The Coulee Region Community Pharmacy Asthma Intervention study.
To determine whether community pharmacist-initiated interventions containing a recommendation to adjust prescribed asthma therapy are more helpful to prescribers than similar communications without such a recommendation. Prospective, multicenter, quasi-experimental design with posttest. Wisconsin and Minnesota. 33 community and clinic pharmacies throughout the Coulee Region of Wisconsin and Minnesota enrolled eligible patients from October 1, 2004, to January 31, 2005. Patients were between 12 and 60 years of age, had used three or more short-acting beta-agonist (SABA) canisters with-in the previous 90 days, and did not meet any exclusion criteria. Based on an evaluation of each patient's inhaler technique and adherence to controller medications, pharmacists sent to the prescriber a fax containing a recommendation (for patients with proper technique and appropriate adherence to prescribed controller medications) or information (for those who had any combination of inappropriate inhaler technique or inappropriate adherence). Health care professionals' yes-or-no response to the question, "Do you find this form helpful for making clinical decisions?" Pharmacists offered to enroll 235 patients who were identified as meeting preliminary inclusion criteria. Of those, 112 people met exclusion criteria, 28 were not interested in their pharmacists' involvement, 13 stated that they did not have time to participate, 11 took the forms home but did not return them, and 11 other patients were excluded by the pharmacists for other reasons. The remaining 60 patients were in enrolled in the study, 60 faxes were sent from 16 pharmacies, and 40 of those were analyzed further. For 24 recommendation faxes sent, prescribers rated 15 as helpful (62.5%) and 4 as not helpful (16.7%). Of 16 informational faxes sent, 10 were marked helpful (62.5%) and 2 were marked not helpful (12.5%). Recommendation and informational faxes were overall helpful to health care professionals in making clinical decisions. Respondents found the two types of faxed interventions as equally helpful, suggesting that pharmaceutical care initiated by community pharmacists is helpful to prescribers.


Intravitreal use of bone marrow mononuclear fraction containing CD34+ stem cells in patients with atrophic age-related macular degeneration.
To evaluate the therapeutic potential and safety of intravitreal injections of bone marrow mononuclear fraction (BMMF) containing CD34+ cells in patients with atrophic age-related macular degeneration (AMD). Ten patients with atrophic AMD and best-corrected visual acuity (BCVA) in the worse-seeing eye of ≤20/100 were enrolled in this study. The bone marrow from all patients was aspirated and processed for mononuclear cell separation. A 0.1 mL suspension of BMMF CD34+ cells was injected into the vitreous cavity of the worse-seeing eye. Patients were evaluated at Baseline and 1,3,6,9 and 12 months after injection. Ophthalmic evaluation included BCVA measurement, microperimetry, infrared imaging, fundus autofluorescence and SD-optical coherence tomography at all study visits. Fluorescein angiography was performed at Baseline and at 6 and 12 months after intravitreal therapy. All patients completed the 6-month follow-up, and six completed the 12-month follow-up. Prior to the injection, mean BCVA was 1.18 logMAR (20/320-1), ranging from 20/125 to 20/640-2, and improved significantly at every follow-up visit, including the 12-month one, when BCVA was 1.0 logMAR (20/200) (P<0.05). Mean sensitivity threshold also improved significantly at 6, 9 and 12 months after treatment (P<0.05). Considering the area of atrophy identified by fundus autofluorescence, significant mean BCVA and mean sensitivity threshold improvement were observed in patients with the smallest areas of atrophy. Fluorescein angiography did not identify choroidal new vessels or tumor growth. The use of intravitreal BMMF injections in patients with AMD is safe and is associated with significant improvement in BCVA and macular sensitivity threshold. Patients with small areas of atrophy have a better response. The paracrine effect of CD34+ cells may explain the functional improvement observed; however, larger series of patients are necessary to confirm these preliminary findings.


Embryonic Valproate Exposure Alters Mesencephalic Dopaminergic Neurons Distribution and Septal Dopaminergic Gene Expression in Domestic Chicks.
In recent years, the role of the dopaminergic system in the regulation of social behavior is being progressively outlined, and dysfunctions of the dopaminergic system are increasingly associated with neurodevelopmental disorders, including autism spectrum disorder (ASD). To study the role of the dopaminergic (DA) system in an animal model of ASD, we investigated the effects of embryonic exposure to valproic acid (VPA) on the postnatal development of the mesencephalic DA system in the domestic chick. We found that VPA affected the rostro-caudal distribution of DA neurons, without changing the expression levels of several dopaminergic markers in the mesencephalon. We also investigated a potential consequence of this altered DA neuronal distribution in the septum, a social brain area previously associated to social behavior in several vertebrate species, describing alterations in the expression of genes linked to DA neurotransmission. These findings support the emerging hypothesis of a role of DA dysfunction in ASD pathogenesis. Together with previous studies showing impairments of early social orienting behavior, these data also support the use of the domestic chick model to investigate the neurobiological mechanisms potentially involved in early ASD symptoms.


Chronic Serotonergic Overstimulation Mimicking Panic Attacks in a Patient with Parkinson's Disease Receiving Additional Antidepressant Treatment with Moclobemide.
The pharmacological treatment options of Parkinson's disease (PD) have considerably evolved during the last decades. However, therapeutic regimes are complicated due to individual differences in disease progression as well as the occurrence of complex nonmotor impairments such as mood and anxiety disorders. Antidepressants in particular are commonly prescribed for the treatment of depressive symptoms and anxiety in PD. Case Presentation. In this case report, we describe a case of a 62-year-old female patient with PD and history of depressive symptoms for which she had been treated with moclobemide concurrent with anti-Parkinson medications pramipexole, rasagiline, and L-DOPA+benserazide retard. An increase in the dosage of moclobemide 12 months prior to admission progressively led to serotonergic overstimulation and psychovegetative exacerbations mimicking the clinical picture of an anxiety spectrum disorder. After moclobemide and rasagiline were discontinued based on the hypothesis of serotonergic overstimulation, the patient's psychovegetative symptoms subsided. The specific pharmacological regime in this case probably caused drug-drug interactions resulting in a plethora of psychovegetative symptoms. Likely due to the delayed onset of adverse effects, physicians had difficulties in determining the pharmacologically induced serotonin toxicity. This case report emphasizes the complexity of pharmacological treatments and the importance of drug-drug interaction awareness in the treatment of PD patients with complicating nonmotor dysfunctions such as depression.


[Pregnancy after conisation for atypical epithelial processes of the uterine cervix (author's transl)].
At the First Department of Obstetrics and Gynecology, University of Vienna Medical School, 148 females aged under 35 years at the time of conisation were examined between 1963 and 1974 to determine their desire for children, their fertility status and the course of pregnancy. After conisation a total of only 42 females (28,4%) wanted children. Of 104 patients with preinvasive carcinoma, a desire for children was reported by no more than 21 (20,2%); among the cases with dysplasia, the number of women desiring children was equally 21 (47,7%). By the end of 1976, after a followup period of 1 to 13 years, 16 of 42 females wanting children failed to conceive, while the remaining 26 gave birth to 20 children. Judging from our admittedly small material, conisation thus apparently has no effect on conception. However, the course of pregnancy was found to be impaired in some cases by the incompetent cervical function. Twelve patients required a Shirodkar operation, which failed to prevent late abortion in 2 cases and premature delivery in 4. Nine women gave birth at or at best 3 weeks before term without preventive methods.


Establishment of a diabetes mellitus type 1 model in the common marmoset.
Common marmosets have attracted considerable attention as a small standard primate model in biomedical research. However, no marmoset diabetes model is available. Here, we established a marmoset diabetes model via the combination of partial pancreatectomy and intravenous streptozotocin (STZ). A partial pancreatectomy was performed in 11 common marmosets and multiple STZ doses were intravenously administered. Diabetes was diagnosed upon sustained hyperglycaemia (nonfasting blood glucose level >200 mg/dl). Blood glucose and biochemistry were periodically assessed, in addition to glucose tolerance testing, continual blood glucose determination using a continuous glucose monitoring system, urine testing and histological evaluation. In 8 of the 11 animals (73%), diabetes mellitus was induced. The diabetic marmosets also showed abnormal intravenous and oral glucose tolerance test results. Blood glucose levels decreased in response to human insulin administration. The hyperglycaemic state was irreversible and persisted for more than 3 months, and the animals' condition was manageable via daily insulin administration. Thus, diabetes can be successfully induced and maintained in the common marmoset via partial pancreatectomy and STZ administration. This protocol effectively generates a valuable animal model for studying disease pathogenesis, risk factors and therapeutic interventions, including islet transplantation.


[A quick algorithm for detecting macro-particles distributed rarefiedly].
This paper presents a simple and quick algorithm, based on the principle of OR operation, for detecting macro-particles when the distribution of macro-particled is few and scattered. Counting and measuring the basic size parameters of macro-particles will be simultaneously accomplished by scanning the macroparticle image only once time.


Painful vascular compression syndrome of the sciatic nerve caused by gluteal varicosities.
The authors report three patients with chronic sciatic pain without focal neurologic deficit. Sitting or lying on the affected side provoked pain, and standing and walking relieved it. MRI revealed varicotic gluteal vessels compressing the sciatic nerve. Decompression of the nerve resulted in complete and permanent pain relief. Sciatic or buttock pain in patients with varicosities and pain provocation in the sitting or lying position suggests this neurovascular compression syndrome.


Cervical paraspinal muscle abnormalities and symptom duration: a multivariate analysis.
The purpose of this study was to determine whether paraspinal and other major proximal and distal muscle spontaneous activity (SA) is related to cervical radiculopathy (CR) symptom duration. A multivariate analysis of 124 (retrospectively identified) electrodiagnostically confirmed CRs was used to test these hypotheses. The results showed no evidence of correlation between SA and symptom duration for any of the upper limb muscles analyzed.


Upregulation of cell division cycle 20 in cisplatin resistance-induced epithelial-mesenchymal transition in osteosarcoma cells.
Cell division cycle 20 homologue (Cdc20) is characterized as an oncoprotein that is involved in carcinogenesis. Accumulated evidence reveals that Cdc20 plays an oncogenic role by governing cell growth, apoptosis, motility, and metastasis. The role of Cdc20 in drug resistance is elusive. In the present study, we exploited whether Cdc20 is involved in the cisplatin (DDP) resistance-induced epithelial-mesenchymal transition (EMT) of osteosarcoma cells. We found that DDP resistant U2OS and MG63 cells underwent EMT. Moreover, DDP-resistant cells exhibit the mesenchymal features such as enhanced attachment and detachment and increased invasion activity and migration. Mechanistically, Cdc20 was highly expressed in DDP-resistant osteosarcoma cells compared to parental cells. Consistently, downregulation of CdcC20 in DDP-resistant cells reversed the EMT phenotypes and changed the expression of EMT biomarkers. Our studies provide evidence for targeting Cdc20 as a promising approach to enhancing drug sensitivity for the treatment of osteosarcoma.


