Surgical treatment of severe angular kyphosis with myelopathy: anterior and posterior approach with pedicle screw instrumentation.
Retrospective study. To evaluate the outcomes of anterior decompression and fusion followed by posterior instrumented fusion using pedicle screws without intentional correction of severe angular kyphosis deformity with myelopathy. Treatment of severe angular kyphosis with myelopathy is extremely difficult and dangerous. Although surgical circumferential spinal osteotomy via a single posterior approach has been reported in several studies, serious neurologic complications are a possible outcome. Among 51 patients surgically treated for angular kyphosis from 1988 to 2004, 16 patients (follow-up period, 32-168 months; mean, 72 months) with severe (>70 degrees ) angular kyphosis with progressive myelopathic symptoms underwent anterior decompression and fusion, followed by posterior pedicle screw instrumentation and bone graft without attempted correction of the deformity. Radiologic assessment, clinical findings including pain and daily activity scores, and neurologic status using the modified Frankel grade were analyzed before surgery and at the last follow-up. Curve progression or nonunion did not occur in any of the cases. The mean pain and daily activity score were 3.1 and 2.3 before surgery and 4.7 and 4.2 after surgery, respectively. The modified Frankel grade indicated that every patient but one had improved neurologic function by one or more grades. Nine (75%) of 12 patients with ankle clonus, 10 (71%) of 14 patients with Babinski sign, and 6 (55%) of 11 patients with bowel and bladder dysfunction showed full improvement at the last follow-up. Postoperative complications included 1 screw pullout case and 2 infection cases which resolved without incidence. Anterior decompression and fusion followed by posterior pedicle screw instrumentation and fusion without correction effectively improved neurologic symptoms and halted progression of kyphotic deformity in cases of severe angular kyphosis with myelopathy.


Adherence to Benzathine Penicillin G Secondary Prophylaxis and Its Determinants in Patients with Rheumatic Heart Disease at a Cardiac Center of an Ethiopian Tertiary Care Teaching Hospital.
Benzathine penicillin G (BPG) monthly administration is the most effective method for secondary prophylaxis against acute rheumatic fever (ARF). BPG's efficacy largely depends on adherence to treatment. This study was aimed at assessing adherence to BPG prophylaxis and its determinants among adult patients with rheumatic heart disease. An institutional cross-sectional study design was used. One hundred and forty-five patients receiving monthly BPG at the Adult Cardiac Clinic of Tikur Anbessa Specialized Hospital (TASH) were interviewed. Their 1-year BPG prophylaxis administration record was also reviewed. The rate of adherence to BPG injection was determined by calculating the percentage of the administered drug from the total expected doses. Data were entered and analyzed using Statistical Package for Social Sciences (SPSS) software version 25. Both descriptive and logistic regression analyses were computed to describe different variables and assess factors associated with adherence, respectively. A p-value <0.05 was used to declare association. Among a total of 145 study participants involved, the majority (76.6%) of them had been receiving BPG for the last 10 years. The average adherence rate to monthly BPG injection was 80.60% with a range of 0% to 100%. However, only 101 (69.7%) of participants were taking ≥80% of their prescribed monthly BPG prophylaxis doses. Study participants with informal education 1.10 (0.023-46.96) and secondary school education 0.89 (0.10-8.11) were more and less likely to adhere to BPG injection, respectively, when compared with those who attended higher education programs. The regression analysis showed patients who were not admitted to the hospital (AOR: 26.22; CI: 2.55-269.70; p=0.006) and once admitted patients (AOR: 50.08; CI: 2.87-873.77; p=0.007) were more likely to adhere to their BPG injections than those admitted twice or more. The study participants who waited until the next appointment were also less adherent (AOR: 0.02; CI: 0.00-0.13; p=0.000) than those who went a few days later for receiving the missed/late dose. The adherence rate to BPG injection among RHD patients was found to be high (80.60%). Patients' admission status and their action on missed and/or late doses were found to be important determinants of adherence in this study.


Anti-Hu paraneoplastic syndrome presenting with brainstem-cerebellar symptoms and Lambert-Eaton myasthenic syndrome.
Paraneoplastic syndrome (PNS) with two distinct neurological features was reported in a 50-year-old man who presented initially with vertigo, ataxia, dysarthria, tremor, confusion, urinary retention and hypotension. Pulmonary X-ray findings, class IIIb sputum cytology, and positive anti-Hu antibody established the diagnosis of PNS associated with small-cell lung cancer (SCLC). Two cycles of combined chemotherapy resulted in shrinkage of the lung tumor together with complete recovery of neurological symptoms and disappearance of anti-Hu antibody. Relapse of SCLC 4 months later with re-appearance of anti-Hu antibody required additional chemotherapy and irradiation. Eight months later, when multiple liver metastasis of SCLC was noticed, muscular weakness with positive waxing phenomenon compatible with Lambert-Eaton myasthenic syndrome (LEMS) developed. Postmortem examinations revealed residual SCLC in the primary lung, and massive liver metastasis with generalized lymph node involvement, but no tumors in the CNS. In the cerebellum, there was a slight loss of Purkinje cells with torpedo formation but without apparent lymphocytic infiltration. The present PNS was unique in that the relapse of SCLC was accompanied by the appearance of anti-Hu antibody, and that initial signs of brainstem-cerebellar symptoms, encephalopathy and autonomic failure were replaced by LEMS coinciding with the tumor recurrence.


Public knowledge, belief, and preventive practices regarding dengue: Findings from a community-based survey in rural Bangladesh.
Dengue fever, the most prevalent mosquito-borne viral infection, is a recurrent public health threat in Bangladesh. Despite the government's efforts, dengue fever outbreaks are on the upswing, and people's knowledge and preventive practices regarding the disease at the rural community level are unclear. The objective of this study was to assess the level of knowledge, belief and preventive practices regarding dengue and associated factors among community people from rural Bangladesh. A cross-sectional survey was conducted involving 401 people using a convenient sampling technique from three unions of Savar from August to September 2021. Participants' responses were collected through face-to-face interviews using a pre-tested structured questionnaire that included information related to socio-demographics, dengue-related knowledge, preventive practices, as well as the health belief model (HBM) constructs. Multiple linear regression analysis was performed to determine the factors associated with the knowledge and preventive practices of dengue. Overall, participants (mean age = 33.47 ± 12.96 years; age range = 18-75 years) correctly answered 66.15% of the knowledge questions regarding dengue. Higher education, travel to dengue-risk regions, and self-efficacy under the HBM construct were all shown to be strongly associated with dengue knowledge. Regarding HBM constructs, about 80% of the participants perceived dengue as dangerous, but less than half (41.4%) believed themselves susceptible to dengue. Considering perceived barriers, 73.07% of the participants believed their residential area was not suitable for Aedes mosquito breeding. Nearly all (93.52%) believed they always kept their surrounding area clean as part of self-efficacy. Moreover, on average participants engaged in 53.69% of all dengue preventive practices. Being older, female, having a higher education, being a service holder, having a good quality of house structure, and perceived susceptibility as well as self-efficacy under the HBM construct were all factors in participants' dengue prevention activities. Participants' dengue preventative practices were shown to be significantly influenced by their knowledge. The findings of this study found a moderate level of knowledge regarding dengue among the community people. Despite having good practices in several aspects of dengue prevention among the participants, the overall score was not sufficient. This suggests that there is a pressing need for expanded education outreach aimed at increasing public awareness of dengue and encourage preventive practices within rural communities in Bangladesh.


Quality, oxidative markers and DNA damage (DNA) fragmentation of red deer thawed spermatozoa after incubation at 37 °C in presence of several antioxidants.
Antioxidants may be useful for supplementing sperm extenders. We have tested dehydroascorbic acid (DHA), TEMPOL, N-acetyl-cysteine (NAC) and rutin on epididymal spermatozoa from red deer, during incubation at 37 °C. Cryopreserved spermatozoa were thawed, washed and incubated with 1 mM or 0.1 mM of each antioxidant, including oxidative stress (Fe(2+)/ascorbate). Motility (CASA and clustering of subpopulations), viability, mitochondrial membrane potential, and acrosomal status were assessed at 2 and 4 h. Lipoperoxidation, intracellular reactive oxygen species (ROS) and DNA damage (DNA) status (TUNEL) were checked at 4 h. Oxidative stress increased ROS, lipoperoxidation and DNA damage. Overall, antioxidants negatively affected motility and physiological parameters. Only DHA 1 mm protected motility, increasing the fast and progressive subpopulation. However, it had a detrimental effect on acrosomal and DNA status, in absence of oxidative stress. Tempol and rutin efficiently reduced lipoperoxidation, ROS, and DNA damage in presence of oxidative stress. NAC was not as efficient as TEMPOL or rutin reducing lipoperoxidation or protecting DNA, and did not reduce ROS, but its negative effects were lower than the other antioxidants when used at 1 mm, increasing the subpopulation of hyperactivated-like spermatozoa at 2 h. Our results show that these antioxidants have mixed effects when spermatozoa are incubated at physiological temperatures. DHA may not be suitable because of prooxidant effects, but TEMPOL, NAC and rutin may be considered for cryopreservation trials. In general, exposure of red deer spermatozoa to these antioxidants should be limited to low temperatures, when only protective effects may develop.


Evaluation of a novel dry eye model induced by oral administration of finasteride.
Dry eye is a common eye disease, and suitable animal models are indispensable for investigating the pathogenesis and developing treatments for dry eye. The present study was conducted to develop an androgen deficiency dry eye model induced by finasteride, and to evaluate ocular surface status and inflammatory cytokine gene expression in the lacrimal gland using a cytokine antibody array system. The results revealed that the antiandrogenic drug finasteride induced significant tear deficiency, and the histopathology results revealed significant inflammatory cell infiltration in the lacrimal gland. The cytokine antibody array system identified increased B7‑2 (also known as cluster of differentiation 86), interleukin (IL)‑1β, IL‑4, IL‑6, IL‑10, matrix metalloproteinase‑8, Fas ligand, tumor necrosis factor (TNF)‑α and metalloproteinase inhibitor 1 levels in the lacrimal gland of the dry eye model. These cytokines were validated as candidate markers through the use of western blot analysis and reverse transcription‑quantitative polymerase chain reaction. Both analyses confirmed a significant increase in proinflammatory cytokines, including IL‑1β, IL‑6 and TNF‑α, and anti‑inflammatory cytokines, including IL‑4 and IL‑10. The aforementioned data suggested that inflammation in antiandrogenic models resulted from a balance between inflammatory and anti‑inflammatory responses. Thus, direct finasteride administration may produce an applicable model for dry eye mediated by androgen deficiency. In addition, there may be a correlation between sex, steroid deficiency and the inflammatory response. The findings of the present study have provided useful information for the pathogenesis and diagnosis of dry eye mediated by androgen deficiency.


