The impact of the electronic media on primary dental care in the 21st century.
This paper attempts to predict how electronic media will impact on primary dental care in the twenty-first century. The predictions for the next 10 years are based on developments currently in train or on the premise that equipment and techniques, which have been recently introduced and are at present used by relatively few, will be used by many by 2010. During this decade, the impact of electronic media is considered in the areas of patient support, diagnosis, treatment planning, provision of treatment and its maintenance, quality control and practice management. The paper then speculates briefly about how dentists in primary dental care might practise in the year 2100. It concludes that although electronic media are likely to play an increasingly important role, a clinician's skills, knowledge and ability to communicate with patients will remain the keys to successful practice for the foreseeable future.


New Energy Efficient Housing Has Reduced Carbon Footprints in Outer but Not in Inner Urban Areas.
Avoiding urban sprawl and increasing density are often considered as effective means to mitigate climate change through urban planning. However, there have been rapid technological changes in the fields of housing energy and private driving, and the development is continuing. In this study, we analyze the carbon footprints of the residents living in new housing in different urban forms in Finland. We compare the new housing to existing housing stock. In all areas, the emissions from housing energy were significantly lower in new buildings. However, in the inner urban areas the high level of consumption, mostly due to higher affluence, reverse the gains of energy efficient new housing. The smallest carbon footprints were found in newly built outer and peri-urban areas, also when income level differences were taken into account. Rather than strengthening the juxtaposition of urban and suburban areas, we suggest that it would be smarter to recognize the strengths and weaknesses of both modes of living and develop a more systemic strategy that would result in greater sustainability in both areas. Since such strategy does not exist yet, it should be researched and practically developed. It would be beneficial to focus on area specific mitigation measures.


Patient education in rural community hospitals: registered nurses' attitudes and degrees of comfort.
This study examined whether academic preparation, years of experience, or job role influenced registered nurses' attitudes regarding patient education, the frequency of assuming teaching roles, and the degree of comfort in providing patient education. This quantitative study used a survey tool sent to 412 registered nurses in five rural community hospitals. There were 273 surveys returned (66.3%). Data were analyzed using descriptive statistics, factor analysis, and analysis of variance with post hoc testing. Role ambiguity emerged with a significant difference based on educational preparation. Job role showed a significant difference in competency and comfort with patient education. Years of experience yielded significant differences in the registered nurses' degree of comfort in teaching within two of the three factors.


Outplacement: could it happen to me?
In summary, the typical outplacement client is the typical healthcare executive. These days, almost any healthcare professional is vulnerable to termination. No one can take a career for granted, so be prepared. If possible, begin career planning at an earlier age. Be conscious of potential career obstacles and develop strategies to confront and compensate for them.


The Antileukemic Effect of Xestoquinone, A Marine-Derived Polycyclic Quinone-Type Metabolite, Is Mediated through ROS-Induced Inhibition of HSP-90.
Xestoquinone is a polycyclic quinone-type metabolite with a reported antitumor effect. We tested the cytotoxic activity of xestoquinone on a series of hematological cancer cell lines. The antileukemic effect of xestoquinone was evaluated in vitro and in vivo. This marine metabolite suppressed the proliferation of Molt-4, K562, and Sup-T1 cells with IC50 values of 2.95 ± 0.21, 6.22 ± 0.21, and 8.58 ± 0.60 µM, respectively, as demonstrated by MTT assay. In the cell-free system, it inhibited the activity of topoisomerase I (Topo I) and II (Topo II) by 50% after treatment with 0.235 and 0.094 μM, respectively. The flow cytometric analysis indicated that the cytotoxic effect of xestoquinone was mediated through the induction of multiple apoptotic pathways in Molt-4 cells. The pretreatment of Molt-4 cells with N-acetyl cysteine (NAC) diminished the disruption of the mitochondrial membrane potential (MMP) and apoptosis, as well as retaining the expression of both Topo I and II. In the nude mice xenograft model, the administration of xestoquinone (1 μg/g) significantly attenuated tumor growth by 31.2% compared with the solvent control. Molecular docking, Western blotting, and thermal shift assay verified the catalytic inhibitory activity of xestoquinone by high binding affinity to HSP-90 and Topo I/II. Our findings indicated that xestoquinone targeted leukemia cancer cells through multiple pathways, suggesting its potential application as an antileukemic drug lead.


Cloning and genomic characterization of Felis domesticus papillomavirus type 1.
A novel papillomavirus was cloned from hyperkeratotic cutaneous lesions of a Persian domestic cat. The Felis domesticus papillomavirus (FdPV-1) genome counts 8300 bp and has a typical genome structure with an early region (E1, E2, E4, E6, E7), a late region (L1, L2), and a noncoding upstream regulatory region (URR or NCR1) between the end of L1 and the beginning of E6. The FdPV-1 also shows an unusual second noncoding region (NCR2) of 1.3 kb, situated between the end of E2 and the beginning of L2. This NCR2 is uniquely related to a similar region in the canine oral papillomavirus (COPV). Phylogenetic analysis places FdPV-1 together with COPV, the cottontail rabbit papillomavirus, human papillomavirus type 1 (HPV-1), and HPV-63 in the group of the benign cutaneous papillomaviruses. The position of FdPV-1 in the phylogenetic tree allows us to hypothesize that already in an early phase of the papillomavirus molecular evolution, a split occurred into viruses with a dual tropism primarily for cutaneous epithelia but also secondarily for mucosal surfaces, and viruses with a specific monotropism for mucosal surfaces. The close relationship between FdPV-1 and COPV, and between their Canidae and Felidae hosts, supports the hypothesis that papillomaviruses have speciated and coevolved together with their hosts throughout vertebrate evolution. A papillomavirus mutation rate of 0.73 to 0.96 x 10(-8) nucleotide substitutions per base per year was calculated.


Role of transient receptor potential melastatin 2 (TRPM2) channels in visceral nociception and hypersensitivity.
Transient receptor potential melastatin 2 (TRPM2) is a thermosensitive, Ca2+-permeable cation channel. TRPM2 contributes to the pathogenesis of inflammatory bowel disease, and inflammatory and neuropathic pain. We hypothesized that TRPM2 is important for visceral nociception and the development of visceral hypersensitivity. Therefore, we investigated the expression of TRPM2 channels and their involvement in visceral nociception in normal physiology and under pathological conditions that cause visceral hypersensitivity in rats. TRPM2 immunoreactivities were detected in the mucosa and muscle layer of the rat gastrointestinal tract. TRPM2 immunopositive cell bodies were almost completely co-localized with calretinin- and NeuN-positive cells in the myenteric plexus. We found that the majority of the TRPM2-immunoreactive cells were double-labeled with the retrograde marker fluorogold in lumbar 6/sacral 1 dorsal root ganglia (DRG), indicating that TRPM2 is expressed in spinal primary afferents innervating the distal colon. Subtypes of TRPM2-immunopositive DRG neurons were labeled by the A-fiber marker NF200, the C-fiber marker IB4, substance P, calcitonin gene-related peptide, or P2X3 receptor. We found that oral administration of the TRPM2 inhibitor econazole (30mg/kg) reduced the visceromotor response (VMR) to noxious colorectal distention (CRD) at 80mmHg in control rats. Expression of TRPM2 in the mucosa of the distal colon was increased in a trinitrobenzene sulfonic acid-induced colitis model. The VMR to CRD significantly increased in colitis model rats compared with control rats at 40, 60, and 80mmHg. Econazole restored visceral hypersensitivity to the control level. Furthermore, TRPM2-deficient mice showed significantly attenuated trinitrobenzene sulfonic acid induced visceral hypersensitivity compared with wild-type mice. In conclusion, TRPM2 channels contribute to visceral nociception in response to noxious stimuli under normal conditions and visceral hypersensitivity in pathological conditions.


Prognostic significance of prenatal ultrasound in fetal arthrogryposis multiplex congenita.
Fetal arthrogryposis multiplex congenita (AMC) describes a heterogeneous disease entity characterized by multiple contractures affecting at least two different body areas. The aim of our study was to identify additional sonographic abnormalities in fetuses with AMC Type I-III associated with an unfavorable prognosis and to describe when those signs were first detected. This retrospective study included 41 pregnancies of suspected AMC diagnosed 1999-2017 at our tertiary referral center. The affected pregnancies were divided into the 3 AMC subgroups; the time of detection and outcome were analyzed. Prenatal sonograms, pediatric charts, genetic tests, and autopsy reports were studied. Pregnancy outcome data were verifiable in 34 out of 41 cases; in 27 cases, AMC was confirmed. Hydrops was present in 50% of postnatally deceased fetuses, 53% of cases resulting in termination of pregnancy vs. 0% of the surviving 8 children. Absent stomach filling was found in 67% of the children with neonatal death. After subcategorization, the limb-involvement-only-group, 8% showed hydrops vs. 100% in system anomaly group vs. 70% in neuromuscular dysfunction cohort (p = 0.001). Scoliosis, nuchal edema, and absent stomach filling were significantly indicating for a neurological etiology. In addition to disease-defining sonographic findings, those with prognostic significance were identified. Hydrops, nuchal edema, scoliosis and absent stomach filling were associated with unfavorable outcomes implicating a neuromuscular etiology. This knowledge can help to predict the further course of the disease and support patient counseling.


Prophylactic effect of imidapril on stroke in stroke-prone spontaneously hypertensive rats.
It has been reported that some angiotensin converting enzyme inhibitors can prevent stroke-prone spontaneously hypertensive rats from stroke at much higher doses than clinical doses used for hypertension therapy. This study was performed to investigate the prophylactic effectiveness of imidapril against stroke in comparison with enalapril. Salt-loaded stroke-prone spontaneously hypertensive rats were orally given imidapril (0.5, 1, 2, and 5 mg/kg per day), enalapril (2 and 5 mg/kg per day), or hydralazine (5 mg/kg per day). Stroke signs were scored, and blood pressure, protein concentration, and N-acetyl-beta-D-glucosaminidase activity in urine were measured. After 2 weeks of medication, angiotensin converting enzyme activities in the aorta were measured 24 hours after dosing. In the control group, severe hypertension developed, and all rats died within 12 weeks because of stroke. Imidapril and enalapril dose-dependently decreased the stroke-related mortality, and both agents at 5 mg/kg per day showed excellent prophylaxis, although they did not inhibit hypertensive development. Imidapril at 0.5 mg/kg per day significantly prevented stroke to almost the same extent as enalapril at 2 mg/kg per day or hydralazine at 5 mg/kg per day. Imidapril dose-dependently suppressed the elevation of the two urinary indexes, which was followed by stroke. Imidapril inhibited enzyme activity in the aorta more strongly than did enalapril at the same dose. Imidapril prevented the incidence of stroke in stroke-prone spontaneously hypertensive rats at a dose of 0.5 mg/kg per day or more by amelioration of kidney dysfunction. Reduction of blood pressure is not necessary, although enzyme inhibition in the vasculature may partly relate to the effect.


