Prospects for Clinical Development of Stat5 Inhibitor IST5-002: High Transcriptomic Specificity in Prostate Cancer and Low Toxicity In Vivo.
Stat5 is of significant interest in the search for new therapeutics for prostate cancer (PC) and hematopoietic disorders. We evaluated the transcriptomic specificity of the Stat5a/b inhibitor IST5-002 (IST5) in PC, defined more closely its mechanisms of action, and investigated the in vivo toxicity of IST5 for further optimization for clinical development. The transcriptomic specificity of IST5 vs. genetic Stat5 knockdown was evaluated by RNA-seq analysis, which showed high similarity with the Pearson correlation coefficient ranging from 0.98-0.99. The potency of IST5 vs. its derivative lacking the phosphate group in suppressing Stat5 was evaluated in two separate but complementary assays. The inhibitory activity of IST5 against kinases was investigated in cell-free assays followed by more focused evaluation in a cell-based assay. IST5 has no specific inhibitory activity against 54 kinases, while suppressing Stat5 phosphorylation and subsequent dimerization in PC cells. The phosphate group was not critical for the biological activity of IST5 in cells. The acute, sub-chronic and chronic toxicity studies of IST5 were carried out in mice. IST5 did not cause any significant toxic effects or changes in the blood profiles. The present work supports further optimization of IST5 for oral bioavailability for clinical development for therapies for solid tumors, hematological and myeloproliferative disorders.


LAD coronary artery myocardial bridging and apical ballooning syndrome.
This study sought to evaluate the prevalence and potential role of myocardial bridging in the pathogenesis of apical ballooning syndrome (ABS). ABS is characterized by reversible left ventricular dysfunction, frequently precipitated by a stressful event, but the pathogenesis remains still unclear. Forty-two consecutive patients (40 female, mean age 66 ± 7 years) with ABS underwent echocardiography, cardiac magnetic resonance, coronary angiography (CA) with intravascular ultrasound, and computed tomography angiography (CTA). Myocardial bridging was diagnosed by CA when a dynamic compression phenomenon was observed in the coronary artery and by CTA when a segment of coronary artery was completely (full encasement) or incompletely (partial encasement) surrounded by the myocardium. The prevalence of myocardial bridging detected by CTA and CA in ABS patients was compared with 401 controls without ABS who underwent both CTA and CA. Myocardial bridging by CTA was observed in 32 ABS patients (76%): 23 with partial encasement and 9 with full encasement. All myocardial bridging was located in the mid segment of the left anterior descending coronary artery (LAD) with a mean length of 17 ± 9 mm. CA revealed myocardial bridging in 17 subjects (40%) (9 with partial encasement and 8 with full encasement by CTA). All subjects in which dynamic compression was observed by CA showed myocardial bridging by CTA, while none of the subjects with negative findings for myocardial bridging by CTA revealed dynamic compression by CA. Compared with controls, ABS patients showed a significant higher prevalence of myocardial bridging in the LAD either by CA (40% vs. 8%; p < 0.001) or by CTA (76% vs. 31%; p < 0.001). Our study showed that myocardial bridging of the LAD is a frequent finding in ABS patients as revealed both by CA and, mostly, by CTA, suggesting a role of myocardial bridging as potential substrate in the pathogenesis of ABS.


An epistatic effect of the female specific loci on the development of autoimmune vasculitis and antinuclear autoantibody in murine lupus.
To identify the genetic loci regulating the incidence and severity of renal autoimmune vasculitis developed in murine lupus. Vasculitis of renal arteries was histopathologically evaluated in MRL/Mp-Fas(lpr) (MRL/lpr), C57BL/6-Fas(lpr) (B6/lpr), (MRL/lpr x B6/lpr) F1, and MRL/lpr x (MRL/lpr x B6/lpr) F1 backcross mice. Using genomic DNA samples of the backcross mice, genome-wide scans, association studies, and linkage analyses were carried out based on genotypes of polymorphic microsatellite markers. Correlations of vasculitis grade and levels of various autoantibodies were also evaluated. Two recessive susceptibility loci of the MRL allele were identified on chromosomes 4 and 1, which had previously been defined as the autoimmune related loci termed Arvm1 and Sle-1/Nba2, respectively. The former was epistatic to the latter in a female specific manner. The titre of antinuclear autoantibody (ANA) in IgG class, but not ANA in IgM class or anti-dsDNA in either IgG or IgM class, correlated significantly with vasculitis grade. The present loci have been reported in previous studies using a different set of murine strains, suggesting that they are of importance in the development of autoimmune vasculitis in murine models. The concomitance of autoimmune vasculitis and IgG ANA suggests a shared genetic factor regulating these traits.


Choroidal osteoma with CNVM - Successful treatment with intravitreal Bevacizumab.
Twenty-seven years old healthy woman presented with complaints of sudden painless blurred vision in right eye for 1 week. On examination, visual acuity was 20/30 in the right eye and 20/20 in left eye. Fundus examination OS was normal; OD demonstrated a flat, opaque, yellowish parapapillary choroidal lesion with grayish membrane associated with minimal subretinal fluid suggestive of a CNVM in the center. B-scan ultrasonography revealed findings consistent with a choroidal osteoma. Fundus fluorescein angiography of the right eye revealed a relatively well-defined area of hyperfluorescence that increased in size and intensity in the later phases suggestive of active extrafoveal CNVM. Optical coherence tomography confirmed the extrafoveal CNVM with subfoveal fluid. She was treated with intravitreal Bevacizumab OD. At the 2 weeks visit, vision OD improved to 20/20. The FFA and OCT revealed a resolved CNVM. Intravitreal Bevacizumab may be an effective alternative in the management of CNVM secondary to choroidal osteoma.


The effect of soil type on adipocere formation.
Adipocere refers to a postmortem product which forms from body fat in the later stages of decomposition. Factors present in the surrounding decomposition environment will influence adipocere formation and may accelerate or retard the process of conversion. One such factor important in burial environments is the type of grave soil in which the burial has taken place. This study was conducted to investigate the influence of various soil types on the formation of adipocere in grave soils. X-ray diffraction and particle size analysis were used to characterise the soils which were essentially chosen on the basis of grain size. Infrared spectroscopy, inductively coupled plasma-mass spectrometry, and gas chromatography-mass spectrometry were used to investigate the lipid profile and chemical composition of adipocere developed from decomposing tissue. The results suggest that adipocere is able to form in various soil types and that particular soil environments may accelerate its formation.


RNA topology remolds electrostatic stabilization of viruses.
Simple RNA viruses efficiently encapsulate their genome into a nano-sized protein shell: the capsid. Spontaneous coassembly of the genome and the capsid proteins is driven predominantly by electrostatic interactions between the negatively charged RNA and the positively charged inner capsid wall. Using field theoretic formulation we show that the inherently branched RNA secondary structure allows viruses to maximize the amount of encapsulated genome and make assembly more efficient, allowing viral RNAs to out-compete cellular RNAs during replication in infected host cells.


[Follow-up after urolithiasis management].
Urinary stones often affect younger people. Because the risk of recurrence is high, regular follow-up is important for individuals at risk. To summarize the extent of urinary stones and the health and economic impact in the population; to provide recommendations for general and stone-specific follow-up. Analysis and discussion of publications and guideline recommendations. The risk of recurrence after a stone attack can be high depending on the risk profile. An initial metabolic workup should be performed promptly after stone therapy. General dietary management should be intensified by stone-specific dietary management depending on the risk profile. Nutritional counseling may be helpful. Imaging after stone therapy is used to monitor the success of treatment and detect recurrences early. Since the risk of recurrence can vary greatly depending on the stone composition, not only the type of imaging but also its frequency should be adjusted accordingly. The same applies to the various stone therapies, which help determine the frequency and type of imaging follow-up. Exact guidelines and cost-effectiveness analyses of follow-up examinations after stone therapy are unfortunately missing. Acute urolithiasis represents an excruciating experience for patients. Accordingly, their willingness to undergo metaphylaxis and follow-up shortly after the event is strong. Since the risk of recurrence after a stone attack can be very high, regular follow-up after stone therapy is essential. The frequency of follow-up should be adapted to the probability of stone recurrence.


Vertebral Body Stapling versus Bracing for Patients with High-Risk Moderate Idiopathic Scoliosis.
We report a comparison study of vertebral body stapling (VBS) versus a matched bracing cohort for immature patients with moderate (25 to 44°) idiopathic scoliosis (IS). 42 of 49 consecutive patients (86%) with IS were treated with VBS and followed for a minimum of 2 years. They were compared to 121 braced patients meeting identical inclusion criteria. 52 patients (66 curves) were matched according to age at start of treatment (10.6 years versus 11.1 years, resp. [P = 0.07]) and gender. For thoracic curves 25-34°, VBS had a success rate (defined as curve progression <10°) of 81% versus 61% for bracing (P = 0.16). In thoracic curves 35-44°, VBS and bracing both had a poor success rate. For lumbar curves, success rates were similar in both groups for curves measuring 25-34°. In this comparison of two cohorts of patients with high-risk (Risser 0-1) moderate IS (25-44°), in smaller thoracic curves (25-34°) VBS provided better results as a clinical trend as compared to bracing. VBS was found not to be effective for thoracic curves ≥35°. For lumbar curves measuring 25-34°, results appear to be similar for both VBS and bracing, at 80% success.


Health-related quality of life and physical ability among pregnant women with and without back pain in late pregnancy.
Back pain during late pregnancy is a frequent clinical problem. Very little is known about the impact of this symptom on the quality of life among pregnant women with back pain. To study the influence of back pain and physical ability on quality of life in late pregnancy. One hundred and sixty women in the 34th-37th week of pregnancy and attending two different midwife receptions, were asked to fill out questionnaires including: general questions about background factors, the Disability Rating Index (DRI) to score the physical ability, and The Nottingham Health Profile (NHP) for assessing health-related quality of life. Two groups were defined, with and without back pain. One hundred and thirty-six (85%) out of 160 screened women returned the questionnaire for evaluation. The 69 (51%) women with back pain rated significantly (p < 0.05) higher on the DRI; on NHP part I, sub scales sleep, energy, pain, physical functioning and total score; and on NHP part II, aspects occupation, ability to perform jobs around the house, social life and hobbies compared with women without back pain. Irrespective of back pain the pregnant women studied featured lower quality of life (QOL) compared with published data on healthy women. Among the women with back problems, who had the most impaired QOL, the factors affecting QOL were mostly related to physical ability.


