chlorobenzyl)-1H-1,2,3-triazole-4,5-dicarboxylate (6 g) compounds were found to be the most promising derivatives on the XO enzyme inhibition with IC50 values 0.71 and 0.73 μM, respectively. Moreover, the double docking procedure was to evaluate compound modes of inhibition and their interactions with the protein (XO) at atomic level. Surprisingly, the docking results showed a good correlation with IC50 [correlation coefficient (R2 = 0.7455)]. Also, the docking results exhibited that the 5c, 6f and 6 g have lowest docking scores -4.790, -4.755, and -4.730, respectively. These data were in agreement with the IC50 values. These results give promising beginning stages to assist in the improvement of novel and powerful inhibitor against XO.


The Stretta procedure versus proton pump inhibitors and laparoscopic Nissen fundoplication in the management of gastroesophageal reflux disease: a cost-effectiveness analysis.
The Stretta procedure is an endoscopic therapy for gastroesophageal reflux disease. To evaluate the cost-effectiveness of the Stretta procedure and that of competing strategies in the long-term management of gastroesophageal reflux disease. A Markov model was designed to estimate costs and health outcomes in Canadian patients with gastroesophageal reflux disease over five years, from a Ministry of Health perspective. Strategies included the use of daily proton pump inhibitors (PPIs), laparoscopic Nissen fundoplication (LNF) and the Stretta procedure. Probabilities and utilities were derived from the literature. Costs are expressed in 2006 Canadian dollars. Units of effectiveness were symptom-free months (SFMs) and quality-adjusted life years (QALYs), using a five-year time horizon. In the analysis that used SFMs, the strategy using PPIs exhibited the lowest costs ($40 per SFM) and the greatest number of SFMs, thus dominating both the LNF and Stretta systems. But the cost-effectiveness analysis using QALYs as the measure of effectiveness showed that PPIs presented the lowest cost-effectiveness ratio, while both the LNF and Stretta strategies were associated with very high incremental costs (approximately $353,000 and $393,000, respectively) to achieve an additional QALY. However, the PPI strategy did not dominate the two other strategies, which were associated with better effectiveness. If SFMs are used as the measure of effectiveness, PPIs dominate the Stretta and LNF strategies. However, if QALYs are used, the PPIs still present the lowest cost and LNF gives the best effectiveness. Regardless of the units of effectiveness or utility used in the present cost analysis, an approach of prescribing PPIs appears to be the preferred strategy.


Evaluation of the role of black carbon in attenuating bioaccumulation of polycyclic aromatic hydrocarbons from field-contaminated sediments.
The significance of black carbon (BC) for the bioavailability of polycyclic aromatic hydrocarbons (PAHs) was examined by using historically contaminated intact sediment cores in laboratory exposure experiments with the deposit-feeding amphipod Monoporeia affinis. Log values of amphipod biota-sediment accumulation factors (BSAFs) were significantly related to log BC, whereas log BSAFs were related to log octanol-water partition coefficients only in background sediments containing less BC. In the background sediments, the BSAF for polycyclic aromatic hydrocarbons (PAHs) was 1 to 2 for phenanthrene, with lower values for more hydrophobic PAHs, indicating an increase in nonequilibrium conditions with increasing PAH molecular size. For the near-equilibrated phenanthrene and fluoranthene, higher BSAFs were measured during exposure to background sediments, with BSAF decreasing to <0.1 in contaminated sediments in the Stockholm waterways. In situ caged mussels (Dreissena polymorpha) exhibited field BSAF values (relative to sediment-trap-collected suspended matter) for polychlorinated biphenyls (PCBs) of 0.1 to 0.4, but for PAHs of similar hydrophobicity and molecular size, the field BSAFs were much lower and in the range 0.002 to 0.05. This PAH-PCB dichotomy is consistent with recently reported much stronger binding to diesel soot (a form of BC) for PAHs than for PCBs of equal hydrophobicities. Lower BSAFs for the near-equilibrated PAHs (phenanthrene and fluoranthene) in the urban sediments relative to the background sediments were consistent with the larger presence of BC in the urban sediments. This study provides the first linked BSAF-BC field data that supports a causal relationship between strong soot sorption and reduced bioavailability for PAHs.


HFE gene variants, iron, and lipids: a novel connection in Alzheimer's disease.
Iron accumulation and associated oxidative stress in the brain have been consistently found in several neurodegenerative diseases. Multiple genetic studies have been undertaken to try to identify a cause of neurodegenerative diseases but direct connections have been rare. In the iron field, variants in the HFE gene that give rise to a protein involved in cellular iron regulation, are associated with iron accumulation in multiple organs including the brain. There is also substantial epidemiological, genetic, and molecular evidence of disruption of cholesterol homeostasis in several neurodegenerative diseases, in particular Alzheimer's disease (AD). Despite the efforts that have been made to identify factors that can trigger the pathological events associated with neurodegenerative diseases they remain mostly unknown. Because molecular phenotypes such as oxidative stress, synaptic failure, neuronal loss, and cognitive decline, characteristics associated with AD, have been shown to result from disruption of a number of pathways, one can easily argue that the phenotype seen may not arise from a linear sequence of events. Therefore, a multi-targeted approach is needed to understand a complex disorder like AD. This can be achieved only when knowledge about interactions between the different pathways and the potential influence of environmental factors on them becomes available. Toward this end, this review discusses what is known about the roles and interactions of iron and cholesterol in neurodegenerative diseases. It highlights the effects of gene variants of HFE (H63D- and C282Y-HFE) on iron and cholesterol metabolism and how they may contribute to understanding the etiology of complex neurodegenerative diseases.


A comparison of intrathecal dexmedetomidine, clonidine, and fentanyl as adjuvants to hyperbaric bupivacaine for lower limb surgery: A double blind controlled study.
Various adjuvants are being used with local anesthetics for prolongation of intraoperative and postoperative analgesia. Dexmedetomidine, the highly selective 2 adrenergic agonist is a new neuraxial adjuvant gaining popularity. The study was conducted in prospective, double blind manner. It included 120 American Society of Anesthesiology (ASA) class I and II patients undergoing lower limb surgery under spinal anesthesia after approval from hospital ethics committee with written and informed consent of patients. The patients were randomly allocated into four groups (30 patients each). Group BS received 12.5 mg hyperbaric bupivacaine with normal saline, group BF received 12.5 mg bupivacaine with 25 g fentanyl, group BC received 12.5 mg of bupivacaine supplemented 30 g clonidine, and group BD received 12.5 mg bupivacaine plus 5 g dexmedetomidine. The onset time to reach peak sensory and motor level, the regression time of sensory and motor block, hemodynamic changes, and side effects were recorded. Patients in Group BD had significantly longer sensory and motor block times than patients in Groups BC, BF, and BS with Groups BC and BF having comparable duration of sensory and motor block. The mean time of two segment sensory block regression was 147 ± 21 min in Group BD, 117 ± 22 in Group BC, 119 ± 23 in Group BF, and 102 ± 17 in Group BS (P > 0.0001). The regression time of motor block to reach modified Bromage zero (0) was 275 ± 25, 199 ± 26, 196 ± 27, 161 ± 20 in Group BD, BC, BF, and BS, respectively (P > 0.0001). The onset times to reach T8 dermatome and modified Bromage 3 motor block were not significantly different between the groups. Dexmedetomidine group showed significantly less and delayed requirement of rescue analgesic. Intrathecal dexmedetomidine is associated with prolonged motor and sensory block, hemodynamic stability, and reduced demand of rescue analgesics in 24 h as compared to clonidine, fentanyl, or lone bupivacaine.