Modeling the polymerase chain reaction.
We introduce a mathematical model to treat the polymerase chain reaction (PCR), where we regard the accumulation of new molecules during a PCR cycle as a randomly bifurcating tree. This model enables us to compute an approximate formula for the distribution of the number of replications that have occurred between a pair of molecules, which depends on the efficiency lambda of the reaction, the number N0 of template molecules at the beginning of the PCR and the number c of PCR cycles. The reliability of the approximation is tested by computer simulations. Finally, to model the effect of the intrinsic error rate of the polymerase, we superimpose a substitution process on the tree. The resulting closed formula for the distribution of pairwise differences of sequences as a function of error rate mu and efficiency lambda can be used to estimate the error rate, if lambda is known.


Movements of wolves at the northern extreme of the species' range, including during four months of darkness.
Information about wolf (Canis lupus) movements anywhere near the northern extreme of the species' range in the High Arctic (>75°N latitude) are lacking. There, wolves prey primarily on muskoxen (Ovibos moschatus) and must survive 4 months of 24 hr/day winter darkness and temperatures reaching -53 C. The extent to which wolves remain active and prey on muskoxen during the dark period are unknown, for the closest area where information is available about winter wolf movements is >2,250 km south. We studied a pack of ≥20 wolves on Ellesmere Island, Nunavut, Canada (80°N latitude) from July 2009 through mid-April 2010 by collaring a lead wolf with a Global Positioning System (GPS)/Argos radio collar. The collar recorded the wolf's precise locations at 6:00 a.m. and 6:00 p.m. daily and transmitted the locations by satellite to our email. Straight-line distances between consecutive 12-hr locations varied between 0 and 76 km. Mean (SE) linear distance between consecutive locations (n = 554) was 11 (0.5) km. Total minimum distance traveled was 5,979 km, and total area covered was 6,640 km(2), the largest wolf range reported. The wolf and presumably his pack once made a 263-km (straight-line distance) foray to the southeast during 19-28 January 2010, returning 29 January to 1 February at an average of 41 km/day straight-line distances between 12-hr locations. This study produced the first detailed movement information about any large mammal in the High Arctic, and the average movements during the dark period did not differ from those afterwards. Wolf movements during the dark period in the highest latitudes match those of the other seasons and generally those of wolves in lower latitudes, and, at least with the gross movements measurable by our methods, the 4-month period without direct sunlight produced little change in movements.


Medical risk factors in perinatal mortality in Kuwait: a case-controlled study from Al-Jahra district.
This study is the first of its kind in Kuwait. It evaluates various risk factors associated with perinatal mortality (PNM) in the Al-Jahra district hospital during the period January 1995-December 1997. Risks associated with PNM were age above 30, parity above 8, history of abortion or perinatal death, lack of antenatal care, presence of chronic maternal disease, hydramnios, antepartum haemorrhage, breech presentation and low Apgar scores. The effect of the appropriate preventative programmes involving highlighting women at risk of perinatal mortality and probable intervention are discussed.


Prevention of bone loss by zoledronic acid in premenopausal women undergoing adjuvant chemotherapy persist up to one year following discontinuing treatment.
Adjuvant chemotherapy is associated with significant reductions in bone mineral density (BMD) in premenopausal women with breast cancer (BC) that is prevented with zoledronic acid (ZA) every 3 months for 1 yr. The aim of the study was to examine the effect on BMD of discontinuing ZA during the subsequent year. We conducted a randomized, double-blind trial. Premenopausal women (mean age, 42 yr) undergoing adjuvant chemotherapy for BC participated in the study. ZA (4 mg iv every 3 months) vs. placebo was administered for 12 months. We measured percentage change in BMD and bone turnover markers at 12 and 24 months (1 yr after last infusion). Of 101 women randomized, 85 completed 12-month and 62 completed 24-month evaluations. In the placebo group, serum C-telopeptide (CTX) increased progressively over the first 12 months, returned toward baseline but remained significantly above baseline by 24 months. Lumbar spine BMD decreased from baseline by 5.5% at 12 and 6.3% at 24 months. Similarly, by 24 months, total hip and femoral neck BMD declined by 2.6 and 2.4%, respectively. In ZA patients, BMD remained stable (P < 0.0001 compared to placebo). Serum CTX declined significantly by 6 months, but returned to baseline by 12 months, remaining there at 24 months. Premenopausal women receiving chemotherapy for BC sustained significant bone loss during the first year, without recovery during the second year. ZA effectively prevented bone loss during the first year of chemotherapy. BMD remained stable 1 yr after completion of ZA. Serum CTX increased significantly by 12 and 24 months. More frequent administration may be required to suppress bone resorption in this patient population.


An elasmobranchian somatostatin: primary structure and tissue distribution in Torpedo marmorata.
Extracts of brain, stomach, pancreas, and intestine from Torpedo marmorata, an elasmobranchian cartilaginous fish, contained somatostatin-like immunoreactivity. Gel filtration studies demonstrated that material with the elution volume of somatostatin-14 was the only component detected in all tissue extracts. This result contrasts with the situation in mammals where prosomatostatin is processed to multiple molecular forms in a tissue-specific manner. Somatostatin from pancreas and gut was purified to homogeneity and amino acid sequence analysis indicated that T. marmorata somatostatin from both tissues has the same structure as somatostatin-14 isolated from the higher vertebrates. Further examination of other lower vertebrate species is required in order to test the hypothesis that the ability to regulate the production of multiple forms of a regulatory peptide from a single precursor molecule developed only relatively late in evolution.


Design, Structural Optimization, and Characterization of the First Selective Macrocyclic Neurotensin Receptor Type 2 Non-opioid Analgesic.
Neurotensin (NT) receptor type 2 (NTS2) represents an attractive target for the development of new NT-based analgesics. Here, we report the synthesis and functional in vivo characterization of the first constrained NTS2-selective macrocyclic NT analog. While most chemical optimization studies rely on the NT(8-13) fragment, we focused on NT(7-12) as a scaffold to design NTS2-selective macrocyclic peptides. Replacement of Ile12 by Leu, and Pro7/Pro10 by allylglycine residues followed by cyclization via ring-closing metathesis led to macrocycle 4, which exhibits good affinity for NTS2 (50 nM), high selectivity over NTS1 (>100 μM), and improved stability compared to NT(8-13). In vivo profiling in rats reveals that macrocycle 4 produces potent analgesia in three distinct rodent pain models, without causing the undesired effects associated with NTS1 activation. We further provide evidence of its non-opioid antinociceptive activity, therefore highlighting the strong therapeutic potential of NTS2-selective analogs for the management of acute and chronic pain.


The epigenetic implication in coronavirus infection and therapy.
Epigenetics is a relatively new field of science that studies the genetic and non-genetic aspects related to heritable phenotypic changes, frequently caused by environmental and metabolic factors. In the host, the epigenetic machinery can regulate gene expression through a series of reversible epigenetic modifications, such as histone methylation and acetylation, DNA/RNA methylation, chromatin remodeling, and non-coding RNAs. The coronavirus disease 19 (COVID-19) is a highly transmittable and pathogenic viral infection. The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which emerged in Wuhan, China, and spread worldwide, causes it. COVID-19 severity and consequences largely depend on patient age and health status. In this review, we will summarize and comparatively analyze how viruses regulate the host epigenome. Mainly, we will be focusing on highly pathogenic respiratory RNA virus infections such as coronaviruses. In this context, epigenetic alterations might play an essential role in the onset of coronavirus disease complications. Although many therapeutic approaches are under study, more research is urgently needed to identify effective vaccine or safer chemotherapeutic drugs, including epigenetic drugs, to cope with this viral outbreak and to develop pre- and post-exposure prophylaxis against COVID-19.


Evaluation of the woman's drop-in service in Benarty, Fife.
A survey of the health needs of women aged between 16 and 64 years of age in the Benarty area was carried out by the Department of Public Health in Fife. In response to the findings of this survey and in particular to the expressed wish for a drop-in service to be made available and for access to self-help groups and counselling sessions, a multi-agency project was established in the Benarty area of Fife. Two drop-in centres were set up, in a local community centre and in a primary care clinic, and were staffed by health visitors, social workers and staff from the community education department. The centres were each open twice a week for 2-3 hours on each occasion and crèche facilities were made available. The aims of the service were to provide counselling on a one-to-one basis, to establish self-help groups based on the expressed needs of women and to refer people on to the most appropriate services, if necessary. The service was established on a pilot basis and an essential component of the project was an evaluation of the service. To evaluate the service a community survey was carried out involving a random sample of 370 women taken from the community health index, and a register was kept to record details of attendances. Two hundred and sixty-five women were successfully interviewed, a response rate of 72 per cent. The major finding of concern was that 63 per cent of women had not heard of the drop-in service, suggesting that the advertising of the centres had been ineffective. Analysis of the clinic register showed that a total of only 77 women had attended the two drop-in centres over a 12-month period. Owing to the low attendance rates, the service was disbanded after one year of operation. It is possible that these low rates may be explained, at least in part, by the fact that a large number of local social services had been developed in the Benarty area since the time of the needs assessment survey in 1991. The introduction of these new local services within this area may have met many of the needs of women who otherwise may have made use of the drop-in service. The results of the survey underline that the introduction of a new service needs to be underpinned by an effective communication strategy which is realistically budgeted and maintained over a period of time if there is to be successful penetration of the messages within the community. One successful aspect of the pilot project was the improved working relationships between the statutory health and social services staff who collaborated in the operation of the service.


