Entomopathogenicity and Biological Attributes of Himalayan Treasured Fungus Ophiocordyceps sinensis (Yarsagumba).
Members of the entomophagous fungi are considered very crucial in the fungal domain relative to their natural phenomenon and economic perspectives; however, inadequate knowledge of their mechanisms of interaction keeps them lagging behind in parallel studies of fungi associated with agro-ecology, forest pathology and medical biology. Ophiocordyceps sinensis (syn. Cordyceps sinensis), an intricate fungus-caterpillar complex after it parasitizes the larva of the moth, is a highly prized medicinal fungus known widely for ages due to its peculiar biochemical assets. Recent technological innovations have significantly contributed a great deal to profiling the variable clinical importance of this fungus and other related fungi with similar medicinal potential. However, a detailed mechanism behind fungal pathogenicity and fungal-insect interactions seems rather ambiguous and is poorly justified, demanding special attention. The goal of the present review is to divulge an update on the published data and provides promising insights on different biological events that have remained underemphasized in previous reviews on fungal biology with relation to life-history trade-offs, host specialization and selection pressures. The infection of larvae by a fungus is not a unique event in Cordyceps; hence, other fungal species are also reviewed for effective comparison. Conceivably, the rationale and approaches behind the inheritance of pharmacological abilities acquired and stored within the insect framework at a time when they are completely hijacked and consumed by fungal parasites, and the molecular mechanisms involved therein, are clearly documented.


Renal function in very old critically ill patients.
Current demographic change leads to higher number of elderly patients admitted to an ICU. Among other organs also the kidneys show age-related changes, which are associated with a decline in various aspects of renal function. The purpose of this review is to provide an overview of structural and functional changes in elderly and also to specifically address the increased risk of acute kidney injury (AKI) in this population. Ageing in the kidneys is affected by many different factors, such as low grade chronic inflammation, called inflammageing, and various comorbidities. Nevertheless, a decrease of glomerular filtration rate (GFR) occurs independent of the presence of comorbidities and a steady decline of GFR has been reported in both healthy men and women. Pharmacodynamic of many drugs is altered by these changes. Additionally the rate of diuretic resistance appears to be increased. The cause of AKI occurrence in older age is, multifactorial and includes preventable triggers (hypovolemia, hypotension, nephrotoxins) as well as changes associated with aging. Age-related alterations of the kidneys were found at microscopic and macroscopic levels of the cell. These changes lead to a reduced renal reserve and subsequently to an increased vulnerability of aged kidneys when an additional stressor is added. Age is an independent risk factor for developing AKI. Physicians should take into account the altered renal function in elderly patients and take renal protective measures at an early stage.


Toward patient-specific myocardial models of the heart.
This article presents a framework for building patient-specific models of the myocardium, to help diagnosis, therapy planning, and procedure guidance. The aim is to be able to introduce such models in clinical applications. Thus, there is a need to design models that can be adjusted from clinical data, images, or signals, which are sparse and noisy. The authors describe the three main components of a myocardial model: the anatomy, the electrophysiology, and the biomechanics. For each of these components, the authors try to obtain the best balance between prior knowledge and observable parameters to be able to adjust these models to patient data. To achieve this, there is a need to design models with the right level of complexity and a computational cost compatible with clinical constraints.


Effects of Mental Fatigue on Endurance Performance in the Heat.
Mental fatigue is a psychobiological state caused by prolonged periods of demanding cognitive activity and has been observed to decrease time trial (TT) endurance performance by ∼3.5% in normal ambient temperatures. Recently, it has been suggested that heat may augment the negative effect of mental fatigue on cognitive performance, raising the question whether it may also amplify the effect of mental fatigue on TT performance. In 30°C and 30% relative humidity, 10 endurance-trained male athletes (mean ± SD; age = 22 ± 3 yr, Wmax = 332 ± 41 W) completed two experimental conditions: intervention (I; 45-min Stroop task) and control (C; 45-min documentary). Pre- and postintervention/control, cognitive performance was followed up with a 5-min Flanker task. Thereafter, subjects cycled for 45 min at a fixed pace equal to 60% Wmax, immediately followed by a self-paced TT in which they had to produce a fixed amount of work (equal to cycling 15 min at 80% Wmax) as fast as possible. Self-reported mental fatigue was significantly higher after I compared with C (P < 0.05). Moreover EEG measures also indicated the occurrence of mental fatigue during the Stroop (P < 0.05). TT did not differ between conditions (I = 906 ± 30 s, C = 916 ± 29 s). Throughout exercise, physiological (HR, blood lactate, core, and skin temperature) and perceptual measures (perception of effort and thermal sensation) were not affected by mental fatigue. No negative effects of mild mental fatigue were observed on performance and the physiological and perceptual responses to endurance exercise in the heat. Most plausibly, mild mental fatigue does not reduce endurance performance when the brain is already stressed by a hot environment.


Minimally invasive repair of pectus excavatum in adults: a review article of presentation, workup, and surgical treatment.
Pectus excavatum (Pex) is one of the most common congenital deformities of the chest wall, with pectus constituting 90% of all chest wall deformities and excavatum being reported in almost 1:400 to 1:1,000 live births with predominant occurrence in males up to five times more than in females. Depending on the severity, presentation varies from mild cosmetic complaints to life limiting cardiopulmonary symptoms. Patients may develop symptoms as they age, and these symptoms may worsen over the years. A technique for minimally invasive repair for pectus excavatum (MIRPE) was introduced with the concept of temporarily implanting metal bars to correct the deformity. This has rapidly become the standard of care for the pediatric and adolescent patients. The use of MIRPE in adults, however, has been slower to adopt and more controversial. This is largely due to the increased calcification and rigidity of the chest wall in adults which can make the repair more complex and lead to a higher risk of complications. We present a literature review of the presentation, workup, and surgical treatment of adult patients with Pex undergoing MIRPE. Adult patients can, with advanced preoperative evaluations and technique modifications, undergo a highly successful repair resulting in symptom resolution and satisfying results.


[Acute anterior cruciate ligament rupture: repair or reconstruction?]
In the case of persistent complaints of instability due to a rupture of the anterior cruciate ligament (ACL), surgical treatment can be opted for, in which reconstruction with a body's own tendon graft (autograft) is the gold standard. New information has created renewed interest in the primary repair of an ACL rupture. Potential advantages of repair of the ACL rupture compared with a reconstruction are the restoration of the complex natural anatomy including the proprioception of the native ACL, and no donor site morbidity. Biomechanical studies show that when suturing an ACL rupture, intra-articular augmentation is important to protect the repaired ACL during healing. Given the results of randomized studies comparing the ACL suture technique including augmentation with the ACL reconstruction, it can be concluded that the nowadays used suture technique in combination with an augmentation could be an alternative treatment to the current gold standard, the ACL reconstruction.


Targeting monocyte recruitment in CNS autoimmune disease.
Monocytes and macrophages play a pathogenic role in a number of autoimmune inflammatory diseases. Recent studies in experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis, have identified a critical chemokine-mediated mechanism of monocyte homing to the central nervous system (CNS). Here, we summarize the current findings in EAE, develop a rationale for targeting the chemokine axis in order to treat CNS inflammatory disease, and review currently available molecule-specific therapeutics that inhibit monocyte trafficking to the CNS.


Effect of evidence and changes in reimbursement on the rate of arthroscopy for osteoarthritis.
The efficacy of arthroscopic debridement or lavage for knee osteoarthritis (OA) was cast into doubt after publication of several randomized controlled trials beginning in 2002. The authors set out to determine whether evidence of ineffectiveness, along with subsequent changes in reimbursement, were followed by changes in utilization rates of arthroscopy for patients with OA. Cohort study (prevalence); Level of evidence, 2. The Florida State Ambulatory Surgery Database was used to examine population-based rates of knee arthroscopy from 2000 to 2008 for patients with and without the diagnosis of OA; data were stratified between public and private payers. These trends were compared with patients who underwent arthroscopy for other diagnoses and were also compared with patients whose arthritis was not the primary indication for surgery. A 39% decrease in the adjusted population-based rate of knee arthroscopy for OA was observed, from 12.2 per 100,000 adults in 2000 (95% CI, 9.9-14.4) to 7.7 per 100,000 adults in 2008 (95% CI, 6.7-8.6). The overall rate among individuals with a primary diagnosis of OA significantly decreased for both public (P < .001) and private insurance (P = .001) and the rate of this decrease was similar between the two insurance types (P = .610). Although the unadjusted rates for all knee arthroscopy increased over the study period, the rate of increase was slowed in the years following the publication of several randomized controlled trials and subsequent changes in reimbursement. The average effect on arthroscopy rates attributed to these events was a reduction in 12 per 100,000 private arthroscopies (95% CI, -16.3 to 40.6; P = .404) and 35.7 per 100,000 publicly insured arthroscopies (95% CI, 15.0-56.4; P = .001). Evidence of the lack of efficacy of arthroscopy for knee OA, along with changes in reimbursement, preceded a significant decline in the population-based rates of this procedure in both publicly and privately insured patients in Florida.


[Effects of bridge parts on the gingiva].
Over the past few years, preparation and insertion of a dental bridges have been considerably modified and rationalized due to new methods and techniques. The former requirements the shape of pontics hat to meet are no longer fully valid. The behavior of the various materials (metals, resins, ceramics) in the mouth and especially towards the gingiva has been tested sufficiently. Knowledge regarding the functional conditions (flushing of the gingiva underneath bridges, turgor, abutment mobility, pulsation) has considerably increased in the past few years. Therefore recommendations regarding the shaping of pontics can be formulated that meet the anatomic, physiologic, and hygienic conditions as well as the esthetic wishes of the patients.