Conformation of N6-methyladenine, a base involved in DNA modification: restriction processes.
Crystal structures of N(6),N(9)-dimethyladenine and N(6)-methyladenine hydrochloride were determined from three-dimensional x-ray diffraction data. The bases assume a conformation in which the N(6)-methyl group blocks one of the hydrogen-bonding sites normally used by adenine to form Watson-Crick pairs with thymine in double-helical DNA. When in this conformation, N(6)-methyladenine residues might alter the secondary structure of DNA. thereby preventing the scission of modified DNA's by restriction enzymes.


[Cerebral hemometabolism: variability in the acute phase of traumatic coma].
to evaluate the interrelationships between cerebral and systemic hemometabolic alterations in patients with severe traumatic brain injury managed according to a standardized therapeutic protocol. prospective, interventional study in patients with traumatic coma. a general Intensive Care Unit in a teaching hospital. twenty-seven patients (21M e 6F), aging 14 - 58 years, with severe acute brain trauma, presenting with three to eight points on the Glasgow Coma Scale, were prospectively evaluated according to a cumulative protocol for the management of acute intracranial hypertension, where intracranial pressure (ICP) and cerebral extraction of oxygen (CEO2) were routinely measured. Hemometabolic interrelationships involving mean arterial pressure (MAP), ICP, arterial carbon dioxide tension (PaCO2), CEO2, cerebral perfusion pressure (CPP) and systemic extraction of oxygen (SEO2) were analyzed. routine therapeutic procedures. no correlation was found between CEO2 and CPP (r = -0.07; p = 0.41). There was a significant negative correlation between PaCO2 and CEO2 (r = -0.24; p = 0.005) and a positive correlation between SEO2 and CEO2 (r = 0.24; p = 0.01). The mortality rate in this group of patients was 25.9% (7/27). 1) CPP and CEO2 are unrelated; 2) CEO2 and PaCO2 are closely related; 3) during optimized hyperventilation, CEO2 and SEO2 are coupled.


Activation of TRPA1 channels by the fatty acid amide hydrolase inhibitor 3'-carbamoylbiphenyl-3-yl cyclohexylcarbamate (URB597).
As a member of the transient receptor potential (TRP) ion channel superfamily, the ligand-gated ion channel TRPA1 has been implicated in nociceptive function and pain states. The endogenous ligands that activate TRPA1 remain unknown. However, various agonists have been identified, including environmental irritants (e.g., acrolein) and ingredients of pungent natural products [e.g., allyl isothiocyanate (ITC), cinnamaldehyde, allicin, and gingerol]. In general, these agents are either highly reactive, nonselective, or not potent or efficacious, significantly limiting their utilities in the study of TRPA1 channel properties and biological functions. In a search for novel TRPA1 agonists, we identified 3'-carbamoylbiphenyl-3-yl cyclohexylcarbamate (URB597), a potent and systemically active inhibitor of fatty acid amide hydrolase (FAAH). This enzyme is responsible for anandamide degradation and therefore has been pursued as an antinociceptive and antiepileptic drug target. Using Ca(2+) influx assays and patch-clamp techniques, we demonstrated that URB597 could activate heterologously expressed human and rat TRPA1 channels, whereas two other FAAH inhibitors (i.e., URB532 and Compound 7) had no effect. When applied to inside-out membrane patches expressing rat TRPA1, URB597 elicited single-channel activities with a unitary conductance of 40 pS. Furthermore, URB597 activated TRPA1 channels endogenously expressed in a population of rat dorsal root ganglion neurons that also responded to ITC. In contrast to its effect on TRPA1, URB597 inhibited TRPM8 and had no effects on TRPV1 or TRPV4. Thus, we conclude that URB597 is a novel agonist of TRPA1 and probably activates the channel through a direct gating mechanism.


Lymphokine-activated killer cells: determination of their tumor cytolytic capacity by a clonogenic microassay using agar capillaries.
A lymphokine activated killer (LAK) cell assay has been developed using a clonogenic microassay in agar-containing capillaries with KB tumor target cells. The assay avoids the problems of the commonly used 51Cr release assay and mimics physiological conditions more closely. The assay procedure has been optimized, resulting in the following conditions: LAK cells are generated by incubating nonadherent peripheral blood mononuclear cells from normal donors with 20 U/ml interleukin-2 for 3 days and cocultivated with 10(4) KB human squamous carcinoma cells/ml at 5:1, 10:1, and 20:1 effector:target ratios for 24 h. The cocultivation mixture is then seeded into agar-containing glass capillaries, allowing undamaged tumor cells to form colonies. The colony number is proportional to the number of tumor cells seeded. The present microassay requires up to 90% less cells and agent quantities compared with other clonogenic assays. It thus provides a useful tool to quantitate LAK cell activity and its alteration by immunomodulatory agents.


The study of gemcitabine in combination with other chemotherapeutic agents as an effective treatment for prostate cancer.
Gemcitabine has demonstrated clinical activity against several common cancers. Our studies examine the ability of gemcitabine, both alone and in combination with other chemotherapeutic agents, to inhibit the in vitro and in vivo growth of several prostate cancer cell lines. Cultures of LNCaP, PC-3 or MLL cells were exposed to either gemcitabine or other appropriate agents for specified amounts of time. Cells were lysed and nuclei counted utilizing a Coulter Counter. For in vivo experiments, animals were injected with 1 x 10(5) MLL cells subcutaneously into the right flank. Animals were treated as indicated for 14 days. Tumors were then excised, weighed and measured. In both human (PC-3 and LNCaP) and rat prostate (MLL) cancer cell lines our studies demonstrated gemcitabine had a strong effect in vitro, with an IC50 of approximately 500 nM in the human lines and 10 nM in MLL cells. In vivo, studies using the Dunning prostate cancer model in Copenhagen rats resulted in a dose response inhibition of tumor growth, with an 80% decrease in tumor size in rats treated with gemcitabine at 10 mg/kg. Our results demonstrated the potent activity of gemcitabine against prostate cancer in the Dunning rat model and suggest the addition of paclitaxel may not aid in this activity.


[Successful treatment of cutaneous leishmaniasis with amphotericin B; a case of unresponsive to pentavalent antimony therapy].
Cutaneous Leishmaniasis (CL) is a skin infection caused by various species of Leishmania parasites, which is transmitted by infected Phlebotomus sandfly bites. Pentavalent antimonials (meglumine antimoniate and sodium stibogluconate) are used for the treatment of adult CL patients as an effective and safe method. Liposomal amphotericin B is an alternative for the treatment of choice in cutaneous leishmaniasis cases which pentavalan antimony contraindicated or unresponsive to pentavalent antimony therapy. In this study, successful treatment with systemic liposomal amphotericin B of a cutaneous leishmaniasis case developing local side effects related both systemic and intralesional meglumine antimonate treatment was presented.


Monoclonal antibodies against the major glycoprotein (gp350/220) of Epstein-Barr virus neutralize infectivity.
Hybridomas producing antibodies against Epstein-Barr virus (EBV) have been produced. They have been screened for production of antibodies against the EBV-associated membrane antigens that are present on EBV producer cell lines. For the screening test we used a double-antibody radioimmunoassay with 125I-labeled rabbit anti-mouse Ig as the second step. Positive cultures were cloned and one such clone, C1, was used for further study. C1 antibody neutralizes EBV in vitro and immunoprecipitates both gp350 (the major glycoprotein in B95-8 cells) and gp220 (the major glycoprotein in P3HR-1 cells) from the membrane antigen complex, suggesting that these molecules are antigenically related. The presence of gp350/220 both on the plasma membrane and in the cytoplasm may be detected by immunofluorescence with C1 antibody.


RETINAL DEEP CAPILLARY ISCHEMIA ASSOCIATED WITH AN OCCLUDED CONGENITAL RETINAL MACROVESSEL.
To report the case of a patient with an occluded congenital retinal macrovessel accompanied by retinal deep capillary ischemia. A 38-year-old woman presented with a 2-day history of a paracentral scotoma of her right eye. Fundus photograph showed a dilated congenital retinal macrovessel with arteriovenous anastomosis, an intravascular white region indicating the thrombus at arteriovenous anastomotic region, and an area of retinal whitening temporal to the fovea. The spectral domain optical coherence tomography images through the area of retinal whitening showed a thickening and highly reflectivity at the level of the inner nuclear layer, which is likely due to the deep capillary ischemia. After 6 weeks, spectral domain optical coherence tomography images through the same area demonstrated a thinning and atrophy of only the inner nuclear layer, and the patient's paracentral scotoma persisted. Acute capillary hemodynamic changes caused deep capillary ischemia. The spectral domain optical coherence tomography showed a highly reflective lesion at the level of the inner nuclear layer in the acute phase.


[Cervico-uterine cancer and age].
A retrospective study of 182 cases of invasive squamous cell carcinoma of the uterine cervix and 133 cases cases of in situ carcinoma, based on histological classification studies and their relation with mean age, during 1985-1994, is reported in a second level Hospital in Rio Blanco, Veracruz, Mexico. The mean age of invasive cervix carcinoma is 50.2 years and the mean age is not the same in the different clinical stages, stage I 45.1 years; stage II 48.6 years; stage III 54.9 years and stage IV 57.4 years. This finding maybe has clinical importance. The mean age of in situ carcinoma is 43.9 years, late when compare with other series in the literature. Plan some considerations about mass screening cervical cancer program in Mexico.


An assessment of the individual and collective effects of variants on height using twins and a developmentally informative study design.
In a sample of 3,187 twins and 3,294 of their parents, we sought to investigate association of both individual variants and a genotype-based height score involving 176 of the 180 common genetic variants with adult height identified recently by the GIANT consortium. First, longitudinal observations on height spanning pre-adolescence through adulthood in the twin sample allowed us to investigate the separate effects of the previously identified SNPs on pre-pubertal height and pubertal growth spurt. We show that the effect of SNPs identified by the GIANT consortium is primarily on prepubertal height. Only one SNP, rs7759938 in LIN28B, approached a significant association with pubertal growth. Second, we show how using the twin data to control statistically for environmental variance can provide insight into the ultimate magnitude of SNP effects and consequently the genetic architecture of a phenotype. Specifically, we computed a genetic score by weighting SNPs according to their effects as assessed via meta-analysis. This weighted score accounted for 9.2% of the phenotypic variance in height, but 14.3% of the corresponding genetic variance. Longitudinal samples will be needed to understand the developmental context of common genetic variants identified through GWAS, while genetically informative designs will be helpful in accurately characterizing the extent to which these variants account for genetic, and not just phenotypic, variance.