[Perforation of sigmoid diverticula. A complication following allogenic kidney transplantation].
In the early post-operative follow-up after allogenic kidney transplantation sigmoid perforation due to diverticula is a life-threatening complication. As immunosuppression is indispensable perforation is favoured. Due to pharmacotherapy the risk of sepsis is implied because clinical symptoms might be masked. Reference is made in this paper to four cases to describe clinical course, diagnostic and surgical approaches as well as diagnostic-therapeutic consequences for the patient of the waiting list.


Chondrogenic differentiation of mouse induced pluripotent stem cells using the three-dimensional culture with ultra-purified alginate gel.
As articular cartilages have rarely healed by themselves because of their characteristics of avascularity and low cell density, surgical intervention is ideal for patients with cartilaginous injuries. Because of structural characteristics of the cartilage tissue, a three-dimensional culture of stem cells in biomaterials is a favorable system on cartilage tissue engineering. Induced pluripotent stem cells (iPSCs) are a new cell source in cartilage tissue engineering for its characteristics of self-renewal capability and pluripotency. However, the optimal cultivation condition for chondrogenesis of iPSCs is still unknown. Here we show that a novel chondrogenic differentiation method of iPSCs using the combination of three-dimensional cultivation in ultra-purified alginate gel (UPAL gel) and multi-step differentiation via mesenchymal stem cell-like cells (iPS-MSCs) could efficiently and specifically differentiate iPSCs into chondrocytes. The iPS-MSCs in UPAL gel culture sequentially enhanced the expression of chondrogenic marker without the upregulation of that of osteogenic and adipogenic marker and histologically showed homogeneous chondrogenic extracellular matrix formation. Our results suggest that the pluripotency of iPSCs can be controlled when iPSCs are differentiated into iPS-MSCs before embedding in UPAL gel. These results lead to the establishment of an efficient three-dimensional system to engineer artificial cartilage tissue from iPSCs for cartilage regeneration. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1086-1093, 2019.


Life span extension and reduced neuronal death after weekly intraventricular cyclosporin injections in the G93A transgenic mouse model of amyotrophic lateral sclerosis.
The authors investigated whether cyclosporin A (CsA), a cyclophilin ligand with mitochondrial permeability transition pore-blocking and calcineurin-inhibiting properties, affects motor function, neuronal death, and life span in the G93A transgenic mouse model of familial amyotrophic lateral sclerosis (FALS). The G93A mice received weekly intracerebroventricular injections of CsA (20 microg/mouse/week) starting at the age of 65 days, and physical performance on an exercise wheel was monitored beginning at 84 days of age. Mice were allowed to survive for clinical observation of body weight, hindlimb weakness, and life span or until a defined end stage or were killed at 110 days of age for histological analysis. Treatment with CsA significantly delayed the onset of hindlimb weakness and also extended the time from its onset to paralysis. The overall life span of CsA-treated G93A mice was significantly extended, by 12% compared with vehicle-treated transgenic littermates. The CsA also prolonged physical performance on the exercise wheel and delayed weight loss. Histologically, there was significant preservation of both cervical and lumbar spine motor neurons and also tyrosine hydroxylase-positive dopaminergic substantia nigra neurons in 110-day-old CsA-treated mice compared with their transgenic littermates. The local administration of CsA directly into the brain ventricles is an effective means of central nervous system drug delivery (because CsA does not readily cross the blood-brain barrier), which in this study ameliorated clinical and neuropathological features of FALS in G93A mice. The remarkably low intrathecal CsA dose required for neuroprotection reduces potential adverse effects of systemic immunosuppression or nephrotoxicity seen with chronic systemic delivery of the drug.


Single limb performance following contralateral bimanual limb training.
Recent studies on intermanual transfer of reaching movements suggest that this transfer is conducted over an "extrinsic" coordinate system. We hypothesize that training reaching movements in a force field with both hands at the same time, in the same position (bimanual grip) will be more beneficial in promoting transfer of the learned skill to the dominant hand than training the unimpaired limb on the same movements in the same force field since the representation of the movement should be invariant of the limb. However, unlike intermanual transfer, bimanual transfer has the potential to involve infinite number of actuator combinations, or joint configurations, interfering with consistent transfer. The efficacy of this method of transfer has implications for people with hemiparesis since the less-affected arm could potentially "instruct" the more-affected arm how to move. Here, we report on an experiment that evaluates and compares the skill transfer between limbs in a reaching task: 1) intermanual transfer (from the nondominant to the dominant hand) and 2) bimanual transfer (from a bimanual grip to the dominant hand) with healthy subjects. We used two methods from which to judge the transfer: performance in the presence of the force field or by errors made during "catch trials" when the forces were unexpectedly removed as subjects changed hands (known as after effects of adaptation). We found only a small amount of transfer (20% of that seen in the practiced limb) with both types of training, and surprisingly there was no significant difference in the movement accuracy between these two training methods. Moreover, the direction of the after effects supports the assertion that the nervous system generalizes these movements in an extrinsic coordinate system. Accordingly, the limb must experience the dynamics singularly in order to develop an internal model.


Bcl-2 supports survival and metabolic fitness of quiescent tissue-resident ILC3.
Group 3 innate lymphoid cells (ILC3) are potent effector cells with critical roles in enforcing immunity, barrier integrity and tissue homeostasis along the gastrointestinal tract. ILC3 are considered primarily tissue-resident cells, seeding the gastrointestinal tract during embryonic stages and early life. However, the mechanisms through which mature ILC3 are maintained within adult tissues are poorly understood. Here, we report that lymphoid tissue-inducer-like (LTi-like) ILC3 exhibit minimal turnover in the healthy adult intestinal tract, persist for extended periods of time, and display a quiescent phenotype. Strikingly, during enteric bacterial infection LTi-like ILC3 also exhibit negligible hematopoietic replenishment and remain non-proliferative, despite robustly producing cytokines. Survival of LTi-like ILC3 was found to be dependent upon the balance between the metabolic activity required to drive effector function and anti-apoptotic programs. Notably, the pro-survival protein B-cell lymphoma-2 (Bcl-2) was required for the survival of LTi-like ILC3 ex vivo but was rendered partially dispensable if mitochondrial respiration was inhibited. Together we demonstrate LTi-like ILC3 are a tissue-resident, quiescent population that persist independently of hematopoietic replenishment to survive within the intestinal microenvironment.


The cleavage of HuR interferes with its transportin-2-mediated nuclear import and promotes muscle fiber formation.
Although the function of posttranscriptional processes in regulating the expression of genes involved in muscle fiber formation (myogenesis) is well accepted, the mechanisms by which these effects are mediated remain elusive. Here, we uncover such a mechanism and show that during myogenesis, a fraction of the posttranscriptional regulator human antigen R (HuR) is cleaved in a caspase-dependent manner in both cell culture and animal models. Disruption of caspase activity in cultured myoblasts or knocking out the caspase-3 gene in mice significantly reduced HuR cleavage and the cytoplasmic accumulation of HuR in muscle fibers. The non-cleavable isoform of HuR, HuRD226A, failed to reestablish the myogenic potential of HuR-depleted myoblasts. HuR cleavage generates two fragments: HuR-cleavage product 1 (HuR-CP1) (24 kDa) and HuR-CP2 (8 kDa). Here, we show that one of these fragments (HuR-CP1) binds to the HuR import factor transportin-2 (TRN2) allowing HuR to accumulate in the cytoplasm. As this cytoplasmic accumulation is required for the promyogenic function of HuR, our data support a model, whereby during the transition phase from myoblasts to myotubes, a proportion of HuR is cleaved to generate HuR-CP1. By interfering with the TRN2-mediated import of HuR, this CP helps non-cleaved HuR accumulate in the cytoplasm thus promoting myogenesis.


Novel drug resistance pattern associated with the mutations K70G and M184V in human immunodeficiency virus type 1 reverse transcriptase.
We describe an unusual pathway of human immunodeficiency virus type 1 reverse transcriptase resistance during therapy with tenofovir-emtricitabine, characterized initially by the mutations K70E and M184V and later by K70G and M184V, with the two mutations coexisting on the same viral genome. Phenotypic resistance to lamivudine, emtricitabine, abacavir, didanosine, and tenofovir was observed, whereas susceptibility to zidovudine and stavudine was preserved.


Combined Application of Monopolar Radiofrequency Technology and Injective Carboxytherapy in the Correction of Involutive Skin Changes.
In aesthetic medicine, high-power instrumental technologies that exert a significant positive effect with a minimal rehabilitation period are becoming more popular in the correction of involutive changes of the skin. Such methods include monopolar radiofrequency therapy. However, high temperature can lead to the development of unfavorable events and complications. The study aimed to design and evaluate a combined method of monopolar radiofrequency therapy and injective carboxytherapy in patients with local adverse events (edema and neuropathy) in the facial area. The study included 72 female patients aged 38 to 52 years old that earlier received monopolar radiofrequency therapy in the facial region for the correction of involutive changes in the skin and who developed edema and neuropathy in the area of radiofrequency impact. Four groups received injectable carboxytherapy locally, in the projection of lymph nodes, or in combination. Combined application of monopolar radiofrequency therapy in the facial region and an extended protocol of carboxytherapy as local application or application in the projection of regional lymph nodes exerts a significant positive effect in the short-term and long-term study period reducing the period of rehabilitation. This was demonstrated by a statistically significant reduction of the intradermal edema and quick regression of pain syndrome in the studied group with the extended protocol of carboxytherapy in comparison with other studied groups. It is feasible to apply an extended protocol of carboxytherapy (locally, in the area of expressed manifestation, and in the projection of regional lymph nodes) in patients with local edema and neuropathy that developed after received monopolar radiofrequency therapy in the facial region, which significantly reduces the rehabilitation period and contributes to faster reduction of local edema and neuropathy and provides a stable clinical result.