Antiproliferative effects of inducible nitric oxide synthase inhibition on decidualization in pseudopregnant rats.
The aim of this study was to assess the involvement in decidual proliferation of nitric oxide (NO), a regulator of many cellular processes, that is synthesized from L-arginine by NO synthase. The investigation was conducted on pseudopregnant (PG) rats in which the decidual cell reaction, the basis for the decidualization process, was surgically induced by uterine trauma on PG Day 4. Groups of animals (n = 5) were pretreated with either 2 doses/day of N(G)-nitro-L-arginine methyl ester (L-NAME) that inhibits NO synthase, or twice daily doses of L-NAME plus L-arginine combined. Drug application times coincided with 3 hr after lights on or 3 hr before lights off. The two treatment regimens (PG Days 1-4 or 5-8) respectively preceded or followed decidual induction. Animals were sacrificed at mid-light on PG Day 9, the day of maximal growth response to the deciduogenic stimulus. Parallel, time-dependent increases in both NO synthase activity and decidual growth occurred mainly in the endometrium. L-NAME produced reductions in endometrial and myometrial growth that were reversed by the combined L-NAME plus L-arginine treatments. These inhibitory effects by L-NAME were caused by only the pretraumal (PG Days 1-4) administration. Hormonally, circulating progesterone levels were similarly affected by this early treatment and may also contribute to the reduced decidual sensitivity. In contrast, serum estradiol, along with the zinc metalloenzymes, alkaline phosphatase and the matrix metalloproteinases--prominent decidualization biomarkers--were all unaffected by either the pre- or post-decidual induction dosings. The study demonstrates that inducible NO synthase/endogenous NO may physiologically participate in uterine metabolism during the decidual cell reaction. Moreover, by virtue of L-NAME inhibition of the decidual response, it appears that NO synthase/NO may influence decidual growth either by directly increasing uterine sensitivity to the deciduogenic stimulus or by indirectly affecting endometrial vascularity and subsequent availability of decidual metabolites.


Secrets of succulence.
Succulent plants are iconic components of the florae of many terrestrial ecosystems, but despite having caused fascination and prompted investigation for centuries, they still harbour many secrets in terms of physiological function and evolution. Tackling these mysteries is important, as this will not only provide insights into the dynamics and details of the convergent evolution of a major adaptive syndrome, but also inform efforts to conserve endangered biodiversity and utilize the unique physiological characteristics of succulents for biofuel and biomass production. Here I review advances in the phylogeny and organismal biology of succulent plants, and discuss how insights from recent work in the wider fields of plant hydraulics and photosynthetic physiology may relate to succulents. The potential for the exploration of mechanistic relationships between anatomical structure and physiological function to improve our understanding of the constraints that have shaped the evolution of succulence is highlighted. Finally, attention is drawn to how new methodologies and technologies provide exciting opportunities to address the wide range of outstanding questions in succulent plant biology.


Molecular Insights into Therapeutic Potentials of Hybrid Compounds Targeting Alzheimer's Disease.
Alzheimer's disease (AD) is one of the most complex progressive neurological disorders involving degeneration of neuronal connections in brain cells leading to cell death. AD is predominantly detected among elder people (> 65 years), mostly diagnosed with the symptoms of memory loss and cognitive dysfunctions. The multifarious pathogenesis of AD comprises the accumulation of pathogenic proteins, decreased neurotransmission, oxidative stress, and neuroinflammation. The conventional therapeutic approaches are limited to symptomatic benefits and are ineffective against disease progression. In recent years, researchers have shown immense interest in the designing and fabrication of various novel therapeutics comprised of naturally isolated hybrid molecules. Hybrid therapeutic compounds are developed from the combination of pharmacophores isolated from bioactive moieties which specifically target and block various AD-associated pathogenic pathways. The method of designing hybrid molecules has numerous advantages over conventional multitarget drug development methods. In comparison to in silico high throughput screening, hybrid molecules generate quicker results and are also less expensive than fragment-based drug development. Designing hybrid-multitargeted therapeutic compounds is thus a prospective approach in developing an effective treatment for AD. Nevertheless, several issues must be addressed, and additional researches should be conducted to develop hybrid therapeutic compounds for clinical usage while keeping other off-target adverse effects in mind. In this review, we have summarized the recent progress on synthesis of hybrid compounds, their molecular mechanism, and therapeutic potential in AD. Using synoptic tables, figures, and schemes, the review presents therapeutic promise and potential for the development of many disease-modifying hybrids into next-generation medicines for AD.


Isolation of monoclonal antibodies monospecific for bovine alpha-lactalbumin.
Monoclonal antibodies were generated against purified bovine alpha-lactalbumin. Three antibodies reactive only to alpha-lactalbumin were selected. Two of the antibodies appeared to be species monospecific and bound with only bovine alpha-lactalbumin. The third monoclonal recognized both bovine and human alpha-lactalbumin with a 2:1 preference for bovine alpha-lactalbumin. Two of the monoclonals (48-60, 48-68) bound to different epitopes with high affinity (Ka = 8 x 10(11), 5.3 x 10(12) M-1). The third monoclonal (48-22), which was of isotype IgA, had an epitope similar to that of 48-60 but with an apparent affinity of approximately 4 x 10(12) M-1. These antibodies should prove extremely useful adjuncts in structural studies of bovine alpha-lactalbumin.


Vacuum ultraviolet pulsed field ionization-photoelectron and infrared-photoinduced Rydberg ionization study of trans-1,3-butadiene.
The vacuum ultraviolet (VUV) laser pulsed field ionization-photoelectron (PFI-PE) spectrum of trans-1,3-butadiene (trans-CH(2)[Double Bond]CHCH[Double Bond]CH(2)) has been measured in the region of 0-1700 cm(-1) above its ionization energy (IE) to probe the vibrational modes nu(i) (+) (i=1-18) of trans-CH(2)[Double Bond]CHCH[Double Bond]CH(2) (+). The high-frequency vibrational modes nu(i) (+) (i=19, 22, and 23) of trans-CH(2)[Double Bond]CHCH[Double Bond]CH(2) (+) have also been probed by the VUV-infrared-photoinduced Rydberg ionization (VUV-IR-PIRI) measurement. On the basis of the semiempirical simulation of the origin VUV-PFI-PE band, the IE(trans-CH(2)[Double Bond]CHCH[Double Bond]CH(2)) is determined to be 73 150.1+/-1.5 cm(-1) (9.06946+/-0.00019 eV). This value has been used to benchmark the state-of-the-art theoretical IE prediction based on the CCSD(T,Full)/CBS procedures, the calculation of which is reported in the present study. The vibrational bands observed in the VUV-PFI-PE and VUV-IR-PIRI spectra were assigned based on ab initio anharmonic vibrational frequencies and Franck-Condon factor calculations for the photoionization transitions. Combining the VUV-PFI-PE and VUV-IR-PIRI measurements, 17 fundamental vibrational frequencies of trans-CH(2)[Double Bond]CHCH[Double Bond]CH(2) (+) have been determined, including nu(1) (+)=182+/-3, nu(2) (+)=300+/-3, nu(3) (+)=428+/-3, nu(4) (+)=514+/-3, nu(5) (+)=554+/-5, nu(6) (+)=901+/-3, nu(7) (+)=928+/-5, nu(8) (+)=994+/-3, nu(9) (+)=1008+/-5, nu(10) (+)=1094+/-5, nu(13) (+)=1258+/-3, nu(14) (+)=1293+/-3, nu(16) (+)=1479+/-3, nu(18) (+)=1620+/-3, nu(19) (+)=2985+/-10, nu(22) (+)=3030+/-10, and nu(23) (+)=3105+/-10 cm(-1).


Identification of a polyketide biosynthesis gene cluster by transcriptional regulator activation in Aspergillus terreus.
In filamentous fungi, the secondary metabolism is environmentally sensitive. Most of the biosynthetic gene clusters of secondary metabolites are silent under laboratory conditions. In this study, a highly conserved naphthopyrone PKS ATEG_06206 was identified in the genome sequence of A. terreus MEFC01. This gene is silent under laboratory conditions. To study the function of this PKS, we activated the silent biosynthetic pathway by replacing the promoter of cluster-specific transcriptional factor ATEG_06205 in A. terreus MEFC01. With this strategy, we confirmed that the products of this cryptic PKS are naphthoquinones. These naphthoquinones are soluble pigments, which could be secreted into the agar medium and culture broth. For this reason, the colour of mycelium and conidia of the activated mutant was significantly darker than that of the parental strain. The gene cluster and biosynthetic pathway were further elucidated through the reverse genetics approach and enzymatic assay in vitro.


Sodium/hydrogen-exchanger inhibition during cardioplegic arrest and cardiopulmonary bypass: an experimental study.
We sought to determine whether pretreatment with a sodium/hydrogen-exchange inhibitor (EMD 96 785) improves myocardial performance and reduces myocardial edema after cardioplegic arrest and cardiopulmonary bypass. Anesthetized dogs (n = 13) were instrumented with vascular catheters, myocardial ultrasonic crystals, and left ventricular micromanometers to measure preload recruitable stroke work, maximum rate of pressure rise (positive and negative), and left ventricular end-diastolic volume and pressure. Cardiac output was measured by means of thermodilution. Myocardial tissue water content was determined from sequential biopsy. After baseline measurements, hypothermic (28 degrees C) cardiopulmonary bypass was initiated. Cardioplegic arrest (4 degrees C Bretschneider crystalloid cardioplegic solution) was maintained for 2 hours, followed by reperfusion-rewarming and separation from cardiopulmonary bypass. Preload recruitable stroke work and myocardial tissue water content were measured at 30, 60, and 120 minutes after bypass. EMD 96 785 (3 mg/kg) was given 15 minutes before bypass, and 2 micromol was given in the cardioplegic solution. Control animals received the same volume of saline vehicle. Arterial-coronary sinus lactate difference was similar in both animals receiving EMD 96 785 and control animals, suggesting equivalent myocardial ischemia in each group. Myocardial tissue water content increased from baseline in both animals receiving EMD 96 785 and control animals with cardiopulmonary bypass and cardioplegic arrest but was statistically lower in animals receiving EMD 96 785 compared with control animals (range, 1.0%-1.5% lower in animals receiving EMD 96 785). Preload recruitable stroke work decreased from baseline (97 +/- 2 mm Hg) at 30 (59 +/- 6 mm Hg) and 60 (72 +/- 9 mm Hg) minutes after cardiopulmonary bypass and cardioplegic arrest in control animals; preload recruitable stroke work did not decrease from baseline (98 +/- 2 mm Hg) in animals receiving EMD 96 785 and was statistically greater at 30 (88 +/- 5 mm Hg) and 60 (99 +/- 4 mm Hg) minutes after bypass and arrest compared with control animals. Sodium/hydrogen-exchanger inhibition decreases myocardial edema immediately after cardiopulmonary bypass and cardioplegic arrest and improves preload recruitable stroke work. Sodium/hydrogen-exchange inhibition during cardiac procedures with cardiopulmonary bypass and cardioplegic arrest may be a useful adjunct to improve myocardial performance in the immediate postbypass or arrest period.