The combination of dietary conjugated linoleic acid and treadmill exercise lowers gain in body fat mass and enhances lean body mass in high fat-fed male Balb/C mice.
Nearly half of the U.S. adult population is overweight or obese, which may be related to increased energy intake combined with lack of physical activity. Obesity increases the risk of several chronic diseases including diabetes, coronary heart disease, hypertension, and stroke. Conjugated linoleic acids (CLA) were shown to decrease fat and increase lean mass in several animal studies. However, the effects of CLA in combination with exercise (Ex) on body composition have not been studied in an animal model. We examined the effect of a low concentration of either safflower oil as control (0.5%) or mixed isomers of CLA (0.4%) along with treadmill exercise on body composition in male Balb/C mice fed a high-fat diet (20% corn oil) in a 2 x 2 factorial design. CLA consumption lowered change in fat mass (P < 0.001) confirming the results of other studies, and change in fat mass decreased further (P < 0.001) with CLA and exercise. Change in lean mass did not increase with exercise alone; it increased, although not significantly, with CLA alone and increased significantly (P < 0.05) due to the combination of CLA and exercise. This effect was accompanied by decreased serum leptin levels and lower leptin mRNA expression in peritoneal fat (P < 0.001). Serum insulin, glucose, tumor necrosis factor (TNF)-alpha, and interleukin-6 were lower in CLA-fed mice than in controls (P < 0.05), whereas serum TNF-alpha was increased by exercise (P < 0.05). Exercise increased oxygen consumption and energy expenditure when measured under resting conditions (P < 0.05). In summary, the combination of dietary CLA and exercise decreased fat mass and increased lean mass in mice fed a high-fat diet, and these effects may be related in part to decreased serum leptin and exercise-induced increases in oxygen consumption and energy expenditure.


[Effect of total triterpenoids of Chaenomeles speciosa on PPARγ/SIRT1/NF-κBp65 signaling pathway and intestinal mucosal barrier of ulcerative colitis induced by DSS in mice].
To observe the effect of total triterpenoids of Chaenomeles speciosa on PPARγ/SIRT1/NF-κBp65 signaling pathway and intestinal mucosal barrier of ulcerative colitis induced by dextran sulfate sodium (DSS) in mice, C57BL/6 mice were randomly divided into normal group, model group, total triterpenoids of C. speciosa (50, 100 mg·kg⁻¹) groups and sulfasalazine (250 mg·kg⁻¹) group. The ulcerative colitis (UC) model was induced by orally administering 2.5% DSS to the experimental mice, and the corresponding drugs were given to each group 3 days before the administration with 2.5% DSS. The normal group and the model group were given the equal volume of 0.5% carboxymethyl cellulose sodium solution by gavage continuously for 10 days, q.d. The general conditions of the mice were observed on a daily basis, and the disease activity index (DAI) score was recorded. On the 10th day after the treatment, mice were put to death, the contents of TNF-α, IL-1β, IL-6, IFN-γ, IL-4 and IL-10 in the blood were detected, colon length was measured, colon mucosa damage index (CMDI) score was calculated, and MPO activity detection and histomorphology analysis were conducted. Real-time PCR was applied to detect the mRNA expressions of E-cadherin, occluding,MUC2 and TFF3; the protein expressions of SIRT1, IKKβ, p-IKKβ, IκBα, p-IκBα and cytosol and nucleus PPARγ, NF-κBp65 in intestinal tissue were detected by western blot. The results indicated that total triterpenoids of C. speciosa (50, 100 mg·kg⁻¹) could significantly improve the general conditions of UC mice, reduce the DAI, CMDI and histopathological scores, increase the colon length, reduce the colonic mucosa ulcers, erosion and inflammatory infiltration, restore the normal intestinal mucosal barrier function, reduce the contents of TNF-α, IL-1β, IL-6, IFN-γ, increase the contents of IL-4 and IL-10 in the blood, inhibit MPO activity in colon tissue, up-regulate the mRNA expressions of E-cadherin, occludin, MUC2 and TFF3 in colon tissue, down-regulate the protein expressions of cytosol PPARγ, tissue p-IKKβ, p-IκBα and nucleus NF-κBp65 in the colon tissue, decrease the p-IKKβ/IKKβ and p-IκBα/IκBα ratios, up-regulate the protein expressions of nucleus PPARγ, tissue SIRT1 and cytosol NF-κBp65 (P<0.05 or P<0.01, respectively), with a dose-effect relationship between the total triterpenoids of C. speciosa treated groups. These findings suggested that total triterpenoids of C. speciosa had a significantly therapeutic effect on UC mice induced by DSS, its mechanism might be related to the regulation of PPARγ/SIRT1/NF-κBp65 signaling pathway, the inhibition of pro-inflammatory factor formation and the up-regulation of protein expression of protective factors.


How Japanese nurses provide care: a practice based on continuously knowing the patient.
Criticisms of the nursing process as a problem-solving approach have emerged recently. This study aimed to identify and describe a way of nursing based on the clinical practice of selected nurses in Japan. Data were collected using semi-structured interviews and observations at one 300-bed Japanese hospital in 1999. The purposive sample consisted of 24 female nurses. Data analysis occurred simultaneously with data collection, and questioning and constant comparison were used for data analysis. Codes were clustered into categories and relationships among these were identified. In the final stage of the analysis, two group interviews with participants were carried out to enhance credibility. This study identified a Japanese way of nursing intended to help patients explore and realize meanings and values of their experiences with illness. When nurses first contacted a patient, they quickly formed a patient image, but altered it each time they obtained new patient information. A patient image consisted of the patient's subjective world (the patient's perspective) and the holistic patient (nurses' perspectives of the patient). The nurses sometimes pursued strategies to know the patient's subjective world. The target, direction, conditions and ways of nursing care were decided based on continuously knowing the patient. The nurses related their knowledge and thoughts to the patient, and by talking with the patient promoted the patient's consideration and participation, and empowered the patient. Nurses continued attending to patients even when they could not provide specific nursing interventions. Knowing the patient was found to be especially important in determining nursing care. The model described in this study does not contradict the nursing process as a systematic approach to problem-solving. Rather, it has some alternatives that might be useful in providing individual care in Japan.


