Transfection of the gene for B7-1 but not B7-2 can induce immunity to murine malignant mesothelioma.
Transfection of the genes encoding the co-stimulatory molecules B7-1 and B7-2 has enhanced the development of immunity to a variety of experimental tumors, although most of these were inherently immunogenic. We have determined the effect of expression of these genes on the induction of immunity to 2 non-immunogenic murine malignant mesothelioma (MM) cell lines (AC29 and AB1). We had previously shown that B7-1 transfection into AC29 delayed but did not prevent tumor development by certain of the transfectant clones. Here we demonstrate that over-expression of B7-1 can inhibit tumor development by certain AB1-B7-1 clones, that inhibition of transfectant growth is dependent on CD4+ and CD8+ T cells and that mice that reject some of these transfectant clones are capable of rejecting subsequent inocula of the parental cell line, AB1. The transfectant clones can generate tumor-specific cytotoxic T cells. By contrast, expression of B7-2 in several clones derived from either AB1 or AC29 had no significant effect on the development of tumors in vivo. Our data are consistent with data from other systems that show differences in the effect of modification by B7-1 or B7-2 on the modulation of anti-tumor immune responses. They demonstrate that such modifications can induce protective immunity against an MM cell line but confirm the intra- and inter-tumoral heterogeneity in the effect of genetic modification on the induction of immunity. Our observations are relevant to human MM because these cell lines have been derived from asbestos-induced tumors and share many properties with human cell lines of the same histological type.


Impact of polypharmacy on occurrence of delirium in elderly emergency patients.
To examine associations between polypharmacy and delirium diagnosed in elderly patients hospitalized in geriatric acute care unit after emergency hospital admission. Study design was an observational cohort study in the acute geriatric care unit of a university hospital. We included 410 consecutive patients admitted to the acute geriatric ward during 9 months. Within 72 hours of each patient's hospitalization, a clinically trained geriatrician collected the following data: sociodemographic details (age, sex, type of residence), predisposing factors for delirium, main cause of hospitalization, and current medications. Polypharmacy was defined as 6 or more drugs a day. Delirium was assessed by a geriatrician using the Confusion Assessment Method and was diagnosed on the basis of clinical history with an acute change in usual functional status, behavioral observation, and clinical and cognitive assessment. Nearly 25% of hospitalized patients had delirium. The Confusion Assessment Method was positive in 69% of patients receiving polypharmacy and in 30% of those not receiving polypharmacy, a relative risk of 2.33. The proportion of elderly patients receiving polypharmacy was 58.53%. In our study, polypharmacy is an independent risk factor for delirium in a population of elderly patients after emergency admission. In the geriatric population, delirium is an underestimated scourge and because of its medicosocial and economic consequences and its impact on morbidity and mortality, we need to give increased attention to the prevention and control of polypharmacy, which is a predisposing factor for delirium.


Extreme synchronization events in a Kuramoto model: The interplay between resource constraints and explosive transitions.
Many living and artificial systems possess structural and dynamical properties of complex networks. One of the most exciting living networked systems is the brain, in which synchronization is an essential mechanism of its normal functioning. On the other hand, excessive synchronization in neural networks reflects undesired pathological activity, including various forms of epilepsy. In this context, network-theoretical approach and dynamical modeling may uncover deep insight into the origins of synchronization-related brain disorders. However, many models do not account for the resource consumption needed for the neural networks to synchronize. To fill this gap, we introduce a phenomenological Kuramoto model evolving under the excitability resource constraints. We demonstrate that the interplay between increased excitability and explosive synchronization induced by the hierarchical organization of the network forces the system to generate short-living extreme synchronization events, which are well-known signs of epileptic brain activity. Finally, we establish that the network units occupying the medium levels of hierarchy most strongly contribute to the birth of extreme events emphasizing the focal nature of their origin.


The management of hyperkinetic children: a trial of dietary therapy.
The standard techniques in the management of hyperkinetic children are not uniformly successful. Recently, there has been considerable interest in dietary therapy. The diet, low in artificial colours, and flavours and in naturally occurring salicylates has been adapted for use in New Zealand. Ten hyperkinetic children have been treated with the diet, five of whom improved dramatically and are now off all other therapy. Their response to accidental and deliberate challenge supports the hypothesis that the dietary regime described has been responsible for their improvement.


Effects of external pressure loading on human skin blood flow measured by 133Xe clearance.
Forearm skin blood flow was measured during external pressure loading in normal human subjects using 133Xe washout from intracutaneous injection sites. Pressures ranging between 5 and 150 mmHg were applied through a 3-cm-diameter disc placed over the site of flow determination. The pressure was maintained constant by a servo-controlled loading mechanism. Flow decreased with pressures from 5 to 10 and 30 to 150 mmHg, but remained constant with pressures from 10 to 30 mmHg. Reactive hyperemia occurred following removal of pressures of 90 mmHg or greater, but did not occur following removal of lower pressures. The pressure-flow curve for parasacral skin of paraplegic subjects closely paralleled the pressure-flow curve of normal skin at pressures tested: 5-15 mmHg. These data are interpreted to demonstrate autoregulation of skin blood flow. Autoregulation in parasacral skin of paraplegic subjects suggests a peripheral mechanism. The occurrence of hyperemia at pressures which exceed the ability of skin to autoregulate suggests that both autoregulation and post occlusion hyperemia may have the same mechanism.


Role of the carboxy-terminal portion of the HIV-1 transmembrane protein in viral transmission and cytopathogenicity.
The transmembrane glycoprotein (gp41) of human immunodeficiency virus type-1 (HIV-1) has a long cytoplasmic domain of unknown functional significance. To investigate the role of the carboxy-terminal (C-terminal) portion of the HIV-1 envelope protein in viral replication, infectivity, and cytopathogenicity, we examined the properties of a panel of mutants with variable deletions in the 3'-env region. Deletion of the C-terminal 76 amino acids did not abolish production of reverse transcriptase upon transfection of COS-1 cells. Deletion of the C-terminal 6-14 amino acids appeared sufficient to alter the replication pattern, infectivity, and cytopathogenicity of some clones. The data suggest that conformational determinants or specific sequences are responsible for the observed changes, rather than simply the length of the gp41 cytoplasmic tail.


Site-Specific Management of Miscanthus Genotypes for Combustion and Anaerobic Digestion: A Comparison of Energy Yields.
In Europe, the perennial C4 grass miscanthus is currently mainly cultivated for energy generation via combustion. In recent years, anaerobic digestion has been identified as a promising alternative utilization pathway. Anaerobic digestion produces a higher-value intermediate (biogas), which can be upgraded to biomethane, stored in the existing natural gas infrastructure and further utilized as a transport fuel or in combined heat and power plants. However, the upgrading of the solid biomass into gaseous fuel leads to conversion-related energy losses, the level of which depends on the cultivation parameters genotype, location, and harvest date. Thus, site-specific crop management needs to be adapted to the intended utilization pathway. The objectives of this paper are to quantify (i) the impact of genotype, location and harvest date on energy yields of anaerobic digestion and combustion and (ii) the conversion losses of upgrading solid biomass into biogas. For this purpose, five miscanthus genotypes (OPM 3, 6, 9, 11, 14), three cultivation locations (Adana, Moscow, Stuttgart), and up to six harvest dates (August-March) were assessed. Anaerobic digestion yielded, on average, 35% less energy than combustion. Genotype, location, and harvest date all had significant impacts on the energy yield. For both, this is determined by dry matter yield and ash content and additionally by substrate-specific methane yield for anaerobic digestion and moisture content for combustion. Averaged over all locations and genotypes, an early harvest in August led to 25% and a late harvest to 45% conversion losses. However, each utilization option has its own optimal harvest date, determined by biomass yield, biomass quality, and cutting tolerance. By applying an autumn green harvest for anaerobic digestion and a delayed harvest for combustion, the conversion-related energy loss was reduced to an average of 18%. This clearly shows that the delayed harvest required to maintain biomass quality for combustion is accompanied by high energy losses through yield reduction over winter. The pre-winter harvest applied in the biogas utilization pathway avoids these yield losses and largely compensates for the conversion-related energy losses of anaerobic digestion.


Parenting with a physical disability: A scoping review of assessment methods.
Daily childcare can be challenging for parents with a physical disability who have young children. Occupational therapists are valuable facilitators to family participation. However, occupational therapists have reported significant gaps in knowledge when documenting the parenting role of parents with a physical disability in occupational therapy practice. This study explored and described the parenting assessment methods used with parents with a physical disability in the scientific literature. A scoping review was conducted, and search results were reviewed by two separate reviewers. The search strategy was applied to five databases (Embase, CINAHL, MEDLINE, HaPI, PsycInfo). Numerical and thematic analyses were conducted. Four thousand one hundred fifty articles were screened, and 73 relevant scientific articles were included. Seventy-six assessment methods were identified, including 20 assessment instruments with few reported population-specific psychometric studies. Most assessments were conducted via interviews (n = 45), followed by questionnaires (n = 27), and only six were performance based. Parenting practices and experience were the two dimensions most assessed, with little attention given to parenting responsibility. Mothers with multiple sclerosis, spinal cord injury, rheumatoid arthritis, and cerebral palsy were the most assessed. Further research is needed to develop specific, multidimensional, and validated parenting assessments for all parents with a physical disability, including performance-based assessments. Formal assessments should be conducted by professionals, including occupational therapists, who have the necessary training.


T cells specific for alpha-beta interface regions of hemoglobin recognize the isolated subunit but not the tetramer and indicate presentation without processing.
Processing of a protein antigen into fragments is believed to be a prerequisite for its presentation by the antigen-presenting cell to the T cell. This model would predict that, in oligomeric proteins, T cells prepared with specificity for regions that are buried within subunit association surfaces should recognize the respective regions in vitro equally well on the isolated subunit or on the oligomer. Three hemoglobin (Hb) alpha-chain synthetic peptides, corresponding to areas that are situated either completely [alpha-(31-45)] or partially [alpha-(41-45) and alpha-(81-95)] within the interface between the alpha and beta subunits of Hb, and a fourth peptide representing a completely exposed area in tetrameric Hb were used as immunogens in SJL/J (H-2s) mice. Peptide-primed T cells were passaged in vitro with the respective peptide to obtain peptide-specific T-lymphocyte lines. T-cell clones were isolated from these lines by limiting dilution. T-cell lines and clones that were specific for buried regions in the subunit association surfaces recognized the free peptide and the isolated subunit but not the Hb tetramer. On the other hand, T cells with specificity against regions that are not involved in subunit interaction and are completely exposed in the tetramer recognized the peptide, the isolated subunit, and the oligomeric protein equally well. The responses of the T-cell lines and clones were major histocompatibility complex-restricted. Since the same x-irradiated antigen-presenting cells were employed, the results could not be attributed to differences or defects in Hb processing. The findings indicate that in vitro the native (unprocessed and undissociated) oligomeric protein was the trigger of major histocompatibility complex-restricted T-cell responses.