Subsistence ecology and carrying capacity in two Papua New Guinea populations.
This article examines the mechanisms of subsistence adaptation of two Papua New Guinea populations, the Metroxylon sago-depending lowland Gidra and the taro-monoculture Mountain Ok, surviving in low population densities of 0.5 and 1.4 persons per km2. Observation of the groups' land use systems strongly suggests that their population densities have not been far below the carrying capacity, although the territory of each population is markedly heterogeneous. Both groups have maintained their sustainable food production not only for resource management but also for survival at a population level, either expanding their territory or changing the sustainable level in tandem with changes of subsistence system.


Interaction between Chlamydia pneumoniae seropositivity, inflammation and risk factors for atherosclerosis in patients with severe coronary stenosis.
To investigate whether Chlamydia pneumoniae (Cpn) seropositivity in patients with suspected coronary artery disease (CAD) (n = 81) is associated with increases in markers of inflammation, the severity of coronary atherosclerosis, and traditional risk factors for cardiovascular events. The severity of coronary atherosclerosis was ranked by Gensini score. Inflammation and endothelial dysfunction were evaluated using white blood cell counts and levels of high-sensitivity C-reactive protein (hs-CRP), ferritin, tumour necrosis factor-alpha (TNF-alpha), interleukins 1beta and 6 (IL-1beta, IL-6), soluble intercellular adhesion molecule-1 (sICAM-1), E-selectin and oxidized LDL (oxLDL), and these were compared between Cpn-seropositive and seronegative individuals. IgA and IgG Cpn seropositivity were significantly associated with the presence of CAD (p = 0.005) and were independent predictive factors for the severity of coronary atherosclerosis (p = 0.005). Elevated levels of IL-6 (p = 0.027) and triglyceride (p = 0.038) and low levels of high-density lipoprotein cholesterol (HDL-C) (p = 0.038) were significantly predicted by Cpn IgA and IgG seropositivity. Seropositivity for Cpn is a risk factor for patients with significant angiographically documented coronary stenosis. Additionally, Cpn seropositivity was significantly associated with dyslipidemia and elevated IL-6, known risk factors for CAD. These observations indicate that Cpn infection may be one entry point to the causal or contributory pathways that lead to atherosclerosis and its clinical manifestations.


Frontal lobe functions and dysfunctions.
Frontal lobe syndromes with personality change are well known for about 150 years but mysteries of their underlying anatomophysiological mechanisms have started to unfold in recent years. The frontal lobe accommodates an extension of the primary motor (precentral) cortex, the premotor region and the interhemispherically located supplementary motor region, both of them forming area 6 and its subdivisions. The anterior and inferior frontal structures (and also the eye field, area 8) belong to the prefrontal region. The prefrontal cortex is also involved in motor action: in its initiation, planning, designing and sequencing rather than its mere execution. This requires drive and initiative to move, their deficits resulting in moderate to extreme apathy. Forces of motivation are likely to be mediated via the fronto-orbital cortex (known as an extension of the temporo-limbic system) which also exerts inhibitory influences on prefrontal functioning, and disinhibitory frontal lobe syndromes (from tactlessness to aggression) are the result of frontobasal impairment. A special form of frontal-motor cortex disconnection may occur in childhood: in the rare Rett syndrome and, with limitation to the prefrontal cortex, in the common Attention Deficit Hyperactivity Disorder (ADHD). The initiation of movement is based upon the constant influx of afferent-sensory messages from posterior cerebral regions and strong mesiodorsal thalamic connections, providing information for each following initiatory prefrontal motor impulse which depends on such information from the past moment. This "Working Memory" appears to be the keystone of mental and motor prefrontal function. Becoming unnecessary in the next moments, the afferent signals undergo immediate extinction due to inhibitory fronto-orbital impulses. It is assumed that the classical absence attack with generalized spike-waves of frontal onset causes a "suspension of the working memory" and thus permits immediate postictal recuperation of frontal functions. The gap between afferent and efferent signals in the working memory is likely to permit neurocognitive-processes and, in Homo sapiens, a widened gap is thought to provide a basis for reflection and cogitation uniquely human properties.


Bypassing hazard of housekeeping genes: their evaluation in rat granule neurons treated with cerebrospinal fluid of multiple sclerosis subjects.
Gene expression studies employing real-time PCR has become an intrinsic part of biomedical research. Appropriate normalization of target gene transcript(s) based on stably expressed housekeeping genes is crucial in individual experimental conditions to obtain accurate results. In multiple sclerosis (MS), several gene expression studies have been undertaken, however, the suitability of housekeeping genes to express stably in this disease is not yet explored. Recent research suggests that their expression level may vary under different experimental conditions. Hence it is indispensible to evaluate their expression stability to accurately normalize target gene transcripts. The present study aims to evaluate the expression stability of seven housekeeping genes in rat granule neurons treated with cerebrospinal fluid of MS patients. The selected reference genes were quantified by real time PCR and their expression stability was assessed using GeNorm and NormFinder algorithms. GeNorm identified transferrin receptor (Tfrc) and microglobulin beta-2 (B2m) the most stable genes followed by ribosomal protein L19 (Rpl19) whereas β-actin (ActB) and glyceraldehyde-3-phosphate-dehydrogenase (Gapdh) the most fluctuated ones in these neurons. NormFinder identified Tfrc as the best invariable gene followed by B2m and Rpl19. ActB and Gapdh were the least stable genes as analyzed by NormFinder algorithm. Both methods reported Tfrc and B2m the most stably expressed genes and Gapdh the least stable one. Altogether our data demonstrate the significance of pre-validation of housekeeping genes for accurate normalization and indicates Tfrc and B2m as best endogenous controls in MS. ActB and Gapdh are not recommended in gene expression studies related to current one.


Immunological, paracrine and endocrine aspects of testicular immune privilege.
Protection of the spermatogenic cells from the host immune response is fundamental to male fertility. Significantly, this protection extends to the tolerance of foreign tissue grafts placed within the testicular environment, a phenomenon that is called 'immune privilege'. This privilege of the testis appears to involve several levels of immune control, encompassing the normal mechanisms of immune tolerance, antigen sequestration behind the blood-testis barrier, reduced immune activation, localised immunosuppression and antigen-specific immunoregulation. Central to these regulatory processes are the somatic cells of the testis, particularly the Sertoli cells, and testicular secretions, including androgens, cytokines, peptides and bioactive lipids. Failure of these protective mechanisms, which may be precipitated by trauma, inflammation or infection, or as the consequence of genetic factors, can lead to androgen deficiency, infertility and autoimmunity.


Unicystic Ameloblastoma of Mandible with an Unusual Diverse Histopathology: A Rare Case Report.
Ameloblastomas of jaws are benign odontogenic tumours with four clinical variants being solid multicystic type, unicystic type, extra osseous type and desmoplastic type. Unicystic ameloblastoma accounts for only 13% of all the known cases in the scientific literature. Follicular and plexiform patterns are the commonly seen histopathological patterns in unicystic ameloblastoma. Though rare in itself, presence of granular cells along with acanthomatous changes occurring in unicystic ameloblastoma is a rare phenomenon. We present a rare case report of unicystic ameloblastoma of right mandible with an unusual histopathology. It exhibited both luminal and mural types as well as both acanthomatous and granular cell changes found together. As occurrence of unicystic ameloblastoma of jaws with such varied histopathology is rare, their course, clinical outcome, prognosis and recurrence rate are not clear. Documentation of more such cases in literature may make pathogenesis and nature of these lesions more insightful.


Assessment of water, sanitation and hygiene in HCFs: which tool to follow?
Water, sanitation and hygiene (WASH) is important to improve and maintain the quality of health care services. Improving and managing WASH services require strong and consistent monitoring mechanisms to measure progress and direct efforts where needs are greatest. Although several tools are available to assess WASH in health care facilities (HCFs), there is always a dilemma among the program managers to select an appropriate tool for the assessment of WASH. Thus, it was aimed to perform a descriptive review of all available WASH assessment tools and assist in reaching a consensus for an optimal tool to assess WASH in HCFs. For this descriptive review, PubMed, ScopeMed and Google Scholar were used to search all available tools for the assessment of WASH. All the tools available online since 1991 till July 2018 were included in the review. Globally, nine different WASH assessment tools were retrieved. The majority of them have their self-limitations on the basis of 11 selected indicators and were examined in all the retrieved tools. There are variability and overlapping components within the specific tools. Very few survey instruments including human resource (HR), supply, budget, patient/staff satisfaction and documentation for appropriateness of WASH were found to be neglected. The majority of instruments were based on the subjective assessment of WASH validating with microbiological surveillance and photo documentation. The descriptive review suggests that various tools are available for the assessment of WASH but none of them seem to be complete with all indicators and to have consensus for the elements. Therefore, there is a need to develop a robust and comprehensive tool for the assessment of WASH in HCFs.


Effects of obesity phenotype on coronary heart disease risk factors in response to weight loss.
To determine whether there is a difference in risk-factor improvement for coronary heart disease (CHD) between the intra-abdominal fat (IF) and subcutaneous fat (SF) obesity phenotypes after weight loss. Subjects included 55 mildly obese women (body mass index, 25 to 36 kg/m(2); age range, 34 to 63 years) who had at least two of three CHD risk factors [systolic blood pressure (SBP), >140 mm Hg; total cholesterol (TC), >220 mg/dL; fasting plasma glucose, >110 mg/dL). Using computed tomography, IF obesity was classified as > or =110 cm(2) of the IF area measured; subjects with <110 cm(2) were classified as having SF obesity. The IF and SF obesity groups were divided into diet-only and diet-plus-exercise groups. Assays and measurements were performed before and after a 14-week (98-day) intervention. Weight was reduced by 7 to 10 kg in each group. The IF and SF areas, SBP, diastolic blood pressure, TC, and low-density lipoprotein-cholesterol were significantly reduced in all groups (p < 0.01). Reduction in IF area was greater in IF obesity than in SF obesity, whereas no differences were observed in the improvement of CHD risk factors. Sample sizes needed for observing a significant difference for SBP, TC, triglycerides, and fasting plasma glucose were greater than the number of subjects in this study. Our results suggest that the influence of the obesity phenotype on improving CHD risk factors is not apparent. A larger study is needed to prove the validity of this finding.