A Proposed Neurologic Pathway for Scalp Acupuncture: Trigeminal Nerve-Meninges-Cerebrospinal Fluid-Contacting Neurons-Brain.
Objective: Scalp acupuncture is a somatic stimulation therapy that produces prominent clinical effects when used to treat cerebral diseases. However, this acupuncture's therapeutic mechanisms have not yet been well-addressed. Scalp acupoints are innervated by the trigeminal nerve, which is coincident with the intracranial sensory afferents as well as with the meningeal vessels. In recent years, cerebrospinal fluid-contacting neurons have been found and proved to transmit allergic substances between brain the parenchyma and meninges, representing a possible network between scalp acupuncture and the brain. The aim of the current study was to observe the connections between scalp acupoints and the meninges and to establish a possible mechanism for scalp acupuncture. Materials and Methods: Twenty-five adult Sprague-Dawley rats were used for the present study. Evans Blue dye (Sigma Chemical Co, St. Louis, MO) was injected though each rat's caudal vein after trigeminal stimulation for plasma extravasation observation. Cerebral blood flow (CBF) values of the rat's brain surface were measured at different timepoints before and after electroacupuncture (EA) on GB 15 (Toulinqi) or ST 36 (Zusanli). Results: These preliminary studies indicated that neurogenic plasma extravasation on a rat's skin and dura mater after mechanical or electrical stimulation of the trigeminal nerves is a reliable way to show the pathologic connection between scalp acupoints and the meninges. Moreover, CBF of the rat's brain surface is increased significantly after EA stimulation at GB 15 (Toulinqi), which is located in the receptive field of the supraorbital nerve. Conclusions: These findings suggest that the mechanism of scalp acupuncture might lie in the specific neurologic pathway that could be termed as trigeminal nerve-meninges-cerebrospinal fluid-contacting neurons-brain, which is a possible shortcut to brain functional regulation and cerebral disease treatment.


A case of supplement-induced hepatotoxicity.
A 45-year-old Caucasian male presented with a two-week history of jaundice and right-upper quadrant (RUQ) abdominal pain. Transaminases and biliary enzymes were markedly elevated with hyperferritinemia and mildly elevated INR. Imaging tests showed no significant abnormality. He denied prescription or over-the-counter (OTC) medication use, but he had been taking at least 9 dietary supplements for 12 months. Other causes of liver disease were excluded. His supplements were discontinued, and his liver-associated enzymes significantly markedly improved over the next 6 weeks and remained normal after one year suggesting supplement-induced hepatotoxicity. Due to the number of supplements, no specific agent could be identified as the primary cause of his liver injury. This case illustrates the importance of inquiring and educating patients of the potential harmful risks of over-the-counter medications and supplements.


Investigation of new cytogenetic biomarkers specific to high-LET radiation using in vivo and in vitro exposed human lymphocytes.
To find detectable cytogenetic biomarkers that can offer information about the radiation quality of in vivo exposure retrospectively. Chromosome-type aberrations of peripheral lymphocytes of uterine cancer patients that received internal gamma- and external X-ray therapy or carbon beam therapy and of victims severely exposed to neutrons and gamma-rays in a criticality accident that occurred in Tokai-mura, Japan were analysed. Data obtained from in vitro irradiation experiments using 60Co gamma-rays and 10 MeV neutrons were compared with the in vivo exposure data. The ratio of acentric rings to dicentric chromosomes (termed RaD ratio) and that of excess fragments to dicentrics (termed EfD ratio) showed significant (p < 0.05) differences between the two groups of cancer patients, and these ratios for accidental victims were in between the values of the two groups of cancer patients. The in vitro studies using doses equivalent to 1 - 3 Gy of gamma-rays have confirmed that the EfD ratios were increased with the high LET (linear energy transfer) and RaD ratios decreased. The present data show that the RaD and EfD ratios can be used as cytogenetic biomarkers of exposure to high-LET radiation at least within a few years of exposure.


Long-term results after conservative aortic valve repair for aortic regurgitation with ventricular septal defect.
Aortic valve repair was performed in 61 patients having aortic regurgitation (AR) associated with ventricular septal defect (VSD). Preoperative regurgitation was classified according to the Sellers' classification and grade I was in 3 patients, grade II in 19, grade III in 34, and grade IV in 5 patients. Forty-six patients underwent only plication of aortic valve, and in 15 patients the commissuroplasty was added to reinforce the free edge of the cusp. Furthermore, aortoplasty (aortic annuloplasty) was performed in 11. Actuarial survival rate and freedom from reoperation rate were 91.6% and 87.2%, respectively at 10 years after the initial repair. The rate of freedom from deterioration for 22 patients showing grade I or II of AR before the initial operation was 86.4% at 1 year, 76.7% at 5 and 10 years, while the rate for 36 patients with grade III or more severe AR was 91.7% at 1 year, 77.4% at 5 years and 63.9% at 10 years. The rate at 10 years after operation between the two groups was different significantly (p < 0.05). Twenty among 22 patients having grade I or II of AR before operation were in NYHA class I, while 23 of 30 survivors with grade III or IV of AR were in class I, 6 in class II, and 1 in class III. Eight patients received reoperation and four of them underwent repeated conservative aortic valve repair, and one received aortic valve replacement at reoperation. Five of 7 survivors with reoperation improved in NYHA class I and 2 in class II. These results suggested that careful follow-up was required especially for the first 10 years after the initial operation in patients showing preoperative severe AR and receiving aortic repair.


Statistical inference for tumor growth inhibition T/C ratio.
The tumor growth inhibition T/C ratio is commonly used to quantify treatment effects in drug screening tumor xenograft experiments. The T/C ratio is converted to an antitumor activity rating using an arbitrary cutoff point and often without any formal statistical inference. Here, we applied a nonparametric bootstrap method and a small sample likelihood ratio statistic to make a statistical inference of the T/C ratio, including both hypothesis testing and a confidence interval estimate. Furthermore, sample size and power are also discussed for statistical design of tumor xenograft experiments. Tumor xenograft data from an actual experiment were analyzed to illustrate the application.


An analysis of discourses shaping mental health practitioners.
A mental health practitioner (MHP) role was introduced to health services in southern England in 2003. The paper will discuss the initial phase within a longitudinal research study. A discursive approach will be adopted in order to understand how healthcare discourses constrain and provide possibilities for the emergence of a new worker role in mental health. The manner in which MHPs understand and talk about their work is socially constructed in interaction and constantly being modified by competing discourses. This paper will analyse three overarching health discourses, namely, the biomedical, person-centred and psychological discourses that have shaped MHP trainees. Discourses intersect to inform the role, where practices of nursing, psychology, medicine and occupational therapy are combined. Thus, the inclusion of physical, psychological and person-centred components of care serve as a multifaceted approach to care. This form of interprofessionalism leads MHPs one step closer in the advance towards an interdisciplinary discourse of holistic care.


Epidemiological measures in planning: observations from Sweden.
This article reviews how epidemiological measures can be used in health planning. Theoretical considerations are discussed together with empirical data from Sweden. Formulation of targets, priority settings, resource allocation and monitoring systems are some ways in which epidemiological data can improve health planning. One important lesson for planning is that problems related to health, inequalities in health, and access to care, must be made visible to politicians, health personnel and the public. Further, there is a need to complement a national health policy with a decentralized planning system that takes local conditions and needs into consideration.


Aerosol-induced laser breakdown thresholds: effect of resonant particles.
Laser intensity thresholds for the onset of stimulated Raman scattering and the breakdown in resonant micro-meter-sized droplets are reduced to below those for nonresonant droplets by a factor of ~ 3. This reduction is most likely caused by the enhancement of electromagnetic energy (photon) densities within the droplets over and above that in nonresonant droplets. The magnitude of the threshold reduction for breakdown is consistent with the assertion that (1) input (pump) wavelength resonances that initiate plasma have cavity Q's of ~ 10(4) and (2) finite regions of high-electromagnetic-energy density within the droplet, with dimensions of the order of the Debye length, are required to initiate plasma.


Nephrotoxicity following carboplatin use in children: is routine monitoring of renal function necessary?
Carboplatin is an effective chemotherapeutic agent against many solid tumours. Although it is thought to be less nephrotoxic than its precursor cisplatin, current paediatric treatment protocols require regular monitoring of renal glomerular function during and after carboplatin use. Because accurate assessment of renal function in children requires measurement of isotope-clearance glomerular filtration rates (GFRs), routine monitoring is costly and time consuming. We studied 26 paediatric patients who were receiving chemotherapy that included 500-600 mg/m2 of carboplatin per course. 51Cr-EDTA GFRs were measured initially and after one to seven courses (median four). There was no measurable difference between renal function before and after carboplatin (P = 0.8). Our study shows that routine monitoring of renal glomerular function is unnecessary. Carboplatin use in patients who have had unilateral nephrectomy as part of their treatment is also discussed. Paediatric oncology literature concerning nephrotoxicity and carboplatin is reviewed.


Is patient-specific pre-operative preparation feasible in a clinical environment? A systematic review and meta-analysis.
Technical difficulty of an operation is associated with patient and disease characteristics, indicating the necessity for surgeons to exercise patient-specific preparation. Such methods have been shown to be effective in the simulation suite, however, application in a real clinical environment has been sporadic. This systematic review attempts to answer if patient-specific preparation in challenging surgical procedures is feasible. A systematic review of OvidMedline, Embase and all Evidence Based Medicine review databases, was conducted in search of studies who described surgical rehearsals in all specialties. Following the application of defined inclusion and exclusion criteria relevant data were extracted and summarised. Descriptive synthesis was performed for all included studies and meta-analysis of data was applied when possible. Of fourty-nine studies included, thirty-seven were case-series, ten were non-randomised comparative trials and two randomised controlled trials. Accuracy of applied methods ranged from 66.7 to 100% and a good outcome was seen in 60-100% of operations. Meta-analysis of studies comparing rehearsals to real procedures (same patients) showed that simulated procedures were significantly faster than real ones (SMD = -1.56 [-2.19, -0.93] p < 0.00001) but were similar in other outcomes (fluoroscopy time: SMD = -0.1 [-0.63, 0.42] p = 0.7, fluoroscopy volume: SMD = -0.43[-0.97, 0.11], p = 0.12). Meta-analysis of studies comparing pre-operative rehearsals to standard treatment (two distinct groups of patients), demonstrated that real procedures were performed quicker if pre-operative rehearsal took place (SMD = -0.47 [-0.79, -0.16], P = 0.003) but the immediate clinical outcome was similar for practiced and not practiced operations (SMD =0.03[-0.23, 0.29], p = 0.82). Current evidence suggests that patient-specific pre-operative preparation is feasible and safe and decreases operational time.