Internal fixation of shaft humerus fractures by dynamic compression plate or interlocking intramedullary nail: a prospective, randomised study.
Compare the results of internal fixation of shaft of humerus fractures using dynamic compression plating (DCP) or antegrade interlocking intramedullary nail (IMN). Fifty patients with diaphyseal fracture of the shaft of the humerus and fulfilling the inclusion criterion were randomly assigned to one of the two groups. Twenty-five patients were managed with closed antegrade interlocking intramedullary nail, and 25 underwent open reduction and internal fixation using dynamic compression plating. The mean age of patients with IMN fixation was 37.28 years (SD 12.26) and 37.72 years (SD 12.70) for those who underwent plating. Road traffic accident was the most common mode of injury in both groups. There was a statistically significant difference between the two groups with respect to duration of hospital stay, operative time and blood loss. There was no significant difference between the two groups in terms of union or complications. The functional assessment at the end of 1 year between the two groups did not show any significant difference in outcome. Antegrade interlocking IMN and DCP fixation are comparable when managing diaphyseal shaft of humerus fractures with respect to union rates and complications. Although shoulder related complications are more in the IMN group, however, it is associated with shorter hospital stay, lesser operative time and less blood loss. This makes interlocking IMN an effective option in managing these fractures.


The GH-releasing effect of ghrelin, a natural GH secretagogue, is only blunted by the infusion of exogenous somatostatin in humans.
Ghrelin, a 28-amino-acid peptide purified from the stomach and showing a unique structure with an n-octanoyl ester at the serine 3 residue, is a natural ligand of the GH secretagogue (GHS) receptor (GHS-R). Ghrelin strongly stimulates GH secretion in both animals and humans, showing a synergistic effect with GH-releasing hormone (GHRH) but no interaction with synthetic GHS. However, the activity of ghrelin as well as that of non-natural GHS is not fully specific for GH; ghrelin also induces a stimulatory effect on lactotroph and corticotroph secretion, at least in humans. To further clarify the mechanisms underlying the GH-releasing activity of this natural GHS, we studied the effects of somatostatin (SS, 2.0 microg/kg/h from -30 to +90 min) on the endocrine responses to ghrelin (1.0 microg/kg i.v. at 0 min) in seven normal young male volunteers [age (mean +/- SEM) 28.6 +/- 2.9 years; body mass index (BMI) 22.1 +/- 0.8 kg/m2]. In the same subjects, the effect of SS on the GH response to GHRH (1.0 microm/kg i.v. at 0 min) was also studied. Blood samples were taken every 15 min from -30 up to +120 min. GH levels were assayed at each time point in all sessions; PRL, ACTH and cortisol levels were assayed after ghrelin administration alone and during SS infusion. The GH response to ghrelin (hAUC0'-->120' 2695.0 +/- 492.6 microg min/l) was higher (P < 0.01) than that after GHRH (757.1 +/- 44.1 microg min/l). SS infusion almost abolished the GH response to GHRH (177.0 +/- 37.7 microg min/l, P < 0.01); the GH response to ghrelin was inhibited by SS (993.8 +/- 248.5 microg min/l, P < 0.01) but GH levels remained higher (P < 0.05) than with GHRH. Ghrelin induced significant increases in PRL, ACTH and cortisol levels and these responses were not modified by SS. Ghrelin, a natural GHS-R ligand, exerts a strong stimulatory effect on GH secretion in humans and this effect is only blunted by an exogenous somatostatin dose which almost abolishes the GH response to GHRH. The stimulatory effect of ghrelin on lactotroph and corticotroph secretion is refractory to exogenous somatostatin, indicating that these effects occur through pathways independent of somatostatinergic influence.


Body fluid biomarkers in multiple sclerosis: how far we have come and how they could affect the clinic now and in the future.
Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system, which affects over 2.5 million people worldwide. Although MS has been extensively studied, many challenges still remain in regards to treatment, diagnosis and prognosis. Typically, prognosis and individual responses to treatment are evaluated by clinical tests such as the expanded disability status scale, MRI and presence of oligoclonal bands in the cerebrospinal fluid. However, none of these measures correlates strongly with treatment efficacy or disease progression across heterogeneous patient populations and subtypes of MS. Numerous studies over the past decades have attempted to identify sensitive and specific biomarkers for diagnosis, prognosis and treatment efficacy of MS. The objective of this article is to review and discuss the current literature on body fluid biomarkers in MS, including research on potential biomarker candidates in the areas of miRNA, mRNA, lipids and proteins.


Diaphragm-like strictures of the ileum associated with NSAID use: a rare complication.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed for many conditions including arthritis. A rare complication of their use is diaphragm-like strictures of the small and large intestines. A 65-year-old woman with a 12-year history of arthritis came to us with a 35-pound weight loss and anorexia. She had been taking piroxicam for 3 years. Evaluation including enteroclysis revealed multiple mid-ileal diaphragm-like strictures and proximal small bowel dilatation. The symptoms persisted despite discontinuance of the drug. Abdominal exploration with intraoperative enteroscopy revealed five ileal strictures within a short segment of bowel. Resection was done and completion enteroscopy showed no other strictures. The patient recovered uneventfully and had full resolution of the symptoms. We discuss the difficulties in diagnosis and management of this drug complication and briefly review the literature.


The evolution of empathy research: Models, muddles, and mechanisms.
The word empathy enters the English language in 1909, translated incompletely from German by a British-born psychologist interested in introspection. In the ensuing 100+ years, the term has been defined in a range of different ways by researchers and scholars. The biopsychosocial framework developed by George Engel comes closest to capturing empathy as a biological, psychological and social phenomenon. In this paper, I explore the psychological and social/communicative dimensions of empathy. Psychologists ask the question, How does the capacity for empathy vary across individuals? By contrast, interaction scholars ask, How is empathy communicated from one person (a healthcare provider) to another (a sufferer)? A communication focus involves the accuracy and impact of empathic communication as evidenced in a sufferer's response. The two views of empathy, as a quality or capacity or as co-created in interaction, are contradictory, and are a source of confusion and contentiousness in the research literature. As in theoretical physics, where an as yet unresolved 80year controversy has marked the debate about whether light is a particle or wave, research on empathy will likely remain paradoxical, unresolved and a source of creativity and innovation in the science and art of human caring.


Minimising donor-site morbidity following limbs' injuries with keystone perforator island flap reconstruction.
Plastic surgeons strive to choose better techniques to reconstruct the defects of the limbs, minimising the wound healing problems, improving the aesthetic and functional outcome with less complications. This study refers to the use of keystone perforator island flap (KPIF) in limbs' reconstruction, their harvesting technique to minimise donor-site morbidity, maximise the functional and cosmetic outcome, and will point on the most important indications and advantages. Between January 2014 and June 2020, a number of 28 cases were treated in our department, with simple or complex defects of the limbs. The database included patients' demographics, comorbidities, aetiology, characteristics of the flap, surgical factors, follow-up period and flap outcomes. We performed 28 KPIFs, 14 of type I, 12 of type IIA, 1 of type III, and 1 of type IV, with an average size of 69 cm2 (ranged from 1.25 cm2 to 318 cm2 ). Trauma was the major cause of the defects. One flap exhibited approximately 4% partial superficial necrosis. All donor sites healed without any adverse events. All patients were satisfied with the functional and aesthetic results. The KPIFs provide a simple and effective method of wound closure by using tissues of similar texture, thickness and colour. Preserving the main artery and the underlying muscle, this flap reduces the donor site morbidity. The use of KPIFs seems to be one of the most suitable choices whenever possible.


Calcium and membrane-binding properties of monomeric and multimeric annexin II.
The calcium-dependent interaction of several annexins with membranes was studied. A novel technique was developed that allowed estimation of calcium binding to aggregating systems. This consisted of immobilized phospholipids on phenyl-Sepharose. Proteins associated with this affinity gel in the presence of radioactive calcium and were eluted with the same buffer containing excess EGTA. This produced an elution profile with a peak of excess calcium. Protein extinction coefficients were estimated in order to quantitate the protein more accurately. Association of annexin II with the membrane was of very high affinity and involved a calcium stoichiometry of 11 +/- 1 at 12.5 microM free Ca2+ and 10 +/- 2 at 50 microM free Ca2+. (AII)2(p11)2, a heterotetramer of two annexin II and two p11 subunits, bound 12 +/- 1 Ca2+ at 12.5 microM Ca2+ and 15 +/- 1 Ca2+ at 50 microM Ca2+. These stoichiometries showed a pattern of "all or none" calcium binding where the number of calcium ions bound to a protein-membrane complex was virtually independent of the free calcium concentration or the density of protein on the membrane. (AII)2(p11)2 contains two annexin II subunits so that calcium stoichiometry was not directly related to the number of potential sites. (AII)2(p11)2 required less calcium to support membrane binding than did annexin II. Thus, dimerization of the membrane binding unit may be needed for annexins to function at intracellular calcium levels. Annexin VI contains twice as many putative calcium binding units as annexin V and the same pattern of behavior occurred for this pair of proteins. At 25 microM free calcium, (AII)2(p11)2 alone bound no detectable calcium (< 0.1 mol of calcium/mol of protein) and annexin II bound only 0.3-0.6 calcium ions.(ABSTRACT TRUNCATED AT 250 WORDS)


Investigating the meaning of 'good' or 'very good' patient evaluations of care in English general practice: a mixed methods study.
To examine concordance between responses to patient experience survey items evaluating doctors' interpersonal skills, and subsequent patient interview accounts of their experiences of care. Mixed methods study integrating data from patient questionnaires completed immediately after a video-recorded face-to-face consultation with a general practitioner (GP) and subsequent interviews with the same patients which included playback of the recording. 12 general practices in rural, urban and inner city locations in six areas in England. 50 patients (66% female, aged 19-96 years) consulting face-to-face with 32 participating GPs. Positive responses to interpersonal skills items in a postconsultation questionnaire ('good' and 'very good') were compared with experiences reported during subsequent video elicitation interview (categorised as positive, negative or neutral by independent clinical raters) when reviewing that aspect of care. We extracted 230 textual statements from 50 interview transcripts which related to the evaluation of GPs' interpersonal skills. Raters classified 70.9% (n=163) of these statements as positive, 19.6% (n=45) neutral and 9.6% (n=22) negative. Comments made by individual patients during interviews did not always express the same sentiment as their responses to the questionnaire. Where questionnaire responses indicated that interpersonal skills were 'very good', 84.6% of interview statements concerning that item were classified as positive. However, where patients rated interpersonal skills as 'good', only 41.9% of interview statements were classified as positive, and 18.9% as negative. Positive responses on patient experience questionnaires can mask important negative experiences which patients describe in subsequent interviews. The interpretation of absolute patient experience scores in feedback and public reporting should be done with caution, and clinicians should not be complacent following receipt of 'good' feedback. Relative scores are more easily interpretable when used to compare the performance of providers.