Direct and indirect effects of routine vaccination of children with 7-valent pneumococcal conjugate vaccine on incidence of invasive pneumococcal disease--United States, 1998-2003.
Streptococcus pneumoniae (pneumococcus) is a leading cause of pneumonia and meningitis in the United States and disproportionately affects young children and the elderly. In 2000, a 7-valent pneumococcal conjugate vaccine (PCV7) was licensed in the United States for routine use in children aged <5 years. Surveillance data from 2001 and 2002 indicated substantial declines in invasive pneumococcal disease (IPD) in children and adults compared with prevaccine years . This report updates assessment of the impact of PCV7 on IPD through 2003 by using population-based data from the Active Bacterial Core surveillance (ABCs) of the Emerging Infections Program Network, a cooperative surveillance program conducted by several state health departments and CDC. The results of this analysis indicated that 1) routine vaccination of young children with PCV7 continued to result in statistically significant declines in incidence of IPD through 2003 in the age group targeted for vaccination and among older children and adults, 2) the vaccine prevented more than twice as many IPD cases in 2003 through indirect effects on pneumococcal transmission (i.e., herd immunity) than through its direct effect of protecting vaccinated children, and 3) increases in disease caused by pneumococcal serotypes not included in the vaccine (i.e., replacement disease) occurred in certain populations but were small compared with overall declines in vaccine-serotype disease. Ongoing surveillance is needed to assess whether reductions in vaccine-serotype IPD are sustained and whether replacement disease will erode the substantial benefits of routine vaccination.


Critical function of a Chlamydomonas reinhardtii putative polyphosphate polymerase subunit during nutrient deprivation.
Forward genetics was used to isolate Chlamydomonas reinhardtii mutants with altered abilities to acclimate to sulfur (S) deficiency. The ars76 mutant has a deletion that eliminates several genes, including VACUOLAR TRANSPORTER CHAPERONE1 (VTC1), which encodes a component of a polyphosphate polymerase complex. The ars76 mutant cannot accumulate arylsulfatase protein or mRNA and shows marked alterations in levels of many transcripts encoded by genes induced during S deprivation. The mutant also shows little acidocalcisome formation compared with wild-type, S-deprived cells and dies more rapidly than wild-type cells following exposure to S-, phosphorus-, or nitrogen (N)-deficient conditions. Furthermore, the mutant does not accumulate periplasmic L-amino acid oxidase during N deprivation. Introduction of the VTC1 gene specifically complements the ars76 phenotypes, suggesting that normal acidocalcisome formation in cells deprived of S requires VTC1. Our data also indicate that a deficiency in acidocalcisome function impacts trafficking of periplasmic proteins, which can then feed back on the transcription of the genes encoding these proteins. These results and the reported function of vacuoles in degradation processes suggest a major role of the acidocalcisome in reshaping the cell during acclimation to changing environmental conditions.


Feline lower airway disease: a retrospective study of 22 naturally occurring cases from Greece.
In this retrospective study of 22 cats with lower airway disease of either intermittent (23%) or persistent nature (77%), the Siamese breed (55%) was significantly over-represented. Females (68%) were slightly but not significantly over-represented. No significant association was found between the clinical stage of disease and the physical findings, thoracic radiographic changes or the response to treatment. Cough, the most common presenting complaint, was the only symptom detected in the cats with intermittent disease, yet the two most severely affected animals did not show it. Thoracic auscultation did not reveal any abnormality in 41% of the cats. Haematology revealed eosinophilia in 46% of the cats. A bronchial pattern was the most common radiographic abnormality (73%), followed by alveolar (32%) and interstitial patterns (23%). Interestingly, thoracic radiographs were normal in 23% of the cats. The combination of short-term corticosteroids and bronchodilators resulted in complete and long-term remission of symptoms in nine cats, while the other 11 required ongoing medication because of relatively frequent relapses. One of the remaining two cats died during an asthmatic crisis, while the other was lost to follow up.


Biotin as a Reactive Handle to Selectively Label Proteins and DNA with Small Molecules.
Biotin is a common functional handle for bioconjugation to proteins and DNA, but its uses are limited to protein-containing conjugation partners such as streptavidin and derivatives thereof. Recently, oxaziridine reagents were developed that selectively conjugate the thioether of methionines on the surface of proteins, a method termed redox-activated chemical tagging (ReACT). These reagents generate sulfimide linkages that range in stability depending on the solvent accessibility and substitutions on the oxaziridine. Here we show that oxaziridine reagents react rapidly with the thioether in biotin to produce sulfimide products that are stable for more than 10 d at 37 °C. This method, which we call biotin redox-activated chemical tagging (BioReACT), expands the utility of biotin labeling and enables a predictable and stable chemical conjugation to biomolecules without the need to screen for a suitable methionine conjugation site. We demonstrate the versatility of this approach by producing a fluorescently labeled antibody, an antibody-drug conjugate, and a small molecule-conjugated oligonucleotide. We anticipate that BioReACT will be useful to rapidly introduce biorthogonal handles into biomolecules using biotin, a functional group that is widespread and straightforward to install.


Fine mapping of the N-terminal cytotoxicity region of Clostridium perfringens enterotoxin by site-directed mutagenesis.
Clostridium perfringens enterotoxin (CPE) has a unique mechanism of action that results in the formation of large, sodium dodecyl sulfate-resistant complexes involving tight junction proteins; those complexes then induce plasma membrane permeability alterations in host intestinal epithelial cells, leading to cell death and epithelial desquamation. Previous deletion and point mutational studies mapped CPE receptor binding activity to the toxin's extreme C terminus. Those earlier analyses also determined that an N-terminal CPE region between residues D45 and G53 is required for large complex formation and cytotoxicity. To more finely map this N-terminal cytotoxicity region, site-directed mutagenesis was performed with recombinant CPE (rCPE). Alanine-scanning mutagenesis produced one rCPE variant, D48A, that failed to form large complexes or induce cytotoxicity, despite having normal ability to bind and form the small complex. Two saturation variants, D48E and D48N, also had a phenotype resembling that of the D48A variant, indicating that both size and charge are important at CPE residue 48. Another alanine substitution rCPE variant, I51A, was highly attenuated for large complex formation and cytotoxicity, but rCPE saturation variants I51L and I51V displayed a normal large complex formation and cytotoxicity phenotype. Collectively, these mutagenesis results identify a core CPE sequence extending from residues G47 to I51 that directly participates in large complex formation and cytotoxicity.


[Acute abdomen: emergency laparoscopy or observation?].
Acute abdomen accounts for 13-40% of all emergency surgical admissions. The aim of this prospective randomised controlled study was to examine the role of early laparoscopy in the management of acute abdomen compared with the more traditional active observation approach. From July 1993 to August 2004, 522 patients consecutively admitted with acute abdomen were randomised to either early laparoscopy (260 patients) (group 1) or active observation and non-invasive investigation (262 patients) (group 2). Baseline investigations included a full blood count, a pregnancy test in women of child-bearing age, and chest and/or abdominal radiography, if indicated clinically. Sixty-two patients in the laparoscopy group underwent a total of 116 radiological investigations compared with a total of 558 investigations in all patients in the observation group (p < 0.05). In the observation group, 34.7% of patients remained without a clear diagnosis compared with 4.2% of patients in the early laparoscopy group (p < 0.0001). The morbidity rate was 1.1% in group 1 and 27% in group 2 (p < 0.0001). The duration of hospital stay was significantly shorter in group 1 (3.1 vs 7.3 days) (p < 0.01). Eight patients in group 1 required readmission (total readmission: 46 days) compared with 58 patients in group 2 with a total readmission of 201 days (p < 0.05). Early laparoscopy is valuable in the management of acute abdomen. It affords significantly higher diagnostic accuracy and a greater improvement in quality of life than the more traditional observation approach.


Inhibition of Death-associated Protein Kinase 1 protects against Epileptic Seizures in mice.
Epilepsy is a chronic encephalopathy and one of the most common neurological disorders. Death-associated protein kinase 1 (DAPK1) expression has been shown to be upregulated in the brains of human epilepsy patients compared with those of normal subjects. However, little is known about the impact of DAPK1 on epileptic seizure conditions. In this study, we aim to clarify whether and how DAPK1 is regulated in epilepsy and whether targeting DAPK1 expression or activity has a protective effect against epilepsy using seizure animal models. Here, we found that cortical and hippocampal DAPK1 activity but not DAPK1 expression was increased immediately after convulsive pentylenetetrazol (PTZ) exposure in mice. However, DAPK1 overexpression was found after chronic low-dose PTZ insults during the kindling paradigm. The suppression of DAPK1 expression by genetic knockout significantly reduced PTZ-induced seizure phenotypes and the development of kindled seizures. Moreover, pharmacological inhibition of DAPK1 activity exerted rapid antiepileptic effects in both acute and chronic epilepsy mouse models. Mechanistically, PTZ stimulated the phosphorylation of NR2B through DAPK1 activation. Combined together, these results suggest that DAPK1 regulation is a novel mechanism for the control of both acute and chronic epilepsy and provide new therapeutic strategies for the treatment of human epilepsy.


Endophytic Beauveria bassiana in Foliar-Treated Citrus limon Plants Acting as a Growth Suppressor to Three Successive Generations of Diaphorina citri Kuwayama (Hemiptera: Liviidae).
Entomopathogenic fungi are commonly applied as inundative sprays to protect plants against insect pests. Their artificial establishment as fungal endophytes to provide other benefits to the host plants aside mere protection against the primary pests has also been widely demonstrated. In the present study, two fungal strains of Beauveria bassiana and one strain of Isaria fumosorosea were assessed in a pathogenicity test against adults of Asian citrus psyllid (Diaphorina citri) and found to induce 50% reduction in the survival rate of D. citri adults within 5 days of exposure. The ability of the three fungal strains to endophytically colonize Citrus limon, the impact on plant growth and the effects of systemic colonization on 3 successive generations of D. citri feeding on colonized plants was evaluated. Citrus seedlings at 4 months post-planting were inoculated with each of the fungal strains via foliar spraying. Both strains of B. bassiana successfully colonized the seedlings. One of the B. bassiana strains (BB Fafu-13) was sustained up to 12 weeks in the colonized seedlings, whereas the other B. bassiana strain (BB Fafu-16) was only recovered up to 8 weeks post-inoculation. Isaria fumosorosea (IF Fafu-1) failed to colonize the plant. Both strains of B. bassiana induced significant improvement in plant height and flush production in endophytically colonized seedlings. In addition, endophytic B. bassiana caused 10-15% D. citri adult mortality within 7 days of exposure. Female D. citri feeding on B. bassiana challenged plants laid fewer eggs as compared to those feeding on endophyte-free seedlings, while reduction in adult emergence was recorded on B. bassiana treated plants. With this study, we present the first evidence of B. bassiana artificial establishment as fungal endophyte in citrus plants and its negative effects on D. citri.