The heparan sulfate proteoglycan syndecan is an in vivo ligand for the Drosophila LAR receptor tyrosine phosphatase.
Receptor tyrosine phosphatases (RPTPs) are essential for axon guidance and synaptogenesis in Drosophila. Each guidance decision made by embryonic motor axons during outgrowth to their muscle targets requires a specific subset of the five neural RPTPs. The logic underlying these requirements, however, is still unclear, partially because the ligands recognized by RPTPs at growth cone choice points have not been identified. RPTPs in general are still "orphan receptors" because, while they have been found to interact in vitro with many different proteins, their in vivo ligands are unknown. Here we use a new type of deficiency screen to identify the transmembrane heparan sulfate proteoglycan Syndecan (Sdc) as a ligand for the neuronal RPTP LAR. LAR interacts with the glycosaminoglycan chains of Syndecan in vitro with nanomolar affinity. Genetic interaction studies using Sdc and Lar LOF mutations demonstrate that Sdc contributes to LAR's function in motor axon guidance. We also show that overexpression of Sdc on muscles generates the same phenotype as overexpression of LAR in neurons and that genetic removal of LAR suppresses the phenotype produced by ectopic muscle Sdc. Finally, we show that there is at least one additional, nonproteoglycan, ligand for LAR encoded in the genome. Taken together, our results demonstrate that Sdc on muscles can interact with neuronal LAR in vivo and that binding to Sdc increases LAR's signaling efficacy. Thus, Sdc is a ligand that can act in trans to positively regulate signal transduction through LAR within neuronal growth cones.


Autonomic neuropathy in experimental models of diabetes mellitus.
Autonomic neuropathy complicates diabetes by increasing patient morbidity and mortality. Surprisingly, considering its importance, development and exploitation of animal models has lagged behind the wealth of information collected for somatic symmetrical sensory neuropathy. Nonetheless, animal studies have resulted in a variety of insights into the pathogenesis, neuropathology, and pathophysiology of diabetic autonomic neuropathy (DAN) with significant and, in some cases, remarkable correspondence between rodent models and human disease. Particularly in the study of alimentary dysfunction, findings in intrinsic intramural ganglia, interstitial cells of Cajal and the extrinsic parasympathetic and sympathetic ganglia serving the bowel vie for recognition as the chief mechanism. A body of work focused on neuropathologic findings in experimental animals and human subjects has demonstrated that axonal and dendritic pathology in sympathetic ganglia with relative neuron preservation represents one of the neuropathologic hallmarks of DAN but it is unlikely to represent the entire story. There is a surprising selectivity of the diabetic process for subpopulations of neurons and nerve terminals within intramural, parasympathetic, and sympathetic ganglia and innervation of end organs, afflicting some while sparing others, and differing between vascular and other targets within individual end organs. Rather than resulting from a simple deficit in one limb of an effector pathway, autonomic dysfunction may proceed from the inability to integrate portions of several complex pathways. The selectivity of the diabetic process appears to confound a simple global explanation (e.g., ischemia) of DAN. Although the search for a single unifying pathogenetic hypothesis continues, it is possible that autonomic neuropathy will have multiple pathogenetic mechanisms whose interplay may require therapies consisting of a cocktail of drugs. The role of multiple neurotrophic substances, antioxidants (general or pathway specific), inhibitors of formation of advanced glycosylation end products and drugs affecting the polyol pathway may be complex and therapeutic elements may have both salutary and untoward effects. This review has attempted to present the background and current findings and hypotheses, focusing on autonomic elements including and beyond the typical parasympathetic and sympathetic nervous systems to include visceral sensory and enteric nervous systems.


[MALDI-TOF-MS combined with WCX technique in diagnosing pituitary adenoma].
Application of matrix assisted laser desorption ionization time of flight mass spectrometry enhancement (MALDI-TOF-MS) combined with WCX nanometer magnetic bead technique, screening of the serum biomarkers in pituitary adenoma, to establish a serum protein fingerprint classification decision tree. Analyse the serum samples of 40 cases of pituitary adenoma and 60 cases of healthy adult and find the different protein peaks, then to establish the diagnosis model and the classification decision tree of pituitary adenomas. A total of 42 differences in protein peaks were identified in the experimental and control group (P < 0.01). The diagnosis model of pituitary adenomas was established by three protein peaks (3382.0, 4601.9, 9191.2). The model could screen the pituitary adenoma out of the normal population. The sensitivity was 90.00% and the specificity was 88.30%. By the double blind experimental validation, the model could diagnose the pituitary adenoma and the sensitivity was 88%, the specificity was 83.30%. Significantly different protein peaks can be screened out between pituitary adenoma cases and healthy controls using MALDI-TOF-MS combined with WCX technique, and these protein peaks may be used as a pituitary adenoma detection, follow-up indicator.


Can metabolic function and physical fitness improve without weight loss for inactive, obese, Hispanic adolescents? A feasibility study.
A case series that examines the effects of a 12-week combined resistance and aerobic training program for four sedentary obese, Hispanic adolescents without weight loss. Baseline and post-intervention anthropometric, metabolic and physical fitness measures were obtained. Body composition, hepatic, visceral, and intramuscular fat contents were analyzed via imaging. Fasting levels of alanine transaminase (ALT), insulin, glucose, free fatty acids, triglycerides, high- and low-density lipoproteins (LDL), and C-reactive protein were obtained via blood samples. Two subjects decreased their glucose levels by 1.86% and 4.06%. Subjects 1, 3, and 4 increased their lean body mass by 4.12%, 9.70%, and 5.48%. ALT was reduced 13.0%, 16.0%, and 35.7% for subjects 2, 3, and 4, respectively. LDLs were reduced by 37.7%, 4.5%, and 7.5% for subjects 1, 2, and 3. Triglycerides were reduced by 25.4%, 37.8%, and 4.6% for subjects 1, 2, and 3. Visceral fat reductions by 16.5%, 14.2%, and 13.0% occurred for subjects 1, 2, and 3. C-reactive protein was reduced for subjects 1, 2, and 3 by 19.4%, 16.3%, and 32.0%. Expected directions of change were made for most indicators of metabolic function and body composition, but measures of physical fitness improved for all four subjects.


Difference in Tryptophan-nicotinamide Conversion According to Dietary Nitrogen Sources; Casein, Casein Hydrolysate, and Mixtures of Amino Acids.
We investigated whether the fate of tryptophan (Trp) to nicotinamide (Nam) is changeable according to nitrogen sources or not. Male rats were fed with a nicotinic acid-free diet (Trp content was arranged at about 234mg/100g of diet) containing casein, casein hydrolysates, or mixtures of amino acids (simulating the amino acid pattern of casein) for 12 days. From the urinary excretion of Nam and its metabolites, the conversion ratio was calculated. The conversion ratio was lower in the groups fed with the casein hydrolysate diets than in the groups fed with the casein and amino acid diets. In order to find the reason, the urinary excretion of kynurenic acid, xanthurenic acid, anthranilic acid, and 3-hydroxyanthranilic acid from the upper part of the Trp-Nam conversion pathway, the contents of free Trp in whole blood, and eight kinds of enzyme activities involved in the Trp-Nam pathway were measured. From these results, it is considered that the reason why the conversion ratio was lower in the casein hydrolysate group is due to the lower concentration of free Trp in whole blood and the higher activity of aminocarboxymuconate-semialdehyde decarboxylase. As is known that this enzyme activity is induced by adrenal cortical hormone, it was suggested that the release of this hormone is stimulated by feeding the casein hydrolysate diet.


Profiling lipidomic changes in dengue-resistant and dengue-susceptible strains of Colombian Aedes aegypti after dengue virus challenge.
The mosquito Aedes aegypti is the primary vector for all four serotypes of dengue viruses (DENV1-4), which infect millions across the globe each year. Traditional insecticide programs have been transiently effective at minimizing cases; however, insecticide resistance and habitat expansion have caused cases of DENV to surge over the last decade. There is an urgent need to develop novel vector control measures, but these are contingent on a detailed understanding of host-parasite interactions. Here, we have utilized lipidomics to survey the profiles of naturally DENV-resistant (Cali-MIB) or susceptible (Cali-S) populations of Ae. aegypti, isolated from Cali, Colombia, when fed on blood meals containing DENV. Control insects were fed on a DENV-free blood meal. Midguts were dissected from Cali-MIB and Cali-S females at three time points post-infectious blood meal, 18, 24 and 36h, to identify changes in the lipidome at key times associated with the entry, replication and exit of DENV from midgut cells. We used principal component analysis to visualize broad patterns in lipidomic profiles between the treatment groups, and significance analysis of microarray to determine lipids that were altered in response to viral challenge. These data can be used to identify molecules or metabolic pathways particular to the susceptible or refractory phenotypes, and possibly lead to the generation of stable, DENV-resistant strains of Ae. aegypti.


CSF immunoglobulins G in multiple sclerosis.
Three different methods were compared to detect an intrathecal IgG synthesis in cerebrospinal fluid of patients with Multiple Sclerosis. A preliminary investigation was carried out on serum and cerebrospinal fluid proteins fractionated by means of analytical isotachophoresis. This technique shows many advantages but isoelectrofocusing is still the most available technique in diagnostic trials.


HAC1 and HAF1 Histone Acetyltransferases Have Different Roles in UV-B Responses in Arabidopsis.
Arabidopsis has 12 histone acetyltransferases grouped in four families: the GNAT/HAG, the MYST/HAM, the p300/CBP/HAC and the TAFII250/HAF families. We previously showed that ham1 and ham2 mutants accumulated higher damaged DNA after UV-B exposure than WT plants. In contrast, hag3 RNA interference transgenic plants showed less DNA damage and lower inhibition of plant growth by UV-B, and increased levels of UV-B-absorbing compounds. These results demonstrated that HAM1, HAM2, and HAG3 participate in UV-B-induced DNA damage repair and signaling. In this work, to further explore the role of histone acetylation in UV-B responses, a putative function of other acetyltransferases of the HAC and the HAF families was analyzed. Neither HAC nor HAF acetyltrasferases participate in DNA damage and repair after UV-B radiation in Arabidopsis. Despite this, haf1 mutants presented lower inhibition of leaf and root growth by UV-B, with altered expression of E2F transcription factors. On the other hand, hac1 plants showed a delay in flowering time after UV-B exposure and changes in FLC and SOC1 expression patterns. Our data indicate that HAC1 and HAF1 have crucial roles for in UV-B signaling, confirming that, directly or indirectly, both enzymes also have a role in UV-B responses.