Evolution of Concepts and Technologies in Ophthalmic Laser Therapy.
Ophthalmology was the first medical specialty to adopt lasers right after their invention more than 50 years ago, and they gradually revolutionized ocular imaging, diagnostics, therapy, and surgery. Challenging precision, safety, and selectivity requirements for ocular therapeutic and surgical procedures keep advancing the laser technologies, which in turn continue enabling novel applications for the preservation and restoration of sight. Modern lasers can provide single-cell-layer selectivity in therapy, submicrometer precision in three-dimensional image-guided surgery, and nondamaging retinal therapy under optoacoustic temperature control. This article reviews the evolution of laser technologies; progress in understanding of the laser-tissue interactions; and concepts, misconceptions, and accidental discoveries that led to modern therapeutic and surgical applications of lasers in ophthalmology. It begins with a brief historical overview, followed by a description of the laser-tissue interactions and corresponding ophthalmic applications.


Traumatic stress: a personal view from combat.
What follows is my personal account of the effects of traumatic stress disorder as it is caused by the effects of combat. I tell it in the first person because it is the most effective way to emphasize the highly personal, traumatic nature of combat stress and because it is my own story. I have endeavored to explain how combat stress occurs, what happens to the individual as a result and how a person can recover from its effects. I offer my story because I think that there are thousands of men who have been in offensive combat, who may have lived my life, but who have not had the opportunity to tell their story about why they hurt.


Adherence to guidelines regarding anticoagulation and risk factors for progression of atrial fibrillation in a nurse-led clinic.
Atrial fibrillation (AF) is the commonest cardiac arrhythmia associated with an increased risk of stroke. Evidence suggests that management in a specialty clinic improves clinical outcomes of patients. To assess level of adherence to evidence-based guidelines regarding anticoagulation and the risk factors for progression of AF in a nurse-led AF clinic. A retrospective analysis was conducted on clinical records of 136 patients seen at the AF clinic to determine their risk factors and progression of AF (change in AF type to more advanced types) during follow up. Additionally, the proportion of patients with CHA2 DS2 -VASC score (congestive heart failure, hypertension, age ≥75 (doubled), diabetes mellitus, stroke (doubled)-vascular disease, age 65-74 years, sex category (female)) of ≥2 who were prescribed anticoagulants according to European Society of Cardiology guidelines before and after attending the clinic was determined. Rate of anticoagulation in patients with CHA2 DS2 -VASC score of ≥2 after attending the clinic (91.3%) was significantly higher than the rate before attending the clinic (79.3%) (P = 0.0076). Mean age in those with AF progression (72.5 ± 9.4) was higher than those without AF progression (66.9 ± 13.9) (P = 0.0072). Rate of AF progression was higher in those with obesity (body mass index ≥30 kg/m2 ) (P = 0.0364) and those with excessive alcohol intake (>2 standard drinks) (P = 0.0039). History of hypertension was not a significant predictor of AF progression (P = 0.7507). Management of AF in a nurse-led clinic was associated with high level of adherence to anticoagulation guidelines. Age, obesity and excessive alcohol intake were significant predictors for progression of AF.


Differences in the phenotype between children with familial defective apolipoprotein B-100 and familial hypercholesterolemia.
Familial defective apolipoprotein B-100 (FDB) is a dominantly inherited genetic disorder resulting from a point mutation in the apolipoprotein (apo) B gene and is associated with significantly elevated plasma total and LDL cholesterol levels. Despite numerous descriptions outlining the phenotype of children with familial hypercholesterolemia (FH), no study has described the biochemical and clinical phenotype in a cohort of children with FDB. The phenotypes of FH and FDB, therefore, have not been compared in children. We have studied a cohort of 38 Dutch children (all <20 years old) with FDB from 21 different families. Lipid and lipoprotein levels and the clinical phenotype were compared with 97 age-matched FH heterozygotes, as defined by molecular analysis, and with age-matched non-FDB, non-FH control subjects. Female FDB carriers (n=23) had significantly lower total cholesterol (P<.001), LDL cholesterol (P=.001), total cholesterol:HDL ratio (P<.001), and apoB levels (P=.001) than age-matched female FH heterozygotes (n=50). Similar results were noted in male FDB carriers (n=15) compared with male FH heterozygotes (n=47; P=.005, P=.007, P=.014, and P=.074, respectively). Within the FDB group, female FDB heterozygotes had higher LDL cholesterol (P=.038) and a trend to higher total cholesterol levels (P=.165) than age-matched males. Both male and female FDB carriers had significantly higher total cholesterol, LDL cholesterol, and total cholesterol:HDL ratio than age- and sex-matched control subjects, which was evident even in children <10 years of age, providing additional evidence that this mutation is penetrant in early life. These results provide evidence for a milder biochemical phenotype in children with FDB than in children with FH. The phenotype observed is intermediate between that of control subjects and FH heterozygotes matched for age and sex. As the incidence of coronary artery disease is related to both the extent and duration of cholesterol elevation, our findings might explain in part the lower incidence of clinical atherosclerosis seen in adults with this condition than in adults with FH.


Rising mortality from injury in urban China: demographic burden, underlying causes and policy implications.
In urban China, mortality from injuries has increased over the past five decades. By contrast, life expectancy has continued to increase and has come to nearly equal life expectancy in developed countries. Currently, most of the life expectancy lost due to injury (65%) in urban China would be recovered if injury rates were the same as in countries with low injury-related mortality. Fundamentally, the rising trend in urban injury mortality in China reflects a continued focus on injury treatment rather than prevention in the face of fast socioeconomic development and increasing exposure to risk factors for injury. Despite improved injury prevention legislation and a "Safe Community" campaign, urban China needs to modify its approach to urban injury management and focus on prevention. The gap between urban China and countries with low injury mortality can be closed by means of legislation, strengthened law enforcement and the establishment of safer communities. Risks affecting children and migrants deserve greater attention, and the government needs to allocate more resources to injury prevention, especially to urban areas in the central-west region of China. Based on the population size of urban China, measures for the prevention of injury mortality would save an annual 436.4 million years of life.


Outcome for repeated biopsy of the prostate: roles of serum PSA, small atypical glands, and prostatic intraepithelial neoplasia.
We studied the relationships between the outcome in the last follow-up prostate biopsy specimen and serum prostate-specific antigen (PSA), prostatic intraepithelial neoplasia (PIN), and atypical small acinar proliferations (ASAPs) at the occasion of the initial biopsy in 244 cases in which the initial specimen was negative for tumor and at least 1 follow-up biopsy was done. PSA levels and ASAPs were significantly associated with cancer in the follow-up biopsy specimen (<P < .005; logistic regression analysis); however, the presence of PIN in the initial biopsy specimen did not relate to cancer in the follow-up specimen (P > .1). Thus, the probability that a follow-up biopsy demonstrates cancer depends on PSA and ASAPs, and even when ASAPs are present, serum PSA exerts an influence. For example, low PSA values, 5 ng/mL (5 mug/L) or less, are associated with low probabilities of a positive follow-up biopsy result, even when ASAPs were present in the first biopsy specimen. For higher PSA values, the presence of ASAPs dramatically increases the probability of a positive follow-up biopsy result compared with cases with no atypia or PIN in the first biopsy specimen.


Changes in the expression of B cell surface markers on complement receptor-positive and complement receptor-negative B cells induced by phorbol myristate acetate.
The ability of phorbol myristate acetate (PMA) to induce changes in the expression of B cell surface markers on CR- and CR+ B cells from normal mice in an in vitro culture system was examined. The markers studied were CR, sIgM, sIgD, and sIa. CR- B cells acquired the CR after overnight incubation with PMA. A twofold increase in sIa expression on CR- and CR+ B cells was also noted, whereas the staining intensity of sIgM and sIgD decreased on both B cell populations. These changes in the expression of surface markers took place without detectable increases in cell proliferation, cell size, or RNA content. Furthermore, the same effects were observed when CR- and CR+ B cells were prepared from a small B cell population purified by elutriation. It therefore appears that PMA can exert its effect directly on small, resting B cells.


Birth trauma and brain damage.
Birth trauma is a rare primary cause of perinatal death, occurring at most only once in every 1000-2000 births. As a cause of brain damage and later handicap it is often difficult to dissociate injury at birth from the concomitant effects of asphyxia, growth retardation or preterm delivery. A continuum of reproductive casualty has been postulated, but for trauma is not proven. Among children with cerebral palsy and severe mental retardation trauma may be implicated in a few cases, possibly 1-2 of 1000 deliveries. Vaginal breech delivery has been related to a higher incidence of minimal brain damage syndromes and some of this damage probably has its origin in perinatal trauma. The pregnancies where there is particular risk of birth trauma include those where the infant is large for gestational age, has intrauterine growth retardation, is delivered preterm, is vaginally delivered in breech presentation or is from multiple gestation. Particular care must be given to diagnosis and preventive measures in these cases and competent handling is required if the disaster of brain damage caused by traumatic birth is to be minimized.


Expression of rat and mouse cathepsin B precursors in Escherichia coli.
Vectors for the expression of mouse preprocathepsin B and rat procathepsin B, under the control of a modified lac operon regulatory region, in plasmid pKK233-2 were constructed. In rapidly growing cells induction of preprocathepsin B was cytotoxic. Immune precipitable cathepsin B, compatible in size with that expected for the unglycosylated proenzyme, was produced in both constructs. However, pepsin digestion of extracts did not produce any cathepsin B activity, indicating either that the recombinant forms are not correctly folded or were produced at such low levels that activity could not be detected.