The effects of cost sharing on access to care among childless adults.
To analyze the impact of public health insurance expansions and the use of enrollee cost sharing on insurance status and receipt of clinically indicated preventive screenings and physician services. This study uses Behavioral Risk Factor Surveillance System (BRFSS) data from 1997 to 2007. This study uses multivariate difference-in-difference logistic regression modeling of pooled cross-sectional time series data. The effect of the expansions on insurance status and access to care is identified by cross-state variation in program implementation, as well as cross-state and within-state variation in program eligibility criteria over time. Childless adult expansions, regardless of cost-sharing levels, reduced uninsurance rates and decreased the likelihood that childless adults needed to see a physician but did not because of cost. Expansions with traditional public insurance cost-sharing requirements increased the use of preventive screenings, while expansions with increased cost-sharing requirements did not. Cost-sharing requirements did not have an impact on the ability to see a physician when needed, but they played an important role in the utilization of preventive services. Expanding public health insurance to low-income, childless adults presents a promising policy opportunity, but there are trade-offs between the efficiencies obtained through increased cost sharing and the potential inefficiencies due to the lower use of preventive services.


Estimates and Temporal Trend for US Nationwide 30-Day Hospital Readmission Among Patients With Ischemic and Hemorrhagic Stroke.
Readmission reduction is linked to improved quality of care, saves cost, and is a desirable patient-centered outcome. Nationally representative readmission metrics for patients with stroke are unavailable to date. Such estimates are necessary for benchmarking performance. To provide US nationwide estimates and a temporal trend for overall, planned, and potentially preventable 30-day hospital readmission among patients with ischemic and hemorrhagic stroke; to investigate the association between hospitals' stroke discharge volume, teaching status, and 30-day readmission; and to highlight reasons for 30-day readmission and explore the association of 30-day readmission in terms of mortality, length of stay, and cost of care among patients with stroke. Cohort, year-wise analysis of the Nationwide Readmissions Database between January 1, 2010, and September 30, 2015. The setting was a population-based cohort study providing national estimates of 30-day readmission. The database represents 50% of all US hospitalizations from 22 geographically dispersed states. Participants were adult (≥18 years) patients with a primary discharge diagnosis of intracerebral hemorrhage, acute ischemic stroke, or subarachnoid hemorrhage. Hospitals were categorized by their annual stroke discharge volume and were classified as teaching hospitals if they had an American Medical Association-approved residency program or had a ratio of full-time equivalent interns and residents to beds of 0.25 or higher. Readmission was defined as any admission within 30 days of index hospitalization discharge. Using Centers for Medicare & Medicaid Services-defined algorithms, events were classified as planned or unplanned and as potentially preventable. Based on study criteria, 2 078 854 eligible patients were included (mean [SE] age, 70.02 [0.07] years; 51.9% female). Thirty-day readmission was highest for patients with intracerebral hemorrhage (13.70%; 95% CI, 13.40%-13.99%), followed by patients with acute ischemic stroke (12.44%; 95% CI, 12.33%-12.55%) and patients with subarachnoid hemorrhage (11.48%; 95% CI, 11.01%-11.96%). On average, there was a 3.3% annual decline in readmission between 2010 and 2014, which was statistically significant for the period of investigation (odds ratio, 0.96; 95% CI, 0.95-0.97). Patients discharged from nonteaching hospitals with high stroke discharge volume were at a significantly higher risk of 30-day readmission, and the top 2 reasons for readmission were acute cerebrovascular disease and septicemia. This study suggests that nationally representative readmission metrics can be used to benchmark hospitals' performance, and a temporal trend of 3.3% may be used to evaluate the effectiveness of readmission reduction strategies.


Effect of microabrasion on the staining susceptibility of enamel: An in vitro study.
Background. Enamel microabrasion can eliminate enamel irregularities and discoloration. This study evaluated the staining susceptibility of enamel after microabrasion using different clinical protocols. Methods. A total of 210 extracted bovine incisors were used in this study. The teeth were randomly divided into five groups of 42 teeth each (n=42), including group 1: control (no treatment), group 2: microabrasion, group 3: microabrasion + fluoride polishing, group 4: macroabrasion (fine-grit diamond bur) + microabrasion, and group 5: macroabrasion (finegrit diamond bur) + microabrasion + fluoride polishing. The groups were then randomly divided into two subgroups for discoloration procedures: coffee and distilled water (n=21). A spectrophotometric evaluation was carried out at baseline and on the 1st, 7th, 14th, and 28th days of the staining period. Statistical analyses were performed using repeated-measures ANOVA and the post hoc Bonferroni test at a significance level of 0.05. Results. The greatest color change was observed in group 2 specimens, which were immersed in coffee solutions. The color change values for groups 3, 4, and 5 specimens, which were immersed in distilled water, were higher than those in group 1 specimens (P<0.05). The fluoride polishing + enamel microabrasion treatment groups (groups 3 and 5) exhibited greater resistance to color changes than the matched non-fluoride-polished groups (groups 2 and 4) (P<0.05). Conclusions. The teeth that underwent enamel microabrasion treatment and were polished with fluoride gel became more resistant to color changes. Our findings confirm that enamel microabrasion treatment is a conservative method for localized discoloration.


Disruption of MyD88 signaling suppresses hemophagocytic lymphohistiocytosis in mice.
Hemophagocytic lymphohistiocytosis (HLH) is a rare inflammatory disorder with a poor prognosis for affected individuals. To find a means of suppressing the clinical phenotype, we investigated the cellular and molecular mechanisms leading to HLH in Unc13d(jinx/jinx) mice, in which cytolytic function of NK and CD8(+) T cells is impaired. Unc13d(jinx/jinx) mutants infected with lymphochoriomeningitis virus (LCMV) present typical clinical features of HLH, including splenomegaly, elevated serum IFNγ, and anemia. Proteins mediating cell-cell contact, cytokine signaling or Toll-like receptor (TLR) signaling were analyzed. We show that neither the integrin CD18, which is involved in adhesion between antigen-presenting cells and effector T cells, nor tumor necrosis factor (TNF) made nonredundant contributions to the disease phenotype. Disruption of IFNγ signaling reduced immune cell activation in Unc13d(jinx/jinx) mice, but also resulted in uncontrolled viral proliferation and exaggerated release of inflammatory cytokines. Abrogating the function of myeloid differentiation primary response gene 88 (MyD88) in Unc13d(jinx/jinx) mice suppressed immune cell activation and controlled cytokine production in an IL-1 receptor 1 (IL-1R1)-independent way. Our findings implicate MyD88 as the key initiator of myeloid and lymphoid proliferation in HLH, and suggest that blockade of this signaling molecule may reduce immunopathology in patients.


[EDP-adapted grid model of the brain for topographic analysis of lesions on the cranial computer tomogram].
A method for the recording and statistical evaluation of computer tomographic morphological data is described. The lesions demonstrated by computer tomography are transferred to a sectional model of the brain on which a grid is superimposed. The sections and grid are then transferred to the Evaluscope (Siemens) and the original CT lesion is recorded with a light-pen and then stored. Statistical evaluation of the data can be carried out centrally and can be combined with the results of other clinical studies.