Comparing questionnaires for the assessment of acute mountain sickness.
Exposure to high altitude in nonacclimatized subjects may lead to acute mountain sickness (AMS). AMS is a syndrome characterized by headache accompanied by one or more other symptoms, such as light-headedness, dizziness, loss of appetite, nausea, vomiting, fatigue, lassitude, and trouble sleeping. Assessing the presence and degree of AMS can be done using self-administered questionnaires like the Lake Louise Questionnaire (LLQ) and the Environmental Symptoms Questionnaire-III (ESQ-III). We compared LLQ and ESQ-III in 266 trekkers of different nationalities trekking over a 5400-m-high pass to assess if the two questionnaires identify the same population as suffering from AMS and to see whether using English questionnaires poses problems for nonnative English-speaking persons. The use of English questionnaires by nonnative English speakers influenced the outcome for some nationalities. For criterion scores yielding similar prevalence of AMS, ESQ-III labeled 20% of cases differently (AMS or no AMS) when compared to LLQ. Correlations between similar individual questions of ESQ-III and LLQ were variable, and there was considerable scatter between ESQ-III and LLQ scores. In conclusion, English questionnaires may pose problems in some international settings, and ESQ-III and LLQ may identify different populations as suffering from AMS.


Physiological Evaluation of Personal Protective Ensembles Recommended for Use in West Africa.
Personal protective equipment (PPE) provides health care workers with a barrier to prevent human contact with viruses like Ebola and potential transmission of the disease. However, PPE can also introduce an additional physiological burden from potentially increased heat stress. This study evaluated the human physiological and subjective responses to continuous light exercise within environmental conditions similar to those in West Africa while wearing 3 different, commonly used PPE ensembles (E1, E2, and E3). Six healthy individuals were tested in an environmental chamber (32°C, 92% relative humidity) while walking (3 METs, 2.5 mph, 0% incline) on a treadmill for 60 minutes. All subjects wore medical scrubs and PPE items. E1 also had a face shield and fluid-resistant surgical gown; E2 additionally included goggles, coverall, and separate hood; and E3 also contained a highly impermeable coverall, separate hood, and surgical mask cover over the N95 respirator. Heart rate and core temperature at the end of the exercise were significantly higher for E2 and E3 than for E1. Subjective perceptions of heat and exertion were significantly higher for E2 and E3 than for E1. Heat stress and PPE training, as well as the implementation of a work-to-rest ratio that avoids dehydration and possible heat stress issues, are recommended. (Disaster Med Public Health Preparedness. 2017;11:580-586).


Arthroscopically-assisted treatment of pediatric lateral humeral condyle fractures.
Pediatric lateral humeral condyle fractures are common injuries. Current treatment recommendations include nonoperative treatment for nondisplaced Milch type 1 fractures; however, truly nondisplaced fractures may be rare. Although closed reduction and percutaneous pinning under arthrographic visualization are most commonly used, anatomical reconstitution of the articular surface may require a lateral Kocher approach. This approach may compromise the vascularity of the distal fragment. To avoid this catastrophic complication while still obtaining anatomical articular surface reduction, we have investigated a new technique in which the lateral condyle fracture is reduced arthroscopically, allowing visualization of the articular surface without the soft tissue dissection required with open approaches. The fracture is then percutaneously pinned and immobilized as previously recommended. Six skeletally immature patients with lateral humeral condyle fractures underwent arthroscopic reduction and percutaneous pinning. The mean age of the patients was 48 months (range, 21-69 months). There were 2 girls and 4 boys. Surgery was performed on 4 left and 2 right elbows. The mean follow-up was 32 weeks (range, 21-44 weeks). Postoperatively, all patients were placed in a long arm cast for 4 weeks. Pins and casts were removed at 4 weeks, and motion was begun. Elbow radiographs were evaluated for fracture healing, articular congruity, malunion, growth disturbance, and presence of avascular necrosis. Range of motion, function, pain, and cosmetic deformity were recorded. All patients had full active and passive range of motion. There was no difference in range of motion compared with the contralateral side (P < 0.05). All fractures healed radiographically by 4 weeks. There were no cases of nonunion or malunion. No patients developed cubitus varus. One patient developed radiolucency of the capitellum. There were no other complications. Arthroscopic reduction and percutaneous fixation of pediatric lateral humeral condyle fractures may offer a safe and effective alternative to open treatment with decreased soft tissue stripping and a possibly decreased risk of malunion or avascular necrosis. Level IV.


Immunotherapies catering to the unmet medical need of cold colorectal cancer.
As a common malignant tumor of gastrointestinal tract, the incidence of colorectal cancer (CRC) has gradually increased in recent years. In western developed countries, it has even become the second largest malignant tumor next to lung cancer. Immunotherapy is a hot topic in the field of cancer therapy, including immune checkpoint blockade (ICB), adoptive cell therapy (ACT), cancer vaccines and cytokines, aiming to improve the ability of the immune system to recognize, target and eliminate cancer cells. However, cold CRC, which accounts for a high proportion of CRC, is not so reactive to it. The development of immunotherapy to prevent cancer cells from forming "immune escape" pathways to the immune system in cold CRC, has been under increasing study attention. There is proof that an organic combination of radiotherapy, chemotherapy, and several immunotherapies can considerably boost the immune system's capacity to eradicate tumor cells. In this review, we summarized the role of immunotherapy in colorectal cancer. In addition, we propose a breakthrough and strategy to improve the role of immunotherapy in cold CRC based on its characteristics.


Comparison of Corneal Epithelial Thickness Map Measured by Spectral Domain Optical Coherence Tomography in Healthy, Subclinical and Early Keratoconus Subjects.
The aim of this study was to compare epithelial thickness map obtained by Spectral Domain Optical Coherence Tomography (SD-OCT) of eyes with myopic astigmatism but without keratoconus, subclinical and early keratoconus. Sixty-three eyes were divided into three groups; myopic astigmatism without keratoconus, subclinical and early keratoconus. Corneal epithelial thickness map was obtained by SD-OCT for all patients and compared between the 3 groups. Mean ± Standard Deviation of epithelial thickness in the area of minimum corneal epithelial thickness, in the one eighth part of the inferior (I) and in the one eighth part of the temporal (T) were 56.64±2.82 µm, 59.00±3.24 µm and 60.40±4.93 µm respectively in subclinical group. Three parameters on epithelial maps obtained by SD-OCT was significantly different in the 2 groups: I and T corneal epithelial thickness map was thicker in subclinical keratoconus (P<0.02 and P<0.02 respectively). Epithelial map uniformity indices were different between the groups, as Superior-I, Superonasal-Inferotemporal were lower (P<0.00 and P< 0.01 respectively) but T-nasal was higher in the subclinical group (P<0.02). The area with minimum epithelial thickness had a significantly lower amount in early keratoconus group compared to the other two groups (P<0.00). In conclusion, corneal epithelial thickness map provided early detection of keratoconus in the subclinical stage with compensatory epithelial thickening of inferior and one eighth of temporal compared to total corneal thickness and changes in epithelial map uniformity indices may lead to early detection of subclinical keratoconus from normal cornea.


Left ventricular hypertrophy: major risk factor in patients with hypertension: update and practical clinical applications.
Left ventricular hypertrophy is a maladaptive response to chronic pressure overload and an important risk factor for atrial fibrillation, diastolic heart failure, systolic heart failure, and sudden death in patients with hypertension. Since not all patients with hypertension develop left ventricular hypertrophy, there are clinical findings that should be kept in mind that may alert the physician to the presence of left ventricular hypertrophy so a more definitive evaluation can be performed using an echocardiogram or cardiovascular magnetic resonance. Controlling arterial pressure, sodium restriction, and weight loss independently facilitate the regression of left ventricular hypertrophy. Choice of antihypertensive agents may be important when treating a patient with hypertensive left ventricular hypertrophy. Angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers followed by calcium channel antagonists most rapidly facilitate the regression of left ventricular hypertrophy. With the regression of left ventricular hypertrophy, diastolic function and coronary flow reserve usually improve, and cardiovascular risk decreases.


Metabolic effects of intravenous proinsulin.
Proinsulin induced hypoglycemia was characterized in eight healthy male volunteers. Proinsulin cleared slower from the circulation than insulin. The metabolic effects on plasma glucose, free fatty acids, glycerol, 3-hydroxybutyrate, potassium, and phosphate occurred slower. The anti-lipolytic effect of proinsulin was longer than that of insulin (2P less than 0.001). The hormonal responses of epinephrine, norepinephrine, prolactin, hGH, and cortisol were attenuated following proinsulin. The amount of epinephrine secreted during counterregulation and the amount of lactate produced in response to beta-stimulation were both correlated to the fall of plasma glucose (2P less than 0.005). Stress symptoms were milder after proinsulin (2P less than 0.01). The data obtained are consistent with the hypothesis that the slower kinetics of proinsulin cause slower metabolic effects. The assumption of non-insulin-like effects of a differing pattern of insulin-like effects is not necessitated by the results of this study.


Evidence for involvement of proline cis-trans isomerization in the slow unfolding reaction of RNase A.
The three exposed tyrosines of RNase A have been converted to nitrotyrosines by reaction with tetranitromethane, and the changes in the ionization properties of these nitrotyrosines have been used to follow the kinetics of unfolding of the nitrated protein. It is found that the nitrotyrosines not only are sensitive to the overall disruption of the protein structure, which occurs in a faster reaction, but also serve as reporter groups for the slower reaction which takes place in the unfolded state. This slower reaction corresponds to the formation of the slow-refolding species of the unfolded protein. The kinetic properties of the slower reaction--guanidine-dependence of the rate and activation ethalpy--are similar to those of the proline cis-trans isomerization in a model peptide determined in the same conditions. It is concluded that proline cis-trans isomerization is indeed the rate-limiting factor for the formation of the slow-refolding species. Because the influence of proline cis-trans isomerization on the properties of the nitrotyrosines in the unfolded protein is probably due to a local effect, it is suggested that most of the optical changes observed during this slow unfolding reaction arise from the effect of the cis-trans isomerization of the Asn113-Pro114 bond on the properties of nitrotyrosine 115.