Nodulocystic acne and hidradenitis suppurativa treated with acitretin: a case report.
Nodulocystic acne is a dermatologic disease that can result in significant damage to the skin of the face, chest, and back. Hidradenitis suppurativa is a scarring disease of the skin that causes deep cysts and abscesses on the axillae and anogenital areas. We review a case of a patient with severe nodulocystic facial acne and hidradenitis suppurativa that was treated with 2 full courses of isotretinoin. Although the patient's condition improved, some draining cysts persisted on the face and groin. Because of the inability of isotretinoin to achieve long-term remission of the patient's condition, acitretin was considered as a possible maintenance drug. The patient was almost completely improved after 5 months' therapy with acitretin, which also was effectively used for ongoing maintenance. Acitretin may be a promising treatment for severe nodulocystic acne and hidradenitis suppurativa, which require long-term suppression when isotretinoin fails to give long-term remission.


Amphibious Transport of Fluids and Solids by Soft Magnetic Carpets.
One of the major challenges in modern robotics is controlling micromanipulation by active and adaptive materials. In the respiratory system, such actuation enables pathogen clearance by means of motile cilia. While various types of artificial cilia have been engineered recently, they often involve complex manufacturing protocols and focus on transporting liquids only. Here, soft magnetic carpets are created via an easy self-assembly route based on the Rosensweig instability. These carpets can transport not only liquids but also solid objects that are larger and heavier than the artificial cilia, using a crowd-surfing effect.This amphibious transportation is locally and reconfigurably tunable by simple micromagnets or advanced programmable magnetic fields with a high degree of spatial resolution. Two surprising cargo reversal effects are identified and modeled due to collective ciliary motion and nontrivial elastohydrodynamics. While the active carpets are generally applicable to integrated control systems for transport, mixing, and sorting, these effects can also be exploited for microfluidic viscosimetry and elastometry.


[Magnet stimulation therapy: a simple solution for the treatment of stress and urge incontinence?].
Magnet stimulation therapy has been offered as a new, conservative therapy for stress and urge incontinence in Germany since 2001. Focussed, pulsating magnetic fields are used to stimulate the musculature of the floor of the pelvis. This publication describes our initial experience with this method. We treated 27 patients with magnetic stimulation. The individual patient sits clothed on a therapy-chair and is treated for 20 min twice a week for 2 weeks. The best results were recorded in female patients with grades I and II stress incontinence who could not actively flex their pelvic-floor musculature during physiotherapy. A marked reduction in the frequency of micturition was obtained in 67% of patients with urge incontinence symptoms and non-responsiveness to anticholinergic therapy. Patients with a non-organically tangible pelvic-pain-syndrome did not benefit from the therapy. Magnet stimulation therapy can act as a useful addition to conservative therapies for stress and urge incontinence. It is free of complications and does not involve the insertion of an electrode into the patient as is the case for vaginal and anal electrostimulation. However, this method does not appear to be useful for chronic, non-specific pain in the lower pelvis.


Angular pregnancy.
Angular pregnancy, a type of cornual pregnancy, is a rare obstetric complication that can be life-threatening. In this situation, the embryo is implanted in the lateral angle of the uterine cavity, medial to the uterotubal junction and round ligament. Angular pregnancy must be distinguished from interstitial pregnancy, in which the embryo is implanted lateral to the round ligament. The report presented here describes a case of angular pregnancy that was diagnosed by endovaginal ultrasonography and magnetic resonance imaging. Laparoscopy can be useful for guiding dilatation and curettage in angular pregnancies, and may circumvent the need for invasive surgery or hysterectomy.


Never Gonna Give You Up - Current Developments in Covalent Protein Kinase Inhibitors.
Covalent inhibitors have recently seen a revival in medicinal chemistry. Inhibitors addressing non-catalytic cysteine residues with weakly reactive electrophiles have been very successfully employed to target protein kinases, one of the major druggable protein families. Here we provide an overview of irreversible and reversible covalent protein kinase inhibitors in clinical development and beyond. We further spotlight recent advances in targeting amino acids other than cysteine and the reactive groups utilized in covalent protein kinase inhibitors.


A transposon-derived DNA polymerase from Entamoeba histolytica displays intrinsic strand displacement, processivity and lesion bypass.
Entamoeba histolytica encodes four family B2 DNA polymerases that vary in amino acid length from 813 to 1279. These DNA polymerases contain a N-terminal domain with no homology to other proteins and a C-terminal domain with high amino acid identity to archetypical family B2 DNA polymerases. A phylogenetic analysis indicates that these family B2 DNA polymerases are grouped with DNA polymerases from transposable elements dubbed Polintons or Mavericks. In this work, we report the cloning and biochemical characterization of the smallest family B2 DNA polymerase from E. histolytica. To facilitate its characterization we subcloned its 660 amino acids C-terminal region that comprises the complete exonuclease and DNA polymerization domains, dubbed throughout this work as EhDNApolB2. We found that EhDNApolB2 displays remarkable strand displacement, processivity and efficiently bypasses the DNA lesions: 8-oxo guanosine and abasic site.Family B2 DNA polymerases from T. vaginalis, G. lambia and E. histolytica contain a Terminal Region Protein 2 (TPR2) motif twice the length of the TPR2 from φ29 DNA polymerase. Deletion studies demonstrate that as in φ29 DNA polymerase, the TPR2 motif of EhDNApolB2 is solely responsible of strand displacement and processivity. Interestingly the TPR2 of EhDNApolB2 is also responsible for efficient abasic site bypass. These data suggests that the 21 extra amino acids of the TPR2 motif may shape the active site of EhDNApolB2 to efficiently incorporate and extended opposite an abasic site. Herein we demonstrate that an open reading frame derived from Politons-Mavericks in parasitic protozoa encode a functional enzyme and our findings support the notion that the introduction of novel motifs in DNA polymerases can confer specialized properties to a conserved scaffold.


Incipient Albuminuria in Persons with Newly Diagnosed Type 2 Diabetes Mellitus: A 5-Year Retrospective Cohort Study.
This study aimed to determine the 5-year incidence of albuminuria among Asian persons with newly diagnosed type 2 diabetes mellitus (DM), and to identify the risk factors at diagnosis for progression to albuminuria. A retrospective 5-year closed cohort study was conducted among 1016 persons aged ≥18 years old who were diagnosed with type 2 DM between 1 January 2007 and 31 December 2009 at primary care facilities in Singapore. The cumulative incidence of progression from normoalbuminuria to albuminuria-termed "progression"-was determined. The risk factors associated with progression were evaluated using multiple logistic regression analysis. A total of 541 (53.2%) participants were men. The mean (SD) onset age of type 2 DM was 54 (11) years. From diagnosis of type 2 DM, the 5-year cumulative incidence of progression was 17.3% and mean (SD) duration to progression was 2.88 (1.23) years. Higher onset age (OR 1.02; 95% CI, 1.00-1.04), history of hypertension (OR, 1.88; 95% CI, 1.32-2.70) and higher glycated haemoglobin (HbA1c) (OR, 1.17; 95% CI, 1.09-1.26) at diagnosis were associated with progression. In addition, being on angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) treatment at baseline modified the effect of hypertension on progression. This study highlighted the importance of early screening and treatment of diabetes as well as prevention of hypertension, which could potentially delay the onset of microalbuminuria in persons with type 2 DM. Persons on ACEI or ARB treatment should continue to be monitored regularly for progression to albuminuria.


The microbiota-derived metabolite indole decreases mucosal inflammation and injury in a murine model of NSAID enteropathy.
Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most frequently used classes of medications in the world. Unfortunately, NSAIDs induce an enteropathy associated with high morbidity and mortality. Although the pathophysiology of this condition involves the interaction of the gut epithelium, microbiota, and NSAIDs, the precise mechanisms by which microbiota influence NSAID enteropathy are unclear. One possible mechanism is that the microbiota may attenuate the severity of disease by specific metabolite-mediated regulation of host inflammation and injury. The microbiota-derived tryptophan-metabolite indole is abundant in the healthy mammalian gut and positively influences intestinal health. We thus examined the effects of indole administration on NSAID enteropathy. Mice (n = 5 per group) were treated once daily for 7 days with an NSAID (indomethacin; 5 mg/kg), indole (20 mg/kg), indomethacin plus indole, or vehicle only (control). Outcomes compared among groups included: microscopic pathology; fecal calprotectin concentration; proportion of neutrophils in the spleen and mesenteric lymph nodes; fecal microbiota composition and diversity; small intestinal mucosal transcriptome; and, fecal tryptophan metabolites. Co-administration of indole with indomethacin: significantly reduced mucosal pathology scores, fecal calprotectin concentrations, and neutrophilic infiltration of the spleen and mesenteric lymph nodes induced by indomethacin; modulated NSAID-induced perturbation of the microbiota, fecal metabolites, and inferred metagenome; and, abrogated a pro-inflammatory gene expression profile in the small intestinal mucosa induced by indomethacin. The microbiota-derived metabolite indole attenuated multiple deleterious effects of NSAID enteropathy, including modulating inflammation mediated by innate immune responses and altering indomethacin-induced shift of the microbiota.


Polyphenols and Their Metabolites in Renal Diseases: An Overview.
Kidney diseases constitute a worldwide public health problem, contributing to morbidity and mortality. The present study aimed to provide an overview of the published data regarding the potential beneficial effects of polyphenols on major kidney diseases, namely acute kidney injury, chronic kidney disease, diabetic nephropathy, renal cancer, and drug-induced nephrotoxicity. This study consists of a bibliographical review including in vitro and in vivo studies dealing with the effects of individual compounds. An analysis of the polyphenol metabolome in human urine was also conducted to estimate those compounds that are most likely to be responsible for the kidney protective effects of polyphenols. The biological effects of polyphenols can be highly attributed to the modulation of specific signaling cascades including those involved in oxidative stress responses, anti-inflammation processes, and apoptosis. There is increasing evidence that polyphenols afford great potential in renal disease protection. However, this evidence (especially when in vitro studies are involved) should be considered with caution before its clinical translation, particularly due to the unfavorable pharmacokinetics and extensive metabolization that polyphenols undergo in the human body. Future research should consider polyphenols and their metabolites that indeed reach kidney tissues.