Prevalence of sinusitis and efficacy of intranasal corticosteroid treatment on asthmatic symptoms in asthmatic patients with rhinosinusitis: a pilot study.
Prevalence of sinusitis on sinus computed tomography (CT) in asthmatic patients and efficacy of intranasal corticosteroid treatment on asthmatic symptoms in asthmatic patients with rhinosinusitis on sinus CT is unclear. Sinus CT of asthmatic patients were evaluated using the Lund-Mackay system (LMS). Intranasal corticosteroid treatment (mometasone furoate) was newly added to symptomatic asthmatic patients with rhinosinusitis treated without intranasal corticosteroids, and the findings of the Asthma Control Test (ACT), Asthma Control Questionnaire in 5 items (ACQ5), spirometry, and sinus CT were evaluated before and 3 months after additional intranasal corticosteroid treatment. In a total of 160 asthmatic patients, rhinosinusitis and maxillary, ethmoidal, sphenoidal, and frontal sinusitis were observed in 75.0%, 70.0%, 53.1%, 33.1%, and 28.8%, respectively. Nasal symptoms and rhinophonia were observed in 81.9% and 72.5%, respectively, and patients with nasal symptoms and those with rhinophonia both showed significantly higher LMS scores in each sinus. Chronic rhinosinusitis (CRS) was observed in 66.9%, and these patients had significantly more severe asthma than the patients without CRS. In patients with CRS, patients with rhinophonia showed significantly higher LMS scores than those without rhinophonia. ACT, ACQ5, and the value of the forced expiratory volume in 1 second (FEV1) all significantly improved 3 months after the additive intranasal corticosteroid treatment in 24 patients, despite the fact that their LMS scores remained unchanged. Additive intranasal corticosteroid treatment may be an effective treatment option for symptomatic asthmatic patients with rhinosinusitis.


Phosphorylation of Threonine343 Is Crucial for OCT4 Interaction with SOX2 in the Maintenance of Mouse Embryonic Stem Cell Pluripotency.
OCT4 is required to maintain the pluripotency of embryonic stem cells (ESCs); yet, overdose-expression of OCT4 induces ESC differentiation toward primitive endoderm. The molecular mechanism underlying this differentiation switch is not fully understood. Here, we found that substitution of threonine343 by alanine (T343A), but not aspartic acid (T343D), caused a significant loss of OCT4-phosphorylation signal in ESCs. Loss of such OCT4-phosphorylation compromises its interaction with SOX2 but promotes interaction with SOX17. We therefore propose that threonine343-based OCT4-phosphorylation is crucial for the maintenance of ESC pluripotency. This OCT4-phosphorylation-based mechanism may provide insight into the regulation of lineage specification during early embryonic development.


Healing of normal and osteopenic bone with titanium implant and low-level laser therapy (GaAlAs): a histomorphometric study in rats.
The study investigates the influence of low-level laser therapy (LLLT) on bone healing in the femur of osteopenic and normal rats with titanium implants. Ovariectomy and control group were randomly submitted to LLLT, which was applied by gallium-aluminum-arsenium (GaAlAs) laser at the surgical site before and after placing the implant, for seven times. Histomorphometric and statistical analysis were performed. Most irradiated groups showed higher values than the nonirradiated groups. The GaAlAs infrared diode laser may improve the osseointegration process in osteopenic and normal bone, particularly based on its effects in the initial phase of bone formation.


C. elegans telomeres contain G-strand and C-strand overhangs that are bound by distinct proteins.
Single-strand extensions of the G strand of telomeres are known to be critical for chromosome-end protection and length regulation. Here, we report that in C. elegans, chromosome termini possess 3' G-strand overhangs as well as 5' C-strand overhangs. C tails are as abundant as G tails and are generated by a well-regulated process. These two classes of overhangs are bound by two single-stranded DNA binding proteins, CeOB1 and CeOB2, which exhibit specificity for G-rich or C-rich telomeric DNA. Strains of worms deleted for CeOB1 have elongated telomeres as well as extended G tails, whereas CeOB2 deficiency leads to telomere-length heterogeneity. Both CeOB1 and CeOB2 contain OB (oligo-saccharide/oligo-nucleotide binding) folds, which exhibit structural similarity to the second and first OB folds of the mammalian telomere binding protein hPOT1, respectively. Our results suggest that C. elegans telomere homeostasis relies on a novel mechanism that involves 5' and 3' single-stranded termini.


Applying aviation factors to oral and maxillofacial surgery--the human element.
There are many similarities between flying commercial aircraft and surgery, particularly in relation to minimising risk, and managing potentially fatal or catastrophic complications, or both. Since 1979, the development of Crew Resource Management (CRM) has improved air safety significantly by reducing human factors that are responsible for error. Similar developments in the operating theatre have, to a certain extent, lagged behind aviation, and it is well recognised that we can learn much from the industry. An increasing number of publications on aviation factors relate to surgery but to our knowledge there is a lack of research in our own specialty. We discuss how aviation principles related to human factors can be translated to the operating theatre to improve teamwork and safety for patients. Clinical research is clearly needed to develop this fascinating area more fully.


Endobag use in laparoscopic gynecological surgeries: a systematic review.
The purpose of this systematic review was to assess the characteristics of endobags present in the market, the weight of specimen removed, complications of the operations and time required for in-bag morcellation in women undergoing laparoscopic gynecologic surgeries. We performed a systematic review, including prospective and retrospective studies, with or without randomized allocation of the patients, using endobags in laparoscopic gynecologic surgeries. We extracted data about study design, type and price of bag used, type of surgical procedure, specimen weight, mean time for morcellation and for total surgical procedure, complications. We included 11 studies, including a total of 1160 patients, in which the investigators used MorSafe, Endocatch II autosuture, More-Cell-Safe, Endocatch, EcoSac and LapBag. A wide range of specimens were morcellated with the largest successfully morcellated specimen weighing 2314 gr. Only half of the studies comparing uncontained and contained morcellation found a significant increase of total operative time. Finally, the number of complications was not increased when endobag was used. According to our systematic review, in-bag (contained) morcellation can be considered as a safe and unexpensive option, associated with a very low number of complications, even with large specimens.


The evolution of crassulacean acid metabolism inAeonium inferred from carbon isotope composition and enzyme activities.
Variation in crassulacean acid metabolism (CAM) was investigated in thirtyAeonium species under controlled, well-watered conditions. Carbon isotope ratios and the specific activities of the CAM enzymes phosphoenolpyruvate carboxylase (PEPC) and malic enzyme ME_ are highly correlated and indicate a large variation in CAM. The δ13C values range from -13.6 to -27.1‰; PEPC and ME activities vary seven- and five-fold, respectively. Since these observations were made under controlled conditions, the differences are genetically determined and represent adaptations to different habitats. The CAM activity of the species is correlated with the characteristics of their natural habitats. CAM activity is also highly correlated with the growth- and life-forms of the species and accordingly agrees well with the infrageneric classifications which are partly based on these characters. Our results support the hypothesis that the Sempervivoideae have evolved from an EurasiaticSedum, which used C3 photosynthesis or weak CAM, and that evolution withinAeonium was from undifferentiatedSedum-like dwarf shrubs with C3 photosynthesis to woody candelabrum-shaped shrubs exhibiting strong CAM. The monocarpic, rosulate species with intermediate CAM may have evolved via an independent secondary route.


Size distribution and molecular associations of plasma fibronectin and fibronectin crosslinked by transglutaminase 2.
Fibronectin (FN) is a ubiquitously expressed cell adhesion protein capable of assembling into large, extended fibrillar networks as part of an extracellular matrix (ECM) that regulates cell behavior. FN is a substrate for certain members of the transglutaminase family of protein-crosslinking enzymes-enzymes which can modify the ability of FN to support cell adhesion. In this study, we have analyzed the thermo-chemical stability of plasma FN in its noncrosslinked form, and after crosslinking by transglutaminase 2 (TG2), using dynamic light scattering. We report that FN is found in a generally globular (8.7 nm hydrodynamic radius), dimerized form in aqueous solutions, but unfolds into a linear arrangement at high ionic (1 M NaCl) and chaotropic (5 M urea) environments. FN conformation remained stable after multiple heating and cooling cycles ranging from 4 to 60 degrees C. Crosslinking of FN with TG2 formed large, multimeric complexes having high chemical stability in aqueous, high ionic and chaotropic environments, demonstrating that this covalent modification stabilizes FN. Given recent data that substrate (e.g. ECM) rigidity profoundly affects cell differentiation and behavior, we further studied how TG2 crosslinking affects the molecular rigidity of FN by obtaining atomic force microscopy nanoindentation measurements from untreated and crosslinked FN samples embedded in acrylamide gels. We demonstrate that TG2-mediated crosslinking of FN significantly increases Young's modulus (of elasticity), an observation of increased rigidity having important implications with respect to the biological role of ECM protein-crosslinking in cell signaling and guiding cell differentiation.


Homogeneous and isotropic cosmology in general teleparallel gravity.
We derive the most general homogeneous and isotropic teleparallel geometries, defined by a metric and a flat, affine connection. We find that there are five branches of connection solutions, which are connected via several limits, and can further be restricted to the torsion-free and metric-compatible cases. We apply our results to several classes of general teleparallel gravity theories and derive their cosmological dynamics for all five branches. Our results show that for large subclasses of these theories the dynamics reduce to that of closely related metric or symmetric teleparallel gravity theories, while for other subclasses up to two new scalar degrees of freedom participate in the cosmological dynamics.


Contribution of periphytic biofilm of paddy soils to carbon dioxide fixation and methane emissions.
Rice paddies are major contributors to anthropogenic greenhouse gas emissions via methane (CH4) flux. The accurate quantification of CH4 emissions from rice paddies remains problematic, in part due to uncertainties and omissions in the contribution of microbial aggregates on the soil surface to carbon fluxes. Herein, we comprehensively evaluated the contribution of one form of microbial aggregates, periphytic biofilm (PB), to carbon dioxide (CO2) and CH4 emissions from paddies distributed across three climatic zones, and quantified the pathways that drive net CH4 production as well as CO2 fixation. We found that PB accounted for 7.1%-38.5% of CH4 emissions and 7.2%-12.7% of CO2 fixation in the rice paddies. During their growth phase, PB fixed CO2 and increased the redox potential, which promoted aerobic CH4 oxidation. During the decay phase, PB degradation reduced redox potential and increased soil organic carbon availability, which promoted methanogenic microbial community growth and metabolism and increased CH4 emissions. Overall, PB acted as a biotic converter of atmospheric CO2 to CH4, and aggravated carbon emissions by up to 2,318 kg CO2 equiv ha-1 season-1. Our results provide proof-of-concept evidence for the discrimination of the contributions of surface microbial aggregates (i.e., PB) from soil microbes, and a profound foundation for the estimation and simulation of carbon fluxes in a potential novel approach to the mitigation of CH4 emissions by manipulating PB growth.