Social inequalities and the early provision and dispersal of COVID-19 vaccinations in the United States: A population trends study.
In December 2020 the U.S. began a massive COVID-19 vaccination campaign, an action that researchers felt could catalyze inequalities in COVID-19 vaccination utilization. While vaccines have the potential to be accessible regardless of social status, the objective of this study was to examine how and when socioeconomic status (SES) and racial/ethnic inequalities would emerge in vaccination distribution. Population vaccination rates reported at the county level by the Centers for Disease Control and Prevention across 46 states on 3/30/2021. Correlates included SES, the share of the population who were Black, Hispanic, Female, or aged ≥65 years, and urbanicity (thousands of residents per square mile). Multivariable-adjusted analyses relied on zero-inflated negative binomial regression to estimate the odds of providing any vaccine, and vaccination rate ratios (aVRR) comparing the distribution rate for vaccinations across the U.S. Across the U.S., 16.3 % of adults and 37.9 % of adults aged 65 and older were vaccinated in lower SES counties, while 20.45 % of all adults and 48.15 % of adults aged 65 and older were vaccinated in higher SES counties. Inequalities emerged after 41 days, when < 2 % of Americans were vaccinated. Multivariable-adjusted analyses revealed that higher SES was associated with improved vaccination distribution (aVRR = 1.127, [1.100-1.155], p < 1E-06), while increases in the percent reporting Black or Hispanic race/ethnicity was associated with lower vaccination distribution (aVRR = 0.998, [0.996-0.999], p = 1.03E-04). Social inequalities in COVID-19 vaccines reflect an inefficient and inequitable distribution of these technologies. Future efforts to improve health should recognize the central role of social factors in impacting vaccine delivery.


Performance comparisons of nano-LC systems, electrospray sources and LC-MS-MS platforms.
Selecting a suitable nano-liquid chromatography system (LC), ionization source and mass spectrometer for LC-tandem mass spectrometry (MS-MS) studies is complicated by numerous competing technologies. This study compares four popular nano-LC systems, four ionization sources and three MS facilities that use completely different LC-MS-MS systems. Statistically significant differences in LC performance were identified with similarly performing Proxeon, Waters and Eksigent nanoLC-Ultra systems [retention time routinely at 0.7-0.9% relative standard deviation (RSD)], and all outperformed the Eksigent nanoLC-2D (RSD ∼2%). In addition, compatibility issues were identified between the Bruker HCT ion trap mass spectrometer and both the Eksigent nanoLC-2D and the Bruker nanoelectrospray source. The electrospray source itself had an unexpected and striking effect on chromatographic reproducibility on the Bruker HCT ion trap. The New Objective nanospray source significantly outperformed the Bruker nanospray source in retention time RSD (1% RSD versus 14% RSD, respectively); and the Bruker nebulized nanospray source outperformed both of these traditional, non-nebulized sources (0.5% RSD in retention time). Finally, to provide useful benchmarks for overall proteomics sensitivity, different LC-MS-MS platforms were compared by analyzing a range of concentrations of tryptic digests of bovine serum albumin at three MS facilities. The results indicate that similar sensitivity can be realized with a Bruker HCT-Ultra ion trap, a Thermo LTQ-Velos Linear ion trap and a Thermo LTQ-Orbitrap XL-ETD.


[Determination of volatile nitrosamines in urine through gas chromatography-mass spectrometry].
To establish a detection method based on gas chromatography-mass spectrometry (GC-MS) for concentrations of volatile nitrosamine compounds in urine, and apply it to the test of real samples. Target compounds dichloromethane in urine samples was extracted with dichloromethane through liquid-liquid extraction, then the dichloromethane extract was filtrated, evaporated with nitrogen at 40°C to dryness, and the volume was set with 0.2 ml dichloromethane. Analysis of nine volatile nitroso-compounds were performed with GC-MS under selected ion monitoring mode, external reference method was used for quantification, and the detection limit, repeatability and sensitivity were evaluated. In addition, nine volatile nitroso-compounds of 92 urine samples in a town of Anhui province were measured. A good linear range of 2 - 200 ng/ml (with correlation coefficient 0.9985 - 0.9999) were obtained for the above mentioned nine kinds of analyte, and the lowest examination concentration was 0.05 - 0.50 ng/ml. The addition standard recoveries were 68%-102% with the RSD of 0.4% - 5.5% (n = 3). The detection limits were 0.001 - 0.013 ng/ml urine. The detection rate of N-nitrosodimethylamine (NDMA), N-nitrosomethylethylamine (NMEA), N-nitrosodiethylamine (NDEA), N-nitrosodi-n-propylamine (NDPA), N-nitrosopyrrolidine (NPYR), N-nitrosomorpholine (NMOR), N-nitrosopiperidine (NPIP), N-nitrosodi-n-butylamine (NDBA) and N-nitrosodiphenylamine (NDPhA) were 71% (65), 74% (68), 65% (60), 80% (73), 92% (85), 78% (72), 76% (70), 87% (80), 98% (90), respectively, with the results (0.27 ± 0.12), (0.75 ± 0.29), (0.06 ± 0.02), (0.16 ± 0.07), (23.66 ± 5.18), (1.01 ± 0.35), (0.38 ± 0.11), (2.47 ± 0.52) and (15.13 ± 3.48) nmol/g creatinine. A gas chromatography-mass spectrometry detect method was developed for low level volatile nitrosamines in urine samples.


In vivo effects of amtolmetin guacyl on lipid peroxidation and antioxidant defence systems in different models of gastrointestinal injury.
1. The in vivo effects of the non-steroid anti-inflammatory drug (NSAID) amtolmetin guacyl (AMG) on lipid peroxidation (LP) and on antioxidant enzyme and non-enzyme defence systems were investigated in models of stomach and colon damages, induced by other NSAIDs, by ethanol or by 2,4,6-trinitrobenzenesulfonic acid (TNBS). 2. Indomethacin increased LP, glutathione peroxidase (GSH-PX) and glucose-6-phosphate dehydrogenase (Glu-6-P-DH) activities and decreased glutathione levels in gastric mucosa. Pretreatment with AMG normalized some of the parameters affected by indomethacin. 3. Treatment of rats with ethanol for 0.5 h led to a decrease in glutathione levels as well as activities of glutathione reductase and Glu-6-P-DH in gastric mucosa. AMG, administered 0.5 h before ethanol, limited the adverse actions of ethanol. 4. Amtolmetin guacyl failed to abolish the TNBS-induced changes in the followed-up parameters in colon mucosa and liver, but additional alterations (as with tolmetin) were not observed. 5. The beneficial profile of AMG in the various experimental models of free radical-induced damage investigated in this study suggests the possibility that this drug might possess antioxidant activity.


Anxiety sensitivity and treatment outcome in panic disorder.
The purpose of this study was to examine the relationship between change in anxiety sensitivity, as measured by the Anxiety Sensitivity Index (ASI), and treatment outcome in a sample of 106 subjects with a DSM-III-R diagnosis of panic disorder (with or without agoraphobia) who were participants in an evaluation study of cognitive-behavioral treatment. Results revealed that subjects who received active treatment had significantly lower anxiety sensitivity scores at post-treatment than the wait-list control group. We also examined change in anxiety sensitivity from pre- to post-treatment in reference to Clinical Global Improvement (CGI) ratings and with the effect size statistic. Subjects who showed improvement based on CGI ratings also demonstrated a reduction in anxiety sensitivity. Furthermore, the effect sizes obtained with the ASI were greater in magnitude than those obtained with other widely used anxiety self-report measures. Taken together, the finds supported the use of the Anxiety Sensitivity Index as a treatment outcome measure in panic disorder research.


Two Cases of Surgical Correction of Recurrent Mitral Regurgitation due to Failed Catheter- Delivered Mitral Clip (MitraClip).
From April 2018 to February 2021, 150 patients underwent MitraClip implantation for severe functional mitral regurgitation (MR) at our hospital. Two of our patients, an 85-year-old man and an 84-year-old woman, developed a single leaflet device attachment in the acute phase after the implantation and had severe residual MR requiring surgical correction. The recurrent MR was first pointed out on day 5 and day 4, and the duration between MitraClip implantation and surgery was 13 and 55 days, respectively. Due to strong adhesions with the clips and severe valve damage after MitraClip implantation, both cases underwent mitral valve replacement with a good postoperative course. In patients with a high-risk baseline profile, surgical mitral valve replacement after failed MitraClip implantation should be considered at an optimal timing, and a detailed echocardiographic follow-up is required.


Gαi3 signaling is associated with sexual dimorphic expression of the clock-controlled output gene Dbp in murine liver.
The albumin D-box binding protein (DBP) is a member of the PAR bZip (proline and acidic amino acid-rich basic leucine zipper) transcription factor family and functions as important regulator of circadian core and output gene expression. Gene expression of DBP itself is under the control of E-box-dependent binding by the Bmal1-Clock heterodimer and CRE-dependent binding by the cAMP responsive element binding protein (CREB). However, the signaling mechanism mediating CREB-dependent regulation of DBP expression in the peripheral clock remains elusive. In this study, we examined the role of the GPCR (G-protein-coupled receptor)/Gαi3 (Galphai3) controlled cAMP-CREB signaling pathway in the regulation of hepatic expression of core clock and clock-regulated genes, including Dbp. Analysis of circadian gene expression revealed that rhythmicity of hepatic transcript levels of the majority of core clock (including Per1) and clock-regulated genes were not affected by Gαi3 deficiency. Consistently, the period length of primary Gαi3 deficient tail fibroblasts expressing a Bmal1-Luciferase reporter was not affected. Interestingly, however, Gαi3 deficient female but not male mice showed a tendentiously increased activation of CREB (nuclear pSer133-CREB) accompanied by an advanced peak in Dbp gene expression and elevated mRNA levels of the cytochrome P450 family member Cyp3a11, a target gene of DBP. Accordingly, selective inhibition of CREB led to a strongly decreased expression of DBP and CYP3A4 (human Cyp3a11 homologue) in HepG2 liver cells. In summary, our data suggest that the Gαi3-pCREB signalling pathway functions as a regulator of sexual-dimorphic expression of DBP and its xenobiotic target enzymes Cyp3a11/CYP3A4.


Dry powder aerosol containing muco-inert particles for excipient enhanced growth pulmonary drug delivery.
Tenacious sputum poses a critical diffusion barrier for aerosol antibiotics used to treat cystic fibrosis (CF) lung infection. We conducted a proof-of-concept study using dense poly(ethylene glycol) coated polystyrene nanoparticles (PS-PEG NPs) as model muco-inert particles (MIPs) formulated as a powder using an excipient enhanced growth (EEG) strategy, aiming to minimize extrathoracic airway loss, maximize deposition in the airway and further overcome the sputum barrier in the CF lungs. The EEG aerosol formulation containing PS-PEG MIPs was prepared by spray drying and produced discrete spherical particles with geometric diameter of approximately 2 μm; and >80% of the powder dose was delivered from a new small-animal dry powder inhaler (DPI). The MIPs released from the EEG aerosol had human airway mucus and CF sputum diffusion properties comparable to the suspension formulation. These properties make this formulation a promising pulmonary drug delivery system for CF lung infections.