Soluble factor requirements for the autostimulatory growth of B lymphoblasts immortalized by Epstein-Barr virus.
B lymphoblasts immortalized by the Epstein-Barr virus (EBV) exhibit autocrine growth stimulation--that is they release a soluble activity to which they respond by growth. A minimally supplemented serum-free medium conditioned by lymphoblastoid cells in their log phase of growth (LCL-CM) was found to contain autostimulatory activity allowing us to explore the mechanism of autocrine growth for these cell-types in defined conditions. Below cell densities capable of supporting autonomous growth, continued proliferation in serum-free medium was dependent on both added LCL-CM and transferrin. Neither activity alone was capable of sustaining growth. At higher cell densities, transferrin by itself was sufficient to maintain the autocrine loop. The action of the autostimulatory factor appeared to reside in its ability to prime cells continually for a proliferative response to transferrin by enhancing the expression of transferrin receptors at the lymphoblast surfaces. The implications of these findings for normal B cell physiology and their possible relation to oncogenesis are discussed.


Coronary artery spasm during acute myocardial infarction.
A 51 year old man presented with unstable angina. Following initial improvement, the patient had prolonged, continuous chest pain resulting in myocardial infarction. During the evolving myocardial infarction, coronary angiography was performed and demonstrated coronary spasm superimposed on a high-grade atherosclerotic lesion. The role of coronary spasm in the etiology of myocardial infarction is discussed. Subsequent aorto-coronary bypass surgery was performed uneventfully.


Barriers to Guideline-Based Use of Proton Pump Inhibitors to Prevent Upper Gastrointestinal Bleeding.
Gastrointestinal (GI) bleeding is one of the most common serious adverse drug events. Guidelines recommend proton pump inhibitor (PPI) gastroprotection to prevent upper GI bleeding in high-risk patients, but this practice is underused. To explore prescribing practices and barriers to the use of PPI gastroprotection, including dynamics within and across specialties, we conducted semistructured interviews with physicians in 4 specialties at a single institution. We performed thematic analysis of barriers, organized around the theoretical domains framework. The sample included 5 primary care physicians (PCPs), 4 cardiologists, 3 gastroenterologists, and 3 vascular surgeons. Most PCPs, gastroenterologists, and vascular surgeons seldom prescribed PPI gastroprotection. Cardiologists varied most in their use of PPI gastroprotection, with some prescribing it consistently and others never. Major barriers related to the following 3 themes: (1) knowledge, (2) decision processes, and (3) professional role. Knowledge of guidelines was greatest among cardiologists and gastroenterologists and low among PCPs and vascular surgeons, and PCPs tended to focus on adverse effects associated with PPIs, which made them reluctant to prescribe them. For cardiologists, prevention of bleeding was usually a priority, but they sometimes deferred prescribing to others. For the other 3 specialties, PPI gastroprotection was a low priority. There was unclear delineation of responsibility for prescribing gastroprotection between specialties. Major barriers to PPI gastroprotection relate to knowledge, decision processes, and professional role, which operate differentially across specialties. Multicomponent interventions will likely be necessary to improve guideline-based use of PPIs to prevent upper GI bleeding.VISUAL ABSTRACT.


Glucagon-Like Peptide-1 Receptor Agonist and Risk of Diabetic Retinopathy in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis of Randomized Placebo-Controlled Trials.
Glucagon-like peptide 1 receptor agonists (GLP-1RAs) exhibit glucose-lowering, weight-reducing, and blood pressure-lowering effects. Nevertheless, a debate exists concerning the association between GLP-1RA treatment and the risk of diabetic retinopathy (DR) in patients diagnosed with type 2 diabetes mellitus (T2DM). To ascertain the risk of DR in patients with T2DM undergoing GLP-1RA treatment, we conducted a meta-analysis utilizing data derived from randomized placebo-controlled studies (RCTs). A comprehensive literature search was conducted using PubMed, Cochrane Library, Web of Science, and EMBASE. We focused on RCTs involving the use of GLP-1RAs in patients with T2DM. Utilizing R software, we compared the risk of DR among T2DM patients undergoing GLP-1RA treatment. The Cochrane risk of bias method was employed to assess the research quality. The meta-analysis incorporated data from 20 RCTs, encompassing a total of 24,832 T2DM patients. Across all included trials, randomization to GLP-1 RA treatment did not demonstrate an increased risk of DR (odds ratio = 1.17; 95% CI 0.98-1.39). Furthermore, no significant heterogeneity or publication bias was detected in the analysis. The results of this systematic review and meta-analysis indicate that the administration of GLP-1 RA is not associated with an increased risk of DR. PROSPERO REGISTRATION IDENTIFIER: CRD42023413199.


The riboflavin analog roseoflavin targets an FMN-riboswitch and blocks Listeria monocytogenes growth, but also stimulates virulence gene-expression and infection.
During recent years, riboswitches have emerged as potential targets for novel antibacterial substances. In this study, we investigated how one flavin analog, roseoflavin, affected the gene-expression, growth and infectivity of the human bacterial pathogen Listeria monocytogenes to determine the potential of this analog to function as an antibacterial substance. The results indicate that roseoflavin has a profound inhibiting effect on the growth of L. monocytogenes at very low concentrations. Also, expression of the gene located downstream of the FMN riboswitch, a riboflavin transporter, was blocked by the addition of roseoflavin. Base-substitution mutations in the FMN riboswitch allowed the bacteria to grow in the presence of roseoflavin, showing that roseoflavin targeted the FMN riboswitch directly. Surprisingly, we found that roseoflavin stimulated L. monocytogenes virulence gene expression and infection abilities in a mechanism independent of the FMN riboswitch. Our results suggest that roseoflavin can block growth but also enhance Listeria virulence.


No effect of albinism on sedative-hypnotic sensitivity to ethanol and anesthetics.
Studies using the long-sleep (LS) X short-sleep (SS) (LSXSS) recombinant inbred mice and inbred long-sleep (ILS) by inbred short-sleep (ISS) intercrosses have found genetic linkage between Tyr albinism (c/c) and differential sensitivity to sedative-hypnotic doses of ethanol and general anesthetics. This linkage could be due to a gene or genes near Tyr or Tyr itself. With regard to the latter possibility, the absence of tyrosinase activity (encoded by Tyr) in albinos could alter tyrosine availability and thus the rate-limiting step in catecholamine synthesis. In addition, albinism is associated with altered brain development that could have pleiotropic effects on behavior. Therefore, in this study, we asked whether albinism affects sedative-hypnotic sensitivity. Loss of righting reflex (LORR) duration was measured using doses of ethanol (4.1 g/kg), pentobarbital (70 mg/kg), isoflurane (2 g/kg), and etomidate (20 mg/kg) that were previously associated with differential sensitivity of albino versus nonalbino mice. Tyr transgenics (c/c, Tg(Tyr+)) were backcrossed to ISS (c/c) to compare pigmented (c/c, Tg(Tyr+)) and albino (c/c) mice in the context of an ISS-like background. ISS was also crossed with C57BL/6 (B6) mice heterozygous for a spontaneous albino mutation (c2j) to compare pigmented (c/+) and albino (c/c2j) mice. Pigmented B6 (c2j/+ and +/+) and albino B6 (c2j/c2j) mice were also compared (pentobarbital). For each sedative hypnotic, albinism had no effect on LORR duration. Each expected difference was ruled out at the 95% or 99% confidence level. For each sedative hypnotic, males were more sensitive than females even though the effect size was usually smaller than the expected albino effect size, arguing empirically that the inability to detect an albino effect was not due to systematic error or an insufficient number of mice. We conclude that the differential sensitivity associated with albinism is most likely due to a gene or genes near Tyr rather than Tyr itself.


Prevalence of Pre-pregnancy Obesity, 2011-2014.
Obesity before and during pregnancy increases risk among mothers for poor health outcomes, such as diabetes, high blood pressure, and cardiovascular disease. To describe trends in pre-pregnancy obesity rates among women in Wisconsin. Cross-sectional data from Wisconsin birth certificates were analyzed. Prevalence of pre-pregnancy obesity (defined as body mass index ≥ 30) among Wisconsin women who gave birth from 2011 through 2014 was compared across demographic and geographic dimensions. Overall, 27.8% of Wisconsin women who gave birth during 2011-2014 were obese. Obesity rates were highest among 40- to 44-year-old women (31.8%), women with a high school/ GED diploma (32.8 %), American Indian/Alaska Native women (43.9%), and women with 5 or more pregnancies (35.4%). Obesity rates varied by county of residence (highest in Forest County, 45.2%) and city of residence (highest in the city of Racine, 34.8%). There are significant socioeconomic, racial, and geographic disparities in pre-pregnancy obesity among women who give birth in Wisconsin.


A comparison of purified valyl-transfer ribonucleic acid synthetase from Bacillus stearothermophilus and from Escherichia coli.
The purification of valyl-tRNA synthetase from Bacillus stearothermophilus is described. The protein was greater than 90% homogeneous on polyacrylamide-gel electrophoresis after more than 850-fold purification. It has a molecular weight of 110000, and no evidence was found for the presence of subunit structure. The properties of the purified enzyme were compared with those of purified valyl-tRNA synthetase from Escherichia coli. The thermal stability, pH-stability and dependence of activity on the temperature and pH of the assay are reported. The two enzymes recognize and charge tRNA(Val) from crude tRNA of the mesophile E. coli and of the thermophile B. stearothermophilus, indiscriminately. The gel-filtration method was extended to measure the binding of tRNA to synthetase directly. Binding constants for tRNA(Val) to valyl-tRNA synthetase from B. stearothermophilus were determined between 5 degrees and 60 degrees C.


Interleukin-12 suppresses immunoglobulin E production but enhances immunoglobulin G4 production by human peripheral blood mononuclear cells.
The effect of interleukin-12 (IL-12) on human immunoglobulin G4 (IgG4) and IgE production was examined with cells derived from filarial patients and European controls. IL-12 inhibited IgE release but enhanced IgG4 production in cultures of peripheral blood mononuclear cells stimulated with anti-CD2 plus IL-2. When purified T- and B-cell cocultures were examined, IL-12 again markedly enhanced IgG4, whereas IgE production was no longer inhibited.


Modulation of bone metabolism by two chemically distinct lipopolysaccharide fractions from Bacteroides gingivalis.
Two separate species of lipopolysaccharide (LPS) from Bacteroides gingivalis 381 have been isolated. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated not only the heterogeneity of each species, but also that they represented high- and low-molecular-weight LPS entities. Although both contained the same carbohydrate and fatty acid components, the proportions of these differed between the LPS species. The direct effects of these two species in modulation of bone resorption and bone collagen and noncollagen protein synthesis have been examined. In a bone resorption assay, these two species stimulated 45Ca release from prelabeled fetal rat bones in a concentration range of 0.5 to 3.0 micrograms/ml. The two LPS species also elicited a 30 to 40% reduction in collagen protein formation at 10 micrograms/ml. Responses of the same order of magnitude were observed with LPS from Salmonella minnesota at 10 micrograms/ml. The higher-molecular-weight LPS species also significantly inhibited noncollagen protein formation. This is the first report that LPS from B. gingivalis 381, a suspected periodontal pathogen, inhibits bone collagen formation and, in conjunction with the bone resorption potency, further implicates LPS in alveolar bone loss associated with periodontal disease.