The Association Between Urinary Tract Infection and Overactive Bladder Treatment.
Background: Overactive bladder (OAB) syndrome is defined as urinary urgency, with or without urge incontinence in the absence of an underlying pathological or metabolic cause. Treatment for OAB involves anti-muscarinic agents and beta 3-adrenoceptor agonists. As a previous study showed that treatment may increase the risk of urinary tract infection (UTI), we conducted a nationwide, population-based, retrospective study to assess UTI risk associated with OAB medication adherence, and different types of OAB medication. Methods: The source of data was medical records from National Health Insurance Research Database (NHIRD). Patients who were diagnosed with OAB in outpatient records from January 1, 2014 to December 31, 2016 were included. Outpatient visits included an attendance at primary care or the emergency department. The index date was the first prescription medication for OAB treatment after diagnosis. The targeted population was those diagnosed with OAB, and targeted drugs were anti-muscarinic agent (including flavoxate, oxybutynin, propiverine, solifenacin, tolterodine, and trospium) and mirabegron. Adherence was assessed based on the proportion of days covered in 12 months among mirabegron and anti-muscarinic agents. A multivariate Cox proportional-hazards model was used to compare the risk of UTI with OAB medication adherence, and different types of OAB medication. Results: There were 39,975 outpatients diagnosed with OAB in the database from 2014 to 2016. Excluding those younger than 20 years old and for whom the information was incomplete in the database, 21,869 patients were included in the final OAB cohort. Overall, risk of UTI was not influenced by the targeted drugs or adherence during the follow-up period, regardless of UTI history or sex. Conclusion: OAB is a common problem in Taiwan. After 12 months of follow-up, there was no difference between anticholinergic medications and beta-3 agonists, nor between high and low adherence in the risk of UTI.


Nosocomial Infections with Aeromonas hydrophila from Leeches.
The manner in which leeches are maintained before they are used for therapy has not been studied as a factor contributing to nosocomial infections. A 5-year retrospective survey of Aeromonas hydrophila nosocomial infections at a hospital in Marseille, France, revealed infections in 5 (4.1%) of an estimated 122 patients treated with leeches in the Hand Surgery Unit and 2 (2.4%) of an estimated 85 patients treated with leeches in other hospital units. The retrospective survey showed that the Hand Surgery Unit was the only unit that had its own aquarium for maintaining leeches; this aquarium was filled with tap water contaminated with Aeromonas species and was not regularly disinfected or cleaned. Leeches used in other units were maintained in noncarbonated water in a transport device. Use of leeches kept in aquariums that are filled with tap water and not disinfected or cleaned regularly may be linked to A. hydrophila infections.


Clinical evaluation of the NobelActive implant system: a case series of 107 consecutively placed implants and a review of the implant features.
The purpose of this paper is to (1) introduce the features of this new implant, (2) investigate the clinical benefits as advertised by the manufacturer in comparison with traditional root form implants, and (3) provide guidelines for its use. One hundred seven NobelActive implants were placed in 67 consecutive patients with type I-IV bone within 8 months. Cases also include implants placed in sinus grafts, ridges with insufficient thickness and facial bone loss and were placed with delayed and immediate loading. Parameters were assessed to determine whether we could confirm the manufacturer's statements on this implant system. Results obtained with 107 implants of 3.5, 4.3, and 5 mm diameters with 10- to 15-mm lengths placed in different types of bone with delayed and immediate loading demonstrated a final insertion torque from 15 to 70 Ncm. All types of bone allowed "redirection" of the implant but were limited in the bone with higher density. According to the manufacturer, this new design of the NobelActive implant has high initial stability, bone condensing properties, redirecting capability, built-in platform shifting, and dual-function prosthetic connections. After investigating these 5 statements within the limits of our study, we were able to confirm these claims, but with some recommendations for the clinical use and placement of these implants.


Effects of Nutrient and Water Supply During Fruit Development on Metabolite Composition in Tomato Fruits (Solanum lycopersicum L.) Grown in Magnesium Excess Soils.
Tomato cultivation in the greenhouse or field may experience high surplus salts, including magnesium (Mg2+), which may result in differences in the growth and metabolite composition of fruits. This study hypothesized that decreasing the supply of nutrients and/or water would enhance tomato fruit quality in soils with excess Mg2+ that are frequently encountered in the field and aimed to find better supply conditions. For tomato plants cultivated in plastic pots using a plastic film house soil, the fertilizer supply varied in either the nitrogen (N) or potassium (K) concentration, which were either 0.1 (lowest) or 0.75 times (lower) than the standard fertilizer concentrations. Water was supplied either at 30 (sufficient) or 80 kPa (limited) of the soil water potential. Lycopene content on a dry-weight basis (mg/kg) was enhanced by the combination of lowest N supply and sufficient water supply. However, this enhancement was not occurred by the combination of the lowest N supply and limited water supply. Sugars and organic acids were decreased by limiting the water supply. Therefore, we carefully suggest that an adjustment of nitrogen with sufficient watering could be one of strategies to enhance fruit quality in excess Mg2+ soils.


First- and second-order clustering transitions for a system with infinite-range attractive interaction.
We consider a Hamiltonian system made of N classical particles moving in two dimensions, coupled via an infinite-range interaction gauged by a parameter A. This system shows a low energy phase with most of the particles trapped in a unique cluster. At higher energy it exhibits a transition towards a homogenous phase. For sufficiently strong coupling A, an intermediate phase characterized by two clusters appears. Depending on the value of A, the observed transitions can be either second or first order in the canonical ensemble. In the latter case, microcanonical results differ dramatically from canonical ones. However, a canonical analysis, extended to metastable and unstable states, is able to describe the microcanonical equilibrium phase. In particular, a microcanonical negative specific heat regime is observed in the proximity of the transition whenever it is canonically discontinuous. In this regime, microcanonically stable states are shown to correspond to saddles of the Helmholtz free energy, located inside the spinodal region.


Highly Selective Hydrogenation of CO2 to Ethanol via Designed Bifunctional Ir1-In2O3 Single-Atom Catalyst.
Recently, CO2 hydrogenation for the controlled growth of the carbon chain to produce high-value C2 or C2+ products has attracted great interest, where achieving high selectivity for a specific product remains a challenge, especially for ethanol. Herein, we have designed a bifunctional Ir1-In2O3 single-atom catalyst, integrating two active catalytic centers by anchoring the monatomic Ir onto the In2O3 carrier. This Ir1-In2O3 single-atom catalyst is efficient for the hydrogenation of CO2 in liquid, yielding a high selectivity for ethanol (>99%) with an excellent initial turnover frequency (481 h-1). Characterization shows that the isolated Ir atom couples with the adjacent oxygen vacancy forming a Lewis acid-base pair, which activates the CO2 and forms the intermediate species of carbonyl (CO*) adsorbed on the Ir atom. Coupling this CO* with the methoxide adsorbed on the In2O3 forms a C-C bond. The strategy of this effective bifunctional single-atom catalyst by synergistically utilizing the distinct catalytic roles of the single-atom site and the substrates provides a new avenue in catalyst design for complex catalysis.


In vivo pharmacodynamic evaluation of antidepressants based on flux mitochondrial Cys in living mice via near infrared fluorescence imaging.
The establishment of an objective and effective approach is imperative for depression diagnosis and anti-depressant efficacy evaluation, which might eliminate the drawbacks of current clinical diagnoses that rest on subjective scales. Oxidative stress may lead to depression with an excess of oxidants, but correspondingly, reductants play essential roles in retaining redox homeostasis, one of which is mitochondrial cysteine (Cys). Therefore, real-time and in situ monitoring of mitochondrial Cys fluctuations in the mouse brain is expected to achieve effective diagnosis and pharmacodynamic evaluation of depression. Herein, we developed a near-infrared fluorescence imaging probe (CSS) for the detection of mitochondrial Cys in the mouse brain. CSS is responsive to changes in the level of Cys at 705 nm and has high sensitivity, selectivity, temporal-spatial resolution and deep tissue penetration. Utilizing the probe, we revealed that the concentration of mitochondrial Cys decreased in the brains of mice with depression. Importantly, in the brains of depressed mice with three antidepressants, varying levels of Cys were observed, indicating different antidepressant efficacies. Altogether, this work affords a convincing strategy for the precise diagnosis of depression and pharmacodynamic evaluation of antidepressants.


Plant-based foods as a source of lipotropes for human nutrition: a survey of in vivo studies.
Increased consumption of plant products is associated with lower chronic disease prevalence. This is attributed to the great diversity of healthy phytochemicals present in these foods. The most investigated physiological effects have been their antioxidant, anti-carcinogenic, hypolipidemic, and hypoglycemic properties. Although less studied in humans, some compounds were very early on shown to be lipotropic in animals, i.e., the capacity to hasten the removal of fat from liver and/or reduce hepatic lipid synthesis or deposits by mainly increasing phospholipid synthesis via the transmethylation pathway for triglyceride-rich lipoprotein exportation from the liver and enhanced fatty acid β-oxidation and/or down- and up-regulation of genes involved in lipogenic and fatty acid oxidation enzyme synthesis, respectively. The main plant lipotropes are choline, betaine, myo-inositol, methionine, and carnitine. Magnesium, niacin, pantothenate, and folates also indirectly support the overall lipotropic effect. The exhaustive review of rat studies investigating phytochemical effect on hepatic lipid metabolism suggests that some fatty acids, acetic acid, melatonin, phytic acid, some fiber compounds, oligofructose, resistant starch, some phenolic acids, flavonoids, lignans, stilbenes, curcumin, saponins, coumarin, some plant extracts, and some solid foods may be lipotropic. However, this remains to be confirmed in humans, for whom intervention studies are practically non-existent. Supplemental materials are available for this article. Go to the publisher's online edition of Critical Reviews in Food Science and Nutrition® to view the free supplemental file.


Development of electrochemical high-speed atomic force microscopy for visualizing dynamic processes of battery electrode materials.
Development of lithium ion batteries with ultrafast charging rate as well as high energy/power densities and long cycle-life is one of the imperative works in the field of batteries. To achieve this goal, it requires not only to develop new electrode materials but also to develop nano-characterization techniques that are capable of investigating the dynamic evolution of the surface/interface morphology and property of fast charging electrode materials during battery operation. Although electrochemical atomic force microscopy (EC-AFM) holds high spatial resolution, its imaging speed is too slow to visualize dynamics occurring on the timescale of minutes. In this article, we present an electrochemical high-speed AFM (EC-HS-AFM), developed by addressing key technologies involving optical detection of small cantilever deflection, dual scanner capable of high-speed and wide-range imaging, and electrochemical cell with three electrodes. EC-HS-AFM imaging from 1 fpm to ∼1 fps with a maximum scan range of 40 × 40 µm2 has been stably and reliably realized. Dynamic morphological changes in the LiMn2O4 nanoparticles during cyclic voltammetry measurements in the 0.5 mol/l Li2SO4 solution were successfully visualized. This technique will provide the possibility of tracking dynamic processes of fast charging battery materials and other surface/interface processes such as the formation of the solid electrolyte interphase layer.