Predictive performances of ALS and BLS termination of resuscitation rules in out-of-hospital cardiac arrest for different resuscitation protocols.
Resuscitation guidance has advanced; however, the predictive performance of the termination of resuscitation (TOR) rule has not been validated for different resuscitation protocols published by the American Heart Association (AHA). A retrospective study validating the basic life support (BLS) and advanced life support (ALS) TOR rules was conducted using an Utstein-style database in Tainan city, Taiwan. Adult patients with nontraumatic out-of-hospital cardiac arrests from January 1, 2015, to December 31, 2015, (using the AHA 2010 resuscitation protocol) and from January 1, 2020, to December 31, 2020, (using the AHA 2015 resuscitation protocol) were included. The characteristics of rule performance were calculated, including sensitivity, specificity, positive predictive value (PPV) and negative predictive value. Among 1260 eligible OHCA patients in 2015, 757 met the BLS TOR rule and 124 met the ALS TOR rule. The specificity and PPV for predicting unfavorable neurological outcomes were 61.1% and 99.0%, respectively, for the BLS TOR rule and 93.8% and 99.2%, respectively, for the ALS TOR rule. A total of 970 OHCA patients were enrolled in 2020, of whom 438 met the BLS TOR rule and 104 met the ALS TOR rule. The specificity and PPV for predicting unfavorable neurological outcomes were 85.7% and 100%, respectively, for the BLS TOR rule and 99.5% and 100%, respectively, for the ALS TOR rule. Both the BLS and ALS TOR rules performed better when using the 2015 AHA resuscitation protocols compared to the 2010 protocols, with increased PPVs and decreased false-positive rates in predicting survival to discharge and good neurological outcomes at discharge. The BLS and ALS TOR rules can perform differently while the resuscitation protocols are updated. As the concepts and practices of resuscitation progress, the BLS and ALS TOR rules should be evaluated and validated accordingly.


Pressure and temperature dependence of H-atom tunneling in the Debye approximation. Barrier preparation and media reorganization.
In the frame of the radiationless transitions modified theory, the analytical expression of a rate constant of the chemical reaction with an atom tunneling is found for the case of a continuous spectrum of a phonon subsystem. Two mechanisms of temperature dependence of a rate constant are taken into account, the oscillations of the potential barrier of the reaction at the intermolecular vibrations and media reorganization. The simple expressions for temperature and pressure dependencies of a rate constant are obtained in the special case of lattice motion-the Debye model. The well-known Marcus expression for the rate constant of an electron transfer in the Debye phonon spectrum is deduced first. The pressure dependence of the reorganization energy of the media is derived. Comparison of the theoretical results with the literature experimental data on H-atom tunneling in the fluorene-acridine crystal, taking into account four promotive modes (translational, librational, and two low-frequency intramolecular modes at 95 and 238 cm(-1)) and the frequency dependence of the Grueneisen parameter, is fulfilled. Good agreement of the theory and experiments is observed.


Effects of growth hormone administration on wool growth in merino sheep.
The effects of daily administration of 10 mg of highly purified ovine growth hormone (GH) for a period of 4 weeks on wool growth have been measured in 12 Merino ewes fed either a calculated maintenance energy intake or 1.6 times this amount (six on each ration). Concentrations of hormones, glucose, urea, alpha-amino N and amino acids in the blood were monitored and faeces and urine collected for measurement of nitrogen balance. Wool growth rate decreased by 20% during the 4 weeks of GH treatment in sheep fed the high energy diet, largely because of reduced wool fibre diameter. This was followed by restoration of normal growth and then an increase of up to 20% above control levels, a response which persisted for 12 weeks following cessation of GH administration, and which was due to increases in both fibre length and diameter. GH administration caused marked increases in plasma concentrations of GH, insulin and somatomedin C, glucose and free fatty acids, all of which returned to basal levels following cessation of GH administration. No consistent changes in plasma concentration of T3, T4, cortisol, prolactin or alpha amino N were detected. Plasma urea and methionine levels decreased during GH treatment and returned to, or were raised above, basal levels after the GH treatment period. GH injection also resulted in a net retention of N during treatment, followed by a transient period of net N loss. The GH-induced changes in wool growth may be caused by a change in the partitioning of amino acids between the muscle mass and the skin. No other contributing factor(s) were identified.


Regulation of Protein Secretion Systems Mediated by Cyclic Diguanylate in Plant-Interacting Bacteria.
The ubiquitous second messenger cyclic diguanylate (c-di-GMP) is involved in the regulation of different processes in bacteria. In phytopathogens, intracellular fluctuations in the concentration of this molecule contribute to the lifestyle switching from a motile and virulent stage to a sessile and biofilm-forming phase. Among the virulence mechanisms used by bacterial pathogens, different specific type secretion systems (TSSs) and the effector proteins that they translocate are included. Some of these TSS are conceived to suppress host immune responses during bacterial colonization. The modulation of the expression of secretion systems components and/or effector proteins can be influenced by c-di-GMP levels at transcriptional, translational, or post-translational levels and can take place directly by binding to specific or global regulators, or via transducer proteins. Different genera of plant-interacting bacteria have been analyzed to shed some light in the implications of c-di-GMP in the regulation of host plant colonization through protein secretion systems. Expression of (1) adhesins secreted by Type 1 secretion systems to bind the host plant in Pectobacterium (formerly Erwinia) and some beneficial Pseudomonas strains; (2) catalytic exoproteins delivered by Type 2 secretion systems to break plant cell wall in Dickeya; (3) effectors secreted by Type 3 secretion systems to suppress plant immunity in Xanthomonas; or (4) the activity of Type 6 secretion systems to export an ATPase in Pseudomonas, are finely tuned by c-di-GMP levels. In this minireview, we summarize the knowledge available about the implications of c-di-GMP in the regulation of protein secretion in different plant-interacting bacteria. Topic: Secretion systems and effector proteins of phytopathogenic and beneficial bacteria regulated by NSM.


A phase II study of preoperative chemotherapy with modified FOLFOX6 followed by surgery and postoperative chemoradiation in patients with localized gastric adenocarcinoma.
The optimal neoadjuvant and adjuvant treatment for gastric cancer remains controversial. We conducted a phase II study using preoperative chemotherapy with modified FOLFOX6 followed by surgical resection and postoperative chemoradiation in patients with gastric carcinoma. Preoperative chemotherapy (two or three cycles) consisted of a 2-h infusion of oxaliplatin (100 mg/m2) and folinic acid (100 mg/m2) followed by a 46-h continuous infusion of 5-fluorouracil (5-FU; 2,400 mg/m2). Surgical resection was planned 4 weeks after the last chemotherapy cycle. Patients underwent postsurgical chemoradiation, receiving a total dose of 45 Gy and 5-FU continuous infusion (350 mg/m2/day). The primary end points were feasibility, overall response rate, and R0 resectability rate after preoperative chemotherapy. The secondary end points were tolerability, treatment-associated complications, disease-free survival, and overall survival. Nineteen patients were enrolled in this study. After neoadjuvant treatment, four patients (21.1%) experienced progressive disease, six patients (31.6%) showed partial remission, and nine patients (47.3%) showed stable disease. In 15 patients (78.9%) R0 resectability could be achieved. Eleven of these patients (73.3%) were able to undergo postoperative chemoradiation. Notably, eight (72.7%) of these patients were disease free and alive at median follow-up of 60 months. Chemotherapy associated neutropenia, neutropenic fever, and anastomotic dehiscence were observed. The combination of preoperative chemotherapy and postoperative chemoradiation is feasible in a significant subset of gastric cancer patients.


IGF-I, IGF-I-binding proteins and GH-binding protein in malnourished elderly patients with inflammation receiving refeeding therapy.
To investigate the mechanisms determining the success or failure of refeeding therapy in malnourished elderly patients with inflammation by studying changes in plasma IGF-I, GH-binding protein (GHBP) and IGF-binding protein (IGFBP) levels and IGFBP-3 proteolysis. We studied 15 severely malnourished hospitalized elderly patients. Weight, food intake, plasma albumin, transthyretin, C-reactive protein (CRP), orosomucoid, interleukin-6 (IL-6), IGF-I, intact and proteolytically degraded IGFBP-3 and GHBP levels were determined on admission and during refeeding therapy designed to increase food intake to 40 kcal/kg body weight per day (15% protein). Plasma IGF-I, IGFBP-3 and GHBP levels were significantly low for age on admission in all malnourished elderly patients. They increased in nine patients as nutritional status improved (albuminemia >30 g/l; transthyretinemia >200 mg/l or weight gain >5% of initial body weight) and levels of inflammation markers decreased (group 1). In contrast, plasma IGF-I, IGFBP-3 and GHBP levels remained low in six patients in whom nutritional status failed to improve and levels of inflammation markers increased (group 2). IGF-I showed greater variations than IGFBP-3 or GHBP with respect to nutritional status. High plasma CRP and IL-6 levels were associated with high levels of IGFBP-3 proteolysis. Efficient refeeding therapy was associated with a significant increase in IGF-I plasma levels. In patients with severe and persistent inflammation, high levels of proteolysis of IGFBP-3 may have contributed to the low plasma IGF-I levels, persistence of hypercatabolism and lack of improvement in nutritional status.


Significant contribution of genomic rearrangements in SLC3A1 and SLC7A9 to the etiology of cystinuria.
Cystinuria is an inherited disorder of defective renal reabsorption of cystine and the dibasic amino acids. Recently, SLC3A1 and SLC7A9 have been identified as responsible genes. While point mutations in the two genes are well known to cause cystinuria, only a few studies are aimed on the identification of gross genomic alterations. Here, we report our results of a systematic screening for deletions and duplications in SLC3A1 and SLC7A9 by quantitative real-time polymerase chain reaction (PCR). We screened a cohort of 49 cystinurics for copy number deviations in the genes SLC3A1 and SLC7A9 by quantitative real-time PCR assays using fluorogenic 5' nuclease chemistry. The detected duplication in SLC3A1 was analyzed in detail by further real-time assays, reverse transcription (RT)-PCR and direct sequencing. In seven patients, we could identify a large duplication in SLC3A1 spanning from intron 4 to intron 9. This tandem duplication was accompanied by a small inversion of 25 bp and a 2 bp deletion in intron 9. As a formation mechanism, we presume that the inversion in intron 9 and several Alu sequences neighbored to the affected region provoke a chromatin structure that stimulates the duplication event. In addition to the SLC3A1 duplication, we observed deletions in SLC7A9 in three patients. The frequency of genomic rearrangements in our patient population illustrates the significant contribution of large genomic alterations to the mutation spectrum in cystinuria. As we could show, quantitative real-time PCR is a reliable and effective tool for the identification of unbalanced genomic rearrangements.