IRF5 knockdown reverses TDP-related phenotypes partially by increasing TBK1 expression.
Interferon-regulatory factor 5 (IRF5) participates in the regulation of apoptosis, affects the phenotype of inflammatory macrophages and plays an essential role in the inflammatory response. However, the role of IRF5 in the progression of amyotrophic lateral sclerosis (ALS) remains largely unknown. Here, we show that IRF5 mainly accumulated in the nucleus in cells expressing the truncated 25 kD C-terminal fragments of TDP-43 (TDP-25, named TDP-25 cells hereafter). IRF5 knockdown using a lentivirus carrying an shRNA in TDP-25 cells exerted a protective effect and reduced the level of the apoptosis-related protein cleaved caspase-9 and the cell cycle arrest protein p21, while increasing the expression of the antioxidant transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) and its target molecule glutamate-cysteine ligase modulatory subunit (GCLM). Furthermore, IRF5-knockdown cells showed improved mitochondrial swelling and cristae dilation. In addition, we found that IRF5 mediated neuronal injury partly through the negative regulation of TANK-binding kinase 1 (TBK1). These data indicate that the loss of IRF5 in TDP-25 cells exerts a protective effect mainly by inhibiting apoptosis, regulating cell cycle arrest and alleviating oxidative stress.


Dopamine affects the change of pain-related electrical activity induced by morphine dependence.
Morphine is among the most effective analgesics. However, many evidences suggest that, besides the well-know analgesic activity, repeated opioids treatment can induce some side effects such as dependence, hyperalgesia and tolerance. The mechanism of noxious information transmission in the central nervous system after dependence is not clear. An important neurotransmitter, dopamine (DA) participates not only in the process of opioid dependence but also in pain modulation in the central nervous system. In the present study we observed changes of electrical activities of pain-excitation neurons (PENs) and pain-inhibition neurons (PINs) in the caudate nucleus (Cd) following the development of morphine dependence. We also observed the role of DA on these changes. Our results revealed that both the latency of PEN discharges and the inhibitory duration of PIN discharges decreased, and the net increased values of PEN and PIN discharges increased in the Cd of morphine dependent rats. Those demonstrated that electrical activities of both PENs and PINs increased in morphine dependent rats. DA inhibited the electrical activities of PENs and enhanced those of PINs in morphine dependent rats.


The lumbo-gluteal adipose body.
The lumbo-gluteal adipose body (LGAB) is a well-delineated fatty structure, in the lumbo-gluteal trigone, encroaching on the upper part of the gluteal region and flank. The aim of this study was to compare the gross and histological anatomy of the LGAB with that of other well-defined adipose bodies of the human body. The macroscopic study using dissections and slices in the main three planes in adults was supplemented by microscopic study of histological slices taken from fetuses and neonates. The forms and limits of the LGAB are defined, along with its structure. The LGAB appears to act as a filling structure, lining the hypodermis in the regions that it covers.


Interaction between the Cdk2/cyclin A complex and a small molecule derived from the pRb2/p130 spacer domain: a theoretical model.
Retinoblastoma (RB) family proteins pRb, p107 and pRb2/p130 are important cellular factors which play a well-recognized role as tumor and growth suppressors. These proteins are actively involved in the negative control of the cell cycle and their function is modulated via complex homeostatic processes, most of them involving post-translational regulation of their phosphorylation status. Interestingly, the family members p107 and pRb2/p130 share the ability to physically interact and inhibit the kinase activity of the Cdk2/Cyclin A and Cdk2/Cyclin E complexes. Regarding pRb2/p130, its inhibitory effect on Cdk2/Cyclin A activity has been attributed to the "spacer" region. Recently, a 39 aa-long pRb2/p130 spacer-derived peptide (Spa310, aa 641-679) was selected as the sequence responsible for Cdk2/Cyclin A inhibition. Following the identification of this active sequence, here we propose a computer-generated three-dimensional model of the interaction between the Cdk2/Cyclin A complex and the N-terminal nine-amino acid sequence of the Spa310 peptide. We believe this model to be useful for the rational development of peptide or peptidomimetic kinase inhibitors for negative cell cycle modulation in cancer cells.


Postoperative portal vein thrombosis in patients with hepatosplenic mansonic schistosomiasis: relationship with intraoperative portal pressure and flow. A prospective study.
Portal vein thrombosis is a frequent postoperative complication after esophagogastric devascularization with splenectomy. The aim of this study was to analyze biochemical, hematological, coagulation blood tests and intraoperative portal vein hemodynamics after surgical treatment of hepatosplenic Mansonic schistosomal portal hypertension. Forty patients with hepatosplenic schistosomiasis with indication for surgical treatment were prospectively studied. All patients underwent routine pre- and postoperative biochemical, hematologic, coagulation blood tests and intraoperative portal hemodynamic evaluation (portal pressure and portal flow) before and after esophagogastric devascularization and splenectomy using a 4-F thermodilution catheter introduced inside the portal vein. Portal vein thrombosis, diagnosed by routine postoperative Doppler ultrasonography was found in 22 patients (55%). It was partial in nineteen and total in three. In patients with postoperative portal thrombosis, we observed a reduction in portal flow of 971 +/- 592 mL/min (42 +/- 16%) at the end of the surgery, while this reduction was of 720 +/- 644mL/ min (33 +/- 30%) in those with postoperative pervious portal vein (p = 0.245). The decrease in portal pressure was the same in both groups: 7.2 +/- 3.0 mmHg (23 +/- 10%) and 7.6 +/- 3.8 mmHg (27 +/- 14%) with and without thrombosis respectively (p=0.759). There was also no significant difference between patients with and without portal vein thrombosis regarding pre- and postoperative hemoglobin level or platelet levels, coagulation tests, portal vein diameter and spleen's weight. Portal vein thrombosis was observed in 55% of the patients but this complication did not show any correlation with the decrease in portal flow or pressure or with biochemical, hematologic, coagulation blood tests, portal vein diameter or spleen's weight.


[Choroidal calcification associated to chondrocalcinosis].
Chondrocalcinosis is a common joint condition in people over 50, characterized by the deposition of calcium pyrophosphate crystals that causes calcification in cartilage structures. Although its prevalence in the general population is 5%, sclerochoroidal calcifications are a rare finding in this pathology. Describe the case of a 60-year-old man with choroidal calcification in the left eye, associated with radiological findings of chondrocalcinosis, whose metabolic report showed parameters compatible with hyperparathyroidism. Male patient from Mexico City, smoker for 45 years, with medical history of calcium pyrophosphate deposition disease at age 16, attended routine eye examination. A left eye funduscopy revealed an irregularly shaped white-yellowish subretinal lesion with well-defined edges inside the upper temporal arch. Ophthalmological paraclinical studies were performed, and a choroidal hyperreflectic paramacular plate image, which did not involve the retina layers, was corroborated with five-line optical coherence tomography. Although the lesions are asymptomatic and do not require treatment, it is of great importance to make a differential diagnosis with choroidal metastases, choroidal melanoma, choroidal osteoma and lymphoma, since these pathologies do require more aggressive treatment.


Male rainbow darters (Etheostoma caeruleum) prefer larger conspecific females.
Female mate choice is a well studied mechanism of sexual selection that can affect the evolution of male secondary sexual traits. However, males also exhibit selective mate choice in some animals, which can affect the evolution of female phenotypes. We tested for evidence of intraspecific male mate choice in the Rainbow Darter (Percidae: Etheostoma caeruleum). Males of numerous darter species have been shown to prefer conspecific over heterospecific females; however, intraspecific preferences in males have not yet been demonstrated in this genus. This study investigated male preference for indicators of female fecundity, specifically female size. We found that male Rainbow Darters prefer larger females, both in dichotomous choice tests, when access between individuals was prevented, and in unrestricted behavioral tests with full access to females. Notably, however, the dichotomous trials were not repeatable; males only displayed a significant preference for larger females in the first dichotomous trial and in the unrestricted trial. We discuss our results in light of experimental methods and the role of male mate choice in sexual selection.


Caregiver Stigma and Burden in Memory Disorders: An Evaluation of the Effects of Caregiver Type and Gender.
Despite considerable gains in public awareness of dementia, dementia patients and their caregivers continue to be stigmatized. Previous work has explored stigma and burden among adult children of persons with dementia in Israel, but no similar data exist for spousal caregivers or caregivers in general in the United States. This study examines the differences in stigma and burden experienced by spousal and adult child caregivers and male and female caregivers of persons with dementia. Eighty-two caregivers were given the Zarit Burden Inventory Short Form (ZBI) and the Caregiver Section of the Family Stigma in Alzheimer's Disease Scale (FS-ADS-C). Scores on the FS-ADS-C and ZBI were positively correlated (r s = .51, p < .001). Female caregivers reported experiencing more stigma on the FS-ADS-C (t(80) = -4.37, p < .001) and more burden on the ZBI (t(80) = -2.68, p = .009) compared to male caregivers, and adult child caregivers reported experiencing more stigma on the FS-ADS-C (t(30.8) = -2.22, p = .034) and more burden on the ZBI (t(80) = -2.65, p = .010) than spousal caregivers. These results reinforce the importance of support for caregivers, particularly adult child and female caregivers who may experience higher levels of stigma and burden.


Visnagin ameliorates myocardial ischemia/reperfusion injury through the promotion of autophagy and the inhibition of apoptosis.
Visnagin is a furanochromone and one of the main compounds of Ammi visnaga L. that had been used to treat nephrolithiasis in Ancient Egypt. Nowadays, visnagin was widely used to treat angina pectoris, urolithiasis and hypertriglyceridemia. The potential mechanisms of visnagin involved in inflammation and cardiovascular disease were also identified. But the protective effect of visnagin on myocardial ischemia/reperfusion injury has not been confirmed. Our aim was, for the first time, to investigate the potential protective effect of visnagin on cardiac function after myocardial ischemia-reperfusion injury in a rat model, and to identify its underlying mechanism involving the inhibition of apoptosis and induction of autophagy. Thirty SD rats were randomly divided into sham group, ischemia/reperfusion group (IR), ischemia/reperfusion with visnagin (IR + visnagin) group. Myocardial ischemia/Reperfusion injury model was established. Hemodynamic measurements and echocardiography were used to analyze cardiac function, TUNEL staining and caspase activity, LC3 dots were detected with immunofluorescence staining, LC3 expression was evaluated by western blot analysis, transmission electron microscopy (TEM) was used to detect autophagosomes. Compared with the sham group and visnagin group, the cardiac dysfunction, LC3II, autophagy flow in the IR+ visnagin group increased significantly (P<0.01), but the activity of caspase-3 and caspase-9 and the apoptotic in the IR + visnagin group decreased significantly (P<0.01). In conclusion, visnagin may play a protective role in ischemia/reperfusion injury by inducing autophagy and reducing apoptosis.