Presynaptic terminals in hyaline cells of normal and overstimulated chick inner ears.
Hyaline cells are non-sensory epithelial cells of the vibrating part of the basilar membrane of chicks; they receive an extensive efferent innervation. Although these anatomical features suggest roles in auditory transduction, very little is known about the function of these cells. One possible way to understand function is by lesion experiments. We used synapsin-specific antibodies to study changes that occur in the pattern of efferent innervation in hyaline cells after lesion of the sensory epithelium induced by acoustic overstimulation. We found only small changes in hyaline cells after such trauma. These included a small increase in size and a small decrease in density of nerve terminals on hyaline cells. This suggests that hyaline cells and their nerve terminals are less susceptible to acoustic trauma than hair cells. Using neurofilament-specific antibodies we found little or no trauma-induced change in the density of nerve fibres that cross the basilar papilla and reach the hyaline cell region. This finding suggested that trauma to the hair cells does not necessarily lead to changes in the efferent fibres that cross the papilla and extend into the hyaline cell region. Using the trauma and the morphological parameters studied here, it appears that a moderate lesion in the hair cell region in the avian inner ear does not influence the hyaline cells or their innervation.


Retention of tissue texture change after cervical muscle energy and high velocity low amplitude intervention: implications for treatment intervals.
When choosing to incorporate osteopathic manipulative treatment (OMT) into a patient's care, the risk-to-benefit ratio, the choice of treatment technique, as well as the frequency of treatments are always taken into consideration. This has been even more important during the COVID-19 pandemic, in which social distancing has been the best preventative measure to decrease exposure. By increasing treatment intervals, one could not only limit possible exposure/spread of viruses but also decrease the overall cost to the system as well as to the individual. This is an expansion of a previous study in which quantifiable changes in cervical hysteresis characteristics post-OMT were documented utilizing a durometer (Ultralign SA201®; Sigma Instruments; Cranberry, PA USA). This study compared two treatment modalities, muscle energy (ME) and high-velocity low-amplitude (HVLA) postcervical treatment. Subjects in this study were allowed to re-enroll, provided that they could be treated utilizing the alternate treatment modality. By allowing repeat subjects, analysis of the data for lasting effects of OMT could be observed. To determine whether a significant change in cervical hysteresis would be observed after each treatment regardless of a short treatment interval. A total of 34 subjects were retrospectively noted to be repeat subjects from a larger, 213-subject study. These 34 subjects were repeat participants who were treated with two different direct-treatment modalities 7-10 days apart. Each subject was randomly assigned to receive a single-segmental ME or HVLA treatment technique directed toward a cervical (C) segment (C3-C5 only). Subjects were objectively measured pretreatment in all cervical segments utilizing the Ultralign SA201®, then treated with cervical OMT to a single segment, and finally reassessed at all cervical levels with the Ultralign SA201® posttreatment to assess for change in cervical hysteresis. Statistically significant or suggestive changes (p-values 0.01-0.08) with good clinical effect size (0.30 or greater) were noted in all four components of the Ultralign SA201® at multiple cervical levels after the first treatment, but only one component (frequency) had a statistically significant change after the second treatment (AA cervical level, p-value 0.01) with good clinical effect size (0.45). However, when comparing the post-first-treatment values to the pre-second-treatment values, no statistically significant differences (p-value 0.10 or higher) were observed between them. Statistically significant changes were noted after the first treatment; however, when comparing cervical hysteresis changes after the first treatment to the cervical hysteresis values prior to the second treatment delivered 7-10 days later, there were no statistically significant or suggestive changes. This data suggest that several post-OMT changes noted after the first treatment were still in effect and may indicate that follow-up visits for direct manipulation may be deferred for a least two weeks.


Bisphosphonates can block the deterioration in implant fixation after withdrawal of intermittent doses of parathyroid hormone.
We have examined the deterioration of implant fixation after withdrawal of parathyroid hormone (PTH) in rats. First, the pull-out force for stainless-steel screws in the proximal tibia was measured at different times after withdrawal. The stimulatory effect of PTH on fixation was lost after 16 days. We then studied whether bisphosphonates could block this withdrawal effect. Mechanical and histomorphometric measurements were conducted for five weeks after implantation. Subcutaneous injections were given daily. Specimens treated with either PTH or saline during the first two weeks showed no difference in the mechanical or histological results (pull-out force 76 N vs 81 N; bone volume density 19% vs 20%). Treatment with PTH for two weeks followed by pamidronate almost doubled the pull-out force (152 N; p < 0.001) and the bone volume density (37%; ANOVA, p < 0.001). Pamidronate alone did not have this effect (89 N and 25%, respectively). Thus, the deterioration can be blocked by bisphosphonates. The clinical implications are discussed.


Brain histology.
In this article we summarise nervous system histology in health and disease and acquaint the reader with developments in the staining techniques that are in current use, particularly immunostains. Although clinicians do not need to know the details of stain appearances, some familiarity with these aspects of neuropathology is invaluable in interpreting the reports they receive from the laboratory, as well as reminding them of the amazing beauty of the central nervous system's microscopic structure.


Spatial control of a classical electron state in a Rydberg atom by adiabatic synchronization.
An adiabatic synchronization approach is used to control orbital eccentricity and inclination of a highly excited electron in a hydrogen atom. The approach is based on persisting nonlinear phase locking (autoresonance) between spatially uniform, chirped frequency oscillating electric field, and the classical Keplerian motion of the electron in the atom. Efficient control in three dimensions is achieved by slow passage through and capture into different resonances. Scenarios guaranteeing the capture and continuing synchronization in the system are outlined, all requiring the driving field amplitude to exceed a threshold. The threshold scales as A(3/4), where A is the sweep rate of the driving frequency at resonance. The adiabatic synchronization allows one to accelerate the electron gradually by using dipolar fields, until approaching the stochastic ionization limit.


The Effect of School Bullying on Pupils' Perceived Stress and Wellbeing During the Covid-19 Pandemic: A Longitudinal Study.
Establishing how the Covid-19 pandemic and related lockdowns have affected adolescent mental health is a key societal priority. Though numerous studies have examined this topic, few have focused on the wellbeing of pupils who experience school bullying. This is particularly important as pupils who experience bullying represent a vulnerable group at increased risk of mental illness. Therefore, we sought to investigate the relationship between experience of bullying and adolescent wellbeing during lockdown and subsequent re-opening of schools. We used the TeenCovidLife dataset to examine the relationship between experience of bullying and pupils' perceived stress and wellbeing across three timepoints. Pupils aged 12-17 (n = 255) completed surveys during the first Covid-19 lockdown (May-July 2020), when they returned to school after the first lockdown (August-October 2020), and during the summer term of 2021 (May-June 2021). Perceived stress was higher in the group of pupils that experienced bullying than in the group that did not, though this difference between groups was smaller during lockdown than when pupils were attending school in person. Pupils who were bullied showed lower wellbeing across all timepoints. For the full sample of pupils, wellbeing was lowest (and perceived stress highest) at Time 3, one year after the first Covid-19 lockdown. The findings challenge previous assumptions that Covid-19 lockdowns were associated with a generalised decline in adolescent mental health. Instead, the picture is more nuanced, with perceived stress, though not wellbeing, varying according pupils' experiences of school bullying.