If it goes up, must it come down? Chronic stress and the hypothalamic-pituitary-adrenocortical axis in humans.
The notion that chronic stress fosters disease by activating the hypothalamic-pituitary-adrenocortical (HPA) axis is featured prominently in many theories. The research linking chronic stress and HPA function is contradictory, however, with some studies reporting increased activation, and others reporting the opposite. This meta-analysis showed that much of the variability is attributable to stressor and person features. Timing is an especially critical element, as hormonal activity is elevated at stressor onset but reduces as time passes. Stressors that threaten physical integrity, involve trauma, and are uncontrollable elicit a high, flat diurnal profile of cortisol secretion. Finally, HPA activity is shaped by a person's response to the situation; it increases with subjective distress but is lower in persons with posttraumatic stress disorder.


Mechanistic or mammalian target of rapamycin (mTOR) may determine robustness in young male mice at the cost of accelerated aging.
Males, who are bigger and stronger than females, live shorter in most species from flies to mammals including humans. Cellular mass growth is driven in part by mTOR (Target of Rapamycin). When developmental growth is completed, then, instead of growth, mTOR drives aging, manifested by increased cellular functions, such as hyper-secretion by fibroblasts, thus altering homeostasis, leading to age-related diseases and death. We hypothesize that MTOR activity is elevated in male mice compared with females. Noteworthy, 6 months old males were 28 % heavier than females. Also levels of phosphorylated S6 (pS6) and phospho-AKT (p-AKT, Ser 473), markers of the mTOR activity, were higher in male organs tested. Levels of pS6 were highly variable among mice and correlated with body weight and p-AKT. With age, the difference between levels of pS6 between sexes tended to minimize, albeit males still had hyperactive mTOR. Unlike fasting, the intraperitoneal (i.p.) administration of rapamycin eliminated pS6 in all organs of all females measured by immunoblotting and immunohistochemistry without affecting p-AKT and blood insulin. Although i.p. rapamycin dramatically decreased levels of pS6 in males too, it was still detectable by immunoblotting upon longer exposure. Our study demonstrated that both tissue p-AKT and pS6 were higher in young male mice and were associated with increased body weight and insulin. These data can explain bigger body size and faster aging in males. Our data suggest higher efficacy of rapamycin compared to fasting. Higher sensitivity of females to rapamycin may explain more pronounced life extension by rapamycin observed in females compared to males in several studies.


High-dose weekly fractionation radiotherapy in advanced cancer of the uterine cervix.
A trial comparing two different radiotherapy techniques and schedules in the treatment of 83 patients with advanced cancer of the uterine cervix (stage IIIB) employing external irradiation alone is described. The one technique, used routinely in this department, employed a conventional daily fractionation schedule while the other used a high-dose weekly fractionation regimen. The techniques are described. The aim of the trial was to compare the efficacy and morbidity of these two methods of treatment. Dose distribution curves in cross-section and midsagittal planes are shown and calculations or equivalent doses at various selected points using Ellis's nominal single-dose formula are tabulated. The 2-year survival figures were 33% for the daily fractionation technique and 22% for the weekly regimen. Serious late complication rates were 6% for the daily regimen and 22% for the weekly schedule. These differences are not statistically significant. Late complication rates in the weekly fractionation regimen appeared to be lower than figures quoted by other authors. Local control within the irradiated volume was better in the group treated by the daily fractionation method.


Targeting of Phospholipase D1 Ameliorates Collagen-Induced Arthritis via Modulation of Treg and Th17 Cell Imbalance and Suppression of Osteoclastogenesis.
Phospholipase D1 (PLD1) plays a crucial role in various inflammatory and autoimmune diseases. Rheumatoid arthritis (RA) is a chronic and systemic autoimmune disease. However, the role of PLD1 in the pathogenesis of RA remains unknown. Here, we first investigated the role and effects of PLD1 in collagen-induced arthritis (CIA) and found that genetic and pharmacological inhibition of PLD1 in DBA1/J mice with CIA reduced the incidence of CIA, decreased the clinical score, and abrogated disease symptoms including infiltration of leukocytes, synovial inflammation, bone erosion, and cartilage destruction. Moreover, ablation and inhibition of PLD1 suppressed the production of type II collagen-specific IgG2a autoantibody and proinflammatory cytokines, accompanied by an increase in the regulatory T (Treg) cell population and a decrease in the Th17 cell population in CIA mice. The PLD1 inhibitor also promoted differentiation of Treg cells and suppressed differentiation of Th17 cells in vitro. Furthermore, the PLD1 inhibitor attenuated pathologic bone destruction in CIA mice by suppressing osteoclastogenesis and bone resorption. Thus, our findings indicate that the targeting of PLD1 can ameliorate CIA by modulating the imbalance of Treg and Th17 cells and suppressing osteoclastogenesis, which might be a novel strategy to treat autoimmune diseases, such as RA.


Connection between quasisymmetric magnetic fields and anisotropic pressure equilibria in fusion plasmas.
The stellarator as a concept of magnetic confinement fusion requires careful design to confine particles effectively. A design possibility is to equip the magnetic field with a property known as quasisymmetry. Though it is generally believed that a steady-state quasisymmetric equilibrium can only be exact locally (unless the system has a direction of continuous symmetry such as the tokamak), we suggest in this work that a change in the equilibrium paradigm can ameliorate this limitation. We demonstrate that there exists a deep physical connection between quasisymmetry and magnetostatic equilibria with anisotropic pressure, extending beyond the isotropic pressure equilibria commonly considered.


Can Medial Temporal Impairment Be an Imaging Red Flag for Neurodegeneration in Disproportionately Enlarged Subarachnoid Space Hydrocephalus?
The differentiation of idiopathic normal pressure hydrocephalus (iNPH) from neurodegenerative diseases such as Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) is often challenging because of their non-specific symptoms. Therefore, various neuroradiological markers other than ventriculomegaly have been proposed. Despite the utility of disproportionately enlarged subarachnoid-space hydrocephalus (DESH) for the appropriate selection of shunt surgery candidates, the specificity and neuropathology of this finding have not been sufficiently evaluated. Investigation of the clinicopathological features and comparison of the neuroradiological findings between DESH with postmortem neuropathological diagnoses (pDESH) and clinically-diagnosed iNPH (ciNPH) patients are the main purposes of this study. In addition to the retrospective evaluation of clinicopathological information, quantitative, semiquantitative, and qualitative magnetic resonance imaging (MRI) indices were compared between pathologically-investigated 10 patients with pDESH and 10 patients with ciNPHResults:Excluding one patient with multiple cerebral infarctions, the postmortem neuropathological diagnoses of the pathologically-investigated patients were mainly neurodegenerative diseases (five AD, one DLB with AD pathologies, one DLB, one argyrophilic grain disease, and one Huntington's disease). In addition to the common neuroradiological featuresConclusion:Hippocampal atrophy and deformation with temporal horn enlargement seem to be characteristic neuroradiological findings of long-standing severely demented patients with DESH and neurodegenerative diseases, mainly advanced-stage AD.


Lipoic acid as a potential first agent for protection from mycotoxins and treatment of mycotoxicosis.
Mycotoxins--toxic substances produced by fungi or molds--are ubiquitous in the environment and are capable of damaging multiple biochemical mechanisms, resulting in a variety of human symptoms referred to collectively as "mycotoxicosis." In fact, mycotoxins mimic multiple xenobiotics, not only with respect to their ultimate damage, but also in their routes of detoxification. This suggests potential therapeutic options for the challenging treatment of mycotoxicosis. In this brief review, the author examines the use of lipoic acid as an example of an inexpensive and available nutrient that has been shown to protect against, or reverse, the adverse health effects of mycotoxins.


Elevated Plus Maze Test Combined with Video Tracking Software to Investigate the Anxiolytic Effect of Exogenous Ketogenic Supplements.
The overall goal of this study is to describe the methodology of the elevated plus maze (EPM) test in combination with a video tracking software. The purpose of the method is to document the effect of various potential anxiolytic treatments on laboratory rodent models. The EPM test is based on the rodents' proclivity toward protected, enclosed dark spaces and unconditioned fear of open spaces and heights, and their innate intense motivation to explore novel environments. The EPM test is a widely used behavioral test for investigating the anxiolytic or anxiogenic responses of rodents given drugs that are known to affect behavior. Observation demonstrating a decreased proportion of time spent on closed arms, an increased proportion of time spent on open arms, a reduced number of entries to closed arms, and an elevated number of entries to open arms measured by the EPM test may reflect reduced anxiety levels. Using this method, the effect of exogenous ketone supplements on anxiety-related behavior is tested in Sprague Dawley (SPD) rats. Exogenous ketone supplements are chronically fed to the rats for 83 days or subchronically and acutely orally gavaged, daily for 7 days, before conducting the EPM test. Behavioral data collection is performed using the SMART video tracking system by a blinded observer at the end of the treatments. The main findings indicate that the EPM test is an effective method to detect the ketone supplement-induced anxiolytic effect and can be considered a sensitive measure to assess changes in anxiety behavior associated with drug- or metabolic-based therapies.


The effect of individual enabling and support on empowerment and depression severity in persons with affective disorders: outcome of a randomized control trial.
To evaluate the effect of Individual Enabling and Support (IES) on empowerment and depression severity as compared to Traditional Vocational Rehabilitation (TVR) in people with affective disorders at 12 months follow-up. Additionally, longitudinal changes within the intervention groups and the correlation over time between empowerment and depression severity were evaluated. A single-blind randomized controlled trial of two intervention groups, IES (n = 33) and TVR (n = 28), was performed with measurement points at baseline, 6, and 12 months. Individuals with affective disorders, including depression and bipolar disorder diagnoses were included. The Empowerment Scale and Montgomery-Åsberg Depression Self-Rating Scale were administered, and Intention-To-Treat analysis was applied. The study was registered with the trial number ISRCTN93470551. There was a statistically significant difference between the intervention groups on empowerment and depression severity at 12 months. Within-group analysis showed that IES-participants increased their perceived empowerment and decreased their depression severity between measurement points, this was not seen among TVR-participants. A moderate, inverse relationship was detected between empowerment and depression. IES is more effective in increasing empowerment and decreasing depression severity after a 12-month intervention than is TVR. This study was limited by a small sample size and larger trials in different contexts are needed.