Duplex Ultrasound Studies Are Neither Necessary or Sufficient for the Diagnosis of Neurogenic Thoracic Outlet Syndrome.
Duplex ultrasound (DU) is used in the diagnosis of neurogenic thoracic outlet syndrome (NTOS) to measure compression of the subclavian artery (SCA) which is thought to strengthen the NTOS diagnosis. However, the value of DU in NTOS remains unclear. A retrospective review of a prospectively acquired database from the TOS center of the Catharina Hospital Eindhoven was performed of patients referred between January 2017 and December 2019. Only "proven NTOS" patients, defined as a successful response to thoracic outlet decompression (TOD) surgery based on patient-reported outcomes (NRS pain scale, CBSQ and DASH score) were included to exclude wrongfully diagnosed NTOS patient. The presence of vascular symptoms (defined as discoloration, edema or temperature changes of the hand or fingers), results of provocative maneuvers, and outcome of DU was used for analysis. To assess the link between vascular symptoms and compression on DU, a chi-squared test was performed. Further, we looked for a correlation between vascular symptoms, compression on DU and clinical outcome using a repeated measures analysis of variance (ANOVA). Vascular symptoms were seen in 49 of 133 patients (36.8%). In total, 51 of 133 patients (38.3%) had at least 50% variation in SCA peak systolic velocity (PSV) during DU at the level of SCA stenosis. SCA occlusion was seen in 11 patients (8.3%) during provocative maneuvers. The presence of clinical "arterial symptoms" was not significantly correlated with vascular laboratory findings, neither for alterations in PSV during DU (P = 0.245) nor for positional SCA occlusion (P = 0.540). No statistically significant correlations between the degree of SCA stenosis and postoperative outcomes, as measured with the DASH, CBSQ, or NRS scale for pain were found (P = 0.787). The role of DU in the work-up of NTOS in patients with vascular complaints is questionable. Changes in flow velocities are seen in NTOS patients and do not correlate with "vascular symptoms" or clinical outcome.


Murine pulmonary adenoma bioassay of potentially effective agents against slow-growing solid tumors.
An in vitro-in vivo system for screening potentially effective drugs against solid tumors is described. Drug toxicity to plateau-phase pulmonary adenoma cells is used as an in vitro screen for potential activity against solid tumors, since both plateau phase cultured cell populations and solid tumors are composed predominantly of nondividing cells. The effect of drugs with in vitro activity on the rate of appearance of urethan-induced adenomas on the lung surface of strain A mice in vivo is used to assess drug efficacy in the treatment of solid tumors, taking into consideration drug toxicity to and drug metabolism by the host. Arabinosylcytosine and hydroxyurea were ineffective against plateau phase cells in vitro, even at high concentrations (5 to 10 mg/ml), and did not affect pulmonary adenoma growth in vivo, even at toxic doses (arabinosylcytosine, 80 mg/kg; hydroxyurea, 800 mg/kg), as would be expected with these cell cycle-active drugs. Adriamycin, an effective agent against human solid tumors, was cytotoxic to plateau phase cultured cells (0% survivors at 1 mug/ml), and a dose of 2 mg/kg completely inhibited pulmonary adenoma growth in mice. Thus, this pulmonary adenoma bioassay would appear to effectively select for drugs which may be active against solid tumors in humans.


Depressive morbidity and gender in community-dwelling Brazilian elderly: systematic review and meta-analysis.
Although studies indicate that community-dwelling elderly have a lower prevalence of major depression compared with younger age groups, prevalence estimates in Brazil show that clinically significant depressive symptoms (CSDS) and depression are frequent in the older population. However, a systematic review and meta-analysis of prevalence of and factors associated with depressive disorders and symptoms in elderly Brazilians has not previously been reported. The aims were (i) to perform a survey of studies dating from 1991 to 2009 on the prevalence of depressive disorders and CSDS in elderly Brazilians residing in the community; (ii) to determine depression prevalence and identify associated factors; and (iii) develop a meta-analysis to indicate the combined prevalence and the influence of gender on depressive morbidity in this population. Studies were selected from articles dated between January 1991 and May 2009, extracted from Medline, LILACS and SciELO databases. A total of 17 studies were found, 13 with CSDS, 1 with major depression alone and 3 with major depression and dysthymia, involving the evaluation of 15,491 elderly people. The average age of participants varied between 66.5 and 84.0 years. Prevalence rates of 7.0% for major depression, 26.0% for CSDS, and 3.3% for dysthymia were found. The odds ratios for major depression and CSDS were greater among women. There was a significant association between major depression or CSDS and cardiovascular diseases. The review indicates greater prevalence of both major depression and CSDS compared to rates reported in the international literature, while the prevalence of dysthymia was found to be similar. The high prevalence of CSDS and its significant association with cardiovascular diseases reinforces the importance of evaluating subthreshold depressive symptoms in the elderly in the community.


Evolution of the cephalopod head complex by assembly of multiple molluscan body parts: Evidence from Nautilus embryonic development.
Cephalopod head parts are among the most complex occurring in all invertebrates. Hypotheses for the evolutionary process require a drastic body-plan transition in relation to the life-style changes from benthos to active nekton. Determining these transitions, however, has been elusive because of scarcity of fossil records of soft tissues and lack of some of the early developmental stages of the basal species. Here we report the first embryological evidence in the nautiloid cephalopod Nautilus pompilius for the morphological development of the head complex by a unique assembly of multiple archetypical molluscan body parts. Using a specialized aquarium system, we successfully obtained a series of developmental stages that enabled us to test previous controversial scenarios. Our results demonstrate that the embryonic organs exhibit body plans that are primarily bilateral and antero-posteriorly elongated at stereotyped positions. The distinct cephalic compartment, foot, brain cords, mantle, and shell resemble the body plans of monoplacophorans and basal gastropods. The numerous digital tentacles of Nautilus develop from simple serial and spatially-patterned bud-like anlagen along the anterior-posterior axis, indicating that origins of digital tentacles or arms of all other cephalopods develop not from the head but from the foot. In middle and late embryos, the primary body plans largely change to those of juveniles or adults, and finally form a "head" complex assembled by anlagen of the foot, cephalic hood, collar, hyponome (funnel), and the foot-derived epidermal covers. We suggest that extensions of the collar-funnel compartment and free epidermal folds derived from multiple topological foot regions may play an important role in forming the head complex, which is thought to be an important feature during the body plan transition.


Prevalence of antibiotic resistance genes in the bacterial flora of integrated fish farming environments of Pakistan and Tanzania.
The use of a wide variety of antimicrobials in human and veterinary medicine, including aquaculture, has led to the emergence of antibiotic resistant pathogens. In the present study, bacteria from water, sediments, and fish were collected from fish farms in Pakistan and Tanzania with no recorded history of antibiotic use. The isolates were screened for the presence of resistance genes against various antimicrobials used in aquaculture and animal husbandry. Resistant isolates selected by disk diffusion and genotyped by Southern hybridization were further screened by polymerase chain reaction (PCR) and amplicon sequencing. The prominent resistance genes identified encoded tetracycline [tetA(A) and tetA(G)], trimethoprim [dfrA1, dfrA5, dfrA7, dfrA12, and dfrA15], amoxicillin [bla(TEM)], streptomycin [strA-strB], chloramphenicol [cat-1], and erythromycin resistance [mefA]. The int1 gene was found in more than 30% of the bacterial isolates in association with gene cassettes. MAR indices ranged from 0.2 to 1. The bla(NDM-1) gene was not identified in ertapenem resistant isolates. It is hypothesized that integrated fish farming practices utilizing domestic farm and poultry waste along with antibiotic residues from animal husbandry may have contributed to a pool of resistance genes in the aquaculture systems studied.


Hyoscine butylbromide versus acetaminophen for nonspecific colicky abdominal pain in children: a randomized controlled trial.
Less than two-thirds of children with abdominal pain in the emergency department receive analgesia. We sought to determine whether hyoscine butylbromide was superior to acetaminophen for children with nonspecific colicky abdominal pain. We randomly allocated children aged 8-17 years with nonspecific colicky abdominal pain who presented to the pediatric emergency department of London Health Sciences Centre, London, Ontario to receive hyoscine butylbromide, 10 mg given orally, or acetaminophen, 15 mg/kg given orally (maximum 975 mg). We considered the minimal clinically important difference for the primary outcome (self-reported pain at 80 min) to be 13 mm on a 100 mm visual analogue scale. Secondary outcomes included administration of rescue analgesia, adverse effects and pain score less than 30 mm at 80 minutes. A total of 236 participants (120 in the hyoscine butylbromide group and 116 in the acetaminophen group) were included in the trial. The mean visual analogue scale scores at 80 minutes were 29 mm (standard deviation [SD] 26 mm) and 30 mm (SD 29 mm) with hyoscine butylbromide and acetaminophen, respectively (adjusted difference 1, 95% confidence interval -7 to 7). Rescue analgesia was administered to 4 participants (3.3%) in the hyoscine butylbromide group and 1 participant (0.9%) in the acetaminophen groups (p = 0.2). We found no significant differences in rates of adverse effects between hyoscine butylbromide (32/116 [27.6%]) and acetaminophen (28/115 [24.3]) (p = 0.5); no serious adverse effects were observed. The proportion with a pain score less than 30 mm at 80 minutes was 66 (55.0%) with hyoscine butylbromide and 63 (54.3%) with acetaminophen (p = 0.9). Hyoscine butylbromide was not superior to acetaminophen in this setting. Both agents were associated with clinically important pain reduction, and either can be considered for children presenting to the emergency department with nonspecific colicky abdominal pain. Trial registration: Clinicaltrials.gov, no. NCT02582307.


Invasive fungal laryngopharyngitis resulting in laryngeal destruction with complete laryngotracheal separation: Report of a case.
As the treatment of hematopoietic cancers evolves, otolaryngologists will see a higher incidence of opportunistic infections. We discuss a case of invasive fungal disease that invaded the larynx, pharynx, trachea, and pulmonary parenchyma after chemotherapy. The patient, a 46-year-old woman, presented 1 week after undergoing induction chemotherapy. Her initial symptoms were odynophagia and dysphagia. Despite encouraging findings on physical examination, her health rapidly declined and she required an urgent tracheotomy and multiple operations to address spreading necrosis. Because of her inability to heal, she was not a candidate for laryngectomy, so she was treated with conservative management. The patient was then lost to follow-up, but she returned 5 months later with laryngeal destruction and a complete laryngotracheal separation. While noninvasive fungal laryngitis is routinely encountered, its invasive counterpart is rare. The literature demonstrates that some cases completely resolve with medical therapy alone but that surgery is necessary in others. We recommend surgical debridement of all necrotic tissue.