Exploring the feasibility of using evidence-based feeding practices to promote children's healthy eating in holiday clubs.
Encouraging healthy eating is a public health priority in the United Kingdom (UK), given the high prevalence of poor diet and overweight/obesity among school-aged children. Holiday clubs are organisations providing childcare and activities during the school holidays and frequently provide food to children at risk of food insecurity, primarily through government-funded programmes like the Holiday Activities and Food programme. However, the research suggests that holiday clubs could do more to maximise opportunities to promote children's healthy eating by using evidence-based feeding practices. During August-September 2020, video-based interviews were conducted exploring staff perceptions of the feasibility of using four evidence-based feeding practices to promote children's healthy eating: modelling; involvement in food choice; involvement in food preparation and cooking and involvement in meal planning. Feasibility was assessed using four dimensions of a feasibility framework (acceptability, demand, practicality and implementation). UK holiday clubs. Twenty-five staff actively involved in delivering UK holiday clubs (project leaders, coordinators, cooks and coaches/youth workers). Staff generally reported good acceptability (dimension 1) and demand (dimension 2) for the feeding practices. However, the practicality (dimension 3) of using the practices was dependent on various factors (logistics, resources, staff readiness, children, peers and parents). Promisingly, in the fourth feasibility dimension (implementation), staff provided numerous practical solutions to overcome these barriers. Evidence-based feeding practices can be implemented in numerous ways and are therefore generally feasible in holiday clubs. Holiday clubs should be empowered to use evidence-based feeding practices through training resources, sharing networks and provision of sustainable funding.


The Drosophila kinesin-like protein KLP67A is essential for mitotic and male meiotic spindle assembly.
We have performed a mutational analysis together with RNA interference to determine the role of the kinesin-like protein KLP67A in Drosophila cell division. During both mitosis and male meiosis, Klp67A mutations cause an increase in MT length and disrupt discrete aspects of spindle assembly, as well as cytokinesis. Mutant cells exhibit greatly enlarged metaphase spindle as a result of excessive MT polymerization. The analysis of both living and fixed cells also shows perturbations in centrosome separation, chromosome segregation, and central spindle assembly. These data demonstrate that the MT plus end-directed motor KLP67A is essential for spindle assembly during mitosis and male meiosis and suggest that the regulation of MT plus-end polymerization is a key determinant of spindle architecture throughout cell division.


Low-loss germanium strip waveguides on silicon for the mid-infrared.
Mid-infrared photonics in silicon needs low-loss integrated waveguides. While monocrystalline germanium waveguides on silicon have been proposed, experimental realization has not been reported. Here we demonstrate a germanium strip waveguide on a silicon substrate. It is designed for single mode transmission of light in transverse magnetic (TM) polarization generated from quantum cascade lasers at a wavelength of 5.8 μm. The propagation losses were measured with the Fabry-Perot resonance method. The lowest achieved propagation loss is 2.5 dB/cm, while the bending loss is measured to be 0.12 dB for a 90° bend with a radius of 115 μm.


Using item response theory to understand comorbidity among anxiety and unipolar mood disorders.
The authors hypothesized that anxiety and unipolar mood disorders are often comorbid because each disorder indicates a broad, higher order factor. In a clinical subsample of the nationally representative National Comorbidity Survey participants (N = 251), a one-factor model fit the correlations among 7 dichotomous anxiety and unipolar mood diagnoses. Following the lead provided by literature on the structure of emotional and behavioral problems in children, we labeled this factor internalizing. Item response theory was used to explore how each diagnosis mapped onto the internalizing factor. The test information function derived from the 7 diagnoses suggested that they measure primarily the higher end of the factor. In addition, very high scores on internalizing (meeting criteria for 6-7 disorders) were associated with increased social costs, a phenomenon not well captured by the "comorbidity" concept. The results underscore the need to develop clinical assessment instruments that span the full range of the internalizing factor and measure both the shared and distinctive features of anxiety and unipolar mood disorders in a graded, continuous fashion.


Blood data trends of children in Fukushima after the Great East Japan Earthquake: Fukushima health management survey.
After the Great East Japan Earthquake on March 11, 2011 and the subsequent accident at the Tokyo Electric Power Company-operated Daiichi Nuclear Power Plant, the Fukushima Prefecture government initiated the Fukushima Health Management Survey (FHMS) to assess the long-term health effects of the disaster on Fukushima residents. The blood tests of children aged ≤15 years between 2011 and 2012 did not reveal any changes regarding peripheral blood data; however, long-term monitoring is still necessary. Therefore, this study aimed to investigate the long-term health status of children aged ≤15 years who had evacuated the Fukushima Prefecture. From 2011 to 2018, 71,250 evacuees aged 15 years or younger participated in the FMHS and were subjected to blood tests. By analyzing the data of the comprehensive health check survey managed by the FHMS, we examined the changes in hemoglobin (Hb) levels, white blood cell (WBC) counts, including fractions, and platelet (PLT) counts among children from 2011 to 2018. Minor fluctuations in Hb levels, PLT counts, and WBC counts were observed during the study period, but the central 95% intervals of distribution of the laboratory values were generally within previously reported reference intervals. In particular, there was no increase in the proportions of patients with anemia, polycythemia, or deviating WBC counts. From 2011 to 2018, there was no increase in the percentages of children with anemia, polycythemia, or deviating WBC counts among the Fukushima Prefecture evacuees.


Insights into ZmWAKL in maize kernel development: genome-wide investigation and GA-mediated transcription.
The functional roles of the Wall Associated Kinase (WAK) and Wall Associated Kinase Like (WAKL) families in cellular expansion and developmental processes have been well-established. However, the molecular regulation of these kinases in maize development is limited due to the absence of comprehensive genome-wide studies. Through an in-depth analysis, we identified 58 maize WAKL genes, and classified them into three distinct phylogenetic clusters. Moreover, structural prediction analysis showed functional conservation among WAKLs across maize. Promoter analysis uncovered the existence of cis-acting elements associated with the transcriptional regulation of ZmWAKL genes by Gibberellic acid (GA). To further elucidate the role of WAKL genes in maize kernels, we focused on three highly expressed genes, viz ZmWAKL38, ZmWAKL42 and ZmWAKL52. Co-expression analyses revealed that their expression patterns exhibited a remarkable correlation with GA-responsive transcription factors (TF) TF5, TF6, and TF8, which displayed preferential expression in kernels. RT-qPCR analysis validated the upregulation of ZmWAKL38, ZmWAKL42, ZmWAKL52, TF5, TF6, and TF8 following GA treatment. Additionally, ZmWAKL52 showed significant increase of transcription in the present of TF8, with ZmWAKL52 localizing in both the plasma membrane and cell wall. TF5 positively regulated ZmWAKL38, while TF6 positively regulated ZmWAKL42. Collectively, these findings provide novel insights into the characterization and regulatory mechanisms of specific ZmWAKL genes involved in maize kernel development, offering prospects for their utilization in maize breeding programs.