Epidemiology of depression among infertile and fertile couples in Shiraz, southern Iran.
Depression is considered as one of the main psychological disorders associated with infertility. Depression may play a significant role in the life of infertile individuals, their infertility treatment follow-up and in their hopefulness for the future; it may also influence the intensity and continuousness of the mutual relationship of the affected couple. This study was done to determine the depression rate and make a comparison between infertile and fertile couples with respect to the same. The depression rate was evaluated between two groups--infertile couples (case group) and fertile couples (control group). Ninety-one infertile couples (cases) and 9l fertile ones (controls) were randomly enrolled in our study. Beck depression inventory (BDI) and demographic information were provided. We used Chi-square, t-test; and one-way Analysis of Variance (ANOVA) was performed to find out significant difference between infertility duration in various couples and its effect on the score of depression. The BDI mean difference between infertile and fertile couples was significant (P=0.015). It was significantly more among couples with infertility from 1-3 years' duration compared to those with infertility of 1-year duration or less. Regarding the high rate of depression among infertile couples, it seems necessary to pay more attention to infertility centers that offer psychological and psychiatric services.


Difference of Liver and Kidney Metabolic Profiling in Chronic Atrophic Gastritis Rats between Acupuncture and Moxibustion Treatment.
Acupuncture and moxibustion proved to be very effective in chronic atrophic gastritis (CAG). According to the Chinese traditional medicine theory, chronic diseases have an influence on the function of liver and kidney. However, there is little research to demonstrate this theory. This study is aimed at assessing the 1H NMR-based metabolic profiling in liver and kidney of CAG rats and comparing the difference between electroacupuncture and moxibustion treatment. Male SD rats were subjected to CAG modeling by intragastric administration of mixture of 2% sodium salicylate and 30% alcohol coupled with compulsive sporting and irregular fasting for 12 weeks and then treated by electroacupuncture or moxibustion at Liangmen (ST 21) and Zusanli (ST 36) acupoints for 2 weeks. A 1H NMR analysis of liver and kidney samples along with histopathological examination and molecular biological assay was employed to assess and compare the therapeutic effects of electroacupuncture and moxibustion. CAG brought characterization of metabolomic signatures in liver and kidney of rats. Both electroacupuncture and moxibustion treatment were found to normalize the CAG-induced changes by restoring energy metabolism, neurotransmitter metabolism, antioxidation metabolism, and other metabolism, while the moxibustion treatment reversed more metabolites related to energy metabolism in liver than electroacupuncture treatment. CAG did have influence on liver and kidney of rats. Both of these treatments had good effects on CAG by reversing the CAG-induced perturbation in liver and kidney. For regulating the energy metabolism in liver, the moxibustion played more important role than electroacupuncture treatment.


Interval cancer after two rounds of a Swedish population-based screening program using gender-specific cut-off levels in fecal immunochemical test.
To evaluate interval cancer (IC) after two screening rounds of the Swedish population-based screening program of Stockholm-Gotland applying gender-specific cut-off levels in the fecal immunochemical test (FIT). All 60- to 69-year-olds invited to screening 2015-2019 were included. The cut-off level for a positive test was 40 µg/g in women and 80 µg/g in men. Screening-detected colorectal cancers (SD CRCs) and ICs were verified in the Swedish Colorectal Cancer Register, and the follow-up time was two years from invitation. The test sensitivity, the IC rate (ICs per 10,000 screening negatives) and the IC incidence (ICs per 100,000 person-years) relative to the background CRC incidence were assessed by gender and age. The FIT levels were compared in men and women for CRCs diagnosed within one year of the sample. In the second screening round, 229,187 were invited, and SD CRCs and ICs were diagnosed in 193 and 144, respectively. The IC rate was 8.9 (7.4-10.3) and test sensitivity 0.61 (0.55-0.66), and was similar in men and women. For two screening rounds, the IC rate was significantly higher in men than in women, but the IC incidence/ background CRC incidence was similar in both genders. The FIT levels in female participants with CRC were significantly lower overall, and in early-staged CRCs as compared to men, and proximal localization was more common in women. In multivariable analysis, FIT levels were significantly lower in proximal CRCs. Over two rounds, the IC incidence relative to the background CRC incidence was similar in men and women supporting a gender-specific screening strategy. The results could be explained by lower FIT levels in women due to proximal CRC localization.


Screening cleavage of Factor XIII V34X Activation Peptides by thrombin mutants: A strategy for controlling fibrin architecture.
In blood coagulation, thrombin converts fibrinogen into fibrin monomers that polymerize into a clot network. Thrombin also activates Factor XIII by cleaving the R37-G38 peptide bond of the Activation Peptide (AP) segment. The resultant transglutaminase introduces covalent crosslinks into the fibrin clot. A strategy to modify clot architecture would be to design FXIII AP sequences that are easier or more difficult to be thrombin-cleaved thus controlling initiation of crosslinking. To aid in this design process, FXIII V34X (28-41) Activation Peptides were kinetically ranked for cleavage by wild-type thrombin and several anticoagulant mutants. Thrombin-catalyzed hydrolysis of aromatic FXIII F34, W34, and Y34 APs was compared with V34 and L34. Cardioprotective FXIII L34 remained the variant most readily cleaved by wild-type thrombin. The potent anticoagulant thrombins W215A and W215A/E217A (missing a key substrate platform for binding fibrinogen) were best able to hydrolyze FXIII F34 and W34 APs. Thrombin I174A and L99A could effectively accommodate FXIII W34 and Y34 APs yielding kinetic parameters comparable to FXIII AP L34 with wild-type thrombin. None of the aromatic FXIII V34X APs could be hydrolyzed by thrombin Y60aA. FXIII F34 and W34 are promising candidates for FXIII - anticoagulant thrombin systems that could permit FXIII-catalyzed crosslinking in the presence of reduced fibrin formation. By contrast, FXIII Y34 with thrombin (Y60aA or W215A/E217A) could help assure that both fibrin clot formation and protein crosslinking are hindered. Regulating the activation of FXIII is predicted to be a strategy for helping to control fibrin clot architecture and its neighboring environments.


Blade-Related Vertebral Fracture After Anterior Cervical Discectomy and Fusion with a Zero-Profile Cage: A Case Report.
We present a case of a 79-year-old man with degenerative cervical myelopathy treated with anterior cervical discectomy and fusion (ACDF) using a zero-profile cage. Postoperatively, the patient experienced a rare complication of anchoring blade-related adjacent vertebral fracture leading to construct failure and recurrence of myelopathic symptoms, necessitating revision surgery. This case emphasizes the importance of precision in the surgical technique, specifically in the placement of Caspar pins and anchoring blades. It also underscores the need for a high index of suspicion for potential hardware-related complications in patients presenting with recurring symptoms post-ACDF, contributing to the understanding of such rare complications.


Regulation of Toll-like receptor-2 expression in chronic hepatitis B by the precore protein.
Toll-like receptors (TLRs) play a key role in the innate immune response. The aim of this study was to examine the expression of TLR2 and TLR4 in chronic hepatitis B (CHB). The TLR2 and TLR4 expression on hepatocytes and Kupffer cells from fresh liver biopsies was measured from 21 patients with untreated hepatitis B e antigen (HBeAg)-positive and HBeAg-negative CHB. Parallel studies were also undertaken on monocytes from their peripheral blood. Expression of TLR2 on hepatocytes, Kupffer cells, and peripheral monocytes was significantly reduced in patients with HBeAg-positive CHB in comparison with HBeAg-negative CHB and controls, whereas it was significantly increased in HBeAg-negative CHB compared with controls. The level of TLR4 expression did not differ significantly between the groups. These results were confirmed in vitro using hepatic cell lines transduced with recombinant HBV baculovirus expressing wild-type HBV (HBeAg-positive), precore stop codon (G1896A) mutant HBV (HBeAg-negative). The functional relevance of these findings was established by the demonstration of significantly reduced cytokine production (TNF-alpha) and phospho-p38 kinase expression in the presence of the HBeAg. In the absence of HBeAg, HBV replication was associated with up-regulation of the TLR2 pathway leading to increased TNF-alpha production. This study demonstrates a potentially important interaction between HBeAg, HBV, and the innate immune response.


Prognostic Significance of MiR-34a Expression in Patients with Gastric Cancer after Radical Gastrectomy.
MiR-34a dysregulation has been implicated in tumorigenesis and progression of gastric cancer, but its role in prognosis of patients with gastric cancer remains unknown. The aim of this study was to investigate the expression and prognostic significance of miR-34a in gastric cancer patients after radical gastrectomy. Quantitative real-time polymerase chain reaction was performed to detect the expression of miR-34a in human gastric cancer cell lines and tissues in 76 patients with gastric adenocarcinoma from China. Results are assessed for association with clinical features and overall survival (OS) using Kaplan-Meier analysis. Prognostic values of miR-34a expression and clinical outcomes were evaluated by Cox regression analysis. A molecular prognostic stratification scheme incorporating miR-34a expression was determined using receiver operating characteristic analysis. The results show that the expression level of miR-34a was decreased in human gastric cancer cell lines and tissues, and down-regulated expression of miR-34a was associated with Lauren classification (P = 0.034). Decreased miR-34a expression in gastric cancer tissues was positively correlated with poor OS of gastric cancer patients (P = 0.013). Further multivariate Cox regression analysis suggested that miR-34a expression was an independent prognostic indicator for gastric cancer (P = 0.027). Applying the prognostic value of miR-34a expression to tumor node metastasis (TNM) stage system showed a better prognostic value in patients with gastric cancer than miR-34a expression (P = 0.0435) or TNM stage (P = 0.0249) alone. The results reinforce the critical role for the down-regulated miR-34a expression in gastric cancer and suggest that miR-34a could be a prognostic indicator for this disease.


PET Image Reconstruction and Deformable Motion Correction Using Unorganized Point Clouds.
Quantitative positron emission tomography imaging often requires correcting the image data for deformable motion. With cyclic motion, this is traditionally achieved by separating the coincidence data into a relatively small number of gates, and incorporating the inter-gate image transformation matrices into the reconstruction algorithm. In the presence of non-cyclic deformable motion, this approach may be impractical due to a large number of required gates. In this paper, we propose an alternative approach to iterative image reconstruction with correction for deformable motion, wherein unorganized point clouds are used to model the imaged objects in the image space, and motion is corrected for explicitly by introducing a time-dependence into the point coordinates. The image function is represented using constant basis functions with finite support determined by the boundaries of the Voronoi cells in the point cloud. We validate the quantitative accuracy and stability of the proposed approach by reconstructing noise-free and noisy projection data from digital and physical phantoms. The point-cloud-based maximum likelihood expectation maximization (MLEM) and one-pass list-mode ordered-subset expectation maximization (OSEM) algorithms are validated. The results demonstrate that images reconstructed using the proposed method are quantitatively stable, with noise and convergence properties comparable to image reconstruction based on the use of rectangular and radially-symmetric basis functions.