Autonomic dysreflexia triggered by an unstable lumbar spine in a quadriplegic patient.
A 40 year-old man with C5 complete quadriplegia, had L2-L3 pyogenic spondylitis treated with debridement and fusion of the lumbar spine with left iliac bone graft. Three months later he developed symptoms of autonomic dysreflexia, including headache, cold sweating, and hypertension whenever he was in an upright position. These symptoms resolved after lying down. Roentgenograms of the lumbar spine revealed absorption of the bone graft at the L2-L3 level. A spinal stabilization procedure was done after eight weeks of antibiotic therapy under the impression of unstable spine caused by pyogenic spondylitis. Symptoms were relieved immediately following the surgery. This report may be helpful for physicians caring for quadriplegic patients with autonomic dysreflexia induced by an unstable spine.


Dengue in Bali: Clinical characteristics and genetic diversity of circulating dengue viruses.
A high number of dengue cases are reported annually in Bali. Despite the endemicity, limited data on dengue is available for Bali localities. Molecular surveillance study was conducted to explore the clinical and virological characteristics of dengue patients in urban Denpasar and rural Gianyar areas in Bali during the peak season in 2015. A total of 205 adult dengue-suspected patients were recruited in a prospective cross-sectional study. Demographic and clinical information were obtained, and dengue screening was performed using NS1 and IgM/IgG ELISAs. Viral RNA was subsequently extracted from patients' sera for serotyping using conventional RT-PCR and Simplexa Dengue real-time RT-PCR, followed by genotyping with sequencing method. We confirmed 161 patients as having dengue by NS1 and RT-PCR. Among 154 samples successfully serotyped, the DENV-3 was predominant, followed by DENV-1, DENV-2, and DENV-4. Serotype predominance was different between Denpasar and Gianyar. Genotyping results classify DENV-1 isolates into Genotype I and DENV-2 as Cosmopolitan Genotype. The classification grouped isolates into Genotype I and II for DENV-3 and DENV-4, respectively. Clinical parameters showed no relationship between infecting serotypes and severity. We observed the genetic diversity of circulating DENV isolates and their relatedness with historical data and importation to other countries. Our data highlights the role of this tourist destination as a potential source of dengue transmission in the region.


Role of Autoantibodies in Neurodegenerative Dementia: An Emerging Association.
In the background of an emerging role for immune dysregulation in neurodegenerative dementias, this study aimed to investigate the relationship between systemic autoimmunity and dementia. The objective was to study the frequency and profile of disease-specific autoantibodies in Alzheimer's dementia (AD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB). Immunological testing was performed in a large cohort of neurodegenerative dementia diagnosed based on standard clinical and imaging criteria. Patients were evaluated for the presence of autoantibodies specific for systemic autoimmune diseases that included anti-extractable nuclear antibody profile, rheumatoid factor antibody (RA), perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA), and cytoplasmic anti-neutrophil cytoplasmic antibody (c-ANCA) in serum. Of 174 patients with degenerative dementia (FTD = 114, AD = 53, and DLB = 7) evaluated with immunological testing, 18.9% (n = 33) were seropositive for autoantibodies. The common antibodies detected were anti-Scl-70 (25%), anti-Ro-52 (18.7%), anti-nRNP-Sm (12.5%), and anti-CENP-B (9.3%). There were no significant systemic complaints in the majority of patients. A wider range of antibodies were positive in FTD compared to AD and DLB. While no difference was observed in the mean age, sex, or duration of illness between seropositive and negative patients, family history of dementia was more frequent among seronegative patients. Our findings indicate an emerging role for immune dysregulation in patients with classical neurodegenerative dementias, especially those with FTD. These autoantibodies could play a role in immune degradation of protein aggregates that characterize neurodegeneration. Study findings emphasize the need to explore the complex relationship between systemic autoimmunity and neurodegenerative dementia.


Primary central nervous system lymphoma treated with high-dose methotrexate, high-dose busulfan/thiotepa, autologous stem-cell transplantation and response-adapted whole-brain radiotherapy: results of the multicenter Ostdeutsche Studiengruppe Hamato-Onkologie OSHO-53 phase II study.
We investigated the efficacy and safety of tandem high-dose methotrexate (HD-MTX) induction followed by high-dose busulfan/thiotepa (HD-BuTT) with autologous peripheral blood stem-cell transplantation (aPBSCT) and response-adapted whole-brain radiation therapy (WBRT) in patients with newly diagnosed primary central nervous system lymphoma. Twenty-three patients were treated with HD-MTX on days 1 and 10. In case of at least a partial remission (PR), HD-BuTT followed by aPBSCT was given. Patients without response to induction or without complete remission (CR) after HD-BuTT received WBRT. Sixteen patients received HD-MTX and HD-BuTT achieving a CR/PR rate of 69%/13%. CR/PR rates for all patients (n = 23) were 70%/13%. There were three deaths during therapy. With longer follow-up three neurotoxic deaths occurred in irradiated patients (n = 9), while no persistent neurotoxicity was seen after HD-BuTT without subsequent WBRT. At a median follow-up of 15 months (range 1-69) median event-free survival (EFS) and overall survival (OS) for all patients were 17 and 20 months (Kaplan-Meier), after HD-BuTT 27 months and "not reached", respectively. Estimated 2-year EFS and OS were 45% and 48% for all patients versus 56% and 61% for the HD-BuTT group, respectively. MTX induction followed by HD-BuTT is an effective and very short time-on-treatment regimen. Median survival for patients treated with high-dose chemotherapy is not reached yet. The induction regimen needs optimisation. In this study WBRT was associated with a high incidence of severe neurotoxicity.


[Hypoglycaemia without ketosis. A case report].
Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) is a rare disease, inherited as autosomal-recessive trait, with variable clinical presentation including severe hypoglycaemia, cardiomyopathy, sudden infant death, progressive liver failure, 'Reye like' syndrome, neuromyopathy, muscle weakness and rhabdomyolysis. We report a 3 years old male patient admitted to our emergency department with vomiting, hypotonia and prostration, after a common respiratory infection. The presence of hypoketotic hypoglycaemia and elevated liver enzymes in the admission motivated a metabolic study. We found an abnormal low lactate/pyruvate ratio, decreased serum carnitine and dicarboxylic aciduria leading to the diagnosis of a fatty acid oxidation disorder (LCHADD). The molecular study of HADHA gene revealed homozygosity for the G1528C mutation in the patient DNA, and heterozygosity in both parents. The diagnosis of a fatty acid oxidation disorder must be considered in the presence of vomiting associated with excessive prostration specially if there is hypoketotic hypoglycaemia or familiar sudden infant death history. Physicians should be aware about these conditions and for the importance of measuring both glycaemia and ketone bodies during the evaluation of high risk situations.


Fourier transform ion cyclotron resonance: state of the art.
This short review summarizes recent and projected advances in Fourier transform ion cyclotron resonance mass spectrometry instrumentation and applications, ranging from petroleomics to proteomics. More details are available from the cited primary literature and topical reviews.


[The etiology and pathogenesis of sporadic inclusion body myositis].
Sporadic inclusion body myositis (sIBM) is the most common acquired muscle disease in older individuals. Muscle weakness and atrophy in the quadriceps, wrist flexor, and finger flexors are the typical clinical findings in sIBM. The etiology and pathogenesis of sIBM are still poorly understood; however, genetic factors, aging, and environmental factors might possibly play a role. The pathological characteristics of sIBM include two unique features: inflammatory changes in muscle fibers, and cytoplasmic and intranuclear inclusions containing several Alzheimer-type proteins. Based on these pathological findings, there is a continuing debate on whether sIBM is primarily a T cell-mediated inflammatory myositis or a myodegenerative disorder characterized by abnormal protein aggregation, presence of inclusions bodies, and secondary inflammation. Unfortunately, sIBM is also generally refractory to immune therapy.


Coronavirus disease 2019 (COVID-19) in a pregnant women with treatment resistance thrombocytopenic purpura with and suspicion to HELLP syndrome: a case report.
Coronavirus disease 2019 (COVID-19) still is a global emergency. According to the studies, pregnant women are of the at risk populations and any underlying disease(s) might even worsen their condition. The aim of this study is reporting a complex case of immune thrombocytopenic purpura (ITP) during pregnancy who has been diagnosed with COVID-19 as well as suspicion of HELLP syndrome. A 24-year-old woman with a platelet count of 6000/mL and resistance to conventional therapies was referred. A day after starting 0.5 g/day of methylprednisolone for her, fever and a decrease in SpO2 presented. According to the paraclinical investigations, COVID-19 was diagnosed and the conventional COVID-19 treatments started for her (the methylprednisolone pulse stopped). Due to the increased liver enzymes and low platelet count, with suspicion of HELLP syndrome, cesarean section surgery was performed which resulted in a healthy neonate. Then, the methylprednisolone pulse was restarted for and she developed an increase in the platelet count. It is not clear how COVID-19 and pregnancy affected the patient's condition and the underlying disease; however, it seems the delivery and/or restarting the methylprednisolone pulses caused improvement in her condition.


The use of 15-methylated derivative of prostaglandin F2a for the therapeutic termination of pregnancy and management of late fetal death.
The administration of 15-me-PGF 2a for the therapeutic termination of pregnancy and management of intrauterine death of the embryo during the second and third trimester of pregnancy was studied in 92 patients. Of these, 52 came because of intrauterine death with an average gestational age of 28.7 weeks while the rest came for therapeutic termination of pregnancy with an average gestational age of 21 weeks. Successful abortion was achieved in 90 patients. The mean abortion induction time was 7.3 hours for patients with intrauterine death and 12.6 hours for the patients who came for therapeutic termination. The results and complications of the intramuscular administration of the 15-me-PFG2a are analysed in the present work.


The Influence of Leader-Follower Cognitive Style Similarity on Followers' Organizational Citizenship Behaviors.
While cognitive style congruence has been highlighted as a potentially important variable influencing performance outcomes in work-related contexts, studies of its influence are scarce. This paper examines the influence of leader-follower cognitive style similarity on followers' organizational citizenship behaviors (OCBs). Data from 430 leader-follower dyads were analyzed using polynomial regression and response surface analysis. Results demonstrate that congruence of leader/follower cognitive style is a predictor of follower OCBs. Organizations may therefore benefit from considering issues of similarity of cognitive styles in their attempts to develop effective leader-follower partnerships leading to increased OCBs and concomitant improvements in both individual and organizational level success.


Pegylated interferon de novo-induce autoimmune haemolytic anaemia in chronic hepatitis C patient.
A 55-year-old Egyptian woman with chronic hepatitis C undergoing treatment with pegylated interferon (Peg-IFN) alfa-2a plus ribavirin was referred to our hospital on November 2010 with prolonged easy fatigability and an attack of syncope; she had no prior history of autoimmune disorders or allergy. Laboratory investigations documented the presence of Peg-IFN induced autoimmune haemolytic anaemia and autoimmune thyroiditis. Intravenous γ globulin (IVGG) failed to correct the autoimmune process; on the other hand steroid therapy dramatically corrected both haematological and thyroid values, and step down the immune process. Our report indicated that Peg-IFN de novo-induce autoimmune haemolysis, documenting a previous report. IVGG failed to step down the immune process in our case.