Temporal and other factors that influence the time doctors take to prescribe using an electronic prescribing system.
A computerized physician order entry (CPOE) system with embedded clinical decision support can reduce medication errors in hospitals, but might increase the time taken to generate orders. We aimed to quantify the effects of temporal (month, day of week, hour of shift) and other factors (grade of doctor, prior experience with the system, alert characteristics, and shift type) on the time taken to generate a prescription order. A large university teaching hospital using a locally developed CPOE system with an extensive audit database. We retrospectively analyzed prescription orders from the audit database between August 2011 and July 2012. The geometric mean time taken to generate a prescription order within the CPOE system was 11.75 s (95% CI 11.72 to 11.78). Time to prescribe was most affected by the display of high-level (24.59 s (24.43 to 24.76); p<0.001) or previously unseen (18.87 s (18.78 to 18.96); p<0.001) alerts. Prescribers took significantly less time at weekends (11.29 s (11.23 to 11.35)) than on weekdays (11.88 s (11.84 to 11.91); p<0.001), in the first (11.25 s (11.16 to 11.34); p<0.001) and final (11.56 s (11.47 to 11.66); p<0.001) hour of their shifts, and after the first month of using the system. The display of alerts, prescribing experience, system familiarity, and environment all affect the time taken to generate a prescription order. Our study reinforces the need for appropriate alerts to be presented to individuals at an appropriate place in the workflow, in order to improve prescribing efficiency.


Aldose reductases influence prostaglandin F2α levels and adipocyte differentiation in male mouse and human species.
Aldose reductases (AKR1B) are widely expressed oxidoreductases whose physiological function remains elusive. Some isoforms are genuine prostaglandin F2α (PGF2α) synthases, suggesting they might influence adipose homeostasis because PGF2α inhibits adipogenesis. This was shown by Akr1b7 gene ablation in the mouse, which resulted in increased adiposity related to a lower PGF2α content in fat. Yet humans have no ortholog gene for Akr1b7, so the role of aldose reductases in human adipose homeostasis remains to be explored. We analyzed expression of genes encoding human and mouse aldose reductase isoforms in adipose tissues and differentiating adipocytes to assess conserved mechanisms regulating PGF2α synthesis and adipogenesis. The Akr1b3 gene encoded the most abundant isoform in mouse adipose tissue, whereas Akr1b7 encoded the only isoform enriched in the stromal vascular fraction. Most mouse aldose reductase gene expression peaked in early adipogenesis of 3T3-L1 cells and diminished with differentiation. In contrast with its mouse ortholog Akr1b3, AKR1B1 expression increased throughout differentiation of human multipotent adipose-derived stem cells, paralleling PGF2α release, whereas PGF2α receptor (FP) levels collapsed in early differentiation. Pharmacological inhibition of aldose reductase using Statil altered PGF2α production and enhanced human multipotent adipose-derived stem adipocyte differentiation. As expected, the adipogenic effects of Statil were counteracted by an FP agonist (cloprostenol). Thus, in both species aldose reductase-dependent PGF2α production could be important in early differentiation to restrict adipogenesis. PGF2α antiadipogenic signaling could then be toned down through the FP receptor or aldose reductases down-regulation in human and mouse cells, respectively. Our data suggest that aldose reductase inhibitors could have obesogenic potential.


A skin marker for geriatric cancer.
Dermatomyositis must be differentiated from a number of other diseases, including lupus erythematosus, myxedema, and contact dermatitis. Mixed connective-tissue disease also may be seen as a proximal myopathy and has similar skin findings. Satisfactory treatment of the underlying malignancy often results in disappearance or easier control of the dermatomyositis. The initial treatment step, however, is high-dose corticosteroids combined with oral immunosuppressives to control muscular and cutaneous inflammation.


Immunity to bovine herpesvirus 1: I. Viral lifecycle and innate immunity.
Bovine herpesvirus 1 (BHV-1) causes a variety of diseases and is globally distributed. It infects via mucosal epithelium, leading to rapid lytic replication and latent infection, primarily in sensory ganglia. Large amounts of virus can be excreted by the host on primary infection or upon recrudescence of latent infection, resulting in disease spread. The bovine immune response to BHV-1 is rapid, robust, balanced, and long-lasting. The innate immune system is the first to respond to the infection, with type I interferons (IFNs), inflammatory cytokines, killing of infected host cells, and priming of a balanced adaptive immune response. The virus possesses a variety of immune evasion strategies, including inhibition of type I IFN production, chemokine and complement binding, infection of macrophages and neutrophils, and latency. BHV-1 immune suppression contributes to the severity of its disease manifestations and to the bovine respiratory disease complex, the leading cause of cattle death loss in the USA.


Humoral immune responses and CD27+ B cells in children with DiGeorge syndrome (22q11.2 deletion syndrome).
The spectrum of T-cell abnormalities in 22q11.2 syndrome is quite broad, ranging from profound and life threatening to non-existent defects. Humoral abnormalities have been described in some of these patients, although no data are currently available on their phenotypical and functional B cell subsets. The purpose of this study was to investigate humoral immune function in a cohort of 13 children with DiGeorge syndrome by immunophenotyping B and by analysing their functionality in vivo. Humoral immunity was assessed by serum immunoglobulin evaluation, IgG subclasses determination, and testing of specific antibody titers to recall antigens. B cells were analyzed by flow cytometry and the relevant percentage of membrane surface expression of CD27, IgM, IgD was evaluated. In our cohort, one of 13 children (7.7%) had a complete IgA deficiency, four of 13 (30.7%) had minor immunoglobulin abnormalities, and five (38%) had an impaired production of specific antibodies. Five of 13 children (38%) had recurrent infections. Interestingly, peripheral CD27+ B cells were reduced in our patients as compared with age-matched healthy controls, and this decrement was statistically significant for IgM+ IgD+ CD27+ B cells. Immunoglobulin abnormalities were associated with the occurrence of recurrent infections. We conclude that a significant proportion of patients with DiGeorge syndrome have defective humoral immunity, which may represent an additional pathogenic mechanism underlying the increased susceptibility to infections. Whether the decreased CD27+ B-cell subset might be one of the defects that contribute to impaired humoral immunity, and to susceptibility to infection remains to be elucidated.