Evaluation of Interleukin-23 and JAKs/STATs/SOCSs/ROR-γt Expression in Type 2 Diabetes Mellitus Patients Treated With or Without Sitagliptin.
The production of interleukin-23 (IL-23) and the expression levels of related genes were evaluated in type 2 diabetes mellitus patients. The correlations between them were also determined. Thirty patients without sitagliptin (sitagliptin negative; SN), 30 patients with sitagliptin (sitagliptin positive; SP), and 30 healthy controls (HCs) were recruited. The level of IL-23 in the supernatant of anti CD3-activated peripheral blood mononuclear cells (PBMCs) was assessed using enzyme-linked immunosorbent assay. The expressions of IL-23, JAK1/JAK2/TYK2, STAT1/STAT3, ROR-γt, and SOCS1/SOCS3 in PBMCs were evaluated by real-time polymerase chain reaction. The production of IL-23 and the expressions of IL-23, JAK2, STAT3, and ROR-γt were observed to be enhanced in SN patients versus HCs, while the levels were decreased in SP patients versus SN patients (P < 0.05). SOCS1 and SOCS3 expressions were lower in SN patients than HCs, and their expressions were elevated in SP patients versus SN patients (P < 0.05). In SN patients, positive correlations between the IL-23 with fasting plasma glucose and HbA1c were observed, and JAK2/STAT3/ROR-γt were positively correlated with IL-23. JAK2, STAT3, and ROR-γt were positively related to each other and were negatively related to SOCS3. Enhanced IL-23/JAK2/STAT3/ROR-γt and reduced SOCS1/SOCS3 were found in SN patients. Sitagliptin may regulate the IL-23 and related gene expression.


The association between baseline circulating progenitor cells and vascular function: The role of aging and risk factors.
To investigate the cross-sectional and longitudinal relationships between vascular function and circulating progenitor cell (CPC) counts with respect to aging and exposure to risk factors. In 797 adult participants, CPCs were enumerated by flow cytometry as CD45med mononuclear cells expressing CD34 epitope and its subsets co-expressing CD133, and chemokine C-X-C motif receptor 4 (CXCR4+). Arterial stiffness was evaluated by tonometry-derived pulse wave velocity (PWV) and microvascular function was assessed as digital reactive hyperemia index (RHI). In cross-sectional analyses, for every doubling in CD34+ cell counts, PWV was 15% higher and RHI was 9% lower, after adjusting for baseline characteristics and risk factors (p for all < 0.01). There were significant CPC-by-age-by-risk factor interactions (p <0.05) for both vascular measures. Among younger subjects (< 48 years), CPC counts were higher in those with risk factors and vascular function was better in those with higher compared to those with lower CPC counts (p for all < 0.0l). In contrast, in older participants, CPCs were not higher in those with risk factors, and vascular function was worse compared to the younger age group. A lower CPC count at baseline was an independent predictor of worsening vascular function during 2-year follow-up. A higher CPC count in the presence of risk factors is associated with better vascular function among younger individuals. There is no increase in CPC count with risk factors in older individuals who have worse vascular function. Moreover, a higher CPC count is associated with less vascular dysfunction with aging.


Rebirth of the translational machinery: The importance of recycling ribosomes.
Translation of the genetic code occurs in a cycle where ribosomes engage mRNAs, synthesize protein, and then disengage in order to repeat the process again. The final part of this process-ribosome recycling, where ribosomes dissociate from mRNAs-involves a complex molecular choreography of specific protein factors to remove the large and small subunits of the ribosome in a coordinated fashion. Errors in this process can lead to the accumulation of ribosomes at stop codons or translation of downstream open reading frames (ORFs). Ribosome recycling is also critical when a ribosome stalls during the elongation phase of translation and must be rescued to allow continued translation of the mRNA. Here we discuss the molecular interactions that drive ribosome recycling, and their regulation in the cell. We also examine the consequences of inefficient recycling with regards to disease, and its functional roles in synthesis of novel peptides, regulation of gene expression, and control of mRNA-associated proteins. Alterations in ribosome recycling efficiency have the potential to impact many cellular functions but additional work is needed to understand how this regulatory power is utilized.


Renin-Angiotensin System and Coronavirus Disease 2019: A Narrative Review.
Although clinical manifestations of the 2019 novel coronavirus disease pandemic (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), are mainly respiratory symptoms, patients can also develop severe cardiovascular damage. Therefore, understanding the damage caused by SARS-COV-2 to the cardiovascular system and the underlying mechanisms is fundamental. The cardiovascular damage may be related to the imbalance of the renin-angiotensin-system (RAS) as this virus binds the Angiotensin-Converting-Enzyme 2 (ACE2), expressed on the lung alveolar epithelial cells, to enter into cells. Virus internalization may cause a downregulation of ACE2 on host cell surface that could lead to a local increased level of angiotensin II (AII) and a reduced level of angiotensin 1-7 (A1-7). An imbalance between these angiotensins may be responsible for the lung and heart damage. Pharmacological strategies that interfere with the viral attachment to ACE2 (umifenovir and hydroxychloroquine/chloroquine) or that modulate the RAS (analogous of A1-7 and ACE2, losartan) are in clinical development for COVID-19. The use of RAS inhibitors has also become a matter of public concern as these drugs may increase the mRNA expression and levels of ACE2 and impact the virulence and transmission of SARS-COV-2. Data on the effect of RAS inhibitors on ACE2 mRNA expression are scarce. Scientific societies expressed their opinion on continuing the therapy with RAS inhibitors in patients with COVID-19 and underlying cardiovascular diseases. In conclusion, RAS may play a role in SARS-COV-2-induced cardiac and pulmonary damage. Further studies are needed to better understand the role of RAS in COVID-19 and to guide decision on the use of RAS inhibitors.


Restriction of bacteriophage plaque formation in Streptomyces spp.
Several Streptomyces species that produce restriction endonucleases were characterized for their ability to propagate 10 different broad host range bacteriophages. Each species displayed a different pattern of plaque formation. A restrictionless mutant of S. albus G allowed plaque formation by all 10 phages, whereas the wild-type strain showed plaques with only 2 phages. DNA isolated from three of the phages was analyzed for the presence of restriction sites for Streptomyces species-encoded enzymes, and a very strong correlation was established between the failure to form plaques on Streptomyces species that produced particular restriction enzymes and the presence of the corresponding restriction sites in the phage DNA. Also, the phages that lacked restriction sites in their DNA generally formed plaques on the corresponding restriction endonuclease-producing hosts at high efficiency. The DNAs from the three phages analyzed also generally contained either many or no restriction sites for the Streptomyces species-produced enzymes, suggesting a strong evolutionary trend to either eliminate all or tolerate many restriction sites. The data indicate that restriction plays a major role in host range determination for Streptomyces phages. Analysis of bacteriophage host ranges of many other uncharacterized Streptomyces hosts has identified four relatively nonrestricting hosts, at least two of which may be suitable hosts for gene cloning. The data also suggest that several restriction systems remain to be identified in the genus Streptomyces.


A vision transformer for lightning intensity estimation using 3D weather radar.
Lightning has strong destructive powers; its blast wave, high temperature, and high voltage can pose a great threat to human production, life, and personal safety. The destructive power of high-intensity lightning is much greater than that of low-intensity lightning. The estimation of lightning intensity can provide an important reference for determining the lightning protection level and lightning disaster risk assessment. Lightning is a type of small-scale severe convective weather phenomenon. Weather radar is one of the best monitoring systems that can frequently sample the detailed three-dimensional (3D) structures of convective storms, with a small spatial scale and short lifetime at high temporal and spatial resolutions. Therefore, it is possible to extract the 3D spatial feature strongly correlated with lightning from 3D weather radar for estimating lightning intensity. This paper proposes a Vision Transformer model for lightning intensity estimation that can automatically estimate lightning intensity from 3D weather radar data. In an experiment, we transferred the task of estimating lightning intensity into a multicategory classification task. A framework was designed to produce lightning feature samples for model input from 3D weather radar and lightning location data. Then, the Synthetic Minority Over-Sampling Technique (SMOTE) algorithm was used to balance and optimize the sample distribution. Finally, samples were input into the proposed lightning intensity estimation model based on Vision Transformer for training and evaluation. Experimental results show that the proposed model based on Vision Transformers performs well with lightning intensity estimation.


New automatic heat flow calorimeter.
A calorimeter was developed which is capable of measuring heats of reaction with high precision, without making use of a precision thermostat. In comparison with conventional heat flow calorimeters, the measuring time is reduced considerably by electronic means. The reproducibility is comparable to that of adiabatic calorimeters, while the operation is easier because no filling and weighing of water and temperature readings are necessary. The final result is indicated automatically.


Growth Rate of Cosmological Perturbations at z∼0.1 from a New Observational Test.
Spatial variations in the distribution of galaxy luminosities, estimated from redshifts as distance proxies, are correlated with the peculiar velocity field. Comparing these variations with the peculiar velocities inferred from galaxy redshift surveys is a powerful test of gravity and dark-energy theories on cosmological scales. Using ∼2×10(5) galaxies from the SDSS Data Release 7, we perform this test in the framework of gravitational instability to estimate the normalized growth rate of density perturbations fσ8=0.37±0.13 at z∼0.1, which is in agreement with the cold dark matter model with a cosmological constant. This unique measurement is complementary to those obtained with more traditional methods, including clustering analysis. The estimated accuracy at z∼0.1 is competitive with other methods when applied to similar data sets.