Epigenetic impacts of stress priming of the neuroinflammatory response to sarin surrogate in mice: a model of Gulf War illness.
Gulf War illness (GWI) is an archetypal, medically unexplained, chronic condition characterised by persistent sickness behaviour and neuroimmune and neuroinflammatory components. An estimated 25-32% of the over 900,000 veterans of the 1991 Gulf War fulfil the requirements of a GWI diagnosis. It has been hypothesised that the high physical and psychological stress of combat may have increased vulnerability to irreversible acetylcholinesterase (AChE) inhibitors leading to a priming of the neuroimmune system. A number of studies have linked high levels of psychophysiological stress and toxicant exposures to epigenetic modifications that regulate gene expression. Recent research in a mouse model of GWI has shown that pre-exposure with the stress hormone corticosterone (CORT) causes an increase in expression of specific chemokines and cytokines in response to diisopropyl fluorophosphate (DFP), a sarin surrogate and irreversible AChE inhibitor. C57BL/6J mice were exposed to CORT for 4 days, and exposed to DFP on day 5, before sacrifice 6 h later. The transcriptome was examined using RNA-seq, and the epigenome was examined using reduced representation bisulfite sequencing and H3K27ac ChIP-seq. We show transcriptional, histone modification (H3K27ac) and DNA methylation changes in genes related to the immune and neuronal system, potentially relevant to neuroinflammatory and cognitive symptoms of GWI. Further evidence suggests altered proportions of myelinating oligodendrocytes in the frontal cortex, perhaps connected to white matter deficits seen in GWI sufferers. Our findings may reflect the early changes which occurred in GWI veterans, and we observe alterations in several pathways altered in GWI sufferers. These close links to changes seen in veterans with GWI indicates that this model reflects the environmental exposures related to GWI and may provide a model for biomarker development and testing future treatments.


Comparison of probability and likelihood models for peptide identification from tandem mass spectrometry data.
We evaluate statistical models used in two-hypothesis tests for identifying peptides from tandem mass spectrometry data. The null hypothesis H(0), that a peptide matches a spectrum by chance, requires information on the probability of by-chance matches between peptide fragments and peaks in the spectrum. Likewise, the alternate hypothesis H(A), that the spectrum is due to a particular peptide, requires probabilities that the peptide fragments would indeed be observed if it was the causative agent. We compare models for these probabilities by determining the identification rates produced by the models using an independent data set. The initial models use different probabilities depending on fragment ion type, but uniform probabilities for each ion type across all of the labile bonds along the backbone. More sophisticated models for probabilities under both H(A) and H(0) are introduced that do not assume uniform probabilities for each ion type. In addition, the performance of these models using a standard likelihood model is compared to an information theory approach derived from the likelihood model. Also, a simple but effective model for incorporating peak intensities is described. Finally, a support-vector machine is used to discriminate between correct and incorrect identifications based on multiple characteristics of the scoring functions. The results are shown to reduce the misidentification rate significantly when compared to a benchmark cross-correlation based approach.


Cholinergic mediation of growth hormone secretion elicited by arginine, clonidine, and physical exercise in man.
The role of acetylcholine in human GH secretion was studied with atropine, which selectively blocks cholinergic muscarinic receptors and crosses the blood-brain barrier. Paired tests were performed in 22 normal subjects divided into 4 groups. The stimuli employed were arginine (30 g/30 min, iv), clonidine (300 micrograms, orally), physical exercise for 20 min, and saline. In the second test, atropine (1 mg, im) was administered before GH stimulation. Arginine elicited a GH secretory peak of 16.6 +/- 5 ng/ml (mean +/- SEM), which was completely blocked when atropine was administered with arginine (0.9 +/- 0.1 ng/ml). Atropine did not, however, modify the PRL secretory response; peak levels after arginine and atropine plus arginine were 16.3 +/- 3.1 and 16.8 +/- 2.5 ng/ml, respectively. Clonidine elicited a GH secretory peak (11.8 +/- 2.7 ng/ml) which also was blocked by pretreatment with atropine (1.2 +/- 0.2 ng/ml). Neither clonidine nor clonidine plus atropine altered PRL secretion. GH levels also were sharply increased after physical exercise, with a peak level of 19.4 +/- 4.9 ng/ml. Atropine completely blocked exercise-induced GH secretion (2 +/- 0.9 ng/ml). Atropine alone did not modify GH or PRL values compared with saline administration. The potency of the atropine-induced suppression of GH secretion by three different stimuli, each with presumably different mechanisms of action, suggests that acetylcholine plays an important role in the regulation of GH secretion.


JOURNAL CLUB: CT dose optimization for whole-body PET/CT examinations.
OBJECTIVE. The objective of this study was to optimize CT protocols for whole-body PET/CT by reducing radiation dose while minimizing effects on image quality. MATERIALS AND METHODS. Before protocol optimization, a survey of 140 consecutive patients was conducted to establish the baseline dose from a whole-body PET/CT examination. Another sample of 100 patients was surveyed to evaluate the reduction of radiation dose after implementation of the new protocol. Effective dose from the CT component of the examination was estimated using dose-length product (DLP) values from reports generated by the scanner and anatomy-specific conversion factors. Twenty-six patients who underwent studies before and after the optimization were included in an analysis of image quality. All 26 patients had maintained the same weight between the examinations and were scanned in the same position using a similar technique except for the changes made for CT dose optimization. The studies were randomized and blinded for an experienced PET and CT reader who graded the imaging quality of anatomic structures. RESULTS. CT protocol optimization resulted in a 32% reduction of the mean CT radiation dose: The mean effective dose was reduced from 8.1 to 5.5 mSv. The blinded analysis of image quality showed no clinically significant degradation of the lower-dose studies. The only structures visualized statistically better on the higher-dose CT scans were the carotid arteries and the region of the posterior triangle. CONCLUSION. The results of this study showed that optimization of CT acquisition can effectively reduce radiation dose in a whole-body PET/CT examination without significantly sacrificing image quality.


Role of interleukin-23-dependent antifungal immune responses in dendritic cell-vaccinated mice.
CD40 ligand (CD40L) transduction of antigen-pulsed dendritic cells (DCs) can result in antigen-specific humoral immune responses even in CD4(+) T-cell-depleted settings. Here, we show that CD40L transduction of DCs results in the induction of interleukin-12p40 (IL-12p40), IL-12p70, and IL-23. Using DCs that were deficient in IL-12p40, IL-12p35, or IL-23p19, we show that these molecules are dispensable for primary IgG1 responses to Pneumocystis, but IgG2c was dependent on IL-12p40 and IL-23p19 but not IL-12p35. Antigen-specific recall responses in CD4-deficient mice were critically dependent on IL-12p40 and IL-23p19 expression in DCs and were not affected by the lack of IL-12p35. To confirm that this defect in recall was due to IL-23, transduction of IL-12p40(-/-) DCs with a recombinant adenovirus expressing functional IL-23 restored recall responses in DC-vaccinated CD4-deficient mice. These data show that DC-produced IL-23 is critical for vaccine-induced antigen-specific IgG2c and recall antibody responses in the setting of CD4(+) T-cell depletion.


Effectiveness and safety of non-vitamin K antagonist oral anticoagulants and warfarin in atrial fibrillation: a Scandinavian population-based cohort study.
Using Scandinavian population-based registries, we assessed risk of stroke/systemic embolism (SE) and bleeding with non-vitamin K antagonist oral anticoagulants compared with warfarin in anticoagulation-naïve patients with atrial fibrillation (AF). This historical cohort study included 219 545 AF patients [median age 74 years; 43% women; mean CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke or transient ischaemic attack, vascular disease, age 65-74 years, sex category) score 3.3] initiating apixaban, dabigatran, rivaroxaban, or warfarin in Denmark, Norway, and Sweden (1 January 2013 to 31 December 2016). The primary endpoints were stroke/SE and major bleeding. The median follow-up times were 9.7 (3.9-21.5) months for stroke/SE and 9.6 (3.8-21.3) months for bleeding. Apixaban and warfarin initiators were older and had higher CHA2DS2-VASc scores compared with dabigatran and rivaroxaban initiators. After 1:1 propensity score matching, three cohorts were created: apixaban-warfarin (n = 111 162), dabigatran-warfarin (n = 56 856), and rivaroxaban-warfarin (n = 61 198). Adjusted hazard ratios (HRs) were estimated using a Cox regression. For stroke/SE, adjusted HRs against warfarin were 0.96 [95% confidence interval (CI): 0.87-1.06] for apixaban, 0.89 (95% CI: 0.80-1.00) for dabigatran, and 1.03 (95% CI: 0.92-1.14) for rivaroxaban. For major bleeding, the HRs against warfarin were 0.73 (95% CI: 0.67-0.78) for apixaban, 0.89 (95% CI: 0.82-0.97) for dabigatran, and 1.15 (95% CI: 1.07-1.25) for rivaroxaban. The results in the dabigatran cohort did not hold in all dose-defined subgroups. In this large Scandinavian study among AF patients initiating oral anticoagulation, those initiating dabigatran, apixaban, and rivaroxaban had similar rates of stroke/SE to patients initiating warfarin. Rates of major bleeding were lower with apixaban and dabigatran and higher with rivaroxaban, each compared with warfarin.


Differential estradiol requirement for the induction of estrus behavior and the luteinizing hormone surge in two breeds of sheep.
For a better understanding of the mechanisms that lead to the preovulatory GnRH/LH surge and estrus behavior, the minimum estradiol (E) requirements (dose and duration) to induce each of these events were determined and compared between two breeds of ewes having either single (Ile de France) or multiple (Romanov) ovulations. The ewes were initially studied during a natural estrus cycle, and were then ovariectomized and run through successive artificial estrus cycles. For these artificial cycles the duration and amplitude of the follucular phase E increase were manipulated by E implants. Under all conditions, the onset of estrus behavior was similar in the two breeds, although its duration was longer in Romanov ewes. While a moderate E signal (6 cm for 12 h) induced an LH surge in 10/10 Ile de France ewes, a larger E signal (12 cm for 12 h) was minimally effective in Romanov ewes (4/10). Additional studies revealed that a small E signal (3 cm for 6 h) induced full estrus behavior in all Romanov ewes but was completely ineffective in Ile de France animals (0/10). Higher doses and mostly longer durations of the E signal (12 cm for 24 h) were required to induce a surge in all the Romanov ewes. These results demonstrate a clear difference in the E requirement for the induction of estrus behavior and the LH surge between breeds of ewes that have different ovulation rates. These data provide compelling evidence that, in one breed, the neuronal systems that regulate both events require different estrogen signals.