[Progress of nanometer vector polyethylenimine applied in gene therapy].
Polyethylenimine (PEI) is a kind of nanometer nonviral vector frequently applied in gene transfection. It is simple and easy to prepare and to modify and relatively safe compared to viral vectors. In recent years, PEI has been utilized in many research areas for gene delivery to stem cells in vitro or targeted gene delivery to cells in the brain. This review reveals that the cytotoxicity and low transfection efficiency of PEI requires to be improved. However brain-targeted modification indicates the promising prospect of PEI for gene therapy in cerebrovascular diseases.


Mask-Based versus Frame-Based Gamma Knife ICON Radiosurgery in Brain Metastases: A Prospective Randomized Trial.
Radiosurgery is performed with a diversity of instruments relying usually either on a stereotactic frame or a mask for patient head fixation. Comfort and safety efficacy of the 2 systems have never been rigorously evaluated and compared. Between February 2016 and January 2017, 58 patients presenting with nonsmall cell lung cancer brain metastases have been treated by Gamma Knife radiosurgery (GKS) with random use of a frame or a mask for fixation were included patients older than 18, with <5 brain metastases (at the exclusion of brainstem and optic pathway's locations) and no earlier history of radiotherapy. The primary outcome measure was the pain scale assessment (PSA) at the beginning of the GKS procedure. The PSA at the beginning of the GKS procedure was not different between the 2 groups. The PSA at the day before GKS, before magnetic resonance imaging, just after frame application, and the day after radiosurgery (departure) has shown no difference between the 2 groups. At the end of the radiosurgery itself (just after frame or mask removal) and 1 h after, the mean pain scale was higher in patients treated with the frame (p < 0.05 and p < 0.001, respectively) but 2 patients were not able to tolerate the mask discomfort and had to be treated with frame. Tumor control and morbidity probability were demonstrated to be no difference between the 2 groups in this population of patients with BM not in highly functional area. The median of the extra dose to the body due to the cone-beam computed tomography was 7.5 mGy with a maximum of 35 mGy in patients treated with a mask fixation (null in the others treated with frame). Mask fixation was associated to longer treatment time although the beam on time was not different between the 2 groups. In selected patients, with brain oligo-metastases out of critical location, single-dose mask-based GKS can be done with a comfort and a safety efficacy comparable to frame-based GKS. There seems to be no clear patient data that confirm the value of the mask system with regards to comfort.


Assessment of very early response evaluation with 18F-FDG-PET/CT predicts survival in erlotinib treated NSCLC patients-A comparison of methods.
We evaluated whether changes in 18F-Fluoro-D-Glucose (18F-FDG)-uptake evaluated early during erlotinib treatment predict survival in non-small cell lung cancer (NSCLC) patients. Positron emission tomography (PET)/CT scans from 56 NSCLC patients before and after 7-10 days of erlotinib treatment were analyzed with four different methods: Visual evaluation and percentage change in lean body mass corrected standardized uptake values (SULs): SULpeak, SULmax and total lesion glycolysis (TLG). The semi-quantitative parameters abilities to predict progression free survival (PFS) and overall survival (OS) were compared and we found that percentage change in SULpeak, SULmax and TLG all correlated with PFS and OS with the strongest correlation found for TLG (R=0.51, P < 0.001). The highest area under the curve (AUC) for predicting OS was for TLG (0.70 (0.56-0.85)) with a sensitivity of 0.68 and a specificity of 079. All methods except visual evaluation, SULpeak at 15% and 30%, and TLG at 40% cut-off separates the survival curves for the response categories for PFS. For OS, visual evaluation and SULmax did not, whereas TLG at 4 different cut-off levels and SULpeak at the three lowest cut-off levels did. Early change in 18F-FDG-uptake during erlotinib correlated to both PFS and OS. TLG, as suggested by PERCIST 1.0, shows the strongest correlation to survival, whereas visual evaluation seems to be less sensitive at this very early time-point, but lower cut-off levels for discriminating between response categories seem to be relevant as we find that 20-25% change for both response and progression is optimal.


A mapping review of international guidance on the management and care of amyotrophic lateral sclerosis (ALS).
Management of ALS is suboptimal. Consequently, quality improvement interventions are needed to improve ALS care. An evidence-based insight into how patients should be managed is essential when developing quality improvement interventions. Therefore, this study aimed to map, categorize and summarize international guidance on the management and care of ALS and to identify gaps in this guidance by means of a mapping review. Literature was searched for clinical practice guidelines, quality indicators and evidence-based clinical summaries. A content analysis and meta-synthesis of the included literature was performed. Interventions and outcomes used in the management and care of ALS were identified and categorized. Furthermore, the amount of guidance underpinning these interventions and outcomes was analysed. Six clinical practice guidelines, one set of quality indicators and three evidence-based clinical summaries were identified. The results demonstrated that certain domains in ALS care, mainly disease-specific domains such as breathing and swallowing, are extensively addressed in the literature whereas other subjects, such as care coordination, receive little attention. In conclusion, this mapping review provides a scientific basis for targeting and developing the clinical content of a quality improvement intervention for the management of ALS.


A large molecular cluster with high proton release capacity.
We present a single molecular polyoxometalate cluster (K41[(P2W12Nb6O62)6{Mn3(OH)3(H2O)6}4{Mn3Na(H2O)16}]·26H2O) with controllable release of a large number of protons (∼40 per molecule) in its aqueous solution upon addition of a base. The deprotonation/protonation process is reversible with the clusters remaining intact. This molecule can also absorb up to 11 protons per cluster when an acid, HCl, was added to its original aqueous solution. To the best of our knowledge, such large proton absorption/release capacity along with excellent stability is unprecedented.


A Hearing Loss Prevention Outreach Program for Farmers and Motorsports Enthusiasts.
Many farmers and motorsports enthusiasts in rural areas attend tractor pulls, which are loud motorsport competitions using tractors and trucks with powerful, modified engines. The high noise levels experienced by farmers and motorsports fans in their recreational and occupational activities are not addressed by traditional hearing conservation programs. The University of Wisconsin-Madison audiology group has established an annual hearing loss prevention outreach project at the Dairyland Super National Truck and Tractor Pull in Tomah, Wisconsin. The objectives of the outreach are to provide hearing protection to those at the tractor pull, to document tractor pull noise levels, and to encourage tractor pull attendees to use hearing protection at work and in their other recreational activities. This study establishes that hearing loss prevention outreach at tractor pulls is necessary due to the high noise levels during the competitions. The number of earplugs distributed and the percentage of individuals who accept them indicates that this outreach is effective in the short term. It is yet to be determined if this type of hearing loss prevention project can create long-term shifts in cultural attitudes about rural noise and lead to increased hearing protection usage in the occupational and recreational lives of tractor pull attendees.


[The development of complex technique of evaluation of virulence of parahemolytic vibrio].
The article deals with results of studying parahemolytic vibrio separatedfrom different sources according their phenotype and genotype attributes associated with virulence. In certain cases the mismatch of results of Kanagava tests and polymerase chain reaction test of gene tdh was established. The need in virulence complex evaluation is substantiated. This complex has to include detection of hemolytic activity in Kanagava test and urease activity on the Kristensen medium and polymerase chain reaction detection of genes tdh and trh. The developed complex technique is described. The formula of pathogenic strains is established Three alternatives of virulent parahemolytic vibrio are given. The test-strains Vibrio parahaemolyticus are proposed as control in testing phenotype and genotype strains according virulence signs.


Marine dinoflagellates show induced life-history shifts to escape parasite infection in response to water-borne signals.
Many dinoflagellate species form dormant resting cysts as a part of their life cycle, and in some freshwater species, hatching of these cysts can be delayed by the presence of water-borne signals from grazing zooplankton. Some marine dinoflagellates can form temporary cysts, which may function to resist unfavourable short-term environmental conditions. We investigated whether the marine dinoflagellate Alexandrium ostenfeldii is able to induce an increased resistance to the parasitic flagellate Parvilucifera infectans by forming temporary cysts. We performed several laboratory experiments where dinoflagellates were exposed either to direct contact with parasites or to filtered water from cultures of parasite-infected conspecifics (parasite-derived signals). Infection by P. infectans is lethal to motile A. ostenfeldii cells, but temporary cysts were more resistant to parasite infection. Furthermore, A. ostenfeldii induced a shift in life-history stage (from motile cells to temporary cysts) when exposed to parasite-derived water-borne signals. The response was relaxed within a couple of hours, indicating that A. ostenfeldii may use this behaviour as a short-term escape mechanism to avoid parasite infection. The results suggest that intraspecies chemical communication evoked by biotic interactions can be an important mechanism controlling life-history shifts in marine dinoflagellates, which may have implications for the development of toxic algal blooms.


Responsiveness of the ten-metre walk test, Step Test and Motor Assessment Scale in inpatient care after stroke.
Responsiveness of a measurement tool is its ability to detect change over time. The aim of this study was to determine the responsiveness and floor/ceiling effects of the ten-metre walk test (10mWT), Step Test and Motor Assessment Scale (MAS) lower limb items. An inception cohort study was conducted, including 190 stroke survivors admitted to a comprehensive stroke unit. The 10mWT, Step Test and MAS were administered within 48 hours of admission and repeated in the 48 hours before discharge. Responsiveness was analysed with Effect Size (ES), Standardised Response Mean (SRM) and a median-based Effect Size (mES). Floor/ceiling effects were calculated as the percentage of participants scoring the lowest/highest possible scores. Responsiveness of each outcome measure varied according to the statistic used. Values for the 10mWT were ES 1.44, SRM 0.93, mES 0.45; the step test ES 1.99, SRM 0.88, mES 0.36; MAS sit-to-stand (item 4) score ES 1.27, SRM 1.00, mES 0.50; and for MAS item 5 (walking) ES 1.43, SRM 1.10, mES 0.50. The MAS item 3 (sitting balance) was moderately responsive in all analyses (ES 0.72, SRM 0.71, mES 0.50). The MAS mobility score (summed items 3-5) consistently showed large responsiveness (ES 1.42, SRM 1.16, mES 0.92). The Step Test had the highest proportion of participants who didn't change (46%) and item 4 of the MAS showed the largest ceiling effect on discharge (44%). Most measures were able to detect change in motor performance during inpatient stroke rehabilitation but the MAS mobility score was the only measure that demonstrated large responsiveness and no marked floor or ceiling effects.