The Effect of Short-Term Dietary Fructose Supplementation on Gastric Emptying Rate and Gastrointestinal Hormone Responses in Healthy Men.
This study aimed to examine gastric emptying rate and gastrointestinal hormone responses to fructose and glucose ingestion following 3 days of dietary fructose supplementation. Using the 13C-breath test method, gastric emptying rates of equicaloric fructose and glucose solutions were measured in 10 healthy men with prior fructose supplementation (fructose supplement, FS; glucose supplement, GS) and without prior fructose supplementation (fructose control, FC; glucose control, GC). In addition, circulating concentrations of acylated ghrelin (GHR), glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and insulin were determined, as well as leptin, lactate, and triglycerides. Increased dietary fructose ingestion resulted in accelerated gastric emptying rate of a fructose solution but not a glucose solution. No differences in GIP, GLP-1, or insulin incremental area under curve (iAUC) were found between control and supplement trials for either fructose or glucose ingestion. However, a trend for lower ghrelin iAUC was observed for FS compared to FC. In addition, a trend of lower GHR concentration was observed at 45 min for FS compared to FC and GHR concentration for GS was greater than GC at 10 min. The accelerated gastric emptying rate of fructose following short-term supplementation with fructose may be partially explained by subtle changes in delayed postprandial ghrelin suppression.


Immunotherapy in inoperable stage III non-small cell lung cancer: a review.
The leading cause of cancer-related deaths in the United States continues to be lung cancer. Approximately 25-30% of patients are diagnosed with locally advanced non-small cell lung cancer (NSCLC). Concurrent chemoradiation with a platinum-based doublet is the current standard of care for patients with inoperable stage III NSCLC. Unfortunately, only 15-20% of patients treated with definitive chemoradiation are alive at 5 years. Thus, there has been a major unmet need in this area. In this article, we summarize the current status and ongoing clinical trials incorporating immunotherapy into the management of inoperable stage III NSCLC, and we also present our perspective on the future directions.


Depth of reading within the gingival sulcus of seven intraoral scanners: An in vitro study.
This in vitro study aimed to evaluate the depth of reading of intraoral scanners (IOSs) inside the gingival sulcus. A knife-edge preparation for a full crown was performed on a Frasaco model. The gingival sulcus of the scanned model was modified using a dedicated software (Model Creator, Exocad DentalCAD 2.4 Plovdiv) by setting the coronal (CW) and apical (AW) widths and sulcus depths (D). Two dental models with different sulcus depths (1 mm or 2 mm) were printed using the digital light processing (DLP) technique. Each model was scanned ten times with seven IOSs: Emerald, Trios3, Carestrem 3600, Dentalwings, Condor, True Definition Scanner (TDS), and Omnicam. Measurements of D values were performed using 3Shape 3D viewer software. The normality of the data distribution was evaluated using the Shapiro-Wilk test (P<.05). A nonparametric Levene test was performed to check for homoscedasticity. The data were statistically analyzed with Kruskal-Wallis test (α=.05) and Nemenyi's test. All IOSs were able to read within the 1 mm-deep gingival sulcus, albeit with some statistically significant differences (P<.001). Only Trios3 was able to read the 2 mm-deep gingival sulcus (P<.001). The depth of reading of different IOSs can vary significantly. In the model with a 2-mm sulcus, even in the absence of oral fluids, the depth of reading is incomplete, suggesting that deep preparations into the sulcus are difficult to detect with IOSs.


Strain induced crystallization of polymers at and above the crystallization temperature by coarse-grained simulations.
We examine the behavior of short and long polymers by means of coarse-grained computer simulations of a by-polyvinyl alcohol inspired model. In particular, we focus on the structural changes in the monomer and polymer scales during cooling and the application of uni-axial true strain. The straining of long polymers results in the formation of a semi-crystalline system at temperatures well above the crystallization temperature, which allows for the study of strain induced crystallization.


An electron microscope study of lymphatic tissue in runt disease.
The thymus, spleen, and lymph nodes were studied in runt disease induced by a graft of intravenously injected homologous splenic cells into newborn rats and mice. Adult Long-Evans cells (70 x 10(6)) were injected into Sprague-Dawley rats. Adult DBA cells (7 x 10(6)) were injected into C57BL/6 mice. Runted rats were sacrificed at 14 to 28 days of age; mice at 10 to 20 days. The thymic cortex is depleted of small lymphocytes. Those remaining are severely damaged and phagocytized. Evidence of damage includes swelling of mitochondria, myelin figure formation, margination of chromatin, and sharp angulation in nuclear contour. Large numbers of macrophages are present. Epithelial-reticular cells which envelop small cortical blood vessels are often retracted, with the result that the most peripheral layer in the thymic-blood barrier suffers abnormally large gaps. Lymphocytes of the periarterial lymphatic sheaths of spleen and of the cortex of lymph nodes are reduced in number and damaged. Vast numbers of plasma cells and many lymphocytes are evident throughout lymph nodes, in the periarterial lymphatic sheaths, and in the marginal zone and red pulp of the spleen. Plasma cells are of different sizes, the larger having dilated sacs of endoplasmic reticulum. Lymphocytes are small to medium in size. They contain, in varying quantity, ribosomes and smooth membrane-bounded cytoplasmic vesicles approximately 350 to 500 A in diameter. Most plasma cells and lymphocytes are damaged and many of these are phagocytized. Many lymphocytes in lymph nodes, however, show no evidence of damage. Reticular cells and other fixed cells of the connective tissues seldom appear affected. Thus, the major cell types reacting in runt disease are lymphocytes, plasma cells, and histiocytes or macrophages. It appears, therefore, that both the delayed and immediate types of sensitivity play a part in this disease.


Assessment of cardiac autonomic nervous system involvement in systemic sclerosis via exercise heart rate recovery.
To assess exercise heart rate recovery (HRR) indices in patients with systemic sclerosis (SSc) for an assessment of their cardiac autonomic function. Thirty-five patients with diffuse or limited SSc and 35 healthy controls were enrolled. All subjects underwent exercise testing and transthoracic echocardiography. The HRR indices were calculated by subtracting the first- (HRR1), second- (HRR2) and third-minute (HRR3) heart rates from the maximal heart rate. The SSc and control groups were similar in age (45.2 ± 11.6 vs. 43.9 ± 10.0 years), had identical gender ratios (31 female/4 male in both groups) and similar left ventricular ejection fraction (66.5 ± 5.1 vs. 67.7 ± 5.9%). The mean HRR1 (21.8 ± 4.4 vs. 27.7 ± 4.3 bpm, p = 0.001), HRR2 (43.8 ± 6.3 vs. 47.6 ± 4.4 bpm, p = 0.004) and HRR3 (58.8 ± 10.3 vs. 63.6 ± 7.3 bpm, p = 0.031) values were significantly lower in the SSc group than in the healthy controls. HRR indices were similar in the limited and diffuse SSc subgroups. The patients with SSc had lower HRR indices than normal subjects. Cardiac autonomic functions might be involved in SSc, even in patients without cardiac symptoms.


A Case-Control Study of the Luteinizing Hormone Level in Luteinizing Hormone Receptor Gene (rs2293275) Polymorphism in Polycystic Ovarian Syndrome Females.
Polycystic ovary syndrome (PCOS) is a common heterogeneous disorder characterized by chronic anovulation, infertility, polycystic ovaries, and hyperandrogenic signs. The aim of this study was to determine the association of luteinizing hormone/chorionic gonadotropin hormone receptor LHCGR polymorphism (rs2293275) with oligomenorrhea, amenorrhea, hirsutism, acne, infertility, LH, LH/FSH ratio, and body mass index (BMI) among PCOS females. This genetic case-control study recruited 55 PCOS and 55 control females, diagnosed based on the Rotterdam criteria. LH and FSH were measured by the Roche cobas c 502 automated analyzer. Genotypic analysis was carried out using the polymerase chain reaction-restriction fragment length polymorphism and restriction endonuclease digestion. BMI was higher for PCOS patients (28.5 ± 6.59) compared to controls (25.1 ± 5.77), and ovulatory dysfunction was seen among 90% of PCOS females. Oligomenorrhea was common in PCOS (73%), and hirsutism and acne were detected in PCOS (80% and 40%; respectively). LH ≥10 were recoded among 51%, while LH/FSH ≥1.5 was recorded among 33% PCOS females. There is a statistical difference between rs2293275 polymorphism in the AG genotype between PCOS patients and controls. PCOS patients have a significantly higher mean LH level compared to controls (8.36 ± 4.86 and 5.67 ± 2.51, respectively) and showed higher LH/FSH value (1.46 ± 0.81) compared to (0.87 ± 0.30) controls. GG and AG genotypes of LHCGR showed statistically significant higher LH (8.22 ± 4.11; 9.02 ± 3.87) and LH/FSH values (1.57 ± 0.56; 1.64 ± 0.89) compared to controls. LHCGR (rs2293275) GA and GG genetic variants could modulate the hormonal levels of PCOS LH levels and the LH/FSH ratio and associated with hirsutism, oligomenorrhea, BMI, and LH/FSH ratio as risk factors.


A lesson in treating the whole patient: Todd Nicholson's story.
The authors present a patients story to demonstrate the usefulness of a complete patient approach, incorporating V.A.C. therapy, to achieving clinical success from the patients perspective. The article discusses why a total patient approach is important and therapeutic flexibility increases the chance of a successful outcome for all involved.


Peroral endoscopic myotomy and fundoplication: a novel NOTES procedure.
Peroral endoscopic myotomy (POEM) has become the minimally invasive endoscopic treatment for achalasia; however, gastroesophageal reflux (GER) post-POEM has been reported. A pilot study was conducted in which an endoscopic fundoplication was added to the standard POEM (POEM + F) procedure to overcome this issue. We report the technical details of POEM + F and short-term safety results. POEM + F was performed in 21 patients. After completing myotomy, the endoscope was advanced from the submucosal tunnel into the peritoneal cavity. A partial mechanical barrier was created by retracting the anterior gastric wall at the esophagogastric junction with the use of endoclips and an endoloop. POEM + F was technically feasible in all cases and created a visually recognizable fundoplication. The clinical course after POEM + F was uneventful. No immediate or delayed complications occurred. POEM + F may help mitigate the post-POEM incidence of GER and serve as a minimally invasive endoscopic alternative to a laparoscopic Heller-Dor procedure. This is the largest case series of peroral natural orifice transluminal endoscopic surgery without laparoscopic assistance in the human foregut.


Homology of E2 gene in 8 child-mother pairs infected with hepatitis C virus.
The frequency of genetic homology of hepatitis C virus (HCV) E2 gene in 8 child-mother pairs was investigated. The route of HCV infection of all children suggested mother-to-child infection by their past history. In this study, we analyzed at least 5 complementary DNA (cDNA) clones for each case. In 6 of the 8 (75%) child-mother pairs, for the region between hypervariable region (HVR)-1 and HVR-2, the similarity of the nucleotide sequence of all 5 cDNA clones between each child and the mother was higher than that between the child and the other children, the other mothers and the sequences from GenBank. One of the 8 (13%) child-mother pairs showed a great similarity in parts of all cDNA clones. This was also confirmed by phylogenetic analyses of the sequences of cDNA clones from families and that from GenBank. These results suggested that the homology search of nucleotide sequence of this region was useful to confirm mother-to-child transmission of HCV.