Removal of hydrogen sulfide in the gas phase by carbide slag modified bentonite.
Bentonite-based adsorbents for the removal of hydrogen sulfide (H2S) were prepared by a wet-mixing method using carbide slag as the active component. The effects of carbide slag content, calcination temperature, calcination time, and reaction temperature on the H2S adsorption capacity were investigated. The results showed that compared with the blank bentonite adsorbent, the carbide slag-modified bentonite-based adsorbent enhanced the chemisorption of H2S. The adsorption capacity of the carbide slag modified bentonite adsorbent (2.50 mg g-1) was more than 40 times higher than that of the blank bentonite-based adsorbent (0.06 mg g-1) under optimal conditions. The optimal conditions for H2S removal were 3 : 5 ratio of carbide slag-to-bentonite, calcination temperature of 450 °C for 2 h, and reaction temperature of 95 °C. H2S was mainly removed in the mesopores and macropores of the adsorbent and was finally transformed to CaS and sulfate on the adsorbent surface. The adsorption process of H2S followed the Freundlich adsorption isotherm equation and Bangham adsorption kinetic model.


A comprehensive approach for clustering analysis using follower-leading clustering algorithm (FLCA): Bibliometric analysis.
There are 3 issues in bibliometrics that need to be addressed: The lack of a clear definition for author collaborations in cluster analysis that takes into account collaborations with and without self-connections; The need to develop a simple yet effective clustering algorithm for use in coword analysis, and; The inadequacy of general bibliometrics in regard to comparing research achievements and identifying articles that are worth reading and recommended for readers. The study aimed to put forth a clustering algorithm for cluster analysis (called following leader clustering [FLCA], a follower-leading clustering algorithm), examine the dissimilarities in cluster outcomes when considering collaborations with and without self-connections in cluster analysis, and demonstrate the application of the clustering algorithm in bibliometrics. The study involved a search for articles and review articles published in JMIR Medical Informatics between 2016 and 2022, conducted using the Web of Science core collections. To identify author collaborations (ACs) and themes over the past 7 years, the study utilized the FLCA algorithm. With the 3 objectives of; Comparing the results obtained from scenarios with and without self-connections; Applying the FLCA algorithm in ACs and themes, and; Reporting the findings using traditional bibliometric approaches based on counts and citations, and all plots were created using R. The study found a significant difference in cluster outcomes between the 2 scenarios with and without self-connections, with a 53.8% overlap (14 out of the top 20 countries in ACs). The top clusters were led by Yonsei University in South Korea, Grang Luo from the US, and model in institutes, authors, and themes over the past 7 years. The top entities with the most publications in JMIR Medical Informatics were the United States, Yonsei University in South Korea, Medical School, and Grang Luo from the US. The FLCA algorithm proposed in this study offers researchers a comprehensive approach to exploring and comprehending the complex connections among authors or keywords. The study suggests that future research on ACs with cluster analysis should employ FLCA and R visualizations.


Increased formation of corpora lutea in neurokinin 1-receptor deficient mice.
There is evidence to suggest that the tachykinin-receptor system may be involved in female reproduction. Recently, we have shown that the mRNA transcripts of the preprotachykinin-A which encodes substance P (SP), a member of the tachykinin family, and of NK1-R (preferred receptor of SP) are expressed in the bovine corpus luteum (CL) of early developmental stage. The question arises whether the system is expressed at the protein level and influences the ovulatory process and CL formation. For this reason, ovaries from a mouse mutant in which the NK1-R gene had been disrupted were studied. By using RT-PCR, mRNA expression of NK1-R was confirmed in both the ovary and the uterus of wild-type mice. Weaning frequency and litter size, as recorded over 6 months, were similar in both groups. However, counting of CL in serial paraffin sections revealed a significant higher number of CL in the NK1-R deficient mice in comparison to the wild-type group (P < 0.01). The increased formation of CL in NK1-R deficient mice corresponded to a considerable number of CL with retained oocyte not found in ovaries of the wild-type group. We conclude: The CL with a retained oocyte may indicate that the muscular apparatus of the preovulatory follicle plays a role in oocyte expulsion and that contractility of the follicle wall is deficient in the mutant group. Our observation may have implications for the luteinized unruptured follicle syndrome in humans.


Efficacy of Real-Time Computer-Aided Detection of Colorectal Neoplasia in a Randomized Trial.
One-fourth of colorectal neoplasias are missed during screening colonoscopies; these can develop into colorectal cancer (CRC). Deep learning systems allow for real-time computer-aided detection (CADe) of polyps with high accuracy. We performed a multicenter, randomized trial to assess the safety and efficacy of a CADe system in detection of colorectal neoplasias during real-time colonoscopy. We analyzed data from 685 subjects (61.32 ± 10.2 years old; 337 men) undergoing screening colonoscopies for CRC, post-polypectomy surveillance, or workup due to positive results from a fecal immunochemical test or signs or symptoms of CRC, at 3 centers in Italy from September through November 2019. Patients were randomly assigned (1:1) to groups who underwent high-definition colonoscopies with the CADe system or without (controls). The CADe system included an artificial intelligence-based medical device (GI-Genius, Medtronic) trained to process colonoscopy images and superimpose them, in real time, on the endoscopy display a green box over suspected lesions. A minimum withdrawal time of 6 minutes was required. Lesions were collected and histopathology findings were used as the reference standard. The primary outcome was adenoma detection rate (ADR, the percentage of patients with at least 1 histologically proven adenoma or carcinoma). Secondary outcomes were adenomas detected per colonoscopy, non-neoplastic resection rate, and withdrawal time. The ADR was significantly higher in the CADe group (54.8%) than in the control group (40.4%) (relative risk [RR], 1.30; 95% confidence interval [CI], 1.14-1.45). Adenomas detected per colonoscopy were significantly higher in the CADe group (mean, 1.07 ±1.54) than in the control group (mean 0.71 ± 1.20) (incidence rate ratio, 1.46; 95% CI, 1.15-1.86). Adenomas 5 mm or smaller were detected in a significantly higher proportion of subjects in the CADe group (33.7%) than in the control group (26.5%; RR, 1.26; 95% CI, 1.01-1.52), as were adenomas of 6 to 9 mm (detected in 10.6% of subjects in the CADe group vs 5.8% in the control group; RR, 1.78; 95% CI, 1.09-2.86), regardless of morphology or location. There was no significant difference between groups in withdrawal time (417 ± 101 seconds for the CADe group vs 435 ± 149 for controls; P = .1) or proportion of subjects with resection of non-neoplastic lesions (26.0% in the CADe group vs 28.7% of controls; RR, 1.00; 95% CI, 0.90-1.12). In a multicenter, randomized trial, we found that including CADe in real-time colonoscopy significantly increases ADR and adenomas detected per colonoscopy without increasing withdrawal time. ClinicalTrials.gov no: 04079478.


[Port wine stains or capillary malformations: surgical treatment].
Capillary malformations do not demand mostly any therapeutics. For aesthetic reasons, family or child can demand a treatment to ease even to remove the unsightly character of the lesion. In this context, the means employees must be simple and not engender aftereffects more unaesthetic than the lesion. The pulsed dye laser fulfils perfectly this conditions by improving the color of the lesion without touching the texture of the skin. However it's a treatment requiring many sessions over 2-3 years. Surgery keeps an interest for the treatment of capillary malformations resistant to laser (in particular on the limbs) or to treat soft tissues hyperplasia met in certain cervicofacial locations. The surgery uses the whole techniques of plastic surgery classified from the most simple to the most complicated: excision-suture in one time or iterative, excision and coverage by a skin graft, use of skin expansion techniques with local flaps.


Topical pimecrolimus lacks genotoxicity and cytotoxicity by means of micronucleus erythrocyte rodent assay.
Topical pimecrolimus is an alternative treatment of atopic dermatitis. However, rare cases of malignancy have been reported with their use. This study was performed to investigate the possible geno- or cytotoxic effect in mouse bone marrow caused by systemic absorption of pimecrolimus 1% cream. In order to determine this, induction of micronucleated erythrocytes (MNE) in mouse peripheral blood was determined after the cutaneous application of three different doses, daily for 5 consecutive days. No differences were found in frequencies of polychromatic erythrocytes, MNE, and micronucleated polychromatic erythrocytes in the different groups of study. In conclusion, under described conditions, no geno- or cytotoxic effects were detected after the cutaneous application of pimecrolimus.


The Association of Physician Orders for Life-Sustaining Treatment With Intensity of Treatment Among Patients Presenting to the Emergency Department.
Physician Orders for Life-Sustaining Treatment (POLST) forms are intended to help prevent the provision of unwanted medical interventions among patients with advanced illness or frailty who are approaching the end of life. We seek to evaluate how POLST form completion, treatment limitations, or both influence intensity of treatment among patients who present to the emergency department (ED). This was a retrospective cohort study of adults who presented to the ED at an academic medical center in Oregon between April 2015 and October 2016. POLST form completion and treatment limitations were the main exposures. Primary outcome was hospital admission; secondary outcomes included ICU admission and a composite measure of aggressive treatment. A total of 26,128 patients were included; 1,769 (6.8%) had completed POLST forms. Among patients with POLST, 52.1% had full treatment orders, and 6.4% had their forms accessed before admission. POLST form completion was not associated with hospital admission (adjusted odds ratio [aOR]=0.97; 95% confidence interval [CI] 0.84 to 1.12), ICU admission (aOR=0.82; 95% CI 0.55 to 1.22), or aggressive treatment (aOR=1.06; 95% CI 0.75 to 1.51). Compared with POLST forms with full treatment orders, those with treatment limitations were not associated with hospital admission (aOR=1.12; 95% CI 0.92 to 1.37) or aggressive treatment (aOR=0.87; 95% CI 0.5 to 1.52), but were associated with lower odds of ICU admission (aOR=0.31; 95% CI 0.16 to 0.61). Among patients presenting to the ED with POLST, the majority of POLST forms had orders for full treatment and were not accessed by emergency providers. These findings may partially explain why we found no association of POLST with treatment intensity. However, treatment limitations on POLST forms were associated with reduced odds of ICU admission. Implementation and accessibility of POLST forms are crucial when considering their effect on the provision of treatment consistent with patients' preferences.