Coapplication of lidocaine and the permanently charged sodium channel blocker QX-314 produces a long-lasting nociceptive blockade in rodents.
Nociceptive-selective local anesthesia is produced by entry of the permanently charged lidocaine-derivative QX-314 into nociceptors when coadministered with capsaicin, a transient receptor potential vanilloid 1 (TRPV1) channel agonist. However, the pain evoked by capsaicin before establishment of the QX-314-mediated block would limit clinical utility. Because TRPV1 channels are also activated by lidocaine, the authors tested whether lidocaine can substitute for capsaicin to introduce QX-314 into nociceptors through TRPV1 channels and produce selective analgesia. Lidocaine (0.5% [17.5 mM], 1% [35 mM], and 2% [70 mM]) alone, QX-314 (0.2% [5.8 mM]) alone, and a combination of the two were injected subcutaneously and adjacent to the sciatic nerve in rats and mice. Mechanical and thermal responsiveness were measured, as was motor block. Coapplication of 0.2% QX-314 with lidocaine prolonged the nociceptive block relative to lidocaine alone, an effect attenuated in TRPV1 knockout mice. The 0.2% QX-314 alone had no effect when injected intraplantary or perineurally, and it produced only weak short-lasting inhibition of the cutaneous trunci muscle reflex. Perisciatic nerve injection of lidocaine with QX-314 produced a differential nociceptive block much longer than the transient motor block, lasting 2 h (for 1% lidocaine) to 9 h (2% lidocaine). Triple application of lidocaine, QX-314, and capsaicin further increased the duration of the differential block. Coapplication of lidocaine and its quaternary derivative QX-314 produces a long-lasting, predominantly nociceptor-selective block, likely by facilitating QX-314 entry through TRPV1 channels. Delivery of QX-314 into nociceptors by using lidocaine instead of capsaicin produces sustained regional analgesia without nocifensive behavior.


Extraneural metastases of primary central nervous system tumors identified by fine needle aspiration: a retrospective analysis.
Extraneural metastasis (EM) of primary central nervous system (PCNS) neoplasms is rare and signifies a poor clinical outcome. Due to its infrequent occurrence, relatively few reports on the cytomorphology of these neoplasms have been published. We describe a series of 19 cases from 16 patients at a single, large tertiary care center. A retrospective analysis of 19 cases of metastases from PCNS neoplasms identified on fine needle aspiration (FNA) in 8 male and 8 female patients aged 14-72 years (mean age 39.6) from 1989 to 2013 was conducted to further characterize the cytomorphologic features identified at metastatic sites. Six different PCNS neoplasms were identified: meningioma, glioblastoma, hemangiopericytoma (HPC), oligodendroglioma, medulloblastoma, and retinoblastoma. The mean latency period between the diagnoses of the primary and first metastatic tumors was 7.4 years (range 0-15). The most common PCNS malignancy responsible for EM was HPC. The most common metastatic sites were the lung (31%) and soft tissue/bone (31%). EM of PCNS tumors is extremely rare. FNA allows for quick, safe and accurate diagnosis. Cytomorphologic features are characteristic, and in conjunction with the clinical history and immunohistochemistry, an accurate diagnosis was obtained in 100% of the cases.


An OAIS-Based Hospital Information System on the Cloud: Analysis of a NoSQL Column-Oriented Approach.
The Open Archive Information System (OAIS) is a reference model for organizing people and resources in a system, and it is already adopted in care centers and medical systems to efficiently manage clinical data, medical personnel, and patients. Archival storage systems are typically implemented using traditional relational database systems, but the relation-oriented technology strongly limits the efficiency in the management of huge amount of patients' clinical data, especially in emerging cloud-based, that are distributed. In this paper, we present an OAIS healthcare architecture useful to manage a huge amount of HL7 clinical documents in a scalable way. Specifically, it is based on a NoSQL column-oriented Data Base Management System deployed in the cloud, thus to benefit from a big tables and wide rows available over a virtual distributed infrastructure. We developed a prototype of the proposed architecture at the IRCCS, and we evaluated its efficiency in a real case of study.


Breastfeeding: A Review of Its Physiology and Galactogogue Plants in View of Traditional Persian Medicine.
The beneficial effects of breastfeeding for the infant and mother are well recognized. Many natural products are reputed to be galactogogue agents in major Traditional Persian Medicine (TPM) textbooks. The aim of this study is to review those medicinal plants that are reported to be effective in increasing breast milk in TPM and to compare the data from TPM texts with the findings of modern pharmacological and clinical research. Data on the medicinal plants used to increase breast milk were obtained from major TPM textbooks. A detailed search in PubMed, Science Direct, Scopus, Google Scholar, and Web of Science databases was performed to confirm the effects of medicinal plants mentioned in TPM on lactation in view of the identified pharmacological actions. Foeniculum vulgare, Anethum graveolens, Pimpinella anisum, Nigella sativa, and Vitex agnus-castus are among the most effective galactogogue TPM plants. Many pharmacologically relevant activities have been reported for these herbs. The use of traditional knowledge can pave the way toward finding effective phytopharmaceuticals for increasing breast milk.


Dietary variety impairs habituation in children.
The purpose of these studies was to test the hypothesis that dietary variety decreases the rate of habituation and increases energy intake in children. In Experiment 1, salivation in response to the same or a variety of food cues was measured followed by consumption of the study food(s). In Experiment 2, children responded in a computer task to earn points for the same or a variety of low or high energy density foods, which were then consumed. Salivation, number of responses, and energy intake were measured. Participants in the same groups habituated faster than those in the variety groups (p = .05), and in Experiment 2, the effect of variety was independent of energy density. Participants in the variety groups also consumed more energy than those in the same groups in both experiments (p = .05). Dietary variety disrupted habituation and increased energy intake in children. In addition, the response to dietary variety was independent of energy density, suggesting that increasing variety of low energy density foods may increase consumption.


Profile and rural exposure for nursing and allied health students at two Australian Universities: A retrospective cohort study.
Linking enrolment and professional placement data for students' from 2 universities, this study compares characteristics across universities and health disciplines. The study explores associations between students' location of origin and frequency, duration and type of placements. Retrospective cohort data linkage. Two Australian universities, Monash University and the University of Newcastle. Students who completed medical radiation science, nursing, occupational therapy, pharmacy or physiotherapy at either university between 2 February 2017 and 28 February 2018. Location of origin, university and discipline of enrolment. Main measures were whether graduates had multiple rural placements, number of rural placements and cumulative rural placement days. Location of origin, discipline and university of enrolment were the main explanatory variables. Secondary dependent variables were age, sex, socio-economic indices for location of origin, and available placements. A total of 1,315 students were included, of which 22.1% were of rural origin. The odds of rural origin students undertaking a rural placement was more than 4.5 times greater than for urban origin students. A higher proportion of rural origin students had multiple rural placement (56.0% vs 14.9%), with a higher mean number of rural placement days. Public hospitals were the most common placement type, with fewer in primary care, mental health or aged care. There is a positive association between rural origin and rural placements in nursing and allied health. To help strengthen recruitment and retention of graduates this association could be further exploited, while being inclusive of non-rural students.


Inhibition of myocardin-related transcription factor/serum response factor signaling decreases lung fibrosis and promotes mesenchymal cell apoptosis.
Myofibroblasts are crucial to the pathogenesis of tissue fibrosis. Their formation of stress fibers results in the release of myocardin-related transcription factor (MRTF), a transcriptional coactivator of serum response factor (SRF). MRTF-A (Mkl1)-deficient mice are protected from lung fibrosis. We hypothesized that the SRF/MRTF pathway inhibitor CCG-203971 would modulate myofibroblast function in vitro and limit lung fibrosis in vivo. Normal and idiopathic pulmonary fibrosis lung fibroblasts were treated with/without CCG-203971 (N-[4-chlorophenyl]-1-[3-(2-furanyl)benzoyl]-3-piperidine carboxamide) and/or Fas-activating antibody in the presence/absence of transforming growth factor (TGF)-β1, and apoptosis was assessed. In vivo studies examined the effect of therapeutically administered CCG-203971 on lung fibrosis in two distinct murine models of fibrosis induced by bleomycin or targeted type II alveolar epithelial injury. In vitro, CCG-203971 prevented nuclear localization of MRTF-A; increased the apoptotic susceptibility of normal and idiopathic pulmonary fibrosis fibroblasts; blocked TGF-β1-induced myofibroblast differentiation; and inhibited TGF-β1-induced expression of fibronectin, X-linked inhibitor of apoptosis, and plasminogen activator inhibitor-1. TGF-β1 did not protect fibroblasts or myofibroblasts from apoptosis in the presence of CCG-203971. In vivo, CCG-203971 significantly reduced lung collagen content in both murine models while decreasing alveolar plasminogen activator inhibitor-1 and promoting myofibroblast apoptosis. These data support a central role of the SRF/MRTF pathway in the pathobiology of lung fibrosis and suggest that its inhibition can help resolve lung fibrosis by promoting fibroblast apoptosis.


Patterns of drug use and abuse among aging adults with and without HIV: a latent class analysis of a US Veteran cohort.
This study characterized the extent and patterns of self-reported drug use among aging adults with and without HIV, assessed differences in patterns by HIV status, and examined pattern correlates. Data derived from 6351 HIV-infected and uninfected adults enrolled in an eight-site matched cohort, the Veterans Aging Cohort Study (VACS). Using clinical variables from electronic medical records and socio-demographics, drug use consequences, and frequency of drug use from baseline surveys, we performed latent class analyses (LCA) stratified by HIV status and adjusted for clinical and socio-demographic covariates. Participants were, on average, age 50 (range 22-86), primarily male (95%) and African-American (64%). Five distinct patterns emerged: non-users, past primarily marijuana users, past multidrug users, current high consequence multidrug users, and current low consequence primarily marijuana users. HIV status strongly influenced class membership. Non-users were most prevalent among HIV uninfected (36.4%) and current high consequence multidrug users (25.5%) were most prevalent among HIV-infected. While problems of obesity marked those not currently using drugs, current users experienced higher prevalences of medical or mental health disorders. Multimorbidity was highest among past and current multidrug users. HIV-infected participants were more likely than HIV-uninfected participants to be current low consequence primarily marijuana users. In this sample, active drug use and abuse were common. HIV-infected and uninfected Veterans differed on extent and patterns of drug use and on important characteristics within identified classes. Findings have the potential to inform screening and intervention efforts in aging drug users with and without HIV.