Atrophoderma of Pasini and Pierini. An immunopathologic case study.
Atrophoderma of Pasini and Pierini (APP) is a rare and distinctive form of dermal atrophy of uncertain origin. In only one previous report have immunopathologic methods been used to study a case of atrophoderma of Pasini and Pierini, and on the basis of the results obtained it was concluded that immunologic mechanisms were relevant to the pathogenesis of the condition. A detailed investigation of a case of atrophoderma of Pasini and Pierini was conducted using immunofluorescence and immunoperoxidase techniques. The epidermal Langerhans cells were abundant and expressed polyclonal immunoglobulin M on the cell-surface membrane. Biopsy of the same lesion was repeated 6 months later and revealed staining for immunoglobulins A and M and also for C3. This pattern of staining could not be reproduced in a range of other atrophic or scarring cutaneous lesions. Immunophenotypic analysis of the mild perivascular mononuclear cell infiltrate revealed an aberrant T-cell phenotype of uncertain significance.


Effects of vitamin D supplementation on ovarian reserve markers in infertile women with diminished ovarian reserve.
The purpose of this study was to evaluate the effects of vitamin D supplementation on ovarian reserve markers, including serum anti-Mullerian hormone (AMH) level, follicle-stimulating hormone (FSH) level, and antral follicle count (AFC), in infertile women with diminished ovarian reserve and vitamin D deficiency.A prospective, nonrandomized, cross-sectional study was conducted. Women aged 18 to 41 years who were unable to become pregnant after 12 months of sexual intercourse and had normal tubal patency, partners with normal semen analysis, diminished ovarian reserve, and 25-hydroxyvitamin D [25(OH)D] deficiency were included. Eligible patients' AFC and serum levels of AMH, FSH, 25(OH)D, 1,25-dihydroxyvitamin D [1,25(OH)D], calcium, phosphate, alkaline phosphatase, and parathormone were assessed before and after administration of 300,000 IU of vitamin D ampules. Changes in the parameter values after vitamin D supplementation were compared with the initial levels.The study was conducted in 62 of the 142 participants. The AFC and AMH, 25(OH)D, 1,25(OH)D, phosphate (P < .01), and calcium levels (P < .05) were statistically significantly increased after vitamin D supplementation. Statistically significant decreases in FSH (P < .01) and alkaline phosphatase levels (P < .05) were observed after vitamin D supplementation. No statistically significant correlations were found between 25(OH)D level and AFC, 1,25(OH)D level, AMH level, and FSH level before and after supplementation (P > .05).As improvements in the ovarian reserve markers were obtained with vitamin D supplementation, vitamin D might be considered as a fertility treatment for patients with diminished ovarian reserve and vitamin D deficiency.


Photoacoustic imaging systems based on clinical ultrasound platform.
Photoacoustic imaging has drawn a significant amount of attention due to its unique capacity for functional, metabolic, and molecular imaging, which is achieved by the combination of optical excitation and acoustic detection. With both strengths of light and ultrasound, photoacoustic images can provide strong optical contrast at high ultrasound resolution in deep tissue. As photoacoustic imaging can be used to visualize complementary information to ultrasound imaging using the same data acquisition process, several studies have been conducted on combining photoacoustic imaging with existing clinical ultrasound systems. This review highlights our development of a photoacoustic/ultrasound dual-modal imaging system, various features and functionalities implemented for clinical translation, and preclinical/clinical studies performed by using the systems.


Pulmonary thromboendarterectomy in pediatric patients: Report of three cases.
Kumbasar U, Aypar E, Karagöz T, Demircin M, Doğan R. Pulmonary thromboendarterectomy in pediatric patients: Report of three cases. Turk J Pediatr 2018; 60: 604-607. Chronic thromboembolic pulmonary hypertension (CTEPH), which occurs due to impartial resolution of the pulmonary thrombus, is a rare type of pulmonary hypertension. However, most patients have an excellent long-term survival following pulmonary thromboendarterectomy (PTE). Pulmonary emboli and associated CTEPH is unusual in the pediatric population and is mostly reveals an underlying thrombophilic state. PTE is also recognized as the best therapeutic option in this subgroup of patients. In this case series, we report three young patients who had successfully undergone PTE due to pulmonary emboli and associated CTEPH.


A model of non-exclusive binding of agonist and antagonist on G-protein coupled receptors.
A modified concept of functioning of G-protein coupled receptors is presented, on the assumption that agonistic and antagonistic effects of drugs are related to their interaction with two separate receptor sites that exist simultaneously on a single receptor molecule and possess different ligand-specificity patterns. This proposal distinguishes between agonists and antagonists as binding at one of these sites triggers the receptor response, whereas the other site elicits another response leading to the receptor blockade. As these sites are simultaneously present on a single receptor molecule the formation of a ternary complex between agonist, antagonist and receptor is possible. Practical consequences of this concept are analysed with reference to experimental data on muscarinic acetylcholine receptors.


Efficacy of baking soda-containing chewing gum in removing natural tooth stain.
A 14-week, double-blind, randomized clinical trial was conducted with 126 healthy volunteers to compare the efficacy of twice-daily use of 3 baking soda-containing chewing gums in removing natural tooth stain when used in conjunction with a program of regular oral hygiene. All 3 chewing gums significantly reduced extrinsic stain (P < .0001) and improved the whitened appearance of teeth (P < .0001) at both the 2-week interim and the final 4-week evaluations. ARM & HAMMER DENTAL CARE The Baking Soda Gum (AHDC) reduced dental stain by 70.8%, compared to reductions of 71.9% and 65.3%, after use of 2 experimental gum formulations. Whitened appearance improved by 1.73 shade tabs using AHDC gum, and up to 2.49 shade tabs with the experimental formulations. These results suggest that the use of baking soda-containing gum after meals, in conjunction with good oral hygiene, can improve both extrinsic dental staining and the whitened appearance of teeth.


The distribution, metabolism and function of creatine in the male mammalian reproductive tract: a review.
Creatine is widely distributed throughout the male reproductive system in several mammalian species, and proteins involved in its metabolism and transport have been reported in a number of cell and tissue types. Creatine is synthesized within some organs, incorporating nitrogen from amino acid metabolism. Although creatine metabolism is obligatory for the motility of sea urchin spermatozoa, this does not appear to be the case for mammals. The possible functions of creatine within the reproductive tract are discussed.


Effect of stimulation of endogenous melatonin secretion during constant light exposure on 6-sulphatoxymelatonin rhythmicity in rats.
When light is presented unexpectedly at night to rats, melatonin production and secretion is acutely inhibited and the time of onset of production on the subsequent night is altered. In a series of experiments, we examined the effects of 6-12 hr light (200 lux) at night on melatonin metabolite excretion (6-sulphatoxymelatonin, aMT.6S). During the light exposure, we administered isoproterenol to stimulate endogenous production of melatonin by the pineal gland to determine if replacement of melatonin would block any phase shifting effects of the light. Exposure to 6 hr of light either during the first or second half of the night suppressed aMT.6S excretion during the light treatment and delayed the onset of melatonin secretion by 3.7 +/- 0.6 and 2.5 +/- 0.6 hr, respectively, compared to a change of 0.5 +/- 0.1 hr in animals maintained in darkness. Twelve hours light exposure (i.e. one night of continuous light) suppressed aMT.6S excretion completely and resulted in a delay in the onset the next night of 2.1 +/- 0.7 hr. When propranolol (10 mg/kg) was administered at 2-hr intervals during darkness, aMT.6S excretion was suppressed throughout the night, but on the subsequent release into constant darkness the onset of excretion was not delayed (0.6 +/- 0.1 hr delay). Administration of isoproterenol (10 mg/kg) to animals in constant light, at the time of expected lights off (CT12), and 5 hr later (CT17) resulted in an increase in melatonin production and aMT.6S excretion that was similar in duration and amount to the control night. The stimulation of endogenous melatonin production failed to block the phase shifting effects of the light exposure and, in fact, appeared to potentiate the delay at least on the first night (4.2 +/- 0.9 hr). The timing of the release into constant darkness following the light treatment had an unexpected effect on melatonin production on the cycle after treatment. Thus, animals exposed to 12 hr light and released into darkness at the normal time of lights off as above had a delay of about 2 hr and excreted 71 +/- 18% of the aMT.6S excreted on a control night. Animals released into darkness at the expected time of lights on failed to excrete more than 20 pmol/hr(i.e. no onset of excretion could be determined) at any time on the first subjective night after light treatment, which was no different from the excretion during the light treatment. On the next subjective night, the onset was delayed as expected and the amount of aMT.6S produced was restored. Treatment with isoproterenol at CT12 and CT17 failed to affect either the amount of aMT.6S excreted on the first subjective night after light treatment or the phase delay on the second night after treatment. The failure to produce melatonin on the first subjective night after 12 hr light exposure and release into darkness at CTO was not due to failure at the level of the pineal gland since injection ofisoproterenol at CT12 and CT17 on the first subjective night after light restored the normal amount of melatonin production. These results suggest that the absence of melatonin during light stimulation at night is not responsible for the phase delay in melatonin production and excretion on subsequent nights. The basis of the failure of the rats to commence melatonin production following 12 hr extended light exposure followed immediately by continuous darkness is not known.


Boys with reading disabilities and/or ADHD: distinctions in early childhood.
We examined distinctions in the early childhood characteristics of boys with reading disabilities (RD) and/or attention-deficit/ hyperactivity disorder (ADHD). A four-group mixed design consisting of boys identified at age 11 with reading disabilities only (RD only; n = 46), reading disabilities and ADHD (RD/ADHD; n = 16), ADHD only (n = 20), and a comparison group (n = 281) was utilized. Differences on receptive and expressive language and temperament for ages 3 and 5 were investigated. Analyses indicated that the boys from the RD-only group performed worse on measures of receptive and expressive language. The results also indicated that boys from the RD/ADHD groups consistently performed worse on measures of receptive language and exhibited more behaviors indicative of an undercontrolled temperament. In summary, we suggest that reading disabilities and ADHD represent moderately unique disorders that frequently co-occur and are characterized by distinct developmental pathways.


Acidosis in a patient with cholera: a need to redefine concepts.
A patient presented with cholera and a severe degree of ECF volume contraction. Despite large losses of bicarbonate (HCO3-)-containing diarrhoeal fluid, laboratory acid-base values were remarkably close to normal. A detailed analysis emphasizing principles of physiology and a quantitative approach provided new insights and eventually better definitions of metabolic and respiratory acidosis. A shift in focus from HCO3- concentration to HCO3- content in the extracellular fluid (ECF) compartment revealed the presence of metabolic acidosis. Central to this analysis was an emphasis on the haematocrit to enable a more accurate estimate of the degree of ECF volume contraction. The latter also revealed 'contraction' metabolic alkalosis, which masked the underlying metabolic acidosis. The presence of a respiratory acidosis of the tissue type was evident from the raised venous PCO2, which was not surprising once the magnitude of the ECF contraction had been appreciated. 'Bad buffering', as defined by Professor McCance, was the immediate danger and prompted swift action to restore an effective circulation. The haematocrit and the venous PCO2 also contribute valuable information to monitor the response to therapy. Nevertheless, there were still dangers to be discovered when an in-depth analysis suggested that the administration of isotonic saline would introduce an unanticipated danger for the patient.