Lipoprotein analysis in bodybuilders.
The use of anabolic steroids to augment athletic performance is widespread. It is known that these drugs can adversely affect lipoproteins in normal volunteers, leading to increased cholesterol and low density lipoprotein and depressed high density lipoprotein. It has been shown that endurance type exercise can lead to beneficial effects on lipoproteins but the effects of power exercise are less clear-cut and made more difficult to interpret by prior anabolic steroid use. This paper details the lipoprotein results in 24 subjects, eight sedentary controls, eight non-steroid and eight steroid using bodybuilders. The results revealed no significant difference between sedentary controls and non-steroid bodybuilders suggesting that this form of training does not cause beneficial effects on lipoproteins. However, the steroid-using groups had higher cholesterol and low density lipoprotein, with lower high density lipoprotein, high density lipoprotein2, high density lipoprotein3 and high density lipoprotein2/high density lipoprotein3 ratios compared to the other two groups. The long-term effects of such results may be an increased risk of atherosclerosis and requires long-term follow-up.


A high affinity, antidote-controllable prothrombin and thrombin-binding RNA aptamer inhibits thrombin generation and thrombin activity.
The conversion of prothrombin to thrombin is one of two non-duplicated enzymatic reactions during coagulation. Thrombin has long been considered an optimal anticoagulant target because it plays a crucial role in fibrin clot formation by catalyzing the cleavage of fibrinogen, upstream coagulation cofactors and platelet receptors. Although a number of anti-thrombin therapeutics exist, it is challenging to use them clinically due to their propensity to induce bleeding. Previously, we isolated a modified RNA aptamer (R9D-14) that binds prothrombin with high affinity and is a potent anticoagulant in vitro. We sought to explore the structure of R9D-14 and elucidate its anticoagulant mechanism(s). In addition to designing an optimized aptamer (RNA(R9D-14T)), we also explored whether complementary antidote oligonucleotides can rapidly modulate the optimized aptamer's anticoagulant activity. RNA(R9D-14T) binds prothrombin and thrombin pro/exosite I with high affinity and inhibits both thrombin generation and thrombin exosite I-mediated activity (i.e. fibrin clot formation, feedback activity and platelet activation). RNA(R9D-14T) significantly prolongs the aPTT, PT and TCT clotting assays, and is a more potent inhibitor than the thrombin exosite I DNA aptamer ARC-183. Moreover, a complementary oligonucleotide antidote can rapidly (< 2 min) and durably (>2 h) reverse RNA(R9D-14T) anticoagulation in vitro. Powerful anticoagulation, in conjunction with antidote reversibility, suggests that RNA(R9D-14T) may be ideal for clinical anticoagulation in settings that require rapid and robust anticoagulation, such as cardiopulmonary bypass, deep vein thrombosis, stroke or percutaneous coronary intervention.


N-Heterocyclic Carbene (NHC)-Catalyzed Transformations Involving Azolium Enolates.
The recent advances in the N-heterocyclic carbene (NHC)-organocatalyzed generation of azolium enolate intermediates and their subsequent interception with electrophiles are highlighted. The NHC-bound azolium intermediates are generated by the addition of NHCs to suitably substituted aldehydes, acid derivatives or ketenes. A broad range of coupling partners can intercept the azolium enolates to form [2+n] cycloadducts (n=2,3,4) and various α-functionalized compounds. The enantioselective synthesis of the target compounds are achieved with the use of chiral NHCs. Herein, we summarized the development that occurred in this subclass of NHC catalysis.


Spontaneous desorption and phase transitions of self-assembled alkanethiol and alicyclic thiol monolayers chemisorbed on Au(111) in ultrahigh vacuum at room temperature.
Scanning tunneling microscopy (STM) and X-ray photoelectron spectroscopy (XPS) were used to examine the surface structure and adsorption conditions of hexanethiol (HT) and cyclohexanethiol (CHT) self-assembled monolayers (SAMs) on Au(111) as a function of storage period in ultrahigh vacuum (UHV) conditions of 3×10(-7) Pa at room temperature (RT). STM imaging revealed that after storage for 7 days, HT SAMs underwent phase transitions from c(4×2) phase to low coverage 4×√3 phase. This transition is due to a structural rearrangement of hexanethiolates that results from the spontaneous desorption of chemisorbed HT molecules on Au(111) surface. XPS measurements showed approximately 28% reduction in sulfur coverage, which indicates desorption of hexanethiolates from the surfaces. Contrary to HT SAMs, the structural order of CHT SAMs with (5×2√3)R35° phase completely disappeared after storage for 3 or 7 days. XPS results show desorption of more than 80% of the cyclohexanethiolates, even after storage for 3 days. We found that spontaneous desorption of CHT molecules on Au(111) in UHV at RT occurred quickly, whereas spontaneous desorption of HT molecules was much slower. Thermal desorption spectroscopy (TDS) results suggest CHT SAMs in UHV at RT can desorb more efficiently than HT SAMs due to formation of thiol desorption fragments that result from chemical reactions between surface hydrogen atoms and thiolates on Au(111) surfaces. This study clearly demonstrated that organic thiols chemisorbed on gold surfaces are desorbed spontaneously in UHV at RT and van der Waals interactions play an important role in determining the structural stability of thiolate SAMs in UHV.


Arabidopsis thaliana contains a large family of germin-like proteins: characterization of cDNA and genomic sequences encoding 12 unique family members.
We have identified 39 Arabidopsis thaliana ESTs encoding germin-like proteins (GLPs) and have completely sequenced 25 of these cDNAs. Our analysis demonstrates that the Arabidopsis genome contains a gene family with at least 12 GLP genes. Comparisons with other known germins and germin-like proteins indicate that these Arabidopsis GLP subfamilies are unique from wheat germin. All other known GLPs fall into one of these subfamilies. The translated GLPs show approximately 35% amino acid identity with other GLPs outside of their subfamily and significantly higher levels of identity within their respective subfamily. The 3' ends of many of the GLP cDNAs are heterogeneous and several sites of polyadenylation are used. Ten of the GLPs have N-terminal signal sequences and most appear to be exported from the cell. Structurally, the GLPs are predicted to have a high content of beta-pleated sheet. Seven conserved regions of beta-sheet were found in each of the GLP proteins along with alpha-helices located at both N- and C-termini. These same structural elements are also conserved in wheat germin. With one exception, all GLP family members contain at least one N-glycosylation site. All of these sites are conserved in an unstructured loop between beta-1 and beta-2. Genes for two of these GLPs were identified in genomic sequences previously deposited in the GenBank. The GLP3b gene is physically linked to the polyubiquitin 4 gene. The 3' end of the GLP3b mRNA is only 0.5 kb from the ubq4 start of transcription. Analysis of the GLP3b promoter shows the presence of a single putative auxin-response sequence located at -124 to -111 upstream from the 5' end of the GLP3b mRNA. The GLP9 gene was identified in an Arabidopsis contig from Chromosome 4.


Virulence Profiles and Antimicrobial Resistance of Streptococcus agalactiae Infective and Colonizing Strains from Argentina.
Streptococcus agalactiae (GBS) is a colonizing agent in pregnant women, the main cause of invasive neonatal infections, and the reason of serious diseases in non-pregnant adults. Several virulence determinants are involved in the pathogenesis. These include capsular polysaccharide, surface-localized proteins, and toxins. Penicillin is considered the first choice antibiotic for the treatment and prophylaxis; erythromycin, clindamycin and fluoroquinolones are recommended alternatives for penicillin-allergic GBS carriers or patients. Our objective was to investigate the virulence genetic characteristics and the antimicrobial susceptibility of 162 GBS colonizing and infective isolates recovered in Argentina. Serotypes Ia and III were the most prevalent ones, followed by Ib, II, V, IV and non-typeable. In relation to the 13 virulence genes screened, cpsA, cylE, hylB, lmb, and scpB were the most prevalent and could be postulated as vaccine epitopes; bca, rib, bac, hvgA, spb1, PI, PI-2a, and PI-2b were detected in lesser frequencies. No significant association was found between serotypes or virulence genes and colonizing or infective isolates but, on the contrary, significant association was observed between some genes and the most prevalent serotypes, la and III. The cluster analysis showed 52 virulence profiles and, antimicrobial resistance tests, 16 profiles, some with up to 4 resistances. Tetracycline resistance was significantly associated with colonizing isolates. Genes tetM and ermB conferring resistance to tetracyclines and macrolides, respectively, were the most commonly identified. Our findings show that GBS colonizing and infective isolates circulating in Argentina share similar features in terms of serotype and virulence genes and show a high level of antimicrobial resistance.


[Possibility of using the etiological factor and the function of the immune system in assessing the pathogenetic treatment of chronic suppurative sinusitis].
The etiologic profile and state of the immune system of the patients with different forms of sinusitis treated at the Moscow Research Institute of the Ear, Throat and Nose in 1983-1985 were studied. The treatment of the patients with a combination of penicillin and dimexide was shown to be efficient. Differences between the humoral factors of the nonspecific defence and between the indices of the cell reactivity of the patients before and after the treatment were revealed.


Contamination of intravenous fluid with Sporothrix schenckii.
Fungi are known to contaminate intravenous (IV) solutions, particularly when there is a defect in the bottle or bag. On occasion several millilitres of such solutions have been infused into patients before the recognition of clumps in the fluid led to termination of the infusion. We wish to report the case of a patient accidentally infused with 100 ml of a solution that on subsequent culture yielded both Penicillium species, a previously recorded contaminant, and Sporothrix schenckii, a recognised pathogen. To our knowledge, this is the first report of an IV solution contaminated with S. schenckii.


The prevalence and significance of Brunn's nests, cystitis cystica and squamous metaplasia in normal bladders.
The frequency of Brunn's nests, cystitis cystica and squamous metaplasia was studied by multiple histologic sections in 100 grossly normal bladders obtained at postmortem examination. Of the 100 bladders 93 per cent had at least 1 of the 3 proliferative changes. Brunn's nests and cystitis cystica were seen in 89 and 60 per cent of the bladders, respectively, most often at the bladder neck and trigone. Non-keratinizing squamous metaplasia of the vaginal type was seen almost exclusively on the trigone and bladder neck in 46 per cent of the premenopausal and postmenopausal women but in only 7 per cent of the men. There was no satisfactory evidence that inflammation was casually associated with these changes. These findings suggest that Brunn's nests, cystitis cystica and squamous metaplasia of the vaginal type in women are normal variants of bladder urothelium and have no precancerous potential.