Balloon embolectomy catheters in small arteries. II. Comparison of fluid-filled and gas-filled balloons.
Balloon embolectomy catheters were studied in 3 mm dog carotid arteries to compare liquid-filled balloons with gas-filled balloons. Balloons were filled with syringes containing 1 cc fluid (1F), 1 cc gas (1G), and 50 cc gas (50G). Results showed that lateral wall pressures (LWPs) were precisely controlled with fluid-filled balloons but were poorly controlled with gas-filled balloons because gas-filled balloons exhibited spontaneous changes in diameter and LWP. Also, when Edwards 4F balloons were filled in clinically satisfactory criteria, out of direct vision, the following LWPs (in millimeters of mercury) were obtained: 54.4 +/- 8 with 1F, 95.2 +/- 13.8 with 1G, and 216 +/- 19.8 with 50G following balloon inflation; 28.1 +/- 5.7 with 1F and 34.2 +/- 7.1 with 1G following balloon deflation. Balloons filled with 50G collapsed completely during balloon deflation. Statistically lower (P less than 0.05) LWPs were obtained with fluid-filled balloons versus gas-filled balloons and with deflation versus inflation. Gas-filled balloons produced slightly lower shear forces than did fluid-filled balloons (P less than 0.05), but only through regions of stenosis and only at low LWPs-namely 25 and 75 mm Hg LWP. Gas-filled balloons produced no reduction in shear force at higher LWPs. It was concluded that fluid-filled balloons are preferable to gas-filled balloons for use in the operating room because fluid-filled balloons provide lower LWPs greater surgeon control, and only slightly increased shear forces. With both fluid-filled and gas-filled balloons, lower LWPs can be achieved by distending balloons to apparently satisfactory levels and then deflating them to slightly lower levels.


[Steroid balance in breast cancers of varying histological structure].
Patients with breast cancer in stage I--II of various histological structure showed varied hormonal disturbances. In adenocarcinoma a high level of classic estrogens or total phenolsteroids was noted. In low differentiated cancers (solid, scirrhus) the values of estrogens excretion were considerably lower, but, if correlated with other hormones (androsterone), a relative hyperestrogenization is observed. Scirrhous cancers are characterized by the increased 17-ketogenic steroids excretion. The character of hormonal disturbances concomitant with the predominant development of certain breast tumor structures (adenocarcinoma, solid cancer, scirrhus) is identical for the patients being in their reproductive and menopausal period.


Model Parameter Estimation As Features to Predict the Duration of Epileptic Seizures From Onset.
The durations of epileptic seizures are linked to severity and risk for patients. It is unclear if the spatiotemporal evolution of a seizure has any relationship with its duration. Understanding such mechanisms may help reveal treatments for reducing the duration of a seizure. Here, we present a novel method to predict whether a seizure is going to be short or long at its onset using features that can be interpreted in the parameter space of a brain model. The parameters of a Jansen-Rit neural mass model were tracked given intracranial electroencephalography (iEEG) signals, and were processed as time series features using MINIROCKET. By analysing 2954 seizures from 10 patients, patient-specific classifiers were built to predict if a seizure would be short or long given 7 s of iEEG at seizure onset. The method achieved an area under the receiver operating characteristic curve (AUC) greater than 0.6 for five of 10 patients. The behaviour in the parameter space has shown different mechanisms are associated with short/long seizures.Clinical relevance-This shows that it is possible to classify whether a seizure will be short or long based on its early characteristics. Timely interventions and treatments can be applied if the duration of the seizures can be predicted.


"A Psychopath by Any Other Name?": Juror Perceptions of the DSM-5 "Limited Prosocial Emotions" Specifier.
DSM-5 recently added the specifier "Limited Prosocial Emotions" (LPE) to the Conduct Disorder (CD) diagnosis, yet little is known about how these traits will affect attitudes toward CD youth. Laypersons attending jury duty (N = 326) were randomly assigned to one of four case vignette conditions in which a male juvenile offender was identified as having (a) CD symptoms only, (b) CD symptoms plus a diagnostic label, (c) CD symptoms plus a diagnostic label and description of LPE traits, or (d) CD symptoms plus a description of LPE traits and a "psychopath" label. LPE traits led to more negative perceptions of the youth (e.g., more dangerous, evil, and psychopathic) and adding the psychopath label to the LPE specifier resulted in somewhat stronger support for punishment and mandated treatment. The LPE specifier may provide useful diagnostic information, but these findings raise serious concerns that it will stigmatize youth in the legal system.


The 4P-syndrome. Case description and literature review.
The microdeletion 4p16 has been found in two rare syndromes. Until now they were considered as two different syndromes: the Wolf-Hirschhorn syndrome (WHS) and the Pitt-Rogers-Danks (PRDS) syndrome characterized by a growth retardation before and after birth, microcrania, seizures, characteristic face with thin mouth, maxillary hypoplasia, short and large philtrum, characteristic nose and mental retardation. A case with 4p-16 microdeletion with phenotype characteristics similar to PRDS is reported. The patients described as PRDS are sometimes less seriously affected than patients with WHS. In fact, cases of death are not indicated in the first year of life, internal malformations are less frequent and the face lacks the typical Greek warrior helmet Recent studies have shown that WSS and PRDS are due to the absence of similar if not identical genetic segments and the clinical differences observed could be the outcome of an allele variation on the remaining homologous part.


[Disc electrophoresis of collagen protein (author's transl)].
The composition of proteins extracted from tendon collagen is investigated by disc electrophoresis. No qualitative differences can be demonstrated between young and old collagen. The action of formaldehyde and methionine on the tendons has no effect on the electrophoretic picture.


Patient-Reported Reasons for Antihypertensive Medication Change: A Quantitative Study Using Social Media.
Hypertension is the leading cause of heart disease in the world, and discontinuation or nonadherence of antihypertensive medication constitutes a significant global health concern. Patients with hypertension have high rates of medication nonadherence. Studies of reasons for nonadherence using traditional surveys are limited, can be expensive, and suffer from response, white-coat, and recall biases. Mining relevant posts by patients on social media is inexpensive and less impacted by the pressures and biases of formal surveys, which may provide direct insights into factors that lead to non-compliance with antihypertensive medication. This study examined medication ratings posted to WebMD, an online health forum that allows patients to post medication reviews. We used a previously developed natural language processing classifier to extract indications and reasons for changes in angiotensin receptor II blocker (ARB) and angiotensin-converting enzyme inhibitor (ACEI) treatments. After extraction, ratings were manually annotated and compared with data from the US Food and Drug administration (FDA) Adverse Events Reporting System (FAERS) public database. From a collection of 343,459 WebMD reviews, we automatically extracted 1867 posts mentioning changes in ACEIs or ARBs, and manually reviewed the 300 most recent posts regarding ACEI treatments and the 300 most recent posts regarding ARB treatments. After excluding posts that only mentioned a dose change or were a false-positive mention, 142 posts in the ARBs dataset and 187 posts in the ACEIs dataset remained. The majority of posts (97% ARBs, 91% ACEIs) indicated experiencing an adverse event as the reason for medication change. The most common adverse events reported mapped to the Medical Dictionary for Regulatory Activities were "musculoskeletal and connective tissue disorders" like muscle and joint pain for ARBs, and "respiratory, thoracic, and mediastinal disorders" like cough and shortness of breath for ACEIs. These categories also had the largest differences in percentage points, appearing more frequently on WebMD data than FDA data (p < 0.001). Musculoskeletal and respiratory symptoms were the most commonly reported adverse effects in social media postings associated with drug discontinuation. Managing such symptoms is a potential target of interventions seeking to improve medication persistence.


YAP-Dependent BiP Induction Is Involved in Nicotine-Mediated Oral Cancer Malignancy.
Cigarette smoking is a significant risk factor for the development and progression of oral cancer. Previous studies have reported an association between nicotine and malignancy in oral cancer. Recent studies have also demonstrated that nicotine can induce endoplasmic reticulum (ER) stress in tumor cells. Binding immunoglobulin protein (BiP) acts as a master regulator of ER stress and is frequently overexpressed in oral cancer cell lines and tissues. However, the effect of nicotine on BiP in oral cancer is unknown. Therefore, this study aimed to evaluate the role of BiP and its underlying regulatory mechanisms in nicotine-induced oral cancer progression. Our results showed that nicotine significantly induced the expression of BiP in time- and dose-dependent manners in oral squamous cell carcinoma (OSCC) cells. In addition, BiP was involved in nicotine-mediated OSCC malignancy, and depletion of BiP expression remarkably suppressed nicotine-induced malignant behaviors, including epithelial-mesenchymal transition (EMT) change, migration, and invasion. In vivo, BiP silencing abrogated nicotine-induced tumor growth and EMT switch in nude mice. Moreover, nicotine stimulated BiP expression through the activation of the YAP-TEAD transcriptional complex. Mechanistically, we observed that nicotine regulated YAP nuclear translocation and its interaction with TEAD through α7-nAChR-Akt signaling, subsequently resulting in increased TEAD occupancy on the HSPA5 promoter and elevated promoter activity. These observations suggest that BiP is involved in nicotine-induced oral cancer malignancy and may have therapeutic potential in tobacco-related oral cancer.


Spinal cord injury in hypertonic newborns after antenatal hypoxia-ischemia in a rabbit model of cerebral palsy.
While antenatal hypoxia-ischemia (H-I) is a well-established cause of brain injury, the effects of H-I on the spinal cord remain undefined. This study examined whether hypertonia in rabbits was accompanied by changes in spinal architecture. Rabbit dams underwent global fetal H-I at embryonic day 25 for 40min. High resolution diffusion tensor imaging was performed on fixed neonatal CNS. Fractional anisotropy (FA) and regional volumetric measurements were compared between kits with and without hypertonia after H-I and sham controls using Tract Based Spatial Statistics. Hypertonic kits showed evidence of damage from hypoxia not only in the brain, but in spinal cord as well. Hypertonic kits showed reduced FA and thickness in corticospinal tracts, external capsule, fimbria, and in white and gray matter of both cervical and lumbar spinal cord. Dorsal white matter of the spinal cord was the exception, where there was thickening and increased FA in hypertonic kits. Direct damage to the spinal cord was demonstrated in a subset of dams imaged during H-I with a 3T magnetic resonance scanner, where apparent diffusion coefficient in fetal spinal cords acutely decreased during hypoxia. Hypertonic kits showed subsequent decreases in lumbar motoneuron counts and extensive TUNEL- and Fluoro-Jade C-positive labeling was present in the spinal cord 48h after H-I, demonstrating spinal neurodegeneration. We speculate that global H-I causes significant loss of both spinal white and gray matter in hypertonic newborns due to direct H-I injury to the spinal cord as well as due to upstream brain injury and consequent loss of descending projections.