Hypertonicity-induced expression of aquaporin 3 in MDCK cells.
Aquaporins (AQPs) are water channel proteins that participate in water transport. In the principal cells of the kidney collecting duct, water reabsorption is mediated by the combined action of AQP2 in the apical membrane and both AQP3 and AQP4 in the basolateral membrane, and the expression of AQP2 and AQP3 is regulated by antidiuretic hormone and water restriction. The effect of hypertonicity on AQP3 expression in Madin-Darby canine kidney (MDCK) epithelial cells was investigated by exposing the cells to hypertonic medium containing raffinose or NaCl. Northern blot and immunoblot analyses revealed that the amounts of AQP3 mRNA and AQP3 protein, respectively, were markedly increased by exposure of cells to hypertonicity. These effects were maximal at 12 and 24 h, respectively. Immunofluorescence and immunoelectron microscopy also demonstrated that the abundance of AQP3 protein was increased in cells incubated in hypertonic medium and that the protein was localized at the basolateral plasma membrane. These results indicate that the expression of AQP3 is upregulated by hypertonicity.


Shifts in Abundance and Diversity of Soil Ammonia-Oxidizing Bacteria and Archaea Associated with Land Restoration in a Semi-Arid Ecosystem.
The Grain to Green Project (GGP) is an unprecedented land restoration action in China. The project converted large areas (ca 10 million ha) of steep-sloped/degraded farmland and barren land into forest and grassland resulting in ecological benefits such as a reduction in severe soil erosion. It may also affect soil microorganisms involved in ammonia oxidization, which is a key step in the global nitrogen cycle. The methods for restoration that are typically adopted in semi-arid regions include abandoning farmland and growing drought tolerant grass (Lolium perenne L.) or shrubs (Caragana korshinskii Kom.). In the present study, the effects of these methods on the abundance and diversity of ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA) were evaluated via quantitative real-time PCR, terminal restriction fragment length polymorphism and clone library analysis of amoA genes. Comparisons were made between soil samples from three restored lands and the adjacent farmland in Inner Mongolia. Both the abundance and community composition of AOB were significantly different between the restored lands and the adjacent control. Significantly lower nitrification activity was observed for the restored land. Clone library analysis revealed that all AOB amoA gene sequences were affiliated with Nitrosospira. Abundance of the populations that were associated with Nitrosospira sp. Nv6 which had possibly adapted to high concentrations of inorganic nitrogen, decreased on the restored land. Only a slight difference in the AOB communities was observed between the restored land with and without the shrub (Caragana korshinskii Kom.). A minor effect of land restoration on AOA was observed. In summary, land restoration negatively affected the abundance of AOB and soil nitrification activities, suggesting the potential role of GGP in the leaching of nitrates, and in the emission of N2O in related terrestrial ecosystems.


Acute injection-related infections requiring hospitalisation among people who inject drugs: Clinical features, microbiology and management.
People who inject drugs are at risk of hospitalisation with injection-related infections (IRI). We audited the clinical features, microbiology and management of IRI at a tertiary service in Melbourne to describe the burden and identify quality improvement opportunities. We performed retrospective review of IRI admissions from January 2017 to April 2019. We extracted admissions where ICD-10 codes or triage text suggested injecting drug use, and the diagnosis suggested IRI. We reviewed these for eligibility and extracted data using a standardised form. We performed mixed-effects logistic regression to determine predictors of unplanned discharge. From 574 extracted candidate admissions, 226 were eligible, representing 178 patients. Median age was 41 years (interquartile range 36-47), 66% (117/178) male and 49% (111/226) had unstable housing. Over 50% (96/178) had a psychiatric diagnosis and 35% (62/178) were on opioid agonist therapy (OAT) on admission. Skin and soft tissue infection was the most common IRI (119/205, 58%), followed by bacteraemia (36/205, 18%) and endocarditis (26/205, 13%). Management included addictions review (143/226, 63%), blood-borne virus screening (115/226, 51%), surgery (77/226, 34%) and OAT commencement (68/226, 30%). Aggression events (54/226, 15%) and unplanned discharge (69/226, 30%) complicated some admissions. Opioid use without OAT was associated with almost 3-fold increased odds of unplanned discharge compared to no opioid use (odds ratio 2.90, 95% confidence interval 1.23, 6.85, p = 0.015). Comorbidities associated with IRI may be amenable to opportunistic intervention during hospitalisation. Further research is needed to develop optimal models of care for this vulnerable patient group.


Tissue biomarkers in renal cell carcinoma: issues and solutions.
Renal cell carcinoma (RCC) is an aggressive malignancy that is associated with a high rate of metastasis. Although several promising therapeutic strategies are now available for the treatment of patients with metastatic kidney cancer, the prognosis of these patients remains poor. Research is ongoing to identify RCC-specific biomarkers that can improve early diagnosis, surveillance of tumor progression, and prediction of patient prognosis. The identification of biomarkers that may predict response to specific therapies also will be useful in stratifying patients with RCC for treatment selection. Unfortunately, biomarker detection and measurement in kidney tumor tissues can be biased significantly by the lack of standardization in tissue sample acquisition, storage, and analysis. Consequently, the establishment of standardized operating procedures is necessary to maximize the accuracy of tissue-based biomarker assays. Herein, the authors discuss current issues in tissue-based translational research aimed at identifying clinically useful biomarkers for kidney cancer.


Contributions of sucrose synthase and invertase to the metabolism of sucrose in developing leaves : estimation by alternate substrate utilization.
The relative contributions of invertase and sucrose synthase to initial cleavage of phloem-imported sucrose was calculated for sink leaves of soybean (Glycine max L. Merr cv Wye) and sugar beet (Beta vulgaris L. monohybrid). Invertase from yeast hydrolyzed sucrose 4200 times faster than 1'-deoxy-1'-fluorosucrose (FS) while sucrose cleavage by sucrose synthase from developing soybean leaves proceeded only 3.6 times faster than cleavage of FS. [(14)C]Sucrose and [(14)C]FS, used as tracers of sucrose, were transported at identical rates to developing leaves through the phloem. The rate of label incorporation into insoluble products varied with leaf age from 3.4 to 8.0 times faster when [(14)C]sucrose was supplied than when [(14)C]FS was supplied. The discrimination in metabolism was related to enzymatic discriminations against FS to calculate the relative contributions of invertase and sucrose synthase to sucrose cleavage. In the youngest soybean leaves measured, 4% of final laminar length (FLL), all cleavage was by sucrose synthase. Invertase contribution to sucrose metabolism was 47% by 7.6% FLL, increased to 54% by 11% FLL, then declined to 42% for the remainder of the import phase. In sugar beet sink leaves at 30% FLL invertase contribution to sucrose metabolism was 58%.


[The adequate diagnostic criterion of mediastinal lymph node size for detection of metastasis in primary lung cancer].
The size of lymph node is one of the most important factor in evaluation of lymph node metastasis in lung cancer. The most appropriate size for detecting lung cancer lymph node metastasis was studied by 2403 dissected lymph nodes in 75 operated cases of lung cancer. From the result of Receiver Operating Characteristic (ROC) curve analysis, long-axis diameter of the lymph node showed higher accuracy of diagnosis of metastasis than short-axis diameter. Metastasis of squamous cell carcinoma was diagnosed more accurately than that of adenocarcinoma. The most adequate threshold for detection of metastasis in squamous cell carcinoma was 10 mm in long-axis diameter with sensitivity of 73.8% and specificity of 78%. On the other hand, that of adenocarcinoma was 7 mm in long-axis diameter with sensitivity of 65.7% and specificity of 55.9%. That threshold value of adenocarcinoma was approximate to the value of normal lymph node size in the mediastinum. It was suggested that the size for detection of lymph node metastasis was depended upon histological type, and detection of lymph node metastasis in adenocarcinoma was extremely difficult.


Patient-controlled analgesic infusion pumps.
Patient-controlled analgesic (PCA) infusion devices allow patients to self-administer narcotic analgesics within the limits prescribed by the physician. PCA therapy is typically used for postoperative, obstetric, terminally ill, and trauma patients. PCA pumps deliver solutions intravenously, subcutaneously, or epidurally and allow patient activation by means of a pendant button on a cord connected to the pump or a button directly on the pump. We evaluated nine PCA pumps from six suppliers. Three of these pumps are syringe-type, while the others use cassette-based fluid delivery. Because PCA pumps have often been cited as examples of devices that contribute to medical error (the most significant risk connected with PCA infusion is overmedication), the accident resistance of each device weighed heavily in our testing. The pumps we tested exhibit varying levels of performance, resistance to accidents and tampering, and ease of use. We rate six of them Acceptable. While none of the six units stands out as ideal, they meet most of our criteria, and we consider them somewhat better choices than the rest. We rate one other pump Acceptable (with Conditions) because, in one of its operating modes, it has a drawback that could be dangerous to patients; we consider its use acceptable only if the hospital doesn't employ the operating mode in question. Finally, we rate two pumps Not Recommended because they both have a significant number of disadvantages.