A proof-of-principle study on implementing polymerase chain displacement reaction (PCDR) to improve forensic low-template DNA analysis.
Polymerase chain reaction (PCR) plays an important role in forensic DNA analysis. However, the amplification of low-template DNA (LTDNA) samples usually encounters unsatisfactory results for the limited efficiency of PCR, which would interfere with the subsequent profile interpretation. Polymerase chain displacement reaction (PCDR) is a highly-efficient technique characterized by combining PCR and strand displacement reaction into a single PCDR cycle. This study explored the feasibility of PCDR for improving forensic LTDNA analysis. STR markers commonly used in forensic genetics were subjected to PCDR amplification and capillary electrophoresis detection. The results of singleplex reactions indicated that PCDR surpassed original PCR in efficiency for STR amplification. The average peak height of alleles in PCDR profiles was linearly correlated to the number of outer primers adopted for initiating the strand displacement process. Further, we assessed the multiplexing potential of PCDR by incorporating 17 STRs included in the expanded CODIS core loci and Amelogenin gene into a multiplex PCDR system. For pristine DNA templates ranged from 200 pg to 12.5 pg, the multiplex PCDR system consistently exhibited higher allele peak height as well as less allele dropout compared to the multiplex PCR references. Meanwhile, a significant reduction of stutter ratio was extensively observed in PCDR profiles. We also tested mock casework samples to verify the practical ability of multiplex PCDR for LTDNA detection. With DNA input varying from 48.1 pg to 6.6 pg, the multiplex PCDR system consistently obtained more allelic information than multiplex PCR methods. Our data collectively suggested that it is feasible to apply PCDR in forensic LTDNA analysis.


Computed tomography-ultrasound fusion brachytherapy: description and evolution of the technique.
In this manuscript, we describe our computed tomography (CT)-ultrasound (US) fusion prostate brachytherapy method and report the updated dosimetry result and trend. This cohort of 132 consecutive patients received CT-US fusion prostate brachytherapy from the first author (DBF) from December 2002 to August 2006. The technique consists of a hybrid preplanned and intraoperative dynamic dosimetry method, which initially delivers a standard preplanned source distribution, and then uses interval CT-based source identification dosimetry, fused to an identically spaced intraoperative US volume study series, to direct remedial sources that correct initial dosimetry deficiencies. The median and minimum prostate Day 0 prostate volume of interest receiving 100% of prescribed dose (V(100)) results in this patient cohort measured 98.26% and 92.61%, respectively, with all Day 0 prostate dose received by 90% of the volume of interest (D(90)) results exceeding 100% of the prescribed dose, and the maximum Day 0 prostate D(90) value measuring 128% of the prescribed dose. During the period of this analysis, a trend to the decreased quantity of dynamic remedial millicuries per case was identified, with the total sources decreasing from 116% to 106% of the preplanned level, resulting in minimal V(100) and D(90) decreases, while continuing to exceed the minimum Day 0 dosimetry requirements. CT-US fusion dynamic prostate brachytherapy represents a consistent prostate brachytherapy dosimetry delivery mechanism, creating a tight lower and upper bound to the final Day 0 prostate V(100) and D(90) parameters. The practice and pitfalls of this technique are discussed in detail.


PD-1 Inhibitors in Elderly and Immunocompromised Patients with Advanced or Metastatic Cutaneous Squamous Cell Carcinoma.
Cutaneous squamous cell carcinoma (cSCC) of the skin is the second most common form of skin cancer, with aging and prolonged exposure to ultraviolet rays being the main causes of the disease. Cemiplimab and pembrolizumab recently gained regulatory approval for the treatment of locally advanced and metastatic cSCC-conditions that are not treatable by surgical resection and/or radiotherapy. Although the results from the clinical trials have been promising, these studies have not included immunosuppressed, elderly patients. In this study, we included all immunocompromised and immunocompetent patients over the age of 75 years diagnosed with locally advanced or metastatic cSCC and treated with cemiplimab or pembrolizumab. The median duration of follow-up from cSCC diagnosis was 35.6 months, 82.9% of patients were male, and the median age was 83 years old. The median progression-free survival was 8.94 months. The incidence of treatment-related adverse events was 85.6%, the majority of which were grades 1 or 2. The disease control rate was 91.4%, the complete response rate was 17.1%, the partial response rate was 51.4%, the stable disease rate was 23%, and the progressive disease rate was 8.7%. Based on this study, cemiplimab and pembrolizumab for the treatment of locally advanced or metastatic cSCC in elderly, immunocompromised patients are efficacious, with acceptable safety profiles.


Gender difference in the effects of chronic diseases on daily physical activity patterns in older adults: analysis of objectively measured physical activity in NHATS 2021.
Many chronic diseases have detrimental impact on the physical activity (PA) patterns of older adults. Often such diseases have different degrees of severity in males and females. Quantifying this gender difference would not only enhance our understanding of diseases but would also help design individual-specific PA interventions, thereby improving health outcomes for both genders. PA data for 747 participants from round 11 (2021) of the National Health and Aging Trends Study were analyzed. Multilevel functional regression models were used to study gender difference in the effects of chronic diseases on daily PA patterns while adjusting for confounders. Females with dementia (or Alzheimer's disease), hypertension, heart and lung disease had lower PA at different times of day compared to females without these diseases, whereas males with and without these diseases had comparable daily PA. Males with diabetes had higher midnight PA and lower noon PA compared to males without diabetes, while females' PA with and without diabetes were similar. Our analysis demonstrates that although for most diseases, the daily PA patterns of individuals with the disease are negatively altered compared to healthy individuals, the extent of decline varies by gender and time of day. Designing personalized physical activity interventions considering gender and diurnal PA pattern can potentially improve quality of life across both genders.


[Hidradenoma papilliferum. Report of two cases and review of literature].
We bring two cases of hidradenoma papilliferum, rare injury. We describe the clinical, histopathological and a review of the available literature on the condition.


Differential expression of NMDA receptor subunits between neurons containing and not containing enkephalin in the mouse embryo spinal cord.
We transfected cultures of mouse spinal cord slices with the enhanced green fluorescent protein (GFP) gene driven by the promoter for preproenkephalin, using the particle-mediated gene transfer system adapted for small neurons in the superficial dorsal horn, and observations were made after 4-6 days in vitro. A considerable number of cells in the superficial dorsal horn were observed to express GFP fluorescence, reminiscent of the previously reported distribution of enkephalinergic neurons in the spinal cord. The number of GFP-expressing neurons increased in response to forskolin application. Reverse transcription-polymerase chain reaction (RT-PCR) analysis of single neurons revealed that the N-methyl-d-aspartate (NMDA) receptor NR2B subunit is expressed more frequently in enkephalinergic neurons, and the NR2A subunit more frequently in non-enkephalinergic neurons. These observations suggest that expression of NMDA receptor subunits is controlled differentially in distinct populations of neurochemically identified neurons in the spinal cord. Biolistic particle-mediated gene transfection seems useful for identifying neuronal phenotypes in organotypic cultures of the spinal cord.


Ultrasonographic diagnosis of glossoptosis in fetuses with Pierre Robin sequence in early and mid pregnancy.
This study was undertaken to describe the sonographic features of fetal glossoptosis in the Pierre Robin sequence. Fetal sonography was prospectively performed in 8000 consecutive pregnancies at 14 to 24 weeks' gestation. In addition we retrospectively reevaluated ultrasound recordings of 4 fetuses from other hospitals, in which the diagnosis of Pierre Robin sequence was overlooked at 22 weeks' gestation. Glossoptosis was defined as a posteriorly displaced tongue that never reached the anterior mandibular alveolar ridge while watching the fetal profile. Micrognathia, which is a component of the sequence, was subjectively defined. Glossoptosis with micrognathia was detected in 2 fetuses in the prospective group at 14 and 15 weeks' gestation. Both pregnancies were terminated; the diagnosis was confirmed in 1 case where postmortem examination was performed. There were no false-negative diagnoses in the other 7.998 fetuses. Glossoptosis and micrognathia were observed in the 4 retrospective cases. Sonographic identification of glossoptosis with fetal micrognathia suggests the possibility of Pierre Robin sequence.


Kinesins: Motor Proteins as Novel Target for the Treatment of Chronic Pain.
Kinesins are one of the neoteric and efficacious targets recently reported to play an important role in the initiation and progression of chronic pain. Kinesins are anterograde microtubule-based motor proteins that are involved in trafficking of receptors including nociceptors and progression of pain. The specific kinesin and regulatory proteins interplay is crucial for the delivery of nociceptors to the synapse. If this complex and less understood interplay is inhibited, it may result in a decrease in central sensitization, and thus attenuation of pain. This review is focused on the transportation process of receptors/cargos, the role of regulatory proteins influencing the respective kinesin, and their relationship with chronic pain. The review also features specific strategies adopted by researchers for targeting kinesin and chronic pain. Considering the recent preclinical success of kinesin inhibition in pain, it is expected that inhibitors for kinesin or enzymes responsible for kinesin activation could be developed or repurposed as alternative, safe, and potential therapies for the treatment of chronic pain.


Characteristics of the assistance to pilgrims in the National Sanctuary of Our Lady of Aparecida, São Paulo, Brazil, 2011-2014.
to describe the characteristics of the health assistance for pilgrims visiting the National Sanctuary of Our Lady of Aparecida and to investigate health care strategies in periods of peak of religious tourism. a descriptive study using outpatient medical records from 2011 to 2014, for a detailed analysis for the month of October 2014 and the operational documents for health care in periods of mass events in the medical clinic of the Sanctuary. 95,011 people were assisted in the period, 2,266 in October 2014; the higher demand for assistance was from elderly individuals (33%), women (59%), and people from the Brazilian Southeast region (79%); there were no operational documents for specific actions for this period. the large number of visitors, associated with the frequency of mass events and the absence of an operating plan, may pose a serious public health scenario for that region.


[Effect of intracisternal administration of antisera against neurospecific enolase (protein 14-3-2) on avoidance behavior in rats].
The antisera to three isoenzymes (alpha alpha, alpha gamma, and gamma gamma) of the rat neurospecific enolase were studied. gamma gamma-antiserum administered into the brain cistern (8 microliters) prior to learning, in contrast to two other antisera, impaired the retrieval of passive avoidance response within 1-28 days after learning. Maximal amnestic effect occurred in the first 3 days. Probable mechanisms of the neurospecific enolase participation in the formation of memory traces, are discussed.