Axonal injury alters the extracellular glial environment of the axon initial segment and allows substantial mitochondrial influx into axon initial segment.
The axon initial segment (AIS) is structurally and functionally distinct from other regions of the axon, yet alterations in the milieu of the AIS after brain injury have not been well characterized. In this study, we have examined extracellular and intracellular changes in the AIS after hypoglossal nerve injury. Microglial adhesions to the AIS were rarely observed in healthy controls, whereas microglial adhesions to the AIS became apparent in the axonal injury model. Regarding intra-AIS morphology, we focused on mitochondria because mitochondrial flow into the injured axon appears critical for axonal regeneration. To visualize mitochondria specifically in injured axons, we used Atf3:BAC transgenic mice whose mitochondria were labeled with GFP in response to nerve injury. These mice clearly showed mitochondrial localization in the AIS after nerve injury. To precisely confirm the light microscopic observations, we performed three-dimensional ultrastructural analysis using focused ion beam/scanning electron microscopy (FIB/SEM). Although the healthy AIS was not surrounded by microglia, tight microglial adhesions with thick processes adhering to the AIS were observed after injury. FIB/SEM simultaneously allowed the observation of mitochondrial localization in the AIS. In the AIS of non-injured neurons, few mitochondria were observed, whereas mitochondria were abundantly localized in the cell body, axon hillock, and axon. Intriguingly, in the injured AIS, numerous mitochondria were observed throughout the AIS. Taken together, axonal injury changes the extracellular glial environment surrounding the AIS and intracellular mitochondrial localization in the AIS. These changes would be crucial responses, perhaps for injured neurons to regenerate after axonal injury.


Artificial neural networks for diagnosis and prognosis in prostate cancer.
The application of artificial neural networks (ANNs), especially feed-forward neural networks (FFNNs), has become very popular for diagnosis and prognosis in clinical medicine, often accompanied by exaggerated statements of their potential. The excitement stems mainly from the fact that ANNs were developed as attempts to model the decision process of the human brain. Traditionally, logistic regression models and proportional hazard regression models have been used in these applications. In this article, FFNNs are introduced as flexible, nonlinear regression models and necessary precautions for their use are discussed. Furthermore, the results of a literature survey of applications of ANNs in prostate cancer published between 1999 and 2001 are described; most applications suffer from methodologic deficiencies. It is concluded that there is so far no evidence that the application of ANNs provide real progress in the field of diagnosis and prognosis in prostate cancer.


Multispecies Coexistence without Diffuse Competition; or, Why Phylogenetic Signal and Trait Clustering Weaken Coexistence.
Related and phenotypically similar species often compete more strongly than unrelated and dissimilar species. Much is unknown about the community-level implications of such complex interactions. Here, we study how they affect community dynamics differently from diffuse interactions (competing equally with all heterospecifics). We derive results for a model that applies to many forms of density dependence and also examine specific cases using a site-occupancy model of forest dynamics. The results indicate that nondiffuse competition produces three effects that will not occur under diffuse competition: first, the central niche effect-if a species has high niche overlap with several competitors, then its average fitness is reduced; second, the common competitor effect-if a species has high niche overlap with more common species, then its average fitness is reduced (these two effects are usually equalizing, because more favorable niches are likely to contain more species and more abundant species); and, finally, the community redistribution effect-when a species falls to low density, the relative abundance of its competitors will change, altering its ability to recover. The community redistribution effect usually undermines coexistence, because the community will usually become dominated by an invader's closest competitors. This study provides both instructions for measuring these effects in the field and a framework for analyzing how phylogenetic signal, trait-based niche axes, and other forms of nondiffuse competition affect coexistence.


Nuclear Quantum Effects in Water Reorientation and Hydrogen-Bond Dynamics.
We combine classical and ring polymer molecular dynamics simulations with the molecular jump model to provide a molecular description of the nuclear quantum effects (NQEs) on water reorientation and hydrogen-bond dynamics in liquid H2O and D2O. We show that while the net NQE is negligible in D2O, it leads to a ∼13% acceleration in H2O dynamics compared to a classical description. Large angular jumps-exchanging hydrogen-bond partners-are the dominant reorientation pathway (just as in a classical description); the faster reorientation dynamics arise from the increased jump rate constant. NQEs do not change the jump amplitude distribution, and no significant tunneling is found. The faster jump dynamics are quantitatively related to decreased structuring of the OO radial distribution function when NQEs are included. This is explained, via a jump model analysis, by competition between the effects of water's librational and OH stretch mode zero-point energies on the hydrogen-bond strength.


Solution-based low-temperature synthesis of germanium nanorods and nanowires.
The Ga-assisted formation of Ge nanorods and nanowires in solution has been demonstrated and a catalytic activity of the Ga seeds was observed. The synthesis of anisotropic single-crystalline Ge nanostructures was achieved at temperatures as low as 170 °C. Gallium not only serves as nucleation seed but is also incorporated in the Ge nanowires in higher concentrations than its thermodynamic solubility limit.


Enhanced Purification of Recombinant Rat NADPH-P450 Reductase by Using a Hexahistidine-Tag.
NADPH-P450 reductase (NPR) transfers electrons from NADPH to cytochrome P450 and heme oxygenase enzymes to support their catalytic activities. This protein is localized within the endoplasmic reticulum membrane and utilizes FMN, FAD, and NADPH as cofactors. Although NPR is essential toward enabling the biochemical and pharmacological analyses of P450 enzymes, its production as a recombinant purified protein requires a series of tedious efforts and a high cost due to the use of NADP+ in the affinity chromatography process. In the present study, the rat NPR clone containing a 6× Histidine-tag (NPR-His) was constructed and heterologously expressed. The NPR-His protein was purified using Ni2+-affinity chromatography, and its functional features were characterized. A single band at 78 kDa was observed from SDS-PAGE and the purified protein displayed a maximum absorbance at 455 nm, indicating the presence of an oxidized flavin cofactor. Cytochrome c and nitroblue tetrazolium were reduced by purified NPR-His in an NADPH-dependent manner. The purified NPR-His successfully supported the catalytic activities of human P450 1A2 and 2A6 and fungal CYP52A21, yielding results similar to those obtained using conventional purified rat reductase. This study will facilitate the use of recombinant NPR-His protein in the various fields of P450 research.


The Reaction Thermodynamics during Plating Al on Graphene Process.
This research explored a novel chemical reduction of organic aluminum for plating Al on a graphene surface. The thermodynamics of the Al plating reaction process were studied. The Al plating process consisted of two stages: the first was to prepare (C₂H₅)₃Al. In this reaction, the ΔH(enthalpy) was 10.64 kcal/mol, the ΔG(Gibbs free energy) was 19.87 kcal/mol and the ΔS(entropy) was 30.9 cal/(mol·K); this was an endothermic reaction. In the second stage, the (C₂H₅)₃Al decomposed into Al atoms, which were gradually deposited on the surface of the graphene and the Al plating formed. At 298.15 K, the ΔH was -20.21 kcal/mol, the ΔG was -54.822 kcal/mol, the ΔS was 116.08 cal/(mol·K) and the enthalpy change was negative, thus indicating an endothermic reaction.


Disseminated Mucormycosis with Positive Aspergillus Galactomannan.
We describe a case of disseminated mucormycosis (Apophysomyces elegans) diagnosed on autopsy, in a man who had been working in construction with undiagnosed neutropenia from hairy-cell leukemia, which is rarely associated with invasive mold infections. Galactomannan values in both blood and bronchoalveolar lavage were strongly positive. There is an unmet need for accurate noninvasive fungal diagnostic tests. Detailed history, including occupational exposures, can be more informative than laboratory workup.


AZD3463, an IGF-1R inhibitor, suppresses breast cancer metastasis to bone via modulation of the PI3K-Akt pathway.
The bone-derived insulin-like growth factor I (IGF-1) and its receptor IGF-1R play a crucial role in promoting the survival and proliferation of cancer cells, and have thus been considered as prime targets for the development of novel antitumor therapeutics. By using the MDA-MB-231BO cell line, which is the osteotropic metastatic variant of the human breast adenocarcinoma cell line MDA-MB-231, and an in vivo model of breast cancer metastasis to bone, the current study evaluated the effect of AZD3463, an IGF-1R inhibitor, used alone or in combination with zoledronic acid (ZA), on the regulation of IGF-1R associated signal pathway and treatment of bone metastases (BM). Cell proliferation and invasion were measured by methyl thiazolyl tetrazolium (MTT) and Transwell assay respectively. Apoptotic cell number was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL). AZD3463 was shown to alleviate IGF-1R phosphorylation promoted by IGF-1 treatment in MDA-MB-231BO cells in a dose-dependent manner. In both the cells and the mouse model, 5 nM of AZD3463 stimulated cell apoptosis and suppressed proliferation on a level similar to that of 100 µM of ZA. Remarkably, the combined use of AZD3463 and ZA exhibited a synergistic effect and greater antitumor activity compared to when they were employed individually. Mechanistic investigations indicated that the apoptosis-inducing activity of AZD3463 could be associated to its role in the activation of the phosphoinositide 3-kinase (PI3K)-Akt signaling pathway. These findings suggested that AZD3463 could serve as a promising therapeutic molecule for treating BM in breast cancer patients, particularly when applied in conjunction with ZA or other antitumor agents.


Statistical mechanics of fluids adsorbed in planar wedges: finite contact angle.
I consider the statistical mechanics of inhomogeneous fluids applied to fluids adsorbed in planar wedges. Exact results are described that belong to an infinite subset of models defined as the intersection of any two identical semi-infinite planar wall-fluid potentials. This geometry is interesting as a generic example of adsorption onto structured interfaces and of interfacial phase transitions controlled by the substrate geometry. Previously described virial theorems are extended to the case of a general wall-fluid model. This enables the consideration of wedge filling when Young's contact angle far from the wedge apex is finite. The virial theorems generate two important relations: the wedge sum rules. The first sum rule links the interfacial free energy far from the wedge apex to the structure induced at the apex. The second sum rule links the free energy of the apex region to the structure induced by the apex. When Young's contact angle at the wedge walls is finite these relations further yield an exact result for the macroscopic contact angle in terms of the nanoscopic structure at the three-phase contact line (the intersection of the liquid-vapor surface with a wedge wall): the contact angle sum rule. These exact results are of direct relevance to computer simulation studies of adsorbed films. In addition, they take on special significance in the vicinity of continuous interfacial phase transitions: an approach to complete filling and the filling transition at bulk liquid-vapor coexistence.