Profile of Acute Asthma Exacerbation in Drug Users.
The characteristics of patients who use heroin, cocaine, or both and present with acute asthma exacerbations have not been well studied. In this retrospective study, we aimed to study the demographic characteristics of this patient population, the characteristics of their asthma attack, and the risk factors for the need for invasive mechanical ventilation in this patient population. We reviewed the charts of patients discharged from an inner-city hospital with a diagnosis of acute asthma exacerbation. Individuals who used either heroin or cocaine or both within 24 hours of presenting to the emergency department were identified as a cohort of drug users. The rest were classified as non-drug users. Both groups were compared, and a univariate analysis was performed. To assess the predictive value of drug use for the need for intubation in the presence of confounding factors, logistic regression analysis was performed to identify whether using cocaine or heroin or both was an individual predictor for the need for invasive ventilation. Data from 218 patients were analyzed. Drug users (n = 85) were younger (mean age in years 43.9 vs. 50.5, P < 0.01), predominantly male (63.5% vs. 33.8%, P < 0.01), and more likely to be cigarette smokers (90.6% vs. 57.6%, P < 0.01). A medical history of intubation and admissions to the intensive care unit (ICU) was more common among drug users (56.5% vs. 29.3%, P < 0.01 and 54.1% vs. 38.3%, P < 0.03, respectively). Drug use was associated with increased need for invasive mechanical ventilation (35% vs. 23.3%, P = 0.05). Non-drug users were more likely to be using inhaled corticosteroids (48.9% vs. 32.9%, P = 0.03) and had longitudinal care established with a primary care provider (50.6% vs. 68.9%, P < 0.01). After adjusting for a history of mechanical ventilation, history of ICU admission, use of systemic corticosteroids, smoking, and acute physiological assessment and chronic health evaluation 2 score, drug use remained predictive for the need for mechanical ventilation (P = 0.026). Acute asthma exacerbations triggered by cocaine and heroin should be treated aggressively because they represent a cohort with poor follow-up and undertreated asthma as outpatients and are associated with increased need for invasive mechanical ventilation and ICU admission during acute exacerbation.


Studies of the thymus in Chagas' disease: III. Colonization of the thymus and other lymphoid organs of adult and newborn mice by Trypanosoma cruzi.
Among newborn and adult euthymic and athymic mice infected intraperitoneally with 10(2) or 10(4) trypomastigotes, neonates and adult athymic animals exhibited greater susceptibility with heavier colonization of central and peripheral lymphoid organs. Contiguity was also found to be a significant factor in colonization: after similar inocula, the parasitic load in the thymus was comparable in adults and neonates when the former were infected by subcutaneous injection in the anterior neck. In the nude athymic mice, the Y (reticulotropic) strain and the CL (myotropic) strain exhibited similar invasiveness, suggesting that the host immune response modulated the tissular tropism of these strains seen in the heterozygous littermates (Nu/+). The bone marrow was heavily infected; parasites were found in chondrocytes and cells of the mononucleate phagocytic system. Ultrastructural studies of infected thymus specimens showed that the corticomedullary architecture was unaltered and that both macrophages and epithelial cells were infected: both these cell types were infected in vitro.


Nutritional Regulation of Organelle Biogenesis in Euglena: REPRESSION OF CHLOROPHYLL AND NADP-GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE SYNTHESIS.
Nitrogen deficiency and the presence of specific organic carbon sources prevent chloroplast development in Euglena. In exponentially growing cultures, chlorophyll levels were low and independent of the nitrogen content of the growth medium. Chlorophyll levels increased in stationary phase and the amount of chlorophyll formed was proportional to the initial nitrogen content of the growth medium; the greater the concentration of nitrogen, the greater the amount of chlorophyll synthesized during stationary phase. Washing experiments demonstrated that the major nutritional factor inhibiting chlorophyll synthesis in stationary phase cultures grown on medium containing a high carbon to nitrogen ratio was the absence of nitrogen rather than the presence of utilizable organic carbon.The light-induced synthesis of chlorophyll and of NADP-glyceraldehyde-3-phosphate dehydrogenase was inhibited when acetate or ethanol was added at the time of exposure of dark-grown resting cells to light. Malate addition, however, stimulated chlorophyll and enzyme synthesis. Both cell number and total cell protein increased after ethanol, acetate, or malate addition, indicating that the resting cells were not nitrogen-deficient. Ethanol and acetate specifically repress light-induced chlorophyll synthesis. NADP-glyceraldehyde-3-phosphate dehydrogenase synthesis was inhibited at a time, the first 24 hours of light exposure, when chlorophyll synthesis was unaffected by carbon addition.


Temporal changes in incidence and prevalence of intellectual disability between two birth cohorts in Northern Finland.
We followed two separate, genetically homogeneous cohorts of children born in 1966 (n = 11,965) and 1985-1986 (n = 9,432) in Northern Finland to determine temporal changes in the incidence and prevalence of subcategories of intellectual disability within the same geographic area. The children were followed up to the age of 11.5 years. Similar study design, data ascertainment methods, and definition of intellectual disability were used. There was no change in the total incidence (12.62/1,000 in each) or in total prevalence (11.03/1,000 vs. 11.23/1,000) of intellectual disability. However, in the subcategories of intellectual disability, there was a shift from severe and moderate towards mild; whereas profound intellectual disability remained at the same level. The temporal changes followed generally similar patterns by gender.


[Insulin secretion: mechanisms of regulation].
REGULATION OF INSULIN SECRETION: Beta cells are unique endocrine cells. They respond positively, in terms of insulin secretion, not only to changes in the extracellular glucose concentration, but also to activators of the phospholipase C (cholecystokinin or acetylcholine), and to activators of adenylate cyclase (glucagon, glucagon-like peptide-1, or gastric inhibitory polypeptide). Major messengers which mediate glucose action for insulin release are Ca2+, adenosine triphosphate (ATP) and diacylglycerol (DAG). MAJOR PATHWAYS OF INSULIN RELEASE STIMULATION: There are four major pathways involved in stimulation of insulin release. The first pathway is KATP channel-dependent pathway in which increased blood glucose concentrations and increased b-cell metabolism result in a change in intracellular ATP/ADP ratio. This is a contributory factor in closure of ATP-dependent K+ channels, depolarization of b-cell membrane, in increased voltage-dependent L-type Ca2+ channel activity. Increased Ca2+ influx results in increased intracellular Ca2+ and stimulated insulin release. KATP channel-independent pathway augments Ca(2+) -stimulated insulin secretion of KATP channel-dependent pathway. Major potentiation of release results from hormonal and peptidergic activation of receptors linked to adenylyl cyclase. Adenylyl cyclase activity is stimulated by hormones such as vasoactive intestinal peptide (VIP), glucagon-like peptide-1 (GLP-1), and so on. These hormones, acting via G protein, stimulate adenylyl cyclase, thus causing a rise in cyclic adenosine monophosphate (cAMP) and activation of protein kinase A (PKA). Increased activity of PKA results in potentiation of insulin secretion.


Pediatric preoperative risk factors to predict postoperative ICU admission and death from a multicenter retrospective study.
Although some studies have investigated the potential predictors of perioperative mortality, there are few specifically for pediatrics. The aim of the retrospective study was to analyze potential preoperative risk factors and to develop a pediatric preoperative risk prediction score (PRPS), and to predict postoperative ICU admission and the incidence of perioperative death in pediatric patients. Patients who postoperatively admitted to ICU or died (occurred within 30 days after the surgery) from 263 607 pediatric surgical patients with age from 1 day to 14 years old in eight centers in China from October 2010 to September 2013 were retrospectively analyzed. About 5500 non-ICU admission and death patients were randomly selected from those 263 607 patients as controls for analysis comparison. Independent risk factors and a risk model were derived from these analyses, and were further assessed with the likelihood ratio test and the area under the receiver operating characteristic (ROC) curve. There were 1812 ICU admission or death patients but 187 patients' records are incomplete. There were 487 patients with incomplete records among 5500 controls. Collectively, data from 6626 patients were enrolled in final analyses. With multiple logistic regression analysis, age, ASA physical status, SpO2 , prematurity, and unfasted status were found to be independent predictors for critical patients. The AUC value of 0.905 indicated excellent predictive performance between critical and noncritical predictors. Our study revealed that age, ASA physical status, SpO2 , prematurity, and unfasted status are risk factors to predict postoperative ICU admission and death in pediatric patients.


Angiographic-pathologic correlations after elective percutaneous transluminal coronary angioplasty.
The local effect of coronary angioplasty is evaluated on the basis of postangioplasty angiograms. Smooth-walled dilation is considered to represent minimal or no injury, whereas intraluminal haziness corresponds with wall laceration. This study correlates the preangioplasty and postangioplasty angiograms with the histopathology of the target sites. The study includes 12 patients, each undergoing an elective procedure, and covers 19 angioplasty sites. Smooth-walled dilation and intraluminal haziness were not mutually exclusive. The angiograms were interpreted as smooth-walled dilation (n = 3), smooth-walled dilation with intraluminal haziness (n = 4), intraluminal and extraluminal haziness (n = 5), extraluminal dissection (n = 5), spiraltype dissection (n = 1), and aneurysm (n = 1). The histology of the arterial segments revealed wall laceration in all. Smooth-walled dilation without intraluminal haziness correlated with laceration limited to the intima in two, but with medial injury in one. Smooth-walled dilation with intraluminal haziness correlated with laceration limited to the intima in two and with medial injury in two. Intraluminal and extraluminal haziness corresponded with extensive laceration with deep involvement of the media in each. Extraluminal dissection correlated with a dissection along the shoulder area of the plaque, creating a broad-based flap. The spiral-type dissection corresponded with a true dissection into the plaque-free media. The aneurysm correlated with partial washout of an atherosclerotic plaque. The angiographic image of intraluminal and extraluminal haziness indicates extensive medial laceration. Smooth-walled dilation, with or without intraluminal haziness, is not a reliable indicator. The study emphasizes the need to reconsider the interpretations of postangioplasty coronary angiograms.


Organ distribution of aminopeptidase A and dipeptidyl peptidase IV in normal mice.
The hydrolases aminopeptidase A and dipeptidyl peptidase IV, both present in the kidney on the brush borders of the proximal tubule epithelial cells and podocytes, are involved in the induction of experimental membranous glomerulonephritis in the mouse. However, little is known about their (co)distribution in other tissues and their function in health and disease. A detailed insight into the localization of these two enzymes is a prerequisite to elucidation of their function. Therefore, we investigated the presence and co-distribution of aminopeptidase A and dipeptidyl peptidase IV by immunohistology with two different rat monoclonal antibodies, the specificity of which was determined by an immunodepletion technique. In addition, the molecular weight of the hydrolases; was analyzed by SDS-PAGE after isolation by solid-phase immunoprecipitation from glomeruli, renal brush borders, and thymus. Both hydrolases showed different molecular weights in renal corpuscle, renal brush borders, and thymic cells. A widespread organ distribution of the two hydrolases was observed, with co-localization in kidney, liver, small intestine, thymus, brain, spleen, and lymph nodes, either on the same cells or on different cells in the same organ. This distribution and partial co-localization suggests that the two hydrolases, acting either alone or in concert, have a role in many diverse biological processes.