Phytochemical study and biological effects of the essential oil of Fraxinus dimorpha Coss & Durieu §.
The present study describes the phytochemical study, antioxidant and antimicrobial activities of Fraxinus dimorpha essential oil, obtained from the leaves collected in the High Atlas Mountains. Forty compounds representing 86.2% with (E)-nerolidol as a major constituent and 29 compounds corresponding to 80.3% with eugenol as main components were identified from Ait M'hamed and from Siti Fadma, respectively. The F. dimorpha essential oil presents IC50 using DPPH varying from 5.33 to 6.03 mg/mL and EC50 using FRAP varying from 0.83 to 1.21 mg/mL. The antimicrobial activity of the oil was evaluated for ten microorganisms showed that the oil had a moderate potential activity. Fungal strains are more sensitive to the investigated oils, with a MIC varied between 1.8 and 3.8 mg/mL.


Sweet's syndrome associated with Hashimoto's thyroiditis.
Sweet's syndrome or acute febrile neutrophilic dermatosis is characterised by the abrupt onset of painful erythematous plaques or nodules, pyrexia (>38°F) and histopathologic evidence of a dense neutrophilic infiltrate without vasculitis. It has been reported in association with many diseases, however, its association with Hashimoto's thyroiditis is rare. A 47-year-old Filipino woman with a 30-year history of an asymptomatic anterior neck mass developed painful, erythematous annular plaques on her arms with associated fever. Skin biopsy confirmed the diagnosis of Sweet's syndrome. The anterior neck mass was confirmed to be Hashimoto's thyroiditis. This is a rare association with only two reported cases in the literature. There are no published cases in the Philippines on Sweet's syndrome and Hashimoto's thyroiditis to date.


Analysis of two-level systems and mechanical loss in amorphous ZrO2-doped Ta2O5 by non-cage-breaking and cage-breaking transitions.
The energy landscape of ZrO2-doped amorphous Ta2O5 is explored in this work. With models corresponding to experimental concentrations of 50% Zr and 50% Ta cations, we search for, gather, and analyze two-level systems (TLSs) from molecular dynamic simulations. The mechanical loss function is calculated for each TLS individually. The results show that TLS with low asymmetry and large elastic coupling constants contribute the most to mechanical loss. We identify these as "bad actors." The higher barriers relate to the mechanical loss at higher temperatures. The concept of the oxygen cage that describes the local structural environment surrounding a metal ion is introduced. The existence of a drastic change in local environment, or a cage-breaking process, enables us to understand the double peaks present in the asymmetry distribution and provides a pictorial interpretation to distinguish two types of TLS. Quantitatively, a cage-breaking event is related to at least one large distance change in an atom-atom pair, and non-cage-breaking transitions have only small rearrangements. The majority of TLSs are cage-breaking transitions, but non-cage-breaking TLS transitions show higher average mechanical loss in ZrO2-doped Ta2O5. By decomposing the contributions to mechanical loss, we find that the low temperature loss peak near 40 K mainly comes from non-cage-breaking TLS transitions and the second loss peak near 120 K originates from cage-breaking TLS transitions. This finding is important for understanding the interplay between the atomic structure of TLS and mechanical loss.


Prevalence estimation of microsatellite instability in colorectal cancers using tissue microarray based methods - A tertiary care center experience.
Microsatellite instability (MSI) pathway is known to be implicated in carcinogenesis of 15% colorectal carcinomas (CRC), including 2%-3% of cases of Lynch syndrome, as per western literature. MSI status has important prognostic and therapeutic implications. The prevalence of MSI in Indian CRC patients is unknown. We aimed to determine the prevalence by studying 231 consecutive unselected cases of CRC. Tissue microarrays using duplicate cores per case for 141 cases, and whole tissue sections for 90 cases, were used. Immunohistochemistry with four mismatch repair (MMR) markers - MLH1, MSH2, MSH6, and PMS2 was performed. Molecular analysis for MSI status was performed in 18 randomly selected cases. Correlation with various clinical and histopathological features was done using univariate and multivariate analysis. Loss of MMR immunohistochemical (IHC) was seen in 53/231 cases, i.e. 22.94% (95% confidence interval 17.52%-28.36%). MLH1-PMS2 dual loss comprised 13.9%, MSH2-MSH6 7.4%, and isolated PMS2 loss in 1.73% of cases. Univariate analysis showed significant association with age (<60 years), right-sided tumor location, histologic type, high grade, the presence of severe intratumoral lymphocytic (ITL) and peri-tumoral lymphocytic response, and N0 nodal stage. On multivariate analysis, independent variables were age < 60 years, right-sided location, and severe ITL. Molecular testing for MSI corroborated with the IHC results. The study results show a slightly higher prevalence of MSI-H phenotype, compared to Western literature, stressing the need for more widespread testing for better clinical management and identification of possible hereditary colon cancer syndrome.


Trout red blood cells treated with proteases fuse when placed on glass slides.
Treatment of trout red blood cells (RBC) with proteases and polyethylene glycol (PEG) either successively or concurrently caused cell fusion. Neither PEG nor protease treatment alone brought about the fusion of cells in suspension. However, incubation of RBC on glass slides with proteases caused extensive fusion.


TLG-S criteria are superior to both EORTC and PERCIST for predicting outcomes in patients with metastatic lung adenocarcinoma treated with erlotinib.
In this retrospective review of prospectively collected data, we sought to investigate whether early FDG-PET assessment of treatment response based on total lesion glycolysis measured using a systemic approach (TLG-S) would be superior to either local assessment with EORTC (European Organization for Research and Treatment of Cancer) criteria or single-lesion assessment with PERCIST (PET Response Criteria in Solid Tumors) for predicting clinical outcomes in patients with metastatic lung adenocarcinoma treated with erlotinib. We also examined the effect of bone flares on tumor response evaluation by single-lesion assessment with PERCIST in patients with metastatic bone lesions. We performed a retrospective review of prospectively collected data from 23 patients with metastatic lung adenocarcinoma treated with erlotinib. All participants underwent FDG-PET imaging at baseline and on days 14 and 56 after completion of erlotinib treatment. In addition, diagnostic CT scans were performed at baseline and on day 56. FDG-PET response was assessed with TLG-S, EORTC, and PERCIST criteria. Response assessment based on RECIST 1.1 (Response Evaluation Criteria in Solid Tumors) from diagnostic CT imaging was used as the reference standard. Two-year progression-free survival (PFS) and overall survival (OS) served as the main outcome measures. We identified 13 patients with bone metastases. Of these, four (31 %) with persistent bone uptake due to bone flares on day 14 were erroneously classified as non-responders according to the PERCIST criteria, but they were correctly classified as responders according to both the EORTC and TLG-S criteria. Patients who were classified as responders on day 14 based on TLG-S criteria had higher rates of 2-year PFS (26.7 % vs. 0 %, P = 0.007) and OS (40.0 % vs. 7.7 %, P = 0.018). Similar rates were observed in patients who showed a response on day 56 based on CT imaging according to the RECIST criteria. Patients classified as responders on day 14 according to the EORTC criteria on FDG-PET imaging had better rates of 2-year OS than did non-responders (36.4 % vs. 8.3 %, P = 0.015). TLG-S criteria may be of greater help in predicting survival outcomes than other forms of assessment. Bone flares, which can interfere with the interpretation of treatment response based on PERCIST criteria, are not uncommon in patients with metastatic lung adenocarcinoma treated with erlotinib.


The impact of a diagnostic decision support system on the consultation: perceptions of GPs and patients.
Clinical decision support systems (DSS) aimed at supporting diagnosis are not widely used. This is mainly due to usability issues and lack of integration into clinical work and the electronic health record (EHR). In this study we examined the usability and acceptability of a diagnostic DSS prototype integrated with the EHR and in comparison with the EHR alone. Thirty-four General Practitioners (GPs) consulted with 6 standardised patients (SPs) using only their EHR system (baseline session); on another day, they consulted with 6 different but matched for difficulty SPs, using the EHR with the integrated DSS prototype (DSS session). GPs were interviewed twice (at the end of each session), and completed the Post-Study System Usability Questionnaire at the end of the DSS session. The SPs completed the Consultation Satisfaction Questionnaire after each consultation. The majority of GPs (74%) found the DSS useful: it helped them consider more diagnoses and ask more targeted questions. They considered three user interface features to be the most useful: (1) integration with the EHR; (2) suggested diagnoses to consider at the start of the consultation and; (3) the checklist of symptoms and signs in relation to each suggested diagnosis. There were also criticisms: half of the GPs felt that the DSS changed their consultation style, by requiring them to code symptoms and signs while interacting with the patient. SPs sometimes commented that GPs were looking at their computer more than at them; this comment was made more often in the DSS session (15%) than in the baseline session (3%). Nevertheless, SP ratings on the satisfaction questionnaire did not differ between the two sessions. To use the DSS effectively, GPs would need to adapt their consultation style, so that they code more information during rather than at the end of the consultation. This presents a potential barrier to adoption. Training GPs to use the system in a patient-centred way, as well as improvement of the DSS interface itself, could facilitate coding. To enhance patient acceptability, patients should be informed about the potential of the DSS to improve diagnostic accuracy.


Ge-on-Si and Ge-on-SOI thermo-optic phase shifters for the mid-infrared.
Germanium-on-silicon thermo-optic phase shifters are demonstrated in the 5 μm wavelength range. Basic phase shifters require 700 mW of power for a 2π phase shift. The required power is brought down to 80 mW by complete undercut using focused ion beam. Finally an efficient thermo-optic phase shifter is demonstrated on the germanium on SOI platform. A tuning power (for a 2π phase shift) of 105 mW is achieved for a Ge-on-SOI structure which is lowered to 16 mW for a free standing phase shifter.


Polymorphism in 3-acetyl-4-hydroxy-2H-chromen-2-one.
A new polymorph (denoted polymorph II) of 3-acetyl-4-hydroxy-2H-chromen-2-one, C11H8O4, was obtained unexpectedly during an attempt to recrystallize the compound from salt-melted ice, and the structure is compared with that of the original polymorph (denoted polymorph I) [Lyssenko & Antipin (2001). Russ. Chem. Bull. 50, 418-431]. Strong intramolecular O-H...O hydrogen bonds are observed equally in the two polymorphs [O...O = 2.4263 (13) Å in polymorph II and 2.442 (1) Å in polymorph I], with a slight delocalization of the hydroxy H atom towards the ketonic O atom in polymorph II [H...O = 1.32 (2) Å in polymorph II and 1.45 (3) Å in polymorph I]. In both crystal structures, the packing of the molecules is dominated and stabilized by weak intermolecular C-H...O hydrogen bonds. Additional π-π stacking interactions between the keto-enol hydrogen-bonded rings stabilize polymorph I [the centres are separated by 3.28 (1) Å], while polymorph II is stabilized by interactions between α-pyrone rings, which are parallel to one another and separated by 3.670 (5) Å.