Hematopoietic growth factor inducible neurokinin-1 (Gpnmb/Osteoactivin) is a biomarker of progressive renal injury across species.
We sought to find a urinary biomarker for chronic kidney disease and tested hematopoietic growth factor inducible neurokinin-1 (HGFIN, also known as Gpnmb/Osteoactivin) as it was found to be a kidney injury biomarker in microarray studies. Here, we studied whether HGFIN is a marker of kidney disease progression. Its increase in kidney disease was confirmed by real-time PCR after 5/6 nephrectomy, in streptozotocin-induced diabetes, and in patients with chronic kidney disease. In the remnant kidney, HGFIN mRNA increased over time reflecting lesion chronicity. HGFIN was identified in the infarct portion of the remnant kidney in infiltrating hematopoietic interstitial cells, and in distal nephron tubules of the viable remnant kidney expressed de novo with increasing time. In vitro, it localized to cytoplasmic vesicles and cell membranes. Epithelial cells lining distal tubules and sloughed luminal tubule cells of patients expressed HGFIN protein. The urine HGFIN-to-creatinine ratio increased over time after 5/6 nephrectomy; increased in patients with proteinuric and polycystic kidney disease; and remained detectable in urine after prolonged freezer storage. The urine HGFIN-to-creatinine ratio compared favorably with the urine neutrophil gelatinase-associated lipocalin (NGAL)-to-creatinine ratio (both measured by commercial enzyme-linked immunosorbent assays (ELISAs)), and correlated strongly with proteinuria, but weakly with estimated glomerular filtration rate and serum creatinine. Thus, HGFIN may be a biomarker of progressive kidney disease.


B vitamins and berries and age-related neurodegenerative disorders.
To assess the effects, associations, mechanisms of action, and safety of B vitamins and, separately, berries and their constituents on age-related neurocognitive disorders-primarily Alzheimer's (AD) and Parkinson's disease (PD). MEDLINE and CAB Abstracts. Additional studies were identified from reference lists and technical experts. Vitamins B1, B2, B6, B12, and folate, and a dozen types of berries and their constituents were evaluated. Human, animal, and in vitro studies were evaluated. Outcomes of interest from human studies were neurocognitive function or diagnosis with AD, cognitive decline, PD, or related conditions. Intervention studies, associations between dietary intake and outcomes, and associations between B vitamin levels and outcomes were evaluated. Specific mechanisms of action were evaluated in animal and in vitro studies. Studies were extracted for study design, demographics, intervention or predictor, and neurocognitive outcomes. Studies were graded for quality and applicability. In animal studies, deficiencies in vitamins B1 or folate generally cause neurological dysfunction; supplementation with B6, B12, or folate may improve neurocognitive function. In animal experiments folate and B12 protect against genetic deficiencies used to model AD; thiamine and folate also affect neurovascular function and health. Human studies were generally of poor quality. Weak evidence suggests possible benefits of B1 supplementation and injected B12 in AD. The effects of B6 and folate are unclear. Overall, dietary intake studies do not support an association between B vitamin intake and AD. Studies evaluating B vitamin status were mostly inadequate due to poor study design. Overall, studies do not support an association between B vitamin status and age-related neurocognitive disorders. Only one study evaluated human berry consumption, finding no association with PD. Animal studies of berries have almost all been conducted by the same research group. Several berry constituents have been shown to affect brain and nerve tissue function. Blueberry and strawberry extract were protective of markers of disease, although effects on neurocognitive tests were less consistent. Berry extracts may protect against the deleterious effects of compounds associated with AD. Reporting of adverse events was uncommon. When reported, actual adverse events from B vitamins were rare and minor. The current research on B vitamins is largely inadequate to confidently assess their mechanisms of action on age-related neurocognitive disorders, their associations with disease, or their effectiveness as supplements. B vitamin supplementation may be of value for neurocognitive function, but the evidence is inconclusive.


β-Sulfonamido Functionalized Aspartate Analogues as Excitatory Amino Acid Transporter Inhibitors: Distinct Subtype Selectivity Profiles Arising from Subtle Structural Differences.
In this study inspired by previous work on 3-substituted Asp analogues, we designed and synthesized a total of 32 β-sulfonamide Asp analogues and characterized their pharmacological properties at the excitatory amino acid transporter subtypes EAAT1, EAAT2, and EAAT3. In addition to several potent EAAT inhibitors displaying IC50 values ∼1 μM at all three subtypes, this elaborate structure-activity relationship also identified analogues exhibiting distinct preferences or selectivities for specific transporter subtypes. Introduction of two fluorine atoms on the phenyl ring yielded analogue 4y that displayed an IC50 of 0.8 μM at EAAT1 with a 14- and 9-fold preference over EAAT2 and EAAT3, respectively. Conversely, the m-CF3-phenyl analogue 4r was a potent selective EAAT2-inhibitor (IC50 = 2.8 μM) exhibiting 30- and 50-fold selectivity over EAAT1 and EAAT3, respectively. In conclusion, even small structural differences in these β-sulfonamide Asp analogues provide analogues with diverse EAAT subtype selectivity profiles.


Comparison of the learning curves and frustration level in performing laparoscopic and robotic training skills by experts and novices.
Robotic assistance may provide for distinct technical advantages over conventional laparoscopic technique. The goals of this study were (1) to objectively evaluate the difference in the learning curves by novice and expert surgeons in performing fundamental laparoscopic skills using conventional laparoscopic surgery (CLS) and robotic-assisted laparoscopic surgery (RALS) and (2) to evaluate the surgeons' frustration level in performing these tasks. Twelve experienced and 31 novices in laparoscopy were prospectively evaluated in performing three standardized laparoscopic tasks in five consecutive, weekly training sessions. Analysis of the learning curves was based on the magnitude, rate, and quickness in performance improvement. The participant's frustration and mood were also evaluated during and after every session. For the novice participants, RALS allowed for shorter time to task completion and greater accuracy. However, significant and rapid improvement in performance as measured by magnitude, rate, and quickness at each session was also seen with CLS. For the experienced surgeons, RALS only provided a slight improvement in performance. For all participants, the use of RALS was associated with less number of sessions in which they felt frustrated, less number of frustration episodes during a session, lower frustration score during and after the session, and higher good mood score. The advantages of RALS may be of most benefit when doing more complex tasks and by less experienced surgeons. RALS should not be used as a replacement for CLS but rather in specific situations in which it has the greatest advantages.


Cardiac preconditioning during percutaneous coronary interventions.
Ischemic preconditioning (PC) is a polygenic defensive cellular adaptive phenomenon of the heart to ischemic stress, whereby the heart changes its phenotype to become more resistant to subsequent ischemia. Early and late of PC represent two chronologically and pathophysiologically distinct phases of this phenomenon, which can be recruited pharmacologically. We represent a post hoc analysis examining the late PC-mimetic effects of nitroglycerin (NTG) on peri-procedural myocardial necrosis during percutaneous coronary intervention (PCI). A group of 66 patients presenting with angina were randomized, 24 h prior to a scheduled PCI for single obstructive CAD, to a 4 h pretreatment with intravenous NTG or saline. Measurements of electrocardiographic ST-segment shifts, echocardiographic regional wall motion and angina scores demonstrated that NTG pre-treatment preconditioned the heart by rendering it resistant to ischemia during balloon inflations. NTG-pretreated patients exhibited trends towards lower average peak CK (131.1 vs. 188.6 U/L, P = 0.38) and CK-MB levels (7.1 vs. 12.6 ng/ml, P = 0.40). NTG, however, had no significant impact on the incidence of post-procedural MI or any cardiac enzyme elevation. The exploitation of ischemic and pharmacological PC may prove a useful strategy to confer cardioprotection during high-risk PCI and is worth exploring.