[A collective review of Vibrio vulnificus infection in Japan].
Vibrio vulnificus is found globally in marine coastal waters. Infection with this organism, via ingestion of raw shellfish or exposure to marine water, can cause necrotizing fasciitis and sepsis, which have high mortality and short latency. In Japan, many cases have been reported since 1980, mainly from hospitals in western prefectures. However, because of the sporadic nature of infection outbreaks, a thorough epidemiologic survey has not been done. We studied the epidemiological and clinical characteristics of Vibrio vulnificus infections reported in Japan from 1975 to 2005. We identified 185 cases using the medical article search engines Ichushi (Japan Medical Abstracts Society), CiNii (Citation Information by National Institute of Informatics), and PubMed over 30 years. The median age of patients was 59. The number of male patients was eight times the number of female patients; however, no significant difference in mortality was found between genders. In yearly distributions of patients, 20 cases were reported in 2001, a year in which we experienced more rainfall and a longer rainy season in Northern Kyushu. In monthly distribution, about 80% of cases were reported from July to September when sea water temperatures rise. About 40% of cases were reported in four prefectures around the Ariake Sea. The underlying disease indicated liver dysfunction in 90% of patients, but mortality was the same regardless of the infection pathway (oral ingestion or wound). Because of its rapid aggravation and high mortality rate, public education is important to prevent new cases. It is also highly recommended that patients with preexisting liver dysfunction avoid raw fish and limit exposure to marine water during the summer.


Evaluating a Web-based cognitive-behavioral therapy for maladaptive perfectionism in university students.
This study assessed a Web-based cognitive-behavioral therapy (CBT) for maladaptive perfectionism, investigating perfectionism, anxiety, depression, negative automatic thoughts, and perceived stress. Participants were undergraduate students defined as maladaptive perfectionists through a screening questionnaire at an urban university. The data were collected from July 2009 to August 2010. Forty-seven maladaptive perfectionists were randomly assigned to a 12-week CBT or a wait-list control group and assessed via questionnaires at pre- and postintervention. Statistical procedures included t tests, Pearson correlations, and analysis of covariance. At the postintervention measure, the CBT group demonstrated significant decreases in anxiety sensitivity and negative automatic thoughts compared to the control group. Within the CBT group, changes in perfectionism scores were significantly correlated with positive changes in depression, anxiety, stress, and automatic thoughts. The treatment group improved on psychological outcomes, demonstrating the effectiveness of a Web-based CBT for perfectionism in a university setting.


Benign transient hyperphosphatasia and HIV infection.
The disorder, benign transient hyperphosphatasia, has been defined previously as a condition occurring in a normal child with spontaneous, transient elevation of alkaline phosphatase. We report three cases of hyperphosphatasia in patients with congenital HIV infection and underlying liver disease which appear to satisfy the criteria for benign transient hyperphosphatasia despite the presence of chronic disease. These three children, when compared with three normal children with transient hyperphosphatasia exhibited similar patterns of change in serum alkaline phosphatase. Extreme elevation of serum alkaline phosphatase in HIV infected patients does not of itself suggest alterations in clinical status nor indicate the need for extensive evaluation.


Liver fat has a stronger association with risk factors for type 2 diabetes in African-American compared with Hispanic adolescents.
Although overweight and obese African-Americans (AAs) have less visceral adipose tissue (VAT) and liver fat (LF) than Hispanics, they have a similar risk for type 2 diabetes. We examined ethnic differences in the association between VAT and LF with risk factors for type 2 diabetes to help explain this paradox. We conducted a cross-sectional study in an academic pediatric care facility. Subjects were overweight and obese AA (n = 131; 15.5 ± 3.3 years old) and Hispanic adolescents (n = 227; 14.7 ± 3.0 years old). Outcome measures included insulin sensitivity (SI), acute insulin response (AIR), and disposition index (DI) by frequently sampled i.v. glucose tolerance test and minimal modeling. LF, not VAT, was inversely associated with SI, and the effect of high LF compared with low was more pronounced in AAs (P(interaction) < .05). In Hispanics, high LF was associated with a 24% lower SI (P < .01) and a 31% increase in AIR (P < .01) and was not associated with DI (P = .35). In AAs, high LF was associated with a 49% lower SI (P < .001), was not associated with an increase in AIR (P = .25), and was associated with a 42% lower DI (P < .01), indicating failure of compensatory insulin secretion/clearance in response to insulin resistance. Prediabetes changed the relationship between high/low LF and DI in Hispanics (P(interaction) = .002) but not AAs such that prediabetic Hispanics with high LF had a 43% lower DI (P = .03) with no difference in those without prediabetes (P = .06). LF has a stronger effect on SI compared with VAT. Our results suggest that the impact of high LF on poor β-cell compensation is more pronounced in AAs. In Hispanics, the combination of high LF and prediabetes contributes to poor β-cell compensation.


Mutagenesis and structural modeling implicate RME-8 IWN domains as conformational control points.
After endocytosis, transmembrane cargo is differentially sorted into degradative or recycling pathways. This process is facilitated by recruitment into physically distinct degradative or recycling microdomains on the limiting membrane of individual endosomes. Endosomal sorting complexes required for transport (ESCRT) mark the degradative microdomain, while the recycling domain is marked by the retromer complex and associated proteins RME-8 and SNX-1. The separation of endosomal microdomains is also controlled by RME-8 and SNX-1, at least in part via removal of degradative component HRS/HGRS-1 from the recycling microdomain. This activity is likely due to recruitment and activation of chaperone Hsc70 on the endosome by the RME-8 DNAJ domain. To better understand the mechanism of RME-8 function we performed a new phylogenetic analysis of RME-8 and identified new conserved sequence features. In a complementary approach, we performed structure-function analysis that identified the C-terminus as important for microdomain localization and likely substrate binding, while N-terminal sequences beyond the known single N-terminal PH-like domain are important for endosome recruitment. Random mutagenesis identified IWN4, and by analogy IWN3, to be important for the autoinhibitory DNAJ domain binding, with IWN3 playing a critical role in HRS uncoating activity. Combining AlphaFold structural predictions with in vivo mutation analysis of RME-8, we propose a model whereby SNX-1 and the IWN domains control the conformation of RME-8 and hence the productive exposure of the DNAJ domain. Furthermore, we propose that the activation of RME-8 is cyclical, with SNX-1 acting as an activator and a target of RME-8 uncoating activity.


Triplet-triplet annihilation upconversion in CdS-decorated SiO2 nanocapsules for sub-bandgap photocatalysis.
This study reports the first successful nanoscale encapsulation of triplet-triplet annihilation upconversion (TTA-UC) medium within a rigid silica shell using a self-assembly microemulsion process. These newly synthesized nanocapsules present a few critical advances that could be instrumental for a wide range of aqueous-based photonics applications, including photocatalysis, artificial photosynthesis, and bioimaging. The nanocapsules form a homogeneous suspension that can produce intense, diffuse UC emission in water without deoxygenation, closely resembling conventional TTA-UC processes that have been performed in deoxygenated organic solvents. The silica shell provides sites for further surface modification, which allows, when combined with its nanoscale dimension and structural rigidity, this TTA-UC system to acquire various useful functionalities. A benchmark TTA-UC pair, palladium(II) tetraphenyltetrabenzoporphyrin as a sensitizer and perylene as an acceptor, was used to demonstrate efficient red-to-blue (635 nm, 1.95 eV → 470 nm, 2.6 eV) upconversion in the oxygen-rich aqueous phase. The nanocapsule surface was further functionalized with cadmium sulfide nanoparticles (Eg = 2.4 eV) to demonstrate sub-bandgap sensitization and subsequent aqueous-phase catalytic oxidation.


The Current State of Sensing, Health Management, and Control for Small-To-Medium-Sized Manufacturers.
The development of digital technologies for manufacturing has been challenged by the difficulty of navigating the breadth of new technologies available to industry. This difficulty is compounded by technologies developed without a good understanding of the capabilities and limitations of the manufacturing environment, especially within small-to-medium enterprises (SMEs). This paper describes industrial case studies conducted to identify the needs, priorities, and constraints of manufacturing SMEs in the areas of performance measurement, condition monitoring, diagnosis, and prognosis. These case studies focused on contract and original equipment manufacturers with less than 500 employees from several industrial sectors. Solution and equipment providers and National Institute of Standards and Technology (NIST) Hollings Manufacturing Extension Partnership (MEP) centers were also included. Each case study involved discussions with key shop-floor personnel as well as site visits with some participants. The case studies highlight SME's strong need for access to appropriate data to better understand and plan manufacturing operations. They also help define industrially-relevant use cases in several areas of manufacturing operations, including scheduling support, maintenance planning, resource budgeting, and workforce augmentation.


Medicine, Value, and Knowledge in the Veterinary Clinic: Questions for and From Medical Anthropology and the Medical Humanities.
The welcome development of the veterinary humanities, and veterinary anthropology specifically, raises the question of its potential relationship with the now well-established field(s) of the medical humanities, and of medical anthropology. Although there are national variations, the term "medical humanities" generally refers to either the tapping of the humanities to improve medical education by developing, through engagement with the humanities like literature and visual art, skills in empathy, visualization and expressivity, or alternatively, it refers to the application of humanities approaches of cultural critique to the presumptions, practices and institutions of the human medical world to denaturalize the ideologies of knowledge that contemporary human medicine professions depend upon. This article reflects on the potential impact that the development of a veterinary medical humanities could have on the field of (human) medical humanities and vice versa. Could such a development force a re-conception of notions of agency, of consent, and of the position of "patient" when the (human based) medical humanities is expanded to include both human and veterinary medicine? What would the potential usefulness, or limitations, both in conceptual and in applied terms, be of constructing a multi-species notion of "medical humanities?" What can such a comparative approach offer to veterinary medicine, in practice and in terms of the curricula of veterinary training? To reflect on these questions, this article draws on my multiple years of fieldwork in veterinary clinics and classrooms to first lay out the constituent components of the formal practice of contemporary veterinary medicine (at least in the U.S.) in terms of the roles that species specificity and relations to humans play in the delivery of care, and then seeks to center the animal in these practices to ask questions about consent, resistance, veterinary obligation, and the role of finance in comparison with human medicine. These similarities and differences will form the basis for a consideration of the effects of enlarging the medical humanities to encompass more than one species.