IL-4 and IgE-anti-IgE modulation of 15(S)-hydroxyeicosatetraenoic acid release by mononuclear phagocytes.
IL-4 modulates the synthesis of IgE, the expression of CD23, and the release of 15(S)-hydroxyeicosatetraenoic (15[S]-HETE). We evaluated the release of 15(S)-HETE by IL-4-stimulated monocytes and verified whether the observed increase in 15(S)-HETE release after passive sensitization and anti-IgE challenge of IL-4-treated monocytes was secondary to an increased CD23 expression. Human monocytes were incubated for 24, 48, and 72 hours with IL-4 (10 ng/mL) with or without an IgE-anti-IgE stimulation. We evaluated CD23 expression by immunocytochemistry and 15(S)-HETE release by HPLC and RIA. To prove that the increase in 15(S)-HETE release was due to the effect of IL-4 on CD23, we performed experiments with an anti-CD23 blocking mAb. CD23 expression and 15(S)-HETE release were significantly increased by IL-4, reaching a peak after 72 hours (P <.02). After passive sensitization with human IgE and anti-IgE challenge, IL-4-stimulated monocytes released higher amounts of 15(S)-HETE than IL-4-unstimulated monocytes (P <.02). Pretreatment with the anti-human B-cell CD23 MHM6 mAb caused a dose-dependent inhibition of 15(S)-HETE release. This study shows that immunologic challenge of IL-4-treated, passively sensitized monocytes results in a CD23-dependent additional increase of 15(S)-HETE release, indicating the presence of a synergistic effect of IL-4 on CD23 expression and 15(S)-HETE production.


A split-face comparison of fractional erbium: YAG laser plus Kligman's formula vs. Kligman's formula monotherapy for facial melasma.
Melasma is a chronic hyperpigmentation disorder. Although several treatment methods are used for patients, it remains a challenging problem for physicians. Erbium-YAG laser is one of the laser treatment methods that proved its efficacy in melasma treatment. We aimed to compare the efficacy of combining the fractional Er: YAG laser and Kligman's formula with Kligman's formula alone in the treatment of melasma. Twenty female patients with bilateral melasma were randomly treated in a split-face controlled manner with a fractional Er: YAG laser followed by Kligman's formula on one side and Kligman's formula on the other side. All patients received three laser sessions with four-week intervals. The efficacy of treatments was determined through photographs, Visioface, and Melasma Area Severity Index (MASI) score, all performed at baseline and three months after the end of laser sessions. Fractional Er: YAG laser and Kligman's formula showed a significant decrease in MASI score than Kligman's formula alone (P = 0.005). There was a significant decrease in cheek Visioface score on Er: YAG laser and Kligman's formula vs Kligman's formula (P = 0.02). However, the Patient Global Assessment Scale of both sides was not statistically significant (P = 0.23). The combination of Fractional Er: YAG laser with Kligman's formula is an effective treatment method for melasma.


Enhanced recovery after microdiscectomy: reductions in opioid use, length of stay and cost.
Enhanced recovery after surgery (ERAS) protocols are widely used worldwide. Recently, studies of the ERAS program in spinal surgery subspecialties have been reported. The aim of this study was to evaluate the impacts of ERAS in minimally invasive microdiscectomy (MD) surgery. This was a retrospective cohort study of patients undergoing MD at a single center. From March 2018 to March 2021, 286 patients were in the ERAS group. A total of 140 patients from March 2017 to February 2018 were in the conventional group. The outcomes included length of stay (LOS), the postoperative numeric rating scale (NRS), complications, 30-day readmission rate, 30-day reoperation rate and cost. Moreover, perioperative factors were also evaluated. Compared with the conventional group, the LOS and cost were reduced in the ERAS group. There were no significant differences in the NRS, complication rate, 30-day readmission or reoperation rates between the groups. Furthermore, postoperative drainage volume, and postoperative opioid use were lower in the ERAS group. The ERAS protocol for MD surgery reduces LOS, cost and opioid use and accelerates patient recovery.


The Society of Thoracic Surgeons General Thoracic Surgery Database: 2022 Update on Outcomes and Research.
The Society of Thoracic Surgeons General Thoracic Surgery Database (STS GTSD) remains the largest and most robust thoracic surgical database in the world. Participating sites receive risk-adjusted performance reports for benchmarking and quality improvement initiatives. The GTSD also provides several mechanisms for high-quality clinical research using data from 274 participant sites and 781,000 procedures since its inception in 2002. Participant sites are audited at random annually for completeness and accuracy. Over the last year and a half, the GTSD Task Force continued to refine the data collection process, implementing an updated data collection form in July 2021, ensuring high data fidelity while minimizing data entry burden. In addition, the STS Workforce on National Databases has supported a robust GTSD-based research program, which led to eight scholarly publications in 2021. This report provides an update on volume trends, outcomes, and database initiatives as well as a summary of research productivity resulting from the GTSD over the preceding year.


Updates in the Management of Perioperative Vasoplegic Syndrome.
Vasoplegic syndrome occurs relatively frequently in cardiac surgery, liver transplant, major noncardiac surgery, in post-return of spontaneous circulation situations, and in pateints with sepsis. It is paramount for the anesthesiologist to understand both the pathophysiology of vasoplegia and the different treatment strategies available for rescuing a patient from life-threatening hypotension.


Lupus mastitis and antiphospholipid syndrome treated with anticoagulation and immunosuppression: a case report.
Systemic lupus erythematosus is an autoimmune disease that can have cutaneous and systemic manifestations. Lupus panniculitis, also known as lupus mastitis, is a subset of chronic cutaneous lupus erythematosus that involves inflammation of the subcutaneous fat. The pathogenesis of lupus mastitis is not fully understood. Diagnosis involves a combination of skin manifestations, imaging, and pathologic confirmation. Treatment typically includes steroids and antimalarials, with more severe disease requiring additional immunosuppressive medications. This report highlights a case of lupus mastitis treated with rituximab and a possible relationship between this disease process and thrombotic disease. A 48-year-old African American female with systemic lupus erythematosus and antiphospholipid syndrome presented with new breast lesion. Mammography revealed calcifications and increased density with coarse trabecular pattern. Breast biopsy showed features of cutaneous lupus and occlusive vasculopathy. The patient was diagnosed with lupus mastitis and treated with anticoagulation, rituximab, mycophenolate mofetil, and quinacrine with resolution of her symptoms. This patient experienced improvement in her breast symptoms with combination therapy including rituximab. There are only two other cases reported in literature of patients with lupus mastitis responding to rituximab, highlighting the possible role of B cell depleting therapy for those who have contraindications to standard treatments for lupus mastitis. While the pathophysiology of lupus mastitis is thought to be immune driven, some literature suggests that associated thrombosis commonly seen may be due to a physiologic overlap similar to antiphospholipid syndrome. The possible relationship between antiphospholipid syndrome and lupus mastitis and the use of antiplatelet and anticoagulation therapy is discussed and may warrant further investigation.


Biomechanical comparison of an angular stable plate with augmented and non-augmented screws in a newly developed shoulder test bench.
The proximal humeral fracture is one of the most common fractures. Although there are a number of treatment options available, the clinical outcomes in geriatric patients are still unsatisfactory. Therefore, the aim of this study was to investigate the biomechanical behaviour of an angular stable plate with either augmented or non-augmented screws using two different fracture models in a shoulder test bench with active muscle forces. Six paired fresh-frozen humeri were loaded into a shoulder test bench simulating ab- and adduction between 15 and 45° induced by active muscle forces. The bone mineral density was measured by a quantitative CT. A two-part fracture model (stable and an unstable) was used to investigate the different biomechanical behaviours of the PHILOS plate, either utilising cannulated screws, allowing in situ augmentation, or without utilising augmented screws. Four screws were augmented with 0.5ml PMMA cement. The in vitro-measured resulting forces in the glenoid fossa were comparable to the in vivo forces generated in shoulder arthroplasties. Under stable conditions, the per cycle motion and varus impaction tilting showed no significant difference. In the unstable state, the augmented group showed a maximum of 0.81° per cycle motion and a maximum varus impaction of -1.46° compared to the non-augmented maximum of 2.31° per cycle motion and maximum varus impaction of -4.26° (P<0.05). In an unstable fracture model under dynamic testing conditions, augmentation leads to a decreased per cycle motion and varus impaction of the humeral head.


Association between polymorphism of the vitamin D metabolism gene CYP27B1 and HLA-B27-associated uveitis. Is a state of relative immunodeficiency pathogenic in HLA B27-positive uveitis?
Polymorphisms of the vitamin D metabolism gene CYP27B1 showed associations with multiple autoimmune diseases. The aim of this study was to investigate a possible association between the rs703842 A>G polymorphism of the CYP27B1 gene and HLA-B27-associated uveitis. One hundred fifty-nine patients with HLA-B27-associated uveitis, 138 HLA-B27-negative controls and 100 HLA-B27-positive controls were recruited for this retrospective case-control study. Main outcome parameters were genotype distribution and allelic frequencies determined by polymerase chain reaction. Carriers of the rs703842G allele were found significantly more often in patients with HLA-B27-associated uveitis than in HLA-B27-positive controls (p = 0.03). Between patients and HLA-B27-negative controls no significant difference in the genotype distribution of the rs703842 A>G polymorphism was found (p = 0.97). Our data suggest that the rs703842 A>G polymorphism may play a role in HLA-B27-associated uveitis.


Clinical evaluation of insecticide-impregnated tags attached to chains and used as backrubbers for control of Haematobia irritans.
Fenvalerate and permethrin insecticide tags were tested for horn fly (Haemotobia irritans) control. Three fenvalerate-impregnated ear tags attached to a chain and used as a backrubber controlled horn flies on steers for 8 weeks, and six tags provided 18 weeks control. Ten tags impregnated with permethrin failed to control horn flies. The choice of insecticide in tags attached to chains and used as backrubbers for horn fly control may be important, as fenvalerate and permethrin (both pyrethroids) varied in effectiveness.


QSAR based docking studies of marine algal anticancer compounds as inhibitors of protein kinase B (PKBβ).
Marine algae are prolific source of bioactive secondary metabolites and are found to be active against different cancer cell lines. QSAR studies will explicate the significance of a particular class of descriptor in eliciting anticancer activity against a cancer type. Marine algal compounds showing anticancer activity against six different cancer cell lines namely MCF-7, A431, HeLa, HT-29, P388 and A549 taken from Seaweed metabolite database were subjected to comprehensive QSAR modeling studies. A hybrid-GA (genetic algorithm) optimization technique for descriptor space reduction and multiple linear regression analysis (MLR) approach was used as fitness functions. Cell lines HeLa and MCF-7 showed good statistical quality (R(2)∼0.75, Q(2)∼0.65) followed by A431, HT29 and P388 cell lines with reasonable statistical values (R(2)∼0.70, Q(2)∼0.60). The models developed were interpretable, with good statistical and predictive significance. Molecular descriptor analyses revealed that Baumann's alignment-independent topological descriptors had a major role in variation of activity along with other descriptors. Incidentally, earlier QSAR analysis on a variety of chemically diverse PKBα inhibitors revealed Baumann's alignment-independent topological descriptors that differentiated the molecules binding to Protein kinase B (PKBα) kinase or PH domain, hence a docking study of two crystal structures of PKBβ was performed for identification of novel ATP-competitive inhibitors of PKBβ. Five compounds had a good docking score and Callophycin A showed better ligand efficiency than other PKBβ inhibitors. Furthermore in silico pharmacokinetic and toxicity studies also showed that Callophycin A had a high drug score (0.85) compared to the other inhibitors. These results encourages discovering novel inhibitors for cancer therapeutic targets by screening metabolites from marine algae.