Expanding the concept of neuroprotection for acute ischemic stroke: The pivotal roles of reperfusion and the collateral circulation.
This review surveys the efforts taken to achieve clinically efficacious protection of the ischemic brain and underscores the necessity of expanding our purview to include the essential role of cerebral perfusion and the collateral circulation. We consider the development of quantitative strategies to measure cerebral perfusion at the regional and local levels and the application of these methods to elucidate flow-related thresholds of ischemic viability and to characterize the ischemic penumbra. We stress that the modern concept of neuroprotection must consider perfusion, the necessary substrate upon which ischemic brain survival depends. We survey the major mechanistic approaches to neuroprotection and review clinical neuroprotection trials, focusing on those phase 3 multicenter clinical trials for acute ischemic stroke that have been completed or terminated. We review the evolution of thrombolytic therapies; consider the lessons learned from the initial, negative multicenter trials of endovascular therapy; and emphasize the highly successful positive trials that have finally established a clinical role for endovascular clot removal. As these studies point to the brain's collateral circulation as key to successful reperfusion, we next review the anatomy and pathophysiology of collateral perfusion as it relates to ischemic infarction, as well as the molecular and genetic influences on collateral development. We discuss the current MR and CT-based diagnostic methods for assessing the collateral circulation and the prognostic significance of collaterals in ischemic stroke, and we consider past and possible future therapeutic directions.


Alteration of endosomal trafficking is associated with early-onset parkinsonism caused by SYNJ1 mutations.
Recently, a new form of autosomal recessive early-onset parkinsonism (PARK20), due to mutations in the gene encoding the phosphoinositide phosphatase, Synaptojanin 1 (Synj1), has been reported. Several genes responsible for hereditary forms of Parkinson's disease are implicated in distinct steps of the endolysosomal pathway. However, the nature and the degree of endocytic membrane trafficking impairment in early-onset parkinsonism remains elusive. Here, we show that depletion of Synj1 causes drastic alterations of early endosomes, which become enlarged and more numerous, while it does not affect the morphology of late endosomes both in non-neuronal and neuronal cells. Moreover, Synj1 loss impairs the recycling of transferrin, while it does not alter the trafficking of the epidermal growth factor receptor. The ectopic expression of Synj1 restores the functions of early endosomes, and rescues these trafficking defects in depleted cells. Importantly, the same alterations of early endosomal compartments and trafficking defects occur in fibroblasts of PARK20 patients. Our data indicate that Synj1 plays a crucial role in regulating the homeostasis and functions of early endosomal compartments in different cell types, and highlight defective cellular pathways in PARK20. In addition, they strengthen the link between endosomal trafficking and Parkinson's disease.


Frequency Of Uropathogens Showing Resistance To Nitrofurantoin.
Urinary tract infection (UTI) caused by bacteria is the commonest infection accountable for the unforeseen healthcare cost throughout the globe. Nitrofurantoin is being studied as a solution to the perpetually increasing threat of antimicrobial resistance. The objectives of this study were to determine the frequency of urinary isolates causing UTI and their susceptibility pattern against Nitrofurantoin. Data of all isolates reported as uropathogens from April 1, to December 31, 2021, was collected through Electronic Medical Record system of Shalamar Hospital, Lahore. Results of Nitrofurantoin susceptibility were recorded to find the resistance pattern of bacterial isolates. Out of a total of 3,221 samples, 672 (20.9%) were positive with significant bacteriuria. Of the positive samples, 418 (62.2%) were collected from females and 254 (37.8%) from males, with female to male ratio of 1.65:1. The number of female patients was higher in adult age. Of the positive samples, E. coli was the commonest isolate seen in 390 (58%) of samples, followed by Enterococcus spp. 92 (13.7%), Klebsiella spp. 86 (12.8%), Pseudomonas spp. 35 (5.2%), Staphylococcus saprophyticus 24 (3.6%), Proteus spp. 21 (3.1%), Citrobacter spp. 15 (2.2%), and Acinetobacter spp. 9 (1.3%). Overall, 587 (87.4%) isolates were sensitive to Nitrofurantoin. However, it showed increased resistance to 28 (32.6%) isolates of Klebsiella spp. E. coli remains the commonest uropathogen. In conclusion, Nitrofurantoin can be used to treat UTI caused by common bacterial pathogens except Klebsiella spp.


How frequent are outbreaks of nosocomial infection in community hospitals?
A statistical algorithm was used to identify potentially important clusters among nosocomial infections reported each month by 7 community hospitals. Epidemiologic review and on-site investigations distinguished outbreaks of clinical disease from factitious clusters. In 1 year, 8 outbreaks were confirmed. They involved 82 patients--approximately 2% of patients with nosocomial infections and 0.09% of all discharges. One true outbreak occurred for every 12,000 discharges--at least 1 outbreak per year for the average community hospital. Five (63%) outbreaks were recognized independently by the hospitals' infection control personnel. Four (50%) resolved spontaneously; the hospitals' own control measures were necessary in 2; and 2 resolved only after an outside investigation. Organized surveillance appears necessary to detect some outbreaks, and control measures are needed to stop many. Since, however, outbreaks account for such a small proportion of nosocomial infections, infection control programs should be sufficiently staffed and managed so that most of the effort is directed toward the surveillance and control of endemic infection problems, but with adequate resources remaining to respond to outbreaks when they occur.


Exercise is inversely associated with functional dyspepsia among a sample of Chinese male armed police recruits.
There is no study evaluating the association between exercise and functional dyspepsia (FD) based on the Rome IV criteria. We aimed to investigate the prevalence of FD and evaluate the association between exercise and FD based on Rome IV criteria among a sample of Chinese armed police recruits. An on-site questionnaire survey on FD among a sample of Chinese armed police recruits was conducted based on the Rome IV criteria in 2021. Potential confounders included age, body mass index (BMI), race, marriage, education, smoking, and drinking variables were adjusted. A total of 2594 recruits were enrolled, including 46 FD participants and 2548 non-FD participants. In the model adjusted for all demographic variables among participants excluding irritable bowel syndrome (IBS) and functional constipation (FC), compared with no exercise participants, 1 h < each exercise time ≤ 2 h (OR = 0.15, 95% CI: 0.03-0.77, P = 0.0230) was inversely associated with FD and compared with no exercise participants, mild exercise (OR = 0.09, 95% CI: 0.01-0.71, P = 0.0220) was significantly inversely associated with FD. The incidence rate of FD in this sample Chinese armed police recruits was 1.77%, and 1 h < each exercise time ≤ 2 h and mild intensity exercise were independently inversely associated with FD. However, the causal relationship needs to be verified by further randomized controlled trials.