New Depsides and Neuroactive Phenolic Glucosides from the Flower Buds of Rugosa Rose ( Rosa rugosa).
The flower buds of Rosa rugosa Thunb. have been commonly used as a source of rose oil and as an ingredient in tea in eastern Asia, including China, Japan, and Korea. Repeated chromatography of a hot water extract from the flower buds of R. rugosa led to the isolation and characterization of three new depside glucosides, rosarugosides A-C (1-3), along with three phenolic compounds, one ionone glucoside, four flavonoids, and two tannins having known chemical structures. Linarionoside A and 2-phenylethyl-(6- O-galloyl)-β-d-glucopyranoside were isolated from R. rugosa for the first time in this study. The structures of the new compounds 1-3 were elucidated by interpreting one- and two-dimensional nuclear magnetic resonance spectroscopic and mass spectrometric data. Among the isolates, a new depside glucoside (1) and two major phenolic glucosides (4 and 5) improved MK-801-induced sensorimotor gating deficits, which were measured via an acoustic startle response test in mice.


Wing flexibility reduces the energetic requirements of insect flight.
Flapping insect wings deform under aerodynamic as well as inertial-elastic forces. This deformation is thought to improve power economy and reduce the energetic costs of flight. However, many flapping wing models employ rigid body simplifications or demand excessive computational power, and are consequently unable to identify the influence of flexibility on flight energetics. Here, we derive a reduced-order model capable of estimating the driving torques and corresponding power of flapping, flexible insect wings. We validate this model by actuating a tobacco hornworm hawkmoth Manduca sexta (L.) forewing with a custom single-degree-of-freedom mechanical flapper. Our model predicts measured torques and instantaneous power with reasonable accuracy. Moreover, the flexible wing model predicts experimental trends that rigid body models cannot, which suggests compliance should not be neglected when considering flight dynamics at this scale. Next, we use our model to investigate flight energetics with realistic flapping kinematics. We find that when the natural frequency of the wing is roughly three times that of the flapping frequency, flexibility can reduce energy expenditures by almost 25% compared to a rigid wing if negative work is stored as potential energy and subsequently released to do positive work. The wing itself can store about 30% of the 1200 [Formula: see text]J of total energy required over a wingbeat. Peak potential energy storage occurs immediately before stroke reversal. We estimate that for a moth weighing 1.5-2.5 g, the peak instantaneous power required for flight is 75-125 W kg-1. However, these peak values are likely lower in natural insect flight, where the wing is able to exchange strain energy with the compliant thorax. Our findings highlight the importance of flexibility in flapping wing micro aerial vehicle design and suggest tuned flexibility can greatly improve vehicle efficiency.


Differentiation between Transudate and Exudate in Pericardial Effusion has almost no Diagnostic Value in Contemporary Medicine.
The biochemical analysis of pericardial fluid for differentiating transudate from exudate is often ordered and interpreted according to the criteria extrapolated from pleural effusions. However, the validity of this discrimination when applied to pericardial effusion is under question. Patients who underwent pericardiocentesis between January 2004 and February 2014 were identified. Among them, 216 had essential medical records available and constituted the study population. The parameters specifically analyzed were the following: lactate dehydrogenase, total protein and glucose concentrations in both pericardial fluid and serum; pericardial fluid/serum ratios of lactate dehydrogenase and total protein content; and pH and specific gravity of pericardial fluid. Eighty-one percent of pericardial effusions were classified as exudate according to Light's criteria. Both exudate and transudate fluid characteristics were possible for all etiological causes except for tuberculosis in which all were exudates. Although multiple cutoff points for all parameters were tested, significant overlap between different causes persisted (all having an area under the receiver operating characteristic curve of < 0.7). Thus, a reasonable accuracy to differentiate one cause from another could not be achieved. Although often ordered, the biochemical analysis of pericardial fluid has almost no diagnostic value to distinguish among causes of pericardial effusion in contemporary medicine.


The effects of video game experience and active stereoscopy on performance in combat identification tasks.
We investigated the effects of active stereoscopic simulation-based training and individual differences in video game experience on multiple indices of combat identification (CID) performance. Fratricide is a major problem in combat operations involving military vehicles. In this research, we aimed to evaluate the effects of training on CID performance in order to reduce fratricide errors. Individuals were trained on 12 combat vehicles in a simulation, which were presented via either a non-stereoscopic or active stereoscopic display using NVIDIA's GeForce shutter glass technology. Self-report was used to assess video game experience, leading to four between-subjects groups: high video game experience with stereoscopy, low video game experience with stereoscopy, high video game experience without stereoscopy, and low video game experience without stereoscopy. We then tested participants on their memory of each vehicle's alliance and name across multiple measures, including photographs and videos. There was a main effect for both video game experience and stereoscopy across many of the dependent measures. Further, we found interactions between video game experience and stereoscopic training, such that those individuals with high video game experience in the non-stereoscopic group had the highest performance outcomes in the sample on multiple dependent measures. This study suggests that individual differences in video game experience may be predictive of enhanced performance in CID tasks. Selection based on video game experience in CID tasks may be a useful strategy for future military training. Future research should investigate the generalizability of these effects, such as identification through unmanned vehicle sensors.


The effect of chemotherapy on status of estrogen receptors in primary tumors and lymph node metastases of human ductal breast cancer.
The aim of the study was the evaluation of ERalpha and ERbeta expression in primary tumors and lymph node metastases of breast cancer as well as the assessment of the influence of preoperative chemotherapy on these receptors with regard to changes in morphological appearance of primary tumors and their metastases. Immunohistochemical examinations were conducted on surgically removed ductal invasive breast cancers and their lymph node metastases of 135 patients. Seventy-one patients were spared preoperative chemotherapy which was administered to other 64 patients. Primary breast cancers with preoperative chemotherapy showed lower mean percentage of cells with a positive reaction to ERalpha and ERbeta as compared to primary tumors without preoperative chemotherapy. There were positive correlations among primary tumors and lymph node metastases regardless of preoperative chemotherapy applied. On the other hand, ERalpha and ERbeta expressions were negatively correlated in primary tumors without chemotherapy in contrast to primary tumors after chemotherapy. Furthermore, it was observed that preoperative chemotherapy was responsible for significantly less damage to lymph node metastases of breast cancer in comparison to primary tumors. In cases of such advanced damage of primary tumors that made determination of estrogen receptor expression impossible, their evaluation was performed on metastases to regional lymph nodes. Although preoperative chemotherapy did not severely impair estrogen receptor expression, presented changes of their distribution are a sufficient reason for simultaneous labeling of estrogen receptors in both primary tumors and metastases due to various sensitivity to chemotherapy of primary cancers in comparison with involved lymph nodes.


The impact of advanced proteomics in the search for markers and therapeutic targets of bladder cancer.
Bladder cancer is the most common cancer of the urinary tract and can be avoided through proper surveillance and monitoring. Several genetic factors are known to contribute to the progression of bladder cancer, many of which produce molecules that serve as cancer biomarkers. Blood, urine, and tissue are commonly analyzed for the presence of biomarkers, which can be derived from either the nucleus or the mitochondria. Recent advances in proteomics have facilitated the high-throughput profiling of data generated from bladder cancer-related proteins or peptides in parallel with high sensitivity and specificity, providing a wealth of information for biomarker discovery and validation. However, the transmission of screening results from one laboratory to another remains the main disadvantage of these methods, a fact that emphasizes the need for consistent and standardized procedures as suggested by the Human Proteome Organization. This review summarizes the latest discoveries and progress of biomarker identification for the early diagnosis, projected prognosis, and therapeutic response of bladder cancer, informs the readers of the current status of proteomic-based biomarker findings, and suggests avenues for future work.


Dynamic Alterations in Spontaneous Neural Activity in Multiple Brain Networks in Subacute Stroke Patients: A Resting-State fMRI Study.
Objective: To examine whether subacute stroke patients would exhibit abnormal dynamic characteristics of brain activity relative to healthy controls (HC) and to investigate whether the altered dynamic regional indexes were associated with clinical behavior in stroke patients. Methods: The dynamic amplitude of low-frequency fluctuations (dALFF) and dynamic regional homogeneity (dReHo) in 42 subacute stroke patients and 55 healthy controls were compared. Correlation analyses between dALFF and dReHo in regions showing significant intergroup differences and clinical scores (i.e., the National Institutes of Health Stroke Scale, Fugl-Meyer assessment and lesion volume size) were conducted in stroke patients. Receiver operating characteristic (ROC) curve analysis was used to determine the potential value of altered dynamic regional indexes to identify stroke patients. Results: Significantly dALFF in the bilateral cerebellum posterior lobe (CPL), ipsilesional superior parietal lobe, ipsilesional inferior temporal gyrus (ITG), the midline supplementary motor area (SMA), ipsilesional putamen and lentiform nucleus were detected in stroke patients compared to HC. Relative to the HC group, the stroke patients showed significant differences in dReHo in the contralesional rectal gyrus, contralesional ITG, contralesional pons, ipsilesional middle frontal gyrus (MFG). Significant correlations between dALFF variability in midline SMA and Fugl-Meyer assessment (FMA) scores or between dReHo variability in the ipsilesional MFG and FMA scores were detected in stroke patients. Furthermore, the ROC curve revealed that dynamic ALFF at SMA and ReHo at ipsilesional MFG might have the potential to distinguish stroke patients. Conclusion: The pattern of intrinsic brain activity variability is altered in stroke patients compared with HC, and dynamic ALFF/ReHo might be potential tools to assess stroke patients' motor function.