Magnetic resonance angiography (MRA) in renally impaired patients: when and how.
Magnetic resonance angiography (MRA) and NSF in renally impaired patients have a close relationship due to the frequent coincidence of vascular and renal pathologies, the relatively large amount of contrast media applied and the delayed excretion. The date of the first NSF cases described in literature falls into the development of multi-stationary MRA--an investigation that requested multiple bolus injections or one large bolus of the contrast agent. It is therefore easily understood that NSF was regarded initially as possible complication of MRA. A review on the history of MRA is presented and various techniques for MRA are described. While many neuroradiological indications can be solved by native MRA, most angiographic indications throughout the body rely on the application of intravenous contrast agents. The paper discusses options for alternative methods in vascular imaging and offers guidelines for patients with renal impairment. NSF must always be balanced versus the outcome of an investigation, respectively versus the outcome of a denied MRA. Moreover, in patients with chronic kidney disease (CKD) and a proper justification for a vascular investigation, neither CT angiography nor DSA should replace MRA. Restrictions in contrast media dose for CKD patients are mandatory and obviously reduce the risk of NSF. Gadolinium-based contrast agents with lower stability are now contraindicated in patients with reduced renal function. The role of blood pool agents is under evaluation. Since the awareness of the new disease grew over the last year, radiologists were able to reduce the number of newly diagnosed NSF cases by more careful consideration of contrast application and agent in renally impaired patients, which gives hope that NSF can be avoided by respecting some easy rules.


Ochratoxin A Dietary Exposure of Ten Population Groups in the Czech Republic: Comparison with Data over the World.
Ochratoxin A is a nephrotoxic and renal carcinogenic mycotoxin and is a common contaminant of various food commodities. Eighty six kinds of foodstuffs (1032 food samples) were collected in 2011-2013. High-performance liquid chromatography with fluorescence detection was used for ochratoxin A determination. Limit of quantification of the method varied between 0.01-0.2 μg/kg depending on the food matrices. The most exposed population is children aged 4-6 years old. Globally for this group, the maximum ochratoxin A dietary exposure for "average consumer" was estimated at 3.3 ng/kg bw/day (lower bound, considering the analytical values below the limit of quantification as 0) and 3.9 ng/kg bw/day (middle bound, considering the analytical values below the limit of quantification as 1/2 limit of quantification). Important sources of exposure for this latter group include grain-based products, confectionery, meat products and fruit juice. The dietary intake for "high consumers" in the group 4-6 years old was estimated from grains and grain-based products at 19.8 ng/kg bw/day (middle bound), from tea at 12.0 ng/kg bw/day (middle bound) and from confectionery at 6.5 ng/kg bw/day (middle bound). For men aged 18-59 years old beer was the main contributor with an intake of 2.60 ng/kg bw/day ("high consumers", middle bound). Tea and grain-based products were identified to be the main contributors for dietary exposure in women aged 18-59 years old. Coffee and wine were identified as a higher contributor of the OTA intake in the population group of women aged 18-59 years old compared to the other population groups.


First experience with Walrus balloon guide catheter in a whole-body flow model.
Flow arrest using a balloon guide catheter (BGC) in mechanical thrombectomy (MT) due to large vessel occlusion has been associated with better outcomes. Known limitations of currently commercially available BGCs are incompatibility with large bore aspiration catheters (AC) and lack of distal flexibility. Walrus presents variable stiffness and compatibility with large bore AC. The goal of this study is to describe the first experience with Walrus in a realistic stroke simulation model. A full-length modular vascular model under physiological conditions was used. 8F+-Walrus inner-diameter (ID) 0.087in 95 cm combined with 6F-Sofia AC ID 0.070in 131 cm and an 8F-Flowgate2 BGC ID 0.084in 95 cm with a 5F-Sofia AC ID 0.055in 125 cm were used to perform aspiration MT. User surveys, access to target and occlusion site, technique, time of delivery, anatomical change, and catheter kick-back were assessed. Seven neuroradiologists with average of 10 years-experience in MT performed primary aspiration using the above-mentioned combinations in three different anatomies (N = 41). All operators would likely (29%) or very likely (71%) use again Walrus in combination with large bore AC and the majority (86%) found its navigability easier than with other BGCs. Time to reach final BGC position and catheter kick-back did not differ significantly among anatomies or catheter combinations (p > 0.05). However, Walrus was more likely to reach ICA petrous segment (p < 0.05) and intracranial occlusion with AC (p < 0.01). The Walrus combined with large bore AC presented significantly better distal access and navigability for primary aspiration in an in vitro stroke model.


[A study on DNA damage of mouse livers induced by methylmercury].
To study the DNA damage induced by methylmercury (MeHg) in mouse hepatocytes. The single cell gel electrophoresis (SCGE) was used to study the DNA damage of mouse hepatocytes when treated with different doses in vivo and in vitro. After treated with high, middle and low doses of MeHg for 12 h in vivo (i.p.), the proportion of DNA damage was increased and the ratio of living cells was decreased; and both effects showed significantly dose-effect relationships. Similar effects were found when different MeHg doses were administered to hepatocytes in vitro for 1 h. MeHg induces DNA damage in mouse hepatocytes.


Anatomic Factors Contributing to External Iliac Artery Endofibrosis in High-Performance Athletes.
External iliac artery endofibrosis (EIAE) classically presents in cyclists with intimal thickening of the affected arteries. We investigated possible anatomical predisposing factors including psoas muscle hypertrophy, arterial tortuosity, inguinal ligament compression, and arterial kinking via a case-control comparison of symptomatic and contralateral limbs. All patients with unilateral EIAE treated surgically at our institution were reviewed. Each patient's symptomatic side was compared with their contralateral side using paired t-tests. Psoas hypertrophy was quantified by the transverse cross-sectional area (CSA) at L4, L5, and S1 vertebral levels, and inguinal ligament compression was measured as the anterior-posterior distance between the inguinal ligament and underlying bone. Tortuosity index for diseased segments and arterial kinking were measured on TeraRecon. Of 33 patients operated on for EIAE from 2004 to 2021, 27 with available imaging presented with unilateral disease, more commonly left-sided (63%). Most (96%) had external iliac involvement and 26% had ≥2 segments affected: 19% common iliac artery, 15% common femoral artery. The symptomatic limb had greater mean L5 psoas CSA (1,450 mm2 vs. 1,396 mm2, mean difference 54 mm2, P = 0.039). There were no significant differences in L4 or S1 psoas hypertrophy, tortuosity, inguinal ligament compression, or arterial kinking. 63% underwent patch angioplasty, and 85% underwent additional inguinal ligament release. 84% reported postoperative satisfaction, which was associated with a greater difference in psoas hypertrophy at L4 (P = 0.022). Psoas muscle hypertrophy is most pronounced at L5 and is associated with symptomatic EIAE. Preferential hypertrophy of the affected side correlates with improved outcomes, suggesting psoas muscle hypertrophy as a marker of disease severity.


Identification of novel RNA viruses in alfalfa (Medicago sativa): an Alphapartitivirus, a Deltapartitivirus, and a Marafivirus.
Genomic RNA molecules of plant RNA viruses are often co-isolated with the host RNAs, and their sequences can be detected in plant transcriptome datasets. Here, an alfalfa (Medicago sativa) transcriptome dataset was analyzed and three new RNA viruses were identified, which were named Medicago sativa alphapartitivirus 1 (MsAPV1), Medicago sativa deltapartitivirus 1 (MsDPV1), and Medicago sativa marafivirus 1 (MsMV1). The RNA-dependent RNA polymerases of MsAPV1, MsDPV1, and MsMV1 showed about 68%, 58%, and 46% amino acid sequence identity, respectively, with their closest virus species. Sequence similarity and phylogenetic analyses indicated that MsAPV1, MsDPV1, and MsMV1 were novel RNA virus species that belong to the genus Alphapartitivirus of the family Partitiviridae, the genus Deltapartitivirus of the family Partitiviridae, and the genus Marafivirus of the family Tymoviridae, respectively. The bioinformatics procedure applied in this study may facilitate the identification of novel RNA viruses from plant transcriptome data.


Chemotypes of Veillonella lipopolysaccharides.
Lipopolysaccharides (LPS) were isolated by phenol-water extraction from 34 strains of Veillonella, and examined by paper chromatography and colorimetric methods for the presence of neutral sugars, amino sugars and 2-keto-3-deoxy-octonate (KDO). Several preparations were also examined for neutral sugars by gas liquid chromatography. The LPS had in common glucosamine, galactosamine, L-glycero-D-manno-heptose glucose and KDO. Most LPS contained galactose, and a few rhamnose. D-glycero-D-manno-heptose was found in LPS from one of the strains. Based on the sugar composition of the LPS, the Veillonella strains could be classified into four chemotypes.


Cost-Effectiveness of Thrombopoietin Mimetics in Patients with Thrombocytopenia: A Systematic Review.
Thrombopoietin (TPO) mimetics are a potential alternative to platelet transfusion to minimize blood loss in patients with thrombocytopenia. This systematic review aimed to evaluate the cost-effectiveness of TPO mimetics, compared with not using TPO mimetics, in adult patients with thrombocytopenia. Eight databases and registries were searched for full economic evaluations (EEs) and randomized controlled trials (RCTs). Incremental cost-effectiveness ratios (ICERs) were synthesized as cost per quality-adjusted life year gained (QALY) or as cost per health outcome (e.g. bleeding event avoided). Included studies were critically appraised using the Philips reporting checklist. Eighteen evaluations from nine different countries were included, evaluating the cost-effectiveness of TPO mimetics compared with no TPO, watch-and-rescue therapy, the standard of care, rituximab, splenectomy or platelet transfusion. ICERs varied from a dominant strategy (i.e. cost-saving and more effective), to an incremental cost per QALY/health outcome of EUR 25,000-50,000, EUR 75,000-750,000 and EUR > 1 million, to a dominated strategy (cost-increasing and less effective). Few evaluations (n = 2, 10%) addressed the four principal types of uncertainty (methodological, structural, heterogeneity and parameter). Parameter uncertainty was most frequently reported (80%), followed by heterogeneity (45%), structural uncertainty (43%) and methodological uncertainty (28%). Cost-effectiveness of TPO mimetics in adult patients with thrombocytopenia ranged from a dominant strategy to a significant incremental cost per QALY/health outcome or a strategy that is clinically inferior and has increased costs. Future validation and tackling the uncertainty of these models with country-specific cost data and up-to-date efficacy and safety data are needed to increase the generalizability.