SBF-1 exerts strong anticervical cancer effect through inducing endoplasmic reticulum stress-associated cell death via targeting sarco/endoplasmic reticulum Ca(2+)-ATPase 2.
Cervical cancer is one of the most common carcinomas in the genital system. In the present study, we report that SBF-1, a synthetic steroidal glycoside, has a strong antigrowth activity against human cervical cancer cells in vitro and in vivo. SBF-1 suppressed the growth, migration and colony formation of HeLa cells. In addition, severe endoplasmic reticulum (ER) stress was triggered by SBF-1, and 4-phenyl-butyric acid, a chemical chaperone, partially reversed SBF-1-induced cell death. To uncover the target protein of SBF-1, the compound was labeled with biotin. The biotin-labeled SBF-1 bound to sarco/ER Ca(2+)-ATPase 2 (SERCA2) and colocalized with SERCA2 in HeLa cells. Moreover, SBF-1 inhibited SERCA activity, depleted ER Ca2+ and increased cytosolic Ca2+ levels. 1,2-Bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, a chelator of Ca2+, partially blocked SBF-1-induced ER stress and growth inhibition. Importantly, knockdown of SERCA2 increased the sensitivity of HeLa cells to SBF-1-induced ER stress and cell death, whereas overexpression of SERCA2 decreased this sensitivity. Furthermore, SBF-1 induced growth suppression and apoptosis in HeLa xenografts, which is closely related to the induction of ER stress and inhibition of SERCA activity. Finally, SERCA2 expression was elevated in human cervical cancer tissues (n=299) and lymph node metastasis (n=8), as compared with normal cervix tissues (n=23), with a positive correlation with clinical stages. In all, these results suggest that SBF-1 disrupts Ca2+ homeostasis and causes ER stress-associated cell death through directly binding to SERCA2 and inhibiting SERCA activity. Our findings also indicate that SERCA2 is a potential therapeutic target for human cervical cancer.


Attention difficulties and mood-related ruminative response style in adolescents with unipolar depression.
Depressed adults may show impairment in switching attention from one task to another. Rumination on negative thoughts is associated with the onset and persistence of depressive episodes. It is unclear if such mood-related ruminations are specifically associated with slowed ability in switching attention from one task to another. Adolescents with current unipolar depression (n = 40) were compared with age and sex-matched controls (n = 38) on tests of attention and general cognitive abilities and completed the mood-related ruminative response style questionnaire. Compared to controls, depressed participants were significantly slower at switching attention. There was no association between attentional switching and mood-related ruminations and both processes contributed to the likelihood of being depressed. Findings were not accounted for by slowness in reading and speaking, the effects of antidepressants nor being more careful on tasks. Depressed adolescents demonstrate dual deficits in mood-related ruminative thinking and attention. Further studies are needed to investigate whether higher ruminations are associated with attention impairments in emotionally-valent attentional switching tasks, and whether both processes precede the emergence of clinical disorder.


Sexual Orientation and Gender Identity Change Efforts and Suicide Morbidity Among Sexual and Gender Minority Adults in Colombia.
Purpose: We assessed the association between sexual orientation and gender identity change efforts (SOGICE) experiences and lifetime suicide morbidity among sexual and gender minority (SGM) groups in Colombia. Methods: A sample of 4160 SGM Colombian adults responded to an online cross-sectional survey. We used binary logistic regression to assess the relationship between SOGICE and suicide morbidity for the overall sample and stratified by SGM group. Results: We found a high prevalence of suicidal ideation (56%), suicide planning (54%), suicide attempt (25%), and SOGICE experiences (22%). There were significant differences in the prevalence of suicide morbidity and SOGICE experiences across SGM groups, with transgender men and gender nonbinary participants being generally most at risk. SOGICE experiences were associated with 69% increased odds of suicidal ideation, 55% increased odds of suicide planning, and 76% increased odds of suicide attempt. Stratified analyses by SGM group showed that the association of SOGICE experiences with suicide morbidity varied by SGM group, and it was particularly detrimental for cisgender sexual minority men. Conclusions: Suicide morbidity among SGM adults in Colombia is high, with rates that are 8-22 times higher than in the general population. SOGICE experiences further exacerbate suicide risk. The study findings highlight the need to design and implement policies affirming diverse sexual orientation and gender identities in Colombia and to ban SOGICE practices. These findings also highlight the importance of recognizing the variability within SGM groups and the need to examine these groups separately rather than treating them as a monolithic group.


Reactions of beta-propiolactone, beta-butyrolactone and gamma-butyrolactone with nucleic acids.
Reactivity of beta-propiolactone, beta-butyrolactone and gamma-butyrolactone with guanosine, RNA, DNA and 4-(p-nitrobenzyl)pyridine was studied. beta-Propiolactone was 50--100 times more reactive with all the nucleophiles than beta-butyrolactone whereas gamma-butyrolactone was completely inactive. The rate of alkylation by the lactones was guanosine greater than RNA = denatured DNA greater than double-stranded DNA. The type of the adducts formed were characterized by fluorescence and ultraviolet spectroscopy. Similar alkylation products were formed by the two lactones. The main sites alkylated were N-1 at adenosine, N-3 at cytidine and N-7 at guanosine. The results suggest that the carcinogenic potency of the lactones correlates with their reactivity rather than with specificity of the adducts formed.


Evaluation of urinary enzymes in dogs with early renal disorder.
We investigated urinary N-acetyl-beta-D-glucosaminidase NAG (EC 18.104.22.168), gamma-glutamyl transpeptidase gamma-GTP (EC 220.127.116.11) and glycyl-prolyl dipeptidyl aminopeptidase GP-DAP (EC 22.214.171.124) in dogs with heartworm disease and renal failure. In the renal failure dogs, the NAG, gamma-GTP and GP-DAP index were significantly higher than those in the healthy dogs. In the heartworm disease dogs with normal chest X-rays (HW I), none of the enzyme values was significantly different from those of the healthy controls. In the dogs with heartworm disease showing abnormal heart shadows on their chest X-rays (HW II), enzyme values were significantly higher than those in the healthy dogs (P < 0.01) and the HW I dogs (P < 0.01). Thus, these urinary enzymes tests are available for the early detection of renal disorders.


The functional impact of mental imagery on conscious perception.
Mental imagery has been proposed to contribute to a variety of high-level cognitive functions, including memory encoding and retrieval, navigation, spatial planning, and even social communication and language comprehension. However, it is debated whether mental imagery relies on the same sensory representations as perception, and if so, what functional consequences such an overlap might have on perception itself. We report novel evidence that single instances of imagery can have a pronounced facilitatory influence on subsequent conscious perception. Either seeing or imagining a specific pattern could strongly bias which of two competing stimuli reach awareness during binocular rivalry. Effects of imagery and perception were location and orientation specific, accumulated in strength over time, and survived an intervening visual task lasting several seconds prior to presentation of the rivalry display. Interestingly, effects of imagery differed from those of feature-based attention. The results demonstrate that imagery, in the absence of any incoming visual signals, leads to the formation of a short-term sensory trace that can bias future perception, suggesting a means by which high-level processes that support imagination and memory retrieval may shape low-level sensory representations.


Effect of water migration between arabinoxylans and gluten on baking quality of whole wheat bread detected by magnetic resonance imaging (MRI).
A new method, a magnetic resonance imaging (MRI) technique characterized by T(2) relaxation time, was developed to study the water migration mechanism between arabinoxylan (AX) gels and gluten matrix in a whole wheat dough (WWD) system prepared from whole wheat flour (WWF) of different particle sizes. The water sequestration of AX gels in wheat bran was verified by the bran fortification test. The evaluations of baking quality of whole wheat bread (WWB) made from WWF with different particle sizes were performed by using SEM, FT-IR, and RP-HPLC techniques. Results showed that the WWB made from WWF of average particle size of 96.99 μm had better baking quality than those of the breads made from WWF of two other particle sizes, 50.21 and 235.40 μm. T(2) relaxation time testing indicated that the decreased particle size of WWF increased the water absorption of AX gels, which led to water migration from the gluten network to the AX gels and resulted in inferior baking quality of WWB.


[Hemizona assay for evaluating fertilizing capacity of human spermatozoa].
The hemizona assay (HZA), which tests the binding capacity of human spermatozoa to the zona pellucida, is described. This assay has very high sensitivity (86-100%) in predicting fertilizing capacity in the in vitro fertilization (IVF) system. It is recommended that it be carried out on semen samples before entering the IVF program. In addition, it can also help evaluate unexplained infertility and assess the quality of ova. The necessity for a control fertilized sample in each HZA might complicate the assay. To simplify the test, the use of sperm from the sperm bank was investigated. It was shown that fresh and frozen-thawed sperm have the same capacity to bind to the hemizonae. Thus, frozen donor semen preserved in the sperm bank can be used for controlling the HZA.


The discrimination between different blood-CSF barrier dysfunctions and inflammatory reactions of the CNS by a recent evaluation graph for the protein profile of cerebrospinal fluid.
A graph for the evaluation of the CSF-protein profile is presented as a basic program for the clinical-neurochemical laboratory. The graph has the following advantages: Simultaneous information on the functional state of the blood-CSF barrier and the inflammatory response of the CNS; maximal sensitivity for the determination of a pathological local IgG production in CNS--with the possibility of calculating the IgG fraction in CSF originating from the CNS; minimal number of protein assays necessary (albumin and IgG in serum and CSF); suitable for the demonstration of the course of the disease in a single patient as well as for demonstration of a group of cases for statistical purposes. Complementary chemical investigations and the correspondence with the clinical diagnosis are discussed for a number of typical cases. Two different types of blood-CSF barrier dysfunctions are discriminated by a proportional and a dis-proportionate increase of the CSF/serum protein concentration gradients.


Quantifying trophoblast migration: In vitro approaches to address in vivo situations.
When trophoblasts migrate and invade in vivo, they do so by interacting with a range of other cell types, extracellular matrix proteins, chemotactic factors and physical forces such as fluid shear stress. These factors combine to influence overall trophoblast migration and invasion into the decidua, which in turn determines the success of spiral artery remodelling, and pregnancy itself. Our understanding of these important but complex processes is limited by the simplified conditions in which we often study cell migration in vitro, and many discrepancies are observed between different in vitro models in the literature. On top of these experimental considerations, the migration of individual trophoblasts can vary widely. While time-lapse microscopy provides a wealth of information on trophoblast migration, manual tracking of individual cell migration is a time consuming task that ultimately restricts the numbers of cells quantified, and thus the ability to extract meaningful information from the data. However, the development of automated imaging algorithms is likely to aid our ability to accurately interpret trophoblast migration in vitro, and better allow us to relate these observations to in vivo scenarios. This commentary discusses the advantages and disadvantages of techniques commonly used to quantify trophoblast migration and invasion, both from a cell biology and a mathematical perspective, and examines how such techniques could be improved to help us relate trophoblast migration more accurately to in vivo function in the future.