Photodynamic therapy in colorectal cancer treatment: the state of the art in clinical trials.
Photodynamic therapy (PDT) is used in many different oncologic fields. Also in gastroenterology, where have been a few attempts to treat both the premalignant lesion and advanced colorectal cancer. This review aims to give a general overview of the PDT application to colorectal cancer in the field of clinical trials to emphasize its curative, and insufficiently exploited potential. Literature on PDT for colorectal cancer with the following medical subject headings search terms: colorectal cancer, photodynamic therapy, clinical trials was reviewed. The articles were selected by their relevance to the topic. There are many positive and promising trial results from I to II/III phase for the use of PDT in colorectal cancer both in less advanced tumors as well as in the palliative therapy of advanced lesions. PDT seems to be a safe and a feasible treatment option for colorectal cancer. Theoretical assumptions confirmed by many results of preclinical studies taking into consideration an increasing number of analyzed clinical trials, should lead to the development of optimized standards by using PDT in colorectal cancer treatment.


The PPAR alpha gene is associated with triglyceride, low-density cholesterol and inflammation marker response to fenofibrate intervention: the GOLDN study.
As a peroxisome proliferator-activated receptor alpha (PPARα) agonist, fenofibrate favorably modulates dyslipidemia and inflammation markers, which are associated with cardiovascular risk. To determine whether variation in the PPARα receptor gene was associated with lipid and inflammatory marker response, we conducted a 3-week trial of fenofibrate in 861 men and women. Mixed linear models that controlled for age and sex, as well as family pedigree and study center, were constructed using single-nucleotide polymorphisms (SNPs) in the PPARα gene as predictors and changes in fasting triglycerides (TGs), cholesterol and inflammatory markers as outcomes. Significant associations with low-density cholesterol and interleukin-2 (P<0.001) responses to fenofibrate were found. Although there were suggestive associations with tumor necrosis factor-alpha and TG responses (P<0.05), these did not survive the correction for multiple testing. We conclude that variants in the PPARα gene may contribute to future pharmacogenomic paradigms seeking to predict fenofibrate responders from both an anti-dyslipidemic and anti-inflammatory perspective.


Immunostimulatory effect of methanol extract of Curculigo orchioides on immunosuppressed mice.
The methanol extract of rhizomes of Curculigo orchioides Gaertn. (Amaryllidaceae) holds potential as a protective agent against cytotoxic drugs. The extract when studied on humoral and cell mediated immunity in normal, as well as cyclophosphamide-induced immunosuppressed mice produced an increase in humoral antibody (HA) titre, delayed type hypersensitivity (DTH) and levels of WBC in a dose dependent manner.


Malaria: Global progress 2000 - 2015 and future challenges.
2015 was the target year for malaria goals set by the World Health Assembly and other international institutions to reduce malaria incidence and mortality. A review of progress indicates that malaria programme financing and coverage have been transformed since the beginning of the millennium, and have contributed to substantial reductions in the burden of disease. Investments in malaria programmes increased by more than 2.5 times between 2005 and 2014 from US$ 960 million to US$ 2.5 billion, allowing an expansion in malaria prevention, diagnostic testing and treatment programmes. In 2015 more than half of the population of sub-Saharan Africa slept under insecticide-treated mosquito nets, compared to just 2 % in 2000. Increased availability of rapid diagnostic tests and antimalarial medicines has allowed many more people to access timely and appropriate treatment. Malaria incidence rates have decreased by 37 % globally and mortality rates by 60 % since 2000. It is estimated that 70 % of the reductions in numbers of cases in sub-Saharan Africa can be attributed to malaria interventions. Reductions in malaria incidence and mortality rates have been made in every WHO region and almost every country. However, decreases in malaria case incidence and mortality rates were slowest in countries that had the largest numbers of malaria cases and deaths in 2000; reductions in incidence need to be greatly accelerated in these countries to achieve future malaria targets. Progress is made challenging because malaria is concentrated in countries and areas with the least resourced health systems and the least ability to pay for system improvements. Malaria interventions are nevertheless highly cost-effective and have not only led to significant reductions in the incidence of the disease but are estimated to have saved about US$ 900 million in malaria case management costs to public providers in sub-Saharan Africa between 2000 and 2014. Investments in malaria programmes can not only reduce malaria morbidity and mortality, thereby contributing to the health targets of the Sustainable Development Goals, but they can also transform the well-being and livelihood of some of the poorest communities across the globe.


The tempo of puberty and its relationship to adolescent health and well-being: A systematic review.
Emerging evidence suggests that pubertal tempo, that is rate of passage through puberty, has relevance to adolescent mood and behaviour. However, its wider health and developmental significance remain unclear. This systematic review sought to clarify the relationship of pubertal tempo to indicators of health and development, and to document tempo definitions and pubertal durations reported in the literature. Eight electronic databases were searched from earliest record to July 2018. Study eligibility: healthy participants; age 8-21 years; ≥2 longitudinal measures of puberty; analysis of tempo against a health or developmental indicator. Thirty-eight studies met eligibility, and these reported on diverse tempo definitions and seven health- and development-related domains. Data sets with varying tempo definitions converged on an association of rapid pubertal progression to: (a) higher adiposity during childhood and adolescence in both sexes; and (b) lower psychosocial well-being in adolescent males. Later thelarche unanimously predicted faster progression to menarche in females, but this compensation was largely undetected when alternate definitions of pubertal timing and/or tempo were used. Duration of puberty ranged from 2.5-4.1 years. Pubertal tempo may be clinically relevant when considering trajectories of adiposity and psychosocial well-being among adolescents, especially males. Consensus on the definition of tempo would facilitate between-study comparisons.


Risks of loosening of a prosthetic glenoid implanted in retroversion.
Osteoarthritis of the shoulder is frequently associated with posterior glenoid wear, which may be difficult to correct during shoulder arthroplasty. This study was designed to evaluate the risks that a prosthetic glenoid implanted in retroversion will loosen. The scapula, the humerus, the rotator cuff, and a total shoulder prosthesis were reconstructed with a 3-dimensional finite element model. The glenoid was placed in 5 different angles of retroversion (0 degrees , 5 degrees , 10 degrees , 15 degrees , and 20 degrees ). Location of the glenohumeral contact point, articular pressure, bone and cement stress, and micromotion around the glenoid implant were calculated during internal and external rotation. Glenoid retroversion induced a posterior displacement of the glenohumeral contact point during internal and external rotation, inducing a significant increase of stress within the cement mantel (+326%) and within the glenoid bone (+162%). Furthermore, a major increase of micromotion was measured at the bone-cement interface (+706%). According to this study, glenoid retroversion exceeding 10 degrees should be corrected during total shoulder arthroplasty. If the correction is impossible, not replacing the glenoid should be considered.


Predictors of adolescent breakfast consumption: longitudinal findings from Project EAT.
To identify predictors of breakfast consumption among adolescents. Five-year longitudinal study Project EAT (Eating Among Teens). Baseline surveys were completed in Minneapolis-St. Paul schools and by mail at follow-up by youth (n = 800) transitioning from middle to high school. Linear regression models examined associations between baseline predictors and follow-up breakfast consumption. Frequency of breakfast consumption at follow-up was positively associated with baseline breakfast consumption and inversely associated with baseline weight concerns (P < .01). Perceptions of being too rushed in the morning to eat a healthful breakfast were associated with lower breakfast frequency 5 years later among girls (P < .01). After adjusting for baseline breakfast consumption, none of the associations with predictor variables remained statistically significant. Early adolescence is an important time to establish regular breakfast consumption. Interventions aimed at increasing breakfast consumption should include messages about healthful weight management and ideas for quick, healthful breakfasts.


Low appendicular skeletal muscle index increases the risk of carotid artery plaque in postmenopausal women with and without hypertension/hyperglycemia: a retrospective study.
This study aimed to evaluate whether the low appendicular skeletal muscle index (ASMI) is closely associated with the risk of carotid artery plaque (CAP) in postmenopausal women with and without hypertension/hyperglycemia stratified by body mass index (BMI) categories. A total of 2048 Chinese postmenopausal women aged 40-88 years were eventually enrolled in this retrospective study. Skeletal muscle mass was estimated by using segmental multifrequency bioelectrical impedance analysis. ASMI was defined as follows: appendicular skeletal muscle mass(kg)/[height(m)]2. CAP was assessed by B-mode ultrasound. We explored the association between ASMI quartiles or low skeletal muscle mass and the risk of CAP by using multivariate-adjusted logistic regression models. A potential nonlinear relationship was also tested using restricted cubic spline regression. CAP was observed in 289/1074 (26.9%) normal-weight and 319/974 (32.8%) overweight/obese postmenopausal women. Individuals with CAP had significantly lower ASMI values than those without (P < 0.001). The ASMI value also showed a linear relationship with the CAP risk in postmenopausal women stratified by BMI category (Pfor non-linearity > 0.05). In comparison with the highest ASMI quartile, the lowest ASMI quartile was significantly associated with a high risk of CAP development in non-hypertensive individuals with normal weight (odds ratio [OR] = 2.43; 95% confidence interval [CI]: 1.44 ~ 4.12) or overweight/obesity (OR = 4.82, 95% CI: 2.79 ~ 8.33), hypertensive individuals with normal weight (OR = 5.90, 95% CI: 1.46 ~ 11.49) or overweight/obesity (OR = 7.63, 95% CI: 1.62 ~ 35.86), non-hyperglycemic individuals with normal weight (OR = 2.61, 95% CI: 1.54 ~ 4.43) or overweight/obesity (OR = 2.94, 95% CI: 1.84 ~ 4.70), and hyperglycemic individuals with normal weight (OR = 6.66, 95% CI: 1.08 ~ 41.10) or overweight/obesity (OR = 8.11, 95% CI: 2.69 ~ 24.49). Moreover, low skeletal muscle was independently associated with the risk of CAP in postmenopausal women, regardless of the BMI category. ASMI was inversely associated with the risk of CAP development in postmenopausal women, especially in patients with high blood sugar and/or hypertension, indicating that skeletal muscle mass maintenance may contribute to prevention of CAP in postmenopausal women.